USP25 attenuates anti-GBM nephritis in mice by negative feedback regulation of Th17 cell differentiation.

PURPOSE: This study aimed to elucidate the role of USP25 in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). METHODS: USP25-deficient anti-GBM GN mice were generated, and their nephritis progression was monitored. Naïve CD4+ T cells were isolated from spleen lymphocytes and stimulated to differentiate into Th1, Th2, and Th17 cells. This approach was used to investigate the impact of USP25 on CD4+ T lymphocyte differentiation in vitro. Furthermore, changes in USP25 expression were monitored during Th17 differentiation, both in vivo and in vitro. RESULTS: USP25-/- mice with anti-GBM GN exhibited accelerated renal function deterioration, increased infiltration of Th1 and Th17 cells, and elevated RORγt transcription. In vitro experiments demonstrated that USP25-/- CD4+ T lymphocytes had a higher proportion for Th17 cell differentiation and exhibited higher RORγt levels upon stimulation. Wild-type mice with anti-GBM GN showed higher USP25 levels compared to healthy mice, and a positive correlation was observed between USP25 levels and Th17 cell counts. Similar trends were observed in vitro. CONCLUSION: USP25 plays a crucial role in mitigating renal histopathological and functional damage during anti-GBM GN in mice. This protective effect is primarily attributed to USP25's ability to inhibit the differentiation of naïve CD4+ T cells into Th17 cells. The underlying mechanism may involve the downregulation of RORγt. Additionally, during increased inflammatory responses or Th17 cell differentiation, USP25 expression is activated, forming a negative feedback regulatory loop that attenuates immune activation.

Research on Flesh Texture and Quality Traits of Kiwifruit (cv. Xuxiang) with Fluctuating Temperatures during Cold Storage.

Kiwifruits are often exposed to various temperature fluctuations (TFs) during postharvest transportation and storage. To evaluate the effect of TFs on the qualities of kiwifruits during storage, kiwifruits were stored at 2 °C, 2 °C or 5 °C (TF2 °C-5 °C, alternating every 12 h), 2 °C or 7 °C (TF2 °C-7 °C, alternating every 12 h) for 3 d before long time storage at 2 °C. Observations revealed that kiwifruits stored at a constant 2 °C showed the lowest loss of weight and vitamin C because of minimized ethylene production and respiratory rate compared with that of TF2 °C-5 °C and TF2 °C-7 °C. Moreover, the results of RT-qPCR verified that the expression levels of genes encoding polygalacturonase, ß-galacturonidase, and pectin methylesterase were significantly increased by the treatment of TF. Hence, TF accelerated the degradation of cell walls, softening, translucency, and relative conductivity of the flesh of kiwifruits. In addition, the impact of TF2 °C-7 °C on kiwifruits was more significant relative to TF2 °C-5 °C. The present study provides a theoretical basis for kiwifruit during cold storage.

Designing of a functional paper-tip substrate for sensitive surface-enhanced Raman spectroscopy (SERS) detection.

A simple and flexible fabrication method of paper SERS substrate was developed by nanoparticles (NPs) droplet self-assembly at the paper tip with a temperature gradient (PTTG). We turned the drawback of the coffee ring effect into an effective way of preparing paper SERS substrate. When the NPs droplets were continuously dripped onto the PTTG, NPs were densely and uniformly distributed at the paper-tip front based on the combination of gravity and the coffee ring effect, which could achieve 91.2-fold improvement of SERS performance compared to a flat filter paper. Meanwhile, the analytes could also be enriched at the paper-tip front, which could achieve 9.3-fold signal enhancement compared to the paper-tip tail. Thus, the PTTG realized an excellent signal amplification for SERS detection. The paper-tip SERS substrate combined with a portable Raman spectrometer yielded an excellent analytical enhancement factor of 1.15 × 105 with the detection limit of 10 nM Rhodamine 6G (R6G). The whole fabrication procedure was completed within 2 h, and the paper-tip substrate showed a satisfactory substrate-to-substrate reproducibility with a relative standard deviation (RSD) of 5.13% (n = 10). It was successfully applied for quantitatively detecting real samples of oxytetracycline and malachite green with recoveries of 83.84-105.25% (n = 3). Meanwhile, we further evaluated the SERS performance of the PTTG using a laboratory-based Raman spectrometer, and it could realize the detection as low as 10 pM R6G. The proposed paper-tip substrate would offer a promising potential application for the on-site SERS analysis of food safety and environmental health.

Integrated Microfluidic Chip for Rapid Antimicrobial Susceptibility Testing Directly from Positive Blood Cultures.

Rapid and accurate antimicrobial prescriptions are critical for bloodstream infection (BSI) patients, as they can guide drug use and decrease mortality significantly. The traditional antimicrobial susceptibility testing (AST) for BSI is time-consuming and tedious, taking 2-3 days. Avoiding lengthy monoclonal cultures and shortening the drug sensitivity incubation time are keys to accelerating the AST. Here, we introduced a bacteria separation integrated AST (BSI-AST) chip, which could extract bacteria directly from positive blood cultures (PBCs) within 10 min and quickly give susceptibility information within 3 h. The integrated chip includes a bacteria separation chamber, multiple AST chambers, and connection channels. The separator gel was first preloaded into the bacteria separation chamber, enabling the swift separation of bacteria cells from PBCs through on-chip centrifugation. Then, the bacteria suspension was distributed in the AST chambers with preloaded antibiotics through a quick vacuum-assisted aliquoting strategy. Through centrifuge-assisted on-chip enrichment, detectable growth of the phenotype under different antibiotics could be easily observed in the taper tips of AST chambers within a few hours. As a proof of concept, direct AST from artificial PBCs with Escherichia coli against 18 antibiotics was performed on the BSI-AST chip, and the whole process from bacteria extraction to AST result output was less than 3.5 h. Moreover, the integrated chip was successfully applied to the diagnosis of clinical PBCs, showing 93.3% categorical agreement with clinical standard methods. The reliable and fast pathogen characterization of the integrated chip suggested its great potential application in clinical diagnosis.

Association between monocyte lymphocyte ratio and abdominal aortic calcification in US adults: A cross-sectional study.

BACKGROUND: This study aimed to evaluate the association between Monocyte Lymphocyte Ratio (MLR) and Abdominal Aortic Calcification (AAC) in adults over 40 years of age in the United States. METHODS: Data were collected from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). AAC was quantified by the Kauppila score system based on dual-energy X-Ray absorptiometry. Severe AAC was defined as a total AAC score > 6. The lymphocyte count and monocyte count can be directly obtained from laboratory data files. Multivariable logistic regression models were used to determine the association between MLR and the AAC score and severe AAC. RESULTS: A total of 3,045 participants were included in the present study. After adjusting for multiple covariates, MLR was positively associated with higher AAC score (ß = 0.21, 95% CI 0.07, 0.34, p = 0.0032) and the odds of severe AAC increased by 14% per 0.1 unit increase in the MLR (OR = 1.14, 95% CI 1.00, 1.31, p = 0.0541). The Odds Ratio (OR) (95% CI) of severe AAC for participants in MLR tertile 3 was 1.88 (1.02, 3.47) compared with those in tertile 1 (p for trend = 0.0341). Subgroup analyses showed that a stronger association was detected in the elderly compared with non-elderly (p for interaction = 0.0346) and diabetes compared with non-diabetes (borderline significant p for interaction = 0.0578). CONCLUSION: In adults in the United States, MLR was associated with higher AAC scores and a higher probability of severe AAC. MLR may become a promising tool to predict the risk of AAC.

PsERF1B-PsMYB10.1-PsbHLH3 module enhances anthocyanin biosynthesis in the flesh-reddening of amber-fleshed plum (cv. Friar) fruit in response to cold storage.

Flesh-reddening usually occurs in the amber-fleshed plum (Prunus salicina Lindl.) fruit during cold storage but not during ambient storage direct after harvest. It is not clear how postharvest cold signal is mediated to regulate the anthocyanin biosynthesis in the forming of flesh-reddening yet. In this study, anthocyanins dramatically accumulated and ethylene produced in the 'Friar' plums during cold storage, in comparison with plums directly stored at ambient temperature. Expression of genes associated with anthocyanin biosynthesis, as well as transcription factors of PsMYB10.1, PsbHLH3, and PsERF1B were strongly stimulated to upregulated in the plums in the period of cold storage. Suppression of ethylene act with 1-methylcyclopropene greatly suppressed flesh-reddening and downregulated the expression of these genes. Transient overexpression and virus-induced gene silencing assays in plum flesh indicated that PsMYB10.1 encodes a positive regulator of anthocyanin accumulation. The transient overexpression of PsERF1B, coupled with PsMYB10.1 and PsbHLH3, could further prompt the anthocyanin biosynthesis in a tobacco leaf system. Results from yeast two-hybrid and luciferase complementation assays verified that PsERF1B directly interacted with PsMYB10.1. PsERF1B and PsMYB10.1 enhanced the activity of the promoter of PsUFGT individually, and the enhancement was prompted by the co-action of PsERF1B and PsMYB10.1. Overall, the stimulation of the PsERF1B-PsMYB10.1-PsbHLH3 module mediated cold signal in the transcriptomic supervision of the anthocyanin biosynthesis in the 'Friar' plums. The results thereby revealed the underlying mechanism of the postharvest alteration of the flesh phenotype of 'Friar' plums subjected to low temperature.

Human embryonic stem cell-derived mesenchymal stem cell secretome reverts silica-induced airway epithelial cell injury by regulating Bmi1 signaling.

Silicosis is an irreversible chronic pulmonary disease caused by long-term inhalation and deposition of silica particles, which is currently incurable. The exhaustion of airway epithelial stem cells plays a pathogenetic role in silicosis. In present study, we investigated therapeutic effects and potential mechanism of human embryonic stem cell (hESC)-derived MSC-likes immune and matrix regulatory cells (IMRCs) (hESC-MSC-IMRCs), a type of manufacturable MSCs for clinical application in silicosis mice. Our results showed that the transplantation of hESC-MSC-IMRCs led the alleviation of silica-induced silicosis in mice, accompanied by inhibiting epithelia-mesenchymal transition (EMT), activating B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) signaling and airway epithelial cell regeneration. In consistence, the secretome of hESC-MSC-IMRC exhibited abilities to restore the potency and plasticity of primary human bronchial epithelial cells (HBECs) proliferation and differentiation following the SiO2 -induced HBECs injury. Mechanistically, the secretome resolved the SiO2 -induced HBECs injury through the activation of BMI1 signaling and restoration of airway basal cell proliferation and differentiation. Moreover, the activation of BMI1 significantly enhanced the capacity of HBEC proliferation and differentiation to multiple airway epithelial cell types in organoids. Cytokine array revealed that DKK1, VEGF, uPAR, IL-8, Serpin E1, MCP-1 and Tsp-1 were the main factors in the hESC-MSC-IMRC secretome. These results demonstrated a potential therapeutic effect of hESC-MSC-IMRCs and their secretome for silicosis, in part through a mechanism by activating Bmi1 signaling to revert the exhaustion of airway epithelial stem cells, subsequentially enhance the potency and plasticity of lung epithelial stem cells.

Secretome of hESC-Derived MSC-like Immune and Matrix Regulatory Cells Mitigate Pulmonary Fibrosis through Antioxidant and Anti-Inflammatory Effects.

Oxidative stress and inflammation are major drivers in the pathogenesis and progression of pulmonary fibrosis (PF). The mesenchymal stem cell (MSC) secretome has regenerative potential and immunomodulatory functions. Human embryonic stem cell (hESC)-derived MSC-like immune and matrix regulatory cells (IMRCs) are manufacturable with large-scale good manufacturing practice (GMP) preparation. In the present study, the antioxidative and anti-inflammatory properties and the therapeutic effect of the secretome of hESC-MSC-IMRC-derived conditioned culture medium (CM) (hESC-MSC-IMRC-CM) were investigated. Results revealed the capacities of hESC-MSC-IMRC-CM to reduce bleomycin (BLM)-induced reactive oxygen species (ROS), extracellular matrix (ECM) deposition, and epithelial-mesenchymal transition (EMT) in A549 cells. The administration of concentrated hESC-MSC-IMRC-CM significantly alleviated the pathogenesis of PF in lungs of BLM-injured mice, as accessed by pathohistological changes and the expression of ECM and EMT. A mechanistic study further demonstrated that the hESC-MSC-IMRC-CM was able to inhibit BLM-induced ROS and pro-inflammatory cytokines, accompanied by a reduced expression of Nox4, Nrf2, Ho-1, and components of the Tlr4/MyD88 signaling cascade. These results provide a proof of concept for the hESC-MSC-IMRC-derived secretome treatment of PF, in part mediated by their antioxidative and anti-inflammatory effects. This study thus reinforces the development of ready-to-use, cell-free hESC-MSC-IMRC secretome biomedicine for the treatment of PF in clinical settings.

Grass-legume mixture and nitrogen application improve yield, quality, and water and nitrogen utilization efficiency of grazed pastures in the loess plateau.

Grazing on cultivated grassland is a green agricultural model. However, in China's Loess Plateau, the type of cultivated grassland suitable for grazing and the amount of nitrogen application is still unclear, which has led to the failure of this model to be widely implemented. In this context, we set up an experiment using three grass planting types, including monoculture of alfalfa (Medicago sativa L.), monoculture of brome (Bromus inermis L.), and mixed planting of the two forages. Under each planting type, there were six management measures: grazing and no nitrogen application (GN1), grazing and 80 kg ha-1 nitrogen application (GN2), grazing and 160 kg ha-1 nitrogen application (GN3), cutting and no nitrogen application (MN1), cutting and 80 kg ha-1 nitrogen application (MN2), and cutting and 160 kg ha-1 nitrogen application (MN3). To explore the impacts of these treatments on pastures, we studied the effects on the yield, quality, and water use efficiency of the three cultivated grasslands. Results showed that alfalfa monoculture and alfalfa-brome mixed sowing grassland resulted in significantly higher hay yield, crude protein yield, water use efficiency (WUE), precipitation use efficiency (PUE), nitrogen use efficiency (NUE), and agronomic efficiency of nitrogen (AEN) as compared to brome monoculture grassland. In addition, the crude protein, ether extract, and crude ash content of alfalfa monoculture and alfalfa-brome mixture were increased significantly while the contents of neutral detergent fiber (NDF) were reduced, thereby increasing the relative feed value (RFV) during the two years. The forage hay yield, crude protein yield, ether extract, crude ash content, RFV, PUE, and WUE were significantly higher with GN1, GN2, and GN3 treatments than that with MN1 treatment. In contrast, the NDF and acid detergent fiber (ADF) content was significantly lower than the MN1 treatment. Furthermore, the fresh forage yield, crude protein yield, PUE, and WUE of GN3 treatment were significantly higher than that of GN1 and GN2 treatments in both years, while the NUE and AEN were significantly higher in GN2 and GN3 treatments than that of MN3 treatment. Based on these results, alfalfa-brome mixed cropping with the application of 160 kg ha-1 nitrogen under grazing conditions is an appropriate management practice for improving the forage yield, quality, and water- and nitrogen utilization efficiency of cultivated grassland in the Loess Plateau of China. This integrated management model is applicable to the cultivation and utilization of mixed grassland on nutrient-poor land in the Loess Plateau.

Bent-Capillary-Centrifugal-Driven Monodisperse Droplet Generator with Its Application for Digital LAMP Assay.

We developed a bent-capillary-centrifugal-driven (BCCD) monodisperse droplet generator, which could achieve a perfect combination of driving and segmentation for the dispersed phase only using a rotating bent capillary immersed in the continuous phase (mineral oil). The sample could flow continuously to the bent-capillary outlet to form the droplet precursors, which were segmented into homogeneous droplets in the continuous phase. Through the investigation of influence factors on droplet size and stability, we found that the droplet size could be conveniently controlled by the rotational speed of the bent capillary. The droplet volumes could be adjusted with the range from 34 pL to 1 µL, and the coefficient variations (CVs) were less than 3%. Meanwhile, the BCCD droplet generator could realize the controllable droplet output with a high-efficiency sample utilization of 99.75 ± 1.15%, which offered a significant advantage in reducing the waste of precious samples in the droplet generation process. We validated this system with a digital loop-mediated isothermal amplification (dLAMP) assay for the absolute quantification of Mycobacterium tuberculosis complex nucleic acids. The results demonstrated that the BCCD droplet generator was easy to build, was of low cost, and was convenient to operate, as well as avoided sample loss and cross-contamination by coupling with a 96-well plate. Overall, the present platform, as a simple chip-free droplet generator, will provide an especially valuable droplet generation solution for biochemical applications based on droplets.

Soluble Urokinase Plasminogen Activator Receptor Contributes to ANCA-positive IgG-mediated Glomerular Endothelial Activation through TLR4 Pathway.

BACKGROUND: The soluble urokinase plasminogen activator receptor (suPAR), a biomarker of inflammation, has been found to be a potential prognostic factor of renal function progression. Our previous study showed that plasma suPAR levels were significantly associated with disease activity and prognosis in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). OBJECTIVE: This study aimed to explore whether urokinase plasminogen activator receptor (uPAR) participated in MPO-ANCA-induced glomerular endothelial cell (GEnC) injury, which is one of the most important aspects in the pathogenesis of AAV. METHODS: GEnC activation and injury were analyzed by measuring the mRNA levels of ICAM-1 and VCAM-1. Permeability experiments were performed to detect endothelial monolayer activation in number. The expression of TLR4 was detected. In addition, TLR4 siRNA and TLR4 inhibitors were employed to determine its role. Bioinformatics methods were used for further analysis. RESULTS: Compared with a single stimulation, uPAR could further increase the expression of ICAM-1 and VCAM-1 mRNA levels, increase endothelial monolayer permeability and impair tight junctions in GEnCs stimulated with MPO-ANCA-positive IgG. The expression of TLR4 was upregulated by uPAR and MPO-ANCApositive IgG stimulation. TLR4 siRNA significantly reduced the expression of ICAM-1 and VCAM-1 mRNA levels induced by uPAR and MPO-ANCA-positive IgG. The TLR4 antagonist significantly downregulated the levels of ICAM-1 mRNA in cells and sICAM-1 in the supernatants of GEnCs treated with uPAR plus MPOANCA- positive IgG. PLAUR is a core gene in bioinformatics analysis. CONCLUSION: uPAR protein can enhance the GEnC activation and injury induced by MPO-ANCA-positive IgG through the TLR4 pathway, indicating that suPAR may be involved in the pathogenesis of AAV and that su- PAR might be regarded as a potential therapeutic target.

Association between monocyte lymphocyte ratio and abdominal aortic calcification in US adults: A cross-sectional study

Abstract Background This study aimed to evaluate the association between Monocyte Lymphocyte Ratio (MLR) and Abdominal Aortic Calcification (AAC) in adults over 40 years of age in the United States. Methods Data were collected from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). AAC was quantified by the Kauppila score system based on dual-energy X-Ray absorptiometry. Severe AAC was defined as a total AAC score > 6. The lymphocyte count and monocyte count can be directly obtained from laboratory data files. Multivariable logistic regression models were used to determine the association between MLR and the AAC score and severe AAC. Results A total of 3,045 participants were included in the present study. After adjusting for multiple covariates, MLR was positively associated with higher AAC score (β = 0.21, 95% CI 0.07, 0.34, p = 0.0032) and the odds of severe AAC increased by 14% per 0.1 unit increase in the MLR (OR = 1.14, 95% CI 1.00, 1.31, p = 0.0541). The Odds Ratio (OR) (95% CI) of severe AAC for participants in MLR tertile 3 was 1.88 (1.02, 3.47) compared with those in tertile 1 (p for trend = 0.0341). Subgroup analyses showed that a stronger association was detected in the elderly compared with non-elderly (p for interaction = 0.0346) and diabetes compared with non-diabetes (borderline significant p for interaction = 0.0578). Conclusion In adults in the United States, MLR was associated with higher AAC scores and a higher probability of severe AAC. MLR may become a promising tool to predict the risk of AAC.

Target-induced gold nanoparticles colorimetric sensing coupled with aptamer for rapid and high-sensitivity detecting kanamycin.

Herein we report a novel colorimetric sensing strategy for the detection of kanamycin (kana) based on target-induced gold nanoparticles (AuNPs) coupled with aptamers. Aptamer-functionalized AuNPs, as the colorimetric probe, showed a distinct red shift with addition of kana, which avoiding the tedious and unnecessary additive-induced process. To study the interaction between kana and AuNPs and the effects of the specific aptamer adsorption, a series of experiments including UV-vis absorbance and surface enhanced Raman spectroscopy (SERS) were performed. Based on the results, a new alternative view is proposed that kana can directly induce the aggregation of aptamer-wrapped AuNPs, attributed to the co-adsorption of kana and aptamer on the surface of AuNPs. The proposed colorimetric sensing exhibited high selectivity and sensitivity for kanamycin assay with a wide linear range from 10.0 nM to 4.0 µM, and the limit of detection (LOD) reached 4.0 nM. Moreover, the whole detection process could be completed within 5 min, and it also achieved excellent performance in real samples detection with recoveries in the range of 86.22-109.89%. The results indicate that target-induced AuNPs colorimetric sensing coupled with aptamers for the direct detection of kana is simple, rapid and high-sensitivity, has the promising potential applications in the fields of food safety and environmental monitoring.

A smartphone-assisted microarray immunosensor coupled with GO-based multi-stage signal amplification strategy for high-sensitivity detection of okadaic acid.

Okadaic acid (OA) is one of the main virulence factors of diarrheal shellfish toxins (DSP), which can cause acute carcinogenic or teratogenic effects after ingestion of contaminated shellfish. Therefore, high-sensitivity and fast detection of OA is a key to preventing the occurrence of safety accidents. In this paper, we effectively established a smartphone-assisted microarray immunosensor combined with an indirect competitive ELISA (iELISA) for quantitative colorimetric detection of OA. To further improve the detection sensitivity and match the smartphone imaging, a novel graphene oxide (GO) composite probe was developed to realize the multi-stage signal amplification. The system exhibited a wide linear range for the detection of OA (0.02-33.6 ng ·mL-1) with low detection limit of 0.02 ng ·mL-1. The recovery of OA in spiked shellfish samples was in the range of 80%-103.5%, which indicates the good applicability of this biosensor. The whole detection system has advantages of simplicity, low cost, high sensitivity and portability, which is expected to be a powerful alternative tool for on-site detecting and early warning of the pollution of marine products.

Aptamer-based signal amplification strategies coupled with microchips for high-sensitivity bioanalytical applications: A review.

With their advantages in specificity, high stability and easy screening, aptamers are becoming increasingly popular recognition elements for biosensor platforms. At the same time, microchips as the new analytical detection platforms have achieved significant growth in the past decades. At present, with the intersection of aptamer and microfluidic technology, aptamer-based high-sensitivity bioanalysis on microchips exhibits a great application potential in biomedical science and environmental fields. In this review, we highlight the recent progress in high-sensitivity bioanalytical applications based on aptamer signal amplification strategies on microchips. Furthermore, the main challenges in the practical application are discussed, and the development in the future is prospected.

Improved Breakdown Strength of Polypropylene Film by Polycyclic Compounds Addition for Power Capacitors.

In this paper, an improved method for the electric performance of polypropylene (PP) film was proposed to promote the safety and stability of power capacitors. Modified PP films containing three different polycyclic compounds were prepared, which showed good thermal properties and decreased DC conductivity. The DC breakdown strength of the modified PP films under both positive and negative voltage is increased compared with that of the original film. The deep traps introduced by polycyclic compounds and the decreased carrier mobility give an explanation of the decreased DC conductivity. A quantum chemistry calculation was further performed to clarify the mechanism for improving electrical performance, presenting that polycyclic compounds with a high electron affinity and low ionization energy can capture high-energy electrons, protecting the PP molecular chain from attack, and then increase the breakdown strength. It is concluded that the modified PP films by polycyclic compounds have great potential in improving the insulating properties of power capacitors.

Association between body mass index and cardio-metabolic risk factors among subjects in Wuhan, China: A cross-sectional study.

ABSTRACT: The aim of this study is to evaluate the association between body mass index (BMI) and cardio-metabolic risk factors and to determine the optimal BMI cut-off values in male and female subjects in Wuhan, China.We conducted a retrospective cross-sectional analysis of 20218 adult subjects (aged 18-85 years, 12717 men of them) who had health examinations at the health management center of Tongji Hospital of Wuhan in 2017. Multivariate logistic regression analysis was preformed to calculate the odds ratios (ORs) of cardio-metabolic risk factors. Receiver operating characteristic curve was used to determine the area under the receiver operating characteristic curve and optimal cut-off values for BMI predictive of cardio-metabolic risk factors.Of the 20218 participants, the percentage of males with overweight and obesity was as twice as that of females and the prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, and hyperuricemia was significantly higher in males than females (27.18% vs 17.69%, 7.88% vs 4.16%, 41.97% vs 15.20%, and 34.50% vs 9.93%, respectively). Multivariate logistic regression analysis showed that higher BMI was a significant risk factor for hypertension (OR:1.27, 95% confidence intervals [CI]: 1.25-1.29), DM (OR:1.25, 95% CI:1.22-1.28), dyslipidemia (OR:1.26, 95% CI:1.25-1.28), and hyperuricemia (OR:1.25, 95% CI:1.23-1.27) after adjusting for age in both sexes. But in overweight or obesity status, females had higher ORs for hypertension and DM, and lower ORs for dyslipidemia than that in males. The optimal cut-off values of BMI for the presence of cardio-metabolic risk factors were among 24.25 to 25.35 kg/m2 in males, which were higher than in females among 22.85 to 23.45 kg/m2.The association between BMI and cardio-metabolic risk factors is different by gender. It is necessary to determine appropriate threshold for overweight status in men and women separately.

Development and validation of a simplified nomogram predicting individual critical illness of risk in COVID-19: A retrospective study.

This study aims to screen useful predictors of critical cases among coronavirus disease 2019 (COVID-19) patients and to develop a simple-to-use nomogram for clinical utility. A retrospective study was conducted that consisted of a primary cohort with 315 COVID-19 patients and two validation cohorts with 69 and 123 patients, respectively. Logistic regression analyses were used to identify the independent risks of progression to critical. An individualized prediction model was developed, and calibration, decision curve, and clinical impact curves were used to assess the performance of the model. External validations for the predictive nomogram were also provided. The variables of age, comorbid diseases, neutrophil-to-lymphocyte ratio, d-dimer, C-reactive protein, and platelet count were estimated to be independent predictors of progression to critical, which were incorporated to establish a model of the nomogram. It demonstrated good discrimination (with a C-index of 0.923) and calibration. Good discrimination (C-index, 0.882 and 0.906) and calibration were also noted on applying the nomogram in two validation cohorts. The clinical relevance of the nomogram was justified by the decision curve and clinical impact curve analysis. This study presents an individualized prediction nomogram incorporating six clinical characteristics, which can be conveniently applied to assess an individual's risk of progressing to critical COVID-19.

Elevated atherogenic index and higher triglyceride increase risk of kidney function decline: a 7-year cohort study in Chinese adults.

OBJECTIVE: This study explored whether lipid disorders or an elevated atherogenic index of plasma (AIP, a risk factor for cardiovascular diseases) could predict major kidney function decline. METHODS: We conducted a retrospective 7-year cohort study of 3712 Chinese adults followed up between 2010 and 2017. Major kidney function decline was defined as a ≥ 30% reduction in the estimated glomerular filtration rate (eGFR) from baseline. Multivariable logistic regression models were used to evaluate the relationship between lipid profiles and major kidney function decline. Smoking habits, waist circumference, and physical activity were not assessed. RESULTS: During the 7-year follow-up, 1.70% (n = 63) of the participants developed major kidney function decline. After adjustment for potential confounders, the odds ratios (ORs) for developing eGFR decline with per standard deviation increase were 1.23 [95% confidence interval (CI): 1.06-1.43] for triglyceride and 2.55 (95% CI: 1.01-6.42) for AIP in all participants. Furthermore, in the stratified analysis, we found sex-related differences; triglyceride and AIP were only independently associated with the risk of eGFR decline in men (OR, 1.27, 95% CI: 1.08-1.48; OR, 3.98, 95% CI: 1.22-12.99, respectively). When the participants were divided into groups according to the baseline lipid status, association was observed only between abnormal AIP and eGFR decline (all p values < 0.05). CONCLUSION: Our findings suggest that a higher serum triglyceride level or an elevated AIP increases the risk of major kidney function decline in Chinese men with normal kidney function. Thus, assessment of AIP may help identify the risk of eGFR decline.

Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China.

The primary goals of this study were to evaluate the gender- and age-related differences in homocysteine concentration in the general population of China and possible influencing factors. A total of 7872 subjects, divided into male and female groups, participated in this retrospective study. The average homocysteine level, prevalence of hyperhomocysteinemia, and independent factors affecting homocysteine concentration were analyzed. The homocysteine level was significantly higher in males than in females in each age range (aged 20-30, aged 30-40, aged 40-50, aged 50-60, aged 60-80, aged over 80) (P < 0.0001), and the trend did not abate with age. The homocysteine concentration first decreased and then increased, being lowest at 30-50 years of age and significantly increased after 50 years of age. Factors associated with homocysteine concentration in males were smoking status (current smokers versus ex-smokers: ß: 0.112), estimated glomerular filtration rate (ß = - 0.192), blood urea nitrogen (ß = - 0.14), diastolic blood pressure (ß = - 0.113), free triiodothyronine (ß = - 0.091), serum potassium (ß = - 0.107) and cystatin C (ß = 0.173). In females, independent factors associated with homocysteine concentration were cystatin C (ß = 0.319), albumin (ß = 0.227), free thyroxine (ß = 0.179), age (ß = 0.148), free triiodothyronine (ß = - 0.217) and serum potassium (ß = - 0.153). The homocysteine level was significantly higher in males than in females and increased markedly after 50 years of age in both groups. The independent factors associated with increased homocysteine concentration differed between males and females.