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Xu-Lin Wang,1,&ast; Ling-Ling Dai,2,&ast; Yan-Na Li,1 Jian-Wen Zhang,1 Ming-Cui Qu,1 Yao-Yao Zhou,1 Na Xing1 1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Xing, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, People’s Republic of China, Tel +8613949095172, Email 16427485@qq.comPurpose: This study aimed to compare the efficacy of remimazolam and propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery.Patients and Methods: This was a single-center, open-label, non-inferiority, randomized clinical trial. Patients aged ≥ 18 years who underwent outpatient gynecological surgery with sedation were enrolled. Participants were randomly assigned to be sedated with remimazolam or propofol. The primary endpoint was the immediate postoperative anesthesia satisfaction score, evaluated through the Iowa Satisfaction with Anesthesia Scale (ISAS).Results: 168 patients were randomly allocated to either the remimazolam group (n = 84) or the propofol group (n = 84). The mean (standard deviation) ISAS scores immediately after surgery were 1.7 (0.6) for the remimazolam group and 2.0 (0.7) for the propofol group (difference, – 0.2; 97.5% confidence interval [CI]: – 0.5 to – 0.0; p = 0.02), indicating non-inferiority. The length of post-anesthesia care unit (PACU) stay was longer in the remimazolam group than in the propofol group (27.6 [9.1] min vs 22.4 [7.0] min; difference, 5.2 [95% CI: 2.7 to 7.6] min; p < 0.001). High-intensity injection pain was less frequently observed in the remimazolam group than in the propofol group (3.6% vs 45.2%; difference, – 41.7% [95% CI: – 54.2% to – 29.1%]; p < 0.001). The nausea score was higher in the remimazolam group immediately after surgery than in the propofol group. Pain, nausea, sleep quality, anxiety, and depression scores were higher in the remimazolam group than in the propofol group on postoperative day 1. The incidence of adverse events and other secondary endpoints was comparable between the two groups.Conclusion: Remimazolam was non-inferior to propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery. Therefore, it should be considered as a new sedation alternative in such procedures.Keywords: remimazolam, propofol, patient satisfaction, outpatient gynecological surgery, sedation

Ying-Yan Zhou,1,&ast; Jing-Hua Sun,2,&ast; Li Wang,1 Yan-Yan Cheng1 1Department of Cardiovascular Medicine, Haikou Third People’s Hospital, Haikou, 571700, People’s Republic of China; 2Department of Laboratory Medicine, First Medical Centre of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Yan Cheng, Department of Cardiovascular Medicine, Haikou Third People’s Hospital, Haikou, 571700, People’s Republic of China, Email cyy570775779@163.comObjective: The present study is to explore the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk.Methods: This research were selected 80 CHD patients as the observation group and 130 healthy people who participated in normal physical examination during the same period as the control group. NQO1 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In addition, we conducted a meta-analysis to summarize the results of three relevant previously published adult population studies on the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk.Results: There were three genotypes (CC, CT, and TT) for NQO1 C609T polymorphism. The significant associations were found in TT genotype and T allele (all p< 0.05). Specifically, People with the TT genotype have 2.06 times CHD risk as those with the CC genotype. And People with the T allele have 1.62 times CHD risk as those with the C allele. No significant association was found by any genetic models in the meta-analysis (all p > 0.05).Conclusion: NQO1 gene polymorphism increased the CHD risk in a Chinese population. Combined with individual gene polymorphism, the accuracy of risk assessment for CHD can be improved and individualized health education can be provided for CHD patients by nurses.Keywords: NQO1, gene polymorphism, coronary heart disease, meta-analysis, nursing

Xiao-qiu Yan,1 Ying-yin Zhou,2,3 Ke Zhang,4 Guan-yu Cui2,3,5 1Department of Students’ Affairs, School of Education, Wenzhou University, Wenzhou, People’s Republic of China; 2Department of Psychology, School of Education, Wenzhou University, Wenzhou, People’s Republic of China; 3Research Center for Psychology and Behavior, Wenzhou University, Wenzhou, People’s Republic of China; 4Department of Education, School of Education, Wenzhou University, Wenzhou, People’s Republic of China; 5Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Guan-yu Cui, Email xchcgy@126.comIntroduction: Some students in current society do not pursue careers related to their majors after graduation, which may be the result of low professional commitment of college students, and the teaching enthusiasm of college teachers presented in the classroom may influence students’ professional commitment. This study considered the effect of teacher enthusiasm on students’ emotional state of boredom during class and its effect on students’ engagement in learning. This correlational study aims to explore the relationship between perceived teacher enthusiasm and professional commitment as mediated by class-related boredom and learning engagement.Methods: This study is a correlational design and adopts regression analysis. The respondents were college students (n=358; 68% female, 22% male) of different grades and majors from universities in Wenzhou, China. Questionnaires about perceived teacher enthusiasm, professional commitment, class-related boredom and learning engagement were adopted to measure the study variables.Results: The results reveal that although there is no significant direct influence between perceived teacher enthusiasm and professional commitment, perceived teacher enthusiasm affects students’ professional commitment through students’ class-related boredom and learning engagement, and there is an indirect and statistically significant correlation between them.Conclusion: This study provides insight into the facilitative effect of teachers’ increased enthusiasm on students’ professional commitment and how this facilitative effect is triggered through the mediating role of class related boredom and learning engagement. Future research should explore the theoretical and teaching significance and how to guide and enhance students’ professional commitment.Keywords: perceived teacher enthusiasm, class-related boredom, learning engagement, professional commitment

Li-Ping Chen,1,2 Hong Wang,1 Yi Zhang,2 Qiu-Xiang Chen,3 Tie-Su Lin,4 Zong-Qin Liu,5 Yang-Yang Zhou1 1Department of Rheumatology and Immunology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 2Chemical Biology Research Center, Department of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 3Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 4Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 5Department of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China Background: ceRNAs have emerged as pivotal players in the regulation of gene expression and play a crucial role in the physiology and development of various cancers. Nevertheless, the function and underlying mechanisms of ceRNAs in esophageal cancer (EC) are still largely unknown. Methods: In this study, profiles of DEmRNAs, DElncRNAs, and DEmiRNAs between normal and EC tumor tissue samples were obtained from the Cancer Genome Atlas database using the DESeq package in R by setting the adjusted P2 as the cutoff. The ceRNA network (ceRNet) was initially constructed to reveal the interaction of these ceRNAs during carcinogenesis based on the bioinformatics of miRcode, miRDB, miRTarBase, and TargetScan. Then, independent microarray data of GSE6188, GSE89102, and GSE92396 and correlation analysis were used to validate molecular biomarkers in the initial ceRNet. Finally, a least absolute shrinkage and selection operator logistic regression model was built using an oncogenic ceRNet to diagnose EC more accurately. Results: We successfully constructed an oncogenic ceRNet of EC, crosstalk of hsa-miR372-centered CADM2-ADAMTS9-AS2 and hsa-miR145-centered SERPINE1-PVT1. In addition, the risk-score model −0.0053*log2(CADM2)+0.0168*log2(SERPINE1)-0.0073*log2(ADAMTS9-AS2)+0.0905*log2(PVT1)+0.0047*log2(hsa-miR372)–0.0193*log2(hsa-miR145), (log2[gene count]) could improve diagnosis of EC with an AUC of 0.988. Conclusion: We identified two novel pairs of ceRNAs in EC and its role of diagnosis. The pairs of hsa-miR372-centered CADM2-ADAMTS9-AS2 and hsa-miR145-centered SERPINE1-PVT1 were likely potential carcinogenic mechanisms of EC, and their joint detection could improve diagnostic accuracy. Keywords: competitive endogenous RNA network, esophagus cancer, LASSO regression model, diagnosis

Yong-ming Zou,1 Jia Liu,2 Zhi-yan Tian,1 Da Lu,1 Yu-ying Zhou1 1Department of Neurology, TianJin HuangHu Hospital, TianJin, People’s Republic of China; 2Department of Neurology, Xuan Wu Hospital, Beijing, People’s Republic of China Background: Parkinson’s disease (PD) is a common neurodegenerative disease, and obtaining accurate epidemiological data for this disease is very important for policy-making in public health. The purpose of this study was to determine the prevalence and incidence of PD in the People’s Republic of China and explore possible future research directions.Methods: We systematically retrieved studies of the prevalence and incidence of PD in the People’s Republic of China, Taiwan, and Hong Kong, and standardized the data according to the world’s population in 2000.Results: Fifteen eligible studies were retrieved. Most were cross-sectional studies, and two thirds of the research was from the People’s Republic of China. The prevalence of PD was reported in all the studies, but only two studies reported incidence data. The prevalence of PD in the People’s Republic of China ranged from 16 to 440.3/100,000, and the annual incidence ranged from 1.5 to 8.7/100,000.Conclusion: The prevalence of PD in the People’s Republic of China has been widely investigated in the studies published to date. However, due to methodological heterogeneity, the data reported by the different studies are not comparable. There is still a lack of information on the incidence of PD in the People’s Republic of China. Therefore, future research is required to answer this question. Keywords: Parkinson’s disease, prevalence, incidence, People’s Republic of China

Yuanyuan Zhou,1,2 Hongchang Yao,1 Jianshe Wang,1 Dalu Wang,1 Qian Liu,1 Zhongjun Li11College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Enviromental and Municipal Engineering, North China University of Water Resources and Electric Power, Zhengzhou, People’s Republic of ChinaAbstract: In bone tissue engineering, collagen/hydroxyapatite (HAP) fibrous composite obtained via electrospinning method has been demonstrated to support the cells’ adhesion and bone regeneration. However, electrospinning of natural collagen often requires the use of cytotoxic organic solvents, and the HAP crystals were usually aggregated and randomly distributed within a fibrous matrix of collagen, limiting their clinical potential. Here, an effective and greener method for the preparation of collagen/HAP composite fibers was developed for the first time, and this green product not only had 40 times higher mechanical properties than that previously reported, but also had an excellent microstructure similar to that of natural bone. By dissolving type I collagen in environmentally friendly phosphate buffered saline/ethanol solution instead of the frequently-used cytotoxic organic solvents, followed with the key step of desalination, co-electrospinning the collagen solution with the HAP sol, generates a collagen/HAP composite with a uniform and continuous fibrous morphology. Interestingly, the nano-HAP needles were found to preferentially orient along the longitudinal direction of the collagen fibers, which mimicked the nanostructure of natural bones. Based on the characterization of the related products, the formation mechanism for this novel phenomenon was proposed. After cross-linking with 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride/N-hydroxysuccinimide, the obtained composite exhibited a significant enhancement in mechanical properties. In addition, the biocompatibility of the obtained composite fibers was evaluated by in vitro culture of the human myeloma cells (U2-OS). Taken together, the process outlined herein provides an effective, non-toxic approach for the fabrication of collagen/HAP composite nanofibers that could be good candidates for bone tissue engineering.Keywords: collagen, hydroxyapatite, electrospinning, nanofibers, biomaterials

The objective of this study is to provide catheterization with a three-dimensional (3D) guiding image and reduce the collision probability between the catheter tip and vascular wall. A bidirectional steerable catheter was integrated with two magnetic position-tracking sensors on both sides of its bending segment. The tracking information was displayed on the guiding image, which helped the surgeons to determine the relative position between the catheter tip and surrounding vessels. The navigation path was generated on the basis of the vascular skeleton. Moreover, along the path, a series of guiding circular planes were set as the guidance for the catheter. Three operations (bending, advancing, and twisting) were jointly conducted to get the catheter through these guiding planes in turn and eventually into the target vessel. The effectiveness of the proposed navigation method was verified by experiments implemented in an aorta vascular phantom. The navigation system has a mean error of 0.19 mm, a root mean square of 0.49 mm, and a standard deviation of 0.46 mm. [ABSTRACT FROM AUTHOR]

Background: In China, Tongguanteng injection (TGT) is widely used in the treatment or adjuvant treatment of various types of cancer. However, the effect and mechanism of TGT in osteosarcoma is not clear., Methods: The 143B and MG-63 cells were treated with different concentrations of TGT. Cell proliferation, migration, invasion and apoptosis were detected using CCK8 assay, transwell assay and flow cytometry. Differentially expressed genes (DEGs) were screened using RNA sequencing (RNA-seq). The identified mRNA and protein expression associated with the IRE1/CHOP pathway was validated by RT-PCR and western blot assay. To explore the underlying mechanisms, 4-phenylbutyric acid (4-PBA) was selected as a specific endoplasmic reticulum (ER) stress inhibitor. Small interfering RNA (siRNA) or pEX-3-ERN1 plasmid was transfected into 143B cells to silence or overexpress IRE1, respectively. The potential downstream proteins, including CHOP, and apoptosis associated proteins, caspase-3 and PARP1 were determined. Furthermore, the effect of TGT was demonstrated in 143B cell tumor-bearing mice in vivo. H&E staining, TUNEL staining and immunohistochemistry were conducted in tumor tissues obtained from the xenograft mouse model., Results: TGT was shown to dramatically suppress the proliferation, migration and invasion, and induce apoptosis of osteosarcoma 143B and MG-63 cells in vitro. The identified DEGs included HSPA5 (encoding BiP) and ERN1 (encoding the IRE1 protein), as well as apoptosis-associated gene DDIT3 (encoding the CHOP protein). The term "IRE1-mediated unfolded protein response" was screened to be the most enriched biological process GO term. The expression of ER stress-associated proteins including ATF6, BiP, p-IRE1, XBP1s and CHOP, as well as apoptosis-associated cleaved caspase-3 and cleaved PARP1 proteins, was significantly upregulated by TGT treatment in osteosarcoma 143B cells, suggesting that TGT might promote the apoptosis of osteosarcoma 143B cells through the IRE1/CHOP pathway. Furthermore, knocking down IRE1 with si-IRE1 or inhibiting of ER stress with 4-PBA suppressed the expression of ATF6, BiP, XBP1s and CHOP induced by TGT, as well as the expression of cleaved caspase-3 and cleaved PARP1. On the contrary, overexpressing IRE1 promoted CHOP expression and induced osteosarcoma cell apoptosis. Consistent with in vitro results, TGT dramatically inhibited the tumor growth and promoted the expression of p-IRE1 and CHOP in tumor-bearing mice., Conclusion: The findings suggest that TGT exerts an anti-osteosarcoma effect in vitro and in vivo. The underlying mechanism might be associated with the activation of IRE1/CHOP pathway in ER stress. Our findings suggest that targeting IRE1/CHOP pathway might be a potential novel approach for osteosarcoma treatment., Competing Interests: Declarations Ethics approval and consent to participate The animal researches were accredited by the Animal Welfare Ethics Committee of Shanghai Sixth People’s Hospital (No. SYXK 2018-0028). All animal experiments were conducted rigorously in compliance with Provision and General Recommendation of Chinese Experimental Animals Administration Legislation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: This study aimed to determine whether radiation therapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH) in patients with left breast cancer., Methods and Materials: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104 of 136 plans were selected for RP model training. A total of 32 of 136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH., Results: Two RP models were established for post-breast-conserving surgery (BCS) and post-modified radical mastectomy. There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the 2 plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < .05) and moderately correlated in patients after postmodified radical mastectomy (0.46 ≤ r ≤ 0.58, P <.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the 2 surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy., Conclusions: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH., (Published by Elsevier Inc.)

The recent discovery of superconductivity and magnetism in trilayer rhombohedral graphene (RG) establishes an ideal, untwisted platform to study strong correlation electronic phenomena. However, the correlated effects in multilayer RG have received limited attention, and, particularly, the evolution of the correlations with increasing layer number remains an unresolved question. Here we show the observation of layer-dependent electronic structures and correlations-under surprising liquid nitrogen temperature-in RG multilayers from 3 to 9 layers by using scanning tunnelling microscopy and spectroscopy. We explicitly determine layer-enhanced low-energy flat bands and interlayer coupling strengths. The former directly demonstrates the further flattening of low-energy bands in thicker RG, and the latter indicates the presence of varying interlayer interactions in RG multilayers. Moreover, we find significant splittings of the flat bands, ranging from ~50 meV to 80 meV, at 77 K when they are partially filled, indicating the emergence of interaction-induced strongly correlated states. Particularly, the strength of the correlated states is notably enhanced in thicker RG and reaches its maximum in the six-layer, validating directly theoretical predictions and establishing abundant new candidates for strongly correlated systems. Our results provide valuable insights into the layer dependence of the electronic properties in RG and demonstrate it as a suitable system for investigating robust and highly accessible correlated phases., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The German cockroach Blattella germanica is a notorious urban health pest that has developed resistance to multiple pesticides. Thus, novel non-lethal pest control agents are urgently needed. Olfaction interference via disruption of sex pheromone recognition-related genes offers a promising approach. The German cockroach has a unique courtship behavior in which female adults emit contact sex pheromones (CSPs) in response to antennal touching, which subsequently triggers distinctive male sex behavioral responses. Due to the limited volatility of CSPs, the molecular mechanisms underlying their recognition and the specific olfactory pathways activated remain poorly defined. Although the odorant receptor coreceptor (Orco) is critical for most insect olfaction, sensory neuron membrane proteins (SNMPs), in particular SNMP1, also play crucial roles in sex pheromone recognition in moths and flies. While multiple SNMP1 homologs have been identified in multiple insect species, they have yet to be fully functionally characterized in cockroaches., Results: In this study, RNA-interference (RNAi)-mediated knockdown of BgerOrco reduced both the electrophysiology responses and courtship behaviors of males, indicating CSP perception proceeds via an olfaction pathway. Similar RNAi knockdown of BgerSNMP1e and BgerSNMP1d, which are predominantly expressed in male antennae, revealed critical roles in perceiving the major component of the Blattella germanica CSP blend. Unlike BgerSNMP1e, BgerSNMP1d was also found to function in the perception of the minor CSP component. Molecular docking analyses revealed no differences in the binding affinities of BgerSNMP1d for the major and minor CSP components, whereas the binding affinities of BgerSNMP1e displayed clear selectivity for the major component., Conclusion: Our results show that the olfactory pathway is critical for CSP recognition and that two male-enriched SNMP genes, BgerSNMP1e and BgerSNMP1d, are crucial factors mediating the male response to CSP stimulation in German cockroaches. This study lays a foundation for studying the mechanisms of CSP recognition and provides novel molecular targets with potential to be exploited as disruptors of courtship behavior. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Composting is widely applied in recycling ever-increasing sewage sludge. However, the insufficient elimination of antibiotics and antibiotic resistance genes (ARGs) in conventional compost fertilizer poses considerable threat to agriculture safety and human health. Here we investigated the efficacy and potential mechanisms in the removal of antibiotics and ARGs from sludge in hyperthermophilic composting (HTC) plant. Our results demonstrated that the HTC product was of high maturity. HTC led to complete elimination of antibiotics and potential pathogens, as well as removal of 98.8 % of ARGs and 88.1 % of mobile genetic elements (MGEs). The enrichment of antibiotic-degrading candidates and related metabolic functions during HTC suggested that biodegradation played a crucial role in antibiotic removal. Redundancy analysis (RDA) and structural equation modelling (SEM) revealed that the reduction of ARGs was attributed to the decline of ARG-associated bacteria, mainly due to the high-temperature selection. These findings highlight the feasibility of HTC in sludge recycling and provide a deeper understanding of its mechanism in simultaneous removal of antibiotics and ARGs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking., Methods: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed., Results: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR., Conclusions: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Koulaouzidis: Consultant for Jinshan Science & Technology LTD, and lecture honoraria from Medtronic. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Thymic egress is a crucial process for thymocyte maturation, strictly regulated by sphingosine-1-phosphate lyase (S1PL). Recently, cystathionine γ-lyase (CSE), one of the enzymes producing hydrogen sulfide (H 2 S), has emerged as a vital immune process regulator. However, the molecular connection between CSE, H 2 S and thymic egress remains largely unexplored. In this study, we investigated the regulatory function of CSE in the thymic egress of immune cells. We showed that genetic knockout of CSE or pharmacological inhibition by CSE enzyme inhibitor NSC4056 or D,L-propargylglycine (PAG) significantly enhanced the migration of mature lymphocytes and monocytes from the thymus to the peripheral blood, and this redistribution effect could be reversed by treatment with NaHS, an exogenous donor of H 2 S. In addition, the CSE-generated H 2 S significantly increased the levels of S1P in the peripheral blood, thymus and spleen of mice, suppressed the production of proinflammatory cytokines and rescued pathogen-induced sepsis in cells and in vivo. Notably, H 2 S or polysulfide inhibited S1PL activity in cells and an in vitro purified enzyme assay. We found that this inhibition relied on a newly identified C 203 XC 205 redox motif adjacent to the enzyme's active site, shedding light on the biochemical mechanism of S1PL regulation. In conclusion, this study uncovers a new function and mechanism for CSE-derived H 2 S in thymic egress and provides a potential drug target for treating S1P-related immune diseases., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The identification of predictors for immunotherapy is often hampered by the absence of control groups in many studies, making it difficult to distinguish between prognostic and predictive biomarkers. This study presents biomarker analyses from the phase 3 CONTINUUM trial (NCT03700476), the first to show that adding anti-PD-1 (aPD1) to chemoradiotherapy (CRT) improves event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma. A dynamic single-cell atlas was profiled using mass cytometry on peripheral blood mononuclear cell samples from 12 pairs of matched relapsing and non-relapsing patients in the aPD1-CRT arm. Using a supervised representation learning algorithm, we identified a Ki67 + proliferating regulatory T cells (Tregs) population expressing high levels of activated and immunosuppressive molecules including FOXP3, CD38, HLA-DR, CD39, and PD-1, whose abundance correlated with treatment outcome. The frequency of these Ki67 + Tregs was significantly higher at baseline and increased during treatment in patients who relapsed compared to non-relapsers. Further validation through flow cytometry (n = 120) confirmed the predictive value of this Treg subset. Multiplex immunohistochemistry (n = 249) demonstrated that Ki67 + Tregs in tumors could predict immunotherapy benefit, with aPD1 improving EFS only in patients with low baseline levels of Ki67 + Tregs. These findings were further validated in the multicenter phase 3 DIPPER trial (n = 262, NCT03427827) and the phase 3 OAK trial of anti-PD-L1 immunotherapy in NSCLC, underscoring the predictive value of Ki67 + Treg frequency in identifying the beneficiaries of immunotherapy and potentially guiding personalized treatment strategies., (© 2024. The Author(s).)

Bupleurum , belonging to the Apiaceae, is widely distributed across the Eurasian continent. The origin and species diversification of Bupleurum in East Asia, remain incompletely resolved due to the limited samples in previous studies. To address these issues, we have reconstructed a robust phylogenetic framework for Bupleurum in East Asia based on the ITS and three plastid genes. Our phylogenetic analysis confirms the monophyly of Bupleurum with strong support. Both ITS and chloroplast dataset divided the Bupleurum in East Asia into East Asia Group I and East Asia Group II in this study. The divergence time and ancestral area reconstruction of ITS dataset indicated that the Bupleurum originated in the Mediterranean basin and its adjacent areas around 50.33 Ma. subg. Penninervia and subg. Bupleurum diverged at about 44.35 Ma, which may be related to the collision of India with the Eurasian continent. Both East Asia Group I and East Asia Group II originated from a common ancestor in the Mediterranean, East Asia Group I divergence around 12.95 Ma; East Asia Group II divergence around 13.32 Ma. The character reconstruction showed that the morphological characters and altitude distribution analyzed in this study exhibit a scattered distribution in East Asian Group I and East Asian Group II. Additionally, diversification rate analysis shows that the East Asian Group I and East Asian Group II exhibited no significant shifts in diversification rates in the evolutionary history according to ITS and combined dataset. Both molecular and morphological data supports that East Asian Bupleurum is a museum taxon, meaning that the species diversity of East Asian Bupleurum has gradually accumulated over time., Competing Interests: The authors have declared that no competing interests exist., (Yong-xiu Song, Ceng-yue Yang, Yu-Yang Zhou, Yan Yu.)

The takeout (TO) gene family impacts diverse physiological and behavioral functions in insects, yet specific olfactory-associated roles for the family have yet to be fully elucidated. To provide insights into TO function in rice planthoppers, the genomes of three rice planthoppers (white-backed planthopper, brown planthopper and small brown planthopper) were searched for TO homologs and their degree of conservation assessed via chromosomal localization, exon-intron boundaries, phylogenetic relationships and protein domains/motifs. We performed a tissue-specific expression analysis of the 20 TO genes in the white-backed planthopper (WBPH, Sogatella furcifera) and found that SfTO17 is enriched in adult antennae. RNAi-mediated knockdown of SfTO17 impaired WBPH olfaction and reduced host-seeking responses following exposure to rice plants. The binding profile of β-ionone, hexyl benzoate and benzyl benzoate with recombinant SfTO17 was evaluated via competitive fluorescence binding assays. Conformational prediction of SfTO17 coupled with molecular docking analyses revealed several amino acid residues potentially critical for odorant binding. This study demonstrates the olfactory function of SfTO17 in WBPH and highlights its potential as a target for controlling this rice pest. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Two new guaiane-type sesquiterpene glycosides, atractylodes guaianoside I ( 1 ) and atractylodes guaianoside II ( 2 ), along with eleven known sesquiterpenes ( 3 - 13 ), were isolated from Atractylodes Japonica Koidz. ex Kitam. The structures of these two new compounds were elucidated by extensive spectroscopic analyses and mass spectrometric techniques. And their absolute configurations were confirmed by electronic circular dichroism (ECD) calculations. In addition, the isolated compounds were evaluated for their cytotoxic activities against three cancer cell lines HT-29, A-549, and MCF-7. Results showed that new compound 2 had inhibitory effects on three types of cancer cells, while new compound 1 only had inhibitory effects on HT-29 and MCF-7.

Background and Purpose: Subclinical hypothyroidism (SCH) has been identified to be associated with implantation failure, in which the dysfunction of trophoblast cells is involved. In this study, the transcriptomics of aborted placenta from SCH rats were analyzed. Jupiter microtubule-associated homolog 2 (JPT2) was downregulated in the aborted placenta. This study aims to investigate its role in SCH-associated miscarriage., Methods: Spontaneous abortion was observed in SCH rats generated by thyroidectomy combined with levothyroxine administration. The transcriptomics analysis was performed using aborted placenta. Afterward, the effects of JPT2 on trophoblast cells were explored using gain-and loss-of-function experiments., Results: Transcriptomics analysis showed 1286 downregulated genes and 2300 upregulated genes in the aborted placenta, and JPT2 was significantly downregulated in the aborted placenta from SCH rats. Afterward, gain-and loss-of-function experiments exhibited that overexpression of JPT2 promoted the proliferation, migration, invasion, spheroid formation of HTR-8/SVneo trophoblast cells and their attachment to endometrial stromal cells, while these biological behaviors were suppressed by JPT2 knockdown. Furthermore, JPT2 accelerated the transcription of leptin receptor (LEPR), and activated signal transducer and activator of transcription 3 (STAT3) signal in a transcription factor AP-2γ-dependent manner. In addition, silencing of LEPR abolished the role of JPT2., Conclusion: Our results revealed that JPT2, which was downregulated in the aborted placenta from SCH rats, promoted proliferation, migration, invasion, spheroid formation, and attachment of trophoblast cells via regulating LEPR/STAT3 axis as a transcription co-factor. It is indicated that low expression of JPT2 may contribute to the abortion in individuals with SCH., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

The clustered regularly interspaced small palindromic repeats (CRISPR) / CRISPR-associated nuclease 9 (Cas9)-mediated gene editing technology has revolutionized the study of fundamental biological questions in various insects. Diverse approaches have been developed to deliver the single-guide RNA (sgRNA) and Cas9 to the nucleus of insect embryos or oocytes to achieve gene editing, including the predominant embryonic injection methods and alternative protocols through parental ovary delivery. However, a systematic comparative study of these approaches is limited, especially within a given insect. Here, we focused on revealing the detailed differences in CRISPR/Cas9-mediated gene editing between the embryo and ovary delivery methods in the beetle Tribolium castaneum, using the cardinal and tyrosine hydroxylase (TH) as reporter genes. We demonstrated that both genes could be efficiently edited by delivering Cas9/sgRNA ribonucleoproteins to the embryos by microinjection, leading to the mutant phenotypes and indels in the target gene sites. Next, the Cas9/sgRNA complex, coupled with a nanocarrier called Branched Amphiphilic Peptide Capsules (BAPC), were delivered to the ovaries of parental females to examine the efficacy of BAPC-mediated gene editing. Although we observed that a small number of beetles' progeny targeting the cardinal exhibited the expected white-eye phenotype, unexpectedly, no target DNA indels were found following subsequent sequencing analysis. In addition, we adopted a novel approach termed "direct parental" CRISPR (DIPA-CRISPR). However, we still failed to find gene-editing events in the cardinal or TH gene-targeted insects. Our results indicate that the conventional embryonic injection of CRISPR is an effective method to initiate genome editing in T. castaneum. However, it is inefficient by the parental ovary delivery approach., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Background: Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated., Methods: Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC., Results: A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18-0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16-0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08-0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021)., Conclusions: High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis., (© 2024. The Author(s).)

Objective: To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies. Methods: Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA). Results: A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography ( OR= 0.26, 0.27; 95% CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery ( OR= 0.43, 0.44; 95% CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI ( OR= 0.58, 0.52; 95% CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z -curve for balanced solution (cumulative Z= 3.38) crossed the TSA monitoring boundary ( Z= 3.29). Conclusion: Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na + -H + exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis., Competing Interests: Disclosure Statement None declared., (Copyright © 2024. Published by Elsevier Inc.)

Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABA A R) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the β2 subunit of GABA A R. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABA A R channel function, we conducted transient expression experiments using GABA A R subunits in HEK293T cells. The GABA A Rs containing mutant β2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABA A R containing the β2 (F224S) subunit was significantly smaller compared to the wild type GABA A R. We propose that GABRB2 variant F224S is pathogenic and GABA A Rs containing this β2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

The catalytic regio- and enantioselective hydrocarboxylation of alkenes with carbon dioxide is a straightforward strategy to construct enantioenriched α-chiral carboxylic acids but remains a big challenge. Herein we report the first example of catalytic highly enantio- and site-selective remote hydrocarboxylation of a wide range of readily available unactivated alkenes with abundant and renewable CO 2 under mild conditions enabled by the SaBOX/Ni catalyst. The key to this success is utilizing the chiral SaBOX ligand, which combines with nickel to simultaneously control both chain-walking and the enantioselectivity of carboxylation. This process directly furnishes a range of different alkyl-chain-substituted or benzo-fused α-chiral carboxylic acids bearing various functional groups in high yields and regio- and enantioselectivities. Furthermore, the synthetic utility of this methodology was demonstrated by the concise synthesis of the antiplatelet aggregation drug ( R )-indobufen from commercial starting materials.

Chemical investigation on the 95% ethanol extract of green walnut husks of Juglans mandshurica Maxim. led to the isolation of two new diarylheptanoid compounds, including Juglanin K ( 1 ) and Myricananin I ( 2 ), together with ten known compounds ( 3-13 ). Their structures were elucidated by extensive analyses of comprehensive spectroscopic methods. The isolated compounds were evaluated for their antibacterial activities against Escherichia coli and Staphylococcus aureus . The results showed that compound 2 had moderate antibacterial activity with the MIC values of 0.313 and 0.156 mg/mL, respectively. compounds 1 , 3 - 7 and 13 showed weakly antibacterial activities against Escherichia coli and Staphylococcus aureus with the MIC values of 0.625-2.5 mg/mL.

A pair of water-stable and highly porous homochiral fluorescent silver-organic framework enantiomers, namely, R -Ag-BPA-TPyPE ( R - 1 ) and S -Ag-BPA-TPyPE ( S - 1 ), had been prepared as enantioselective fluorescence sensors. Combining homochiral 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BPA) with an AIE-based ligand tetrakis[4-(pyridin-4-yl)phenyl]ethene (TPyPE) in complexes R - 1 and S - 1 made them possess favorable circularly polarized luminescence (CPL) properties, and their CPL spectra were almost mirror images of each other. The luminescence dissymmetry factors ( g lum ) are ±2.2 × 10 -3 for R - 1 and S - 1, and the absolute fluorescence quantum yields (Φ Fs ) are 32.0% for R - 1 and S - 1 , respectively. Complex R - 1 could enantioselectively recognize two enantiomers of amino acids in water or DMF with high Stern-Volmer constants of 236-573 M -1 and enantioselectivity ratios of 1.40-1.78.

Background: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder., Methods: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline., Discussion: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023)., (© 2024. The Author(s).)

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC 50 values in the range of 25.15-88.85 μM except for 9-12., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Vacuolar-type (H + )-ATPase (vATPase) is a conserved multi-subunit eukaryotic enzyme composed of 14 subunits that form a functional complex consisting of an ATP-hydrolytic domain (V1) and a proton-translocation domain (V0). ATP hydrolysis and subsequent H + translocation rely heavily on a fully assembled V1/V0 complex. Since vATPase is crucial for insect survival, it is a viable molecular target for pest control. However, detailed functional analyses of the 14 subunits and their suitability for pest control have not been fully explored in a single insect species. In this study, we identified 22 vATPase subunit transcripts that correspond to 13 subunits (A1, A2, B, C, D, E, F, G, H, a1, a2, c and d) in the white-backed planthopper (WBPH), Sogatella furcifera, a major hemipteran pest of rice. RNAi screens using microinjection and spray-based methods revealed that the SfVHA-F, SfVHA-a2 and SfVHA-c2 subunits are critical. Furthermore, star polymer (SPc) nanoparticles were utilized to conduct spray-induced and nanoparticle-delivered gene silencing (SI-NDGS) to evaluate the pest control efficacy of RNAi targeting the SfVHA-F, SfVHA-a2 and SfVHA-c2 transcripts. Target mRNA levels and vATPase enzymatic activity were both reduced. Honeydew excreta was likewise reduced in WBPH treated with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. To assess the environmental safety of the nanoparticle-wrapped dsRNAs, Cyrtorhinus lividipennis Reuter, a major natural enemy of planthoppers, was also sprayed with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. Post-spray effects of dsSfVHA-a2 and dsSfVHA-c2 on C. lividipennis were innocuous. This study identifies SfVHA-a2 and SfVHA-c2 as promising targets for biorational control of WBPH and lays the foundation for developing environment-friendly RNAi biopesticides., Competing Interests: Declaration of competing interest Peng He reports financial support was provided by Guizhou University. Peng He reports a relationship with Guizhou University that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To explore the effect of the "internet + health education system" in nursing care after stapler circumcision., Methods: A total of 260 patients underwent stapler circumcision in the Outpatient Department of our hospital from January 2022 to July 2022, of whom 130 received routine nursing after operation (the control group), and the other 130 internet + medical nursing service based on the internet + health education system (the experimental group). We followed up the patients on the 1st, 3rd, 7th and 30th day after surgery, recorded their Visual Analogue Scale (VAS) scores within 24 hours postoperatively, their satisfaction scores with surgery and nursing, the incidence of complications and falloff of the stapler nails, and compared them between the two groups., Results: The postoperative VAS scores of the patients and the incidences of postoperative edema, bleeding, infection and other complications were significantly lower (P < 0.05), the falloff of the stapler nails markedly sooner, and the patients' satisfaction scores with surgery and nursing service remarkably higher (P < 0.05) in the experimental than in the control group (P < 0.05)., Conclusion: The application of the internet + health education system in nursing care after stapler circumcision can impart relevant knowledge to the patients, enhance their self-care ability, effectively reduce postoperative complications, and improve the patients' satisfaction with surgery and nursing service.

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 μm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

This study aimed to investigate the effects of microtubule associated tumor suppressor 1 (MTUS1) on hemeoxygenase 1 (HMOX1) expression and hemin-induced apoptosis of vascular endothelial cells and its regulatory mechanism. RNA sequencing, RT-qPCR and Western blot were used to assess altered genes of hemin binding proteins, the expression of cAMP response element-binding protein (CREB) and nuclear respiratory factor 2 (NRF2), hemin-induced HMOX1 expression in MTUS1 knockdown human umbilical vein endothelial cells (HUVEC), and the effect of overexpression of CREB and NRF2 on HMOX1 expression in MTUS1 knockdown 293T cells. The effect of MTUS1 or HMOX1 knockdown on hemin-induced apoptosis in HUVEC, and the overexpression of NRF2 on hemin-induced apoptosis in MTUS1 knockdown 293T cells were assayed with CCK8 and Western blot. The results showed that MTUS1 was knocked down significantly in HUVEC by siRNA (P < 0.01), accompanied by decreased HMOX1 expression (P < 0.01). The increased HMOX1 expression induced by hemin was also inhibited by MTUS1 knockdown (P < 0.01). And the apoptosis of HUVEC induced by hemin was amplified by MTUS1 or HMOX1 knockdown (P < 0.01). Moreover the expression of CREB and NRF2 were both inhibited by MTUS1 knockdown in HUVEC (P < 0.01). The decreased HMOX1 regulated by MTUS1 knockdown could be rescued partly by overexpression of NRF2 (P < 0.01), however, not by overexpression of CREB. And the MTUS1 knockdown mediated decreased 293T cells viability induced by hemin could be partly rescued by NRF2 overexpression (P < 0.01). These results suggest that MTUS1 can inhibit hemin-induced apoptosis of HUVEC, and the mechanism maybe related to MTUS1/NRF2/HMOX1 pathway.

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene., (© 2024 Wiley Periodicals LLC.)

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1-2), and dictameudesmnosides F, G, and H (3-5), along with seven known sesquiterpenoids (6-12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC 50 values of 3.49 ± 0.10 and 6.42 ± 1.23 μM, respectively. Additionally, compounds 2, 7, and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 μM., Competing Interests: Declaration of competing interest Ye Sun and Yan Liu contributed equally to this study. No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier B.V.)

Objective To establish a model for predicting the growth of pulmonary ground-glass nodules (GGN) based on the clinical visualization parameters extracted by the 3D reconstruction technique and to verify the prediction performance of the model. Methods A retrospective analysis was carried out for 354 cases of pulmonary GGN followed up regularly in the outpatient of pulmonary nodules in Zhoushan Hospital of Zhejiang Province from March 2015 to December 2022.The semi-automatic segmentation method of 3D Slicer was employed to extract the quantitative imaging features of nodules.According to the follow-up results,the nodules were classified into a resting group and a growing group.Furthermore,the nodules were classified into a training set and a test set by the simple random method at a ratio of 7∶3.Clinical and imaging parameters were used to establish a prediction model,and the prediction performance of the model was tested on the validation set. Results A total of 119 males and 235 females were included,with a median age of 55.0 (47.0,63.0) years and the mean follow-up of (48.4±16.3) months.There were 247 cases in the training set and 107 cases in the test set.The binary Logistic regression analysis showed that age (95% CI =1.010-1.092, P =0.015) and mass (95% CI =1.002-1.067, P =0.035) were independent predictors of nodular growth.The mass (M) of nodules was calculated according to the formula M=V×(CT mean +1000)×0.001 (where V is the volume,V=3/4πR 3 ,R:radius).Therefore,the logit prediction model was established as ln[ P /(1- P )]=-1.300+0.043×age+0.257×two-dimensional diameter+0.007×CT mean .The Hosmer-Lemeshow goodness of fit test was performed to test the fitting degree of the model for the measured data in the validation set ( χ 2 =4.515, P =0.808).The check plot was established for the prediction model,which showed the area under receiver-operating characteristic curve being 0.702. Conclusions The results of this study indicate that patient age and nodule mass are independent risk factors for promoting the growth of pulmonary GGN.A model for predicting the growth possibility of GGN is established and evaluated,which provides a basis for the formulation of GGN management strategies.

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica . RNAi knockdown of B. germanica black ( Bgblack ) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.

Background: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed., Purpose: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies., Methods: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-β-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results., Results: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine., Conclusion: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier GmbH.)