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Yuan Gao,1,2,* Ting-Lin Zhang,3,* Hong-Jian Zhang,1,2,* Jie Gao,3 Peng-Fei Yang1,2,4 1Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 4Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Fei Yang, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China, Tel +86-15921196312, Fax +86-2131161784, Email 15921196312@163.com Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China, Tel/Fax +86-21-31162092, Email gaojiehighclea@smmu.edu.cnAbstract: Ischemic stroke, a condition that often leads to severe nerve damage, induces complex pathological and physiological changes in nerve tissue. The mature central nervous system (CNS) lacks intrinsic regenerative capacity, resulting in a poor prognosis and long-term neurological impairments. There is no available therapy that can fully restore CNS functionality. However, the utilization of injectable hydrogels has emerged as a promising strategy for nerve repair and regeneration. Injectable hydrogels possess exceptional properties, such as biocompatibility, tunable mechanical properties, and the ability to provide a supportive environment for cell growth and tissue regeneration. Recently, various hydrogel-based tissue engineering approaches, including cell encapsulation, controlled release of therapeutic factors, and incorporation of bioactive molecules, have demonstrated great potential in the treatment of CNS injuries caused by ischemic stroke. This article aims to provide a comprehensive review of the application and development of injectable hydrogels for the treatment of ischemic stroke-induced CNS injuries, shedding light on their therapeutic prospects, challenges, recent advancements, and future directions. Additionally, it will discuss the underlying mechanisms involved in hydrogel-mediated nerve repair and regeneration, as well as the need for further preclinical and clinical studies to validate their efficacy and safety.Keywords: ischemic stroke, central nervous system, hydrogels, neural restoration, nerve regeneration

Chao Gao,1,* Yan Liu,2,* Ting-Lin Zhang,3,* Yi Luo,2,4,* Jie Gao,3,* Jian-Jian Chu,1 Bao-Feng Gong,1 Xiao-Han Chen,1 Tong Yin,1 Jian Zhang,2 You Yin1 1Department of Neurology, Second Affiliated Hospital (Shanghai Changzheng Hospital) of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai Jiao Tong University of Medicine, Shanghai, People’s Republic of China; 3Changhai Clinical Research Unit, Shanghai Changhai Hospital of Naval Medical University, Shanghai, People’s Republic of China; 4New Drug Discovery and Development, Biotheus Inc., Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: You Yin; Jian Zhang, Tel +86-21-81885463 ; +86- 21-25077150, Email yinyou179@163.com; zhangjian@xinhuamed.com.cnAbstract: Current therapies for Alzheimer’s disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed. Keywords: Alzheimer’s disease, nanoparticles, blood‒brain barrier, liposomes, bionanotechnology, neurodegenerative diseases

Bo-Wen Zheng,1,2 Min-Liang Yang,2 Wei Huang,3 Bo-Yv Zheng,4 Tao-Lan Zhang,5 Jing Li,2 Guo-Hua Lv,2 Yi-Guo Yan,1,* Ming-Xiang Zou1,* 1Department of Spine Surgery, The First Affiliated Hospital, University of South China, Hengyang, 421001, People’s Republic of China; 2Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 3Health and Management Centre, The First Affiliated Hospital, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Orthopedics Surgery, General Hospital of the Central Theater Command, Wuhan, 430061, People’s Republic of China; 5Department of Radiation Oncology, Indiana University School of Medicine, IU Simon Comprehensive Cancer Center, Indianapolis, IN, 46202, USA*These authors contributed equally to this workCorrespondence: Ming-Xiang ZouDepartment of Spine Surgery, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang, Hunan, 421001, People’s Republic of ChinaTel +86 73485295624Fax +86 73482654334Email zouwei8887@126.comYi-Guo YanDepartment of Spine Surgery, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang, Hunan, 421001, People’s Republic of China, +86 73485295624, +86 73482654334Email yan_yiguo@qq.comObjective: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients.Methods: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features.Results: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan–Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance.Conclusion: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.Keywords: chondroblastoma, tumor-associated macrophages, tumor immune microenvironment, prognostic factors, survival analysis

The existence of a strong internal magnetic field allows probing of the interior through both long term changes of and short period fluctuations in that magnetic field. Venus, while Earth's twin in many ways, lacks such a strong intrinsic magnetic field, but perhaps short period fluctuations can still be used to probe the electrical conductivity of the interior. Toward the end of the Venus Express mission, an aerobraking campaign took the spacecraft below the ionosphere into the very weakly electrically conducting atmosphere. As the spacecraft descended from 150 to 140 km altitude, the magnetic field became weaker on average and less noisy. Below 140 km, the median field strength became steady but the short period fluctuations continued to weaken. The weakness of the fluctuations indicates they might not be useful for electromagnetic sounding of the atmosphere from a high altitude platform such as a plane or balloon, but possibly could be attempted on a lander.

As the development of underground space progresses, newly constructed waterways inevitably intersect with existing tunnels, posing significant challenges to the safety of underlying tunnels and making deformation control a critical issue in engineering design and construction. This study investigates the impact of waterway foundation pit excavation on the deformation of underlying tunnels. The research considers not only the vertical unloading at the bottom of the pit but also the horizontal unloading from the four side walls, which induces additional vertical stress fields in the underlying soil. These additional stresses are applied to the tunnel structure, modeled as a Pasternak elastic foundation beam, and the vertical tunnel deformation due to excavation unloading is calculated using the finite difference method. To validate the analytical results, a three-dimensional numerical model is employed. Furthermore, the study analyzes deformation trends under varying excavation sizes and the relative positions of the foundation pit and tunnel. The findings demonstrate that the proposed method provides a highly accurate, cost-effective, and efficient solution for predicting tunnel deformation during the excavation of small foundation pits. This research offers valuable insights for the design and assessment of underground structures in urban environments., (© 2024. The Author(s).)

Currently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1 high tumor cell counts and SPP1 + macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1 + macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD)., Methods: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo., Results: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF + ECMO-neutrophil counts and ACKR3 + effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors., Conclusions: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR. Methods: This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants' near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye's damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level. Results: A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β =0.136, P= 0.003), near vision ( β =0.163, P <0.001), visual adaptation ( β =0.092, P= 0.042), subjective vision ( β =0.120, P= 0.009) and stereo vision ( β =0.094, P= 0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion: Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

Glyphosate (GLY) is the most universally used herbicide worldwide and its application has caused extensive pollution to the ecological environment. Increasing evidence has revealed the multi-organ toxicity of GLY in different species, but its male reproductive toxicity in avian species remains unknown. Thus, in vivo and in vitro studies were conducted to clarify this issue. Data firstly showed that chronic GLY exposure caused testicular pathological damage. Intriguingly, we identified and verified a marked down-regulation gap junction gene Connexin 43 (Cx43) in GLY-exposed rooster testis by transcriptome analysis. Cx43 generated by Sertoli cells acts as a key component of blood-testis barrier (BTB). To further investigate the cause of GLY-induced downregulation of Cx43 to disrupt BTB, we found that autophagy activation is revealed in GLY-exposed rooster testis and primary avian Sertoli cells. Moreover, GLY-induced Cx43 downregulation was significantly alleviated by ATG5 knockdown or CQ administration, respectively, demonstrating that GLY-induced autophagy activation contributed to Cx43 degradation. Mechanistically, GLY-induced autophagy activation and resultant Cx43 degradation was due to its direct interaction with ER-α. In summary, these findings demonstrate that chronic GLY exposure activates autophagy to induce Cx43 degradation, which causes BTB damage and resultant reproductive toxicity in roosters., 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: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses., Methods: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used., Results: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen., Conclusions: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This work was supported by the National Natural Science Foundation of China (82003802 to T.-L.Z. and 82002364 to M.-X.Z.), Natural Science Foundation of Hunan Province (2019JJ50542 and 2023JJ50156 to T.-L.Z., 2023JJ40596 to C.X., 2023JJ40587 to W.H., and 2021JJ40509 to M.-X.Z.), Hunan Provincial Natural Science Foundation for Excellent Youth Scholars (2023JJ20035 to M.-X.Z.), Clinical Research 4310 Program of the First Affiliated Hospital of the University of South China (20224310NHYCG04 to T.-L.Z.), Project for Clinical Research of Hunan Provincial Health Commission (20201978 to T.-L.Z., 20201962 to C.X. and 20201956 to M.-X.Z.), the Science and Technology Innovation Program of Hunan Province (2023RC3172 to M.-X.Z.), and Research Foundation of Education Bureau of Hunan Province (22B0441 to W.H.). The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I29)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

To investigate the concentration characteristics and sources of metal elements in PM 2.5 during winter heavy pollution in the southern Sichuan urban agglomeration (Zigong, Luzhou, Neijiang, and Yibin), the metal elements in PM 2.5 were measured using membrane sampling methods from December 30, 2018 to January 14, 2019, and the enrichment factor method (EF) and positive matrix factorization(PMF) were applied to investigate the sources of metal elements. The metal element observation data of Zigong in the same period of 2015 were also used to investigate the changes in metal element pollution and enrichment in Zigong in the middle and end of the implementation of China's Air Pollution Prevention and Control Action Plan. The main findings were as follows:① The concentrations and percentages of metal elements in particulate matter in different cities did not differ significantly. The elements with higher concentrations in the four cities showed similarities, with Al, Sb, and Fe at the top. From the comparison of different observation periods in Zigong, the concentrations of all elements except Tl changed. ② The results of the enrichment factor calculation showed that the enrichment of the elements Cr (Zigong and Yibin), Ni, Cu, As, Se, Ag, Cd, Sb, Tl, and Pb in the urban agglomeration was high. The comparison of the enrichment levels of elements in Zigong for different observation periods showed that the enrichment levels of all elements, except Cu, tended to decrease in the winter observation period of 2018. ③ The results of PMF source analysis showed that the metal elements in each city mainly originated from dust sources, coal-fired sources, industrial sources, and traffic sources, whereas there was a mixed contribution among the sources. The contribution of the main sources differed among cities, in which Zigong was dominated by traffic dust sources and mixed sources, Luzhou was dominated by industrial sources, Neijiang had a similar contribution from different sources, and Yibin was dominated by traffic sources.

Background: The prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension., Methods: 132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity., Results: The feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively., Conclusions: Radiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD., (© 2024. The Author(s).)

The growing accumulation of plastic waste in the environment has created novel habitats known as the "plastisphere", where microorganisms can thrive. Concerns are rising about the potential for pathogenic microorganisms to proliferate in the plastisphere, posing risks to human health. However, our knowledge regarding the virulence and pathogenic potential of these microorganisms in the plastisphere remains limited. This study quantified the abundance of virulence factor genes (VFGs) in the plastisphere and its surrounding environments (water and soil) to better assess pathogenic risks. Our findings revealed a selective enrichment of VFGs in the plastisphere, which were attributed to the specific microbial community assembled. The presence of arsenic and ciprofloxacin in the plastisphere exerted additional co-selective pressures, intensifying the enrichment of VFGs. Notably, VFGs that encoded multiple functions or enhanced the survival of host microorganisms (e.g., encoding adherence functions) tended to accumulate in the plastisphere. These versatile and environmentally adaptable VFGs are more likely to be favored by bacteria in the environment, warranting increased attention in future investigations due to their potential for widespread dissemination. In terms of virulence and pathogenicity, this research offers new insights into evaluating pathogen-related risks in the plastisphere., 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 © 2023 Elsevier B.V. All rights reserved.)

Antibiotic-resistance genes (ARGs) are world-wide contaminants posing potential health risks. Quaternary ammonium compounds (QACs) and heavy metals can apply selective pressure on antibiotic resistance. However, there is a lack of evidence regarding their coupled effect on changes in ARGs and virulence factor genes (VFGs) in various soil types and their plastispheres. Herein, we conducted a microcosm experiment to explore the abundances and profiles of ARGs and VFGs in soil plastispheres from three distinct types of soils amended with Cu and disinfectants. The plastispheres enriched the ARGs' abundance compared to soils and stimulated the coupling effect of combined pollutants on promoting the abundances of ARGs and VFGs. Horizontal gene transfer inevitably accelerates the propagation of ARGs and VFGs in plastispheres under pollutant stress. In plastispheres, combined exposure to disinfectants and Cu increased some potential pathogens' relative abundances. Moreover, the combined effect of disinfectants and Cu on ARGs and VFGs changed with soil type in plastispheres, emphasising the necessity to incorporate soil type considerations into health risk assessments for ARGs and VFGs. Overall, this study highlights the high health risks of ARGs under the selective pressure of combined pollutants in plastispheres and provides valuable insights for future risk assessments related to antibiotic resistance., 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 © 2023 Elsevier B.V. All rights reserved.)

Pleiotropic drug resistance (PDR) family proteins have been extensively studied for their roles in transporting hydrophobic substances, including carotenoids. Overexpression of the PDR family regulator Pdr3p was recently found to boost the biosynthesis of carotenoids, which could not be explained by enhanced product secretion due to the meager extracellular proportions. To provide insights into the possible mechanism, comparative transcriptomics, reverse metabolic engineering, and electrophoretic mobility shift assay (EMSA) were conducted. Transcriptomic data suggested an unexpected correlation between Pdr3p overexpression and the transcriptional levels of GAL promoter-driven genes. This assumption was verified using mCherry and the lycopene synthetic pathway as the reporters. qRT-PCR and EMSA provided further evidence for the activation of GAL promoters by Pdr3p binding to their upstream activation sequences (UASs). This work gives insight into the mechanism of Pdr3p-promoted carotenoid production and highlights the complicated metabolic networking between transcriptional factors and promoters in yeast.

Background: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression., Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma., Results: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes., Conclusions: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the efficiency of the four domestic language models, ERNIE Bot, ChatGLM2, Spark Desk and Qwen-14B-Chat, all with a massive user base and significant social attention, in response to consultations about PCa-related perioperative nursing and health education., Methods: We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases, and inputted the questions into each of the four language models for simulation consultation. Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy, comprehensiveness, understandability, humanistic care, and case analysis. We evaluated and compared the performance of the four models using visualization tools and statistical analyses., Results: All the models generated high-quality texts with no misleading information and exhibited satisfactory performance. Qwen-14B-Chat scored the highest in all aspects and showed relatively stable outputs in multiple tests compared with ChatGLM2. Spark Desk performed well in terms of understandability but lacked comprehensiveness and humanistic care. Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis. The overall performance of ERNIE Bot was slightly inferior. All things considered, Qwen-14B-Chat was superior to the other three models in consultations about PCa-related perioperative nursing and health education., Conclusion: In PCa-related perioperative nursing, large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support, so as to improve the patient compliance and the quality of clinical treatment and nursing.

Objective: To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods: The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture ( n =5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3 rd to 6 th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 ( n =3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated ( n =5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results: Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS ( P <0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel ( P <0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone ( P <0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced ( P <0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased ( P <0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group ( P <0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group ( P <0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group ( P <0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions: The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.

Antibiotic resistance in plant-associated microbiomes poses significant risks for agricultural ecosystems and human health. Although accumulating evidence suggests a role for plant genotypes in shaping their microbiome, almost nothing is known about how the changes of plant genetic information affect the co-evolved plant microbiome carrying antibiotic resistance genes (ARGs). Here, we selected 16 wheat cultivars and experimentally explored the impact of host genetic variation on phyllosphere microbiome, ARGs, and metabolites. Our results demonstrated that host genetic variation significantly influenced the phyllosphere resistomes. Wheat genotypes exhibiting high phyllosphere ARGs were linked to elevated Pseudomonas populations, along with increased abundances of Pseudomonas aeruginosa biofilm formation genes. Further analysis of 350 Pseudomonas spp. genomes from diverse habitats at a global scale revealed that nearly all strains possess multiple ARGs, virulence factor genes (VFGs), and mobile genetic elements (MGEs) on their genomes, albeit with lower nucleotide diversity compared to other species. These findings suggested that the proliferation of Pseudomonas spp. in the phyllosphere significantly contributed to antibiotic resistance. We further observed direct links between the upregulated leaf metabolite DIMBOA-Glc, Pseudomonas spp., and enrichment of phyllosphere ARGs, which were corroborated by microcosm experiments demonstrating that DIMBOA-Glc significantly enhanced the relative abundance of Pseudomonas spp. Overall, alterations in leaf metabolites resulting from genetic variation throughout plant evolution may drive the development of highly specialized microbial communities capable of enriching phyllosphere ARGs. This study enhances our understanding of how plants actively shape microbial communities and clarifies the impact of host genetic variation on the plant resistomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Purpose: To compare image quality, iodine intake, and radiation dose in overweight and obese patients undergoing abdominal computed tomography (CT) enhancement using different scanning modes and contrast medium., Methods: Ninety overweight and obese patients (25 kg/m2≤body mass index (BMI)< 30 kg/m2 and BMI≥30 kg/m2) who underwent abdominal CT-enhanced examinations were randomized into three groups (A, B, and C) of 30 each and scanned using gemstone spectral imaging (GSI) +320 mgI/ml, 100 kVp + 370 mgI/ml, and 120 kVp + 370 mgI/ml, respectively. Reconstruct monochromatic energy images of group A at 50-70 keV (5 keV interval). The iodine intake and radiation dose of each group were recorded and calculated. The CT values, contrast-to-noise ratios (CNRs), and subjective scores of each subgroup image in group A versus images in groups B and C were by using one-way analysis of variance or Kruskal-Wallis H test, and the optimal keV of group A was selected., Results: The dual-phase CT values and CNRs of each part in group A were higher than or similar to those in groups B and C at 50-60 keV, and similar to or lower than those in groups B and C at 65 keV and 70 keV. The subjective scores of the dual-phase images in group A were lower than those of groups B and C at 50 keV and 55 keV, whereas no significant difference was seen at 60-70 keV. Compared to groups B and C, the iodine intake in group A decreased by 12.5% and 13.3%, respectively. The effective doses in groups A and B were 24.7% and 25.8% lower than those in group C, respectively., Conclusion: GSI +320 mgI/ml for abdominal CT-enhanced in overweight patients satisfies image quality while reducing iodine intake and radiation dose, and the optimal keV was 60 keV.

The chemistry underlying bone mineral formation in vertebrates is the reaction of calcium phosphate precipitation. In a near-neutral solution, an amorphous phase and hydroxyapatite nanoparticles appear successively, and the reaction system containing either of the two kinds of precipitates is in a non-equilibrium state. Here, we propose a pseudo-equilibrium approach to the solution chemistry of the precipitation reactions. We employed two series of reaction systems, collected samples at various stages, and analyzed the solution chemistry data on the basis of a simplified model of reaction. We derived two types of pseudo-equilibrium equations from the two series, respectively. These equations reveal the existence of multiple structural units in a precipitate particle and correlate the ionic product with the surface proportion per structural unit ( m ). The surface proportion, in turn, is related to the whole particle through a particle-surface equation. Notably, the two types of pseudo-equilibrium constants have the common expression of " K d = ionic product" if the number of the structural units ( u ) is large enough. Together, these findings have revealed some aspects of the non-equilibrium thermodynamics of precipitation reactions, indicating the solution chemistry route to the equilibrium state. The concept of the multi-unit particle may shed new light on the study of precipitation reactions of other slightly soluble electrolytes. And the relationship between the ionic product and the surface proportion of a structural unit is not only fundamental in chemistry, but may also apply to non-equilibrium systems in nature and biology, such as marine sedimentation, human vascular calcification, and bone mineral metabolism.

Zanthoxylum motuoense (Tibetan prickly ash, MTHJ), different from the Chinese prickly ash species, is distributed only in the Tibet. Now the chemical characterization and antibacterial activity of MTHJ extracts were analyzed for the first time. As a result, Schinifoline (12) , γ -Fagarine (8) , ( 2E,7E,9E )-6 S-Hydroxy- N -(2-methylpropyl)-11-oxo-2, 7, 9-Dodecatrienamide (6) , and Neoechinulin A (17) were found to be the major different factors by untarget LC-MS metabolomics together with quantitative analysis on target. These four compounds were also the major antibacterial constituents. Then, the antimicrobial activity of MTHJ fractions was evaluated with colony forming units (CFU), fluorescence microscopy imaging, SEM and investigating the potential food preservation. Nutritional composition, colour and sensory evaluation of extract-treated samples were evaluated along storage time. The results suggested the MTHJ may be used for meat products preservation, and the scores were significantly higher for its unique flavor, which offered a promising choice for food safety, preservation and reducing foodborne illness., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Hypoxic-ischemic encephalopathy, which predisposes to neonatal death and neurological sequelae, has a high morbidity, but there is still a lack of effective prevention and treatment in clinical practice. To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy, in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats. First, based on the conventional Rice-Vannucci model of hypoxic-ischemic encephalopathy, we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge. Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins. We also performed transmission electron microscopy and found typical characteristics of ferroptosis, including mitochondrial shrinkage, ruptured mitochondrial membranes, and reduced or absent mitochondrial cristae. Further, both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein, which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage. Finally, we found that ferroptosis-related Ferritin (Fth1) and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury. Based on these results, it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion. Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system., Competing Interests: None

Background: ChatGPT, powered by the GPT model and Transformer architecture, has demonstrated remarkable performance in the domains of medicine and healthcare, providing customized and informative responses. In our study, we investigated the potential of ChatGPT in the field of neurosurgery, focusing on its applications at the patient, neurosurgery student/resident, and neurosurgeon levels., Method: The authors conducted inquiries with ChatGPT from the viewpoints of patients, neurosurgery students/residents, and neurosurgeons, covering a range of topics, such as disease diagnosis, treatment options, prognosis, rehabilitation, and patient care. The authors also explored concepts related to neurosurgery, including fundamental principles and clinical aspects, as well as tools and techniques to enhance the skills of neurosurgery students/residents. Additionally, the authors examined disease-specific medical interventions and the decision-making processes involved in clinical practice., Results: The authors received individual responses from ChatGPT, but they tended to be shallow and repetitive, lacking depth and personalization. Furthermore, ChatGPT may struggle to discern a patient's emotional state, hindering the establishment of rapport and the delivery of appropriate care. The language used in the medical field is influenced by technical and cultural factors, and biases in the training data can result in skewed or inaccurate responses. Additionally, ChatGPT's limitations include the inability to conduct physical examinations or interpret diagnostic images, potentially overlooking complex details and individual nuances in each patient's case. Moreover, its absence in the surgical setting limits its practical utility., Conclusion: Although ChatGPT is a powerful language model, it cannot substitute for the expertise and experience of trained medical professionals. It lacks the capability to perform physical examinations, make diagnoses, administer treatments, establish trust, provide emotional support, and assist in the recovery process. Moreover, the implementation of Artificial Intelligence in healthcare necessitates careful consideration of legal and ethical concerns. While recognizing the potential of ChatGPT, additional training with comprehensive data is necessary to fully maximize its capabilities., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

To understand the heavy metal pollution status of Dongjiang Lake, the contents and species of heavy metals in the surface sediments were investigated during September 2021, and the heavy metal pollution level and potential ecological risk were evaluated. The results showed that Cd, Pb, As, Cu, Zn, Ni, and Cr contents were in the range of 0.40-34.1, 14.8-1688, 6.99-1155, 6.89-280, 26.2-1739, 6.29-55.4, and 23.3-44.8 mg·kg -1 , respectively, with extremely uneven spatial distributions. The highest contents of Cd, Pb, As, Zn, Cu, and Ni were found in the site adjacent to Yaogangxian tungsten ore. The proportion of metal species with bioavailability was high, in which Cd in acid-soluble species was 46.7%-71.5% and Pb in reducible species was 46.8%-67.0%. The bioavailable species of Cu, Zn, Ni, and Cr were 35%-68%, 42%-72%, 26%-51%, and 6%-30%, respectively, although they primarily existed in residual species. According to the geo-accumulation index ( I geo ), there was a moderate or extreme pollution status of Cd in all sites, moderate or extreme pollution status of Pb in 90% of sites, and moderate pollution status of As, Cu, and Zn in 30% of sites. The ecological risk factor ( E r i ) of Cd showed high potential ecological risk in all sites with significantly high potential ecological risk in 80% of sites. Moreover, As and Pb had significantly high potential ecological risk, and Cu had moderate potential ecological risk in S7, which was adjacent to Yaogangxian tungsten ore. There was a high total potential ecological risk in all sites and significantly high potential ecological risk in 50% of sites. Therefore, the surface sediments of Dongjiang Lake were under the combined pollution of Cd, Pb, As, Zn, and Cu with high bioavailability and high total potential ecological risk.

Background: As ultrasound-guided percutaneous liver biopsy (PLB) has become a standard and important method in the management of liver disease in our country, a periodical audit of the major complications is needed., Aim: To determine the annual incidence of major complications following ultrasound-guided PLB and to identify variables that are significantly associated with an increased risk of major complications., Methods: A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021. The major complication rate and all-cause 30-d mortality rate were determined. Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB., Results: In this audit of 1857 liver biopsies, 10 cases (0.53%) of major complications occurred following ultrasound-guided PLB. The overall all-cause mortality rate at 30 d after PLB was 0.27% (5 cases). Two cases (0.11%) were attributed to major hemorrhage within 7 d after liver biopsy. Fibrinogen less than 2 g/L [odds ratio (OR): 17.226; 95% confidence interval (CI): 2.647-112.102; P = 0.003], post-biopsy hemoglobin level (OR: 0.963; 95%CI: 0.942-0.985; P = 0.001), obstructive jaundice (OR: 6.698; 95%CI: 1.133-39.596; P = 0.036), application of anticoagulants/antiplatelet medications (OR: 24.078; 95%CI: 1.678-345.495; P = 0.019) and age (OR: 1.096; 95%CI: 1.012-1.187; P = 0.025) were statistically associated with the incidence of major complications after PLB., Conclusion: In conclusion, the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely, with a major complication rate within the accepted range. Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

To seek new high energetic materials, N-methylene-C-bridged nitrogen-rich heterocycle 1-((4,5-diamino-4 H -1,2,4-triazol-3-yl)methyl)-1 H -1,2,4-triazol-3,5-diamine (DATMTDA) (2) was first synthesized, and two copper coordination compounds ([Cu 12 (OH) 4 (ClO 4 ) 4 (H 2 O) 4 (DATMTDA) 12 ](ClO 4 ) 16 ·12H 2 O (3) and [Cu 3 (OH)(ClO 4 )(DATMTDA) 3 ](ClO 4 ) 3 (NO 3 ) (4)) based on 2 were formed by introducing different anions. These compounds were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction analysis. The crystal structures of compounds 3 and 4 are similar and crystallize in monoclinic systems with the P 2 1 / c space group, while the central copper atoms show different coordination behaviors. However, the structure of compounds 3 and 4 is analogous to a three dimensional structure owing to the O atom of OH - , forming coordinate bonds with three copper cations. The NBO charge of 2 was calculated using density functional theory to understand its coordination modes. The Hirshfeld surface calculation reveals that 3 and 4 have strong intermolecular interactions. The thermal decomposition processes, non-isothermal kinetics, and enthalpies of formation and sensitivities of these compounds were investigated. By introducing one NO 3 - of compound 4 to replace one ClO 4 - in compound 3, compound 4 shows lower density and lower decomposition peak temperature but lower sensitivity and a higher formation enthalpy than compound 3. The complex 4 possesses an outstanding catalytic effect for the decomposition of AP than that of complex 3. The results illustrate the possibility of introducing various anions into energetic coordination compounds for the regulation of energetic materials., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Purpose: To conduct a comparative study of image quality, radiation dose, and iodine intake in hepatic computed tomographic angiography (CTA) of overweight patients with different Gemstone Spectral Imaging (GSI) noise indexes combined with different concentrations of contrast medium., Materials and Methods: Ninety patients with a body mass index of ≥ 25 kg/m 2 were divided into three groups (A, B and C), each with 30 patients. The three groups underwent hepatic CTA with different NI of 7, 11 and 15, respectively, and were injected with different iodine concentrations of 370, 350 and 320 mgI/mL, respectively. Five sets of images at 40-60 keV (interval, 5 keV) were reconstructed in each group. The CT value, image noise, contrast-to-noise ratio (CNR) and subjective score of the hepatic artery and vein, and portal vein in different monochromatic image sets were analyzed to select the optimal energy level in each group. The differences in CT value, image noise, CNR and a subjective score of hepatic artery and vein, portal vein in the optimal monochromatic images among the three groups were compared, the volume CT dose index (CTDIvol) and dose-length product (DLP) were recorded, and the effective dose and iodine intake were calculated., Results: The 40 keV was determined to be the optimal energy level for the monochromatic image sets in each group. No significant group differences were noted in the CT value, image noise, CNR, and subjective image scores of the hepatic artery and vein, and portal vein for the optimal monochromatic images (P > 0.05). Compared with group A, the effective dose and iodine intake in group B were reduced by 50.18% and 9.3%, and by 58.12% and 14.23% in group C, respectively., Conclusion: A low-concentration contrast medium combined with a high-noise GSI index in hepatic CTA of overweight patients can reduce the radiation dose and iodine intake while ensuring image quality., (© 2023. The Author(s) under exclusive licence to Japan Radiological Society.)

Study Design: Retrospective pooled analysis of individual patient data., Objectives: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients., Methods: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center., Results: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables., Conclusion: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

Terpenoids are a diverse group of compounds with isoprene units as basic building blocks. They are widely used in the food, feed, pharmaceutical, and cosmetic industries due to their diverse biological functions such as antioxidant, anticancer, and immune enhancement. With an increase in understanding the biosynthetic pathways of terpenoids and advances in synthetic biology techniques, microbial cell factories have been built for the heterologous production of terpenoids, with the oleaginous yeast Yarrowia lipolytica emerging as an outstanding chassis. In this paper, recent progress in the development of Y. lipolytica cell factories for terpenoid production with a focus on the advances in novel synbio tools and metabolic engineering strategies toward enhanced terpenoid biosynthesis is reviewed.

Background: Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB)., Objective: To investigate the correlation of TGR with clinicopathological features, immune microenvironment, prognosis, and response to denosumab treatment of spinal GCTB., Methods: A total of 128 patients with spinal GCTB treated at 5 centers from 2011 to 2021 were included. TGR was assessed by 2 independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1, and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival and overall survival), clinicopathological features, and denosumab treatment responsiveness., Results: High TGR predicted both poor progression-free survival and overall survival (both P < .001). In addition, TGR was associated with postoperative neurological dysfunction ( P < .001), Enneking staging ( P = .016), denosumab treatment responsiveness ( P = .035), and the number of CD3 + ( P < .001), PD-1 + ( P = .009), PD-L1 + ( P < .001), and FoxP3 + tumor-infiltrating lymphocyte ( P = .02). Importantly, TGR outperformed the traditional Enneking, Campanacci, and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB., Conclusion: These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases., (© 2023. The Author(s).)

Recent extensive evidence suggests that ambient fine particulate matter (PM2.5, with an aerodynamic diameter ≤2.5 μm) may be neurotoxic to the brain and cause central nervous system damage, contributing to neurodevelopmental disorders, such as autism spectrum disorders, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and mental disorders, such as schizophrenia, depression, and bipolar disorder. PM2.5 can enter the brain via various pathways, including the blood-brain barrier, olfactory system, and gut-brain axis, leading to adverse effects on the CNS. Studies in humans and animals have revealed that PM2.5-mediated mechanisms, including neuroinflammation, oxidative stress, systemic inflammation, and gut flora dysbiosis, play a crucial role in CNS damage. Additionally, PM2.5 exposure can induce epigenetic alterations, such as hypomethylation of DNA, which may contribute to the pathogenesis of some CNS damage. Through literature analysis, we suggest that promising therapeutic targets for alleviating PM2.5-induced neurological damage include inhibiting microglia overactivation, regulating gut microbiota with antibiotics, and targeting signaling pathways, such as PKA/CREB/BDNF and WNT/β-catenin. Additionally, several studies have observed an association between PM2.5 exposure and epigenetic changes in neuropsychiatric disorders. This review summarizes and discusses the association between PM2.5 exposure and CNS damage, including the possible mechanisms by which PM2.5 causes neurotoxicity.

Objective: To explore the value of applying computed tomography (CT) radiomics based on different CT-enhanced phases to determine the immunotherapeutic efficacy of non-small cell lung cancer (NSCLC)., Methods: 106 patients with NSCLC who underwent immunotherapy are randomly divided into training (74) and validation (32) groups. CT-enhanced arterial and venous phase images of patients before treatment are collected. Region-of-interest (ROI) is segmented on the CT-enhanced images, and the radiomic features are extracted. One-way analysis of variance and least absolute shrinkage and selection operator (LASSO) are used to screen the optimal radiomics features and analyze the association between radiomics features and immunotherapy efficacy. The area under receiver-operated characteristic curves (AUC) along with the sensitivity and specificity are computed to evaluate diagnostic effectiveness., Results: LASSO regression analysis screens and selects 6 and 8 optimal features in the arterial and venous phases images, respectively. Applying to the training group, AUCs based on CT-enhanced arterial and venous phase images are 0.867 (95% CI:0.82-0.94) and 0.880 (95% CI:0.86-0.91) with the sensitivities of 73.91% and 76.19%, and specificities of 66.67% and 72.19%, respectively, while in validation group, AUCs of the arterial and venous phase images are 0.732 (95% CI:0.71-0.78) and 0.832 (95% CI:0.78-0.91) with sensitivities of 75.00% and 76.00%, and specificities of 73.07% and 75.00%, respectively. There are no significant differences between AUC values computed from arterial phases and venous phases images in both training and validation groups (P < 0.05)., Conclusion: The optimally selected radiomics features computed from CT-enhanced different-phase images can provide new imaging marks to evaluate efficacy of the targeted therapy in NSCLC with a high diagnostic value.

Solar greenhouses are important in the vegetable production and widely used for the counter-season production in the world. However, the CO 2 consumed by crops for photosynthesis after sunrise is not supplemented and becomes chronically deficient due to the airtight structure of solar greenhouses. Vegetable crops cannot effectively utilize light resources under low-CO 2 environment, and this incapability results in reduced photosynthetic efficiency and crop yield. We used cucumber as a model plant and generated several sets of transgenic cucumber plants overexpressing individual genes, including β-carbonic anhydrase 1 ( CsβCA1 ), β-carbonic anhydrase 4 ( CsβCA4 ), and sedoheptulose-1,7-bisphosphatase ( CsSBP ); fructose-1,6-bisphosphate aldolase ( CsFBA ), and CsβCA1 co-expressing plants; CsβCA4 , CsSBP , and CsFBA co-expressing plants ( 14SF ). The results showed that the overexpression of CsβCA1 , CsβCA4 , and 14SF exhibited higher photosynthetic and biomass yield in transgenic cucumber plants under low-CO 2 environment. Further enhancements in photosynthesis and biomass yield were observed in 14SF transgenic plants under low-CO 2 environment. The net photosynthesis biomass yield and photosynthetic rate increased by 49% and 79% compared with those of the WT. However, the transgenic cucumbers of overexpressing CsFBA and CsSBP showed insignificant differences in photosynthesis and biomass yield compared with the WT under low-CO 2 .environment. Photosynthesis, fluorescence parameters, and enzymatic measurements indicated that CsβCA1 , CsβCA4 , CsSBP , and CsFBA had cumulative effects in photosynthetic carbon assimilation under low-CO 2 environment. Co-expression of this four genes ( CsβCA1 , CsβCA4 , CsSBP , and CsFBA ) can increase the carboxylation activity of RuBisCO and promote the regeneration of RuBP. As a result, the 14SF transgenic plants showed a higher net photosynthetic rate and biomass yield even under low-CO 2 environment.These findings demonstrate the possibility of cultivating crops with high photosynthetic efficiency by manipulating genes involved in the photosynthetic carbon assimilation metabolic pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Wang, Feng, Guo, Guan, Zhang, Li, Xing, Sun and Tan.)

Immunotherapy has shown great promise in treating various types of malignant tumors. However, some patients with gastrointestinal cancer have been known to experience rapid disease progression after treatment, a situation referred to as hyperprogressive disease (HPD). This minireview focuses on the definitions and potential mechanisms of HPD, natural disease progression in gastrointestinal malignancies, and tumor immunological microenvironment., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

To characterize IncI1 and IncF18:A-:B1 multidrug-resistance plasmids from an avian Escherichia coli isolate, antibiotic susceptibility testing, conjugation assays, transformation assays, S1-PFGE, and WGS analysis were performed. The 119,457-bp plasmid pEC014-1 with a multidrug-resistance region (MRR) containing four different segments interspersed with six IS26 elements, belonged to incompatibility group I1 and sequence type 71. The 154,516-bp plasmid pEC014-2 with two replicons, typed as FII-18 and FIB-1, carried 14 resistance determinants including bla TEM-1b , bla OXA-1 , oqxAB, dfrA17, aac(6')-Ib-cr, sul1, sul2, tet(A), floR, catB3, hph(aph(4)-Ia), aacC4(aac(3)-IV), aadA5, arr-3, and a merEDACPTR loci in MRR, and additionally encoded three virulence loci: iroNEDCB, sitABCD, and iucABCD-iutA. Plasmid stability assays showed that pEC014-1 and pEC014-2 were stable in recipient E. coli C600 for at least 15 days of passage. Competition assays were carried out to evaluate the fitness impact of pEC014-2 carriage in vitro, revealing a decrease in host fitness. Growth kinetics showed that the growth rate for pEC014-1 or/and pEC014-2 bearing cells was significantly slower than that of the E. coli C600 host strain in the exponential stage (p < 0.01), with only cells carrying pEC014-1 sustaining rapid growth after 6 h of exponential growth. Our findings highlight the mosaic structures of epidemic plasmid IncI1/ST71 and F18:A-:B1 lineages and contribute to a better understanding of the evolution and dissemination of these multidrug resistance and virulence plasmids., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival., Materials and Methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS)., Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The χ 2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child-Pugh grade, and lymph node metastasis correlated with survival., Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC., Competing Interests: None

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC., Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from the Surveillance Epidemiology and End Results database, with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general U.S., Population: Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM., Results: A total of 563,298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among the competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during the study period. While age, surgery, other/unknown race and tumors located at the transverse colon positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, a more recent year (2001-2015) of diagnosis, a grade II or III CRC, rectal cancer, or multiple primary or distant tumors experienced a lower risk of CVSM., Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM that may be helpful for risk stratification and the therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Background: Depression is a common mental disorder and is one of the main causes of disability. Berberine (BBR), the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects. This study was to investigate the hypothesis that BBR treats depressive-like behavior by shifting the balance of the kynurenine (KYN)/serotonin (5-HT) pathway toward the 5-HT pathway through downregulated indoleamine 2,3-dioxygenase 1 (IDO1), monoamine oxidase A (MAOA) and upregulated dopamine decarboxylase (DDC) in hippocampus., Method: A chronic unpredictable mild stress (CUMS) mice model of depression was established via 21 days unpredictable stimulation. Then the mice were randomly assigned into six groups, namely control, model, fluoxetine [FLU, (10 mg/kg)], BBRL (25 mg/kg), BBRM (50 mg/kg), and BBRH (100 mg/kg) groups. Behavioral assessments were conducted to evaluate the antidepressant effects of BBR. The levels of 5-HT, KYN, tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were estimated using high performance liquid chromatography (HPLC). The mRNA and protein levels of DDC, MAOA and IDO1 in hippocampus were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot (WB), respectively., Result: The results showed that a successful CUMS mice model was established through 21 days of continuous unpredictable stimulation, as indicated by the significant decrease in locomotor activity and increase in immobility time, reduction in body weight and sucrose preference rate etc. Compared with the normal group, the concentrations of KYN/TRP had significantly increased (p ## <0.01) and 5-HT/5-HIAA had decreased (p # <0.05) at day 21 in the control group, but then improved after drug treatment with FLU and BBR. Compared with the normal group, the mRNA of IDO1 and MAOA were significantly upregulated (p # <0.05) in the control group, MAOA and IDO1 gene were downregulated by FLU and BBR treatment. Protein expressions of IDO1 and MAOA was significantly increased (p # <0.05) and DDC downregulated (p ## <0.01). BBR treatment downregulated IDO1 and MAOA, upregulated DDC., Conclusions: BBR reversed the abnormalities of the KYN/5-HT pathway in depressed mice and achieved an excellent antidepressant effect. Its direct impact may be observed as changes in biological indicators in mice hippocampus tissue., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To study the application value of metagenomic next-generation sequencing (mNGS) in children with severe infectious diseases., Methods: An analysis was performed on the clinical data and laboratory test results of 29 children with severe infection who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to December 2020. Conventional pathogen culture was performed for the 29 specimens (27 peripheral blood specimens and 2 pleural effusion specimens) from the 29 children, and mNGS pathogen detection was performed at the same time., Results: Among the 29 children, 2 tested positive by conventional pathogen culture with 2 strains of pathogen, and the detection rate was 7% (2/29); however, 20 children tested positive by mNGS with 38 strains of pathogen, and the detection rate was 69% (20/29). The pathogen detection rate of mNGS was significantly higher than that of conventional pathogen culture ( P <0.05), and mNGS could detect the viruses, fungi, and other special pathogens that conventional pathogen culture failed to detect, such as Orientia tsutsugamushi . The univariate analysis showed that gender, routine blood test results, C-reactive protein, procalcitonin, D-dimer, radiological findings, and whether antibiotics were used before admission did not affect the results of mNGS ( P >0.05)., Conclusions: Compared with conventional pathogen culture, mNGS is more sensitive for pathogen detection, with fewer interference factors. Therefore, it is a better pathogenic diagnosis method for severe infectious diseases in children.