AIM:To observe the effects of sargentgloryvine stem extracts (SSE) on the hepatoma cell line HepG-2 in vitro andin vivo and determine its mechanisms of action.METHODS:Cultured HepG-2 cells treated with SSE were analys...AIM:To observe the effects of sargentgloryvine stem extracts (SSE) on the hepatoma cell line HepG-2 in vitro andin vivo and determine its mechanisms of action.METHODS:Cultured HepG-2 cells treated with SSE were analysed by 3-(4,5-Dimethyl-thiazol-2-yl)-2,5Diphenyltetrazolium bromide and clone formation assay.The cell cycle and apoptosis analysis were conducted by flow cytometric,TdT-Mediated dUTP Nick End Labeling and acridine orange/ethidium bromide staining methods,and protein expression was examined by both reverse transcriptase-polymerase chain reaction and Western blotting.The pathological changes of the tumor cells were observed by haematoxylin and eosin staining.Tumor growth inhibition and side effects were determined in a xenograft mouse model.RESULTS:SSE treatment could not only inhibit HepG-2 cell proliferation in a doseand time-dependent manner but also induce apoptosis and cell cycle arrest at the S phase.The number of colonies formed by SSEtreated tumor cells was fewer than that of the controls (P<0.05).SSE induced caspase-dependent apoptosis accompanied by a significant decrease in Bcl-xl and Mcl-1 and elevation of Bak expression (P<0.05).Tumor necrosis factor α in the xenograft tumor tissue and the liver functions of SSE-treated mice showed no significant changes at week 8 compared with the control group (P>0.05).Systemic administration of SSE could inhibit the HepG-2 xenograft tumor growth with no obvious toxic side effects on normal tissues.CONCLUSION:SSE can induce apoptosis of HepG-2 cells in vitro and in vivo through decreasing expression of Bcl-xl and Mcl-1 and increasing expression of Bax.展开更多
Objective： The aim of our study was to investigate the effect of Cinobufacini injection on the proliferat（on and apoptosis of human hepatocarcinoma HepG-2 cells. Methods： Cells proliferation was assessed by MTT ass...Objective： The aim of our study was to investigate the effect of Cinobufacini injection on the proliferat（on and apoptosis of human hepatocarcinoma HepG-2 cells. Methods： Cells proliferation was assessed by MTT assay, cells morphologic was observed by the inverted microscopy, Annexin V/PI stain was used to detect the apoptosis and necrosis of the tumor ceils. The expression of TOPOI mRNA and TOPO Ⅱ mRNAwere examined by RT-PCR. Results： Cinobufacini injection significantly inhibited HepG-2 cells proliferation in dose- and time-dependent ways. After Cinobufacini injection intervention, HepG-2 cells showed typical morphological changes： cells changed from polygon into round, chromatin looseness and karyolysis were observed. The percentages of apoptosis were 88.49%, 76.02%, 61.73% corresponding to the 48 h interference of 0.42 μg/mL, 0.21 μg/mL, 0.105 μg/mL Cinobufacini injection, perspectively. RT-PCR assay showed that Cinobufacini injection down-regulated TOPOI and TOPO Ⅱ expression at mRNA level. Conclusion： Cinobufacini can inhibit human hepatocarcinoma HepG-2 cells growth and induce tumor cells apoptosis, the mechanism of which might partly relate to the down-regulation of TOPOI mRNA and TOPO Ⅰ mRNA induced by Cinobufacini injection.展开更多
Objective： The aim of our study was to investigate the effect of Cinobufacini injection on the proliferation and cell cycle of human hepatoma HepG-2 cells. Methods： Cell proliferation was assessed by MTT assay, cell...Objective： The aim of our study was to investigate the effect of Cinobufacini injection on the proliferation and cell cycle of human hepatoma HepG-2 cells. Methods： Cell proliferation was assessed by MTT assay, cell cycle distribution was detected by the flow cytometry （FCM）. The expression of Cyclin A, CDK2 mRNA levels were examined by RT-PCR. Quantitative colorimetric assay was used to analyze Cyclin NCDK2 activity in HepG-2 cells. Results： Cinobufacini injection significantly inhibited HepG-2 cells proliferation in dose- and time-dependent ways; FCM analysis showed Cinobufacini injection induced cell cycle arrest at S phase; RT-PCR assay showed Cinobufacini injection down-regulated Cyclin A, CDK2 expression at mRNA levels; Quantitative colorimetric assay showed Cinobufacini injection deceased Cyclin NCDK2 activity in HepG-2 cells. Conclusion： Cinobufacini injection can inhibit human hepatoma HepG-2 cells growth, induce cell apoptosis and induce cell cycle arrest at S phase, the mechanism of which might be partly related to the down-regulation of Cyclin A, CDK2 mRNA expression and inhibition of Cyclin A/CDK2 activity.展开更多
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 combinat...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.展开更多
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 mus...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.展开更多
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)...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.展开更多
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)pat...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.展开更多
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),Dapaglif...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.展开更多
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 an...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.展开更多
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 extract...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.展开更多
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...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.展开更多
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 solutionprocess...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.展开更多
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...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.展开更多
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 hi...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.展开更多
The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epith...The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epithelium undergo a series of significant changes, including cell proliferation and apoptosis. However, the molecular mechanisms are not yet fully understood. In this study, a higher circRNA3669 level was observed in PE than in RE of goats. Functional assays revealed that this overexpression promoted the proliferation of goat endometrial epithelial cells(GEECs) by activating the expression of genes related to the PI3K/AKT-mTOR and MAPK pathways,thereby inhibiting apoptosis in vitro. Furthermore, circRNA3669 functioned as a competing endogenous RNA(ceRNA) to upregulate Reticulocalbin-2(RCN2) expression at the post-transcriptional level by interacting with and downregulating miR-26a in GEECs. In addition, RCN2, which is highly expressed in the PE of goats, was found to be regulated by β-estradiol(E2) and progesterone(P4). Our results demonstrated that RCN2 also affected the key proteins PI3K, AKT, mTOR, JNK, and P38 in the PI3K/AKT-mTOR and MAPK pathways, thereby facilitating GEECs proliferation and suppressing their apoptosis in vitro. Collectively, we constructed a new circRNA3669-miR-26aRCN2 regulatory network in GEECs, which further provides strong evidence that circRNA could potentially play a crucial regulatory role in the development of RE in goats.展开更多
Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene ...Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.展开更多
AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect ...AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ET.METHODS:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1.An injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in vitro.Cells were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/L.Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)stimulation.The levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time points.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of RGCs.Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after ONT.Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo.CONCLUSION:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the greatest effect being at 10μmol/L.ET plays an antioxidant role by inhibiting iNOS,up-regulating Nrf2/HO-1,decreasing the production of acrolein,and increasing the scavenge of acrolein.展开更多
Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport cha...Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.展开更多
Background:Cochlear hair cell injury is a common pathological feature of hearing loss.The basic helix-loop-helix family,member e40(Bhlhe40),a gene belonging to the basic helix-loop-helix(bHLH)family,exhibits strong tr...Background:Cochlear hair cell injury is a common pathological feature of hearing loss.The basic helix-loop-helix family,member e40(Bhlhe40),a gene belonging to the basic helix-loop-helix(bHLH)family,exhibits strong transcriptional repression activity.Methods:Oxidative damage,in House Ear Institute-Organ of Corti 1(HEI-OC1)cells,was caused using hydrogen peroxide(H2O2).The Ad-Bhlhe40 particles were constructed to overexpress Bhlhe40 in HEI-OC1 cells.Various assays including cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay(TUNEL),flow cytometry,immunofluorescence,and corresponding commercial kits were employed to investigate the impacts of Bhlhe40 on cell viability,apoptosis,oxidative stress levels,mitochondrial membrane potential and cellular senescence.Additionally,a dual-luciferase reporter assay was performed to confirm the targeting of the histone deacetylases 2(Hdac2)by Bhlhe40.Results:The results revealed that Bhlhe40 was downregulated in H_(2)O_(2)-treated HEI-OC1 cells,but its overexpression improved cell viability and mitigated H_(2)O_(2)-induced oxidative injury in HEI-OC1 cells with increase of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GPx)activities and decrease of reactive oxygen species(ROS)levels.Besides,overexpression of Bhlhe40 suppressed H_(2)O_(2)-triggered cell senescence,as evidenced by the fact that the upregulation of P53,P21,and P16 in HEI-OC1 cells treated with H2O2 were all alleviated by Bhlhe40 overexpression.And we further verified that overexpression of Bhlhe40 could inhibit the expression of Hdac2,which may be related to the repression of Hdac2 transcription.Conclusion:This study suggests that Bhlhe40 plays a protective role against senescence and oxidative damage in cochlear hair cells exposed to H2O2.展开更多
The interfaces between the inorganic metal oxide and organic photoactive layer are of outmost importance for efficiency and stability in organic solar cells(OSCs).Tin oxide(SnO_(2))is one of the promising candidates f...The interfaces between the inorganic metal oxide and organic photoactive layer are of outmost importance for efficiency and stability in organic solar cells(OSCs).Tin oxide(SnO_(2))is one of the promising candidates for the electron transport layer(ETL)in high-performance inverted OSCs.When a solution-processed SnO_(2)ETL is employed,however,the presence of interfacial defects and suboptimal interfacial contact can lower the power conversion efficiency(PCE)and operational stability of OSCs.Herein,highly efficient and stable inverted OSCs by modification of the SnO_(2)surface with ultraviolet(UV)-curable acrylate oligomers(SAR and OCS)are demonstrated.The highest PCEs of 16.6%and 17.0%are achieved in PM6:Y6-BO OSCs with the SAR and OCS,respectively,outperforming a device with a bare SnO_(2)ETL(PCE 13.8%).The remarkable enhancement of PCEs is attributed to the optimized interfacial contact,leading to mitigated surface defects.More strikingly,improved light-soaking and thermal stability strongly correlated with the interfacial defects are demonstrated for OSCs based on SnO_(2)/UV cross-linked resins compared to OSCs utilizing bare SnO_(2).We believe that UV cross-linking oligomers will play a key role as interfacial modifiers in the future fabrication of large-area and flexible OSCs with high efficiency and stability.展开更多
基金Supported by National Science and Technology Key Project for the Development of New Drugs in China,No. 2009ZX09103-422
文摘AIM:To observe the effects of sargentgloryvine stem extracts (SSE) on the hepatoma cell line HepG-2 in vitro andin vivo and determine its mechanisms of action.METHODS:Cultured HepG-2 cells treated with SSE were analysed by 3-(4,5-Dimethyl-thiazol-2-yl)-2,5Diphenyltetrazolium bromide and clone formation assay.The cell cycle and apoptosis analysis were conducted by flow cytometric,TdT-Mediated dUTP Nick End Labeling and acridine orange/ethidium bromide staining methods,and protein expression was examined by both reverse transcriptase-polymerase chain reaction and Western blotting.The pathological changes of the tumor cells were observed by haematoxylin and eosin staining.Tumor growth inhibition and side effects were determined in a xenograft mouse model.RESULTS:SSE treatment could not only inhibit HepG-2 cell proliferation in a doseand time-dependent manner but also induce apoptosis and cell cycle arrest at the S phase.The number of colonies formed by SSEtreated tumor cells was fewer than that of the controls (P<0.05).SSE induced caspase-dependent apoptosis accompanied by a significant decrease in Bcl-xl and Mcl-1 and elevation of Bak expression (P<0.05).Tumor necrosis factor α in the xenograft tumor tissue and the liver functions of SSE-treated mice showed no significant changes at week 8 compared with the control group (P>0.05).Systemic administration of SSE could inhibit the HepG-2 xenograft tumor growth with no obvious toxic side effects on normal tissues.CONCLUSION:SSE can induce apoptosis of HepG-2 cells in vitro and in vivo through decreasing expression of Bcl-xl and Mcl-1 and increasing expression of Bax.
文摘Objective： The aim of our study was to investigate the effect of Cinobufacini injection on the proliferat（on and apoptosis of human hepatocarcinoma HepG-2 cells. Methods： Cells proliferation was assessed by MTT assay, cells morphologic was observed by the inverted microscopy, Annexin V/PI stain was used to detect the apoptosis and necrosis of the tumor ceils. The expression of TOPOI mRNA and TOPO Ⅱ mRNAwere examined by RT-PCR. Results： Cinobufacini injection significantly inhibited HepG-2 cells proliferation in dose- and time-dependent ways. After Cinobufacini injection intervention, HepG-2 cells showed typical morphological changes： cells changed from polygon into round, chromatin looseness and karyolysis were observed. The percentages of apoptosis were 88.49%, 76.02%, 61.73% corresponding to the 48 h interference of 0.42 μg/mL, 0.21 μg/mL, 0.105 μg/mL Cinobufacini injection, perspectively. RT-PCR assay showed that Cinobufacini injection down-regulated TOPOI and TOPO Ⅱ expression at mRNA level. Conclusion： Cinobufacini can inhibit human hepatocarcinoma HepG-2 cells growth and induce tumor cells apoptosis, the mechanism of which might partly relate to the down-regulation of TOPOI mRNA and TOPO Ⅰ mRNA induced by Cinobufacini injection.
文摘Objective： The aim of our study was to investigate the effect of Cinobufacini injection on the proliferation and cell cycle of human hepatoma HepG-2 cells. Methods： Cell proliferation was assessed by MTT assay, cell cycle distribution was detected by the flow cytometry （FCM）. The expression of Cyclin A, CDK2 mRNA levels were examined by RT-PCR. Quantitative colorimetric assay was used to analyze Cyclin NCDK2 activity in HepG-2 cells. Results： Cinobufacini injection significantly inhibited HepG-2 cells proliferation in dose- and time-dependent ways; FCM analysis showed Cinobufacini injection induced cell cycle arrest at S phase; RT-PCR assay showed Cinobufacini injection down-regulated Cyclin A, CDK2 expression at mRNA levels; Quantitative colorimetric assay showed Cinobufacini injection deceased Cyclin NCDK2 activity in HepG-2 cells. Conclusion： Cinobufacini injection can inhibit human hepatoma HepG-2 cells growth, induce cell apoptosis and induce cell cycle arrest at S phase, the mechanism of which might be partly related to the down-regulation of Cyclin A, CDK2 mRNA expression and inhibition of Cyclin A/CDK2 activity.
基金financially supported by the National Key Research and Development Program of China(2021YFD2100904)the National Natural Science Foundation of China(31871729,32172147)+2 种基金the Modern Agriculture key Project of Jiangsu Province of China(BE2022317)the Modern Agricultural Industrial Technology System Construction Project of Jiangsu Province of China(JATS[2021]522)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘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.
基金supported by the National Natural Science Foundation of China(22279025,21773048)the Natural Science Foundation of Heilongjiang Province(LH2021A013)+1 种基金the Sichuan Science and Technology Program(2021YFSY0022)the Fundamental Research Funds for the Central Universities(2023FRFK06005,HIT.NSRIF202204)。
文摘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.
基金supported by the Open Project Program of the State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science and Technology(No.SKLFNS-KF-202201)the Open Project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,China(No.GMU-2022-HJZ-06)。
文摘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.
基金funded by the Deanship of Scientific Research(DSR),King Abdulaziz University,Jeddah,Saudi Arabia,under Grant No.KEP-1-166-41The authors,therefore,acknowledge DSR,with thanks for their technical and financial support.
文摘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.
基金supported by the open project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,China (GMU-2022-HJZ-06)。
文摘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.
基金supported by the National Research Foundation of Korea(NRF)under the Ministry of ScienceICT&Future Planning(Basic Science Research Program[No.2021R1A5A6002853],[No.2022R1A2C3004964],[No.2022R1C1C2008126],[No.2022M3H4A1A03074093])
文摘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.
基金supported by the National Natural Science Foundation of China (U22A20142)the Fundamental Research Funds for the Central Universities (2023JC007)。
文摘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.
基金The authors acknowledge the financial support by the National Natural Science Foundation of China(52161145408 and 21975038)the Research and Innovation Team Project of Dalian University of Technology(DUT2022TB10)+2 种基金the Fundamental Research Funds for the Central Universities(DUT22QN213)the Innovation Technology Fund(MRP/040/21X)the Green Technology Fund(GTF202020164)for their financial support。
文摘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.
基金supported by grants from National Innovation Program for College Students(202210367076)Graduate Student Research Innovation Program of Bengbu Medical College(Byycxz22016)the National Natural Science Foundation of China(82072585),and the Key Research Project of Bengbu Medical College(No.2020byzd029).
文摘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.
基金supported by Natural Science Foundation of Shaanxi Province(No.2023-JC-YB-743 and No.2021JQ-905).
文摘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.
基金supported by the China Postdoctoral Science Foundation(2019M653776 and 2020M673516)the Natural Science Basis Research Plan in Shaanxi Province of China(2023-JC-QN-0181)+1 种基金the Shaanxi Livestock and Poultry Breeding Double-chain Fusion Key Project,China(2022GD-TSLD-46-0202)the Natural Science Fundation of Tibet Autonomous Region,China(XZ202101ZR0063G)。
文摘The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epithelium undergo a series of significant changes, including cell proliferation and apoptosis. However, the molecular mechanisms are not yet fully understood. In this study, a higher circRNA3669 level was observed in PE than in RE of goats. Functional assays revealed that this overexpression promoted the proliferation of goat endometrial epithelial cells(GEECs) by activating the expression of genes related to the PI3K/AKT-mTOR and MAPK pathways,thereby inhibiting apoptosis in vitro. Furthermore, circRNA3669 functioned as a competing endogenous RNA(ceRNA) to upregulate Reticulocalbin-2(RCN2) expression at the post-transcriptional level by interacting with and downregulating miR-26a in GEECs. In addition, RCN2, which is highly expressed in the PE of goats, was found to be regulated by β-estradiol(E2) and progesterone(P4). Our results demonstrated that RCN2 also affected the key proteins PI3K, AKT, mTOR, JNK, and P38 in the PI3K/AKT-mTOR and MAPK pathways, thereby facilitating GEECs proliferation and suppressing their apoptosis in vitro. Collectively, we constructed a new circRNA3669-miR-26aRCN2 regulatory network in GEECs, which further provides strong evidence that circRNA could potentially play a crucial regulatory role in the development of RE in goats.
基金This research was partly supported by the Fundamental Research Funds of Shandong University(21510078614097)the Shandong Natural Science Foundation General Project(ZR2022MC093).
文摘Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.
基金Supported by the Ministry of Science and Technology of China(No.2021ZD0203104)the Science and Technology Plan Project of Shaanxi Province of China(No.2022SF-497)Xi’an Medical University Doctoral Research Fund(No.2020DOC18).
文摘AIM:To determine whether etomidate(ET)has a protective effect on retinal ganglion cells(RGCs)injured with hydrogen peroxide(H_(2)O_(2))and to explore the potential mechanism underlying the antioxidative stress effect of ET.METHODS:Cultured RGCs were identified by double immunofluorescent labeling of microtubule-associated protein 2 and Thy1.1.An injury model of H_(2)O_(2)-induced RGCs oxidative stress was established in vitro.Cells were pretreated with different concentrations of ET(1,5,and 10μmol/L)for 4h,followed by further exposure to H_(2)O_(2)at 1000μmol/L.Cell counting kit 8 and Annexin V/propidium iodide assays were applied to detect the viabilities and apoptosis rates of the RGCs at 12,24,and 48h after H_(2)O_(2)stimulation.The levels of nitric oxide,malondialdehyde,and glutathione in culture media were measured at these time points.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blot were performed to observe the effects of ET on the messenger RNA and protein expression of inducible nitric oxide synthase(iNOS),nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),glutathione peroxidase 1 and the level of conjugated acrolein in RGCs at 12,24,and 48h after H_(2)O_(2)stimulation and in the retina at 12h after optic nerve transection(ONT).RESULTS:The applications of 5 and 10μmol/L of ET significantly increased the viability of RGCs.Results from qRT-PCR indicated a decrease in the expression of iNOS and an increase in the expressions of Nrf2 and HO-1 in ETpretreated RGCs at 12,24 and 48h after H_(2)O_(2)stimulation,as well as in ET-treated retinas at 12h after ONT.Western blot analysis revealed a decrease in the expression of iNOS and levels of conjugated acrolein,along with an increase in the expressions of Nrf2 and HO-1 in ET-pretreated RGCs in vitro and ET-treated retinas in vivo.CONCLUSION:ET is a neuroprotective agent in primary cultured RGCs injured by H_(2)O_(2).The effect of ET is dosedependent with the greatest effect being at 10μmol/L.ET plays an antioxidant role by inhibiting iNOS,up-regulating Nrf2/HO-1,decreasing the production of acrolein,and increasing the scavenge of acrolein.
基金supported by the National Key R&D Program of China(2022YFA2105900)the National Natural Science Foundation of China(22178197)。
文摘Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.
基金This research was supported by the Special Fund for Economic and Technological Development of Longgang District,Shenzhen(LGKCYLWS2021000030).
文摘Background:Cochlear hair cell injury is a common pathological feature of hearing loss.The basic helix-loop-helix family,member e40(Bhlhe40),a gene belonging to the basic helix-loop-helix(bHLH)family,exhibits strong transcriptional repression activity.Methods:Oxidative damage,in House Ear Institute-Organ of Corti 1(HEI-OC1)cells,was caused using hydrogen peroxide(H2O2).The Ad-Bhlhe40 particles were constructed to overexpress Bhlhe40 in HEI-OC1 cells.Various assays including cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay(TUNEL),flow cytometry,immunofluorescence,and corresponding commercial kits were employed to investigate the impacts of Bhlhe40 on cell viability,apoptosis,oxidative stress levels,mitochondrial membrane potential and cellular senescence.Additionally,a dual-luciferase reporter assay was performed to confirm the targeting of the histone deacetylases 2(Hdac2)by Bhlhe40.Results:The results revealed that Bhlhe40 was downregulated in H_(2)O_(2)-treated HEI-OC1 cells,but its overexpression improved cell viability and mitigated H_(2)O_(2)-induced oxidative injury in HEI-OC1 cells with increase of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GPx)activities and decrease of reactive oxygen species(ROS)levels.Besides,overexpression of Bhlhe40 suppressed H_(2)O_(2)-triggered cell senescence,as evidenced by the fact that the upregulation of P53,P21,and P16 in HEI-OC1 cells treated with H2O2 were all alleviated by Bhlhe40 overexpression.And we further verified that overexpression of Bhlhe40 could inhibit the expression of Hdac2,which may be related to the repression of Hdac2 transcription.Conclusion:This study suggests that Bhlhe40 plays a protective role against senescence and oxidative damage in cochlear hair cells exposed to H2O2.
基金the Partnership for Skills in Applied Sciences,Engineering and Technology(PASET)-Regional Scholarship Innovation Fund(RSIF)(World Bank PASET No.IP22-15)supported by the National Research Foundation(NRF)(NRF-2021R1A2C2091787 and NRF-2022M3H4A1A03076280)+1 种基金the Korea Research Institute of Chemical Technology(KRICT)of the Republic of Korea(No.KS2422-10)the National Research Council of Science and Technology(Grant No.Global-23-007)of Republic of Korea。
文摘The interfaces between the inorganic metal oxide and organic photoactive layer are of outmost importance for efficiency and stability in organic solar cells(OSCs).Tin oxide(SnO_(2))is one of the promising candidates for the electron transport layer(ETL)in high-performance inverted OSCs.When a solution-processed SnO_(2)ETL is employed,however,the presence of interfacial defects and suboptimal interfacial contact can lower the power conversion efficiency(PCE)and operational stability of OSCs.Herein,highly efficient and stable inverted OSCs by modification of the SnO_(2)surface with ultraviolet(UV)-curable acrylate oligomers(SAR and OCS)are demonstrated.The highest PCEs of 16.6%and 17.0%are achieved in PM6:Y6-BO OSCs with the SAR and OCS,respectively,outperforming a device with a bare SnO_(2)ETL(PCE 13.8%).The remarkable enhancement of PCEs is attributed to the optimized interfacial contact,leading to mitigated surface defects.More strikingly,improved light-soaking and thermal stability strongly correlated with the interfacial defects are demonstrated for OSCs based on SnO_(2)/UV cross-linked resins compared to OSCs utilizing bare SnO_(2).We believe that UV cross-linking oligomers will play a key role as interfacial modifiers in the future fabrication of large-area and flexible OSCs with high efficiency and stability.
