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Objectives: Sleep health and other lifestyle behaviours are gaining increasing attention in public health, particularly for cancer prevention, but a comprehensive assessment is lacking. Methods: The study included 380,042 UK Biobank participants. A healthy sleep score was constructed based on five sleep factors: chronotype, sleep duration, insomnia, snoring, and daytime dozing. A healthy lifestyle score was constructed based on four lifestyle factors: smoking, alcohol consumption, diet and physical activity. The effect of healthy sleep and lifestyle on cancer risk was examined by Cox proportional hazard models. Results: Both healthy sleep and lifestyle patterns were significantly associated with a reduced risk of overall cancer and specific cancer sites. Participants with healthy sleep and lifestyle patterns had a lower risk of overall cancer (HR = 0.72, 95% CI = 0.68–0.77), liver cancer (HR = 0.53, 95% CI = 0.31–0.90), bladder cancer (HR = 0.61, 95% CI = 0.47–0.79), lung cancer (HR = 0.22, 95% CI = 0.19–0.27), and colorectal cancer (HR = 0.80, 95% CI = 0.66–0.96) compared to those with unhealthy patterns. Conclusion: Our findings highlight the importance of public health education and interventions to improve sleep and other lifestyle behaviours for cancer prevention. [ABSTRACT FROM AUTHOR]

Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most common dementia in the aged population and is characterizd by hidden attack and progressive development. Some studies showed that exosomal microRNAs(miRNAs) regulates the shearing of amyloid precusor protein,deposition of beta-amyloid peptides(Aβ) and phosphorylation of Tau protein, influencing the generation of neuritic plaques and neurofibrillary tangles. In addition, special miRNAs can be transpor-ted by exsome across blood-brain-barrier and inhibit Tau phosphorylation. Measuring the expression profile of exosomal miRNAs in the peripheral blood may be a non-invasive diagnosis and treatment method of AD.

Previous studies have demonstrated strong associations between host genetic factors and Epstein–Barr virus (EBV) VCA‐IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA‐IgA on NPC risk is not well understood. In this two‐stage case–control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome‐wide association study‐derived polygenic risk score [PRS]) and EBV VCA‐IgA antibody level in the NPC risk. We employed a four‐way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA‐IgA. We consistently found a significant interaction between the PRS and EBV VCA‐IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85–3.10; replication population: SI = 3.10, 95% CI = 2.17–4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA‐IgA antibody. We also observed an obvious dose–response relationship between the PRS and EBV VCA‐IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic‐EBV interaction, while the risk effects mediated by EBV VCA‐IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA‐IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk. [ABSTRACT FROM AUTHOR]

In order to make the synthetic route of Thiamidol more efficient and easier to scale up, a new method was developed. The compound 2,4-dihydroxyacetophenone was dissolved in ethyl acetate and brominated with cupric bromide. After bromination, the mixture was filtered to remove cuprous bromide. The obtained ethyl acetate solution containing 2-bromo-1-(2, 4-dihydroxyphenyl) ethanone was directly reacted with (2-methylpropanoyl) thiourea to obtain the precipitate of Thiamidol hydrobromide. The precipitate was neutralized by deacidification and recrystallized to afford Thiamidol with high purity. In addition, in the screening of fertilitypromoting substances, Thiamidol was found to be effective in protecting human sperm from motility loss in vitro. This suggests that it may have potential application in fertility protection and promotion. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) molecules are essential for presenting Epstein−Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA‐bound EBV peptides and NPC risk through in silico HLA‐peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA‐target sequencing was performed. HLA‐peptide binding prediction for EBV, followed by peptidome‐wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high‐risk mutations were analyzed. We found that NPC‐associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA‐A alleles (p = 3.10 × 10−4 for immunogenic proteins and p = 8.10 × 10−5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC‐risk effect (padj = 3.77 × 10−4) and supertype A03 presented an NPC‐protective effect (padj = 4.89 × 10−4). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC‐risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC‐risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development. [ABSTRACT FROM AUTHOR]

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case–control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52–4.25) and OR = 1.54 (1.02–2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome. [ABSTRACT FROM AUTHOR]

The 3C-like protease (also known as Mpro) plays a key role in SARS-CoV-2 replication and has similar substrates across mutant coronaviruses, making it an ideal drug target. We synthesized 19 thiazolidinedione derivatives via the Knoevenagel condensations and Mitsunobu reactions as potential 3C-like protease inhibitors. The activity of these inhibitors is screened in vitro by employing the enzymatic screening model of 3C-like protease using fluorescence resonance energy transfer. Dithiothreitol is included in the enzymatic reaction system to avoid non-specific enzymatic inhibition. Active inhibitors with diverse activity are found in this series of compounds, and two representative inhibitors with potent inhibitory activity are highlighted. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is an evolutionarily conserved and multifunctional factor across species. We previously reported that Emc10 knockout (KO) leads to mouse male infertility. Emc10-null spermatozoa exhibit multiple aspects of dysfunction, including reduced sperm motility. Two subunits of a Na/K-ATPase, ATP1A4 and ATP1B3, are nearly absent in Emc10 KO spermatozoa. Here, two isoforms of EMC10 were characterized in the mouse testis and epididymis: the membrane-bound (mEMC10) and secreted (scEMC10) isoforms. We present evidence that mEMC10, rather than scEMC10, is required for cytoplasm sodium homeostasis by positively regulating ATP1B3 expression in germ cells. Intra-testis mEMC10 overexpression rescued the sperm motility defect caused by Emc10 KO, while exogenous recombinant scEMC10 protein could not improve the motility of spermatozoa from either Emc10 KO mouse or asthenospermic subjects. Clinically, there is a positive association between ATP1B3 and EMC10 protein levels in human spermatozoa, whereas no correlation was proven between seminal plasma scEMC10 levels and sperm motility. These results highlight the important role of the membrane-bound EMC10 isoform in maintaining cytoplasm sodium homeostasis and sperm motility. Based on the present results, the mEMC10-Na, K/ATPase α4β3 axis is proposed as a novel mechanism underlying the regulation of cytoplasmic sodium and sperm motility, and its components seem to have therapeutic potential for asthenospermia. [ABSTRACT FROM AUTHOR]

Background: An increasing number of children and adolescents have reported mental health problems, and resilience is a protective factor against these problems. Therefore, the aim of the study is to verify the effect of peer education based on adolescent health education on adolescent resilience. Method: A cluster randomized controlled trial was conducted including 1,613 students who were divided into an intervention group (19 classes, 732 participants) and a control group (24 classes, 881 participants). One-year peer education was performed in the intervention group, and the control group had no interventions. The Resilience Scale for Chinese Adolescents by Yueqin Hu and a self-designed basic information questionnaire were used to collect data. Chi-square test and rank-sum test were used to compare the differences of demographic characteristics between the two groups. A linear mixed model was used to compare the changes of resilience between the two groups after intervention, and the intra-cluster correlation coefficient (ICC) was calculated. A generalized linear mixed model (GLMM) was used to verify the effect of peer education on adolescent resilience. The significance was set at P < 0.05. Results: After intervention, compared with the control group, the intervention group showed significant improvement in target focus, emotion adjustment, interpersonal assistance and total resilience (P < 0.05). The ICC range was 0.003 to 0.034. The GLMM results indicated that peer education based on adolescent health education had significant effects on adolescents' target focus (β = 0.893, P = 0.002), emotional adjustment (β = 1.766, P < 0.001), interpersonal assistance (β = 1.722, P = 0.016) and total mental resilience (β = 5.391, P < 0.001), and the effect was greater for boys than for girls. Conclusions: Peer education based on adolescent health education is effective for improving adolescents' target focus, emotional adjustment, interpersonal assistance, and total resilience, especially for males. Future research should devote more attention to positive cognition and family support as well as gender differences. [ABSTRACT FROM AUTHOR]

Public health of human beings is threatened by superbugs. Novel human beta-defensins, which contribute to host defense against pathogen invasion and innate immune protection, might be a potent natural candidate pool for new antibiotic lead screening. In the present work, we successfully expressed and purified a novel human beta-defensin, DEFB120, using the IMPACT-TWIN system in Escherichia coli and identified the purified homogeneous proteins using MALDI-TOF mass spectrometry. Then, we performed the fundamental studies on the structure and biological functions for the DEFB120 peptide. The recombinant DEFB120 peptide showed wide antimicrobial effects against E. coli, Staphylococcus aureus and Candida albicans strains without significant hemolytic activity. Furthermore, the high lipopolysaccharide (LPS)-binding affinity in vitro indicated that DEFB120 might be associated with the inhibition of LPS-induced inflammatory response. These results may pave a way for exploiting the essential physiological functions of DEFB120 and also for the development of natural antibiotic pools. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Acetamiprid (ACE) and imidacloprid (IMI) are two major members in the family of neonicotinoid pesticides, which are synthesized with a higher selectivity to insects. The present study determined and compared in vitro effects of ACE, IMI and nicotine on mammalian reproduction by using an integrated testing strategy for reproductive toxicology, which covered sperm quality, sperm penetration into oocytes and preimplantation embryonic development. Direct chemical exposure (500 µM or 5 mM) on spermatozoa during capacitation was performed, and in vitro fertilization (IVF) process, zygotes and 2-cell embryos were respectively incubated with chemical-supplemented medium until blastocyst formation to evaluate the reproductive toxicity of these chemicals and monitor the stages mainly affected. Generally, treatment of 500 µM or 5 mM chemicals for 30 min did not change sperm motility and DNA integrity significantly but the fertilization ability in in vitro fertilization (IVF) process, indicating that IVF process could detect and distinguish subtle effect of spermatozoa exposed to different chemicals. Culture experiment in the presence of chemicals in medium showed that fertilization process and zygotes are adversely affected by direct exposure of chemicals (P<0.05), in an order of nicotine>IMI>ACE, whereas developmental progression of 2-cell stage embryos was similar to controls (P>0.05). These findings unveiled the hazardous effects of neonicotinoid pesticides exposure on mammalian sperm fertilization ability as well as embryonic development, raising the concerns that neonicotinoid pesticides may pose reproductive risks on human reproductive health, especially in professional populations. [ABSTRACT FROM AUTHOR]

Apple pectins, proteins and catechins were combined in model systems, and the resulting hazes were measured by spectrophotometric method, a zeta potential and particle size analyzer and Ostwald viscosimeter. The amount of hazes formed depends on the concentrations of both protein and pectin. The cooperative hydrogen bonding between the numerous hydroxyl groups of pectins and hydrone and the gel-like structure developed by pectin induced the solvation or solubilization of polymers, and the protein molecule has a fixed number of polyphenol binding sites. The influence of pectin relative molecular mass and degree of esterification on the formation of suspended particles is prominent, and this makes the number of hydroxyl groups and charge of pectin which is concerned with combining protein and catechin to change a lot. More haze was observed when model systems were heated, suggesting that hydrophobic groups of protein are beneficial to their binding with phenols and pectins. The pH value affects the charged state of the protein and pectin, which influences the combination of pectin–gliadin–catechin. [ABSTRACT FROM PUBLISHER]

Approximately 40-50 β-defensins are predominantly expressed in the male reproductive system of mammals. This selective expression raises the question as to the roles of these molecules in innate immunity and fertility in the male reproductive tract. Rat β-defensin 22 is an epididymis-specific β-defensin expressed in segments 12-14 of the epididymis. This protein contains both β-defensin and lectin signature sequences, yet its antimicrobial activity and carbohydrate-binding ability have not been shown. We herein demonstrated the antimicrobial activity of recombinant rat β-defensin 22 against Escherichia coli and Candida albicans. Its lectin-like activity was also investigated by demonstrating its binding ability with heparin beads. This heparin-binding activity implies some potential roles for this defensin in determining the fertilisation capabilities of sperm. [ABSTRACT FROM AUTHOR]