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Abstract Background Aging is a multifaceted process that affects all organ systems. With the increasing trend of population aging, aging-related diseases have resulted in significant medical challenges and socioeconomic burdens. Mesenchymal stromal cells (MSCs), due to their antioxidative stress, immunoregulatory, and tissue repair capabilities, hold promise as a potential anti-aging intervention. Methods In this study, we transplanted MSCs into naturally aged rats at 24 months, and subsequently examined levels of aging-related factors such as β-galactosidase, superoxide dismutase, p16, p21 and malondialdehyde in multiple organs. Additionally, we assessed various aging-related phenotypes in these aged rats, including immune senescence, lipid deposition, myocardial fibrosis, and tissue damage. We also conducted a 16 S ribosomal ribonucleic acid (rRNA) analysis to study the composition of gut microbiota. Results The results indicated that MSCs significantly reduced the levels of aging-associated and oxidative stress-related factors in multiple organs such as the heart, liver, and lungs of naturally aging rats. Furthermore, they mitigated chronic tissue damage and inflammation caused by aging, reduced levels of liver lipid deposition and myocardial fibrosis, alleviated aging-associated immunodeficiency and immune cell apoptosis, and positively influenced the gut microbiota composition towards a more youthful state. This research underscores the diverse anti-aging effects of MSCs, including oxidative stress reduction, tissue repair, metabolic regulation, and improvement of immune functions, shedding light on the underlying anti-aging mechanisms associated with MSCs. Conclusions The study confirms that MSCs hold great promise as a potential anti-aging approach, offering the possibility of extending lifespan and improving the quality of life in the elderly population.

Seismic monitoring has been instrumental in various domains such as natural earthquake early warning, mineral mining safety assessment, and hydraulic fracturing impact evaluation. However, the monitoring data often exhibit low signal-to-noise ratio (SNR) and large volume. Developing an efficient, high-precision, and universally applicable seismic waveform automatic classification network model becomes significant and practical. We propose a physical interpretable time-frequency deep convolutional recurrent neural network (TF-DCRNN) model which consists of an integration of a time-frequency convolutional (TFconv) layer and a convolutional recurrent neural network (CRNN). Subsequently, we evaluate the classification performance by comparing five network models, including convolutional neural network (CNN) and long short-term memory (LSTM), using Ricker wavelet datasets with varying SNR levels ( $- 15~\sim ~0$ dB). Our findings verify the superiority of the TF-DCRNN model in the classification of strong interference environment from both numerical and physical simulation. Moreover, integrating multiple network models or incorporating a TFconv layer can moderately enhance the classification performance, which provides the direction for network model optimization.

The composition of the gut microbiota varies among end-stage renal disease (ESRD) patients on the basis of their mode of renal replacement therapy (RRT), with notably more pronounced dysbiosis occurring in those undergoing hemodialysis (HD). Interventions such as dialysis catheters, unstable hemodynamics, strict dietary restrictions, and pharmacotherapy significantly alter the intestinal microenvironment, thus disrupting the gut microbiota composition in HD patients. The gut microbiota may influence HD-related complications, including cardiovascular disease (CVD), infections, anemia, and malnutrition, through mechanisms such as bacterial translocation, immune regulation, and the production of gut microbial metabolites, thereby affecting both the quality of life and the prognosis of patients. This review focuses on alterations in the gut microbiota and its metabolites in HD patients. Additionally, understanding the impact of the gut microbiota on the complications of HD could provide insights into the development of novel treatment strategies to prevent or alleviate complications in HD patients.

Background: Efficiently increasing the production of clinical-grade mesenchymal stem cells (MSCs) is crucial for clinical applications. Challenges with the current planar culture methods include scalability issues, labour intensity, concerns related to cell senescence, and heterogeneous responses. This study aimed to establish a large-scale production system for MSC generation. In addition, a comparative analysis of the biological differences between MSCs cultured under various conditions was conducted. Methods and materials: We developed a GMP-grade three-dimensional hypoxic large-scale production (TDHLSP) system for MSCs using self-fabricated glass microcarriers and a multifunctional bioreactor. Different parameters, including cell viability, cell diameter, immunophenotype, morphology, karyotype, and tumourigenicity were assessed in MSCs cultured using different methods. Single-cell RNA sequencing (scRNA-seq) revealed pathways and genes associated with the enhanced functionality of MSCs cultured in three dimensions under hypoxic conditions (3D_Hypo MSCs). Moreover, CD142 knockdown in 3D_Hypo MSCs confirmed its in vitro functions. Results: Inoculating 2 × 108 MSCs into a 2.6 L bioreactor in the TDHLSP system resulted in a final scale of 4.6 × 109 3D_Hypo MSCs by day 10. The 3D_Hypo MSCs retained characteristics of the 2D MSCs, demonstrating their genomic stability and non-tumourigenicity. Interestingly, the subpopulations of 3D_Hypo MSCs exhibited a more uniform distribution and a closer relationship than those of 2D MSCs. The heterogeneity of MSCs was strongly correlated with ‘cell cycle’ and ‘stroma/mesenchyme’, with 3D_Hypo MSCs expressing higher levels of activated stroma genes. Compared to 2D MSCs, 3D_Hypo MSCs demonstrated enhanced capabilities in blood vessel formation, TGF-β1 secretion, and inhibition of BV2 proliferation, with maintenance of Senescence-Associated β-Galactosidase (SA-β-gal) negativity. However, the enhanced functions of 3D_Hypo MSCs decreased upon the downregulation of CD142 expression. Conclusion: The TDHLSP system led to a high overall production of MSCs and promoted uniform distribution of MSC clusters. This cultivation method also enhanced key cellular properties, such as angiogenesis, immunosuppression, and anti-aging. These functionally improved and uniform MSC subpopulations provide a solid basis for the clinical application of stem cell therapies.

Recent developments in electric vehicles have heightened the need for high-efficiency heat pump technology to improve cruising range and cabinet thermal comfort. As the key component for a heat pump system, compressor has a significant impact on heat pump system performance. In this work, a numerical model of a heat pump system consisting of a variable displacement compressor (VDC) model, a variable speed compressor (VSC) model, and a heat exchanger model is presented to compare the two major types of compressor. The simulation is executed across a diverse array of conditions to assess the performance disparity between two variants of compressors, particularly in challenging environments. The proposed model is validated based on the experimental data from a heat pump test rig which compressor section can be replaced with a prototype VDC or VSC based on validation demands. Overall, the modeling results demonstrate a favorable alignment with the measurements. The simulated power input of VDC under heat and cooling mode has a mean absolute percentage error (MPAE) of 4.4% and 6.0%, respectively, while the MAPEs for VSC under heating and cooling modes are 3.2%, and 4.5%. The modelling results indicate that the VDC system shows superior performance in specific mass flow rate, compressor power input, and system efficiency, especially at part load conditions.

Lactarius hatsudake (LH), a great wild endemic fungus, contains rich nutritional components with medicinal properties. The effects of LH on body weight, liver weight, liver injury, blood lipids, and gut microbiota in C57BL/6 mice fed a high-fat diet (HFD) for 8 weeks was examined in this research. Though there was no clear impact on weight loss, the findings indicate that LH treatment effectively decreased liver damage caused by HFD, as well as lowered serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels. Additionally, it positively influenced gut microbiota to resemble that of mice on a normal diet. In HFD-fed mice, LH markedly boosted the levels of Parabacteroides, unclassified Muribaculaceae, Oscillibacter, and unclassified Oscillospiraceae, while reducing the abundance of Lachnospiraceae NK4A136 group and Erysipelatoclostridium, as well as the ratio of Firmicutes to Bacteroidetes. Further analysis of correlation indicate a possible connection between obesity and gut microbiota. Obesity-related indices show a positive association with unclassified Eubacterium coprostanoligenes group, Blautia, and Erysipelatoclostridium, while displaying a negative correlation with unclassified Muribaculaceae, unclassified Clostridia vadinBB60 group, Helicobacter, Oscillibacter, unclassified Ruminococcaceae, Parabacteroides, and unclassified Oscillospiraceae. The results suggest that LH can help combat obesity and may have the potential to be utilized as a functional food.

Enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and CV-A10 belong to the main prevailing types causing hand-foot-and-mouth disease. Since EV-A71 monovalent vaccine does not confer cross-protection, developing a multivalent vaccine is essential. In this study, a trivalent chimeric virus-like particle of EV-A71 (EV-A71-VLPCHI3) was constructed based on EV-A71-VLP backbone by replacing the corresponding surface loops with CV-A16 VP1 G-H, CV-A10 VP1 B-C and E-F loops, which are critical for immunogenic neutralization. The baculovirus-insect cell expression system was employed for EV-A71-VLPCHI3 production. EV-A71-VLPCHI3 was purified by sucrose density gradient and observed by transmission electron microscopy. The immunogenicity and protective efficacy of EV-A71-VLPCHI3 were evaluated in mice. Our results revealed that EV-A71-VLPCHI3 had a similar morphology to inactivated EV-A71 particles and could induce specific IgG antibodies against EV-A71, CV-A16 and CV-A10 in mice. More importantly, EV-A71-VLPCHI3 enhanced cross-reactive protection against CV-A16 and CV-A10, by 20 % and 40 %, compared to inactivated EV-A71 counterparts, respectively. In conclusion, the successful construction of EV-A71-VLPCHI3 suggested that loop-dependent heterologous protection could be transferred by loops replacement on the surface of viral capsid. This strategy may also supplement the development of multivalent vaccines against other infectious viral diseases.

Abstract Background Headache during hemodialysis (HDH) is prevalent but not negligible. Despite the high prevalence of dialysis headaches, they have rarely been studied. Therefore, this study aimed to evaluate the prevalence, risk factors, and clinical characteristics of HDH and reappraise the HDH diagnostic criteria in the International Classification of Headache Disorders 3 (ICHD-3). Methods One hundred and fifty-four patients completed this randomized cross-sectional study. Consecutive patients who underwent haemodialysis were assessed using a semi-structured questionnaire. The patients were administered face-to-face questionnaires while undergoing dialysis. Results This study included 154 patients. Before commencing dialysis, 3.24% (5/154) of the patients had migraine without aura, 1.29% (2/154) had menstrual-related migraine, 0.6% (1/154) had tension-type headaches, and 0.6% (1/154) had an unclassifiable headache. One case (0.6%) of headache resolved after dialysis treatment. HDH was diagnosed in 9.09% (14/154) of the patients. Headache after haemodialysis (HAH) was reported in 6.49% (10/154) of patients. The most prevalent features of HDH were frontal or temporal location, bilateral headaches, dull and throbbing nature, and moderate severity. HDH started at a mean of 2.33 ± 0.79 h after dialysis commenced. The average headache duration was 6.56 ± 1.57 h (median = 3.0 h), with 66.67% of the patients reporting a duration of ≤4 h. HDH was more prevalent in females than males (P = 0.01, P

Abstract Background Coxsackievirus A10 (CV-A10) is a leading cause of hand, foot, and mouth disease (HFMD). It is necessary to identify neutralizing epitopes to investigate and develop an epitope-based vaccine against CV-A10. The viral protein VP1 is the immunodominant capsid protein and contains the critical neutralizing epitope. However, neutralizing epitopes within VP1 protein of CV-A10 have not been well characterized. Methods Bioinformatics techniques were applied to predict linear epitopes on the CV-A10 VP1 protein. The advanced structural features of epitopes were analyzed by three-dimensional (3D) modeling. The anticipated epitope peptides were synthesized and used to immunize mice as antigens. ELISA and micro-neutralization assay were used to determine the specific IgG antibody and neutralizing antibody titers. The protective efficacy of the epitope peptides in vivo was evaluated using a passive immunization/challenge assay. Results Three linear epitopes (EP3, EP4, and EP5) were predicted on CV-A10 VP1, all spatially exposed on the capsid surface, and exhibited adequate immunogenicity. However, only EP4, corresponding to residues 162–176 of VP1, demonstrated potent neutralization against CV-A10. To determine the neutralizing capacity of EP4 further, EP4 double-peptide was synthesized and injected into mice. The mean neutralizing antibody titer of the anti-EP4 double-peptide sera was 1:50.79, which provided 40% protection against lethal infection with CV-A10 in neonatal mice. In addition, sequence and advanced structural analysis revealed that EP4 was highly conserved among representative strains of CV-A10 and localized in the EF loop region of VP1, like EV-A71 SP55 or CV-A16 PEP55. Conclusions These data demonstrate that EP4 is a specific linear neutralizing epitope on CV-A10 VP1. Its protective efficacy can be enhanced by increasing its copy number, which will be the foundation for developing a CV-A10 epitope-based vaccine.

When water diversion projects become important part of the water network around the world, the effective operation and management of the projects play important roles in giving full play to the optimal allocation of water resources. For the operation and management of water transfer, the decision-making of water supply chain under the scenario of economic benefit, producer surplus, and water quality utility should be considered simultaneously. According to the idea of supply chain, this paper regards water transfer operation management as a water supply chain composed of water transfer companies, water supply companies, and consumers. From the perspective of social welfare and water quality utility, a comprehensive optimization and coordination decision model for water transfer is proposed. Taking the South-to-North Water Diversion Project as the research object, the cost-sharing contract is designed, and the Stackelberg game method is used to optimize the decision-making and coordination of the water supply chain. The results show that when the concern coefficient and the cost-sharing ratio are evaluated within a given feasible value region, the profits of both the water transfer company and the water supply company can be improved. The feasible value interval of the concern coefficient decreases with the increase in the cost-bearing proportion. When the concern coefficient increases, the profit of the water transfer company decreases, while profit of the water supply company, water quality, consumer surplus, water quality utility, and utility of the water transfer company increase gradually. The results provide valuable references for water transfer decision-making.

Agricultural drought risk assessment is helpful in quantitatively understanding agricultural drought and scientifically guiding disaster prevention and mitigation. Therefore, according to the characteristics of attribute uncertainty and index weight subjectivity in agricultural drought risk assessment, an attribute interval identification model combined with grey relational analysis was established to evaluate agricultural drought risk. Firstly, the agricultural drought risk evaluation index system was established from four aspects: disaster, exposure, vulnerability and resistance. Then, the objective weights of the indicators were calculated using the grey relational method. Finally, the agricultural drought risk in Zhengzhou was evaluated by qualitative analysis and probabilistic analysis. Qualitative analysis results showed that the agricultural drought risk in Zhengzhou is at the level of moderate drought. The probability analysis showed that the probability of Zhengzhou City being in a moderate drought is 79.5%, and the probability of being in a severe drought is 20.5%. In addition, the superiority of the attribute interval identification model in agricultural drought risk assessment was further verified by comparative analysis. This research provides a new method for regional agricultural drought risk assessment. Furthermore, it can provide support for management departments to further understand the regional drought risk level and improve the efficiency of drought risk management. HIGHLIGHTS The probability corresponding to the agricultural drought risk level should be considered.; Interval values are used instead of fixed values to quantify the evaluation indicators.; Gray correlation is introduced to construct an interval attribute recognition and evaluation model.; The construction of an evaluation index system is very important.; The dynamic changes of indicator values should be taken seriously.;

Abstract Background Pyroptosis is a highly programmed inflammatory cell death process that represents an innate immune response. In this study, the occurrence of pyroptosis in rat mesangial cells (RMCs) and the effect of Huaier (Trametes robiniophia Murr) on this process were investigated. Methods RMCs were incubated with OX7 antibodies (0.5 μg/ml, 2.5 μg/ml, 10 μg/ml), normal rat serum (NRS) and Huaier (1 mg/ml, 5 mg/ml, 10 mg/ml). RMC morphology was observed under a light microscope and by immunofluorescence. Lactate dehydrogenase (LDH) release was assessed using the CytoTox 96 Non-Radioactive Cytotoxicity Assay Kit. Western blot assays were performed, and then the RMCs were incubated with the methylase DNMT3B and the demethylase 5-aza-2′-deoxycytidine. Results Morphological, LDH, immunofluorescence and western blot analyses showed that RMCs were lysed when stimulated with OX7 antibodies and NRS. RMC lysis released inflammatory cytokines (interleukin-18, interleukin-1β, monocyte chemoattractant protein-1 and intracellular adhesion molecule-1), and Huaier protected RMCs by controlling lysis and the levels of inflammatory cytokines. Lysis was mediated by pyroptosis due to the positive expression of GSDME. The methylase DNMT3B reduced the expression of GSDME induced by OX7 together with NRS. Furthermore, Huaier significantly suppressed the expression of GSDME, which was increased by 5-aza-2’-deoxycytidine. Conclusions Pyroptosis might occur in RMCs, and Huaier can protect RMCs by upregulating the methylation of a group of molecules.

Diabetic nephropathy (DN), as the one of most common complications of diabetes, is generally diagnosed based on a longstanding duration, albuminuria, and decreased kidney function. Some patients with the comorbidities of diabetes and other primary renal diseases have similar clinical features to DN, which is defined as non-diabetic renal disease (NDRD). It is necessary to distinguish between DN and NDRD, considering they differ in their pathological characteristics, treatment regimes, and prognosis. Renal biopsy provides a gold standard; however, it is difficult for this to be conducted in all patients. Therefore, it is necessary to discover non-invasive biomarkers that can distinguish between DN and NDRD. In this research, the urinary exosomes were isolated from the midstream morning urine based on ultracentrifugation combined with 0.22 μm membrane filtration. Data-independent acquisition-based quantitative proteomics were used to define the proteome profile of urinary exosomes from DN (n = 12) and NDRD (n = 15) patients diagnosed with renal biopsy and Type 2 diabetes mellitus (T2DM) patients without renal damage (n = 9), as well as healthy people (n = 12). In each sample, 3372 ± 722.1 proteins were identified on average. We isolated 371 urinary exosome proteins that were significantly and differentially expressed between DN and NDRD patients, and bioinformatic analysis revealed them to be mainly enriched in the immune and metabolic pathways. The use of least absolute shrinkage and selection operator (LASSO) logistic regression further identified phytanoyl-CoA dioxygenase domain containing 1 (PHYHD1) as the differential diagnostic biomarker, the efficacy of which was verified with another cohort including eight DN patients, five NDRD patients, seven T2DM patients, and nine healthy people. Additionally, a concentration above 1.203 μg/L was established for DN based on the ELISA method. Furthermore, of the 19 significantly different expressed urinary exosome proteins selected by using the protein–protein interaction network and LASSO logistic regression, 13 of them were significantly related to clinical indicators that could reflect the level of renal function and hyperglycemic management.

Abstract Background Patients with both diabetes mellitus (DM) and kidney disease could have diabetic nephropathy (DN) or non-diabetic renal disease (NDRD). IgA nephropathy (IgAN) and membranous nephropathy (MN) are the major types of NDRD. No ideal noninvasive diagnostic model exists for differentiating them. Our study sought to construct diagnostic models for these diseases and to identify noninvasive biomarkers that can reflect the severity and prognosis of DN. Methods The diagnostic models were constructed using logistic regression analysis and were validated in an external cohort by receiver operating characteristic curve analysis method. The associations between these microRNAs and disease severity and prognosis were explored using Pearson correlation analysis, Cox regression, Kaplan–Meier survival curves, and log-rank tests. Results Our diagnostic models showed that miR-95-3p, miR-185-5p, miR-1246, and miR-631 could serve as simple and noninvasive tools to distinguish patients with DM, DN, DM with IgAN, and DM with MN. The areas under the curve of the diagnostic models for the four diseases were 0.995, 0.863, 0.859, and 0.792, respectively. The miR-95-3p level was positively correlated with the estimated glomerular filtration rate (p

Diabetic nephropathy (DN) is a major microvascular complication of both type 1 and type 2 diabetes mellitus and is the most frequent cause of end-stage renal disease with an increasing prevalence. Presently there is no non-invasive method for differential diagnosis, and an efficient target therapy is lacking. Extracellular vesicles (EV), including exosomes, microvesicles, and apoptotic bodies, are present in various body fluids such as blood, cerebrospinal fluid, and urine. Proteins in EV are speculated to be involved in various processes of disease and reflect the original cells’ physiological states and pathological conditions. This systematic review is based on urinary extracellular vesicles studies, which enrolled patients with DN and investigated the proteins in urinary EV. We systematically reviewed articles from the PubMed, Embase, Web of Science databases, and China National Knowledge Infrastructure (CNKI) database until January 4, 2022. The article quality was appraised according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The methodology of samples, isolation and purification techniques of urinary EV, and characterization methods are summarized. Molecular functions, biological processes, and pathways were enriched in all retrievable urinary EV proteins. Protein-protein interaction analysis (PPI) revealed pathways of potential biomarkers. A total of 539 articles were retrieved, and 13 eligible records were enrolled in this systematic review and meta-analysis. And two studies performed mass spectrometry to obtain the proteome profile. Two of them enrolled only T1DM patients, two studies enrolled both patients with T1DM and T2DM, and other the nine studies focused on T2DM patients. In total 988 participants were enrolled, and DN was diagnosed according to UACR, UAER, or decreased GFR. Totally 579 urinary EV proteins were detected and 28 of them showed a potential value to be biomarkers. The results of bioinformatics analysis revealed that urinary EV may participate in DN through various pathways such as angiogenesis, biogenesis of EV, renin-angiotensin system, fluid shear stress and atherosclerosis, collagen degradation, and immune system. Besides that, it is necessary to report results compliant with the guideline of ISEV, in orderto assure repeatability and help for further studies. This systematic review concordance with previous studies and the results of meta-analysis may help to value the methodology details when urinary EV proteins were reported, and also help to deepen the understanding of urinary EV proteins in DN.

Systems where both time-reversal symmetry and inversion symmetry are broken can exhibit a magneto-chiral effect; however, this is usually weak. Here, Lan et al demonstrate a significantly enhanced excitonic magnetochiral effect in twisted bilayer tungsten disulphide on a ferromagnetic substrate.

Discriminating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) can help provide more specific treatments. However, there are no ideal biomarkers for their differentiation. Thus, the aim of this study was to identify biomarkers for diagnosing and predicting the progression of DN by investigating different salivary glycopatterns. Lectin microarrays were used to screen different glycopatterns in patients with DN or NDRD. The results were validated by lectin blotting. Logistic regression and artificial neural network analyses were used to construct diagnostic models and were validated in in another cohort. Pearson’s correlation analysis, Cox regression, and Kaplan–Meier survival curves were used to analyse the correlation between lectins, and disease severity and progression. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses were used to identify corresponding glycoproteins and predict their function. Both the logistic regression model and the artificial neural network model achieved high diagnostic accuracy. The levels of Aleuria aurantia lectin (AAL), Lycopersicon esculentum lectin (LEL), Lens culinaris lectin (LCA), Vicia villosa lectin (VVA), and Narcissus pseudonarcissus lectin (NPA) were significantly correlated with the clinical and pathological parameters related to DN severity. A high level of LCA and a low level of LEL were associated with a higher risk of progression to end-stage renal disease. Glycopatterns in the saliva could be a non-invasive tool for distinguishing between DN and NDRD. The AAL, LEL, LCA, VVA, and NPA levels could reflect the severity of DN, and the LEL and LCA levels could indicate the prognosis of DN.

Background: Stroke-associated pneumonia (SAP) is associated with poor prognosis after acute ischemic stroke (AIS).Purpose: This study aimed to describe the parameters of coagulation function and evaluate the association between the fibrinogen-to-albumin ratio (FAR) and SAP in patients with AIS.Patients and methods: A total of 932 consecutive patients with AIS were included. Coagulation parameters were measured at admission. All patients were classified into two groups according to the optimal cutoff FAR point at which the sum of the specificity and sensitivity was highest. Propensity score matching (PSM) was performed to balance potential confounding factors. Univariate and multivariate logistic regression analyses were applied to identify predictors of SAP.Results: A total of 100 (10.7%) patients were diagnosed with SAP. The data showed that fibrinogen, FAR, and D-dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT) were higher in patients with SAP, while albumin was much lower. Patients with SAP showed a significantly increased FAR when compared with non-SAP (P < 0.001). Patients were assigned to groups of high FAR (≥0.0977) and low FAR (

Drug-induced nephrotoxicity is an important and increasing cause of acute kidney injury (AKI), which accounts for approximately 20% of hospitalized patients. Previous reviews studies on immunity and AKI focused mainly on ischemia-reperfusion (IR), whereas no systematic review addressing drug-induced AKI and its related immune mechanisms is available. Recent studies have provided a deeper understanding on the mechanisms of drug-induced AKI, among which acute tubular interstitial injury induced by the breakdown of innate immunity was reported to play an important role. Emerging research on mesenchymal stem cell (MSC) therapy has revealed its potential as treatment for drug-induced AKI. MSCs can inhibit kidney damage by regulating the innate immune balance, promoting kidney repair, and preventing kidney fibrosis. However, it is important to note that there are various sources of MSCs, which impacts on the immunomodulatory ability of the cells. This review aims to address the immune pathogenesis of drug-induced AKI versus that of IR-induced AKI, and to explore the immunomodulatory effects and therapeutic potential of MSCs for drug-induced AKI.

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg’s funnel plot and Egger’s linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.

The microstructure of a mixed KCl and K2SO4 aqueous solution was studied using X-ray scattering (XRS), Raman spectroscopy, and molecular dynamics simulation (MD). Reduced structure functions [F(Q)], reduced pair distribution functions [G(r)], Raman spectrum, and pair distribution functions (PDF) were obtained. The XRS results show that the main peak (r = 2.81 Å) of G(r) shifted to the right of the axis (r = 3.15 Å) with increased KCl and decreased K2SO4. The main peak was at r = 3.15 Å when the KCl concentration was 26.00% and the K2SO4 concentration was 0.00%. It is speculated that this phenomenon was caused by the main interaction changing, from K-OW (r = 2.80 Å) and OW-OW (r = 2.80 Å), to Cl−-OW (r = 3.14 Å) and K+-Cl− (r = 3.15 Å). According to the trend of the hydrogen bond structure in the Raman spectrum, when the concentration of KCl was high and K2SO4 was low, the destruction of the tetrahedral hydrogen bond network in the solution was more serious. This shows that the destruction strength of the anion to the hydrogen bond network structure in solution was Cl− > SO42−. In the MD simulations, the coordination number of OW-OW decreased with increasing KCl concentration, indicating that the tetrahedral hydrogen bond network was severely disrupted, which confirmed the results of the Raman spectroscopy. The hydration radius and coordination number of SO42− in the mixed solution were larger than Cl−, thus revealing the reason why the solubility of KCl in water was greater than that of K2SO4 at room temperature.

PurposeLower serum vitamin D has been reported to be associated with stroke. This study aimed to analyze the risk factors of vitamin deficiency in Chinese stroke patients, and further analyze its impact in different gender and their clinical variables.Methods982 stroke patients were enrolled. Laboratory parameters such as serum vitamin D, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), ApoA-I/ApoB, cholesterol (CH), fibrinogen (FIB), blood glucose (Glu), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were collected and recorded. The severity of stroke was assessed by National Institute of Health Stroke Scale (NIHSS) score. Based on their serum vitamin D level, patients were divided into three groups: Vitamin D deficiency (

Background No studies have examined the practicality of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations for the estimated glomerular filtration rate (eGFR) in a large sample of centenarians. We aim to investigate the differences among the equations and suggest the most suitable equation for centenarians and near-centenarians. Methods A total of 966 centenarians and 787 near-centenarians were enrolled, and the eGFR was calculated using the three equations mentioned above. Agreement among the equations was investigated with the κ statistic and Bland–Altman plots. Sources of discrepancy were investigated using a partial correlation analysis. Results The three equations for assessing eGFR are not considered interchangeable in centenarians and near-centenarians. Δ(MDRD, CKD-EPI) and Δ(MDRD, BIS1) increased with age, but Δ(CKD-EPI, BIS1) was relatively stable with age. Δ(MDRD, CKD-EPI) and Δ(MDRD, BIS1) were considerable in subjects with Scr levels less than 0.7 mg/dL and decreased with the Scr level. A considerable difference between CKD-EPI and BIS1 was observed for participants with Scr levels ranging from 0.5 to 1.5 mg/dL. This difference increased with Scr levels ranging from 0.5 to 0.7 mg/dL, was relatively stable for Scr levels ranging from 0.7 to 0.9 mg/dL, and decreased with Scr levels ranging from 0.9 to 1.5 mg/dL. The differences in the three comparisons were all greater in women than in men (p 95 years old who have no risk factors for cardiovascular disease; the BIS1 equation to calculate the eGFR for elderly individuals younger than 94 years old who have risk factors for cardiovascular disease; the CKD-EPI equation to calculate the eGFR of elderly individuals with Scr levels greater than 1.5 mg/dL; and the BIS1 equation to calculate the eGFR of older women with Scr levels less than 0.7 mg/dL.

Background. This meta-analysis was performed to obtain a more comprehensive estimation of the role of the single nucleotide polymorphism (SNP) rs2241766 in the ADIPOQ gene in the occurrence of diabetic kidney disease (DKD). Methods. Relevant studies were identified from digital databases such as Embase, PubMed, Medline, Cochrane Library, Google Scholar, WanFang, and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were pooled by means of fixed- or random-effects models. Interstudy heterogeneity was examined using the Q test and I2 statistic, and sensitivity analysis was implemented to test the statistical stability of the overall estimates. Begg’s funnel plot and Egger’s test were applied to inspect potential publication bias among the included studies. Results. The overall ORs reflected a positive correlation between the ADIPOQ rs2241766 polymorphism and susceptibility to DKD in the GG vs. TT and GG vs. TT+TG comparisons (OR=1.51, 95%CI=1.16−1.95; OR=1.43, 95%CI=1.11−1.85). After stratification analyses by ethnicity and disease type, a similar trend was also revealed in the Caucasian and African subgroups as well as in the type 2 diabetes mellitus (T2DM) subgroup. Conclusion. The ADIPOQ rs2241766 polymorphism may be associated with an increased risk of DKD, especially in Caucasian and African populations as well as in T2DM patients.

Background/Aims: IgA nephropathy is the most prevalent form of primary glomerulonephritis worldwide. Among patients with kidney disease, hypertension is one of the most important risk factors of disease progression. Considering the limited evidence regarding the appropriate blood pressure (BP) goal for patients with IgA nephropathy, our aim was to critically appraise the potential BP goal in IgA nephropathy. Methods: We performed a retrospective analysis of the BP data from 1055 patients with IgA nephropathy, extracted from the database of a nationwide, multi-center, cross-sectional study, including 61 tertiary hospitals in China. Hypertension was defined by a BP ≥140/90 mmHg. Three BP cutoff levels were evaluated as control values: < 140/90 mmHg, < 130/80 mmHg and < 125/75 mmHg. The primary outcome of our study was the prevalence of BP control among patients with a 24-h proteinuria < 1 g/d or ≥ 1 g/d. Multivariate logistic regression analysis was used to identify demographic and clinical factors associated with a decrease in renal function for the different target levels of BP. Results: The overall prevalence of hypertension was 63.3%. BP was controlled under 140/90 mmHg in 49.1% of patients, with 34.3% of patients with proteinuria < 1 g/d reaching the target BP < 130/80 mmHg and only 12.9% of patients with proteinuria > 1 g/d achieving a BP < 125/75 mmHg. Among patients with proteinuria < 1 g/d, the adjusted odds ratios (OR) and 95% confidence interval (95% CI) of a decrease in renal function, for the 3 target BP levels, were as follows (P > 0.05): < 140/90 mmHg, 0.9 (0.5 - 1.6); < 130/80 mmHg, 1.0 (0.5 - 1.8); and < 125/75 mmHg, 1.0 (0.5 - 2.0). With proteinuria ≥1 g/d, the adjusted ORs (95%CI) of attaining the BP targets of < 140/90 mmHg, < 130/80 mmHg and < 125/75 mmHg were 0.4 (0.2 - 0.6), 0.2 (0.1 - 0.4) and 0.3 (0.1 - 0.5), respectively (P < 0.05). Conclusion: Hypertension was common in IgA nephropathy and hypertensive control was suboptimal. Our result supports a benefit of intensive control of BP < 130/80 mmHg for patients with proteinuria ≥1 g/d. However, in patients with proteinuria < 1 g/d, a renoprotective effect of this BP goal was not identified.

Background: Hydrophobins are small proteins secreted by filamentous fungi, which show a highly surface activity. Because of the signally self-assembling abilities and surface activities, hydrophobins were considered as candidates in many aspects, for example, stabilizing foams and emulsions in food products. Lentinus tuber-regium, known as tiger milk mushroom, is both an edible and medicinal sclerotium-producing mushroom. Up to now, the hydrophobins of L. tuber-regium have not been identified. Results: In this paper, a Class I hydrophobin gene, Ltr.hyd, was cloned from L. tuber-regium and expressed in the yeast-like cells of Tremella fuciformis mediated by Agrobacterium tumefaciens. The expression vector pGEH-GH was under the control of T. fuciformis glyceraldehyde-3-phosphate dehydrogenase gene (gpd) promoter. The integration of Ltr.hyd into the genome of T. fuciformis was confirmed by PCR, Southern blot, fluorescence observation and quantitative real-time PCR (qRT-PCR). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that recombinant hydrophobin rLtr.HYD with an expected molecular mass of 13 kDa was extracted. The yield of rLtr.HYD was 0.66 mg/g dry weight. The emulsifying activity of rLtr.HYD was better than the typical food emulsifiers sodium caseinate and Tween 20. Conclusions: We evaluated the emulsifying property of hydrophobin Ltr.HYD, which can be potentially used as a food emulsifier. Keywords: Agrobacterium tumefaciens, Emulsifier, Expression vector, Filamentous fungi, Gel electrophoresis, Glyceraldehyde-3-phosphate dehydrogenase, Heterogenous expression, Hydrophobin, Quantitative real-time PCR, Southern blot, Surface activity

Background. Mesangial cells play a prominent role in the development of inflammatory diseases and autoimmune disorders of the kidney. Mesangial cells perform the essential functions of helping to ensure that the glomerular structure is stable and regulating capillary flow, and activated mesangial cells acquire proinflammatory activities. We investigated whether activated mesangial cells display immune properties and control the development of T cell immunity. Methods. Flow cytometry analysis was used to study the expression of antigen-presenting cell surface markers and costimulatory molecules in mesangial cells. CD4+ T cell activation induced by mesangial cells was detected in terms of T cell proliferation and cytokine production. Results. IFN-γ-treated mesangial cells express membrane proteins involved in antigen presentation and T cell activation, including MHC-II, ICAM-1, CD40, and CD80. This finding suggests that activated mesangial cells can take up and present antigenic peptides to initiate CD4+ T cell responses and thus act as nonprofessional antigen-presenting cells. Polarization of naïve CD4+ T cells (Th0 cells) towards the Th1 phenotype was induced by coculture with activated mesangial cells, and the resulting Th1 cells showed increased mRNA and protein expression of inflammation-associated genes. Conclusion. Mesangial cells can present antigen and modulate CD4+ T lymphocyte proliferation and differentiation. Interactions between mesangial cells and T cells are essential for sustaining the inflammatory response in a variety of glomerulonephritides. Therefore, mesangial cells might participate in immune function in the kidney.

It has long been believed that kidney function is linked to brain activity. Clinical studies demonstrate that patients with chronic kidney disease (CKD) are more prone to cognitive impairment and Alzheimer’s disease (AD), and the degree of cognitive impairment is closely related to CKD progression and renal failure. Moreover, the fact that cognitive function in CKD patients is significantly improved after successful kidney transplantation reveals a linkage between CKD and AD. However, the mechanisms behind this linkage are unclear. The physiological function of the kidney is to maintain the stability of the internal environment, including the cerebrovascular circulation, whereas abnormal kidney function often leads to ischemia and hypoxia. Many CKD patients experience chronic hypoxia, and many urinary toxins accumulate after renal function is impaired. In this mini review, we will propose a novel perspective on the association between AD and CKD and the connection between the kidney and brain.

Background The importance of circulating antibodies as biomarkers of kidney disease has recently been recognized. However, no study has systematically described the methodology of sample preparation and storage regarding antibodies as biomarkers of kidney disease. It remains unknown whether repetitive freeze-thaw cycles, physical disturbances, storage at different temperatures or for different periods of time, or haemolytic or turbid serum samples affect antibody measurements. The aim of this study was to investigate the stabilities of antibodies associated with kidney disease in serum samples under various relevant clinical and research conditions. Methods We stored serum samples in the following different conditions: repetitive freeze-thaw cycles (1, 6 or 12 times), long-term storage (7 or 12 months at −80 °C), physical disturbance (1 or 8 h), and storage at 4 °C (1, 3 or 6 weeks) and room temperature (1 or 7 days). The stabilities of the anti-phospholipase A2 receptor (anti-PLA2R), anti-glomerular basement membrane, anti-myeloperoxidase and anti-proteinase 3 antibodies were evaluated with enzyme-linked immunosorbent assays (ELISA). Results We found that repetitive freeze-thaw cycles did not have a significant effect on the stabilities of the abovementioned antibodies in clear serum samples. The ELISA readings of haemolytic and turbid serum samples tended to increase and decrease, respectively. Neither long-term storage at −80 °C nor physical disturbance had a significant effect on anti-PLA2R antibody stability in sealed serum samples. The concentrations of most of these antibodies increased in unsealed serum samples that were stored at 4 °C for more than 6 weeks or at room temperature for more than 7 days. Discussion Our findings revealed that the abovementioned circulating antibodies that are used as biomarkers for kidney disease had stable physicochemical properties, structures and immunoreactivities such that they were not influenced by repetitive freeze-thaw cycles, physical disturbances or long-term storage at −80 °C. However, the ELISA readings tended to change for haemolytic, turbid and unsealed serum samples.

Background Minimal change disease (MCD) is a kind of nephrotic syndrome (NS). In this study, we aimed to establish a mathematical diagnostic model based on biological parameters to classify MCD. Methods A total of 798 NS patients were divided into MCD group and control group. The comparison of biological indicators between two groups were performed with t-tests. Logistic regression was used to establish the diagnostic model, and the diagnostic value of the model was estimated using receiver operating characteristic (ROC) analysis. Results Thirteen indicators including Anti-phospholipase A2 receptor (anti-PLA2R) (P = 0.000), Total protein (TP) (P = 0.000), Albumin (ALB) (P = 0.000), Direct bilirubin (DB) (P = 0.002), Creatinine (Cr) (P = 0.000), Total cholesterol (CH) (P = 0.000), Lactate dehydrogenase (LDH) (P = 0.007), High density lipoprotein cholesterol (HDL) (P = 0.000), Low density lipoprotein cholesterol (LDL) (P = 0.000), Thrombin time (TT) (P = 0.000), Plasma fibrinogen (FIB) (P = 0.000), Immunoglobulin A (IgA) (P = 0.008) and Complement 3 (C3) (P = 0.019) were significantly correlated with MCD. Furthermore, the area under ROC curves of CH, HDL, LDL, TT and FIB were more than 0.70. Logistic analysis demonstrated that CH and TT were risk factors for MCD. According to the ROC of “CH+TT”, the AUC was 0.827, with the sensitivity of 83.0% and the specificity of 69.8% (P = 0.000). Conclusion The established diagnostic model with CH and TT could be used for classified diagnosis of MCD.

Diabetic nephropathy is a major cause of chronic kidney disease and end-stage kidney disease. However, so little is known about alterations of the glycopatterns in urine with the development of diabetic nephropathy. Presently, we interrogated glycopatterns in urine specimens using a lectin microarray. The results showed that expression levels of Siaα2-6Gal/GalNAc recognized by SNA exhibited significantly increased tendency with the development of diabetic nephropathy; moreover, SNA blotting indicated glycoproteins (90 kDa, 70 kDa, and 40 kDa) in urine may contribute to this alteration. Furthermore, the glycopatterns of (GlcNAc)2–4 recognized by STL exhibited difference between diabetic and nondiabetic nephropathy. The results of urinary protein microarray fabricated by another 48 urine specimens also indicated (GlcNAc)2–4 is a potential indictor to differentiate the patients with diabetic nephropathy from nondiabetic nephropathy. Furtherly, STL blotting showed that the 50 kDa glycoproteins were correlated with this alteration. In conclusion, our data provide pivotal information to monitor the development of diabetic nephropathy and distinguish between diabetic nephropathy and nondiabetic renal disease based on precise alterations of glycopatterns in urinary proteins, but further studies are needed in this regard.

BACKGROUND: Heparin-induced thrombocytopenia is an immune response mediated by anti-PF4/heparin antibody, which is clinically characterized by thrombocytopenia and thromboembolic events. In this study, a prospective and multi-center clinical investigation 1) determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, 2) identified the related risk factors, and 3) further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients. METHODS: The serum anti-PF4/heparin antibody was measured in 661 patients from nine hemodialysis centers, detected by IgG-specific ELISA and followed by confirmation with excess heparin. Risk factors of these patients were analyzed. Based on a two-year follow-up, the association between the anti-PF4/heparin antibody and bleeding, thromboembolic events, and risk of death in the patients was investigated. RESULTS: 1) The positivity rate of the anti-PF4/heparin antibody in maintenance hemodialysis patients was 5.6%. With diabetes as an independent risk factor, the positivity rate of the anti-PF4/heparin antibody decreased in the patients undergoing weekly dialyses ≥3 times. 2) The positivity rate of the anti-PF4/heparin antibody was not related to the occurrence of clinical thromboembolic events and was not a risk factor for death within two years in maintenance hemodialysis patients. 3) Negativity for the anti-PF4/heparin antibody combined with a reduction of the platelet count or combined with the administration of antiplatelet drugs yielded a significant increase in bleeding events. However, the composite determination of the anti-PF4/heparin antibody and thrombocytopenia, as well as the administration of antiplatelet drugs, was not predictive for the risk of thromboembolic events in the maintenance hemodialysis patients. CONCLUSIONS: A single detection of the anti-PF4/heparin antibody did not predict the occurrence of clinical bleeding, thromboembolic events, or risk of death in the maintenance hemodialysis patients.

BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.