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Feng Cai,1 Li-Li Xu,1 Xin Tang,2 Lin-Lin Wang1 1Department of Laboratory Medicine, Kongjiang Hospital, Shanghai, 200093, People’s Republic of China; 2Shanghai Libai Biotechnology Co., Ltd, Shanghai, 200444, People’s Republic of ChinaCorrespondence: Lin-Lin Wang, Department of Laboratory Medicine, Kongjiang Hospital, No. 480 Shuangyang Road, Yangpu District, Shanghai, 200093, People’s Republic of China, Tel +86 2165434597 Ext 8136, Email wang11linlin@163.comObjective: To investigate the diagnostic value of urinary Wilms’ tumour-1 (WT-1) and mu-glutathione S-transferase (Mu-GST) gene expression for detecting kidney injury in type 2 diabetes mellitus (T2DM).Methods: Patients treated between October 2022 and June 2023 were divided into two groups: a diabetic nephropathy (DN) group (105 patients) and a diabetes mellitus (DM) group (100 patients). Additionally, 100 healthy individuals undergoing routine medical check-ups were selected as the control group. The urinary albumin/creatinine ratio (ACR), as well as urinary WT-1 and Mu-GST expression levels, were measured. The sensitivity and specificity of these markers for predicting renal injury were evaluated.Results: The levels of ACR, WT-1 and Mu-GST in the DN group were significantly higher than those in the DM and control groups. The ACR in the DM group was also significantly higher than that in the control group (P < 0.05), and WT-1 and Mu-GST gene expression levels demonstrated a positive correlation with ACR (r = 0.391 and 0.342, respectively). The sensitivity and specificity of WT-1 were 74% and 95%, respectively, whereas those of Mu-GST were 70% and 96%, respectively. The combined detection of WT-1 and Mu-GST yielded a sensitivity of 82% and a specificity of 97%.Conclusion: The levels of WT-1 and Mu-GST gene expression are closely related to T2DM kidney injury, helping to identify the location of kidney injury to some extent, which provides valuable information for the clinical diagnosis and treatment of kidney injury.Keywords: type 2 diabetes mellitus kidney injury, urinary microalbumin/creatinine ratio, wilms’ tumour-1, mu-glutathione S-transferase, diagnosis

Yu-Xin Li,1 Jun Xiong,2 Zheng Zhang,2 Kai Liao,2 Xiao-Hong Zhou,2 Jun Li,2 Jie Xiang,2 Ling-Ling Xu2 1Graduate School, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 2College of Acupuncture and Massage, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Jun Xiong, College of Acupuncture and Massage, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China, Email xiongjun196071@163.comBackground: Acupuncture and moxibustion has been applied worldwide in the treatment of various pain diseases including lumbar disc herniation (LDH) and other pain, However, there has been no bibliometric analysis on this aspect in the past five years. Therefore, this study was carried out for finding research trends and fronts in this field using Citespace and VOSviewer.Methods: Publications about acupuncture therapy for LDH were extracted from the Web of Science database and PubMed with an unlimited time frame. A bibliometric analysis and visualization of results was conducted using CiteSpace 6.1.R3 and VOSviewer 1.6.18 on the information of the annual publication, countries, journals, institutions, authors, references, and keywords.Results: A total of 127 publications were included, and the number of publications had increased noticeably over the past 30 years and reached a peak in the past 3 years. The most productive country with the most publications was China, whose Medical University was the institution with the highest volume of publications. The most productive author was Chen Rixin, while the most-cited author was Kreiner DS. Chinese Acupuncture and Moxibustion was the journal with the most publications, and Spine Journal was the most frequently cited journal. In cited references, an article published in The New England Journal of Medicine by Deyo RA had the most citations and the highest centrality. Of the keywords, the five most frequently used keywords include lumbar disc herniation, acupuncture, low back pain, intervertebral disc displacement, and management.Conclusion: Acupuncture and moxibustion can help to relieve symptoms in patients. However, this field is in the early stages of development and requires more high-quality research studies and international collaborations. In addition, exploring the effectiveness and mechanism of acupuncture for LDH is the hot trend in the future.Keywords: acupuncture, lumbar disc herniation, bibliometric analysis, Traditional Chinese Medicine

Ling-Ling Xu,1– 4,&ast; Yao Yan,1– 3,&ast; Yu-Min Yuan,1– 3 Ying Li,1– 3 Jun Jiang,1– 3 Li-Cai Zhang1– 3 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, People’s Republic of China; 4Department of Anesthesiology, Nanjing Gaochun People’s Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Cai Zhang, Email licaizhang001@163.comObjective: To assess the receptors of TRPV1 and GABAB1 receptors that were colocalized in cerebrospinal fluid contacting nucleus (CSF-contact nucleus) of chronic inflammatory pain (CIP) rats bringing inspiration for reducing chronic pain.Methods: A rat model of CIP was constructed by plantar injection of complete Freund’s adjuvant (CFA), and the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured 1, 3, 5, 7, 10, and 14 days after plantar injection. In the first part of the experiment, rats with CIP were divided into the immunofluorescence group and the coimmunoprecipitation (Co-IP) group (n = 6). Rats in the immunofluorescence group were injected with the retrograde tracer CB conjugated with Alexa Fluor 594 into the lateral ventricle two days before the injection of CFA into the plantar surface of the left paw. Three days later, rats that exhibited hyperalgesia were perfused, and their brains were extracted and used for double immunofluorescence staining of the CSF-contacting nucleus. Rats in the Co-IP group were anesthetized and dissected 3 days after CFA injection, and fresh brain segments containing the CSF-contacting nucleus were collected for Co-IP to assess the colocalization of TRPV1 and GABAB1 in the CSF-contacting nucleus (n = 6). In the second part of the experiment, SD rats were divided into the normal saline group (control group) and the CFA group. Fresh CSF-contacting nucleus-containing tissues were collected for Western blot analysis 3 days after plantar injection to observe the changes in TRPV1 and GABAB1 expression in the CSF-contacting nucleus.Results: TRPV1 and GABAB1 were co-expressed in the CSF-contacting nucleus in rats with CIP, and their expression was upregulated.Conclusion: TRPV1 and GABAB1 in the CSF-contacting nucleus are jointly involved in CIP in rats, and there is a direct or indirect link between TRPV1 and GABAB1.Keywords: cerebrospinal fluid-contacting nucleus, TRPV1 receptor, GABAB1 receptor, chronic inflammatory pain

Qing Huang, Liu-li Xu, Ting Wu, Yun-Zhu Mu Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People’s Republic of ChinaCorrespondence: Yun-Zhu Mu, Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +8615984833231, Email hymyz77@163.comAbstract: Striae distensae (stretch marks/striae gravidarum) is one of the common cosmetic problems that can cause psychological distress and anxiety to patients due to its disfiguring damage, especially for women. The etiology of striae distensae is currently unknown, and risk factors include low maternal age, family history of stretch marks, excessive weight gain during pregnancy, and high neonatal weight. This article reviews the latest literature on the most commonly used, most popular, and novel treatment modalities and analyzes the hot spots and difficulties in striae distensae treatment in recent years. Topical treatment modalities are mainly used as an adjunctive treatment. Ablative lasers and non-ablative lasers are the most popular, among which picosecond has been tried in striae distensae treatment in the last two years. Combined treatment modalities are currently a hot spot for SD treatment, and microneedle radiofrequency and fractional CO2 laser combined with other treatments are the most common. Microneedle radiofrequency is the most commonly used and achieved therapeutic effect among the combined treatment modalities.Keywords: striae distensae, stretch marks, striae gravidarum, treatment

Yong-Fang Li,1,&ast; Qin-Yi Wang,1,&ast; Lu-Lu Xu,2 Chun Yue,2 Li Hu,2 Na Ding,1 Yan-Yi Yang,2 Xiao-Li Qu,1 Zhi-Feng Sheng1,2 1National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, Health Management Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Health Management Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Feng Sheng, Tel +86-13574806523, Email shengzhifeng@csu.edu.cnPurpose: Fragility fractures, the most serious complication of osteoporosis, affect life quality and increase medical expenses and economic burden. Strategies to identify populations with very low bone mineral density (T-scores

Dong-Ping Li,1,* Ying-Ling Chen,1,* Hong-Yue Jiang,1,* Yun Chen,1 Xiao-Qing Zeng,1 Li-Li Xu,1 Yang Ye,2 Chang-Qiang Ke,2 Ge Lin,3 Ji-Yao Wang,1,4 Hong Gao1,41Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2State Key Laboratory of Drug Research & Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong, People’s Republic of China; 3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR; 4Evidance-based Medicine Center of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work Purpose: To investigate the mitochondria-related mechanism of Gynura segetum (GS)-induced apoptosis and the protective effect of phosphocreatine (PCr), a mitochondrial respiration regulator.Methods: First, the mechanism was explored in human hepatocyte cell line. The mitochondrial oxidative stress was determined by fluorescence assay. The level of sirtuin 3 (SIRT3), acetylated superoxide dismutase 2 (Ac-SOD2), SOD2, and apoptosis were detected by Western blotting. Mito-TEMPO and cell lines of viral vector-mediated overexpression of SIRT3 and SIRT3H248Y, were used to further verify the mechanism of GS-induced apoptosis. GS-induced liver injury mice models were built by GS through intragastric administration and interfered by PCr through intraperitoneal injection. A total of 30 C57BL/6J mice were assigned to 5 groups and treated with either saline, PCr (100 mg/kg), GS (30 g/kg), or PCr (50 or 100 mg/kg)+GS (30 g/kg). Liver hematoxylin and eosin (HE) staining, immunohistochemical analysis, and blood biochemical evaluation were performed.Results: GS induced hepatocyte apoptosis and elevated levels of mitochondrial ROS in L-02 cells. The expression of SIRT3 was decreased. Downregulation of SIRT3 was associated with increased levels of Ac-SOD2, which is the inactivated enzymatic form of SOD2. Conversely, when overexpressing SIRT3 in GS-treated cells, SOD2 activity was restored, and mitochondrial ROS levels and hepatocyte apoptosis declined. Upon administration of PCr to GS-treated cells, they exhibited a significant upregulation of SIRT3 and were protected against apoptosis. In animal experiments, serum ALT level and mitochondrial ROS of the mice treated with GS and 50 mg/kg PCr were significantly attenuated compared with only GS treated. The changes in SIRT3 expression were also consistent with the in vitro results. In addition, immunohistochemical analysis of the mouse liver showed that Ac-SOD2 was decreased in the PCr and GS co-treated group compared with GS treated group.Conclusion: GS caused liver injury by dysregulating mitochondrial ROS generation via a SIRT3-SOD2 pathway. PCr is a potential agent to treat GS-induced liver injury by mitochondrial protection.Keywords: Gynura segetum, apoptosis, mitochondrial, ROS, SIRT3, phosphocreatine

OBJECTIVE: To evaluate the effect of Jianpi Huoxue decoction (JHD)-containing serum on tumor necrosis factor-alpha (TNF-alpha) secretion and endotoxin receptor gene expression in RAW264.7 cells induced by lipopolysaccharide (LPS). METHODS: The cytotoxicity of blank-control serum and JHD-containing serum at different concentrations were evaluated through the lactate dehydrogenase (LDH) assay in RAW264.7 cells. RAW264.7 cells were divided into six groups: 5% blank-control serum group (C1, n=3), 5% blank-control serum plus LPS group (L1, n=4), 5% JHD-containing serum plus LPS group (J1, n=4), 10% blank-control serum group (C2, n=3), 10% blank-control serum plus LPS group (L2, n=4), and 10% JHD-containing serum plus LPS group (J2, n=4). After cultured with the corresponding serum for 1 h, cells in L1, L2, J1 and J2 were treated with LPS (0.1 microg/mL) for 12 h without rinse. The supernate, cells, protein and RNA were collected for assay. TNF-alpha in the culture supernate was assayed by the enzyme linked immunosorbent assay (ELISA). Protein expression of TNF-alpha in RAW cells was detected by Western-blot. TNF-alpha, Toll-like receptor 2 (TLR2), TLR4 and CD14 mRNA expression in RAW cells were detected by real-time RT-PCR. RESULTS: The LDH assay supported that cultured for 24 h or less with the JHD-containing serum at the concentration of 10% or lower, RAW264.7 cells showed no cytotoxicity. After stimulation with LPS for 2 h, TNF-alpha in the culture supernate of the 5% blank-control serum plus LPS group (L1, P=0.03), 10% blank-control serum plus LPS group (L2, P=0.002) and in the cell layer (P=0.01) of these groups increased remarkably. After stimulation with LPS for 1 h, the mRNA expression of TNF-alpha (P=0.004), TLR (P=0.03), CD14 (P=0.004) was up-regulated obviously. In the 10% JHD-containing serum plus LPS group (J2), the protein expression of TNF-alpha in both supernate (P=0.04) and cell layer (P=0.04), gene expression of TNF-alpha (P=0.03), TLR4 (P=0.001), CD14 (P=0.001) were all inhibited. On the other hand, the TLR2 mRNA expression was not up-regulated after LPS stimulation in the 10% blank-control serum plus LPS group (L2). CONCLUSION: JHD-containing serum inhibited the LPS-induced cytokines expression in RAW264.7 which was probably associated with its inhibitory effect on the mRNA expression of LPS receptors TLR and CD14. [ABSTRACT FROM AUTHOR]

Sample relatedness is a major confounder in genome-wide association studies (GWAS), potentially leading to inflated type I error rates if not appropriately controlled. A common strategy is to incorporate a random effect related to genetic relatedness matrix (GRM) into regression models. However, this approach is challenging for large-scale GWAS of complex traits, such as longitudinal traits. Here we propose a scalable and accurate analysis framework, SPA GRM , which controls for sample relatedness via a precise approximation of the joint distribution of genotypes. SPA GRM can utilize GRM-free models and thus is applicable to various trait types and statistical methods, including linear mixed models and generalized estimation equations for longitudinal traits. A hybrid strategy incorporating saddlepoint approximation greatly increases the accuracy to analyze low-frequency and rare genetic variants, especially in unbalanced phenotypic distributions. We also introduce SPA GRM(CCT) to aggregate the results following different models via Cauchy combination test. Extensive simulations and real data analyses demonstrated that SPA GRM maintains well-controlled type I error rates and SPA GRM(CCT) can serve as a broadly effective method. Applying SPA GRM to 79 longitudinal traits extracted from UK Biobank primary care data, we identified 7,463 genetic loci, making a pioneering attempt to conduct GWAS for these traits as longitudinal traits., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Abstract: The global prevalence of heart failure is still growing, which imposes a heavy economic burden. The role of microRNA-146b (miR-146b) in HF remain largely unknown. This study aims to explore the role and mechanism of miR-146b in HF. Method: We applied Reverse transcription-polymerase chain reaction (RT-PCR) to search for differential microRNAs between myocardial tissues of heart failure patients and controls. We also used RT-PCR to detect the miR-146b expression in primary neonatal mouse cardiomyocytes (NMCMs) and mice models of doxorubicin induced HF. In vivo experiments, echocardiography was performed at baseline and weeks 6. After that we harvested mice' heart and evaluated the cardiomyocyte with hematoxylin and eosin (HE), Masson trichrome staining and TUNEL staining. Through bioinformatics analysis, we found HIF-1α might be the target gene of miR-146b which validated by luciferase reporter gene assay. Subsequently, mRNA and protein expression levels of HIF-1α were detected by overexpression or inhibition of miR-146b in primary NMCMs. Results: We found that miR-146b expression was decreased in myocardial tissues of HF patients compared with controls (p < 0.01). MiR-146b levels were notably down regulated in HF models. MiR-146b knockout mice showed a more pronounced decrease in cardiac function and more severe myocardial fibrosis and apoptosis than wild type. Meanwhile, over expression or repression of miR-146b in primary neonatal mouse cardiomyocytes could inhibit or upregulate HIF-1α mRNA and protein expression. Conclusion: Our study shows that miR-146b may be a protective factor for cardiomyocytes by modulating HIF-1α., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Objectives: Although patients with arthritis have significantly increased cardiovascular disease (CVD) risk, effective prediction tools remain limited. This study aimed to evaluate the predictive value of the Metabolic Score for Insulin Resistance (METS-IR) for CVD events among Chinese patients with arthritis., Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a 7-year prospective cohort study (2011-2018) involving 1,059 patients with arthritis. The primary exposure was baseline METS-IR, and the primary outcome was incident CVD. Multivariate Cox regression models were used to analyze the association between METS-IR and CVD risk, adjusting for demographic characteristics and lifestyle factors., Results: After adjusting for confounding factors, each quartile increase in METS-IR was associated with a 36% increased risk of CVD (HR = 1.36,95%CI : 1.14-1.61, p< 0.001). Compared with the lowest quartile, the highest quartile showed a 63% increased risk (HR = 1.63,95%CI : 1.12-2.37, p< 0.05), demonstrating a significant dose-response relationship (p for trend < 0.05)., Conclusion: METS-IR serves as an effective tool for predicting CVD risk among Chinese patients with arthritis, providing new strategies for early risk identification and prevention., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines, accessing analogs capable of mimicking ortho- and meta-substituted anilines remains challenging due to the lack of a versatile and modular synthetic methods. Herein, we present a modular approach to access a diverse array of saturated bioisosteres of anilines via photoelectrochemical-induced decarboxylative C(sp 3 )-N Coupling. The success of this reaction hinges on the merging the cooperative ligand-to-metal charge transfer (LMCT) with copper-catalyzed amination. Notably, this net-oxidative C(sp 3 )-N forming reaction operates under mild electrode potentials and proceeds through hydrogen evolution, eliminating the need for external chemical oxidants. Our research enables the facile decarboxylative amination of a set of sp 3 -rich small-ring cage carboxylic acids, thus offering a versatile bioisosteric replacement for ortho-, meta-, and para-substituted anilines and di(hetero)aryl amines., Competing Interests: Competing interests: A Chinese patent application on this work has been filed by Shanghai Jiao Tong University (application no. 202311813231X), with M.S., K.-N.Y., J.W., M. H.L. listed as inventors. The patent covers the discovery of this new reaction, the scope of both reactants and their applications in the drug development. The remaining authors declare no competing interests., (© 2025. The Author(s).)

This study introduces a novel methodology for the direct construction of tetrasubstituted centers, utilizing secondary C(sp 3 )-H and C(sp 2 )-H substrates, specifically indolin-2-ones and indoles, through an innovative oxidative cross-coupling reaction. Facilitated by a straightforward copper salt catalyst, this reaction proceeds efficiently at a mild temperature of 40 °C under operationally streamlined conditions. Emphasizing sustainability, this method is notably enhanced by employing air (molecular oxygen) as an eco-friendly oxidant. In this approach, air (molecular oxygen) not only serves as the terminal oxidant but also as the oxygen donor in the synthesis of oxygen-containing compounds.

Background: There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin deglu-dec/aspart (IDegAsp) therapy, with insufficient data from the Chinese popu-lation., Aim: To demonstrate the efficacy, safety, and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus (T2DM)., Methods: In this 12-week open-label, non-randomized, single-center, pilot study, patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp. Insulin doses, hemoglobin A1c (HbA1c) levels, fasting blood glucose (FBG), hypoglycemic events, a Diabetes Treatment Satisfaction Questionnaire, and other parameters were assessed at baseline and 12-weeks., Results: This study included 21 participants. A marked enhancement was observed in the FBG level ( P = 0.02), daily total insulin dose ( P = 0.03), and overall diabetes treatment satisfaction ( P < 0.01) in the participants who switched to IDegAsp. There was a decrease in HbA1c levels (7.6 ± 1.1 vs 7.4 ± 0.9, P = 0.31) and the frequency of hypoglycemic events of those who switched to IDegAsp decreased, however, there was no statistically significant difference., Conclusion: The present findings suggest that treatment with IDegAsp enhances clinical outcomes, particularly FBG levels, daily cumulative insulin dose, and overall satisfaction with diabetes treatment., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

The therapeutic effectiveness of acupuncture relies on both safety and stability, making these factors essential in acupuncture manipulation research. However, manual manipulation introduces unavoidable inaccuracies, which can impact the reliability of research findings. To address this challenge, a unique lifting and thrusting manipulation control cannula was designed in this study, offering flexible adjustment of movement amplitude. The cannula was created using 3D printing technology, and its effectiveness in maintaining stability was verified by recording the acupuncture needle's movement range with optical sensor technology. The study's results show that the control cannula significantly enhances the stability of acupuncture manipulation, reducing human error. This innovation suggests that the cannula could serve as a valuable auxiliary tool for ensuring both the precision and safety of acupuncture-related experimental research. Its adoption could also contribute to the standardization of acupuncture practices, ensuring more consistent and accurate research outcomes, which is essential for future advancements in acupuncture research and clinical applications.

Background: Primary Sjogren's syndrome (pSS) and autoimmune thyroiditis (AIT) share overlapping genetic and immunological profiles. This retrospective study evaluates the efficacy of machine learning algorithms, with a focus on the Random Forest Classifier, to predict the presence of thyroid-specific autoantibodies (TPOAb and TgAb) in pSS patients., Methods: A total of 96 patients with pSS were included in the retrospective study. All participants underwent a complete clinical and laboratory evaluation. All participants underwent thyroid function tests, including TPOAb and TgAb, and were accordingly divided into positive and negative thyroid autoantibody groups. Four machine learning algorithms were then used to analyze the risk factors affecting patients with pSS with positive and negative for thyroid autoantibodies., Results: The results indicated that the Random Forest Classifier algorithm (AUC = 0.755) outperformed the other three machine learning algorithms. The random forest classifier indicated Age, IgG, C4 and dry mouth were the main factors influencing the prediction of positive thyroid autoantibodies in pSS patients. It is feasible to predict AIT in pSS using machine learning algorithms., Conclusions: Analyzing clinical and laboratory data from 96 pSS patients, the Random Forest model demonstrated superior performance (AUC = 0.755), identifying age, IgG levels, complement component 4 (C4), and absence of dry mouth as primary predictors. This approach offers a promising tool for early identification and management of AIT in pSS patients., Trial Registration: This retrospective study was approved and monitored by the Ethics Committee of The Third Affiliated Hospital of Sun Yat-sen University (No.II2023-254-02)., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the Ethics Committee of The Third Affiliated Hospital of Sun Yat-sen University (No.II2023-254-02). Because of the retrospective nature of the study, the requirement for informed consent was waived. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Dyspnea-related kinesiophobia refers to restrictions or avoidance of activities due to fear of dyspnea and is prevalent among older adults with chronic obstructive pulmonary disease (COPD). Hence, there is a need to identify subgroups of dyspnea-related kinesiophobia among older adults with COPD to support the development of strategies to increase activity levels., Objective: The purpose of this study was to investigate dyspnea-related kinesiophobia among older adults with COPD, explore heterogeneity in kinesiophobia within subgroups of this population, and analyze the characteristics of different subgroups of kinesiophobia., Method: This cross-sectional study was conducted from November to December 2023 in Fenyang City, Shanxi Province, China, via face-to-face questionnaire surveys of hospitalized adults with COPD aged over 60 years in four secondary or tertiary hospitals. The Breathlessness Beliefs Questionnaire (BBQ) was used to measure dyspnea-related kinesiophobia. Latent profile analysis was employed to classify the subgroups. CChi-square tests and binary logistic regression were used to examine the effects of sociodemographic factors, marital status, education, income, daily activities, general health, and COPD severity across different profiles., Results: A total of 384 older adults with COPD (Male N = 228, aged 60-88) were included in the study. Their average BBQ score was (39.15±5.59). Latent profile analysis identified two groups: 230 participants (59.9 %) in the low-level kinesiophobia group (C1) and 154 participants (40.1 %) in the high-level kinesiophobia group (C2). Multivariable stepwise binary logistic regression analysis revealed that older adults with COPD who engaged in exercise less than three days weekly reported an average monthly household income of <3000 CNY, unmarried status (including unmarried, divorced, or widowed), a Charlson Comorbidity Index (CCI) >1, more than three exacerbations within one year or with moderate (GOLD 2 Criteria)-severe (GOLD3) COPD were more likely to be the high-level kinesiophobia group (p < 0.05)., Conclusion: Dyspnea-related kinesiophobia manifests in two groups among older adults. Targeted interventions for different subgroups should be further developed to promote health and reduce nursing burdens., Competing Interests: Declaration of competing interest The authors have disclosed that there are no competing financial interests or personal relationships that might have influenced the work presented in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25-31% of the cell population within 8-10 weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates pro-inflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling has a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Fifteen undescribed sesquiterpenoid monomers, including six pairs of sesquiterpenoid enantiomers (1a/1b-3a/3b and 5a/5b-7a/7b) and three analogues (4, 8, and 9), together with two known sesquiterpenoid dimers (10 and 11) were isolated from the whole plant of Chloranthus henryi Hemsl. Their structures were characterized by spectroscopic data analysis, ECD calculations, and single crystal X-Ray diffractions. Compounds 1a and 1b were highly aromatic cadinane-type sesquiterpenoids. At a concentration of 10 μM, compounds 8, 10, and 11 exhibited potent neuroprotective activity against H 2 O 2 -induced PC12 cell damage. Compounds 10 and 11 significantly decreased the level of ROS. In addition, compound 11 increased the levels of p-AMPK, p-SIRT1, and SIRT3 in the H 2 O 2 -induced PC12 cell damage via activated the AMPK/SIRT signaling pathway., 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.)

Exosome-based drug delivery holds significant promise for cancer chemotherapy. However, current methods for loading drugs into exosomes are inefficient and cost-prohibitive for practical application. In this study, boron clusters are mixed with doxorubicin (DOX) and exosomes, enabling the efficient encapsulation of DOX into exosomes through a superchaotropic effect. Exosomes loaded with DOX and boron clusters (EDB) exhibit superior permeability and the ability to deliver higher concentrations of DOX into DOX-resistant breast cancer cells. Mechanistic analysis reveals that boron clusters form a supramolecular complex with DOX, which facilitates sustained drug release and effectively inhibits P-glycoprotein-mediated DOX efflux. As a result, EDB significantly enhance apoptosis in DOX-resistant breast cancer cells and suppress tumor growth in cases where DOX alone is ineffective, thereby extending the survival of nude mice. In summary, boron clusters effectively facilitate the incorporation of DOX into exosomes and inhibit DOX efflux, offering a novel strategy to overcome DOX resistance., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Oxidative stress and microglial activation are critical pathomechanisms in ischemic white matter injury. Microglia, as resident immune cells in the brain, are the main cells undergoing oxidative stress response. However, the role and molecular mechanism of oxidative stress in microglia have not been clearly elucidated during white matter ischemia., Methods: Extensive histological analysis of the corpus callosum was performed in BCAS mice at different time points to assess white matter injury, oxidative stress and microglial activation. Flow cytometric sorting and transcriptomic sequencing were combined to explore the underlying mechanisms regulating microglial oxidative stress and functional phenotypes. The expression of critical molecule in microglia was regulated using Cx3cr1 CreER mice and clinical-stage drugs to assess its effect on white matter injury and cognitive function., Results: Our study identified nuclear factor erythroid-2 related factor 2 (Nrf2) as a key transcription factor regulating oxidative stress and functional phenotype in microglia. Interestingly, we found that the sustained decrease in transiently upregulated expression of Nrf2 following chronic cerebral hypoperfusion resulted in abnormal microglial activation and white matter injury. In addition, high loads of myelin debris promoted lipid peroxidation and ferroptosis in microglia with diminished antioxidant function. Microglia with pharmacologically or genetically stimulated Nrf2 expression exhibited enhanced resistance to ferroptosis and pro-regenerative properties to myelination due to lipid and iron metabolism reprogramming., Conclusion: Weakened Nrf2-mediated antioxidant responses in microglia induced metabolic disturbances and ferroptosis during chronic cerebral hypoperfusion. Targeted enhancement of Nrf2 expression in microglia may be a potential therapeutic strategy for ischemic white matter injury., 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. Published by Elsevier B.V.)

Objective: Our study aimed to evaluate the effectiveness and safety of transcutaneous auricular vagus nerve stimulation (taVNS) for treating mild to moderate depression in patients with epilepsy (PWE)., Methods: A single-arm, prospective, multi-center, pre-post controlled study was conducted in Eastern China. After a four-week baseline period, PWE with mild to moderate depression began treatment with taVNS, administered for 30 min, three times daily, over a 12-week period. The primary outcome measure was the change in 24-item Hamilton Depression Rating Scale (HAMD) scores from baseline to week 12. Secondary outcomes included the response and remission rates for depression at week 12, as well as changes in the 14-item Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) scores, and seizure frequency at weeks 4 and 12 compared to baseline. Adverse events (AEs) were recorded to assess the safety of taVNS. Both modified Intention-To-Treat (mITT) and Per-Protocol (PP) analyses were employed., Results: Sixty-nine participants were enrolled in this study. Of these, 61 (88.4 %) completed the 4-week treatment phase, and 50 (72.5 %) finished the 12-week treatment phase. In the mITT analysis, HAMD scores significantly decreased by 4.54 ± 7.44 (p < 0.001) from baseline to week 12, with clinical response in 16 (26.2 %) and remission in 15 (24.6 %) patients. HAMA scores also decreased significantly by week 4 (3.23 ± 5.18, p < 0.001) and week 12 (4.95 ± 6.78, p < 0.001). PSQI scores and seizure frequency showed non-significant changes at week 4, but seizure frequency decreased significantly by week 12 (0.03 ± 10.47, p = 0.038). In the PP analysis, similar improvements were observed. After 12 weeks of taVNS compared to baseline, HAMD scores decreased significantly by 5.32 ± 8.98 (p < 0.001), with 32 % of patients achieving a clinical response and 24 % achieving clinical remission. And HAMA scores also decreased by 5.66 ± 7.54 (p < 0.001), seizure frequency by 0.14 ± 11.03 (p = 0.018), and PSQI scores by 1.06 ± 4.14 (p = 0.076).There was a significant increase in QOLIE-31 scores by 5.17 ± 14.71 (p = 0.020). Ten (14.5 %) patients experienced non-serious adverse events, the most common of which was ear pain (n = 4); one patient withdrew due to tinnitus enhancement; all resolved after reducing the stimulation intensity or stopping the treatment., Conclusion: Our study suggests that taVNS may effectively improve depressive symptoms in PWE. This may be an efficacious and safe treatment for mild to moderate depression in PWE., 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 Inc. All rights reserved.)

This study systematically retrieved the clinical studies in the treatment of idiopathic pulmonary fibrosis(IPF) with traditional Chinese medicine(TCM) and employed evidence mapping to summarize the overall research status and deficiencies of TCM in treating IPF. CNKI, VIP, SinoMed, Wanfang, PubMed, Web of Science, Cochrane Library, and EMbase were searched for the relevant studies published from inception to February 20, 2024. The distribution characteristics of the evidence were analyzed and presented through charts combined with words. A total of 323 studies were included, including 295 randomized controlled trials(RCTs) and 28 Meta-analysis. The number of publications in this field rose with fluctuations, yet the proportion of core papers was low, and the research lacked the attention of foreign researchers. There were scant cross-regional collaboration between researchers and insufficient attention from relevant departments. The included RCT generally had low quality, with small sample sizes, short treatment courses, and insufficient attention to acute exacerbation and complications of IPF. In addition, few studies employed TCM alone, and the TCM syndromes remained to be standardized. A considerable number of outcome indicators were involved in the publications, while the majority of them failed to emphasize the disparity between primary and secondary outcome indicators. There were diverse reference standards for the comprehensive indicators among the outcome indicators, and insufficient attention was paid to long-term prognosis and health economic indicators. The included Meta-analysis concluded that TCM had potential clinical efficacy in treating IPF. However, the methodological credibility grading and the GRADE grading results of outcome indicators were low. The results suggested that TCM demonstrated certain advantages in the treatment of IPF, while the quality of the included studies was not high. In the future, clinical research protocols should be standardized and registered. Multicenter, large-sample, and follow-up clinical studies should be conducted. The research reports should refer to relevant reporting standards to improve the quality and generate high-level evidence, thus providing a reference for the clinical application of TCM in the treatment of IPF.

Background: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ce prop ) required to suppress response to cervical dilation in patients undergoing hysteroscopy., Methods: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg -1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 μg⋅kg -1 , and a target-controlled propofol infusion. The initial target Ce prop was 3.5 μg·mL -1 and was increased or decreased in subsequent patients by steps of 0.5 μg·mL -1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ce prop that suppressed response to cervical dilation in 50% of patients (EC 50 )., Results: The EC 50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg -1 (2.08 [95% confidence interval, CI, 1.88-2.28] μg·mL -1 ), 0.15 mg⋅kg -1 (1.83 [1.56-2.10] μg·mL -1 ), and 0.2 mg⋅kg -1 (1.43 [1.27-1.58] μg·mL -1 ) remimazolam than those given 0 mg⋅kg -1 (3.67 [3.49-3.86] μg·mL -1 ) or 0.05 mg⋅kg -1 (3.47 [3.28-3.67] μg·mL -1 ) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg -1 decreased EC 50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg -1 ). Propofol consumption was lower in patients given 0.1 mg⋅kg -1 (4.15 [3.51-5.44] mg·kg -1 ), 0.15 mg⋅kg -1 (3.54 [3.16-4.46] mg·kg -1 ), and 0.2 mg⋅kg -1 (2.74 [1.73-4.01] mg·kg -1 ) remimazolam than those given 0 mg⋅kg -1 (6.09 [4.99-7.35] mg·kg -1 ) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups., Conclusions: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg -1 reduced the EC 50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Recent advances in ultrasound technology have led to widespread adoption of ultrasonic energy devices in liver resections. While various studies have assessed the comparative advantages of ultrasonic devices and traditional clamp-crushing, their findings vary. Moreover, a specific systematic review on this topic has not yet been conducted., Objectives: This study aims to present a comprehensive, up-to-date analysis comparing outcomes between ultrasonic devices and conventional clamp-crushing methods in liver resection, based on currently available literature., Patients and Methods: We conducted a systematic literature search in databases such as PubMed, Embase, Web of Science, and CNKI up to November 2023. Studies that compared the efficacy or safety of ultrasonic devices against traditional clamp-crushing methods in hepatectomy were included. The analysis covered intraoperative outcomes like operating time, blood loss, and transfusion rate, as well as postoperative outcomes such as complication rate, mortality, postoperative bleeding, and bile leakage. Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK) and Stata 17.0 (Stata Corp, College Station, TX, USA) were used for data analysis., Results: Thirteen studies, involving a total of 1,417 patients (630 using ultrasonic devices and 787 using clamp-crushing methods), were included. The clamp-crush method resulted in a shorter operation time. Contrarily, the ultrasonic device group experienced reduced blood loss and lower transfusion rates. Postoperatively, there was no significant difference in mortality or postoperative bleeding between the groups. However, the ultrasonic group had a lower overall complication rate, particularly a reduced incidence of bile leakage. Overall, the ultrasonic devices were associated with improved perioperative outcomes., Conclusions: The findings suggest that ultrasonic devices provide better outcomes in hepatectomy compared to traditional clamp-crushing techniques. Nonetheless, large-scale randomized controlled trials are needed to confirm these results due to potential heterogeneity and biases. The choice of using ultrasonic devices should consider the surgeon's experience and individual patient circumstances., Competing Interests: Declarations Ethics approval and consent to participate Ethical review and approval were not required for the study of human participants in accordance with the local legislation and institutional requirements. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The mitochondrial dynamic imbalance is an important cause of myocardial ischaemia/reperfusion (I/R) injury and dysfunction. Psmb8, as one of the immunoproteasome catalytic subunits, is a key regulator of protein homoeostasis, inflammation and some cardiac diseases. Here, we found that the expression level and activity of Psmb8 were significantly reduced in the heart of I/R mice and in subjects with myocardial infarction (MI). Cardiomyocyte-specific Psmb8 overexpression in mice markedly ameliorated I/R-mediated cardiac injury and dysfunction, which was accompanied by reduced mitochondrial division via the downregulation of dynamin-related protein-1 (Drp1). However, Psmb8 knockout (KO) mice exhibited the opposite changes. The effects of Psmb8 on mitochondrial fission and apoptosis was confirmed in primary cardiomyocytes with overexpression or knockdown of Psmb8 in vitro. Mechanistically, Psmb8 was directly associated with Drp1 and enhanced its degradation, which subsequently suppressed I/R-mediated mitochondrial fission and cardiac injury. Conversely, knockdown of Drp1 in Psmb8-KO mice restored I/R-induced cardiac dysfunction and mitochondrial dynamic imbalance. Our study identified a new cardioprotective role of Psmb8 in cardiac I/R damage through targeting Drp1, and highlight that increasing Psmb8 activity may constitute a promising therapy for ischaemic heart disease., (© 2024. The Author(s).)

Background: Major depressive disorder (MDD) is a substantial global health concern, and its treatment is complicated by the variability in individual response to antidepressants., Aim: To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes., Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search across PubMed, EMBASE, Web of Science, and the Cochrane Library was conducted without date restrictions, utilizing key terms related to MDD, serotonin 1A receptor polymorphism (5-HTR1A), C-1019G polymorphism, and antidepressant response. Studies meeting inclusion criteria were thoroughly screened, and quality assessed using the Newcastle-Ottawa Scale. Statistical analyses, including χ 2 and I² values, were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly., Results: The initial search yielded 1216 articles, with 11 studies meeting criteria for inclusion. Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy. The heterogeneity was low to moderate, and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests., Conclusion: This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD. The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

With the advancement of computer technology and imaging equipment, ultrasound has emerged as a crucial tool in breast cancer diagnosis. To gain deeper insights into the research landscape of ultrasound in breast cancer diagnosis, this study employed bibliometric methods for a comprehensive analysis spanning from 2004 to 2024, analyzing 3523 articles from 2176 institutions in 82 countries/regions. Over this period, publications on ultrasound diagnosis of breast cancer showed a fluctuating growth trend from 2004 to 2024. Notably, China, Seoul National University and Kim EK emerged as leading contributors in ultrasound for breast cancer detection, with the most published and cited journals being Ultrasound Med Biol and Radiology. The research spots in this area included "breast lesion", "dense breast" and "breast-conserving surgery", while "machine learning", "ultrasonic imaging", "convolutional neural network", "case report", "pathological complete response", "deep learning", "artificial intelligence" and "classification" are anticipated to become future research frontiers. This groundbreaking bibliometric analysis and visualization of ultrasonic breast cancer diagnosis publications offer clinical medical professionals a reliable research focus and direction.

Ovarian cancer is the fifth most prevalent cancer in women. Chemotherapy is a major treatment option for patients with advanced ovarian cancer (OC). Quinoline-2-thione and its derivatives are potential candidates for tumor therapy. In this study, we investigated the anticancer activity of the quinoline-2-thione derivative KA3D against ovarian cancer. The effect of KA3D on the viability of ovarian cancer cells was evaluated using MTT assay, and its effects on apoptosis and the cell cycle were detected using flow cytometry. Western blotting was performed to identify apoptosis-and cell cycle-related proteins altered by KA3D treatment. A xenograft model was used to verify the inhibitory effect of KA3D in vivo. H&E staining, biochemical indicator detection, and blood cell counts were used to observe the toxicity and side effects of KA3D. KA3D treatment impeded cell viability, induced apoptosis, and impeded the G2 phase of the cell cycle in ovarian cancer cells. Mechanistically, we found that KA3D enhanced the expression of proapoptotic molecules such as BAX and Caspase 3, while antiapoptotic proteins such as BCL2 were inhibited. The G0/G1 phase-related protein cyclin D1 was reduced and the G2 phase-related protein cyclin B1 was upregulated. In vivo, KA3D displayed potent anticancer activity, with no apparent toxicity in BABLC/c nude mice bearing SKOV3 cells. KA3D demonstrated remarkable chemotherapeutic drug efficacy in terms of significant cancer suppression in vitro and in vivo with low toxicity., (© 2024. The Author(s).)

Objective: We aimed to describe jaw function characteristics in patients with anterior disc displacement without reduction (ADDWoR) using the jaw function limitation scale (JFLS), and to investigate the effects of biopsychosocial risk factors on limited jaw function., Design: In this cross-sectional study of 636 patients with ADDWoR (females, 568; males, 68), we used the JFLS to assess jaw function. Behavioral, psychological, sociodemographic, and biomedical data were collected. Multivariate logistic regression analysis was used to determine risk factors affecting limited jaw function. A receiver operating characteristic curve was used to evaluate the predictive effect of these risk factors., Results: ADDWoR-associated limitations included restricted jaw mobility and mastication, which exceeded median global functional limitations scale scores, especially mouth opening to bite an apple and chewing tough food. Females had greater limitations in jaw mobility, verbal and emotional communication, and overall. Multivariate logistic regression analysis findings indicated that oral behaviors, anxiety, sex, pain intensity, and maximal mouth opening (MMO) were predictive of limited jaw function (area under the curve, 72 %)., Conclusion: Patients with ADDWoR reported mastication and jaw mobility restrictions, with females having more pronounced limitations, and specific risk factors identified as significant predictors of jaw function limitations. Along with pain relief and improvement in MMO, appropriate psychological counseling and oral behavioral correction facilitates recovery of jaw function in such patients., Competing Interests: Declaration of Competing Interest The authors state that they have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Inherently chiral medium-ring derivatives have important applications in many research fields, such as materials science, molecular recognition, and asymmetric catalysis. However, the enantioselective assembly of these molecules, especially by organocatalytic strategies, remains a formidable challenge, and few methods are available. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) formal high-order (5 + 3) annulation of 1-(2-indolyl)naphthalen-2-ols with ynals. In the presence of an NHC pre-catalyst, base, Lewis acid and oxidant, this protocol enables the catalytic formation of C-C and C-O bonds, providing practical and facile access to an array of inherently chiral saddle-shaped eight-membered lactones featuring an oxocin-2-one scaffold with structural diversity in good efficiency and excellent enantiocontrol. Moreover, the scale-up preparation and representative late-stage transformations of the eight-membered lactones further demonstrate the application potential of this synthetic technology., (© 2024. The Author(s).)

The development of facile and convenient atom-economical methods for the preparation of organosulfur compounds from CS 2 is a challenging endeavor. Herein, a one-pot, environmentally friendly method to access S -aryl/alkyl dithiocarbamates has been demonstrated by a three-component coupling involving aryl/alkyl thiols, CS 2 and amines in the presence of a common base K 2 CO 3 . The transformation process can proceed in an H 2 O-DMAc (3 : 1) mixed solvent without requiring any catalysts or extensive prefunctionalization of reactants. The protocol is operationally simple and affords dithiocarbamates with various moieties (including aryl, aliphatic, heteroaryl and alkenyl) in good yields.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis., 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 © 2024 Zhu, Lin, Xie, Wang, Zhang, Xu, Xu and Lv.)

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

Herein, six previously undescribed steroids (1-6), were isolated from leaves and twigs of Aphanamixis polystachya (Wall.) R. N. Parker (Meliaceae). Their structures were elucidated by comprehensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, UV, and IR. Antiviral activity of these compounds were evaluated. Compounds 1-6 showed varying degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M pro ) at 200 μM., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier B.V.)

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination., (© 2024. The Author(s).)

Introduction: Currently, the development of new antiviral drugs against COVID-19 remains of significant importance. In traditional Chinese medicine, the herb Euphorbia fischeriana Steud is often used for antiviral treatment, yet its therapeutic effect against the COVID-19 has been scarcely studied. Therefore, this study focuses on the roots of E. fischeriana Steud, exploring its chemical composition, antiviral activity against COVID-19, and the underlying basis of its antiviral activity., Methods: Isolation and purification of phytochemicals from E. fischeriana Steud. The elucidation of their configurations was achieved through a comprehensive suite of 1D and 2D NMR spectroscopic analyses as well as X-ray diffraction. Performed cytopathic effect assays of SARS-CoV-2 using Vero E6 cells. Used molecular docking to screen for small molecule ligands with binding to SARS-CoV-2 RdRp. Microscale thermophoresis (MST) was used to determine the dissociation constant Kd., Results: Ultimately, nine new ent-atisane-type diterpenoid compounds were isolated from E. fischeriana Steud, named Eupfisenoids A-I (compounds 1-9). The compound of 1 was established as a C-19-degraded ent-atisane-type diterpenoid. During the evaluation of these compounds for their antiviral activity against COVID-19, compound 1 exhibited significant antiviral activity. Furthermore, with the aid of computer virtual screening and microscale thermophoresis (MST) technology, it was found that this compound could directly bind to the RNA-dependent RNA polymerase (RdRp, NSP12) of the COVID-19, a key enzyme in virus replication. This suggests that the compound inhibits virus replication by targeting RdRp., Discussion: Through this research, not only has our understanding of the antiviral components and material basis of E. fischeriana Steud been enriched, but also the potential of atisane-type diterpenoid compounds as antiviral agents against COVID-19 has been discovered. The findings mentioned above will provide valuable insights for the development of drugs against COVID-19., 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 © 2024 Ruan, Xiang, Zhang, Fan, Ren, Zhao, Sun, Wu, Xu, Qiao, Jing, Hao and Chen.)