Search

In the electrocatalytic CO 2 reduction reaction (CO 2 RR), the strategic design of a catalytic well capable of regulating the overall confinement effects of catalytic sites holds significant promise for enhancing multiple-electron transfer and C─C coupling efficiency, particularly for the generation of C 2+ products. Here, a series of Cu-salphen-based covalent organic frameworks (COFs) featuring hydroxyl-induced catalytic well are synthesized, which demonstrate successful application in electrocatalytic CO 2 RR to yield multiple-electron transferred products. The meticulously engineered catalytic well, facilitated by multi-hydroxyl groups, manifests robust confinement effects, facilitating selective adsorption, enrichment, and activation of CO 2 , intermediate stabilization, and reduction of energy barriers for electrocatalytic CO 2 RR. Specifically, product selectivity can be finely tuned from CH 4 to C 2 H 4 by modulating the levels of catalytic well, with CuPc-DFP-4OH-Cu exhibiting the most pronounced catalytic well effect, yielding a high 56.86% faradaic efficiency (FE) for C 2 H 4 at -0.7 V, while CuPc-DFP-Cu, with the weakest catalytic well effect, achieves a 75.24% FE for CH 4 at -1.0 V. Notably, the attained FE for C 2 H 4 (56.86%) surpasses that of all reported COFs to date. Complemented by theoretical calculations and in situ tests, this study delves deeply into the pivotal roles of hydroxyl-induced catalytic well with confinement effects., (© 2024 Wiley‐VCH GmbH.)

Background: A significant research gap exists regarding the role of tissue exosomes in intrauterine adhesions (IUAs). This study aims to investigate the involvement of miR-195-5p and its regulatory network in IUAs through the analysis of tissue exosomes., Methods: Exosomes from rat uterine tissue with intrauterine adhesions were analyzed via transcriptomics to identify downstream target genes of miR-195-5p, cross-referencing with the human endometrial transcriptomics database GSE224093. Dual luciferase labeling confirmed miRNA-target gene interactions. The therapeutic efficacy of a miR-195-5p agonist was assessed in vivo through HE staining, Masson staining, and mating tests. The mechanisms underlying extracellular matrix (ECM) deposition and myofibroblast transdifferentiation in endometrial fibrosis were investigated both in vitro and in vivo using RT-PCR, Western Blot, immunofluorescence, and immunohistochemistry. Migration ability of endometrial stromal cells was evaluated using CCK8, scratch tests, and Transwell assays. Finally, the clinical potential of miR-195-5p was compared with autologous adipose-derived mesenchymal stem cells., Results: The expression of miR-195-5p in uterine tissue exosomes from intrauterine adhesions was found to be decreased. Treatment with a miR-195-5p agonist resulted in improved endometrial health, reduced fibrosis, increased glandular density, and enhanced birth rates in rats. Both in vivo and in vitro experiments confirmed that miR-195-5p decreased ECM deposition, reduced myofibroblast transdifferentiation, and inhibited the migration of endometrial stromal cells. This was achieved through the downregulation of YAP expression in the Hippo pathway and the upregulation of Smad7. Notably, the therapeutic efficacy of miR-195-5p agonists was comparable to that of stem cell therapy, offering promising avenues for clinical application., Conclusions: Differential expression of miR-195-5p in tissue exosomes can reduce ECM deposition and myofibroblast transdifferentiation, improving endometrial fibrosis by regulating the YAP-Smad7 pathway in the Hippo signaling cascade., Competing Interests: Declarations. Ethics approval and consent to participate: This study involves the collection of human endometrium and animal as part of the project titled ‘Study on the mechanism of miR-195-5p improving the epithelial-mesenchymal transformation of endometrial adhesion through YAP-SMAD7, which was approved by the Second Affiliated Hospital of Fujian Medical University Animal Care Committee (Approval No. and Date: 2023-179, May 18, 2023). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Horizontal gene transfer (HGT) mediated diversification is a critical force driving evolutionary and ecological processes. However, how HGT might relate to anthropogenic activity such as nitrogen addition, and its subsequent effect on functional diversity and cooccurrence networks remain unknown. Here we approach this knowledge gap by blending bacterial 16S rRNA gene amplicon and shotgun metagenomes from a platform of cessation of nitrogen additions and continuous nitrogen additions. We found that bacterial HGT events, functional genes, and virus diversities increased whereas bacterial taxonomic diversity decreased by nitrogen additions, resulting in a counterintuitive strong negative association between bacterial taxonomic and functional diversities. Nitrogen additions, especially the ceased one, complexified the cooccurrence network by increasing the contribution of vitamin B12 auxotrophic Acidobacteria, indicating cross-feeding. These findings advance our perceptions of the causes and consequences of the diversification process in community ecology., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In this study, we analyzed the dynamic molecular epidemiology of herpangina based on pharyngeal swabs and demographic data collected from children with herpangina monitored in Tongzhou district in China from January 2021 to December 2022. A total of 1022 herpangina cases were diagnosed. Out of 225 samples collected, 56.4% (127/225) were positive for non-polio enterovirus, with seven genotypes identified: coxsackievirus A4 (CV-A4), CV-A6, CV-A10, CV-A2, CV-A16, CV-B3, and CV-A8. The predominant genotypes associated with herpangina changed during and after the COVID-19 pandemic, with the predominant genotypes being CV-A4 and CV-A6 in 2021 and CV-A10 and CV-A6 in 2022., Competing Interests: Declarations Conflict of interest The authors declare there are no competing interests. Ethical approval All of the participants provided informed consent. The Peking University Institutional Review Board Office granted ethical approval to carry out the study within its facilities (IRB00001052-19005)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Posaconazole enteric-coated tablet and oral suspension are two oral drugs in the treatment of invasive fungal infections (IFIs). This study compared the effectiveness and safety between posaconazole enteric-coated tablet and oral suspension, and provided a real world basis for the clinical practice. A retrospective cohort study was performed on IFIs patients treated with posaconazole enteric-coated tablet or oral suspension. The primary endpoints were in-hospital mortality, treatment discontinuation rate and clinical effective rate. The secondary endpoints were adverse events incidence (liver dysfunction, renal dysfunction and hypokalemia). One hundred and forty-four patients were totally included and divided into enteric-coated tablet group (n = 46) and oral suspension group (n = 98). There was no significant difference in effectiveness and safety between two groups. The female (OR = 0.130, P = 0.018) and diabetes mellitus (OR = 4.242, P = 0.003) were independently associated with combined in-hospital mortality/treatment discontinuation rate. The renal replacement therapy (OR = 10.071, P = 0.006), hypoalbuminemia (OR = 6.646, P = 0.002) and posaconazole duration (OR = 1.119, P = 0.002) were risk factors for liver dysfunction. The posaconazole enteric-coated tablet has comparable effectiveness and safety with oral suspension in IFIs, which need large-scale cases studies to confirm in the future., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The bioaccumulation and trophic transfer of pollutants in marine ecosystem members determine their ultimate ecological risks. Food web bioaccumulation models are widely used in scientific and regulatory programs to assess the bioaccumulation and ecological risks of pollutants at the ecosystem scale. The food web models are mainly established through concentration- and fugacity-based modeling approaches and include some chemical, food web-related, physiological and environmental factors. The models applied in the "forward approach" predict bioaccumulation and conduct internal exposure level-based ecological risk assessment (IEL-ERA), whereas those in the "reverse approach" are used to back-calculate the IEL-based predicted no-effect concentrations (PNECs) or environmental criteria. However, some challenges still exist in the application of food web model integrated risk assessment, including the lack of standardized/generalized frameworks, the lack of chemical- and species-specific toxicokinetic data and internal exposure (or tissue residue)-based toxicity data, and the lack of uncertainty-control methods in model estimation and parameterization. There are urgent requirements to improve models, integrate methods and update study designs in the assessment and prediction of "system-scale risks" of marine emerging organic pollutants., 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.)

Autoimmune diseases are characterized by the body's immune system attacking its own cells, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). In recent studies, regulatory B cells (Bregs), which play a vital role in maintaining peripheral tolerance and controlling persistent autoimmune diseases (ADs), have shown great potential in treating ADs. This review synthesizes the latest advancements in targeted therapies for ADs, with a particular emphasis on the subgroups, phenotypic markers, and signal pathways associated with Bregs. Following an examination of these elements, the discussion pivots to innovative Breg-based therapeutic approaches for the management of ADs., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Differential counting (DC) of different cell types in bone marrow (BM) aspiration smears is crucial for diagnosing hematological diseases. However, a clinically applicable method for automatic DC has yet to be developed., Objective: This study developed and validated an artificial intelligence (AI)-based algorithm for identifying and classifying nucleated cells in BM smears., Methods: In the development phase, a mask region-based convolutional neural network (Mask R-CNN)-based AI model was trained to detect and classify individual BM cells. We used a large data set of expert-annotated images representing a variety of disease categories. The BM slides were stained with Liu's stain or Wright-Giemsa stain. Consensus meetings were held to ensure experts from different institutes applied consistent criteria in classifying cells. Subsequently, the performance of the AI algorithm in identifying cell images and determining cell ratios was evaluated using a multinational clinical dataset., Results: The AI model was trained on 542 slides (85.1 % stained with Liu's stain and 14.9 % with Wright-Giemsa stain) containing 597,222 annotated cells. It achieved an accuracy of 0.94 for the testing dataset containing 26,170 cells. The performance of the AI model was further validated using another multinational real-world dataset (data obtained from three centers in Taiwan and one in the United States) comprising 200,639 cells. The AI model achieved an accuracy of 0.881 in classifying individual cells and demonstrated high precision in classifying blasts (0.927), bands and polymorphonuclear neutrophils (0.955), plasma cells (0.930), and lymphocytes (0.789). When the differential counting percentage of each cell type was assessed, a strong correlation (ρ > 0.8) between the AI and manual methods was observed for most cell categories., Conclusions: In this study, an AI algorithm was developed and clinically validated using large, multinational datasets. Our algorithm can locate and classify BM cells simultaneously and has potential clinical applicability for automating BM differential counting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NTUH and aetherAI Co., Ltd. own the intellectual property and possible commercial profit of the AI-based product derived from this study. Authors who are employees of the manufacturer of the AI-based product (aetherAI Co., Ltd.) contributed to study design, data annotation, software development, and website development for annotation, AI model development, clinical research, manuscript writing, manuscript review, and manuscript editing., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus , can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout., Competing Interests: YF, XL, JL, QM, XW, YZ, YZ, HL, DX, WM, JC, LW, QD, LB, MK, KM, ZL, HY, QC, YZ, LY, QT, WW No competing interests declared, XJ, JC Affiliated with Biotech Co. Ltd; the author has no financial interests to declare, PZ Affiliated with Chimelong Group Co; the author has no financial interests to declare, (© 2024, Fu et al.)

Background: The persistently rising complication, pseudotumor, after hip arthroplasty required surgeons' vigilance. Although the remaining controversial relationship between metal ions and pseudotumor, metal ion detection had been widely employed in clinic. The aim of this study is to evaluate the correlation between metal ions and pseudotumor, as well as the effectiveness of metal ion analysis in the screening and diagnosis of pseudotumor through systematic review and meta-analysis., Methods: The Medline and Embase databases were searched for studies evaluating metal ions and patients with pseudotumors after hip arthroplasty. A systematic review of risk ratio and diagnostic performance for metal ions was conducted., Results: Seven studies were included in the systematic review. The mean Methodological Index for Non-Randomized Studies (MINORS) score of the included studies was 19 (range, 14 to 22). Pooled risk ratio (RR) value was 2.01(95% CI: 1.25-3.24; P = 0.004) for cobalt ions level and 1.44 (95% CI: 1.10-1.88; P = 0.008) for chromium ions level. The pooled sensitivity, specificity and the area under the curve (AUC) for cobalt and chromium ions were determined to be 0.59, 0.82, 0.73 and 0.34, 0.82, 0.56, respectively., Conclusions: The metal ions level has a low diagnostic value. It is of certain value for confirmation, but should not be used as a routine screening indicator. The diagnostic value of cobalt ions is higher than that of chromium., Level of Evidence: Diagnostic Level IV., (© 2024. The Author(s).)

A novel actinomycete, designated strain ZYX-F-249 T , was isolated from the gill of a leopard coral grouper in Yongxing Island, Hainan Province, China. Based on 16S rRNA gene sequence analysis, strain ZYX-F-249 T belonged to the genus Microbispora , with high similarities to Microbispora rosea ATCC 12950 T (98.7 %), Microbispora hainanensis 211020 T (98.5 %), Microbispora clausenae CLES2 T (98.4 %), Microbispora bryophytorum NEAU-TX2-2 T (98.1 %) and Microbispora oryzae RL4-1S T (98.0 %). Phylogenetic analysis of the 16S rRNA gene sequence of strain ZYX-F-249 T showed that the strain formed a stable subclade with Microbispora rosea ATCC 12950 T in the genus Microbispora . The cell wall of the novel isolate contained meso -diaminopimelic acid, while whole-cell sugars were madurose, glucose and ribose. The predominant menaquinones were MK-9(H 6 ), MK-9(H 4 ), MK-9(H 2 ) and MK-9(H 0 ). The characteristic phospholipids (PLs) were phosphatidylethanolamine, phosphatidylinositol, diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylinositol mannoside, glycophospholipids and an unknown PL. The major cellular fatty acids (>10%) were iso -C 16 : 0 and iso -C 18 : 0 . Genome sequencing showed a DNA G+C content of 71.6%. The low average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values demonstrated that strain ZYX-F-249 T could be readily distinguished from closely related species. Based on data from these phylogenetic, chemotaxonomic and physiological characteristics, strain ZYX-F-249 T represents a novel species of the genus Microbispora , for which the name Microbispora maris sp. nov. is proposed. The type strain is ZYX-F-249 T (=CCTCC AA 2023030 T =JCM 36778 T ).

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nanocluster catalysts typically face challenges in balancing stability with catalytic efficiency. This study introduces a unique bismuth-oxo cluster, solely protected by two ring-opened calixarenes, which demonstrates not only enhanced structural stability but also superior catalytic performance in the sustained conversion of CO 2 to HCOOH via electrocatalysis. For the first time, we reveal that under specific solvothermal conditions, tert -butylcalix[8]arene (TBC[8]) can undergo in situ oxidative cleavage of its C-C bond, leading to ring-opened polyphenolic molecules. These molecules serve as protective ligands for the bismuth-oxo cluster, bestowing exceptional structural stability and offering a more flexible and diverse configuration compared to intact TBC[8]. This adaptability promotes the exposure of active bismuth sites on the cluster surface, enhancing catalytic efficiency. Notably, the Bi 10 cluster, featuring a monobismuth active site, achieves an exceptional formate production efficiency of 98.79% at -1.25 V vs RHE while maintaining superb durability over 8 h. The stability and catalytic processes of Bi 10 surpass those of the Bi 13 cluster, which is structurally reinforced by two intact TBC[8] molecules and stabilized by four benzoic ligands. Through in situ infrared spectroscopy and density functional theory calculations, we demonstrate that the monobismuth active site in Bi 10 more effectively stabilizes the *OCHO intermediate, thereby promoting the electrocatalytic reduction of CO 2 to HCOOH compared to Bi 13 . This comparative performance underscores the potential of ring-opened calixarene ligands in enhancing the functionality of nanocluster catalysts.

Introduction: This study aims to establish, execute, and assess the effectiveness of a perioperative enhanced recovery after surgery (ERAS) clinical care pathway in breast reconstruction patients with LD flap breast cancer treatment. The goal is to improve early recovery outcomes, reduce hospitalization time, and enhance patient satisfaction by implementing a standardized approach to postoperative care., Methods: This study was conducted at the University of Malaya Medical Center. The outcomes of 21 breast cancer patients who underwent autologous reconstructive breast surgery with the latissimus dorsi (LD) flap within six months before the implementation of the ERAS pathway (pre-ERAS) were compared with 26 patients who underwent the same surgery with the ultrasound-guided erector spinae plane (ESP) block for the (ERAS protocol implementation) cohort. The study was conducted from November 2019 to October 2020. The length of hospital stay, amount of analgesic usage, and incidence of postoperative nausea vomiting (PONV) were recorded., Results: The implementation of the ERAS clinical care pathway resulted in shorter hospital stays compared with the preceding care. On average, ERAS patients were mostly discharged on Day 2 post-surgery, whereas pre-ERAS patients were mostly discharged on Day 7. ERAS patients had a lower incidence of PONV from Days 1 to 5, starting with 88.5% not experiencing the condition on Days 1 and 2 and increasing to 100% on Day 5. All pre-ERAS patients experienced PONV in the first 5 days post-surgery. Fewer ERAS patients required antiemetics post-surgery (88.5%) compared with pre-ERAS patients (42.9%)., Conclusion: The implementation of the ERAS protocol as part of clinical care in autologous reconstructive breast surgery with the LD flap can improve recovery by shortening hospital stay, decreasing the use of analgesia, and alleviating PONV., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Four new isocoumarin derivatives 12-O-acetyl-isocitreoisocoumarinol (1), (+)-(10R)-O-acetyl-diaportinol (2-a), (-)-(10S)-O-acetyl-diaportinol (2-b), peyroisocoumarin E (3) and new stereoconfigurations of three isocoumarin derivatives desmethyldichlorodiaportinol A (4), threo-monochlorodiaportinol A (5-a), erytheo-monochlorodiaportinol A (5-b), together with nine known ones (6-14), were separated from the rice fermentation of endophytic fungus Diaporthe arengae M2 isolated from Camellia oleifera. The structures of new compounds were determined by extensive spectroscopic analyses including nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Compounds 4, 7, 8, 12, 13 exhibited definite inhibition against five strains of bacteria with the MIC values range from 16 μg/mL to 64 μg/mL., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: The aim of this study was to evaluate the impact of health Qigong on vascular elasticity, blood lipid levels, and cardiac function in middle-aged and elderly women. By comparing various indicators preintervention and postintervention, the research provides valuable insights into the effectiveness of health Qigong in enhancing cardiovascular health within this demographic., Methods: A total of 40 middle-aged and elderly women were randomly assigned to 2 groups. The experimental group, consisting of 20 women, practiced health Qigong combined with Tibetan dance for 12 weeks, 3 times per week, with each session lasting 60 minutes. The control group, also consisting of 20 women, continued their regular routines without any exercise intervention. Cardiovascular function metrics were subsequently compared between the 2 groups., Results: (1) Pulse wave velocity: in the experimental group, significant improvements were observed, particularly in the right ankle (P =.02 for left ankle, P =.00 for right ankle). The control group showed no significant differences (P =.08 for both ankles); (2) blood lipid levels: the experimental group demonstrated significant reductions in total cholesterol and triglyceride levels (P =.00 for both), while the control group showed no significant changes (P =.59 for total cholesterol, P =.71 for triglycerides). There were significant differences in high-density lipoprotein levels between the experimental and control groups (P =.00 and .01, respectively); (3) cardiac function: significant improvements were noted in cardiac output (Teich) and stroke volume (Teich) in the experimental group (P =.00 for both), while the control group showed no significant differences (P =.71 for cardiac output, P =.06 for stroke volume)., Conclusion: Health Qigong, integrated with dance exercise effectively enhances pulse wave velocity, blood lipid levels, and cardiac function in middle-aged and elderly women. These findings suggest that incorporating such exercises may contribute to the prevention or delay of atherosclerosis and cardiovascular disease in this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This review explores calixarenes, a prominent family of third-generation supramolecules celebrated for their distinct hollow, cavity-shaped structures. These macrocycles are intricately assembled by linking multiple phenolic units orthogonally through methylene (-CH 2 -), sulfur (-S-), or sulfonyl (-SO 2 -) bridges. This structural framework plays a pivotal role in the intricate assembly of nanoclusters, significantly advancing the field of cluster chemistry. A key focus of current research is the remarkable ability of calixarenes to stabilize titanium-oxo clusters. Our review details the application of calixarenes in constructing titanium-oxo cluster structures, emphasizing how these clusters, when encapsulated within calixarenes, exploit flexible coordination sites for structural modifications and serve as foundational units for more complex assemblies. Additionally, we investigate how these calixarene-stabilized metal-oxo clusters function as versatile scaffolds for catalytically active metal ions, facilitating the creation of bimetallic nanoclusters. These clusters not only exhibit unique structural diversity but also demonstrate exceptional catalytic efficiency. This review aims to inspire ongoing exploration and innovation in the use of calixarenes for the synthesis and application of advanced cluster materials.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition., (© 2024. The Author(s).)

Background: Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP)., Methods: This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used., Results: Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P < 0.0001; [OR] = 1.090; 95% [CI]: 1.037, 1.146; P = 0.0007; [OR] = 1.802; 95% [CI]: 1.240, 2.618; P = 0.0020). The nonlinear association between LAP and DR was further illustrated using an S-shaped curve by smoothing curve fitting, with the inflection point of the curve located at 63.4. Subgroup analyses and interaction tests were performed with full variable adjustment (P > 0.05 for all interactions)., Conclusion: Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR., (© 2024. The Author(s).)

Accurately identifying the metal doping effects within heterogeneous catalysts presents a formidable challenge due to the complex nature of controlling the interfacial chemistry at the molecular level. Herein, we use two sets of atomically precise nanoclusters to demonstrate the impact of Sb doping on the electrocatalytic CO 2 reduction activity in Ag nanoclusters. Leveraging the unique properties of the thiacalix[4]arene, we have pioneered a methodology for incorporating catalytic Ag 1+ and Sb 3+ sites, culminating in the synthesis of the pioneering Sb-Ag bimetallic cluster, Sb 2 Ag 11 . We refined this structure by replacing the two Sb 3+ sites with Na + sites, resulting in a Na 2 Ag 10 cluster. Broadening our investigative scope, we isolated the core components from both Sb 2 Ag 11 and Na 2 Ag 10 and obtained two clusters: Sb 2 Ag 4 and Ag 4 . The subtle compositional variations between two pairs of structurally analogous clusters, Sb 2 Ag 11 and Na 2 Ag 10 , as well as Sb 2 Ag 4 and Ag 4 , create opportunities to investigate how the Sb doping impacts the catalytic activity of Ag clusters. Clearly, compared to the undoped clusters, those doped with Sb exhibit higher catalytic current densities and enhanced CO selectivity. The theoretical calculations suggest that Sb doping can enhance the adsorption barrier of *H, thereby inhibiting hydrogen evolution activity and conversely promoting eCO 2 RR to CO activity.

Rapid and continuous droplet shedding is crucial for many applications, including thermal management, water harvesting, and microfluidics, among others. Superhydrophobic surfaces, though effective, suffer from droplet pinning at high subcooling temperature ( T sub ). Conversely, slippery liquid-like surfaces covalently bonded with flexible hydrophobic molecules show high stability and low droplet adhesion attributed to their dense and ultrasmooth water repellent polymer chains, enhancing dropwise condensation and rapid shedding. In this work, linear poly(dimethylsiloxane) chains of various viscosities are covalently bonded onto silicon substrates to form thin and smooth monolayer coated surfaces. The formation of the monolayer is characterized by cryogenic transmission electron microscopy. On these surfaces a very low contact angle hysteresis is reported within wide surface temperature ranges as well as continuous dropwise condensation at ultrahigh T sub of 60 K. In particular, one of the highest condensation heat fluxes of 1392.60 kW·m -2 and a heat transfer coefficient of 23.21 kW·m -2 ·K -1 at ultrahigh T sub of 60 K is reported. The experimental heat transfer performance is further compared to the theoretical heat transfer via the individual droplets with the droplet distribution elucidated via both macroscopic observations as well as environmental scanning electron microscopy. Finally, only a mild decrease in the heat transfer coefficient of 20.3% after 100 h of condensation test at T sub of 60 K is reported. Slippery liquid-like surfaces promote droplet shedding and sustain dropwise condensation at high T sub without flooding empowered by the lower frictional forces, addressing challenges in heat transfer performance and durability.

Background: Ankylosing spondylitis (AS) is a connective tissue disease that primarily affects spinal joints, peripheral joints, and paravertebral soft tissues, leading to joint stiffness and spinal deformity. Growing evidence has implicated gut microbiota in the regulation of AS, though the underlying mechanisms remain poorly understood., Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, China Science and Technology Journal Database (VIP), and China National Knowledge Internet (CNKI) databases from the time the databases were created until 30 July 2023. To evaluate changes in α-diversity and the abundance of certain microbiota families in AS, standardized mean difference (SMD) and 95% confidence interval (CI) calculations were made. Meta-analyses were performed using STATA 12.0 and the quality of the literature was assessed by following systematic review guidelines., Results: This systematic review and meta-analysis included 47 studies, providing insights into the gut microbiota composition in patients with AS compared to healthy controls (HCs). Our findings indicate a significant reduction in gut microbial diversity in patients with AS, as evidenced by a decrease in both richness and evenness. Specifically, the Shannon index showed a moderate decrease (SMD = -0.27, 95% CI: -0.49, -0.04; P < 0.001), suggesting a less diverse microbial ecosystem in patients with AS. The Chao1 index further confirmed this trend, with a larger effect size (SMD = -0.44, 95% CI: -0.80, -0.07; P < 0.001), indicating a lower species richness. The Simpson index also reflected a significant reduction in evenness (SMD = -0.30, 95% CI: -0.53, -0.06; P < 0.001). Additionally, patients with AS who received anti-rheumatic combination treatment exhibited a more pronounced reduction in α-diversity compared to untreated patients, highlighting the potential impact of this treatment on gut microbiota balance. In terms of specific microbial families, we observed a significant decrease in the abundance of Bifidobacterium (SMD = -0.42, 95% CI: -2.37, 1.52; P < 0.001), which is known for its beneficial effects on gut health. Conversely, an increase in the abundance of Bacteroidetes was noted (SMD = 0.42, 95% CI: -0.93, 1.76; P < 0.001), suggesting a possible shift in the gut microbiota composition that may be associated with AS pathophysiology., Conclusion: Our analysis revealed changes in α-diversity and the relative abundance of specific bacteria in AS. This suggests that targeting the gut microbiota could provide new therapeutic opportunities for treating AS., Systematic Review Registration: https://www.crd.york.ac.uk./PROSPERO/, identifier CRD42023450028., 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 Su, Zhang, Qiao, Song, Shi, Wang, Wang and Zhang.)

Objective: This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma (DLBCL), a common and heterogeneous malignancy of the adult lymphohematopoietic system. Given the limitations of current therapies, there is a pressing need to develop new and effective drugs for DLBCL treatment., Methods: A series of pyrrolidone derivatives were synthesized, and their antitumor activities were assessed, particularly against DLBCL cell lines. Structure-activity relationship (SAR) analysis was conducted to identify key structural components essential for activity. The most promising compound, referred to as compound 7, was selected for further mechanistic studies. The expression levels of relevant mRNA and protein were detected by RT-qPCR and Western blotting, and the expression of mitochondrial membrane potential and ROS was detected using flow cytometry for further assessment of cell cycle arrest and apoptosis., Results: The compound 7 exhibited good antitumor activity among the synthesized derivatives, specifically in DLBCL cell lines. SAR analysis highlighted the critical role of α, β-unsaturated ketones in the antitumor efficacy of these compounds. Mechanistically, compound 7 was found to induce significant DNA damage, trigger an inflammatory response, cause mitochondrial dysfunction, and disrupt cell cycle progression, ultimately leading to apoptosis of DLBCL cells., Conclusion: The compound 7 has good antitumor activity and can induce multiple cellular mechanisms leading to cancer cell death. These findings warrant further investigation of the compound 7 as a potential therapeutic agent for DLBCL., (© 2024. Huazhong University of Science and Technology.)

Introduction: Psoriatic arthritis (PsA) is a debilitating chronic condition characterized by inflammation of the joints, bones, enthesis, and skin. The pivotal role of interleukin-23 (IL-23) in the pathogenesis of PsA has become increasingly evident. This proinflammatory cytokine is markedly elevated in patients with PsA, suggesting its potential as a therapeutic target. Consequently, IL-23 inhibitors have emerged as promising first-line biologic treatments for PsA., Areas Covered: This review delves into the immunopathogenic mechanisms of IL-23 at the cellular and molecular levels in PsA. Furthermore, it provides the recent efficacy and safety profiles of IL-23 inhibitors. We conducted a literature search in PubMed for the following terms: 'IL-23 and psoriatic arthritis,' 'Ustekinumab,' 'Guselkumab,' 'Risankizumab,' and 'Tildrakizumab.' In addition, we retrieved clinical trials involving IL-23 inhibitors registered in ClinicalTrials.gov, EudraCT, and ICTRP., Expert Opinion: Despite the promising outcomes observed with IL-23 inhibitors, several challenges persist. The long-term effects of these agents require further investigation through prospective studies, and their limited accessibility worldwide necessitates urgent attention. Additionally, ongoing research is warranted to explore other potential drug targets within the IL-23/IL-23 R axis. The development of reliable biomarkers could greatly enhance early detection, tailored management strategies, and personalized treatment approaches for patients with PsA.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Various genetic and epigenetic changes associated with genomic instability (GI), including DNA damage repair defects, chromosomal instability, and mitochondrial GI, contribute to development and progression of cancer. These alterations not only result in DNA leakage into the cytoplasm, either directly or through micronuclei, but also trigger downstream inflammatory signals, such as the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Apart from directly inducing DNA damage to eliminate cancer cells, radiotherapy (RT) exerts its antitumor effects through intracellular DNA damage sensing mechanisms, leading to the activation of downstream inflammatory signaling pathways. This not only enables local tumor control but also reshapes the immune microenvironment, triggering systemic immune responses. The combination of RT and immunotherapy has emerged as a promising approach to increase the probability of abscopal effects, where distant tumors respond to treatment due to the systemic immunomodulatory effects. This review emphasizes the importance of GI in cancer biology and elucidates the mechanisms by which RT induces GI remodeling of the immune microenvironment. By elucidating the mechanisms of GI and RT-induced immune responses, we aim to emphasize the crucial importance of this approach in modern oncology. Understanding the impact of GI on tumor biological behavior and therapeutic response, as well as the possibility of activating systemic anti-tumor immunity through RT, will pave the way for the development of new treatment strategies and improve prognosis for patients., 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.)

Objective: To explore the clinicopathological features and prognosis of TFE3-rearranged renal cell carcinomas (TFE3-rRCC)., Methods: In this retrospective observational study, the data of patients with TFE3-rRCC admitted to Xijing Hospital from January 2010 to October 2023 were collected, encompassing the general information, pathological diagnosis, immunohistochemistry, and the results of FISH detection. The treatment information and survival data of the patients were recorded during the follow-up., Results: A total of 55 patients with TFE3-rRCC were enrolled, among whom 25 were males and 30 were females. TFE3 FISH assay suggested the disruption of the TFE3 gene. Fifty-four patients underwent surgical resection of kidney lesions, while 1 patient did not. By the end of follow-up in December 2023, 3 patients were lost to follow-up, 28 patients remained alive, and 24 patients had died. Among the 52 patients followed up, 31 developed metastases, involving lymph nodes, liver, bone, lung, peritoneum, pleura, adrenal gland, and brain. The 1-year and 5-year survival rates of the patients were 84.6% and 50.6%, respectively. In this study, there were 31 patients with TFE3-rRCC recurrence or metastasis. Median PFS was 7 and 13 months in the VEGFR-TKI and VEGFR-TKI+ ICI groups, respectively. The median OS was 12 months in the VEGFR-TKI treatment group. The median OS data of VEGFR-TKI+ ICI group has not been reached. The ORR and DCR was 25%, 66.7% in the VEGFR-TKI group. The ORR and DCR was 33.3%, 77.8% in the VEGFR-TKI+ ICI group., Conclusion: TFE3-rRCC is a rare subtype of malignant renal tumor. The diagnosis mainly relies on pathological morphology, immunohistochemistry, and the detection of TFE3 gene disruption by FISH. In terms of treatment, surgery is the primary approach, and lymph nodes, liver, and bone are the main metastatic sites. VEGFR-TKI+ICI treatment might be an option of recurrent or metastatic TFE3-rRCC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hydrogen sulfide (H 2 S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H 2 S alleviates skeletal muscle ageing by regulating autophagy has not been reported., Methods: Mice were administered 150 mg/kg/day of D-galactose (D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H 2 S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot., Results: NaHS was found to effectively restore the H 2 S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the β-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1., Conclusions: H 2 S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Infectious diseases persistently pose global threats, and it is imperative to accelerate the professionalization of public health workforce. This study aimed to develop and validate the infectious disease control competency scale (IDCCS) for public health professionals to fill a theoretical gap and elevate practical capabilities by informing public health professionals' development goals., Methods: The initial item pool was generated through a literature review, and categorized into three dimensions (knowledge, practical skills, and leadership) based on the competency iceberg model and public health leadership framework. A two-round Delphi process was conducted to determine indicators within the scale. A pilot survey was utilized for item analysis and exploratory factor analysis (EFA). A formal survey was employed for confirmatory factor analysis (CFA). The weight value of each indicator was calculated using the analytic hierarchy process., Results: An initial scale with three primary items, 14 secondary items, and 81 tertiary items was generated. Twenty experts participated in the two rounds of the Delphi process. Authority coefficients exceeded 0.9 in both rounds. Kendall's W was 0.29 and 0.19, respectively (both P < 0.001). Item analysis presented a Cronbach's Alpha of 0.98, with corrected item-total correlation coefficients ranging from 0.33 to 0.78. EFA demonstrated that cumulative variance explanations for the four primary dimensions (knowledge, practical skills, leadership, and personal quality) were 77.463%, 73.976%, 81.174%, and 68.654%, respectively. CFA indicated that all composite reliability values and average variance extracted surpassed 0.8 and 0.5, respectively. The standardized factor loadings of the items ranged from 0.630 to 0.977. Among the seven model fit indices, each of the four dimensions satisfied at least five criteria. A final three-level scale comprising four primary items, 14 secondary items, and 64 tertiary items was constructed. The weight values for the four primary items were 0.4064, 0.2878, 0.2082, and 0.0981, respectively., Conclusions: The IDCCS was established to evaluate the competencies of knowledge, practical skills, leadership, and personal quality for public health professionals in infectious disease control. This scale demonstrates good reliability and validity, and can be used for performance evaluation, recruitment processes, curriculum development, and individual self-assessment., (© 2024. The Author(s).)

Acute promyelocytic leukemia (APL) is marked by a block at the promyelocyte stage. Treatments like ATRA and ATO face resistance and relapse issues. Plastrum testudinis , a traditional Chinese medicine, may offer therapeutic potential. This study investigated xtr-miR-22-3p from P. testudinis for treating APL. High expression of xtr-miR-22-3p was confirmed, with target prediction indicating interactions with key genes, including PML. xtr-miR-22-3p reduced HL-60 leukemia cell growth, altered the cell cycle, and selectively inhibited HL-60 proliferation while promoting BMSC growth, suggesting its potential as a targeted APL therapy.

Background: Gliomas are the most common primary central nervous system neoplasm. Despite recent advances in the diagnosis and treatment of gliomas, patient prognosis remains dismal. Therefore, it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes., Aim: To investigate the association between oligodendrocyte transcription factor 2 (Olig2) expression and the outcomes of glioma patients., Methods: The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were searched for studies (published up to October 2023) that investigated the relationship between Olig2 expression and prognosis of glioma patients. The quality of the studies was assessed using the Newcastle Ottawa Scale. Data analyses were performed using Stata Version 12.0 software., Results: A total of 1205 glioma patients from six studies were included in the meta-analysis. High Olig2 expression was associated with better outcomes in glioma patients [hazard ratio (HR): 0.81; 95% (confidence interval) CI: 0.51-1.27; P = 0.000]. Furthermore, the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients (HR: 1.34; 95%CI: 0.79-2.27) and better prognosis in Asian patients (HR: 0.43; 95%CI: 0.22-0.84). The sensitivity analysis showed that no single study had a significant effect on pooled HR, and there was also no indication of publication bias according to the Egger's and Begger's P value test or funnel plot test., Conclusion: High Olig2 expression may have a positive impact on the prognosis of glioma patients, and should be investigated further as a prognostic biomarker and therapeutic target for glioma., Competing Interests: Conflict-of-interest statement: The authors deny any conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pyrrolocarbazole skeletons are well known to possess a variety of biological activities that might be therapeutically useful in the treatment of cancers. Herein, an acid-catalyzed stereoselective hydroarylation/Diels-Alder cycloaddition/aromatization of ynamide-indoles is described. We newly designed and synthesized a variety of piperazine-fused pyrrolocarbazole derivatives that could be further applied to the synthesis of potent Wee1 inhibitors.

A new steroid named persteroid ( 1 ) and seven known compounds ( 2 - 8 ) were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. The structure of 1 was determined by HRESIMS, NMR, and ECD calculations. Compound 1 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 46.31 ± 0.52 μM. Moreover, compound 1 potently suppressed nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The cytotoxicity and antibacterial activity of all isolates were tested.

Two new indole-diterpenoids, penpaxilloids F and G (1 and 2), along with 11 known analogues (3-13), were isolated from the marine fungus Penicillium sp. ZYX-Z-718. The structures of the new compounds were identified by extensive spectroscopic analyses including HR-ESI-MS, UV, and NMR, as well as theoretical NMR chemical shifts and ECD calculations. Compounds 6 and 10 showed antibacterial activity against Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, and MRSA with MIC values ranging from 16.0-32.0 μg/mL., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120 minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the "Dazhui" (DU20), "Baihui" (DU26) and "Renzhong" (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72 hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1β, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypothesis: Despite its importance in colloid and interface science, contact line pinning remains poorly understood, especially in the presence of a precursor film. We hypothesized that this is due to a lack of an experimental method capable of directly observing their physics at the nanoscale., Methods: Using coherence scanning interferometry, we visualized the three-dimensional behavior of contact lines with a precursor film near a nanogroove structure composed of flat terrace surfaces and steps with an inclination angle of 30° while achieving nanoscale vertical resolution., Findings: We found that even when the contact line is pinned at the edge of the step, the precursor film is not and advances beyond the edge. Furthermore, we discovered that the precursor film has two distinct effects on contact line motion. Specifically, the precursor film facilitates depinning when the contact line descends the step - a contact angle change was 0.9°, only 3.0% of the value predicted by a classical theory of contact angle at a solid edge. This ultra-early depinning is attributed to the formation of a new liquid film past the edge, driven by the progression of the precursor film that overcomes the pinning effect. In contrast, when the contact line ascends the step, the precursor film acts as a resistance to movement due to steric interaction., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

To explore impact of the propensity to coronavirus disease 2019 (COVID-19) vaccine/vaccination on influenza vaccination from willingness to behavior after COVID-19 pandemic among older adults in rural China. A combined study involving a cross-sectional survey for the willingness of influenza vaccination, a health education momentary intervention and a community intervention program were conducted from September 11 th to 16 th , 2023 among rural older adults in China. Totally 3138 individuals were investigated in this study with 1923 (61.3%) willing to receive influenza vaccination. After the momentary intervention, 47.8% (582/1215) individuals changed to be willing to receive influenza vaccination. There were 1440 (78.8%) vaccinated. The influenza vaccination willingness rate was significantly higher in the participants willing to receive COVID-19 vaccine booster dose vaccination than the participants unwilling to (69.4% vs . 37.7%, adjusted OR [aOR] = 2.671, 95% CI 2.211-3.227, p  < .001), as well as for the influenza vaccination willingness change rate (52.2% vs . 41.7%, aOR = 1.303, 95% CI 1.022-1.662, p  < .05) and the influenza vaccination behavior rate (79.7% vs . 74.9%, aOR = 1.337, 95% CI 1.002-1.784, p  < .05). The influenza vaccination behavior rate was significantly higher in those positive toward COVID-19 vaccine effectiveness or safety overall (80.0% vs . 74.9%, aOR = 1.394, 95% CI 1.065-1.823; 80.6% vs . 70.9%, aOR = 1.850, 95% CI 1.395-2.454; both p  < .05). There was a positive impact of COVID-19 vaccine/vaccination on influenza vaccination from willingness to behavior among the older adults in rural China after COVID-19 pandemic, suggesting that integrating health education of related pathogens and vaccines might promote influenza vaccination.

Objective: Previous neuroimaging studies have identified significant alterations in brain functional activity in retinal detachment (RD) patients, these investigations predominantly concentrated on local functional activity changes. The potential directional alterations in functional connectivity within the primary visual cortex (V1) in RD patients remain to be elucidated., Methods: In this study, we employed seed-based functional connectivity analysis along with Granger causality analysis to examine the directional alterations in dynamic functional connectivity (dFC) within the V1 region of patients diagnosed with RD. Finally, a support vector machine algorithm was utilized to classify patients with RD and healthy controls (HCs)., Results: RD patients exhibited heightened dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) between the Visual Network (VN) and default mode network (DMN), as well as within the VN, compared to HCs. Conversely, dFC between VN and auditory network (AN) decreased, and dEC between VN and sensorimotor network (SMN) significantly reduced. In state 4, RD patients had higher frequency. Notably, variations in dFC originating from the left V1 region proved diagnostically effective, achieving an AUC of 0.786., Conclusion: This study reveals significant alterations in the connectivity between the VN and the default mode network in patients with RD. These changes may disrupt visual information processing and higher cognitive integration in RD patients. Additionally, alterations in the left V1 region and whole-brain dFC show promising potential in aiding the diagnosis of RD. These findings offer valuable insights into the neural mechanisms underlying visual and cognitive impairments associated with RD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To assess the global and regional burden of hip fractures associated with type 1 diabetes (T1D) from 1990 to 2021., Materials and Methods: The population attributable fraction was calculated by combining the published risk ratio with T1D prevalence (age ≥ 20 years) from the Global Burden of Disease study to estimate the T1D-associated hip-fracture burden. Trends were assessed using the age-standardized incidence rate (ASIR) and estimated annual percentage change (EAPC)., Results: The global incidence of T1D-related hip fractures was 290 180 in 2021 with an ASIR of 3.96 (95% confidence interval: 1.92-5.87) per 100 000 population and a male-to-female ratio of 0.54. At the super-regional level, the highest incidence (204 610) and ASIR (13.09 per 100 000 population; 6.40-25.53) were observed in high-income regions, in particular in Australasia and Western Europe. Notably, Australasia exhibited the highest EAPC, 2.90% in T1D-associated ASIR, followed by East Asia (2.73%). The incidence among those aged 45-64 years grew significantly in 14 regions over the past decade. Nationally, the ASIR increased in 166 countries from 1990 to 2021., Conclusions: High-income regions experienced the greatest burden of T1D-associated hip fracture, while Australasia and East Asia witnessed the largest increase over the last 32 years. Prioritizing the promotion of T1D treatment and hip-fracture screening for middle-aged females living with T1D is crucial in these regions., (© 2024 John Wiley & Sons Ltd.)

Delta like non-canonical Notch ligand 1 (DLK1), as a member of epidermal growth factor-like family, plays a critical role in somatic growth, tissue development and possibly tissue renewal. Though previous studies had indicated that DLK1 contributed to adipogenesis and myogenesis, it's still controversial whether DLK1 affects angiogenesis and how it interacts with Notch signaling with numerous conflicting reports from different models. Based on our preliminary finding that DLK1 expression was up-regulated in mice ischemic gastrocnemius and in the border zone of infarcted myocardium, we administered either recombinant DLK1 (rDLK1) or PBS in C57BL/6 mice after establishment of hindlimb ischemia (HLI) and myocardial infarction (MI), respectively. Exogenous rDLK1 administration significantly improved both blood perfusion of mice ischemic hindlimbs and muscle motor function on the 3rd, 7th day after HLI, by promoting neovascularization. Similar effect on neovascularization was verified in mice on the 28th day after MI as well as improvement of cardiac failure. Correspondingly, the number of CD34 + KDR + cells, indicated as endothelial progenitor cells (EPCs), was significantly in mice ischemic gastrocnemius by rDLK1 administration, which was abrogated by DAPT as the specific inhibitor of Notch intracellular domain (NICD). Furthermore, bone marrow mononuclear cells were obtained from C57BL/6 mice and differentiated to EPCs ex vivo. Incubation with rDLK1 triggered Notch1 mRNA and NICD protein expressions in EPCs as exposed to hypoxia and serum deprivation, promoting EPCs proliferation, migration, anti-apoptosis and tube formation. Otherwise, rDLK1 incubation significantly decreased intracellular and mitochondrial reactive oxygen species, increased ATP content and mitochondrial membrane potential, downregulated short isoform of OPA-1 expression whereas upregulated mitofusin (-1, -2) expression in EPCs by Notch1 signaling, which were all abrogated by DAPT. In summary, the present study unveils the pro-angiogenesis and its mechanism of rDLK1 through activation of Notch1 signaling in endothelial progenitor cells., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: The use of clinical samples was approved by the Institutional Ethics Committee of Second Affiliated Hospital of Zhejiang University. All animal experiments were approved by Zhejiang University Institutional Animal Care and Use Committee (approval No. 2023-1969). All methods and experimental protocols were carried out in accordance with the guidelines and regulations of the Care and Use of Laboratory Animals of Zhejiang University., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed., Methods: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed., Results: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability., Conclusions: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS., Competing Interests: Declarations. Ethical approval: This study was approved by the Ethics Committee of Fudan university Zhongshan Hospital (approval number: B2022-506). Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Few studies focused on human papillomavirus (HPV) in male patients. This study aimed to explore the detection rate and genotyping of HPV among male patients in Beijing to provide a reference for formulating prevention strategies for HPV infection. The cross-sectional study was conducted in Beijing Chaoyang Hospital from November 2015 to March 2023. It covered male patients from the urology and dermatology departments. Fifteen high-risk HPV genotypes were detected by the multiplex real-time polymerase chain reaction method. The overall detection rate of HPV was 25.19% (1288/5114, 95% confidence interval [CI] 24.00%-26.38%), of which the single infection rate was 16.99% (869/5114, 95% CI 15.97%-18.05%) and the co-infection rate was 8.19% (419/5114, 95% CI 7.46%-8.98%). The detection rate of HPV was 40.77% (521/1278), 35.58% (58/163), 32.69% (101/309), 31.91% (60/188), 12.63% (299/2367), and 32.35% (131/405) among male patients with balanitis, warts, rash, urethritis, prostatitis, and other urinary inflammation, respectively ( P  < 0.001). The top five HPV genotypes were HPV-52, HPV-58, HPV-16, HPV-51, and HPV-66. After the first positive HPV test, the proportion of male patients who turned negative was 22.47% within 3 months, 26.40% within 3-6 months, 24.72% within 6-12 months, 17.98% within 12-24 months, and 8.43% more than 24 months. The detection rate of HPV was high among male patients from the urology and dermatology departments in Beijing, which should be considered to develop HPV vaccines with better prevention effects.

To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60-90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30-60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively., (© 2024. The Author(s).)

Background: The incidence of adenocarcinoma of the esophagogastric junction (AEJ) is increasing, and with poor prognosis. Lymph node status (LNs) is particularly important for planning treatment and evaluating the prognosis of patients with AEJ. However, the use of radiomic based on enhanced computed tomography (CT) to predict the preoperative lymph node metastasis (PLNM) status of the AEJ has yet to be reported., Purpose: We sought to investigate the value of radiomic features based on enhanced CT in the accurate prediction of PLNM in patients with AEJ., Methods: Clinical features and enhanced CT data of 235 patients with AEJ from October 2017 to May 2023 were retrospectively analyzed. The data were randomly assigned to the training cohort (n = 164) or the external testing cohort (n = 71) at a ratio of 7:3. A CT-report model, clinical model, radiomic model, and radiomic-clinical combined model were developed to predict PLNM in patients with AEJ. Univariate and multivariate logistic regression were used to screen for independent clinical risk factors. Least absolute shrinkage and selection operator (LASSO) regression was used to select the radiomic features. Finally, a nomogram for the preoperative prediction of PLNM in AEJ was constructed by combining Radiomics-score and clinical risk factors. The models were evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration curve, and decision curve analyses., Results: A total of 181 patients (181/235, 77.02%) had LNM. In the testing cohort, the AUC of the radiomic-clinical model was 0.863 [95% confidence interval (CI) = 0.738-0.957], and the radiomic model (0.816; 95% CI = 0.681-0.929), clinical model (0.792; 95% CI = 0.677-0.888), and CT-report model (0.755; 95% CI = 0.647-0.840)., Conclusion: The radiomic-clinical model is a feasible method for predicting PLNM in patients with AEJ, helping to guide clinical decision-making and personalized treatment planning., (© 2024 American Association of Physicists in Medicine.)

Background: Difficult-to-treat Rheumatoid arthritis (D2T RA) is primarily characterised by failure of at least two different mechanism of action biologic/targeted synthetic disease-modifying antirheumatic drug (DMARDs) with evidence of active/progressive disease. While a variety of drugs have been used in previous studies to treat D2T RA, there has been no systematic summary of these drugs. This study conducted a systematic review of randomized controlled trials aimed at analyzing the efficacy and safety of individual therapeutic agents for the treatment of D2T RA and recommending the optimal therapeutic dose., Methods: The English databases were searched for studies on the treatment of D2T RA published between the date of the database's establishment and March, 2024. This study uses R 3.1.2 for data analysis, and the rjags package runs JAGS 3.4.0.20. The study fitted a stochastic effects Bayesian network meta-analysis for each outcome measure., Result: A total of 42 studies were included in this study. Compared with placebo, the improvement of Disease Activity Score of 28 Joints (DAS28) score is ranked from high to low as tocilizumab, baricitinib and opinercept. The improvement of American College of Rheumatology 50 response (ACR50) score in patients with drug use was ranked from good to poor as follows: olokizumab, tocilizumab, adalimumab, baricitinib, and upadacitinib, and 8 mg/4w tocilizumab demonstrated the best efficacy. Notably, rituximab is generally the safest drug. Janus kinase (JAK) inhibitors and T cell costimulation modulators are effective in D2T RA refractory to biologic DMARDs, while JAK inhibitors and interleukin-6 (IL-6) inhibitors show effectiveness in D2T RA refractory to csDMARDs., Conclusion: Tocilizumab and rituximab have better efficacy and safety in the treatment of D2T RA, and the 8 mg/4w dose of tocilizumab may be the first choice for achieving disease remission., (© 2024. The Author(s).)

Background: Ileal atresia is a congenital abnormality where there is significant stenosis or complete absence of a portion of the ileum. The overall diagnostic accuracy of prenatal ultrasound in detecting jejunal and ileal atresia is low. We report a case of ileal atresia diagnosed prenatally by ultrasound examination with the "keyboard sign" and "coffee bean sign"., Case Summary: We report a case of ileal atresia diagnosed in utero at 31 weeks' of gestation. Prenatal ultrasound examination revealed two rows of intestines arranged in an 'S' shape in the middle abdomen. The inner diameters were 1.7 cm and 1.6 cm, respectively. A typical "keyboard sign" was observed. The intestine canal behind the "keyboard sign" showed an irregular strong echo. There was no normal intestinal wall structure, showing a typical "coffee bean sign". Termination of the pregnancy and autopsy findings confirmed the diagnosis., Conclusion: The prenatal diagnosis of ileal atresia is difficult. The sonographic features of the "keyboard sign" and "coffee bean sign" are helpful in diagnosing the location of congenital jejunal and ileal atresia., 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.)

Objectives: To observe the effect of moxibustion at "Zusanli "(ST36) on the plasma amino acid metabolism in rats with knee osteoarthritis (KOA), and to explore the amino acid metabolism mechanism of moxibustion in repairing cartilage injury in KOA., Methods: A total of 30 SD rats were randomly divided into normal, model and moxibustion groups, with 10 rats in each group. Rats in the model and moxibustion groups were injected with the mixture of L-cysteine and papain into bilateral knee joint cavity to make the KOA model. The moxibustion group received moxibustion at bilateral ST36 for 30 min, once daily for 30 days. At the end of the experiment, the swelling degree of knee joint was calculated, the mechanical pain threshold was measured by the Von Frey filament, the cartilage tissue injury was observed by HE staining, the matrix metalloproteinase-13 (MMP-13) content in the synovial tissue was detected by enzyme-linked immunosorbent assay (ELISA), and the differential amino acid metabolites in plasma were detected and screened by liquid chromatography-mass spectrometry (LC-MS)., Results: Compared with the normal group, the model group showed irregular cartilage surface, decreased number of chondrocytes, uneven distribution, and local clusters of chondrocytes；the contour of the tide line was blurred. The degree of joint swelling in the model group was higher than that in the normal group ( P <0.01), the mechanical pain threshold was lower ( P <0.01), and the content of MMP-13 in synovial tissue was higher ( P <0.01). The contents of proline and tryptophan in the model group were down-regulated ( P <0.01, P <0.05). Compared with the model group, the cartilage tissue damage and knee joint swelling were decreased( P <0.05), mechanical pain threshold was increased( P <0.05), MMP-13 content in synovial tissue and levels of glutamate and histidine expression were decreased ( P <0.01, P <0.05)., Conclusions: Moxibustion at ST36 significantly alleviated arthritis-related swelling and pain in KOA model rats, attenuated cartilage damage, and regulated levels of certain plasma amino acid metabolites. Moxibustion may regulate KOA cartilage synthesis and degradation through amino acid metabolic pathways such as proline, tryptophan, glutamate and histidine, exerting anti-inflammatory, analgesic, and protection of cartilage injury effects.

One of the main characteristics of diabetic kidney disease (DKD) is abnormal renal tubular fatty acid metabolism, especially defective fatty acid oxidation (FAO), accelerating tubular injury and tubulointerstitial fibrosis. Thiosulfate sulfurtransferase (TST), a mitochondrial enzyme essential for sulfur transfer, is reduced in metabolic diseases like diabetes and obesity. However, the potential role of TST in regulating fatty acid metabolic abnormalities in DKD remains unclear. Here, our data revealed decreased TST expression in the renal cortex of DKD patients. TST deficiency exacerbated tubular impairment in both diabetic and renal fibrosis mouse models, while sodium thiosulfate treatment or TST overexpression mitigated renal tubular injury with high-glucose exposure. TST downregulation mediated the decrease in S-sulfhydration of very long-chain specific acyl-CoA dehydrogenase, resulting in mitochondrial FAO dysfunction. This sequence of events exacerbates the progression of tubulointerstitial injury in DKD. Together, our findings demonstrate TST as a regulator of renal tubular injury in DKD., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)