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.

Multi Location Field Evaluation of BC1F2 Sorghum Populations for Striga Resistance in Niger

In Niger, a landlocked country, sorghum is the second staple food cultivated over the country by smallholder farmer. The crop is important for human and animal consumption. Despite its importance, the crop is affected by biotic and abiotic constraints. Among those constraints, striga has a high impact on yield. In fact, to survive, farmers are growing their local preferred sorghum varieties wish is highly sensible to the weed. Striga management is a challenge that requires a permanent solution. In addition, the development of high-yielding Striga resistant genotypes will be appreciated by farmers. The development of striga resistance will be based on the breeding population performances under farmer’s diverse environmental conditions adaptation. The main objective of this study is to evaluate two breeding populations for striga resistance in two different environments at Boulke and Dibissou in Tahoua region, to identify the early and high-yielding striga tolerant genotypes under natural infestation.

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.

Study of the Multidrug Resistance of Enterobacteria Isolated from Waters and Tilapia Fishes from Fish Farms in the Sud-Comoé Region, Côte d’Ivoire

Microbial resistance to antibiotics is a global problem that threatens the lives of millions of people and affects several sectors, including aquaculture. The aim of the present study is to contribute to the monitoring of multi-resistant enterobacterial strains circulating in fish ponds in the Sud-Comoé region of south-eastern Côte d’Ivoire, more specifically in the Aboisso and Tiapoum departments. To this end, 20 samples of Tilapia fish (Oreochromis niloticus) and 60 samples of farm water were collected from 5 fish farms in the Sud-Comoé region. Microbiological analyses were based on the isolation and identification of enterobacteria on Mac Conkey + Ceftazidime medium. These analyses resulted in the isolation of 73 strains of enterobacteria, including 58 from fish and 15 from fish pond water samples. Antibiotic sensitivity tests carried out on enterobacteria isolated from water and fish samples showed high levels of resistance (100%) to the beta-lactam family (Amoxicilin + clavulanic acid, Ceftazidime). Klebsiella pneumoniae and Enterobacter spp. showed resistance to Ciprofloxacins (100%) and (25%) respectively. The study also showed that strains of Enterobacteriaceae were resistant to all 3 families of antibiotics, notably Beta-lactams, Fluoro-quinolones and Aminosides. The presence of multi-resistant Enterobacteriaceae in fish and pond water samples represents a public health risk.

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.

Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

Mobile genetic elements facilitate the transmission of antibiotic resistance genes in multidrug-resistant Enterobacteriaceae from duck farms

Multidrug-resistant(MDR)Enterobacteriaceae critically threaten duck farming and public health.The phenotypes,genotypes,and associated mobile genetic elements(MGEs)of MDR Enterobacteriaceae isolated from 6 duck farms in Zhejiang Province,China,were investigated.A total of 215 isolates were identified as Escherichia coli(64.65%),Klebsiella pneumoniae(12.09%),Proteus mirabilis(10.23%),Salmonella(8.84%),and Enterobacter cloacae(4.19%).Meanwhile,all isolates were resistant to at least two antibiotics.Most isolates carried tet(A)(85.12%),blaTEM(78.60%)and sul1(67.44%)resistance genes.Gene co-occurrence analysis showed that the resistance genes were associated with IS26 and integrons.A conjugative IncFII plasmid pSDM004 containing all the above MGEs was detected in Proteus mirabilis isolate SDM004.This isolate was resistant to 18 antibiotics and carried the blaNDM-5 gene.MGEs,especially plasmids,are the primary antibiotic resistance gene transmission route in duck farms.These findings provide a theoretical basis for the rational use of antibiotics in farms which are substantial for evaluating public health and food safety.

Identification of FDA-Approved Drugs as Modulators of Multidrug Resistance Protein 2 (MRP2/ABCC2) Expression Levels in MRP2-Overexpressing Cells: Preliminary Data

Multidrug Resistance Protein 2 (MRP2) is an ATP-dependent transmembrane protein that plays a pivotal role in the efflux of a wide variety of physiological substrates across the plasma membrane. Several studies have shown that MRP2 can significantly affect the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of many therapeutic drugs and chemicals found in the environment and diet. This transporter can also efflux newly developed anticancer agents that target specific signaling pathways and are major clinical markers associated with multidrug resistance (MDR) of several types of cancers. MDR remains a major limitation to the advancement of the combinatorial chemotherapy regimen in cancer treatment. In addition to anticancer agents, MRP2 reduces the efficacy of various drug classes such as antivirals, antimalarials, and antibiotics. The unique role of MRP2 and its contribution to MDR makes it essential to profile drug-transporter interactions for all new and promising drugs. Thus, this current research seeks to identify modulators of MRP2 protein expression levels using cell-based assays. A unique recently approved FDA library (372 drugs) was screened using a high-throughput In-Cell ELISA assay to determine the effect of these therapeutic agents on protein expression levels of MRP2. A total of 49 FDA drugs altered MRP2 protein expression levels by more than 50% representing 13.17% of the compounds screened. Among the identified hits, thirty-nine (39) drugs increased protein expression levels whereas 10 drugs lowered protein expression levels of MRP2 after drug treatment. Our findings from this initial drug screening showed that modulators of MRP2 peregrinate multiple drug families and signify the importance of profiling drug interactions with this transporter. Data from this study provides essential information to improve combinatorial drug therapy and precision medicine as well as reduce the drug toxicity of various cancer chemotherapies.

Apatinib reduces liver cancer cell multidrug resistance by modulating NF-κB signaling pathway

Objectives:This investigation aimed to elucidate the inhibitory impact of apatinib on the multidrug resistance of liver cancer both in vivo and in vitro.Methods:To establish a Hep3B/5-Fu resistant cell line,5-Fu concentrations were gradually increased in the culture media.Hep3B/5-Fu cells drug resistance and its alleviation by apatinib were confirmed via flow cytometry and Cell Counting Kit 8(CCK8)test.Further,Nuclear factor kappa B(NF-κB)siRNA was transfected into Hep3B/5-Fu cells to assess alterations in the expression of multidrug resistance(MDR)-related genes and proteins.Nude mice were injected with Hep3B/5-Fu cells to establish subcutaneous xenograft tumors and then categorized into 8 treatment groups.The treatments included oxaliplatin,5-Fu,and apatinib.In the tumor tissues,the expression of MDRrelated genes was elucidated via qRT-PCR,immunohistochemistry,and Western blot analyses.Results:The apatinibtreated mice indicated slower tumor growth with smaller size compared to the control group.Both the in vivo and in vitro investigations revealed that the apatinib-treated groups had reduced expression of MDR genes GST-pi,LRP,MDR1,and p-p65.Conclusions:Apatinib effectively suppresses MDR in human hepatic cancer cells by modulating the expression of genes related to MDR,potentially by suppressing the NF-κB signaling pathway.

Multiscale Study on Low Temperature Crack Resistance Mechanism of Steel Slag Asphalt Mixture

The objective of this paper was to study low temperature crack resistance mechanism of steel slag asphalt mixture(SAM).Thermal stress restrained specimen test(TSRST)and three-point bending test were carried out to evaluate the low-temperature crack resistance of SAM and basalt asphalt mixture(BAM).Based on the digital image correlation technique(DIC),the strain field distribution and crack propagation of SAM were analyzed from the microscopic point of view,and a new index,crack length factor(C),was proposed to evaluate the crack resistance of the asphalt mixture.The crystal phase composition and microstructure of steel slag aggregate(SA)and basalt aggregate(BA)were studied by X-ray diffraction(XRD)and scanning electron microscopy(SEM)to explore the low-temperature crack resistance mechanism of SAM.Results show that the low-temperature crack resistance of SAM is better than that of BAM;SAM has good integrity and persistent elastic deformation,and its bending failure mode is a hysteretic quasi-brittle failure;The SA surface is evenly distributed with pores and has surface roughness.SA has the composition phase of alkaline aggregate-calcite(CaCO3),so it has good adhesion to asphalt,which reveals the mechanism of excellent low-temperature crack resistance of SAM.

Isolated Lumbar Extension Resistance Training Is Effective at Improving Extension Power and Disability in Subjects with Diagnosed Lumbar Multifidus Dysfunction

Background: Lumbar multifidus dysfunction is a prevalent cause of disability in individuals with lower back pain. Previous research highlights the benefits of isolated lumbar extension training for non-specific lower back pain, however, studies examining its efficacy in lumbar multifidus dysfunction are lacking. Objective: To evaluate the effectiveness of isolated lumbar extension resistance training on disability and strength in individuals with lumbar multifidus dysfunction. Methods: Subjects underwent a physiotherapy led structured rehabilitation program incorporating isolated lumbar extension. Sessions were conducted twice weekly targeting momentary muscular failure with time under load 90 - 120 seconds and progressions aimed at 5 - 10 lbs increments. Outcomes were assessed using the Oswestry Disability Index and lumbar extension strength testing at baseline and after 12 weeks, with statistical analysis using t-test and chi-squared 2 × 2. Results: Forty-five subjects (24 male, 21 female) with a median age of 48 completed the intervention. Improvements were noted in Oswestry Disability Index scores (median pre: 24, post: 15) and maximal lumbar extension strength (median pre: 122 lb, post: 186 lb), with p ≤ 0.05. Overall, 89% showed improvement in disability scores, 67% moved to a better disability category, and 51% saw at least a 50% increase in strength. No significant gender differences were observed. Conclusions: Isolated lumbar extension resistance training is effective at improving extension power and disability in subjects with lumbar multifidus dysfunction.

Multi-field dynamic modeling and numerical simulation of aluminum alloy resistance spot welding

In order to explore the influence of welding parameters and to investigate the Al alloy (AA) nugget formation process, a comprehensive model involving electrical-thermal-mechanical and metallurgical analysis was established to numerically display the resistance spot welding (RSW) process within multiple fields and understand the AA-RSW physics. A multi-disciplinary finite element method (FEM) framework and a empirical sub-model were built to analyze the affecting factors on weld nugget and the underlying nature of welding physics with dynamic simulation procedure. Specifically, a counter-intuitive phenomenon of the resistance time-variation caused by the transient inverse virtual variation (TIVV) effect was highlighted and analyzed on the basis of welding current and temperature distribution simulation. The empirical model describing the TIVV phenomenon was used for modifying the dynamic resistance simulation during the AA spot welding process. The numerical and experimental results show that the proposed multi-field FEM model agrees with the measured AA welding feature, and the modified dynamic resistance model captures the physics of nugget growth and the electrical-thermal behavior under varying welding current and fluctuating heat input.

Establishment and Application of a Multiplex PCR System for the Detection of Blast Resistance Genes Pi-ta and Pi-b in Rice

Rice blast is one of the important diseases in major rice producing areas of China. The main blast resistance genes Pi-ta and Pi-b showed broad-spectrum and durable resistance to rice blast in many rice growing areas of China, which have been widely utilized in rice breeding and commercial production. In this study, on the basis of detection and verification of the genotypes of 22 rice varieties har- boring known blast resistance genes （Pi-ta and Pi-b） and blast susceptibility genes （pi-ta and pi-b）, two multiple PCR systems for these genes were established by us- ing the functional markers of blast resistance genes Pi-ta and Pi-b as well as blast susceptibility genes pi-ta and pi-b, respectively. Specifically, multiple PCR system I could simultaneously detect blast resistance genes Pi-ta and Pi-b, while system II could detect simultaneously blast susceptibility genes pi-ta and pi-b. In addition, the genotypes of 336 high generation breeding materials were detected with these two multiple PCR systems. The results were highly consistent with those of conventional single mark detection, indicating that these two multiplex PCR systems were stable, reliable and time-saving. The established multiplex PCR systems may serve as a rapid and efficient method to identify and screen rice germplasm resources and can be applied in marker-assisted selection to polymerize multiple genes for blast resis- tance in rice breeding.

Survey of Multidrug Resistance and Class I Integron Prevalence in Chicken-derived Salmonella

[Objective] This study aimed to investigate the multidrug resistance and prevalence of class I integrons in Salmonel a. [Method] Salmonel a strains were isolated from chicken farms in Shandong Province. Kauffmann-White classification method was employed to analyze the serotypes of Salmonel a strains. Minimum in-hibition concentration （MIC） of Salmonel a strains against 19 common antimicrobial drugs was analyzed determined with microdilution method. The class I integrons and carried drug resistance gene cassettes were detected by PCR. [Result] A total of 311 Salmonel a strains were isolated and classified into two serotypes, including 133 Salmonel a Indiana strains and 178 Salmonel a Enteritidis strains. Drug sensitivity test showed that the isolated Salmonel a strains were general y resistant to sulfadiazine, sulfamethoxazole, nalidixic acid, ampicil in, tetracycline, doxycycline and trimethoprim, with a multidrug resistance rate of 91.0% （283/311）; 99% strains were sensitive to amikacin and colistin. PCR assay indicated that the detection rate of class I integrons was 65.0% （202/311）; the positive rate of class I integrons in Salmonel a strains with multidrug resistance was 92.6%; among 202 positive strains, six strains carried gene cassette dfr17-aadA5. [Conclusion] According to the above results, class I integrons exist general y in Salmonel a and are closely associated with the multidrug resistance of Salmonel a strains.

Structure-activity Relationship of Phenothiazines for Inhibition of Protein Kinase C and Reversal of Multidrug Resistance

Studies on structure-activity relationship of phenothiazines (PTZs) forinhibition of protein kinase C (PKC) and reversal of multidrug resistance (MDR) has been made invitro. The results showed that the order of potency of reversal effect of PTZs on MDR is as follows:2-COC_3 H_7 > 2-CF_3 > 2-COCH_3 > H. The type of piperazinyl substitution also significantlyaffected potency against MDR. The results show the order: CH_3 > COOC_2 H_5 > C_2 H_4 OH. Inaddition, PKC plays a marked role in diverse cellular process including MDR. Some derivatives of PTZwas tested for inhibition of PKC, of which PTZ11 showed the highest inhibitory effect of MDR andPKC, implying a potential reversal agent of MDR for tumor therapy in the future. We also tried toexplore the possible binding model of PTZs to PKC. Our molecular-modeling study preliminarilysuggests how these PTZs bind to PKC and provides a structural basis for the design of high affinityPKC-modulator. The infor-mation may be used in the rational design of more effective drugs.