A Double Perovskite Single Crystal CsCuAgI3.

Eco-friendly halide double perovskites are attracting significant attention as potential substitutes for traditional lead-based halide perovskites. However, their typically wide or indirect band gap limits further technological advancement. This study presents a new, eco-friendly, all-inorganic millimeter-scale CsCuAgI3 single crystal (SC). The crystal exhibits a direct band gap of 2.02 eV at the G-point, markedly superior to that of traditional double perovskites. The absorption and photoluminescence spectra further corroborate its band gap attributes. Owing to the B-site Cu-Ag disorder, the crystal possesses a higher Urbach energy (119 meV), indicative of structural disorder. CsCuAgI3 exhibits a wide Stokes shift of 230 nm, a wide full width at half-maximum (fwhm) of 152 nm, a long fluorescence lifetime of 7.29 µs, and excellent stability. In addition, a photoelectric detection prototype was prepared using a CsCuAgI3 single crystal. Using a 375 nm laser as the excitation source, the device showed a very sensitive photoelectric response, clocking in at (0.37/0.21) seconds. This work offers new insights into developing novel lead-free double perovskite single crystals and exploring their potential applications.

Macrophage-derived exosomes promote activation of NLRP3 inflammasome and autophagy deficiency of mesangial cells in diabetic nephropathy.

Dysfunction of mesangial cells plays a significant role in the glomerular lesions and is implicated in the pathophysiology of diabetic nephropathy (DN). Macrophages infiltration is the main pathological feature of DN, which can ultimately lead to renal inflammation. Recent studies suggest that the crosstalk between kidney resident cells and inflammatory cells influences the development of DN, and that controlling this crosstalk may help treat DN. Here, we found that DN mice appeared renal pathological damage, including dilation of mesangial matrix and significant infiltration of macrophages, accompanied by increased inflammatory response, NLRP3 inflammasome activation and autophagy deficiency. Additionally, mesangial cells internalized exosomes from high glucose (HG) treated macrophage, resulting the activation of inflammatory cytokines and NLRP3 inflammasome and deficiency of autophagy in vitro and in vivo. Moreover, C57BL/6 mice injected HG-stimulated macrophages-derived exosomes exhibited renal dysfunction and mesangial matrix expansion. Taken together, the present study demonstrated that mesangial cells responded to HG treated macrophage-derived exosomes by promoting the activation of NLRP3 inflammasome and autophagy deficiency, thereby participating in the development of DN.

Scutellarin Alleviates Ischemic Brain Injury in the Acute Phase by Affecting the Activity of Neurotransmitters in Neurons.

Cerebral ischemic stroke is a common neuron loss disease that is caused by the interruption of the blood supply to the brain. In order to enhance the CIS outcome, both identifying the treatment target of ischemic brain damage in the acute phase and developing effective therapies are urgently needed. Scutellarin had been found to be beneficial to ischemic injuries and has been shown to have potent effects in clinical application on both stroke and myocardial infarction. However, whether scutellarin improves ischemic brain damage in the acute phase remains unknown. In this study, the protective effects of scutellarin on ischemic brain damage in the acute phase (within 12 h) were illustrated. In middle cerebral artery occlusion and reperfusion (MCAO/R) modeling rats, the Z-Longa score was significantly down-regulated by 25% and 23.1%, and the brain infarct size was reduced by 26.95 ± 0.03% and 25.63 ± 0.02% when responding to high-dose and low-dose scutellarin treatments, respectively. H&E and TUNEL staining results indicated that the neuron loss of the ischemic region was improved under scutellarin treatment. In order to investigate the mechanism of scutellarin's effects on ischemic brain damage in the acute phase, changes in proteins and metabolites were analyzed. The suppression of scutellarin on the glutamate-inducing excitatory amino acid toxicity was strongly indicated in the study of both proteomics and metabolomics. A molecular docking experiment presented strong interactions between scutellarin and glutamate receptors, which score much higher than those of memantine. Further, by performing a parallel reaction monitoring-mass spectrometry (PRM-MS) study on both the cortex and hippocampus tissue of the ischemic region, we screened the scutellarin-regulating molecules that are involved in both the release and transportation of neurotransmitters. It was found that the aberrant levels of glutamate receptors, including EAAT2, GRIN1, GRIN2B, and GRM1, as well as of other glutamatergic pathway-involving proteins, including CAMKK2, PSD95, and nNOS, were significantly regulated in the ischemic cortex. In the hippocampus, EAAT2, GRIN1, nNOS, and CAM were significantly regulated. Taken together, scutellarin exerts potent effects on ischemic brain damage in the acute phase by regulating the activity of neurotransmitters and reducing the toxicity of excitatory amino acids in in neurons.

Recent Advances on Transition-Metal-Based Layered Double Hydroxides Nanosheets for Electrocatalytic Energy Conversion.

Transition-metal-based layered double hydroxides (TM-LDHs) nanosheets are promising electrocatalysts in the renewable electrochemical energy conversion system, which are regarded as alternatives to noble metal-based materials. In this review, recent advances on effective and facile strategies to rationally design TM-LDHs nanosheets as electrocatalysts, such as increasing the number of active sties, improving the utilization of active sites (atomic-scale catalysts), modulating the electron configurations, and controlling the lattice facets, are summarized and compared. Then, the utilization of these fabricated TM-LDHs nanosheets for oxygen evolution reaction, hydrogen evolution reaction, urea oxidation reaction, nitrogen reduction reaction, small molecule oxidations, and biomass derivatives upgrading is articulated through systematically discussing the corresponding fundamental design principles and reaction mechanism. Finally, the existing challenges in increasing the density of catalytically active sites and future prospects of TM-LDHs nanosheets-based electrocatalysts in each application are also commented.

The landscape of immune cell infiltration in the glomerulus of diabetic nephropathy: evidence based on bioinformatics.

BACKGROUND: Increasing evidence suggests that immune cell infiltration contributes to the pathogenesis and progression of diabetic nephropathy (DN). We aim to unveil the immune infiltration pattern in the glomerulus of DN and provide potential targets for immunotherapy. METHODS: Infiltrating percentage of 22 types of immune cell in the glomerulus tissues were estimated by the CIBERSORT algorithm based on three transcriptome datasets mined from the GEO database. Differentially expressed genes (DEGs) were identified by the "limma" package. Then immune-related DEGs were identified by intersecting DEGs with immune-related genes (downloaded from Immport database). The protein-protein interactions of Immune-related DEGs were explored using the STRING database and visualized by Cytoscape. The enrichment analyses for KEGG pathways and GO terms were carried out by the gene set enrichment analysis (GSEA) method. RESULTS: 11 types of immune cell were revealed to be significantly altered in the glomerulus tissues of DN (Up: B cells memory, T cells gamma delta, NK cells activated, Macrophages.M1, Macrophages M2, Dendritic cells resting, Mast cells resting; Down: B cells naive, NK cells resting, Mast cells activated, Neutrophils). Several pathways related to immune, autophagy and metabolic process were significantly activated. Moreover, 6 hub genes with a medium to strong correlation with renal function (eGFR) were identified (SERPINA3, LTF, C3, PTGDS, EGF and ALB). CONCLUSION: In the glomerulus of DN, the immune infiltration pattern changed significantly. A complicated and tightly regulated network of immune cells exists in the pathological of DN. The hub genes identified here will facilitate the development of immunotherapy.

Salvianolic acid B attenuates membranous nephropathy by activating renal autophagy via microRNA-145-5p/phosphatidylinositol 3-kinase/AKT pathway.

The abnormal proliferation and inflammatory response of the mesangial cells play a crucial role in the progression of membranous nephropathy (MN). Herein, this study aimed to investigate the therapeutic effect of Salvianolic acid B (SalB) on MN-induced mesangial abnormalities and its underlying mechanisms. MN models were established in cationic bovine serum albumin-induced Sprague-Dawley rats and lipopolysaccharide-induced human mesangial cells (HMCs). Following SalB and microRNA-145-5p antagomir treatment, kidney function was investigated by 24-hours urine protein, serum creatinine, and blood urea nitrogen. Pathological changes of kidney were investigated by Periodic acid Schiff staining. CD68 and IgG were detected by immunofluorescence in glomerulus. Mesangial autophagosomes were observed by transmission electron microscope. MicroRNA-145-5p inhibitor, mimic, LY294002, and SalB were used to treat with HMCs. In kidney and HMCs, IL-1 ß, IL-2, IL-6, TNF-α and microRNA-145-5p was detected by quantitative real-time PCR. Phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, AKT, beclin1, and microtubule-associated protein light chain 3 (LC3) levels were detected by Western blot. HMCs proliferation and cycle were detected by Cell Counting Kit-8 and flow cytometry. LC3 were detected by LC3-dual-fluorescent adenovirus in HMCs. Our results showed that SalB significantly ameliorated kidney function and pathological changes. Furthermore, it significantly alleviated proliferation, inflammation and activated autophagy in mesangial cells. Moreover, microRNA-145-5p antagomir accentuated MN while microRNA-145-5p inhibitor and LY294002 encouraged proliferation and inflammation through PI3K/AKT pathway in HMCs. Collectively, our study demonstrated that SalB activated renal autophagy to reduce cell proliferation and inflammation of MN, which was mediated by microRNA-145-5p to inhibit PI3K/AKT pathway, and ultimately attenuated MN.

Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B.

BACKGROUND: Whether interferon (IFN)-α therapy is better than nucleos(t)ide analogs (NAs) in the prevention of adverse outcomes, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is still uncertain or controversial. This study aimed to compare the cumulative incidence of adverse outcomes in patients with CHB on IFN-α- and NA-based therapies. METHODS: This was a retrospective study of patients with CHB on antivirals. Patients treated with IFN-α (IFN-α or peginterferon-α) with or without NAs were defined as the IFN-α group, and those only receiving NAs were defined as the NAs group. Propensity score matching (PSM) was used to minimize baseline bias. Cox regression models were performed to select possible factors related to adverse outcomes development. RESULTS: All 1247 patients were divided into the IFN-α (n = 877) and NAs (n = 370) groups. 26patients (20 and 6 in the NAs and IFN-α groups) developed adverse outcomes (decompensated cirrhosis, liver failure, HCC, liver transplantation and deaths) during a median follow-up of 5.2 years. The cumulative adverse outcomes occurrence at 10 years was significantly lower in the IFN-α group than in the NAs group in all (1.1% vs. 11.9%, P <0.001) and treatment-naïve (1.1% vs. 12.4%, P <0.001) patients. Similar trends were observed after PSM and differentiation of cirrhosis. Multivariate analysis before and after PSM showed that IFN-α-based treatment was independently associated with a lower adverse outcomes incidence (before/after PSM: P = 0.001/P = 0.002). HCC risk stratification analyses revealed that the superiority of IFN-α in preventing HCC was more significant in patients with high-risk HCC. CONCLUSIONS: IFN-α-based therapy was superior to NAs in preventing adverse outcomes in patients with CHB regardless of cirrhosis, and in reducing HCC in those with a high risk of HCC.

The Relationship between Hepatic Myeloid-Derived Suppressor Cells and Clinicopathological Parameters in Patients with Chronic Liver Disease.

Myeloid-derived suppressor cells (MDSCs) have attracted attention due to their important role in inflammation. Several studies have investigated the involvement of MDSCs in chronic liver disease. However, due to the difference of MDSC phenotypes, patient types, and sample sources among the studies, the results are inconsistent and controversial. We took advantage of a large well-defined cohort of 98 (24 patients with CHB, 18 with NAFLD, 13 with HCC, 16 with PBC, and 27 with AIH) patients with liver inflammation and 12 healthy controls to investigate the expression of MDSCs, and the relationships between the expression of hepatic MDSCs and the clinical characteristics were analyzed. We found that the expression of CD11b+CD33+ MDSCs is closely related to chronic liver disease and positively correlated with clinical parameters such as ALT, AST, and globulin. Ultimately, the present study suggests that hepatic CD11b+CD33+ MDSCs are increased in HCC and AIH and positively correlate with the liver stages of hepatitis activity and liver fibrosis stage.

JAK/STAT pathway promotes the progression of diabetic kidney disease via autophagy in podocytes.

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes and an important cause of end-stage renal disease. Previous studies have shown that the damage to podocyte autophagy is related to the pathogenesis of DKD, and this damage is closely mediated by the Janus kinase (JAK)/signal transductors and the transcription (STAT) signaling pathway. Here, the underlying molecular mechanism of the JAK/STAT signaling pathway regulating podocyte autophagy was investigated. In the present study, compared to controls, DKD mice showed glomerular hypertrophy, increased kidney weight/weight ratio, and increased urinary protein levels, as well as decreased desmin and synaptopodin expression. Meanwhile, levels of triglyceride, total cholesterol, reduced glutathione, and malondialdehyde were also increased in the serum of DKD mice. Further, a lower number of autophagosomes, reduced expression of MAP1LC3 (LC3) in glomeruli, and increased expression of JAK/STAT pathway-related proteins, namely JAK1, JAK2, STAT1, STAT3, STAT5, and STAT6, were observed in DKD mice. In the in vitro experiments, we observed impaired autophagy, enhanced apoptosis, and activated JAK/STAT pathway in podocytes under high glucose conditions. Studies using ruxolitinib inhibitors have showed that suppression of the JAK/STAT pathway in podocytes subjected to high glucose could increase autophagic flux and autophagy-related protein expression. Taken together, the present study demonstrates that high glucose inhibits autophagy by activating the JAK/STAT pathway in mice and podocytes, thereby preventing the efficient removal of damaged proteins and organelles from the body to prevent apoptosis, and ultimately aggravating the progression of podocyte injury and DKD.

[Effect of Valeriana jatamansi extract on fecal UPLC-MS/MS metabolomics in rats with diarrheal irritable bowel syndrome].

The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.

Impact of Hepatic Steatosis on the Antiviral Effects of PEG-IFNα-2a in Patients with Chronic Hepatitis B and the Associated Mechanism.

OBJECTIVE: To investigate the risk factors for hepatic steatosis in chronic hepatitis B (CHB), to determine its correlation with liver necroinflammation and fibrosis and response to peginterferon alpha-2a (PEG-IFNα-2a) antiviral therapy, and to explore the mechanisms underlying the poor antiviral effect of PEG-IFNα-2a in CHB patients with hepatic steatosis. METHODS: We analysed the impact of hepatic steatosis on the antiviral effect of PEG-IFNα-2a on CHB patients in a cohort of 226 patients who underwent pretherapeutic liver biopsy. To assess the complete response (CR), virological response (VR), and biochemical response (BR), the 226 patients were treated with PEG-IFNα-2a for 48 weeks and were followed-up for 24 weeks. The expressions of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue were detected in all patients to explore the possible mechanism of hepatic steatosis with regard to antiviral effects. RESULTS: The patients were divided into four groups based on the severity of hepatic steatosis: 119 with no steatosis, 76 with mild steatosis, 22 with moderate steatosis, and 9 with severe steatosis. In the hepatic steatosis groups, the proportions of male patients, patients aged >40 years, patients with hyperuricaemia, patients with a BMI > 23 kg/m2, and total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) levels were significantly higher than those in the group without steatosis, whereas the alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were significantly lower than those in the group without steatosis. The multivariate analysis results indicated that a BMI > 23 kg/m2 was independently associated with CHB patients with hepatic steatosis; the levels of baseline AST and UA were independently associated with CHB patients with significant hepatic steatosis, and the baseline AST level was independently associated with significant liver fibrosis. After 48 weeks of treatment and 24 weeks of follow-up, the rates of CR, VR, and BR had gradually decreased, whereas the severity of hepatic steatosis had increased. CONCLUSION: Hepatic steatosis can reduce the efficacy of PEG-IFNα-2a in the treatment of CHB patients, and its mechanism may be related to the different HBcAg expression patterns in liver tissue.

Transformation of functional groups and environmentally persistent free radicals in hydrothermal carbonisation of lignin.

In this study, lignin was selected as the main component of waste biomass to synthesise carbonaceous adsorbents with environmentally persistent free radicals (EPFRs) through hydrothermal carbonisation (HTC) under different conditions. The HTC method with Fe(III) doping was superior for promoting dehydration and decarboxylation of lignin hydrochar than that with HTC Cu(II) doping. The deconstruction of oxygen-containing groups of lignin was reduced while esterification was enhanced by Fe(III). The Fe(III) addition was conducive to the formation of EPFRs as carbon-centred radicals with an adjacent oxygen atom and oxygen-centred radicals. A comparison of lignin with cellulose and d-xylose suggests that the formed EPFRs on lignin hydrochar were derived from their phenolic hydroxyl groups. A high removal efficiency of bisphenol A by lignin hydrochar was observed owing to oxygen-centred radicals, which activated H2O2 to produce OH. These results will facilitate the design and application of novel hydrochar materials with EPFRs.

Lignin valorization for the production of renewable chemicals: State-of-the-art review and future prospects.

Lignin is an abundant biomass resource in aromatic structure with a low price in market, which can serve as renewable precursors of value-added products. However, valorization rate of annually produced lignin is less than 2%, suggesting the need for technological advancement to capitalize lignin as a versatile feedstock. In recent years, efficient utilization of lignin has attracted wide attention. This paper summarizes the research advances in the utilization of lignin resources (mainly in the last three years), with a particular emphasis on two major approaches of lignin utilization: catalytic degradation into aromatics and thermochemical treatment for carbon material production. Hydrogenolysis, direct pyrolysis, hydrothermal liquefaction, and hydrothermal carbonization of lignin are discussed in detail. Based on this critical review, future research directions and development prospects are proposed for sustainable and cost-effective lignin valorization.