The authors regret to report a mistake in the text and an associated change necessary to section 3.6 of the paper.On page 1766 in the right-hand column,line 4,the heading of subsection 3.6“GmWRKY40 represses the expr...The authors regret to report a mistake in the text and an associated change necessary to section 3.6 of the paper.On page 1766 in the right-hand column,line 4,the heading of subsection 3.6“GmWRKY40 represses the expression of PR genes”should be changed to“GmWRKY40 promotes the expression of PR genes”.The authors would like to apologize for any inconvenience caused.展开更多
In Africa, each year, there are estimated to be more than 91 million cases of salmonellosis and 137,000 cases of death. The problem of antibiotic resistance in Salmonella strains is a threat to public health. The obje...In Africa, each year, there are estimated to be more than 91 million cases of salmonellosis and 137,000 cases of death. The problem of antibiotic resistance in Salmonella strains is a threat to public health. The objective of this study is to evaluate the antibiotic resistance profile of Salmonella strains isolated in biological products analyzed at the National Laboratory of Clinical Biology and Public Health (NLCBPH) in Bangui. This is, therefore, a cross-sectional study with a descriptive aim, running from January to December 2022. It focused on the strains of Salmonella isolated and identified in stools, urines, and blood samples. For each strain of Salmonella isolated, an antibiogram was carried out following the recommendations of the French Society of Microbiology (CASFM, 2022). A total of 93 strains of Salmonella have been recorded. The age group 0 - 9 years was 29% and that of >50 years was 11%. The median age of patients was 30 years with a minimum of 1 and a maximum of 78 years. The female gender was more represented at 52.69% than the male gender at 47.31%, i.e. a sex ratio of 0.89 (M/F). Salmonella strains were much more isolated in stools at 62% followed by urines at 29% and blood at 6%. Salmonella arizonae strains were more represented with 52%. Salmonella strains have a resistance rate to Tetracycline of 62.37% followed by Penicillins of 50%. The rate of multi-antibiotic resistance of the Salmonella strains isolated represented 48.38%. Salmonella spp. strains were multi-resistant at 58.69% followed by Salmonella arizonae strains at 47.91%. There is a significant association between the different families of antibiotics and Salmonella strains (p < 0.05). According to the results obtained, Penicillins, Phenicoles, and Cyclins had a high rate of resistance on Salmonella strains. No strain-producing Broad Spectrum Beta-lactamase has been isolated. Salmonella strains represent a zoonotic health danger, constitute a public health problem and remain a current subject. This germ is resistant to the antibiotics used. It is, therefore, essential to emphasize monitoring the resistance of these germs in the Central African Republic (CAR) to improve the health of the population.展开更多
Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enter...Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.展开更多
To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Po...To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.展开更多
Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h...Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.展开更多
Direct methanol fuel cells(DMFC) are widely considered to be an ideal green energy conversion device but their widespread applications are limited by the high price of the Pt-based catalysts and the instability in ter...Direct methanol fuel cells(DMFC) are widely considered to be an ideal green energy conversion device but their widespread applications are limited by the high price of the Pt-based catalysts and the instability in terms of surface CO toxicity in long-term operation.Herein,the PtFe alloy nanoparticles(NPs) with small particle size(~4.12 nm) supported on carbon black catalysts with different Pt/Fe atomic ratios(Pt_(1)Fe_(2)/C,Pt_(3)Fe_(4)/C,Pt_(1)Fe_(1)/C,and Pt_(2)Fe_(1)/C) are successfully prepared for enhanced anti-CO poisoning during methanol oxidation reaction(MOR).The optimal atomic ratio of Pt/Fe for the MOR is 1:2,and the mass activity of Pt_(1)Fe_(2)/C(5.40 A mg_(Pt)^(-1)) is 13.5 times higher than that of conventional commercial Pt/C(Pt/C-JM)(0.40 A mg_(Pt)^(-1)).The introduction of Fe into the Pt lattice forms the PtFe alloy phase,and the electron density of Pt is reduced after forming the PtFe alloy.In-situ Fourier transform infrared results indicate that the addition of oxyphilic metal Fe has reduced the adsorption of reactant molecules on Pt during the MOR.The doping of Fe atoms helps to desorb toxic intermediates and regenerate Pt active sites,promoting the cleavage of C-O bonds with good selectivity of CO_(2)(58.1%).Moreover,the Pt_(1)Fe_(2)/C catalyst exhibits higher CO tolerance,methanol electrooxidation activity,and long-term stability than other Pt_(x)Fe_(y)/C catalysts.展开更多
In this study,the effects of stacked nanosheets and the surrounding interphase zone on the resistance of the contact region between nanosheets and the tunneling conductivity of samples are evaluated with developed equ...In this study,the effects of stacked nanosheets and the surrounding interphase zone on the resistance of the contact region between nanosheets and the tunneling conductivity of samples are evaluated with developed equations superior to those previously reported.The contact resistance and nanocomposite conductivity are modeled by several influencing factors,including stack properties,interphase depth,tunneling size,and contact diameter.The developed model's accuracy is verified through numerous experimental measurements.To further validate the models and establish correlations between parameters,the effects of all the variables on contact resistance and nanocomposite conductivity are analyzed.Notably,the contact resistance is primarily dependent on the polymer tunnel resistivity,contact area,and tunneling size.The dimensions of the graphene nanosheets significantly influence the conductivity,which ranges from 0 S/m to90 S/m.An increased number of nanosheets in stacks and a larger gap between them enhance the nanocomposite's conductivity.Furthermore,the thicker interphase and smaller tunneling size can lead to higher sample conductivity due to their optimistic effects on the percolation threshold and network efficacy.展开更多
WRKY transcription factors,transcriptional regulators unique to plants,play an important role in defense response to pathogen infection.However,the resistance mechanisms of WRKY genes in sugarcane remain unclear.In th...WRKY transcription factors,transcriptional regulators unique to plants,play an important role in defense response to pathogen infection.However,the resistance mechanisms of WRKY genes in sugarcane remain unclear.In the present study,gene ontology(GO)enrichment analysis revealed that WRKY gene family in sugarcane was extensively involved in the response to biotic stress and in defense response.We identified gene ScWRKY4,a classⅡc member of the WRKY gene family,in sugarcane cultivar ROC22.This gene was induced by salicylic acid(SA)and methyl jasmonate(MeJA)stress.Interestingly,expression of ScWRKY4 was down-regulated in smut-resistant sugarcane cultivars but up-regulated in smutsusceptible sugarcane cultivars infected with Sporisorium scitamineum.Moreover,stable overexpression of the ScWRKY4 gene in Nicotiana benthamiana enhanced susceptibility to Fusarium solani var.coeruleum and caused down-regulated expression of immune marker-related genes.Transcriptome analysis indicated suppressed expression of most JAZ genes in the signal transduction pathway.ScWRKY4 interacted with ScJAZ13 to repress its expression.We thus hypothesized that the ScWRKY4 gene was involved in the regulatory network of plant disease resistance,most likely through the JA signaling pathway.The present study depicting the molecular involvement of ScWRKY4 in sugarcane disease resistance lays a foundation for future investigation.展开更多
A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to impr...A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to improve explosion resistance.Moreover,the current challenge is quantifying microstructural changes'effects on explosion resistance and incorporating microstructural changes into finite element models.This work aims to tune microstructures to improve explosion resistance and elucidate their anti-explosion mechanism,and find a suitable method to incorporate microstructural changes into finite element models.In this work,we systematically study the deformation and failure characteristics of TC4 ELI plates with varying microstructures using an air explosion test and LS-DYNA finite element modeling.The Johnson-Cook(JC)constitutive parameters are used to quantify the effects of microstructural changes on explosion resistance and incorporate microstructural changes into finite element models.Because of the heat treatment,one plate has equiaxed microstructure and the other has bimodal microstructure.The convex of the plate after the explosion has a quadratic relationship with the charge mass,and the simulation results demonstrate high reliability,with the error less than 17.5%.Therefore,it is feasible to obtain corresponding JC constitutive parameters based on the differences in microstructures and mechanical properties and characterize the effects of microstructural changes on explosion resistance.The bimodal target exhibits excellent deformation resistance.The response of bimodal microstructure to the shock wave may be more intense under explosive loading.The well-coordinated structure of the bimodal target enhances its resistance to deformation.展开更多
With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic ...With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.展开更多
In order to clarify the fatigue damage evolution of concrete exposed to flexural fatigue loads,ultrasonic pulse velocity(UPV),impact-echo technology and surface electrical resistance(SR) method were used.Damage variab...In order to clarify the fatigue damage evolution of concrete exposed to flexural fatigue loads,ultrasonic pulse velocity(UPV),impact-echo technology and surface electrical resistance(SR) method were used.Damage variable based on the change of velocity of ultrasonic pulse(Du) and impact elastic wave(Di)were defined according to the classical damage theory.The influences of stress level,loading frequency and concrete strength on damage variable were measured.The experimental results show that Du and Di both present a three-stages trend for concrete exposed to fatigue loads.Since impact elastic wave is more sensitive to the microstructure damage in stage Ⅲ,the critical damage variable,i e,the damage variable before the final fracture of concrete of Di is slightly higher than that of Du.Meanwhile,the evolution of SR of concrete exposed to fatigue loads were analyzed and the relationship between SR and Du,SR and Di of concrete exposed to fatigue loads were established.It is found that the SR of concrete was decreased with the increasing fatigue cycles,indicating that surface electrical resistance method can also be applied to describe the damage of ballastless track concrete exposed to fatigue loads.展开更多
Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug r...Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.展开更多
Alginate oligosaccharides(AOS)enhance drought resistance in wheat(Triticum aestivum L.),but the definite mechanisms remain largely unknown.The physiological and transcriptome responses of wheat seedlings treated with ...Alginate oligosaccharides(AOS)enhance drought resistance in wheat(Triticum aestivum L.),but the definite mechanisms remain largely unknown.The physiological and transcriptome responses of wheat seedlings treated with AOS were analyzed under drought stress simulated with polyethylene glycol-6000.The results showed that AOS promoted the growth of wheat seedlings and reduced oxidative damage by improving peroxidase and superoxide dismutase activities under drought stress.A total of 10,064 and 15,208 differentially expressed unigenes(DEGs)obtained from the AOS treatment and control samples at 24 and 72 h after dehydration,respectively,were mainly enriched in the biosynthesis of secondary metabolites(phenylpropanoid biosynthesis,flavonoid biosynthesis),carbohydrate metabolism(starch and sucrose metabolism,carbon fixation in photosynthetic organisms),lipid metabolism(fatty acid elongation,biosynthesis of unsaturated fatty acids,alpha-linolenic acid metabolism,cutin,suberine and wax biosynthesis),and signaling transduction pathways.The up-regulated genes were related to,for example,chlorophyll a-b binding protein,amylosynthease,phosphotransferase,peroxidase,phenylalanine ammonia lyase,flavone synthase,glutathione synthetase.Signaling molecules(including MAPK,plant hormones,H_(2)O_(2) and calcium)and transcription factors(mainly including NAC,MYB,MYB-related,WRKY,bZIP family members)were involved in the AOS-induced wheat drought resistance.The results obtained in this study help underpin the mechanisms of wheat drought resistance improved by AOS,and provides a theoretical basis for the application of AOS as an environmentally sustainable biological method to improve drought resistance in agriculture.展开更多
[Objectives]The paper was to investigate the development of Panonychus citri resistance to commonly used pesticides in major citrus producing areas in China,and to screen out new green and efficient agents for its con...[Objectives]The paper was to investigate the development of Panonychus citri resistance to commonly used pesticides in major citrus producing areas in China,and to screen out new green and efficient agents for its control and prevention.[Methods]The resistance changes of field populations of P.citri to abamectin,pyridaben,and bifenazate in 12 locations across five provinces in China were compared using the leaf disc impregnation method.[Results]P.citri in the tested areas exhibited the most severe resistance to abamectin,with approximately 91.7%of the field populations showing high levels of resistance to abamectin(112.1-560.5 times);50%of P.citri populations exhibited high levels of resistance to pyridaben(123.0-202.7 times),while the remaining populations showed intermediate levels of resistance(25.6-80.3 times);except for the Zhejiang Xiangshan 2019 and Jiangxi Yudu 2019 populations,which exhibited a medium level of resistance to bifenazate,the remaining 10 monitored populations demonstrated a high level of resistance to bifenazate(140.4-686.1 times).[Conclusions]It is advisable to discontinue the use of abamectin and bifenazate due to significant resistance observed in populations of P.citri monitored in 12 locations across 5 provinces.It is recommended to reduce the frequency of pyridaben use and alternate with other acaricides that have different mechanisms of action due to the varying degrees of resistance developed.展开更多
Magnesia-calcium materials have stable hot performance,good resistance to the erosion and corrosion of liquid steel and steel slag,and a special role in purifying liquid steel,so they are widely used in iron and steel...Magnesia-calcium materials have stable hot performance,good resistance to the erosion and corrosion of liquid steel and steel slag,and a special role in purifying liquid steel,so they are widely used in iron and steel industry.However,hydration of magnesia-calcium materials seriously restricts their use,so researches have been done to improve their hydration resistance,obtaining a series of achievements.In this paper,the improvements on the hydration resistance of magnesia-calcium materials by additives in recent 20 years were presented,and their mechanisms were summarized.展开更多
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty...Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.展开更多
Artificial vegetation restoration is the main measure for vegetation restoration and soil and water conservation in alpine mine dumps on the Qinghai-Tibet Plateau,China.However,there are few reports on the dynamic cha...Artificial vegetation restoration is the main measure for vegetation restoration and soil and water conservation in alpine mine dumps on the Qinghai-Tibet Plateau,China.However,there are few reports on the dynamic changes and the influencing factors of the soil reinforcement effect of plant species after artificial vegetation restoration under different recovery periods.We selected dump areas of the Delni Copper Mine in Qinghai Province,China to study the relationship between the shear strength and the peak displacement of the root-soil composite on the slope during the recovery period,and the influence of the root traits and soil physical properties on the shear resistance characteristics of the root-soil composite via in situ direct shear tests.The results indicate that the shear strength and peak displacement of the rooted soil initially decreased and then increased with the increase of the recovery period.The shear strength of the rooted soil and the recovery period exhibited a quadratic function relationship.There is no significant function relationship between the peak displacement and the recovery period.Significant positive correlations(P<0.05)exists between the shear strength of the root-soil composite and the root biomass density,root volume density,and root area ratio,and they show significant linear correlations(P<0.05).There are no significant correlations(P>0.05)between the shear strength of the root-soil composite and the root length density,and the root volume ratio of the coarse roots to the fine roots.A significant negative linear correlation(P<0.05)exists between the peak displacement of the rooted soil and the coarse-grain content,but no significant correlations(P>0.05)with the root traits,other soil physical property indices(the moisture content and dry density of the soil),and slope gradient.The coarse-grain content is the main factor controlling the peak displacement of the rooted soil.展开更多
Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of bo...Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.展开更多
Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a cru...Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic significance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining specific inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the specific cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.展开更多
BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is ...BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.展开更多
文摘The authors regret to report a mistake in the text and an associated change necessary to section 3.6 of the paper.On page 1766 in the right-hand column,line 4,the heading of subsection 3.6“GmWRKY40 represses the expression of PR genes”should be changed to“GmWRKY40 promotes the expression of PR genes”.The authors would like to apologize for any inconvenience caused.
文摘In Africa, each year, there are estimated to be more than 91 million cases of salmonellosis and 137,000 cases of death. The problem of antibiotic resistance in Salmonella strains is a threat to public health. The objective of this study is to evaluate the antibiotic resistance profile of Salmonella strains isolated in biological products analyzed at the National Laboratory of Clinical Biology and Public Health (NLCBPH) in Bangui. This is, therefore, a cross-sectional study with a descriptive aim, running from January to December 2022. It focused on the strains of Salmonella isolated and identified in stools, urines, and blood samples. For each strain of Salmonella isolated, an antibiogram was carried out following the recommendations of the French Society of Microbiology (CASFM, 2022). A total of 93 strains of Salmonella have been recorded. The age group 0 - 9 years was 29% and that of >50 years was 11%. The median age of patients was 30 years with a minimum of 1 and a maximum of 78 years. The female gender was more represented at 52.69% than the male gender at 47.31%, i.e. a sex ratio of 0.89 (M/F). Salmonella strains were much more isolated in stools at 62% followed by urines at 29% and blood at 6%. Salmonella arizonae strains were more represented with 52%. Salmonella strains have a resistance rate to Tetracycline of 62.37% followed by Penicillins of 50%. The rate of multi-antibiotic resistance of the Salmonella strains isolated represented 48.38%. Salmonella spp. strains were multi-resistant at 58.69% followed by Salmonella arizonae strains at 47.91%. There is a significant association between the different families of antibiotics and Salmonella strains (p < 0.05). According to the results obtained, Penicillins, Phenicoles, and Cyclins had a high rate of resistance on Salmonella strains. No strain-producing Broad Spectrum Beta-lactamase has been isolated. Salmonella strains represent a zoonotic health danger, constitute a public health problem and remain a current subject. This germ is resistant to the antibiotics used. It is, therefore, essential to emphasize monitoring the resistance of these germs in the Central African Republic (CAR) to improve the health of the population.
基金supported by the National Key Research and Development Program of China(2022YFF0710505)The Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001)the Talents Introduction Projects of Hebei Agricultural University,China(YJ201945)。
文摘Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.
基金supported by the National Natural Science Foundation of China(31770164)Jiangsu Province’s Innovation Program(JSSCTD202142).
文摘To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.
文摘Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.
基金supported by the National Natural Science Foundation of China(22162012 and 22202089)the Youth Jinggang Scholars Program in Jiangxi Province([2019]57)+6 种基金the Thousand Talents Plan of Jiangxi Province(jxsq2019201083)the Natural Science Foundation of Jiangxi Province for Distinguished Young Scholars(20224ACB213005)the Program of Qingjiang Excellent Young Talents,Jiangxi University of Science and Technology(JXUSTQJBJ2019002)the Research Foundation of Education Bureau of Jiangxi Province of China(GJJ210833)the Foundation of State Key Laboratory of Physical Chemistry of Solid Surfaces(202022)the China Postdoctoral Science Foundation(2021M693893)the Jiangxi Provincial Key Laboratory of Functional Molecular Materials Chemistry(20212BCD42018)。
文摘Direct methanol fuel cells(DMFC) are widely considered to be an ideal green energy conversion device but their widespread applications are limited by the high price of the Pt-based catalysts and the instability in terms of surface CO toxicity in long-term operation.Herein,the PtFe alloy nanoparticles(NPs) with small particle size(~4.12 nm) supported on carbon black catalysts with different Pt/Fe atomic ratios(Pt_(1)Fe_(2)/C,Pt_(3)Fe_(4)/C,Pt_(1)Fe_(1)/C,and Pt_(2)Fe_(1)/C) are successfully prepared for enhanced anti-CO poisoning during methanol oxidation reaction(MOR).The optimal atomic ratio of Pt/Fe for the MOR is 1:2,and the mass activity of Pt_(1)Fe_(2)/C(5.40 A mg_(Pt)^(-1)) is 13.5 times higher than that of conventional commercial Pt/C(Pt/C-JM)(0.40 A mg_(Pt)^(-1)).The introduction of Fe into the Pt lattice forms the PtFe alloy phase,and the electron density of Pt is reduced after forming the PtFe alloy.In-situ Fourier transform infrared results indicate that the addition of oxyphilic metal Fe has reduced the adsorption of reactant molecules on Pt during the MOR.The doping of Fe atoms helps to desorb toxic intermediates and regenerate Pt active sites,promoting the cleavage of C-O bonds with good selectivity of CO_(2)(58.1%).Moreover,the Pt_(1)Fe_(2)/C catalyst exhibits higher CO tolerance,methanol electrooxidation activity,and long-term stability than other Pt_(x)Fe_(y)/C catalysts.
基金the Basic Science Research Program through the National Research Foundation(NRF)of Korea funded by the Ministry of Education,Science,and Technology(No.2022R1A2C1004437)the Ministry of Science and ICT(MSIT)of Korea Government(No.2022M3J7A1062940)。
文摘In this study,the effects of stacked nanosheets and the surrounding interphase zone on the resistance of the contact region between nanosheets and the tunneling conductivity of samples are evaluated with developed equations superior to those previously reported.The contact resistance and nanocomposite conductivity are modeled by several influencing factors,including stack properties,interphase depth,tunneling size,and contact diameter.The developed model's accuracy is verified through numerous experimental measurements.To further validate the models and establish correlations between parameters,the effects of all the variables on contact resistance and nanocomposite conductivity are analyzed.Notably,the contact resistance is primarily dependent on the polymer tunnel resistivity,contact area,and tunneling size.The dimensions of the graphene nanosheets significantly influence the conductivity,which ranges from 0 S/m to90 S/m.An increased number of nanosheets in stacks and a larger gap between them enhance the nanocomposite's conductivity.Furthermore,the thicker interphase and smaller tunneling size can lead to higher sample conductivity due to their optimistic effects on the percolation threshold and network efficacy.
基金supported by the National Key Research and Development Program of China(2022YFD2301100 and 2019YFD1000503)the Natural Science Foundation of Fujian Province(2021J01137)+1 种基金the Special Fund for Science and Technology Innovation of Fujian Agriculture and Forestry University(CXZX2020081A)the China Agriculture Research System(CARS-17).
文摘WRKY transcription factors,transcriptional regulators unique to plants,play an important role in defense response to pathogen infection.However,the resistance mechanisms of WRKY genes in sugarcane remain unclear.In the present study,gene ontology(GO)enrichment analysis revealed that WRKY gene family in sugarcane was extensively involved in the response to biotic stress and in defense response.We identified gene ScWRKY4,a classⅡc member of the WRKY gene family,in sugarcane cultivar ROC22.This gene was induced by salicylic acid(SA)and methyl jasmonate(MeJA)stress.Interestingly,expression of ScWRKY4 was down-regulated in smut-resistant sugarcane cultivars but up-regulated in smutsusceptible sugarcane cultivars infected with Sporisorium scitamineum.Moreover,stable overexpression of the ScWRKY4 gene in Nicotiana benthamiana enhanced susceptibility to Fusarium solani var.coeruleum and caused down-regulated expression of immune marker-related genes.Transcriptome analysis indicated suppressed expression of most JAZ genes in the signal transduction pathway.ScWRKY4 interacted with ScJAZ13 to repress its expression.We thus hypothesized that the ScWRKY4 gene was involved in the regulatory network of plant disease resistance,most likely through the JA signaling pathway.The present study depicting the molecular involvement of ScWRKY4 in sugarcane disease resistance lays a foundation for future investigation.
基金National Key Laboratory of Science and Technology on Materials under Shock and Impact(Grant No.WDZC2022-4)to provide fund for conducting experiments。
文摘A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to improve explosion resistance.Moreover,the current challenge is quantifying microstructural changes'effects on explosion resistance and incorporating microstructural changes into finite element models.This work aims to tune microstructures to improve explosion resistance and elucidate their anti-explosion mechanism,and find a suitable method to incorporate microstructural changes into finite element models.In this work,we systematically study the deformation and failure characteristics of TC4 ELI plates with varying microstructures using an air explosion test and LS-DYNA finite element modeling.The Johnson-Cook(JC)constitutive parameters are used to quantify the effects of microstructural changes on explosion resistance and incorporate microstructural changes into finite element models.Because of the heat treatment,one plate has equiaxed microstructure and the other has bimodal microstructure.The convex of the plate after the explosion has a quadratic relationship with the charge mass,and the simulation results demonstrate high reliability,with the error less than 17.5%.Therefore,it is feasible to obtain corresponding JC constitutive parameters based on the differences in microstructures and mechanical properties and characterize the effects of microstructural changes on explosion resistance.The bimodal target exhibits excellent deformation resistance.The response of bimodal microstructure to the shock wave may be more intense under explosive loading.The well-coordinated structure of the bimodal target enhances its resistance to deformation.
基金by National Natural Science Foundation of China(81803224)Young Scholars Program of Shandong University(2018WLJH33)to X.G.+3 种基金National Natural Science Foundation of China(81973031)Cheeloo Young Scholar Program of Shandong University(21320089963054)to H.W.Young Scholars Program of Shandong University(2018WLJH34)the Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology(LMDBKF-2019-05)to L.D.
文摘With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.
基金Funded by the National Natural Science Foundation of China(Nos.U1934206,52208299,and 52108260)the 2021 Tencent XPLORER PRIZE。
文摘In order to clarify the fatigue damage evolution of concrete exposed to flexural fatigue loads,ultrasonic pulse velocity(UPV),impact-echo technology and surface electrical resistance(SR) method were used.Damage variable based on the change of velocity of ultrasonic pulse(Du) and impact elastic wave(Di)were defined according to the classical damage theory.The influences of stress level,loading frequency and concrete strength on damage variable were measured.The experimental results show that Du and Di both present a three-stages trend for concrete exposed to fatigue loads.Since impact elastic wave is more sensitive to the microstructure damage in stage Ⅲ,the critical damage variable,i e,the damage variable before the final fracture of concrete of Di is slightly higher than that of Du.Meanwhile,the evolution of SR of concrete exposed to fatigue loads were analyzed and the relationship between SR and Du,SR and Di of concrete exposed to fatigue loads were established.It is found that the SR of concrete was decreased with the increasing fatigue cycles,indicating that surface electrical resistance method can also be applied to describe the damage of ballastless track concrete exposed to fatigue loads.
基金Research Projects-Joint Fund for Applied Basic Research of Kunming Medical University,Yunnan Provincial Department of Science and Technology(No.2018FE001(-113),No.202301AY070001-098)Open project of Yunnan Clinical Medical Center(Nos.2020LCZXKF-XY02,XY06,XY16+1 种基金2022LCZXKF-XY02)Yunnan Health Training Project of High Level Talents(No.D–2018018).
文摘Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.
基金This research was funded and supported by the National Natural Science Foundation of China(Grant Number 32001443)Zhengzhou Major Science and Technology Innovation Project of Henan Province of China(Grant Number 2020CXZX0085)Science and Technology Inovation Team of Henan Academy of Agricultural Sciences(Grant Number 2024TD2).
文摘Alginate oligosaccharides(AOS)enhance drought resistance in wheat(Triticum aestivum L.),but the definite mechanisms remain largely unknown.The physiological and transcriptome responses of wheat seedlings treated with AOS were analyzed under drought stress simulated with polyethylene glycol-6000.The results showed that AOS promoted the growth of wheat seedlings and reduced oxidative damage by improving peroxidase and superoxide dismutase activities under drought stress.A total of 10,064 and 15,208 differentially expressed unigenes(DEGs)obtained from the AOS treatment and control samples at 24 and 72 h after dehydration,respectively,were mainly enriched in the biosynthesis of secondary metabolites(phenylpropanoid biosynthesis,flavonoid biosynthesis),carbohydrate metabolism(starch and sucrose metabolism,carbon fixation in photosynthetic organisms),lipid metabolism(fatty acid elongation,biosynthesis of unsaturated fatty acids,alpha-linolenic acid metabolism,cutin,suberine and wax biosynthesis),and signaling transduction pathways.The up-regulated genes were related to,for example,chlorophyll a-b binding protein,amylosynthease,phosphotransferase,peroxidase,phenylalanine ammonia lyase,flavone synthase,glutathione synthetase.Signaling molecules(including MAPK,plant hormones,H_(2)O_(2) and calcium)and transcription factors(mainly including NAC,MYB,MYB-related,WRKY,bZIP family members)were involved in the AOS-induced wheat drought resistance.The results obtained in this study help underpin the mechanisms of wheat drought resistance improved by AOS,and provides a theoretical basis for the application of AOS as an environmentally sustainable biological method to improve drought resistance in agriculture.
基金Guangxi Agricultural Science and Technology Self-financing Project(Z2022128)Fund Project of Guangxi Citrus Breeding and Cultivation Engineering Technology Research Center(2022A003).
文摘[Objectives]The paper was to investigate the development of Panonychus citri resistance to commonly used pesticides in major citrus producing areas in China,and to screen out new green and efficient agents for its control and prevention.[Methods]The resistance changes of field populations of P.citri to abamectin,pyridaben,and bifenazate in 12 locations across five provinces in China were compared using the leaf disc impregnation method.[Results]P.citri in the tested areas exhibited the most severe resistance to abamectin,with approximately 91.7%of the field populations showing high levels of resistance to abamectin(112.1-560.5 times);50%of P.citri populations exhibited high levels of resistance to pyridaben(123.0-202.7 times),while the remaining populations showed intermediate levels of resistance(25.6-80.3 times);except for the Zhejiang Xiangshan 2019 and Jiangxi Yudu 2019 populations,which exhibited a medium level of resistance to bifenazate,the remaining 10 monitored populations demonstrated a high level of resistance to bifenazate(140.4-686.1 times).[Conclusions]It is advisable to discontinue the use of abamectin and bifenazate due to significant resistance observed in populations of P.citri monitored in 12 locations across 5 provinces.It is recommended to reduce the frequency of pyridaben use and alternate with other acaricides that have different mechanisms of action due to the varying degrees of resistance developed.
文摘Magnesia-calcium materials have stable hot performance,good resistance to the erosion and corrosion of liquid steel and steel slag,and a special role in purifying liquid steel,so they are widely used in iron and steel industry.However,hydration of magnesia-calcium materials seriously restricts their use,so researches have been done to improve their hydration resistance,obtaining a series of achievements.In this paper,the improvements on the hydration resistance of magnesia-calcium materials by additives in recent 20 years were presented,and their mechanisms were summarized.
文摘Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.
基金supported by the Project of Qinghai Science&Technology Department(Grant No.2021-ZJ-956Q).
文摘Artificial vegetation restoration is the main measure for vegetation restoration and soil and water conservation in alpine mine dumps on the Qinghai-Tibet Plateau,China.However,there are few reports on the dynamic changes and the influencing factors of the soil reinforcement effect of plant species after artificial vegetation restoration under different recovery periods.We selected dump areas of the Delni Copper Mine in Qinghai Province,China to study the relationship between the shear strength and the peak displacement of the root-soil composite on the slope during the recovery period,and the influence of the root traits and soil physical properties on the shear resistance characteristics of the root-soil composite via in situ direct shear tests.The results indicate that the shear strength and peak displacement of the rooted soil initially decreased and then increased with the increase of the recovery period.The shear strength of the rooted soil and the recovery period exhibited a quadratic function relationship.There is no significant function relationship between the peak displacement and the recovery period.Significant positive correlations(P<0.05)exists between the shear strength of the root-soil composite and the root biomass density,root volume density,and root area ratio,and they show significant linear correlations(P<0.05).There are no significant correlations(P>0.05)between the shear strength of the root-soil composite and the root length density,and the root volume ratio of the coarse roots to the fine roots.A significant negative linear correlation(P<0.05)exists between the peak displacement of the rooted soil and the coarse-grain content,but no significant correlations(P>0.05)with the root traits,other soil physical property indices(the moisture content and dry density of the soil),and slope gradient.The coarse-grain content is the main factor controlling the peak displacement of the rooted soil.
基金supported by the Global Select Project(No.DJK-LX-2022001)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.
基金This work was supported by the Major Subject of Science and Technology of Anhui Province(Grant Number:201903a07020030).
文摘Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic significance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining specific inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the specific cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2020MH147National Natural Science Foundation of China,No.82002343.
文摘BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.
