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Abstract 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.

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.

In the process of ascending and descending in deep-sea submerging and lifting cage nets, accompanied by changes in water pressure, pressure is one of the crucial environmental factors affecting the physiology and growth of fish. It directly relates to the comfort of farmed fish in the cage, thereby influencing the quality of aquaculture, especially for high-demanding species on the culture environment like the Larimichthys crocea. Investigating the stress level changes exhibited by L.crocea under environmental pressure variations, understanding the limit tolerance pressure, and its changes, can provide a theoretical basis for the design, application, and increased production of deep-sea submersible cage nets and L.crocea aquaculture. This study explores the effects of varying submersion depths (0–20 m) and speeds (0.6, 1, 1.3, 2, 4 m/min) on the behavioral responses of L.crocea in deep-sea cage environments. Key findings demonstrate that increased submersion depths and speeds significantly influence the physical behaviors and stress responses of the species. At submersion depths of 15 meters and 20 meters, the average swimming speed of the L.crocea exceeds 0.05 meters per second, the tail movement frequency is 1.42 times that of normal pressure, and the gasping frequency exceeds 20%., and at the highest speed of 4 m/min, the swimming speed reaches 0.0902 m/s—3.76 times greater than under normal pressure. The study determines that a submersion depth of 10 meters and a submersion speed of 0.6 meters per minute can minimize stress responses, providing critical insights for optimizing deep-sea aquaculture operations of L.crocea. These results offer valuable guidelines for the design and management of submersible cage systems.

To investigate the effects of the interaction between water quality and gill function of large yellow croaker during transportation in packaging bags, a total of 186 large yellow croakers weighing 120.0 ± 28.0 g were randomly divided into two groups: a control group (tanks with a water treatment system to maintain normal water quality) and treatment groups subjected to simulated transport for 0, 6, 12, 18, and 24 hours at a temperature of 20°C. The results revealed that prolonging the transport duration (beyond 6 hours) caused significant changes in dissolved oxygen (DO), total ammonia nitrogen (TAN) and pH levels in the water. Beyond 6 hours of transport, gill tissue damage increased, and the histomorphological characteristics of the gills were altered. Regarding osmoregulation, the activities of Ca2+/Mg2+-ATPase and Na+/K+-ATPase were notably reduced in the treatment groups, indicating compromised osmoregulatory function of the gill tissue during transport. However, changes in lactic acid (LD) and lactate dehydrogenase (LDH) were not statistically significant, and fish did not experience hypoxia during packaging bag transport. In terms of antioxidant activity, the treatment groups exhibited significantly lower activities of catalase (CAT) and superoxide dismutase (SOD) after 24 hours, as well as increased malondialdehyde (MDA) content after 18 hours. This reduction in antioxidant capacity led to cellular membrane damage in the gill tissue. Furthermore, acid phosphatase (ACP) activity showed a notable decline from 12 hours onwards in immune indicators, while lysozyme (LZM) activity experienced a substantial decrease at 24 hours. Correlation analysis revealed a significant correlation between the osmoregulation, antioxidant capacity, and immune response of gill tissue with elevated TAN levels and reduced pH. In conclusion, the levels of TAN and pH experience notable alterations after 6 hours of transportation, which may lead to impairment of gill function in large yellow croakers. Hence, we advise limiting the transportation of large yellow croakers to less than 6 hours at 20°C.

Abstract 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.

Abstract Various human activities have led to multiple contamination of natural water systems. The present study investigated the effect of a novel multifunctional biochar to treat nutrients, oil, and harmful algae in water. Specifically, magnesium (Mg) and biosurfactant rhamnolipid (RL) were incorporated into biochar, including Mg-biochar, RL-biochar, and Mg-RL-biochar. Their adsorption efficiency on phosphate and total petroleum hydrocarbons (TPH) was evaluated in separate batch studies. Also, the inhibition effect of RL-modified biochars on cyanobacteria was investigated. The results showed that Mg-impregnated biochar showed high adsorption capacity on phosphate (118 mg g−1), while RL-modified biochar significantly reduced TPH (especially aromatic and light aliphatic fraction) with adsorption capacity of 44.4 mg g−1. The inhibition effects of biochar composites on algae in water without contaminants were in order of Mg-RL-biochar > RL-biochar > biochar with biomass reduction ranging 61–64%. Overall, Mg-RL-biochar was suggested based on this study due to its ability to remove PO4 3− and TPH, and inhibit the growth of toxic algae. Graphical abstract

Abstract. 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.

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

The study aimed to investigate the effects of temperature and dissolved oxygen on juvenile largemouth bass during transportation. The experiment involved four temperature groups: 20, 15, 10, and 5 °C. We analyzed the effects of acute and uniform cooling on fish behavior to determine the optimal approach for cooling. Then, we simulated transport under different temperature conditions while measuring the dissolved oxygen level and metabolic rate until all the fish died. The results showed that acute cooling significantly influenced the tail-beat frequency of fish compared with uniform cooling, while abnormal behaviors such as increased swimming, attempted jumping out of the water, and loss of balance were observed. As the transport temperature reduced, the oxygen consumption rate of fish significantly changed at 10 °C, being 2.6 times lower than at 15 °C, with values of 0.10 ± 0.02 and 0.47 ± 0.07 mg·g−1·h−1, respectively. The critical oxygen threshold (Pcrit) of fish were 1.90 ± 0.12, 1.61 ± 0.04, 1.15 ± 0.09, and 1.12 ± 0.25 mg·L−1 at 5, 10, 15, and 20 °C. In addition, below Pcrit, hypoxia-led behavior changes and oxygen consumption rate reduction were observed at every transport temperature. The findings suggest that the optimal low temperature can reduce metabolism and improve the hypoxia tolerance of juvenile largemouth bass. We recommend transporting largemouth bass at an optimal low temperature (15 °C), monitoring fish behavior, and maintaining oxygen levels above Pcrit during transport to prevent stress.

To improve the heat exchange effect of energy piles in coastal areas, a new energy pile with a combination of long and short heat exchanger tubes is proposed. This technology combines the characteristics of implanted pile construction and arranges heat exchanger tubes of different lengths inside and outside the precast pipe pile, which can make full use of the geological conditions in coastal areas. Finite element analysis was applied for a project in a deep, soft soil ground to study the effectiveness of the new combined energy pile technology. The influences of the combined heat exchanger tubes and groundwater seepage conditions on the heat transfer and stress state of the energy pile were analyzed. The results show that the deformation and internal force of the pile body are closely related to temperature change. The temperature change is determined by heat transfer, which is closely related to the arrangement of heat exchanger tubes and underground water flow. With the increase of groundwater seepage velocity, the heat taken away by the heat exchanger tubes gradually increases; thus, the heat exchange between the heat exchanger tubes and the pile body decreases. The inner heat exchanger tube of the pile leads to an increase in heat exchange. However, as the length of the inner heat exchanger tube increases from 40 m to 80 m, the heat exchange decreases. The research results provide technical support for further development of the new energy pile technology.

Background and aimtRNA-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/resultstiRNA-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.ConclusionstiRNA-Gly-GCC is a mediator of HASMCs phenotypic switching by targeting CBX3 and inhibition of tiRNA-Gly-GCC suppresses neointimal formation.

The mechanical construction method for a subway contact channel has the advantages of a short construction period and high safety, and is more and more being applied in coastal soft-soil areas. In order to explore the suitability of this method in inland areas, a full-scale model test platform is used to simulate the shield-cutting construction process of the subway contact channel. The convergence deformation of the segments and the strain of the reinforcement and concrete are tested, so as to analyze the internal force and deformation law of the tunnel structure during cutting construction. The influence of the steel ring on the deformation of the subway contact channel is also studied. It is found that the segment convergence at the top is less than that at the waist position, and the convergence deformation of the waist is less than 30 mm; the internal force of the segment redistributes and the axial force mainly decreases during the cutting process; the stress state may change from compression to tension. The segment structure of the main tunnel, the supporting structure in the tunnel, and the stiffness of the steel-ring-lined composite pipe segment have little influence on the cutting force of the contact channel. The research results provide the corresponding technical indexes for the construction of a contact channel by the mechanical method, as well as a reference for the design and optimization of a steel-ring-lined composite pipe segment.

Summary: 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.

PurposeThis 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.MethodThis 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.ResultsA 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

Mounting evidence shows that MicroRNAs (miRNAs) and their target genes are aberrantly expressed in many cancers and are linked to tumor occurrence and progression, especially in esophageal cancer (EC). This study purposed to explore new biomarkers related to the prognosis of EC and to uncover their potential mechanisms in promoting tumor progression. We identified 162 differentially expressed miRNAs and 4555 differentially expressed mRNAs in EC. Then, a risk model involving three miRNAs (miR‐4521, miR‐3682‐3p, and miR‐1269a) was designed to predict prognosis in EC patients. Furthermore, 7 target genes (Rho GTPase‐activating protein 24, Chromobox 3, Contactin‐associated protein 2, ELOVL fatty acid elongase 5, LIF receptor subunit alpha, transmembrane protein 44, and transmembrane protein 67) were selected for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to reveal their potential mechanisms in promoting EC progression. After a series of correlation analyses, miRNA target genes were found to be significantly positively or negatively associated with immune infiltration, tumor microenvironment, cancer stemness properties, and tumor mutation burden at different degrees in EC. To further elucidate the role of miRNA signature in cancer progression, we performed a pan‐cancer analysis to determine whether these genes exert similar effects on other tumors. Interestingly, the miRNA target genes altered expression on tumor immunity; however, pan‐cancer progression was the same as that of EC. Thus, we explored the immune landscape of the miRNA signature and its target genes in EC and pan‐cancer. These findings demonstrated the versatility and effectiveness of our model in various cancers and provided a new direction for cancer management.

Endothelial dysfunction is a key accessory to diabetic cardiovascular complications, and the regulatory role of the extracellular vesicles (EVs) from the innate immune system is growing. We tested whether EVs derived from high glucose-induced monocytes could shuttle microRNAs and impair endothelial cells. EVs from high glucose- and basal glucose-treated THP-1 cells (HG-THP-1 EVs and BG-THP-1 EVs) were isolated and identified. After coculture with THP-1 EVs, human umbilical vein endothelial cells (HUVECs) were tested by proliferation, migration, reactive oxygen species (ROS) detection assays, and western blot for Nrf2/NLRP3 signaling. MiR-142-5p was predicted by miRNAs databases and further verified by RT–qPCR and dual-luciferase reporter gene assays that inhibit Nrf2 expression. The regulation of miR-142-5p in HUVECs was further evaluated. A type 1 diabetes mellitus (T1DM) mouse model was developed for miR-142-5p inhibition. Aorta tissue was harvested for hematoxylin-eosin staining and immunohistochemistry of interleukin-1β (IL-1β). Compared to BG-THP-1 EVs, HG-THP-1 EVs significantly reduced migration and increased ROS production in HUVECs but did not affect proliferation. HG-THP-1 EVs induced suppression of Nrf2 signaling and NLRP3 signaling activation. RT–qPCR results showed that HG-THP-1 EVs overexpressed miR-142-5p in HUVECs. The transfection of miR-142-5p mimics into HUVECs exhibited consistent regulatory effects on HG-THP-1 EVs, whereas miR-142-5p inhibitors demonstrated protective effects. The miR-142-5p antagomir significantly reduced the IL-1β level in T1DM aortas despite morphological changes. To conclude, miR-142-5p transferred by high glucose-induced monocyte EVs participates in diabetic endothelial damage. The inhibition of miR-142-5p could be a potential adjuvant to diabetic cardiovascular protection.

Abstract Objective To investigate the epidemiologic characteristics of deep venous thrombosis (DVT) in elderly patients with femoral neck fracture. Methods Retrospective analysis was performed on elderly patients with femoral neck fractures admitted to two institutions from January 2016 to October 2019. Duplex ultrasonography (DUS) was used to detect DVT. Patients’ hospitalization medical records were retrieved to collect the data, which were related to demographics, comorbidities, injury and laboratory results on admission. Patients with preoperative DVT were defined as the case group and those without DVT as control group, and compared using the univariate analyses. Multivariate logistic regression analysis was used to identify the independent factors associated with DVT. Results Totally, 980 patients met the predefined criteria and were included. Sixty-seven patients were diagnosed to have preoperative DVT, with incidence of 6.8% for overall, 1.7% for proximal and 5.1% for distal DVT. The mean time from injury to diagnosis of DVT was 6.0 ± 4.7 days (median, 5.0). Most (76.1%) patients with DVT had thrombi solely in the injured extremity, in contrast with 14.9% (10/67) in the uninjured and 9.0% (6/67) in both injured and uninjured extremity. Multivariate analysis showed chronic renal insufficiency (OR, 3.37; 95%CI, 1.57 to 7.28), current smoking status (OR, 2.42; 95%CI, 1.23 to 5.63), time from injury to DUS (OR, 1.26; 95%CI, 1.07 to 1.61) and PLT > 220*109/L (OR, 1.94; 95%CI, 1.31 to 3.77) were independent factors for DVT. Conclusion Preoperative DVT is not very prevalent following elderly femoral neck fractures, but with a certain proportion in the uninjured extremity, necessitating the more attention. These identified risk factors aid in patient counseling, individualized risk assessment and risk stratification, and should be kept in mind.

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/β-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/β-catenin signaling and maintaining the VSMC contractile phenotype.

Abstract Background Cigarette smoke (CS) exposure impairs serum lipid profiles and the function of vascular endothelial cells, which accelerates the atherosclerosis. However, the precise mechanism and effect on the expression of low-density lipoprotein receptor (LDLR) in the liver by CS exposure is still unclear. Methods In this study, adult male C57BL/6 J mice were divided into three groups, with one group being exposed to CS for 6 weeks. HepG2 cells were treated with CS extract at concentrations of 1, 2.5, 5, and 10%. Results The serum levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) for the CS-exposure group were significantly higher than those in the control group (P

Herein, we discuss the facile and general protocol to construct monodisperse chitosan-coated selenium nanoparticles (SeNPs@CS) without the need for dialysis in wet-chemical system and also investigate the toxicity of SeNPs@CS on enterocyte cells. The crystalline structure, morphology, and composition of the obtained product were examined by XRD, SEM-EDX, TEM, XPS and FT-IR, respectively, which indicates uniform and strong stability performance of the non-dialysis requiring SeNPs@CS. Intestinal porcine epithelial cells (IPEC-J2) were conducted to compare the cytotoxicity of SeNPs@CS and selenite at desired concentrations (ranging from 0.625 to 100 μM) for 4, 8, 12, and 24 h. The cytotoxicity study reveals that SeNPs@CS exhibited lower cytotoxicity than selenite in IPEC-J2 cells. From the further cell apoptosis examination, high concentration of SeNPs@CS (100 μM), compared with the selenite, did not affect related protein expressions in JNK/p38 MAPK signaling pathway, which is critical in predisposing mammalian cells to apoptosis. All the physio-chemical characterization and biological determination demonstrated that the non-dialysis requiring SeNPs@CS possesses the potentials to serve as safe and effective pharmaceutical or nutritional application. Keywords: Selenium nanoparticles, Non-dialysis requiring, Characterization, Cytotoxicity, Apoptosis, IPEC-J2 cells

Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid artery and further reduce the arterial lumen. Ischemic stroke due to severe CAS and cerebral ischemic/reperfusion (I/R) injury after the revascularization of CAS also adversely affect clinical outcomes. Melatonin is a pluripotent agent with potent anti-inflammatory, anti-oxidative, and neuroprotective properties. Although there is a shortage of direct clinical evidence demonstrating the benefits of melatonin in CAS patients, previous studies have shown that melatonin may be beneficial for patients with CAS in terms of reducing endothelial damage, stabilizing arterial plaque, mitigating the harm from CAS-related ischemic stroke and cerebral I/R injury, and alleviating the adverse effects of the related risk factors. Additional pre-clinical and clinical are required to confirm this speculation.

Elucidating the major drivers of bryophyte distribution is the first step to protecting bryophyte diversity. Topography, forest, substrates (ground, tree trunks, roots, rocks, and rotten wood), and spatial factor, which factors are the major drivers of bryophyte distribution? In this study, 53 plots were set in 400 m2 along the elevation gradient in Xiaoqinling, China. All bryophytes in the plots were collected and identified. Regression analysis was used to examine the relationship between bryophyte and substrate diversity. We compared the patterns of overall bryophyte diversity and diversity of bryophytes found on the ground, tree, and rock along elevational gradients. Canonical correspondence analysis was applied to relate species composition to selected environmental variables. The importance of topography, forest, substrates, and spatial factors was determined by variance partitioning. A total of 1378 bryophyte specimens were collected, and 240 species were identified. Bryophyte diversity was closely related to substrate diversity. The overall bryophyte diversity significantly increased with elevation; however, the response varied among ground, tree, and rock bryophytes. Tree diversity and herb layer were considered important environmental factors in determining bryophyte distribution. Species abundance was best explained by stand structure (17%), and species diversity was best explained by stand structure (35%) and substrate (40%). Results directly indicated that substrate diversity can improve bryophyte species diversity. The effects of micro-habitat formed by stand structure and substrate diversity were higher than those of spatial processes and topography factors on bryophyte distribution. This study proved that the determinant factors influencing bryophyte diversity reflect the trends in recent forest management, providing a real opportunity to improve forest biodiversity conservation.

The hydrodynamic characteristics of a delta or estuary are mainly governed by discharges of rivers and water level at the sea (or lake) boundaries. A joint probability approach is widely applied to quantify the high water level frequency in deltas. In the approach the relevant hydrodynamic loading variables, namely the astronomical tides, the wind induced storm surge and the river flows, are jointly investigated. The joint probability distribution is used to generate a large number of scenarios of boundary conditions which can drive a deterministic model to derive the water levels at locations of interest. The resulting water levels as well as their associated joint probabilities can be inverted to the high water level frequency curve. However, in the joint probability distribution, marginal distributions may contain large statistical uncertainties due to their relevant parameters being estimated from a limited length of data. In the case of the Rhine Delta, a nonparametric bootstrap method is applied to quantify the statistical uncertainties in three critical marginal distributions: wind induced storm surge peak level, wind induced storm surge duration and River Rhine discharge. The uncertainties are incorporated into the marginal distributions with a Monte Carlo integration method. Further the uncertainty-incorporated marginal distributions are used for the high water level frequency assessment. Compared to previous studies, water levels for given return periods are much higher. The uncertainty differs in each marginal distribution and its impact on the high water level frequency curve also varies.

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 cysteineconjugated 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 highthroughput 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 highthroughput analysis, enabling an in-depth understanding of ADC stability and safety in vivo. [ABSTRACT FROM AUTHOR]

In this work, we report a straightforward in situ leaching strategy to achieve rapid structure self-reconstruction of NiRu--OH/NF. The asprepared electrode shows excellent OER performance with a low overpotential of 321 mV at 100 mA cm-2. It can deliver 10 mA cm-2 at 1.53 V in a water-alkali electrolyzer as the anode and operates steadily at 100 mA cm-2 with a small cell voltage for 50 h. [ABSTRACT FROM AUTHOR]