HIF-1α and adaptor protein LIM and senescent cell antigen-like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.

Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Diagnostic performance of the gallbladder reporting and data system combined with color doppler flow imaging for gallbladder cancer in the Asian population.

Purpose: Evaluating the performance of the Gallbladder Reporting and Data System (GB-RADS) combined with Color Doppler Flow Imaging (CDFI) for the diagnosis of gallbladder wall thickening disease in an Asian population. Methods: In this study, the lesions were classified and the actual incidence rate of malignant tumors was calculated for each GB-RADS category, following the guidelines provided by GB-RADS. To evaluate the diagnostic performance of GB-RADS and GB-RADS combined with CDFI, we plotted Receiver Operator Characteristic (ROC) curves. The sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (AC) were also calculated. Inter-observer agreement (IRA) between the two observers was assessed using Kappa values. Results: The incidence of malignancy risk for GB-RADS 2, 3, 4, and 5 was 9%, 12.5%, 72.2%, and 100%. The AUC for GB-RADS was 0.855 (95% CI: 0.800-0.900), with a sensitivity of 82.5%, a specificity of 84.6%, and an accuracy of 83.8%. The AUC of GB-RADS combined with CDFI was 0.965 (95% CI: 0.930-0.985), with a sensitivity of 96.2%, a specificity of 94.6%, and an accuracy of 95.2%. The AUC, sensitivity, specificity, and accuracy of GB-RADS combined with CDFI for diagnosing gallbladder malignancy were higher than those of GB-RADS alone, and the differences were statistically significant (all P < 0.05). The IRA was excellent between the two observers (Kappa = 0.870). Conclusions: GB-RADS combined with CDFI demonstrated excellent diagnostic accuracy when it comes to distinguishing various diseases that caused gallbladder wall thickening in the Asian population, which has good clinical value and can improve the detection rate of malignant tumors in patients with gallbladder wall thickening.

FEN1 upregulation mediated by SUMO2 via antagonizing proteasomal degradation promotes hepatocellular carcinoma stemness.

PURPOSE: Metastasis of hepatocellular carcinoma (HCC) critically impacts the survival prognosis of patients, with the pivotal role of hepatocellular carcinoma stem cells in initiating invasive metastatic behaviors. The Flap Endonuclease 1 (FEN1) is delineated as a metallonuclease, quintessential for myriad cellular processes including DNA replication, DNA synthesis, DNA damage rectification, Okazaki fragment maturation, baseexcision repair, and the preservation of genomic stability. Furthermore, it has been recognized as an oncogene in a diverse range of malignancies. Our antecedent research has highlighted a pronounced overexpression of protein FEN1 in hepatocellular carcinoma, where it amplifies the invasiveness and metastatic potential of liver cancer cells. However, its precise role in liver cancer stem cells (LCSCs) remains an enigma and requires further investigation. METHODS: To rigorously evaluate the stemness attributes of LCSCs, we employed sphere formation assays and flow cytometric evaluations. Both CD133+ and CD133- cell populations were discerningly isolated utilizing immunomagnetic bead separation techniques. The expression levels of pertinent genes were assayed via real-time quantitative PCR (RT-qPCR) and western blot analyses, while the expression profiles in hepatocellular carcinoma tissues were gauged using immunohistochemistry. Subsequent immunoprecipitation, in conjunction with mass spectrometry, ascertained the concurrent binding of proteins FEN1 and Small ubiquitin-related modifier 2 (SUMO2) in HCC cells. Lastly, the impact of SUMO2 on proteasomal degradation pathway of FEN1 was validated by supplementing MG132. RESULTS: Our empirical findings substantiate that protein FEN1 is profusely expressed in spheroids and CD133+ cells. In vitro investigations demonstrate that the upregulation of protein FEN1 unequivocally augments the stemness of LCSCs. In a congruent in vivo context, elevation of FEN1 noticeably enhances the tumorigenic potential of LCSCs. Conversely, inhibiting protein FEN1 resulted in a marked reduction in LCSC stemness. From a mechanistic perspective, there exists a salient positive correlation between the protein expression of FEN1 and SUMO2 in liver cancer tissues. Furthermore, the level of SUMO2-mediated modification of FEN1 is pronouncedly elevated in LCSCs. Interestingly, SUMO2 has the ability to bind to FEN1, leading to a inhibition in the proteasomal degradation pathway of FEN1 and an enhancement in its protein expression. However, it is noteworthy that this interaction does not affect the mRNA level of FEN1. CONCLUSION: In summation, our research elucidates that protein FEN1 is an effector in augmenting the stemness of LCSCs. Consequently, strategic attenuation of protein FEN1 might proffer a pioneering approach for the efficacious elimination of LCSCs.

Autophagy-related protein PlATG2 regulates the vegetative growth, sporangial cleavage, autophagosome formation, and pathogenicity of peronophythora litchii.

Autophagy is an intracellular degradation process that is important for the development and pathogenicity of phytopathogenic fungi and for the defence response of plants. However, the molecular mechanisms underlying autophagy in the pathogenicity of the plant pathogenic oomycete Peronophythora litchii, the causal agent of litchi downy blight, have not been well characterized. In this study, the autophagy-related protein ATG2 homolog, PlATG2, was identified and characterized using a CRISPR/Cas9-mediated gene replacement strategy in P. litchii. A monodansylcadaverine (MDC) staining assay indicated that deletion of PlATG2 abolished autophagosome formation. Infection assays demonstrated that ΔPlatg2 mutants showed significantly impaired pathogenicity in litchi leaves and fruits. Further studies have revealed that PlATG2 participates in radial growth and asexual/sexual development of P. litchii. Moreover, zoospore release and cytoplasmic cleavage of sporangia were considerably lower in the ΔPlatg2 mutants than in the wild-type strain by FM4-64 staining. Taken together, our results revealed that PlATG2 plays a pivotal role in vegetative growth, sporangia and oospore production, zoospore release, sporangial cleavage, and plant infection of P. litchii. This study advances our understanding of the pathogenicity mechanisms of the phytopathogenic oomycete P. litchii and is conducive to the development of effective control strategies.

Critical Solvation Structures Arrested Active Molecules for Reversible Zn Electrochemistry.

Aqueous Zn-ion batteries (AZIBs) have attracted increasing attention in next-generation energy storage systems due to their high safety and economic. Unfortunately, the side reactions, dendrites and hydrogen evolution effects at the zinc anode interface in aqueous electrolytes seriously hinder the application of aqueous zinc-ion batteries. Here, we report a critical solvation strategy to achieve reversible zinc electrochemistry by introducing a small polar molecule acetonitrile to form a "catcher" to arrest active molecules (bound water molecules). The stable solvation structure of [Zn(H2O)6]2+ is capable of maintaining and completely inhibiting free water molecules. When [Zn(H2O)6]2+ is partially desolvated in the Helmholtz outer layer, the separated active molecules will be arrested by the "catcher" formed by the strong hydrogen bond N-H bond, ensuring the stable desolvation of Zn2+. The Zn||Zn symmetric battery can stably cycle for 2250 h at 1 mAh cm-2, Zn||V6O13 full battery achieved a capacity retention rate of 99.2% after 10,000 cycles at 10 A g-1. This paper proposes a novel critical solvation strategy that paves the route for the construction of high-performance AZIBs.

Associations between the platelet/high-density lipoprotein cholesterol ratio and likelihood of nephrolithiasis: a cross-sectional analysis in United States adults.

Aims: The primary objective of this study was to investigate the relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR) and the prevalence of nephrolithiasis within the adult population of the United States. Methods: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. The analysis included a non-pregnant population aged 20 years or older, providing proper PHR index and nephrolithiasis data. The research utilized subgroup analyses and weighted univariate and multivariable logistic regression to evaluate the independent association between the PHR and the susceptibility to nephrolithiasis. Results: The study comprised 30,899 participants with an average PHR value of 19.30 ± 0.11. The overall prevalence rate of nephrolithiasis was estimated at 9.98% with an increase in the higher PHR tertiles (T1, 8.49%; T2, 10.11%; T3, 11.38%, P < 0.0001). An elevated PHR level was closely linked with a higher susceptibility to nephrolithiasis. Compared with patients in T1, and after adjusting for potential confounders in model 2, the corresponding odds ratio for nephrolithiasis in T3 was 1.48 (95% CI: 1.06 to 2.08), with a P-value = 0.02. The results of the interaction tests revealed a significant impact of chronic kidney disease on the relationship between PHR and nephrolithiasis. Furthermore, the restricted cubic spline analyses exhibited a positive, non-linear correlation between PHR and the risk of nephrolithiasis. Conclusion: A convenient biomarker, the PHR, was independently associated with nephrolithiasis and could be a novel biomarker in predicting occurrence in clinical decision.

Revealing a Novel Methylated Integrin Alpha-8 Related to Extracellular Matrix and Anoikis Resistance Using Proteomic Analysis in the Immune Microenvironment of Lung Adenocarcinoma.

Genomic epigenetics of extracellular matrix (ECM) play an important role in lung adenocarcinoma (LUAD). Our study identified a signature of potential prognostic genes associated with ECM and constructed immune risk-related prognosis model in LUAD. We downloaded mRNAs transcriptome data, miRNAs expression data, and clinical patient information for LUAD based on The Cancer Genome Atlas. "Limma, clusterProfiler, ggplot2" R packages and GSEA were used to analyze meaningful genes and explore potential biological function. A competing endogenous RNA network was constructed to reveal the mechanism of ECM-related genes. Combined with clinical LUAD patients' characteristics, univariate and multivariate Cox regression analyses were used to build prognostic immune risk model. Next, we calculated AUC value of ROC curve, and explored survival probability of different risk groups. A total of 2966 mRNAs were differently expressed in LUAD samples and normal samples. Function enrichment analyses proved mRNAs were associated with many tumor pathways, such as cell adhesion, vascular smooth muscle contraction, and cell cycle. There were 18 mRNAs related to ECM receptor signaling pathway, and 7 mRNAs expressions were correlated with EGFR expression, but only 5mRNAs were associated with the long-term prognosis. Based on Integrin alpha-8 (ITGA8) molecule, we identified potential 3 miRNAs from several databases. The promoter of ITGA8 was higher-methylated and lower-expressed in LUAD. And lower-expressed group has poor prognosis for patients. 66 immunomodulators related to ITGA8 were performed to construct immune correlation prediction model (p < 0.05). Comprehensive analyses of ITGA8 revealed it combined focal adhesion kinase to activate PI3K/AKT signaling pathway to influence the occurrence and development of LUAD. A novel immune prognostic model about ITGA8 was constructed and verified in LUAD patients. Combined with non-coding genes and genomic epigenetics, identification of potential biomarkers provided new light on therapeutic strategy for clinical patients.

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

Objective: Observational studies have reported that chronic obstructive pulmonary disease (COPD) is often accompanied by autoimmune diseases, but the causal relationships between them remain uncertain. In this Mendelian study, we aimed to investigate the potential causal relationship between COPD and four common autoimmune diseases. Methods: We conducted an analysis of summary data on COPD and autoimmune disease using publicly available genome-wide association studies (GWAS) summary data. We initially employed the inverse- variance weighted method as the primary approach to establish the causal impact of COPD on autoimmune diseases in the sample and conducted additional sensitivity analyses to examine the robustness of the results. Subsequently, we performed reverse Mendelian randomization (MR) analyses for the four autoimmune diseases. Finally, the potential for bidirectional causal relationships was assessed. Results: Our MR analysis revealed no significant causal relationship between COPD and any of the studied autoimmune diseases. However, reverse MR results indicated a significant association between rheumatoid arthritis (RA), osteoarthritis (OA) and the risk of developing COPD, with respective odds ratios (OR) of 377.313 (95% CI, 6.625-21487.932, P = 0.004) for RA and 11.097 (95% CI, 1.583-77.796, P = 0.015) for OA. Sensitivity analyses confirmed the robustness of the results. Conclusion: Our findings support a potential causal relationship between autoimmune diseases and COPD, highlighting the importance of considering comorbidities in clinical management of COPD.

Corrigendum: Associations between omega-3 fatty acids and insulin resistance and body composition in women with polycystic ovary syndrome.

[This corrects the article DOI: 10.3389/fnut.2022.1016943.].

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.

Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice.

Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant. There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals, but different results were also reported, along with inconsistent reports regarding its neurotoxicity. Here, we investigated thyroid disrupting effects and neurotoxicity of TBBPA (5, 50, 500 µg/(kg·day)) to male mice following maternal and direct exposure through drinking water, with the anti-thyroid drug propylthiouracil (PTU) as the positive control. On postnatal day (PND) 15, we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups. The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum. During puberty and adulthood, the thyroid morphological alterations became more pronounced in the TBBPA-treated animals, accompanied by decreased serum thyroid hormone levels. Furthermore, the 50 and 500 µg/(kg·day) TBBPA groups showed a significant decrease in the serum level of serotonin, a neurotransmitter associated with anxiety behaviors. Correspondingly, the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35, but this neurobehavioral alteration disappeared on PND 56. Moreover, no changes in neurobehavioral parameters tested were found in TBBPA-treated animals at puberty and adulthood. Altogether, all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice, suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.

Potential regulatory role of epigenetic modifications in aging-related heart failure.

Heart failure (HF) is a serious clinical syndrome and a serious development or advanced stage of various heart diseases. Aging is an independent factor that causes pathological damage in cardiomyopathy and participates in the occurrence of HF at the molecular level by affecting mechanisms such as telomere shortening and mitochondrial dysfunction. Epigenetic changes have a significant impact on the aging process, and there is increasing evidence that genetic and epigenetic changes are key features of aging and aging-related diseases. Epigenetic modifications can affect genetic information by changing the chromatin state without changing the DNA sequence. Most of the genetic loci that are highly associated with cardiovascular diseases (CVD) are located in non-coding regions of the genome; therefore, the epigenetic mechanism of CVD has attracted much attention. In this review, we focus on the molecular mechanisms of HF during aging and epigenetic modifications mediating aging-related HF, emphasizing that epigenetic mechanisms play an important role in the pathogenesis of aging-related CVD and can be used as potential diagnostic and prognostic biomarkers, as well as therapeutic targets.

Bioaccumulation and Male Reproductive Toxicity of the New Brominated Flame Retardant Tetrabromobisphenol A-Bis(2,3-dibromo-2-methylpropyl ether) in Comparison with Hexabromocyclododecane.

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.

Suramin inhibits phenotypic transformation of vascular smooth muscle cells and neointima hyperplasia by suppressing transforming growth factor beta receptor 1 /Smad2/3 pathway activation.

Vascular smooth muscle cells (VSMCs) contribute to neointimal hyperplasia (NIH) after vascular injury, a common feature of vascular remodelling disorders. Suramin is known to exert antitumour effects by inhibiting the proliferation of various tumour cells; however, its effects and mechanism on VSMCs remain unclear. This study investigated the effects of suramin on human aortic smooth muscle cells (HASMCs), rat aortic smooth muscle cells (RASMCs) and NIH to examine its suitability for the prevention of vascular remodelling disorders. In vitro, suramin administration reduced platelet-derived growth factor type BB (PDGF-BB)-stimulated proliferation, migration, and dedifferentiation of VSMCs through a transforming growth factor beta receptor 1 (TGFBR1)/Smad2/3-dependent pathway. Suramin dramatically inhibited NIH ligation in the left common carotid artery (LCCA) vivo. Therefore, our results indicate that suramin protects against the development of pathological vascular remodelling by attenuating VSMCs proliferation, migration, and phenotypic transformation and may be used as a potential medicine for the treatment of NIH.

Transcriptomic analysis reveals the effects of maternal exposure to bisphenol AF on hypothalamic development in male neonatal mice.

Fragmented data suggest that bisphenol AF (BPAF), a chemical widely used in a variety of products, might have potential impacts on the hypothalamus. Here, we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing. We found that maternal exposure to approximately 50 µg/(kg·day) BPAF from postanal day (PND) 0 to PND 15 altered the hypothalamic transcriptome, primarily involving the pathways and genes associated with extracellular matrix (ECM) and intercellular adhesion, neuroendocrine regulation, and neurological processes. Further RNA analysis confirmed the changes in the expression levels of concerned genes. Importantly, we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue. All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism. Interestingly, 5000 µg/(kg·day) BPAF caused slighter, non-significant or even inverse alterations than the low dose of 50 µg/(kg·day), displaying a dose-independent effect. Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose. Overall, our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.

Measurement of urinary exosomal phospholipase A2 receptor is a sensitive method for diagnosis of PLA2R-associated membranous nephropathy.

Background: The discovery of phospholipase A2 receptor (PLA2R) and its antibody (aPLA2Rab) has paved the way for diagnosing PLA2R-associated membranous nephropathy (PLA2R-MN) with a high specificity of 98%. However, the sensitivity was only 40% to 83.9%, and there is ongoing discussion around determining the optimal threshold for diagnosis. Recent advancements in the use of exosomes, a novel form of "liquid biopsy," have shown great promise in identifying markers for various medical conditions. Methods: Protein mass spectrometry and western blot were applied to verify the existence of PLA2R antigen in the urine exosome. We then evaluated the efficacy of urinary exosomal PLA2R antigen alone or combined with serum aPLA2Rab level to diagnose PLA2R-MN. Results: The urinary exosomes contained a high abundance of PLA2R antigen as evidenced by protein mass spectrometry and western blot in 85 PLA2R-MN patients vs the disease controls (14 secondary MN patients, 22 non-MN patients and 4 PLA2R-negative MN patients) and 20 healthy controls. Of note, urinary exosomal PLA2R antigen abundance also had a good consistency with the PLA2R antigen level in the renal specimens of PLA2R-MN patients. The sensitivity of urinary exosomal PLA2R for diagnosing PLA2R-MN reached 95.4%, whereas the specificity was 63.3%. Combining detection of the urinary exosomal PLA2R and serum aPLA2Rab could develop a more sensitive diagnostic method for PLA2R-MN, especially for patients with serum aPLA2Rab ranging from 2 to 20 RU/mL. Conclusions: Measurement of urinary exosomal PLA2R could be a sensitive method for the diagnosis of PLA2R-MN.

FeNi decorated nitrogen-doped hollow carbon spheres as ultra-stable bifunctional oxygen electrocatalyst for rechargeable zinc-air battery with 2.7% decay after 300 hours cycling.

Research on non-noble metal bifunctional electrocatalysts with high efficiency and long-lasting stability is crucial for many energy storage devices such as zinc-air batteries. In this report, nitrogen-doped porous hollow carbon spheres with a size of about 300 nm were fabricated using a modified Stöber method and decorated with an FeNi alloy through a pyrolytic reduction process, resulting in a promising bifunctional electrocatalyst for both the oxygen evolution reaction and oxygen reduction reaction. The as-prepared FeNi@NHCS electrocatalyst exhibits excellent bifunctional activity in KOH electrolyte, attributed to its mesoporous structure, large specific surface area, and the strong coupling between the FeNi nanoalloy and nitrogen-doped carbon carriers. The electrocatalyst demonstrates excellent ORR performance with E1/2 = 0.828 V and OER activity with Ej=10 mA = 1.51 V. A zinc-air battery using FeNi@NHCS as the air electrode achieves an open-circuit voltage of 1.432 V and a maximum power density of 181.8 mW cm-2. After 300 h of galvanostatic charge-discharge cycles, the charge-discharge voltage gap (ΔU) of the battery had only decayed by 2.7%, demonstrating superior cycling stability.