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Background: Microalbuminuria is a common clinical symptom that manifests in the early stages of diabetic kidney disease (DKD) and is also the main feature of glomerular endothelial cells (GECs) injury. There is increasing evidence that the transcytosis of albumin across GECs is closely related to the formation of albuminuria. Our previous studies have shown that angiopoietin 2 (ANGPT2) can inhibit albumin transcytosis across renal tubular epithelial cells by activating caveolin 1 (CAV1) phosphorylation during high glucose (HG) exposure. The role of ANGPT2 in albumin transcytosis across GECs remains unclear. Losartan significantly reduces albuminuria, but the mechanism has not been clarified. Methods: We established an in vitro albumin transcytosis model to investigate the change in albumin transcytosis across human renal glomerular endothelial cells (hrGECs) under normal glucose (NG), high glucose (HG) and losartan intervention. We knocked down ANGPT2 and CAV1 to evaluate their roles in albumin transcytosis across hrGECs and verified the relationship between them. In vivo, DKD mouse models were established and treated with different doses of losartan. Immunohistochemistry and Western blot were used to detect the expression of ANGPT2 and CAV1. Results: In vitro, the transcytosis of albumin across hrGECs was significantly increased under high glucose stimulation, and losartan inhibited this process. The expression of ANGPT2 and CAV1 were both increased in hrGECs under HG conditions and losartan intervention reduced the expression of them. Moreover, ANGPT2 downregulation reduced albumin transcytosis in hrGECs by regulating CAV1 expression. In vivo, the expression of ANGPT2 and CAV1 in the glomerulus was both increased significantly in DKD mice. Compared with DKD mice, losartan treatment reduced albuminuria and decreased the expression of ANGPT2 and CAV1 in a dose-dependent manner. Conclusions: ANGPT2 exacerbated albumin transcytosis across GECs by increasing CAV1 expression during HG exposure, thereby increasing albuminuria. Losartan reduces albumin transcytosis and albuminuria formation in DKD by inhibiting the upregulation of ANGPT2 under HG conditions. Our findings suggest that ANGPT2 and CAV1 may be novel therapeutic targets for diabetic albuminuria. In addition, we provide new evidence to elaborate on the mechanism of losartan in the development of DKD. Resumen: Antecedentes: La microalbuminuria es un síntoma clínico común que se manifiesta en las fases tempranas de la enfermedad renal diabética (ERD), y también es característica del daño de las células endoteliales glomerulares (GEC). Existe evidencia creciente en cuanto a que la transcitosis de la albúmina a través de las GEC está estrechamente relacionada con la formación de albuminuria. Nuestros estudios previos reflejaron que angiopoyetina 2 (ANGPT2) puede inhibir la transcitosis de la albúmina a través de las células epiteliales tubulares renales activando la fosforilación de caveolina 1 (CAV1) durante la exposición a hiperglucemia (HG). El rol de ANGPT2 en la transcitosis de la albúmina a través de las GEC resulta incierto. Losartan reduce considerablemente la albuminuria, aunque no se ha esclarecido el mecanismo. Métodos: Establecimos un modelo in vitro de transcitosis de la albúmina para investigar el cambio de dicho mecanismo a través de las células endoteliales glomerulares renales humanas (hrGEC) en condiciones de glucosa normal (GN), hiperglucemia (HG) e intervención de losartan. Realizamos breakdown de ANGPT2 y CAV1 para evaluar sus roles en la transcitosis de la albúmina a través de las hrGEC, y verificamos la relación entre ellas. Se establecieron modelos in vivo de ratones con ERD, tratados con diferentes dosis de losartan. Se utilizaron pruebas de inmunohistoquímica e inmunotransferencia para detectar la expresión de ANGPT2 y CAV1. Resultados: In vitro, la transcitosis de la albúmina a través de hrGEC se incrementó considerablemente en condiciones de estimulación de la hiperglucemia, inhibiendo losartan este proceso. La expresión de ANGPT2 y CAV1 se incrementó en las hrGEC en condiciones de HG, reduciendo la intervención de losartan la expresión de ambas. Además, la regulación decreciente de ANGPT2 redujo la transcitosis de la albúmina en las hrGEC, regulando la expresión de CAV1. In vivo, la expresión de ANGPT2 y CAV1 en los glomérulos se incrementó considerablemente en los ratones con ERD. En comparación con los ratones con ERD, el tratamiento de losartan redujo la albuminuria y disminuyó la expresión de ANGPT2 y CAV1 dependiendo de la dosis. Conclusiones: ANGPT2 exacerbó la transcitosis de la albúmina a través de las GEC, incrementando la expresión de CAV1 durante la exposición a HG, y aumentando por tanto la albuminuria. Losartan reduce la transcitosis de la albúmina y la formación de albuminuria en la ERD, inhibiendo la regulación creciente de ANGPT2 en condiciones de HG. Nuestros hallazgos sugieren que ANGPT2 y CAV1 pueden ser objetivos terapéuticos noveles para la albuminuria diabética. Además, aportamos evidencia nueva para elaborar el mecanismo de losartan en el desarrollo de la ERD.

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According to the nonlinear output characteristics of photovoltaic cells, combined with artificial intelligence algorithm the MPPT（Maximum Power Point Tracking）control algorithm based on fuzzy variable step size is proposed, which enables the system to quickly track the maximum power point and improve the energy conversion efficiency of photovoltaic system. This paper designs a small-scale photovoltaic power generation system. The main circuit of the system consists of Perovskite Solar Panels, DC voltage regulator circuit, storage battery and one-way full bridge inverter circuit. The control circuit consists of sun-seeking, inverter and maximum power tracking on constant voltage. Proteus simulation software is used to simulate the sun-seeking part, the inverting part, the general control unit, the keys and the display interface. The results indicate that the functions of the small-scale photovoltaic power generation system can be achieved very well.

ABSTRACT In this study, we examined the effects of lactic acid bacteria (LAB) inoculant and beet pulp (BP) on the quality of yacon (Smallanthus sonchifolius) residue silage. Yacon silage was prepared using a small-scale system of silage fermentation, and the treatments were as follows: control silage without any additive and silages with LAB inoculant Chikuso-1 (Lactobacillus plantarum, 5 mg/kg, fresh matter basis), BP (30% fresh matter basis), and LAB+BP. Silages were opened on days 3, 5, 7, 15, 30, and 60 of fermentation. The chemical composition, organic acid content, and in vitro ruminal digestion of the 60-day silage were determined. The pH of LAB-treated silage was lower than that of the silage without LAB. Furthermore, the LAB-treated silage presented the lowest ammonia-N concentration among the four types of silages, and it inhibited the growth of harmful bacteria including molds and clostridia during the early stages of fermentation. The BP-treated silage had lower contents of crude protein and ether extract than the silage without BP. The 60-day silage inoculated with LAB had the highest in vitro dry matter (DM) digestibility among the four silages, and the production of methane was lower than that of the silage treated with BP. The pH showed a tendency toward stabilization after 30 days of fermentation, although the concentration of lactic acid exhibited fluctuations during fermentation. The results suggest that the addition of LAB and BP can improve the fermentation quality of yacon silage, and the yacon silage with LAB might increase in vitro DM digestibility, but decrease in vitro ruminal methane production.

Background: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community., Methods: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/μL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma., Results: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results., Conclusions: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Although patients with advanced liver disease have been included in studies evaluating fibrates for the treatment of primary biliary cholangitis (PBC), the frequency of biochemical responses and adverse effects for this group of patients was not reported separately and comprehensively., Aims: to evaluate the efficacy and safety of additional fenofibrate therapy in patients with advanced and ursodeoxycholic acid (UDCA)-refractory PBC., Methods: Patients were analyzed retrospectively to determine the clinical therapeutic effects of UDCA with additional fenofibrate therapy versus continued UDCA monotherapy. The liver transplantation (LT)-free survival and the alkaline phosphatase (ALP) normalization rates were estimated using Cox regression analyses and Kaplan-Meier plots with inverse probability of treatment weighting (IPTW)., Results: A total of 118 patients were included: 54 received UDCA alone and 64 received UDCA in combination with fenofibrate therapy. In the fenofibrate and UDCA groups, 37% and 11% of patients with advanced and UDCA-refractory PBC, respectively, achieved ALP normalization (P=0.001). Additional fenofibrate therapy improved both LT-free survival and ALP normalization rate after IPTW (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.07-0.75, P=0.015; and HR: 11.66, 95% CI: 5.02-27.06, P=0.001, respectively). These effects were supported by parallel changes in the rates of liver decompensation and histologic progression, and the United Kingdom (UK)-PBC and Globe risk scores. During the follow-up period, serum levels of ALP and aminotransferase decreased significantly, while total bilirubin, albumin, platelet, serum creatinine, and estimated glomerular filtration rate remained stable in fenofibrate-treated participants. No fenofibrate-related significant adverse events were observed in our cohort., Conclusions: Additional fenofibrate therapy significantly improved LT-free survival and ALP normalization in patients with advanced and UDCA-refractory PBC. Furthermore, adding-on fenofibrate therapy appeared to be safe and well tolerated in this population., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Background: Novel coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. At the peak of the outbreak in Wuhan (January and February), there are two types of COVID-19 patients: laboratory confirmation and clinical diagnosis. This study aims to compare and analyze the clinical outcomes and characteristics of confirmed and clinically diagnosed COVID-19 patients to determine whether they are of the same type and require equal treatment. More importantly, the prognostic factors of COVID-19 patients are explored., Methods: A total of 194 hospitalized patients with COVID-19 pneumonia were retrospectively studied. Demographic data, clinical characteristcs, laboratory results and prognostic information were collected by electronic medical record system and analyzed., Results: Among 194 subjects included, 173 were confirmed and 21 were clinically diagnosed. There were no significant differences in clinical outcomes (mortality rate 39[22.54%] vs 7[33.33%], P=0.272) and hospital stay (19.00 vs 16.90 days, P=0.411) between the confirmed and clinically diagnosed group, and prognostic factors were similar between them. Older age, lower albumin levels, higher serum Lactate dehydrogenase (LDH) levels, higher D-D levels, longer prothrombin time (PT), higher IL-6 levels, lower T cells indicated poor prognosis in patients with COVID-19 pneumonia. NK cell has the highest AUC among all measured indicators (NK AUC=0.926, P<0.001)., Conclusion: Laboratory-confirmed and clinically diagnosed COVID-19 patients are similar in clinical outcomes and most clinical characteristics. They are of the same type and require equal treatment. Age, AST, LDH, BUN, PT, D-D, IL6, white blood cell and neutrophil counts, T cell and T cell subset counts can efficiently predict clinical outcomes., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)