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.

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.

Influence of laser shock peening on microstructure and high-temperature oxidation resistance of Ti45Al8Nb alloy fabricated via laser melting deposition

Laser shock peening(LSP)was used to enhance the high-temperature oxidation resistance of laser melting deposited Ti45Al8Nb alloy.The microstructure and high-temperature oxidation behavior of the as-deposited Ti45Al8Nb alloy before and after LSP were investigated by scanning electron microscopy,X-ray diffraction,and electron backscatter diffraction.The results indicated that the rate of mass gain in the as-deposited sample after LSP exhibited a decrease when exposed to an oxidation temperature of 900℃,implying that LSP-treated samples exhibited superior oxidation resistance at high temperatures.A gradient structure with a fine-grain layer,a deformed-grain layer,and a coarse-grain layer was formed in the LSP-treated sample,which facilitated the diffusion of the Al atom during oxidation,leading to the formation of a dense Al_(2)O_(3)layer on the surface.The mechanism of improvement in the oxidation resistance of the as-deposited Ti45Al8Nb alloy via LSP was discussed.

Corrosion resistance and antibacterial properties of Ti−3Cu alloy prepared by selective laser melting

The corrosion resistance and antibacterial properties of Ti−3Cu alloy prepared by selective laser melting were evaluated using electrochemical experiments and a variety of antibacterial characterization.It is found that the charge transfer resistance of Ti−3Cu alloy was 4.89×10^(5)Ω∙cm^(2),which was doubled the data obtained by CP-Ti alloy.The antibacterial rates of Ti−3Cu alloy against S.mutans and P.gingivalis were 45.0%and 54.5%.And the antibacterial rates increased with the prolongation of cultivation time,reaching up to 62.8%and 68.6%,respectively.The in-situ nano Ti_(2)Cu precipitates were homogeneously distributed in the matrix of the Ti−3Cu alloy,which was the key reason of increasing the corrosion resistance.Additionally,the microscale electric fields between theα-Ti matrix and the Ti_(2)Cu was responsible for the enhancement of the antibacterial properties.

Research Progress of Massage Therapy for Obesity-Induced Insulin Resistance

By searching the relevant literature in recent ten years,this paper summarizes the research progress of massage in the treatment of obesity-induced insulin resistance,in order to provide more basis for massage in the treatment of obesity-induced insulin resistance.

Genome-wide investigation of defensin genes in apple(Malus×domestica Borkh.) and in vivo analyses show that MdDEF25 confers resistance to Fusarium solani

Apple replant disease is a complex soil syndrome that occurs when the same fields are repeatedly utilized for apple orchard cultivation.It can be caused by various pathogens,and Fusarium solani is the main pathogen.Fusarium solani disrupts the structure and function of the orchard soil ecosystem and inhibits the growth and development of apple trees,significantly impacting the quality and yield of apples.In this study,we conducted a transcriptome comparison between uninoculated apple saplings and those inoculated with F:solani.The differentially expressed genes were mainly enriched in processes such as response to symbiotic fungus.Plant defensins are antimicrobial peptides,but their roles during F.solani infection remain unclear.We performed a genome-wide identification of apple defensin genes and identified 25 genes with the conserved motif of eight cysteine residues.In wildtype apple rootstock inoculated with F.solani,the root surface cells experienced severe damage,and showed significant differences in the total root length,total root projection area,root tips,root forks,and total root surface area compared to the control group.qRT-PCR analysis revealed that MdDEF3 and MdDEF25 were triggered in response to F.solani infection in apples.Subcellular localization showed specific expression of the MdDEF3-YFP and MdDEF25-YFP proteins on the cell membrane.Overexpressing theMdDEF25-YFP fusiongene enhanced resistance against F.solani in apple,providing a new strategy for the future prevention and biological control of apple replantdisease.

Microbiota in patients with cefuroxime resistance and anal fistula revealed by 16S ribosomal DNA

BACKGROUND Anal fistula is increasingly prevalent due to modern lifestyle factors,and surgery remains the primary treatment.However,the rising incidence of antibiotic resistance,particularly to cefuroxime,complicates perioperative management.The role of gut microbiota in influencing this resistance is not well understood.AIM To investigate the relationship between gut microbiota composition and cefuroxime resistance in anal fistula patients and to assess probiotic intervention impact.METHODS This study included 30 anal fistula patients categorized into cefuroxime-sensitive(Cefur-S)and cefuroxime-resistant(Cefur-NS)groups.Gut microbiota samples were collected during colonoscopy,and 16S ribosomal DNA sequencing was performed to analyze microbial diversity.Patients in the Cefur-NS group received a 7-day course of Clostridium butyricum tablets.Post-intervention,microbial composition and cefuroxime resistance were reassessed.RESULTS Alpha and beta diversity analyses showed no significant differences in microbial diversity between the Cefur-S and Cefur-NS groups.However,effect size analysis identified Roseburia and Butyricicoccus as dominant genera in the Cefur-S group,with higher butyrate production potentially protecting against cefuroxime resistance.Post-intervention,the Cefur-NS group showed a significant reduction in cefuroxime resistance,improved stool consistency,and reduced bowel movement frequency.CONCLUSION This study suggests that specific gut microbiota,particularly Butyricicoccus and Roseburia,may mitigate cefuroxime resistance in anal fistula patients by increasing butyrate production.Probiotic intervention targeting gut microbiota composition presents a promising strategy for reducing antibiotic resistance and improving clinical outcomes.

Influence of a non-free field subsurface seismic history on the liquefaction resistance of sandy soils

Seismic-induced liquefaction of sandy soils can fail foundations in the vicinity of buildings.To investigate the effect of a non-free field subsurface seismic history on the ability of saturated sandy soils to resist liquefaction,four shaking events with different accelerations were input to the sandy soils in the non-free-field.The results of the study revealed that:(1)Shallow soils that are not free-field undergo acceleration amplification effects after being subjected to seismic loading.(2)Building overburden pressure reduces the sensitivity of the shallow soils directly below in small and moderate earthquakes,which are more prone to rearranging and forming unstable structures under strong seismic effects.The excess pore pressure response on the load side resembles that of a free site,with the depth range of the liquefaction strength of soils affected by the seismic history,increasing progressively as input seismic intensity increases.(3)After experiencing earthquakes of different intensities,the excess pore pressure directly below the building overburden pressure at 0.1 m and 0.2 m is greater than that at the side.At the same time,the side of the building structure is more prone to liquefaction than the soil directly below it.

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.

Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects

Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR–insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

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.

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.

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.

Utilizing resequencing big data to facilitate Brassica vegetable breeding:tracing introgression pedigree and developing highly specific markers for clubroot resistance

Clubroot caused by Plasmodiophora brassicae is a devastating disease of Cruciferous crops.Developing cultivars with clubroot resistance(CR)is the most effective control measure.For the two major Brassica vegetable species B.rapa and B.oleracea,several commercial cultivars with unclear CR pedigrees have been intensively used as CR donors in breeding.However,the continuous occurrence of CR-breaking makes the CR pedigree underlying these cultivars one of the breeders'most urgent concerns.The complex intraspecific diversity of these two major Brassica vegetables has also limited the applicability of CR markers in different breeding programs.Here we first traced the pedigree underlying two kinds of CR that have been widely applied in breeding by linkage and introgression analyses based on public resequencing data.In B.rapa,a major locus CRzi8 underlying the CR of the commercial CR donor‘DegaoCR117’was identified.CRzi8 was further shown to have been introgressed from turnip(B.rapa ssp.rapifera)and that it carried a potential functional allele of Crr1a.The turnip introgression carried CRb^(c),sharing the same coding sequence with the CRb that was also identified from chromosome C07 of B.oleracea CR cultivars with different morphotypes.Within natural populations,variation analysis of linkage intervals of CRzi8,PbBa8.1,CRb,and CRb^(c)yielded easily resolved InDel markers(>20 bp)for these fundamental CR genes.The specificity of these markers was tested in diverse cultivars panels,and each exhibited high reliability in breeding.Our research demonstrates the value of the practice of applying resequencing big data to solve urgent concerns in breeding programs.

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.

The OsBSK1-2-MAPK module regulates blast resistance in rice

Receptor-like cytoplasmic kinase OsBSK1-2 was reported to play an important role in regulation of response to rice blast,but the signaling pathway remained unknown.In this study,we identified OsMAPKKK18 and previously uncharacterized MAPKKKs OsMAPKKK16 and OsMAPKKK19 that interact with OsBSK1-2.Expression of all three MAPKKKs was induced by Magnaporthe oryzae infection,and all three induced cell death when transiently expressed in Nicotiana benthamiana leaves.Knockout of OsMAPKKK16 and OsMAPKKK18 compromised blast resistance and overexpression of OsMAPKKK19 increased blast resistance,indicating that all three MAPKKKs are involved in regulation of rice blast response.Furthermore,both OsMAPKKK16 and OsMAPKKK19 interacted with and phosphorylated OsMKK4 and OsMKK5,and chitin-induced MAPK activation was suppressed in osmapkkk16 and osbsk1-2 mutants.OsMAPKKK18 was earlier reported to interact with and phosphorylate OsMKK4 and affect chitin-induced MAPK activation,suggesting that OsBSK1-2 is involved in regulation of immunity through multiple MAPK signaling pathways.Unlike BSK1 in Arabidopsis,OsBSK1-2 was not involved in response to avirulent M.oryzae strains.Taken together,our results revealed important roles of OsMAPKKK16/18/19 and a OsBSK1-2-OsMAPKKK16/18/19-OsMKK4/5 module in regulating response to rice blast.

Molecular Mechanism of Rice Necrotic Lesion for Optimized Yield and Disease Resistance

How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually comes at the expense of yield.Currently,many necrotic lesion mutants in rice have been identified,and these genes are involved in disease resistance pathways.This review provides a detailed introduction to the characteristics,classification,and molecular mechanisms of necrotic lesion formation.Additionally,we review the molecular regulatory pathways of genes involved in rice disease resistance.Concurrently,we summarize the relationship between resistance and yield in rice using newly developed gene editing methods.We discuss a rational and precise breeding strategy to better utilize molecular design technology for breeding disease-resistant and high-yield rice varieties.

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.