Relationship between Life's Essential 8 and metabolic syndrome among older Americans (NHANES, 2007-2010): navigating biological aging and inflammation.

Background: Metabolic syndrome (MetS) is a global health concern, and it is particularly harmful to middle-aged and elderly individuals. Life Element Eight (LE8), a measure to improve cardiovascular health, may offer benefits for MetS. Herein, we examined the relationship between LE8 and MetS among middle-aged and elderly individuals, and elucidated the role of biological aging and inflammation in this process. Methods: We obtained the LE8 scores of 2,901 Americans, along with their biological aging indicators (Biological age, Phenotypic age, Serum Klotho), and computed their inflammatory indicators SII, DII. Using logistic regression model, we assessed the association among inflammatory markers, Biological aging, LE8 and MetS. Additionally, we generated restricted cubic spline (RCS) plots to display trends in significant variables in logistic regression. Using parallel mediation analysis, we evaluated the possible mediating role of various factors in the risk relationship between LE8 and MetS. Results: Our examination revealed that higher LE8 scores were associated with a lower incidence of MetS in a fully adjusted model. The high LE8 subgroup had a 79.73% reduction in the risk of MetS compared to the low subgroup with an OR = 0.2027 (95% Cl 0.0871, 0.4714), with similar correlations between health factor scores and MetS risk. Biological aging mediated the associations between LE8, health behaviors and health factor scores and MetS risk. Conclusion: A rise in the LE8 score among middle-aged and elderly individuals is a protective factor for MetS, and this association may be partially mediated by biological aging, suggesting that LE8 may reduce the risk of MetS by ameliorating aging.

A Bioinspired Design of Protective Al2O3/Polyurethane Hierarchical Composite Film Through Layer-By-Layer Deposition.

Structural materials such as ceramics, metals, and carbon fiber-reinforced plastics (CFRP) are frequently threatened by large compressive and impact forces. Energy absorption layers, i.e., polyurethane and silicone foams with excellent damping properties, are applied on the surfaces of different substrates to absorb energy. However, the amount of energy dissipation and penetration resistance are limited in commercial polyurethane foams. Herein, a distinctive nacre-like architecture design strategy is proposed by integrating hard porous ceramic frameworks and flexible polyurethane buffers to improve energy absorption and impact resistance. Experimental investigations reveal the bioinspired designs exhibit optimized hardness, strength, and modulus compared to that of polyurethane. Due to the multiscale energy dissipation mechanisms, the resulting normalized absorbed energy (≈8.557 MJ m-3) is ≈20 times higher than polyurethane foams under 50% quasi-static compression. The bioinspired composites provide superior protection for structural materials (CFRP, glass, and steel), surpassing polyurethane films under impact loadings. It is shown CFRP coated with the designed materials can withstand more than ten impact loadings (in energy of 10 J) without obvious damage, which otherwise delaminates after a single impact. This biomimetic design strategy holds the potential to offer valuable insights for the development of lightweight, energy-absorbent, and impact-resistant materials.

Adverse Events of Oral GLP-1 Receptor Agonist (Semaglutide Tablets): A Real-World Study Based on FAERS from 2019 to 2023.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous preparations can only be subcutaneously injected. Oral administration of GLP-1RAs semaglutide helps to broaden treatment options, but its safety in the real world still needs to be observed. This study is based on FDA adverse event reporting system (FAERS) database to mine adverse drug events (ADE) of oral semaglutide, and provide references for the clinical safe use of this drug. METHODS: To analyze the signal quality of oral semaglutide, which is a drug used in the FAERS database from the third quarter of 2019 to the third quarter of 2023, we collected ADE data and performed data mining by using disproportionate analysis. Then, we standardized the data and used a variety of signal-quantification techniques, including reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian belief propagation neural network (BCPNN), and multiple empirical Bayesian gamma Poisson contractions (MGPS), for further analysis. RESULTS: We screened 2398 reports on the use of semaglutide tablets, involving a total of 5653 ADE. These reports were mainly submitted by consumers, and the reporting country was mainly the United States. A total of 23 system organ classes (SOC) and 93 preferred terms (PT) were mined for the signals of semaglutide tablets. The three most common SOC were gastrointestinal disorders, general disorders and administration site conditions, and investigations. At the PT level, metabolism and nutrition disorders exhibit the highest number of signals, with the top three being thyroid cyst, acute cholecystitis, and ketosis. Gastrointestinal disorders rank second, primarily involving eructation, pancreatitis, impaired gastric emptying, and regurgitation. In addition, vith nerve paralysis occurs and the signal intensity is high. CONCLUSIONS: Our study provides a deeper and broader understanding of the safety of oral semaglutide. The results of the ROR, PRR, BCPNN, and MGPS algorithms exhibit high consistency, with metabolism and nutrition-related disorders having the highest number of signals. The conclusions align with the technical specifications of the product. Notably, other unexpected effects are reported, including acute cholecystitis, paralysis of the abducens nerve, and positional vertigo.

The shape of Nature's stingers revealed.

Stinger-like structures in living organisms evolved convergently across taxa for both defensive and offensive purposes, with the main goal being penetration and damage. Our observations over a broad range of taxa and sizes, from microscopic radiolarians to narwhals, reveal a self-similar geometry of the stinger extremity: the diameter (d) increases along the distance from the tip (x) following a power law [Formula: see text] , with the tapering exponent varying universally between 2 and 3. We demonstrate, through analytical and experimental mechanics involving three-dimensional (3D) printing, that this geometry optimizes the stinger's performance; it represents a trade-off between the propensity to buckle, for n smaller than 2, and increased penetration force, for n greater than 3. Moreover, we find that this optimal tapering exponent does not depend on stinger size and aspect ratio (base diameter over length). We conclude that for Nature's stingers, composed of biological materials with moduli ranging from hundreds of megapascals to ten gigapascals, the necessity for a power-law contour increases with sharpness to ensure sufficient stability for penetration of skin-like tissues. Our results offer a solution to the puzzle underlying this universal geometric trait of biological stingers and may provide a new strategy to design needle-like structures for engineering or medical applications.

Comparison of sentinel lymph node distribution and lymphatic drainage pathway between high- and low-risk endometrial cancers.

PURPOSE: This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. METHODS: In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. RESULTS: The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. CONCLUSION: The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping.

Dynamic compression of soft layered materials yields tunable and spatiotemporally evolving surface patterns.

Soft layered systems buckling to form surface patterns has been widely studied under quasistatic loading. Here, we study the dynamic formation of wrinkles in a stiff-film-on-viscoelastic-substrate system as a function of impact velocity. We observe a spatiotemporally varying range of wavelengths, which display impactor velocity dependence and exceed the range exhibited under quasistatic loading. Simulations suggest the importance of both inertial and viscoelastic effects. Film damage is also examined, and we find that it can tailor dynamic buckling behavior. We expect our work to have applications to soft elastoelectronic and optic systems and open routes for nanofabrication.

In Vitro Antifungal Activity of Azoles and Other Antifungal Agents Against Pathogenic Yeasts from Vulvovaginal Candidiasis in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE: Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS: Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS: 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS: C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Is Urban Greening an Effective Solution to Enhance Environmental Comfort and Improve Air Quality?

Urban greening has often been proposed as a cost-effective solution to improve environmental comfort, but may also deteriorate air quality. Quantifying these two opposing effects of urban greening is necessary to develop successful environmental policies for specific mega-city clusters. In this study, a high-resolution regional climate and air quality model (WRF-Chem, v4.0.3) was employed to test three scenarios aimed at quantifying the impact of land-use change and biogenic emissions from urban greening on regional climate and air quality. It was found that urban greening could effectively decrease the near-surface temperature by up to 0.45 °C, but the increased biogenic volatile organic compound (BVOC) emissions offset some of this cooling effect (by up to 65%). Land-use change due to urban greening dominated the improvement in human comfort but worsened diffusion conditions to result in the convergence of fine particulate matter in specific areas. The selection of low-emission tree species may be imperative, although increased emissions from urban greening will not change the sensitivity of ozone to precursors under the current scenario of anthropogenic emissions. This is because BVOC emissions due to urban greening will become a more important source of pollution with the development of clean energy and the popularity of low-carbon lifestyles.

Adjuvant chemoradiotherapy versus chemotherapy alone in stage III endometrial cancer: A systematic review and meta-analysis.

OBJECTIVE: To discuss the impact of chemoradiotherapy (CRT) on the survival of patients with stage III endometrial cancer (EC) compared with chemotherapy (CT) alone. METHODS: Articles involving adjuvant CRT versus CT on survival in stage III EC were retrieved from PubMed and EMBASE. Hazard ratios (HRs) of overall survival (OS) and relapse-free survival (RFS) were collected and pooled, and publication bias was measured by Begg's and Egger's test. Quality of researches was measured by the Newcastle-Ottawa scale and the modified Jadad scale. RESULTS: Eleven were included in the statistical analysis. A significant advantage of CRT over CT on OS was shown (HR 0.59, 95% CI 0.49-0.70). Further subgroup analysis suggested the advantage was mostly associated with stage IIIC (HR 0.63, 95% CI 0.52, 0.76]). A similar result favoring CRT was also reached on RFS (HR 0.66, 95% CI 0.47-0.93). No significant publication bias was observed. CONCLUSION: CRT was associated with a better OS and RFS than CT alone in stage III EC patients.

A Programmable Liquid Crystal Elastomer Metamaterials With Soft Elasticity.

Liquid crystal elastomers (LCEs) are a rubbery network of polymers with ordered liquid crystal mesogens. The combination of rubber elasticity and the anisotropic liquid crystalline order gives exceptional mechanical properties, like soft elasticity, where near-constant stress accompanies large elastic deformation in the material. However, the soft elasticity in LCEs is often bounded by the intrinsic molecular interactions and structures, limiting the range of programmable mechanical properties and functionalities. Here, we demonstrate that the semi-soft elasticity of LCEs can be integrated into the framework of metamaterials to realize markedly programmabilities. Under uniaxial deformation, each state of the building blocks in metamaterials and the molecular composition of the nematic LCEs is associated with a distinctly different stress-strain relation that is fully elastic. Taking advantage of the tunable bending and stretching deformation enabled by the geometry of the building blocks and the semi-soft elasticity of the nematic LCE in the metamaterials, we can engineer the local stretch and stress at an unmet level of their counterpart composed by elastomers. Numerical simulations and analytical models are developed to relate the metamaterial geometries and the LCE soft elasticity to the mechanical responses. In addition, an elastic region with near-zero stiffness up to a stretch of 1.4 can be designed by connecting the compliant responses due to bending deformation and the soft elasticity in the LCE. We expect that the specialized mechanical tunability enabled by the LCE metamaterials can facilitate the development of advanced forms of mechanical metamaterials and impact the design of robotic systems.

Unidirectional Elimination of Hydrogen by a Giant Local Field Saves First- and Last-Mile Performances of Semiconductor Devices.

Hydrogen, the smallest element, easily forms bonds to host/dopant atoms in semiconductors, which strongly passivates the original electronic characteristics and deteriorates the final reliability. Here, we demonstrate a concept of unidirectional elimination of hydrogen from semiconductor wafers as well as electronic chips through a giant local electric field induced by compact chloridions. We reveal an interactive behavior of chloridions, which can rapidly approach and take hydrogen atoms away from the device surface. A universal and simple technique based on a solution-mediated three-electrode system achieves efficient hydrogen elimination from various semiconductor wafers (p-GaN, p-AlGaN, SiC, and AlInP) and also complete light emitting diodes (LEDs). The p-type conductivity and light output efficiency of H-eliminated UVC LEDs have been significantly enhanced, and the lifetime is almost doubled. Moreover, we confirm that under a one-second irradiation of UVC LEDs, bacteria and COVID-19 coronavirus can be completely killed (>99.93%). This technology will accelerate the further development of the semiconductor-based electronic industry.

Characterization of the complete mitogenome of Gymnocypris dobula (Günther, 1868) (Cypriniformes: Cyprinidae).

Gymnocypris dobula, classified into the highly specialized Schizothoracine fish, is endemic to Tibet, China. The complete mitochondrial DNA sequence of G. dobula was 16,728 base pairs in length and comprised 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes as well as one control region as in a typical vertebrate mitochondrial DNA gene. The ML and BI trees showed that G. dobula was most closely related to Gymnocypris scleracanthus within the highly specialized group. This mitogenome provides new molecular data for further taxonomic and phylogenetic studies of Schizothoracine fish.

Diagnostic value of procalcitonin for bacterial infections in patients undergoing hemodialysis: a systematic review and meta-analysis.

BACKGROUND: The diagnostic value of procalcitonin (PCT) in patients undergoing hemodialysis (HD) remains unclear. METHODS: We searched multiple databases (PubMed, EMBASE, and Cochrane Library) for studies published through August 2021 that evaluated the diagnostic performance of PCT in patients undergoing HD and having suspected bacterial infections. The bivariate fixed effects model was used to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curves. RESULTS: We identified a total of 1799 studies, of which seven diagnostic studies comprised 1444 patients and 430 bacterial infection episodes. Bivariate pooled sensitivity and specificity for PCT were 0.90 (95% CI: 0.85-0.94) and 0.83 (95% CI: 0.56-0.95), respectively. Furthermore, pooled DOR, PLR, NLR, and area under the curve (AUC) were 47 (95% CI: 11-209), 5.4 (95% CI: 1.7-16.9), 0.12 (95% CI: 0.07-0.20), and 0.92 (95% CI: 0.90-0.94), respectively. We also compared the diagnostic accuracy of PCT and C-reactive protein (CRP), and our results showed that the diagnostic accuracy parameters for PCT were significantly higher than those for CRP. CONCLUSIONS: PCT is a useful marker for diagnosis of bacterial infections in patients undergoing HD at a cutoff value of 1.5 ng/ml.

Phase-transforming metamaterial with magnetic interactions.

Solid-solid phase transformations can affect energy transduction and change material properties (e.g., superelasticity in shape memory alloys and soft elasticity in liquid crystal elastomers). Traditionally, phase-transforming materials are based on atomic- or molecular-level thermodynamic and kinetic mechanisms. Here, we develop elasto-magnetic metamaterials that display phase transformation behaviors due to nonlinear interactions between internal elastic structures and embedded, macroscale magnetic domains. These phase transitions, similar to those in shape memory alloys and liquid crystal elastomers, have beneficial changes in strain state and mechanical properties that can drive actuations and manage overall energy transduction. The constitutive response of the elasto-magnetic metamaterial changes as the phase transitions occur, resulting in a nonmonotonic stress-strain relation that can be harnessed to enhance or mitigate energy storage and release under high-strain-rate events, such as impulsive recoil and impact. Using a Landau free energy-based predictive model, we develop a quantitative phase map that relates the geometry and magnetic interactions to the phase transformation. Our work demonstrates how controllable phase transitions in metamaterials offer performance capabilities in energy management and programmable material properties for high-rate applications.

Characterization of the complete mitogenome of Gammarus lacustris (G.O. Sars, 1863) (Amphipoda: Gammaridae) and its phylogenetic position within Amphipoda.

Gammarus lacustris is native to the Qinghai-Tibet Plateau (QTP), widely distributed in alpine lakes. The complete mitochondrial DNA sequence of G. lacustris was 15,349 base pairs in length and comprised 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region. The BI tree showed that G. lacustris was most closely related to Gammarus duebeni, and indicated that Gammarus, Gmelinoides, Brachyuropus, Pallaseopsis, and Eulimnogammarus evolved from a common ancestor. The mitogenome of G. lacustris provides new molecular data for further taxonomic and phylogenetic studies of Amphipoda.

GPS-ZTD data assimilation and its impact on wintertime haze prediction over North China Plain using WRF 3DVAR and CMAQ modeling system.

Severe haze frequently hits the North China Plain (NCP), especially in winter during recent years. Meteorological factors affect aerosol formation and its optical properties, and accurate meteorological fields are imperative for accurate aerosol simulations. The impacts of Global Positioning System Zenith Total Delay (GPS-ZTD) data assimilation on meteorology and aerosol simulations were evaluated in this study using the WRF-CMAQ (the Weather Research and Forecasting model and Community Multiscale Air Quality) modelling system over the NCP during 01-31 December 2019. After bias correction, GSP-ZTD data were assimilated into the WRF model using the 3DVAR technique. Two sensitivity tests (CTR and ZTD) were conducted. The WRF model had generally acceptable performance for surface and upper air meteorological variables, PM2.5 and visibility. From the aspect of BIAS, STDE, RMSE, and R, the assimilation of ZTD data improved the underestimation of ground relative humidity (RH). The improvement was more pronounced in the first 18 forecast hours. The mean RH BIAS decreased by 8%. Surface pressure was also improved in ZTD. The influence of ZTD data assimilation on ground temperature and wind tended to be neutral. The BIAS of ZTD decreased by 3% after data assimilation while STED or RMSE increased slightly. After ZTD data assimilation, the PM2.5 underestimation decreased by 3.4% over NCP. And station mean BIAS or RMSE of PM2.5 decreased at more than 70% stations. After ZTD data assimilation, the visibility overestimation was reduced by 2.5%. And more than 81% stations over had lower visibility BIAS or RMSE. Station mean PM2.5 mass concentration increased by 1.5% in ZTD. The primary aerosol species increased by approximately 1%, and most secondary aerosol species increased by greater than 2% affected by both aerosol physical and chemical process. Although the improvement of PM2.5 seems marginal from the perspective of regional or temporal average, the contribution of ZTD data assimilation on specific pollution episodes at specific stations can be great. The improvement of PM2.5 troughs was in the range of 1-5 µg/m3, while the overestimation of PM2.5 peaks was reduced by few up to dozens µg/m3. This will contribute to the extreme value prediction during pollution episode.

Carbon nanoparticles combined with indocyanine green for sentinel lymph node detection in endometrial carcinoma.

OBJECTIVE: To evaluate the feasibility and clinical value of the combination of carbon nanoparticles (CNPs) and indocyanine green (ICG) for identifying sentinel lymph nodes (SLNs) in endometrial cancer. MATERIALS AND METHODS: About 153 patients with endometrial cancer were recruited from July 2015 to May 2019. All patients underwent SLN biopsy according to the SLN algorithm for surgical staging with ICG and/or CNPs. The detection rate, factors associated with the detection rate, sensitivity, and negative predictive value (NPV) of SLNs were analyzed. RESULTS: The detection rates of SLNs with the combined method were the highest among the different methods. As calculated per hemipelvis, the sensitivity and NPV with ICG alone or with ICG plus CNPs were 100%. With CNP, tumor Grade 3 and laparoscopy were related to unsuccessful overall SLN mapping while tumor diameter greater than 2 cm and laparoscopy were statistically associated with failed bilateral mapping. With ICG, a higher body mass index was significantly associated with unsuccessful bilateral detection of SLN. CONCLUSION: SLN assessment in endometrial cancer is feasible and safe with high sensitivity and high NPV when ICG and CNPs are combined and in low-risk patients. It is a superior option to use CNPs in laparotomy for patients with endometrial cancer.

Tripterygium glycoside suppresses epithelial­to­mesenchymal transition of diabetic kidney disease podocytes by targeting autophagy through the mTOR/Twist1 pathway.

Tripterygium glycoside (TG) is a traditional Chinese medicine extract with immunosuppressive, anti­inflammatory and anti­renal fibrosis effects. Epithelial­mesenchymal transition (EMT) and cell apoptosis are considered to be the major cause of podocyte injury in diabetic kidney disease (DKD). However, it remains unknown as to whether TG is able to alleviate podocyte injury to prevent DKD progression. Therefore, the present study aimed to clarify the podocyte protective effects of TG on DKD. TG, Twist1 small interfering RNA (siRNA) and Twist1 overexpression vector were added to DKD mouse serum­induced podocytes in vitro. Autophagic and EMT activities were evaluated by immunofluorescence staining and western blot analysis. Apoptotic activity was evaluated by Annexin V­FITC/PI flow cytometric analysis. The results revealed that after treatment with DKD mouse serum, autophagy was decreased, whereas EMT and apoptotic rate were increased, in podocytes. In addition, Twist1 expression was increased in DKD­induced podocytes. Furthermore, following Twist1­small interfering RNA transfection, the DKD­induced podocyte EMT and apoptotic rate were markedly reduced, indicating that Twist1 may be a promising therapeutic target for DKD. The present results also revealed that overexpression of Twist1 increased podocyte apoptosis, although this was decreased after TG treatment, indicating that TG may exhibit a protective effect on podocytes by inhibiting the Twist1 signaling pathway. After the addition of 3­benzyl­5­((2­nitrophenoxy) methyl)­dihydrofuran­2(3H)­one, an activator of mTORC1, the effects of TG on podocyte EMT, apoptosis and the autophagy were reversed. These findings indicated that TG may alleviate EMT and apoptosis by upregulating autophagy through the mTOR/Twist1 signaling pathway in DKD.

ATF4-dependent heme-oxygenase-1 attenuates diabetic nephropathy by inducing autophagy and inhibiting apoptosis in podocyte.

AIM: Podocyte injury plays an important role in diabetic nephropathy (DN), yet the underlying molecular mechanisms of podocyte injury in DN is not clear. Here, we investigated the role of activating transcription factor 4 (ATF4) and HO-1 in DN-induced podocyte injury. METHODS: Protein expression was measured by western blotting (WB) and immunofluorescence. Cellular apoptosis was quantified by flow cytometry. ATF4 siRNA knockdown and HO-1 overexpression in podocyte were employed to evaluate the role of ER stress in DN-induced apoptosis and autophagy response. Urinary protein levels, nephrin expression, serum creatinine and BUN were evaluated and glomerulosclerosis was quantified by Periodic Acid-Schiff staining. RESULTS: Expression of ATF4 was increased in podocytes exposed to serum from DN mice. ATF4 knockdown enhanced DN-induced podocyte apoptosis. HO-1 overexpression reduced the decline of DN-induced podocyte autophagy and inhibited apoptosis and the beneficial effects of HO-1 overexpression in DN were blocked by ATF4 knockdown. The diabetic mice were significantly ameliorated by HO-1 agonist hemin treatment. CONCLUSIONS: ATF4 induces autophagy by enhancing the expression of HO-1, and inhibits podocyte apoptosis in DN. Treatment with the HO-1 agonist reduced proteinuria, apoptosis, and enhanced autophagy response, and thus improved renal function in DN mice.

The safety and efficacy of low-dose mineralocorticoid receptor antagonists in dialysis patients: A meta-analysis.

INTRODUCTION: Our aim was to evaluate the safety and efficacy of low-dose mineralocorticoid receptor antagonists (MRAs) in dialysis patients. METHODS: We systematically searched PubMed, EMBASE, and Cochrane libraries for clinical trials on the use of MRAs in dialysis patients. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. RESULTS: We identified nine randomized controlled trials including 1128 chronic dialysis patients. In terms of safety, when hyperkalemia was defined as serum potassium level ≥5.5 mmol/L, low-dose MRAs were significantly associated with hyperkalemia (relative risk [RR] 1.76, 95% confidence intervals [CI] 1.07-2.89, P = .02); however, when hyperkalemia was defined as serum potassium level ≥6.0 mmol/L or serum potassium level ≥6.5 mmol/L, no significant association was observed between low-dose MRAs and hyperkalemia (RR 1.40, 95% CI 0.83-2.37, P = .20; RR 1.98, 95% CI 0.91-4.30, P = .09, respectively). Use of low-dose MRAs can reduce cardiovascular mortality by 54% compared with the control group (0.46, 95% CI 0.28-0.76, P = .003). Similarly, the RR of all-cause mortality for the low-dose MRAs group was 0.48 (95% CI 0.33-0.72, P = .0003). CONCLUSION: Low-dose MRAs may benefit dialysis patients without significantly increasing moderate to severe hyperkalemia.