Understanding the Molecular Landscape of Endometriosis: A Bioinformatics Approach to Uncover Signaling Pathways and Hub Genes.

Background: Endometriosis is a chronic gynecological disorder characterized by the ectopic growth of endometrial tissue outside the uterus, leading to debilitating pain and infertility in affected women. Despite its prevalence and clinical significance, the molecular mechanisms underlying the progression of endometriosis remain poorly understood. This study employs bioinformatics tools and molecular docking simulations to unravel the intricate genetic and molecular networks associated with endometriosis progression. Objectives: The primary objectives of this research are to identify differentially expressed genes (DEGs) linked to endometriosis, elucidate associated biological pathways using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), construct a Protein-Protein Interaction (PPI) network to identify hub genes, and perform molecular docking simulations to explore potential ligand-protein interactions associated with endometriosis. Methods: Microarray data from Homo sapiens, specifically Accession: GDS3092 Series = GSE5108 (Platform: GPL2895), were retrieved from the NCBI Gene Expression Omnibus (GEO). The data underwent rigorous preprocessing and DEG analysis using NCBI GEO2. Database for Annotation, Visualization, and Integrated Discovery analysis was employed for functional annotation, and a PPI network was constructed using the STITCH database and Cytoscape 3.8.2. Molecular docking simulations against target proteins associated with endometriosis were conducted using MVD 7.0. Results: A total of 1 911 unique elements were identified as DEGs associated with endometriosis from the microarray data. Database for Annotation, Visualization, and Integrated Discovery analysis revealed pathways and biological characteristics positively and negatively correlated with endometriosis. Hub genes, including BCL2, CCNA2, CDK7, EGF, GAS6, MAP3K7, and TAB2, were identified through PPI network analysis. Molecular docking simulations highlighted potential ligands, such as Quercetin-3-o-galactopyranoside and Kushenol E, exhibiting favorable interactions with target proteins associated with endometriosis. Conclusions: This study provides insights into the molecular signatures, pathways, and hub genes associated with endometriosis. Utilizing DAVID in this study clarifies biological pathways associated with endometriosis, revealing insights into intricate genetic networks. Molecular docking simulations identified ligands for further exploration in therapeutic interventions. The consistent efficacy of these ligands across diverse targets suggests broad-spectrum effectiveness, encouraging further exploration for potential therapeutic interventions. The study contributes to a deeper understanding of endometriosis pathogenesis, paving the way for targeted therapies and precision medicine approaches to improve patient outcomes. These findings advance our understanding of the molecular mechanisms in endometriosis (EMS), offering promising avenues for future research and therapeutic development in addressing this complex condition.

Anisotropy of Additively Manufactured Metallic Materials.

Additive manufacturing (AM) is a technology that builds parts layer by layer. Over the past decade, metal additive manufacturing (AM) technology has developed rapidly to form a complete industry chain. AM metal parts are employed in a multitude of industries, including biomedical, aerospace, automotive, marine, and offshore. The design of components can be improved to a greater extent than is possible with existing manufacturing processes, which can result in a significant enhancement of performance. Studies on the anisotropy of additively manufactured metallic materials have been reported, and they describe the advantages and disadvantages of preparing different metallic materials using additive manufacturing processes; however, there are few in-depth and comprehensive studies that summarize the microstructural and mechanical properties of different types of additively manufactured metallic materials in the same article. This paper begins by outlining the intricate relationship between the additive manufacturing process, microstructure, and metal properties. It then explains the fundamental principles of powder bed fusion (PBF) and directed energy deposition (DED). It goes on to describe the molten pool and heat-affected zone in the additive manufacturing process and analyzes their effects on the microstructure of the formed parts. Subsequently, the mechanical properties and typical microstructures of additively manufactured titanium alloys, stainless steel, magnesium-aluminum alloys, and high-temperature alloys, along with their anisotropy, are summarized and presented. The summary indicates that the factors leading to the anisotropy of the mechanical properties of metallic AM parts are either their unique microstructural features or manufacturing defects. This anisotropy can be improved by post-heat treatment. Finally, the most recent research on the subject of metal AM anisotropy is presented.

One-Pot Synthesis of C@BiOBr for Efficient Photocatalytic Degradation of Phenol.

This work describes the synthesis of C@BiOBr using glucose as the carbon precursor by a repeatable one-step hydrothermal method. Characterization studies indicate that the structure of BiOBr did not change after the carbon layer was encapsulated on the surface. The highest activity is achieved at 1.2-C@BiOBr, with 97% of phenol (50 mg·L-1) degrading within 90 min, and the degradation amount of phenol is determined to be 48.5 mg·g-1 with a speed of 0.54 mg·g-1·min-1. The useful species of phenol degradation are studied and assigned to •O2-, 1O2, and h+. The effect of coated carbon layer for photocatalytic degradation of phenol over BiOBr is studied by photoelectrochemical experiments, fluorescence spectra, and density functional theory (DFT) calculations. It is attributed to the good conductivity of carbon, enhanced separation of the photocarriers by carbon coating, and thermodynamically favorable reactive oxygen species (ROS) production on the surface of carbon. This work demonstrates that carbon coating is an effective strategy to improve the photocatalytic activity of BiOBr and reveals the detailed mechanism.

Dynamic impacts of public health events on price fluctuations in broiler industry Chain in China: Evidence from COVID-19 epidemic.

Using weekly data from January 2020 to December 2021 on the prices of various links in the Chinese broiler industry chain and the COVID-19 epidemic, we employed a time-varying parametric vector auto-regressive (TVP-VAR) model to investigate the dynamic effects of public health events on price fluctuations of upstream, midstream, and downstream products in the Chinese broiler industry chain. Our findings showed that the COVID-19 epidemic had different effects on the prices of various broiler products, both in direction and magnitude, at different lags and time intervals. Chicken and live chicken prices were impacted the most, followed by broiler chick prices, while broiler feed prices were impacted the least. The epidemic constantly impacted broiler chick and chicken prices, while its effect on live chicken prices was initially negative but turned positive afterwards. Additionally, the impact of the COVID-19 epidemic on broiler product prices consistently increased with more extended lag periods. The impulse responses at different epidemic time points were heterogeneous. With the results of this study, policy recommendations can be suggested to relevant government departments to optimize the prevention and control measures for public health emergencies and ensure price stability in the broiler industry.

Oxford Nanopore Technologies (ONT) Full-length Transcriptomics Shows Electroacupuncture ameliorates Lipid Metabolic Disorder through Suppressing Hepatic Pdia3/Perk/Qrich1 Expression in Rats.

BACKGROUND: The incidence of dyslipidemia increases after menopause. Electroacupuncture (EA) has been recommended for menopause-related disease. However, the positive effect on lipid metabolism disorders is still unclear. OBJECTIVES: To investigate the underlying mechanism of EA treatment on lipid metabolism disorders through ONT full-length transcriptome sequencing Methods: Adult female SD rats were randomly divided into Ctrl, sham operation+high-fat feed(Sham+HFD), Ovariectomized+high-fat feed (OVX+HFD), Ovariectomized+high-fat feed + Atorvastatin (OVX+HFD+ATO) and OVX+HFD+EA groups. Periovarian adipose tissue around the bilateral ovaries of rats in the Sham+HFD group was resected. Rats in the OVX+HFD, OVX+HFD+ATO and OVX+HFD+EA groups were subjected to bilateral oophorectomy to prepare the ovariectomized rat model. Treatment was applied to rats in the OVX+HFD+EA group. ST36, PC6, SP6, BL18 and ST40 were the selected acupoints. Daily food intake and body weights of rats were recorded. The samples were collected 30 days after treatment. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) were detected to assess the improvement of lipid metabolism disorders. HE and oil red O staining were used to stain the liver tissues. Total RNA was extracted from liver tissues, and its transcriptional changes were determined by high-throughput sequencing. Additionally, RTÁqPCR and immunofluorescence staining were used to verify the crucial signal pathway screened by the ONT fullÁlength transcriptome sequencing. RESULTS: EA treatment resulted in a lowered weight of perirenal fat and liver and a significant improvement in the color of the liver. In addition, EA could improve the lipid profile and hepatic steatosis in OVX+HFD rats. According to fullÁlength transcriptome sequencing, 2292 genes showed differential expression in the OVX+HFD group; of these, 1121 were upregulated and 1171 down-regulated. 609 DEGs were found in the OVX+HFD+EA group compared to the OVX+HFD group; 235 up-regulated and 374 down-regulated. We also found that 77 genes are significantly upregulated after EA intervention through Venn map analysis (including Agtr1a, Pdia3, etc.), which may be the targeted genes for EA treatment of lipid metabolism disorders. Finally, we verified the expression of Pdia3, Perk and Qrich1 levels in liver tissues. HFD feeding could increase the expression of Pdia3 and its downstream signal pathways molecular Perk and Qrich1. But these effects were reversed by EA treatment, the results demonstrated that the expression of pdia3, Perk, as well as Qrich1 of OVX+HFD rats had a decreasing trend after EA treatment. CONCLUSIONS: EA could ameliorate lipid metabolic disorder in OVX+HFD rats. The Pdia3/Perk/Qrich1 signal pathway may play crucial roles in the improvement of lipid metabolism disorder of OVX+HFD rats after EA treatment.

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin.

Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.

Comparison of two ablation procedures combined with high ligation and foam sclerotherapy and compression therapy for patients with venous leg ulcers.

AIM: To compare the ablation techniques' efficacy of endovenous microwave ablation (EMA) combined with high ligation (HL), foam sclerotherapy (FS) and compression therapy (CT) and endovenous laser ablation (EVLA) combined with HL-FS-CT in the treatment of VLUs. METHOD: 301 consecutive patients with VLUs from 2013 to 2022 in a 3200-bed hospital were intervened by EMA combined with HL-FS-CT and EVLA combined with HL-FS-CT were retrospectively compared. RESULTS: One hundred thirty-four patients underwent EMA+HL-FS-CT and 167 patients underwent EVLA+HL-FS-CT. The primary outcome of the ulcer healing time was 1.45(0.75-1.5) months and 1.86(0.5-2.5) months, respectively, in the two groups (HR for ulcer healing was 1.26, 95% CI [0.96-1.66], p = 0.097). Secondary outcomes included that no significant difference was found in ulcer recurrence and GSV recanalization and complications between the two groups, and the postoperative VCSS and AVVQ were significantly lower than the baseline values in the respective groups (p = 0.0001). CONCLUSION: EMA+HL-FS-CT and EVLA+HL-FS-CT are both effective at treating VLUs. Both of the two comprehensive treatments were beneficial to the healing of ulcers, but no evidence showed which one was superior in the ulcer healing time.

Short-term efficacy of endovascular procedures for lower extremity thromboangiitis obliterans (Buerger's disease).

PURPOSE: Although thrombolysis obliterans (TAO) has been recognized for more than a century, there is no optimal treatment for this disease. The aim of this report was to compare the short-term efficacies of catheter-directed thrombolysis (CDT), percutaneous transluminal angioplasty (PTA) and CDT+PTA in treating TAO disease. METHOD: Consecutive patients with TAO treated at Ganzhou People's Hospital between 2012 and 2022 were included in this retrospective study. According to the information provided in the medical records, endovascular procedures included CDT, PTA or CDT+PTA. One-year follow-up outcomes of the patients with TAO who underwent endovascular procedures were compared. The primary outcome was major adverse limb event (MALE) and the secondary outcomes were the technical success, complications, ABI at 1 week after surgery and minor amputation. RESULTS: Sixty-nine patients with TAO were assessed for inclusion in our single-center study from 2012 to 2022 and received endovascular procedures. Among them, 22 patients underwent CDT, 21 patients underwent PTA, and 26 patients underwent PTA+CDT. The one-year follow-up revealed significant differences in the MALE-free survival rates among the three groups, particularly between the CDT group and the PTA+CDT group (the hazard ratio (HR) for MALE-free survival was 0.173, 95% CI [0.050-0.599], p = 0.006). The technical success rates of the three groups were 63.6%, 90.5%, and 92.3%, respectively. There were differences in the ABI at one week after surgery among the three groups. CONCLUSIONS: Endovascular procedures are effective for TAO in the short term. The effectiveness of CDT alone is suboptimal; combining CDT with PTA achieves the most favorable endovascular treatment outcome; while the effectiveness of PTA falls in between these two procedures.

Causal Relationship Between Endometriosis and Pelvic Inflammatory Diseases: Mendelian Randomization Study.

Objective: This study explores the causal relationship between endometriosis and pelvic inflammatory diseases (PID). Methods: The study utilized genome-wide association study (GWAS) datasets for endometriosis ("finn-b-N14_ENDOMETRIOSIS") and PID ("finn-b-N14_OTHFEMPELINF"). Subsequently, two-sample Mendelian randomization (MR) analyses were conducted using inverse variance weighting (IVW), Egger regression (MR-Egger), and weighted median (WM) methods. Heterogeneity was evaluated using Cochran's Q test, and in case of detected outliers, they were removed for re-evaluation of MR causality. Results: From the endometriosis GWAS dataset, 33 single nucleotide polymorphisms (SNPs) were selected as instrumental variables. All three methods, IVW (OR = 1.39, P < 1×10-8), MR-Egger (OR = 1.41, P = 0.003), and WM (OR = 1.37, P = 1.16×10-5) confirmed a causal relationship between endometriosis and PID. The association between endometriosis and pelvic inflammation remained unaffected by the exclusion of individual SNPs. Lastly, Cochran's Q test and funnel plots showed no evidence of SNP asymmetry. Conclusion: The results of the MR analysis support a potential causal relationship between endometriosis and an increased risk of PID.

Screening and optimization of shark nanobodies against SARS-CoV-2 spike RBD.

SARS-CoV-2 continues to threaten human health, antibody therapy is one way to control the infection. Because new SARS-CoV-2 mutations are constantly emerging, there is an urgent need to develop broadly neutralizing antibodies to block the viral entry into host cells. VNAR from sharks is the smallest natural antigen binding domain, with the advantages of small size, flexible paratopes, good stability, and low manufacturing cost. Here, we used recombinant SARS-CoV-2 Spike-RBD to immunize sharks and constructed a VNAR phage display library. VNAR R1C2, selected from the library, efficiently binds to the RBD domain and blocks the infection of ACE2-positive cells by pseudovirus. Next, homologous bivalent VNARs were constructed through the tandem fusion of two R1C2 units, which enhanced both the affinity and neutralizing activity of R1C2. R1C2 was predicted to bind to a relatively conserved region within the RBD. By introducing mutations at four key binding sites within the CDR3 and HV2 regions of R1C2, the affinity and neutralizing activity of R1C2 were significantly improved. Furthermore, R1C2 also exhibits an effective capacity of binding to the Omicron variants (BA.2 and XBB.1). Together, these results suggest that R1C2 could serve as a valuable candidate for preventing and treating SARS-CoV-2 infections.

Site-Specifically Modified Peptide Inhibitors of Protein Tyrosine Phosphatase 1B and T-Cell Protein Tyrosine Phosphatase with Enhanced Stability and Improved In Vivo Long-Acting Activity.

Protein tyrosine phosphatase 1B (PTP1B) and TC-PTP can function in a coordinated manner to regulate diverse biological processes including insulin and leptin signaling, T-cell activation, and tumor antigen presentation, which makes them potential targets for several therapeutic applications. We have previously demonstrated that the lipidated BimBH3 peptide analogues were a new class of promising PTP1B inhibitors with once-weekly antidiabetic potency. Herein, we chemically synthesized two series of BimBH3 analogues via site-specific modification and studied their structure-activity relationship. The screened analogues S2, S6, A2-14, A2-17, A2-20, and A2-21 exhibited an improved PTP1B/TC-PTP dual inhibitory activity and achieved good stability in the plasma of mice and dogs, which indicated long-acting potential. In mouse models of type 2 diabetes mellitus (T2DM), the selected analogues S6, S7, A2-20, and A2-21 with an excellent target activity and plasma stability generated once-weekly therapeutic potency for T2DM at lower dosage (0.5 µmol/kg). In addition, evidence was provided to confirm the cell permeability and targeted enrichment of the BimBH3 analogues. In summary, we report here that site-specific modification and long fatty acid conjugation afforded cell-permeable peptidomimetic analogues of BimBH3 with enhanced stability, in vivo activity, and long-acting pharmacokinetic profile. Our findings could guide the further optimization of BimBH3 analogues and provide a proof-of-concept for PTP1B/TC-PTP targeting as a new therapeutic approach for T2DM, which may facilitate the discovery and development of alternative once-weekly anti-T2DM drug candidates.

Overcoming strength-ductility tradeoff with high pressure thermal treatment.

Conventional material processing approaches often achieve strengthening of materials at the cost of reduced ductility. Here, we show that high-pressure and high-temperature (HPHT) treatment can help overcome the strength-ductility trade-off in structural materials. We report an initially strong-yet-brittle eutectic high entropy alloy simultaneously doubling its strength to 1150 MPa and its tensile ductility to 36% after the HPHT treatment. Such strength-ductility synergy is attributed to the HPHT-induced formation of a hierarchically patterned microstructure with coherent interfaces, which promotes multiple deformation mechanisms, including dislocations, stacking faults, microbands and deformation twins, at multiple length scales. More importantly, the HPHT-induced microstructure helps relieve stress concentration at the interfaces, thereby arresting interfacial cracking commonly observed in traditional eutectic high entropy alloys. These findings suggest a new direction of research in employing HPHT techniques to help develop next generation structural materials.

Comprehensive analysis of phenotypes and transcriptome characteristics reveal the best atopic dermatitis mouse model induced by MC903.

BACKGROUND: Although several mouse models of exogenous-agent-induced atopic dermatitis (AD) are currently available, the lack of certainty regarding their similarity with human AD has limited their scientific value. Thus, comprehensive evaluation of the characteristics of mouse models and their similarity with human AD is essential. OBJECTIVE: To compare six different exogenous-agent-induced AD mouse models and find out the optimum models for study. METHODS: Female BALB/c mice underwent induction of AD-like dermatitis by MC903 alone or in combination with ovalbumin (OVA), dinitrofluorobenzene (DNFB) alone or in combination with OVA, OVA alone, or Staphylococcus aureus. Gross phenotype, total immunoglobulin E (IgE) level, histopathological manifestations, and skin lesion transcriptome were analyzed, and metagenomic sequencing of the gut microbiome was performed. RESULTS: The DNFB plus OVA model showed the highest disease severity, while the OVA model showed the lowest severity. The MC903 and MC903 plus OVA models showed high expression of T-helper (Th)2- and Th17-related genes; the DNFB and DNFB plus OVA models showed upregulation of Th1-, Th2-, and Th17-related genes; while the S. aureus inoculation model showed more enhanced Th1 and Th17 immune responses. In contrast to the other models, the OVA-induced model showed the lowest expression levels of inflammation-related genes, while the MC903 model shared the largest overlap with human AD profiles. The intestinal microbiota of all groups showed significant differences after modeling. CONCLUSION: Each AD mouse model exhibited different characteristics. The MC903 model was the best to recapitulate most features of human AD among these exogenous-agent-induced AD models.

Senescent fibroblasts and innate immune cell activation might play a role in the pathogenesis of elderly atopic dermatitis.

BACKGROUND: Elderly atopic dermatitis (AD) is a subtype of AD defined by age (≥ 60 years). The molecular characteristics of elderly AD remain to be clarified. OBJECTIVE: We sought to characterize the molecular features of skin lesions and peripheral blood mononuclear cells (PBMCs) in patients with AD across different age, focusing on elderly AD. METHODS: Skin and PBMCs samples were used for RNA sequencing. Analysis of differentially expressed genes and gene set variation analysis were performed. Immunofluorescence staining, quantitative real-time PCR (qRT-PCR), flow cytometry and transwell assay were used for validation. RESULTS: Compared with healthy controls, the skin transcriptome of AD patients showed common signatures of AD, like barrier dysfunction and enhanced Th1/Th2/Th17 immune pathways. In PBMCs, the expression of Th1/Th2 response genes was more remarkable in adult AD, while expression of Th17-related genes was significantly higher in childhood AD. The gene modules associated with natural killer (NK) cells were downregulated in elderly AD. In skin lesions, elderly AD exhibited enrichment of macrophages, fibroblasts and senescence-associated secretory phenotype (SASP) related genes. The correlation among fibroblasts, SASP and innate immune cells were revealed by the co-localization of fibroblasts, macrophages and NK cells in the lesions across different age groups. Fibroblasts under inflammation or senescence could induce stronger chemotaxis of macrophages and NK cells. CONCLUSION: We identified the molecular phenotypes of skin lesions and PBMCs in elderly AD individuals. Fibroblasts, innate immune cells, and SASP might play important roles in the pathogenesis of elderly AD.

Design of Selective PARP-1 Inhibitors and Antitumor Studies.

Designing selective PARP-1 inhibitors has become a new strategy for anticancer drug development. By sequence comparison of PARP-1 and PARP-2, we identified a possible selective site (S site) consisting of several different amino acid residues of α-5 helix and D-loop. Targeting this S site, 140 compounds were designed, synthesized, and characterized for their anticancer activities and mechanisms. Compound I16 showed the highest PARP-1 enzyme inhibitory activity (IC50 = 12.38 ± 1.33 nM) and optimal selectivity index over PARP-2 (SI = 155.74). Oral administration of I16 (25 mg/kg) showed high inhibition rates of Hela and SK-OV-3 tumor cell xenograft models, both of which were higher than those of the oral positive drug Olaparib (50 mg/kg). In addition, I16 has an excellent safety profile, without significant toxicity at high oral doses. These findings provide a novel design strategy and chemotype for the development of safe, efficient, and highly selective PARP-1 inhibitors.

Photothermal-responsive lignin-based polyurethane with mechanically robust, fast self-healing, solid-state plasticity and shape-memory performance.

In light of the depletion of petrochemical resources and increase in environmental pollution, there has been a significant focus on utilizing natural biomass, specifically lignin, to develop sustainable and functional materials. This research presents the development of a lignin-based polyurethane (DLPU) with photothermal-responsiveness by incorporating lignin and oxime-carbamate bonds into polyurethane network. The abundant hydrogen bonds between lignin and the polyurethane matrix, along with its cross-linked structure, contribute to DLPU's excellent mechanical strength (30.2 MPa) and toughness (118.7 MJ·m-3). Moreover, the excellent photothermal conversion ability of DLPU (54.4 %) activates dynamic reversible behavior of oxime-carbamate bonds and hydrogen bonds, thereby endowing DLPU with exceptional self-healing performance. After 15 min of near-infrared irradiation, DLPU achieves self-healing efficiencies of 96.0 % for tensile strength and 96.3 % for elongation at break. Additionally, DLPU exhibits photocontrolled solid-state plasticity as well as an excellent phototriggered shape-memory effect (70 s), with shape fixity and recovery ratios reaching 98.8 % and 95.3 %, respectively. By exploiting the spatial controllability and photothermal-responsiveness of DLPU, we demonstrate multi-dimensional responsive materials with self-healing and shape-shifting properties. This work not only promotes the development of multi-functional polyurethanes but also provides a pathway for the high-value utilization of lignin.

Relationship between long-term shift work; night work; sleep deficiency and stroke: A systematic review and meta-analysis.

BACKGROUND: The association between shift/night work and the risk of stroke is not supported by strong evidence. OBJECTIVE: This study aimed to obtain evidence of a potential relationship between shift/night shift work and the risk of stroke. METHODS: We searched PubMed, Embase, the Cochrane Library and Web of science databases for eligible studies from inception to January 19, 2024. We followed the statement in the Preferred Reporting Items for Systematic Evaluations and Meta-Analysis (PRISMA). STATA 14.0 software was used for meta-analysis. RESULTS: A total of five studies involving 700,742 subjects were included in this meta-analysis. We found that shift/night workers had a 1.08 times higher risk of stroke than non-shift/night workers (RR: 1.08; 95 % CI: 1.05-1.10; P < 0.001). CONCLUSION: Shift/night work may be a risk factor for stroke. More objective prospective studies are needed to further support this result.

Efficacy of probiotic supplements on Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of probiotics supplementation in the treatment of Parkinson's disease (PD). METHODS: We searched China National Knowledge Infrastructure (CNKI), Weipu (VIP) database, Wanfang Database, Sinomed (CBM), PubMed, Embase, Cochrane library and Web of Science databases for eligible studies from inception to January 4th, 2024. Randomized controlled trials (RCTS) comparing the effects of probiotic supplements and placebo in patients with PD. Meta-analysis was conducted with the software Review Manager 5.4. The quality assessment was performed according to Cochrane risk of bias tool. RESULTS: A total of 11 RCTs with 756 PD patients were included in this study. We found that probiotics could increase the number of complete bowel movements (CBMs) per week and improved the scores of Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) (SMD = 0.73, 95 % CI: 0.54 to 0.92, P < 0.00001, I2 = 45 %; SMD = - 0.79, 95 % CI: - 1.19 to - 0.39, P < 0.001, I2 = 55 %, respectively) compared with the placebo group. However, there was no significant difference between the two groups in improving fecal traits and defecation efforts in PD patients (SMD = 0.87, 95 % CI: 0.01 to 1.74, P = 0.05, I2 = 94 %; SMD = 1.24, 95 % CI: - 1.58 to 4.06, P > 0.05, I2 = 98 %, respectively). In terms of PD composite scale scores: after treatment, there was no significant difference in Movement Disorder Society-Unified-Parkinson Disease Rating Scale Ⅲ score (MDS-UPDRSⅢ) between the probiotic group and the placebo group (SMD = - 0.09, 95 % CI: - 0.35 to 0.16, P > 0.05, I2 = 0 %). CONCLUSIONS: In conclusion, based on the overall results of the available RCTs studies, our results suggested the potential value of probiotics in improving constipation symptoms in PD patients. Therefore, probiotics may be one of the adjuvant therapy for PD-related constipation patients. The findings of this study provide more proof supporting the effectiveness of probiotics, encouraging probiotics to be utilized alone or in combination with other therapies in clinical practice for PD patients. However, more well-designed RCTs with large sample sizes are required.

Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Genetic mechanism of body size variation in groupers: Insights from phylotranscriptomics.

Animal body size variation is of particular interest in evolutionary biology, but the genetic basis remains largely unknown. Previous studies have shown the presence of two parallel evolutionary genetic clusters within the fish genus Epinephelus with evident divergence in body size, providing an excellent opportunity to investigate the genetic basis of body size variation in vertebrates. Herein, we performed phylotranscriptomic analysis and reconstructed the phylogeny of 13 epinephelids originating from the South China Sea. Two genetic clades with an estimated divergence time of approximately 15.4 million years ago were correlated with large and small body size, respectively. A total of 180 rapidly evolving genes and two positively selected genes were identified between the two groups. Functional enrichment analyses of these candidate genes revealed distinct enrichment categories between the two groups. These pathways and genes may play important roles in body size variation in groupers through complex regulatory networks. Based on our results, we speculate that the ancestors of the two divergent groups of groupers may have adapted to different environments through habitat selection, leading to genetic variations in metabolic patterns, organ development, and lifespan, resulting in body size divergence between the two locally adapted populations. These findings provide important insights into the genetic mechanisms underlying body size variation in groupers and species differentiation.