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Li Ye,1 Xiwei Sun,2 Yiping Li,1 Yali Zeng,1 Lacuo Zhuoma,1 Dinglun Zhou,2 Qinying He,3 Ju Wang,4 Wei Yang,1 Hang Yu,1 Yihui Yang,1 Shu Liang,1 Dan Yuan1 1Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 2West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Center for AIDS/STD Control and Prevention, Chengdu Center for Disease Control and Prevention, Chengdu, Sichuan, People’s Republic of China; 4Center for AIDS/STD Control and Prevention, Liangshan Center for Disease Control and Prevention, Xichang, Sichuan, People’s Republic of ChinaCorrespondence: Dan Yuan; Shu Liang, Email ydtv1130@163.com; liangshu523@163.comBackground: Sichuan Province was severely affected by the HIV, and there was a scarcity of data regarding the survival time and influencing factors for People Living with HIV/AIDS (PLWH) in Sichuan Province who have received Antiretroviral Therapy (ART). Therefore, it is necessary to conduct a survival analysis for PLWH receiving ART.Methods: A retrospective cohort study was conducted on PLWH who had received ART≥ 6 months in Sichuan Province from January 1, 2003, to December 31, 2022. The Kaplan-Meier method was used to calculate median survival time and plot survival curves, while a Cox proportional hazards regression model was applied to analyze factors affecting survival time. Bilateral tests were performed, with P≤ 0.05 considered statistically significant.Results: The cumulative survival rates at 1, 3, 5, and 10 years for the 223,386 subjects were 94.54%, 89.07%, 84.82%, and 76.44%, respectively. Multivariate analysis using the Cox regression model indicated lower mortality risks for females (HR=0.59, 95% CI: 0.54– 0.65), homosexual transmission (HR=0.43, 95% CI: 0.33– 0.55), and baseline BMI≥ 24 (HR=0.81, 95% CI: 0.72– 0.90). Higher mortality risks were associated with age≥ 50 years at diagnosis (HR=3.21, 95% CI: 2.94– 3.50), being unmarried or divorced (HR=1.23, 95% CI: 1.11– 1.37), living separately (HR=1.32, 95% CI: 1.22– 1.43), baseline BMI < 18.5 (HR=1.27, 95% CI: 1.13– 1.41), presence of single-drug resistance (HR=1.25, 95% CI: 1.15– 1.36), baseline WHO stage IV (HR=1.27, 95% CI: 1.09– 1.47), and a diagnosis-to-treatment interval > 12 months (HR=1.27, 95% CI: 1.15– 1.41). Compared to those with CD4(+) T cell count of 200– 350cells/μL, 350– 500cells/μL, and > 500cells/μL at baseline, individuals with < 200cells/μL had higher mortality risks (HR=0.73, 95% CI: 0.67– 0.79; HR=0.57, 95% CI: 0.51– 0.64; and HR=0.58, 95% CI: 0.51– 0.66, respectively).Conclusion: The survival rate for PLWH receiving ART in Sichuan Province was relatively high. Male gender, age over 50 at diagnosis, being unmarried, divorced, or living separately, presence of single-drug resistance, low baseline BMI, baseline CD4+ T cell < 200cells/μL, baseline WHO stage IV, and a diagnosis-to-treatment interval > 12 months were risk factors for the survival of PLWH.Keywords: PLWH, antiretroviral therapy, survival analysis

Under the background of the “carbon peaking and carbon neutrality goals”, the salt cavern is an important place for geological storage and carbon sequestration. The limited knowledge of the quantity and quality of the salt cavern and immature investigation technology constrains the development and utilization of salt cavern. After analyzing the geological exploration reports on major salt mines, reserves reports, enterprise annual reports, and research articles, a scientific understanding and basic judgment of the amount and utilizability of salt caverns in China are obtained; a technical system of salt cavern resource survey is established through a test with comprehensive detection technology in the concentrated area of salt cavern. The results show that salt cavern resources in China are characterized by abundant reserves, wide distribution, feasible burial depth, and convenient utilization on large scale. The most abundant salt cavern resources occur in the east and central regions. The national salt cavern resources are divided into levels I, II, and III by using an availability evaluation method system of salt cavern resource. Level I accounting for about 29.4%, is mainly distributed in Jiangsu, Hubei, Henan, and other provinces in east and central China. Salt cavern resources in level I are preferred for development and utilization. Level II accounting for about 65.4%, is widely distributed in southwest, northwest, and centra China, and can be used as a prospective area for development and utilization. Salt cavern resources in level III accounting for about 5.2%, are not suitable for development and utilization. Ground geophysical exploration, which can identify the characteristics of the regional geology, salt layer geology, hydrogeology, and salt cavity distribution of the salt mining area, guides the site selection on the salt cavern construction; geophysical exploration of high precision, which can obtain the information of salt mine levels and cavity structure, benefit the construction and operation detection of storage. This study provides the basic data and technical support for the planning and development of salt cavern resources in China.

Abstract Background During the prolonged COVID-19 pandemic, hospitals became focal points for normalised prevention and control. In this study, we investigated the feasibility of an inpatient bed reservation system for cancer patients that was developed in the department?s public WeChat account. We also explored its role in improving operational efficiency and nursing quality management, as well as in optimising nursing workforce deployment. Methods We utilised WeChat to facilitate communication between cancer patients and health care professionals. Furthermore, we collected data on admissions, discharges, average number of hospitalisation days, bed utilisation rate, and the number of bed days occupied by hospitalised patients through the hospital information system and nurses? working hours and competency levels through the nurse scheduling system. The average nursing hours per patient per day were calculated. Through the inpatient bed reservation system, the number of accepted admissions, denied admissions, and cancelled admissions from the reservation system were collected. The impact of the bed reservation system on the department?s operational efficiency was analysed by comparing the number of hospitalisation discharges before and after reservations, as well as the average hospitalisation and bed utilisation rates. By comparing nurses? working hours per month and average nursing hours per patient per day, the system?s impact on nurses? working hours and nursing quality indicators was analysed. Results The average hospitalisation length, bed utilisation rate, and nurses? working hours were significantly lower, and the average number of nursing hours per patient per day was significantly higher after the implementation of the reservation system. The full-cycle bed information management model for cancer patients did not affect the number of discharged patients. Conclusion Patients? ability to reserve bed types from home in advance using the department?s official WeChat-based inpatient bed reservation system allowed nurses to prepare for their work ahead of time. This in turn improved the operational efficiency of the department and nursing quality, and it optimised the deployment of the nursing workforce

Juying Zhang,1 Xia Luo,1 Xin Yang,1 Hanmei Li,1 Qiong Jiang,1 You Yang,1 Menglin Luo,1 Zijun Ma,1 Ping He,1 Linli Feng,1 Ling Li,1 Maochun Zhang,1 Yang Li,2,3 Jinhong Yu1,3 1Department of Ultrasound, Affiliated Hospital of North Sichuan Medical College, Innovation Centre for Science and Technology of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 3Department of Ultrasound, Yuechi People’s Hospital, Guangan, Sichuan, 638300, People’s Republic of ChinaCorrespondence: Jinhong Yu, Email yujinhong@nsmc.edu.cnPurpose: The incidence of hepatocellular carcinoma (HCC) is continuously increasing, and the mortality rate remains high. Thus, more effective strategies are needed to improve the treatment of HCC.Methods: In this study, we report the use of a visualized glypican-3 (GPC3)-targeting nanodelivery system (named GC-NBs) in combination with sonodynamic therapy (SDT) to enhance the therapeutic efficacy for treating HCC. The obtained nanodelivery system could actively target hepatocellular carcinoma cells and achieve ultrasound imaging through phase changes into nanobubbles under low-intensity ultrasound irradiation. Meanwhile, the released chlorine e6 (Ce6) after the nanobubbles collapse could lead to the generation of reactive oxygen species (ROS) under ultrasound irradiation to induce SDT.Results: Both in vitro and in vivo experiments have shown that GC-NBs can accumulate in tumour areas and achieve sonodynamic antitumour therapy under the navigation action of glypican-3-antibody (GPC3-Ab). Furthermore, in vitro and in vivo experiments did not show significant biological toxicity of the nanodelivery system. Moreover, GC-NBs can be imaged with ultrasound, providing personalized treatment monitoring.Conclusion: GC-NBs enable a visualized antitumour strategy from a targeted sonodynamic perspective by combining tumour-specific targeting and stimuli-responsive controlled release into a single system. Keywords: Glypican-3, nanodelivery system, ultrasound imaging, sonodynamic therapy, hepatocellular carcinoma

Qiu Chen,1 Ji-Lei Zhang,1 Jie-Shun Yang,2 Qing Jin,1 Jun Yang,3 Qiang Xue,1 Xue-feng Guang1 1Department of Cardiology, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Key Laboratory of Cardiovascular Disease of Yunnan Province, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Qiang Xue; Xue-feng Guang, Department of Cardiology, Yan’ an Hospital Affiliated to Kunming Medical University, No. 245 Renmin Dong Road, Kunming, Yunnan Province, 650051, People’s Republic of China, Email xueqiang3513@126.com; gxfyayy@163.comPurpose: Necroptosis, a monitored form of inflammatory cell death, contributes to coronary heart disease (CHD) progression. This study examined the potential of using necroptosis genes as diagnostic markers for CHD and sought to elucidate the underlying roles.Methods: Through bioinformatic analysis of GSE20680 and GSE20681, we first identified the differentially expressed genes (DEGs) related to necroptosis in CHD. Hub genes were identified using least absolute shrinkage and selection operator (LASSO) regression and random forest analysis after studying immune infiltration and transcription factor-miRNA interaction networks according to the DEGs. Quantitative polymerase chain reaction and immunohistochemistry were used to further investigate hub gene expression in vivo, for which a diagnostic model was constructed and the predictive efficacy was validated. Finally, the CHD group was categorized into high- and low-score groups in accordance with the single-sample gene set enrichment analysis (ssGSEA) score of the necroptosis genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GSEA, and further immune infiltration analyses were performed on the two groups to explore the possible roles of hub genes.Results: Based on the results of the LASSO regression and random forest analyses, four genes were used to construct a diagnostic model to establish a nomogram. Additionally, an extensive analysis of all seventeen necroptosis genes revealed notable distinctions in expression between high-risk and low-risk groups. Evaluation of immune infiltration revealed that neutrophils, monocytes, B cells, and activated dendritic cells were highly distributed in the peripheral blood of patients with CHD. Specifically, the high CHD score group exhibited greater neutrophil and monocyte infiltration. Conversely, the high-score group showed lower infiltration of M0 and M2 macrophages, CD8+ T, plasma, and resting mast cells.Conclusion: TLR3, MLKL, HMGB1, and NDRG2 may be prospective biomarkers for CHD diagnosis. These findings offer plausible explanations for the role of necroptosis in CHD progression through immune infiltration and inflammatory response.Keywords: atherosclerosis, cell death, inflammations, diagnostic biomarkers, necroptosis, immune infiltration

Dongrui Xu,1,&ast; Xiaoyi Yang,1,&ast; Wenjuan Wu,2 Jiankang Yang1 1School of Basic Medical Sciences, Dali University, Dali, Yunnan, People’s Republic of China; 2Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiankang Yang, School of Basic Medical Sciences, Dali University, Dali, Yunnan, People’s Republic of China, Email jkyang1984@126.com Wenjuan Wu, Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email wuwj1021@126.comBackground: Despite the availability of numerous therapies, the treatment of acne vulgaris remains challenging. Novel drug targets for acne vulgaris are still needed.Methods: We conducted a Mendelian randomization analysis to explore possible drug targets for acne vulgaris. We utilized summary statistics obtained from the dataset of acne vulgaris, including 399,413 individuals of European ancestry. We gathered genetic instruments for 566 plasma proteins from genome-wide association studies. In order to strengthen the findings from Mendelian randomization, various methods were employed, including bidirectional Mendelian randomization analysis, Bayesian co-localization, phenotype scanning, and single-cell analysis. These methods facilitated the identification of reverse causality, the search for reported variant-trait associations, and the determination of the cell types that is the primary source of protein. Furthermore, using the plasma proteins in the deCODE cohort, we conducted a replication of the Mendelian randomization analysis as an external validation.Results: At the significance level of Bonferroni (P < 8.83× 10− 5), a protein-acne pair was discovered through Mendelian randomization analysis. In plasma, increasing TIMP4 (OR = 1.15; 95% CI, 1.09– 1.21; P = 1.01× 10− 7) increased the risk of acne vulgaris. The absence of reverse causality was observed in the TIMP4 protein. According to Bayesian co-localization analysis, TIMP4 shared the same variant with acne vulgaris (PPH4 = 0.93). TIMP4 was replicated in deCODE cohort (OR = 1.17; 95% CI, 1.10– 1.24; P = 1.48× 10− 7). Single-cell analysis revealed that TIMP4 was predominantly detected in myeloid cells in blood, and was detected in almost all cell types in skin tissue.Conclusion: The integrative analysis revealed that the level of plasma TIMP4 has a direct influence on the risk of developing acne vulgaris. This implies that TIMP4 protein could serve as a potential target for the development of drugs aimed at treating acne vulgaris.Keywords: plasma proteome, acne vulgaris, drug target, biomarker, Mendelian randomization, TIMP4

Abstract Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Abstract Background Foot-and-mouth disease (FMD) is a devastating disease affecting cloven-hoofed animals, that leads to significant economic losses in affected countries and regions. Currently, there is an evident inclination towards the utilization of nanoparticles as powerful platforms for innovative vaccine development. Therefore, this study developed a ferritin-based nanoparticle (FNP) vaccine that displays a neutralizing epitope of foot-and-mouth disease virus (FMDV) VP1 (aa 140–158) on the surface of FNP, and evaluated the immunogenicity and protective efficacy of these FNPs in mouse and guinea pig models to provide a strategy for developing potential FMD vaccines. Results This study expressed the recombinant proteins Hpf, HPF-NE and HPF-T34E via an E. coli expression system. The results showed that the recombinant proteins Hpf, Hpf-NE and Hpf-T34E could be effectively assembled into nanoparticles. Subsequently, we evaluated the immunogenicity of the Hpf, Hpf-NE and Hpf-T34E proteins in mice, as well as the immunogenicity and protectiveness of the Hpf-T34E protein in guinea pigs. The results of the mouse experiment showed that the immune efficacy in the Hpf-T34E group was greater than the Hpf-NE group. The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs. Conclusions The Hpf-T34E nanoparticles stand out as a superior choice for a subunit vaccine candidate against FMD, offering effective protection in FMDV-infected model animals. FNP-based vaccines exhibit excellent safety and immunogenicity, thus representing a promising strategy for the continued development of highly efficient and safe FMD vaccines.

Yuan Gao,1– 3,&ast; Ce Zong,1,&ast; Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Yuncheng Ni,1,&ast; Ranglang Huang,2,&ast; Shuang Yang,3 Xiao Yan Yang,3 Shan Zeng,3 An Yao,3 Jie Huang,3 Guoping Yang3,4 1Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 3Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Huang; Guoping Yang, Email cellahuang1988@163.com; ygp9880@126.comBackground: Oliceridine is a novel G protein‐biased ligand μ-opioid receptor agonist. This study aimed to assess the pharmacokinetics and safety profile of single-ascending doses of oliceridine fumarate injection in Chinese patients with chronic non-cancer pain.Methods: Conducted as a single-center, open-label trial, this study administered single doses of 0.75, 1.5, and 3.0 mg to 32 adult participants. The trial was conducted in two parts. First, we conducted a preliminary test comprising the administration of a single dose of 0.75mg to 2 participants. Then, we conducted the main trial involving intravenous administration of escalating doses of oliceridine fumarate (0.75 to 3 mg) to 30 participants. Pharmacokinetic (PK) parameters were derived using non-compartmental analysis. Additionally, the safety evaluation encompassed the monitoring of adverse events (AEs).Results: 32 participants were included in the PK and safety analyses. Following a 2-min intravenous infusion of oliceridine fumarate injection (0.75, 1.5, or 3 mg), Cmax and Tmax ranged from 51.293 to 81.914 ng/mL and 0.034 to 0.083 h, respectively. AUC0-t and half-life (t1/2) increased more than proportionally with dosage (1.85– 2.084 h). Treatment emergent adverse events (TEAEs) were found to be consistent with the commonly reported adverse effects of opioids, both post-administration and as documented in the original trials conducted in the United States. Critically, no serious adverse events were observed.Conclusion: Oliceridine demonstrated comparable PK parameters and a consistent PK profile in the Chinese population, in line with the PK results observed in the original trials conducted in the United States. Oliceridine was safe and well tolerated in Chinese patients with chronic non-cancer pain at doses ranging from 0.75 mg to 3.0 mg.Trial Registration: The trial is registered at chictr.org.cn (ChiCTR2100047180).Keywords: pharmacokinetics, oliceridine, chronic pain, G-protein-biased ligand, phase I trial

Song Wang,1,&ast; Xiang Zhang,1,&ast; Bo Qu,2,&ast; Kunhai Yang,1 Yongrong Hu,1 Hao Liu,2 Juntao Hong,2 Hao Niu,3 Hongsheng Yang2 1School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China; 3Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Niu, Computer Science of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Email 13438368112@139.com Hongsheng Yang, Department of Orthopaedics, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, People’s Republic of China, Email hongsheng228@163.comPurpose: This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality.Methods: PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores’ effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF.Results: In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718).Conclusion: The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.Keywords: muscle quality, osteoporosis, magnetic resonance imaging, dual-energy X-ray absorptiometry, vertebral bone quality score, osteosarcopenia

AIM: To evaluate the safety and efficacy of ultrasonic cycloplasty(UCP)combined with anti-vascular endothelial growth factor(VEGF)+ panretinal photocoagulation(PRP)in the treatment of advanced neovascular glaucoma(NVG).METHODS: Retrospective study. A total of 45 patients(45 eyes)with advanced NVG who received surgery in our hospital from August 2020 to September 2022 were collected and divided into UCP+ anti-VEGF +PRP group(16 patients, 16 eyes), transscleral cyclophotocoagulation(TCP)+anti-VEGF+PRP group(20 patients, 20 eyes), UCP alone group(9 patients, 9 eyes). The intraocular pressure, pain scores, postoperative medication, effective rate, total success rate and the incidence of complications of the patients in the three groups were compared before surgery and at 1 d, 1 wk, 1 and 3 mo after surgery.RESULTS: There was no significant difference in preoperative intraocular pressure, pain scores and preoperative medication of patients in the three groups(all P>0.05). While there were statistical significance in the intraocular pressure and pain scores at 1 d, 1 wk, 1 and 3 mo after surgery(all P0.05).CONCLUSION: UCP combined with anti-VEGF +PRP and TCP combined with anti-VEGF +PRP showed comparable efficacy in reducing intraocular pressure in advanced NVG. UCP combined with anti-VEGF+PRP was more effective in relieving pain and with no serious complications in advanced NVG. UCP alone can effectively control intraocular pressure and alleviate the pain of patients in the early postoperative period, but long-term control still requires anti-VEGF+PRP.

AIM: To analyze changes in the ocular surface parameters of keratoconus after long-term wearing of rigid gas permeable contact lens(RGPCL).METHODS:Prospective case study. A total of 113 keratoconus patients(213 eyes)fitted with RGPCL in the optometry center of Gansu Provincial Hospital from January 2018 to January 2022 were included. They were divided into three groups according to the severity of keratoconus, including 42 cases(80 eyes)in mild keratoconus group, 54 cases(102 eyes)in moderate keratoconus group and 17 cases(31 eyes)in severe keratoconus group. Furthermore, the non-invasive tear break-up time(NIBUT), non-invasive tear meniscus height(NITMH), red eye index, lipid layer thickness, fluorescent corneal staining, meibomian gland secretory function, Schirmer I test and ocular surface disease index(OSDI)scores were observed by Keratograph analyzer before and after wearing RGPCL for 1 wk, 1, 3, 6, 12 mo, respectively.RESULTS: There were no statistical significance in the age, NIBUT, NITMH, lipid layer thickness, meibomian gland secretory function and Schirmer I test among the three groups(P>0.05), while there were statistical significance in the sphere, cylinder, spherical equivalent, best corrected visual acuity(BCVA), non-contact intraocular pressure(IOPNCT), anterior, posterior corneal surface Kmax, corneal surface thickness at the thinnest point, eye redness index, fluorescent corneal staining, and OSDI(P

Abstract [Objective] The study aims to elucidate the regulatory mechanism of the double petal trait in rose. We cloned an AG homologous gene RcAGL61, which was previously screened and related to flower development, and examined its function. [Methods] qRT-PCR was used to analyze the expression of RcAGL61 in flower buds of the double-petaled lines and single-petaled lines in Rosa chinensis ‘Zhaiye Tengben Yuejihua’ × R. chinensis‘Old Blush’ population. RcAGL61 was cloned from the double-petaled lines and single-petal lines, and bioinformatics analysis, subcellular localization, and VIGS experiments were carried out. [Results] (1) The expression of RcAGL61 was higher in the five developmental stages of the singlepetaled line than the double-petaled line, and the expression was higher in S4-S5 stages than in S1-S3 stages in the single-petaled line. (2) The coding sequence of RcAGL61 was the same in the double-petaled line and single-petaled line, with a length of 495 bp, which had a similarity of 30.75% with RcAG. RcAGL61 encoded 164 amino acids, which contained a conserved MADS-box, belonging to the MADS-box family. (3) RcAGL61 was localized in the nucleus. (4) When silenced by VIGS technique in R. chinensis ‘Old Blush’, the petalized stamens and petal numbers were increased, while the stamen numbers were decreased. The number of sepals and pistils had no significant change. [Conclusion] RcAGL61 is involved in regulating the transition between stamens and petal primordiums, and affects the number of petals in R. chinensis.

Abstract Simultaneously achieving high sensitivity and detection speed with traditional solid-state biosensors is usually limited since the target molecules must passively diffuse to the sensor surface before they can be detected. Microfluidic techniques have been applied to shorten the diffusion time by continuously moving molecules through the biosensing regions. However, the binding efficiencies of the biomolecules are still limited by the inherent laminar flow inside microscale channels. In this study, focused traveling surface acoustic waves were directed into an acoustic microfluidic chip, which could continuously enrich the target molecules into a constriction zone for immediate detection of the immune reactions, thus significantly improving the detection sensitivity and speed. To demonstrate the enhancement of biosensing, we first developed an acoustic microfluidic chip integrated with a focused interdigital transducer; this transducer had the ability to capture more than 91% of passed microbeads. Subsequently, polystyrene microbeads were pre-captured with human IgG molecules at different concentrations and loaded for detection on the chip. As representative results, ~0.63, 2.62, 11.78, and 19.75 seconds were needed to accumulate significant numbers of microbeads pre-captured with human IgG molecules at concentrations of 100, 10, 1, and 0.1 ng/mL (~0.7 pM), respectively; this process was faster than the other methods at the hour level and more sensitive than the other methods at the nanomolar level. Our results indicated that the proposed method could significantly improve both the sensitivity and speed, revealing the importance of selective enrichment strategies for rapid biosensing of rare molecules.

Abstract Schizophrenia (SCZ), which affects approximately 1% of the world’s population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

Microwave dielectric ceramics, owing to their ability to serve as dielectrics in microwave circuits, are widely used in communications, navigation, radar, satellite, and other fields as a key foundational material in modern communications technology.Grounded in an analysis of the current state of microwave dielectric ceramics and their corresponding industry both in China and abroad,this study identifies the challenges faced in the development of these ceramics in China and proposes a strategy for the independent development of microwave dielectric ceramics, encompassing development goals, strategies, key directions, and a development roadmap.The study aims to promote the development of microwave dielectric ceramics, facilitate the shift of the product structure from mid- to high-end products, and achieve breakthroughs in high-performance microwave dielectric ceramics preparation techniques and the independent production of upstream high-purity raw materials. Recommendations for research include strengthening the basic research and application foundations of microwave dielectric ceramics, enhancing innovative research and development in key areas of microwave communications, actively planning for 6G dielectric ceramics, and strengthening the development of the industry’s ecosystem.

Composite sandwich structures are widely used in the aerospace field due to their advantages of high strength, lightweight, and fatigue resistance. However, these structures are prone to damage with very-low-energy impacts. In order to improve the impact resistance of aircraft skin structure, a low-velocity impact resistance of sandwich structure specimens was tested by means of drop hammer impact, and the impact damage area was scanned by ultrasonic C-scan, and obtains the impact damage of specimens with different impact energies and different ply sequences. Combined with the Hashin failure criterion, the finite element equivalent model of composite sandwich structure under low-velocity impact was established. The errors between the simulation results and the C-scan results of the test piece were less than 10%, in which the experimental measurements and numerical predictions were in close agreement. Finally, the finite element equivalent model was applied to optimize the application of model sandwich, which was used for fuselage skin of a certain electric aircraft. The total thickness of the laminate structure remains unchanged before and after optimization, but the impact resistance was significantly enhanced. The ±45° lay-up was beneficial for the structure to absorb the impact energy.

Abstract Heart disease is the world’s leading cause of death. Diagnostic models based on electrocardiograms (ECGs) are often limited by the scarcity of high-quality data and issues of data imbalance. To address these challenges, we propose a conditional generative adversarial network (CECG-GAN). This strategy enables the generation of samples that closely approximate the distribution of ECG data. Additionally, CECG-GAN addresses waveform jitter, slow processing speeds, and dataset imbalance issues through the integration of a transformer architecture. We evaluated this approach using two datasets: MIT-BIH and CSPC2020. The experimental results demonstrate that CECG-GAN achieves outstanding performance metrics. Notably, the percentage root mean square difference (PRD) reached 55.048, indicating a high degree of similarity between generated and actual ECG waveforms. Additionally, the Fréchet distance (FD) was approximately 1.139, the root mean square error (RMSE) registered at 0.232, and the mean absolute error (MAE) was recorded at 0.166.

Xinyan Hu,1,&ast; Yanling Sui,1,&ast; Xinhao Yang,1 Zhengyu Yang,2 Qiuting Wang,2 Jiehong Yuan,2 Maoyu Li,1 Xiaotong Ma,1 Chengxuan Qiu,3 Qinjian Sun1 1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 3Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden&ast;These authors contributed equally to this workCorrespondence: Qinjian Sun, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Email sqj1210@163.comBackground: The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease.Methods: This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques.Results: The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13– 1.90, P = 0.004; P for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40– 64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42– 2.98, P < 0.001; P for trend < 0.001).Conclusion: A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40– 64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention. Keywords: C-reactive protein, albumin, plaque, atherosclerotic, cohort study

Luxun Yang,1,&ast; Haiying Ran,2,&ast; Yaru Yin,1 Jing Liu,1 Binghui Lu,1 Xi Ran,3 Shenglin Luo,1 Weidong Wang,4 Zhangyou Yang,5 Rong Li1 1Institute of Combined Injury, National Key Laboratory of Trauma and Chemical Poisoning, Army Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Biomedical Analysis Center, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Department of Medical Laboratory, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 4Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, 610041, People’s Republic of China; 5Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhangyou Yang, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, People’s Republic of China, Email yangzhangyou@cqmu.edu.cn Rong Li, Army Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People’s Republic of China, Tel +86-13883996627, Fax +8623-68753127, Email lrong361@126.comPurpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.Keywords: radioprotective effect, ceria nanoclusters, mitochondria targeting, oxidative stress, superoxide dismutase

Xi-Ding Yang,1,2 Yong-Yu Yang1,3 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Phase I Clinical Trial Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Provincial Engineering Research Central of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yong-Yu Yang, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email yongyuyang@csu.edu.cnPurpose: The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use.Methodology: The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (Cmax), time to Cmax, half-life (t1/2), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies.Results: Semaglutide has a predictable pharmacokinetic profile with a long t1/2 that allows for once-weekly subcutaneous administration. The AUC and Cmax of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug–drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this.Conclusion: This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.Keywords: Pharmacokinetics, semaglutide, curve plasma concentrations, type 2 diabetes, obesity, glucagon-like peptide-1, drug–drug interaction

Yanzhao Zhou,1,&ast; Jingzhong Ouyang,2– 4,&ast; Hongcai Yang,5,&ast; Zhengzheng Wang,2,&ast; Yi Yang,3,4,&ast; Qingjun Li,2 Haitao Zhao,6 Jinxue Zhou,2 Qiang Li1 1Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Li, Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China, Email liqiang@tjmuch.com Jinxue Zhou, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, People’s Republic of China, Email zhoujx888@126.comPurpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions.Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models.Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI.Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.Keywords: hepatocellular carcinoma, immunotherapy, body mass index, body composition, obesity paradox

Bo Zhang,1,2 Minmin Guo,2 Ting Dong,2 Huajuan Yang,2 Qiujuan Zhang,2 Quanxin Yang,2 Xiaoqian Zhou,2 Cuiping Mao,2 Ming Zhang1 1Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Department of Medical Imaging, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of ChinaCorrespondence: Ming Zhang, Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email zmmri@163.comPurpose: Chronic low back pain (cLBP) is a recurring and intractable disease that is often accompanied by emotional and cognitive disorders such as depression and anxiety. The nucleus accumbens (NAc) plays an important role in mediating emotional and cognitive processes and analgesia. This study investigated the resting-state functional connectivity (rsFC) and effective connectivity (EC) of NAc and its subregions in cLBP.Methods: Thirty-four cLBP patients and 34 age- and sex-matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based rsFC and Dynamic Causal Modelling (DCM) were used to examine the alteration of the rsFC and EC of the NAc.Results: Our results showed that the cLBP group had increased rsFC of the bilateral NAc-left superior frontal cortex (SFC), orbital frontal cortex (OFC), left angular gyrus, the left NAc-bilateral middle temporal gyrus, as well as decreased rsFC of left NAc-left supramarginal gyrus, right precentral gyrus, left cerebellum, brainstem (medulla oblongata), and right insula pathways compared with the HC; the results of the subregions were largely consistent with the whole NAc. In addition, the rsFC of the left NAc-left SFC was negatively correlated with Hamilton’s Depression Scale (HAMD) scores (r = − 0.402, p = 0.018), and the rsFC of left NAc-OFC was positively correlated with present pain intensity scores (r = 0.406, p = 0.017) in the cLBP group. DCM showed that the cLBP group showed significantly increased EC from the left cerebellum to the right NAc (p = 0.012) as compared with HC.Conclusion: Overall, our findings demonstrate aberrant rsFC and EC between NAc and regions that are associated with emotional regulation and cognitive processing in individuals with cLBP, underscoring the pivotal roles of emotion and cognition in cLBP.Keywords: low back pain, nucleus accumbens, resting-state functional connectivity, dynamic causal modelling

Abstract Objective To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. Methods Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. Results Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. Conclusion It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

Xiaoqing Peng,1– 4,&ast; Yuanyuan Yang,3,4,&ast; Ruirui Hou,1 Longbiao Zhang,1 Can Shen,3 Xiaoyan Yang,3 Zhigang Luo,5 Zongzhi Yin,3,4 Yunxia Cao3,4 1School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China; 2Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, Hefei, Anhui, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4The Key National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, People’s Republic of China; 5Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunxia Cao; Zongzhi Yin, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Sushan District, Hefei, Anhui, People’s Republic of China, Email caoyunxia5972@ahmu.edu.cn; yinzongzhi@ahmu.edu.cnAbstract: Mitochondrial carrier homolog 2 (MTCH2) is a member of the solute carrier 25 family, located on the outer mitochondrial membrane. MTCH2 was first identified in 2000. The development in MTCH2 research is rapidly increasing. The most well-known role of MTCH2 is linking to the pro-apoptosis BID to facilitate mitochondrial apoptosis. Genetic variants in MTCH2 have been investigated for their association with metabolic and neurodegenerative diseases, however, no intervention or therapeutic suggestions were provided. Recent studies revealed the physiological and pathological function of MTCH2 in metabolic diseases, neurodegenerative diseases, cancers, embryonic development and reproduction via regulating mitochondrial apoptosis, metabolic shift between glycolysis and oxidative phosphorylation, mitochondrial fusion/fission, epithelial-mesenchymal transition, etc. This review endeavors to assess a total of 131 published articles to summarise the structure and physiological/pathological role of MTCH2, which has not previously been conducted. This review concludes that MTCH2 plays a crucial role in metabolic diseases, neurodegenerative diseases, cancers, embryonic development and reproduction, and the predominant molecular mechanism is regulation of mitochondrial function. This review gives a comprehensive state of current knowledgement on MTCH2, which will promote the therapeutic research of MTCH2. Keywords: Mimp, MTCH2, mitochondrial carrier homolog 2, BID, apoptosis

Lin Tang,1,&ast; Jian Liu,2,&ast; Hui Yang,2,&ast; Hong-Qing Zhao,3 Chao Hu,4 Si-Jing Ma,5 Yu-Hui Qing,6 Lei Yang,1 Rong-Rong Zhou,5 Shui-Han Zhang6 1Hospital-Made Preparations Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 2Medical Innovation Experiment Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 3Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 4Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 5The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 6Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Rong Zhou; Shui-Han Zhang, Tel +86-0731-85920129, Email rrzhou0823@163.com; zhangshuihan0220@126.comPurpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin–eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut–brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters. Keywords: Baihe Dihuang decoction, 16S rRNA, metabolomics, anxiety, neurotransmitter

Nan Jiang,1,2 Chun Mei Yang,1,2 Jia Le Wang,1,2 Xiao Fei Ye,1 Bin Yang1,2 1Children’s Medical Centre of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2The Fifth Clinical College Affiliated to Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Bin Yang, Children’s Medical Centre of Anhui Medical University, The Fifth Clinical College Affiliated to Anhui Medical University, Hefei, People’s Republic of China, Tel +86-13866127496, Email yangbin691202@163.comPurpose: To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction.Patients and methods: 107 children 6– 14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children’s Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT).Results: Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P< 0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= − 0.253, P< 0.01), while they were positively correlated with total reaction time (ρ=0.367, P< 0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=− 0.344 P< 0.01; ρ=− 0.418 P< 0.01).Conclusion: Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.Keywords: SeLECTS, attention network function, sleep disorders, CSHQ

Abstract Background Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. Methods This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. Results During the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27). Conclusions Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Abstract During the restoration of iron cultural relics, the removal of rust from these artifacts is necessary. However, this rust removal process may lead to inconsistent local color on the iron relics. To address this, mending materials are applied to treat the surface, ensuring consistent local color. In the surface treatment of iron cultural relics, a significant challenge lies in modulating the color of these mending materials. The corrosion products of Yuquan Iron Pagoda are mainly Fe3O4, γ-FeO(OH), α-FeO(OH) and α-Fe2O3, with contents of 13.1, 16.1, 40.2 and 30.6%, respectively. Due to their structural stability and suitable color characteristics, Fe3O4 and α-Fe2O3 are selected as the primary raw materials for the repair material. This study employs machine learning methods to predict the color of mending materials corresponding to varying contents of α-Fe2O3, Fe3O4, and epoxy resin. The Artificial Neural Network (ANN), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boost Machine (LightGBM) algorithms are utilized to develop the model, and the predictive performance of these three algorithms is compared. XGBoost exhibits the best prediction performance, achieving a square correlation coefficient (R2) of 0.94238 and a mean absolute error (MAE) of 0.68485. Additionally, the SHapley Additive exPlanations (SHAP) method is employed to analyze the most crucial raw material affecting the color of mending materials, which is identified as Fe3O4. The study illustrates the specific process of employing this model by applying it to the surface treatment of the Yuquan Iron Pagoda, demonstrating the practicality of the model. This model can be applied to assist in the surface treatment of other iron cultural relics.

Abstract Background Plant microbiota contributes to plant growth and health, including enhancing plant resistance to various diseases. Despite remarkable progress in understanding diseases resistance in plants, the precise role of rhizosphere microbiota in enhancing watermelon resistance against soil-borne diseases remains unclear. Here, we constructed a synthetic community (SynCom) of 16 core bacterial strains obtained from the rhizosphere of grafted watermelon plants. We further simplified SynCom and investigated the role of bacteria with synergistic interactions in promoting plant growth through a simple synthetic community. Results Our results demonstrated that the SynCom significantly enhanced the growth and disease resistance of ungrafted watermelon grown in non-sterile soil. Furthermore, analysis of the amplicon and metagenome data revealed the pivotal role of Pseudomonas in enhancing plant health, as evidenced by a significant increase in the relative abundance and biofilm-forming pathways of Pseudomonas post-SynCom inoculation. Based on in vitro co-culture experiments and bacterial metabolomic analysis, we selected Pseudomonas along with seven other members of the SynCom that exhibited synergistic effects with Pseudomonas. It enabled us to further refine the initially constructed SynCom into a simplified SynCom comprising the eight selected bacterial species. Notably, the plant-promoting effects of simplified SynCom were similar to those of the initial SynCom. Furthermore, the simplified SynCom protected plants through synergistic effects of bacteria. Conclusions Our findings suggest that the SynCom proliferate in the rhizosphere and mitigate soil-borne diseases through microbial synergistic interactions, highlighting the potential of synergistic effects between microorganisms in enhancing plant health. This study provides a novel insight into using the functional SynCom as a promising solution for sustainable agriculture. Video Abstract

Chengxue He,1,2,&ast; YanHui Guo,3,&ast; Nina Zhou,2,&ast; Zhen Wang,4,&ast; Teli Liu,2 Xiaoxia Xu,2 Feng Wang,2 Hua Zhu,2 Zhi Yang,1,2 Xianteng Yang,1,5 Lei Xia2 1Medical College, Guizhou University, Guiyang, GuiZhou Province, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Hepato-Pancreato-Biliary Surgery, Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 5Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, GuiZhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xia; Zhi Yang, Tel +86 010-88197852 ; +86 010-88196196, Email xialei9012288@126.com; pekyz@163.comBackground: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target.Methods and Results: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89Zr (half-life: 100.8 hours) and chelation of Mn2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67± 3.45 for PET and 6.63± 0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups.Conclusion: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT. Keywords: theranostics, PET/MRI, melanin nanoparticles, photothermal therapy

Min Liu,1,2 Bo Liu,2 Ziyang Liu,3 Zhen Yang,2 Thomas J Webster,4 Huan Zhou,2 Lei Yang2 1School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People’s Republic of China; 2Center for Health Science and Engineering, Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China; 3Department of Orthopedics, Tianjin Hospital, Tianjin, People’s Republic of China; 4School of Engineering, Saveetha University, Chennai, IndiaCorrespondence: Huan Zhou; Lei Yang, Center for Health Science and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China, Email zhouhuan@hebut.edu.cn; ylei@hebut.edu.cnIntroduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation.Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement.Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa.Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.Keywords: shape memory, interbody fusion cage, NIR responsive, calcium phosphate cement, minimally invasive

Yi Yang,1 Jingxian Wang,1 Qing Su,1 Jinhuan Yang,2,3 Zhiyuan Bo,2,3 Chongming Zheng,2,3 Yitong Xie,2,3 Kaiwen Chen,2,3 Juejin Wang,1 Gang Chen,2,3 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 3Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health, Wenzhou Medical University, Nanliu Road, Chashan Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-86699-358, Email wang.yi@wmu.edu.cn Gang Chen, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Nanbaixiang Street, Ouhai District, Wenzhou City, Zhejiang Province, 325035, People’s Republic of China, Fax +86(577)-55579-555, Email chen.gang@wmu.edu.cnBackground: Primary liver cancer (PLC) is a fatal malignancy, sleep quality and gut microbiota were shown to be associated with PLC. However, the mechanism of how sleep quality affects PLC is unclear. This study aims to investigate the mediation/moderation effects of gut microbiota on sleep quality and the occurrence of PLC.Methods: The causality of sleep quality and the occurrence of PLC was detected through the Mendelian randomization (MR) analysis based on the data including 305,359 individuals (Finland Database) and 456,348 participants (UK Biobank). The primary method used for MR analysis was inverse-variance weighted analysis. Gut microbiota’ mediation/moderation effects were uncovered in the case–control study including 254 patients with PLC and 193 people with benign liver diseases through the mediation/moderation effect analyses. People’s sleep quality was evaluated through the Pittsburgh sleep quality index (PSQI).Results: Poor sleep quality could lead to PLC through the MR analysis (P = 0.026). The case–control study uncovered that Actinobacteria had mediation effects on the relationship between PSQI score, self-sleep quality, and the occurrence of PLC (P = 0.048, P = 0.046). Actinobacteria and Bifidobacterium could inhibit the development of PLC caused by short night sleep duration (P = 0.021, P = 0.022). Erysipelotrichales could weaken the influence of daytime dysfunction on PLC (P = 0.033). Roseburia modulated the contribution of nocturnal insomnia and poor sleep quality to PLC (P = 0.009, P = 0.017).Conclusion: Poor sleep quality was associated with PLC. Gut microbiota’ mediation/moderation effects on poor sleep quality and the occurrence of PLC prompted an insightful idea for the prevention of PLC.Keywords: primary liver cancer, sleep quality, gut microbiota, Mendelian randomization, mediation/moderation effect

Combining multiple crop protection Unmanned Aerial Vehicles (UAVs) as a team for a scheduled spraying mission over farmland now is a common way to significantly increase efficiency. However, given some issues such as different configurations, irregular borders, and especially varying pesticide requirements, it is more important and more complex than other multi-Agent Systems (MASs) in common use. In this work, we focus on the mission arrangement of UAVs, which is the foundation of other high-level cooperations, systematically propose Efficiency-first Spraying Mission Arrangement Problem (ESMAP), and try to construct a united problem framework for the mission arrangement of crop protection UAVs. Besides, to characterise the differences in sub-areas, the varying pesticide requirement per unit is well considered based on Normalized Difference Vegetation Index (NDVI). Firstly, the mathematical model of multiple crop-protection UAVs is established and ESMAP is defined. Furthermore, an acquisition method of a farmland’s NDVI map is proposed, and the calculation method of pesticide volume based on NDVI is discussed. Secondly, an improved Genetic Algorithm (GA) is proposed to solve ESMAP, and a comparable combination algorithm is introduced. Numerical simulations for algorithm analysis are carried out within MATLAB, and it is determined that the proposed GA is more efficient and accurate than the latter. Finally, a mission arrangement tested with three UAVs was carried out to validate the effectiveness of the proposed GA in spraying operation. Test results illustrated that it performed well, which took only 90.6 % of the operation time taken by the combination algorithm.

ObjectiveFarmland consolidation for agricultural mechanization in hilly and mountainous areas can alter the landscape pattern, elevation, slope and microgeomorphology of cultivated land. It is of great significance to assess the ecological risk of cultivated land to provide data reference for the subsequent farmland consolidation for agricultural mechanization. This study aims to assess the ecological risk of cultivated land before and after farmland consolidation for agricultural mechanization in hilly and mountainous areas, and to explore the relationship between cultivated land ecological risk and cultivated land slope.MethodsTwenty counties in Tongnan district of Chongqing city was selected as the assessment units. Based on the land use data in 2010 and 2020 as two periods, ArcGIS 10.8 and Excel software were used to calculate landscape pattern indices. The weights for each index were determined by entropy weight method, and an ecological risk assessment model was constructed, which was used to reveal the temporal and spatial change characteristics of ecological risk. Based on the principle of mathematical statistics, the correlation analysis between cultivated land ecological risk and cultivated land slope was carried out, which aimed to explore the relationship between cultivated land ecological risk and cultivated land slope.Results and DiscussionsComparing to 2010, patch density (PD), division (D), fractal dimension (FD), and edge density (ED) of cultivated land all decreased in 2020, while meant Patch Size (MPS) increased, indicating an increase in the contiguity of cultivated land. The mean shape index (MSI) of cultivated land increased, indicating that the shape of cultivated land tended to be complicated. The landscape disturbance index (U) decreased from 0.97 to 0.94, indicating that the overall resistance to disturbances in cultivated land has increased. The landscape vulnerability index (V) increased from 2.96 to 3.20, indicating that the structure of cultivated land become more fragile. The ecological risk value of cultivated land decreased from 3.10 to 3.01, indicating the farmland consolidation for agricultural mechanization effectively improved the landscape pattern of cultivated land and enhanced the safety of the agricultural ecosystem. During the two periods, the ecological risk areas were primarily composed of low-risk and relatively low-risk zones. The area of low-risk zones increased by 6.44%, mainly expanding towards the northern part, while the area of relatively low-risk zones increased by 6.17%, primarily spreading towards the central-eastern and southeastern part. The area of moderate-risk zones increased by 24.4%, mainly extending towards the western and northwestern part, while the area of relatively high-risk zones decreased by 60.70%, with some new additions spreading towards the northeastern part. The area of high-risk zones increased by 16.30%, with some new additions extending towards the northwest part. Overall, the ecological safety zones of cultivated relatively increased. The cultivated land slope was primarily concentrated in the range of 2° to 25°. On the one hand, when the cultivated land slope was less than 15°, the proportion of the slope area was negatively correlated with the ecological risk value. On the other hand, when the slope was above 15°, the proportion of the slope area was positively correlated with the ecological risk value. In 2010, there was a highly significant correlation between the proportion of slope area and ecological risk value for cultivated land slope within the ranges of 5° to 8°, 15° to 25°, and above 25°, with corresponding correlation coefficients of 0.592, 0.609, and 0.849, respectively. In 2020, there was a highly significant correlation between the proportion of slope area and ecological risk value for cultivated land slope within the ranges of 2° to 5°, 5° to 8°, 15° to 25°, and above 25°, with corresponding correlation coefficients of 0.534, 0.667, 0.729, and 0.839, respectively.ConclusionsThe assessment of cultivated land ecological risk in Tongnan district of Chongqing city before and after the farmland consolidation for agricultural mechanization, as well as the analysis of the correlation between ecological risk and cultivated land slope, demonstrate that the farmland consolidation for agricultural mechanization can reduce cultivated land ecological risk, and the proportion of cultivated land slope can be an important basis for precision guidance in the farmland consolidation for agricultural mechanization. Considering the occurrence of moderate sheet erosion from a slope of 5° and intense erosion from a slope of 10° to 15°, and taking into account the reduction of ecological risk value and the actual topographic conditions, the subsequent farmland consolidation for agricultural mechanization in Tongnan district should focus on areas with cultivated land slope ranging from 5° to 8° and 15° to 25°.

Abstract Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice (Gch1 fl/fl ; Sftpa1-Cre +/− mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice (Gch1 lsl/lsl ; Sftpa1-Cre +/− mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury.

Mengnan Li,1,2,&ast; Xifeng Yang,1,2,&ast; Ru Li,1,2 Baofeng Wu,1,2 Jinxuan Hao,1,2 Yijie Qi,1,2 Tao Bai,1 Luyang Yang,1 Yi Zhang,3 Yunfeng Liu1,4 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Clinical Research Center of Endocrine and Metabolic Diseases in Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comPurpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids.Patients and Methods: 50 patients with newly diagnosed Graves’ disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis.Results: The results showed that the following indexes changed significantly at different time points: visceral fat area, subcutaneous fat area, free triiodothyronine, free thyroxine, thyroid stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, body weight, neck circumference, body mass index, waist circumference, and drug dose (All P< 0.001). We found that free triiodothyronine and free thyroxine were significantly negatively associated with abdominal fat area (P< 0.01). There was no significant correlation between drug dose and abdominal fat area (P> 0.05). Total cholesterol and low-density lipoprotein were significantly positively associated with abdominal fat area (P< 0.01). However, high-density lipoprotein (P=0.06) was not correlated with abdominal fat area. Moreover, the results showed a significant negative correlation between thyroid hormones and lipids (P< 0.001).Conclusion: After anti-thyroid medicine treatment, patients had elevated visceral fat area and subcutaneous fat area and altered lipid profiles. These changes may be one of the reasons why metabolic and cardiovascular diseases remain increased after thyroid function is restored.Keywords: visceral fat area, subcutaneous fat area, thyroid hormones, lipids, Graves’ disease

Abstract Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of “fear and worry about choriocarcinoma recurrence”. We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration N/A.

Abstract Low efficiency and spectral instability caused by the surface defects have been considerable issues for the mixed‐halogen blue emitting perovskite quantum dots light‐emitting diodes (PeQLEDs). Here, an in situ surface passivation to perovskite quantum dots (PeQDs) is realized by introducing the metal cations competitive lattice occupancy assisted with acid‐etching, in which the long‐chain, insulating and weakly bond surface ligands are removed by addition of octanoic acid (OTAC). Meanwhile, the dissolved A‐site cations (Na+) compete with the protonated oleyl amine and are subsequently anchored to the surface vacancies. The preadded lead bromide, acting as inorganic ligands, demonstrates strong bonding to the uncoordinated surface ions. The as‐synthesized PeQDs show the boosted photoluminescence quantum yield (PLQY) and superior stability with longer lifetime. As a result, the PeQLEDs (470 nm) based on the OTAC‐Na PeQDs exhibit an external quantum efficiency of 8.42% in the mixed halogen PeQDs (CsPb(BrxCl1−x)3). Moreover, the device exhibits superior spectra stability with negligible shift. Our competition mechanism in combination with in situ passivation strategy paves a new way for improving the performance of blue PeQLEDs.

Abstract The neocortex comprises six cortical layers that play a crucial role in information processing; however, it remains unclear whether laminar processing is consistent across all regions within a single cortex. In this study, we demonstrate diverse laminar response patterns in the primary visual cortex (V1) of three male macaque monkeys when exposed to visual stimuli at different spatial frequencies (SFs). These response patterns can be categorized into two groups. One group exhibit suppressed responses in the output layers for all SFs, while the other type shows amplified responses specifically at high SFs. Further analysis suggests that both magnocellular (M) and parvocellular (P) pathways contribute to the suppressive effect through feedforward mechanisms, whereas amplification is specific to local recurrent mechanisms within the parvocellular pathway. These findings highlight the non-uniform distribution of neural mechanisms involved in laminar processing and emphasize how pathway-specific amplification selectively enhances representations of high-SF information in primate V1.

Yixue Huang,&ast; Wenhao Wang,&ast; Linlin Zhang,&ast; Yun Teng, Zihao Zhan, Huilin Yang, Peng Yang Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Yang; Huilin Yang, Department of Orthopaedics, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Tel +86 512 67972157, Email ypspine@163.com; szyhlspine@163.comBackground: To determine the factors in posterior ligamentous complex indicating lumbar instability in patients diagnosed with degenerative spondylolisthesis on conventional magnetic resonance imaging (MRI).Methods: We retrospectively analyzed patients who underwent PLIF surgery for degenerative spondylolisthesis at our institution between 2018 and 2020 and who had complete eligible preoperative imaging data for review and study, including lumbar MRI and anteroposterior and flexion-extension radiographs.Results: Fifty-three patients were confirmed to have lumbar instability (Unstable Group, 44%), while sixty-seven patients (Stable Group, 56%) did not have instability on radiographs. The patients in the stable group had more advanced status of the degeneration of intervertebral disc than in the unstable group (p< 0.05). The degeneration of supraspinous ligament (SSL) was more severe in the unstable group (p< 0.05). Compared with the patients with rotatory instability, advanced degeneration of interspinous ligament (ISL) and SSL was observed in patients with translatory instability (p< 0.05). However, there was no significant difference with regard to the height of the spinous process and the interspinous distance in patients with or without instability.Conclusion: This MRI analysis showed that abnormal segmental motion is closely associated with the pathological characteristics of supraspinal ligament. Advanced degeneration of SSL in patients with degenerative spondylolisthesis should raise the suspicion for lumbar instability and additional evaluations. The status of ISL and ligamentum flavum (LF) may not be helpful for the diagnosis of lumbar instability. Functional radiographs combined with MRI may provide valuable information when diagnosing lumbar instability in patients with mechanical back pain.Keywords: interspinous distance, lumbar instability, MRI, posterior ligament complex, spinal process

Longfei Fan,1 Zhongqiang Qin,1 Di Wu,1 Yunchuan Yang,2 Yigang Zhang,2 Bo Xie,1 Jingyu Qian,1 Jianzhu Wei,1 Zhaoying Wang,1 Peipei Yang,1 Zhen Qian,1 Mu Yuan,1 Ziyi Zhu,1 Yulin Tan,1 Yi Tan2 1Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of ChinaCorrespondence: Yi Tan, Email doctortanyi2007@126.comPurpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC).Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators.Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators.Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.Keywords: hepatocellular carcinoma, leucyl-tRNA synthetase 1, bioinformatics analysis, biomarker, the cancer genome atlas

Zihan Zhou,1,2,&ast; Yuhui Wang,2,3,&ast; Yongsheng Wang,1,2 Bo Yang,4 Chuchu Xu,1,2 Shuqin Wang,1,2 Wanchun Yang1,2 1Department of Respiratory and Critical Care Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical College of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Cardiology, Hefei Hospital Affiliated to Anhui Medical University, Hefei, The Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China; 4Affiliated Hospital of West Anhui Health Vocational College, The Second People’s Hospital of Lu’an City, Lu’an, 237005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanchun Yang, Department of Respiratory and Critical Care Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China, Email hfey2023@163.comPurpose: To develop and validate a nomogram for assessing the risk of developing hypercapnic respiratory failure (HRF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Patients and Methods: From January 2019 to August 2023, a total of 334 AECOPD patients were enrolled in this research. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to determine independent predictors and develop a nomogram. This nomogram was appraised by the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer–Lemeshow goodness-of-fit test (HL test), decision curve analysis (DCA), and clinical impact curve (CIC). The enhanced bootstrap method was used for internal validation.Results: Sex, prognostic nutritional index (PNI), hematocrit (HCT), and activities of daily living (ADL) were independent predictors of HRF in AECOPD patients. The developed nomogram based on the above predictors showed good performance. The AUCs for the training, internal, and external validation cohorts were 0.841, 0.884, and 0.852, respectively. The calibration curves and HL test showed excellent concordance. The DCA and CIC showed excellent clinical usefulness. Finally, a dynamic nomogram was developed (https://a18895635453.shinyapps.io/dynnomapp/).Conclusion: This nomogram based on sex, PNI, HCT, and ADL demonstrated high accuracy and clinical value in predicting HRF. It is a less expensive and more accessible approach to assess the risk of developing HRF in AECOPD patients, which is more suitable for primary hospitals, especially in developing countries with high COPD-related morbidity and mortality.Keywords: acute exacerbation of chronic obstructive pulmonary disease, hypercapnic respiratory failure, nomogram, prediction model