No causal relationship between serum vitamin D levels and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

Background: Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD. Methods: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed. Results: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results. Conclusion: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.

Pharmacokinetics and Bioavailability Study of a Novel Smoothened Inhibitor TPB15 for Treatment of Triple-Negative Breast Cancer in Rats by High Performance Liquid Chromatography-Mass Spectrometry.

BACKGROUND AND OBJECTIVES: Smoothened (SMO), a key component of the hedgehog signaling pathway, represents a therapeutic target for triple negative breast cancer (TNBC), yet the chemotherapy response rate in TNBC patients is only 40-50%, underscoring the urgent need for the development of novel drugs to effectively treat this condition. The novel compound TPB15, an SMO inhibitor derived from [1,2,4] triazolo [4,3-α] pyridines, demonstrated superior anti-TNBC activity and lower toxicity compared to the first SMO inhibitor vismodegib in both in vitro and in vivo. However, the compound's pharmacokinetic properties remain unclear. The present work aims to develop a simple HPLC-MS/MS method to profile the pharmacokinetics and bioavailability of TPB15 in rats as a ground work for further clinical research. METHODS: Separation was performed on an Agilent ZORBAX StableBond C18 column by gradient elution using acetonitrile and 0.1% formic acid as mobile phase at a flow rate of 0.3 mL/min. Multiple reaction monitoring(MRM) in positive mode with the transitions of m/z 454.2 → 100.0, 248.1 → 121.1 was employed to determine TPB15 and internal standard tinidazole, respectively. The specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover of the method was validated. The pharmacokinetics and bioavailability  study of TPB15 were carried out on rats through intravenous injection at the dose of 5 mg/kg and oral gavage at the dose of 25 mg/kg, and the pharmacokinetics parameters were calculated by the non-compartment analysis using the pharmacokinetics software DAS 2.1.1. RESULTS: The values of specificity, intra- and inter- day precision and accuracy, extraction recovery, stability, matrix effect, dilution integrity and carryover satisfied the acceptable limits. The lower limit of quantification of this method was 10 ng/mL with a linear range of 10-2000 ng/mL. The validated method was then applied to pharmacokinetics and bioavailability studies in rat by dosing with gavage (25 mg/kg) and intravenous injection(5 mg/kg), and the oral bioavailability of TBP15 in rat was calculated as 16.4 ± 3.5%. The pharmacokinetic parameters were calculated as following: maximum of plasma concentration (Cmax) (PO: 2787.17 ± 279.45 µg/L), Time to maximum plasma concentration (Tmax) (PO: 4.20 ± 0.90 h), the area under the concentration-time curve 0 to time (AUC0-t) (PO: 17,373.03 ± 2585.18 ng/mL·h, IV: 21,129.79 ± 3360.84 ng/mL·h), the area under the concentration-time curve 0 to infinity (AUC0-∞) (PO: 17,443.85 ± 2597.63 ng/mL·h, IV: 17,443.85 ± 2597.63 ng/mL·h), terminal elimination half-life (t1/2) (PO: 7.26 ± 2.16 h, IV: 4.78 ± 1.09 h). CONCLUSIONS: TPB15, a promising candidate for treating TNBC, has demonstrated outstanding efficacy and safety in vitro and in vivo. This study established a simple, sensitive, and rapid HPLC-MS/MS bioanalytical method, developed and validated in accordance with FDA and EMA guidelines, for conducting pharmacokinetic and bioavailability studies of TPB15. The results revealed a favorable pharmacokinetic profile owing to its long t1/2. Nevertheless, the next phase of research should include formulation screening to enhance bioavailability, as well as clinical trials, metabolism pathway analysis, and assessment of potential drug-drug interactions.

Particle swarm algorithm-based identification method of optimal measurement area of coordinate measuring machine.

A particle swarm algorithm-based identification method for the optimal measurement area of large coordinate measuring machines (CMMs) is proposed in this study to realize the intelligent identification of measurement objects and optimize the measurement position and measurement space using laser tracer multi-station technology. The volumetric error distribution of the planned measurement points in the CMM measurement space is obtained using laser tracer multi-station measurement technology. The volumetric error of the specified step distance measurement points is obtained using the inverse distance weighting (IDW) interpolation algorithm. The quasi-rigid body model of the CMM is solved using the LASSO algorithm to obtain the geometric error of the measurement points in a specified step. A model of individual geometric errors is fitted with least squares. An error optimization model for the measurement points in the CMM space is established. The particle swarm optimization algorithm is employed to optimize the model, and the optimal measurement area of the CMM airspace is determined. The experimental results indicate that, when the measurement space is optimized based on the volume of the object being measured, with dimensions of (35 × 35 × 35) mm3, the optimal measurement area for the CMM, as identified by the particle swarm algorithm, lies within the range of 150 mm < X < 500 mm, 350 mm < Y < 700 mm, and -430 mm < Z < -220 mm. In particular, the optimal measurement area is defined as 280 mm < X < 315 mm, 540 mm < Y < 575 mm, and -400 mm < Z < -365 mm. Comparative experiments utilizing a high-precision standard sphere with a diameter of 19.0049 mm and a sphericity of 50 nm demonstrate that the identified optimal measurement area is consistent with the results obtained through the particle swarm algorithm, thereby validating the correctness of the method proposed in this study.

Nanoscale hyperthermia mesostructures for sustainable antimicrobial design.

Sustainability is critical in addressing global challenges posed by prolonged pandemics that impact health, economies, and the environment. Here, we introduce a molecular engineering approach for thermoregulated antimicrobial management inspired by firewalking rituals. The study uses in situ spectroscopy and multi-scale modeling to validate a hierarchical design. Efficient light-to-thermal energy conversion is achieved by engineering the molecular band structure. Rapid nanoscale hyperthermia is facilitated through thermal engineering. This approach significantly reduces the half-life of pathogens such as Escherichia coli, influenza A, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to 1.4 min while maintaining a low perceived temperature on human skin. Standard disease infection and epidemic models show this technology's potential to flatten outbreak curves and delay peak infection rates, which is crucial during the early stages of pandemics when developing vaccines and antiviral drugs takes time. The scalable manufacturing and broad antimicrobial applicability hold great promise for controlling emerging infectious diseases and diverse bioprotective applications.

Research Progress of Vagal Nerve Regulation Mechanism in Acupuncture Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.

IBD functions as a double-edged sword for food allergy in BALB/c mice model.

Inflammatory bowel disease (IBD) and food allergy (FA) increase in tandem, but the potential impact of IBD on FA remains unclear. We sought to determine the role of IBD on FA. We first assessed the changes of FA-related risk factors in dextran sulphate sodium salt (DSS) induced colitis mice model. Then, we evaluated the role of IBD on FA in mice. FA responses were determined using a clinical allergy score, body temperature change, serum antibody levels, cytokines level and mouse mast cell protease 1 (MMCP-1) concentration. Accumulation of regulatory T cells was tested using flow cytometry. Intestinal changes were identified by histology, immunohistochemistry, gene expression and gut microbial community structure. In DSS-induced colitis mice model, we found the intestinal damage, colonic neutrophil infiltration, and downregulation of splenic Th2 cytokines and Tregs in mesenteric lymph nodes (MLN). Moreover, we also found that IBD can alleviate the FA symptoms and lead to the significant downregulation of Th2 cytokines, serum IgE and MMCP-1. However, IBD exacerbates intestinal injury and promotes the gene expression levels of IL-33 and IL-5 in the small intestine, damages the intestinal tissue structure and aggravates intestinal dysbiosis in FA. IBD functions as a double-edged sword in FA. From the perspective of clinical symptoms and humoral immune responses, IBD can reduce FA response by downregulating Th2 cytokines. But from the perspective of the intestinal immune system, IBD potentially disrupts intestinal tolerance to food antigens by damaging intestinal tissue structure and causing intestinal dysbiosis.

[Analysis of correlation between high expression of nucleoporin 85 (NUP85) and immune cell infiltration in hepatocellular carcinoma].

Objective To investigate the significance of nucleoporin 85 (NUP85) ex-pression in hepatocellular carcinoma (HCC) and analyze its relevance to immune response. Methods A comprehensive analysis was conducted using various online databases to assess the mRNA and protein expression of NUP85 in HCC, as well as its mutation status and prognostic diagnostic value. The immune relevance of NUP85 was evaluated using single-cell sequencing data and resources from the Tumor Immune Estimation Resource (TIMER) and the Gene Expression Profiling Interactive Analysis 2021 (GEPIA2021) databases. The drug sensitivity of NUP85 was analyzed through the Genomic Landscape of Cancer (GSCA) and the Clinical Bioinformatics Home. Co-expressed genes of NUP85 in HCC were filtered using the Hepatocellular Carcinoma Comprehensive Molecular Database (HCCDB), and the correlation between NUP85 and its related genes was analyzed using the R language "limma" package. The gene ontology (GO) functions, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) of NUP85 and its related genes were performed using the R language "clusterProfiler" package. The Clinical Bioinformatics Home was utilized to construct heatmaps and prognostic risk scoring models for NUP85 and its related genes. Results NUP85 mRNA and protein expression were upregulated in HCC, showing high levels across dif-ferent stages and grades, which indicates a poor prognosis for patients. The mutation rate of NUP85 in HCC samples was 19%, significantly affecting the overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) of patients. NUP85 was highly expressed in various immune cells, including macrophages, B cells, and T cells, and was positively correlated with the infiltration levels of multiple immune cells. The expression of NUP85 was significantly correlated with multiple drugs, such as Milademetan (PD0325901), a structural analog of Vemurafenib (PLX4720), and Regorafenib (PD0325901). The GO functions of NUP85 and its co-expressed genes were mainly enriched in organelle fission, nuclear division, and chromosome segregation, while the KEGG pathways were primarily enriched in the cell cycle and kinesin proteins. These factors significantly and unfavorably affected the OS of HCC patients, and the areas under the ROC curve (AUC) for the 1-year, 3-year, and 5-year OS prognostic diagnosis of HCC patients were all greater than 0.7. Conclusion The high expression of NUP85 in HCC is correlated with a poor prognosis and is related to various immune cells and drugs, making it a potential biomarker for di-agnosis, treatment, and prognosis in HCC.

The prognostic role of lymphocyte-to-monocyte ratio in patients with resectable pancreatic cancer: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. Patients and Methods: This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). Results: A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44-0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57-0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66-0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22-0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16-1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47-0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67-0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08-0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47-0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32-0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09-1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54-0.80], I2 = 53%, P = 0.04) and <7 (HR = 0.41, CI [0.23-0.72], I2 = 89%, P < 0.00001), LMR was demonstrated to have predictive value. Conclusion: Despite the observed heterogeneity and potential biases in the included studies, the findings of this study suggest that LMR may serve as a valuable predictor of OS in patients with resectable pancreatic cancer.

The hidden RNA viruses in Blattodea (cockroaches and termites).

The insect order Blattodea (cockroaches and termites) has drawn substantial research attention for their dietary habits and lifestyle of living with or around humans. In the present study, we focused on the discovery of RNA viruses hidden in Blattodea insects using the publicly available RNA sequencing datasets. Overall, 136 distinctive RNA viruses were identified from 36 Blattodea species, of which more than 70 % were most closely related to the invertebrate-associated viral groups within Picornavirales, Sobelivirales, Bunyaviricetes, Jingchuvirales, Durnavirales, Lispiviridae, Orthomyxoviridae, Permutotetraviridae, Flaviviridae and Muvirales. Several viruses were associated with pathogens of vertebrates (Paramyxoviridae), plants (Tymovirales), protozoa (Totiviridae), fungi (Narnaviridae) and bacteria (Norzivirales). Collectively, 93 complete or near-complete viral genomes were retrieved from the datasets, and several viruses appeared to have remarkable temporal and spatial distributions. Interestingly, the newly identified Periplaneta americana dicistrovirus displayed a remarkable distinct bicistronic genome arrangement from the well-recognized dicistroviruses with the translocated structural and non-structural polyprotein encoding open reading frames over the genome. These results significantly enhance our knowledge of RNA virosphere in Blattodea insects, and the novel genome architectures in dicistroviruses and other RNA viruses may break our stereotypes in the understanding of the genomic evolution and the emergence of potential novel viral species.

Further evidence from DNAH12 supports favorable fertility outcomes of infertile males with dynein axonemal heavy chain gene family variants.

Male infertility is a major concern affecting reproductive health. Biallelic deleterious variants of most DNAH gene family members have been linked to male infertility, with intracytoplasmic sperm injection (ICSI) being an efficacious way to achieve offspring. However, the association between DNAH12 and male infertility is still limited. Here, we identified one homozygous variant and two compound heterozygous variants in DNAH12 from three infertile Chinese men. Semen analysis revealed severe asthenozoospermia, abnormal morphology, and structure of sperm flagella. Furthermore, the Dnah12 knock-out mouse revealed severe spermatogenesis failure and validated the same male infertility phenotype. Favorable fertility outcomes were achieved through ICSI in three human individuals and Dnah12 knock-out mice. Collectively, our study indicated that biallelic variants of DNAH12 can induce male infertility in both human beings and mice. Notably, evidence from DNAH12 enhanced that ICSI was an optimal intervention to achieve favorable fertility outcomes for infertile males with DNAH gene family variants.

Network pharmacology- and molecular docking-based exploration of the molecular mechanism underlying Jianpi Yiwei Recipe treatment of gastric cancer.

BACKGROUND: Traditional Chinese medicine (TCM) is widely used as an important complementary and alternative healthcare system for cancer treatment in Asian countries. Network pharmacology, which utilizes various database platforms and computer software to study the interactions between complex drug components in vivo, is particularly useful for studying the pharmacodynamic mechanisms of multi-pathway and multi-target Chinese medicines. AIM: To explore the potential targets and function of Jianpi Yiwei Recipe treatment of gastric cancer (GC) through network pharmacology and molecular docking. METHODS: Data on the components of Jianpi Yiwei Recipe (Radix Astragali, Radix Codonopsis, Agrimonia eupatoria, Atractylodes macrocephala Koidz., Poria cocos, stir-baked rhizoma dioscoreae, Amomum villosum Lour., fried Fructus Aurantii, pericarpium citri reticulatae, Rhizoma Pinelliae Preparata, and Radix Glycyrrhizae Preparata) were collected and screened by using the TCM systems pharmacology database and analysis platform (TCMSP). Then the targets of these compounds were predicted. GC-related targets were screened using the GeneCards database. Venn diagram was used to identify common targets. An active ingredient-core target interaction network and a protein-protein interaction (PPI) network were built. Moreover, we performed gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the core targets and validated them by molecular docking. RESULTS: TCMSP screening revealed 11 active components and 184 targets, whereas GeneCards found 10118 disease-related targets, with 180 shared targets between them. Topology analysis of the PPI network identified 38 targets, including ATK1, TP53, and tumor necrosis factor, as key targets for the treatment of GC by Jianpi Yiwei Recipe. Quercetin, naringenin, luteolin, etc., may be the main active components of Jianpi Yiwei Recipe. GO enrichment analysis identified 2809, 1218, and 553 functions related to biological process, molecular function, and cellular component, respectively. KEGG pathway enrichment analysis revealed 167 related pathways, mainly involved in cancer, endocrine resistance, and AGE-RAGE signaling in diabetic complication. Validation with molecular docking analysis showed docking of key active components with core targets. CONCLUSION: Jianpi Yiwei Recipe plays a therapeutic role in GC through multiple components, targets, and pathways. These findings form a basis for follow-up exploration of Jianpi Yiwei Recipe in the treatment of GC.

Causal effects and metabolites mediators between immune cell and risk of breast cancer: a Mendelian randomization study.

Introduction: The incidence and mortality of female breast cancer remain high, and the immune microenvironment of breast cancer has undergone significant alterations. However, the impact of blood immune cell levels on the risk of breast cancer is not fully understood. Therefor this study aims to investigate the causal relationship between blood immune cell levels and the risk of breast cancer. Methods: A Mendelian randomization (MR) analysis was employed to assess the causal relationship between immune cells and the risk of breast cancer, as along with their potential mediating factors. Genetic statistics of metabolites breast cancer and immune cells were obtained from the GWAS Catalog, while the genome-wide association study (GWAS) statistics of breast cancer were extracted from the UK biobank. Two-sample MR analysis were performed using inverse-variance weighted (IVW) to ascertain the causal association between immune cells and the risk of breast cancer. Furthermore, 1,400 metabolites were analyzed for their mediating role between immune cells and the risk of breast cancer. Results: MR analysis through IVW method revealed that genetically predicted CD24+ CD27+ B cells were associated with a decreased risk of breast cancer (OR = 0.9978, 95% CI: 0.996-0.999, p = 0.001), while IgD- CD38+ B cells were linked to an increased risk of breast cancer (OR = 1.002, 95% CI: 1.001-1.004, p = 0.005). Additional CD14+ CD16+ monocytes were associated with an increased risk of breast cancer (OR = 1.000, 95% CI: 1.000-1.001, p = 0.005). Mediation analysis revealed a positive causal relationship between IgD- CD38+ B cells and Glycerate levels, with the latter also exhibiting a positive causal relationship with the risk of breast cancer (p < 0.05). Conversely, IgD- CD38+ B cells displayed a negative causal relationship with Succinoyltaurine levels, and the latter also demonstrated a negative causal relationship with the risk of breast cancer (p < 0.05). Conclusion: This MR study provides novel genetic evidence supporting a causal relationship between IgD- CD38+ B cells and the risk of BC. Moreover, it is identified that IgD- CD38+ B cells contribute to an increased risk of BC through both positive and negative mediation effects involving Glycerate and Succinoyltaurine.

Symbiodiniaceae and Ruegeria sp. Co-Cultivation to Enhance Nutrient Exchanges in Coral Holobiont.

The symbiotic relationship between corals and their associated microorganisms is crucial for the health of coral reef eco-environmental systems. Recently, there has been a growing interest in unraveling how the manipulation of symbiont nutrient cycling affects the stress tolerance in the holobiont of coral reefs. However, most studies have primarily focused on coral-Symbiodiniaceae-bacterial interactions as a whole, neglecting the interactions between Symbiodiniaceae and bacteria, which remain largely unexplored. In this study, we proposed a hypothesis that there exists an inner symbiotic loop of Symbiodiniaceae and bacteria within the coral symbiotic loop. We conducted experiments to demonstrate how metabolic exchanges between Symbiodiniaceae and bacteria facilitate the nutritional supply necessary for cellular growth. It was seen that the beneficial bacterium, Ruegeria sp., supplied a nitrogen source to the Symbiodiniaceae strain Durusdinium sp., allowing this dinoflagellate to thrive in a nitrogen-free medium. The Ruegeria sp.-Durusdinium sp. interaction was confirmed through 15N-stable isotope probing-single cell Raman spectroscopy, in which 15N infiltrated into the bacterial cells for intracellular metabolism, and eventually the labeled nitrogen source was traced within the macromolecules of Symbiodiniaceae cells. The investigation into Symbiodiniaceae loop interactions validates our hypothesis and contributes to a comprehensive understanding of the intricate coral holobiont. These findings have the potential to enhance the health of coral reefs in the face of global climate change.

High sensitivity distributed dynamic pressure sensor based on dual-linear frequency modulated optical frequency domain reflectometry.

In this Letter, we propose and experimentally demonstrate a highly sensitive distributed dynamic pressure sensor based on a dual-linear frequency modulated optical frequency domain reflectometry (OFDR) and a coating thickness-enhanced single-mode fiber (SMF). A dual-sideband linear frequency modulation (LFM) signal is used to interrogate the sensing fiber, which allows us to obtain a dual-sideband Rayleigh backscattering signal. Due to the opposite slopes of the two LFM sidebands, the Rayleigh backscattering spectra of the two sidebands drift in opposite directions when the fiber is disturbed. By subtracting the frequency shifts of the two spectra, we can double the system's sensitivity. We further enhance the sensitivity by using an SMF with a coating thickness of 200 µm. This results in a pressure sensitivity of 3979 MHz/MPa, a measurement accuracy of 0.76 kPa, and a spatial resolution of 35 cm over a 500 m optical fiber. Our system successfully detected a dynamic pressure change at a sampling rate of 1.25 kHz, demonstrating the sensor's excellent dynamic measuring capabilities.

Association of lifestyle and occupational exposure factors with human semen quality: a cross-sectional study of 1060 participants.

The incidence of male infertility (MI) is rising annually. However, the lifestyle and occupational exposure factors contributing to MI remain incompletely understood. This study explored the effects of self-reported lifestyle and occupational exposure factors on semen quality. Among 1060 subjects invited to participate, 826 were eligible. The participants' general characteristics, lifestyle, and occupational exposure factors were collected immediately before or after semen evaluation through an online questionnaire. Initially, univariate analysis was used to investigate the relationship between the abovementioned factors and semen quality. The results indicated significant associations between low semen quality and various factors, including age, BMI, infertility type and duration, abstinence time, semen and sperm parameters, smoking, alcohol consumption, irregular sleep habits, and frequent exposure to high temperatures and chemicals at work (p < 0.05). Then, multivariate analysis was conducted to identify factors independently associated with low semen quality. Adjustment for relevant confounders was achieved by including factors with a p-value < 0.25 from univariate analyses as covariates in the binomial and ordered logistic regression models. The results suggested that alcohol consumption was a positive factor for sperm concentration (odds ratio [OR] = 0.60; 95% confidence interval [CI] = 0.36-0.99; p = 0.045). The groups with a BMI ≥ 24 and <28 kg/m2 showed a significant decrease in sperm progressive motility when compared to the reference group (BMI < 24 kg/m2) (OR = 0.63; 95% CI = 0.46-0.87, p = 0.005). In addition, the groups that drank green tea <1 time/week (OR = 1.52, 95% CI = 1.05-2.2) and 1-4 times/week (OR = 1.61, 95% CI = 1.02-2.54) exhibited significantly increased sperm DFI values compared with the group that drank green tea 5-7 times/week. In conclusion, these findings underscore the importance of maintaining a normal weight and regularly consuming green tea for men.

Complete genome of a novel mycobacteriophage WXIN isolated in Wuhan, China.

OBJECTIVES: The rising of antibiotic resistance has sparked a renewed interest in mycobacteriophage as alternative therapeutic strategies against mycobacterial infections. So far, the vast majority of mycobacteriophages have been isolated using the model species Mycobacterium smegmatis, implying an overwhelming majority of mycobacteriophages in the environment remain uncultured, unclassified, and their specific hosts and infection strategies are still unknown. This study was undertaken to isolate and characterize novel mycobacteriophages targeting Mycobacterium septicum. DATA DESCRIPTION: Here a novel mycobacteriophage WXIN against M. septicum was isolated from soil samples in Wuhan, China. Whole genome analysis indicates that the phage genome consists of 115,158 bp with a GC content of 61.9%. Of the 260 putative open reading frames, 46 may be associated with phage packaging, structure, lysis, lysogeny, genome modification/replication, and other functional roles. The limited genome-wide similarity, along with phylogenetic trees constructed based on viral proteome and orthologous genes show that phage WXIN represents a novel cluster distantly related to cluster J mycobacteriophages (genus Omegavirus). Overall, these results provide novel insights into the genomic properties of mycobacteriophages, highlighting the great genetic diversity of mycobacteriophages in relation to their hosts.

Deficiency of MFSD6L, an acrosome membrane protein, causes oligoasthenoteratozoospermia in humans and mice.

Oligoasthenoteratozoospermia is an important factor affecting male fertility and has been found to be associated with genetic factors. However, there are still a proportion of oligoasthenoteratozoospermia cases that cannot be explained by known pathogenic genetic variants. Here, we perform genetic analyses and identify bi-allelic loss-of-function variants of MFSD6L from an oligoasthenoteratozoospermia-affected family. Mfsd6l knock-out male mice also present male subfertility with reduced sperm concentration, motility, and deformed acrosomes. Further mechanistic analyses reveal that MFSD6L, as an acrosome membrane protein, plays an important role in the formation of acrosome by interacting with the inner acrosomal membrane protein SPACA1. Moreover, poor embryonic development is consistently observed after intracytoplasmic sperm injection treatment using spermatozoa from the MFSD6L-deficient man and male mice. Collectively, our findings reveal that MFSD6L is required for the anchoring of sperm acrosome and head shaping. The deficiency of MFSD6L affects male fertility and causes oligoasthenoteratozoospermia in humans and mice.

Impact of digital technology innovation on carbon intensity: evidence from China's manufacturing A-share listed enterprises.

Current studies do not provide a consensus on whether digital technology innovation can reduce enterprise carbon intensity despite the rise of the digital economy. This paper examines the role and influence pathway of digital technology innovation on enterprise carbon intensity using data from A-share listed enterprises in China's manufacturing industry from 2012 to 2021. The findings indicate that (1) digital technology innovation has been found to significantly reduce enterprise carbon intensity, as confirmed by numerous robustness and endogeneity tests. However, its inhibitory effect on carbon intensity shows a marginal decreasing trend. (2) In the heterogeneity analysis, it was found that digital technology innovation significantly reduces the carbon intensity of consuming coal, coke, kerosene, and diesel. From various perspectives, including enterprise, industry, and external environment, there are significant differences in the carbon reduction effects of digital technology innovation. (3) The analysis of impact paths reveals that digital technology innovation can affect enterprise carbon intensity through three paths: improving productivity, enhancing green innovation efficiency, and adjusting energy consumption. (4) Upon further analysis, it was discovered that the spillover effect of digital technology innovation is more pronounced in the industry cohort of enterprises. Additionally, digital technology innovation plays a positive role in enhancing enterprise ESG performance. The paper's findings offer empirical evidence and decision-making references for the government to develop reasonable policies for reducing carbon emissions, promoting green and low-carbon enterprise transformation, and actively and steadily achieving the goal of carbon peaking and carbon neutrality.

Detoxification of Aflatoxin B1 by Phytochemicals in Agriculture and Food Science.

Aflatoxin B1 (AFB1), the most toxic and harmful mycotoxin, has a high likelihood of occurring in animal feed and human food, which seriously affects agriculture and food safety and endangers animal and human health. Recently, natural plant products have attracted widespread attention due to their low toxicity, high biocompatibility, and simple composition, indicating significant potential for resisting AFB1. The mechanisms by which these phytochemicals resist toxins mainly involve antioxidative, anti-inflammatory, and antiapoptotic pathways. Moreover, these substances also inhibit the genotoxicity of AFB1 by directly influencing its metabolism in vivo, which contributes to its elimination. Here, we review various phytochemicals that resist AFB1 and their anti-AFB1 mechanisms in different animals, as well as the common characteristics of phytochemicals with anti-AFB1 function. Additionally, the shortcomings of current research and future research directions will be discussed. Overall, this comprehensive summary contributes to the better application of phytochemicals in agriculture and food safety.