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.

Transient extreme insulin resistance in a critically ill patient:A case report

BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.

Microstructure and Wear/corrosion Resistance of Stainless Steel Laser-alloyed with Mn+W_(2)C, Mn+NiWC and Mn+SiC

In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powders were fabricated to improve the wear and corrosion behavior of 1Cr18Ni9Ti steel blades in high speed mixers.Microstructure evolution,phases,element distribution,microhardness,wear and corrosion behavior of the laser alloyed layers were investigated.Results indicated that high Mn steel matrix composites with undissolved W_(2)C,WC and other in-situ formed carbides were formed by LSA with Mn+W_(2)C and Mn+NiWC while SiC totally dissolved into the high Mn matrix when adding Mn+SiC.Ni as the binding phase in Ni-WC powder decreased the crack sensitivity of the alloyed layer as compared with the addition of W_(2)C powder.An improvement in average microhardness was achieved in the matrix in specimen A,B and C,with the value of 615,602 and 277 HV_(0.5),while that of the substrate was 212 HV_(0.5).The increase of microhardness,wear and corrosion resistance is highly corelated to microstructure,formed phases,type and content of carbides,micro-hardness and toughness of the alloyed layers.

Combined BRAF G469A mutation and echinoderm microtubule associated protein like-4-anaplastic lymphoma kinase rearrangement with resistance:A case report and review of literature

BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.Although the anaplastic lymphoma kinase and BRAF mutations are not frequent subtypes in NSCLC,the availability of several targeted-drugs has been confirmed through a series of clinical trials.But little is clear about the proper strategy in rare BRAF G469A mutation,not to mention co-exhibition of anaplastic lymphoma kinase and BRAF G469A mutations,which is extremely rare in NSCLC.CASE SUMMARY We present a patient to stage IVA lung adenocarcinoma with coexisting echinoderm microtubule associated protein like-4 rearrangement and BRAF G469A mutation.She received several targeted drugs with unintended resistance and suffered from unbearable adverse events.CONCLUSION Due to the rarity of co-mutations,the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations,but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.

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.

Selenoprotein P1 as a biomarker of insulin resistance in pediatric obesity:Insights and implications

This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.

Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.

Advances in genotypic antimicrobialresistance testing: a comprehensive review

Antimicrobial resistance(AMR)represents a substantial threat to global public health,complicating the treatment of common infections and leading to prolonged illness and escalated healthcare expenses.To effectively combat AMR,timely and accurate detection is crucial for AMR surveillance and individual-based therapy.Phenotypic antibiotic resistance testing(AST)has long been considered the gold standard in clinical applications,serving as the foundation for clinical AMR diagnosis and optimized therapy.It has significantly contributed to ensuring patients′health and the development of novel antimicrobials.Despite advancements in automated culture-based AST technologies,inherent limitations impede the widespread use of phenotypic AST in AMR surveillance.Genotypic AST technologies offer a promising alternative option,exhibiting advantages of rapidity,high sensitivity,and specificity.With the continuous advancement and expanding applications of genotypic AST technologies,such as microfluidics,mass spectrometry,and high-resolution melting curve analysis,new vigor has been injected into the development and clinical implementation of genotypic AST technologies.In this narrative review,we discuss the principles,applications,and advancements of emerging genotypic AST methods in clinical settings.The comprehensive review aims to highlight the significant scientific potential of emerging genotypic AST technologies in clinical AMR diagnosis,providing insights to enhance existing methods and explore novel approaches.

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.

Application of myxovirus resistance protein A in the etiological diagnosis of infections in adults

BACKGROUND: Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A(MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of Mx A to distinguish viral from bacterial infections.METHODS: We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic(ROC) curve analysis were used to determine the diagnostic value of Mx A, either alone or in combination with C-reactive protein(CRP) or procalcitonin(PCT), in patients with viral, bacterial, or co-infections.RESULTS: The value of MxA(ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections(82.3 [24.5–182.9] vs. 16.4 [10.8–26.5], P<0.0001)(82.3 [24.5–182.9] vs. 28.5 [10.2–106.8], P=0.0237). The area under the curve(AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799(95% confidence interval [95% CI] 0.696–0.903), with a sensitivity of 68.9%(95% CI 54.3%–80.5%) and specificity of 90.0%(95% CI 74.4%–96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus(15.8 [9.6–47.6] ng/mL) and Epstein-Barr virus(12.9 [8.5–21.0] ng/mL) infections.CONCLUSION: Our study showed the diagnostic efficacy of Mx A in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, EpsteinBarr virus and human cytomegalovirus infections did not elicit elevated Mx A expression.

Construction of attapulgite-based one-dimensional nanonetwork composites with corrosion resistance for high-efficiency microwave absorption

Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods embedded with TiO_(2)and polyaniline(PANI)nanoparticles are synthesized via heterogeneous precipitation and in-situ polymerization.The obtained PANI-TiO_(2)-ATP one-di-mensional(1D)nanostructures can intertwine into three-dimensional(3D)conductive network,which favors energy dissipation.The min-imum reflection loss(RL_(min))of the PANI-TiO_(2)-ATP coating(20wt%)reaches-49.36 dB at 9.53 GHz,and the effective absorption band-width(EAB)can reach 6.53 GHz with a thickness of 2.1 mm.The excellent MA properties are attributed to interfacial polarization,mul-tiple loss mechanisms,and good impedance matching induced by the synergistic effect of PANI-TiO_(2)nanoparticle shells and ATP nanor-ods.In addition,salt spray and Tafel polarization curve tests reveal that the PANI-TiO_(2)-ATP coating shows outstanding corrosion resist-ance performance.This study provides a low-cost and high-efficiency strategy for constructing 1D nanonetwork composites for MA and corrosion resistance applications using natural porous ATP nanorods as carriers.

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.