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Abstract Objective We employed a meta-analysis to investigate the risk factors associated with sarcopenia in patients undergoing dialysis. Methods We conducted a search in PubMed, Embase, Cochrane Library, and Web of Science databases. Inclusion criteria included case–control and cohort studies on risk factors for sarcopenia in dialysis patients. The search period spanned from the inception of each database to September 20, 2024. The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS). Data analysis was performed using Stata 15.0. Result A total of 625 articles were screened, with 610 articles excluded based on predefined eligibility criteria, resulting in 15 articles involving 2904 individuals were included in the final analysis, meta-analysis results indicate that older dialysis patients [SMD = 0.76, 95% CI (0.54, 0.99), I2 = 81%, P = 0.001], those with a lower BMI [SMD = -0.50, 95% CI (-0.80, -0.20), I2% = 87.4%, P = 0.02], a lower SMI [SMD = -2.67, 95% CI (-3.87, -1.47), I2% = 98.2%, P = 0.001], and those with diabetes [OR = 1.43, 95% CI (1.13, 1.82), I2% = 48.8%, P = 0.03] are more likely to develop sarcopenia. Conclusion Based on current research, our study found that elderly dialysis patients, those with a lower BMI, lower SMI, and diabetic patients are more likely to develop sarcopenia. These findings highlight the necessity of early intervention for these high-risk groups. However, the study has limitations. Future research should address these limitations and investigate the mechanisms linking these risk factors to sarcopenia to develop targeted prevention and treatment strategies.

Abstract Background Mn2+-mediated chemodynamic therapy (CDT) has been emerged as a promising cancer therapeutic modality that relies heavily on HCO3 − level in the system. Although the physiological buffers (H2CO3/HCO3 −) provide certain amounts of HCO3 −, the acidity of the tumor microenvironment (TME) would seriously affect the HCO3 − ionic equilibrium (H2CO3 ⇌ H+ + HCO3 −). As a result, HCO3 − level in the tumor region is actually insufficient to support effective Mn2+-mediated CDT. Results In this study, a robust nanomodulator MnFe2O4@ZIF-8 (PrSMZ) with the capability of in situ self-regulation HCO3 − is presented to enhance therapeutic efficacy of Mn2+-mediated CDT. Under an acidic tumor microenvironment, PrSMZ could act as a proton sponge to shift the HCO3 − ionic equilibrium to the positive direction, significantly boosting the generation of the HCO3 −. Most importantly, such HCO3 − supply capacity of PrSMZ could be finely modulated by its ZIF-8 shell thickness, resulting in a 1000-fold increase in reactive oxygen species (ROS) generation. Enhanced ROS-dependent CDT efficacy is further amplified by a glutathione (GSH)-depletion ability and the photothermal effect inherited from the inner core MnFe2O4 of PrSMZ to exert the remarkable antitumor effect on mouse models. Conclusions This work addresses the challenge of insufficient HCO3 − in the TME for Mn2+-mediated Fenton catalysts and could provide a promising strategy for designing high-performance Mn2+-mediated CDT agents to treat cancer effectively.

Abstract BamA is the central component of the essential β-barrel assembly machine (BAM), a conserved multi-subunit complex that dynamically inserts and folds β-barrel proteins into the outer membrane of Gram-negative bacteria. Despite recent advances in our mechanistic and structural understanding of BamA, there are few potent and selective tool molecules that can bind to and modulate BamA activity. Here, we explored in vitro selection methods and different BamA/BAM protein formulations to discover peptide macrocycles that kill Escherichia coli by targeting extreme conformational states of BamA. Our studies show that Peptide Targeting BamA-1 (PTB1) targets an extracellular divalent cation-dependent binding site and locks BamA into a closed lateral gate conformation. By contrast, PTB2 targets a luminal binding site and traps BamA into an open lateral gate conformation. Our results will inform future antibiotic discovery efforts targeting BamA and provide a template to prospectively discover modulators of other dynamic integral membrane proteins.

Abstract Background and Aim Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients’ prognoses. Methods and results Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62–2.26 vs. HR: 1.75, 95% CI: 1.43–2.16, P

Abstract Modulating immunosuppression while eliminating residual microscopic tumors is critical for inhibiting the postoperative recurrence of triple‐negative breast cancer (TNBC). Although immunotherapy has shown potential in achieving this goal, due to multiple immunosuppression and poor immunogenicity of apoptosis, a satisfactory anti‐recurrence effect still faces the challenge. Herein, an injectable hydrogel‐encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical‐grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti‐tumor immune response. Following injection of the CP@Gel, the sustained release of CP leads to the autocatalytic generation of reactive oxygen species, resulting in caspase‐3 activation, and the pre‐administered DAC inhibits the methylation of Gsdme to elevate the GSDME protein levels, leading to intense pyroptosis and anti‐tumor immune responses. The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis‐based and injectable hydrogel‐aided strategies for preventing the postoperative recurrence of TNBC.

Background and aimsFerroptosis, a novel concept of programmed cell death proposed in 2012, in kidney disease, has garnered significant attention based on evidence of abnormal iron deposition and lipid peroxidation damage in the kidney. Our study aim to examine the trends and future research directions in the field of ferroptosis in kidney disease, so as to further explore the target or treatment strategy for clinical treatment of kidney disease.Material and MethodsA thorough survey using the Web of Science Core Collection, focusing on literature published between 2012 and 2024 examining the interaction between kidney disease and ferroptosis was conducted. VOSviewer, CiteSpace, and Biblioshiny were used for in-depth scientometric and visualized analyses.ResultsFrom 2012 to 2024, a total of 2,244 articles met the inclusion criteria for final analysis. The number of annual publications in this area of study showed a steady pattern at the beginning of the decade. The top 3 journals with the highest publication output were Renal Failure, Oxidative Medicine And Cellular Longevity, and Biomedicine & Pharmacotherapy. China and the United States had the highest number of publications. Central South University and Guangzhou Medical University as the most active and influential institutions. Documents and citation analysis suggested that Andreas Linkermann, Jolanta Malyszko, and Alberto Ortiz are active researchers, and the research by Scott J. Dixon and Jose Pedro Friedmann Angeli, as the most cited article, are more important drivers in the development of the field. Keywords associated with glutathione, lipid peroxidation, and nitric oxide had high frequency in the early studies. In recent years, however, there has been a shift towards biomarkers, inflammation and necrosis, which indicate current and future research directions in this area.ConclusionThe global landscape of the ferroptosis research in kidney disease from 2012 to 2024 was presented. Basic research and mechanism exploration for renal fibrosis and chronic kidney disease may be a hot spot in the future.

Background and aims Macrophages play a variety of widely concerned roles in the process of chronic kidney disease (CKD). To further understand the research hotspots and development trends regarding the relationship between macrophages and CKD, the role of macrophages in the occurrence and progression of CKD was summarized by bibliometrics in this study.Material and Methods We collected the studies relevant the role of macrophages in CKD from the Web of Science Core Collection, which included 1332 relevant studies from Jan 1st, 2004 to Jul 6th, 2023 in WoSCC. CiteSpace, biblioshiny in R, VOSviewer and SCImago Graphica Beta were used for bibliometric analysis and visualization.Results Monash University from Australia is the most productive institution, while China and the USA are most productive countries. Anders HJ is the most cited author. In terms of the number of co-citations, the top one was “Macrophages: versatile players in renal inflammation and fibrosis” by Patrick Ming-Kuen Tang, published in Nature Reviews Nephrology in 2019. Important keywords of this research topic include inflammation, dendritic cell, oxidative stress, NF-κB, tgf-beta, interstitial fibrosis, glomerulonephritis, diabetic nephropathy. Future research hotspots may include molecular mechanism, acute kidney injury, macrophage polarization, kidney fibrosis.Conclusion This study provides a systematic review of the role of macrophages in CKD and speculates that future research hotspots. Previous studies have focused on the immune function of macrophages and atypia, and metabolic factors (especially iron metabolism within macrophages) have attracted the attention of researchers in recent years and are the forefront of recent research.

Abstract Analyzing three-dimensional excitation-emission matrix (3D-EEM) spectra through machine learning models has drawn increasing attention, whereas the reliability of these machine learning models remains unclear due to their “black box” nature. In this study, the convolutional neural network (CNN) for classifying numbers of fluorescent components in 3D-EEM spectra was interpreted by gradient-weighted class activation mapping (Grad-CAM), guided Grad-CAM, and structured attention graphs (SAGs). Results showed that the original CNN classifier with high classification accuracy may make a classification based on misleading attention to the non-fluorescence area in 3D-EEM spectra. By removing Rayleigh scatterings in 3D-EEM spectra and integrating convolutional block attention module (CBAM) in CNN classifiers, the correct attention of the trained CNN classifier with CBAM greatly increased from 17.6% to 57.2%. This work formulated strategies for improving CNN classifiers associated with environmental fields and would provide great help for water determination in both natural and artificial environments.

Abstract Background Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN. Methods The gene chip data were retrieved from the GEO database using the search term ' diabetic nephropathy ‘. The ' limma ' software package was used to identify differentially expressed genes (DEGs) between DN and control samples. Gene set enrichment analysis (GSEA) was performed on genes obtained from the molecular characteristic database (MSigDB. The R package ‘WGCNA’ was used to identify gene modules associated with tubulointerstitial injury in DN, and it was crossed with immune-related DEGs to identify target genes. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on differentially expressed genes using the ‘ClusterProfiler’ software package in R. Three methods, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest (RF), were used to select immune-related biomarkers for diagnosis. We retrieved the tubulointerstitial dataset from the Nephroseq database to construct an external validation dataset. Unsupervised clustering analysis of the expression levels of immune-related biomarkers was performed using the ‘ConsensusClusterPlus ‘R software package. The urine of patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to March 2023 was collected, and Elisa was used to detect the mRNA expression level of immune-related biomarkers in urine. Pearson correlation analysis was used to detect the effect of immune-related biomarker expression on renal function in DN patients. Results Four microarray datasets from the GEO database are included in the analysis : GSE30122, GSE47185, GSE99340 and GSE104954. These datasets included 63 DN patients and 55 healthy controls. A total of 9415 genes were detected in the data set. We found 153 differentially expressed immune-related genes, of which 112 genes were up-regulated, 41 genes were down-regulated, and 119 overlapping genes were identified. GO analysis showed that they were involved in various biological processes including leukocyte-mediated immunity. KEGG analysis showed that these target genes were mainly involved in the formation of phagosomes in Staphylococcus aureus infection. Among these 119 overlapping genes, machine learning results identified AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1 and FSTL1 as potential tubulointerstitial immune-related biomarkers. External validation suggested that the above markers showed diagnostic efficacy in distinguishing DN patients from healthy controls. Clinical studies have shown that the expression of AGR2, CX3CR1 and FSTL1 in urine samples of DN patients is negatively correlated with GFR, the expression of CX3CR1 and FSTL1 in urine samples of DN is positively correlated with serum creatinine, while the expression of DEFB1 in urine samples of DN is negatively correlated with serum creatinine. In addition, the expression of CX3CR1 in DN urine samples was positively correlated with proteinuria, while the expression of DEFB1 in DN urine samples was negatively correlated with proteinuria. Finally, according to the level of proteinuria, DN patients were divided into nephrotic proteinuria group (n = 24) and subrenal proteinuria group. There were significant differences in urinary AGR2, CCR2 and DEFB1 between the two groups by unpaired t test (P

Abstract Video frame interpolation (VFI) is a technique that synthesises intermediate frames between adjacent original video frames to enhance the temporal super‐resolution of the video. However, existing methods usually rely on heavy model architectures with a large number of parameters. The authors introduce an efficient VFI network based on multiple lightweight convolutional units and a Local three‐scale encoding (LTSE) structure. In particular, the authors introduce a LTSE structure with two‐level attention cascades. This design is tailored to enhance the efficient capture of details and contextual information across diverse scales in images. Secondly, the authors introduce recurrent convolutional layers (RCL) and residual operations, designing the recurrent residual convolutional unit to optimise the LTSE structure. Additionally, a lightweight convolutional unit named separable recurrent residual convolutional unit is introduced to reduce the model parameters. Finally, the authors obtain the three‐scale decoding features from the decoder and warp them for a set of three‐scale pre‐warped maps. The authors fuse them into the synthesis network to generate high‐quality interpolated frames. The experimental results indicate that the proposed approach achieves superior performance with fewer model parameters.

ObjectiveThis study aimed to investigate the relationship between bone metabolism markers, including serum klotho, fibroblast growth factor 23 (FGF23), 25(OH)D3, iPTH, calcium (Ca), and PHOS and the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Additionally, the predictive value of these markers for DKD progression was evaluated.MethodsThis study involved 126 patients with T2DM between May 2021 and March 2023. DKD staging was assessed based on urinary protein excretion rates and estimated glomerular filtration rate (eGFR). The study evaluated serum concentrations of klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS across various stages and examined their relationships with clinical parameters. Receiver operating characteristic (ROC) curve analysis was utilized to determine the predictive accuracy of these bone metabolism markers for DKD. Multivariate linear and logistic regression analyses identified risk factors linked to DKD severity.ResultsAmong the 126 participants, 30 had non-DKD with normal proteinuria, while 96 had DKD, categorized as 31 with stage III DKD (microproteinuria), 34 with stage IV DKD, and 31 with stage V DKD (massive proteinuria). With advancing DKD from stage III to V, levels of klotho, 25(OH)D3, and Ca decreased significantly, whereas FGF23, iPTH and PHOS levels increased markedly. Klotho is significantly positively correlated with eGFR (r = 0.285, P = 0.001.) and negative correlations with serum creatinine (Scr) and UACR (r = -0.255, P = 0.004; r = -0.260, P = 0.011). FGF23 was positively related to systolic blood pressure (SBP) (r = 0.224, P = 0.012), but negatively with eGFR (r = -0.294, P = 0.001). Additionally, 25(OH)D3 exhibited significant negative correlations with several adverse clinical biomarkers, and both iPTH, Ca and PHOS were strongly associated with DKD progression (P

BackgroundDisorders of lipid metabolism play a key role in the initiation and progression of chronic kidney disease (CKD). Recently, research on lipid metabolism in CKD has rapidly increased worldwide. However, comprehensive bibliometric analyses in this field are lacking. Therefore, this study aimed to evaluate publications in the field of lipid metabolism in CKD over the past 20 years based on bibliometric analysis methods to understand the important achievements, popular research topics, and emerging thematic trends.MethodsLiterature on lipid metabolism in CKD, published between 2004 and 2023, was retrieved from the Web of Science Core Collection. The VOSviewer (v.1.6.19), CiteSpace (v.6.3 R1), R language (v.4.3.2), and Bibliometrix (v.4.1.4) packages (https://www.bibliometrix.org) were used for the bibliometric analysis and visualization. Annual output, author, country, institution, journal, cited literature, co-cited literature, and keywords were also included. The citation frequency and H-index were used to evaluate quality and influence.ResultsIn total, 1,285 publications in the field of lipid metabolism in CKD were identified in this study. A total of 7,615 authors from 1,885 institutions in 69 countries and regions published articles in 466 journals. Among them, China was the most productive (368 articles), and the United States had the most citations (17,880 times) and the highest H-index (75). Vaziri Nosratola D, Levi Moshe, Fornoni Alessia, Zhao Yingyong, and Merscher Sandra emerged as core authors. Levi Moshe (2,247 times) and Vaziri Nosratola D (1,969 times) were also authors of the top two most cited publications. The International Journal of Molecular Sciences and Kidney International are the most published and cited journals in this field, respectively. Cardiovascular disease (CVD) and diabetic kidney disease (DKD) have attracted significant attention in the field of lipid metabolism. Oxidative stress, inflammation, insulin resistance, autophagy, and cell death are the key research topics in this field.ConclusionThrough bibliometric analysis, the current status and global trends in lipid metabolism in CKD were demonstrated. CVD and DKD are closely associated with the lipid metabolism of patients with CKD. Future studies should focus on effective CKD treatments using lipid-lowering targets.

Abstract Background Herbal nanoparticles are made from natural herbs/medicinal plants, their extracts, or a combination with other nanoparticle carriers. Compared to traditional herbs, herbal nanoparticles lead to improved bioavailability, enhanced stability, and reduced toxicity. Previous research indicates that herbal medicine nanomaterials are rapidly advancing and making significant progress; however, bibliometric analysis and knowledge mapping for herbal nanoparticles are currently lacking. We performed a bibliometric analysis by retrieving publications related to herbal nanoparticles from the Web of Science Core Collection (WoSCC) database spanning from 2004 to 2023. Data processing was performed using the R package Bibliometrix, VOSviewers, and CiteSpace. Results In total, 1876 articles related to herbal nanoparticles were identified, originating from various countries, with China being the primary contributing country. The number of publications in this field increases annually. Beijing University of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, and Saveetha University in India are prominent research institutions in this domain. The Journal “International Journal of Nanomedicine” has the highest number of publications. The number of authors of these publications reached 8234, with Yan Zhao, Yue Zhang, and Huihua Qu being the most prolific authors and Yan Zhao being the most frequently cited author. “Traditional Chinese medicine,” “drug delivery,” and “green synthesis” are the main research focal points. Themes such as “green synthesis,” “curcumin,” “wound healing,” “drug delivery,” and “carbon dots” may represent emerging research areas. Conclusions Our study findings assist in identifying the latest research frontiers and hot topics, providing valuable references for scholars investigating the role of nanotechnology in herbal medicine. Graphical Abstract

[Objective] In order to improve the formation adaptability of the tunnel boring machine (shorten as TBM) and solve the problem of TBM selection for the west extension section of Qingdao Metro Line 2 (hereinafter referred to as Line 2) in the complex formation offshore, it is necessary to optimize TBM selection and control tunneling parameters. [Method] From the aspects of geological condition adaptability, construction flexibility and excavation efficiency, the TBM types are comprehensively compared and the one suitable for hard rock excavation is selected. In view of the engineering difficulties in the TBM tunneling section of Line 2, such as crossing fracture zone, insufficient starting space, small curvature radius construction and lack of lifting conditions, the TBM is optimized. The range of parameter values including thrust, torque, cutter speed and net tunneling rate of double-shield TBM under different grades of wall rock are determined. [Result & Conclusion] After comprehensive comparison, DSUC type double shield TBM is selected for the construction of Line 2 west extension section in complex offshore strata. This type of TBM has good formation adaptability and flexible support methods. By optimizing cutter head, shield body and back-up train design, improving the starting, disassembling and small curvature radius construction scheme, and improving the advance reinforcement and guidance system, TBM application becomes more economical and reasonable. When the TBM advances in the medium hard rock formation, the thrust and torque can be properly improved to increase the net tunneling rate. The tunneling parameters should be strictly controlled to reduce the disturbance to the palm surface when the TBM passes through fault fracture zone.

ObjectivesThis study was conducted to examine the potential health benefits of thonningianin A (TA) on renal injury and interstitial fibrosis in diabetic nephropathy (DN) mice.MethodsIn this study, a DN mice model was established using male C57BL/6 mice injected with streptozotocin (STZ, 50 mg/kg) intraperitoneally and treated with TA for 12 weeks. Firstly, the therapeutic and anti-fibrotic effects of TA on DN were evaluated. Secondly, the effect of TA on renal inflammation was evaluated and Western blot was used to detect the changes of NLRP3/ASC/Caspase-1 pathway-related protein expressions in kidney. Furthermore, the effect of TA on impairments in the intestinal mucosa barrier was evaluated and the changes of lipopolysaccharide (LPS) levels in feces and serum were detected by ELISA. Finally, 16S rRNA sequencing was used to detect alteration of gut microbiota diversity and abundance in mice after TA treatment.ResultsThe results showed that TA markedly mitigated blood glucose (Glu), decreased 24-h urinary total protein (24hUTP), improved renal dysfunction and kidney index (KI) in DN mice. Furthermore, TA significantly alleviated renal injury and interstitial fibrosis, repressing renal inflammation. Western blot results showed that the NLRP3/ASC/Caspase-1 signaling pathway-related proteins decreased after TA treatment. In addition, TA also ameliorated impairments in the intestinal mucosa barrier and restored the expressions of intestinal tight junction proteins (Claudin-1, Occludin and ZO-1). Subsequently, it reduced LPS levels of DN mice in fecal and serum. Furthermore, 16S rRNA high-throughput sequencing showed that TA modulated gut microbiota dysbiosis and decreased the abundance of Gram-negative bacteria (Proteobacteria and Escherichia-Shigella).ConclusionThis study suggested that TA might exert a beneficial effect on renal interstitial fibrosis in DN mice by modulating gut microbiota dysbiosis, ameliorating impairments in the intestinal mucosa barrier, reducing the production and release of LPS, inhibiting the activation of NLRP3/ASC/Caspase-1 signaling pathway, and repressing renal inflammatory.

Photothermal therapy (PTT) has garnered extensive attention as an efficient strategy for cancer therapy. Unfortunately, there are currently no suitable photothermal agents (PTAs) capable of effectively treating HER2-positive breast cancer (HER2+ BC) due to the challenges in addressing blood circulation and tumor accumulation. Here, we propose a HER2-specific macrophage biomimetic nanoplatform IR820@ZIF-8@EM (AMBP) for enhanced bio-photothermal therapy of HER2+ BC. An anti-HER2 antibody was expressed in engineered macrophages using the transmembrane expression technique. As an efficient PTAs, IR820 dyes were assembled into ZIF-8 as to develop a “nano-thermal-bomb”. Homology modeling methods support that the expressed anti-HER2 antibody can specifically recognize the HER2 receptor. Moreover, antibody-dependent cell-mediated cytotoxicity can also be induced in HER2+ BC cells by AMBP. In vitro fluorescence confocal imaging showed that AMBP promoted the uptake of HER2+ cancer cells while in vivo anti-tumor experiments demonstrated that AMBP efficiently accumulates in the tumor regions. Finally, under spatiotemporally controlled near-infrared (NIR) irradiation, three of the six tumors were eradicated in AMBP-treated mice, demonstrating a safe and effective strategy. In conclusion, our research opens a new paradigm for antibody-specific macrophage, and it is expected that these characteristics will have substantial clinical translation potential for BC treatment.

Background: Patients undergoing hemodialysis (HD) for chronic kidney disease (CKD) often encounter anemia. Roxadustat has not only undergone phase II-III clinical trials in patients suffering from CKD and undergoing HD; a number of post-marketing clinical studies have been conducted using the drug. This article was to assess the effectiveness and safety of roxadustat in managing anemia among patients with CKD undergoing HD. Methods: A thorough search was performed across eight databases, including PubMed, Web of Science, Cochrane Library, Embase, Wan Fang, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQ VIP), and SinoMed to identify randomized clinical trials (RCTs) examining the effectiveness and safety of roxadustat in managing anemia among individuals suffering from CKD and undergoing HD. This search included studies from the inception of these databases to April 2023. Results: Two phase II, one phase III, and 16 post-marketing studies with 1688 participants were included. Serum iron (SI), transferrin, and total iron-binding capacity (TIBC) levels changed from baseline (∆SI, ∆transferrin, and ∆TIBC) and were significantly more increased for roxadustat than for erythropoiesis-stimulating agents (ESAs): MD 2.55, (95% CI 1.51 to 3.60), p < 0.00001; MD 0.55, (95% CI 0.41 to 0.69), p < 0.00001; and MD 6.54, (95% CI 4.50 to 8.59), p < 0.00001, respectively. Roxadustat was not inferior to ESAs with regard to increasing Hb (∆Hb) levels [MD 1.17 (95% CI 0.71 to 1.63), p < 0.00001] (g/dL). No statistically significant distinctions of the ∆ferritin, ∆hepcidin, and transferrin saturation (TSAT) from baseline (∆TSAT) level were identified between roxadustat and ESAs. C-reactive protein (CRP) levels changed from baseline (∆CRP) and were significantly more reduced for roxadustat than for ESAs. As for safety, the analysis indicated no notable difference in the occurrence of adverse events (AEs) and serious adverse events (SAEs) between roxadustat and ESAs. Conclusions: This meta-analysis demonstrated that roxadustat outperformed ESAs in enhancing SI, transferrin, and TIBC levels while also decreasing CRP levels. Roxadustat was not inferior to ESAs in terms of improving Hb levels and safety. These findings suggest that roxadustat was well tolerated and a potent alternative to ESAs in managing anemia among patients suffering from CKD and undergoing HD.

Abstract Background The number of elderly patients diagnosed with breast cancer is increasing worldwide. However, treatment decisions for these patients are highly variable. Although researchers have identified the effects of surgery, radiotherapy, endocrine therapy, and chemotherapy in elderly patients with breast cancer, clinicians still struggle to make appropriate decisions for these patients. Methods We identified 75,525 female breast cancer patients aged ≥ 70 years in the Surveillance, Epidemiology, and End Results (SEER) database treated between January 1, 2010, and December 31, 2016. The patients were further divided into training and testing cohorts. The cumulative occurrence of breast cancer-specific deaths (BCSDs) and other cause-specific deaths (OCSD) was calculated using the cumulative incidence function. In the univariate analysis, risk factors were screened using the Fine-Gray model. In the multivariate analysis for competing risks, the sub-distribution hazard ratio with a 95% confidence interval for each independent predictor associated with BCSD was calculated for the construction of nomograms. Based on the above analyses, a competing risk nomogram was constructed to predict the probability of BCSD in the 1st, 3rd, and 5th years after treatment. During validation, the concordance index (C-index) was selected to quantify the predictive ability of the competing risk model. Results A total of 33,118 patients were included in this study, with 24,838 in the training group and 8,280 in the testing group. Age, race, marital status, cancer grade, tumor stage, node stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor--2 status, and treatment including surgery, radiation, and chemotherapy were used to establish a nomogram. The C-index of 0.852 (0.842-0.862) in the training cohort and 0.876 (0.868-0.892) in the testing cohort indicated satisfactory discriminative ability of the nomogram. Calibration plots showed favorable consistency between the nomogram predictions and actual observations in both the training and validation cohorts. Conclusions Our study identified independent predictors of BCSD in elderly patients with breast cancer. A prognostic nomogram was developed and validated to aid clinical decision-making.

Background: The Jinchan Yishen Tongluo Formula (JCYSTLF) has the effect of delaying senescence in diabetic kidneys. However, the mechanism is not clear. Purpose: Combination methods to investigate the anti-senescence mechanism of JCYSTLF in diabetic kidneys. Methods: The main compounds of JCYSTLF were characterized by LC-MS/MS, and the anti-senescence targets of JCYSTLF were screened via network analysis. Then, we performed in vivo and in vitro experiments to validate the results. Results: The target profiles of compounds were obtained by LC-MS/MS to characterize the primary function of JCYSTLF. Senescence was identified as a key biological functional module of JCYSTLF in the treatment of DN via constructing compounds-target-biological network analysis. Further analysis of senescence-related targets recognized the HIF-1α/autophagy pathway as the core anti-senescence mechanism of JCYSTLF in diabetic kidneys. Animal experiments showed, in comparison with valsartan, JCYSTLF showed an improvement in urinary albumin and renal pathological damage. JCYSTLF enhanced the ability of diabetic kidneys to clear senescence-related proteins via regulating autophagy confirmed by autophagy inhibitor CQ. However, HIF-1α inhibitor 2-ME weakened the role of JCYSLTF in regulating autophagy in diabetic kidneys. Meanwhile, over-expressed HIF-1α in HK-2 cells decreased the levels of SA-β-gal, p21 and p53 induced by AGEs. Upregulated HIF-1α could reverse the blocking of autophagy induced by AGEs in HK-2 cells evaluated by ptfLC3. Conclusion: We provided in vitro and in vivo evidence for the anti-senescence role of JCYSTLF in regulating the HIF-1α/autophagy pathway.

Adeno-associated viruses (AAVs) are non-enveloped ssDNA icosahedral T = 1 viruses used as vectors for clinical gene delivery. Currently, there are over 200 AAV-related clinical trials and six approved biologics on the market. As such new analytical methods are continually being developed to characterize and monitor the quality and purity of manufactured AAV vectors, these include ion-exchange chromatography and Direct Mass Technology. However, these methods require homogeneous analytical standards with a high molecular weight standard comparable to the mass of an AAV capsid. Described here is the design, production, purification, characterization, and the cryo-electron microscopy structure of an AAV1-VP3-only capsid that fulfills this need as a calibrant to determine capsid mass, charge, homogeneity, and transgene packaging characteristics.

Due to their exceptional electronic and optical properties, two-dimensional materials have emerged as one of the most promising candidates for future optoelectronic detection. However, optoelectronic detectors based on two-dimensional transition metal materials still face challenges due to factors such as limited absorption coefficients and carrier recombination. In this study, we combine two-dimensional Bi2O2Se with PbS quantum dots to prepare a hybrid heterojunction, effectively broadening the detection range and significantly enhancing the photoresponse rate. The hybrid photodetector exhibited a remarkable photoresponsivity of 14.89 A/W at 450 nm and demonstrated broadband detection capabilities from visible (405 nm) to near-infrared (1350 nm) light illumination. Moreover, the hybrid device showed reduced photocurrent response and recovery times, highlighting its improved performance over bare Bi2O2Se photodetectors. This work underscores the potential of hybrid heterojunctions for enhancing optoelectronic detection capabilities, paving the way for advanced applications in various fields.

Bacterial cell surface glycoconjugates are critical for cell survival and for interactions between bacteria and their hosts. Consequently, the pathways responsible for their biosynthesis have untapped potential as therapeutic targets. The localization of many glycoconjugate biosynthesis enzymes to the membrane represents a significant challenge for expressing, purifying, and characterizing these enzymes. Here, we leverage cutting-edge detergent-free methods to stabilize, purify, and structurally characterize WbaP, a phosphoglycosyl transferase (PGT) from the Salmonella enterica (LT2) O-antigen biosynthesis. From a functional perspective, these studies establish WbaP as a homodimer, reveal the structural elements responsible for dimerization, shed light on the regulatory role of a domain of unknown function embedded within WbaP, and identify conserved structural motifs between PGTs and functionally unrelated UDP-sugar dehydratases. From a technological perspective, the strategy developed here is generalizable and provides a toolkit for studying other classes of small membrane proteins embedded in liponanoparticles beyond PGTs.

AbstractBackground Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation.Method PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity.Results The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03–1.54, p = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19–2.22, p = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19–2.47, p = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, p = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65–1.17, p = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (r= −0.49; 95% CI= −0.75, −0.24; p

Background: Autophagy is an essential cellular process involving the self-degradation and recycling of organelles, proteins, and cellular debris. Recent research has shown that autophagy plays a significant role in the occurrence and development of kidney diseases. However, there is a lack of bibliometric analysis regarding the relationship between autophagy and kidney diseases.Methods: A bibliometric analysis was conducted by searching for literature related to autophagy and kidney diseases in the Web of Science Core Collection (WoSCC) database from 2000 to 2022. Data processing was carried out using R package “Bibliometrix”, VOSviewers, and CiteSpace.Results: A total of 4,579 articles related to autophagy and kidney diseases were collected from various countries. China and the United States were the main countries contributing to the publications. The number of publications in this field showed a year-on-year increasing trend, with open-access journals playing a major role in driving the literature output. Nanjing Medical University in China, Osaka University in Japan, and the University of Pittsburgh in the United States were the main research institutions. The journal “International journal of molecular sciences” had the highest number of publications, while “Autophagy” was the most influential journal in the field. These articles were authored by 18,583 individuals, with Dong, Zheng; Koya, Daisuke; and Kume, Shinji being the most prolific authors, and Dong, Zheng being the most frequently co-cited author. Research on autophagy mainly focused on diabetic kidney diseases, acute kidney injury, and chronic kidney disease. “Autophagy”, “apoptosis”, and “oxidative stress” were the primary research hotspots. Topics such as “diabetic kidney diseases”, “sepsis”, “ferroptosis”, “nrf2”, “hypertension” and “pi3k” may represent potential future development trends. Research on autophagy has gradually focused on metabolic-related kidney diseases such as diabetic nephropathy and hypertension. Additionally, PI3K, NRF2, and ferroptosis have been recent research directions in the field of autophagy mechanisms.Conclusion: This is the first comprehensive bibliometric study summarizing the relationship between autophagy and kidney diseases. The findings aid in identifying recent research frontiers and hot topics, providing valuable references for scholars investigating the role of autophagy in kidney diseases.

IntroductionGradient vector flow (GVF) has been proven as an effective external force for active contours. However, its smoothness constraint does not take the image structure into account, such that the GVF diffusion is isotropic and cannot preserve weak edges well.MethodsIn this article, an image structure adaptive gradient vector flow (ISAGVF) external force is proposed for active contours. In the proposed ISAGVF model, the smoothness constraint is first reformulated in matrix form, and then the image structure tensor is incorporated. As the structure tensor characterizes the image structure well, the proposed ISAGVF model can be adaptive to image structure, and the ISAGVF snake performs well on weak edge preservation and deep concavity convergence while possessing some other desirable properties of the GVF snake, such as enlarged capture range and insensitivity to initialization.ResultsExperiments on synthetic and real images manifest these properties of the ISAGVF snake.

Diabetic nephropathy (DN) is a complication of diabetes mellitus (DM) and the main cause of excess mortality in patients with type 2 DM. The pathogenesis and progression of DN are closely associated with disorders of glucose and lipid metabolism. As a member of the sirtuin family, SIRT6 has deacetylation, defatty-acylation, and adenosine diphosphate-ribosylation enzyme activities as well as anti-aging and anticancer activities. SIRT6 plays an important role in glucose and lipid metabolism and signaling, especially in DN. SIRT6 improves glucose and lipid metabolism by controlling glycolysis and gluconeogenesis, affecting insulin secretion and transmission and regulating lipid decomposition, transport, and synthesis. Targeting SIRT6 may provide a new therapeutic strategy for DN by improving glucose and lipid metabolism. This review elaborates on the important role of SIRT6 in glucose and lipid metabolism, discusses the potential of SIRT6 as a therapeutic target to improve glucose and lipid metabolism and alleviate DN occurrence and progression of DN, and describes the prospects for future research.

The low-light-level absorption coefficient of OH-contained and H2-impregnated synthetic fused silica material in 193 nm optical lithography application is determined via a laser calorimetry measurement. The fluence and repetition rate dependences of the absorptances of the deep ultraviolet (DUV)-fused silica samples with different thickness are measured. The measured dependences are fitted to a theoretical model, taking into consideration the generation and annealing of laser irradiation induced defects. The surface absorption, the low-light-level linear absorption coefficient, as well as the nonlinear absorption coefficient of the fused silica material are accurately determined via the fitting. The low-light-level linear absorption coefficients determined via the fluence dependence and the repetition rate dependence are in good agreement, demonstrating the reliability of the measured low-light-level absorption coefficient, which is the key parameter to the determination of the internal transmission of the DUV-fused silica material used in the 193 nm optical lithography.

There has been a global decline in fertility rates, with ovulatory disorders emerging as the leading cause, contributing to a global lifetime infertility prevalence of 17.5%. Formation of the primordial follicle pool during early and further development of oocytes after puberty is crucial in determining female fertility and reproductive quality. However, the increasing exposure to environmental toxins (through occupational exposure and ubiquitous chemicals) in daily life is a growing concern; these toxins have been identified as significant risk factors for oogenesis in women. In light of this concern, this review aims to enhance our understanding of female reproductive system diseases and their implications. Specifically, we summarized and categorized the environmental toxins that can affect oogenesis. Here, we provide an overview of oogenesis, highlighting specific stages that may be susceptible to the influence of environmental toxins. Furthermore, we discuss the genetic and molecular mechanisms by which various environmental toxins, including metals, cigarette smoke, and agricultural and industrial toxins, affect female oogenesis. Raising awareness about the potential risks associated with toxin exposure is crucial. However, further research is needed to fully comprehend the mechanisms underlying these effects, including the identification of biomarkers to assess exposure levels and predict reproductive outcomes. By providing a comprehensive overview, this review aims to contribute to a better understanding of the impact of environmental toxins on female oogenesis and guide future research in this field.

Abstract Background Workplace violence is internationally recognised as a major concern for the workforce, which entails serious consequences, and research shows that medical residents are more likely than other doctors to experience violence in the workplace. This study first examines the effectiveness of simulation-based medical education, and then simulation-based medical education combined with behavioural economics as interventions in medical residents' perception of, attitude toward, and self-efficacy in coping with violence in the workplace. Methods A quasi-experimental design was used, 190 participants were randomised into three study groups to respectively test the effect of simulation-based medical education only and simulation-based medical education plus behavioural economics interventions, compared with a control group. Data were obtained from structured questionnaires, including (1) a perception of aggression scale, a management of aggression and violence attitude scale, a general self-efficacy scale, and (2) socio-demographic characteristics. Results The results show that the scores attained by simulation-based medical education (SBME) and simulation-based medical education combined with behavioural economics (SBME + BE) interventions for perception, attitude, and self-efficacy were significantly higher than those in the control group (p

The Internet of Things (IoT) is currently in a stage of rapid development. Hundreds of millions of sensing nodes and intelligent terminals undertake the tasks of sensing and transmitting data. Data collection is the key to realizing data analysis and intelligent application of IoT. The life cycle of IoT is limited by the energy of the IoT nodes in the network. A complex computing model will bring serious or even unbearable burdens to IoT nodes. In this study, we use the data prediction method to explore time correlation data and adjust the appropriate spatial sampling rate on the basis of the spatial correlation of sensory data to further reduce data. Specifically, the improved and optimized DNA-binding protein (DBP) data prediction method can increase the time interval of sensing data to further reduce energy consumption. Based on the spatial characteristics of the sensing data, substituting the data of similar nodes can reduce the sampling rate. The probabilistic wake-up strategy is also adopted to adjust the spatial correlation of the sensing data. On the basis of node priority, an optimized greedy algorithm is proposed to select the appropriate dominating node for eliminating redundant nodes and improving network energy utilization. Experiments have proven that our scheme reduces network energy consumption under the premise of ensuring data reliability.

Background: Previous evidence indicated that emodin has significant advantages for preventing acute kidney injury (AKI). However, the mechanisms responsible for these effects of emodin have yet to be elucidated. Methods: We first used network pharmacology and molecular docking to identify the core targets of emodin for AKI and performed a range of experiments to validate this result. Pretreatment with emodin for 7 days, the rats were treated with bilateral renal artery clipping for 45 min to identify the prevention effect. Hypoxia/reoxygenation (H/R), and vancomycin - induced renal tubular epithelial cells (HK-2 cells) were treated with emodin to explore the related molecular mechanism. Results: Network pharmacology and molecular docking showed that anti-apoptosis might be the core mechanism responsible for the action of emodin on AKI; this anti-apoptotic effect appears to because by regulation p53-related signaling pathway. Our data showed that pretreatment with emodin significantly improved renal function and renal tubular injury in renal I/R model rats (P

Heart rate variability (HRV) is an important marker for assessing the balance of the autonomic nervous system and clinical prognosis, because it can be non-invasively and easily measured, and the results are accurate and valuable. HRV is widely applied in cardiovascular disease fields. Exercise training is an important part of cardiac rehabilitation. Personalized sports rehabilitation therapy can effectively prevent the emergence of cardiovascular diseases, decrease the risk of recurrent cardiovascular events, and ameliorate dysfunction, as well as limitations in life, work, and social participation, caused by adverse cardiovascular events. However, sports rehabilitation can have drawbacks, in that improper training can cause injury, excessive fatigue, or even harmful cardiovascular events. To support future applications, this article reviews recent applications of HRV in sports rehabilitation for cardiovascular diseases.

Cardiovascular and renal impairment are the most common complications of type 2 diabetes mellitus (T2DM). As an emerging class of glucose-lowing agents sodium glucose co-transporter 2 (SGLT2), possesses beneficial effects on cardiovascular and renal outcomes in patients with T2DM. The aim of this study is to assess the efficacy of different SGLT2 inhibitors for cardiovascular and renal outcomes for patients with T2DM when compared with placebo. We performed a systematic search of PubMed, Embase, and the Cochrane library from inception through November 2021. Randomized clinical trials enrolling participants with T2DM were included, in which SGLT2 inhibitors were compared with each other or placebo. The primary outcomes including all-caused mortality, Cardiovascular outcomes (cardiovascular mortality, hospitalization for heart failure), and the renal composite outcomes (worsening persistent microalbuminuria or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death). The data for the outcomes were pooled and recorded as Hazard rations (HRs) with 95% confidence intervals (CLs). Two researcher independently screened the trials and drawn the data. Ten trials enrolling 68,723 patients were included. Compared with placebo groups, Canagliflozin [HR, 0.85 (95%CI, 0.75–0.98)], ertugliflozin [HR, 0.93 (95%CI, 0.78–1.11)], and sotagliflozin [HR, 0.94 (95%CI, 0.79–1.12)] were associated with a reduction in all-cause mortality. Canagliflozin [HR, 0.84 (95%CI, 0.72–0.97)], dapagliflozin [HR, 0.88 (95%CI, 0.79–0.99)], empagliflozin [HR, 0.62 (95%CI, 0.49–0.78)], ertugliflozin [HR, 0.92 (95%CI, 0.77–1.10)], and sotagliflozin [HR, 0.88 (95%CI, 0.73–1.06)] were associated with a reduction in cardiovascular mortality; Canagliflozin [HR, 0.64 (95%CI, 0.53–0.77)], dapagliflozin [HR, 0.71 (95%CI, 0.63–0.81)], empagliflozin [HR, 0.65 (95%CI, 0.50–0.85)], ertugliflozin [HR, 0.70 (95%CI, 0.54–0.90)], and sotagliflozin [HR, 0.66 (95%CI, 0.56–0.77)] were associated with a reduction in hospitalization for heart failure. Dapagliflozin [HR, 0.55 (95%CI, 0.47–0.63)], Empagliflozin [HR, 0.54 (95%CI, 0.39–0.74)], canagliflozin [HR, 0.64 (95%CI, 0.54–0.75)], sotagliflozin [HR, 0.71 (95%CI, 0.46–1.09)], and ertugliflozin [HR, 0.81 (95%CI, 0.63–1.04)] were associated with a reduction in the renal composite outcome. All SGLT2 inhibitors showed a reduction in cardiovascular mortality, hospitalization for heart failure, renal composite outcomes and all-cause mortality. Canagliflozin and empagliflozin seemed to have the same efficacy in reducing hospitalization for heart failure, but empagliflozin had advantage in reducing cardiovascular mortality, whereas dapagliflozin most likely showed the best renal composite outcomes.

Finding the nearest parking location in road networks is one of the most commonly faced challenges in everyday life of green transportation. A main challenge faced by the state-of-the-art existing parking allocation methods is to optimally offer the nearest parking location for a group of $m$ users at the cost of minimal overall traveling time to ensure the traffic and environmental sustainability. In this article, we model it as a Multiple Nearest Parking Location Allocation (MNPLA) problem, and devise a spatial index tree, called SCP-tree, to accelerate the nearest parking location allocation within the users’ time constraints. During the search process in SCP-tree, we build a pruning strategy relevant to the Geographical Preference Estimation, travel time and parking capacity to determine which branch to visit so that the search accuracy can be improved. Considering the users’ behaviors are often impacted by the geographical location and some personalized attribute information, we set the user priority based on them to help the parking officer determine the allocation sequence. We evaluate our allocation scheme using large real-world dataset with on-street parking sensor data, and extensive experimental results reveal (i) a minimum improvement of 15.9%, 1.4%, 96.9%, 160% in parking allocation time, average traveling time, I/O cost and service utility compared to the progressive methods, and (ii) a minimum improvement of 8.9%, 11.1%, 78.2%, 714% in parking allocation time, average traveling time, I/O cost and service utility compared to the baseline methods.

BackgroundThe management of cancer surgeries is under unprecedented challenges during the COVID-19 pandemic, and the breast cancer patients may face a time-delay in the treatment. This retrospective study aimed to present the pattern of time-to-surgery (TTS) and analyze the features of breast cancer patients under the different stages of the COVID-19 pandemic.MethodsPatients who received surgeries for breast cancers at West China Hospital between February 15, 2020 and April 30, 2020 (the outbreak and post-peak stages), and between March 10, 2021 and May 25, 2021 (the normalization stage) were included. TTS was calculated as the time interval between the pathological diagnosis and surgical treatment of breast cancer patients. And the pandemic was divided into three stages based on the time when the patients were pathologically diagnosed and the severity of pandemic at that time point. TTS, demographic and clinicopathological features were collected from medical records.ResultsA total of 367 patients were included. As for demographic features, it demonstrated statistically significant differences in insurance type (p

A multi-grooves barrier-etched structure between barrier layer and passivation layer is proposed in this paper to suppress the hot electron effect at the gate edge on the drain side in the p-GaN gate AlGaN/GaN high-electron-mobility transistor. In the TCAD simulations, the groove structure induces extra electric field concentration region and AlGaN/SiN interface area, which can lower the high electric field peak and electron temperature in the channel at the gate edge, leading to the alleviated capture and release of hot electrons. The static I–V characteristic and dynamic switching performance and breakdown characteristic show that the multi-grooves barrier-etched structure improves the current collapse and switching time and breakdown voltage. Our work exhibits the great potential of multi-grooves barrier-etched structure on the stability and reliability of the AlGaN/GaN HEMT.

Atherosclerosis (AS) is the main pathological cause of acute cardiovascular and cerebrovascular diseases, such as acute myocardial infarction and cerebral apoplexy. As an immune-mediated inflammatory disease, the pathogenesis of AS involves endothelial cell dysfunction, lipid accumulation, foam cell formation, vascular smooth muscle cell (VSMC) migration, and inflammatory factor infiltration. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in lipid metabolism, inflammation, and apoptosis by antagonizing the Wnt/β-catenin pathway and regulating cholesterol efflux and inflammatory factors. Importantly, PPARγ-dependant fatty acid uptake is critical for metabolic programming. Activated PPARγ can exert an anti-atherosclerotic effect by inhibiting the expression of various inflammatory factors, improving endothelial cell function, and restraining the proliferation and migration of VSMCs. Regulatory T cells (Tregs) are the only subset of T lymphocytes that have a completely negative regulatory effect on the autoimmune response. They play a critical role in suppressing excessive immune responses and inflammatory reactions and widely affect AS-associated foam cell formation, plaque rupture, and other processes. Recent studies have shown that PPARγ activation promotes the recruitment of Tregs to reduce inflammation, thereby exerting its anti-atherosclerotic effect. In this review, we provide an overview of the anti-AS roles of PPARγ and Tregs by discussing their pathological mechanisms from the perspective of AS and immune-mediated inflammation, with a focus on basic research and clinical trials of their efficacies alone or in combination in inhibiting atherosclerotic inflammation. Additionally, we explore new ideas for AS treatment and plaque stabilization and establish a foundation for the development of natural PPARγ agonists with Treg recruitment capability.

Lung squamous cell carcinoma (LUSC) is highly malignant with poor prognosis, causing prevalent mortality worldwide. Early-stage lung cancer can be distinguished through reliable early detection to urge timely treatment. Non-coding RNAs (ncRNAs) might play such a vital role in tumor initiation, progression and metastasis that they are becoming an important biomarker in cancer screening. To identify the relation between ncRNAs and the early-stage of LUSC, we analyzed the data from the Cancer Genome Atlas (TCGA) database. We identified 28 microRNAs (miRNAs) and 32 long non-coding RNA (lncRNA) that were specifically expressed in early-stage LUSC, and the relationship was shown by the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. The result derived from Kaplan–Meier survival curves analysis showed that two miRNAs (hsa-miR-22-3p and hsa-miR-552-3p) and a lncRNA (FLJ36000) were negatively correlated with overall survival, but two miRNAs (hsa-miR-27b-5p and hsa-miR-340-5p) and five lncRNAs (CHK8-CPT1B, LINC00167, S NHG15, TTC28-AS1 and WASH7P) were positively associated. Our study provides novel insight for better understanding of early-stage LUSC and facilitates the identification of potential biomarkers for diagnosis and prognosis of early-stage LUSC.

Background: Patients with cancer show greater susceptibility and vulnerability to severe acute respiratory syndrome coronavirus 2 infection. However, data on the vaccination status among patients with breast cancer and any structured analysis of the factors influencing patients’ decisions regarding vaccines are lacking. Methods: This cross-sectional study on patients with breast cancer in China was conducted from 1 June 2022, to 17 June 2022. Every participant completed an online questionnaire about their vaccination status and any adverse reactions, and a scale based on the Health Belief Model (HBM) to assess the vaccination status of respondents and their willingness to receive following doses or boosters. Results: Among the 1132 participants, 55.2% had received a COVID-19 vaccine. The incidence of adverse events per dose was around 40%. Vaccine hesitancy of 61.9% was observed among patients who had not fully received three doses of vaccine or boosters. The only variable found to be associated with vaccine hesitancy was time since diagnosis (p < 0.05). In the HBM scale, vaccine hesitancy was closely related to a low level of perceived susceptibility, a low level of perceived benefit, a high level of perceived barriers and a low level of agreement with doctors’ advice. Conclusions: For patients with breast cancer, perceived susceptibility, benefits and barriers should be prioritized, and the advice from authoritative doctors is a vital cue to action.

Objective: We aimed to evaluate the efficacy of canagliflozin for the treatment of specific cardiovascular and renal outcomes in Type 2 diabetes mellitus (T2DM) patients by means of a systematic review and meta-analysis.Methods: We performed comprehensive searches of PubMed, the Cochrane Library, and Embase for randomized, placebo-controlled trials of the treatment of T2DM with canagliflozin that were published to 28 September 2020. The cardiovascular outcomes recorded were cardiovascular mortality, heart failure, myocardial infarction, and stroke. The renal composite outcomes recorded were end-stage renal disease (ESRD), renal death. The data for the principal cardiovascular outcomes, ESRD, and renal death were pooled and expressed as Hazard ratios (HRs) with 95% confidence intervals (CIs). Two reviewers independently selected the trials and extracted the data.Results: We identified a total of 1,741 publications, leaving 96 for their titles, abstracts and full-text review. Of these, 10 trials met the inclusion criteria and were finally included in our meta-analysis. The meta-analysis showed that canagliflozin significantly reduced the risk of heart failure in T2DM by 36% (HR 0.64, 95% CI 0.53 to 0.77, p = 0.000). The effects of canagliflozin on non-fatal myocardial infarction or non-fatal stroke (HR 0.84, 95% CI: 0.76 to 0.93, p = 0.001), cardiovascular mortality (HR 0.84, 95% CI 0.72 to 0.97, p = 0.021), and myocardial infarction (HR 0.84, 95% CI 0.70 to 1.00, p = 0.045) in patients with T2DM were relatively small, reducing the risks by 16%. In addition, canagliflozin reduced the risk of stroke in T2DM patients by 13% (HR 0.87, 95% CI 0.71 to 1.06, p = 0.166). Moreover, canagliflozin significantly reduced the risk of the composite renal event of ESRD or renal death by 36% (HR 0.64, 95% CI 0.54 to 0.75, p = 0.000).Conclusion: This meta-analysis suggests that canagliflozin protects against cardiovascular and renal outcomes in patients with T2DM.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42020210315]

Membranous nephropathy (MN) is an organ-restricted autoimmune disease mainly caused by circulating autoantibodies against podocyte antigens, including the M-type phospholipase A2 receptor (PLA2R) and thrombospondin domain-containing 7A (THSD7A). Antibodies against PLA2R are present in 70%–80% and against THSD7A in 2% of adult patients, which provides a paradigm shift in molecular diagnosis and management monitoring. Both antigens share some similar characteristics: they are expressed by podocytes and have wide tissue distributions; they are bound by autoantibodies only under nonreducing conditions, and the subtype of most autoantibodies is IgG4. However, the factors triggering autoantibody production as well as the association among air pollution, malignancy, and the pathogenesis of MN remain unclear. In this review, we discuss the similarity between the pathological mechanisms triggered by disparate antigens and their associated diseases. Furthermore, we demonstrated the possibility that PM2.5, malignancy, and gene expression specifically induce exposure of these antigens through conformational changes, molecular mimicry, or increased expression eliciting autoimmune responses. Thus, this review provides novel insights into the pathological mechanism of MN.

Abstract Background Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulopathy worldwide. The study aimed to provide potential molecular biomarkers for IgAN management. Methods The public gene expression profiling GSE58539 was utilized, which contained 17 monocytes samples (8 monocytes samples isolated from IgAN patients and 9 monocytes samples isolated from healthy blood donors). Firstly, differentially expressed genes (DEGs) between the two kinds of samples were identified by limma package. Afterwards, pathway enrichment analysis was implemented. Thereafter, protein-protein interaction (PPI) network was constructed and key nodes in PPI network were predicted using four network centrality analyses. Ultimately, gene functional interaction (FI) was constructed according to expressions in each sample, and then module network was extracted from FI network. Results A total of 678 DEGs were screened out, of these, 72 DEGs were identified as crucial nodes in PPI network that could well distinguish IgAN and healthy samples. In particular, IL6, TNF, IL1B, PRKACA and CCL20 were closely related to pathways such as hematopoietic cell lineage, apoptosis and Toll-like receptor (TLR) signaling pathway. Moreover, 12 genes in the FI network belonged to the 72 identified key nodes, such as CCL20, HDAC10, FPR2 and PRKACA, which were also key genes in 4 module networks. Conclusions Several crucial genes were identified in monocytes of IgAN patients, such as IL6, TNF, IL1B, CCL20, PRKACA, FPR2 and HDAC10. These genes might co-involve in pathways such as TLR and apoptosis signaling during IgAN progression.

Abstract Diabetes increases the risk of Cardio-vascular disease (CVD). CVD is more prevalent in type 2 diabetes (T2D) than type 1 diabetes (T1D), but the mortality risk is higher in T1D than in T2D. The pathophysiology of CVD in T1D is poorly defined. To learn more about biological pathways that are potentially involved in T1D with cardiac dysfunction, we sought to identify differentially expressed genes in the T1D heart. Our study used T1D mice with severe hyperglycemia along with significant deficits in echocardiographic measurements. Microarray analysis of heart tissue RNA revealed that the T1D mice differentially expressed 10 genes compared to control. Using Ingenuity Pathway Analysis (IPA), we showed that these genes were significantly involved in ketogenesis, cardiovascular disease, apoptosis and other toxicology functions. Of these 10 genes, the 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was the highest upregulated gene in T1D heart. IPA analysis showed that HMGCS2 was center to many biological networks and pathways. Our data also suggested that apart from heart, the expression of HMGCS2 was also different in kidney and spleen between control and STZ treated mice. In conclusion, The HMGCS2 molecule may potentially be involved in T1D induced cardiac dysfunction.

Objectives This study aimed to compare the effectiveness of 13 types of immunosuppressive agents used to treat idiopathic membranous nephropathy (IMN) in adults with nephrotic syndrome.Design Systematic review and network meta-analysis.Data sources PubMed, EMbase, Cochrane Library, Web of Science, Clinical trials, SinoMed, Chinese Biomedicine, CNKI, WanFang and Chongqing VIP Information databases were comprehensively searched until February 2018.Eligibility criteria Randomised clinical trials (RCTs) comparing the effects of different immunosuppressive treatments in adult patients with IMN and nephrotic syndrome were included, and all included RCTs had a study-duration of at least 6 months.Data extraction and synthesis Two reviewers independently screened articles, extracted data and assessed study quality. Standard pairwise meta-analysis was performed using DerSimonian-Laird random-effects model.Results This study ultimately included 48 RCTs with 2736 patients and 13 immunosuppressive agents. The network meta-analysis results showed that most regimens, except for leflunomide (LEF), mizoribine (MZB) and steroids (STE), showed significantly higher probabilities of total remission (TR) when compared with non-immunosuppressive therapies (the control group),with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06)for tacrolimus+tripterygium wilfordii (TAC+TW), 2.16 (1.27 to 3.69) foradrenocorticotropic hormone, 2.02 (1.64 to 2.49) for TAC, 2.03 (1.13 to3.64) for azathioprine (AZA), 1.91 (1.46 to 2.50) for cyclosporine (CsA), 1.86 (1.44 to2.42) for mycophenolate mofetil (MMF), 1.85 (1.52 to 2.25) for cyclophosphamide (CTX),1.81 (1.10 to 2.98) for rituximab (RIT), 1.80 (1.38 to 2.33) for TW, 1.72 (1.35 to 2.19) for chlorambucil. As for 24 hours UTP, the direct andindirect comparisons showed that AZA (standard mean difference (SMD), −1.02(95% CI −1.90 to −0.15)), CsA (SMD, −0.70 (95% CI −1.33 to −0.08)),CTX (SMD, −1.01 (95% CI −1.44 to -0.58)), MMF (SMD, −0.98 (95% CI −1.64 to −0.32)), MZB (SMD, −0.97 (95% CI −1.90 to−0.04]), TAC (SMD, −1.16 (95% CI −1.72 to −0.60)) and TAC+TW(SMD, −2.03 (95% CI −2.94 to −1.12)) could significantly superior thancontrol, except for chlorambucil, LEF, RIT and STE. Thechanges of serum creatinine (Scr) was not significantly different between eachtreatments of immunosuppressive agents and the control, except for STE whichhas the possibility of increasing Scr (SMD, 1.00 (95% CI 0.36 to 1.64)).Comparisons among all treatments of immunosuppressive agents showed nostatistical significance in the outcome of relapse. A drenocorticotropichormone (85.1%) showed the lowest probability of relapse under the cumulativeranking curve values among all immunosuppressants. Infection,gastrointestinal symptoms, and bone marrow suppression were the common adverseevents associated with most of the immunosuppressive therapies.Conclusions This study demonstrates that TAC+TW, TAC and CTX are superior to other immunosuppressive agents in terms of TR and 24 hours UTP. Moreover, they are all at risk of infection, gastrointestinal symptoms, and myelosuppression. Furthermore, TAC could increase the risk of glucose intolerance or new-onset diabetes mellitus. Conversely, STE alone, LEF and MZB seem to have little advantage in clinical treatment of IMN.PROSPERO registration number CRD42018094228.

Membranous nephropathy (MN) is the major cause of nephrotic syndrome with special pathological features, caused by the formation of immune complexes in the space between podocytes and the glomerular basement membrane. In idiopathic membranous nephropathy (IMN) the immune complexes are formed by circulating antibodies binding mainly to one of two naturally-expressed podocyte antigens: the M-type receptor for secretory phospholipase A2 (PLA2R1) and the Thrombospondin type-1 domain-containing 7A (THSD7A). Formation of antibodies against PLA2R1 is much more common, accounting for 70–80% of IMN. However, the mechanism of anti-podocyte antibody production in IMN is still unclear. In this review, we emphasize that the exposure of PLA2R1 is critical for triggering the pathogenesis of PLA2R1-associated MN, and propose the potential association between inflammation, pollution and PLA2R1. Our review aims to clarify the current research of these precipitating factors in a way that may suggest future directions for discovering the pathogenesis of MN, leading to additional therapeutic targets and strategies for the prevention and early treatment of MN.

BackgroundTranslocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown. Methods and ResultsIn the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss‐of‐function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild‐type littermates. Moreover, we generated cardiomyocyte‐specific TIM50 transgenic mice in which the hypertrophic and fibrotic phenotypes were all alleviated. Next, we tested reactive oxygen species generation and the activities of the antioxidant enzymes superoxide dismutase and catalase, and also respiratory chain complexes I, II, and IV, finding that all the activities were regulated by TIM50. Meanwhile, expression of the ASK1‐JNK/P38 axis was increased in TIM50‐deficient mice, and TIM50 overexpression decreased the activity of the ASK1‐JNK/P38 axis. Finally, we treated mice with the antioxidant N‐acetyl cysteine to reduce oxidative stress. After N‐acetyl cysteine treatment, the deteriorative hypertrophic and fibrotic phenotypes caused by TIM50 deficiency were all remarkably reversed. ConclusionsThese data indicated that TIM50 could attenuate pathological cardiac hypertrophy primarily by reducing oxidative stress. TIM50 could be a promising target for the prevention and therapy of cardiac hypertrophy and heart failure.

Background: SIRT5 is located in the mitochondria, and plays a crucial role in the regulation of metabolic process and cellular apoptosis. Cardiomyocytes are abundant in mitochondria. However, the role of SIRT5 in oxidative stress-induced apoptosis is still unknown in cardiomyocytes. Methods and Results: Western blots analysis revealed that SIRT5 is significantly down-regulated in cardiomyocytes upon oxidative stress. MTT assay, DAPI staining, and caspase 3/7 activity assay were used to estimate apoptosis development. The result suggested that compared with the wild-type group, SIRT5 knockdown results in a marked reduction in cell viability, and a significant increase in the number of apoptotic cells and the caspase 3/7 activity. Protein immunoprecipitation revealed a direct interaction between Bcl-Xl and SIRT5. Apoptosis assay and western blot anaylsis suggested that SIRT5 levels could affect the levels of Bcl-Xl expression, but have no effect on the apoptosis development in Bcl-Xl knockdown cells. Conclusion: This study reveals a novel role of SIRT5 in the regulation of oxidative stress-induced apoptosis in cardiomyocytes. Pharmacological interventions on SIRT5 expression may be useful in the treatment of oxidative stress-related cardiac injury.