A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism.

Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

Key postnatal magnetic resonance characteristics for differentiating cystic biliary atresia from choledochal cyst.

OBJECTIVES: To analyze the ability of magnetic resonance (MR) to identify cystic biliary atresia (CBA) and choledochal cyst (CC). METHODS: Infants (≤ 1 year old) who were diagnosed with CBA or CC type I/IV from January 2010 to July 2023 were retrospectively reviewed. Imaging characteristics on MR were compared between the CBA and CC groups. Binary logistic regression and the area under the receiver operating characteristic curve (AUC) were analyzed for the identification of CBA. RESULTS: Sixty-three patients with CBA (median age, 30 days) and 172 patients with CC (median age, 60 days) were included. Gallbladder (GB) wall thickness (cutoff, 1.2 mm) showed 98.4% sensitivity and 100% specificity (AUC, 0.998). MR-triangular cord thickness (MR-TCT) (cutoff, 4.1 mm) showed 100% sensitivity and 95.9% specificity (AUC, 0.986). The bile duct loop visualization showed 96.8% sensitivity and 100% specificity (AUC, 0.984). Proximal bile duct (PBD) diameter (cutoff, 1.3 mm) showed 92.1% sensitivity and 95.3% specificity (AUC, 0.977). Cyst wall thickness (cutoff, 1 mm) showed 77.8% sensitivity and 95.3% specificity (AUC, 0.942). The combination of GB wall thickness > 1.2 mm and MR-TCT > 4.1 mm, GB wall thickness > 1.2 mm and loop visualization, GB wall thickness > 1.2 mm, and cyst wall thickness > 1 mm showed 100% sensitivity and 100% specificity (AUC, 1.000). CONCLUSIONS: Imaging characteristics on MR might be used to identify CBA and CC, and the combination of GB wall thickness and MR-TCT, or loop visualization, or cyst wall thickness, has a perfect diagnostic value. CLINICAL RELEVANCE STATEMENT: Early and accurate differentiation of CBA and CC is essential, but current methods rely on inherently subjective ultrasound. Biliary features on MRI allow for an objective, accurate diagnosis.

Dexamethasone and Insulin Modulate Alanine Aminotransferase (ALT) Activity and Alanine Oxidation in C2C12 Cells in a Dose-Dependent Manner.

BACKGROUND: The muscle cells myocytes are differentiated for the purpose of contraction function, which plays a major role in body metabolism and energy haemostasis, through different metabolic pathways, such as glucose and protein metabolic pathways. Alanine aminotransferase (ALT) plays a crucial role by reversibly catalysing transamination between alanine and a-ketoglutarate to form pyruvate and glutamate and by mediating the conversion of these four major intermediate metabolites. ALT plays important roles for energy homeostasis during fasting and prolonged exercise anaerobically, when muscle protein must first be broken down into its constituent amino acids. METHODS: Mouse skeletal myoblast cell line C2C12 was cultured in Dulbecco's modified eagle medium (DMEM) growth medium, supplied with 2% horse serum supplemented with 1 uM insulin, 2 mM glutamine and penicillin and streptomycin antibiotics for seven days. The differentiation medium is refreshed every 24 hours. Then, C2C12 cells were treated with insulin and dexamethasone to examine their effects on myocytes' ALT activity. RESULTS: In our study, we found an impact on ALT activity under different influences, including C2C12 differentiation, dexamethasone and insulin treatments, which shed light on the dynamic interplay between ALT activity, alanine metabolism, and cellular states, like differentiation and stress responses. CONCLUSION: The study provides valuable insights into the dynamic regulation of ALT activity and alanine metabolism in C2C12 cells across differentiation and drug treatments. Further research is encouraged to explore the underlying mechanisms and their implications for muscle function, differentiation and potential therapeutic interventions in metabolic disorders.

Metabolomics reveals early pregnancy biomarkers in sows: a non-invasive diagnostic approach.

In an effort to enhance reproductive management and reduce non-productive periods in swine breeding, this study presents a novel, non-invasive metabolomics approach for the identification of early pregnancy biomarkers in sows. Utilizing an untargeted metabolomics approach with mass spectrometry analysis, we examined saliva samples from pregnant (n = 6) and non-pregnant control sows (n = 6, artificially inseminated with non-viable sperm). Our analysis revealed 286 differentially expressed metabolites, with 152 being up-regulated and 134 down-regulated in the pregnant group. Among these, three metabolites, namely Hyodeoxycholic acid, 2'-deoxyguanosine, and Thymidine, emerged as potential early pregnancy biomarkers. These biomarkers were further evaluated using targeted LC-MS/MS quantification and qualification, accompanied by ROC curve analysis. The study confirmed Hyodeoxycholic acid and 2'-deoxyguanosine as promising biomarkers for early pregnancy detection, offering potential for future implementation in swine production environments. This research establishes a robust theoretical foundation for the development of innovative molecular diagnostic techniques and explores new avenues for molecular genetic breeding and non-invasive diagnostics, ultimately enhancing fertility and productivity in sow herds.

Weekend / holiday effect on stroke mortality in regional Australia: A ten-year retrospective study.

BACKGROUND: There is a deficiency in the evidence from rural and regional centres in Australia on the weekend effect following presentation with acute stroke. OBJECTIVE: To estimate the association between admission over a weekend/holiday and all-cause mortality 3-day, 7-day, 14-day, 1-month, 3-month, 6-month, and 12-month following acute stroke. METHODS: The records of stroke patients admitted to a main regional hospital in Australia from 2010 to 2020 were linked with the National Death Index. Time to death following ischaemic, haemorrhagic, and total stroke at different time points was modelled using Weibull, Exponential, or Gompertz regression based on best model fit determined by Akaike's information criterion. RESULTS: Of 1669 patients, 1273 (76.3%) were admitted on a weekday, and 396 (23.7%) on a weekend/ or holiday. After adjusting for age, sex, and Charlson Comorbidity Index, stroke type and country of birth, admissions over a weekend/holiday following total stroke were significantly associated with an increased risk of dying within three days from admission [hazard ratio (HR): 1.59, 95% confidence interval: 1.01-2.50]. In haemorrhagic stroke, increased risk of death was significantly higher at three days (HR: 2.19, 95% confidence interval: 1.17-4.08), 14 days (HR: 1.73, 95% confidence interval: 1.02-2.93), and 1 month (HR: 1.82, 95% confidence interval: 1.09-3.03) following admission on the weekend/ or holiday compared to those admitted during the weekdays. CONCLUSIONS: This study reports a short-term adverse weekend/holiday effect following admission for haemorrhagic stroke or total stroke. No significant weekend/holiday effect was found in ischaemic stroke.

The network structures of mental and behavioral problems among children and adolescents in China using propensity score matching: A comparison between one-child and multi-child families based on a nationwide survey.

BACKGROUND: Exploring networks of mental and behavioral problems in children and adolescents may identify differences between one-child and multi-child families. This study compared the network structures of mental and behavioral problems in children and adolescents in one-child families versus multi-child families based on a nationwide survey. METHODS: Propensity score matching (PSM) was used to match children and adolescents from one-child families with those from multi-child families. Mental and behavioral problems were assessed using the Achenbach's Child Behavior Checklist (CBCL) with eight syndromal subscales. In the network analysis, strength centrality index was used to estimate central symptoms, and case-dropping bootstrap method was used to assess network stability. RESULTS: The study included 39,648 children and adolescents (19,824 from one-child families and 19,824 from multi-child families). Children and adolescents from multi-child families exhibited different network structure and higher global strength compared to those from one-child families. In one-child families, the most central symptoms were "Social problems", "Anxious/depressed" and "Withdrawn/depressed", while in multi-child families, the most central symptoms were "Social problems", "Rule-breaking behavior" and "Anxious/depressed". CONCLUSION: Differences in mental and behavioral problems among children and adolescents between one-child and multi-child families were found. To address these problems, interventions targeting "Social problems" and "Anxious/depressed" symptoms should be developed for children and adolescents in both one-child and multi-child families, while other interventions targeting "Withdrawn/depressed" and "Rule-breaking behavior" symptoms could be useful for those in one-child and multi-child families, respectively.

Combined influence of depression symptoms and ratio of triglyceride to high-density lipoprotein cholesterol on cardiometabolic multimorbidity: Findings from the China Health and Retirement Longitudinal Study 2011-2018.

BACKGROUND: Previous studies had reported depression symptoms and TG/HDLC ratio may share pathophysiological pathway. The aim was to investigate the combined effects of depression symptoms and TG/HDL-C ratio on the risk of CMM. METHODS: This cohort study extracted data from 2011 to 2018 of CHARLS. The CMM event occurred from 2013 to 2018, defined as suffering from more than one of stroke, cardiac events, and diabetes mellitus. Cox proportional hazards regression models were used to assess the association between the baseline combined effects of depression symptoms and TG/HDL-C ratio with incidence of CMM, stroke, cardiac events, and diabetes mellitus. RESULTS: A total of 8349 participants (3966 men and 4383 women) were included in the study, with a mean age of 58.5 years. During a 7-year follow-up survey, 370 (4.43 %) participants developed CMM. Compared to individuals with no depression symptoms and low TG/HDLC ratio, the multivariable-adjusted HRs (95%CI) for the new-onset CMM for patients with the depression symptoms alone, high TG/HDLC ratio alone, and depression symptoms and high TG/HDLC ratio were 1.37 (95 % CI = 0.95-1.98), 1.62 (95 % CI = 1.22-2.14), 1.94 (95 % CI = 1.39-2.72), respectively (P < 0.001). LIMITATIONS: Firstly, potential confounding factors such as dietary intake and nutrition were not collected at the time of study design. Secondly, exposure to the outcome was self-reported, which may cause recall bias or misclassification. Finally, the population was aged ≥45 years, so the results cannot be generalized to all age groups. CONCLUSION: Our findings indicated that patients with depression and high TG/HDLC ratio had a higher risk of developing CMM.

Preoperative risk factors and cumulative incidence of temporary ileostomy non-closure after sphincter-preserving surgery for rectal cancer: a meta-analysis.

BACKGROUND: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer. MATERIALS AND METHODS: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer. RESULTS: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure. CONCLUSION: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.

Association of hypertension and depression with mortality: an exploratory study with interaction and mediation models.

BACKGROUND: The association of hypertension and depression with mortality has not been fully understood. We aimed to explore the possible independent or joint association of hypertension and depression with mortality. Their interaction effects on mortality and possible mediating role were also investigated. METHODS: Associations of hypertension, depression, and their interaction with all-cause and cardiovascular disease (CVD) mortality were evaluated using multivariate Cox proportional hazards regression models. The mediation analysis was conducted with a Sobel test. RESULTS: A total of 35152 participants were included in the final analysis. Hypertension and depression were independently associated with increased risk of all-cause and CVD mortality. The co-existence of hypertension and depression resulted in a 1.7-fold [95% confidence interval (CI): 1.3-2.1] increase in all-cause mortality and a 2.3-fold (95% CI: 1.4-3.7) increase in CVD mortality compared to those with neither of them. Hypertension and depression showed no significant multiplicative (P for interaction, 0.587) and additive interaction (P for relative excess risk of interaction, 0.243; P for Interaction on additive scale, 0.654) on all-cause mortality, as well as on CVD mortality. Depression did not mediate the relationship between hypertension and all-cause (Z=1.704, P=0.088) and CVD mortality (Z=1.547, P=0.122). Hypertension did not mediate the relationship between all-cause and CVD mortality as well. CONCLUSION: Hypertension and depression were related to all-cause and CVD mortality independently and the co-existence of them increased the risk of mortality. However, there is no interaction effect of them on mortality, and hypertension or depression did not mediate the association of each other with mortality.

Accelerating Oxygen Electrocatalysis Kinetics on Metal-Organic Frameworks via Bond Length Optimization.

Metal-organic frameworks (MOFs) have been developed as an ideal platform for exploration of the relationship between intrinsic structure and catalytic activity, but the limited catalytic activity and stability has hampered their practical use in water splitting. Herein, we develop a bond length adjustment strategy for optimizing naphthalene-based MOFs that synthesized by acid etching Co-naphthalenedicarboxylic acid-based MOFs (donated as AE-CoNDA) to serve as efficient catalyst for water splitting. AE-CoNDA exhibits a low overpotential of 260 mV to reach 10 mA cm-2 and a small Tafel slope of 62 mV dec-1 with excellent stability over 100 h. After integrated AE-CoNDA onto BiVO4, photocurrent density of 4.3 mA cm-2 is achieved at 1.23 V. Experimental investigations demonstrate that the stretched Co-O bond length was found to optimize the orbitals hybridization of Co 3d and O 2p, which accounts for the fast kinetics and high activity. Theoretical calculations reveal that the stretched Co-O bond length strengthens the adsorption of oxygen-contained intermediates at the Co active sites for highly efficient water splitting.

Two new alkaloids from Portulaca oleracea L. and their anti-inflammatory and anticholinesterase activities.

Two new alkaloids identified as 2-(((S,Z)-1-(1H-azirin-1-yl)-5-methylhex-1-en-3-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol and (S,Z)-1-(1H-azirin-1-yl)-5-methylhex-1-en-3-ol, named olerazirin A (1), olerazirin B (2), together with five known alkaloids, identified as cyclo (L-Val-L-Ala) (3), cyclo-(glycyl-L-leucine) (4), cyclo-(Gly-Phe) (5), cyclo (Ser-Phe) (6), (3S,6S)-3-[(1R)-1-hydroxyethyl]-6-(phenyl-methyl)-2,5-piperazinedione (7) were obtained from Portulaca oleracea L. using a range of chromatographic techniques, 1D and 2D NMR, and high-resolution electrospray ionisation time-of-flight mass spectroscopic methods, in which the compounds 3-7 were isolated from P. oleracea for the first time. In addition, the results showed that the compounds 1 and 2 have anti-inflammatory activities and compounds 1-3 and 5-7 exhibit the anticholinesterase activities.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

Design of a multi-electrode dielectric barrier discharge reactor and experimental study on the degradation of atrazine in water.

Atrazine (ATZ) is widely used in agriculture as a triazine herbicide, and its long-term use can cause serious environmental pollution. This paper independently designed a multi-electrode reactor, explored the output power and energy utilization efficiency of the dielectric barrier discharge reactor, and used the dielectric barrier discharge reactor to treat ATZ solution. The results showed that the degradation efficiency of ATZ was 96.39% at 30 min at an initial ATZ concentration of 14 mg/L, an input voltage of 34 kV, an input current of 1.38 mA, an aeration rate of 100 L/h, and a treatment water volume of 150 mL. The degradation of ATZ was significantly increased by the addition of persulfate (PS), Fe2+, and H2O2. After adding radical quenchers (EtOH, p-BQ, and FFA), the degradation efficiency of ATZ decreased, indicating that free radicals (•OH, •O2-, and 1O2) played a key role in the degradation process of ATZ.

Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

The effects of health risk behaviors to excess mortality in the population with depression: A cohort study based on NHANES data.

BACKGROUND: The population with depression had a considerable excess mortality risk. This increased mortality may be attributed to the biological consequences of depression or the substantial prevalence of health risk behaviors (HRBs). This study aimed to quantify the combined effects of four major HRBs - smoking, excessive alcohol use, physical inactivity, and an unhealthy diet - on excess mortality among depressed individuals. METHODS: This study included 35,738 adults from the National Health and Nutrition Examination Survey 2005-06 to 2017-18, with mortality follow-up data censored through 2019. The standardized prevalence of HRBs was calculated for populations with and without depression. Poisson regression models were used to calculate the mortality rate ratio (MRR). Based on model adjusting for socio-demographic factors, the attenuation of MRR was determined after further adjustment for HRBs. RESULTS: A total of 3147 participants were identified as having depression. All HRBs showed a significantly higher prevalence among the population with depression. After adjusting for socio-demographic factors, depression was associated with 1.7 and 1.8 times higher all-cause and cardiovascular disease mortality rate, respectively. Further adjustment for all current HRBs resulted in a 21.9 % reduction in all-cause mortality rate and a 15.4 % decrease in cardiovascular disease mortality rate. LIMITATION: HRBs were reported at a single time point, and we are unable to demonstrate a causal effect. CONCLUSION: At least 1/5 of excess mortality for population with depression was attributable to HRBs. Efforts should be made to address HRBs among population with depression.

Clinical Outcomes of Ileostomy Closure during versus after Adjuvant Chemotherapy in Patients with Rectal Cancer.

Background: Protective ileostomy can effectively prevent severe anastomotic leakage after rectal cancer surgery; however, the optimal timing for ileostomy closure during adjuvant chemotherapy remains unclear. This study aimed to explore the safety and long-term outcomes of early ileostomy closure during adjuvant chemotherapy. Method: Patients who underwent laparoscopic rectal cancer surgery combined with protective ileostomy and adjuvant chemotherapy between April 2017 and April 2021 were retrospectively evaluated. Patients were divided into an early closure group during chemotherapy (group A) and a late closure group after chemotherapy (group B). Results: A total of 215 patients were included in this study, with 115 in group A and 100 in group B. There were no significant differences in demographic and clinical characteristics between the two groups. In group A, durations of stoma status (p < 0.001) and low anterior resection syndrome (LARS) (p < 0.001) were shorter, and rectal stenosis (p=0.036) and stoma-related complications (p=0.007), especially stoma stenosis (p=0.041), were less common. However, compliance with chemotherapy was worse (p=0.009). There were no significant differences in operative time, postoperative hospital stay, postoperative complications, incidence and severity of LARS, disease-free survival, or overall survival between groups. Conclusion: Early ileostomy closure can effectively reduce the duration of stoma status, duration of LARS, rectal stenosis, and stoma-related complications while not affecting surgical complications and oncological outcomes. Ileostomy closure should not be delayed because of adjuvant chemotherapy. However, follow-up should be strengthened to increase compliance and integrity with chemotherapy.

Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation.

The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.

A hemodynamic model of artery bypass graft considering microcirculation function.

BACKGROUND: The incidence of arterial stenosis is increasing year by year. In order to better diagnose and treat arterial stenosis, numerical simulation technology has become a popular method. OBJECTIVE: A novel model is constructed to investigate the influence of microcirculation on the hemodynamics of artery bypass graft. METHODS: In this paper, a severely narrow artery bypass graft model is considered. The geometric shape includes a narrow artery tube and a bypass graft of the same diameter with a 45° suture angle. The fluid-structure interaction model is considered by finite element numerical calculation, and the flow is simulated with microcirculation as the outlet boundary condition. The changes of blood flow velocity, pressure and wall shear stress are analyzed. RESULTS: The results show that blood almost entirely flows into the graft tube and there is no recirculation area at the anastomosis. CONCLUSION: The artery bypass graft model considering microcirculation function could simulate the physiological characteristics of blood flow more reasonably, and it provide helps for clinicians to diagnose and treat arterial stenosis.

The role of deubiquitinases in cardiac disease.

Deubiquitinases are a group of proteins that identify and digest monoubiquitin chains or polyubiquitin chains attached to substrate proteins, preventing the substrate protein from being degraded by the ubiquitin-proteasome system. Deubiquitinases regulate cellular autophagy, metabolism and oxidative stress by acting on different substrate proteins. Recent studies have revealed that deubiquitinases act as a critical regulator in various cardiac diseases, and control the onset and progression of cardiac disease through a board range of mechanism. This review summarizes the function of different deubiquitinases in cardiac disease, including cardiac hypertrophy, myocardial infarction and diabetes mellitus-related cardiac disease. Besides, this review briefly recapitulates the role of deubiquitinases modulators in cardiac disease, providing the potential therapeutic targets in the future.

Numerical simulation of shoegear-rail coupling vibration under different initial contact forces.

As cities have grown, conductor rail power supplies have been widely used in the field of urban rail transit. In order to improve the running performance of trains and reduce the occurrence of accidents, it is necessary to understand the vibration of shoegear-rail system under different initial contact forces and explore the dynamic performance of shoegear-rail system. Therefore, according to the structure of shoegear-rail system, a coupling model of shoegear-rail system is established in this paper. On the basis of the model, the numerical simulation of the shoegear-rail system under different initial contact forces is carried out, and finally the vibration data of the shoegear-rail system under different initial contact forces are obtained. The results show that with the increase of initial contact force in the range of 70-160 N, the vibration amplitude of the electric shoegear and the fluctuation amplitude of the contact force increase, but the maximum absolute shear force value of the conductor rail decreases. It indicates that the lower initial contact force, the better the performance of shoegear-rail system.