A compendium of genetic variations associated with promoter usage across 49 human tissues.

Promoters play a crucial role in regulating gene transcription. However, our understanding of how genetic variants influence alternative promoter selection is still incomplete. In this study, we implement a framework to identify genetic variants that affect the relative usage of alternative promoters, known as promoter usage quantitative trait loci (puQTLs). By constructing an atlas of human puQTLs across 49 different tissues from 838 individuals, we have identified approximately 76,856 independent loci associated with promoter usage, encompassing 602,009 genetic variants. Our study demonstrates that puQTLs represent a distinct type of molecular quantitative trait loci, effectively uncovering regulatory targets and patterns. Furthermore, puQTLs are regulating in a tissue-specific manner and are enriched with binding sites of epigenetic marks and transcription factors, especially those involved in chromatin architecture formation. Notably, we have also found that puQTLs colocalize with complex traits or diseases and contribute to their heritability. Collectively, our findings underscore the significant role of puQTLs in elucidating the molecular mechanisms underlying tissue development and complex diseases.

Genomic and Spatial Analysis on the Recent Transmission of Mycobacterium tuberculosis in Eastern China: A 10-Year Retrospective Population-Based Study.

Purpose: Understanding the mode of Mycobacterium tuberculosis (M. tuberculosis) transmission is crucial for disease prevention and control. Compared to traditional genotyping methods, whole genome sequencing (WGS) provides higher resolution and comprehensive genetic information, enabling the tracing of infection sources and determining of transmission routes to resolve extensive tuberculosis (TB) outbreaks. We conducted a ten-year study on the transmission of M. tuberculosis in a population in eastern China. Patients and Methods: We selected Lianyungang, an eastern city in China, as the study site. Patients diagnosed with active pulmonary TB from 2011 to 2020 were enrolled as the study subjects. We isolated and sequenced 2252 M. tuberculosis. Strains with pairwise genetic distances of less than 12 single nucleotide polymorphisms were defined as genomic clusters and which were considered recent transmissions. Kernel density estimation and K-function analysis were applied to explore the spatial distribution of recently transmitted strains. Results: After excluding non-tuberculous mycobacteria and duplicated samples, 2114 strains were included in the final analysis. These strains comprised lineage 2 (1593, 75.35%) and 4 (521, 24.65%). There were 672 clustered strains, with a recent transmission rate of 31.79%. The logistic regression model showed that the risk of recent transmission was high in students [adjusted odds ratio (aOR): 2.68, 95% confidence interval (CI): 1.63-4.49, P<0.001] and people infected with L2.2.1 strains (aOR: 1.59, 95% CI: 1.20-2.12). Higher spatial aggregation of TB transmission has been concentrated in Haizhou, Donghai, and Guanyun for the past 10 years. Three outbreaks affecting 46 patients were spatially spaced, with 11 to 23 persons each. Different groups exhibited varying geographic distances between the initial and later cases. Conclusion: There are areas with a high risk of transmission for M. tuberculosis in the research site, and the risk varies among different populations. Accurate prevention strategies targeted at specific regions and key populations can help curb the prevalence of TB.

Introduction of a Hydroxyl Self-Sacrificing Surface on Ultrathin Poly(heptazine imide) Nanosheets by KCl Grafting: A New Strategy to Improve the Photocatalytic Production of H2O2.

The generation of H2O2 through photocatalysis is increasingly recognized as a viable approach for addressing the energy and environmental challenges encountered in industrial production processes. In this research, we synthesized ultrathin (1 nm) poly(heptazine imide) (PHI) nanosheets as a photocatalyst by a one-step KCl molten salt process. The utilization of Fourier transform infrared and X-ray photoelectron spectroscopy substantiated that the interlayer-bonded potassium atoms induce polarization in water molecules, facilitating the attachment of hydroxyl groups on the surfaces of nanosheets. These groups serve as self-sacrificing entities, promoting the reaction that leads to the generation of H2O2. The preparation temperature and KCl doping amount factors for the H2O2 generation rate were investigated, and the mechanism of the KCl-bonded structure on photogeneration charge separation transport was analyzed. Owing to the elevated crystallization and the presence of surface self-sacrificing hydroxyl groups, the rate of H2O2 production reaches 6117.5 and 308.35 µmol·g-1·h-1 under visible-light irradiation (λ ≥ 420 nm) in isopropanol solution and pure water, respectively. These rates are 30 and 18.7 times higher than those observed for bulk g-C3N4, respectively. The photocatalytic kinetic processes for H2O2 formation and decomposition were also calculated to investigate the catalyst activities.

MnCe-based catalysts for removal of organic pollutants in urban wastewater by advanced oxidation processes - A critical review.

With Advanced oxidation processes (AOPs) widely promoted, MnCe-based catalysts have received extensive attention under the advantages of high efficiency, stability and economy for refractory organic pollutants present in urban wastewater. Driven by multiple factors such as environmental pollution, technological development, and policy promotion, a systematic review of MnCe-based catalysts is urgently needed in the current research situation. This research provides a critical review of MnCe-based catalysts for removal of organic pollutants in urban wastewater by AOPs. It is found that co-precipitation and sol-gel methods are more appropriate methods for catalyst preparation. Among a host of influence factors, catalyst composition and pH are crucial in the catalytic oxidation processes. The synergistic effect of the free radical pathway and surface catalysis results in better pollutants degradation. It is more valuable to utilize multiple systems for oxidation (e.g., photo-Fenton technology) to improve the catalytic efficiency. This review provides theoretical guidance for MnCe-based catalysts and offers a reference direction for future research in the AOPs of organic pollutants removal from urban wastewater.

Excellent anti-mildew effect of essential oil impregnation on sliced veneer plybamboo and its anti-mildew mechanism.

Sliced bamboo veneer used as a high-end decoration material is a highly innovative material for the deep processing of bamboo. However, bamboo is rich in starch and small molecular soluble sugars, making it susceptible to mildew infection and limiting the wide application of sliced veneer plybamboo. Spice essential oils are considered green and safe antimildew agents, which are cheap and accessible. The natural phenolic substances in plant essential oil have a good inhibitory effect on bamboo mildew. In this study, three types of spice essential oils (clove essential oil, oregano essential oil, and fennel essential oil) were employed, and their antifungal activity against bamboo mildews was assessed using the Oxford cup method, scanning electron microscopy, transmission electron microscopy, and a micro pH meter. The results demonstrated that the diameters of the Inhibition Zone against four common bamboo mildews (AN, Aspergillus niger; TV, Trichoderma viride; PC, Penicillium citrinum; MM, Mixed Mildews) caused by clove essential oil were 25.68 mm, 23.22 mm, 30.68 mm, and 25.43 mm, respectively. As an explanation, clove essential oil can inhibit or eliminate mildew by damaging and disrupting the cell membrane of the bamboo mildew, leading to significant shrinkage, distortion, surface roughness, formation of holes, or partial structural cracks in the mildew's mycelium. Additionally, it may interfere with and disrupt the pH balance of the intracellular and extracellular fluids within the cell. Furthermore, we also report that sliced veneer plybamboo impregnated with clove essential oil on each layer showed fine inhibition rates of 50%, 75%, 100%, and 25% against AN, TV, PC, and MM, respectively. This research underscores a sustainable approach to mildew prevention, crucial for advancing bamboo's utilization in high-value furniture decor applications. IMPORTANCE: Mildew growth in sliced veneer plybamboo poses a significant challenge, particularly in its use for high-end furniture and decor. Traditionally, chemical treatments have been the primary solution though they often raise environmental concerns. Essential oils, with their well-documented antimicrobial properties, have emerged as an important natural and eco-friendly alternative for preventing mildew. These oils inhibit mildew growth effectively while offering a sustainable, non-toxic solution that reduces harm to both the environment and human health. By leveraging essential oils, it becomes possible to extend the lifespan of bamboo products, making them more durable and suitable for broader applications in furniture and decor, all while addressing the ecological limitations of conventional mildew prevention methods.

Adverse events associated with azithromycin and clarithromycin in adults aged ≥65: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population. RESEARCH DESIGN AND METHODS: We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65. RESULTS: A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified. CONCLUSIONS: Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

Association of incretin-based therapies with hepatobiliary disorders among patients with type 2 diabetes: a case series from the FDA adverse event reporting system.

AIM: Incretin therapies, including dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), are crucial for type 2 diabetes treatment. Evidence on their association with gallbladder, biliary diseases and liver injury remains inconsistent. This study evaluated the association between incretin therapies and hepatobiliary adverse events using FDA's Adverse Event Reporting System (FAERS) data. METHODS: Case reports involving incretin therapies and hepatobiliary events from January 2006 to December 2023 were extracted from FAERS. The association between these agents and hepatobiliary adverse events (hAEs) was analyzed using reporting odds ratios and empirical Bayesian geometric means. Descriptive analyses were conducted to characterize the demographic and clinical features of the hAE cases. Additionally, subgroup analyses calculated reporting odds ratios to evaluate the strength of association between specific incretin drugs and hAEs. RESULTS: Among 68,351 case reports associated with incretin-based therapies, 1,327 (1.941%) involved hepatobiliary adverse events. DPP-4 inhibitors demonstrated statistically significant associations with multiple hepatobiliary events like cholelithiasis, cholecystitis chronic, and biliary diseases. In contrast, GLP-1 receptor agonists showed weaker associations, primarily linked to gallbladder and biliary disease risks. Subgroup analyses revealed stronger positive correlations with hepatobiliary events for liraglutide and semaglutide among GLP-1 agonists, and for sitagliptin, linagliptin, and vildagliptin among DPP-4 inhibitors. The pooled reporting odds ratio of 2.85 indicated a positive correlation between these drugs and studied adverse events. CONCLUSIONS: This study found statistically significant associations between DPP-4 inhibitors and hepatobiliary adverse events like cholelithiasis and cholecystitis. GLP-1 agonists showed weaker gallbladder/biliary disorder links but higher acute cholecystitis risk. Subgroup analyses revealed varying correlations among specific drugs, potentially dose-dependent. Further large-scale studies are needed to evaluate class effect differences and elucidate mechanisms for guiding clinical use.

The Effect of Urinary Polycyclic Aromatic Hydrocarbon Metabolites on Lipid Profiles: Does Oxidative Stress Play a Crucial Mediation Role?

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites are associated with oxidative stress; however, epidemiological studies have not reported the impacts of these urinary PAH metabolites on blood lipid levels. This study investigated the relationship between urinary PAH metabolites, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and blood lipid profiles. A total of 109 elderly volunteers were recruited with complete datasets for analysis. Blood and morning urine samples were collected in the winter of 2011. The PAH metabolites, creatinine, and 8-OHdG levels in urine samples were analyzed using Gas Chromatography-Mass Spectrometry, spectrophotometry, and an ELISA kit, respectively. The blood lipid profiles were analyzed using an automatic biochemical analyzer. The relationship between lipid profiles and 8-OHdG was assessed using a two-independent sample nonparametric test, categorized by gender, smoking, and alcohol consumption status. After normalizing the concentration values, a general linear regression model was employed to examine the correlations between PAH metabolites, 8-OHdG, and lipid profiles. A mediation model was developed to investigate the mediating effect of 8-OHdG on the relationship between PAH metabolites and lipid profiles. The median of eight PAH metabolite concentrations in urine samples ranged from 1 to 10 µmol/mol creatinine (Cr). Significant differences in lipid profiles were observed across genders. However, no significant differences were found in smoking or alcohol consumption status for both genders. Linear regression analysis revealed that an increase in the logarithmic concentration of 2-hydroxynaphthalene (2-OHNap), 9-hydroxyfluorene (9-OHFlu), 3-hydroxyfluorene (3-OHFlu), 2-hydroxyfluorene (2-OHFlu), 1-hydroxypyrene (1-OHPyr), and 6-hydroxychrysene (6-OHChr) was associated with an increase in urinary 8-OHdG levels, after adjusting for BMI and age. Specifically, 1-hydroxynaphthalene (1-OHNap) and 1-OHPyr correlated negatively with apolipoprotein A1 (Apo A1). Conversely, 1-OHPyr was positively correlated with low-density lipoprotein cholesterol (LDL-C). In addition, b,c-dihydroxyphenanthrene (2-OHBcPhe) was positively associated with apolipoprotein B (Apo B). Notably, 8-OHdG did not exhibit a significant correlation with lipid profiles. The mediating effect of 8-OHdG on the relationship between hydroxylated PAHs and lipid profiles was not statistically significant. However, the indirect effects of hydroxylated PAHs on blood lipids were statistically substantial, specifically for 1-OHNap to Apo A1 (-0.025, 95% CI: -0.041, -0.009), 1-OHPyr to LDL-C (0.107, 95% CI: 0.011, 0.203), and 2-OHBcPhe to Apo B (0.070, 95% CI: 0.005, 0.135). This study suggests that an increase in urinary PAH metabolites may elevate the levels of urinary 8-OHdG and influence blood lipid profiles. However, no direct relationship was found between 8-OHdG and lipid profiles. The mediation analysis indicated that the effects of PAH metabolites on lipid changes may operate through pathways other than oxidative stress.

A new approach to biotransformation and value of kitchen waste oil driven by gut microorganisms in Hermetia illucens.

Hermetia illucens larvae are known for their ability to recycle organic waste, but their capacity to recover waste oils and the role of gut microorganisms in this process are not fully understood. To gain further insights, the biological recovery of waste frying oil into valuable lipids and the influence of gut bacteria on this biotransformation were investigated. The larvae efficiently digested and absorbed waste frying oil, demonstrating their potential for converting various oils into insect fat. The presence of different fatty acids in their diet significantly altered gut bacterial communities, enriching certain genera such as Actinomyces, Enterococcus, and Providencia. Redundancy analysis revealed that the composition and structure of these bacterial communities were predictive of their function in the biotransformation of fatty acids and the lipid biosynthesis in the larvae. Specific bacteria, including Corynebacterium_1, Providencia, Actinomyces, Escherichia-Shigella, and others, were identified to play specialized roles in the digestion and absorption of fatty acids, contributing to lipid synthesis and storage. These findings highlight the potential of Hermetia illucens in the biological recovery of waste frying oil and underscore the crucial role of gut microbiota in this process, offering a sustainable approach to waste management and bioenergy production.

Impact of admission glucose and 30-day major adverse cardiovascular events on patients with chest pain in an emergency setting: insights from the China EMPACT registry.

Objective: Although the association between admission glucose (AG) and major adverse cardiac events (MACE) is well-documented, its relationship with 30-day MACE in patients presenting with cardiac chest pain remains unclarified. In light of this, this study aims to examine the correlation between AG levels and the incidence of MACE in patients with chest pain in an emergency setting. Materials and methods: We consecutively enrolled patients who presented to the emergency department for chest pain symptoms within 24 h from the EMPACT cohort in Eastern China (clinicaltrials.gov, Identifier: NCT02536677). The primary outcome was 30-day MACE, including all-cause death, recurrent myocardial infarction, urgent target vessel revascularization, stroke, cardiogenic shock, and cardiac arrest (CA). The associations of AG levels with 30-day MACE were analyzed using Kaplan-Meier analysis and Cox regression models. Results: Among 1,705 patients who were included in this study, 154 (9.03%) patients met the primary outcome at 30 days. The average age of the patients was 65.23 ± 12.66 years, with 1,028 (60.29%) being male and 500 (29.33%) having diabetes. The median AG levels were 7.60 mmol/L (interquartile range: 6.30-10.20). Kaplan-Meier survival analysis revealed significant differences in the 30-day MACE risk (P < 0.001 according to the log-rank test). We found that the highest AG level (Q4) was associated with increased MACE risk compared with the lowest AG level [adjusted hazard radio (aHR): 2.14; 95% confidence interval (CI): 1.2-3.815; P = 0.010]. In addition, Q4 level was also associated with increased all-cause death risk (aHR: 3.825; 95% CI: 1.613-9.07; P = 0.002) and increased CA risk (aHR: 3.14; 95% CI: 1.251-7.884; P = 0.015). Conclusions: An elevated AG level significantly correlates with a higher incidence of 30-day MACE in patients with acute chest pain. The findings reveal the importance of managing AG levels to potentially reduce the risk of adverse cardiac events.

A selective mitochondria-targeted fluorescent probe for imaging cysteine in drug-induced liver injury.

Cysteine (Cys) is involved in many physiological processes. It's challenging to detect Cys selectively as it has similar chemical structure with other biothiols such as homocysteine (Hcy) and glutathione (GSH). In this work, a novel fluorescence probe toward mitochondrial cysteine, HPXI-6C, has been developed by employing carbonate as a new recognizing unit and hemicyanine as a chromophore. HPXI-6C exhibits a high selectivity to Cys over hydrogen sulfide, homocysteine and glutathione. The limit of detection toward Cys was determined to be 42 nM. HPXI-6C can localize in mitochondria and produce strong fluorescence peaked at 725 nm in response to Cys in tumor cells. The uptake and generation pathways of Cys in acetaminophen hepatotoxicity cells was revealed by using HPXI-6C. HPXI-6C has been successfully applied in imaging of Cys in drug-induced liver injury in vivo. The research demonstrated that HPXI-6C is powerful in monitoring Cys and is conducive to the early diagnosis of drug-induced liver injury diseases.

Psychometric evaluation of patient-reported experience measures for peri-anesthesia care: A systematic review based on COSMIN guidelines.

BACKGROUND: Patient Reported Experience Measures (PREM) have become a critical component in assessing healthcare quality from the patient's perspective. Accurate and reproducible assessment tools are essential for generating robust and reliable results for evaluating peri-anesthesia patient experiences, identifying associated factors, and assessing the impact of healthcare interventions. However, there is currently no systematic review that consolidates all existing peri-anesthesia PREMs and evaluates their psychometric properties. OBJECTIVE: To identify and assess the psychometric properties of PREMs for peri-anesthesia patients. DESIGN: Systematic review of measurement properties following the COSMIN guidelines. METHODS: Systematic searches were conducted in China National Knowledge Infrastructure, Wanfang, PubMed, Embase, Web of Science, CINAHL, and PsycINFO databases from January 1, 1993, to April 15, 2024. Studies reporting on the development and/or validation of any PREMs for use in the peri-anesthesia period were considered eligible. The measurement properties extracted included data on the item development process, content validity, structural validity, internal consistency, cross-cultural validity, reliability, hypothesis testing and responsiveness. For the same PREM across different studies, reliability coefficients were analyzed using a meta-analysis. The quality assessment, rating of measurement properties, synthesis, and modified grading of the evidence were carried out following the COSMIN methodology for systematic reviews. RESULTS: A total of 26 studies encompassing 16 PREMs were included. Among them, the Patient Satisfaction with Perioperative Anesthetic Care questionnaire (PSPACq), Perception of Quality in Anesthesia (PQA), Sindhvananda General Anesthesia Satisfaction questionnaire, and Daycare Anesthesia Satisfaction (DAS) demonstrated moderate to high-quality evidence of adequate content validity and internal consistency, resulting in strong recommendations. Five PREMs exhibited high-quality evidence of inadequate structural validity and internal consistency, receiving a "not recommended" status. The remaining PREMs were weakly recommended. CONCLUSIONS: This systematic review identified PSPACq and PQA as effective tools for assessing peri-anesthesia experiences in surgical patients, suitable for both research and clinical use. Future studies should focus on thoroughly evaluating the measurement properties of these two PREMs, as many aspects remain underexplored. A high risk of bias was noted in other PREMs, particularly in content validity, structural validity, and reliability, which increases uncertainty in the evidence base. REGISTRATION: This study's protocol has been registered at PROSPERO under the registration number CRD42024537900.

A Novel Targeted Microtubules Transformable Nanopeptide System Yields Strong Anti-Prostate Cancer Effects by Suppressing Nuclear Translocation of Androgen Receptors.

The extended use of androgen deprivation therapy (ADT) may often lead to the progression from castration-sensitive prostate cancer (CSPC) to castration-resistant prostate cancer (CRPC) in prostate cancer. To address this, it is essential to inhibit the nuclear translocation of the androgen receptor (AR) as part of an effective disease-modifying strategy. Microtubules play a central role in facilitating AR nuclear translocation, highlighting their importance as a therapeutic target. In this regard, a designated as the targeted microtubules transformable nanopeptide system (MTN) is developed. This system is designed to disrupt microtubule structure and function through dual-targeting of prostate-specific membrane antigen (PSMA) and ß-tubulin. Initially, MTN targets prostate cells via PSMA and then specifically binds to ß-tubulin within microtubules, leading to the formation of nanofibers. These nanofibers subsequently induce the polymerization of microtubules, thereby disrupting AR transport. Notably, MTN exhibits efficient and prolonged suppression of prostate cancer across the spectrum from CSPC to CRPC, with a highly favorable safety profile in normal cells. These findings highlight the potential of MTN as a novel and promising approach for comprehensive prostate cancer therapy throughout its entire progression.

Polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA) are associated with the PI3K-AKT pathway activation.

Aims: We aimed to elucidate the mechanism leading to polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA). Background: PCOS is an endocrine disorder. Patients with RSA also have a high incidence rate of PCOS, implying that PCOS and RSA may share the same pathological mechanism. Objective: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) and RSA GSE113790 and GSE178535) were downloaded from the Gene Expression Omnibus (GEO) database. Methods: Datasets of PSCO and RSA patients were retrieved from the Gene Expression Omnibus (GEO) database. The "WGCNA" package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the "DAVID" database. The GSEA analysis was performed in "clusterProfiler" package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level. Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Results: The modules related to PCOS and RSA were sectioned by weighted gene co-expression network analysis (WGCNA) and positive correlation modules of PCOS and RSA were all enriched in angiogenesis and Wnt pathways. The GSEA further revealed that these biological processes of angiogenesis, Wnt and regulation of cell cycle were significantly positively correlated with the PCOS and RSA phenotypes. The intersection of the positive correlation modules of PCOS and RSA contained 80 key genes, which were mainly enriched in kinase-related signal pathways and were significant high-expressed in the disease samples. Subsequently, visualization of these genes including PDGFC, GHR, PRLR and ITGA3 showed that these genes were associated with the PI3K-AKT signal pathway. Moreover, the experimental results showed that PRLR had a higher expression in KGN cells, and that knocking PRLR down suppressed cell viability and promoted apoptosis of KGN cells. Conclusion: This study revealed the common pathological mechanisms between PCOS and RSA and explored the role of the PI3K-AKT signaling pathway in the two diseases, providing a new direction for the clinical treatment of PCOS and RSA.

Association of the systemic inflammation and anthropometric measurements with cancer risk: a prospective study in MJ cohort.

Objective: To investigate the specific role of inflammation in the connection between obesity and the overall incidence of cancer. Methods: A total of 356,554 participants in MJ cohort study were included. Systemic inflammation markers from blood samples and anthropometric measurements were determined using professional instruments. The Cox model was adopted to evaluate the association. Results: Over a median follow-up of 8.2 years, 9,048 cancer cases were identified. For individual systemic inflammation biomarkers, the overall cancer risk significantly escalated as blood C-reactive protein (CRP) (hazard ratio (HR)=1.036 (1.017-1.054)) and globulin (GLO) (HR=1.128 (1.105-1.152)) levels increased, and as hemoglobin (HEMO) (HR=0.863 (0.842-0.884)), albumin (ALB) (HR=0.846 (0.829-0.863)) and platelets (PLA) (HR=0.842 (0.827-0.858)) levels decreased. For composite indicators, most of them existed a significant relationship to the overall cancer risk. Most indicators were correlated with the overall cancer and obesity-related cancer risk, but there was a reduction of association with non-obesity related cancer risk. Most of indicators mediated the association between anthropometric measurements and overall cancer risk. Conclusions: Systemic inflammatory state was significantly associated with increased risks of cancer risk. Inflammation biomarkers were found to partly mediate the association between obesity and cancer risk.

Silver nanoparticles modified with MoS2 and ß-cyclodextrin as SERS substrate for rapid determination of cysteamine hydrochloride in meat products.

An efficient Surface-enhanced Raman scattering (SERS) method for the detection of cysteamine hydrochloride (CSH) was developed by synthesizing a composite substrate comprising silver nanoparticles (AgNPs) functionalized with MoS2 and ß-cyclodextrin (ß-CD). The enhanced Raman signals of CSH by ß-CD/MoS2/AgNPs substrate were the contribution of electromagnetic enhancement (EM) as well as chemical enhancement (CM), and the enhancement factor (EF) can reach up to 3.11 × 106 (peak at 633 cm-1). Various instrumental techniques were used to characterize the substrate, such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and ultraviolet visible (UV-vis). The binding of ß-CD/MoS2/AgNPs and CSH was confirmed by UV-vis and Fourier transform infrared (FT-IR). The optimal experimental conditions were determined by single factor experiments as well as response surface model. The influences of different metal ions and analogous drugs on the detection of CSH were investigated. Under optimum conditions, a good linear correlation (R = 0.9997) was established for CSH in the range of 10.00-1000.00 nmol/L, and the limit of detection (LOD) was as low as 0.78 nmol/L (S/N = 3). The contents of CSH in meat samples were detected. The recovery was 96.6-103.1 %, and the relative standard deviation (RSD) of the measurement was 0.7-3.9 % (n = 7).

A Rapid Head Organ Localization System Based on Clinically Realistic Images: A 3D Two Step Progressive Registration Method with CVH Anatomical Knowledge Mapping.

Rapid localization of ROI (Region of Interest) for tomographic medical images (TMIs) is an important foundation for efficient image reading, computer-aided education, and well-informed rights of patients. However, due to the multimodality of clinical TMIs, the complexity of anatomy, and the deformation of organs caused by diseases, it is difficult to have a universal and low-cost method for ROI organ localization. This article focuses on actual concerns of TMIs from medical students, engineers, interdisciplinary researchers, and patients, exploring a universal registration method between the clinical CT/MRI dataset and CVH (Chinese Visible Human) to locate the organ ROI in a low-cost and lightweight way. The proposed method is called Two-step Progressive Registration (TSPR), where the first registration adopts "eye-nose triangle" features to determine the spatial orientation, and the second registration adopts the circular contour to determine the spatial scale, ultimately achieving CVH anatomical knowledge automated mapping. Through experimentation with representative clinical TMIs, the registration results are capable of labeling the ROI in the images well and can adapt to the deformation problem of ROI, as well as local extremum problems that are prone to occur in inter-subject registration. Unlike the ideal requirements for TMIs' data quality in laboratory research, TSPR has good adaptability to incomplete and non-thin-layer quality in real clinical data in a low-cost and lightweight way. This helps medical students, engineers, and interdisciplinary researchers independently browse images, receive computer-aided education, and provide patients with better access to well-informed services, highlighting the potential of digital public health and medical education.

Predictive Biomarkers of Lymph Node Metastasis in Early Gastric Cancer: A Reference of Clinicopathological Characteristics, Protein Expression, Epstein-Barr Virus Status, and Microsatellite Instability.

BACKGROUND/AIM: Predicting lymph node metastasis (LNM) in early gastric cancer (EGC) is crucial for making treatment decisions. This study aimed to confirm risk factors for LNM and identify novel auxiliary biomarkers for predicting LNM in EGC. PATIENTS AND METHODS: We established a training set, comprising 63 patients with LNM-EGC and 274 patients with non-LNM EGC, and a test set, comprising 19 patients with LNM-EGC and 146 non-LNM EGC. Immunohistochemistry for lymphangiogenic and related pathway components (VEGF-C, TGF-ß1, SMAD2/3, VEGF-D, pSTAT3, E-cadherin, CD44, c-MET, YAP, and HER2), in situ hybridization for Epstein-Barr virus-encoded small RNAs, and multiplex PCR for microsatellite instability were conducted. RESULTS: In the training set, Lauren's diffuse/mixed classification, stromal desmoplasia, submucosal invasion ≥500 µm, lymphatic invasion, and high VEGF-C and SMAD2/3 expression were independent risk factors for LNM (p<0.05). A large tumor size, mixed histology, submucosal invasion, perineural invasion, and ulceration were determined as risk factors using univariate analysis (p<0.05). The tumor cutoff size for predicting LNM was 2.65 cm, based on a ROC analysis. The test set study verified that stromal desmoplasia, submucosal invasion, and high VEGF-C expression were independent risk factors for LNM (p<0.05). Moreover, mixed histology, lymphatic invasion, ulceration, and high SMAD 2/3 expression were identified as additional risk factors using univariate analysis (p<0.05). CONCLUSION: Stromal desmoplasia, submucosal invasion, and high VEGF-C expression are potential biomarkers for LNM in EGC. VEGF-C expression might serve as an adjunct biomarker for predicting LNM on forceps-biopsy tissue at initial diagnosis.

The impact of diabetes mellitus on tuberculosis recurrence in Eastern China: a retrospective cohort study.

BACKGROUND: The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a significant global public health issue. This study aims to explore the recurrence risk and related factors of active pulmonary TB, specifically focusing on the impact of DM. METHODS: A retrospective cohort study was conducted in Lianyungang City, Jiangsu Province, Eastern China by recruiting 12,509 individuals with newly diagnosed pulmonary TB between 2011 and 2019. The Cox proportional hazards models were performed to identify risk factors of recurrence and assess the association between DM and recurrence. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: After a median follow-up period of 5.46 years, we observed 439 recurrent cases (incident recurrence rate: 6.62 per 1000 person-years). Males (HR: 1.30, 95% CI: 1.03-1.64), patients aged ≥ 60 years (HR: 1.39, 95% CI: 1.15-1.70), DM (HR: 2.40, 95% CI: 1.68-3.45), and etiologic positivity in the initial episode (HR: 2.42, 95% CI: 2.00-2.92) had a significantly increased risk of recurrence. CONCLUSIONS: Recurrence of pulmonary TB patients who have completed treatment, especially those who also suffer from DM, should be a concern. Enhanced follow-up and targeted surveillance of these high-risk groups are needed.