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.

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..

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.

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.

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.

WEAR FAILURE MECHANISM AND MULTI-IMPACT PROPERTY OF AUTOMOTIVE ENGINE CHAIN

The multi-impact characteristics and failure mechanism of two kinds of automotive engine chain made in China are studied through engine assembly and road-drive tests. The worn surface morphologies of rubbing area between pin, bush and roller are also analyzed based on scanning electron microscope. The results show that the main wear mechanism of automotive engine chain is fatigue wear, and its failure mechanism is the forming, extending and flaking of cracks on top layer of pin and bush. In addition, the material, hot-treatment method and shaping technique for roller have a great influence upon the resistance to multi-impact. Ensuring sufficient strength and plasticity of roller, as well as adopting suitable shaping technique are the effective method to increase its resistance to multi-impact.

Failure mechanism of Mesozoic soft rock roadway in Shajihai coal mine and its surrounding rock control

In view of the buckling failure caused by large deformation of Mesozoic soft rock roadway in Shajihai mining area, such as serious roof fall, rib spalling, floor heave, etc., based on the detail site investigation,theoretical analysis, mineral composition test, microstructure test, water-physical property test and field experiments were carried out. And we revealed the compound failure mechanism of Mesozoic soft rock roadway in Shajihai mining area, namely the molecule expansion-shear slip of weak structural plane-construction disturbance. On this basis, the coupling support technology whose core is constant resistance with large deformation bolt was proposed. The feature of this supporting technology is that a new type of structural composite material was used, which makes the supporting system not only has the ideal deformation characteristics, but also has high supporting resistance. Thus the fully release of plastic energy within surrounding rock and reasonable control of the thickness of the plastic ring were realized. Then the differential deformation between the surrounding rock and support was eliminated by the secondary coupling support of bolt–mesh–cable, and the bolt with high strength was applied in the base angle to control floor. Eventually the collaborative bearing system of surrounding rock–support was formed. Through field tests the validity and rationality of support was also verified.

Nonvolatile Resistive Switching and Physical Mechanism in LaCrO3 Thin Films

Polycrystalline LaCrO3（LCO） thin films are deposited on Pt/Ti/SiO2/Si substrates by pulsed laser deposition and used as the switching material to construct resistive random access memory devices. The unipolar resistive switching（RS） behavior in the Au/LCO/Pt devices exhibits a high resistance ratio of ~104 between the high resistance state（HRS） and low resistance state（LRS） and exhibits excellent endurance/retention characteristics.The conduction mechanism of the HRS in the high voltage range is dominated by the Schottky emission, while the Ohmic conduction dictates the LRS and the low voltage range of HRS. The RS behavior in the Au/LCO/Pt devices can be understood by the formation and rupture of conducting filaments consisting of oxygen vacancies,which is validated by the temperature dependence of resistance and x-ray photoelectron spectroscopy results.Further analysis shows that the reset current IR and reset power PR in the reset processes exhibit a scaling law with the resistance in LRS（R0）, which indicates that the Joule heating effect plays an essential role in the RS behavior of the Au/LCO/Pt devices.

Failure mechanism and supporting measures for large deformation of Tertiary deep soft rock

The Shenbei mining area in China contains typical soft rock from the Tertiary Period. As mining depths increase, deep soft rock roadways are damaged by large deformations and constantly need to be repaired to meet safety requirements, which is a great security risk. In this study, the characteristics of deformation and failure of typical roadway were analyzed, and the fundamental reason for the roadway deformation was that traditional support methods and materials cannot control the large deformation of deep soft rock. Deep soft rock support technology was developed based on constant resistance energy absorption using constant resistance large deformation bolts. The correlative deformation mechanisms of surrounding rock and bolt were analyzed to understand the principle of constant resistance energy absorption. The new technology works well on-site and provides a new method for the excavation of roadwavs in Tertiary deed soft rock.

Failure mechanism and stability control of a large section of very soft roadway surrounding rock shear slip

The measured data and simulation test phenomenon of surrounding rock deformation and failure at the project site indicate that shear failure which firstly occurs in surrounding rock, block slip and second shear failure are the root cause of deformation and damage of supporting structure of the surrounding rock at a large scale. We derived limit load of surrounding rock shear slip failure and reasonable support resistance of given load by means of shear slip line field theory, discussed the main factors which influence the limit load of surrounding rock. Shear slip line field and limit load of circular tunnel surrounding rock were obtained by means of physical simulation test, which agreed well with the theoretical analysis results. Based on the theoretical analysis and physical simulation test, the cause deformation and failure at large scale of Xinshanghai No. 1 coal mine big section ingate was analyzed, and the shear failure resistance and block slip in surrounding rock were proposed as the core technical supporting ideas. Proper range of supporting resistance which came from calculation was suggested. The support scheme which is mainly composed of large grouting anchor, sprayed anchor net support technique and full-face grille concrete finally ended the dilemma of repeated failure and mending of ingate and created critical conditions for smooth production in the coal mine.

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.

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.

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.

Review of resistive switching mechanisms for memristive neuromorphic devices

Memristive devices have attracted intensive attention in developing hardware neuromorphic computing systems with high energy efficiency due to their simple structure,low power consumption,and rich switching dynamics resembling biological synapses and neurons in the last decades.Fruitful demonstrations have been achieved in memristive synapses neurons and neural networks in the last few years.Versatile dynamics are involved in the data processing and storage in biological neurons and synapses,which ask for carefully tuning the switching dynamics of the memristive emulators.Note that switching dynamics of the memristive devices are closely related to switching mechanisms.Herein,from the perspective of switching dynamics modulations,the mainstream switching mechanisms including redox reaction with ion migration and electronic effect have been systemically reviewed.The approaches to tune the switching dynamics in the devices with different mechanisms have been described.Finally,some other mechanisms involved in neuromorphic computing are briefly introduced.

Preparation,Performance and Slag Resistant Mechanism of Low Thermal Conductivity Microporous Corundum

The microporous corundum material was prepared using alumina micro-powder as the main raw material, alumina sol and starch as binders by a wet process, achieving the bulk density of 3.05 g · cm^-3, the apparent porosity of 9. 1%, the closed porosity of 12.3%, the median pore diameter of 0. 43 μm, and the thermal conductivity of 6. 5 W· m^-1· K^-1 at 800 ℃ which is 41.6% lower than that of common corundum. The slag resistance of the microporous corundum material was studied by immersion and compared with that of the common corundum aggregate, and the slag resistant mechanism of microporous corundum material was revealed. The results show that the slag resistance of the microporous corundum material is superior to that of the common corundum aggregate, the SEM and EDX show that on the reaction interface between microporous corundum and molten, slag, a continuous isolation layer with a large quantity of CA2 and CA6 columnar crystals is formed; while the common corundum aggregate reacts with the molten slag interface to form a discontinuous isolation layer of columnar crystals, through which a lot of molten slag corrodes or permeates into the aggregate. The mechanism is mainly that the microporous structure is more advantageous to nucleation and growth of CA2 and CA6 columnar crystals; in the reaction with the aggregate, the molten slag gets saturated and the critical solution thickness of the microporous corundum and the common corundum is 0. 16 μm and 0. 34 μm, respectively, this is caused by the smaller microporous corundum aggregate pores; and the smaller pores also increase the second phase ripening rate of microporous corundum, which is 9. 7 times of that of the common corundum.

Analysis and modeling of resistive switching mechanism oriented to fault tolerance of resistive memory based on memristor

With the progress of the semiconductor industry, resistive memories, especially the memristor, have drawn increasing attention. The resistive memory based on memrsitor has not been commercialized mainly because of data error. Currently, there are more studies focused on fault tolerance of resistive memory. This paper studies the resistive switching mechanism which may have time-varying characteristics. Resistive switching mechanism is analyzed and its respective circuit model is established based on the memristor Spice model.

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.