Wheat cultivar Zhongmai 895 was earlier found to carry YR86 in an 11.6 Mb recombination-suppressed region on chromosome 2AL when crossed with Yangmai 16.To fine-map the YR86 locus,we developed two large F2 populations...Wheat cultivar Zhongmai 895 was earlier found to carry YR86 in an 11.6 Mb recombination-suppressed region on chromosome 2AL when crossed with Yangmai 16.To fine-map the YR86 locus,we developed two large F2 populations from crosses Emai 580/Zhongmai 895 and Avocet S/Zhongmai 895.Remarkably,both populations exhibited suppressed recombination in the same 2AL region.Collinearity analysis across Chinese Spring,Aikang 58,and 10+wheat genomes revealed a 4.1 Mb chromosomal inversion spanning 708.5-712.6 Mb in the Chinese Spring reference genome.Molecular markers were developed in the breakpoint and were used to assess a wheat cultivar panel,revealing that Chinese Spring,Zhongmai 895,and Jimai 22 shared a common sequence named InvCS,whereas Aikang 58,Yangmai 16,Emai 580,and Avocet S shared the sequence named InvAK58.The inverted configuration explained the suppressed recombination observed in all three bi-parental populations.Normal recombination was observed in a Jimai 22/Zhongmai 895 F2 population,facilitating mapping of YR86 to a genetic interval of 0.15 cM corresponding to 710.27-712.56 Mb falling within the inverted region.Thirty-three high-confidence genes were annotated in the interval using the Chinese Spring reference genome,with six identified as potential candidates for YR86 based on genome and transcriptome analyses.These results will accelerate map-based cloning of YR86 and its deployment in wheat breeding.展开更多
Stripe rust, caused by Puccinia striiformis f. sp. tritici(Pst), threatens wheat production worldwide, and resistant varieties tend to become susceptible after a period of cultivation owing to the variation of pathoge...Stripe rust, caused by Puccinia striiformis f. sp. tritici(Pst), threatens wheat production worldwide, and resistant varieties tend to become susceptible after a period of cultivation owing to the variation of pathogen races. In this study, a new resistance gene against Pst race CYR34 was identified and predicted using the descendants of a cross between AS1676, a highly resistant Chinese landrace, and Avocet S, a susceptible cultivar. From a heterozygous plant from a F7recombinant inbred line(RIL) population lacking the Yr18 gene, a near-isogenic line(NIL) population was developed to map the resistance gene. An allstage resistance gene, YrAS1676, was identified on chromosome arm 1AL via bulked-segregant exomecapture sequencing. By analyzing a large NIL population consisting of 6537 plants, the gene was further mapped to the marker interval between KA1A_485.36 and KA1A_490.13, spanning 485.36–490.13 Mb on1AL. A total of 66 annotated genes have been reported in this region. To characterize and predict the candidate gene(s), an RNA-seq was performed using NIL-R and NIL-S seedlings 3 days after CYR34 inoculation. Compared to NIL-S plants, NIL-R plants showed stronger immune reaction and higher expression levels of genes encoding pathogenesis-associated proteins. These differences may help to explain why NIL-R plants were more resistant to Pst race CYR34 than NIL-S plants. By combining fine-mapping and transcriptome sequencing, a calcium-dependent protein kinase gene was finally predicted as the potential candidate gene of YrAS1676. This gene contained a single-nucleotide polymorphism. The candidate gene was more highly expressed in NIL-R than in NIL-S plants. In field experiments with Pst challenge,the YrAS1676 genotype showed mitigation of disease damage and yield loss without adverse effects on tested agronomic traits. These results suggest that YrAS1676 has potential use in wheat stripe rust resistance breeding.展开更多
Aegilops umbellulata(UU)is a wheat wild relative that has potential use in the genetic improvement of wheat.In this study,46 Ae.umbellulata accessions were investigated for stripe rust resistance,heading date(HD),and ...Aegilops umbellulata(UU)is a wheat wild relative that has potential use in the genetic improvement of wheat.In this study,46 Ae.umbellulata accessions were investigated for stripe rust resistance,heading date(HD),and the contents of iron(Fe),zinc(Zn),and seed gluten proteins.Forty-two of the accessions were classified as resistant to stripe rust,while the other four accessions were classified as susceptible to stripe rust in four environments.The average HD of Ae.umbellulata was significantly longer than that of three common wheat cultivars(180.9 d vs.137.0 d),with the exception of PI226500(138.9 d).The Ae.umbellulata accessions also showed high variability in Fe(69.74-348.09 mg kg^(-1))and Zn(49.83-101.65 mg kg^(-1))contents.Three accessions(viz.,PI542362,PI542363,and PI554399)showed relatively higher Fe(230.96-348.09 mg kg^(-1))and Zn(92.46-101.65 mg kg^(-1))contents than the others.The Fe content of Ae.umbellulata was similar to those of Ae.comosa and Ae.markgrafii but higher than those of Ae.tauschii and common wheat.Aegilops umbellulata showed a higher Zn content than Ae.tauschii,Ae.comosa,and common wheat,but a lower content than Ae.markgrafii.Furthermore,Ae.umbellulata had the highest proportion of γ-gliadin among all the species investigated(Ae.umbellulata vs.other species=mean 72.11%vs.49.37%;range:55.33-86.99%vs.29.60-67.91%).These results demonstrated that Ae.umbellulata exhibits great diversity in the investigated traits,so it can provide a potential gene pool for the genetic improvement of these traits in wheat.展开更多
Rye(Secale cereale L., 2n=2x=14, RR) is a significant genetic resource for improving common wheat because of its resistance to multiple diseases and abiotic-stress tolerant traits. The 1RS chromosome from the German c...Rye(Secale cereale L., 2n=2x=14, RR) is a significant genetic resource for improving common wheat because of its resistance to multiple diseases and abiotic-stress tolerant traits. The 1RS chromosome from the German cultivated rye variety Petkus is critical in wheat breeding. However, its weakened disease resistance highlights the need to identify new resources. In the present study, a novel derived line called D27 was developed from common wheat and Mexico Rye.Cytological observations characterized the karyotype of D27 as 2n=42=21 Ⅱ. Genomic in situ hybridization indicated that a pair of whole-arm translocated Mexico Rye chromosomes were inherited typically in the mitotic and meiosis stages of D27. Experiments using fluorescence in situ hybridization(FISH) and gliadin electrophoresis showed that D27 lacked wheat 1DS chromosomes. They were replaced by 1RS chromosomes of Mexico Rye, supported by wheat simple-sequence repeat markers, rye sequence characterized amplified region markers, and wheat 40K SNP array analysis.The wheat 1DS chromosomes could not be detected by molecular markers and wheat SNP array, but the presence of rye 1RS chromosomes was confirmed. Agronomic trait assessments indicated that D27 had a higher tiller number and enhanced stripe rust and powdery mildew resistance. In addition, dough properties analysis showed that replacing 1DS led to higher viscosity and lower dough elasticity in D27, which was beneficial for cake making. In conclusion, the novel cytogenetically stable common wheat–Mexico Rye T1DL·1RS translocation line D27 offers excellent potential as outstanding germplasm in wheat breeding programs focusing on disease resistance and yield improvement. Additionally,it can be valuable for researching the rye 1RS chromosome’s genetic diversity.展开更多
Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is...Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is the best strategy for controlling the disease.In this study,we performed fine mapping and characterization of the all-stage stem rust resistance(Sr)gene Sr8155B1 from the durum wheat line 8155-B1.In seedling tests of biparental populations,Sr8155B1 was effective against six Chinese Pgt races tested.In a segregating population of 5060 gametes,Sr8155B1 was mapped to a 0.06-cM region flanked by markers Pku2772 and Pku43365,corresponding to 1.5-and 2.7-Mb regions in the Svevo and Chinese Spring reference genomes.Both regions include several typical nucleotide-binding leucine-rich repeat(NLR)and protein kinase genes that represent candidate genes.Among them,three NLR genes and three receptor-like protein kinases were highly polymorphic between the parental lines and their transcripts were upregulated in the homozygous resistant line TdR2 relative to its susceptible sister line TdS4.Four markers(Pku2772,Pku43365,Pku2950,and Pku3721)developed in this study,together with seedling resistance responses,correctly predicted Sr8155B1 absence or presence in 78 tetraploid wheat genotypes tested.The presence of Sr8155B1 in tetraploid wheat accessions CItr 14916,PI 197492,and PI 197493 was confirmed by mapping in three F_(2)populations.The genetic map and linked markers developed in this study may accelerate the deployment of Sr8155B1-mediated resistance in wheat breeding programs.展开更多
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 ...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.展开更多
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 re...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.展开更多
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 ...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.展开更多
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 o...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.展开更多
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 inhibit...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.展开更多
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 d...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.展开更多
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 do...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.展开更多
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 developi...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.展开更多
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 proc...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.展开更多
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 pho...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.展开更多
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 o...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.展开更多
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty...Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.展开更多
Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role re...Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role remains unclear. These can provide an ideal setting for the acquisition and dissemination of antibiotic resistance, as they are frequently affected by anthropogenic activities. The objective of this study was to establish a diffusion map of resistance integrons used as genetic markers of resistance associated with antibiotic resistance conferring genes (ARGs). Total DNA extracts from non-cultivable bacterial communities were used for the analyses. These communities were obtained from wastewater samples from 14 sites upstream and downstream of drainage channels or effluents in the cities of Abidjan, Bouaké, and Yamoussoukro. The results obtained correspond to the number of positives among the treated samples (n = 39). Among the genetic markers of dissemination, class 1 integrons were the most evident in 94.8% of samples in Abidjan (93.3%), Bouaké (100%) and Yamoussoukro (91.6%). Class 2 integrons and class 3 integrons were found respectively in 41% and 51% of all samples. Genes coding for β-lactamases and blaTEM was identified in almost all samples at a rate of 97.4%. A co-presence of the three genes blaTEM, blaSHV and blaCTX-M is also remarkable in the sites of the city of Yamoussoukro. Among the genes coding for carbapenemases, only blaKPC 17.94%, blaNDM 30.76% and blaOXA48 38.46% were detected in the samples.展开更多
Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent p...Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.展开更多
Antibiotic resistance poses a significant global health threat, necessitating a thorough understanding of its prevalence in various ecological contexts. Medicinal plants, renowned for their therapeutic properties, hos...Antibiotic resistance poses a significant global health threat, necessitating a thorough understanding of its prevalence in various ecological contexts. Medicinal plants, renowned for their therapeutic properties, host endophytic bacteria that produce bioactive compounds. Understanding antibiotic resistance dynamics in these bacteria is vital for human health and antibiotic efficacy preservation. In this study, we investigated antibiotic resistance profiles in endophytic bacteria from five medicinal plants: Thankuni, Neem, Aparajita, Joba, and Snake plant. We isolated and characterized 113 endophytic bacteria, with varying resistance patterns observed against multiple antibiotics. Notably, 53 strains were multidrug-resistant (MDR), with 14 exhibiting extensive drug resistance (XDR). Thankuni-associated bacteria displayed 44% MDR and 11% XDR, while Neem-associated bacteria showed higher resistance (60% MDR, 13% XDR). Aparajita-associated bacteria had lower resistance (22% MDR, 6% XDR), whereas Joba-associated bacteria exhibited substantial resistance (54% MDR, 14% XDR). Snake plant-associated bacteria showed 7% MDR and 4% XDR. Genus-specific distribution revealed Bacillus (47%), Staphylococcus (21%), and Klebsiella (11%) as major contributors to MDR. Our findings highlight diverse drug resistance patterns among plant-associated bacteria and underscore the complexity of antibiotic resistance dynamics in diverse plant environments. Identification of XDR strains emphasizes the severity of the antibiotic resistance problem, warranting further investigation into contributing factors.展开更多
基金financially supported by the National Key Research and Development Program of China (2022YFD1200900 and 2022YFD1200904)the Agricultural Science and Technology Innovation Program+1 种基金Fundamental Research Funds for Central NonProfit of Institute of Crop Sciences, CAASShijiazhuang S&T Project (232490022A and 232490432A)
文摘Wheat cultivar Zhongmai 895 was earlier found to carry YR86 in an 11.6 Mb recombination-suppressed region on chromosome 2AL when crossed with Yangmai 16.To fine-map the YR86 locus,we developed two large F2 populations from crosses Emai 580/Zhongmai 895 and Avocet S/Zhongmai 895.Remarkably,both populations exhibited suppressed recombination in the same 2AL region.Collinearity analysis across Chinese Spring,Aikang 58,and 10+wheat genomes revealed a 4.1 Mb chromosomal inversion spanning 708.5-712.6 Mb in the Chinese Spring reference genome.Molecular markers were developed in the breakpoint and were used to assess a wheat cultivar panel,revealing that Chinese Spring,Zhongmai 895,and Jimai 22 shared a common sequence named InvCS,whereas Aikang 58,Yangmai 16,Emai 580,and Avocet S shared the sequence named InvAK58.The inverted configuration explained the suppressed recombination observed in all three bi-parental populations.Normal recombination was observed in a Jimai 22/Zhongmai 895 F2 population,facilitating mapping of YR86 to a genetic interval of 0.15 cM corresponding to 710.27-712.56 Mb falling within the inverted region.Thirty-three high-confidence genes were annotated in the interval using the Chinese Spring reference genome,with six identified as potential candidates for YR86 based on genome and transcriptome analyses.These results will accelerate map-based cloning of YR86 and its deployment in wheat breeding.
基金supported by the Major Program of National Agricultural Science and Technology of China (NK20220607)the National Natural Science Foundation of China (32272059 and31971883)the Science and Technology Department of Sichuan Province (2022ZDZX0014, 2021YFYZ0002, 2021YJ0297, and23NSFTD0045)。
文摘Stripe rust, caused by Puccinia striiformis f. sp. tritici(Pst), threatens wheat production worldwide, and resistant varieties tend to become susceptible after a period of cultivation owing to the variation of pathogen races. In this study, a new resistance gene against Pst race CYR34 was identified and predicted using the descendants of a cross between AS1676, a highly resistant Chinese landrace, and Avocet S, a susceptible cultivar. From a heterozygous plant from a F7recombinant inbred line(RIL) population lacking the Yr18 gene, a near-isogenic line(NIL) population was developed to map the resistance gene. An allstage resistance gene, YrAS1676, was identified on chromosome arm 1AL via bulked-segregant exomecapture sequencing. By analyzing a large NIL population consisting of 6537 plants, the gene was further mapped to the marker interval between KA1A_485.36 and KA1A_490.13, spanning 485.36–490.13 Mb on1AL. A total of 66 annotated genes have been reported in this region. To characterize and predict the candidate gene(s), an RNA-seq was performed using NIL-R and NIL-S seedlings 3 days after CYR34 inoculation. Compared to NIL-S plants, NIL-R plants showed stronger immune reaction and higher expression levels of genes encoding pathogenesis-associated proteins. These differences may help to explain why NIL-R plants were more resistant to Pst race CYR34 than NIL-S plants. By combining fine-mapping and transcriptome sequencing, a calcium-dependent protein kinase gene was finally predicted as the potential candidate gene of YrAS1676. This gene contained a single-nucleotide polymorphism. The candidate gene was more highly expressed in NIL-R than in NIL-S plants. In field experiments with Pst challenge,the YrAS1676 genotype showed mitigation of disease damage and yield loss without adverse effects on tested agronomic traits. These results suggest that YrAS1676 has potential use in wheat stripe rust resistance breeding.
基金supported by the National Natural Science Foundation of China(31771783)the Key Research and Development Program of Sichuan Province,China(2021YFYZ0002)the Sichuan Science and Technology Program,China(2018HH0130 and 2022YFH0105)。
文摘Aegilops umbellulata(UU)is a wheat wild relative that has potential use in the genetic improvement of wheat.In this study,46 Ae.umbellulata accessions were investigated for stripe rust resistance,heading date(HD),and the contents of iron(Fe),zinc(Zn),and seed gluten proteins.Forty-two of the accessions were classified as resistant to stripe rust,while the other four accessions were classified as susceptible to stripe rust in four environments.The average HD of Ae.umbellulata was significantly longer than that of three common wheat cultivars(180.9 d vs.137.0 d),with the exception of PI226500(138.9 d).The Ae.umbellulata accessions also showed high variability in Fe(69.74-348.09 mg kg^(-1))and Zn(49.83-101.65 mg kg^(-1))contents.Three accessions(viz.,PI542362,PI542363,and PI554399)showed relatively higher Fe(230.96-348.09 mg kg^(-1))and Zn(92.46-101.65 mg kg^(-1))contents than the others.The Fe content of Ae.umbellulata was similar to those of Ae.comosa and Ae.markgrafii but higher than those of Ae.tauschii and common wheat.Aegilops umbellulata showed a higher Zn content than Ae.tauschii,Ae.comosa,and common wheat,but a lower content than Ae.markgrafii.Furthermore,Ae.umbellulata had the highest proportion of γ-gliadin among all the species investigated(Ae.umbellulata vs.other species=mean 72.11%vs.49.37%;range:55.33-86.99%vs.29.60-67.91%).These results demonstrated that Ae.umbellulata exhibits great diversity in the investigated traits,so it can provide a potential gene pool for the genetic improvement of these traits in wheat.
基金supported by the National Natural Science Foundation of China (31771785)the Key Research and Development Program of Shaanxi, China (2018ZDXM-NY-006)。
文摘Rye(Secale cereale L., 2n=2x=14, RR) is a significant genetic resource for improving common wheat because of its resistance to multiple diseases and abiotic-stress tolerant traits. The 1RS chromosome from the German cultivated rye variety Petkus is critical in wheat breeding. However, its weakened disease resistance highlights the need to identify new resources. In the present study, a novel derived line called D27 was developed from common wheat and Mexico Rye.Cytological observations characterized the karyotype of D27 as 2n=42=21 Ⅱ. Genomic in situ hybridization indicated that a pair of whole-arm translocated Mexico Rye chromosomes were inherited typically in the mitotic and meiosis stages of D27. Experiments using fluorescence in situ hybridization(FISH) and gliadin electrophoresis showed that D27 lacked wheat 1DS chromosomes. They were replaced by 1RS chromosomes of Mexico Rye, supported by wheat simple-sequence repeat markers, rye sequence characterized amplified region markers, and wheat 40K SNP array analysis.The wheat 1DS chromosomes could not be detected by molecular markers and wheat SNP array, but the presence of rye 1RS chromosomes was confirmed. Agronomic trait assessments indicated that D27 had a higher tiller number and enhanced stripe rust and powdery mildew resistance. In addition, dough properties analysis showed that replacing 1DS led to higher viscosity and lower dough elasticity in D27, which was beneficial for cake making. In conclusion, the novel cytogenetically stable common wheat–Mexico Rye T1DL·1RS translocation line D27 offers excellent potential as outstanding germplasm in wheat breeding programs focusing on disease resistance and yield improvement. Additionally,it can be valuable for researching the rye 1RS chromosome’s genetic diversity.
基金the National Key Research and Development Program of China(2022YFD1201300)the Key R&D Program of Shandong Province(ZR202211070163)+1 种基金the Provincial Natural Science Foundation of Shandong(ZR2021ZD30,ZR2021MC056)the Young Taishan Scholars Program of Shandong Province.
文摘Stem rust,caused by Puccinia graminis f.sp.tritici(Pgt),threatens global wheat production.Development of cultivars with increased resistance to stem rust by identification,mapping,and deployment of resistance genes is the best strategy for controlling the disease.In this study,we performed fine mapping and characterization of the all-stage stem rust resistance(Sr)gene Sr8155B1 from the durum wheat line 8155-B1.In seedling tests of biparental populations,Sr8155B1 was effective against six Chinese Pgt races tested.In a segregating population of 5060 gametes,Sr8155B1 was mapped to a 0.06-cM region flanked by markers Pku2772 and Pku43365,corresponding to 1.5-and 2.7-Mb regions in the Svevo and Chinese Spring reference genomes.Both regions include several typical nucleotide-binding leucine-rich repeat(NLR)and protein kinase genes that represent candidate genes.Among them,three NLR genes and three receptor-like protein kinases were highly polymorphic between the parental lines and their transcripts were upregulated in the homozygous resistant line TdR2 relative to its susceptible sister line TdS4.Four markers(Pku2772,Pku43365,Pku2950,and Pku3721)developed in this study,together with seedling resistance responses,correctly predicted Sr8155B1 absence or presence in 78 tetraploid wheat genotypes tested.The presence of Sr8155B1 in tetraploid wheat accessions CItr 14916,PI 197492,and PI 197493 was confirmed by mapping in three F_(2)populations.The genetic map and linked markers developed in this study may accelerate the deployment of Sr8155B1-mediated resistance in wheat breeding programs.
基金suppoited by an Alexander Graliam Bell Canada Graduate Scholarship-Doctoralsupported by an Ontario Graduate Scholarshipsupported by the Canada Research Chairs programme。
文摘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.
基金supported by the National Natural Science Foundation of China(81973839)High Level Chinese Medical Hospital Promotion Project-Special Project on Formulation R&D and New Drug Translation for Medical Institutions(HLCMHPP2023037)Upgrading the Development and Promotion of about 30 Integrated Chinese and Western Medicine Diagnosis and Treatment Programs(Guidelines for the Diagnosis and Treatment of Breast Cancer with the Combination of Traditional Chinese Medicine and Western Medicine)(ZYZB-2022-798).
文摘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.
基金supported by the National Natural Science Foundation of China(22278110)China Postdoctoral Science Foundation(2022M720984)+1 种基金the Natural Science Foundation of Hebei Province of China(B2021202012)Tianjin Technical Innovation Guidance Special Project(20YDTPJC00630).
文摘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.
文摘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.
基金financially supported by the National Natural Science Foundation of China (42207032,52070064)the Key Project of National Natural Science Foundation of China (42330705)+2 种基金Key R&D Project of Hebei Province (21373601D)Advanced Talents Incubation Program of the Hebei University (521100222012)economic support from Collaborative Innovation Center for Baiyangdian Basin Ecological Protection and Beijing-Tianjin-Hebei Sustainable Development and Institute of Life Sciences and Green Development of Hebei University。
文摘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.
基金This work was supported by China Agriculture Research System(CARS-14)the Key Research and Development Project of Henan Province(221111520400)+3 种基金the Henan Provincial Science and Technology Research Project(222102110081)the Zhongyuan Science and Technology Innovation Leading Talent Plan(214200510020)the Key Research Project of the Shennong Laboratory(SN012022-04)the Fund for Distinguished Young Scholars from Henan Academy of Agricultural Sciences(2022JQ01).
文摘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.
基金Fujian Provincial Health and Middleaged and Young Backbone Talents Training Project“The role and Mechanism of C53 in mcRPC Treatment of Drug Resistance”(2019-ZQN-77).
文摘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.
文摘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.
基金the National Natural Science Foundation of China(Grant number 51771178)Shaanxi Outstanding Youth Fund project(Grant number 2021JC-45)+2 种基金Key international cooperation projects in Shaanxi Province(Grant number 2020KWZ-007)the Major Program of Science and Technology in Shaanxi Province(Grant number20191102006)Open Fund of State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body(Grant number 32115019)。
文摘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.
基金supported by the European Regional Development Funds-European Union(ERDF-EU),FATZHEIMER project(EU-LAC HEALTH 2020,16/T010131 to FRdF),“Una manera de hacer Europa”Ministerio de Economía,Industria y Competitividad,Gobierno de Espa?a,Programa Estatal de Investigación,Desarrollo e Innovación Orientada a los Retos de la Sociedad(RTC2019-007329-1 to FRdF)+2 种基金Consejería de Economía,Conocimiento y Universidad,Junta de Andalucía,Plan Andaluz de Investigación,Desarrollo e Innovación(P18TP-5194 to FRdF)Instituto de Salud CarlosⅢ(DTS22/00021 to FRdF)DMV(FI20/00227)holds a“PFIS’’predoctoral contract from the National System of Health,EU-ERDF-Instituto de Salud CarlosⅢ。
文摘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.
基金Supported by Hebei Provincial Health Commission Youth Science and Technology Project,No.20210027.
文摘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.
文摘Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.
文摘Antibiotic resistance has become a major threat to human health worldwide. Environment, particularly the water environment, has long been overlooked as a player in the antibiotic resistance cycle, although its role remains unclear. These can provide an ideal setting for the acquisition and dissemination of antibiotic resistance, as they are frequently affected by anthropogenic activities. The objective of this study was to establish a diffusion map of resistance integrons used as genetic markers of resistance associated with antibiotic resistance conferring genes (ARGs). Total DNA extracts from non-cultivable bacterial communities were used for the analyses. These communities were obtained from wastewater samples from 14 sites upstream and downstream of drainage channels or effluents in the cities of Abidjan, Bouaké, and Yamoussoukro. The results obtained correspond to the number of positives among the treated samples (n = 39). Among the genetic markers of dissemination, class 1 integrons were the most evident in 94.8% of samples in Abidjan (93.3%), Bouaké (100%) and Yamoussoukro (91.6%). Class 2 integrons and class 3 integrons were found respectively in 41% and 51% of all samples. Genes coding for β-lactamases and blaTEM was identified in almost all samples at a rate of 97.4%. A co-presence of the three genes blaTEM, blaSHV and blaCTX-M is also remarkable in the sites of the city of Yamoussoukro. Among the genes coding for carbapenemases, only blaKPC 17.94%, blaNDM 30.76% and blaOXA48 38.46% were detected in the samples.
文摘Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.
文摘Antibiotic resistance poses a significant global health threat, necessitating a thorough understanding of its prevalence in various ecological contexts. Medicinal plants, renowned for their therapeutic properties, host endophytic bacteria that produce bioactive compounds. Understanding antibiotic resistance dynamics in these bacteria is vital for human health and antibiotic efficacy preservation. In this study, we investigated antibiotic resistance profiles in endophytic bacteria from five medicinal plants: Thankuni, Neem, Aparajita, Joba, and Snake plant. We isolated and characterized 113 endophytic bacteria, with varying resistance patterns observed against multiple antibiotics. Notably, 53 strains were multidrug-resistant (MDR), with 14 exhibiting extensive drug resistance (XDR). Thankuni-associated bacteria displayed 44% MDR and 11% XDR, while Neem-associated bacteria showed higher resistance (60% MDR, 13% XDR). Aparajita-associated bacteria had lower resistance (22% MDR, 6% XDR), whereas Joba-associated bacteria exhibited substantial resistance (54% MDR, 14% XDR). Snake plant-associated bacteria showed 7% MDR and 4% XDR. Genus-specific distribution revealed Bacillus (47%), Staphylococcus (21%), and Klebsiella (11%) as major contributors to MDR. Our findings highlight diverse drug resistance patterns among plant-associated bacteria and underscore the complexity of antibiotic resistance dynamics in diverse plant environments. Identification of XDR strains emphasizes the severity of the antibiotic resistance problem, warranting further investigation into contributing factors.