Can the aerosol pollution extreme events be revealed by global reanalysis products?

Extreme aerosol pollution poses significant risks to the climate, environment, and human health. To investigate the formation and impacts of aerosol pollution extreme events (APEE), the reanalysis product presents meticulous spatiotemporal information on the three-dimensional distribution of aerosols. However, there is a lack of comprehensive evaluation and information regarding the data quality of reanalysis products employed in APEE research, as well as limited understanding of their spatial and temporal distribution, variation, and long-term trends. To address this scientific gap, we conducted a global study for distribution and variation patterns of APEE using two widely-used reanalysis products, MERRA-2 (Modern-Era Retrospective Analysis for Research-2) and CAMS (Copernicus Atmospheric Monitoring Service). The APEE was defined here as a day when the daily aerosol optical depth (AOD) exceeding its 90th percentile for a given station and month. Eleven distinct land regions worldwide were selected for evaluation by comparing both reanalysis products with MODIS satellite products and ground-based observations in terms of frequency, intensity, and temporal trends of APEE. The analysis indicates that MERRA-2 and CAMS exhibit high matching rates (70 % and 80 %, respectively) in terms of occurrence timeline for APEE at monthly and seasonal scales, while also exhibiting strong monthly correlation coefficients (>0.65) with ground-based observations over selected regions. The total AOD (-0.002 âˆ¼ -0.123 decade-1), APEE AOD (-0.004 âˆ¼ -0.293 decade-1), and APEE frequency (-0.264 âˆ¼ -1.769 day month-1 decade-1) of both observations and reanalysis products in most regions showed a decreasing trend with various magnitude, except for some regions such as South Asia where the trend is increasing. Based on the aforementioned evaluation, it is evident that reanalysis products are effective and useful in identifying the temporal trends associated with APEE.

DsbA-L ameliorates renal aging and renal fibrosis by maintaining mitochondrial homeostasis.

Renal fibrosis is the final pathological change in renal disease, and aging is closely related to renal fibrosis. Mitochondrial dysfunction has been reported to play an important role in aging, but the exact mechanism remains unclear. Disulfide-bond A oxidoreductase-like protein (DsbA-L) is mainly located in mitochondria and plays an important role in regulating mitochondrial function and endoplasmic reticulum (ER) stress. However, the role of DsbA-L in renal aging has not been reported. In this study, we showed a reduction in DsbA-L expression, the disruption of mitochondrial function and an increase in fibrosis in the kidneys of 12- and 24-month-old mice compared to young mice. Furthermore, the deterioration of mitochondrial dysfunction and fibrosis were observed in DsbA-L-/- mice with D-gal-induced accelerated aging. Transcriptome analysis revealed a decrease in Flt4 expression and inhibition of the PI3K-AKT signaling pathway in DsbA-L-/- mice compared to control mice. Accelerated renal aging could be alleviated by an AKT agonist (SC79) or a mitochondrial protector (MitoQ) in mice with D-gal-induced aging. In vitro, overexpression of DsbA-L in HK-2 cells restored the expression of Flt4, AKT pathway factors, SP1 and PGC-1α and alleviated mitochondrial damage and cell senescence. These beneficial effects were partially blocked by inhibiting Flt4. Finally, activating the AKT pathway or improving mitochondrial function with chemical reagents could alleviate cell senescence. Our results indicate that the DsbA-L/AKT/PGC-1α signaling pathway could be a therapeutic target for age-related renal fibrosis and is associated with mitochondrial dysfunction.

Photoredox/Copper-Catalyzed One-Pot Aminoalkylation/Cyclization of Alkenes with Primary Amines to Synthesize Polysubstituted γ-Lactams.

Visible-light-driven chemical transformation has emerged as a powerful tool for the synthesis of γ-lactams. However, during this transformation, the α-bromoimides need to be pre-prepared. Herein, we report a photoreodox/copper-catalyzed one-pot three-component reaction of alkenes with primary amines for the construction of γ-lactams. In this transformation, the orthoquinones were generated via a photocatalytic pathway, followed by attack by Cu-amido complexes and intramolecular cyclization to give the γ-lactams. This method represents a simple synthetic route displaying broad functional group tolerance, including substrates bearing alcohols, ketones, heterocycles, esters, halides, alkynes, nitriles, ethers, etc.

Mechanism of Ferulic Acid in PI3K/AKT Pathway and Research in Glioblastoma.

Phenolic acids and their analogues in nature exist in many diseases of oxidative stress with beneficial effects on human health (such as cancer). Phenolic acids possess a variety of pharmacological activities, with anti-inflammatory, anticancer and cytotoxic, antioxidant, immunomodulatory, antimicrobial, insecticidal and other biological activities. Numerous in vitro and in vivo studies have shown that because phenolic acids have antioxidant capacity, they can reflect their strong anticancer potential by regulating cell growth and metastasis and promoting cancer cell death. Studies have shown that the consumption of natural polyphenols can significantly reduce the risk of cancer metastasis. A combination of phenolic acids with traditional chemoradiation or other polyphenols may be effective in reducing cancer spread.Ferulic acid is ubiquitous, and widely found in plants, such as angelica, chuanxiong, cohote, three, edge, reed root, tomato, sweet corn, and rice are produced by the metabolism of phenylalanine and tyrosine. It is the most abundant hydroxyl cassia bark-acid acid in the plant kingdom, with anti-inflammatory, antidiabetic, anticancer and antioxidant activity, and polyphenols composed of hydroxyl cassia bark-acid derivatives, flavone-3-alcohol and flavonol retain non-cancer-cells-and-significantly-inhibit glioblastoma viability in a dose-dependent manner, which deserves further investigation as potential anticancer drugs. This paper summarizes the role of ferulic acid in the PI3K / AKT pathway and its mechanism in glioblastoma resistance.

PACS-2 deficiency aggravates tubular injury in diabetic kidney disease by inhibiting ER-phagy.

Autophagy of endoplasmic reticulum (ER-phagy) selectively removes damaged ER through autophagy-lysosome pathway, acting as an adaptive mechanism to alleviate ER stress and restore ER homeostasis. However, the role and precise mechanism of ER-phagy in tubular injury of diabetic kidney disease (DKD) remain obscure. In the present study, we demonstrated that ER-phagy of renal tubular cells was severely impaired in streptozocin (STZ)-induced diabetic mice, with a decreased expression of phosphofurin acidic cluster sorting protein 2 (PACS-2), a membrane trafficking protein which was involved in autophagy, and a reduction of family with sequence similarity 134 member B (FAM134B), one ER-phagy receptor. These changes were further aggravated in mice with proximal tubule specific knockout of Pacs-2 gene. In vitro, transfection of HK-2 cells with PACS-2 overexpression plasmid partially improved the impairment of ER-phagy and the reduction of FAM134B, both of which were induced in high glucose ambience; while the effect was blocked by FAM134B siRNA. Mechanistically, PACS-2 interacted with and promoted the nuclear translocation of transcription factor EB (TFEB), which was reported to activate the expression of FAM134B. Collectively, these data unveiled that PACS-2 deficiency aggravates renal tubular injury in DKD via inhibiting ER-phagy through TFEB/FAM134B pathway.

Predicting osteoporosis preventive behaviors in middle-aged and older urban Shanghai residents: a health belief model-based path analysis in a multi-center population study.

Background: Osteoporosis represents a significant health concern as a widespread metabolic bone condition. In this study, we aim to utilize path analysis to examine the intricate relationships among demographic information, Health Belief Model (HBM) constructs and osteoporosis preventive behavior among Shanghai residents over 40 years of age. Methods: A multi-center population study was conducted in 20 volunteer communities in Shanghai, China. Out of the 2,000 participants who volunteered, 1,903 completed the field survey. Results: 56.0% of participants were females. Their mean age was 63.64 ± 10.30 years. The self-efficacy score among females (42.27 ± 15.82) was also significantly higher than that among males (40.68 ± 15.20). in the pathway analysis. In the path analysis preventive behaviors were significantly predicted by education (ß = 0.082, p < 0.001), knowledge (ß = 0.132, p < 0.001) and self-efficacy (ß = 0.392, p < 0.001). Conclusions: This study highlights the importance of gender, education, knowledge and self-efficacy in promoting OP preventive behaviors using the Health Belief Model. The findings emphasize the need for tailored interventions to address the specific needs of different demographic groups.

Fibroblast growth factor 21 in metabolic syndrome.

Metabolic syndrome is a complex metabolic disorder that often clinically manifests as obesity, insulin resistance/diabetes, hyperlipidemia, and hypertension. With the development of social and economic systems, the incidence of metabolic syndrome is increasing, bringing a heavy medical burden. However, there is still a lack of effective prevention and treatment strategies. Fibroblast growth factor 21 (FGF21) is a member of the human FGF superfamily and is a key protein involved in the maintenance of metabolic homeostasis, including reducing fat mass and lowering hyperglycemia, insulin resistance and dyslipidemia. Here, we review the current regulatory mechanisms of FGF21, summarize its role in obesity, diabetes, hyperlipidemia, and hypertension, and discuss the possibility of FGF21 as a potential target for the treatment of metabolic syndrome.

DsbA-L interacting with catalase in peroxisome improves tubular oxidative damage in diabetic nephropathy.

Peroxisomes are metabolically active organelles that are known for exerting oxidative metabolism, but the precise mechanism remains unclear in diabetic nephropathy (DN). Here, we used proteomics to uncover a correlation between the antioxidant protein disulfide-bond A oxidoreductase-like protein (DsbA-L) and peroxisomal function. In vivo, renal tubular injury, oxidative stress, and cell apoptosis in high-fat diet plus streptozotocin (STZ)-induced diabetic mice were significantly increased, and these changes were accompanied by a "ghost" peroxisomal phenotype, which was further aggravated in DsbA-L-deficient diabetic mice. In vitro, the overexpression of DsbA-L in peroxisomes could improve peroxisomal phenotype and function, reduce oxidative stress and cell apoptosis induced by high glucose (HG, 30 mM) and palmitic acid (PA, 250 µM), but this effect was reversed by 3-Amino-1,2,4-triazole (3-AT, a catalase inhibitor). Mechanistically, DsbA-L regulated the activity of catalase by binding to it, thereby reducing peroxisomal leakage and proteasomal degradation of peroxisomal matrix proteins induced by HG and PA. Additionally, the expression of DsbA-L in renal tubules of patients with DN significantly decreased and was positively correlated with peroxisomal function. Taken together, these results highlight an important role of DsbA-L in ameliorating tubular injury in DN by improving peroxisomal function.

A comparative study of the effects of electronic cigarette and traditional cigarette on the pulmonary functions of C57BL/6 male mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect the lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of Male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into 4 groups. They were exposed to the fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/ml of nicotine and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Mitochondrial homeostasis: a potential target for delaying renal aging.

Mitochondria, which are the energy factories of the cell, participate in many life activities, and the kidney is a high metabolic organ that contains abundant mitochondria. Renal aging is a degenerative process associated with the accumulation of harmful processes. Increasing attention has been given to the role of abnormal mitochondrial homeostasis in renal aging. However, the role of mitochondrial homeostasis in renal aging has not been reviewed in detail. Here, we summarize the current biochemical markers associated with aging and review the changes in renal structure and function during aging. Moreover, we also review in detail the role of mitochondrial homeostasis abnormalities, including mitochondrial function, mitophagy and mitochondria-mediated oxidative stress and inflammation, in renal aging. Finally, we describe some of the current antiaging compounds that target mitochondria and note that maintaining mitochondrial homeostasis is a potential strategy against renal aging.

Endoplasmic reticulum homeostasis: a potential target for diabetic nephropathy.

The endoplasmic reticulum (ER) is the most vigorous organelle in intracellular metabolism and is involved in physiological processes such as protein and lipid synthesis and calcium ion transport. Recently, the abnormal function of the ER has also been reported to be involved in the progression of kidney disease, especially in diabetic nephropathy (DN). Here, we reviewed the function of the ER and summarized the regulation of homeostasis through the UPR and ER-phagy. Then, we also reviewed the role of abnormal ER homeostasis in residential renal cells in DN. Finally, some ER stress activators and inhibitors were also summarized, and the possibility of maintaining ER homeostasis as a potential therapeutic target for DN was discussed.

Myostatin: a potential therapeutic target for metabolic syndrome.

Metabolic syndrome is a complex metabolic disorder, its main clinical manifestations are obesity, hyperglycemia, hypertension and hyperlipidemia. Although metabolic syndrome has been the focus of research in recent decades, it has been proposed that the occurrence and development of metabolic syndrome is related to pathophysiological processes such as insulin resistance, adipose tissue dysfunction and chronic inflammation, but there is still a lack of favorable clinical prevention and treatment measures for metabolic syndrome. Multiple studies have shown that myostatin (MSTN), a member of the TGF-ß family, is involved in the development and development of obesity, hyperlipidemia, diabetes, and hypertension (clinical manifestations of metabolic syndrome), and thus may be a potential therapeutic target for metabolic syndrome. In this review, we describe the transcriptional regulation and receptor binding pathway of MSTN, then introduce the role of MSTN in regulating mitochondrial function and autophagy, review the research progress of MSTN in metabolic syndrome. Finally summarize some MSTN inhibitors under clinical trial and proposed the use of MSTN inhibitor as a potential target for the treatment of metabolic syndrome.

DsbA-L alleviates tubular injury in diabetic nephropathy by activating mitophagy through maintenance of MAM integrity.

Mitochondria-associated endoplasmic reticulum membranes (MAMs) regulate ATG14- and Beclin1-mediated mitophagy and play key roles in the development of diabetic nephropathy (DN). DsbA-L is mainly located in MAMs and plays a role in renoprotection, but whether it activates mitophagy by maintaining MAM integrity remains unclear. In the present study, we found that renal tubular damage was further aggravated in diabetic DsbA-L-/- mice compared with diabetic mice and that this damage was accompanied by disrupted MAM integrity and decreased mitophagy. Furthermore, notably decreased expression of ATG14 and Beclin1 in MAMs extracted from the kidneys of diabetic DsbA-L-/- mice was observed. In vitro, overexpression of DsbA-L reversed the disruption of MAM integrity and enhanced mitophagy in HK-2 cells, a human proximal tubular cell line, after exposure to high-glucose (HG) conditions. Additionally, compared with control mice, DsbA-L-/- mice were exhibited down-regulated expression of helicase with zinc finger 2 (HELZ2) in their kidneys according to transcriptome analysis; HELZ2 serves as a cotranscription factor that synergistically functions with PPARα to promote the expression of mitofusin 2 (MFN-2). Treatment of HK-2 cells with MFN-2 siRNA resulted in MAM uncoupling and decreased mitophagy. Moreover, HG notably reduced the expression of HELZ2 and MFN-2 and inhibited mitophagy, and these effects were partially blocked by overexpression of DsbA-L and altered upon cotreatment with HELZ2 siRNA, HELZ2 overexpression or MK886 (PPARα inhibitor) treatment. These data indicate that DsbA-L alleviates diabetic tubular damage by activating mitophagy through maintenance of MAM integrity via the HELZ2/MFN-2 pathway.

4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling.

BACKGROUND: Septic acute kidney injury (S-AKI) is the leading form of acute kidney failure among hospitalized patients, and the inflammatory response is involved in this process. 4-octyl itaconate (4-OI) is a multi-target itaconate derivative with potent anti-inflammatory action. However, it remains elusive whether and how 4-OI contributes to the regulation of S-AKI. METHODS: We employed a lipopolysaccharide (LPS)-induced AKI murine model and explored the potential renoprotective effect of 4-OI in vivo. In vitro experiments, BUMPT cells, a murine renal tubular cell line, were conducted to examine the effects of 4-OI on inflammation, oxidative stress, and mitophagy. Moreover, STAT3 plasmid was transfected in BUMPT cells to investigate the role of STAT3 signaling in the 4-OI-administrated state. RESULTS: We demonstrate that 4-OI protects against S-AKI through suppressing inflammation and oxidative stress and enhancing mitophagy. 4-OI significantly reduced the levels of Scr, BUN, Ngal as well as the tubular injury in LPS-induced AKI mice. 4-OI restrained inflammation by reducing macrophage infiltration and suppressing the expression of IL-1ß and NLRP3 in the septic kidney. 4-OI also reduced ROS levels, as well as cleaved caspase-3 and boosted antioxidants such as HO-1, and NQO1 in mice. In addition, the 4-OI treatment significantly promoted mitophagy. Mechanistically, 4-OI activated Nrf2 signaling and suppressed phosphorylated STAT3 in vivo and vitro. Molecular docking revealed the binding affinity of 4-OI towards STAT3. ML385, a specific Nrf2 inhibitor, partially repressed the anti-inflammatory and anti-oxidative effects of 4-OI and partially restricted the mitophagy induced by 4-OI in vivo and in vitro. Transfected with STAT3 plasmid partially suppressed mitophagy and the anti-inflammatory effect provoked by 4-OI in vitro. CONCLUSION: These data suggest that 4-OI ameliorates LPS-induced AKI by suppressing inflammation and oxidative stress and enhancing mitophagy through the overactivation of the Nrf2 signaling pathway, and inactivation of STAT3. Our study identifies 4-OI as a promising pharmacologic for S-AKI.

Automatic 3D joint erosion detection for the diagnosis and monitoring of rheumatoid arthritis using hand HR-pQCT images.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. It leads to bone erosion in joints and other complications, which severely affect patients' quality of life. To accurately diagnose and monitor the progression of RA, quantitative imaging and analysis tools are desirable. High-resolution peripheral quantitative computed tomography (HR-pQCT) is such a promising tool for monitoring disease progression in RA. However, automatic erosion detection tools using HR-pQCT images are not yet available. Inspired by the consensus among radiologists on the erosions in HR-pQCT images, in this paper we define erosion as the significant concave regions on the cortical layer, and develop a model-based 3D automatic erosion detection method. It mainly consists of two steps: constructing closed cortical surface, and detecting erosion regions on the surface. In the first step, we propose an initialization-robust region competition methods for joint segmentation, and then fill the surface gaps by using joint bone separation and curvature-based surface alignment. In the second step, we analyze the curvature information of each voxel, and then aggregate the candidate voxels into concave surface regions and use the shape information of the regions to detect the erosions. We perform qualitative assessments of the new method using 59 well-annotated joint volumes. Our method has shown satisfactory and consistent performance compared with the annotations provided by medical experts.

Baicalin Nanocomplexes with an In Situ-Forming Biomimetic Gel Implant for Repair of Calvarial Bone Defects via Localized Sclerostin Inhibition.

In situ-forming hydrogels are highly effective in covering complex and irregular tissue defects. Herein, a biomimetic gel implant (CS-GEL) consisting of methacrylated chondroitin sulfate and gelatin is obtained via visible light irradiation, which displays rapid gelation (∼30 s), suitable mechanical properties, and biological features to support osteoblast attachment and proliferation. Sclerostin is proven to be a viable target to promote osteogenesis. Hence, baicalin, a natural flavonoid with a high affinity to sclerostin, is selected as the therapeutic compound to achieve localized neutralization of sclerostin. To overcome its poor solubility and permeability, a baicalin nanocomplex (BNP) is synthesized using Solutol HS15, which is then dispersed in the CS-GEL to afford a nanocomposite delivery system, i.e., BNP-loaded gel (BNP@CS-GEL). In vitro, BNP significantly downregulated the level of sclerostin in MLO-Y4 osteocytes. In vivo, either CS-GEL or BNP@CS-GEL is proven to effectively promote osteogenesis and angiogenesis in a calvarial critical-sized bone defect rat model, with BNP@CS-GEL showing the best pro-healing effect. Specifically, the BNP@CS-GEL-treated group significantly downregulated the sclerostin level as compared to the sham group (p < 0.05). RANKL expression was also significantly suppressed by BNP in MLO-Y4 cells and BNP@CS-GEL in vivo. Collectively, our study offers a facile and viable gel platform in combination with nanoparticulated baicalin for the localized neutralization of sclerostin to promote bone regeneration and repair.

PACS-2 deficiency in tubular cells aggravates lipid-related kidney injury in diabetic kidney disease.

BACKGROUND: Lipid accumulation in tubular cells plays a key role in diabetic kidney disease (DKD). Targeting lipid metabolism disorders has clinical value in delaying the progression of DKD, but the precise mechanism by which molecules mediate lipid-related kidney injury remains unclear. Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional sorting protein that plays a role in lipid metabolism. This study determined the role of PACS-2 in lipid-related kidney injury in DKD. METHODS: Diabetes was induced by a high-fat diet combined with intraperitoneal injections of streptozotocin (HFD/STZ) in proximal tubule-specific knockout of Pacs-2 mice (PT-Pacs-2-/- mice) and the control mice (Pacs-2fl/fl mice). Transcriptomic analysis was performed between Pacs-2fl/fl mice and PT-Pacs-2-/- mice. RESULTS: Diabetic PT-Pacs-2-/- mice developed more severe tubule injury and proteinuria compared to diabetic Pacs-2fl/fl mice, which accompanied with increasing lipid synthesis, uptake and decreasing cholesterol efflux as well as lipid accumulation in tubules of the kidney. Furthermore, transcriptome analysis showed that the mRNA level of sterol O-acyltransferase 1 (Soat1) was up-regulated in the kidney of control PT-Pacs-2-/- mice. Transfection of HK2 cells with PACS-2 siRNA under high glucose plus palmitic acid (HGPA) condition aggravated lipid deposition and increased the expression of SOAT1 and sterol regulatory element-binding proteins (SREBPs), while the effect was blocked partially in that of co-transfection of SOAT1 siRNA. CONCLUSIONS: PACS-2 has a protective role against lipid-related kidney injury in DKD through SOAT1/SREBPs signaling.

Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease.

Danggui-Shaoyao-San (DSS) is one of traditional Chinese medicine, which recently was found to play a protective role in diabetic kidney disease (DKD). However, the pharmacological mechanisms of DSS remain obscure. This study would explore the molecular mechanisms and bioactive ingredients of DSS in the treatment of DKD through network pharmacology. The potential target genes of DKD were obtained through OMIM database, the DigSee database and the DisGeNET database. DSS-related targets were acquired from the BATMAN-TCM database and the STITCH database. The common targets of DSS and DKD were selected for analysis in the STRING database, and the results were imported into Cytoscape to construct a protein-protein interaction network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis and Gene Ontology (GO) enrichment analysis were carried out to further explore the mechanisms of DSS in treating DKD. Molecular docking was conducted to identify the potential interactions between the compounds and the hub genes. Finally, 162 therapeutic targets of DKD and 550 target genes of DSS were obtained from our screening process. Among this, 28 common targets were considered potential therapeutic targets of DSS for treating DKD. Hub signaling pathways including HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, mTOR signaling pathway, and PI3K-Akt signaling pathway may be involved in the treatment of DKD using DSS. Furthermore, TNF and PPARG, and poricoic acid C and stigmasterol were identified as hub genes and main active components in this network, respectively. In this study, DSS appears to treat DKD by multi-targets and multi-pathways such as inflammatory, oxidative stress, autophagy and fibrosis, which provided a novel perspective for further research of DSS for the treatment of DKD.

Accurate detection of atrial fibrillation events with R-R intervals from ECG signals.

Atrial fibrillation (AF) is a typical category of arrhythmia. Clinical diagnosis of AF is based on the detection of abnormal R-R intervals (RRIs) with an electrocardiogram (ECG). Previous studies considered this detection problem as a classification problem and focused on extracting a number of features. In this study we demonstrate that instead of using any specific numerical characteristic as the input feature, the probability density of RRIs from ECG conserves comprehensive statistical information; hence, is a natural and efficient input feature for AF detection. Incorporated with a support vector machine as the classifier, results on the MIT-BIH database indicates that the proposed method is a simple and accurate approach for AF detection in terms of accuracy, sensitivity, and specificity.

ß-Hydroxybutyrate against Cisplatin-Induced acute kidney injury via inhibiting NLRP3 inflammasome and oxidative stress.

Cisplatin, as a commonly used anticancer drug, can easily lead to acute kidney injury (AKI), and has received more and more attention in clinical practice. ß-hydroxybutyric acid (BHB) is a metabolite in the body and acts as an inhibitor of oxidative stress and NLRP3 inflammasome, reducing inflammatory responses and apoptosis. However, the role of BHB in cisplatin-induced AKI is currently not fully elucidated. In this study, C57BL/6 male mice were randomly divided into normal control group, cisplatin-induced AKI group and AKI with BHB treatment group. Compared to the control, cisplatin-treated mice exhibited high level of serum creatinine, blood urea nitrogen and severe tubular injury, which accompanied with significantly increased expression level of NLRP3, IL-1ß, IL-18, BAX, cleaved-caspase 3, as well as aggravated oxidative stress and renal tubular cell apoptosis. However, these changes were significantly improved in that of BHB treatment. In vitro, our study showed that the expression of cleaved-caspase3, IL-1ß and IL-18 were significantly increased in human proximal tubular epithelial cell line (HK-2) treated with cisplatin compared with the control group, while decreased in cells treated with BHB. Furthermore, a significantly increased expression of cGAS and STING in HK-2 cells treated with cisplatin were found, whereas notably decreased in cells treated with BHB. This data indicates that BHB protects against cisplatin-induced AKI and renal tubular damage mediated by NLRP3 inflammasome and cGAS-STING pathway.