Helicoverpa zea is a major target pest of pyramided transgenic crops expressing Cry1,Cry2 and/or Vip3Aa proteins from Bacillus thuringiensis(Bt)in the United States.Laboratory-selected Cry1Ac/Cry2Ab cross resistance a...Helicoverpa zea is a major target pest of pyramided transgenic crops expressing Cry1,Cry2 and/or Vip3Aa proteins from Bacillus thuringiensis(Bt)in the United States.Laboratory-selected Cry1Ac/Cry2Ab cross resistance and fieldevolved practical dual resistance of H.zea to these two toxins have been widely reported.Whether the widespread Cry1Ac/Cy2Ab dual resistance of H.zea has resulted from the selection of one shared or two independent resistance mechanisms by pyramided Bt crops remains unclear.Cadherin is a well-confirmed receptor of Cry1Ac and a suggested receptor of Cry2Ab in at least three Lepidopteran species.To test whether cadherin may serve as one shared mechanism for the cross and dual resistance of H.zea to Cry1Ac and Cry2Ab,we cloned H.zea cadherin(HzCadherin)cDNA and studied its functional roles in the mode of action of Cry1Ac and Cry2Ab by gain-and lossof-function analyses.Heterologous expression of HzCadherin in H.zea midgut,H.zea fat body and Sf9 cells made all three of these cell lines more susceptible to activated Cry1Ac but not activated Cry2Ab,whereas silencing HzCadherin of H.zea midgut and fat body cells significantly reduced the susceptibility to Cry1Ac but not Cry2Ab.Likewise,suppressing HzCadherin with siRNA made H.zea larvae resistant to Cry1Ac.These results clearly demonstrate that HzCadherin is not a receptor for Cry2Ab,and thus it is unlikely to serve as one shared mechanism for the cross and dual resistance of H.zea to Cry1Ac and Cry2Ab.展开更多
Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most sign...Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.展开更多
How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually come...How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually comes at the expense of yield.Currently,many necrotic lesion mutants in rice have been identified,and these genes are involved in disease resistance pathways.This review provides a detailed introduction to the characteristics,classification,and molecular mechanisms of necrotic lesion formation.Additionally,we review the molecular regulatory pathways of genes involved in rice disease resistance.Concurrently,we summarize the relationship between resistance and yield in rice using newly developed gene editing methods.We discuss a rational and precise breeding strategy to better utilize molecular design technology for breeding disease-resistant and high-yield rice varieties.展开更多
One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon o...One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.展开更多
Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory ca...Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.展开更多
Abiotic stresses, such as drought, salt, extreme temperatures, and heavy metal pollution, are the main environmental factors that limit crop growth and yield. Sorghum, a C4 grass plant with high photosynthetic efficie...Abiotic stresses, such as drought, salt, extreme temperatures, and heavy metal pollution, are the main environmental factors that limit crop growth and yield. Sorghum, a C4 grass plant with high photosynthetic efficiency, can grow in adverse environmental conditions due to its excellent stress resistance characteristics. Therefore, unraveling the stress-resistance mechanism of sorghum could provide a theoretical basis for developing and cultivating various stress-resistant crops. This understanding could also help to create a conducive environment for using marginal soil in agriculture and ensuring food security. In this review, we discuss the adaptation mechanisms of sorghum under drought, salinity, temperature, and soil heavy metal stresses, the specific response to stress, the screening of sorghum-resistant germplasm, and the identification and functional analysis of the relevant genes and quantitative trait loci(QTL). In addition, we discuss the application potential of different stress-tolerant sorghum germplasms reported to date and emphasize the feasibility and potential use in developing and promoting highly stress-tolerant sorghum in marginal soil.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
The objective of this paper was to study low temperature crack resistance mechanism of steel slag asphalt mixture(SAM).Thermal stress restrained specimen test(TSRST)and three-point bending test were carried out to eva...The objective of this paper was to study low temperature crack resistance mechanism of steel slag asphalt mixture(SAM).Thermal stress restrained specimen test(TSRST)and three-point bending test were carried out to evaluate the low-temperature crack resistance of SAM and basalt asphalt mixture(BAM).Based on the digital image correlation technique(DIC),the strain field distribution and crack propagation of SAM were analyzed from the microscopic point of view,and a new index,crack length factor(C),was proposed to evaluate the crack resistance of the asphalt mixture.The crystal phase composition and microstructure of steel slag aggregate(SA)and basalt aggregate(BA)were studied by X-ray diffraction(XRD)and scanning electron microscopy(SEM)to explore the low-temperature crack resistance mechanism of SAM.Results show that the low-temperature crack resistance of SAM is better than that of BAM;SAM has good integrity and persistent elastic deformation,and its bending failure mode is a hysteretic quasi-brittle failure;The SA surface is evenly distributed with pores and has surface roughness.SA has the composition phase of alkaline aggregate-calcite(CaCO3),so it has good adhesion to asphalt,which reveals the mechanism of excellent low-temperature crack resistance of SAM.展开更多
Cucumber is an important vegetable worldwide,and powdery mildew(PM)is a common and serious disease of cucumbers.Breeding disease-resistant cucumber varieties is the most advantageous strategy to control this disease.I...Cucumber is an important vegetable worldwide,and powdery mildew(PM)is a common and serious disease of cucumbers.Breeding disease-resistant cucumber varieties is the most advantageous strategy to control this disease.In recent years,exploration and identification of cucumber PM resistance genes have achieved great advancement,and many genes have been cloned and verified using different methods.However,the resistance mechanism of cucumber PM is still unclear,and many ambiguities need to be elucidated urgently.In this review,we summarized the research advances in PM resistance in cucumbers,including genetic analysis,quantitative trait locus mapping,map-based cloning,transcriptomics,mlo-mediated PM resistance,and mining of noncoding RNAs involved in resistance.Finally,the research directions and the problems that need to be solved in the future were discussed.展开更多
Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and exte...Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.展开更多
Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and...Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.展开更多
Apple ring rot,which is caused by Botryosphaeria dothidea,severely affects apple production.The mechanisms employed in apple cells against B.dothidea remain unknown.In this research,the pathogen infection mode and the...Apple ring rot,which is caused by Botryosphaeria dothidea,severely affects apple production.The mechanisms employed in apple cells against B.dothidea remain unknown.In this research,the pathogen infection mode and the relationship between cell death and disease resistance in‘Fuji’/B.dothidea interaction pathosystem were investigated.By using transmission electron microscopy(TEM),our research showed that the pathogen infects apple cells both intracellularly and extracellularly.However,compared with that in immature fruit,the incidence of hyphae in the interior of mature apple fruit cells increased dramatically,suggesting that cell wall-mediated penetration resistance could be important in apple resistance against B.dothidea.TEM ultrastructural characterization identified the nuclear morphology of programmed cell death induction in both apple fruit and callus cells under B.dothidea infection.Overexpression of MdVDAC2(MDP0000271281),which encodes an outer-membrane localized anion channel protein in mitochondria,significantly promoted cell death under B.dothidea infection and simultaneously inhibited pathogen infection,suggesting that cell death represents a disease resistance mechanism in apple against B.dothidea infection.Furthermore,BdCatalase(KAF4307763),a cytochromeP450 family protein BdCYP52A4(KAF4300696),and subtilisin-domain containing proteinswere identified fromB.dothidea-secreted proteins,which suggested the potential involvement of active oxygen species and phytoalexins in combating B.dothidea infection and triggering or dampening apple resistance.Collectively,our research suggested that cell wall-mediated penetration resistance,programmed cell death machinery and microbial effector-interrelated signaling were among strategies recruited in apple to combat B.dothidea.The current research laid the foundation for further investigations into resistance mechanisms in apple.展开更多
Temozolomide(TMZ)resistance is a major obstacle in glioma treatment.Nuclear protein-1(NUPR1)is a regulator of glioma progression.This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxiatreated gliom...Temozolomide(TMZ)resistance is a major obstacle in glioma treatment.Nuclear protein-1(NUPR1)is a regulator of glioma progression.This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxiatreated glioma cells and its mechanism in modulating autophagy.We treated TMZ-resistant cells U251-TMZ and T98G-TMZ to normoxia or hypoxia and silenced NUPR1 in hypoxia-treated U251-TMZ and T98G-TMZ cells to assess cell viability,proliferation,apoptosis,LC3-II/LC3-I and p62 expressions,and autophagic flux under different concentrations of TMZ.We found that hypoxia upregulated NUPR1 expression and autophagy while NUPR1 silencing suppressed hypoxia-induced TMZ resistance and autophagy in glioma cells.We also investigated the interaction between NUPR1 and lysine demethylase 3A(KDM3A),as well as the enrichments of KDM3A and H3 lysine 9 dimethylation(H3K9me2)in the transcription factor EB(TFEB)promoter region.Our results suggest that hypoxia-induced NUPR1 promotes TFEB transcription by binding to KDM3A and reducing H3K9me2 levels,thereby augmenting glioma cell autophagy and TMZ resistance.Moreover,the overexpression of KDM3A or TFEB promoted glioma cell autophagy.In a xenograft tumor model,silencing NUPR1 suppressed TMZ resistance in glioma cells in vivo.Overall,our findings highlight a mechanism by which NUPR1 enhances glioma cell autophagy and TMZ resistance via the KDM3A/TFEB axis.展开更多
Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary ...Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.展开更多
Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ig...Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.展开更多
In the last decades,vanadium alloyed coatings have been introduced as potential candidates for self-lubrication due to their perfect tribological properties.In this work,the influence of V incorporation on the wear pe...In the last decades,vanadium alloyed coatings have been introduced as potential candidates for self-lubrication due to their perfect tribological properties.In this work,the influence of V incorporation on the wear performance and oxidation resistance of TiSiN/CrN film coatings deposited by direct current(DC)reactive magnetron sputtering is investigated.The results show that vanadium incorporation significantly decreases the oxidation resistance of the coatings.In general,two layers are formed during the oxidation process:i)Ti(V)O_(2) on top,followed by a protective layer,which is subdivided into two layers,Cr_(2)O_(3) and Si-O.ii)The diffusion of V controls the oxidation of V-containing coatings.The addition of vanadium improves the wear resistance of coatings,and the wear rate decreases with increasing V content in the coatings;however,the friction coefficient is independent of the chemical composition of the coatings.The wear of the V-containing coatings is driven by polishing wear.展开更多
This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: ...This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural signal, bringing attention to damage that has been sustained by tissues. However, chronic pain is common in the cancer population, and often serves no good purpose but instead will negatively impact both physical and mental health. The three types of pain: nociceptive, neuropathic, and inflammatory pathways have been investigated, and the knowledge of pain mechanisms allows for the understanding of how it is associated with pain. The purpose of this exploratory literature review is to give insight on how to maximize pain-relieving effects of resistance training. Research has indicated that resistance training modulates pain pathways by upregulating the release of pain-relieving substances including beta-endorphins, anti-inflammatory cytokines, and endocannabinoids. Understanding of the benefits of resistance training may be useful in relieving cancer pain, and reproducing effects of pain-relieving strategies while minimizing the symptoms related to cancer and its treatment.展开更多
Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity ag...Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.展开更多
BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the p...BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the production of PGF_(2α),is involved in the proliferation and growth of a variety of tumors.However,the role of PGFS in Oxa resistance in CRC remains unclear.AIM To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC.METHODS The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels.Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance(HCT116-OxR and HCT8-OxR)and their parental cell lines(HCT116 and HCT8)to assess its influence on cell proliferation,chemoresistance,apoptosis,and DNA damage.For determination of the underlying mechanisms,CRC cells were examined for platinum-DNA adducts and reactive oxygen species(ROS)levels in the presence of a PGFS inhibitor or its products.RESULTS Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues.Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dosedependent manner.Furthermore,overexpression of PGFS in parental CRC cells significantly attenuated Oxainduced proliferative suppression,apoptosis,and DNA damage.In contrast,knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells(HCT116-OxR and HCT8-OxR)accentuated the effect of Oxa treatment in vitro and in vivo.The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa.Treatment with the PGFS-catalyzed product PGF_(2α)reversed the effect of PGFS knockdown on Oxa sensitivity.Interestingly,PGFS inhibited the formation of platinum-DNA adducts in a PGF_(2α)-independent manner.PGF_(2α)exerts its protective effect against DNA damage by reducing ROS levels.CONCLUSION PGFS promotes resistance to Oxa in CRC via both PGF_(2α)-dependent and PGF_(2α)-independent mechanisms.展开更多
Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role re...Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role remains unclear. These can provide an ideal setting for the acquisition and dissemination of antibiotic resistance, as they are frequently affected by anthropogenic activities. The objective of this study was to establish a diffusion map of resistance integrons used as genetic markers of resistance associated with antibiotic resistance conferring genes (ARGs). Total DNA extracts from non-cultivable bacterial communities were used for the analyses. These communities were obtained from wastewater samples from 14 sites upstream and downstream of drainage channels or effluents in the cities of Abidjan, Bouaké, and Yamoussoukro. The results obtained correspond to the number of positives among the treated samples (n = 39). Among the genetic markers of dissemination, class 1 integrons were the most evident in 94.8% of samples in Abidjan (93.3%), Bouaké (100%) and Yamoussoukro (91.6%). Class 2 integrons and class 3 integrons were found respectively in 41% and 51% of all samples. Genes coding for β-lactamases and blaTEM was identified in almost all samples at a rate of 97.4%. A co-presence of the three genes blaTEM, blaSHV and blaCTX-M is also remarkable in the sites of the city of Yamoussoukro. Among the genes coding for carbapenemases, only blaKPC 17.94%, blaNDM 30.76% and blaOXA48 38.46% were detected in the samples.展开更多
基金funded by the USDA National Institute of Food and Agriculture (Hatch Grant ARZT-1360890-H31-164 and multi-state grant ARZ-T1370680-R31-172 (NC246))the National Natural Science Foundation of China (NSFC)–Henan Joint Major Grant (U2004206)+2 种基金the State Key Laboratory of Cotton Biology Open Fund, Zhengzhou University, China (CB2020A06)the Henan Agriculture Research System, China (HARS22-09-G3)the earmarked fund for China Agriculture Research System (CARS-27)
文摘Helicoverpa zea is a major target pest of pyramided transgenic crops expressing Cry1,Cry2 and/or Vip3Aa proteins from Bacillus thuringiensis(Bt)in the United States.Laboratory-selected Cry1Ac/Cry2Ab cross resistance and fieldevolved practical dual resistance of H.zea to these two toxins have been widely reported.Whether the widespread Cry1Ac/Cy2Ab dual resistance of H.zea has resulted from the selection of one shared or two independent resistance mechanisms by pyramided Bt crops remains unclear.Cadherin is a well-confirmed receptor of Cry1Ac and a suggested receptor of Cry2Ab in at least three Lepidopteran species.To test whether cadherin may serve as one shared mechanism for the cross and dual resistance of H.zea to Cry1Ac and Cry2Ab,we cloned H.zea cadherin(HzCadherin)cDNA and studied its functional roles in the mode of action of Cry1Ac and Cry2Ab by gain-and lossof-function analyses.Heterologous expression of HzCadherin in H.zea midgut,H.zea fat body and Sf9 cells made all three of these cell lines more susceptible to activated Cry1Ac but not activated Cry2Ab,whereas silencing HzCadherin of H.zea midgut and fat body cells significantly reduced the susceptibility to Cry1Ac but not Cry2Ab.Likewise,suppressing HzCadherin with siRNA made H.zea larvae resistant to Cry1Ac.These results clearly demonstrate that HzCadherin is not a receptor for Cry2Ab,and thus it is unlikely to serve as one shared mechanism for the cross and dual resistance of H.zea to Cry1Ac and Cry2Ab.
基金This study received support for Open Access Publikationskosten from the DFG.
文摘Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.
基金supported by the National Natural Science Foundation of China(Grant Nos.31971872,32372118,32071993)the QIAN Qian Academician Workstation,the Specific Research fund of the Innovation Platform for Academicians of Hainan Province,China(Grant No.YSPTZX202303)the Key Research and Development Program of Zhejiang Province,China(Grant No.2021C02056)。
文摘How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually comes at the expense of yield.Currently,many necrotic lesion mutants in rice have been identified,and these genes are involved in disease resistance pathways.This review provides a detailed introduction to the characteristics,classification,and molecular mechanisms of necrotic lesion formation.Additionally,we review the molecular regulatory pathways of genes involved in rice disease resistance.Concurrently,we summarize the relationship between resistance and yield in rice using newly developed gene editing methods.We discuss a rational and precise breeding strategy to better utilize molecular design technology for breeding disease-resistant and high-yield rice varieties.
文摘One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.
基金supported by the National Natural Science Foundation of China(11871238,11931019,12371486)。
文摘Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.
基金financial support from the National Key R&D Program of China(2022YFD1201702)the National Natural Science Foundation of China(32272040)the Agricultural Fine Seed Project of Shandong Province,China(2021LZGC006)。
文摘Abiotic stresses, such as drought, salt, extreme temperatures, and heavy metal pollution, are the main environmental factors that limit crop growth and yield. Sorghum, a C4 grass plant with high photosynthetic efficiency, can grow in adverse environmental conditions due to its excellent stress resistance characteristics. Therefore, unraveling the stress-resistance mechanism of sorghum could provide a theoretical basis for developing and cultivating various stress-resistant crops. This understanding could also help to create a conducive environment for using marginal soil in agriculture and ensuring food security. In this review, we discuss the adaptation mechanisms of sorghum under drought, salinity, temperature, and soil heavy metal stresses, the specific response to stress, the screening of sorghum-resistant germplasm, and the identification and functional analysis of the relevant genes and quantitative trait loci(QTL). In addition, we discuss the application potential of different stress-tolerant sorghum germplasms reported to date and emphasize the feasibility and potential use in developing and promoting highly stress-tolerant sorghum in marginal soil.
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Funded by the National Natural Science Foundation of China(No.11962024)Key Technology Project of Inner Mongolia Autonomous Region(No.2019GG031)。
文摘The objective of this paper was to study low temperature crack resistance mechanism of steel slag asphalt mixture(SAM).Thermal stress restrained specimen test(TSRST)and three-point bending test were carried out to evaluate the low-temperature crack resistance of SAM and basalt asphalt mixture(BAM).Based on the digital image correlation technique(DIC),the strain field distribution and crack propagation of SAM were analyzed from the microscopic point of view,and a new index,crack length factor(C),was proposed to evaluate the crack resistance of the asphalt mixture.The crystal phase composition and microstructure of steel slag aggregate(SA)and basalt aggregate(BA)were studied by X-ray diffraction(XRD)and scanning electron microscopy(SEM)to explore the low-temperature crack resistance mechanism of SAM.Results show that the low-temperature crack resistance of SAM is better than that of BAM;SAM has good integrity and persistent elastic deformation,and its bending failure mode is a hysteretic quasi-brittle failure;The SA surface is evenly distributed with pores and has surface roughness.SA has the composition phase of alkaline aggregate-calcite(CaCO3),so it has good adhesion to asphalt,which reveals the mechanism of excellent low-temperature crack resistance of SAM.
基金supported by the National Natural Science Foundation of China(Grant No.31701915)Zhejiang Province Public Welfare Technology Application Research Project(Grant No.LGN19C150007).
文摘Cucumber is an important vegetable worldwide,and powdery mildew(PM)is a common and serious disease of cucumbers.Breeding disease-resistant cucumber varieties is the most advantageous strategy to control this disease.In recent years,exploration and identification of cucumber PM resistance genes have achieved great advancement,and many genes have been cloned and verified using different methods.However,the resistance mechanism of cucumber PM is still unclear,and many ambiguities need to be elucidated urgently.In this review,we summarized the research advances in PM resistance in cucumbers,including genetic analysis,quantitative trait locus mapping,map-based cloning,transcriptomics,mlo-mediated PM resistance,and mining of noncoding RNAs involved in resistance.Finally,the research directions and the problems that need to be solved in the future were discussed.
基金Fundamental Research Program of Shanxi province(No.202103021223339,20210302124435)Shanxi Scholarship Council of China(No.2022-175)+1 种基金Fundamental Research Program of Shanxi Datong University(No.2019Q2,2019Q4)Doctoral Scientific Research Foundation of Shanxi Datong University(No.2018-B-13,2018-B-28)。
文摘Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.
基金Supported by the National Natural Science Foundation of China(No.82260001)Key Special Project Supported by the National Key R&D Plan of the Ministry of Science and Technology(No.2022YFC2305004)。
文摘Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000307)the Natural Science Foundation in China(Grant Nos.31672136 and 31272132).
文摘Apple ring rot,which is caused by Botryosphaeria dothidea,severely affects apple production.The mechanisms employed in apple cells against B.dothidea remain unknown.In this research,the pathogen infection mode and the relationship between cell death and disease resistance in‘Fuji’/B.dothidea interaction pathosystem were investigated.By using transmission electron microscopy(TEM),our research showed that the pathogen infects apple cells both intracellularly and extracellularly.However,compared with that in immature fruit,the incidence of hyphae in the interior of mature apple fruit cells increased dramatically,suggesting that cell wall-mediated penetration resistance could be important in apple resistance against B.dothidea.TEM ultrastructural characterization identified the nuclear morphology of programmed cell death induction in both apple fruit and callus cells under B.dothidea infection.Overexpression of MdVDAC2(MDP0000271281),which encodes an outer-membrane localized anion channel protein in mitochondria,significantly promoted cell death under B.dothidea infection and simultaneously inhibited pathogen infection,suggesting that cell death represents a disease resistance mechanism in apple against B.dothidea infection.Furthermore,BdCatalase(KAF4307763),a cytochromeP450 family protein BdCYP52A4(KAF4300696),and subtilisin-domain containing proteinswere identified fromB.dothidea-secreted proteins,which suggested the potential involvement of active oxygen species and phytoalexins in combating B.dothidea infection and triggering or dampening apple resistance.Collectively,our research suggested that cell wall-mediated penetration resistance,programmed cell death machinery and microbial effector-interrelated signaling were among strategies recruited in apple to combat B.dothidea.The current research laid the foundation for further investigations into resistance mechanisms in apple.
基金supported by Scientific Research Project of Education Department of Liaoning Province(Grant Number LJKZ0854).
文摘Temozolomide(TMZ)resistance is a major obstacle in glioma treatment.Nuclear protein-1(NUPR1)is a regulator of glioma progression.This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxiatreated glioma cells and its mechanism in modulating autophagy.We treated TMZ-resistant cells U251-TMZ and T98G-TMZ to normoxia or hypoxia and silenced NUPR1 in hypoxia-treated U251-TMZ and T98G-TMZ cells to assess cell viability,proliferation,apoptosis,LC3-II/LC3-I and p62 expressions,and autophagic flux under different concentrations of TMZ.We found that hypoxia upregulated NUPR1 expression and autophagy while NUPR1 silencing suppressed hypoxia-induced TMZ resistance and autophagy in glioma cells.We also investigated the interaction between NUPR1 and lysine demethylase 3A(KDM3A),as well as the enrichments of KDM3A and H3 lysine 9 dimethylation(H3K9me2)in the transcription factor EB(TFEB)promoter region.Our results suggest that hypoxia-induced NUPR1 promotes TFEB transcription by binding to KDM3A and reducing H3K9me2 levels,thereby augmenting glioma cell autophagy and TMZ resistance.Moreover,the overexpression of KDM3A or TFEB promoted glioma cell autophagy.In a xenograft tumor model,silencing NUPR1 suppressed TMZ resistance in glioma cells in vivo.Overall,our findings highlight a mechanism by which NUPR1 enhances glioma cell autophagy and TMZ resistance via the KDM3A/TFEB axis.
基金supported by the National Nature Science Foundation of China,the National Key Research and Development Program of China(302001109,2016YFD0300508,2017YFD0301602,2018YFD0301105)the Fujian and Taiwan Cultivation Resources Development and Green Cultivation Coordination Innovation Center,China(Fujian 2011 Project,2015-75)the Natural Science Foundation of Fujian Province,China(2022J01142)。
文摘Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvesting, the timely application of nitrogen fertilizer is fundamental,coupled with moderate field drying for root-vigor preservation and tiller promotion before and after the mechanical harvesting of the main crop.
文摘Exploding foil initiator(EFI)is a kind of advanced device for initiating explosives,but its function is unstable when it comes to directly igniting pyrotechnics.To solve the problem,this research aims to reveal the ignition mechanism of EFIs directly igniting pyrotechnics.An oscilloscope,a photon Doppler velocimetry,and a plasma spectrum measurement system were employed to obtain information of electric characteristics,impact pressure,and plasma temperature.The results of the electric characteristics and the impact pressure were inconsistent with ignition results.The only thing that the ignition success tests had in common was that their plasma all had a relatively long period of high-temperature duration(HTD).It eventually concludes that the ignition mechanism in this research is the microconvection heat transfer rather than the shock initiation,which differs from that of exploding foil initiators detonating explosives.Furthermore,the methods for evaluating the ignition success of semiconductor bridge initiators are not entirely applicable to the tests mentioned in this paper.The HTD is the critical parameter for judging the ignition success,and it is influenced by two factors:the late time discharge and the energy of the electric explosion.The longer time of the late time discharge and the more energy of the electric explosion,the easier it is to expand the HTD,which improves the probability of the ignition success.
基金financially supported by the National Natural Science Foundation of China(Nos.51801081 and 52171071)national funds through FCT of Portugal-Fundacao para a Ciencia e a Tecnologia,under a scientific contract of 2021.04115,CEMMPRE-ref.“UIDB/00285/2020”and LA/P/0112/2020 projects+2 种基金FEDER funds through the COMPETE program-Operational Program on Competitiveness Factorsnational funds through FCT-Foundation for Science and Technology,Outstanding University Young Teachers of“Qing Lan Project”of Jiangsu Province of China,Excellent Talents of“Shenlan Project”of Jiangsu University of Science and Technology of ChinaA part of this study was supported by the Directorate-General of Scientific Research and Technological Development(Algeria)。
文摘In the last decades,vanadium alloyed coatings have been introduced as potential candidates for self-lubrication due to their perfect tribological properties.In this work,the influence of V incorporation on the wear performance and oxidation resistance of TiSiN/CrN film coatings deposited by direct current(DC)reactive magnetron sputtering is investigated.The results show that vanadium incorporation significantly decreases the oxidation resistance of the coatings.In general,two layers are formed during the oxidation process:i)Ti(V)O_(2) on top,followed by a protective layer,which is subdivided into two layers,Cr_(2)O_(3) and Si-O.ii)The diffusion of V controls the oxidation of V-containing coatings.The addition of vanadium improves the wear resistance of coatings,and the wear rate decreases with increasing V content in the coatings;however,the friction coefficient is independent of the chemical composition of the coatings.The wear of the V-containing coatings is driven by polishing wear.
文摘This literature review examines the mechanisms of how exercise, specifically in the form of resistance training, may lead to pain relief in the cancer population. Primary data from three different cancer populations: breast, prostate, and lung, will be examined. A number of experimental studies have been conducted to confirm the effectiveness of resistance training on pain relief as well as the biochemical pathways that relate to this process. In this review, we will examine 5 randomized controlled trials. For the purposes of this review, pain is defined as physical suffering or discomfort associated with illness. Pain is the body’s natural signal, bringing attention to damage that has been sustained by tissues. However, chronic pain is common in the cancer population, and often serves no good purpose but instead will negatively impact both physical and mental health. The three types of pain: nociceptive, neuropathic, and inflammatory pathways have been investigated, and the knowledge of pain mechanisms allows for the understanding of how it is associated with pain. The purpose of this exploratory literature review is to give insight on how to maximize pain-relieving effects of resistance training. Research has indicated that resistance training modulates pain pathways by upregulating the release of pain-relieving substances including beta-endorphins, anti-inflammatory cytokines, and endocannabinoids. Understanding of the benefits of resistance training may be useful in relieving cancer pain, and reproducing effects of pain-relieving strategies while minimizing the symptoms related to cancer and its treatment.
基金supported by National Natural Science Foundation of China(31972021)R&D Projects in Key Areas of Guangdong Province(2019B020212003)+4 种基金the Science and Technology Program of Guangzhou,China(202206010177)Guangdong key research and development program(2021B0202060001)Foshan and agricultural academy cooperation projectGuangdong Modern Agriculture project(2022KJ117)Aquatic Products Center Project of GAAS。
文摘Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans.The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E.coli O157:H7 than using either alone.This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level.The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E.coli O157:H7 found that acid resistance systems in kojic acid were activated,and the cell membrane and genomic DNA were destructed in the cells,resulting in“oxygen starvation”.The oxidative stress response triggered by tea polyphenols inhibited both sulfur uptake and the synthesis of ATP,which affected the bacteria's life metabolic process.Interestingly,we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA,respiration,tricarboxylic acid cycle.The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E.coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.
基金the S and T Program of Hebei,No.22377704DMedical Science Research Project of Hebei Province,No.20190510Postgraduate’s Innovation Fund Project of Hebei Province,No.CXZZBS2021077.
文摘BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the production of PGF_(2α),is involved in the proliferation and growth of a variety of tumors.However,the role of PGFS in Oxa resistance in CRC remains unclear.AIM To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC.METHODS The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels.Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance(HCT116-OxR and HCT8-OxR)and their parental cell lines(HCT116 and HCT8)to assess its influence on cell proliferation,chemoresistance,apoptosis,and DNA damage.For determination of the underlying mechanisms,CRC cells were examined for platinum-DNA adducts and reactive oxygen species(ROS)levels in the presence of a PGFS inhibitor or its products.RESULTS Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues.Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dosedependent manner.Furthermore,overexpression of PGFS in parental CRC cells significantly attenuated Oxainduced proliferative suppression,apoptosis,and DNA damage.In contrast,knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells(HCT116-OxR and HCT8-OxR)accentuated the effect of Oxa treatment in vitro and in vivo.The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa.Treatment with the PGFS-catalyzed product PGF_(2α)reversed the effect of PGFS knockdown on Oxa sensitivity.Interestingly,PGFS inhibited the formation of platinum-DNA adducts in a PGF_(2α)-independent manner.PGF_(2α)exerts its protective effect against DNA damage by reducing ROS levels.CONCLUSION PGFS promotes resistance to Oxa in CRC via both PGF_(2α)-dependent and PGF_(2α)-independent mechanisms.
文摘Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role remains unclear. These can provide an ideal setting for the acquisition and dissemination of antibiotic resistance, as they are frequently affected by anthropogenic activities. The objective of this study was to establish a diffusion map of resistance integrons used as genetic markers of resistance associated with antibiotic resistance conferring genes (ARGs). Total DNA extracts from non-cultivable bacterial communities were used for the analyses. These communities were obtained from wastewater samples from 14 sites upstream and downstream of drainage channels or effluents in the cities of Abidjan, Bouaké, and Yamoussoukro. The results obtained correspond to the number of positives among the treated samples (n = 39). Among the genetic markers of dissemination, class 1 integrons were the most evident in 94.8% of samples in Abidjan (93.3%), Bouaké (100%) and Yamoussoukro (91.6%). Class 2 integrons and class 3 integrons were found respectively in 41% and 51% of all samples. Genes coding for β-lactamases and blaTEM was identified in almost all samples at a rate of 97.4%. A co-presence of the three genes blaTEM, blaSHV and blaCTX-M is also remarkable in the sites of the city of Yamoussoukro. Among the genes coding for carbapenemases, only blaKPC 17.94%, blaNDM 30.76% and blaOXA48 38.46% were detected in the samples.