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.

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.

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.

Natural Products and Antiviral Resistance

Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.

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.

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.

Effect of aging temperature on the microstructures and mechanical properties of ZG12Cr9Mo1Co1NiVNbNB ferritic heat-resistant steel

The effect of aging on the mechanical properties and microstructures of a new ZG12Cr9 MolColNiVNbNB ferritic heat resistant steel was investigated in this work to satisfy the high steam parameters of the ultra-supercritical power plant.The results show that the main precipitates during aging are Fe（Cr,Mo）23C6,V（Nb）C,and（Fe2Mo） Laves in the steel.The amounts of the precipitated phases increase during aging,and correspondingly,the morphologies of phases are similar to be round.Fe（Cr,Mo）23C6 appears along boundaries and grows with increasing temperature.In addition,it is revealed that the martensitic laths are coarsened and eventually happen to be polygonization.The hardness and strength decrease gradually,whereas the plasticity of the steel increases.What＇s more,the hardness of this steel after creep is similar to that of other 9%-12%Cr ferritic steels.Thus,ZG12Cr9 MolColNiVNbNB can be used in the project.

Comparison of Acetylcholinesterase Characteristics Between Resistant and Susceptible Strains of Helicoverpa armigera (Hübner)

The sensitivity of a susceptible and two resistant strains of cotton bollworm, Helicoverpa armigera, to phoxim, malathion and methomyl was determined by a topical application of bioassay method. YG strain, collected from field of Yanggu, Shandong Province of China, possessed 7-, 13- and 20-fold of resistance to the above three antiacetylcholinesterases based on the comparison of LD50 values with a laboratory susceptible strain. There were not significant difference of the specific activity and the Vmax value among the three strains. But the affinity of AChE tO acetylthiocholine （ATCh）, in YG strain was the lowest among the three strains tested. A cDNA encoding partial AChE gene was cloned from the three strains by RT-PCR and there was one nucleotide acid difference between YG strain and other two strains which resulted in no amino acid mutation. This partial AChE gene was used as a probe to perform Southern blot. The results indicated that there was no gene amplification in resistant cotton bollworm. Altered AChE with a decreased sensitivity to inhibitors appeared to be one of important resistance mechanisms in cotton bollworm against OP and carbamate compounds.

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 mechanisms oriented to resistive random-access memory

With the progress of the semiconductor industry,the resistive random-access memory（RAM） has drawn increasing attention.The discovery of the memristor has brought much attention to this study.Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms.We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models.Finally,simulations are presented.We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms,which are applied to explain their resistive switchings.

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.

Overview of Multidrug-Resistant Pseudomonas aeruginosa and Novel Therapeutic Approaches

Gram-negative bacilli Pseudomonas aeruginosa is an important pathogen in hospitalized patients, contributing to their morbidity and mortality due to its multiple resistance mechanisms. Therefore, as therapeutic options become restricted, the search for new agents is a priority. Latterly an accelerated increase in frequency of multidrug-resistant clinical strains has severely limited the availability of therapeutic options. Several in vitro and in vitro studies evaluating the efficacy of different antimicrobials agents and development of vaccines against P. aeruginosa have been reported as novel approaches, such as inhibition of virulence factor expression or inhibition of their metabolic pathways.

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.

Determination of minimum overburden depth for underwater shield tunnel in sands:Comparison between circular and rectangular tunnels

With the development of global urbanization,the utilization of underground space is more critical and attractive for civil purposes.Various shapes of shield tunnels have been gradually proposed to cope with different geological conditions and service purposes of underground structures.Generally,reducing the burial depth of shield tunnel is conducive to construction and cost saving.However,extremely small overburden depth cannot provide sufficient uplift resistance to maintain the stability and serviceability of the tunnel.To this end,this paper firstly reviewed the status of deriving the minimum sand over-burden depth of circular shield tunnel using mechanical equilibrium(ME)method.It revealed that the estimated depth is rather conservative.Then,the uplift resistance mechanism of both circular and rectangular tunnels was deduced theoretically and verified with the model tests.The theoretical uplift resistance is consistent with the experimental values,indicating the feasibility of the proposed equations.Furthermore,the determination of the minimum soil overburden depth of rectangular shield tunnel under various working conditions was presented through integrated ME method,which can provide more reasonable estimations of suggested tunnel burial depth for practical construction.Additionally,optimizations were made for calculating the uplift resistance,and the soil thickness providing uplift resistance is suggested to be adjusted according to the testing results.The results can provide reference for the design and construction of various shapes of shield tunnels in urban underground space exploitation.

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.

Resistive switching properties of SnO_(2)nanowires fabricated by chemical vapor deposition

Resistive switching(RS)devices have great application prospects in the emerging memory field and neuromorphic field,but their stability and unclear RS mechanism limit their relevant applications.In this work,we construct a hydrogenated Au/SnO_(2)nanowire(NW)/Au device with two back-to-back Schottky diodes and investigate the RS characteristics in air and vacuum.We find that the Ion/Io ff ratio increases from 20 to 10^(4)when the read voltage decreases from 3.1 V to^(-1)V under the condition of electric field.Moreover,the rectification ratio can reach as high as 10^4owing to oxygen ion migration modulated by the electric field.The nanodevice also shows non-volatile resistive memory characteristic.The RS mechanism is clarified based on the changes of the Schottky barrier width and height at the interface of Au/SnO_(2)NW/Au device.Our results provide a strategy for designing high-performance memristive devices based on SnO_(2)NWs.

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.

Thermo-Mechanical Properties Study of Stabilized Soil Bricks to Sugar Cane Molasses and Cassava Starch Binders

The current study deals Swith thermo-mechanical properties of stabilized soil small bricks with the help of organic binders of sugar cane molasses and cassava starch. Different formulations of soil concrete have been suggested after the geotechnical characterization of samples of soil was taken. From these, it arises that the studied soil is the most plastically clay (of type A3) according to GTR classification. Samples made of small bricks and measured out at 4%, 6% and 8% of binders (molasses, starch or molasses + starch) have been warmed up to different temperatures (100°C, 150°C, 200°C and 250°C) for the rising of the thermic behavior under different conditions and submitted to crushing testings for the estimation of characteristic resistances to the compression. According to the mechanical behavior, we note an improvement of resistances for small bricks measured 4%, 6% and 8%, of molasses respectively of 32.44%, 32.06% and 23.43% against the value of reference for small bricks without molasses. In the same way, the binder (molasses + starch) also reveals an improvement of resistance to the compression of 13.27%, 26.17% and 26.17%. On the contrary, the stabilization with the starch binder did not bring a significative improvement. According to the thermic influence, the heating at 100°C of stabilized small bricks at 4%, 6% and 8% of molasses, reveals a significative improvement of resistances. Moreover, the stabilization with the starch reveals on the contrary a good behavior for heatings at 150°C and 250°C. In short, for the binder (molasses + starch), it is the heating at 200°C that shows some improvements of remarkable resistances. Different analyses of realized statistics also show the effectivity of obtained results. For all realized formulations, the measuring out at 6% of binders (molasses, or molasses + starch) seems as optimal in front of the best thermo-mechanical revealed properties.

Fighting the enemy: How rice survives the blast pathogen's attack

Global food security is threatened by rice blast disease caused by the filamentous fungus Magnaporthe oryzae.An understanding of rice resistance mechanisms is fundamental to developing strategies for disease control.In this review,we summarize recent advances in pathogen-associated molecular pattern-triggered immunity,effector-triggered immunity,defense regulator-mediated immunity,and effects of nutrient elements on rice blast resistance.We outline strategies used for breeding rice cultivars with improved disease resistance.We also present the major research challenges for rice blast disease resistance and propose approaches for future investigation.