Annexin A1 may contribute to the morphological changes in podocytes by mediating endocytic vesicle fusion and transport via promotion of SNARE assembly in idiopathic membranous nephropathy.

BACKGROUND: Annexin A1 is a membrane-associated calcium-binding protein that participates in the progression of many diseases by facilitating vesicle aggregation. It has been documented that reducing vesicle formation alleviates podocyte injury and albuminuria in idiopathic membranous nephropathy (IMN). However, the role of Annexin A1 (ANXA1) in IMN is unknown. METHODS: Electron microscopy was used to observe the numbers of vesicles in podocytes. The expression of ANXA1 in IMN was investigated by bioinformatics analysis. We validated the hub genes with the Nephroseq V5 online tool and microarray data from the GEO. Immunohistochemical staining and qPCR were performed to measure gene and protein expression. RESULTS: The numbers of vesicles in IMN podocytes were significantly increased. Bioinformatics analysis showed that ANXA1, one of the differentially expressed genes, was upregulated in glomeruli from IMN patients. In the validation database and dataset, we confirmed that ANXA1 expression was upregulated in the glomeruli of IMN patients. We revealed that the increased expression of ANXA1 was negatively correlated with the glomerular filtration rate (GFR) and proteinuria. Moreover, ANXA1 was enriched in the biological process of vesicle fusion, in which the expression of SNAREs and the SNARE complex was increased. Finally, the expression of ANXA1 and genes related to SNAREs and the SNARE complex was upregulated in glomeruli from IMN patients according to immunohistochemical staining and qPCR. CONCLUSION: We conclude that ANXA1 may mediate endocytic vesicle fusion and transport by promoting SNARE assembly, contributing to the morphological changes in podocytes and massive proteinuria in IMN.

Wnt/ß-catenin Pathway Aggravates Renal Fibrosis by Activating PUM2 Transcription to Repress YME1L-mediated Mitochondrial Homeostasis.

Chronic kidney disease (CKD) affects more than 10% of people worldwide and is a leading cause of death. However, the pathogenesis of CKD remains elusive. The oxidative stress and mitochondrial membrane potential were detected using Enzyme-linked immunosorbent assay and JC-1 assay. Co-immunoprecipitation, dual-luciferase assay, chromatin IP, RNA IP and RNA pull-down were used to validate the interactions among genes. Exploiting a H2O2-induced fibrosis model in vitro, PUM2 expression was upregulated in Human kidney 2 cell (HK-2) cells, along with reduced cell viability, enhanced oxidative stress, impaired mitochondrial potential, and upregulated expressions of fibrosis-associated proteins. While PUM2 knockdown reversed the H2O2-induced injury in HK-2 cells. Mechanically, Wnt/ß-catenin pathway activated PUM2 transcription via TCF4. It was further identified that Wnt/ß-catenin pathway inhibited YME1L expression through PUM2-mediated destabilizing of its mRNA. PUM2 aggravated H2O2-induced oxidative stress, mitochondrial dysfunction, and renal fibrosis in HK-2 cell via suppressing YME1L expression. Our study revealed that Wnt/ß-catenin aggravated renal fibrosis by activating PUM2 transcription to repress YME1L-mediated mitochondrial homeostasis, providing novel insights and potential therapeutic targets for the treatment of kidney fibrosis.

DKK3 promotes renal fibrosis by increasing MFF-mediated mitochondrial dysfunction in Wnt/ß-catenin pathway-dependent manner.

BACKGROUND: Chronic kidney disease (CKD) lacks effective treatments and renal fibrosis (RF) is one of CKD's outcomes. Dickkopf 3 (DKK3) has been identified as an agonist in CKD. However, the underlying mechanisms of DKK3 in CKD are not fully understood. METHODS: H2O2-treated HK-2 cells and ureteric obstruction (UUO) mice were used as RF models. Biomarkers, Masson staining, PAS staining, and TUNEL were used to assess kidney function and apoptosis. Oxidative stress and mitochondria function were also evaluated. CCK-8 and flow cytometry were utilized to assess cell viability and apoptosis. Western blotting, IHC, and qRT-PCR were performed to detect molecular expression levels. Immunofluorescence was applied to determine the subcellular localization. Dual luciferase assay, MeRIP, RIP, and ChIP were used to validate the m6A level and the molecule interaction. RESULTS: DKK3 was upregulated in UUO mouse kidney tissue and H2O2-treated HK-2 cells. Knockdown of DKK3 inhibited oxidative stress, maintained mitochondrial homeostasis, and alleviated kidney damage and RF in UUO mice. Furthermore, DKK3 silencing suppressed HK-2 cell apoptosis, oxidative stress, and mitochondria fission. Mechanistically, DKK3 upregulation was related to the high m6A level regulated by METTL3. DKK3 activated TCF4/ß-catenin and enhanced MFF transcriptional expression by binding to its promoter. Overexpression of MFF reversed in the inhibitory effect of DKK3 knockdown on cell damage. CONCLUSION: Upregulation of DKK3 caused by m6A modification activated the Wnt/ß-catenin pathway to increase MFF transcriptional expression, leading to mitochondrial dysfunction and oxidative stress, thereby promoting RF progression.

Moraxella haemolytica sp. nov., isolated from a goat with respiratory disease.

An aerobic, haemolytic, Gram-negative and rod-shaped bacterial strain ZY171148T was isolated from the lung of a dead goat with respiratory disease in Southwest China. The strain grew at 24-39 °C, at pH 6.0-9.0 and in the presence of 0.5-2.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belongs to the genus Moraxella. The nucleotide sequence similarity analysis of the 16S rRNA gene showed that the strain has the highest similarity of 98.1% to Moraxella (M.) caprae ATCC 700019 T. Phylogenomic analysis of 800 single-copy protein sequences indicated that the strain is a member of the genus Moraxella and forms a separated branch on the Moraxella phylogenetic tree. The strain exhibited the highest orthologous average nucleotide identity (OrthoANI) and average amino acid identity (AAI) values of 77.0 and 77.9% to M. nasibovis CCUG 75921T and M. ovis CCUG 354T, respectively. The strain shared the highest digital DNA-DNA hybridization (dDDH) value of 26.2% to M. osloensis CCUG 350T. The genome G + C content of strain ZY171148T was 42.6 mol%. The strain had C18:1 ω9c (41.7%), C18:0 (11.2%), C16:0 (14.1%) and C12:0 3OH (9.7%) as the predominant fatty acids and CoQ-8 as the major respiratory quinone. The strain contained phosphatidylglycerol, phosphatidylethanolamine, cardiolipin, dilysocardiolipin, monolysocardiolipin and phosphatidic acid as the major polar lipids. ß-haemolysis was observed on Columbia blood agar. All results confirmed that strain ZY171148T represents a novel species of the genus Moraxella, for which the name Moraxella haemolytica sp. nov. is proposed, with strain ZY171148T = CCTCC AB 2021471T = CCUG 75920T as the type strain.

DKK3 promotes oxidative stress injury and fibrosis in HK-2 cells by activating NOX4 via ß-catenin/TCF4 signaling.

Oxidative stress and fibrosis may accelerate the progression of chronic kidney disease (CKD). DKK3 is related to regulating renal fibrosis and CKD. However, the molecular mechanism of DKK3 in regulating oxidative stress and fibrosis during CKD development has not been clarified, which deserves to be investigated. Human proximal tubule epithelial cells (HK-2 cells) were treated with H2O2 to establish a cell model of renal fibrosis. The mRNA and protein expressions were analyzed using qRT-PCR and western blot, respectively. Cell viability and apoptosis were evaluated using MTT assay and flow cytometry, respectively. ROS production was estimated using DCFH-DA. The interactions among TCF4, ß-catenin and NOX4 were validated using luciferase activity assay, ChIP and Co-IP. Herein, our results revealed that DKK3 was highly expressed in HK-2 cells treated with H2O2. DKK3 depletion increased H2O2-treated HK-2 cell viability and reduced cell apoptosis, oxidative stress, and fibrosis. Mechanically, DKK3 promoted formation of the ß-catenin/TCF4 complex, and activated NOX4 transcription. Upregulation of NOX4 or TCF4 weakened the inhibitory effect of DKK3 knockdown on oxidative stress and fibrosis in H2O2-stimulated HK-2 cells. All our results suggested that DKK3 accelerated oxidative stress and fibrosis through promoting ß-catenin/TCF4 complex-mediated activation of NOX4 transcription, which could lead to novel molecules and therapeutic targets for CKD.

Clinical and pathological correlation between urinary exosome miR-223 and IgAN patients.

OBJECTIVE: To investigate the association between urine exosome miR-223 and clinical markers with pathological severity of IgA nephropathy (IgAN) in order to offer a new perspective for the evaluation of IgAN patients. MATERIALS AND METHODS: Western blotting and transmission electron microscopy were used to identify the exosomes collected and isolated from subjects' urine. qRT-PCR was then performed to determine the expression level of miR-223. Following that, the relationship between miR-223 expression, clinical markers, and the severity of pathology in IgAN patients was examined. RESULTS: (1) Urine can be used to isolate exosomes since its marker protein was visible by Western blotting, and its size and structure were observable using transmission electron microscopy. (2) Expression levels of miR-223 in urinary exosomes were much higher in IgAN patients than in healthy subjects, and these were also positively correlated with creatinine (Cr) (rho = 0.396; p = 0.006), blood urea nitrogen (BUN) (rho = 0.371; p = 0.011), 24-hour urinary microalbumin (24hU-mALB) (rho = 0.341; p = 0.036), mesangial cell proliferation (rho = 0.359; p = 0.014), glomerular segmental sclerosis (rho = 0.417; p = 0.004), cell/fibroblast crescents (rho = 0.612; p = 0.000), glomerulosclerosis, and renal interstitial fibrosis (rho = 0.331; p = 0.025). CONCLUSION: In urine exosomes, miR-223 might be considered a non-invasive biomarker for the assessment of IgAN disease progression.

Moraxella nasibovis sp. nov., Isolated from a Cow with Respiratory Disease.

Strain ZY190618T, isolated from the nasal cavity of a cow with respiratory disease, was subjected to taxonomic characterization. Cells of the strain were Gram-stain-negative, aerobic and coccus-shaped. Phylogenetic analysis based on 16 S rRNA gene sequences indicated that the strain belonged to the genus Moraxella with the highest similarity of 98.1% to Moraxella nasovis CCUG 75922T. Phylogenomic analysis based on 810 single-copy genes revealed that the strain was a member of the genus Moraxella and formed a deep and separated clade within the genus. The strain showed the highest orthologous average nucleotide identity (OrthoANI) value of 77.1% with Moraxella ovis CCUG 354T and digital DNA-DNA hybridization (dDDH) value of 24.7% with Moraxella equi NCTC 11012T, respectively. The DNA G + C content was 46.5 mol%. The strain optimally grew at 37 °C (temperature range, 24-42 °C), at pH 8.0 (pH range, 6.0-9.0) and with 1.5% (w/v) NaCl (NaCl range, 0.5-3.0%). The strain contained C18:1 ω9c as the sole predominant fatty acid (> 5 %) and CoQ-8 as the major respiratory quinone. The major polar lipids included phosphatidylglycerol, phosphatidylethanolamine, cardiolipin, monolysocardiolipin and hemibismonoacylglycerophosphate. Based on these data, strain ZY190618T clearly represents a novel species in the genus Moraxella, for which the name Moraxella nasibovis sp. nov. (The type strain ZY190618T = CCUG 75921T = CCTCC AB 2021472T) is proposed.

Moraxella nasicaprae sp. nov., Isolated from a Goat with Respiratory Disease.

A novel Gram-stain-negative, aerobic, irregular coccus designated as ZY201224T, was isolated from the nasal cavity of a goat with respiratory disease in a goat farm, located at Jianshui, Yunnan Province, PR China and its taxonomic position was clarified using a polyphasic approach. The strain grew optimally at 37 °C, at pH 8.0 and in the presence of 1% NaCl. Phylogenetic analysis based on 16S rRNA gene sequence and phylogenomic analysis based on 808 single-copy genes revealed that the strain is affiliated to the genus Moraxella and is distinct from the recognized species of the genus. The 16S rRNA gene sequence similarity analysis indicated that the strain is most closely related to Moraxella caviae CCUG 355T with sequence similarity of 98.1%. The genomic OrthoANI and digital DNA-DNA hybridization (dDDH) values between the strain and the type strains of Moraxella species were no higher than 74.7% (Moraxella pluranimalium CCUG 54913T) and 26.0% (Moraxella oblonga NBRC 102422T), respectively. The G + C content of the complete genome sequence was 43.6 mol%. The strain contained CoQ-8 as the major respiratory quinone, and C18:1ω9c, C17:1ω8c, C16:0 and summed feature 3 (C16:1 ω7c and/ or C16:1ω6c) as the predominant fatty acids (> 5%). The major polar lipids comprised phosphatidylglycerol (PG), cardiolipin (CL), monolysocardiolipin (MLCL), phosphatidylethanolamine (PE) and lysophosphatidylglycerol (LPG). Based on these taxonomic characterizations, strain ZY201224T represents a novel species of the genus Moraxella, for which the name Moraxella nasicaprae sp. nov. is proposed. The type strain is ZY201224T (= CCTCC AB 2021474T = NBRC 115473T).

Roles of interferon regulatory factor 4 in the AKI-CKD transition, glomerular diseases and kidney allograft rejection.

Interferon regulatory factor 4 (IRF4) is expressed in immune cells and is a member of the interferon regulatory factor family. Recently, it has been found that IRF4 plays important roles in the acute kidney injury (AKI)-chronic kidney disease (CKD) transition, glomerular diseases and kidney allograft rejection. In particular, the relationship between IRF4 and the AKI-CKD transition has attracted widespread attention. Furthermore, it was also found that the deficiency of IRF4 hindered the transition from AKI to CKD through the suppression of macrophage-to-fibroblast conversion, inhibition of M1-M2 macrophage polarization, and reduction in neutrophil inward flow. Additionally, an examination of the crucial role of IRF4 in glomerular disease was conducted. It was reported that inhibiting IRF4 could alleviate the progression of glomerular disease, and potential physiopathology mechanisms associated with IRF4 were postulated. Lastly, IRF4 was found to have detrimental effects on the development of antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR).

Moraxella nasovis sp. nov., isolated from a sheep with respiratory disease.

A novel Gram-stain-negative, aerobic, coccus-shaped bacteria, designated ZY201115T, was isolated from the nasal cavity of a sheep with respiratory disease in Yunnan Province, south-west China, and its taxonomic affiliation was studied by applying a polyphasic approach. The strain grew at 18-41 °C (optimum, 37 °C), at pH 6.0-9.0 (optimum, pH 8.0) and in 0.5-3.0% (w/v) NaCl (optimum, 1.0 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain is affiliated to the genus Moraxella with highest similarity to Moraxella bovis ATCC 10900T (96.6 %). Phylogenomic analysis based on 811 single-copy genes also indicated that the strain represents a novel species in the genus Moraxella and formed a deep and separated clade with Moraxella caviae NCTC 10293T. The highest genomic orthologous average nucleotide identity and digital DNA-DNA hybridization values between the strain and the type strains in the genus Moraxella were 73.7% (M. caviae NCTC 10293T) and 25.3% (Moraxella osloensis CCUG 350T), respectively. The G+C content of the complete genome sequence was 42.1 mol%. The predominant fatty acids (>5 %) were C18:1 ω9c, C17:1 ω8c, C12:03OH and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major polar lipids were phosphatidylglycerol, cardiolipin, monolysocardiolipin, phosphatidylethanolamine and hemibismonoacylglycerophosphate. The major respiratory quinone was CoQ-8. On the basis of the results of phylogenetic, phenotypic and chemotaxonomic characterizations, strain ZY201115T clearly represents a novel species of the genus Moraxella, for which the name Moraxella nasovis sp. nov. is proposed. The type strain is ZY201115T (=CCTCC AB 2021473T=CCUG 75922T).

MiR-18a-5p Promotes Proliferation, Migration, and Invasion of Endometrial Cancer Cells by Targeting THBD.

The purpose of this study was to elucidate the role that the miR-18a-5p/THBD regulatory pathway plays in endometrial cancer (EC), which could provide a theoretical basis for potential therapeutic targets. Differentially expressed genes in EC tissue and normal tissue were determined by bioinformatics analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to compare the expression of miR-18a-5p and THBD mRNA in normal human endometrial cells and human EC cells. CCK-8 assay was used to compare the proliferative ability of EC cells in different treatment groups. Transwell assay was used to detect the migratory and invasive abilities of EC cells in different treatment groups. Dual-luciferase assay was used to verify the targeting relationship between miR-18a-5p and THBD. Western blot assay was used to detect THBD protein expression level. qRT-PCR results showed that miR-18a-5p was significantly upregulated in EC cells, and expression of its target gene, THBD, was significantly downregulated. CCK-8 and transwell assays showed that miR-18a-5p could enhance the proliferative, migratory, and invasive abilities of EC cells, whereas THBD could weaken those abilities. Dual-luciferase assay confirmed that miR-18a-5p could negatively regulate THBD expression. In addition, rescue experiments revealed that the oncogenic effect of miR-18a-5p on EC cells was inhibited by THBD overexpression. We conclude that miR-18a-5p could promote the proliferation, migration, and invasion of EC cells by targeting and downregulating THBD expression, and the miR-18a-5p/THBD regulatory pathway might be a therapeutic target. The results of this study may serve as a theoretical basis for related drug development.

Physiological responses and transcriptomic changes reveal the mechanisms underlying adaptation of Stylosanthes guianensis to phosphorus deficiency.

BACKGROUND: Phosphorus (P) is an essential macronutrient for plant growth that participates in a series of biological processes. Thus, P deficiency limits crop growth and yield. Although Stylosanthes guianensis (stylo) is an important tropical legume that displays adaptation to low phosphate (Pi) availability, its adaptive mechanisms remain largely unknown. RESULTS: In this study, differences in low-P stress tolerance were investigated using two stylo cultivars ('RY2' and 'RY5') that were grown in hydroponics. Results showed that cultivar RY2 was better adapted to Pi starvation than RY5, as reflected by lower values of relative decrease rates of growth parameters than RY5 at low-P stress, especially for the reduction of shoot and root dry weight. Furthermore, RY2 exhibited higher P acquisition efficiency than RY5 under the same P treatment, although P utilization efficiency was similar between the two cultivars. In addition, better root growth performance and higher leaf and root APase activities were observed with RY2 compared to RY5. Subsequent RNA-seq analysis revealed 8,348 genes that were differentially expressed under P deficient and sufficient conditions in RY2 roots, with many Pi starvation regulated genes associated with P metabolic process, protein modification process, transport and other metabolic processes. A group of differentially expressed genes (DEGs) involved in Pi uptake and Pi homeostasis were identified, such as genes encoding Pi transporter (PT), purple acid phosphatase (PAP), and multidrug and toxin extrusion (MATE). Furthermore, a variety of genes related to transcription factors and regulators involved in Pi signaling, including genes belonging to the PHOSPHATE STARVATION RESPONSE 1-like (PHR1), WRKY and the SYG1/PHO81/XPR1 (SPX) domain, were also regulated by P deficiency in stylo roots. CONCLUSIONS: This study reveals the possible mechanisms underlying the adaptation of stylo to P deficiency. The low-P tolerance in stylo is probably manifested through regulation of root growth, Pi acquisition and cellular Pi homeostasis as well as Pi signaling pathway. The identified genes involved in low-P tolerance can be potentially used to design the breeding strategy for developing P-efficient stylo cultivars to grow on acid soils in the tropics.

Faecalibacter bovis sp. nov., isolated from cow faeces.

A Gram-stain-negative, non-spore-forming, yellow-pigmented, aerobic, pleomorphic rod-shaped bacterium, designated ZY171143T, was isolated from faeces of a cow with diarrhoea in Wenshan, Yunnan Province, south-west China and its taxonomic position was studied. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZY171143T belonged to the family Weeksellaceae and was most closely related to the only species of the genus Faecalibacter, Faecalibacter macacae CCTCC AB 2016016T with a sequence similarity of 97.8 %. The genomic OrthoANI and digital DNA-DNA hybridization values between the strain and F. macacae CCTCC AB 2016016T were 86.2 and 30.5 %, respectively. The genomic G+C content was 31.1 mol%. The predominant fatty acids (>5 %) were C15 : 0 iso, C17 : 0 iso 3OH, C16 : 0, C16 : 1 ω5c and summed feature 3 (C16 : 1 ω7c and/or 16 : 1 ω6c). The major polar lipids were phosphatidylethanolamine, triacylglycerol and sulfonolipid. The sole respiratory quinone was MK-6. These chemotaxonomic characterizations also revealed that strain ZY171143T was a member of the genus Faecalibacter. Based on the phenotypic, chemotaxonomic and genotypic data, strain ZY171143T represents a novel species within the genus Faecalibacter, for which the name Faecalibacter bovis sp. nov. is proposed. The type strain is ZY171143T (=CGMCC 1.13663T=KCTC 62642T).

Suicoccus acidiformans gen. nov., sp. nov., isolated from a sick pig.

A Gram-stain-positive, non-spore-forming, catalase-positive and facultatively anaerobic coccus, designated ZY16052T, was isolated from mesenteric lymph nodes of a sick piglet in Kunming, Yunnan Province, PR China and its taxonomic position was studied by following a polyphasic approach. Optimal growth was observed at 37 °C, pH 8.0 and 2 % NaCl (w/v) on Columbia agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZY16052T formed a separated evolutionary lineage from recognized genera of the family Aerococcaceae and shared low similarity to its closest related species Facklamiasourekii (93.8 %) and Ignavigranum ruoffiae (93.4 %). Phylogenetic analysis based on the housekeeping gene recA indicated that strain ZY16052T represented a deep and distinct evolutionary lineage, and was well separated from all genera in the family Aerococcaceae, with very low sequence similarity(≤73.2 %). Sequence analysis based on the housekeeping gene rpoA indicated that strain ZY16052T shared very low similarity ≤77.0 % to related genera. The genomic OrthoANI values between strain ZY16052T and type species of related genera in the family Aerococcaceae and species in the genus Facklamia were ≤67.77 and ≤68.11 %, respectively. The genomic G+C content was 42.3 mol%. The predominant fatty acids (>5 %) were C16 : 0, C18 : 1ω9c, C14 : 0 and summed feature 5 (C18 : 2ω6,9c and/or C18 : 0 ante). The major polar lipids were digalactosyldiacylglycerol, phosphatidylglycerol, diacylglycerols, triacylglycerol and phosphatidic acid. The peptidoglycan contained the amino acids lysine, glycine, alanine and glutamic acid, which is characteristic of peptidoglycan type A1a. Based on the phylogenetic and phenotypic evidence, we propose that the unknown bacterium be classified as Suicoccus acidiformans gen. nov., sp. nov. The type strain of Suicoccus acidiformans is ZY16052T (=CCTCC AB 2017017T=DSM 105755T).

U-shaped relationship between fasting blood glucose and urinary albumin-to-creatinine ratio in the general United States population.

Objective: The current controversy surrounding the association between fasting blood glucose (FBG) and albuminuria necessitates further investigation. Hence, the primary objective of this study was to examine the relationship between FBG and urinary albumin-to-creatinine ratio (UACR). Methods: A cohort of complete data from National Health and Nutrition Examination Survey (NHANES) participants (1999-2020) was analyzed. Linear regression analyses and a generalized additive model explored the association between FBG and UACR. Furthermore, the stability of this relationship across different populations was assessed. Results: The study involved a total of 20,264 participants who were identified as U.S. citizens. By employing linear regression analysis, a statistically significant relationship was observed between elevated FBG levels and an increase in UACR (P<0.0001). Additionally, using a generalized additive model analysis, a U-shaped correlation between FBG and UACR was identified. Further examination using threshold effect analysis indicated a turning point for FBG at 5.44 mmol/L. A noteworthy finding in multiple populations is the consistent U-shaped association between FBG and UACR, except for individuals with serum uric acid levels ≥420 µmol/L and those who refrain from alcohol consumption. Conclusion: The general U.S. population has a U-shaped nonlinear relationship between FBG and UACR.

Sex disparities in the association between serum cotinine and chronic kidney disease.

INTRODUCTION: Despite the existence of numerous studies highlighting the adverse effects of smoking on kidney function, the investigation of the correlation between serum cotinine and chronic kidney disease (CKD) remains inconclusive due to insufficient evidence. Consequently, the primary objective of this study was to ascertain the association between serum cotinine levels and CKD. METHODS: This study analyzed data from 10900 Americans participating in the National Health and Nutrition Examination Survey between 2005 and 2016. The independent variable under investigation was log serum cotinine, while the dependent variable was the presence of CKD. To investigate the potential linear and non-linear correlations between serum cotinine and CKD, logistic regression models and generalized additive models (GAM) were employed. Furthermore, stratified analyses and interaction tests were conducted to evaluate potential disparities in the relationship between serum cotinine and CKD, based on sex. RESULTS: The median age in the study participants was 49.28 ± 17.96 years, and the median log serum cotinine (ng/mL) was -0.54 ± 1.68. The prevalence of CKD was found to be 17.04%. Multifactorial regression analysis did not show a statistically significant association between log serum cotinine and CKD (OR=1.02; 95% CI: 0.98-1.06, p=0.4387). A statistically significant non-linear association between log serum cotinine and CKD was also not observed in the GAM analysis (p non-linear value=0.091). Subgroup analyses revealed sex differences in the association between log serum cotinine and CKD. Briefly, males had a positive association between log serum cotinine and incident CKD (OR=1.08; 95% CI: 1.02-1.15, p=0.0049). In females, there was a U-shaped association between log serum cotinine and CKD, with an optimal inflection point for log serum cotinine of -0.30 (serum cotinine=0.5 ng/mL). CONCLUSIONS: Cross-sectional analyses of NHANES data showed gender differences in the association between serum cotinine and the development of CKD.

Development of a novel multi-epitope oral DNA vaccine for rabies based on a food-borne microbial vector.

Rabies has been with humans for a long time, and its special transmission route and almost 100 % lethality rate made it once a nightmare for humans. In this study, by predicting the rabies virus glycoprotein outer membrane region and nucleoprotein B-cell antigenic epitopes, the coding sequence of the predicted highly antigenic polypeptide region obtained was assembled using the eukaryotic expression vector pcDNA3.1(-), and then E. coli was used as the delivery vector. The immunogenicity and protective properties of the vaccine were verified by in vivo and in vitro experiments, which demonstrated that the vaccine could produce antibodies in mice and prolong the survival time of mice exposed to the strong virus without any side effects. This study demonstrated that the preparation of an oral rabies DNA vaccine using food-borne microorganisms as a transport vehicle is feasible and could be a new strategy to eradicate rabies starting with wild animals.

Association of nocturia of self-report with estimated glomerular filtration rate: a cross-sectional study from the NHANES 2005-2018.

Nocturia is a manifestation of systemic diseases, in which chronic kidney disease (CKD) is an independent predictor of nocturia due to its osmotic diuretic mechanism. However, to our knowledge, previous studies have not examined the association between nocturia and estimated glomerular filtration rate (eGFR). The purpose of this study was to assess the association between nocturia exposure and eGFR in the general US population. This study presents a cross-sectional analysis of the general US population enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. To account for potential confounding factors, linear regression analysis was conducted to investigate the association between nocturia and eGFR. Stratified analyses and interaction tests were employed to examine the variables of interest. Additionally, sensitivity analyses were conducted across diverse populations. A total of 12,265 individuals were included in the study. After controlling for confounding factors, the results of the linear regression analysis indicated that a single increase in nocturnal voiding frequency was associated with a decrease in eGFR by 2.0 mL/min/1.73 m2. In comparison to individuals with a nocturnal urinary frequency of 0, those who voided 1, 2, 3, 4, and ≥ 5 times at night experienced a decrease in eGFR by 3.1, 5.4, 6.4, 8.6 and 4.0 mL/min/1.73 m2, respectively. Nocturia was found to be associated with a decreased eGFR of 4 mL/min/1.73 m2 when compared to individuals without nocturia. The sensitivity analysis yielded consistent findings regarding the association between nocturia and eGFR in both CKD and non-CKD populations, as well as in hypertensive and non-hypertensive populations. Nevertheless, inconsistent conclusions were observed across various prognostic risk populations within the CKD context. The presence of nocturia and heightened frequency of nocturnal urination have been found to be associated with a decline in eGFR.

Inverted U-shaped relationship between coffee consumption and serum uric acid in American chronic kidney disease population.

Objective: The objective of this study was to examine the contentious relationship between coffee consumption and serum uric acid (SUA) levels, specifically within American population with chronic kidney disease (CKD). Methods: A total of 23,381 participants from the 2001-2018 National Health and Nutrition Examination Survey (NHANES) were selected for inclusion in this investigation. Linear regression models and generalized additive models with smooth curve fitting were employed to analyze the association between log coffee consumption and serum uric acid levels. Furthermore, the robustness of the findings was assessed across diverse populations. Results: The results of the linear regression analysis indicate a positive and marginally statistically significant (p = 0.0307) association between log coffee consumption and SUA, even after controlling for other variables. Furthermore, the generalized additive model revealed a nonlinear relationship characterized by an inverted U-shape between log coffee consumption and SUA. The inflection point, identified as 11.43 g/day, marks the point at which this relationship changes direction. Moreover, this inverted U-shaped relationship was consistently observed across various subgroups, including gender, age (<60 and ≥ 60 years), hypertensive and non-hypertensive individuals, those with and without cardiovascular disease, non-diabetic individuals, and those who consumed coffee with or without caffeine or sugar. Conclusion: An inverse U-shaped correlation has been observed between log coffee consumption and SUA levels. This finding implies that once coffee consumption surpasses a specific threshold, it promotes a decline in SUA levels.

Identification of immune-related molecular clusters and diagnostic markers in chronic kidney disease based on cluster analysis.

Background: Chronic kidney disease (CKD) is a heterogeneous disease with multiple etiologies, risk factors, clinical manifestations, and prognosis. The aim of this study was to identify different immune-related molecular clusters in CKD, their functional immunological properties, and to screen for promising diagnostic markers. Methods: Datasets of 440 CKD patients were obtained from the comprehensive gene expression database. The core immune-related genes (IRGs) were identified by weighted gene co-expression network analysis. We used unsupervised clustering to divide CKD samples into two immune-related subclusters. Then, functional enrichment analysis was performed for differentially expressed genes (DEGs) between clusters. Three machine learning methods (LASSO, RF, and SVM-RFE) and Venn diagrams were applied to filter out 5 significant IRGs with distinguished subtypes. A nomogram diagnostic model was developed, and the prediction effect was verified using calibration curve, decision curve analysis. CIBERSORT was applied to assess the variation in immune cell infiltration among clusters. The expression levels, immune characteristics and immune cell correlation of core diagnostic markers were investigated. Finally, the Nephroseq V5 was used to assess the correlation among core diagnostic markers and renal function. Results: The 15 core IRGs screened were differentially expressed in normal and CKD samples. CKD was classified into two immune-related molecular clusters. Cluster 2 is significantly enriched in biological functions such as leukocyte adhesion and regulation as well as immune activation, and has a severe immune prognosis compared to cluster 1. A nomogram diagnostic model with reliable prediction of immune-related clusters was developed based on five signature genes. The core diagnostic markers LYZ, CTSS, and ISG20 were identified as playing an important role in the immune microenvironment and were shown to correlate meaningfully with immune cell infiltration and renal function. Conclusion: Our study identifies two subtypes of CKD with distinct immune gene expression patterns and provides promising predictive models. Along with the exploration of the role of three promising diagnostic markers in the immune microenvironment of CKD, it is anticipated to provide novel breakthroughs in potential targets for disease treatment.