Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

Cellular models of stress resistance may pave ways to fight neurodegenerative diseases

Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to neurodegeneration.Interestingly,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

The influence of resistance exercise training prescription variables on skeletal muscle mass,strength,and physical function in healthy adults:An umbrella review

Purpose:The aim of this umbrella review was to determine the impact of resistance training(RT)and individual RT prescription variables on muscle mass,strength,and physical function in healthy adults.Methods:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass(or its proxies),strength,and/or physical function in healthy adults aged>18 years.Results:We identified 44 systematic reviews that met our inclusion criteria.The methodological quality of these reviews was assessed using A Measurement Tool to Assess Systematic Reviews;standardized effectiveness statements were generated.We found that RT was consistently a potent stimulus for increasing skeletal muscle mass(4/4 reviews provide some or sufficient evidence),strength(4/6 reviews provided some or sufficient evidence),and physical function(1/1 review provided some evidence).RT load(6/8 reviews provided some or sufficient evidence),weekly frequency(2/4 reviews provided some or sufficient evidence),volume(3/7 reviews provided some or sufficient evidence),and exercise order(1/1 review provided some evidence)impacted RT-induced increases in muscular strength.We discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass,while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle mass.There was insufficient evidence to conclude that time of day,periodization,inter-set rest,set configuration,set end point,contraction velocity/time under tension,or exercise order(only pertaining to hypertrophy)influenced skeletal muscle adaptations.A paucity of data limited insights into the impact of RT prescription variables on physical function.Conclusion:Overall,RT increased muscle mass,strength,and physical function compared to no exercise.RT intensity(load)and weekly frequency impacted RT-induced increases in muscular strength but not muscle hypertrophy.RT volume(number of sets)influenced muscular strength and hypertrophy.

Biomass-enhanced Janus sponge-like hydrogel with salt resistance and highstrength for efficient solar desalination

Interfacial solar-driven evaporation technology shows great potential in the field of industrial seawater desalination, and the development ofefficient and low-cost evaporation materials is key to achieving large-scale applications. Hydrogels are considered to be promising candidates;however, conventional hydrogel-based interfacial solar evaporators have difficulty in simultaneously meeting multiple requirements, including ahigh evaporation rate, salt resistance, and good mechanical properties. In this study, a Janus sponge-like hydrogel solar evaporator (CPAS) withexcellent comprehensive performance was successfully constructed. The introduction of biomass agar (AG) into the polyvinyl alcohol (PVA)hydrogel backbone reduced the enthalpy of water evaporation, optimized the pore structure, and improved the mechanical properties. Meanwhile, by introducing hydrophobic fumed nano-silica aerogel (SA) and a synergistic foaming-crosslinking process, the hydrogel spontaneouslyformed a Janus structure with a hydrophobic surface and hydrophilic bottom properties. Based on the reduction of the evaporation enthalpy andthe modulation of the pore structure, the CPAS evaporation rate reached 3.56 kg m^(-2) h^(-1) under one sun illumination. Most importantly, owingto the hydrophobic top surface and 3D-interconnected porous channels, the evaporator could work stably in high concentrations of salt-water(25 wt% NaCl), showing strong salt resistance. Efficient water evaporation, excellent salt resistance, scalable preparation processes, and low-costraw materials make CPAS extremely promising for practical applications.

Selenium–nitrogen-co-doped carbon dots increase rice seedling growth and salt resistance

Soil salinity seriously affects the utilization of farmland and threatens the crop production.Here,a selenium-nitrogen-co-doped carbon dots was developed,which increased rice seedling growth and alleviated its inhibition by salt stress by foliar spraying.The treatment activated Ca^(2+)and jasmonic acid signaling pathways and increased iron homeostasis,antioxidant defense,and cell wall development of rice seedlings.It could be used to increase crop resistance to environmental stress.

Greatly enhanced corrosion/wear resistances of epoxy coating for Mg alloy through a synergistic effect between functionalized graphene and insulated blocking layer

The poor corrosion and wear resistances of Mg alloys seriously limit their potential applications in various industries.The conventional epoxy coating easily forms many intrinsic defects during the solidification process,which cannot provide sufficient protection.In the current study,we design a double-layer epoxy composite coating on Mg alloy with enhanced anti-corrosion/wear properties,via the spin-assisted assembly technique.The outer layer is functionalized graphene(FG)in waterborne epoxy resin(WEP)and the inner layer is Ce-based conversion(Ce)film.The FG sheets can be homogeneously dispersed within the epoxy matrix to fill the intrinsic defects and improve the barrier capability.The Ce film connects the outer layer with the substrate,showing the transition effect.The corrosion rate of Ce/WEP/FG composite coating is 2131 times lower than that of bare Mg alloy,and the wear rate is decreased by~90%.The improved corrosion resistance is attributed to the labyrinth effect(hindering the penetration of corrosive medium)and the obstruction of galvanic coupling behavior.The synergistic effect derived from the FG sheet and blocking layer exhibits great potential in realizing the improvement of multi-functional integration,which will open up a new avenue for the development of novel composite protection coatings of Mg alloys.

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.

Identification of Fusarium wilt resistance gene SiRLK1 in Sesamum indicum L.

Sesame Fusarium wilt(SFW),caused by Fusarium oxysporum f.sp.sesami(Fos),is one of the most devastating diseases affecting sesame cultivation.Deciphering the genetic control of SFW resistance is pivotal for effective disease management in sesame.An inheritance study on a cross between the highly resistant variety Yuzhi 11 and the highly susceptible accession Sp1 using a Fos pathogenicity group 1 isolate indicated that resistance was conferred by a single dominant allele.The target locus was located in a 1.24 Mb interval on chromosome 3 using a combination of cross-population association mapping and bulked segregant analysis.Fine genetic mapping further narrowed the interval between 21,350 and 21,401 kb.The locus Sindi_0812400 was identified as the SFW resistance gene and officially designated SiRLK1.This gene encodes a specific malectin/receptor-like protein kinase with three putative tandem kinase domains and is considered a kinase fusion protein.Sequence analysis revealed that a high proportion(49.44%)of variants within the locus was located within the kinase domainⅢ,and several of which were evidently associated with the diversity in SFW response,indicating the critical role of kinase domainⅢin expression of disease resistance.These findings provide valuable information for further functional analysis of SFW resistance genes and marker-assisted resistance breeding in sesame.

CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis

Objective:Circular ribose nudeic acids(circRNAs)are implicated in tumor progression and drug resistance of prostate cancer(PCa).The current work explored the function of circ_0005203(aircTHSD4)in the malignancy and docetaxel(DTX)resistance of PCa.Methods:circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real time reverse transcription quantitative polymerase chain reaction(RT-qPCR).In addition,a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells.In addition,we performed a Western blot(WB)assay to detect high mobility.group A2 protein(HMGA2)levels.Besides,functional associations of two molecules were investigated through dual luciferase reporter assay.Cell Counting Kit(CCK)-8,colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells,whereas flow cytometry was performed to determine cell apoptosis.Furthermore,a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells.Results:According to RT-qPCR results,circTHSD4 was up-regulated within PCa tissues and cells,which predicted the dismal prognostic outcome of PCa cases.circTHSD4 silencing within PCa cells markedly suppressed cell growth,migration,and colony fomation.circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model.Further,circTHSD4 silencing enhanced docetaxel(DTX)sensitivity in PCa cells.Furthermore,we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR 203.Conclusion:Together,our findings suggest that cirCTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR 203/HMGA2 axis.

Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

Enhanced wear resistance,antibacterial performance,and biocompatibility using nanotubes containing nano-Ag and bioceramics in vitro

A good Ti-based joint implant should prevent stress shielding and achieve good bioactivity and anti-infection performance.To meet these requirements,the low-elastic-modulus alloy—Ti–35Nb–2Ta–3Zr—was used as the substrate,and functional coatings that contained bioceramics and Ag ions were prepared for coating on TiO_(2)nanotubes(diameter:(80±20)nm and(150±40)nm)using anodization,deposition,and spin-coating methods.The effects of the bioceramics(nano-β-tricalcium phosphate,microhydroxyapatite(micro-HA),and meso-CaSiO_(3))and Ag nanoparticles(size:(50±20)nm)on the antibacterial activity and the tribocorrosion,corrosion,and early in vitro osteogenic behaviors of the nanotubes were investigated.The tribocorrosion and corrosion results showed that the wear rate and corrosive rate were highly dependent on the features of the nanotube surface.Micro-HA showed great wear resistance with a wear rate of(1.26±0.06)×10^(−3)mm^(3)/(N·m)due to adhesive and abrasivewear.Meso-CaSiO_(3)showed enhanced cell adhesion,proliferation,and alkaline phosphatase activity.The coatings that contained nano-Ag exhibited good antibacterial activity with an antibacterial rate of≥89.5%against Escherichia coli.These findings indicate that hybrid coatings may have the potential to accelerate osteogenesis.

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

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

Effect of samarium doping on the activity and sulfur resistance of Ce/MnFeO_(x) catalyst for low-temperature selective catalytic reduction of NO_(x) by ammonia

The self-made MnFeO_(x) catalysts doped with cerium and samarium were prepared by impregnation method for low-temperature selective catalytic reduction(SCR)by NH3.In this work,the surface properties of the series of MnFe-based catalysts were studied.The results indicate Sm-modified catalyst have superior low-temperature SCR activity;NO_(x) conversion maintained at nearby to 100%at 90℃ to 240℃.In addition,The N_(2) selectivity of Sm doping remains above 80%in the range of 60℃ to 150℃.In SO_(2) poisoning test,the NO_(x) conversion can be remained>90%after 10 h of reaction.The XPS,NH_(3)-TPD and H_(2)-TPR results show the catalyst with Sm doping enhances the acid sites and oxidation catalytic sites of mixed oxides serves for improving oxygen vacancies and transfer electrons.In situ diffuse reflaxions infrared Fourier transformations spectroscopy(DRIFTS)results show that NO_(x) is more easily adsorbed on the surface after Sm doping,which provided favorable conditions for the NH_(3)-SCR reaction to proceed.The reaction at the catalyst surface will follow the L-H reaction mechanism by transient reaction test.

Enhanced corrosion resistance of epoxy resin coating via addition of CeO_(2) and benzotriazole

The use of fillers to enhance the corrosion protection of epoxy resins has been widely applied.In this work,cerium dioxide(CeO_(2))and benzotriazole(BTA)were introduced into an epoxy resin to enhance the corrosion resistance of Q235 carbon steel.Scanning electron microscopy results indicated that the CeO_(2) grains were rod-like and ellipsoidal in shape,and the distribution pattern of BTA was analyzed by energy dispersive spectroscope.The dynamic potential polarization curve proved the excellent corrosion resistance of the composite epoxy resin with CeO_(2) and BTA co-addition,and electrochemical impedance spectroscopy test analysis indicated the significantly enhanced long-term corrosion protection performance of the composite coating.And the optimal protective performance was provided by the coating containing 0.3%(mass)CeO_(2) and 20%(mass)BTA,which was attributed to the barrier performance of CeO_(2) particles and the chemical barrier effect of BTA.The formation of corrosion products was analyzed using X-ray diffraction.In addition,the corrosion resistance mechanism of the coating was also discussed in detail.

Dynamic Resistance and Energy Absorption of Sandwich Beam via a Micro-Topology Optimization

The current research of sandwich structures under dynamic loading mainly focus on the response characteristic of structure.The micro-topology of core layers would sufficiently influence the property of sandwich structure.However,the micro deformation and topology mechanism of structural deformation and energy absorption are unclear.In this paper,based on the bi-directional evolutionary structural optimization method and periodic base cell(PBC)technology,a topology optimization frame work is proposed to optimize the core layer of sandwich beams.The objective of the present optimization problem is to maximize shear stiffness of PBC with a volume constraint.The effects of the volume fraction,filter radius,and initial PBC aspect ratio on the micro-topology of the core were discussed.The dynamic response process,core compression,and energy absorption capacity of the sandwich beams under blast impact loading were analyzed by the finite element method.The results demonstrated that the overpressure action stage was coupled with the core compression stage.Under the same loading and mass per unit area,the sandwich beam with a 20%volume fraction core layer had the best blast resistance.The filter radius has a slight effect on the shear stiffness and blast resistances of the sandwich beams.But increasing the filter radius could slightly improve the bending stiffness.Upon changing the initial PBC aspect ratio,there are three ways for PBC evolution:The first is to change the angle between the adjacent bars,the second is to further form holes in the bars,and the third is to combine the first two ways.However,not all three ways can improve the energy absorption capacity of the structure.Changing the aspect ratio of the PBC arbitrarily may lead to worse results.More studies are necessary for further detailed optimization.This research proposes a new topology sandwich beam structure by micro-topology optimization,which has sufficient shear stiffness.The micro mechanism of structural energy absorption is clarified,it is significant for structural energy absorption design.

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.