In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Objective: To develop a simple digital chylous plasma device and validate its ability to accurately, standardly, and non-destructively determine chylous plasma in blood banks and clinical transfusions in hospitals. Methods: A digital chylous plasma assessment device was designed and manufactured. This device was used to measure the chylous degrees of chylous plasma samples before freezing, after freeze-thawing, before viral inactivation, and after viral inactivation. The measured chylosity index values were categorized according to the requirements specified in Appendix A of the Chinese national standard GB 18469-2001 "Quality Requirements for Whole Blood and Blood Components". This process established a digital standard for chylous plasma, enabling the identification of severe, moderate and mild chylous plasma, and non-chylous plasma. Results: The initial simple product of the digital chylous assessment device was successfully designed and manufactured. There was no significant difference in the degree of chylous plasma between pre-freezing 468.11±217.73 lux and post-thawing 538.91±273.39 lux of chylous plasma (P>0.05), or between pre-viral inactivation 858.33±387.79 lux and post-viral inactivation 928.33±166.51 lux of chylous plasma (P>0.05). The median of chylous degree values for plasma chylous index grades 0 to 6 were 45 lux, 250 lux, 620 lux, 835 lux, 1 130 lux, 1 390 lux, and 1 700 lux, respectively. The defined cutoff values/ranges for the chylous degree values corresponding to plasma chylous index grade 0 to 6 were ≤125 lux, 126-465 lux, 466-740 lux, 741-1 000 lux, 1 001-1 233 lux, 1 234-1 560 lux, and ≥1 561 lux. Conclusion: This study successfully developed the initial product of the digital chylous device and established digital standards for classifying chylous plasma. The device demonstrates the potential to meet the needs for assessment of chylous plasma in both blood banks and clinical transfusions in hospitals, thereby promoting the development and application of standardized, non-destructive chylous plasma assessment technology.

OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Ochratoxin A (OTA) is ubiquitous in the food and feed fields. It has strong hepatotoxicity and nephrotoxicity, seriously threatening the health of humans and animals. Enzymatic degradation of mycotoxins is considered to be a promising method to control mycotoxin contaminations. In this study, a new ochratoxin A amidohydrolase from Microbulbifer thermotolerans (MiADH) was obtained. After heterologous expression in Escherichia coli and purification, the recombinant protein was studied regarding the hydrolysis activity, hydrolysis products, enzymatic properties, and substrate binding mode. MiADH can degrade OTA into ochratoxin α (OTα) and phenylalanine, demonstrating a detoxifying ability. It demonstrated the best performance at 70 ℃ and pH 8.0, and Cu²⁺ had the strongest inhibitory effect on the activity of MiADH. MiADH with good thermal stability exhibited huge potential for industrial application. Rational design guided by three-dimensional structural models and substrate docking analysis revealed the important amino acids affecting substrate binding and obtained multiple mutants with improved activity. Among these mutants, V324A had the highest activity, which was 4.2-fold that of the wild type. The identification of MiADH enriches the ochratoxin A degradation enzyme library and provides a new candidate enzyme for the biological detoxification of ochratoxin A in the food and feed industry.
Amidohydrolases/chemistry* ; Ochratoxins/metabolism* ; Substrate Specificity ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Actinomycetales/genetics*

Objective To investigate the inhibitory effects of magnesium citrate(MgCit)on oxidative stress in chronic renal failure(CRF).Methods SD rats were divided into CRF model group,MgCit groups(375 and 750 mg/kg),normal control group,and MgCit control group(750 mg/kg).The morphology of mitochondria in thoracic artery vascular smooth muscle cells(VSMCs)was observed by transmission electron microscopy.The content of superoxide dismutase(SOD)and malonaldehyde(MDA)in rat aorta and plasma was detected by the kit.The VSMCs were divided into normal control group,CRF model group,and MgCit groups(1.5 and 3 mmol/L).The levels of superoxide anion(DHE)and apoptosis were quantitatively detected by flow cytometry.Results Compared with the control groups,the mitochondria were swollen and the cristae fractured or disappeared in the model group;MgCit intervention could reduce mitochondrial swelling,but not cristae fracture.In the model group,SOD level in aorta and plasma decreased(P＜0.05)while MDA level increased(P＜0.05).MgCit intervention could increase SOD in aorta and plasma,but decrease MDA level(P＜0.05).In the CRF environment,the DHE content of VSMCs and apoptosis in CRF model group increased(P＜0.05).MgCit intervention could decrease DHE content and inhibit apoptosis(P＜0.05).Conclusion MgCit inhibits oxidative stress levels in vivo and in vitro in CRF.

Objective To explore the association between visceral adiposity index(VAI)and nonalcoholic fatty liver disease(NAFLD)in lean population and the predictive value of VAI.Methods A total of 2 576 healthy subjects,body mass index(BMI)＜24 kg/m2,from The Second Affiliated Hospital of Xi'an Jiaotong University from June 2020 to May 2021 were randomly included and divided into lean NAFLD(n=213)and healthy control group(n=2 363).According to the VAI quartiles,they were divided into Q1-Q4 groups from low to high.The differences in biochemical parameters and the prevalence of NAFLD were compared among groups.The correlation between VAI and lean NAFLD was analyzed with restricted cubic spline(RCS),and the predictive value of VAI was explored by Logistic regression and receiver operating characteristic(ROC)curve.Results A total of 2 576 participants were included,and the prevalence of lean NAFLD was 8.3％(213 cases).The mean age,male ratio,BMI and waist circumference(WC)from group Q1 to group Q4 were significantly increased in a dose-response relationship(all P＜0.001).Compared with those in group Q1,systolic blood pressure,diastolic blood pressure,white blood cell count,hemoglobin concentration,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transpeptidase,alkaline phosphatase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,blood uric acid,and fasting blood glucose levels in groups Q2 to Q4 were significantly increased,while direct bilirubin and high-density lipoprotein cholesterol levels were gradually decreased(both P＜0.001).The prevalence rate of NAFLD in groups Q1-Q4 was 0.6％,3.3％,7.0％and 22.2％,respectively(P＜0.001).RCS showed that the risk of NAFLD in lean population rose significantly with the increase of VAI(P＜0.001),and there was a nonlinear relationship between them(P for nonlinear＜0.001).Logistic regression showed that after adjusting other confounding factors,the risk of lean NAFLD in groups Q2,Q3 and Q4 was still 2.926 times(95％CI:0.971-8.811),3.435 times(95％CI:1.154-10.230),and 5.920 times(95％CI:1.873-18.719)that Q1 group.ROC curve showed that VAI had a good predictive value for lean NAFLD,with area under the curve of 0.815,critical value of 1.532,diagnostic sensitivity of 77.9％and specificity of 72.8％,which were better than BMI and WC.Conclusion VAI is significantly associated with the risk of NAFLD in lean population,and thus has a good predictive value.It can be used for early screening and diagnosis of lean NAFLD.

【Objective】 To achieve supervision and management of the whole business process of blood center, raise productivity and ensure blood quality by enabling blood center managers comprehensively grasp the key business operation situation of the whole process at anytime and anywhere. 【Methods】 A whole business process supervision and management system was established covering background of preparation, business scope, content of position supervision and management, overall framework design, interface design of management and supervision management, physical database design, program development and online debugging, and was integrated with the blood bank management information system. The display and management were through a mobile APP to record key indicators of business process from blood collection to blood supply timely and comprehensively. Statistical analysis was conducted on total collection volume, total preparation volume and total supply volume, as well as discarding rate of test unqualified and of non-test unqualified (lipemic blood excluded) in 2023 and 2022. 【Results】 We established a mobile APP based on a blood bank management information system for business supervision and management of whole process, and achieved management by phones. After its implementation in 2023, the total collection volume, total preparation volume and total supply volume in 2023 were all higher than those in 2022, with growth rates of 5.88% (13 247/225 454 U), 4.73% (24 156/510 698 U), and 6.70% (34 814/519 914 U), respectively. The discarding rate in 2023 was lower than that in 2022 (0.54%, 2 868/534 854 U) vs (0.60%, 3 047/510 698 U) (P<0.01), and the non-test unqualified discarding rate (lipemic blood excluded) in 2023 was significantly lower than that in 2022(0.12%, 649/534 854 U) vs (0.19%, 991/510 698 U)(P<0.01). 【Conclusion】 The construction of supervision and management system of a whole business process based on blood bank management information system can meet the standardized service needs of managers at anytime and anywhere, continuously raise productivity and the standardization and scientific level of blood bank management, thus ensuring blood supply.

Extracorporeal membrane oxygenation (ECMO) is a critical life support technique for patients with severe cardiopulmonary failure. Establishing a stable ECMO animal model is essential to further investigate the effects of ECMO on the body and provide assistance for optimizing ECMO management strategies and preventing complications in clinical practice. In recent years, rats have been widely used to establish ECMO models due to their low cost and good reproducibility. Therefore, this article provided a comprehensive review of literature on the ECMO rat model, including equipment and experimental management strategies. It offers a theoretical foundation for the development of a stable and mature ECMO rat model in the future.