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Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.

Introduction: This study aimed to elucidate the biological implication of miR-937 in cigarette smoke extract (CSE)-induced human bronchial epithelial (HBE) cells and to further investigate its possible regulatory mechanism. Methods: Public datasets were downloaded to identify differentially expressed genes and subjected to Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis in chronic obstructive pulmonary disease (COPD). Online prediction site and luciferase reporter assay were applied to determine the target correlation between miR-937 and IL1B. RT-qPCR, Western blot and Enzyme-Linked Immunosorbent Assays (ELISA) analyses were used to evaluate the expressions of indicated molecules. HBE cells were exposed with CSE (20 μg/mL) to construct the in vitro COPD model. Cell proliferation and apoptosis were measured through cell counting kit 8 and Annexin-V/propidium iodide (PI) staining assays. Results: IL1B was found to be up-regulated in COPD samples compared with healthy controls and had a high correlation with the TNF and IL-17 pathways according to the data from GSE57148. Moreover, IL1B was predicted to be a target of miR-937, and it was negatively regulated by miR-937. CSE treatment reduced the miR- 937 expression, meanwhile decreased the HBE cells proliferation, enhanced cells apoptosis, and elevated the expression of IL-6, IL-17, and TNF-α. Moreover, in the CSE model, upregulation of miR-937 promoted cells viability, restrained cells apoptosis, and decreased levels of IL-6, IL-17, and TNF-α were noted, which could be abolished by overexpression IL1B. In contrast, inhibiting miR-937 impeded cells proliferation, promoted cells apoptosis and elevated levels of IL-6, IL-17 and TNF-α, which could be rescued by IL1B-knockdown in CSE-induced HBEs. Conclusions: These findings suggest that miR-937 plays a protective role on the HBEs after CSE damage, which may be achieved via targeting IL1B and inhibiting the TNF-α/IL-17 signaling pathway.

Numerous temperate plants now distributed across Eurasia are hypothesized to have originated and migrated from the Qinghai-Tibet Plateau (QTP) and adjacent regions. However, this hypothesis has never been tested through a phylogeographic analysis of a widely distributed species. Here, we use Hippophaë rhamnoides as a model to test this hypothesis. We collected 635 individuals from 63 populations of the nine subspecies of H. rhamnoides. We sequenced two maternally inherited chloroplast (cp) DNA fragments and also the bi-paternally inherited nuclear ribosomal ITS. We recovered five major clades in phylogenetic trees constructed from cpDNA and internal transcribed spacer (ITS) sequence variation. Most sampled individuals of six subspecies that are distributed in northern China, central Asia and Asia Minor/Europe, respectively, comprised monophyletic clades (or subclades) nested within those found in the QTP. Two subspecies in the QTP were paraphyletic, while the placement of another subspecies from the Mongolian Plateau differed between the ITS and cpDNA phylogenetic trees. Our phylogeographic analyses supported an ‘out-of-QTP’ hypothesis for H. rhamnoides followed by allopatric divergence, hybridization and introgression. These findings highlight the complexity of intraspecific evolutions and the importance of the QTP as a center of origin for many temperate plants.

Functionalized cyclic organic carbonates and carbamates are frequently used in a number of transition metal-catalyzed decarboxylative reactions for the construction of interesting molecules. These decarboxylative transformations have attracted more and more research attention in recent years mainly due to their advantages of less waste generation and versatile reactivities. On the basis of previous reviews on this hot topic, the present review will focus on the development of transition metal-catalyzed decarboxylative transformations of functionalized cyclic carbonates and carbamates in the last two years.

Background Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. Methods Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. Results After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P -values, including FSC-A on NKT ( β  = 0.119, 95% CI  = 0.044 ~ 0.194, P  = 0.002), DN (CD4-CD8-) NKT %T cell ( β  = 0.131, 95% CI  = 0.054 ~ 0.208, P  = 9.03 × 10 − 4 ), and SSC-A on lymphocytes ( β  = 0.136, 95% CI  = 0.059 ~ 0.213, P  = 5.43 × 10 − 4 ). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI  = 0.051 ~ 0.203, P  = 1.09 × 10 − 3 ). SCZ also had a causal effect on IgD+ %B cell ( β  = 0.130, 95% CI  = 0.054 ~ 0.207, P  = 8.69 × 10 − 4 ), and DP (CD4 + CD8 + ) %T cell ( β  = 0.131, 95% CI  = 0.054 ~ 0.207, P  = 8.05 × 10 − 4 ). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4 + %T cell ( OR  = 0.986, 95% CI  = 0.979 ~ 0.992, P  = 1.37 × 10 − 5 ), HLA DR on CD14 − CD16 − ( OR  = 0.738 (95% CI  = 0.642 ~ 0.849, P  = 2.00 × 10 − 5 ), CD33 dim HLA DR + CD11b − AC ( OR  = 0.631, 95% CI  = 0.529 ~ 0.753, P  = 3.40 × 10 − 7 ) and activated & resting Treg % CD4 Treg ( OR  = 0.937, 95% CI  = 0.906 ~ 0.970, P  = 1.96 × 10 − 4 ). Conclusions Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

Antibiotic resistance genes (ARGs) and metal(loid) resistance genes (MRGs) coexist in organic fertilized agroecosystems based on their correlations in abundance, yet evidence for the genetic linkage of ARG-MRGs co-selected by organic fertilization remains elusive. Here, an analysis of 511 global agricultural soil metagenomes reveals that organic fertilization correlates with a threefold increase in the number of diverse types of ARG-MRG-carrying contigs (AMCCs) in the microbiome (63 types) compared to non-organic fertilized soils (22 types). Metatranscriptomic data indicates increased expression of AMCCs under higher arsenic stress, with co-regulation of the ARG-MRG pairs. Organic fertilization heightens the coexistence of ARG-MRG in genomic elements through impacting soil properties and ARG and MRG abundances. Accordingly, a comprehensive global map was constructed to delineate the distribution of coexistent ARG-MRGs with virulence factors and mobile genes in metagenome-assembled genomes from agricultural lands. The map unveils a heightened relative abundance and potential pathogenicity risks (range of 4-6) for the spread of coexistent ARG-MRGs in Central North America, Eastern Europe, Western Asia, and Northeast China compared to other regions, which acquire a risk range of 1-3. Our findings highlight that organic fertilization co-selects genetically linked ARGs and MRGs in the global soil microbiome, and underscore the need to mitigate the spread of these co-resistant genes to safeguard public health. In this study, the authors analyzed global metagenomic data from agricultural soils and show that organic fertilization co-selects for antibiotic and metal(loid) resistance genes in genomic elements, while metatranscriptomic data additionally provides evidence for co-regulation of these gene sets.

The pursuit of energy density has driven electric vehicle (EV) batteries from using lithium iron phosphate (LFP) cathodes in early days to ternary layered oxides increasingly rich in nickel; however, it is impossible to forgo the LFP battery due to its unsurpassed safety, as well as its low cost and cobalt-free nature. Here we demonstrate a thermally modulated LFP battery to offer an adequate cruise range per charge that is extendable by 10 min recharge in all climates, essentially guaranteeing EVs that are free of range anxiety. Such a thermally modulated LFP battery designed to operate at a working temperature around 60 °C in any ambient condition promises to be a well-rounded powertrain for mass-market EVs. Furthermore, we reveal that the limited working time at the high temperature presents an opportunity to use graphite of low surface areas, thereby prospectively prolonging the EV lifespan to greater than two million miles. Ternary layered oxides dominate the current automobile batteries but suffer from material scarcity and operational safety. Here the authors report that, when operating at around 60 °C, a low-cost lithium iron phosphate-based battery exhibits ultra-safe, fast rechargeable and long-lasting properties.

Diabetes is a group of metabolic diseases characterised by chronic hyperglycaemia caused by multiple causes, which is caused by insulin secretion and/or utilisation defects. It is characterised by increased fasting and postprandial blood glucose levels due to insulin deficiency or insulin resistance. It is reported that the harm of diabetes mainly comes from its complications, and the cardiovascular disease caused by diabetes is the primary cause of its harm. China has the largest number of diabetic patients in the world, and the prevention and control of diabetes are facing great challenges. In recent years, many kinds of literature have been published abroad, which have proved that coumarin and its derivatives are effective in the treatment of diabetic complications such as nephropathy and cardiovascular disease. In this paper, the types of antidiabetic drugs and the anti-diabetic mechanism of coumarins were reviewed.

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as “Yin and Yang” partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14 ARF in human and p19 ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53. c-Myc and p53 operate in a negative feedback manner to maintain cellular homeostasis. Here, the authors report a long noncoding RNA, MILIP as a downstream target of c-Myc and that MILIP represses p53 to support tumorigenicity.

Cavitation may occur in water-jet pump during operation of water-jet propulsion vessel, and once cavitation occurs, the tip clearance pulsating pressure of the impeller may be intensified, resulting in increased vibration of the water-jet propulsion unit. In this paper, the cavitation pulsating pressure characteristics at different positions in the pump are studied by experiment and numerical simulation, and the pulsating pressure characteristics in tip clearance are mainly researched. Based on Star-CCM+ commercial software, unsteady Reynolds-averaged Navier-Stokes equations(RANS) numerical simulation is carried out, and the feasibility of the numerical simulation method is verified by uncertainty analysis. The results show that the cavitation pulsating pressure near the leading edge of the impeller in the tip clearance is the largest. The variation of the tip clearance pulsating pressure with the intensification of cavitation is studied by numerical simulation, and its mechanism is revealed. A dimensionless coefficient of net positive suction head ( C NPSH ) is proposed, and the study shows that the cavitation pulsation pressure coefficients of pumps of different scales are equal when the working conditions are similar and the C NPSH are equal, which indicates that the cavitation pulsating pressure performance of full scale pump can be predicted by model scale. It is of great significance to evaluate the vibration performance of the full scale water-jet propulsion.