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.

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.

BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism

BACKGROUND Helicobacter pylori(H.pylori)is the main pathogen that causes a variety of upper digestive diseases.The drug resistance rate of H.pylori is increasingly higher,and the eradication rate is increasingly lower.The antimicrobial resistance of H.pylori is an urgent global problem.It has been confirmed that Banxia Xiexin decoction(BXXXT)demonstrates the effects of treating gastrointestinal diseases,inhibiting H.pylori and protecting gastric mucosa.The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H.pylori.AIM To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H.pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT.METHODS The aqueous extract of BXXXT was gained by water decocting method.The inhibitory effect of the aqueous extract on H.pylori was detected by dilution in vitro;drug-resistant H.pylori cells were used to build an acute gastritis model in vivo.Thereafter,the model mice were treated with the aqueous extract of BXXXT.The amount of H.pylori colonization,the repair of gastric mucosal damage,changes of inflammatory factors,apoptosis,etc.,were assessed.In terms of mechanism exploration,the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry;the immune function of peripheral blood cells such as CD3+T and CD4+T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry;the H.pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected.Differently expressed genes were screened and verification was performed thereon with knockout expression.RESULTS The minimum inhibitory concentration of BXXXT aqueous extract against H.pylori was 256-512μg/mL.A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did;the BXXXT aqueous extract have at least 11 ingredients inhibiting H.pylori,including berberine,quercetin,baicalin,luteolin,gallic acid,rosmarinic acid,aloe emodin,etc.,of which berberine,aloe emodin,luteolin and gallic acid have a synergistic effect;BXXXT aqueous extract was found to stimulate the expressions of CD3+T and CD4+T and increase the number of CD4+T/CD8+T in gastritis mice;the detection of transcriptome and proteome,quantitative polymerase chain reaction,Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes,and CagA,VacA,etc.CONCLUSION BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H.pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine,emodin and luteolin,the main components of the extract;the extract could activate the immune function and enhance bactericidal effects;BXXXT aqueous extract,with main targets of BXXXT aqueous extract related to urease,virulence factors,etc.,could reduce the urease and virulence of H.pylori,weaken its colonization,and reduce its inflammatory damage to the gastric mucosa.

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.

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.

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.

Tool wear mechanism in turning of novel wear-resisting aluminum bronze

Tool wear and wear mechanism during the turning of a wear-resisting aluminum bronze have been studied. Tool wear samples were prepared by using M2 high-speed steel and YW1 cemented carbide tools to turn a novel high strength, wear resisting aluminum bronze without coolant and lubricant. Adhesion of workpiece materials was found on tool’s surface. Under the turning condition used in this study major wear mechanisms for turning aluminum bronze using M2 high-speed steel tool are diffusion wear, adhesive wear and plastic deformation and shear on the crater. Partial melting of high-speed steel on the rake plays a role in the tool wear also. Major wear mechanisms for turning aluminum bronze using YW1 cemented carbide tool are diffusion wear, attrition wear and sliding wear. To control the machining temperature is essential to reduce tool wear.

High Tem perature Defor mation Mechanism of Ti-40 Burn Resistant Titaniu m Alloy As-annealing

Ti 40 alloy is a single β phase burn resistant titanium alloy. Its high temperature deformation mechanism and stress strain ( σ ε ) curves were studied by Gleeble 1500 thermal simulator. The results suggest that there are a bit abrupt flow stress drops followed by steady state in Ti 40 alloy as annealing. The magnitude of the flow stress drop increases with strain rate and decreases with temperature. Its deformation activation energies are 174 kJ/mol for 650～850℃ and 276.7 kJ/mol for 950～1000℃, which are close to or bigger than the values for self and solute lattice diffusion in pure β titanium, thereby, the deformation mechanism at temperature range is controlled by lattice diffusion for 650～850℃, or mainly controlled by dynamic recrystallization for 950～1000℃.

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.

Production characteristics and displacement mechanisms of infilling polymer-surfactant-preformed particle gel flooding in post-polymer flooding reservoirs:A review of practice in Ng3 block of Gudao Oilfield

The pilot test of infilling polymer-surfactant-preformed particle gel(PPG)flooding has been successfully implemented after polymer flooding in Ng3 block of Gudao Oilfield in China.However,the production characteristics and displacement mechanisms are still unclear,which restricts its further popularization and application.Aiming at this problem,this paper firstly analyzes the production performance of the pilot test and proposed four response types according to the change of water cut curves,including W-type,U-type,V-type response,and no response.Furthermore,the underlying reasons of these four types are analyzed from the aspects of seepage resistance and sweep efficiency.The overall sweep efficiency of gradual-rising W-type,gradual-decreasing W-type,and early V-type response increases from 0.81 to 0.93,0.55 to 0.89,and 0.94 to 1,respectively.And the sum of seepage resistance along the connection line between production well and injection well for U-type and delayed V-type response increases from 0.0994 to 0.2425,and 0.0677 to 0.1654,respectively.Then,the remaining oil distribution after polymer flooding is summarized into four types on the basis of production and geological characteristics,namely disconnected remaining oil,streamline unswept remaining oil,rhythm remaining oil,and interlayer-controlled remaining oil.Furthermore,the main displacement mechanisms for each type are clarified based on the dimensionless seepage resistance and water absorption profile.Generally,improving connectivity by well pattern infilling is the most important for producing disconnected remaining oil.The synergistic effect of well pattern infilling and polymer-surfactant-PPG flooding increases the dimensionless seepage resistance of water channeling regions and forces the subsequent injected water to turn to regions with streamline unswept remaining oil.The improvement of the water absorption profile by polymer-surfactant-PPG flooding and separated layer water injection contributes to displacing rhythm remaining oil and interlayer-controlled remaining oil.Finally,the paper analyzes the relationships between the remaining oil distribution after polymer flooding and production characteristics of infilling polymer-surfactant-PPG flooding.The study helps to deepen the understanding of infilling polymer-surfactant-PPG flooding and has reference significance for more commercial implementations in the future.

HIGH TEMPERATURE DEFORMATION MECHANISM AND CONSTITUTIVE EQUATION OF Ti-40 BUREN RESISTANT TITANIUM ALLOY

Ti - 40 alloy is a single β phase burn resistant titanium alloy.Its high temperature deformation mech- anism is studied and its stress - strain curves are examined he use of Gleeble - 1500 thermal -simulator. The results reveal that there are abrupt flow stress drops followed b steady state.The magnitude of the flow stress drop increases with strain rote and decreases with temperature.Deformation activation energy, Q, is 247. 5 KJ/mol. The deformation mechanism of Ti - 40 alloy is controlled by the lattice diffusion Its constitutive equation is set up, i. e.

Experimental Study on the Resistance and Splash Performances of Water Collecting Devices for Mechanical Draft Cooling Towers

In recent years,water collecting systems,with the associated advantages of energy saving and noise reduction,have become the foundation for the development of a scheme to optimize the structure of cooling towers.To explore the feasibility of this approach for mechanical draft cooling towers,a small-scale experimental device has been built to study the resistance and splash performances of three U-type water collecting devices(WCDs)for different water flow rates and wind speeds.The experimental results show that within the considered ranges of wind speed and water flow rate,the pressure drop of the different WCDs can vary significantly.The resistance and local splash performances can also be remarkably different.Some recommendations about the most suitable system are provided.Moreover,a regression analysis of the experimental data is conducted,and the resulting fitting formulas for resistance and splash performance of WCD are reported.

Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Obesity and overweight are widespread issues in adults,children,and adolescents globally,and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus(T2DM).Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM.This proinflammatory activation occurs in multiple organs and tissues.Immune cellmediated systemic attack is considered to contribute strongly to impaired insulin secretion,insulin resistance,and other metabolic disorders.This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut,islet,and insulin-targeting organs(adipose tissue,liver,skeletal muscle)in obesity-related T2DM.There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.

High Water Resistance and Enhanced Mechanical Properties of Bio-Based Waterborne Polyurethane Enabled by in-situ Construction of Interpenetrating Polymer Network

In this study,acrylic acid was used as a neutralizer to prepare bio-based WPU with an interpenetrating polymer network structure by thermally induced free radical emulsion polymerization.The effects of the content of acrylic acid on the properties of the resulting waterborne polyurethane-poly(acrylic acid)(WPU-PAA)dispersion and the films were systematically investigated.The results showed that the cross-linking density of the interpenetrating network polymers was increased and the interlocking structure of the soft and hard phase dislocations in the molecular segments of the double networks was tailored with increasing the content of acrylic acid,leading to enhancement of the mechanical properties and water resistance of WPU-PAA films.Notably,with the increase in content of acrylic acid,the tensile strength,Young’s modulus,and toughness of the WPU-PAA-110 film increased by 3 times,and 8 times,and 2.4 times compared with WPU-PAA-80,respectively.The WPU-PAA-100 film showed the best water resistance,and the water absorption rate at 96 h was only 3.27%.This work provided a new design scheme for constructing bio-based WPU materials with excellent properties.

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.

Effect of Acupressure Therapy on Anti-inflammatory Mechanism in Obesity-induced IR Rats

[Objectives] To study the effect of "acupressure therapy" on anti-inflammatory mechanism in obesity-induced IR rats. [Methods] 10 rats were randomly selected and fed with normal diet as blank group, and the remaining 30 rats were fed with high-fat diet for 8 weeks. The obesity-induced IR model was induced and divided into two groups: model group and acupressure group. The acupressure group was treated by "acupressure therapy" three times a week for 6 weeks;the model group was taken 3 times at the same time every week, and the supine binding experiment lasted for 10 min for 6 weeks. Morphological observation was carried out before and after the experiment, mainly observing the general conditions and body weight. After the last intervention, the animals were killed and samples were collected. Western Blot method was used to detect the expression of TNF-α and IL-6 protein in adipose tissue of the three groups. [Results] Compared with the blank group, the expression of TNF-α and IL-6 protein in adipose tissue of the model group increased significantly ( P <0.01);compared with the model group, the expression of TNF-α and IL-6 protein in adipose tissue of the acupressure group decreased significantly ( P <0.01). [Conclusions] After intervening in the obesity-induced IR rats with acupressure method, the status of insulin resistance in obese rats was improved by inhibiting the expression of inflammatory factors.

Ultrasonic solidification mechanism and optimized application performances of ternary Mg_(71.5)Zn_(26.1)Y_(2.4) alloy

One dimensional(1D) and three dimensional(3D) ultrasound sources were applied to the solidification process of Mg_(71.5)Zn_(26.1)Y_(2.4) alloy.The acoustic spectra were in-situ measured, based on which the cavitation intensities and dynamic solidification mechanism were further investigated. With the increase of ultrasonic dimension and amplitude, the primary Mg_(3)Zn_(6)Y phase was significantly refined from petals to nearly pentagonal shape. The sound field measurements showed that the transient cavitation played a decisive role in generating a high local undercooling, which facilitated the formation of icosahedral clusters and promoted the nucleation of primary Mg_(3)Zn_(6)Y phase. The morphological transition of(α-Mg+Mg_(3)Zn_(6)Y) eutectic from lamellar to anomalous structure occurred under 3D ultrasonic condition. The stable cavitation took the main responsibility because the high pressure excited by nonlinearly oscillating bubbles induced the preferential nucleation of α-Mg phase rather than Mg_(3)Zn_(6)Y phase. As compared with its static values, the tensile strength and compression plasticity of this alloy were increased by the factors of 1.9 and 2.1, and its corrosion resistance was also improved with the corrosion current density decreased by one order of magnitude.

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.

Charge transport and bipolar switching mechanism in a Cu/HfO_2/Pt resistive switching cell

Bipolar resistance switching characteristics are investigated in Cu/sputtered-HfO_2/Pt structure in the application of resistive random access memory(RRAM).The conduction mechanism of the structure is characterized to be SCLC conduction.The dependence of resistances in both high resistance state(HRS) and low resistance state(LRS) on the temperature and device area are studied.Then,the composition and chemical bonding state of Cu and Hf at Cu/HfO_2 interface region are analyzed by x-ray photoelectron spectroscopy(XPS).Combining the electrical characteristics and the chemical structure at the interface,a model for the resistive switching effect in Cu/HfO_2/Pt stack is proposed.According to this model,the generation and recovery of oxygen vacancies in the HfO_2 film are responsible for the resistance change.

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

The insecticide chlorantraniliprole exhibits good efficacy and plays an important role in controlling the diamondback moth, Plutella xylostella Linnaeus. However, resistance to chlorantraniliprole has been observed recently in some field 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 significantly 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 i s likely the main detoxification mechanism responsible for resistance to chlorantraniliprole in P. xylostella L., cytochrome P450 monooxygenase(P450) and carboxy-lesterase(Car E) are involved in to some extent.