Constructing a Built-In Electric Field To Accelerate Water Dissociation for Efficient Alkaline Hydrogen Evolution.

The alkaline hydrogen evolution reaction (HER) is intricately linked to the water dissociation kinetics. The quest for new strategies to accelerate this step is a pivotal aspect of enhancing the HER performance. Herein, we designed and synthesized a heterogeneous nickel phosphide/cobalt phosphide nanowire array grown on nickel foam (Ni2P/CoP/NF) to form a p-n junction structure. The built-in electric field (BEF) in the p-n junction optimizes the binding ability of hydrogen and hydroxyl intermediates, efficiently promoting water dissociation for the alkaline HER. Consequently, Ni2P/CoP/NF exhibits a lower overpotential of 58 and 118 mV at 30 and 100 mA cm-2, respectively, and high stability over 40 h at 300 mA cm-2 for the HER in 1 M KOH. Computational calculations combined with experiment results testify that the BEF presence in the p-n junction of Ni2P/CoP/NF effectively promotes water dissociation, regulates intermediate adsorption/desorption, and boosts electron transport. This study presents a rational design approach for high-performance heterogeneous electrocatalysts.

LY86 facilitates ox-LDL-induced lipid accumulation in macrophages by upregulating SREBP2/HMGCR expression.

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response.

The Role of Gut Microbiota in Male Erectile Dysfunction of Rats.

PURPOSE: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. RESULTS: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. CONCLUSIONS: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Intact quantitation of cysteine-conjugated antibody-drug conjugates using native mass spectrometry.

RATIONALE: A common strategy for antibody-drug conjugate (ADC) quantitation from in vivo study samples involves measurement of total antibody, conjugated ADC, and free payload concentrations using multiple reaction monitoring (MRM) mass spectrometry. This not only provides a limited picture of biotransformation but can also involve lengthy method development. Quantitation of ADCs directly at the intact protein level in native conditions using high-resolution mass spectrometers presents the advantage of measuring exposure readout as well as monitoring the change in average drug-to-antibody ratio (DAR) and in vivo stability of new linker payloads with minimal method development. Furthermore, site-specific cysteine-conjugated ADCs often rely on non-covalent association to retain their quaternary structure, which highlights the unique capabilities of native mass spectrometry (nMS) for intact ADC quantitation. METHODS: We developed an intact quantitation workflow involving three stages: automated affinity purification, nMS analysis, and data processing in batch fashion. The sample preparation method was modified to include only volatile ion-pairing reagents in the buffer systems. A capillary size-exclusion chromatography (SEC) column was coupled to a quadrupole time-of-flight high-resolution mass spectrometer for high-throughput nMS analysis. Samples from two mouse pharmacokinetic (PK) studies were analyzed using both intact quantitation workflow and the conventional MRM-based approach. RESULTS: A linear dynamic range of 5-100 µg/mL was achieved using 20 µL of serum sample volume. The results of mouse in vivo PK measurement using the intact quantitation workflow and the MRM-based approach were compared, revealing excellent method agreement. CONCLUSIONS: We demonstrated the feasibility of utilizing nMS for the quantitation of ADCs at the intact protein level in preclinical PK studies. Our results indicate that this intact quantitation workflow can serve as an alternative generic method for high-throughput analysis, enabling an in-depth understanding of ADC stability and safety in vivo.

Brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon for rechargeable Zn-air batteries.

Rational design and preparation of high-performance bifunctional oxygen electrocatalysts with effective sites and excellent mass/electron transfer structures are in demand for Zn-air batteries to overcome the sluggish oxygen reduction/evolution kinetics. Herein, a scalable and facile strategy is proposed to obtain brush-like Co/CoSe nanoheterostructures embedded in N-doped carbon catalysts with optimized active sites and hierarchical nanostructures. Systematic investigation indicates that nanoheterogeneous interfaces with appropriate composition deliver significantly improved electrochemical activity. As a result, a zinc-air battery assembled with the obtained Co/CoSe nanoheterostructures embedded in the N-doped carbon (CoSe/Co@NC-1) catalyst exhibits outstanding electrochemical performance with a peak power density of 215 mW cm-2 and excellent stability for 475 hours (2850 cycles). These results indicate that this strategy is an effective method for fabricating multicomponent and hierarchically nanostructured materials with enhanced catalytic efficiency for advanced energy devices.

Characteristics of Gut Microbiota in Patients with Erectile Dysfunction: A Chinese Pilot Study.

PURPOSE: Little is known about the role of gut microbiota in the pathogenesis of erectile dysfunction (ED). We performed a study to compare taxonomic profiles of gut microbiota of ED and healthy males. MATERIALS AND METHODS: A total of 43 ED patients and 16 healthy controls were enrolled in the study. The 5-item version of the International Index of Erectile Function (IIEF-5) with a cutoff value of 21 was used to evaluate erectile function. All participants underwent nocturnal penile tumescence and rigidity test. Samples of stool were sequenced to determine the gut microbiota. RESULTS: We identified a distinct beta diversity of gut microbiome in ED patients by unweighted UniFrac analysis (R²=0.026, p=0.036). Linear discriminant analysis effect size (LEfse) analysis showed Actinomyces was significantly enriched, whereas Coprococcus_1, Lachnospiraceae_FCS020_group, Lactococcus, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were depleted in ED patients. Actinomyces showed a significant negative correlation with the duration of qualified erection, average maximum rigidity of tip, average maximum rigidity of base, tip tumescence activated unit (TAU), and base TAU. Coprococcus_1, Lachnospiraceae_FCS020_group, Ruminiclostridium_5, and Ruminococcaceae_UCG_002 were significantly correlated with the IIEF-5 score. Ruminiclostridium_5 and Ruminococcaceae_UCG_002 were positively related with average maximum rigidity of tip, average maximum rigidity of base, ΔTumescence of tip, and Tip TAU. Further, a random forest classifier based on the relative abundance of taxa showed good diagnostic efficacy with an area under curve of 0.72. CONCLUSIONS: This pilot study identified evident alterations in the gut microbiome composition of ED patients and found Actinomyces was negatively correlated with erectile function, which may be a key pathogenic bacteria.

The role of extracellular polymeric substances (EPS) in chemical-degradation of persistent organic pollutants in soil: A review.

Persistent organic pollutants (POPs) in soil show high environmental risk due to their high toxicity and low biodegradability. Studies have demonstrated the degradation function of microbial extracellular polymeric substances (EPS) on POPs in various matrices. However, the degradation mechanisms and the factors that influence the process in soil have not been clearly illustrated. In this review, the characteristics of EPS were introduced and the possible mechanisms of EPS on degradation of organic pollutants (e.g., external electron transfer, photodegradation, and enzyme catalysis) were comprehensively discussed. In addition, the environmental conditions (e.g., UV, nutrients, and redox potential) that could influence the production and degradation-related active components of EPS were addressed. Moreover, the current approaches on the application of EPS in biotechnology were summarized. Further, the future perspectives of enhancement on degradation of POPs by regulating EPS were discussed. Overall, this review could provide a new thought on remediation of POPs by widely-existing EPS in soil with low-cost and minimized eco-disturbance.

Biochar-based materials as remediation strategy in petroleum hydrocarbon-contaminated soil and water: Performances, mechanisms, and environmental impact.

Petroleum contamination is considered as a major risk to the health of humans and environment. Biochars as low-cost and eco-friendly carbon materials, have been widely used for the removal of petroleum hydrocarbon in the environment. The purpose of this paper is to review the performance, mechanisms, and potential environmental toxicity of biochar, modified biochar and its integration use with other materials in petroleum contaminated soil and water. Specifically, the use of biochar in oil-contaminated water and soil as well as the factors that could influence the removal ability of biochar were systematically evaluated. In addition, the modification and integrated use of biochar for improving the removal efficiency were summarized from the aspects of sorption, biodegradation, chemical degradation, and reusability. Moreover, the functional impacts and associated ecotoxicity of pristine and modified biochars in various environments were demonstrated. Finally, some shortcoming of current approaches, and future research needs were provided for the future direction and challenges of modified biochar research. Overall, this paper gain insight into biochar application in petroleum remediation from the perspectives of performance enhancement and environmental sustainability.

Comparison of the efficacy and safety of ultrasound-guided CHIVA and traditional HLS in the treatment of varicose veins of lower extremities - a meta-analysis.

OBJECTIVE: Systematic evaluation of the efficacy and safety of conservative hemodynamic cure for venous insufficiency (CHIVA) compared with high ligation and stripping (HLS) in the treatment of varicose veins of lower extremities. METHODS: We conducted a systematic literature search and compared the randomized controlled trial and retrospective cohort study of CHIVA and HLS in the treatment of varicose veins of lower extremities in several databases, including China National Knowledge Infrastructure, Wanfang database, cqvip datebase, PubMed, Cochrane library and EMBASE, to identify articles that might meet the criteria. Meta-analysis was performed using Revman 5.3 and Stata 13.0 software. RESULTS: This Meta-analysis included a total of 14 research articles. This meta-analysis shows that CHIVA requires shorter operation time than HLS [mean difference (MD) = -13.57, 95% confidence interval (CI) (-21.05, -6.10), P = .0004]. There is less blood loss with CHIVA surgery [MD = -21.72, 95% CI (-30.35, -13.09), P < .00001]. The number of incisions made by the CHIVA technique is less [MD = -3.67, 95% CI (-4.03, -3.31), P < .00001]. Patients who underwent CHIVA had a shorter hospital stay [MD = -3.40, 95% CI (-4.72, -2.09), P < .00001]. The relapse rate was lower after CHIVA [OR = 0.36, 95% CI (0.18, 0.70), P = .003]. In terms of postoperative complications, CHIVA has a lower total complication rate [MD = 0.26, 95% CI (0.15, 0.46), P < .00001]. The incidence of deep vein thrombosis was lower after CHIVA [MD = 0.23, 95% CI (0.06, 0.92), P = .04]. CHIVA has a lower incidence of sensory disturbance than HLS [OR = 0.39, 95% CI (0.25, 0.60), P < .0001]. CHIVA technique has less nerve injury rate than HLS [OR = 0.11, 95% CI (0.02, 0.62), P = .01]. The incidence of hematoma was lower after CHIVA [OR = 0.48, 95% CI (0.27, 0.87), P = .02]. Among other metrics, the comparison results of the 2 techniques were similar. CONCLUSION: By comparison, it is found that CHIVA has shorter operation time, less blood loss, and fewer surgical incisions. Patients who underwent CHIVA surgery had shorter hospital stays and lower relapse rates. In terms of complications, the incidence of total complications after CHIVA is lower, and the incidence of postoperative deep vein thrombosis, postoperative sensory, nerve injury, and postoperative hematoma is also lower than that of HLS.

Genital mycoplasma infection: a systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested that genital mycoplasma infections may be associated with male infertility. However, this association remains controversial due to time lapse, sample size, and regional prevalence. OBJECTIVES: This study aimed to systematically evaluate the relationship between genital mycoplasma and male infertility through a meta-analysis and to provide a basis for the clinical management of male infertility. METHODS: We conducted a search on PubMed, EMBASE, the Cochrane Library, and CNKI databases, from January 2000 to June 2023 to identify case-control studies on the interrelationship between genital mycoplasma infection and male infertility. Two independent researchers performed an assessment of the methodological quality of trials according to the Newcastle-Ottawa scale and extracted data strictly based on the inclusion and exclusion criteria, and afterward, we carried out a meta-analysis using Stata 16.0. Pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess this relationship. RESULTS: This meta-analysis included 21 studies from seven countries with a total of 53025 infertility cases and 6435 controls; the age range of the participating men was from 20 to 59 years old. The results obtained showed a higher prevalence of M. genitalium, M. hominis and U. urealyticum infections in infertile men than in the controls, with the opposite result for U. parvum (M. genitalium, OR, 3.438 [95% CI: 1.780, 6.643], with P = 0.000; M. hominis, OR, 1.840 [95% CI: 1.013, 3.343], with P = 0.045; U. urealyticum, OR, 3.278 [95% CI: 2.075, 5.180], with P = 0.000; U. parvum, OR, 1.671 [95% CI: 0.947, 2.950], with P = 0.077). Further, two subgroup analyses also showed that M. hominis and U. urealyticum infections were strongly associated with male infertility in China (M. hominis, P = 0.009; U. urealyticum, P = 0.000); however, M. hominis and U. urealyticum infection was not strongly associated with male infertility worldwide (M. hominis, P = 0.553; U. urealyticum, P = 0.050). CONCLUSION: This meta-analysis revealed that male infertility was significantly associated with M. genitalium, M. hominis and U. urealyticum infections, while U. parvum infection was not. Further, our study showed that genital mycoplasma infection influences male infertility and provides a basis for future treatment.

Diabetes mellitus and adverse outcomes after carotid endarterectomy: A systematic review and meta-analysis.

BACKGROUND: There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the adverse impact of DM on patients with carotid stenosis treated by CEA. METHODS: Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed. RESULTS: A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: [1.13-2.28], prevalence = 2.3%), stroke (ES = 1.55, 95% CI: [1.16-1.55], prevalence = 3.5%), death (ES = 1.70, 95% CI: [1.25-2.31], prevalence =1.2%), and MI (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: [1.04-1.49], prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI. CONCLUSIONS: In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation.

Endoscopic Resection Improved High-Intensity Focused Ultrasound Ablation Outcomes for Prostate Cancer: A Meta-Analysis of Comparative Studies.

PURPOSE: High-intensity focused ultrasound ablation (HIFU) is emerging as more data on its efficacy arises for prostate cancer (PCa). However, it is indefinite whether to combine endoscopic resection and uncertain to say who the ideal candidates are for the combined treatment. Therefore, we aimed to conduct a meta-analysis to compare outcomes of sole HIFU therapy with that of HIFU in combination with endoscopic resection in patients with localized PCa. MATERIALS AND METHODS: Electronic databases were searched following the PRISMA guidelines and PICOS formats. The inclusion criteria were as follows: 1) studies on HIFU for PCa patients; 2) comparative studies on HIFU in combination with endoscopic resection for localized PCa men. Exclusion criteria include non-comparative studies and salvage HIFU therapy. Meta-analysis results were mainly present using forest plots. Sensitivity analysis and Egger's test were adopted to determine the stability and assess the publication bias. RESULTS: Six comparative studies with 767 patients were eligible, including 487 cases in the combination therapy group and 280 cases in the monotherapy group. There was no statistical difference in age, preoperative PSA levels, and prostate volume between two groups. No statistical difference was found in postoperative PSA nadir (MD = -0.02, 95%CI: -0.35 to 0.31, P = 0.90), disease-free survival rate (RR = 0.95, 95%CI: 0.83 to 1.09, P = 0.47), and preoperative IPSS score (MD = -0.69, 95%CI: -1.63 to 0.26, P = 0.15; I2 = 8%) between two groups. The combination therapy group had significantly lower postoperative IPSS score (MD = -5.49, 95%CI: -6.47 to -4.51, P < 0.001) and shorter catheterization time (MD=-13.70, 95%CI: -19.24 to -8.16, P < 0.001) than the monotherapy group. The rates of urinary incontinence (7.4% vs. 13.9%, RR = 0.45, 95%CI: 0.29 to 0.70, P = 0.0004; I2=4%), acute urinary retention (6.8% vs. 10.5%, RR=0.36, 95%CI: 0.14 to 0.89, P = 0.03; I2 = 0%), urinary tract infection (10% vs. 33%, RR = 0.27, 95% CI: 0.18 to 0.4, P < 0.001; I2 = 0%), epididymitis (1.2% vs. 15.7%, RR=0.11, 95% CI: 0.02 to 0.59, P = 0.01; I2 = 0%), and urethral stricture (7.1% vs. 23.2%, RR = 0.3, 95%CI: 0.18 to 0.51, P < 0.001; I2 = 0%) in the combination therapy group were all significantly lower than that in the monotherapy group. Sensitivity analysis revealed findings were convincing and no publication bias (P = 0.62) was observed using Egger's test. CONCLUSION: It appears that the addition of endoscopic resection to the HIFU operation might not impact oncologic outcomes and could show better functional outcomes compared to the HIFU monotherapy in localized PCa patients.

Genome editing HLA alleles for a pilot immunocompatible hESC line in a Chinese hESC bank for cell therapies.

Robust allogeneic immune reactions after transplantation impede the translational pace of human embryonic stem cells (hESCs)-based therapies. Selective genetic editing of human leucocyte antigen (HLA) molecules has been proposed to generate hESCs with immunocompatibility, which, however, has not been specifically designed for the Chinese population yet. Herein, we explored the possibility of customizing immunocompatible hESCs based on Chinese HLA typing characteristics. We generated an immunocompatible hESC line by disrupting HLA-B, HLA-C, and CIITA genes while retaining HLA-A*11:01 (HLA-A*11:01-retained, HLA-A11R ), which covers ~21% of the Chinese population. The immunocompatibility of HLA-A11R hESCs was verified by in vitro co-culture and confirmed in humanized mice with established human immunity. Moreover, we precisely knocked an inducible caspase-9 suicide cassette into HLA-A11R hESCs (iC9-HLA-A11R ) to promote safety. Compared with wide-type hESCs, HLA-A11R hESC-derived endothelial cells elicited much weaker immune responses to human HLA-A11+ T cells, while maintaining HLA-I molecule-mediated inhibitory signals to natural killer (NK) cells. Additionally, iC9-HLA-A11R hESCs could be induced to undergo apoptosis efficiently by AP1903. Both cell lines displayed genomic integrity and low risks of off-target effects. In conclusion, we customized a pilot immunocompatible hESC cell line based on Chinese HLA typing characteristics with safety insurance. This approach provides a basis for establishment of a universal HLA-AR bank of hESCs covering broad populations worldwide and may speed up the clinical application of hESC-based therapies.

Bioanalytical strategy for the characterization and bioanalysis of biologics: a global, nonregulated bioanalytical lab perspective.

Over the past two decades, we have seen an increase in the complexity and diversity of biotherapeutic modalities pursued by biopharmaceutical companies. These biologics are multifaceted and susceptible to post-translational modifications and in vivo biotransformation that could impose challenges for bioanalysis. It is vital to characterize the functionality, stability and biotransformation products of these molecules to enable screening, identify potential liabilities at an early stage and devise a bioanalytical strategy. This article highlights our perspective on characterization and bioanalysis of biologics using hybrid LC-MS in our global nonregulated bioanalytical laboratories. AbbVie's suite of versatile, stage-appropriate characterization assays and quantitative bioanalytical approaches are discussed, along with guidance on their utility in answering project-specific questions to aid in decision-making.

Ant-Neointimal Formation Effects of SLC6A6 in Preventing Vascular Smooth Muscle Cell Proliferation and Migration via Wnt/ß-Catenin Signaling.

Vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of vascular remolding, such as atherosclerosis and restenosis. Solute carrier family 6 member 6 (SLC6A6) is a transmembrane transporter that maintains a variety of physiological functions and is highly expressed in VSMCs. However, its role on VSMCs during neointimal formation remains unknown. In this study, mRNA and protein levels of SLC6A6 were examined using models of VSMC phenotype switching in vivo and in vitro and human artery samples with or without atherosclerosis. SLC6A6 gain- and loss-of-function approaches were performed by adenovirus infection or small interfering RNA (siRNA) transfection, respectively. Reactive oxygen species (ROS), proliferation, migration, and phenotype-related proteins of VSMCs were measured. Vascular stenosis rate and related genes were assessed in a rat vascular balloon injury model overexpressing SLC6A6. SLC6A6 was downregulated in dedifferentiated VSMCs, atherosclerotic vascular tissues, and injured vascular tissues. SLC6A6 suppressed VSMC proliferation and migration, while increasing contractile VSMC proteins. Mechanistically, SLC6A6 overexpression reduced ROS production and inhibited the Wnt/ß-catenin pathway. Furthermore, SLC6A6 overexpression suppressed neointimal formation in vivo. Collectively, overexpression of SLC6A6 suppresses neointimal formation by inhibiting VSMC proliferation and migration via Wnt/ß-catenin signaling and maintaining the VSMC contractile phenotype.

Inhibition of tiRNA-Gly-GCC ameliorates neointimal formation via CBX3-mediated VSMCs phenotypic switching.

Background and aim: tRNA-derived fragments (tRFs) are a new class of non-coding RNAs involved in a variety of pathological processes, but their biological functions and mechanisms in human aortic smooth muscle cells (HASMCs) phenotype transition and vascular intimal hyperplasia are unclear. Methods/results: tiRNA-Gly-GCC is upregulated in synthetic HASMCs, atherosclerotic arteries, plasma, and the balloon injured carotid artery of rats. Functionally, the inhibition of tiRNA-Gly-GCC represses HASMCs proliferation, migration, and reversed dedifferentiation, whereas the overexpression of tiRNA- Gly-GCC have contrary effects. Mechanistically, tiRNA-Gly-GCC performs these functions on HASMCs via downregulating chromobox protein homolog 3 (CBX3). Finally, the inhibition of tiRNA-Gly-GCC could ameliorate neointimal formation after vascular injury in vivo. Conclusions: tiRNA-Gly-GCC is a mediator of HASMCs phenotypic switching by targeting CBX3 and inhibition of tiRNA-Gly-GCC suppresses neointimal formation.

Association between COVID-19 and Male Fertility: Systematic Review and Meta-Analysis of Observational Studies.

PURPOSE: Whether COVID-19 reduces male fertility remains requires further investigation. This meta-analysis and systematic review evaluated the impact of COVID-19 on male fertility. MATERIALS AND METHODS: The literature in PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library up to January 01, 2022 was systematically searched, and a meta-analysis was conducted to investigate the effect of COVID-19 on male fertility. Totally 17 studies with a total of 1,627 patients and 1,535 control subjects were included in our meta-analysis. RESULTS: Regarding sperm quality, COVID-19 decreased the total sperm count (p=0.012), sperm concentration (p=0.001), total motility (p=0.001), progressive sperm motility (p=0.048), and viability (p=0.031). Subgroup analyses showed that different control group populations did not change the results. It was found that during the illness stage of COVID-19, semen volume decreased, and during the recovery stage of COVID-19, sperm concentration and total motility decreased <90 days. We found that sperm concentration and total motility decreased during recovery for ≥90 days. Fever because of COVID-19 significantly reduced sperm concentration and progressive sperm motility, and COVID-19 without fever ≥90 days, the sperm total motility and progressive sperm motility decreased. Regarding disease severity, the moderate type of COVID-19 significantly reduced sperm total motility, but not the mild type. Regarding sex hormones, COVID-19 increased prolactin and estradiol. Subgroup analyses showed that during the illness stage, COVID-19 decreased testosterone (T) levels and increased luteinizing hormone levels. A potential publication bias may have existed in our meta-analysis. CONCLUSIONS: COVID-19 in men significantly reduced sperm quality and caused sex hormone disruption. COVID-19 had long-term effects on sperm quality, especially on sperm concentration and total motility. It is critical to conduct larger multicenter studies to determine the consequences of COVID-19 on male fertility.

Vascular restenosis reduction with platelet membrane coated nanoparticle directed M2 macrophage polarization.

Vascular restenosis is the main factor affecting the prognosis of angioplasty in cardiovascular diseases, and inflammation is a central link in the progression of restenosis. Previous research that applies interleukin 10 (IL10) nanoparticles can effectively regulate local inflammation, but their targeted delivery efficacy remains to be improved. In this study, IL10 nanoparticles were successfully prepared and then coated by a preactive platelet membrane. The ability to target and regulate macrophage polarization has been demonstrated, thereby regulating smooth muscle cell and endothelial cell functions. In vivo experiments were carried out in a carotid artery injury model and verified the above functions and the effect on inhibiting vascular restenosis. Immune regulation-based platelet membrane coated nanoparticle loaded with IL10 proved to be an excellent candidate for targeting vascular injury and holds promise as an innovative drug delivery system for suppressing vascular restenosis.

Relationship between the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio and deep venous thrombosis (DVT) following femoral neck fractures in the elderly.

Purpose: This study aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) was associated with deep venous thrombosis (DVT) following femoral neck fractures in the elderly. Method: This was a retrospective cohort study and used data extracted from the hospitalization electronic medical record and the laboratory biomarker reports. Patients were included if they were aged above 60 years with a definite diagnosis of femoral neck fracture caused by low-energy trauma. Duplex ultrasound scanning was routinely performed to detect the potential DVT. Two independent multivariate logistic regression models were constructed to identify the association of NLR or PLR with the risk of DVT. Results: A total of 708 patients with femoral neck fractures were included, and 112 were found to have DVT, indicating an incidence rate of 15.8%. There were significant differences across five subgroups for NLR or PLR, in terms of age (p = 0.020, 0.006), white blood cell (p < 0.001, =0.006), hemoglobin (p < 0.001, <0.001), and albumin (p < 0.001, <0.001). BMI was tested to be significantly different across subgroups for NLR (p = 0.030) and prevalence of cerebrovascular disease for PLR (p = 0.014). The multivariate analyses demonstrated that not NLR but PLR in Q3 (range, 179-238) was associated with an increased risk of DVT, and the risk for the latter was 1.86 (95%CI, 1.07-3.36). Conclusion: We concluded that a PLR value of 179-238 was associated with a 1.86-fold increased risk of DVT after femoral neck fracture. This study paves the way toward further exploration of inflammatory/immune biomarkers with the risk of DVT in the elderly with trauma.

Efficacy of one-stop endovascular intervention in treatment of left iliac vein compression syndrome complicated with deep venous thrombosis of lower limbs.

OBJECTIVE: To evaluate the clinical effect and safety of one-stop endovascular intervention in treatment of left iliac vein compression syndrome (IVCS) complicated with deep venous thrombosis (DVT) of lower limbs. METHODS: Clinical data of 26 patients with secondary DVT due to IVCS admitted in the Department of Vascular Surgery, Hebei General Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients underwent one-stop endovascular intervention procedure, including ultrasound-guided deep venipuncture, Angiojet catheter aspiration, iliac vein balloon dilation, stent implantation and simultaneous filter retrieval. The operation time and catheter aspiration time were documented; the preoperative and postoperative left lower extremity deep vein venous patency, circumferences of bilateral limbs at 15 cm above the knee and 10 cm below the knee, and the levels of hemoglobin, creatinine, alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin and indirect bilirubin were measured. The incidence of post-thrombotic syndrome (PTS) and iliac vein stent patency were recorded through follow-up. RESULTS: The one-stop endovascular intervention was successfully performed in 26 patients, with the operation time of (171±35) min and the thrombolysis time of (263±89) s. After treatment, the left lower extremity deep vein venous patency, circumferences of bilateral limbs at 15 cm above the knee and 10 cm below the knee were decreased (all P<0.01); the hemoglobin level were decreased, the creatinine, ALT, AST, total bilirubin and indirect bilirubin levels were increased (all P<0.01). Patients were followed up for 1-12 months. Stent thrombosis occurred in 1 patient 7 months after procedure, and the symptoms were improved after conservative treatment; the stents were unobstructed in all patients, 1 patient had stent mural thrombosis, in whom the stent blood flow was not affected. No PTS was observed during the follow-up. CONCLUSIONS: The one-stop endovascular interventional treatment of IVCS complicated with DVT of left lower limb is safe and effective. Attention should be paid to the changes of liver and kidney function caused by catheter aspiration during the treatment, and corresponding intervention should be given in time to avoid the occurrence of related complications.