Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori

BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.

Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

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℃.

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.

Transcriptome approach to understand the potential mechanisms of resistant and susceptible alfalfa(Medicago sativa L.) cultivars in response to aphid feeding

Plant breeding for resistance to agricultural pests is an essential element in the development of integrated crop management systems, however, the molecular and genetic mechanisms underlying resistance are poorly understood. In this pilot study, we conducted a transcriptomic analysis of a resistant （R） and susceptible （S） variety of alfalfa, with （＋A） or without （-A） aphids （totally four treatments）. We used the resistant cultivar Zhongmu t and the susceptible cultivar Soca. A total of 3 549 mRNAs were differentially expressed, of which 1 738 up-regulated and 1 307 down-regulated genes were identified in S＋A/S-A plants, while 543 up-regulated and 331 down-regulated genes were identified in the R＋A/R-A plants. KEGG analysis mapped 112 and 546 differentially expressed genes to 8 and 17 substantially enriched pathways for Zhongmu 1 and Soca, respectively. Six shared pathways were linked to plant resistance traits, including phenylpropanoid biosynthesis associated with salicylic acid synthesis, and linoleic acid metabolism associated with both jasmonic acid and flavonoid biosynthesis. Ultimately, we proposed a preliminary regulatory mechanism of alfalfa cultivar resistance response to aphids feeding based on transcriptome analyses and published documents.

Effect of Dietary Resistant Starch on Prevention and Treatment of Obesity-related Diseases and Its Possible Mechanisms

Overweight or obesity has become a serious public health problem in the world, scientists are concentrating their efforts on exploring novel ways to treat obesity. Nowadays, the availabilities of bariatric surgery and pharmacotherapy have enhanced obesity treatment, but it should has support from diet, physical exercise and lifestyle modification, especially the functional food. Resistant starch, an indigestible starch, has been studied for years for its beneficial effects on regulating blood glucose level and lipid metabolism. The aim of this review is to summarize the effect of resistant starch on weight loss and the possible mechanisms. According to numerous previous studies it could be concluded that resistant starch can reduce fat accumulation, enhance insulin sensitivity, regulate blood glucose level and lipid metabolism. Recent investigations have focused on the possible associations between resistant starch and incretins as well as gut microbiota. Resistant starch seems to be a promising dietary fiber for the prevention or treatment of obesity and its related diseases.

Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer

The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.

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.

Mechanism of drug resistance and reversal with ligustra-zine and cyclosporin A in cisplatin--inducedhuman epithelial ovarian cancer resistant cell line 3Ao/cDDP

Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 mg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.

Inactivation of Resistant Mycobacteria mucogenicum in Water:Chlorine Resistance and Mechanism Analysis

Objective To better understand the mechanism of chlorine resistance of mycobacteria and evaluate the efficiency of various disinfection processes.Methods Inactivation experiments of one strain Mycobacteria mucogenicum,isolated from a drinking water distribution system in South China were conducted with various chlorine disinfectants.Inactivation efficiency and disinfectant residual,as well as the formation of organic chloramines,were measured during the experiments.Results This strain of M.mucogenicum showed high resistance to chlorine.The CT values of 99.9% inactivation by free chlorine,monochloramine and chlorine dioxide were detected as 29.6±1.46,170±6.16,and 10.9±1.55 min（mg/L） respectively,indicating that chlorine dioxide exhibited significantly higher efficiency than free chlorine and monochloramine.It was also found that M.mucogenicum reacted with chlorine disinfectants more slowly than S.aureus,but consumed more chlorine disinfectants during longer time of contact.Lipid analysis of the cell construction revealed that 95.7% of cell membrane lipid of M.mucogenicum was composed of saturated long chain fatty acids.Saturated fatty acids were regarded as more stable and more hydrophilic which enabled the cell membrane to prevent the diffusion of chlorine.Conclusion It was concluded that different compositions of cell membrane might endow M.mucogenicum with a higher chlorine resistance.

Burn-resistant behavior and mechanism of Ti14 alloy

The direct-current simulation burning method was used to investigate the burn-resistant behavior of Ti14 titanium alloy.The results show that Ti14 alloy exhibits a better burn resistance than TC4 alloy（Ti-6A1-4V）.Cu is observed to preferentially migrate to the surface of Ti14 alloy during the burning reaction,and the burned product contains Cu,Cu2O,and TiO2.An oxide layer mainly comprising loose TiO2 is observed beneath the burned product.Meanwhile,Ti2Cu precipitates at grain boundaries near the interface of the oxide layer,preventing the contact between O2 and Ti and forming a rapid diffusion layer near the matrix interface.Consequently,a multiple-layer structure with a Cu-enriched layer（burned product）/Cu-lean layer（oxide layer）/Cu-enriched layer（rapid diffusion layer） configuration is formed in the burn heat-affected zone of Ti14 alloy;this multiple-layer structure is beneficial for preventing O2 diffusion.Furthermore,although A1 can migrate to form A12O3 on the surface of TC4 alloy,the burn-resistant ability of TC4 is unimproved because the Al2O3 is discontinuous and not present in sufficient quantity.

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.

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.

Mutagenic breeding of silver-resistant Acidithiobacillus ferrooxidans and exploration of resistant mechanism

The silver-resistant Acidithiobacillus ferrooxidans were isolated from 22 acid mine drainage (AMD) samples collected from Dexing Copper Mine and Chengmen Mountain Mine, Jiangxi Province, China. Isolate DX16 is obtained from the sample taken from Dexing Copper Mine and still carries out ferrous ion oxidation when incubated in 9K medium containing silver nitrate (240 mg/L). While isolate H1, a less resistant strain taken from Yin Mountain Mine, has a tolerate level of only 60 mg/L. Based on 16S ribosomal DNA sequencing, both bacterial 16SrDNA sequences are 100% similar to Acidithiobacillus ferrooxidans ATCC 23270. Through ultraviolet irradiation induced mutations, isolate mDX16 that is obtained from DX16 carries out ferrous ion oxidation when incubated in 9K medium containing higher concentration of silver nitrate (250 mg/L). When silver-resistant gene (SilC) analysis is carried out on the two isolates, it is seen that this gene was absent in both.

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.

Hygroscopicity-resistant mechanism of an α-starch based composite binder for dry sand molds and cores

Hygroscopicity-resistance of an α-starch based composite binder for dry sand molds (cores) has been studiedexperimentally and theoretically. Focus is placed on the relationship between the hardening structure andhumidity-resistance of the composite binder. The results show that the α-starch composite binder has goodhumidity-resistance due to its special complex structure. SEM observations illustrate that the composite binder consists ofreticular matrix and a ball- or lump-shaped reinforcement phase, and the specific property of the binding membrane withheterogeneous structure is affected by humidity to a small extent. Based on the analyses on the interplays of differentingredients in the binder at hardening, the structure model and hygroscopicity-resistant mechanisms of the hardeningcomposite binder were further proposed. Moreover, the reasons for good humidity-resistance of the composite binderbonded sand are well explained by the humidity-resistant mechanisms.

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.

Investigation on the strengthening mechanism of S30432 austenitic heat-resistant steel

From the viewpoint of energy-saving and environment protection,it is necessary to develop Ultra Super Critical(USC) fossil-fired power plants.In order to ensure the reliable operation of power plants under high steam conditions,good mechanical properties(particularly high creep strength),corrosion resistance and fabricability are generally required for the heat resistant steels used in USC boilers.Among these heat-resistant steels,S30432 austenitic heat-resistant steels are of interest due to high creep strength,excellent oxidation and corrosion resistance at temperatures up to 650 -700℃.In this paper,the strengthening mechanism of S30432 austenitic heat-resistant steel was investigated based on the precipitation behavior of S30432 during aging and creep at 650℃.Results show that the microstructure of as-supplied S30432 steel is austenite,the main precipitation consists of only Nb(C,N).After aged for 10 000 h or crept for 10 712 h,there is a slight increase in the size of fine Nb(C,N),but the transformation from Nb(C,N) to NbCrN does not occur.Aging and creep results in the precipitation ofε-Cu and M_(23)C_6.The coarsening velocity ofε-Cu particles diminishes greatly and they are still very fine in the long-term creep range.With the increase of aging and creep time M_(23)C_6 carbides tend to coarsen gradually.The size of M_(23)C_6 is larger and the coarsening is easier in contrast toε-Cu and Nb(C,N).Nb(C,N) precipitates in the as-supplied microstructure,while aging and creep result in the precipitation ofε-Cu and M_(23)C_6.High creep rupture strength of S30432 steel is attributed to the precipitation hardening ofε-Cu,Nb(C,N) and M_(23)C_6.Extremely,ε-Cu plays an important role in improving the creep rupture strength of S30432,and at least 61%of the creep rupture strength of S30432 at 650℃results from the precipitation hardening ofε-Cu particles.