Cellular evidence and spatial distribution of endosomal biosynthesis and autophagy in intestinal immune barrier cells of crucian carp (Carassiuscarassius).

Crucian carp (Carassius carassius) is an important aquatic economic animal, and the immune barrier function of its intestine has been a focus of research into oral vaccines and drugs. However, the histological structures of the intestinal barrier and its adjacent areas have not been clearly established, and little subcellular evidence is available to elucidate the spatial distribution of intracellular biological processes. In this study, the spatial distribution of autophagy and endosome formation in the intestinal epithelial cells (IECs) of crucian carp were analyzed. These two biological activities are closely related to intestinal homeostasis, immunity, and cell communication. Periodic acid-Schiff (PAS) and Masson's trichrome staining were employed to elucidate the distinctive histological framework of the Crucian carp's myoid cell network, which resides within the subepithelial layer and is characterized by gap junctions. Transmission electron microscopy (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) were used to detect the structural and functional aspects of the IEC in different intestinal segments. TEM and immunohistochemical analyses captured the biogenesis and maturation of early and late endosomes as well as multivesicular bodies (MVBs), as well as the initiation and progression of autophagy, including macroautophagy and mitophagy. The endosome and MVBs-specific marker CD63 and autophagy-related protein LC3 were highly expressed in IECs and were correlated with autophagy and endosome biosynthesis in the apical and basal regions of individual cells, and differed between different intestinal segments. In summary, this study elucidated the ubiquity and morphological characteristics of autophagy and endosome formation across different intestinal segments of crucian carp. A unique myoid cell network beneath the intestinal epithelium in crucian carp was also identified, expanding the histological understanding of this animal's intestinal tract.

Identification of prognostic models for glycosylation-related subtypes and tumor microenvironment infiltration characteristics in clear cell renal cell cancer.

Background: One of the most fatal forms of cancer of the urinary system, renal cell carcinoma (RCC), significantly negatively impacts human health. Recent research reveals that abnormal glycosylation contributes to the growth and spread of tumors. However, there is no information on the function of genes related to glycosylation in RCC. Methods: In this study, we created a technique that can be used to guide the choice of immunotherapy and chemotherapy regimens for RCC patients while predicting their survival prognosis. The Cancer Genome Atlas (TCGA) provided us with patient information, while the GeneCards database allowed us to collect genes involved in glycosylation. GSE29609 was used as external validation to assess the accuracy of prognostic models. The "ConsensusClusterPlus" program created molecular subtypes based on genes relevant to glycosylation discovered using differential expression analysis and univariate Cox analysis. We examined immune cell infiltration as measured by estimate, CIBERSORT, TIMER, and ssGSEA algorithms, Tumor Immune Dysfunction and Exclusion (TIDE) and exclusion of tumour stemness indices (TSIs) based on glycosylation-related molecular subtypes and risk profiles. Stratification, somatic mutation, nomogram creation, and chemotherapy response prediction were carried out based on risk factors. Results: We built and verified 16 gene signatures associated with the prognosis of ccRCC patients, which are independent prognostic variables, and identified glycosylation-related genes by bioinformatics research. Cluster 2 is associated with lower human leukocyte antigen expression, worse overall survival, higher immunological checkpoints, and higher immune escape scores. In addition, cluster 2 had significantly better angiogenic activity, mesenchymal EMT, and stem ability scores. Higher immune checkpoint genes and human leukocyte antigens are associated with lower overall survival and a higher risk score. Higher estimated and immune scores, lesser tumor purity, lower mesenchymal EMT, and higher stem scores were all characteristics of the high-risk group. High amounts of tumor-infiltrating lymphocytes, a high mutation load, and a high copy number alteration frequency were present in the high-risk group.Discussion.According to our research, the 16-gene prognostic signature may be helpful in predicting prognosis and developing individualized treatments for patients with renal clear cell carcinoma, which may result in new personalized management options for these patients.

Association between the platelet/high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: results from NHANES 2017-2020.

The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) (p < 0.05); however, the OR for hepatic fibrosis was not statistically significant (p > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.

Identification and validation of fatty acid metabolism-related lncRNA signatures as a novel prognostic model for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a main subtype of renal cancer, and advanced ccRCC frequently has poor prognosis. Many studies have found that lipid metabolism influences tumor development and treatment. This study was to examine the prognostic and functional significance of genes associated with lipid metabolism in individuals with ccRCC. Using the database TCGA, differentially expressed genes (DEGs) associated with fatty acid metabolism (FAM) were identified. Prognostic risk score models for genes related to FAM were created using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Our findings demonstrate that the prognosis of patients with ccRCC correlate highly with the profiles of FAM-related lncRNAs (AC009166.1, LINC00605, LINC01615, HOXA-AS2, AC103706.1, AC009686.2, AL590094.1, AC093278.2). The prognostic signature can serve as an independent predictive predictor for patients with ccRCC. The predictive signature's diagnostic effectiveness was superior to individual clinicopathological factors. Between the low- and high-risk groups, immunity research revealed a startling difference in terms of cells, function, and checkpoint scores. Chemotherapeutic medications such lapatinib, AZD8055, and WIKI4 had better outcomes for patients in the high-risk group. Overall, the predictive signature can help with clinical selection of immunotherapeutic regimens and chemotherapeutic drugs, improving prognosis prediction for ccRCC patients.

Effect of synovial fluid temperature on wear resistance of different polymer acetabular materials.

In order to investigate the effect of frictional heat on the wear resistance characteristics of polymeric acetabular materials, the tribological tests and wear numerical analysis of three common polymer acetabular materials were carried out under different synovial fluid temperatures. The study results show that XLPE and VE-XLPE exhibit superior wear resistance compared to UHMWPE in high-temperature, heavy load environments. The coefficient of friction of three materials gradually decreases as the temperature of the synovial fluid increases. The wear depth and wear volume of the three materials increased with the increase of the temperature of the synovial fluid, and the forms of wear at 46°C and 55°C were mainly adhesive wear and plastic deformation. The higher temperature of the synovial fluid accelerates the oxidative degradation of the material surface and generates oxidation functional groups, which leads to the breakage of C-C bonds in the surface molecular chains under the sliding shear effect, thus reducing the mechanical properties of the material. Specifically, the surface of the polymer material will soften at a higher ambient temperature, mainly due to the decrease of hardness, and then deteriorate in the friction property, and finally increase the wear rate. Ansys results showed that the volume wear of the three materials increased with the increase of synovial fluid temperature, and the trend could be approximately linear. Numerical calculations predict that VE-XLPE has the highest wear of 0.693 mm3 among the three materials at 37°C, followed by XLPE at 0.568 mm3 and UHMWPE with the lowest wear of 0.478 mm3. At higher synovial fluid temperatures (46°C, 55°C), VE-XLPE still has the largest wear volume among the three materials, while XLPE and UHMWPE have similar wear. The wear cloud pictures showed that the maximum wear volume occurred near the edge of the acetabulum.

Chronic kidney disease-induced muscle atrophy: Molecular mechanisms and promising therapies.

Chronic kidney disease (CKD) is a high-risk chronic catabolic disease due to its high morbidity and mortality. CKD is accompanied by many complications, leading to a poor quality of life, and serious complications may even threaten the life of CKD patients. Muscle atrophy is a common complication of CKD. Muscle atrophy and sarcopenia in CKD patients have complex pathways that are related to multiple mechanisms and related factors. This review not only discusses the mechanisms by which inflammation, oxidative stress, mitochondrial dysfunction promote CKD-induced muscle atrophy but also explores other CKD-related complications, such as metabolic acidosis, vitamin D deficiency, anorexia, and excess angiotensin II, as well as other related factors that play a role in CKD muscle atrophy, such as insulin resistance, hormones, hemodialysis, uremic toxins, intestinal flora imbalance, and miRNA. We highlight potential treatments and drugs that can effectively treat CKD-induced muscle atrophy in terms of complication treatment, nutritional supplementation, physical exercise, and drug intervention, thereby helping to improve the prognosis and quality of life of CKD patients.

Reduced graphene oxide-embedded nerve conduits loaded with bone marrow mesenchymal stem cell-derived extracellular vesicles promote peripheral nerve regeneration.

We previously combined reduced graphene oxide (rGO) with gelatin-methacryloyl (GelMA) and polycaprolactone (PCL) to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved. However, the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting. Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSCs) can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site. In this study, 12 weeks after surgery, sciatic nerve function was measured by electrophysiology and sciatic nerve function index, and myelin sheath and axon regeneration were observed by electron microscopy, immunohistochemistry, and immunofluorescence. The regeneration of microvessel was observed by immunofluorescence. Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function. These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery, and provide a new direction for the curation of peripheral nerve defect in the clinic.

Correlation between lactate dehydrogenase and QTc interval prolongation in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Corrected QT (QTc) interval prolongation is one of the common causes of sudden cardiac death in patients with maintenance hemodialysis (MHD) patients. However, there are few studies on QTc prolongation in MHD patients. The concentration of lactate dehydrogenase (LDH) in hemodialysis population increased, and LDH was associated with the mortality of MHD patients. This study aimed to investigate the relationship between QTc interval prolongation and LDH in MHD patients. METHODS: This is a cross-sectional observational study. Patients who underwent MHD for more than 3 months in the Second Affiliated Hospital of Nantong University from November 2012 to November 2019 with complete data were selected as the research subjects. The patients were divided into the normal QTc interval group and the QTc interval prolongation group. The general data of patients and clinical laboratory indicators were collected retrospectively from the electronic medical record system. Pearson correlation analysis and binary logistic regression were used to analyze the correlation between LDH and QTc interval prolongation; the cut-off value of LDH predicting QTc interval prolongation was calculated by receiver operating characteristic (ROC) curve. RESULTS: The LDH level in the prolonged QTc interval group was significantly higher than that in the normal group (301.96±110.91 vs. 215.39±67.65, t=-8.03, P<0.001). QTc interval and LDH (r=0.386) were positively correlated. Binary logistic regression analysis showed that LDH, serum potassium <4 mmol/L, serum phosphorus, and left ventricular end-diastolic diameter (LVDd) were independent related factors for QTc interval prolongation. The ROC curve results showed that LDH =220 U/L was the best cutoff point for predicting QTc interval prolongation in MHD patients, with a sensitivity of 81.45% and a specificity of 59.35%. Binary logistic regression analysis showed that the LDH >220 U/L group was 6.34 times more likely to have QTc interval prolongation than the LDH ≤220 U/L group (OR 6.34, 95% CI: 3.47-11.58, P<0.001). CONCLUSIONS: LDH in MHD patients is closely related to QTc interval prolongation. Serum LDH, ionic calcium, serum phosphorus and potassium may predict QTc interval prolongation. Monitoring related indicators can remind clinicians to intervene as soon as possible to reduce the potential risk of arrhythmia and sudden cardiac death (SCD).

A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients.

Background: Clear cell renal cell carcinoma (ccRCC) is the main component of renal cell carcinoma (RCC), and advanced ccRCC frequently indicates a poor prognosis. The significance of the CCCH-type zinc finger (CTZF) gene in cancer has been increasingly demonstrated during the past few years. According to studies, targeted radical therapy for cancer treatment may be a revolutionary therapeutic approach. Both lncRNAs and CCCH-type zinc finger genes are essential in ccRCC. However, the predictive role of long non-coding RNA (lncRNA) associated with the CCCH-type zinc finger gene in ccRCC needs further elucidation. This study aims to predict patient prognosis and investigate the immunological profile of ccRCC patients using CCCH-type zinc finger-associated lncRNAs (CTZFLs). Methods: From the Cancer Genome Atlas database, RNA-seq and corresponding clinical and prognostic data of ccRCC patients were downloaded. Univariate and multivariate Cox regression analyses were conducted to acquire CTZFLs for constructing prediction models. The risk model was verified using receiver operating characteristic curve analysis. The Kaplan-Meier method was used to analyze the overall survival (OS) of high-risk and low-risk groups. Multivariate Cox and stratified analyses were used to assess the prognostic value of the predictive feature in the entire cohort and different subgroups. In addition, the relationship between risk scores, immunological status, and treatment response was studied. Results: We constructed a signature consisting of eight CTZFLs (LINC02100, AC002451.1, DBH-AS1, AC105105.3, AL357140.2, LINC00460, DLGAP1-AS2, AL162377.1). The results demonstrated that the prognosis of ccRCC patients was independently predicted by CTZFLs signature and that the prognosis of high-risk groups was poorer than that of the lower group. CTZFLs markers had the highest diagnostic adequacy compared to single clinicopathologic factors, and their AUC (area under the receiver operating characteristic curve) was 0.806. The overall survival of high-risk groups was shorter than that of low-risk groups when patients were divided into groups based on several clinicopathologic factors. There were substantial differences in immunological function, immune cell score, and immune checkpoint expression between high- and low-risk groups. Additionally, Four agents, including ABT737, WIKI4, afuresertib, and GNE 317, were more sensitive in the high-risk group. Conclusion: The Eight-CTZFLs prognostic signature may be a helpful prognostic indicator and may help with medication selection for clear cell renal cell carcinoma.

A Retrospective Study from a Single Center in China to Develop a Nomogram to Predict One-Year Mortality in Patients with End-Stage Renal Disease Who Are Receiving Hemodialysis.

BACKGROUND The prognosis of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) remains Poor. This retrospective study from a single center in China aimed to develop a nomogram to predict one-year mortality in patients with ESRD on HD. MATERIAL AND METHODS We enrolled 299 ethnic Han Chinese ESRD patients undergoing HD at the Second Affiliated Hospital of Nantong University from April 29, 2011 to January 30, 2021. Univariate and multivariate Cox regression analyses were used to select the predictors incorporated in the prediction model to assess the one-year mortality for ESRD patients receiving HD. We used receiver operating characteristic curves, C-index, and calibration curves to evaluate the performance of the nomogram. The predictive performance of the nomogram was also verified in different subgroup populations. RESULTS The median follow-up time was 23.30 months. The 299 ESRD patients receiving HD were divided into a death group (n=96) and a survival group (n=203), and the incidence of death was 32.11%. The main causes of death were cardiovascular disease, inflammation and cancer. A nomogram containing age, alkaline phosphatase, albumin, cystatin C, total bilirubin, and hypersensitive c-reactive protein was established. The performance of this nomogram was reflected by its moderate predictive ability, especially for patients who were male, had a primary disease of chronic glomerulonephritis, and had no history of comorbidities. CONCLUSIONS We developed and validated an easy-to-use nomogram for predicting the one-year mortality of ESRD patients undergoing HD.

The effect of hemolysis on quality control metrics for noninvasive prenatal testing.

BACKGROUND: Noninvasive prenatal testing (NIPT) is the testing of blood samples from pregnant women to screen for fetal risk of chromosomal disorders. Even though in vitro hemolysis of blood specimens is common in clinical laboratories, its influence on NIPT has not been well investigated. METHODS: Peripheral blood samples were collected from 205 pregnant women and categorized according to the concentration of free hemoglobin in the plasma. After performing NIPT using massively parallel sequencing, the quality control metrics were analyzed and compared with samples that did not undergo hemolysis or samples redrawn from the same women. RESULTS: The specimens were divided into four groups based on the concentration of free hemoglobin: Group I (0-1 g/L, n = 53), Group II (1-2 g/L, n = 97), Group III (2-4 g/L, n = 30), and Group IV (> 4 g/L, n = 25). There was no significant difference in the quality control metrics of clinical samples with slight or moderate hemolysis (Group II and III). However, samples with severe hemolysis (Group IV) showed a significantly increased rate of duplicated reads (duplication rate) and fetal fraction, as well as decreased library concentration compared with samples without hemolysis. Moreover, the increase in fetal fraction caused by hemolysis was confirmed by redrawing blood samples in Group IV. CONCLUSION: For NIPT using massively parallel sequencing, samples with slight or moderate hemolysis (≤ 4 g/L) are acceptable. However, careful consideration should be taken regarding the use of severely hemolyzed samples (> 4 g/L), since they might increase the risk of test failure.

MiR-153-3p reduces extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via targeting PAQR3 in diabetic nephropathy.

INTRODUCTION: This study aims to explore the effect and related molecular mechanism of miR-153-3p on high glucose-stimulated human glomerular mesangial cells. MATERIALS AND METHODS: The quantitative real-time polymerase chain reaction (qPCR) assay was employed to check miR-153-3p and PAQR3 expression levels in diabetic nephropathy patients. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was applied to investigate the effects of miR-153-3p transfection or PAQR3 administration on mesangial cell (MC) activity. ELISA assays were used to check the expression levels of extracellular matrix (ECM) related proteins. The bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and check the targeting relationship between miR-153-3p and PAQR3. Western blot assays were applied to check the PAQR3, PI3K and AKT expression after miR-153-3p transfection or PAQR3 administration. RESULTS: The expression level of miR-153-3p was lower in diabetic nephropathy patients, while the expression of PAQR3 was concomitantly higher. Upregulation of miR-153-3p can reduce MC proliferation and ECM accumulation. Further research indicated that miR-153-3p directly regulated PAQR3 expression via coupling with the 3'-UTR of PAQR3. Finally, the fact that miR-153-3p regulates the PI3K/AKT pathway by PAQR3 was confirmed. CONCLUSION: MiR-153-3p regulates the PI3K/AKT pathway through PAQR3, thereby playing a role in regulating cell proliferation and ECM accumulation in high glucose-stimulated MCs.

Association between fibrinogen/albumin ratio and arterial stiffness in patients with type 2 diabetes: A cross-sectional study.

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV). Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness. Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness (p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men (p < .01), while they were insignificant in subgroups of elderly and non-elderly women (p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031-1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g. Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.

Small RNA GcvB Regulates Oxidative Stress Response of Escherichia coli.

Small non-translated regulatory RNAs control plenty of bacterial vital activities. The small RNA GcvB has been extensively studied, indicating the multifaceted roles of GcvB beyond amino acid metabolism. However, few reported GcvB-dependent regulation in minimal medium. Here, by applying a high-resolution RNA-seq assay, we compared the transcriptomes of a wild-type Escherichia coli K-12 strain and its gcvB deletion derivative grown in minimal medium and identified putative targets responding to GcvB, including flu, a determinant gene of auto-aggregation. The following molecular studies and the enhanced auto-aggregation ability of the gcvB knockout strain further substantiated the induced expression of these genes. Intriguingly, the reduced expression of OxyR (the oxidative stress regulator) in the gcvB knockout strain was identified to account for the increased expression of flu. Additionally, GcvB was characterized to up-regulate the expression of OxyR at the translational level. Accordingly, compared to the wild type, the GcvB deletion strain was more sensitive to oxidative stress and lost some its ability to eliminate endogenous reactive oxygen species. Taken together, we reveal that GcvB regulates oxidative stress response by up-regulating OxyR expression. Our findings provide an insight into the diversity of GcvB regulation and add an additional layer to the regulation of OxyR.

The Efficiency of Hydroxychloroquine for the Treatment of Primary Sjögren's Syndrome: A Systematic Review and Meta-Analysis.

Objectives: This meta-analysis was conducted to evaluate the effects of hydroxychloroquine (HCQ) in the treatment of primary Sjögren's syndrome (pSS). Methods: Nine databases were searched for data collection. We used clinical features, including involvement in superficial tissues and visceral systems, and experimental findings, including Schirmer's test, unstimulated salivary flow rate (uSFR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and immunoglobulins (IgG, IgM and IgA) as major outcome measures. The Downs and Black quality assessment tool and RevMan 5.3 were used to assess the methodological quality and statistical analysis, respectively. Results: Thirteen studies with pSS patients, consisting of two randomized controlled studies, four retrospective studies and seven prospective studies were analyzed. Results showed that HCQ treatment significantly improved the oral symptoms of pSS patients compared to non-HCQ treatment (P = 0.003). Similar trends favoring HCQ treatment were observed for uSFR (p = 0.05), CRP (p = 0.0008), ESR (p < 0.00001), IgM (p = 0.007) and IgA (p = 0.05). However, no significant improvement was observed in other clinical features, including ocular involvement, fatigue, articular lesions, pulmonary, neurological and lymphoproliferative symptoms, renal organs and other experimental parameters in the HCQ treatment group compared to the non-HCQ treatment group. Conclusion: HCQ treatment showed moderate efficacy to improve oral symptoms, uSFR, ESR, CRP, IgM and IgA. However, HCQ could not alleviate organ-specific systemic involvement. Systematic Review Registration:We have registered on the PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], and the registration number is identifier [CRD42020205624].

MiR-153-3p reduces extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via targeting PAQR3 in diabetic nephropathy.

INTRODUCTION: This study aims to explore the effect and related molecular mechanism of miR-153-3p on high glucose-stimulated human glomerular mesangial cells. MATERIALS AND METHODS: The quantitative real-time polymerase chain reaction (qPCR) assay was employed to check miR-153-3p and PAQR3 expression levels in diabetic nephropathy patients. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was applied to investigate the effects of miR-153-3p transfection or PAQR3 administration on mesangial cell (MC) activity. ELISA assays were used to check the expression levels of extracellular matrix (ECM) related proteins. The bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and check the targeting relationship between miR-153-3p and PAQR3. Western blot assays were applied to check the PAQR3, PI3K and AKT expression after miR-153-3p transfection or PAQR3 administration. RESULTS: The expression level of miR-153-3p was lower in diabetic nephropathy patients, while the expression of PAQR3 was concomitantly higher. Upregulation of miR-153-3p can reduce MC proliferation and ECM accumulation. Further research indicated that miR-153-3p directly regulated PAQR3 expression via coupling with the 3'-UTR of PAQR3. Finally, the fact that miR-153-3p regulates the PI3K/AKT pathway by PAQR3 was confirmed. CONCLUSION: MiR-153-3p regulates the PI3K/AKT pathway through PAQR3, thereby playing a role in regulating cell proliferation and ECM accumulation in high glucose-stimulated MCs.

Highly Thermally Conductive 3D Printed Graphene Filled Polymer Composites for Scalable Thermal Management Applications.

Efficient thermal transportation in a preferred direction is highly favorable for thermal management issues. The combination of 3D printing and two-dimensional (2D) materials such as graphene, BN, and so on enables infinite possibilities for hierarchically aligned structure programming. In this work, we report the formation of the asymmetrically aligned structure of graphene filled thermoplastic polyurethane (TPU) composites during 3D printing process. The as-printed vertically aligned structure demonstrates a through-plane thermal conductivity (TC) up to 12 W m-1 K-1 at 45 wt % graphene content, which is ∼8 times of that of a horizontally printed structure and surpasses many of the traditional particle reinforced polymer composites. The superior TC is mainly attributed to the anisotropic structure design that benefited from the preferable degree of orientation of graphene and the multiscale dense structure realized by finely controlling the printing parameters. Finite element method (FEM) confirms the essential impact of anisotropic TC design for highly thermal conductive composites. This study provides an effective way to develop 3D printed graphene-based polymer composites for scalable thermal-related applications such as battery thermal management, electric packaging, and so on.

A Clinical Study on the Association of Sodium-Glucose Cotransporter 2 Inhibitors and Acute Kidney Injury Among Diabetic Chinese Population.

PURPOSE: To investigate the association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and acute kidney injury in comparison to other classes of drugs. PATIENTS AND METHODS: A total of 4966 diabetes mellitus patients were investigated for developing Acute Kidney Injury (AKI) who were under prescription with the following class of drugs viz. SGLT2 Inhibitors, Dipeptidyl peptidase-4 (DDP4) inhibitors, Nonsteroidal anti-inflammatory drugs (NSAIDs), first-line drugs and anti-biotics. The primary outcome was based on the hospital encounter and Kidney Disease Improving Global Outcome (KDIGO) threshold values were used to assess the serum creatinine concentration. The secondary outcome was assessed based on the concentration level of serum creatinine after 90 days of hospital admission and evaluation of the KDIGO threshold values. RESULTS: The study observed that the risk of causing AKI for SGLT2 inhibitors was 5.59% which was comparatively low compared to other class of the investigated drugs (DPP4 inhibitors = 6.47%, antibiotics = 6.30%, first-line drugs = 6.82% and NSAIDs = 10.65%). The multivariate analysis observed that ibuprofen, celecoxib, indomethacin, insulin, cephalexin, and alogliptin were mostly associated with an increased rate of AKI. SGLT2 inhibitors have the lowest risk for developing AKI compared to other drugs and control. CONCLUSION: AKI incidence is relatively low after initiation of SLGT2 inhibitors and concludes that regulatory warnings from certain health agencies about its risk for AKI on prescription are unwarranted.

Reduced graphene oxide-GelMA-PCL hybrid nanofibers for peripheral nerve regeneration.

Graphene oxide is currently used in peripheral nerve engineering but has certain limitations, such as cytotoxicity and lack of electrical conductivity, both of which are crucial in regulating nerve-associated cell behaviors. In this work, we engineered reduced graphene oxide-GelMA-PCL nanofiber nerve guidance conduits via electrospinning. rGO incorporated into the GelMA/PCL matrix significantly enhanced the electrical conductivity and biocompatibility of the hybrid materials. In addition, hybrid nanofibers with low concentrations of rGO (0.25 and 0.5 wt%) could significantly improve the proliferation of Schwann cells (RSC96). More importantly, rGO/GelMA/PCL hybrid nanofibers could activate the epithelial-mesenchymal transition (EMT)-related gene expression of Schwann cells (RSC96). From the in vivo study, it was observed that rGO/GelMA/PCL nerve guidance conduits could promote both sensory/motor nerve regeneration and functional recovery in rats. Our composite strategy of combining rGO within a biocompatible nanofiber scaffold is simple but effective in improving tissue engineering outcomes. The rGO/GelMA/PCL hybrid nanofibers have great potential in peripheral nerve tissue engineering. They will also provide an experimental basis for the development of further electrical stimulation in peripheral nerve regeneration.

Ligustilide alleviates podocyte injury via suppressing the SIRT1/NF-κB signaling pathways in rats with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the common chronic microvascular complications of diabetes, and podocyte injury and dysfunction are strictly related to the pathogenesis of DN. Studies have shown that ligustilide (LIG) has anti-inflammatory, antioxidant, and anti-apoptotic activities. This study was designed to investigate the therapeutic effect of LIG in DN rats and their mechanisms. METHODS: DN rat models (n=10) were induced by streptozotocin (STZ) combined with a high-fat diet. Rats in the LIG group were intragastrically administered with LIG daily for eight weeks, and animals in the positive control group were treated with Losartan potassium. The body weight and blood glucose were checked weekly during the treatment. The pathological changes of kidney tissue were observed with hematoxylin and eosin (HE) staining. Blood lipid profiles and renal function-related markers, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), and serum creatinine (Scr) were monitored using a biochemical analyzer. The protein expression of nephrin was determined by immunohistochemistry and Western blotting. Finally, Western blot was used to determine the protein expression of Sirtuin 1 (SIRT1) and nuclear factor-kappa B (NF-κB). RESULTS: Compared with the healthy control group, rats in the DN group have slower weight gain, increased blood sugar level, renal lesions, and impaired renal function, along with decreased nephrin expression, abnormally activated NF-κB, and inhibited SIRT1 protein expression. All the above conditions were improved after intervention with either losartan potassium or LIG. CONCLUSIONS: LIG attenuates podocyte injury by regulating the SIRT1/NF-κB signaling pathway and thereby exerts its protective effect on renal function in DN rats.