Operation optimization of prefabricated light modular radiant heating system:Thermal resistance analysis and numerical study

The utilization of prefabricated light modular radiant heating system has demonstrated significant increases in heat transfer efficiency and energy conservation capabilities.Within prefabricated building construction,this new heating method presents an opportunity for the development of comprehensive facilities.The parameters for evaluating the effectiveness of such a system are the upper surface layer’s heat flux and temperature.In this paper,thermal resistance analysis calculation based on a simplified model for this unique radiant heating system analysis is presented with the heat transfer mechanism’s evaluation.The results obtained from thermal resistance analysis calculation and numerical simulation indicate that the thermal resistance analysis method is highly accurate with temperature discrepancies ranging from 0.44℃ to−0.44℃ and a heat flux discrepancy of less than 7.54%,which can meet the requirements of practical engineering applications,suggesting a foundation for the prefabricated radiant heating system.

Micro-alloying of Zn and Ca in vacuum induction casted bioresorbable Mg system:Perspectives on corrosion resistance,cytocompatibility,and inflammatory response

There is an increasing interest in biodegradable materials,such as magnesium,for orthopaedic implants.This is driven by their potential to address challenges like stress shielding and the need for secondary removal surgery.In this study,biodegradable magnesium alloys were produced using the Vacuum Induction Casting technique.The impact of micro-alloying Zn and Ca in Mg-xZn-0.2Ca(x=0.1,0.2,0.3,and 0.4 wt%)alloys on corrosion resistance,cytocompatibility,and early-stage inflammatory response was investigated.XRD and SEM-EDS analysis confirmed the presence of Ca_(2)Mg_(6)Zn_(3)secondary phases in all alloys.The Mg-0.3Zn-0.2Ca alloy exhibited the lowest corrosion rate and an elastic modulus of 36.8 GPa,resembling that of natural bone.Electrochemical measurements indicated a correlation between grain size and secondary phase volume fraction in explaining corrosion behaviour.In vitro degradation in simulated body fluid(SBF)for 21 days showed hydroxyapatite formation on alloy surfaces,aligning with electrochemical studies.In vitro cytotoxicity tests demonstrated the cytocompatibility of all alloys,with Mg-0.3Zn-0.2Ca having the highest cell viability over a 6-day cell culture.Investigation into the inflammatory response with RAW-Blue macrophages revealed the anti-inflammatory properties of Mg-0.3Zn-0.2Ca alloys.Micro-alloying with 0.3 wt%Zn and 0.2 wt%Ca enhanced mechanical properties,corrosion resistance,cytocompatibility,and immunomodulatory properties.This positions the Mg-0.3Zn-0.2Ca alloy as a promising biodegradable implant for bone fixation applications.

Studies on the temporal,structural,and interacting features of the clubroot resistance gene Rcr1 using CRISPR/Cas9-based systems

Clubroot disease is a severe threat to Brassica crops globally,particularly in western Canada.Genetic resistance,achieved through pyramiding clubroot resistance(CR)genes with different modes of action,is the most important strategy for managing the disease.However,studies on the CR gene functions are quite limited.In this study,we have conducted investigations into the temporal,structural,and interacting features of a newly cloned CR gene,Rcr1,using CRISPR/Cas9 technology.For temporal functionality,we developed a novel CRISPR/Cas9-based binary vector,pHHIGR-Hsp18.2,to deliver Rcr1 into a susceptible canola line(DH12075)and observed that early expression of Rcr1 is critical for conferring resistance.For structural functionality,several independent mutations in specific domains of Rcr1 resulted in loss-offunction,highlighting their importance for CR phenotype.In the study of the interacting features of Rcr1,a cysteine protease gene and its homologous allele in canola were successfully disrupted via CRISPR/Cas9 as an interacting component with Rcr1 protein,resulting in the conversion from clubroot resistant to susceptible in plants carrying intact Rcr1.These results indicated an indispensable role of these two cysteine proteases in Rcr1-mediated resistance response.This study,the first of its kind,provides valuable insights into the functionality of Rcr1.Further,the new vector p HHIGR-Hsp18.2 demonstrated an inducible feature on the removal of add-on traits,which should be useful for functional genomics and other similar research in brassica crops.

Beta-lactam antibiotic resistance among Escherichia coli isolates from patients with urinary tract infections in Vietnam:A systematic review and meta-analysis

Objective:To investigate the evolving patterns of antimicrobial resistance against beta-lactam antibiotics in Escherichia coli isolates from urinary tract infection patients in Vietnam,covering the period from 2005 to 2022.Methods:29 Descriptive studies published between 2010 and 2022 in English and Vietnamese were included in the analysis.Data on resistance rates to beta-lactam antibiotics,including cephalosporins and carbapenems,were extracted and analyzed.Weighted pooled resistance rates were calculated using random-effects models.Annual trends in resistance were assessed using linear regression analysis.Results:Among the beta-lactam antibiotics studied,Escherichia coli exhibited varying levels of resistance,with cephalosporins showing higher resistance rates compared to carbapenems.Weighted pooled resistance rates were 66%for cefotaxime,65%for ceftriaxone,54%for ceftazidime,and 56%for cefepime.In contrast,carbapenems demonstrated lower resistance rates,with weighted pooled resistance rates ranging from 3%to 4%for meropenem,ertapenem,and imipenem.Resistance rates were also observed for amoxicillin/clavulanate(35%),ticarcillin/clavulanate(26%),and piperacillin/tazobactam(12%).Significant annual increases in resistance were noted for imipenem(0.56%,P<0.001).Conclusions:This study highlights the critical issue of antimicrobial resistance in urinary tract infections in Vietnam and emphasizes the importance of prudent antibiotic use and the regular monitoring of resistance patterns.These insights are useful for guiding healthcare professionals in optimizing treatment strategies and for policymakers in formulating evidence-based clinical guidelines to combat antibiotic resistance effectively.

Exploring the impact of rotavirus vaccination on antibiotic prescription and resistance:A comprehensive systematic review

BACKGROUND Rotavirus is a highly contagious virus responsible for a significant burden of acute gastroenteritis,particularly among infants and young children worldwide,however,vaccination against this viral agent is available.Several studies have hypothesized that rotavirus vaccination has been linked to lower rates of antibiotic resistance.AIM To assess the relationship between rotavirus vaccination and antibiotic resistance.METHODS The present systematic review was tailored based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.Several electronic databases(PubMed/MEDLINE,Scopus and Web of Science)were searched independently by two investigators in order to retrieve relevant publications published until April 2023 that investigated the aforementioned research question.RESULTS The comprehensive database search identified a total of 91 records.After the duplicates were removed(n=75),we screened the titles and abstracts of 16 potentially eligible publications.After the irrelevant records were excluded(n=5),we screened the full texts of 11 manuscripts.Finally,5 studies were entered into the qualitative and quantitative analysis.CONCLUSION In conclusion,all the studies support the idea that vaccinations can reduce the need for antibiotic prescriptions which could potentially contribute to mitigating antibiotic resistance.However,to fully comprehend the mechanisms of antibiotic resistance,enhance treatment guidelines,and consider diverse demographic situations,further research is necessary to use evidence-based strategies to fight antibiotic misuse and resistance.

Epidemiology, Clinical Features and Antifungal Resistance Profile of Candida auris in Africa: Systematic Review

Candida auris since it discovery in 2009 is becoming a severe threat to human health due to its very quickly spread, its worldwide high resistance to systemic antifungal drugs. In resource-constrained settings where several conditions are met for its emergence and spread, this worrisome fungus could cause large hospital and/or community-based outbreaks. This review aimed to summarize the available data on C. auris in Africa focusing on its epidemiology and antifungal resistance profile. Major databases were searched for articles on the epidemiology and antifungal resistance profile of C. auris in Africa. Out of 2,521 articles identified 22 met the inclusion criteria. In Africa, nearly 89% of African countries have no published data on C. auris. The prevalence of C. auris in Africa was 8.74%. The case fatality rate of C. auris infection in Africa was 39.46%. The main C. auris risk factors reported in Africa were cardiovascular disease, renal failure, diabetes, HIV, recent intake of antimicrobial drugs, ICU admissions, surgery, hemodialysis, parenteral nutrition and indwelling devices. Four phylogenetic clades were reported in Africa, namely clades I, II, III and IV. Candida auris showed a pan-African very high resistance rate to fluconazole, moderate resistance to amphotericin B, and high susceptibility to echinocandins. Finally, C. auris clade-specific mutations were observed within the ERG2, ERG3, ERG9, ERG11, FKS1, TAC1b and MRR1 genes in Africa. This systematic review showed the presence of C. auris in the African continent and a worrying unavailability of data on this resilient fungus in most African countries.

Geographical Distribution of Arboviruses, Aedes aegypti and Aedes albopictus Vectors and Their Resistance to Insecticides in Africa: A Systematic Review

Background & Objectives: Epidemics of arboviruses such as Dengue, Chikungunya and Zika have been recorded in recent years indicating that Aedes aegypti and Aedes albopictus are both important and very active vectors in Africa. For vector control, insecticides are on the front line, unfortunately, reported resistance jeopardizes the effectiveness of this strategy. The objective of this review was to determine the geographical distribution and insecticide resistance mechanisms of Ae. aegypti and Ae. Albopictus in Africa. Methods: A systematic review of the literature in scientific databases (PubMed, Google Scholar, ScienceDirect, Hinari) allowed us to identify relevant articles on the geographical distribution of Aedes aegypti, Aedes albopictus and arboviral diseases. On the other hand, studies related to insecticides used in vector control against Aedes, associated resistances and their molecular and metabolic mechanisms. Results: A total of 94 studies met the inclusion criteria for this search. Aedes aegypti is reported in most of Africa, and Aedes albopictus in part. There is a re-emergence and outbreak of Arbovirus epidemics in West and Central Africa. The insecticides used were organochlorines, carbamates, organophosphates and pyrethroids. In Aedes, target site insensitivity and metabolic resistance would be the 2 main mechanisms of resistance to these insecticides. Interpretation & Conclusion: Resistance has been recorded in all four major classes of insecticides recommended by WHO for vector control and eradication. New vector control methods such as the use of plant extracts with larvicidal and adulticidal activities, advanced modern biotechnology techniques, and nanobiotechnology need to be developed.

Progressive Collapse Resistance of a New Staggered Story Isolated System

A new staggered isolated system developed from the mid-story isolated system is the new staggered story isolated system. There are not many studies on this structure currently. In this study, an 18-story new staggered story isolated system model is established using SAP2000. The dynamic nonlinear dynamic alternate method is used to analyze the structure against progressive collapse. Results show that the structure has good resistance to progressive collapse, and there is no progressive collapse under each working condition. The progressive collapse does not occur for the case of removing only one vertical structural member of the new staggered of isolated system. The side column has big influence on this isolated structures’ progressive collapse;the removal of vertical structural member of the isolation layer has less impact on the structure than the removal of the bottom vertical structural member. After the removing of the member, the internal force of the structure will be redistributed, and the axial force of the adjacent columns will change obviously, showing a trend of “near large and far small”.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy

Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.

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.

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.

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.

Exercise training mode effects on myokine expression in healthy adults:A systematic review with meta-analysis

Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer suppression.To date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be elucidated.This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.Methods:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April 2023.Eligible studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of change.Results:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically significant.Both aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across myokines.Myokine levels returned to baseline levels within 180 min to 24 h post-exercise.However,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be drawn.Conclusion:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation.Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND Difficulty in obtaining tetracycline,increased adverse reactions,and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy.Therefore,the search for new alternative drugs has become one of the research hotspots.In recent years,minocycline,as a semisynthetic tetracycline,has demonstrated good potential for eradicating Helicobacter pylori(H.pylori)infection,but the systematic evaluation of its role remains lacking.AIM To explore the efficacy,safety,and compliance of minocycline in eradicating H.pylori infection.METHODS We comprehensively retrieved the electronic databases of PubMed,Embase,Web of Science,China National Knowledge Infrastructure,SinoMed,and Wanfang database as of October 30,2023,and finally included 22 research reports on H.pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria.The eradication rates of H.pylori were calculated using a fixed or a random effect model,and the heterogeneity and publication bias of the studies were measured.RESULTS The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H.pylori eradication rates,reaching 82.3%[95%confidence interval(CI):79.7%-85.1%]in the intention-to-treat analysis and 90.0%(95%CI:87.7%-92.4%)in the per-protocol analysis.The overall safety and compliance of the minocycline-containing regimens were good,demonstrating an overall incidence of adverse reactions of 36.5%(95%CI:31.5%-42.2%).Further by traditional meta-analysis,the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects.Most of the adverse reactions were mild to moderate and well-tolerated,and dizziness was relatively prominent in the minocycline-containing regimens(16%).CONCLUSION The minocycline-containing regimens demonstrated good efficacy,safety,and compliance in H.pylori eradication.Minocycline has good potential to replace tetracycline for eradicating H.pylori infection.

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.

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.

Hemodynamic Profiling Using a Cardiac Index–Systemic Vascular Resistance Plot in Patients with Fontan Circulation

Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.