One-Stone-for-Two-Birds Strategy for VSe2 to Enable High Capacity and Long-Life Zinc Storage.

Based on a specific zinc storage mechanism and excellent electronic conductivity, transition metal dichalcogenides, represented by vanadium diselenide, are widely used in aqueous zinc-ion battery (AZIB) energy storage systems. However, most vanadium diselenide cathode materials are presently limited by low specific capacity and poor cycling life. Herein, a simple hydrothermal process has been proposed for obtaining a vanadium diselenide cathode for an AZIB. The interaction of defects and crystal planes enhances zinc storage capacity and reduces the migration energy barrier. Moreover, abundant lamellar structure greatly increases reaction sites and alleviates volume expansion during the electrochemical process. Thus, the as-obtained vanadium diselenide AZIB exhibits an excellent reversible specific capacity of 377 mAh g-1 at 1 A g-1, and ultralong cycle stability of 291 mAh g-1 after 3200 cycles, with a nearly negligible capacity loss. This one-stone-for-two-birds strategy would be expected to be applied to large-scale synthesis of a high-performance zinc-ion battery cathode in the future.

Platelet-rich plasma-derived exosomes boost mesenchymal stem cells to promote peripheral nerve regeneration.

Peripheral nerve injury (PNI) remains a severe clinical problem with debilitating consequences. Mesenchymal stem cell (MSC)-based therapy is promising, but the problems of poor engraftment and insufficient neurotrophic effects need to be overcome. Herein, we isolated platelet-rich plasma-derived exosomes (PRP-Exos), which contain abundant bioactive molecules, and investigated their potential to increase the regenerative capacity of MSCs. We observed that PRP-Exos significantly increased MSC proliferation, viability, and mobility, decreased MSC apoptosis under stress, maintained MSC stemness, and attenuated MSC senescence. In vivo, PRP-Exo-treated MSCs (pExo-MSCs) exhibited an increased retention rate and heightened therapeutic efficacy, as indicated by increased axonal regeneration, remyelination, and recovery of neurological function in a PNI model. In vitro, pExo-MSCs coculture promoted Schwann cell proliferation and dorsal root ganglion axon growth. Moreover, the increased neurotrophic behaviour of pExo-MSCs was mediated by trophic factors, particularly glia-derived neurotrophic factor (GDNF), and PRP-Exos activated the PI3K/Akt signalling pathway in MSCs, leading to the observed phenotypes. These findings demonstrate that PRP-Exos may be novel agents for increasing the ability of MSCs to promote neural repair and regeneration in patients with PNI.

Identification of common and specific fibrosis-related genes in three common chronic kidney diseases.

BACKGROUND: Kidney fibrosis is the common final pathway of virtually all advanced forms of chronic kidney disease (CKD) including diabetic nephropathy (DN), IgA nephropathy (IgAN) and membranous nephropathy (MN), with complex mechanism. Comparative gene expression analysis among these types of CKD may shed light on its pathogenesis. Therefore, we conducted this study aiming at exploring the common and specific fibrosis-related genes involved in different types of CKD. METHODS: Kidney biopsy specimens from patients with different types of CKD and normal control subjects were analyzed using the NanoString nCounter® Human Fibrosis V2 Panel. Genes differentially expressed in all fibrotic DN, IgAN and MN tissues compared to the normal controls were regarded as the common fibrosis-related genes in CKD, whereas genes exclusively differentially expressed in fibrotic DN, IgAN or MN samples were considered to be the specific genes related to fibrosis in DN, IgAN and MN respectively. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of the selected genes. RESULTS: Protein tyrosine phosphatase receptor type C (PTPRC), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), interleukin 10 receptor alpha (IL10RA) and CC chemokine receptor 2 (CCR2) were identified as the potential common genes for kidney fibrosis in different types of CKD, while peroxisome proliferator-activated receptor alpha (PPARA), lactate oxidase (LOX), secreted phosphoprotein 1 (SPP1) were identified as the specific fibrosis-associated genes for DN, IgAN and MN respectively. qRT-PCR demonstrated that the expression levels of these selected genes were consistent with the NanoString analysis. CONCLUSIONS: There were both commonalities and differences in the mechanisms of fibrosis in different types of CKD, the commonalities might be used as the common therapeutic targets for kidney fibrosis in CKD, while the differences might be used as the diagnostic markers for DN, IgAN and MN respectively. Inflammation was highly relevant to the pathogenesis of fibrosis. This study provides further insight into the pathophysiology and treatment of fibrotic kidney disease.

Knowledge mapping of UMOD of English published work from 1985 to 2022: a bibliometric analysis.

BACKGROUND: UMOD is exclusively produced by renal epithelial cells. Recent genome-wide association studies (GWAS) suggested that common variants in UMOD gene are closely connected with the risk of CKD. However, a comprehensive and objective report on the current status of UMOD research is lacking. Therefore, we aim to conduct a bibliometric analysis to quantify and identify the status quo and trending issues of UMOD research in the past. METHODS: We collected data from the Web of Science Core Collection database and used the Online Analysis Platform of Literature Metrology, the Online Analysis Platform of Literature Metrology and Microsoft Excel 2019 to perform bibliometricanalysis and visualization. RESULTS: Based on the data from the WoSCC database from 1985 to 2022, a total of 353 UMOD articles were published in 193 academic journals by 2346 authors from 50 different countries/regions and 396 institutions. The United States published the most papers. Professor Devuyst O from University of Zurich not only published the greatest number of UMOD-related papers but also is among the top 10 co-cited authors. KIDNEY INTERNATIONAL published the most necroptosis studies, and it was also the most cited journal. High-frequency keywords mainly included 'chronic kidney disease', 'Tamm Horsfall protein' and 'mutation'. CONCLUSIONS: The number of UMOD-related articles has steadily increased over the past decades Current UMOD studies focused on Biological relevance of the UMOD to kidney function and potential applications in the risk of CKD mechanisms, these might provide ideas for further research in the UMOD field.

CuCl2-Activated Sustainable Microporous Carbons with Tailorable Multiscale Pores for Effective CO2 Capture.

Porosity is the key factor in determining the CO2 capture capacity for porous carbon-based adsorbents, especially narrow micropores of less than 1.0 nm. Unfortunately, this desired feature is still a great challenge to tailor micropores by an effective, low-corrosion, and environmentally friendly activating agent. Herein, we reported a suitable dynamic porogen of CuCl2 to engineer microporous carbons rich in narrow micropores of <1.0 nm for solving the above problem. The porosity can be easily tuned by varying the concentration of the CuCl2 porogen. The resultant porous carbons exhibited a multiscale micropore size, high micropore volume, and suitable surface nitrogen doping content, especially high-proportioned ultromicropores of <0.7 nm. As adsorbents for capturing CO2, the obtained microporous carbons possess satisfactory CO2 uptake, moderate heat of CO2 adsorption, reasonable CO2/N2 selectivity, and easy regeneration. Our work proposes an alternative way to design porous carbon-based adsorbents for efficiently capturing CO2 from the postcombustion flue gases. More importantly, this work opens up an almost-zero cost and industrially friendly route to convert biowaste into high-added-value adsorbents for CO2 capture in an industrial practical application.

An investigation of the growth status of 19-year-old Idesia polycarpa 'Yuji' plantation forest in the mountainous region of Henan, China.

Plantation forests play an important role in the mitigation of greenhouse gas emissions. Idesia polycarpa Maxim is an emerging woody oil tree species in most Asian countries. The 19-year-old Idesia polycarpa 'Yuji' plantation forest was selected as a sample site. The nutrient contents of the understory soil total carbon (TC), total nitrogen (TN), nitrate nitrogen (NN), organic carbon (OC), available phosphorus (AP), available potassium (AK), and pH were analyzed. Several metrics were measured to quantify the growth status of the forest, such as tree heights (H), clear bole heights (CBH), diameters at breast height (DBH), and male-to-female ratios (MFR). In addition, we harvested the fruits to analyze oil content and fatty acid composition. The results found that the nutrient content of the soil was TC (4.93%), TN (0.42%), NN (43.08 mg kg-1), OC (4.90 g kg-1), AP (13.66 mg kg-1), AK (30.48 mg kg-1), and pH (7.90). The growth characteristics were H (11.75 m), DBH (12.79 cm), and CBH (6.17 m). The MFR was close to 1:1. Besides, the oil content of the fruit and unsaturated fatty acids was 24.08% and 68.49%, respectively. As an alternative tree species, the plantation of Idesia polycarpa offers great potential in artificial afforestation in some particular places with specific forest site conditions.

Portable Electrochemical Sensor for Micromotor Speed Monitoring.

Autonomous movement promotes practical applications of micromotors. Understanding the moving speeds is a crucial step in micromotor studies. The current analysis method relies on an expensive optical microscope, which is limited to laboratory settings. Herein, we have developed a lightweight (0.15 g), portable (2.0 × 3.5 cm2), and low-cost (approximately $0.26) micromotor sensor (µ-Motor sensor), composed of water-sensitive materials for micromotor speed monitoring. Moving micromotors induce fluid flow, enhancing the evaporation rate of the liquid medium. Consequently, a high correlation between motor speed and water molecule concentration above the moving medium has been established. The µ-Motor sensor enables a real-time readout of the moving speed in various settings, with high accuracy (≥95% in the lab and ≥90% in field studies at a local beach). The µ-Motor sensor opens up a new way for detecting micro/nanomachine movements, illuminating future applications of micro/nanorobotics for diverse scenarios.

Eight Typical Aroma Compounds of 'Panguxiang' Pear during Development and Storage Identified via Metabolomic Profiling.

Aroma is an appreciated fruit property, and volatile flavor plays a key role in determining the perception and acceptability of fruit products by consumers. However, metabolite composition that contributes to the aroma in fruit quality is unclear. In this study, we detected 645 volatile organic compounds of 'Panguxiang' pear in total, including esters, alcohols, alkanes, acids, ketones, terpenes and aldehydes. In addition, the levels of sugars, organic acids and amino acids in 'Panguxiang' pear were investigated using high-performance liquid chromatography. In the aroma generation, glucose was the dominant sugar, followed by sucrose and fructose. At the development transferred storage stage, organic acids may not participate in aroma biosynthesis. The amino acids that may play potential roles in aroma substance synthesis are tyrosine and glycine. Through metabolomics analysis at different stages of 'Panguxiang' pear, we selected 65 key metabolites that were significantly related to glucose, sucrose, fructose, tyrosine and glycine, according to the trends of metabolite concentrations. Finally, we chose eight candidate metabolites (e.g., three esters, two aldehydes, one alcohol, one acid and one ketone) as the representative aroma substances of the 'Panguxiang' pear compared to the metabolome of the 'Korla' at stage Z5. Data and results from this study can help better understand the variations in aroma quality among pear varieties and assist in developing breeding programs for pear varieties.

A Simple Nomogram for Predicting Hospital Mortality of Patients Over 80 Years in ICU: An International Multicenter Retrospective Study.

OBJECTIVES: This study aimed to develop and validate an easy-to-use intensive care unit (ICU) illness scoring system to evaluate the in-hospital mortality for very old patients (VOPs, over 80 years old). METHODS: We performed a multicenter retrospective study based on the electronic ICU (eICU) Collaborative Research Database (eICU-CRD), Medical Information Mart for Intensive Care Database (MIMIC-III CareVue and MIMIC-IV), and the Amsterdam University Medical Centers Database (AmsterdamUMCdb). Least Absolute Shrinkage and Selection Operator regression was applied to variables selection. The logistic regression algorithm was used to develop the risk score and a nomogram was further generated to explain the score. RESULTS: We analyzed 23 704 VOPs, including 3 726 deaths (10 183 [13.5% mortality] from eICU-CRD [development set], 12 703 [17.2%] from the MIMIC, and 818 [20.8%] from the AmsterdamUMC [external validation sets]). Thirty-four variables were extracted on the first day of ICU admission, and 10 variables were finally chosen including Glasgow Coma Scale, shock index, respiratory rate, partial pressure of carbon dioxide, lactate, mechanical ventilation (yes vs no), oxygen saturation, Charlson Comorbidity Index, blood urea nitrogen, and urine output. The nomogram was developed based on the 10 variables (area under the receiver operating characteristic curve: training of 0.792, testing of 0.788, MIMIC of 0.764, and AmsterdamUMC of 0.808 [external validating]), which consistently outperformed the Sequential Organ Failure Assessment, acute physiology score III, and simplified acute physiology score II. CONCLUSIONS: We developed and externally validated a nomogram for predicting mortality in VOPs based on 10 commonly measured variables on the first day of ICU admission. It could be a useful tool for clinicians to identify potentially high risks of VOPs.

Optimization strategies of mesenchymal stem cell-based therapy for acute kidney injury.

Considering the high prevalence and the lack of targeted pharmacological management of acute kidney injury (AKI), the search for new therapeutic approaches for it is in urgent demand. Mesenchymal stem cells (MSCs) have been increasingly recognized as a promising candidate for the treatment of AKI. However, clinical translation of MSCs-based therapies is hindered due to the poor retention and survival rates as well as the impaired paracrine ability of MSCs post-delivery. To address these issues, a series of strategies including local administration, three-dimensional culture, and preconditioning have been applied. Owing to the emergence and development of these novel biotechnologies, the effectiveness of MSCs in experimental AKI models is greatly improved. Here, we summarize the different approaches suggested to optimize the efficacy of MSCs therapy, aiming at promoting the therapeutic effects of MSCs on AKI patients.

Diversity Analysis of Leaf Nutrient Endophytes and Metabolites in Dioecious Idesia polycarpa Maxim Leaves during Reproductive Stages.

Leaves are essential vegetative organs of plants. Studying the variations in leaf nutrient content and microbial communities of male and female plants at reproductive stages helps us understand allocation and adaptation strategies. This study aimed to determine the nutrient characteristics and microbial differences in the leaves of male and female Idesia polycarpa at reproductive stages. Seven-year-old female and male plants were used as test materials in this experiment. The samples were collected at three stages: flowering (May), fruit matter accumulation (July), and fruit ripening (October). The nitrogen (TN), phosphorus (TP), potassium (TK), carbon (TC), and the pH of the female and male leaves were analyzed. In addition, the leaf microbial diversity and differential metabolites were determined using the Illumina high-throughput sequencing method and the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method at the reproductive developmental stages. This study found that male and female plant leaves had different TN and TK contents over time but no difference in TC and TP content. The significant differences in bacterial diversity between male and female plants and the richness of the fungi of male plants at the flowering and fruit maturity stages were observed. Proteobacteria, Pseudomonadaceae, Ascomycota, and Aspergillus were the dominant bacteria and fungi in the Idesia polycarpa leaves. The presence of microorganisms differed in the two sexes in different periods. Alphaproteobacteria and Sordariomycetes were the indicator groups for male leaves, and Pseudomonas and Sordariomycetes were the indicator groups for female leaves. Significant differences in phenolic acid were found between male and female leaves. A KEGG enrichment analysis revealed that differential metabolites were enriched in metabolic pathways, amino acid biosynthesis, and the nucleotide metabolism. According to a correlation analysis, leaf TK and TP were strongly correlated with endophytic bacteria abundance and differential metabolite composition. This study revealed the changes in substances and microorganisms in the leaves of male and female plants in their reproductive stages. It provides a theoretical basis for developing and utilizing the leaves of Idesia polycarpa and for field management.

Evaluation of soil and water conservation function in the Wugong mountain meadow based on the comprehensive index method.

Wugong Mountain meadow landscape is well-known both at home and abroad because of its ornamental value. Our study aimed to comprehensively evaluate the function of soil and water conservation at different altitudes of Wugong Mountain meadow soil. The hydro-physical characteristics, including the soil bulk density, porosity, water content, water holding capacity, and permeability of meadow soil at 1600 m-1900 m altitudes, were analyzed. The results showed that the mountain meadow soil's hydro-physiological characteristics and water conservation function significantly differed with altitude. However, the trend of each index did not follow the same law with altitude change. There was a decrease in bulk density of the soil from 1700 m to 1900 m, but a significant increase in porosity and water-holding capacity. Despite the higher porosity and water holding capacity found at 1600 m than at 1700 m and 1800 m, a similar bulk density was found at 1600 m as 1700 m. In addition, the bulk density in the 0-20 cm layer was lower than that in the 20-40 cm layer, while the porosity and water-holding capacity were higher. A higher sequence of soil water conservation capacity was found in soil layers 0-20 cm depth at 1900, 1600, 1800, and 1700 m; in soil layers 20-40 cm depth, it was at 1900, 1800, 1700, and 1600 m. The study found that the sequence of the comprehensive performance of soil water conservation function was at 1900, 1600, 1800, and 1700 m altitudes in the Wugong mountain meadow area. Our comprehensive study of soil water conservation capacity provides a theoretical basis for the rational use of mountain meadow resources in subtropical regions.

Interaction of RARRES1 with ICAM1 modulates macrophages to suppress the progression of kidney renal clear cell carcinoma.

Background: RARRES1 is a tumor suppressor protein, and its expression is suppressed in various tumor cells. However, whether it participates in the immune response in kidney renal clear cell carcinoma (KIRC) is unknown, and the defined mechanism is not clear. Therefore, the mechanism of RARRES1 in KIRC is worthy of investigation. Methods: We analysed the expression and function of RARRES1 with The Cancer Genome Atlas (TCGA) database. The Kaplan-Meier curve was adopted to estimate survival. RARRES1-correlated genes were obtained from the UALCAN database and subjected to Gene Ontology (GO) enrichment and protein-protein interaction (PPI) network analyses. The correlation analysis between tumor-infiltrating immune cells and selected genes were performed with TIMER database. We also investigated the possible function of RARRES1 in KIRC by coculturing Caki-1 cells with THP-1 cells. Immunofluorescence assay was performed to study the RARRES1 expression in difference grade KIRC tissues. Results: The expression of RARRES1 was negatively correlated with survival in KIRC patients. The GO biological process term most significantly enriched with the RARRES1-correlated genes was regulation of cell adhesion. ICAM1, which exhibited a relatively highest correlation with RARRES1, is positively correlated with the infiltration level of macrophages. RARRES1 could enhance the expression of ICAM1 in Caki-1 cells and then induce the activation of M1 THP-1 cells to decrease the viability and induce the apoptosis of Caki-1 cells. Conclusion: RARRES1 plays an antitumor role by promoting ICAM1 expression and inducing the activation of M1 macrophages. We offer insights into the molecular mechanism of KIRC and reveal a potential therapeutic target.

Customizable assembly of free-standing integrated electronics for wearables by phase separation.

The non-solvent induced phase separation method is utilized to produce a free-standing electrode with good conductivity retention during 1000 bending/stretching cycles. The as-prepared electrode has been fabricated for an integrated device consisting of an ethanol fuel cell, a supercapacitor and a motion sensor. This method for fabricating free-standing electronics reveals a cost-effective approach towards wearable devices.

The Molecular Network behind Volatile Aroma Formation in Pear (Pyrus spp. Panguxiang) Revealed by Transcriptome Profiling via Fatty Acid Metabolic Pathways.

Pears are popular table fruits, grown and consumed worldwide for their excellent color, aroma, and taste. Volatile aroma is an important factor affecting fruit quality, and the fatty acid metabolism pathway is important in synthesizing volatile aromas. Most of the white pear varieties cultivated in China are not strongly scented, which significantly affects their overall quality. Panguxiang is a white pear cultivar, but its aroma has unique components and is strong. The study of the mechanisms by which aroma is formed in Panguxiang is, therefore, essential to improving the quality of the fruit. The study analyzed physiological and transcriptome factors to reveal the molecular network behind volatile aroma formation in Panguxiang. The samples of Panguxiang fruit were collected in two (fruit development at 60, 90, 120, and 147 days, and fruit storage at 0, 7, 14, 21, and 28 days) periods. A total of nine sample stages were used for RNA extraction and paired-end sequencing. In addition, RNA quantification and qualification, library preparation and sequencing, data analysis and gene annotation, gene co-expression network analysis, and validation of DEGs through quantitative real-time PCR (qRT-;PCR) were performed in this study. The WGCNA identified yellow functional modules and several biological and metabolic pathways related to fatty acid formation. Finally, we identified seven and eight hub genes in the fatty acid synthesis and fatty acid metabolism pathways, respectively. Further analysis of the co-expression network allowed us to identify several key transcription factors related to the volatile aroma, including AP2/ERF-ERF, C3H, MYB, NAC, C2H2, GRAS, and Trihelix, which may also be involved in the fatty acid synthesis. This study lays a theoretical foundation for studying volatile compounds in pear fruits and provides a theoretical basis for related research in other fruits.

Long-Life Aqueous Zinc-Ion Batteries of Organic Iminodianthraquinone/rGO Cathode Assisted by Zn2+ Binding with Adjacent Molecules.

Organic compounds have been extensively used as zinc-ion battery (ZIB) cathodes due to their high capacities and outstanding properties. Nevertheless, poor electrical conductivity limits their developments. RGO (reduced graphene oxide) can well interact with organic compounds through π-π stacking for furnishing capacious ion diffusion paths and active sites to enhance conductivity and capacity. Herein, a 1,1'-iminodianthraquinone (IDAQ)/rGO composite is utilized as cathode of ZIBs, demonstrating ultrahigh stability with 96% capacity retention after 5000 cycles. Zn2+ and H+ synergetic mechanism in IDAQ/rGO has been deeply discussed by ex situ analysis and theoretical calculation. Consequently, the structure of IDAQ2(H+)6(Zn2+) is the most probable product after discharging progress. Prospectively, the IDAQ/rGO material with excellent stability and good performance would provide new insights into designing advanced ZIBs.

Highly Selective Wearable Alcohol Homologue Sensors Derived from Pt-Coated Truncated Octahedron Au.

Unhealthy alcohol inhalation is among the top 10 causes of preventable death. However, the present alcohol sensors show poor selectivity among alcohol homologues. Herein, Pt-coated truncated octahedron Au (Ptm@Auto) as the electrocatalyst for a highly selective electrochemical sensor toward alcohol homologues has been designed. The alcohol sensor is realized by distinguishing the electro-oxidation behavior of methanol (MeOH), ethanol (EtOH), or isopropanol (2-propanol). Intermediates from alcohols are further oxidized to CO2 by Ptm@Auto, resulting in different oxidation peaks in cyclic voltammograms and successful distinction of alcohols. Ptm@Auto is then modified on wearable glove-based sensors for monitoring actual alcohol samples (MeOH fuel, vodka, and 2-propanol hand sanitizer), with good mechanical performance and repeatability. The exploration of the Ptm@Auto-based wearable alcohol sensor is expected to be suitable for environmental measurement with high selectivity for alcohol homologues or volatile organic compounds.

Soil Quality Assessment in Tourism-Disturbed Subtropical Mountain Meadow Areas of Wugong Mountain, Central Southeast China.

Meadow soil is a vital ecosystem component and can be influenced by meadow vegetation. Evaluating soil quality in mountain meadows subjected to different levels of tourism disturbance is essential for scientific research, ecological restoration, and sustainable management. This study aimed to evaluate meadow soil quality at different tourism-disturbance levels and attempted to establish a minimum data set (MDS) with compatible indicators for soil quality assessment of subtropical mountain meadows. We analyzed fifteen soil physical, chemical, and biological indicators in control check (CK), light disturbance (LD), medium disturbance (MD), and severe disturbance (SD) meadow areas in Wugong Mountain, west of Jiangxi, China. In addition, a soil quality index (SQI) was determined using the established MDS based on the integrated soil quality index. Average soil permeability, soil pH, available nitrogen (AN), available phosphorus (AP), and number of fungal OTUs were finally introduced into the MDS to evaluate meadow soil quality at different tourism-disturbance levels. The study found that the soil of the Wugong Mountain meadow was acidic, the bulk density was loose, and the nutrient content was rich. Additionally, SQI decreased with increase in tourism-disturbance level. The mean SQI values of the Wugong Mountain meadow areas were: CK, 0.612; LD, 0.493; MD, 0.448; and SD, 0.416. Our results demonstrate that the SQI based on the MDS method could be a valuable tool with which to indicate the soil quality of mountain meadow areas, and the SQI can be regarded as a primary indicator of ecological restoration and sustainable management.

Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis.

Introduction: Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia. Methods: We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis. Results: Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = -0.01, 95% confidence interval (CI) = -0.38, 0.35, p = 0.95; MD = 0.15, 95% CI = -0.29, 0.60, p = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients (p < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, p = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, p = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result. Conclusion: Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.

IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis.

Renal inflammation is a critical pathophysiological characteristic of diabetic kidney disease (DKD). The mechanism of the inflammatory response is complicated, and there are few effective treatments for renal inflammation that can be used clinically. Insulin-like growth factor-binding protein 5 (IGFBP5) is an important secretory protein that is related to inflammation and fibrosis in several tissues. Studies have shown that the IGFBP5 level is significantly upregulated in DKD. However, the function of IGFBP5 and its mechanism in DKD remain unclear. Here, we showed that IGFBP5 levels were significantly increased in the kidneys of diabetic mice. Ablation of IGFBP5 alleviated kidney inflammation in DKD mice. Mechanistically, IGFBP5 increased glycolysis, which was characterized by increases in lactic acid and the extracellular acidification rate, by activating the transcription factor early growth response 1 (EGR1) and enhancing the expression of PFKFB3 in endothelial cells. Furthermore, a mutation in PFKFB3 attenuated renal inflammation in DKD mice. Taken together, we provided evidence that IGFBP5 enhanced kidney inflammation through metabolic reprogramming of glomerular endothelial cells. Our results provide new mechanistic insights into the effect of IGFBP5 on kidney and highlight potential therapeutic opportunities for IGFBP5 and the metabolic regulators involved in DKD.