One hundred and thirty-eight rice accessions were screened for resistance to the small brown planthopper (SBPH) (Laodelphax striatellus Fallen) by the modified seedbox screening test. Twenty-five rice accessions w...One hundred and thirty-eight rice accessions were screened for resistance to the small brown planthopper (SBPH) (Laodelphax striatellus Fallen) by the modified seedbox screening test. Twenty-five rice accessions with different levels of resistance to SBPH were detected, accounting for 18.1% of the total accessions, which included 2 highly resistant, 9 resistant and 14 moderately resistant varieties. Compared with indica rice, japonica rice was more susceptible to SBPH. Antixenosis test, antibiosis test and correlation analysis were performed to elucidate the resistance mechanism. The resistant check Rathu Heenati (RHT), highly resistant varieties Mudgo and Kasalath, and resistant variety IR36 expressed strong antixenosis and antibiosis against SBPH, indicating the close relationship between resistance level and these two resistance mechanisms in the four rice varieties. Antibiosis was the dominant resistance pattern in the resistant varieties Daorenqiao and Yangmaogu due to their high antibiosis but low antixenosis. Dular, ASD7 and Milyang 23 had relatively strong antixenosis and antibiosis, indicating the two resistance mechanisms were significant in these three varieties. The resistant DV85 expressed relatively high level of antixenosis but low antibiosis, whereas Zhaiyeqing 8 and Guiyigu conferred only moderate antibiosis and antixenosis to SBPH, suggesting tolerance in these three varieties. Antibiosis and antixenosis governed the resistance to SBPH in the moderately resistant accession 9311. Antixenosis was the main resistance type in V20A. Tolerance was considered to be an important resistance mechanism in Minghui 63 and Yangjing 9538 due to their poor antibiosis and antixenosis resistance. The above accessions with strong antibiosis or antixenosis were the ideal materials for the resistance breeding.展开更多
Drought and shortage of water resources, which restrict the economy, society development and environmental protection, are key factors in arid zones of China. In the arid zones of Western China, researching plant drou...Drought and shortage of water resources, which restrict the economy, society development and environmental protection, are key factors in arid zones of China. In the arid zones of Western China, researching plant drought resistance mechanism, selecting plant species with higher drought resistance, and developing water-saving techniques, are important for environmental improvement and economic development. This paper reviews research advances on drought resistance mechanism of plant species, based on research of morphological, physiological, and ecological adaptation mechanism of plant species under drought stress, such as anatomical structure of root systems and leaves, photosynthesis, antioxidant enzyme system, malondialdehyde (MDA), osmotic adjustment, endogenous hormone, drought-induced proteins and δ^13C. Finally, this paper points out the key field of future research.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
BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)g...BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes mutations.However,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such mutations.CASE SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to mCRPC.Surprisingly,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 months.However,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib resistance.Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor olaparib.CONCLUSIONReverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.展开更多
Magnesia zirconia brick containing 11 wt% zirconia was prepared with magnesia and monoclinic zirconia as starting materials in order to replace the chrome-containing materials for Rtt furnace. The corrosion resistance...Magnesia zirconia brick containing 11 wt% zirconia was prepared with magnesia and monoclinic zirconia as starting materials in order to replace the chrome-containing materials for Rtt furnace. The corrosion resistance of magnesia zirconia brick and fused rebonded magnesia chrome brick (short for magnesia chrome brick) to high, and low basicity slag of RH fitrnace was comparatively researched by rotary slag method and their slag resistance mechanisms were analyzed. The results show that: (1) because the reaction layer containing CaZrO3 forms in magnesia zirconia brick, it has better corrosion resistance to high basicity slag than magnesia chrome brick, however, it has worse corrosion resistance to low basicity slag than magnesia chrome brick; (2) ZrO2 in the magnesia zirconia brick can absorb CaO in the slag, which decrea- ses the basicity of slag and inereases the viscosity of slag, so the degree of slag penetration in magnesia zircon.ia brick decreases ; ( 3 ) there is little zirconia in the slag layer of residual nutgnesia zirconia brick;from working face to original brick layer, the residual magnesia zirconia brick shows three layers: obviotasly deteriorative layer, slightly deteriorative layer, and original brick layer, but the residual magnesia chrome brick only shows two layers : obviously deteriorative layer and original brick layer; the SiO2 content of residual magnesia zirconia brick is the highest in the slightly deteriorative layer, however, the SiO2 content of residual magnesia chrome brick gradually decreases front working face to original brick layer.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
At present,the multiple drug resistance of Acinetobacter baumannii outbreaks worldwide and has intensified the trend,especially in the intensive care unit and burn ward.Generic drug resistant Acinetobacter baumannii i...At present,the multiple drug resistance of Acinetobacter baumannii outbreaks worldwide and has intensified the trend,especially in the intensive care unit and burn ward.Generic drug resistant Acinetobacter baumannii is known as the 21st century gram-negative bacterium“MRSA”,“Superbugs”.In recent years,researches have shown that this is associated with pathogenic bacteria to form biofilms.In this paper,the status of Acinetobacter baumannii infection,biofilm formation,resistance mechanism and prevention in recent years were summarized.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
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
Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use...Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..展开更多
In the fermentation process of biorefinery,industrial strains are normally subjected to adverse environmental stresses,which leads to their slow growth,yield decline,a substantial increase in energy consumption,and ot...In the fermentation process of biorefinery,industrial strains are normally subjected to adverse environmental stresses,which leads to their slow growth,yield decline,a substantial increase in energy consumption,and other negative consequences,which ultimately seriously hamper the development of biorefinery.How to minimize the impact of stress on microorganisms is of great significance.This review not only reveals the damaging effects of different environmental stresses on microbial strains but also introduces commonly used strategies to improve microbial tolerance,including adaptive evolution,reprogramming of the industrial host based on genetic circuits,global transcription machinery engineering(gTME)and bioprocess integration.Furthermore,by integrating the advantages of these strategies and reducing the cost of system operation,the tolerance of industrial strains,combined with production efficiency and process stability,will be greatly improved,and the development prospects of biorefinery will be more widespread.展开更多
Objective: To investigate the antimicrobial susceptibility of 97 clinical Staphylococcus aureus(S. aureus) strains against 14 antimicrobials and corresponding resistance mechanisms.Methods: The antimicrobial susceptib...Objective: To investigate the antimicrobial susceptibility of 97 clinical Staphylococcus aureus(S. aureus) strains against 14 antimicrobials and corresponding resistance mechanisms.Methods: The antimicrobial susceptibility of the isolates was determined using a disk diffusion method and antimicrobial resistance genes were screened by polymerase chain reaction. Mutations responsible for ciprofloxacin and rifampicin resistance were investigated by polymerase chain reaction and DNA sequencing.Results: All isolates were found to be susceptible to vancomycin. Various rates of resistance to penicillin(83.5%), ampicillin(77.3%), erythromycin(63.9%), tetracycline(16.5%), amoxicillin/clavulanic acid(16.5%), ciprofloxacin(15.5%), trimethoprim/sulfamethoxazole(15.5%), oxacillin(13.4%), fusidic acid(12.4%), rifampin(6.2%), clindamycin(6.2%), gentamicin(6.2%) and mupirocin(5.2%) were determined. In addition,different combinations of resistance genes were identified among resistant isolates.Ciprofloxacin resistant isolates had mutations in codon 84(Ser84 Leu) and 106(Gly106 Asp) in the gyr A gene. Mutations in grl A were mostly related to Ser80 Phe substitution. Leu466 Ser mutation in the rpo B gene was detected in all rifampin resistant isolates. All methicillin resistant S. aureus isolates were SCCmec type V.Conclusions: In conclusion, it was determined that the isolates were resistant to different classes of antimicrobials at varying rates and resistance was mediated by different genetic mechanisms. Therefore, continuous monitoring of resistance in S. aureus strains is necessary to control their resistance for clinically important antimicrobials.展开更多
Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mort...Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam(CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.展开更多
As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinaseinhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society ofClin...As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinaseinhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society ofClinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for thefirst-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab anderlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due toseveral different acquired resistance mechanisms, mainly represented by T790M substitutions and METamplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment,MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a rolefor MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatmentalgorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also representanother useful addition.展开更多
Soybean frog eye leaf spot(FLS) has been a major disease and production constralnt in the Northeast of China.The paper reported methods for identifying and evaluating resistant germplasm to the disease,at sometime li...Soybean frog eye leaf spot(FLS) has been a major disease and production constralnt in the Northeast of China.The paper reported methods for identifying and evaluating resistant germplasm to the disease,at sometime listed several resistant cultivars or lines which were resistant to both dominant races (1,7 race)and the mixture of over 8 races. It indicated that the resistance to race 1 or 7 were due to two different single dominant genes,respectively.And in the fied,there were more races,the resistance showed quantitative character.It was proposed the LTP,which was made according to the sizeand number of lesions could be used as an important index in selecting. Using bulked segregants analysis (BSA),the genetic distance between OPSO3 620 and resistant gene to race 7 were identified 8.7cm.The results showed that the resistant cultivars had less number of stoma,closer arrangement of polisade tissue and high cotent of wax.展开更多
Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent p...Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.展开更多
The Ti fire found in high performance engines promotes the development of burn resistant Ti alloys. The burn resistant mechanism of Ti40 alloy is investigated. Ti40 alloy reveals good burn resistance. Its interfacial ...The Ti fire found in high performance engines promotes the development of burn resistant Ti alloys. The burn resistant mechanism of Ti40 alloy is investigated. Ti40 alloy reveals good burn resistance. Its interfacial products between burning products and the matrix are tenacious, which retard the diffusion of oxygen into the matrix. Two burn resistant mechanisms, that is, fast scatter dispersion of heat and suppression of oxygen diffusion, are proposed.展开更多
Yellow stem borer(YSB),Scir-pophaga incertulas(Walker)has be-come the main rice insect pest onceagain along the Changjiang Riversince 1990s.Unfortunately,no ricevariety with resistance to YSB hasbeen reported so far.J...Yellow stem borer(YSB),Scir-pophaga incertulas(Walker)has be-come the main rice insect pest onceagain along the Changjiang Riversince 1990s.Unfortunately,no ricevariety with resistance to YSB hasbeen reported so far.Japonica Zhen-dao 2 with moderate resistance toYSB was found.In 10 rice vari-eties with different resistance levels,YSB individuals showed distinct de-velopmental rates,and the asyn-chronous development even occurredin the same rice variety.In this展开更多
文摘One hundred and thirty-eight rice accessions were screened for resistance to the small brown planthopper (SBPH) (Laodelphax striatellus Fallen) by the modified seedbox screening test. Twenty-five rice accessions with different levels of resistance to SBPH were detected, accounting for 18.1% of the total accessions, which included 2 highly resistant, 9 resistant and 14 moderately resistant varieties. Compared with indica rice, japonica rice was more susceptible to SBPH. Antixenosis test, antibiosis test and correlation analysis were performed to elucidate the resistance mechanism. The resistant check Rathu Heenati (RHT), highly resistant varieties Mudgo and Kasalath, and resistant variety IR36 expressed strong antixenosis and antibiosis against SBPH, indicating the close relationship between resistance level and these two resistance mechanisms in the four rice varieties. Antibiosis was the dominant resistance pattern in the resistant varieties Daorenqiao and Yangmaogu due to their high antibiosis but low antixenosis. Dular, ASD7 and Milyang 23 had relatively strong antixenosis and antibiosis, indicating the two resistance mechanisms were significant in these three varieties. The resistant DV85 expressed relatively high level of antixenosis but low antibiosis, whereas Zhaiyeqing 8 and Guiyigu conferred only moderate antibiosis and antixenosis to SBPH, suggesting tolerance in these three varieties. Antibiosis and antixenosis governed the resistance to SBPH in the moderately resistant accession 9311. Antixenosis was the main resistance type in V20A. Tolerance was considered to be an important resistance mechanism in Minghui 63 and Yangjing 9538 due to their poor antibiosis and antixenosis resistance. The above accessions with strong antibiosis or antixenosis were the ideal materials for the resistance breeding.
基金supported by the Key Project of Research Institute of Forestry,Chinese Academy of Forestry(ZD200908)the National Eleventh "Five-year Plan" Science and Technology Funded Project of the State Forestry Administration,P.R.of China (2006BAD26B0101)
文摘Drought and shortage of water resources, which restrict the economy, society development and environmental protection, are key factors in arid zones of China. In the arid zones of Western China, researching plant drought resistance mechanism, selecting plant species with higher drought resistance, and developing water-saving techniques, are important for environmental improvement and economic development. This paper reviews research advances on drought resistance mechanism of plant species, based on research of morphological, physiological, and ecological adaptation mechanism of plant species under drought stress, such as anatomical structure of root systems and leaves, photosynthesis, antioxidant enzyme system, malondialdehyde (MDA), osmotic adjustment, endogenous hormone, drought-induced proteins and δ^13C. Finally, this paper points out the key field of future research.
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Supported by the Natural Science Foundation of Chongqing,No. cstc2018jcyj AX0781the Major Project of Chongqing Health Committee,No. cstc2016 shmszx130033031+1 种基金the National Natural Science Foundation of China,No. 81302316the Chongqing technological innovation and application development-Major theme projects,No. cstc2019jscxfxydx0008
文摘BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes mutations.However,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such mutations.CASE SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to mCRPC.Surprisingly,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 months.However,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib resistance.Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor olaparib.CONCLUSIONReverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.
文摘Magnesia zirconia brick containing 11 wt% zirconia was prepared with magnesia and monoclinic zirconia as starting materials in order to replace the chrome-containing materials for Rtt furnace. The corrosion resistance of magnesia zirconia brick and fused rebonded magnesia chrome brick (short for magnesia chrome brick) to high, and low basicity slag of RH fitrnace was comparatively researched by rotary slag method and their slag resistance mechanisms were analyzed. The results show that: (1) because the reaction layer containing CaZrO3 forms in magnesia zirconia brick, it has better corrosion resistance to high basicity slag than magnesia chrome brick, however, it has worse corrosion resistance to low basicity slag than magnesia chrome brick; (2) ZrO2 in the magnesia zirconia brick can absorb CaO in the slag, which decrea- ses the basicity of slag and inereases the viscosity of slag, so the degree of slag penetration in magnesia zircon.ia brick decreases ; ( 3 ) there is little zirconia in the slag layer of residual nutgnesia zirconia brick;from working face to original brick layer, the residual magnesia zirconia brick shows three layers: obviotasly deteriorative layer, slightly deteriorative layer, and original brick layer, but the residual magnesia chrome brick only shows two layers : obviously deteriorative layer and original brick layer; the SiO2 content of residual magnesia zirconia brick is the highest in the slightly deteriorative layer, however, the SiO2 content of residual magnesia chrome brick gradually decreases front working face to original brick layer.
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.
文摘At present,the multiple drug resistance of Acinetobacter baumannii outbreaks worldwide and has intensified the trend,especially in the intensive care unit and burn ward.Generic drug resistant Acinetobacter baumannii is known as the 21st century gram-negative bacterium“MRSA”,“Superbugs”.In recent years,researches have shown that this is associated with pathogenic bacteria to form biofilms.In this paper,the status of Acinetobacter baumannii infection,biofilm formation,resistance mechanism and prevention in recent years were summarized.
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.
文摘Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..
基金The authors acknowledge funding support from the National Natural Science Foundation of China(21736002,21576027,21425624).
文摘In the fermentation process of biorefinery,industrial strains are normally subjected to adverse environmental stresses,which leads to their slow growth,yield decline,a substantial increase in energy consumption,and other negative consequences,which ultimately seriously hamper the development of biorefinery.How to minimize the impact of stress on microorganisms is of great significance.This review not only reveals the damaging effects of different environmental stresses on microbial strains but also introduces commonly used strategies to improve microbial tolerance,including adaptive evolution,reprogramming of the industrial host based on genetic circuits,global transcription machinery engineering(gTME)and bioprocess integration.Furthermore,by integrating the advantages of these strategies and reducing the cost of system operation,the tolerance of industrial strains,combined with production efficiency and process stability,will be greatly improved,and the development prospects of biorefinery will be more widespread.
基金supported by the Scientific Research Projects Unit of Mustafa Kemal University,Hatay,Turkey(Project no:47)
文摘Objective: To investigate the antimicrobial susceptibility of 97 clinical Staphylococcus aureus(S. aureus) strains against 14 antimicrobials and corresponding resistance mechanisms.Methods: The antimicrobial susceptibility of the isolates was determined using a disk diffusion method and antimicrobial resistance genes were screened by polymerase chain reaction. Mutations responsible for ciprofloxacin and rifampicin resistance were investigated by polymerase chain reaction and DNA sequencing.Results: All isolates were found to be susceptible to vancomycin. Various rates of resistance to penicillin(83.5%), ampicillin(77.3%), erythromycin(63.9%), tetracycline(16.5%), amoxicillin/clavulanic acid(16.5%), ciprofloxacin(15.5%), trimethoprim/sulfamethoxazole(15.5%), oxacillin(13.4%), fusidic acid(12.4%), rifampin(6.2%), clindamycin(6.2%), gentamicin(6.2%) and mupirocin(5.2%) were determined. In addition,different combinations of resistance genes were identified among resistant isolates.Ciprofloxacin resistant isolates had mutations in codon 84(Ser84 Leu) and 106(Gly106 Asp) in the gyr A gene. Mutations in grl A were mostly related to Ser80 Phe substitution. Leu466 Ser mutation in the rpo B gene was detected in all rifampin resistant isolates. All methicillin resistant S. aureus isolates were SCCmec type V.Conclusions: In conclusion, it was determined that the isolates were resistant to different classes of antimicrobials at varying rates and resistance was mediated by different genetic mechanisms. Therefore, continuous monitoring of resistance in S. aureus strains is necessary to control their resistance for clinically important antimicrobials.
基金supported by the National Key Research and Development Program of China (2017YFC1200200)Major Infectious Diseases such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects (2018ZX10712-001)+1 种基金National Natural Science Foundation of China (81702045 and 81902030)Shenzhen Basic Research projects (JCYJ20190807144409307)
文摘Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam(CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.
文摘As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinaseinhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society ofClinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for thefirst-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab anderlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due toseveral different acquired resistance mechanisms, mainly represented by T790M substitutions and METamplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment,MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a rolefor MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatmentalgorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also representanother useful addition.
文摘Soybean frog eye leaf spot(FLS) has been a major disease and production constralnt in the Northeast of China.The paper reported methods for identifying and evaluating resistant germplasm to the disease,at sometime listed several resistant cultivars or lines which were resistant to both dominant races (1,7 race)and the mixture of over 8 races. It indicated that the resistance to race 1 or 7 were due to two different single dominant genes,respectively.And in the fied,there were more races,the resistance showed quantitative character.It was proposed the LTP,which was made according to the sizeand number of lesions could be used as an important index in selecting. Using bulked segregants analysis (BSA),the genetic distance between OPSO3 620 and resistant gene to race 7 were identified 8.7cm.The results showed that the resistant cultivars had less number of stoma,closer arrangement of polisade tissue and high cotent of wax.
文摘Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.
文摘The Ti fire found in high performance engines promotes the development of burn resistant Ti alloys. The burn resistant mechanism of Ti40 alloy is investigated. Ti40 alloy reveals good burn resistance. Its interfacial products between burning products and the matrix are tenacious, which retard the diffusion of oxygen into the matrix. Two burn resistant mechanisms, that is, fast scatter dispersion of heat and suppression of oxygen diffusion, are proposed.
文摘Yellow stem borer(YSB),Scir-pophaga incertulas(Walker)has be-come the main rice insect pest onceagain along the Changjiang Riversince 1990s.Unfortunately,no ricevariety with resistance to YSB hasbeen reported so far.Japonica Zhen-dao 2 with moderate resistance toYSB was found.In 10 rice vari-eties with different resistance levels,YSB individuals showed distinct de-velopmental rates,and the asyn-chronous development even occurredin the same rice variety.In this