Association of serum uric acid with male sexual hormones and erectile dysfunction: a bidirectional 2-sample Mendelian randomization analysis.

Background: Observational studies indicated that serum uric acid (SUA) was associated with male sexual hormones and erectile dysfunction (ED). However, their relationship was still heterogeneous. Aim: This study conducted 2-sample univariate mendelian randomization (UVMR) and multivariate mendelian randomization (MVMR) to explore the causal relationship between SUA and sexual hormones as well as ED. Methods: Genetic variants associated with SUA were derived from the UK Biobank database (N = 437 354). Outcomes from the IEU Open GWAS and summary data sets were sexual hormones (sex hormone-binding globulin [SHBG], testosterone, estradiol [E2], follicle-stimulating hormone, luteinizing hormone) and ED, with 3301 to 625 650 participants. UVMR analysis primarily utilized the inverse variance weighted method, complemented by MVMR analysis. Thorough sensitivity analyses were carried out to ensure the reliability of results. Moreover, mediation analysis was conducted to estimate the mediated effect between SUA and outcomes. Outcomes: The primary outcomes included results of UVMR and MVMR analysis and mediation analysis, along with sensitivity analyses involving the Cochran Q test, the MR Egger intercept test, leave-1-out analysis, and the MR-PRESSO method (mendelian randomization pleiotropy residual sum and outlier). Results: UVMR analysis revealed that an elevated SUA level could decrease levels of SHBG (ß = -0.10, P = 1.70 × 10-7) and testosterone (ß = -0.10, P = 5.94 × 10-3) and had a positive causal effect on ED (odds ratio, 1.10; P = .018). According to reverse mendelian randomization results, increased levels of SHBG (ß = -0.06, P = 4.82 × 10-4) and E2 (ß = -0.04, P = .037) could also reduce SUA levels. As shown by MVMR analysis, SUA had a negative effect on SHBG and testosterone levels (P < .05), while the significant causal relationship between SUA and ED disappeared. Furthermore, SHBG mediated 98.1% of the effect of SUA on testosterone levels. Results of other mendelian randomization analyses were not statistically significant. No pleiotropy was found by sensitivity analysis in this study. Clinical Implications: Given the causal relationship between SUA and sexual hormones, we must focus on SUA and E2 levels in men, especially patients with hypogonadism and ED. Strengths and Limitations: This study evaluated the causal effect of SUA on male sexual hormones and ED genetically for the first time, clarifying the common biases in observational studies and confirming the negative relationship between SUA and testosterone level. Limitations include a population based on European ancestry, some crossover of the samples, and unobserved confounding factors. Conclusion: Genetic studies provide evidence for the causal relationship between SUA and male sexual hormones (SHBG, testosterone, E2), while the relationship between SUA and ED should be further evaluated.

High-Resolution Haplotyping of the PAH Gene Enables Early Gestation Noninvasive Prenatal Diagnosis of Phenylketonuria and Evolution Analysis of Recurrent Pathogenic Variations.

BACKGROUND: The clinical performance of RHDO-based NIPD for PKU during early gestation remains under-evaluated. Furthermore, studies focused on SNP loci obtained by next-generation sequencing to analyze the genetic evolution of pathogenic variations in PKU is limited. METHODS: Maternal peripheral blood, along with proband and paternal samples, was collected between 7 and 12 weeks of gestation. The PAH gene and surrounding high heterozygosity SNPs were targeted for enrichment and sequencing. Fetal genotypes were inferred using RHDO-based NIPD. High-resolution PAH haplotypes were used for the analysis of two common pathogenic variants in the Chinese population: c.728G>A and c.1238G>C. RESULTS: Sixty one PKU families participated with an average fetal fraction of 6.08%. The median gestational age was 8+6 weeks. RHDO-based NIPD successfully identified fetal genotypes in 59 cases (96.72%, 59/62). Two cases failed because of insufficient informative SNPs. In addition, a recombination event was assessed in one fetus of 59 cases. Six, and three haplotypes were identified for c.728G>A(p.Arg243Gln) and c.1238G>C(p.Arg413Pro), respectively. Hap_3 and hap_8 were identified as the ancestral haplotypes for these pathogenic variants, with other haplotypes arising from mutations or recombination based on these ancestral haplotypes. CONCLUSIONS: This study validates the feasibility of an RHDO-based assay for NIPD of PKU in early pregnancy and introduces its application in the demonstration of founder effects in recurrent pathogenic variations, offering new insights into the evolutionary analysis of PAH variations.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study.

Background: Volatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. Methods: In a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40-75 years, 58% women, enrollment: 2004-2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. Results: There were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. Conclusion: Our findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.

ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC. METHODS: We first conducted analyses utilizing data from both TCGA and GEO datasets to explore ITGB3 expression in ccRCC tissues. Subsequently, we evaluated the association between ITGB3 expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between ITGB3 and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate ITGB3 expression and its association with immune cell infiltration. RESULTS: Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher ITGB3 expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between ITGB3 and immune and methylation-related pathways, while ITGB3 transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and ITGB3 expression. CONCLUSION: Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of ITGB3, coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.

Interference of ATP-Adenosine Axis by Engineered Biohybrid for Amplifying Immunogenic Cell Death-Mediated Antitumor Immunotherapy.

Immunogenic cell death (ICD) often results in the production and accumulation of adenosine (ADO), a byproduct that negatively impacts the therapeutic effect as well as facilitates tumor development and metastasis. Here, an innovative strategy is elaborately developed to effectively activate ICD while avoiding the generation of immunosuppressive adenosine. Specifically, ZIF-90, an ATP-responsive consumer, is synthesized as the core carrier to encapsulate AB680 (CD73 inhibitor) and then coated with an iron-polyphenol layer to prepare the ICD inducer (AZTF), which is further grafted onto prebiotic bacteria via the esterification reaction to obtain the engineered biohybrid (Bc@AZTF). Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (αPD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism.

Strategies to attenuate maladaptive inflammatory response associated with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) initiates an intense inflammatory response due to various factors: conversion from pulsatile to laminar flow, cold cardioplegia, surgical trauma, endotoxemia, ischemia-reperfusion injury, oxidative stress, hypothermia, and contact activation of cells by the extracorporeal circuit. Redundant and overlapping inflammatory cascades amplify the initial response to produce a systemic inflammatory response, heightened by coincident activation of coagulation and fibrinolytic pathways. When unchecked, this inflammatory response can become maladaptive and lead to serious postoperative complications. Concerted research efforts have been made to identify technical refinements and pharmacologic interventions that appropriately attenuate the inflammatory response and ultimately translate to improved clinical outcomes. Surface modification of the extracorporeal circuit to increase biocompatibility, miniaturized circuits with sheer resistance, filtration techniques, and minimally invasive approaches have improved clinical outcomes in specific populations. Pharmacologic adjuncts, including aprotinin, steroids, monoclonal antibodies, and free radical scavengers, show real promise. A multimodal approach incorporating technical, circuit-specific, and pharmacologic strategies will likely yield maximal clinical benefit.

Breast tumor segmentation via deep correlation analysis of multi-sequence MRI.

Precise segmentation of breast tumors from MRI is crucial for breast cancer diagnosis, as it allows for detailed calculation of tumor characteristics such as shape, size, and edges. Current segmentation methodologies face significant challenges in accurately modeling the complex interrelationships inherent in multi-sequence MRI data. This paper presents a hybrid deep network framework with three interconnected modules, aimed at efficiently integrating and exploiting the spatial-temporal features among multiple MRI sequences for breast tumor segmentation. The first module involves an advanced multi-sequence encoder with a densely connected architecture, separating the encoding pathway into multiple streams for individual MRI sequences. To harness the intricate correlations between different sequence features, we propose a sequence-awareness and temporal-awareness method that adeptly fuses spatial-temporal features of MRI in the second multi-scale feature embedding module. Finally, the decoder module engages in the upsampling of feature maps, meticulously refining the resolution to achieve highly precise segmentation of breast tumors. In contrast to other popular methods, the proposed method learns the interrelationships inherent in multi-sequence MRI. We justify the proposed method through extensive experiments. It achieves notable improvements in segmentation performance, with Dice Similarity Coefficient (DSC), Intersection over Union (IoU), and Positive Predictive Value (PPV) scores of 80.57%, 74.08%, and 84.74% respectively.

Enabling AI-Generated Content for Gadolinium-Free Contrast-Enhanced Breast Magnetic Resonance Imaging.

BACKGROUND: There is increasing interest in utilizing AI-generated content for gadolinium-free contrast-enhanced breast MRI. PURPOSE: To develop a generative model for gadolinium-free contrast-enhanced breast MRI and evaluate the diagnostic utility of the generated scans. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-six women with 304 breast MRI examinations (49 ± 13 years, 243/61 for training/testing). FIELD STRENGTH/SEQUENCE: ZOOMit diffusion-weighted imaging (DWI), T1-weighted volumetric interpolated breath-hold examination (T1W VIBE), and axial T2 3D SPACE at 3.0 T. ASSESSMENT: A generative model was developed to generate contrast-enhanced scans using precontrast T1W VIBE and DWI images. The generated and real images were quantitatively compared using the structural similarity index (SSIM), mean absolute error (MAE), and Dice similarity coefficient. Three radiologists with 8, 5, and 5 years of experience independently rated the image quality and lesion visibility on AI-generated and real images within various subgroups using a five-point scale. Four breast radiologists, with 8, 8, 5, and 5 years of experience, independently and blindly interpreted four reading protocols: unenhanced MRI protocol alone and combined with AI-generated scans, abbreviated MRI protocol, and full-MRI protocol. STATISTICAL ANALYSIS: Results were assessed using t-tests and McNemar tests. Using pathology diagnosis as reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each reading protocol. A P value <0.05 was considered significant. RESULTS: In the test set, the generated images showed similarity to the real images (SSIM: 0.935 ± 0.047 [SD], MAE: 0.015 ± 0.012 [SD], and Dice coefficient: 0.726 ± 0.177 [SD]). No significant difference in lesion visibility was observed between real and AI-generated scans of the mass, non-mass, and benign lesion subgroups. Adding AI-generated scans to the unenhanced MRI protocol slightly improved breast cancer detection (sensitivity: 92.86% vs. 85.71%, NPV: 76.92% vs. 70.00%); achieved non-inferior diagnostic utility compared to the AB-MRI protocol and full-protocol (sensitivity: 92.86%, 95.24%; NPV: 75.00%, 81.82%). DATA CONCLUSION: AI-generated gadolinium-free contrast-enhanced breast MRI has potential to improve the sensitivity of unenhanced MRI in detecting breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Cross-sectional study of hepatitis B virus infection in female breast cancer patients in China for the first time diagnosed.

BACKGROUND: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations. METHODS: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups. RESULTS: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups. CONCLUSIONS: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

Role of gut/liver metabolites and gut microbiota in liver fibrosis caused by cholestasis.

AIM OF THE STUDY: Cholestasis induces severe liver injury and subsequent liver fibrosis. However, a comprehensive understanding of the relationships between liver fibrosis and cholestasis-induced changes in metabolites in the gut and fibrotic liver tissue and in the gut microbiota is insufficient. METHODS: Common bile duct ligation (BDL) was employed to establish a cholestatic liver fibrosis model in mice for 26 days. Fibrotic liver tissue and the gut contents were collected. Untargeted metabolomics was conducted for the determination of metabolites in the gut contents and liver tissues. Metagenomics was adopted to explore the gut microbiota. RESULTS: The metabolites in the gut contents and liver tissues between normal and cholestatic liver fibrosis mice were highly distinct. Beta-alanine metabolism and glutathione metabolism were downregulated in the gut of the BDL group. Galactose metabolism, biosynthesis of unsaturated fatty acids, and ABC transporters were upregulated in the gut and downregulated in the liver of the BDL group. Arginine biosynthesis, taurine and hypotaurine metabolism, arginine and proline metabolism, and primary bile acid biosynthesis were downregulated in the gut and upregulated in the liver of the BDL group. Metagenomic analysis revealed that the alpha diversity of the microbiota in the BDL group decreased. The altered structure of the gut microbiota in the BDL group led to the hypofunction of important metabolic pathways (such as folate biosynthesis, histidine metabolism, thiamine metabolism, biotin metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis) and enzymes (such as NADH, DNA helicase, and DNA-directed DNA polymerase). Correlation analyses indicated that certain gut microbes were associated with gut and liver metabolites. CONCLUSIONS: Untargeted metabolomics and metagenomics provided comprehensive information on gut and liver metabolism and gut microbiota in mice with cholestatic liver fibrosis. Therefore, significantly altered bacteria and metabolites may help provide some targets against cholestatic liver fibrosis in the future.

F11R RNA trinucleotide over-edited by ADAR in gastric and colorectal cancers: Cross-cohort validation, gene expression regulation, and diagnostic significance.

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.

Co-pyrolysis Behavior of Coal and Biomass: Synergistic Effect and Kinetic Analysis.

Co-pyrolysis of coal and biomass is an efficient way to utilize resources. This study investigates the co-pyrolysis behavior and kinetics of coal and biomass using thermogravimetric analysis (TGA) and TG-FTIR. Co-pyrolysis of coal and biomass exhibits a synergistic effect. When the biomass is 25%, the weight loss increases, showing a positive synergistic effect. When the biomass is 50%, it exhibits a negative synergistic effect. Increasing the heating rate can promote the generation of a synergistic effect. Co-pyrolysis involves two central pyrolysis stages: stage III (250-380 °C) and stage IV (380-550 °C). Friedman, FWO, KAS, and STA methods are used to calculate the activation energy for stages III and IV. The activation energy (E α) for co-pyrolysis is higher than that for coal or biomass pyrolysis alone. A positive synergistic effect is observed in stage III, while a negative synergistic effect is noted in stage IV. The master curve method determines an accurate reaction order (n) and pre-exponential factor (A) value of Coal75-Bio25. In stage III, E α = 238.81 kJ/mol, n = 2.4, A = 1.30 × 1021 s-1. In stage IV, E α = 37 8.01 kJ/mol, n = 4.0, A = 1.10 × 1027 s-1. The kinetic parameters in stage IV are significantly higher than those in stage III. TG-FTIR is used to analyze the synergistic effect of co-pyrolysis. Compared with coal and biomass pyrolysis separately, the Coal75-Bio25 pyrolysis process releases less CO2 and more CH4. These findings support the synergistic effect of coal and biomass during co-pyrolysis.

Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.

BACKGROUND: Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties. RESULTS: By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level. CONCLUSION: This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.

Robust stability of Boolean networks with data loss and disturbance inputs.

This study discusses the robust stability problem of Boolean networks (BNs) with data loss and disturbances, where data loss is appropriately described by random Bernoulli distribution sequences. Firstly, a BN with data loss and disturbances is converted into an algebraic form via the semi-tensor product (STP) technique. Accordingly, the original system is constructed as a probabilistic augmented system, based on which the problem of stability with probability one for the original system becomes a set stability with probability one for the augmented system. Subsequently, certain criteria are proposed for the robust stability of the systems. Moreover, an algorithm is developed to verify the robust set stability of the augmented system based on truth matrices. Finally, the validity of the obtained results is demonstrated by an illustrative example.

Bibliometric and Visual Analysis of Studies on Ceramic Membranes: A Review.

As a high-performance separation material, the ceramic membrane has played a crucial role in addressing resource, energy, and environmental challenges. Here, we carried out literature retrieval and collection for the research of ceramic membranes based on the Web of Science. The retrieval strategy was quantitatively evaluated from two dimensions: recall and precision. The distributions of publication time, journal, and related subjects were systematically analyzed. With the help of CiteSpace and VOSviewer, the literature was visually analyzed through the co-occurrence map of authors and the cluster network of keywords. The findings indicate a strong correlation between ceramic membrane research and the field of Chemical Engineering. A core group of authors has emerged as prominent contributors in this area of study. Additionally, there is a notable long-tail effect observed in the application of ceramic membranes. Despite their current low-frequency usage and high-volume potential, these applications hold substantial promise for future scientific research and industrial development.

Imbalance polarization of M1/M2 macrophages in miscarried uterus.

BACKGROUND: Lipopolysaccharides (LPS) is well known to manifest a miscarriage-inducing effector during early pregnancy and activate macrophage to induce M1 macrophage polarization. However, the role of macrophage polarization in LPS-related miscarriage-inducing effect is not apparent. METHODS: In this work, gene expression changes and the percentage of M1/M2 macrophages and monocytes in LPS-induced miscarried uterus were firstly analyzed by RNA sequencing (RNA-seq) and Flow Cytometry. To explore the origin that contributes to M1/M2 macrophage differentiation, the expression of monocyte chemotactic protein (MCP-1), CCL3, and CCL4, chemokines related to monocyte/macrophage migration, was tested by quantitative real time PCR (qRT-PCR). RESULTS: We found that percentage of M1 macrophages rose, while the percentage of M2 macrophages declined down in the injected mice uterus. Meanwhile, the percentage of M1 and M2 macrophages showed no significant difference in the spleens of LPS injected mice compared to PBS injected control mice. Expression of Mcp-1, Ccl3, and Ccl4 and numbers of monocytes were remarkably up-regulated in LPS-induced miscarried mice uterus. CONCLUSION: These results indicated that polarization and proportion changes of macrophage in the uterus may contribute to miscarriage. Our work provides new evidence correlating the aberrant regulation of M1/M2 macrophage polarization with deleterious miscarriage-inducing effects. This will help us understand the roles of critical immune cell differentiation in maintaining normal pregnancy.

An Autoclavable and Transparent Thermal Cutter for Reliably Sealing Wet Nanofibrous Membranes.

Sealing wet porous membranes is a major challenge when fabricating cell encapsulation devices. Herein, we report the development of an Autoclavable Transparent Thermal Cutter (ATTC) for reliably sealing wet nanofibrous membranes. Notably, the ATTC is autoclavable and transparent, thus enabling in situ visualization of the sealing process in a sterile environment and ensuring an appropriate seal. In addition, the ATTC could generate smooth, arbitrary-shaped sealing ends with excellent mechanical properties when sealing PA6, PVDF, and TPU nanofibrous tubes and PP microporous membranes. Importantly, the ATTC could reliably seal wet nanofibrous tubes, which can shoulder a burst pressure up to 313.2 ± 19.3 kPa without bursting at the sealing ends. Furthermore, the ATTC sealing process is highly compatible with the fabrication of cell encapsulation devices, as verified by viability, proliferation, cell escape, and cell function tests. We believe that the ATTC could be used to reliably seal cell encapsulation devices with minimal side effects.

Construction of Iron-Scavenging Hydrogel via Thiol-Ene Click Chemistry for Antibiotic-Free Treatment of Bacterial Wound Infection.

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections.

Association between Triglyceride-Glucose Index and risk of all-cause and cardiovascular mortality in adults with prior cardiovascular disease: a cohort study using data from the US National Health and Nutrition Examination Survey, 2007-2018.

OBJECTIVE: The association between the Triglyceride-Glucose (TyG) Index and mortality rates in patients with cardiovascular disease (CVD) remains unclear. This study investigates the association between the TyG index and the incidence of all-cause and CVD-specific mortality among individuals with a history of CVD. DESIGN: Population-based cohort study. SETTING: Data were sourced from the US National Health and Nutrition Examination Survey (2007-2018) and linked mortality data, with follow-up continuing until 31 December 2019. PARTICIPANTS: The study population comprised 3422 individuals aged 20 years or older with a documented history of CVD. OUTCOME MEASURES: We examined the association between the TyG index and the risk of all-cause and cardiovascular mortality. RESULTS: Over a median follow-up of 5.79 years, 1030 deaths occurred, including 339 due to CVD. Cox regression analysis, adjusted for multiple confounders, showed that individuals in the highest TyG index quartile, compared with those in the lowest, had HRs of 0.76 (95% CI: 0.60 to 0.96) for all-cause mortality and 0.58 (95% CI: 0.39 to 0.89) for CVD mortality. There was a significant inverse relationship between higher TyG index levels and lower mortality risks. For each unit increase in the TyG index, the adjusted HRs for all-cause and CVD mortality decreased by 18% (HR 0.82; 95% CI: 0.71 to 0.94) and 27% (HR 0.73; 95% CI: 0.57 to 0.92), respectively. CONCLUSIONS: TyG index values are negatively associated with all-cause and CVD mortality risks among individuals with previous CVD. Further interventional studies are needed to clarify the impact of TyG levels on cardiovascular health.