Antibody-Suppressor CXCR5+CD8+ T Cells Are More Potent Regulators of Humoral Alloimmunity after Kidney Transplant in Mice Compared to CD4+ Regulatory T Cells.

Adoptive cell therapy (ACT), especially with CD4+ regulatory T cells (CD4+ Tregs), is an emerging therapeutic strategy to minimize immunosuppression and promote long-term allograft acceptance, although much research remains to realize its potential. In this study, we investigated the potency of novel Ab-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp) in comparison with conventional CD25highFoxp3+CD4+ Tregs for suppression of humoral alloimmunity in a murine kidney transplant (KTx) model of Ab-mediated rejection (AMR). We examined quantity of peripheral blood, splenic and graft-infiltrating CD8+ TAb-supp, and CD4+ Tregs in KTx recipients and found that high alloantibody-producing CCR5 knockout KTx recipients have significantly fewer post-transplant peripheral blood and splenic CD8+ TAb-supp, as well as fewer splenic and graft-infiltrating CD4+ Tregs compared with wild-type KTx recipients. ACT with alloprimed CXCR5+CD8+ T cells reduced alloantibody titer, splenic alloprimed germinal center (GC) B cell quantity, and improved AMR histology in CCR5 knockout KTx recipients. ACT with alloprimed CD4+ Treg cells improved AMR histology without significantly inhibiting alloantibody production or the quantity of splenic alloprimed GC B cells. Studies with TCR transgenic mice confirmed Ag specificity of CD8+ TAb-supp-mediated effector function. In wild-type recipients, CD8 depletion significantly increased alloantibody titer, GC B cells, and severity of AMR pathology compared with isotype-treated controls. Anti-CD25 mAb treatment also resulted in increased but less pronounced effect on alloantibody titer, quantity of GC B cells, and AMR pathology than CD8 depletion. To our knowledge, this is the first report that CD8+ TAb-supp cells are more potent regulators of humoral alloimmunity than CD4+ Treg cells.

An Ultrasensitive and Efficient microRNA Nanosensor Empowered by the CRISPR/Cas Confined in a Nanopore.

This work presents a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas-nanopipette nano-electrochemistry (Cas = CRISPR-associated proteins) capable of ultrasensitive microRNA detection. Nanoconfinement of the CRISPR/Cas13a within a nanopipette leads to a high catalytic efficacy of ca. 169 times higher than that in bulk electrolyte, contributing to the amplified electrochemical responses. CRISPR/Cas13a-enabled detection of representative microRNA-25 achieves a low limit of detection down to 10 aM. Practical application of this method is further demonstrated for single-cell and real human serum detection. Its general applicability is validated by addressing microRNA-141 and the SARS-CoV-2 RNA gene fragment. This work introduces a new CRISPR/Cas-empowered nanotechnology for ultrasensitive nano-electrochemistry and bioanalysis.

Classification of Molecular Binding Traces for Dynamic Single-Molecule Sensing.

Interference from nonspecific binding imposes a fundamental limit in the sensitivity of biosensors that is dependent on the affinity and specificity of the available sensing probes. The dynamic single-molecule sensing (DSMS) strategy allows ultrasensitive detection of biomarkers at the femtomolar level by identifying specific binding according to molecular binding traces. However, the accuracy in classifying binding traces is not sufficient from separate features, such as the bound lifetime. Here, we establish a DSMS workflow to improve the sensitivity and linearity by classifying molecular binding traces in surface plasmon resonance microscopy with multiple kinetic features. The improvement is achieved by correlation analysis to select key features of binding traces, followed by unsupervised k-clustering. The results show that this unsupervised classification approach improves the sensitivity and linearity in microRNA (hsa-miR155-5p, hsa-miR21-5p, and hsa-miR362-5p) detection to achieve a limit of detection at the subfemtomolar level.

A Bifunctional Wearable Sensor Based on a Nanoporous Membrane for Simultaneous Detection of Sweat Lactate and Temperature.

Wearable sensors for non-invasive, real-time detection of sweat lactate have far-reaching implications in the fields of health care and exercise physiological responses. Here, we propose a wearable electrochemical sensor with gold nanoelectrode arrays fabricated on the nanoporous polycarbonate (PC) membrane by encapsulating lactate oxidase (LOx) in chitosan (CS) hydrogel for detecting body temperature and sweat lactate concurrently. Flexible gold nanoporous electrodes not only enhance electrode area but also offer a nanoconfined space to accelerate the catalytic reaction of LOx and control substrate concentration on the surface of LOx to decrease substrate inhibition. The proposed sensor has a long durability of 13 days and better selectivity for the detection of sweat lactate over a wide linear range (0.01-35 mM) with a low detection limit (0.144 µM). Furthermore, temperature-dependent transmembrane currents passing through the sensor are used to estimate body temperature. We then use multiple linear regression to adjust the effect of temperature on lactate detection and succeed in monitoring lactate molecules in sweat and body temperature during exercise.

Bridging Ionic Current Rectification and Resistive-Pulse Sensing for Reliable Wide-Linearity Detection.

As two mainstream ionic detection techniques, ionic current rectification (ICR) suffers from large fluctuations in trace level detection, while resistive-pulse sensing (RPS) encounters easy clogs in high-concentration detection. By rationally matching the nanopore size with the DNA tetrahedron (TDN), this work bridges the two techniques to achieve reliable detection with wide linearity. As a representative analyte, miRNA-10b could specifically combine with and release TDN from the interior wall, which thus induced the simultaneous generation of distinct ICR and RPS signals. The ICR signals could be attributed to the balance between the effective orifice and surface charge density of the inner wall, while the RPS signals were induced by the complex of miRNA-10b and TDN passing through the nanopore. Such an operation contributed to a wide detection range of 1 fM-1 nM with a good linearity. The feasibility of this method is also validated in single-cell and real plasma detection.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

SARS-CoV-2 reinfection broadens the antibody responses and promotes the phenotypic differentiation of virus-specific memory T cells in adolescents.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation.

BACKGROUND: Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys. METHODS: Differential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes' functions in WiT-49 cells. RESULTS: The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients' prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells. CONCLUSIONS: EMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.

Exposures to drinking water disinfection byproducts and kidney function in Chinese women.

BACKGROUND: Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. OBJECTIVE: To investigate exposures to DBPs in associations with renal function among women. METHODS: A total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed. RESULTS: We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (ß = -1.78%, 95% CI: 3.21%, -0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04). CONCLUSION: Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.

A comprehensive approach to lifestyle intervention based on a calorie-restricted diet ameliorates liver fat in overweight/obese patients with NAFLD: a multicenter randomized controlled trial in China.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.

Exposure to ambient ozone and sperm quality among adult men in China.

BACKGROUND: Limited evidence exists regarding the association between ozone exposure and adverse sperm quality. We aimed to assess the association between ozone exposure and sperm quality, and identify susceptible exposure windows. METHODS: We recruited 32,541 men aged between 22 and 65 years old attending an infertility clinic in Wuhan, Hubei Province, China from 2014 to 2020. Ozone data were obtained from a satellite-based spatiotemporal model. Generalized linear models were used to estimate the association between ozone exposure and sperm quality parameters, including sperm concentration, sperm count, sperm total motility, and sperm progressive motility during the entire stage of sperm development (0-90 days before ejaculation) and three crucial stages (0-9 days, 10-14 days and 70-90 days before ejaculation). Stratified analyses were performed to evaluate whether associations varied by age, body mass index, and education levels. RESULTS: The final analysis included 27,854 adult men. A 10 µg/m3 increase in ozone concentrations during the entire stage of sperm development was associated with a -4.17 % (95 % CI: -4.78 %, -3.57 %) decrease in sperm concentration, -6.54 % (95 % CI: -8.03 %, -5.60 %) decrease in sperm count, -0.50 % (95 % CI: -0.66 %, -0.34 %) decrease in sperm total motility, and -0.07 % (95 % CI: -0.22 %, 0.09 %) decrease in sperm progressive motility. The associations were stronger during 70-90 days before ejaculation and among men with middle school and lower education for sperm concentration. CONCLUSIONS: Ozone exposure was associated with decreased sperm quality among Chinese adult men attending an infertility clinic. These results suggest that ozone may be a risk factor contributing to decreased sperm quality in Chinese men.

Investigation on Combustion Characteristics and Molecular Structures of Heiyanquan Mining Area, Xinjiang, China.

In order to comprehend the molecular composition of coal and better understand the process of coal combustion, this study involved the development of a molecular structure model for Heiyanquan coal in Xinjiang, as well as the optimization and annealing dynamics simulation of the model. Thermogravimetric analysis (TG), Fourier transform infrared spectroscopy (FTIR), and high-resolution transmission electron microscopy (HRTEM) were utilized to investigate the spontaneous combustion characteristics of coal at different temperatures (room temperature, 50-500 °C with 50 °C interval). The findings revealed that the coal primarily consists of aromatic carbon, with the aromatic structure mainly comprising naphthalene, anthracene, and phenanthrene, and the aliphatic carbon mainly consisting of CH2 and CH, along with a small quantity of minerals. The empirical molecular formula of Heiyanquan coal was determined to be C175H125O21N3. After the optimization, the total energy of the model was significantly reduced, and the aromatic layers tended to align in a regular parallel manner, with van der Waals energy playing a crucial role in maintaining structural stability. As the temperature increased, the activation energy of the three stages also increased, with the combustion stage exhibiting the highest activation energy. The presence of hydroxyl groups and oxygen-containing functional groups was found to mainly participate in the reaction, while the content of aromatic hydrocarbons remained relatively stable, C=C exhibited a decreasing trend, and C-O displayed an increasing trend. Moreover, it was observed that 1 × 1 and 2 × 2 were the predominant aromatic stripes in the coal samples, accounting for more than 90% of the total stripes.

Clinical and pathological analyses of 14 cases of angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.

Treatment of diabetic foot ulcers with external application of Chinese herbal medicine: An overview of overlapping systematic reviews.

This overview of systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically collate, appraise and synthesize evidence for the treatment of diabetic foot ulcers (DFUs) with the external application of Chinese herbal medicine (CHM). SRs/MAs of external application of CHM for DFUs were collected by searching Cochrane Library, Web of science, CNKI, PubMed, VIP, Embase and Wanfang. Two independent reviewers carried out the literature selection and data extraction. Subsequently, AMSTAR-2 tool, PRISMA, and GRADE system were applied by two reviewers independently to evaluate the methodological quality, reporting quality, and evidence quality of the included studies, respectively. Eight SRs/MAs met the eligibility criteria and were included. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the flaws of items 2, 4 and 7. The PRISMA system identified protocol and registration weaknesses, as well as search method weaknesses. With GRADE, no high-quality evidence was identified to support the role of external application of CHM for DFUs, and the quality of evidence for the vast majority of outcomes was rated as low or moderate. In conclusion, low- to moderate-quality evidence supports the promise of external application of CHM for the treatment of DFUs. Due to the limitations of the evidence supporting external application of CHM for DFUs, rigorously designed and larger samples of high-quality studies are needed going forward before broad recommendations can be made.

Catalytic ability characterization of in situ synthesized Pt NP coated SBA-15 within a sub-micropipette.

An individual catalytic entity of an n-Pt/SBA-15 composite was synthesized in situ within a sub-micropipette nanoreactor, and its size-dependent catalytic ability was evaluated using the resistance pulse signals of O2 nanobubbles, originating from H2O2 decomposition catalyzed by decorated Pt NPs in the composite.

MRI T2 mapping and shear wave elastography for identifying main pain generator in delayed-onset muscle soreness: muscle or fascia?

INTRODUCTION: The main generator of delayed onset muscle soreness (DOMS) is still unknown. This study aimed to clarify the main generator of DOMS. METHODS: Twelve participants performed eccentric exercise (EE) on lower legs. MRI and ultrasound were used to assess changes of calf muscle and deep fascia before and after EE. These results were then compared to the muscle pain level. RESULTS: Compared to baseline, muscle pain peaked at 24-48 h after EE (downstairs 22.25 ± 6.196, 57.917 ± 9.298, F = 291.168, p < 0.01; resting 5.833 ± 1.899, 5.083 ± 2.429, F = 51.678, p < 0.01). Shear wave speed (SWE) of the deep fascia and T2 values of the gastrocnemius muscle and deep fascia all increased and peaked at 48 h after EE (1.960 ± 0.130, F = 22.293; 50.237 ± 2.963, F = 73.172; 66.328 ± 2.968, F = 231.719, respectively, p < 0.01). These measurements were positively correlated with DOMS (downstairs: r = 0.46, 0.76, 0.87, respectively, p < 0.001; resting: r = 0.42, 0.70, 0.77, respectively, p < 0.001). There was a significant positive correlation between SWE and T2 values of deep fascia (r = 0.54, p < 0.01). CONCLUSION: DOMS is a common result of muscle and fascia injuries. Deep fascia edema and stiffness play a crucial role in DOMS, which can be effectively evaluated MR-T2 and SWE. CRITICAL RELEVANCE STATEMENT: Delayed-onset muscle soreness is a common result of muscle and deep fascia injuries, in which the edema and stiffness of the deep fascia play a crucial role. Both MRI and shear wave elastography can be effectively used to evaluate soft tissue injuries. KEY POINTS: • The deep fascia is the major pain generator of delayed-onset muscle soreness. • There is a significant correlation between fascia injury and delayed-onset muscle soreness. • MRI and shear wave elastography are preferred methods for assessing fascia injuries.

Ambient fine particulate matter constituents and semen quality among adult men in China.

Exposure to ambient fine particulate matter (PM2.5) was associated with decreased semen quality, but the relationship between PM2.5 constituents and semen quality was unclear. We recruited 27,824 adult men attending an infertility clinic in Wuhan, China, between 2014 and 2020. We used a four-dimensional spatiotemporal deep forest model to estimate concentrations of PM2.5 mass and its chemical constituents, including organic matter (OM), black carbon (BC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-). We employed linear regression models to estimate the association between PM2.5 mass and its constituents with various sperm parameters. Exposure to PM2.5 was associated with a reduction in sperm quality, with a percent change of - 5.69% (95% confidence interval [CI]: -8.53%, -2.85%) for sperm density, - 15.09% (95% CI: -22.24%, -7.94%) for sperm total count, - 1.63% (95% CI: -2.36%, -0.91%) for sperm progressive motility, and - 2.30% (95% CI: -3.04%, -1.55%) for sperm total motility. Among specific constituents, exposure to OM, BC, Cl-, or NO3- was associated with a reduction in these four semen quality parameters. The association was more pronounced among older men or individuals with lower levels of education. Our findings suggest that PM2.5 mass and each constituent were associated with decreased semen quality in adult men.

Analysis of network expression and immune infiltration of disulfidptosis-related genes in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a globally prevalent respiratory disease, and programmed cell death plays a pivotal role in the development of COPD. Disulfidptosis is a newly discovered type of cell death that may be associated with the progression of COPD. However, the expression and role of disulfidptosis-related genes (DRGs) in COPD remain unclear. METHODS: The expression of DRGs was identified by analyzing RNA sequencing (RNA-seq) data in COPD. Further, COPD patients were classified into two subtypes by unsupervised cluster analysis to reveal their differences in gene expression and immune infiltration. Meanwhile, hub genes associated with disulfidptosis were screened by weighted gene co-expression network analysis. Subsequently, the hub genes were validated experimentally in cells and animals. In addition, we screened potential therapeutic drugs through the hub genes. RESULTS: We identified two distinct molecular clusters and observed significant differences in immune cell populations between them. In addition, we screened nine hub genes, and experimental validation showed that CDC71, DOHH, PDAP1, and SLC25A39 were significantly upregulated in cigarette smoke-induced COPD mouse lung tissues and bronchial epithelial cells (BEAS-2B) treated with cigarette smoke extract. Finally, we predicted 10 potential small molecule drugs such as Atovaquone, Taurocholic acid, Latamoxef, and Methotrexate. CONCLUSION: We highlighted the strong association between COPD and disulfidptosis, with DRGs demonstrating a discriminative capacity for COPD. Additionally, the expression of certain novel genes, including CDC71, DOHH, PDAP1, and SLC25A39, is linked to COPD and may aid in the diagnosis and assessment of this condition.

Correlation Between NLR Combined with PLR Score and Prognosis of Hepatocellular Carcinoma After Liver Transplantation.

Background: This investigation evaluated the prognostic significance of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and introduced a combined NLR-PLR score to evaluate the correlation between NLR-PLR score and hepatocellular carcinoma (HCC) recurrence. Material/Methods: We enrolled 110 patients who underwent orthotopic liver transplantation (LT) for HCC. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were assessed, and appropriate cut-off values were established. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (≥3.37) and high PLR (≥105.96); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. Results: The median overall survival (OS) of patients with NLR-PLR score of 0, 1 and 2 was 27, 26.5, and 6 months, respectively. The median OS of patients with NLR-PLR score of 2 was shorter than those with 0 (P < 0.001) and 1 (P < 0.001). The median disease-free survival (DFS) time of patients with NLR-PLR score of 0, 1 and 2 was 24.5, 24, and 6 months, The median DFS of patients with NLR-PLR score of 2 was shorter than those with 0 (P = 0.001) and 1 (P = 0.015). Multivariate analysis showed that NLR-PLR score was an independent risk factor for prognosis and survival. Conclusion: NLR, PLR and NLR-PLR score can predict the long-term survival of patients, and NLR-PLR score, having more predictive value than NLR and PLR alone is an independent risk factor for patient survival. more predictive value than NLR and PLR alone.