Tuning Fe3O4 for sustainable cathodic heterogeneous electro-Fenton catalysis by acetylated chitosan.

Peroxidase-like catalysts are safe and low-cost candidates to tackle the dilemma in constructing sustainable cathodic heterogeneous electro-Fenton (CHEF) catalysts for water purification, but the elusive structure-property relationship of enzyme-like catalysts constitutes a pressing challenge for the advancement of CHEF processes in practically relevant water and wastewater treatment. Herein, we probe the origins of catalytic efficiency in the CHEF process by artificially tailoring the peroxidase-like activity of Fe3O4 through a series of acetylated chitosan-based hydrogels, which serve as ecofriendly alternatives to traditional carbon shells. The optimized acetylated chitosan wrapping Fe3O4 hydrogel on the cathode shows an impressive activity and stability in CHEF process, overcoming the complicated and environmentally unfavored procedures in the electro-Fenton-related processes. Structural characterizations and theoretical calculations reveal that the amide group in chitosan can modulate the intrinsic redox capacity of surficial Fe sites on Fe3O4 toward CHEF catalysis via the neutral hydrogen bond. This work provides a sustainable path and molecule-level insight for the rational design of high-efficiency CHEF catalysts and beyond.

The additive function of YIGE2 and YIGE1 in regulating maize ear length.

Ear length (EL) is a key trait that greatly contributes to yield in maize. Although dozens of EL quantitative trait loci have been mapped, very few causal genes have been cloned, and the molecular mechanisms remain largely unknown. Our previous study showed that YIGE1 is involved in sugar and auxin pathways to regulate ear inflorescence meristem (IM) development and thus affects EL in maize. Here, we reveal that YIGE2, the paralog of YIGE1, regulates maize ear development and EL through auxin pathway. Knockout of YIGE2 causes a significant decrease of auxin level, IM length, floret number, EL, and grain yield. yige1 yige2 double mutants had even shorter IM and ears implying that these two genes redundantly regulate IM development and EL. The genes controlling auxin levels are differential expressed in yige1 yige2 double mutants, leading to lower auxin level. These results elucidated the critical role of YIGE2 and the redundancy between YIGE2 and YIGE1 in maize ear development, providing a new genetic resource for maize yield improvement.

Rice kinase OsMRLK63 contributes to drought tolerance by regulating reactive oxygen species production.

Drought is a major adverse environmental factor that plants face in nature but the molecular mechanism by which plants transduce stress signals and further endow themselves with tolerance remains unclear. Malectin/malectin-like domains containing receptor-like kinases (MRLKs) have been proposed to act as receptors in multiple biological signaling pathways, but limited studies show their roles in drought-stress signaling and tolerance. In this study, we demonstrate OsMRLK63 in rice (Oryza sativa L.) functions in drought tolerance by acting as the receptor of 2 rapid alkalization factors, OsRALF45 and OsRALF46. We show OsMRLK63 is a typical receptor-like kinase that positively regulates drought tolerance and reactive oxygen species (ROS) production. OsMRLK63 interacts with and phosphorylates several nicotinamide adenine dinucleotide phosphate (NADPH) oxidases with the primarily phosphorylated site at Ser26 in the N-terminal of RESPIRATORY BURST OXIDASE HOMOLOGUE A (OsRbohA). The application of the 2 small signal peptides (OsRALF45/46) on rice can greatly alleviate the dehydration of plants induced by mimic drought. This function depends on the existence of OsMRLK63 and the NADPH oxidase-dependent ROS production. The 2 RALFs interact with OsMRLK63 by binding to its extracellular domain, suggesting they may act as drought/dehydration signal sensors for the OsMRLK63-mediated process. Our study reveals a OsRALF45/46-OsMRLK63-OsRbohs module which contributes to drought-stress signaling and tolerance in rice.

Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation.

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to diabetes and coronary heart disease. To expand the unclear genetic mechanism underlying AIWG, we conducted a two-stage genome-wide association study in Han Chinese patients with schizophrenia. The study included a discovery cohort of 1936 patients and a validation cohort of 534 patients, with an additional 630 multi-ancestry patients from the CATIE study for external validation. We applied Mendelian randomization (MR) analysis to investigate the relationship between AIWG and antipsychotic-induced lipid changes. Our results identified two novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P = 1.373 × 10-9) and rs3824417 in PTPRD (P = 3.348 × 10-9) in Chinese Han samples. The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. Colocalization analysis suggested that AIWG and type 2 diabetes (T2D) shared a causal variant in PEPD. Polygenic risk scores (PRSs) for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P = 7.58 × 10-4) and triglycerides (P = 2.06 × 10-3) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating antipsychotic-induced lipid changes, PRSs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC = 0.79, R2 = 0.332). Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia.

Autophagy defects at weaning impair complement-dependent synaptic pruning and induce behavior deficits.

Autophagy is crucial for synaptic plasticity and the architecture of dendritic spines. However, the role of autophagy in schizophrenia (SCZ) and the mechanisms through which it affects synaptic function remain unclear. In this study, we identified 995 single nucleotide polymorphisms (SNPs) across 19 autophagy-related genes that are associated with SCZ. Gene Set Enrichment Analysis (GSEA) of data from the Gene Expression Omnibus public database revealed defective autophagy in patients with SCZ. Using a maternal immune activation (MIA) rat model, we observed that autophagy was downregulated during the weaning period, and early-life activation of autophagy with rapamycin restored abnormal behaviors and electrophysiological deficits in adult rats. Additionally, inhibition of autophagy with 3-Methyladenine (3-MA) during the weaning period resulted in aberrant behaviors, abnormal electrophysiology, increased spine density, and reduced microglia-mediated synaptic pruning. Furthermore, 3-MA treatment significantly decreased the expression and synaptosomal content of complement, impaired the recognition of C3b and CR3, indicating that autophagy deficiency disrupts complement-mediated synaptic pruning. Our findings provide evidence for a significant association between SCZ and defective autophagy, highlighting a previously underappreciated role of autophagy in regulating the synaptic and behavioral deficits induced by MIA.

Large-Scale Atomic Strain Defects on Palladium Surfaces for Enhanced Oxygen Reduction and Zinc-Air Batteries.

Designing nano-electrocatalysts rich in surface defects is critical to improve their catalytic performance. However, prevailing synthesis techniques rely heavily on complex procedures that compromise defect extensiveness and uniformity, casting a high demand for methods capable of synthesizing large-scale crystalline defects. An innovative design strategy is herein proposed that induces ample strain/dislocation defects during the growth of palladium (Pd), which is well-known as a good oxygen reduction reaction (ORR) catalyst. The controlled defect engineering on Pd core is achieved by the tensile stress exerted from an intentionally applied Fe3O4 skin layer during synthesis, which changes the surface free energy of Pd to stabilize the defect presence. With such large-scale crystalline defects, this Pd catalyst exhibits significantly higher ORR activity than commercial Pt/C, enabling its promising future in zinc-air battery catalysis. Additionally, the protective Fe3O4 skin covering the catalyst also enhances its catalytic stability. Theoretical calculations show that the superior catalytic property of such defect-engineered Pd is associated with the correspondingly modified adsorption energy of *O intermediates onto its surface, which further improves the reaction rate and thus boosts ORR kinetics. Findings here are expected to provide a paradigm for designing efficient and stable metal catalysts with plentiful large-scale strain defects.

Quantum-Confined Perovskite Nanocrystals Enabled by Negative Catalyst Strategy for Efficient Light-Emitting Diodes.

The perovskite nanocrystals (PeNCs) are emerging as a promising emitter for light-emitting diodes (LEDs) due to their excellent optical and electrical properties. However, the ultrafast growth of PeNCs often results in large sizes exceeding the Bohr diameter, leading to low exciton binding energy and susceptibility to nonradiative recombination, while small-sized PeNCs exhibit a large specific surface area, contributing to an increased defect density. Herein, Zn2+ ions as a negative catalyst to realize quantum-confined FAPbBr3 PeNCs with high photoluminescence quantum yields (PL QY) over 90%. Zn2+ ions exhibit robust coordination with Br- ions is introduced, effectively retarding the participation of Br- ions in the perovskite crystallization process and thus facilitating PeNCs size control. Notably, Zn2+ ions neither incorporate into the perovskite lattice nor are absorbed on the surface of PeNCs. And the reduced growth rate also promotes sufficient octahedral coordination of PeNC that reduces defect density. The LEDs based on these optimized PeNCs exhibits an external quantum efficiency (EQE) of 21.7%, significantly surpassing that of the pristine PeNCs (15.2%). Furthermore, the device lifetime is also extended by twofold. This research presents a novel approach to achieving high-performance optoelectronic devices.

BNIP3+ fibroblasts associated with hypoxia and inflammation predict prognosis and immunotherapy response in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors that lacks effective treatment options. Cancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment, associated with tumor progression, prognosis, and treatment response. This work aimed to explore the novel CAFs-associated target to improve treatment strategies in PDAC. METHODS: The PDAC single-cell sequencing data (CRA001160, n = 35) were downloaded and integrated based on GSA databases to classify fibroblasts into fine subtypes. Functional enrichment analysis and coexpression regulatory network analysis were used to identify the functional phenotypes and biological properties of the different fibroblast subtypes. Fibroblast differentiation trajectories were constructed using pseudochronological analysis to identify initial and terminally differentiated subtypes of fibroblasts. The changes in the proportions of different fibroblast subtypes before and after PDAC immunotherapy were compared in responsive and nonresponding patients, and the relationships between fibroblast subtypes and PDAC immunotherapy responsiveness were determined based on GSA and GEO database. Using molecular biology methods to confirm the effects of BNIP3 on hypoxia and inflammation in CAFs. CAFs were co cultured with pancreatic cancer cells to detect their effects on migration and invasion of pancreatic cancer. RESULTS: Single-cell data analysis divided fibroblasts into six subtypes. The differentiation trajectory suggested that BNIP3+ Fibro subtype exhibited terminal differentiation, and the expression of genes related to hypoxia and the inflammatory response increased gradually with differentiation time. The specific overexpressed genes in the BNIP3+ Fibro subtype were significantly associated with overall and disease progression-free survival in the patients with PDAC. Interestingly, the greater the proportion of the BNIP3+ Fibro subtype was, the worse the response of PDAC patients to immunotherapy, and the CRTL treatment regimen effectively reduced the proportion of the BNIP3+ Fibro subtype. After knocking out BNIP3, the hypoxia markers and inflammatory factors of CAFs were inhibited. Co-culture of CAFs with pancreatic cancer cells can increase the migration and invasion of pancreatic cancer, but this could be reversed by knocking out BNIP3. CONCLUSIONS: This study revealed the BNIP3+ Fibro subtype associated with hypoxia and inflammatory responses, which was closely related to the poor prognosis of patients with PDAC, and identified signature genes that predict the immunotherapy response in PDAC.

ZmWAK02 encoding an RD-WAK protein confers maize resistance against gray leaf spot.

Gray leaf spot (GLS) caused by Cercospora zeina or C. zeae-maydis is a major maize disease throughout the world. Although more than 100 QTLs resistant against GLS have been identified, very few of them have been cloned. Here, we identified a major resistance QTL against GLS, qRglsSB, explaining 58.42% phenotypic variation in SB12×SA101 BC1 F1 population. By fine-mapping, it was narrowed down into a 928 kb region. By using transgenic lines, mutants and complementation lines, it was confirmed that the ZmWAK02 gene, encoding an RD wall-associated kinase, is the responsible gene in qRglsSB resistant against GLS. The introgression of the ZmWAK02 gene into hybrid lines significantly improves their grain yield in the presence of GLS pressure and does not reduce their grain yield in the absence of GLS. In summary, we cloned a gene, ZmWAK02, conferring large effect of GLS resistance and confirmed its great value in maize breeding.

FUSCA3-induced AINTEGUMENTA-like 6 manages seed dormancy and lipid metabolism.

FUSCA 3 (FUS3), a seed master regulator, plays critical role in seed dormancy and oil accumulation. However, its downstream regulation mechanisms remain poorly understood. Here, we explored the roles of AINTEGUMENTA-like 6 (AIL6), a seed transcription factor, in these processes. The activation of AIL6 by FUS3 was demonstrated by dual-LUC assay. Seeds of ail6 mutants showed alterations in fatty acid compositions, and both AtAIL6 (AIL6 from Arabidopsis thaliana) and BnaAIL6 (AIL6 from Brassica napus) rescued the phenotype. Over-expression (OE) of AIL6s reversed changes in seed fatty acid composition. Notably, OE lines showed low seed germination rates down to 12% compared to 100% of wild-type Col-0. Transcriptome analysis of the mutant and an OE line indicated widespread expression changes of genes involved in lipid metabolism and phytohormone pathways. In OE mature seeds, GA4 content decreased more than 15-fold, while abscisic acid and indole-3-acetic acid (IAA) contents clearly increased. Exogenous GA3 treatments did not effectively rescue the low germination rate. Nicking seed coats increased germination rates from 25% to nearly 80% while the wild-type rdr6-11 is 100% and 98% respectively, and elongation of storage time also improved seed germination. Furthermore, dormancy imposed by AIL6 was fully released in the della quintuple mutant. Together, our results indicate AIL6 acts as a manager downstream of FUS3 in seed dormancy and lipid metabolism.

Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke.

AIMS: Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process. METHODS: As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients' blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs. RESULTS: A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients' neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model. CONCLUSIONS: NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS. Video Abstract.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing.

BACKGROUND: Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive. METHODS: A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-ß or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-ß and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently, Phb2SMCKO mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with Phb2flox/flox mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2-hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo. CONCLUSIONS: Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.

Interfacial Regulation of Rice-Grain-like Iron-Nickel Phosphide Nanorods on Phosphorus-Doped Graphene Architectures as Bifunctional Electrocatalysts for Water Splitting.

The design of bimetallic metal-organic frameworks (MOFs) with a hierarchical structure is important to improve the electrocatalytic performance of catalysts due to their synergistic effect on different metal ions. In this work, the catalyst comprises bimetallic iron-nickel MOF-derived FeNi phosphides, intricately integrated with phosphorus-doped reduced graphene oxide architectures (FeNi2P-C/P-rGA) through the hydrothermal and phosphating treatments. The hierarchical architecture of the catalyst is beneficial for exposing active sites and facilitating electron transfer. The FeNi2P-C/P-rGA catalyst exhibits excellent performance in the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline electrolytes. Notably, FeNi2P-C/P-rGA requires only the overpotential of 93 and 210 mV to achieve a current density of 10 mA cm-2 for the HER and OER with small values of Tafel slope and charge transfer resistance, respectively. Furthermore, the catalyst exhibits boosted activity for overall water splitting with a low potential of 1.56 V. This work can be considered to extend the design of multilevel catalysts in the application of water splitting.

Association of modifiable risk factors and infectious diseases among individuals with hypertension: a prospective cohort study.

BACKGROUND: A comprehensive assessment of combined modifiable risk factors in relation to infectious diseases among individuals with hypertension is lacking, and the potential mechanisms of these associations remain unclear. To investigate the prospective associations of a combination of lifestyle behaviors and cardiometabolic factors with the risk of infectious diseases among individuals with hypertension and to estimate whether and to what extent blood biomarkers mediate these associations. METHODS: This cohort study included 147,188 participants with hypertension and complete data on modifiable risk factors from the UK Biobank. Health score was constructed from eight modifiable risk factors, including four lifestyle behaviors (diet, physical activity, smoking, and sleep duration) and four cardiometabolic factors (body mass index, blood lipids, blood glucose, and blood pressure). Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the health score and infectious diseases. The mediation analysis was performed to assess the potential intermediation effects of blood biomarkers. RESULTS: Over a median follow-up of 12.5 years, 27,398 participants with infectious diseases were documented, with 960 respiratory infectious diseases and 7940 digestive infectious diseases. After adjusting for potential confounders, the HR (95% CI) for the highest versus the lowest quartile of health score was 0.64 (0.62, 0.66) for infectious diseases, 0.72 (0.60, 0.86) for respiratory infectious diseases, and 0.66 (0.62, 0.71) for digestive infectious diseases. Stratified factors including duration of hypertension did not modify the associations between the health score and infectious diseases. In addition, biomarkers including inflammation and renal function collectively explained 46.60% of the associations between the combined lifestyle factors and infectious disease risk among individuals with hypertension. CONCLUSIONS AND RELEVANCE: Ideal management of combined modifiable risk factors was associated with lower risks of infectious diseases and might produce profound changes in blood biomarkers among individuals with hypertension. Additionally, specific biomarkers appeared to serve as an intermediate between combined lifestyle factors and infectious diseases. These insights highlighted the important role of a combination of healthy lifestyle and favorable cardiometabolic status in reducing disease burden and facilitated the understanding of biological mechanisms underlying modifiable risk factors with infectious diseases.

The Role of SIRT1 in Leukemia.

OPINION STATEMENT: Leukemia is a type of hematological malignancy (HM) caused by uncontrolled proliferation, apoptosis, and differentiation of hematopoietic stem cells (HSCs). Leukemia cells proliferate greatly in the bone marrow (BM), infiltrate other tissues and organs, and affect the normal hematopoietic function. Although the emergence of new targeted agents and immune agents has improved the prognosis of patients, due to the complex pathogenic factors and heterogeneity of leukemia, there are still some patients with poor prognosis. Recent studies have shown that silent information regulator 1 (SIRT1) is involved in the proliferation, apoptosis, metabolism, and senescence of leukemia cells. As a double-edged sword in leukemia cells, SIRT1 can both promote and inhibit the growth of leukemia cells. Since its mechanism of action has not been elucidated, it is urgent to explore the regulatory mechanism of SIRT1 in leukemia. In this review, we discussed the mechanisms of SIRT1 in different aspects of leukemia, providing a theoretical basis for the treatment of patients with leukemia.

MiR-31-5p alleviates septic cardiomyopathy by targeting BAP1 to inhibit SLC7A11 deubiquitination and ferroptosis.

Septic cardiomyopathy is one of the most severe and common complications in patients with sepsis and poses a great threat to their prognosis. However, the potential mechanisms and effective therapeutic drugs need to be explored. The control of cardiac cell death by miRNAs has emerged as a prominent area of scientific interest in the diagnosis and treatment of heart disorders in recent times. In the present investigation, we discovered that overexpression of miR-31-5p prevented LPS-induced damage to H9C2 cells and that miR-31-5p could inhibit BAP1 production by binding to its 3'-UTR. BRCA1-Associated Protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase. BAP1 upregulation blocked effect of miR-31-5p on H9C2 cell injury. Moreover, BAP1 inhibited the expression of solute carrier family 7 member 11 (SLC7A11) by deubiquitinating histone 2 A (H2Aub) on the promoter of SLC7A11. Furthermore, overexpression of miR-31-5p and downregulation of BAP1 inhibited SLC7A11 mediated ferroptosis. In addition, the downregulation of SLC7A11 reversed the inhibitory effect of miR-31-5p on the expression of myocardial injury and inflammatory factors, and cell apoptosis was reversed. In conclusion, these results indicate that miR-31-5p alleviates malignant development of LPS-induced H9C2 cell injury by targeting BAP1 and regulating SLC7A11 deubiquitination-mediated ferroptosis, which confirmed the protective effect of miR-31-5p on H9C2 cell injury and revealed potential mechanisms that may provide new targets for treatment of septic cardiomyopathy.

Golgi-targeted NIR fluorescent probe with large stokes shift for real-time monitoring of nitric oxide in depression model.

Depression is a debilitating mental illness that poses a serious threat to human health. Nitric Oxide (NO), as an important gasotransmitter, is closely associated with the pathogenesis of depressive disorders. Effective monitoring of NO fluctuation is beneficial for the diagnosis of depression and therapy assessment of antidepressants. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with depression diseases. Herein, we developed a NIR dye TJ730-based fluorescent probe TJ730-Golgi-NO incorporating benzenesulfonamide as a Golgi-targeted moiety and the thiosemicarbazide group for NO detection. The probe exhibited turn-on fluorescence ability and a large Stokes shift of 158 nm, which shows high sensitivity, selectivity, and rapid response (<1 min) for NO detection. TJ730-Golgi-NO could detect exogenous and endogenous NO in cells stimulated by Glu and LPS, and target Golgi apparatus. Moreover, we disclose a significant increase of NO in the depression model and a weak fluorescence evidenced in the fluoxetine-treated depression mice. This study provides a competent tool for studying the function of NO and helping improve the effective treatment of depression diseases.

Perovskite light-emitting diodes with external quantum efficiency exceeding 20 per cent.

Metal halide perovskite materials are an emerging class of solution-processable semiconductors with considerable potential for use in optoelectronic devices1-3. For example, light-emitting diodes (LEDs) based on these materials could see application in flat-panel displays and solid-state lighting, owing to their potential to be made at low cost via facile solution processing, and could provide tunable colours and narrow emission line widths at high photoluminescence quantum yields4-8. However, the highest reported external quantum efficiencies of green- and red-light-emitting perovskite LEDs are around 14 per cent7,9 and 12 per cent8, respectively-still well behind the performance of organic LEDs10-12 and inorganic quantum dot LEDs13. Here we describe visible-light-emitting perovskite LEDs that surpass the quantum efficiency milestone of 20 per cent. This achievement stems from a new strategy for managing the compositional distribution in the device-an approach that simultaneously provides high luminescence and balanced charge injection. Specifically, we mixed a presynthesized CsPbBr3 perovskite with a MABr additive (where MA is CH3NH3), the differing solubilities of which yield sequential crystallization into a CsPbBr3/MABr quasi-core/shell structure. The MABr shell passivates the nonradiative defects that would otherwise be present in CsPbBr3 crystals, boosting the photoluminescence quantum efficiency, while the MABr capping layer enables balanced charge injection. The resulting 20.3 per cent external quantum efficiency represents a substantial step towards the practical application of perovskite LEDs in lighting and display.

A programmable pAgo nuclease with RNA target preference from the psychrotolerant bacterium Mucilaginibacter paludis.

Argonaute (Ago) proteins are programmable nucleases found in eukaryotes and prokaryotes. Prokaryotic Agos (pAgos) share a high degree of structural homology with eukaryotic Agos (eAgos), and eAgos originate from pAgos. Although eAgos exclusively cleave RNA targets, most characterized pAgos cleave DNA targets. This study characterized a novel pAgo, MbpAgo, from the psychrotolerant bacterium Mucilaginibacter paludis which prefers to cleave RNA targets rather than DNA targets. Compared to previously studied Agos, MbpAgo can utilize both 5'phosphorylated(5'P) and 5'hydroxylated(5'OH) DNA guides (gDNAs) to efficiently cleave RNA targets at the canonical cleavage site if the guide is between 15 and 17 nt long. Furthermore, MbpAgo is active at a wide range of temperatures (4-65°C) and displays no obvious preference for the 5'-nucleotide of a guide. Single-nucleotide and most dinucleotide mismatches have no or little effects on cleavage efficiency, except for dinucleotide mismatches at positions 11-13 that dramatically reduce target cleavage. MbpAgo can efficiently cleave highly structured RNA targets using both 5'P and 5'OH gDNAs in the presence of Mg2+ or Mn2+. The biochemical characterization of MbpAgo paves the way for its use in RNA manipulations such as nucleic acid detection and clearance of RNA viruses.