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OBJECTIVE: To construct a predictive model for the improvement of cognitive function in patients with depressive disorder treated with SNRIs, based on emotional regulation abilities, and to provide personalized treatment for depressed patients. METHODS: Clinical data from 170 patients with depressive disorder treated with SNRIs at Tongji Hospital, Shanghai, from December 2017 to May 2023 were collected. Based on whether the MoCA-B total score at 3-6 months post-treatment was at least 2 points higher than at baseline, patients were divided into the cognitive function improved group (n = 80) and the cognitive function not improved group (n = 90). Stepwise logistic regression and LASSO regression were used to select predictive factors, and logistic regression analysis was applied to construct predictive models solely based on emotional regulation abilities, combined with executive functions and HAMD scores. The models were further validated through Bootstrap internal validation, calibration curve plotting, and C-index calculation, and a comparison between the two models was performed. RESULTS: An ER model with an area under the ROC curve of 0.817was established using four emotional regulation ability indicators: the valence of reappraised images, the arousal of negative images, the arousal of neutral images, and the success of reappraisal (arousal). Internal validation using Bootstrap showed a C index of 0.817, and clinical decision curves indicated that this model has a significant net benefit with a probability of improved cognitive function ranging from about 20 to 85%. Additionally, an EREH model including emotional regulation ability, executive function, and HAMD score as predictors was constructed using Lasso and logistic regression methods. This model reached an area under the ROC curve of 0.859and clinical decision curves showed high net benefits with probabilities of improved cognitive function ranging from 10 to 100%. The calibration curves of both models coincided well with the actual curves, with the latter having a higher AUC and significant statistical differences between the two models. CONCLUSION: This study suggests that emotional regulation ability may serve as a predictor for the improvement of cognitive functions in patients with depression depressive disorder treated with SNRIs. However, it is important to note that there may be other factors not covered or included in this study.The predictive model that includes executive functions and HAMD scores offers better differentiation and consistency and is more feasible in clinical practice.

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Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

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Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

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Global aflatoxin B1 (AFB1) contamination is inevitable, and it can significantly damage testicular development. However, the current mechanism is confusing. Here, by integrating the transcriptome, microbiome, and serum metabolome, we comprehensively explain the impact of AFB1 on testis from the gut-metabolism-testis axis. Transcriptome analysis suggested that AFB1 exposure directly causes abnormalities in testicular inflammation-related signalling, such as tumor necrosis factor (TNF) pathway, and proliferation-related signalling pathways, such as phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) pathway, which was verified by immunofluorescence. On the other hand, we found that upregulated inflammatory factors in the intestine after AFB1 exposure were associated with intestinal microbial dysbiosis, especially the enrichment of Bacilli, and enrichment analysis showed that this may be related to NLR family pyrin domain containing 3 (NLRP3)-mediated NOD-like receptor signalling. Also, AFB1 exposure caused blood metabolic disturbances, manifested as decreased hormone levels and increased oxidative stress. Significantly, B. licheniformis has remarkable AFB1 degradation efficiency (> 90%). B. licheniformis treatment is effective in attenuating gut-testis axis damage caused by AFB1 exposure through the above-mentioned signalling pathways. In conclusion, our findings indicate that AFB1 exposure disrupts testicular development through the gut-metabolism-testis axis, and B. licheniformis can effectively degrade AFB1.

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BACKGROUND: Aflatoxin B1 (AFB1), one of the most prevalent contaminants in human and animal food, impairs the immune system, but information on the mechanisms of AFB1-mediated macrophage toxicity is still lacking. METHODS AND RESULTS: In this study, for the first time, we employed whole transcriptome sequencing technology to explore the molecular mechanism by which AFB1 affects the growth of porcine alveolar macrophages (PAM). We found that AFB1 exposure reduced the proliferative capacity of PAM and prevented cell cycle progression. Based on whole transcriptome analysis, RT-qPCR, ICC and RNAi, we verified the role and regulatory mechanism of the competing endogenous RNA (ceRNA) network in the process of AFB1 exposure affecting the growth of PAM. CONCLUSIONS: We found that AFB1 induced MSTRG.43,583, MSTRG.67,490, MSTRG.84,995, and MSTRG.89,935 to competitively bind miR-219a, miR-30b-3p, and miR-30c-1-3p, eliminating the inhibition of its target genes CACNA1S, RYR3, and PRKCG. This activated the calcium signaling pathway to regulate the growth of PAM. These results provide valuable information on the mechanism of AFB1 exposure induced impairment of macrophage function in humans and animals.

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All forms of life produce nanosized extracellular vesicles called exosomes, which are enclosed in lipid bilayer membranes. Exosomes engage in cell-to-cell communication and participate in a variety of physiological and pathological processes. Exosomes function via their bioactive components, which are delivered to target cells in the form of proteins, nucleic acids, and lipids. Exosomes function as drug delivery vehicles due to their unique properties of innate stability, low immunogenicity, biocompatibility, biodistribution, accumulation in desired tissues, low toxicity in normal tissues, and the stimulation of anti-cancer immune responses, and penetration capacity into distance organs. Exosomes mediate cellular communications by delivering various bioactive molecules including oncogenes, oncomiRs, proteins, specific DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), and circular RNA (circRNA). These bioactive substances can be transferred to change the transcriptome of target cells and influence tumor-related signaling pathways. After considering all of the available literature, in this review we discuss the biogenesis, composition, production, and purification of exosomes. We briefly review exosome isolation and purification techniques. We explore great-length exosomes as a mechanism for delivering a variety of substances, including proteins, nucleic acids, small chemicals, and chemotherapeutic drugs. We also talk about the benefits and drawbacks of exosomes. This review concludes with a discussion future perspective and challenges. We hope that this review will provide us a better understanding of the current state of nanomedicine and exosome applications in biomedicine.

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Aflatoxins B1 (AFB1), a type I carcinogen widely present in the environment, not only poses a danger to animal husbandry, but also poses a potential threat to human reproductive health, but its mechanism is still unclear. To address this question, multi-omics were performed on porcine Sertoli cells and mice testis. The data suggest that AFB1 induced testicular damage manifested as decreased expression of GJA1, ZO1 and OCCLUDIN in mice (p < 0.01) and inhibition of porcine Sertoli cell proliferation. Transcriptomic analysis suggested changes in noncoding RNA expression profiles that affect the cell cycle-related Ras/PI3K/Akt signaling pathway after AFB1 exposure both in mice and pigs. Specifically, AFB1 caused abnormal cell cycle of testis with the characterization of decreased expressions of CCNA1, CCNB1 and CDK1 (p < 0.01). Flow cytometry revealed that the G2/M phase was significantly increased after AFB1 exposure. Meanwhile, AFB1 downregulated the expressions of Ras, PI3K and AKT both in porcine Sertoli cell (p < 0.01) and mice testis (p < 0.01). Metabolome analysis verified the alterations in the PI3K/Akt signaling pathway (p < 0.05). Moreover, the joint analysis of metabolome and microbiome found that the changes of metabolites were correlated with the expression of flora. In conclusion, we have demonstrated that AFB1 impairs testicular development via the cell cycle-related Ras/PI3K/Akt signaling.

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Naringin (NAR) is a dihydroflavonoid with various biological activities and pharmacological effects, especially natural antioxidant activity. To gain a better understanding of the effects of NAR on the reproductive system, especially spermatogenesis, we employed western blotting, immunofluorescence, immunohistochemistry, metabolomics and microbiomics to comprehensively dissect the impact of NAR on spermatogenesis. NAR promotes germ cell proliferation and testicular development, and promotes the secretion of sex hormones. Microbiomic and metabonomic analysis showed that NAR improved intestinal microflora and cooperated with serum metabolites to regulate spermatogenesis. Therefore, NAR is beneficial for male reproduction by regulating intestinal microorganisms and serum metabolism.

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Considering that research has mainly focussed on how excessive iron supplementation leads to reproductive cytotoxicity, there is a lack of in-depth research on reproductive system disorders caused by iron deficiency. To gain a better understanding of the effects of iron deficiency on the reproductive system, especially spermatogenesis, we first constructed a mouse model of iron deficiency. We employed multi-omic analysis, including transcriptomics, metabolomics, and microbiomics, to comprehensively dissect the impact of iron deficiency on spermatogenesis. Moreover, we verified our findings in detail using western blot, immunofluorescence, immunohistochemistry, qRT-PCR and other techniques. Microbiomic analysis revealed altered gut microbiota in iron-deficient mice, and functional predictive analysis showed that gut microbiota can regulate spermatogenesis. The transcriptomic data indicated that iron deficiency directly alters expression of meiosis-related genes. Transcriptome data also revealed that iron deficiency indirectly regulates spermatogenesis by affecting hormone synthesis, findings confirmed by metabolomic data, western blot and immunofluorescence. Interestingly, competing endogenous RNA networks also play a vital role in regulating spermatogenesis after iron deficiency. Taken together, the data elucidate that iron deficiency impairs spermatogenesis and increases the risk of male infertility by affecting hormone synthesis and promoting gut microbiota imbalance.

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In this study, the synthesis parameters of the lotus root polysaccharide iron complex (LRPF) were determined and optimized by response surface methodology. Under the optimum preparation conditions, the pH of the solution was 9, the ratio of M (trisodium citrate): m (lotus root polysaccharide) was 0.45, the reaction time was 3 h. UV spectroscopy, thermogravimetry, FT-IR spectroscopy, X-ray diffraction, CD, and NMR were used for the characterization of the LRPF. LRPF has good stability and easily releases iron ions under artificial gastrointestinal conditions. LRPF exhibited antioxidant activity in vitro and can significantly improve the antioxidant activity in vivo. In addition, LRPF has a good effect in the treatment of iron deficiency anemia in model mice, impacts the gut microbiome, and reduces the iron deficiency-induced perniciousness by regulating steroid hormone biosynthesis. Therefore, LRPF can be used as a nutritional supplement to treat and prevent iron-deficiency anemia and improve human immunity.

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Di(2-ethylhexyl)phthalate (DEHP) has proven characteristics of an endocrine-disrupting compound (EDC), which can threaten the reproductive health of humans and other animals. In mammals, a series of chromosomal events occur during the meiotic stage of oocytes. External toxins may enter the body and cause infertility and other related diseases. Therefore, it is crucial to explore the influence of DEHP exposure on the molecular mechanism of germ cell meiosis. We used single-cell RNA sequencing (scRNA-seq) to analyse the ovaries of foetal mice at embryonic day 12.5 (E12.5) and E14.5 after maternal DEHP exposure. DEHP exposure further activated the pathways related to DNA repair in germ cells, increased the expression of genes related to DNA damage and changed the developmental trajectory of germ cells. DEHP exposure may affect the proliferation of pregranulosa (PG) cells. Moreover, DEHP exposure altered the signal transduction between PG cells and germ cells. We showed that DEHP affects meiosis by causing DNA damage in oocytes and disrupting the signal transduction between PG cells and germ cells. These results provide a strong theoretical basis for the prevention and treatment of DEHP-mediated female reproductive health problems.

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Aflatoxin B1 (AFB1) is a type of mycotoxin produced by the fungi Aspergillus flavus and Aspergillus parasiticus and is commonly found in cereals, oils and foodstuffs. In order to understand the toxic effects of AFB1 exposure on Porcine alveolar macrophages (3D4/2 cell), the 3D4/2 cells were exposed to 40 µg/mL AFB1 for 24 h in vitro, and several methods were used for analysis. Edu and TUNEL analysis showed that the proliferation of 3D4/2 cells was significantly inhibited and the apoptosis of 3D4/2 cells was significantly induced after AFB1 exposure compared with that of the control group. Whole-transcriptome analysis was performed to reveal the non-coding RNA alteration in 3D4/2 cells after AFB1 exposure. It was found that the expression of cell-cycle-related and apoptosis-related genes was altered after AFB1 exposure, and lncRNAs and miRNAs were also significantly different among the experimental groups. In particular, AFB1 exposure affected the expression of lncRNAs associated with cellular senescence signaling pathways, such as MSTRG.24315 and MSTRG.80767, as well as related genes, Cxcl8 and Gadd45g. In addition, AFB1 exposure affected the expression of miRNAs associated with immune-related genes, such as miR-181a, miR-331-3p and miR-342, as well as immune-related genes Nfkb1 and Rras2. Moreover, the regulation networks between mRNA-miRNAs and mRNA-lncRNAs were confirmed by the results of RT-qPCR and immunofluorescence. In conclusion, our results here demonstrate that AFB1 exposure impaired proliferation of 3D4/2 cells via the non-coding RNA-mediated pathway.

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With the increasing global incidence of infertility, the influence of environmental factors, lifestyle habits, and nutrients on reproductive health has gradually attracted the attention of researchers. The quantity and quality of sperm play vital roles in male fertility, and both characteristics can be affected by external and internal factors. In this review, the potential role of genetic, environmental, and endocrine factors; nutrients and trace elements in male reproductive health, spermatozoa function, and fertility potency and the underlying mechanisms are considered to provide a theoretical basis for clinical treatment of infertility.

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Galactose is a naturally occurring monosaccharide used to build complex glycans that has not been targeted for labeling as a metabolic reporter. Here, we characterize the cellular modification of proteins by using Ac46AzGal in a dose- and time-dependent manner. It is noted that a vast majority of this labeling of Ac46AzGal occurs intracellularly in a range of mammalian cells. We also provided evidence that this labeling is dependent on not only the enzymes of OGT responsible for O-GlcNAcylation but also the enzymes of GALT and GALE in the Leloir pathway. Notably, we discover that Ac46AzGal is not the direct substrate of OGT, and the labeling results may attribute to UDP-6AzGlc after epimerization of UDP-6AzGal via GALE. Together, these discoveries support the conclusion that Ac46AzGal as an analogue of galactose could metabolically label intracellular O-glycosylation modification, raising the possibility of characterization with impaired functions of the galactose metabolism in the Leloir pathway under certain conditions, such as galactosemias.

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RATIONALE, AIMS AND OBJECTIVES: It is clear there are significant delays in the uptake of best practices as part of routine care in the healthcare system, yet there is conflicting evidence on how to specifically align provider behaviour with best practices. METHOD: We conducted a review of interventions utilized to change any aspect of provider behaviour. To extend prior research, studies were included in the present review if they had an active intervention targeting behaviour change of providers in health or behavioural-health settings and were published between 2001 and 2020. RESULTS: Of 1547 studies, 44 met inclusion criteria. Of 44 studies identified, 28 studies utilized contextually relevant interventions (eg, tailored to a specific provider population). Twenty six interventions with a contextually relevant approach resulted in provider behaviour change. CONCLUSIONS: Findings are promising for encouraging provider behaviour change when interventions are tailored to be contextually relevant, as both single-component and multifaceted interventions were successful when they were contextually relevant. It is critical to conduct additional research to ensure that providers sustain behaviour changes over a long-term beyond an intervention's implementation and evaluation period.

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Objectives: The link between excess adiposity and left ventricular hypertrophy is multifaceted with sparse data among youths. Given that adipokines/hepatokines may influence lipid metabolism in myocardium, we aimed to investigate the relation of the novel hepatokine angiopoietin-like protein 8 (ANGPTL8) and other adipokines with cardiac structure in a cohort of youths and explore to what extent these adipokines/hepatokines affect cardiac structure through lipids. Methods: A total of 551 participants (aged 15-28 years) from the Beijing Child and Adolescent Metabolic Syndrome Study (BCAMS) cohort underwent echocardiographic measurements plus a blood draw assayed for five adipokines/hepatokines including adiponectin, leptin, retinol binding protein 4, fibroblast growth protein 21 and ANGPTL8. Results: Both ANGPTL8 (ß = -0.68 g/m2.7 per z-score, P= 0.015) and leptin (ß = -1.04 g/m2.7 per z-score, P= 0.036) were significantly inversely associated with left ventricular mass index (LVMI) independent of classical risk factors. Total cholesterol and low-density lipoprotein cholesterol significantly mediated the ANGPTL8-LVMI association (proportion: 19.0% and 17.1%, respectively), while the mediation effect of triglyceride on the ANGPTL8-LVMI relationship was strongly moderated by leptin levels, significantly accounting for 20% of the total effect among participants with higher leptin levels. Other adipokines/hepatokines showed no significant association with LVMI after adjustment for body mass index. Conclusions: Our findings suggest ANGPTL8, particularly interacting with leptin, might have a protective role in cardiac remodeling among youths with risk for metabolic syndrome. Our results offer insights into the pathogenesis of the cardiomyopathy and the potential importance of tissue-tissue crosstalk in these effects.

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