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Minglei Ma, Tao Jiang, Dongxue Zhang, Xiaoai Yao, Zhen Wen, Lei Xiu Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Tao Jiang, Email jiangtao@bjsjth.cnObjective: To investigate the association of bedtime with the risk of early-onset diabetes mellitus (DM) and islet beta cell function.Methods: 138 participants with treat-naïve DM were included in this study. All participants underwent a 75g oral glucose tolerance test. Sleep habit was obtained through a standardized questionnaire. Bedtime was categorized as < 22:00, 22:00– 24:00, and ≥ 24:00 in this study. Multivariate logistic regression and multiple linear regression were used to estimate the association between bedtime and risk of early-onset DM and islet beta cell function, respectively.Results: Patients with early-onset DM had a later bedtime than those with late-onset DM. Individuals with bedtime ≥ 24:00 had a higher prevalence of early-onset DM than those with bedtime at 22:00– 24:00 and < 22:00 (51.2% vs 29.3% vs 14.3%, respectively, p = 0.028). The multivariate logistic regression showed that per hour later in bedtime was associated with a 52% increased risk of early-onset DM (p = 0.023). Patients with bedtime after 24:00 had a 146% increased risk of early-onset DM compared to those went to bed between 22:00 to 24:00 (OR = 2.46, 95% CI 1.05 to 5.77, p = 0.039). The multiple linear regression showed that bedtime was independently negatively correlated with late-phase insulin secretion (assessed by disposition index, DI120).Conclusion: Later bedtime was associated with worse late-phase insulin secretion and may be a risk factor for early-onset DM. Proper bedtime to lower risk of early-onset DM deserves further investigation.Keywords: diabetes mellitus, early-onset, sleep, bedtime, islet beta cell function

Minglei Ma, Tao Jiang, Zhen Wen, Dongxue Zhang, Lei Xiu Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Tao Jiang, Email jiangtao@bjsjth.cnObjective: To assess the correlation between body components with insulin resistance (IR) and islet beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM) or pre-diabetes mellitus (pre-DM) and to explore whether this correlation differs in males and females.Methods: 111 newly diagnosed diabetic or pre-diabetic patients were recruited in this cross-sectional study. 75g oral glucose tolerance test was used to determine the diagnosis of DM or pre-DM. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI30) was calculated to assess IR and islet beta cell function, respectively. Whole-body and regional lean mass (LM) and fat mass (FM) were obtained by dual-energy X-ray absorptiometry (DEXA). Partial correlation and multiple linear regression analyses were used to determine the associations between body composition, IR, and islet beta cell function.Results: More body fat and appendicular fat was observed in female patients than in male, though with similar BMI. Legs fat % was negatively correlated with HOMA-IR, whereas legs lean % was positively associated with HOMA-IR in females (r = − 0.673, p = 0.017; r =0.664, p = 0.018, respectively). The regression analysis showed that legs LM was positively correlated with HOMA-IR in females. However, in male patients, android FM was positively correlated with HOMA-IR (r = 0.462, p = 0.007), and trunk LM was negatively associated with DI30 (r = − 0.458, p = 0.007). Nevertheless, no significant correlation was observed between body composition and islet beta cell function in female patients.Conclusion: Android FM was positively correlated with IR only in male patients but not in females. Besides, relative legs fat and LM were independently associated with IR in female patients but not in males. Further studies are needed to explore the underlying mechanism.Keywords: body composition, diabetes mellitus, insulin resistance, islet beta cell function

Lei Xiu, Tao Jiang, Xiao-ai Yao, Zhen Wen Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Tao JiangDepartment of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaEmail jiangtao@bjsjth.cnPurpose: We aimed to analyze the serum vitamin D level in Chinese patients with type 2 diabetes mellitus (T2DM) and discuss its correlation with nonalcoholic fatty liver disease (NAFLD).Patients and Methods: A total of 300 patients with T2DM (92 patients without NAFLD and 208 patients with NAFLD) were enrolled, and 25-hydroxyvitamin D [25-(OH)D] levels were compared between the two groups. Second, the NAFLD fibrosis score (NFS) and fatty liver index (FLI) were used to group patients with T2DM complicated by NAFLD, and the differences in serum 25-(OH)D in patients with different degrees of liver fibrosis were compared. Third, multiple regression analysis was used to analyze the independent predictors of liver fibrosis in patients with T2DM complicated by NAFLD.Results: The level of 25-(OH)D in patients with T2DM complicated by NAFLD was significantly lower than that in patients with T2DM alone. Based on the NFS and FLI, the 25-(OH)D level of the hepatic fibrosis subgroup was significantly lower than that of the subgroup without liver fibrosis. 25-(OH)D was found to be an independent predictor of liver fibrosis in patients with T2DM complicated by NAFLD.Conclusion: The serum 25-(OH)D level in patients with T2DM complicated by NAFLD was significantly reduced, and the 25-(OH)D level showed a gradual downward trend with the degree of liver fibrosis. Low concentrations of 25-(OH)D may be indicative of the degree of liver fibrosis in diabetic patients.Keywords: type 2 diabetes mellitus, nonalcoholic fatty liver disease, 25-hydroxyvitamin D, liver fibrosis

Fowl adenovirus serotype 4 (FAdV-4) is a highly pathogenic virus with a broad host range that causes huge economic losses for the poultry industry worldwide. RNA sequencing has provided valuable and important mechanistic clues regarding FAdV-4–host interactions. However, the pathogenic mechanism and host's responses after FAdV-4 infection remains limited. In this study, we used transcriptome analysis to identify dynamic changes in differentially expressed genes (DEGs) at five characteristic stages (12, 24, 36, 48, and 60 h) post infection (hpi) with FAdV-4. A total of 8,242 DEGs were identified based on comparison of five infection stages: 0 and 12, 12 and 24, 24 and 36, 36 and 48, and 48 and 60 hpi. In addition, at these five important time points, we found 37 common upregulated or downregulated DEGs, suggesting a common role for these genes in host response to viral infection. The predicted function of these DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these DEGs were associated with viral invasion, host metabolic pathways and host immunosuppression. Interestingly, genes involved in viral invasion, probably EGR1, SOCS3, and THBS1, were related to FAdV-4 infection. Validation of nine randomly selected DEGs using quantitative reverse-transcription PCR produced results that were highly consistent with those of RNA sequencing. This transcriptomic profiling provides valuable information for investigating the molecular mechanisms underlying host–FAdV-4 interactions. These data support the current molecular knowledge regarding FAdV-4 infection and chicken defense mechanisms.

Uveal melanoma (UM) is the most common malignant intraocular tumor with the trait of distant metastases. Currently, the standard clinical therapy results in suboptimal outcomes due to ineffective inhibition of tumor metastasis. Thus, developing novel therapeutic modalities for UM remains a critical priority. Herein, we have developed an injectable nanocomposite hydrogel (HA-DOX/LAP gel) through integrating hyaluronic acid-based drug-loaded nanoparticles into an alginate-dopamine gel, delivering the chemotherapeutic drugs, lapatinib and doxorubicin for combinational treatment of UM. HA-DOX/LAP gel is fabricated in situ by a simple injection of the mixed precursor solution into tumor sites and maintains in vivo for more than 21 days. The entrapped drug-loaded nanoparticles can gradually release from HA-DOX/LAP gel, enhancing tumor targeting and penetration, and synchronously releasing lapatinib and doxorubicin into the acidic intracellular environment to synergistically destroy UM cells. In vivo anti-tumor studies conducted in MuM-2B tumor models demonstrated that HA-DOX/LAP gel significantly impedes tumor growth, diminishes postoperative recurrence, and prolongs overall survivals of UM tumor-bearing mice through only single injection. Remarkably, the escaped drug-loaded nanoparticles effectively reduce the risk of tumor metastases. Our findings provide new insights for the development of multifunctional nanocomposite-incorporating combination therapy against UM by targeting tumor recurrence and metastases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Uveal melanoma (UM) is the most common intraocular primary malignancy in adults with highly metastatic characteristics. Currently, there are no effective therapies to prevent metastasis formation in UM, resulting in a poor prognosis. Herein, we report a novel lapatinib-loaded reductive-responsive nanoparticle platform prepared via the self-assembly of amphiphilic hyaluronic acid-cystamine-cholesteryl hemisuccinate conjugate to suppress the distant metastasis of UM. The platform can maintain a stable nanosphere structure in the physiological environment and effectively deliver the drug to UM tumor sites, enhancing intratumoral drug accumulation and penetration. Upon endocytosis, lapatinib-loaded nanoparticles rapidly disintegrate triggered by intracellular glutathione and release the payload, leading to considerable suppression of MuM-2B cell proliferation, invasion, and migration. Systemic administration of lapatinib-loaded nanoparticles into mice bearing lung metastases of UM resulted in significantly higher metastasis suppression compared to free lapatinib, with histological analyses indicating no detectable toxicity. This nanotherapeutic platform is expected to provide a promising approach for the safe and efficient prevention of metastasis in UM., 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.)

Cephalosporin resistance in Neisseria gonorrhoeae has severely compromised the efficacy of World Health Organization (WHO)-recommended therapies. This study aimed to methodologically evaluate the optimized Six-Codon Plus assay, and additionally conducted a multicenter evaluation to assess its clinical application, especially for predicting antimicrobial resistance (AMR). For methodological evaluation, 397 sequence-known N. gonorrhoeae isolates were evaluated for specificity, 17 nongonococcal isolates were assessed for cross-reactivity, 159 uncultured urogenital swabs and urine samples were evaluated for sensitivity at the clinical level. For multicenter evaluation, 773 isolates with confirmed phenotypic data and 718 clinical urogenital swabs collected from four geographical cities were, respectively, utilized for the evaluation of AMR-prediction strategies and the clinical application of the assay. The assay accurately identified specific single-nucleotide polymorphisms in resistance-associated genes, the detection limits dropped to 10 copies/reaction for individual targets. The specificity reached 100% and no cross-reactivity occurred with double-target confirmation. The assay could be directly applied to clinical samples containing over 20 copies/reaction. Multicenter evaluation formulated two optimal strategies for decreased susceptibility prediction in specific scenarios, and one tactic for prediction of resistance and identification of FC428-like strains. High sensitivity of 86.84% (95% CI, 71.11-95.05) and specificity of 99.59% (95% CI, 98.71-99.89) for resistance prediction were demonstrated for ceftriaxone (CRO). Regarding N. gonorrhoeae identification among multicenter swabs, specificity reached 97.53% (95% CI, 95.49-98.69), and sensitivity reached 93.77% (95% CI, 90.04-96.22). The Six-Codon Plus assay exhibited excellent detection performance and formulated optimal AMR-related prediction strategy with regional adaptability, providing critical information for population screening and clinical treatment.

Karenia mikimotoi is a harmful algal bloom (HAB) species that poses a significant threat to marine ecosystems due to its hemolytic toxins. This study isolated Vibrio coralliirubri (ACE001), which demonstrated contact-dependent algicidal effects against K. mikimotoi . Chemotaxis assays revealed ACE001's strong attraction to K. mikimotoi cell membranes, indicating the importance of chemotaxis. ACE001 caused a significant decrease in Chlorophyll a and an increase in reactive oxygen species (ROS), indicating oxidative stress. Scanning electron microscopy showed ACE001 adheres to and penetrates K. mikimotoi , leading to cell rupture. Dual RNA-seq revealed suppression of the type VI secretion system (T6SS) and the upregulation of the Sec secretion system, particularly the yidC and secY genes. Mutant strains lacking these genes exhibited reduced algicidal activity. This study provides the evidence of a Vibrio species with algicidal activity against K. mikimotoi , offering insights into its algicidal mechanisms., 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., (© 2024 The Author(s).)

The objective of this study is to elucidate how Royal jelly (RJ) and 10-hydroxy-2-decanoic acid (10-HDA) prevents diabetic skin dysfunction by modulating the pyroptosis pathway. Type 2 diabetes models are induced by fat diet consumption and low dose of streptozotocin (STZ) in C57BL/6J mice and treated with RJ (100 mg kg -1 day -1 ) and 10-HDA, the major lipid component of royal jelly (100 mg kg -1 day -1 ) for 28 weeks. The results show that serum concentrations of glucose and triglyceride are significantly lower in the RJ group or 10-HDA than diabetes mellitus (DM) group. Compared to the control group, pyroptosis proteins, GSDMD, ASC, Caspase-1, and IL-1β are increased in the skin of the diabetic model, accompanied by the activation of the Wnt/β-catenin signal pathway. Further evaluations by RJ exhibit superior improvement of skin damage, repress activation of the Wnt/β-catenin pathway, and attenuate keratinocyte pyroptosis, but 10-HDA cannot completely suppress the activation of Wnt/β-catenin pathway and pyroptosis, which shows a relatively weak protective effect on skin damage which shows that RJ is a better effect on skin injury after DM., (© 2024 Wiley‐VCH GmbH.)

Corn husk, a by-product of corn starch production and processing, contains high-quality dietary fiber (DF). Our study compares and analyzes the impact of Hericium erinaceus solid-state fermentation (SSF) on the structure and physicochemical characteristics of soluble dietary fiber (SDF) of corn husks. The study also investigates the kinetics of SSF of H. erinaceus in this process. The scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) results revealed significant structural changes in corn husk SDF before and after fermentation, with a significant elevation in the functional group numbers. The data indicate that the fermented corn husk SDF's water-holding, swelling, and oil-holding capacities increased to 1.57, 1.95, and 1.80 times those of the pre-fermentation SDF, respectively. Additionally, the results suggest that changes in extracellular enzyme activity and nutrient composition during SSF of H. erinaceus are closely associated with the mycelium growth stage, with a mutual promotion or inhibition relationship between the two. Our study offers a foundation for corn husk SDF fermentation and is relevant to the bioconversion of maize processing by-products.

The objective of this study was to explore the impact of different persuasive strategies, as delineated in the Elaboration Likelihood Model (ELM), on attentional processes using event-related potentials (ERPs)., Introduction: This study aimed to investigate how central versus peripheral persuasion methods, delivered through rational and emotional persuasion strategies, influence cognitive engagement and information processing during visual search tasks., Methods: Participants were allocated into four groups based on the media type (video vs. text) and the persuasion route (central vs. peripheral). The early and late stages of attentional processing were examined through the N1, P2, and P3 ERP components., Results: The results demonstrated a pronounced N1 amplitude in response to text-based peripheral persuasion, indicating enhanced early attentional engagement. Additionally, parallel search tasks revealed a larger P3 amplitude for central versus peripheral routes, suggesting significant cognitive resource allocation during tasks requiring higher attention., Discussion: These findings underscore the nuanced role of persuasive strategies in modulating attentional resources and cognitive processing. The study offers insights into designing more effective communication messages and highlights the potential for tailored persuasion approaches to influence audience engagement and information processing, with implications for public health campaigns and beyond., 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 Xiu, Chen, Mao, Zhang and Yu.)

The treatment of chronic diabetic wounds is a major challenge due to oxidative stress, persistent hyperglycemia, and susceptibility to bacterial infection. In this study, multifunctional sandwich-structured nanofiber dressings (SNDs) are prepared via electrospinning. The SNDs consisted of an outer layer of hydrophobic polylactic acid (PLA) fibers encapsulating MgB 2 nanosheets (MgB 2 NSs), a middle layer of PLA and polyvinylpyrrolidone (PVP) fibers encapsulating the MgB 2 NSs and metformin hydrochloride complex (MgB 2 -Met), and an inner layer of water-soluble PVP fibers encapsulating MgB 2 -Met. Because of their special sandwich structure, SNDs have high photothermal conversion efficiency (24.13%) and photothermal cycle performance. SNDs also exhibit a photothermal effect, bacteria-targeting effect of MgB 2 , electrostatic attraction ability of metformin hydrochloride (Met), and strong antibacterial activity against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). SNDs can eliminate intracellular reactive oxygen species (ROS) by regulating the hydrogen release from MgB 2 . In addition, SNDs have good biocompatibility, can effectively inhibit the inflammatory factor Interleukin-6 (IL-6), and promote granulation tissue formation, collagen deposition, and diabetic wound healing. These findings offer a promising approach for clinical treatment of diabetic wounds., (© 2024 Wiley‐VCH GmbH.)

Lei Xiu, Xiao-ai Yao, Tao Jiang Department of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Tao JiangDepartment of Endocrinology, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyilu, Yang Fang Dian, Beijing, 100038, People’s Republic of ChinaTel/Fax +86-10-63926692Email jiangtao@bjsjth.cnPurpose: Chinese adults with early-onset type 2 diabetes mellitus have impaired diastolic function. This study aims to analyse the association between serum vitamin D levels and cardiac diastolic dysfunction in Chinese adults with early-onset type 2 diabetes mellitus.Patients and Methods: We enrolled Chinese adults with early-onset type 2 diabetes mellitus in this study. These patients were divided into two groups: those with diastolic dysfunction and those without diastolic dysfunction. We then compared the levels of serum 25-hydroxyvitamin D [25-(OH)D] between the two groups. The correlation between diastolic function and 25-(OH)D was evaluated by Pearson correlation analysis. Finally, binary logistic regression was used to analyse the relationship between the decrease in diastolic function and 25-(OH)D and other indexes in Chinese adults with early-onset type 2 diabetes mellitus.Results: The level of 25-(OH)D in patients with early-onset type 2 diabetes mellitus complicated with cardiac diastolic dysfunction was significantly lower than that in patients without cardiac diastolic dysfunction (P< 0.01). The degree of liver fibrosis in adult patients with early-onset type 2 diabetes mellitus complicated with diastolic dysfunction was significantly higher than that in adult patients without diastolic dysfunction (P< 0.01). Moreover, decreased 25-(OH)D levels were associated with decreased diastolic function in adults with early-onset type 2 diabetes.Conclusion: 25-(OH)-D was identified as an independent predictor of decreased diastolic function in adults with early-onset type 2 diabetes. The serum 25-(OH)D level in adults with early-onset type 2 diabetes was significantly reduced. 25-(OH)D influences the reduction in diastolic function in adults with early-onset type 2 diabetes and can be used as a predictor of decreased diastolic function in such patients.Keywords: early-onset type 2 diabetes in adults, 25-hydroxyvitamin D, decreased diastolic function, non-alcoholic fatty liver disease

Ethnopharmacological Relevance: Haizao, Sargassum, is widely used to treat goiter. Gancao, Glycyrrhizae radix et rhizome, is renowned for reducing toxicity or increasing effects in traditional Chinese medicine. As a classic herb pair, Haizao-Gancao (HG) is a commonly used and effective combined therapy for goiter. The underlying biological mechanisms of HG on goiter is still unclear., Aim of the Study: To explore the effect of HG on goiter, employing molecular docking combined with experimental validation to elucidate the molecular mechanism., Materials and Methods: The rat goiter model was created by gavageing propylthiouracil (PTU) intragastrically for a duration of 14 days. The rats had been separated into six groups: control, model, euthyrox, HG high-dose (HG-H), medium-dose (HG-M) and low-dose (HG-L) group. Based on general observations (such as the rats' living status, body weight, and rectal temperature), the relative weight of the thyroid, thyroid function, hematoxylin-eosin (HE) staining, and transmission electron microscopy (TEM) to view the pathological variations of the thyroid glands, the effect of HG was evaluated. Discovered the chemical composition of HG by UPLC-MS/MS and the possible targets were predicted adopting several databases. Next, we explored their pharmacological mechanisms using molecular docking and validated key targets using western blotting (WB) and co-immunoprecipitation (Co-IP)., Results: HG significantly increased the levels of triiodothyronine(T3), free triiodothyronine (FT3), free thyroxine (FT4), gained body weight and reduced tumescent thyroid glands in PTU-induced rats. The model group pathological changes such as uneven size, irregular shape and disordered arrangement of follicular epithelial cells occurred. However, HG groups thyroid follicles and epithelial cells appeared apparently normal. A variety of characteristic changes of autophagic vesicles appeared in the HG groups as opposed to the model group. In conclusion, the HG-L showed the best therapeutic effect. By UPLC-MS/MS, the major chemical components of HG were identified. The result revealed that HG contained flavonoids, alkaloids, organic acids, phenolic acidsand and terpenoids, etc. The molecular docking results of formononetin and naringenin and Beclin1 protein showed a high interaction of -5.38 kcal/mol and -5.25 kcal/mol. This implies that formononetin and naringenin may have a therapeutic effect in goiter rats by controlling the Beclin1-mediated autophagy. Western Blot (WB) and co-immunoprecipitation (Co-IP) results showed that HG can disrupt Beclin1/class III phosphatidylinositol 3-kinase(PI3KC3) binding and promote Beclin1/B-cell leukemia/lymphoma-2(Bcl-2) complex formation. Taken together, results demonstrate that autophagy inhibition via reducing Beclin1/PI3KC3 formation and increasing Beclin1/Bcl-2 binding activity., Conclusions: HG ameliorates propylthiouracil-induced goiter by regulating the Beclin1-mediated autophagy, thus promoting the autophagy of thyroid cells., 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.)

A non-inferiority trial is usually conducted to investigate whether a new drug/treatment is no worse than a reference drug/treatment by a small, pre-specified, non-inferiority margin. This study aimed to assess the non-inferiority of the difference between two binary-outcome treatments in a matched-pairs design based on the method of variance of estimates recovery (MOVER). The processes for estimating the confidence interval of a single proportion included in the MOVER are the Wilson score interval, Agresti - Coull interval, Jeffreys interval, modified Jeffreys interval, score method with continuity correction, and arcsin interval. The performance of the six MOVER tests, the fiducial test, and the restricted maximum likelihood estimation test were evaluated by comparing their type I error rates and power at different pre-assigned levels and with varying combinations of parameters. The evaluation results showed that the modified Jeffreys MOVER test can be a competitive alternative to the other recommended tests. It can control type I errors well, and its power is not inferior to other methods. The proposed tests were illustrated with three real-world examples.

Ceftriaxone-resistant Neisseria gonorrhoeae FC428-like strains have disseminated across the Asia-Pacific region, with a continuous rise in prevalence during 2015-2022. To mitigate the effect of these strains, we advocate for enhanced molecular diagnostics, expanded surveillance networks, and a regionally coordinated effort to combat the global spread of FC428-like strains.

Introduction: This study aims to determine the etiological, sociodemographic, and clinical characteristics of STIs, and the level of resistance in M. genitalium in Shenzhen, a representative first-tier city of southern China., Methods: A multicenter cross-sectional study was conducted and 7886 sexually active participants attending STI-related departments were involved from 22 hospitals. Nine STI-related organisms including N. gonorrhoeae , C. trachomatis , T. vaginalis , M. genitalium , HSV-1, HSV-2, M. hominis , U. parvum , and U. urealyticum were screened., Results: Being single or divorced was associated with increased detection of N. gonorrhoeae , C . trachomatis , M. genitalium , HSV-1, HSV-2 and M. hominis . Lower education level was associated with increased detection of C. trachomatis , HSV-2 and M. hominis . No insurance coverage was an independent risk factor for T. vaginalis , M. hominis and U. parvum positivity. Three resistance-determining regions related to macrolide and fluoroquinolone were sequenced in 154 M. genitalium positive samples, among which 90.3% harbored mutations related to macrolide or fluroquinolone resistance and 67.5% were multidrug-resistant M. genitalium . A2072G in 23S rRNA and Ser83Ile in parC were the most common mutations. M. hominis was associated with manifestations of bacterial vaginosis in female and epididymitis in male., Conclusions: Single or divorced individuals, those with lower education level and individuals without insurance are higher-risk key populations for STIs. The prevalence of antimicrobial-resistant M. genitalium in Shenzhen is high. Detection of M. hominis increased significantly with lower education level and no health insurance coverage, and it is associated with bacterial vaginosis or epididymitis, indicating that M. hominis deserves further attention., 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 Wang, Zhang, Xiu, Li, Zeng, Li, Cai and Peng.)

Objective: The aim of this study was to determine the poly (ADP-ribose) polymerase inhibitors (PARPis) response and outcome of ovarian cancer (OC) patients with BRCA1/2 germline mutation and a history of breast cancer (BC)., Methods: Thirty-nine OC patients with BRCA1/2 germline mutation and a history of BC were included. The clinicopathological characteristics, PARPis response and prognosis were analyzed., Results: The median interval from BC to OC diagnosis was 115.3 months (range=6.4-310.1). A total of 38 patients (38/39, 97.4%) received platinum-based chemotherapy after surgical removal. The majority of these patients were reported to be platinum sensitive (92.1%, 35/38). 21 patients (53.8%) received PARPis treatment with 16 patients (76.2%) for maintenance treatment and 5 patients (5/21, 23.8%) for salvage treatment. The median duration for PARPis maintenance and salvage treatment was 14.9 months (range=2.0-56.9) and 8.2 months (range=5.2-20.7), respectively. In the entire cohort, 5-year progression-free survival (PFS) and overall survival (OS) rate was 33.1% and 78.9%, respectively. Patients with BRCA1 mutation had a non-significantly worse 5-year PFS (28.6% vs. 45.8%, p=0.346) and 5-year OS (76.9% vs. 83.3%, p=0.426) than those with BRCA2 mutation. In patients with stage III-IV (n=31), first line PARPis maintenance treatment associated with a non-significantly better PFS (median PFS: NR vs. 22.4 months; 5-year PFS: 64.3% vs. 21.9%, p=0.096)., Conclusion: The current study shows that these patients may have a good response to platinum-based chemotherapy and a favorable survival. And these patients can benefit from PARPis treatment and will likely be suitable candidates for PARPis., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To facilitate development of new therapies for this heterogenous disease, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify clinical trial endpoints and analytic strategies across affected organ systems and life impacts via specialized working groups. This review summarizes the proceedings of the Statistical Group and proposes a pathway for development and validation of multi-domain endpoints (MDEs) for potential use in AL amyloidosis clinical trials. Specifically, drawing on candidate domain-specific endpoints recommended by each organ-specific working group, different approaches to constructing MDEs were considered. Future studies were identified to assess the validity, meaningfulness and performance of MDEs through use of natural history and clinical trial data. Ultimately, for drug development, the context of use in a regulatory evaluation, the specific patient population, and the investigational therapeutic mechanism should drive selection of appropriate endpoints. MDEs for AL amyloidosis, once developed and validated, will provide important options for advancing patient-focused drug development in this multi-system disease., (© 2024. The Author(s).)

Chi Zhang,1,* Tao Hu,2,* Leshan Xiu,1 Yamei Li,1 Junping Peng1 1NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurosurgery, Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junping PengNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 6, Rongjing East Street, BDA, Beijing, People’s Republic of ChinaTel/Fax +86 10 67878493Email pengjp@hotmail.comAbstract: Unbiased metagenomic next-generation sequencing (mNGS) has been widely applied in clinical microbiology for infectious disease diagnostics. Some successful applications in central nervous system infections and respiratory tract infections have proved it to be a promising tool for pathogen detection. Here, mNGS was used to confirm the infectious etiology in a case of tuberculous coxitis, which is a common type of extrapulmonary tuberculosis (TB). A 77-year-old Asian male presented with hip pain and fever was diagnosed with smear- and culture-negative tuberculous coxitis based on the evidence of imaging and interferon-γ release assay. At the same time as the anti-TB therapy started, the patient underwent joint clearance surgery. Whole blood and synovial fluid sampled from surgery were kept for bacteriological confirmation using mNGS with high sequencing depth. However, only two paired-end reads from synovial fluid samples were identified as Mycobacterium tuberculosis. Before leaving hospital, the patient was still receiving anti-TB treatment and began to recover. Considering the obvious escalation of the cost and analysis time as the depth of sequencing increases, although we got a positive result here, the scarce number of reads obtained through ultra-deep sequencing indicates its limitations in extrapulmonary tuberculosis.Keywords: extrapulmonary tuberculosis, metagenomics, molecular diagnostic techniques, Mycobacterium tuberculosis

Leshan Xiu,1 Chi Zhang,1 Yamei Li,1 Feng Wang,2 Junping Peng11NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Shenzhen Center for Chronic Disease Control, Shenzhen, People’s Republic of ChinaCorrespondence: Junping PengNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 6 Rongjing Eastern Street, BDA, Beijing 100176, People’s Republic of ChinaTel/fax +86 106 787 8493Email pengjp@hotmail.comPurpose: Sexually transmitted infections (STIs), representing a major global health problem, are caused by different microbes, including bacteria, viruses, and protozoa. Unfortunately, infections of different sexually transmitted pathogens often present similar clinical symptoms, so it is almost impossible to distinguish them clinically. Therefore, the aim of the current study was to develop a sensitive, multitarget, and high-throughput method that can detect various agents responsible for STIs.Methods: We developed and tested a 23-plex PCR coupled with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) assay (sexually transmitted infection-mass spectrometry, STI-MS) that simultaneously targets 11 different agents, including 8 most common clinical pathogens related to STIs (HSV-1, HSV-2, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, and Haemophilus ducreyi) and 3 controversial microorganisms as pathogens (Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum).Results: The results showed that the STI-MS approach can accurately detect the expected agents, without cross-reaction with other organisms. The limit of detection of each STI-MS assay was ranged from 1.739 to 10.009 copies/reaction, using probit analyses. The verification rate for each target organism of the STI-MS ranged from a minimum of 89.3% to a maximum of 100%, using conventional assays and ultrasensitive digital PCR to confirm the STI-MS-positive results. To further evaluate the clinical performance of this assay, 241 clinical specimens (124 urethral/cervical swabs and 117 urine) were tested in parallel using the STI-MS assay and monoplex real-time PCR for each agent. The overall validation parameters of STI-MS were extremely high including sensitivity (from 85.7% to 100%), specificity (from 92.3% to 100%), PPV (from 50% to 100%), and NPV (from 99.1% to 100%) for each target.Conclusion: STI-MS is a useful high-throughput screening tool for detecting mixed infections of STIs and has great potential for application in large-scale epidemiological programs for specific microorganisms of STI.Keywords: sexually transmitted infections, timely diagnosis, MALDI-TOF mass spectrometry, digital PCR, high-throughput

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored., Method: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out., Results: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology., Conclusion: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored., (© 2024. The Author(s).)

Current research on maize germination suffers from long sampling intervals, and the relationship between the starch structure and the processing properties of flour in maize is still unclear. This study observed the effect of germination on the structure and composition of maize starch and the processing properties of maize flour over a 72 h period using a short interval sampling method. At 36 h, the short-range ordered structure, crystallinity, and enthalpy of starch reached the highest values of 1.02, 34.30%, and 9.90 J/g, respectively. At 72 h, the ratios of rapidly-digested starch (RDS) and slowly-digested starch (SDS) enhanced to 29.37% and 28.97%; the RS content reduced to 35.37%; and the flow properties of the starch were improved. This study enhances the understanding of the effects of germination on the processing properties of maize starch and flour, determines the appropriate application, and recommends the use of germination in the food industry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Material independent integrated nonlinear components (MIINC) based on nonlinear polarization evolution (NPE) play an important role in the emerging quantum computing, integrated photonics and ultrafast science. However, to our knowledge, no one has yet employed ultrafast laser direct writing for NPE-based MIINC. Here, for the first time, we finish the MIINC direct writing based on NPE using an ultrafast laser, and we suggest a multi-slice (MS) approach to in-fiber waveplate direct writing that allows for flexible adjustment of the phase difference, the waveplate fast and slow axis, and the stress birefringence value. To complete the measurement of the nonlinear transmittance curve, a polarization-splitter prism is attached to the output light path's back end. The measurement results agree with the theoretical calculation. MIINC based on NPE with arbitrary nonlinear transmittance curves are fabricated via the direct writing method, which is expected to be used in optical chips in the future.

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.

Mitochondria and their related genes (MTRGs) are pivotal in the tumour microenvironment (TME) of cervical cancer, influencing prognosis and treatment response. This study developed a prognostic model using MTRGs to predict overall survival (OS) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), aiming for personalized therapy. Analysing 14 MTRGs like ISCU and NDUFA11 through techniques such as univariate Cox regression, we found that a low mitochondrial (MT) score is associated with better survival, while a high MT score predicts poorer outcomes. The TME score, particularly influenced by CD8 T cells, also correlates with prognosis, with a high score indicating favourable outcomes. The interplay between MT and TME subtypes revealed that the best prognosis is seen in patients with a low MT and high TME score. Our findings highlight the role of MTRGs as potential biomarkers and therapeutic targets in cervical cancer, offering a novel approach to improving patient outcomes through a more nuanced understanding of mitochondrial function and immune interactions within the TME. This model presents a promising avenue for enhancing the precision of prognostic assessments in CESC., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Non-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level., Methods and Results: From January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥ 65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old., Conclusions: STEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression., (Copyright © 2024. Published by Elsevier B.V.)

Background: Photosynthesis is the key to crop yield. The effect of biochar on photosynthetic physiology and soybean yield under continuous cropping is unclear. We conducted a long-term field experiment to investigate the effects of co-application of biochar and fertilizer (BCAF) on these parameters. Five treatments were established: F2 (fertilizer), B1F1 (3 t hm -2 biochar plus fertilizer), B1F2 (3 t hm -2 biochar plus reduced fertilizer), B2F1 (6 t hm -2 biochar plus fertilizer), and B2F2 (6 t hm -2 biochar plus reduced fertilizer)., Results: BCAF increased chlorophyll and leaf area, enhancing soybean photosynthesis. The net photosynthetic rate (P n ), transpiration rate (T r ), stomatal conductance (G s ), water use efficiency (WUE) and intercellular carbon dioxide (CO 2 ) concentration (C i ) were enhanced by BCAF. In addition, BCAF improved soybean photosystem II (PSII) photosynthetic performance, driving force, potential photochemical efficiency (F v /F 0 ), and quantum yield of electron transfer (φ E0 ). Furthermore, BCAF enhanced the accumulation of photosynthetic products, such as soluble proteins, soluble sugars and sucrose content, resulting in higher leaf dry weight. Consequently, BCAF increased the soybean yield, with the highest increase of 41.54% in B2F1. The correlation analysis revealed positive relationships between soybean yield and chlorophyll, leaf area, maximal quantum yield of PSII (F v /F m ), electron transport flux per cross-section at t = 0 (ET 0 /CS 0 ), trapped energy flux per cross-section at t = 0 (TR 0 /CS 0 ), composite blade driving force (DF Total ), and leaf dry weight., Conclusions: We demonstrated that long-term BCAF enhances soybean photosynthesis under continuous planting, reduces fertilizer use and increases yield. This study reveals a novel way and theory to sustainably increase soybean productivity. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Bacterial membrane vesicles (MVs) have attracted increasing attention due to their significant roles in bacterial physiology and pathogenic processes. In this review, we provide an overview of the importance and current research status of MVs in regulating bacterial physiology and pathogenic processes, as well as their crucial roles in environmental adaptation and pathogenic infections. We describe the formation mechanism, composition, structure, and functions of MVs, and discuss the various roles of MVs in bacterial environmental adaptation and pathogenic infections. Additionally, we analyze the limitations and challenges of MV-related research and prospect the potential applications of MVs in environmental adaptation, pathogenic mechanisms, and novel therapeutic strategies. This review emphasizes the significance of understanding and studying MVs for the development of new insights into bacterial environmental adaptation and pathogenic processes. Overall, this review contributes to our understanding of the intricate interplay between bacteria and their environment and provides valuable insights for the development of novel therapeutic strategies targeting bacterial pathogenicity., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xiu, Wu, Lin, Zhang and Huang.)

N6-methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification-mediated autophagy underlying non-small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib-resistant cells (PC9-GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3' untranslated regions (3'-UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

The Shroom (Shrm) family of actin-binding proteins has a unique and highly conserved Apx/Shrm Domain 2 (ASD2) motif. Shroom protein directs the subcellular localization of Rho-associated kinase (ROCK), which remodels the actomyosin cytoskeleton and changes cellular morphology via its ability to phosphorylate and activate non-muscle myosin II. Therefore, the Shrm-ROCK complex is critical for the cellular shape and the development of many tissues, including the neural tube, eye, intestines, heart, and vasculature system. Importantly, the structure and expression of Shrm proteins are also associated with neural tube defects, chronic kidney disease, metastasis of carcinoma, and X-link mental retardation. Therefore, a better understanding of Shrm-mediated signaling transduction pathways is essential for the development of new therapeutic strategies to minimize damage resulting in abnormal Shrm proteins. This paper provides a comprehensive overview of the various Shrm proteins and their roles in morphogenesis and disease., Competing Interests: Conflict of interestThe authors declare no conflict., (© International Human Phenome Institutes (Shanghai) 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: "Gansui Banxia decoction" (GBD) is a classical traditional Chinese medicine formula for treating abnormal accumulation of fluid, such as malignant ascites (MA). Although GBD has shown definite water-expelling effects, its exact underlying mechanism has not been elucidated., Purpose: This study aimed to investigate the drug effects of GBD on MA rats and its underlying mechanisms., Methods: The main chemical composition was determined by ultra-high performance liquid chromatography. The drug effects of GBD was evaluated in the established cancer cell-induced MA rat model. The symptoms were analyzed, and biological samples were collected for detecting immune and inflammation-related indicators by enzyme-linked immunosorbent assays, western blot, and flow cytometry., Results: GBD increased urine discharge, decreased ascites production, and alleviated cachexia. After GBD treatment, the expression of TLR4, MyD88, and NF-кB and the release of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were reduced. In addition, GBD increased G1 phase arrest and inhibit excessive proliferation of cells in bone marrow while alleviating G1 phase arrest and increasing proliferation of cells in the thymus. Correspondingly, the development and maturation of T cells also changed. GBD increased the proportion of mature T-cells (CD4 + CD8 - and CD4 - CD8 + single-positive (SP) T-cells), and decrease the proportion of immature cells (CD4 + CD8 + double-positive (DP) T-cells and CD4 - CD8 - double-negative (DN) T-cells) in the blood or tumor microenvironment (TME, the ascites microenvironment). Finally, we further analysis of immune cell subsets, GBD decreased the proportion of immunosuppressive T-cells in the blood (CD4 + CD25 + Foxp3 + T-cells) and TME (CD8 + CD25 + Foxp3 + T-cells), and increased the proportion of anti-tumor immune cells (CD8 + CD28 + T-cells and NK cells) in the TME., Conclusion: These findings indicated that the drug effects of GBD were attributed to regulating the immune-inflammatory homeostasis, thereby mitigating the destruction of cancer cells and reducing the generation of ascites, which provided theoretical support for the clinical rational application and extended the scientific connotation of "water-expelling" of GBD., Competing Interests: Declaration of competing interest 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 © 2023. Published by Elsevier GmbH.)

Human norovirus (HuNoV) is the leading cause of nonbacterial acute gastroenteritis, which is highly infectious, rapidly evolving, and easily transmitted through feces. The accurate and early detection of HuNoV subtypes is essential for effective treatment, early surveillance, risk assessment, and disease prevention. In this study, a portable multiplex HuNoV detection platform that combines integrated microfluidics and cascade isothermal amplification, using a streamlined protocol for clinical fecal-based diagnosis is presented. To overcome the problems of carryover contamination and the incompatibility between recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP), a Dynamic confined-space-implemented One-pot RPA-LAMP colorimetric detection system (DORLA) is developed by creating a hydrogen bond network. The DORLA system exhibits excellent sensitivity, with detection limits of 10 copies µL -1 and 1 copy µL -1 for HuNoV GI and GII, respectively. In addition, a portable diagnostic platform consisting of a thermostatic control module and an integrated 3D-printed microfluidic chip for specific HuNoV capture, nucleic acid pretreatment, and DORLA detection, which enables simultaneous diagnosis of HuNoV GI and GII is developed. A DORLA-based microfluidic platform exhibits satisfactory performance with high sensitivity and portability, and has high potential for the rapid point-of-care detection of HuNoV in clinical fecal samples, particularly in resource-limited settings., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)