Drug resistance mechanisms in cancers:Execution of prosurvival strategies

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.

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.

Molecular Mechanism of Rice Necrotic Lesion for Optimized Yield and Disease Resistance

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.

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.

Study on Drug Resistance and Relative Mechanisms of Chlamydia Trachomatis

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..

Mechanical Properties and Thermal Shock Resistance of SrAl_(2)Si_(2)O_(8) Reinforced BN Ceramic Composites

Hexagonal boron nitride(h-BN)ceramics have become exceptional materials for heat-resistant components in hypersonic vehicles,owing to their superior thermal stability and excellent dielectric properties.However,their densification during sintering still poses challenges for researchers,and their mechanical properties are rather unsatisfactory.In this study,SrAl_(2)Si_(2)O_(8)(SAS),with low melting point and high strength,was introduced into the h-BN ceramics to facilitate the sintering and reinforce the strength and toughness.Then,BN-SAS ceramic composites were fabricated via hot press sintering using h-BN,SrCO_(3),Al_(2)O_(3),and SiO_(2) as raw materials,and effects of sintering pressure on their microstructure,mechanical property,and thermal property were investigated.The thermal shock resistance of BN-SAS ceramic composites was evaluated.Results show that phases of as-preparedBN-SAS ceramic composites are h-BN and h-SrAl_(2)Si_(2)O_(8).With the increase of sintering pressure,the composites’densities increase,and the mechanical properties shew a rising trend followed by a slight decline.At a sintering pressure of 20 MPa,their bending strength and fracture toughness are(138±4)MPa and(1.84±0.05)MPa·m^(1/2),respectively.Composites sintered at 10 MPa exhibit a low coefficient of thermal expansion,with an average of 2.96×10^(-6) K^(-1) in the temperature range from 200 to 1200℃.The BN-SAS ceramic composites prepared at 20 MPa display higher thermal conductivity from 12.42 to 28.42 W·m^(-1)·K^(-1) within the temperature range from room temperature to 1000℃.Notably,BN-SAS composites exhibit remarkable thermal shock resistance,with residual bending strength peaking and subsequently declining sharply under a thermal shock temperature difference ranging from 600 to 1400℃.The maximum residual bending strength is recorded at a temperature difference of 800℃,with a residual strength retention rate of 101%.As the thermal shock temperature difference increase,the degree of oxidation on the ceramic surface and cracks due to thermal stress are also increased gradually.

Evolution of mechanical properties,localized corrosion resistance and microstructure of a high purity Al-Zn-Mg-Cu alloy during non-isothermal aging

The evolution of mechanical properties,localized corrosion resistance of a high purity Al-Zn-Mg-Cu alloy during non-isothermal aging(NIA)was investigated by hardness test,electrical conductivity test,tensile test,intergranular corrosion test,exfoliation corrosion test,slow strain rate tensile test and electrochemical test,and the mechanism has been discussed based on microstructure examination by optical microscopy,electron back scattered diffraction,scanning electron microscopy and scanning transmission electron microscopy.The NIA treatment includes a heating stage from 40℃to 180℃with a rate of 20℃/h and a cooling stage from 180℃to 40℃with a rate of 10℃/h.The results show that the hardness and strength increase rapidly during the heating stage of NIA since the increasing temperature favors the nucleation and the growth of strengthening precipitates and promotes the transformation of Guinier-Preston(GPI)zones toη'phase.During the cooling stage,the sizes ofη'phase increase with a little change in the number density,leading to a further slight increase of the hardness and strength.As NIA proceeds,the corroded morphology in the alloy changes from a layering feature to a wavy feature,the maximum corrosion depth decreases,and the reason has been analyzed based on the microstructural and microchemical feature of precipitates at grain boundaries and subgrain boundaries.

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.

Study of joining mechanism of ABS polymer and steel/aluminum by resistance spot welding

The joining of metal and polymer is an increasingly important method to get lightweight components in the development of manufacturing industry- nowadays. In this artiele, metal and polymer lap joint was achieved by means of resistance spot welding （RSW） and ultrasonic assistance welding （UAW）. The joining mechanism of lap joint was analyzed by OM, TEM on microstructure at the interface of lap joints and XPS and IR spectra was discussed based on the following different ones： mechanical-interlocking, diffusion bond and coordination bond. The results showed that it was the combined action that played an important role in the effective joining work. Besides, ultrasonic assistance was used in the study to aid welding process based on its high-frequency ultrasonic vibration, which made joints shaping better and improved tensile strength visibly contrast to joints with the same lower heat input parameters.

Helicobacter pylori isolates from ethnic minority patients in Guangxi:Resistance rates,mechanisms,and genotype

AIM: To investigate the rate of Helicobacter pylori (H. pylori) resistance to clarithromycin among ethnic minority patients in Guangxi, explore the underlying mechanisms, and analyze factors influencing genotype distribution of H. pylori isolates.

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.

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.

Antimicrobial resistance and underlying mechanisms in Staphylococcus aureus isolates

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.

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 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.

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.

Corrosion Resistance Mechanism of MgO-CaO Refractories to Refining Slag

Corrosion resistance and penetration resistance of MgO-CaO materials with different CaO contents （22%, 42%, 49%, 53%, in mass）to refining AOD slag or VOD slag were investigated using static crucible technique by visual observation, SEM and XRD. The corrosion resistance and penetration resistance of speci-mens decrease with the increase of CaO content. This may be caused by the formation of C3S and C2S during the reactions between specimens and the slag. The formed C3S and C2S can restrain the further penetration to the matrix. The higher the CaO content, the more the C2S or C3S formed, the lower the porosity of the speci-mens, and the lower the penetration depth and corrosion rate. The corrosion resistance to AOD slag is better than that to VOD slag, because the reaction between AOD slag and the matrix is slighter than that between VOD slag and the matrix.

Advances in Research on Resistance Mechanisms of Bacterial Biofilms

A biofilm refers to a group of organized bacteria attached to the surface of living or inanimate objects and surrounded by some macromolecules. It is rich in organic components such as polysaccharides,peptides and phospholipids,greatly increases the resistance of bacteria to antibacterial drugs,and can cause infections in humans and animals. At present,the measure to prevent the infections is to prevent microbial colonies from adhering to the surface of the objects,which will help to improve the therapeutic effect of clinically serious infectious diseases. In addition,the identification and inhibition of biofilm formation genes is also an important research direction to control such infections. In this paper,molecular mechanisms of bacterial biofilm resistance to drugs that has caused widespread concern were summarized.

Study on asymmetric thermo-physical effect mechanism of intermediate frequency DC resistance spot welding for aluminum alloy

The asymmetric thermo-physical mechanism of the resistance spot welding technique with intermediate frequency(2 kHz)and direct current(RSWIFDC)on the high strength aluminum(Al)alloy TL091 was studied here in view of the Peltier effect.On the basis of the analysis of the electrode cap surface erosion state and the shape-position of the nugget,it was concluded that asymmetric thermo-physical phenomenon occurred on both ends of the nugget,and even had an influence upon the shape-forming coefficient and the vertical position deviation of the nugget,and the erosion degree of the electrode caps.In this work,the relative thermo-physical model of the welding was established combined with the Peltier effect and the spot welding characteristics.Accordingly the relative welding phenomena,such as nugget center deviation and different erosion degree of the electrode cap surface,was explained clearly using the model related with the Peltier effect for the first time.This model provides important theoretical basis for future study and application of Al alloy spot welding,based on which,effective works may be done to promote the quality of the Al alloy welded joints and to obtain favorable control upon parameters of Al alloy welding for electrode caps.

Germplasm Evaluation,Inheritance, Molecular Marker and Mechanism of Resistance to Frog eye Leaf Spot

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.

Investigation of failure mechanism and mechanical properties of resistance spot welded magnesium alloy joints

Resistance .spot u,e/ded magnesium alloy joints can fail in two markedly different failure modes （interfiscialfitilure and button pullout failure） under tensile shear loading conditions. For button pullottt failure, the crack first propagates along cellular dendritic structure of the nugget circumference, and then passes through heat-affected zone （HAZ） and base metal in sequence. The tensile shear load has smaller values under the interracial failure occurring in a small weld nugget as compared to the button pullout failure appearing in a large weld nugget. The tensile shear load increases with the increasing nugget diameter for expulsion free joints. However, for joints which experienced expulsion, the tensile shear load decreases in spite of nugget diameter increasing. Under the equivalent nugget diameter （5. g mm）, the tensile shear load of joints with 9 × 10^-4 g KBF4 addition was increased by around 20% as compared to that of joints without KBF4 addition.