Search

Background: In recent decades, the quality of male semen has decreased worldwide. Air pollution has been linked to lower semen quality in several studies. However, the effects of atmospheric pollutants on different semen characteristics have not always been consistent. The aim of this study was to investigate the association between the Air Quality Index (AQI) and six atmospheric pollutants (PM2.5, PM10, SO2, NO2, CO, and O3), semen quality, and their key exposure window periods. Methods: This study included 1711 semen samples collected at the reproductive clinics of the First Affiliated Hospital of Shanxi Medical University in Taiyuan, Shanxi, China, from October 10, 2021, to September 30, 2022. We evaluated the association of AQI and six atmospheric pollutants with semen quality parameters throughout sperm development and three key exposure windows in men using single-pollutant models, double-pollutant models, and subgroup analyses of semen quality-eligible groups. Results: Both the single-pollutant model and subgroup analyses showed that PM, CO, and O3 levels were negatively correlated with total and progressive motility. At 70–90 d before semen collection, CO exposure and semen volume (β =-1.341, 95 % CI: −1.805, −0.877, P

Abstract Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched‐chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high‐fat diet/low‐dose streptozotocin (HFD/STZ)‐induced T2DM and leptin receptor‐deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label‐free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L‐type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA‐deficiency‐induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Myocardial ischemia (MI) is a significant contributor to ischemic heart diseases like angina pectoris and myocardial infarction. Reactive oxygen species produced during MI can trigger lipid peroxidation, damaging cell structure and function. Salvia miltiorrhiza (SM) has been widely used clinically in the treatment of cardiovascular diseases. However, in the process of rooting, the aboveground parts of this plant are usually discarded by tons. To make better use of these plant resources, the phenolic acids extracted and purified from the aerial part of SM were studied and chemically transformed, and the potential protective effect and possible mechanism of salvianolic acids containing a higher content of salvianolic acid A on MI were obtained. The transformed products of SM stem-leaves total phenolic acids with 8.16 % salvianolic acid A showed a better protective effect on the isoproterenol (ISO)-induced acute MI injury rat model. It can improve ST segment changes and has good antioxidant, anti-inflammatory and anticoagulant effects. In addition, the dysbiosis of gut microbiota and the related metabolic levels of short chain fatty acids (SCFAs), phenylalanine and glycerophospholipids were improved. This was achieved by reducing the abundance of Bacteroides, Faecalibaculum, and L-phenylalanine levels. In addition, the abundance of probiotics in Butyricoccus, Roseburia, and norank_f_Eubacterium_coprostanoligenes_group, as well as the contents of propionic acid and isobutyric acid, LPCs and PCs were increased. In conclusion, total phenolic acids of SM stem-leaves showed protective effects against ISO-induced rats, especially the strongest effect after conversion, which is a new option for the prevention and treatment of MI.

Abstract Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

Background: Xianlian Jiedu Decoction (XLJDD) is a clinical effective prescription for the treatment of colorectal cancer (CRC) for several decades. However, the effective mechanism and targets of action of XLJDD are still unclear. This study aims to discover the pharmacological mechanism of XLJDD by employing a combination of network pharmacology, molecular docking and in vitro and in vivo experimental validation. Methods: Multiple databases, including TCMSP, Swiss Target Prediction, Drugbank, Geencards, Malacards, Therapeutic Target Database (TTD) and Disgenet, were searched and identified the targets of ingredients from XLJDD and the targets associated with CRC. The common targets of ingredients and disease were analyzed, and the visualization network of protein-protein interaction (PPI) were constructed using STRING database and to identified the core targets based on Cytoscape software. Metascape database was employed for GO and KEGG enrichment analysis of common targets. The active ingredients of XLJDD and core targets were verified through molecular docking test. Subsequently, in vitro and in vivo experiments were performed to validate the analysis results using CT-26 and HCT116 cell lines and AOM/DSS mice model. Results: A total of 36 active components and 122 targets were identified for XLJDD, while 1728 targets associated with CRC were obtained. Among them, there were 71 common targets between ingredients and disease. And 19 core targets (AKT1, TNF, PTGS2, CASP3, EGFR, ESR1, MMP9, IL1B, CCND1, PPARG, ERBB2, SIRT1, MMP2, BCL2L1, MAPK1, PPARA, PGR, AR and SERPINE1.) were finally screened from PPI network. GO analysis enriched a total of 99 entries, with 74 related to biological processes, 20 to molecular functions, and 5 to cellular components. The KEGG enrichment pathway analysis demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, inflammation-, and mechanism-related pathways. Molecular docking presented the great bonding ability of 19 key targets with 17 active constituents. Experiments based on CT-26 and HCT116 cells verified that XLJDD could inhibit the proliferation of colorectal cancer cells. In addition, XLJDD inhibited tumor progression in mice. Finally, the results of molecular biology experiments showed that XLJDD could activate the colorectal cancer-related PTEN/AKT/FoXO1 pathway, and up-regulate the expression levels of key genes such as AKT1, TNF, PTGS2 and down-regulate the expression levels of CASP3. Conclusions: This study revealed comprehensively the targets and mechanism for the efficacy of XLJDD in treatment of CRC. Furthermore, the results were achieved through in vitro experiment of CT-26 and HCT116 cell lines, and in vivo experiment of AOM/DSS mice.

Summary: Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

Fat deposition involves the continuous differentiation of adipocytes and lipid accumulation. Studies have shown that microRNA miR-136 and 17β-hydroxysteroid dehydrogenase type 12 (HSD17B12) play important roles in lipid accumulation. However, the regulatory mechanism through which miR-136 targets HSD17B12 during ovine adipogenesis remains unclear. This study aimed to elucidate the role of miR-136 and HSD17B12 in adipogenesis and their relationship in ovine adipose-derived stromal vascular fractions (SVFs). The target relationship between miR-136 and HSD17B12 was predicted and confirmed using bioinformatics and a dual-luciferase reporter assay. The results showed that miR-136 promoted proliferation and inhibited adipogenic differentiation of ovine SVFs. We also found that HSD17B12 inhibited proliferation and promoted adipogenic differentiation of ovine SVFs. Collectively, our results indicate that miR-136 facilitates proliferation and attenuates adipogenic differentiation of ovine SVFs by targeting HSD17B12. These findings provide a theoretical foundation for further elucidation of the regulatory mechanisms of lipid deposition in sheep.

Introduction: Bear bile powder (BBP) is widely used in the clinic and has a hypoglycemic effect, but its mechanism is not clear.Methods: In this study, type 2 diabetes mellitus (T2DM) rats induced by a high-sugar and high-fat diet combined with streptozotocin were given BBP, and biochemical indexes, pathological sections, metabonomics, intestinal microbiota (IM) and short-chain fatty acids (SCFAs) were determined.Results: The results showed that BBP could reduce blood glucose, relieve inflammation, insulin resistance, and lipid metabolism disorder, and alleviate tissue damage of the liver, spleen, kidney, and pancreas in T2DM rats. It is worth noting that BBP can reverse the changes in blood and urine metabolites in T2DM rats, which are mainly related to tryptophan metabolism, pentose and glucuronate interconversions, starch and sucrose metabolism, and glycerophospholipid metabolism. In addition, BBP restored IM disorder in T2DM rats, decreased the abundance of Allobaculum, Blautia, Dubosiella, and Anaerostipes, enriched the abundance of Lactobacillus, Romboutsia, UCG-005, and norank_f__Eggerthellaceae, and increased the concentration of SCFAs in intestinal contents.Discussion: These findings suggest that BBP may improve T2DM by regulating multiple metabolic pathways, IM composition, and SCFAs levels.

Many disease-related genes have been found to be associated with cancer diagnosis, which is useful for understanding the pathophysiology of cancer, generating targeted drugs, and developing new diagnostic and treatment techniques. With the development of the pan-cancer project and the ongoing expansion of sequencing technology, many scientists are focusing on mining common genes from The Cancer Genome Atlas (TCGA) across various cancer types. In this study, we attempted to infer pan-cancer associated genes by examining the microbial model organism Saccharomyces Cerevisiae (Yeast) by homology matching, which was motivated by the benefits of reverse genetics. First, a background network of protein-protein interactions and a pathogenic gene set involving several cancer types in humans and yeast were created. The homology between the human gene and yeast gene was then discovered by homology matching, and its interaction sub-network was obtained. This was undertaken following the principle that the homologous genes of the common ancestor may have similarities in expression. Then, using bidirectional long short-term memory (BiLSTM) in combination with adaptive integration of heterogeneous information, we further explored the topological characteristics of the yeast protein interaction network and presented a node representation score to evaluate the node ability in graphs. Finally, homologous mapping for human genes matched the important genes identified by ensemble classifiers for yeast, which may be thought of as genes connected to all types of cancer. One way to assess the performance of the BiLSTM model is through experiments on the database. On the other hand, enrichment analysis, survival analysis, and other outcomes can be used to confirm the biological importance of the prediction results. You may access the whole experimental protocols and programs at https://github.com/zhuyuan-cug/AI-BiLSTM/tree/master.

Rhizosphere colonization is a pre-requisite for the favorable application of plant growth-promoting rhizobacteria (PGPR). Exchange and mutual recognition of signaling molecules occur frequently between plants and microbes. Here, the luciferase luxAB gene was electrotransformed into the phosphate-solubilizing strain Pseudomonas sp. WS32, a type of plant growth-promoting rhizobacterium with specific affinity for wheat. A labeled WS32 strain (WS32-L) was applied to determine the temporal and spatial traits of colonization within the wheat rhizosphere using rhizoboxes experimentation under natural condition. The effects of colonization on wheat root development and seedling growth were evaluated, and RNA sequencing (RNA-seq) was performed to explore the transcriptional changes that occur in wheat roots under WS32 colonization. The results showed that WS32-L could survive in the wheat rhizosphere for long periods and could expand into new zones following wheat root extension. Significant increases in seedling fresh and dry weight, root fresh and dry weight, root surface area, number of root tips, and phosphorus accumulation in the wheat leaves occurred in response to WS32 rhizosphere colonization. RNA-seq analysis showed that a total of 1485 genes in wheat roots were differentially expressed between the inoculated conditions and the uninoculated conditions. Most of the transcriptional changes occurred for genes annotated to the following functional categories: “phosphorus and other nutrient transport,” “hormone metabolism and organic acid secretion,” “flavonoid signal recognition,” “membrane transport,” and “transcription factor regulation.” These results are therefore valuable to future studies focused on the molecular mechanisms underlying the growth-promoting activities of PGPR on their host plants.

Abstract. Background:. In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks. Methods:. A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered. Results:. The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment. Conclusion:. Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock. Ethics and dissemination:. Ethical permissions are not required as prepublished data are used. OSF registration number:. DOI 10.17605/OSF.IO/SKEZ7

As a member of the miR-29 family, miR-29b regulates global DNA methylation through target DNA methyltransferases (DNMTs) and acts as both a target and a key effector in DNA methylation. In this study, we found that miR-29b-3p expression was inversely correlated with DNMT expression in the heart tissues of patients with congenital heart disease (CHD), but whether it interacts with DNMTs in cardiomyocytes remains unknown. Further results revealed a feedback loop between miR-29b-3p and DNMTs in cardiomyocytes. Moreover, miR-29b-3p inhibitor relieved the deformity of hypomethylated zebrafish and restored the DNA methylation patterns in cardiomyocytes, resulting in increased proliferation and renormalization of gene expression. These results suggest mutual regulation between miR-29b-3p and DNMTs in cardiomyocytes and support the epigenetic normalization of miRNA-based therapy in cardiomyocytes.

Mealworms (Tenebrio molitor) are protein-rich edible insects that have been regarded as novel food ingredients. In this study, high-gluten wheat flour was formulated with dried mealworm powder at various levels (0%, 5%, 10%, 15%, and 20%) to study its influence on the pasting, farinograph, and extensograph properties and microstructure of the dough. A subsequent decrease in the pasting parameters was observed due to starch dilution. The water absorption, dough development time, and dough stability time decreased gradually from 71.9% to 68.67%, 13.6 min to 10.43 min, and 14.1 min to 5.33 min, respectively, with the increase in the substitution of mealworm powder from 0% to 20%. The farinograph characteristics corresponded to a weak gluten network formed through the dilution of gluten by the replacement of wheat flour with a non-gluten ingredient. The stretch ratio of the high-gluten dough increased gradually from 4.37 (M0) to 6.33 (M15). The increased stretching resistance and extensibility of the dough with 5% and 10% mealworm powder indicated that mealworm powder can act as a plasticizer in the gluten network, which might contribute to the decreased strength and increased elasticity and flexibility of the dough network. The bread made with three different baking methods showed similar increases in specific volume and decreased hardness up to the 10% substitution level, owing to the increased elasticity and flexibility of the dough. The GB/T 35869-2018 Rapid-baking method, GB/T 14611-2008 Straight dough method, and automatic bread maker method exhibited the highest specific volumes of 3.70 mL/g, 3.79 mL/g, and 4.14 mL/g when the wheat flour was substituted with 10% mealworm powder. However, 15% and 20% mealworm powder substitution markedly reduced the bread quality owing to the dilution effect and mealworm powder phase separation. These results provide a perspective on the relationship between the rheological properties of mealworm powder-substituted high-gluten dough and application suggestions for insect food development in the food industry.

Electrically conductive hydrogel materials can be used as materials for wearable sensors, which can quickly and accurately detect the activities of human joints and convert these movements into electrical signals. More specifically, they have potential for application in wearable electronic devices and electronic skins. However, a number of challenges remain regarding the preparation of conductive hydrogel materials. In this study, we synthesized the P(BHMP-AM)-Zn2+ hydrogel material in situ via a one-pot method using acrylic monomer derivatives, acrylamide, and zinc ions. The resulting hydrogel exhibited a high cytocompatibility (89%), excellent cyclic tensile properties, satisfactory adhesion properties (3.4 kPa), and good electrical conductivity. Furthermore, the addition of Zn2+ ions imparted antibacterial properties to the hydrogel, with sterilization rates of 65.9 and 10.9% being determined against Escherichia coli and Staphylococcus aureus, respectively. The hydrogel was able to sense the activities of joints or other parts of the human body when attached to the skin, converting these movements into electrical signals to allow the real-time monitoring of motion. This conductive hydrogel material, therefore, exhibits potential for use in wearable electronic devices and electronic skins, among other devices.

Use of thermotolerant strains offers the advantage of conducting production process at elevated temperatures, thereby improving the catalytic efficiency and reducing the energy consumption and the production costs. In the present study, thermotolerance gene groES from the thermophilic strain Bacillus licheniformis B186 was implanted into B. subtilis WB600 to improve its thermotolerance. The engineered strain WB600-pHY-groES displayed reduced doubling time as well as increased specific growth rates and cell viability compared with the control. Our results suggested that introducing heat shock proteins (HSPs) from thermophiles into B. subtilis could be an effective approach to enhance its thermotolerance, thus facilitating the development of multichaperone expression systems for constructing more thermotolerant commercial B. subtilis strains. To the best of our knowledge, this is the first report on improving the thermotolerance of B. subtilis by overexpression of HSPs.

The objective of this study was to compare the effect of pulsatile gonadorelin pump (PGP) and cyclical gonadotropin (human chorionic gonadotropin [HCG]/human menopausal gonadotropin [HMG]) therapy (CGT) on spermatogenesis in congenital hypogonadotropic hypogonadism (CHH) men. Twenty-eight azoospermic CHH males were included in this nonrandomized study. Ten received PGP and 18 received CGT. The primary endpoint was the earliest time spermatogenesis occurred during 24 months of treatment. Spermatogenesis time was significant earlier in the PGP group than the CGT group (median of 6 and 14 months, respectively, χ 2 = 6.711, p = .01). Spermatogenesis occurred in 90% of the PGP group and 83.3% of the CGT group and showed statistically insignificant difference in the superiority analysis and the no-inferior test. Contributing factors significant for spermatogenesis were previous HCG/or testosterone treatment and the peak serum luteinizing hormone level of triptorelin stimulation test at baseline. Although testis volume and penile length increased significantly from baseline, the differences between the two therapies were not significant. There was a tendency for high serum testosterone level, associated with more facial acne and breast tenderness in the CGT group. Skin allergic erythema scleroma was a common side effect of the PGP. In summary, PGP resulted in earlier spermatogenesis and more desirable testosterone levels than CGT.

Biodiesel is a renewable alternative to petroleum diesel fuel that can contribute to carbon dioxide emission reduction and energy supply. Biodiesel is composed of fatty acid alkyl esters, including fatty acid methyl esters (FAMEs) and fatty acid ethyl esters (FAEEs), and is currently produced through the transesterification reaction of methanol (or ethanol) and triacylglycerols (TAGs). TAGs are mainly obtained from oilseed plants and microalgae. A sustainable supply of TAGs is a major bottleneck for current biodiesel production. Here we report the de novo biosynthesis of FAEEs from glucose, which can be derived from lignocellulosic biomass, in genetically engineered Escherichia coli by introduction of the ethanol-producing pathway from Zymomonas mobilis, genetic manipulation to increase the pool of fatty acyl-CoA, and heterologous expression of acyl-coenzyme A: diacylglycerol acyltransferase from Acinetobacter baylyi. An optimized fed-batch microbial fermentation of the modified E. coli strain yielded a titer of 922 mg L(-1) FAEEs that consisted primarily of ethyl palmitate, -oleate, -myristate and -palmitoleate.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter. Author summary: Intravascular catheters are widely used to administer medication and provide nutritional support to patients. However, their clinical use also increases the incidence of bloodstream infections and constitutes a risk factor for Candida albicans infection. Microbial biofilms have been proposed as the primary living style of microbes on a surface, including those on intravascular catheters. Numerous studies focus on identifying microbial factors contributing to C. albicans biofilm formation. However, our understanding of the host factors involved in controlling C. albicans biofilms on the surface of intravascular catheters is limited. In this study, we demonstrated that the biofilms in intravascular catheters removed from candidiasis patients comprised not only C. albicans cells but also human immune cells. Among these catheters, the immune cells interacting with the fungus exhibited different properties of NETosis, a type of neutrophil cell death with antimicrobial activity. We further showed that the catheter isolates exhibited reduced expression of candidalysin. Supplementation of candidalysin promoted NETosis induced by C. albicans biofilms and diminished C. albicans biofilms on a surface. Our findings highlight the implication of neutrophils in eliminating C. albicans biofilms, and point out the benefit of reduced candidalysin expression for C. albicans to persist in intravascular catheters. [ABSTRACT FROM AUTHOR]