Acinetobacter baumannii biofilm resistance mechanisms and prevention and control of progress

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.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

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.

Functional assessment of cadherin as a shared mechanism for cross/dual resistance to Cry1Ac and Cry2Ab in Helicoverpa zea

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.

The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations: acquired resistance mechanisms and strategies to overcome them

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.

Resistance mechanisms and reprogramming of microorganisms for efficient biorefinery under multiple environmental stresses

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.

Epidemiology and Mechanisms of Ceftazidime-Avibactam Resistance in Gram-Negative Bacteria

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.

Genetics,resistance mechanism,and breeding of powdery mildew resistance in cucumbers(Cucumis sativus L.)

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.

Research progress on the drug action and resistance mechanism in Mycobacterium tuberculosis

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.

Pathogenesis and drug resistance mechanism of Burkholderia pseudomallei

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.

Comprehensive Overview of Populus simonii Research in the Recent Years

As an important ecological tree species in northern China, Populus simonii plays a crucial role in maintaining ecological balance and promoting environmental sustainability. The academic community has conducted a series of in-depth studies on this species, covering key areas such as genomics, survival mechanisms, and genetic breeding. Through the analysis of the genomic structure and function of P. simonii, we have not only revealed the molecular basis for its adaptation to harsh environments but also identified key genes that promote its growth and resistance to pests and diseases. Furthermore, exploring the survival mechanisms of P. simonii has deepened our understanding of its stress resistance traits, including how it effectively copes with abiotic stresses such as drought, salinization, and heavy metal pollution. In genetic breeding, significant progress has been made through the application of modern biotechnology, improving the growth rate and wood quality of P. simonii and enhancing its environmental adaptability and disease resistance. These research findings have not only enriched our knowledge of the biological characteristics of P. simonii but also provided a solid scientific foundation for its application in ecological restoration, forestry production, and environmental management.

Evaluation of Rice Germplasm for Resistance to the Small Brown Planthopper (Laodelphax striatellus) and Analysis of Resistance Mechanism

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.

Identification of a novel planthopper resistance gene from wild rice(Oryza rufipogon Griff.)

Rice planthoppers,including brown planthopper(BPH)and white-backed planthopper(WBPH),are the most destructive pests in Asian rice cultivation regions.Planthopper resistance genes that have been mapped and characterized advance our understanding of underlying resistance mechanisms and facilitate the breeding of resistant varieties,thereby contributing to an efficient pest management strategy.In this study,a novel resistance gene Bph38 derived from the wild rice species Oryza rufipogon Griff.was found to confer high resistance to BPH and WBPH.Conventional mapping was performed to identify regions associated with BPH and WBPH resistance,and two mapping efforts led to the same region on chromosome 4 flanked by markers RM16563 and RM16763.Bulked-segregant analysis and next-generation sequencing were performed using the same population to detect the resistance gene.Conventional mapping narrowed the region to a 12.3-Mb segment,and fine mapping using BC1 F2 recombinants identified a 79-kb segment flanked by markers YM112 and YM190.Near-isogenic lines(NILs)carrying Bph38 in the 9311(indica)and BR54(japonica)genetic backgrounds were developed by crossing and backcrossing with marker-assisted selection.The agronomic traits and BPH and WBPH resistance of the NILs were similar to those of the recurrent parents.Mandatory feeding and host-choice tests revealed that Bph38 showed both antibiotic and antixenotic effects in both insects,with stronger effects in indica-background lines.Further fine mapping and characterization of the major gene may result in map-based cloning of the gene and allow its application in breeding insectresistant rice varieties.

Research advances on drought resistance mechanism of plant species in arid zones of China

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.

Biochemical Mechanism of Chlorantraniliprole Resistance in the Diamondback Moth, Plutella xylostella Linnaeus

The insecticide chlorantraniliprole exhibits good efifcacy and plays an important role in controlling the diamondback moth, Plutella xylostella Linnaeus. However, resistance to chlorantraniliprole has been observed recently in some ifeld populations. At present study, diamondback moths with resistance to chlorantraniliprole （resistant ratio （RR） was 82.18） for biochemical assays were selected. The assays were performed to determine potential resistance mechanisms. The results showed that the selected resistant moths （GDLZ-R） and susceptible moth could be synergized by known metabolic inhibitors such as piperonyl butoxide （PBO）, triphenyl phosphate （TPP） and diethyl-maleate （DEM） at different levels （1.68-5.50-fold and 2.20-2.89-fold, respectively）, and DEM showed the maximum synergism in both strains. In enzymes assays, a high level of glutathione-S-transferase （GST） was observed in the resistant moth, in contrast, moths that are susceptible to the insecticide had only 1/3 the GST activity of the resistant moths. The analysis of short-term exposure of chlorantraniliprole on biochemical response in the resistant strain also showed that GST activity was signiifcantly elevated after exposure to a sub-lethal concentration of chlorantraniliprole （about 1/3 LC50, 12 mg L-1） 12 and 24 h, respectively. The results show that there is a strong correlation between the enzyme activity and resistance, and GST is likely the main detoxiifcation mechanism responsible for resistance to chlorantraniliprole in P. xylostella L., cytochrome P450 monooxygenase （P450） and carboxy-lesterase （CarE） are involved in to some extent.

Overall Evaluation of the Effect of Residual Stress Induced by Shot Peening in the Improvement of Fatigue Fracture Resistance for Metallic Materials

Before 1980s,the circular suspension spring in automobile subjected to torsion fatigue load,under the cyclic normal tensile stresses,the majority of fatigue fracture occurred was in normal tensile fracture mode（NTFM）and the fracture surface was under 45°diagonal.Because there exists the interaction between the residual stresses induced by shot peening and the applied cyclic normal tensile stresses in NTFM,which represents as＂stress strengthening mechanism＂,shot peening technology could be used for improving the fatigue fracture resistance（FFR）of springs.However,since 1990s up to date,in addition to regular NTFM,the fatigue fractures occurred of peened springs from time to time are in longitudinal shear fracture mode（LSFM）or transverse shear fracture mode（TSFM）with the increase of applied cyclic shear stresses,which leads to a remarkable decrease of FFR.However,LSFM/TSFM can be avoided effectively by means of shot peening treatment again on the peened springs.The phenomena have been rarely happened before.At present there are few literatures concerning this problem.Based upon the results of force analysis of a spring,there is no interaction between the residual stresses by shot peening and the applied cyclic shear stresses in shear fracture.This;means that the effect of＂stress strengthening mechanism＂for improving the FFR of LSFM/TSFM is disappeared basically.During shot peening,however,both of residual stress and cyclic plastic deformed microstructure are induced synchronously like＂twins＂in the surface layer of a spring.It has been found for the first time by means of force analysis and experimental results that the modified microstructure in the＂twins＂as a＂structure strengthening mechanism＂can improve the FFR of LSFM/TSFM.At the same time,it is;also shown that the optimum technology of shot peening strengthening must have both＂stress strengthening mechanism＂and＂structure strengthening mechanism＂simultaneously so that the FFR of both NTFM and LSFM/TSFM can be improved by shot peening.

Mechanism of Burn Resistance of Alloy Ti40

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 intedecial 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.

Induced Resistance of Tomato against Gray Mold (Botrytis cinerea) by Salicylic Acid (SA)

[ Objective ] The paper was to explore the induced resistance of tomato against gray mold （Botrytis cinerea） by salicylic acid. [ Method ] SA was used as an inducer to treat tomato seedlings, the effects of SA on mycelial diameter and spore germination of B. cinerea were studied, and the changes of 4 defense enzyme activities containing catalase （CAT）, peroxidase （POD）, polyphenol oxidase （PPO） and phenylalanine ammonia lyase （PAL）, as well as malondialdehyde （MDA） content during the production process of induced resistance were also measured. [ Result] SA had no inhibitory effect against spore germination and myce- lial growth of B. cinerea within the concentration range, and the relative induced effect had different degrees of improvement after treatment. The induced effect was the best as B. cinerea was challenged to inoculate at the third day after using 150 mg/L SA in tomato plants, and the duration of resistance was 10 -15 d. After treated by SA, CAT, POD, PPO and PAL first increased and then decreased in systemic induced resistance against B. cinerea, which were significantly higher than control. Meanwhile, MDA content showed ascendant trend in wavy line form. [ Conclusion ] The use of SA within a certain concentration range is safe; CAT, POD, PPO and PAL activities have positive correlation with induced resistance against B. cinerea, the increase of MDA content also has close relationship with the imvrovement of disease resistance.

OXIDATION RESISTANCE AND MECHANICAL PROPERTIES OF Ti_3Al-Nb-Mo-Si ALLOYS

In the present paper,the development of Ti3Al-Nb-Mo-Si alloys for high oxidation resistance is reviewed.Beside of weight gain of alloys with different Nb and Si addition is tested,the evaluation of comprehensive mechanical properties has been taken,include the room-temperature and 700℃ tensile properties,thermal stability,creep rupture and fracture toughness of the alloys,It has shown that the oxidation resistance and mechanical properties were significantly affected by the variation of Nb and Si contents.The composition with the best balance of properties is Ti-24Al-13Nb-1.5Mo-0.5Si and Ti-24Al-15Nb-1.5Mo,which is mush higher than that of Super,α_2 alloy (Ti-25Al-10Nb-3V-1Mo).

RESISTANT MECHANISMS OF CISPLATIN IN HUMAN LUNG ADENOCARCINOMA CELL LINE A_(549)DDP

To study the resistant mechanisms of cisplatin in human lung adenocarcinoma cell line A 549 DDP. A 549 DDP cells was established by stepwise increasing concentration of cisplatin (CDDP) in medium. Interstrand cross linked DNA (ICL) was measured by ethidium bromide fluorescence assay. The intracellular and intranuclear accumulation of cisplatin was measured by atomic absorption spectrometry. The removal of GS X was determined by FCM and fluorescence microscopy. Results: The A 549 DDP cell line was 8.9 fold resistance relative to the parental A 549 cell line. The formation of ICL in A 549 was 6.28 times higher than that in A 549 DDP cells. The intracellular and intranuclear accumulation of cisplatin in A 549 cells was 5.9 times and 4.1 times higher than that in A 549 DDP cells, respectively. The ability of GS X pump pumped GS X complex (GS Pt) in A 549 DDP cells was higher than that in A 549 . The repair rate in A 549 DDP cells was 2 times higher than that in A 549 . Conclusions: Decreased accumulation and increased export of cisplatin might be the main mechanism of cisplatin resistant A 549 DDP cells while the enhanced repair capacity of DNA may play a role in CDDP resistance.

Circulating tumor DNA genomic profiling reveals the complicated olaparib-resistance mechanism in prostate cancer salvage therapy: A case report

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.