Perilipin-2 mediates ferroptosis in oligodendrocyte progenitor cells and myelin injury after ischemic stroke

Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.

Evaluation of the intracellular lipid-lowering effect of polyphenols extract from highland barley in HepG2 cells

Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.

The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.

Boosting oxygen reduction activity and CO_(2) resistance on bismuth ferrite-based perovskite cathode for low-temperature solid oxide fuel cells below 600℃

Developing efficient and stable cathodes for low-temperature solid oxide fuel cells(LT-SOFCs) is of great importance for the practical commercialization.Herein,we propose a series of Sm-modified Bi_(0.7-x)Sm_xSr_(0.3)FeO_(3-δ) perovskites as highly-active catalysts for LT-SOFCs.Sm doping can significantly enhance the electrocata lytic activity and chemical stability of cathode.At 600℃,Bi_(0.675)Sm_(0.025)Sr_(0.3)FeO_(3-δ)(BSSF25) cathode has been found to be the optimum composition with a polarization resistance of 0.098 Ω cm^2,which is only around 22.8% of Bi_(0.7)Sr_(0.3)FeO_(3-δ)(BSF).A full cell utilizing BSSF25 displays an exceptional output density of 790 mW cm^(-2),which can operate continuously over100 h without obvious degradation.The remarkable electrochemical performance observed can be attributed to the improved O_(2) transport kinetics,superior surface oxygen adsorption capacity,as well as O_(2)p band centers in close proximity to the Fermi level.Moreover,larger average bonding energy(ABE) and the presence of highly acidic Bi,Sm,and Fe ions restrict the adsorption of CO_(2) on the cathode surface,resulting in excellent CO_(2) resistivity.This work provides valuable guidance for systematic design of efficient and durable catalysts for LT-SOFCs.

Enhancing performance of low-temperature processed CsPbI2Br all-inorganic perovskite solar cells using polyethylene oxide-modified TiO_(2)

CsPbX_(3)-based(X=I,Br,Cl)inorganic perovskite solar cells(PSCs)prepared by low-temperature process have attracted much attention because of their low cost and excellent thermal stability.However,the high trap state density and serious charge recombination between low-temperature processed TiO_(2)film and inorganic perovskite layer interface seriously restrict the performance of all-inorganic PSCs.Here a thin polyethylene oxide(PEO)layer is employed to modify TiO_(2)film to passivate traps and promote carrier collection.The impacts of PEO layer on microstructure and photoelectric characteristics of TiO_(2)film and related devices are systematically studied.Characterization results suggest that PEO modification can reduce the surface roughness of TiO_(2)film,decrease its average surface potential,and passivate trap states.At optimal conditions,the champion efficiency of CsPbI_(2)Br PSCs with PEO-modified TiO_(2)(PEO-PSCs)has been improved to 11.24%from 9.03%of reference PSCs.Moreover,the hysteresis behavior and charge recombination have been suppressed in PEO-PSCs.

Ultrafine ordered L1_(2)-Pt-Co-Mn ternary intermetallic nanoparticles as high-performance oxygen-reduction electrocatalysts for practical fuel cells

The long-range periodically ordered atomic structures in intermetallic nanoparticles(INPs)can significantly enhance both the electrocatalytic activity and electrochemical stability toward the oxygen reduction reaction(ORR)compared to the disordered atomic structures in ordinary solid-solution alloy NPs.Accordingly,through a facile and scalable synthetic method,a series of carbon-supported ultrafine Pt_3Co_(x)Mn_(1-x)ternary INPs are prepared in this work,which possess the"skin-like"ultrathin Pt shells,the ordered L1_(2) atomic structure,and the high-even dispersion on supports(L1_(2)-Pt_3Co_(x)Mn_(1-x)/~SPt INPs/C).Electrochemical results present that the composition-optimized L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C exhibits the highest electrocata lytic activity among the series,which are also much better than those of the pristine ultrafine Pt/C.Besides,it also has a greatly enhanced electrochemical stability.In addition,the effects of annealing temperature and time are further investigated.More importantly,such superior ORR electrocatalytic performance of L1_(2)-Pt_3Co_(0.7)Mn_(0.3)/~SPt INPs/C are also well demonstrated in practical fuel cells.Physicochemical characterization analyses further reveal the major origins of the greatly enhanced ORR electrocata lytic performance:the Pt-Co-Mn alloy-induced geometric and ligand effects as well as the extremely high L1_(2) atomic-ordering degree.This work not only successfully develops a highly active and stable ordered ternary intermetallic ORR electrocatalyst,but also elucidates the corresponding"structure-function"relationship,which can be further applied in designing other intermetallic(electro)catalysts.

植物同源域指蛋白6对肝癌Hep-G2细胞迁移能力的影响

目的探讨植物同源域指蛋白6(PHF6)对肝癌Hep-G2细胞迁移能力的影响,为临床诊疗提供参考。方法根据癌症基因组图谱(TCGA)数据库分析PHF6在人正常肝脏和肝癌组织的表达情况,以及其表达对300余例肝癌患者近十年生存率的影响。比较siNC组(转染PHF6无义序列)和siPHF6组(转染siRNA-PHF6)细胞PHF6 RNA表达水平,利用划痕和Transwell实验检测两组细胞迁移能力,通过实时荧光定量聚合酶链式反应检测两组细胞上皮间质转化(EMT)相关基因表达情况。结果PHF6在肝癌患者中存在明显过表达现象,高表达PHF6患者存活率降低。转染48 h后,siPHF6组细胞中PHF6 RNA表达水平低于siNC组(P=0.0016)。划痕后12、24、48、72h,siPHF6组细胞划痕距离均大于siNC组,siPHF6组细胞迁移数量小于siNC组。与siNC组相比,siPHF6组细胞神经钙黏蛋白(CDH2)、纤连蛋白(FN1)的表达水平均降低,CDH1的表达水平升高(P<0.0001、P<0.0001、P=0.0018)。结论沉默PHF6可显著抑制肝癌细胞的迁移和EMT进程,靶向PHF6治疗肝癌具有应用前途。

Plantamajoside improves type 2 diabetes mellitus pancreaticβ-cell damage by inhibiting endoplasmic reticulum stress through Dnajc1 up-regulation

BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.

PbrMYB4,a R2R3-MYB protein,regulates pear stone cell lignification through activation of lignin biosynthesis genes

Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.

HMGB2 knockdown ameliorates retinal ganglion cell injury by inhibiting NLRP3 inflammasome activation after retinal ischemia

AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.

Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

Naringin ameliorates H_(2)O_(2)-induced oxidative damage in cells and prolongs the lifespan of female Drosophila melanogaster via the insulin signaling pathway

Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms.The results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in cells.Meanwhile,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde content.Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells.Moreover,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of lysosomes.Furthermore,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.

Acetylacetone-TiO_(2) Promoted Large Area Compatible Cascade Electron Transport Bilayer for Efficient Perovskite Solar Cells

In designing efficient perovskite solar cells(PSCs),the selection of suitable electron transport layers(ETLs)is critical to the final device performance as they determine the driving force for selective charge extraction.SnO_(2)nanoparticles(NPs)based ETLs have been a popular choice for PSCs due to superior electron mobility,but their relatively deep-lying conduction band energy levels(ECB)result in substantial potential loss.Meanwhile,TiO_(2)NPs establish favorable band alignment owing to shallower ECB,but their low intrinsic mobility and abundant surface trap sites impede the final performance.For this reason,constructing a cascaded bilayer ETL is highly desirable for efficient PSCs,as it can rearrange energy levels and exploit on advantages of an individual ETL.In this study,we prepare SnO_(2)NPs and acetylacetone-modified TiO_(2)(Acac-TiO_(2))NPs and implement them as bilayer SnO_(2)/Acac-TiO_(2)(BST)ETL,to assemble cascaded energy band structure.SnO_(2)contributes to rapid charge carrier transport from high electron mobility while Acac-TiO_(2)minimizes band-offset and effectively suppresses interfacial recombination.Accordingly,the optimized BST ETL generates synergistic influence and delivers power conversion efficiency(PCE)as high as 23.14%with open-circuit voltage(V_(oc))reaching 1.14 V.Furthermore,the BST ETL is transferred to a large scale and the corresponding mini module demonstrates peak performance of 18.39%PCE from 25 cm^(2)aperture area.Finally,the BST-based mini module exhibit excellent stability,maintaining 83.1%of its initial efficiency after 1000 h under simultaneous 1 Sun light-soaking and damp heat(85℃/RH 85%)environment.

Crystallization management of CsPbI_(2)Br perovskites by PbAc_(2)-incorporated twice spin-coating process for efficient and stable CsPbI_(2)Br perovskite solar cells

CsPbI_(2)Br perovskite solar cell has been extensively studied due to its exceptional thermal stability and relatively stable perovskite phase structure.However,the presence of bromine leads to a rapid crystallization rate of CsPbI_(2)Br films,resulting in small grain size and high defect density.Additionally,CsPbI_(2)Br demonstrates poor light absorption due to its wide bandgap.Therefore,it is crucial to control the crystallization rate and increase the film thickness to reduce defect density,enhance light absorption,and improve photovoltaic performance.In this study,we utilized a PbAc_(2)-incorporated twice spincoating(PTS) process to address these issues.Initially,PbAc_(2) was added to the CsPbI_(2)Br precursor solution to form a CsPbI_(2)Br film,which was then coated with the CsPbI_(2)Br precursor solution to produce the PTS film,Ac^(-)can delay the perovskite crystallization,leading to the formation of thicker and denser CsPbI_(2)Br films.Moreover,lone-pair electrons of the oxygen atom provided by Ac^(-)formed coordination bonds with under-coordinated Pb~(2+) ions to fill halogen ion vacancies,thereby reducing the defect density.Ultimately,the PTS CsPbI_(2)Br device achieved a peak power conversion efficiency(PCE) of 16.19% and maintained 96.7% of its initial PCE over 1500 h at room temperature under 25% relative humidity without any encapsulation.

Precursor engineering enables high-performance all-inorganic CsPbIBr_(2) perovskite solar cells with a record efficiency approaching 13%

All-inorganic CsPbIBr_(2) perovskite has attracted widespread attention in photovoltaic and other optoelectronic devices because of its superior thermal stability.However,the deposition of high-quality solutionprocessed CsPbIBr_(2) perovskite films with large thicknesses remains challenging.Here,we develop a triple-component precursor(TCP) by employing lead bromide,lead iodide,and cesium bromide,to replace the most commonly used double-component precursor(DCP) consisting of lead bromide and cesium iodide.Remarkably,the TCP system significantly increases the solution concentration to 1.3 M,leading to a larger film thickness(~390 nm) and enhanced light absorption.The resultant CsPbIBr_(2) films were evaluated in planar n-i-p structured solar cells,which exhibit a considerably higher optimal photocurrent density of 11.50 mA cm^(-2) in comparison to that of DCP-based devices(10.69 mA cm^(-2)).By adopting an organic surface passivator,the maximum device efficiency using TCP is further boosted to a record efficiency of 12.8% for CsPbIBr_(2) perovskite solar cells.

Meiotic nuclear divisions 1 suppresses the proliferation and invasion of pancreatic cancer cells via regulating H2A.X variant histone

Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.

Differential Expressed Genes in ECV304 Endothelial-Like Cells Infected with Herpes Simplex Virus Type 2

Herpes simplex virus (HSV), the viral agent causing human genital herpes, recurs easily and poses significant harm to patients, while also being associated with atherosclerosis (AS). Currently, no effective therapy or vaccine exists to combat HSV. Previous studies have demonstrated the presence of HSV and its DNA in AS-diseased tissue, yet the precise pathogenesis of HSV involvement remains unclear. To investigate the genetic mechanism of HSV-induced vascular endothelial injury and AS, a type of human umbilical vein endothelial cells (ECV-304 cells) cultured in vitro were infected with herpes simplex virus type 2 (HSV-2). The effect of HSV-2 on differential gene expression in ECV304 cells was investigated by gene microarray technology during the early stages of infection. The results revealed a total of 462 differentially expressed genes, with 318 genes exhibiting up-regulated expression and 144 genes showing down-regulated expression. Furthermore, bioinformatics analysis revealed that all 462 differentially expressed genes were implicated in 237 distinct biological processes. Notably, 79 of these biological processes demonstrated statistically significant differences (P < 0.05), encompassing critical functions such as protein synthesis, ribosome biogenesis and assembly, as well as DNA and mRNA metabolism. Our findings have unveiled the differentially expressed genes of HSV-2 in ECV304 cells during infection, offering crucial insights into the pathogenic mechanisms underlying HSV-2 invasion of endothelial cells and the pathobiology of AS.

USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells

Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.