We investigated the effects of fly ash(FA)content on the mechanical properties of recycled aggregate concrete(RAC)and its regeneration potential under freeze and thaw(F-T)cycles.The physical properties of second-gener...We investigated the effects of fly ash(FA)content on the mechanical properties of recycled aggregate concrete(RAC)and its regeneration potential under freeze and thaw(F-T)cycles.The physical properties of second-generation recycled concrete aggregates(RCA)were used to analyze the regeneration potential of RAC after F-T cycles.Scanning electron microscopy was used to study the interfacial transition zone microstructure of RAC after F-T cycles.Results showed that adding 20%FA to RAC significantly enhanced its mechanical properties and frost resistance.Before the F-T cycles,the compressive strength of RAC with 20%FA reached 48.3 MPa,exceeding research strength target of 40 MPa.A majority of second-generation RCA with FA had been verified to attain class Ⅲ,which enabled their practical application in non-structural projects such as backfill trenches and road pavement.However,the second-generation RCA with 20%FA can achieve class Ⅱ,making it ideal for 40 MPa structural concrete.展开更多
TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing Ti...TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing TiB_(2)coatings have disadvantages such as high equipment costs,complicated processes,and highly toxic gas emissions.This paper proposes an environmentally friendly method,which requires inexpensive equipment and simple processing,for preparing TiB_(2)coating on molybdenum via electrophoretic deposition within Na3AlF6-based molten salts.The produced TiB_(2)layer had an approximate thickness of 60μm and exhibited high density,outstanding hardness(38.2 GPa)and robust adhesion strength(51 N).Additionally,high-temperature oxidation experiments revealed that,at900℃,the TiB_(2)coating provided effective protection to the molybdenum substrate against oxidation for 3 h.This result indicates that the TiB_(2)coating prepared on molybdenum using molten salt electrophoretic deposition possesses good high-temperature oxidation resistance.展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
Co-based alloy coating was prepared on Zr alloy using laser melting and cladding technique to study the difference in the high-temperature oxidation behavior between pure metal Co coatings and Co-T800 alloy coatings,a...Co-based alloy coating was prepared on Zr alloy using laser melting and cladding technique to study the difference in the high-temperature oxidation behavior between pure metal Co coatings and Co-T800 alloy coatings,as well as the wear resistance of the coatings.Besides,the effect of changing the laser melting process on the coatings was also investigated.The oxidation mass gain at 800–1200℃and the high-temperature oxidation behavior during high-temperature treatment for 1 h of two coated Zr alloy samples were studied.Results show that the Co coating and the Co-T800 coating have better resistance against high-temperature oxidation.After oxidizing at 1000℃for 1 h,the thickness of the oxide layer of the uncoated sample was 241.0μm,whereas that of the sample with Co-based coating is only 11.8–35.5μm.The friction wear test shows that the depth of the abrasion mark of the coated sample is only 1/2 of that of the substrate,indicating that the hardness and wear resistance of the Zr substrate are greatly improved.The disadvantage of Co-based coatings is the inferior corrosion resistance in 3.5wt%NaCl solution.展开更多
BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.展开更多
In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powder...In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powders were fabricated to improve the wear and corrosion behavior of 1Cr18Ni9Ti steel blades in high speed mixers.Microstructure evolution,phases,element distribution,microhardness,wear and corrosion behavior of the laser alloyed layers were investigated.Results indicated that high Mn steel matrix composites with undissolved W_(2)C,WC and other in-situ formed carbides were formed by LSA with Mn+W_(2)C and Mn+NiWC while SiC totally dissolved into the high Mn matrix when adding Mn+SiC.Ni as the binding phase in Ni-WC powder decreased the crack sensitivity of the alloyed layer as compared with the addition of W_(2)C powder.An improvement in average microhardness was achieved in the matrix in specimen A,B and C,with the value of 615,602 and 277 HV_(0.5),while that of the substrate was 212 HV_(0.5).The increase of microhardness,wear and corrosion resistance is highly corelated to microstructure,formed phases,type and content of carbides,micro-hardness and toughness of the alloyed layers.展开更多
BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori(H.pylori)infection.The antibiotic resistance spectrum of H.pylori varies in different regions.We investigated ...BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori(H.pylori)infection.The antibiotic resistance spectrum of H.pylori varies in different regions.We investigated the current status of antibiotic resistance of H.pylori in Hunan Province and analyzed the factors related to such resistance to provide strategies for the accurate clinical treatment of H.pylori infection.AIM To understand the antibiotic resistance of H.pylori in Hunan Province and provide guidance for the clinical treatment of H.pylori infection.METHODS This study selected patients who underwent gastroscopy in five hospitals in Hunan Province from April 2022 to April 2023.The sensitivity of H.pylori to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline was detected using the Agar dilution method.RESULTS H.pylori strains from a total of 566 patients were isolated and identified.The resistance rates of H.pylori strains to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline were 49.2%,37.8%,76.1%,2.3%,1.4%,and 0.7%,respectively.The resistance rates to clarithromycin,levofloxacin,and metronidazole were high in the four regions of Hunan Province,and the overall resistance rates in central Hunan Province were higher than those in other regions.The resistance rates of H.pylori strains to clarithromycin and levofloxacin were significantly different among the different age groups(P<0.05),with the elderly group having a higher resistance rate than the young group.The resistance rate of H.pylori strains to clarithromycin was greater in patients with atrophic gastritis,and the resistance rate to levofloxacin was the lowest in patients with peptic ulcers.CONCLUSION The resistance rate of H.pylori to amoxicillin,clarithromycin,and metronidazole is high in Hunan Province.Age,stomach disease,and H.pylori reinfection may affect the antibiotic resistance of H.pylori.展开更多
Powdery mildew negatively impacts wheat yield and quality.Emmer wheat(Triticum dicoccum),an ancestral species of common wheat,is a gene donor for wheat improvement.Cultivated emmer accession H1-707 exhibited all-stage...Powdery mildew negatively impacts wheat yield and quality.Emmer wheat(Triticum dicoccum),an ancestral species of common wheat,is a gene donor for wheat improvement.Cultivated emmer accession H1-707 exhibited all-stage resistance to powdery mildew over consecutive years.Genetic analysis of H1-707 at the seedling stage revealed a dominant monogenic inheritance pattern,and the underlying gene was designated Pm71.By employing bulked segregant exome sequencing(BSE-Seq)and using 2000 F2:3 families,Pm71 was fine mapped to a 336-kb interval on chromosome arm 6AS by referencing to the durum cv.Svevo RefSeq 1.0.Collinearity analysis revealed high homology in the candidate interval between Svevo and six Triticum species.Among six high-confidence genes annotated within this interval,TRITD6Av1G005050 encoding a GDSL esterase/lipase was identified as a key candidate for Pm71.展开更多
Proton exchange membrane water electrolysis(PEMWE)is one of the most promising strategies to pro-duce green hydrogen energy,and it is crucial to exploit highly conductive and good corrosion-resistant coatings on bipol...Proton exchange membrane water electrolysis(PEMWE)is one of the most promising strategies to pro-duce green hydrogen energy,and it is crucial to exploit highly conductive and good corrosion-resistant coatings on bipolar plates(BPs),one of the core components in PEMWE cells.In this work,NbN coatings are deposited on Ti BPs by magnetron sputtering to improve the corrosion resistance and conductivity,for which the critical process parameters,such as the working pressure,partial nitrogen pressure and de-position temperature are well optimized.It is found that the compact microstructure,highly conductive δ-NbN and uniform nanoparticles play a dominant role in the synergistic improvement of the corrosion resistance and electrical conductivity of NbN coatings.The optimized NbN coatings exhibit excellent cor-rosion resistance with the low corrosion current density of 1.1×10^(-8) A cm^(-2),a high potential value of-0.005 V vs.SCE and a low ICR value of 15.8 mΩcm2@1.5 MPa.Accordingly,NbN coatings can be a promising candidate for the development of the low-cost and high-anti-corrosion Ti BPs of PEMWE.展开更多
Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially ...Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.展开更多
Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment proc...Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.展开更多
Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods e...Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods embedded with TiO_(2)and polyaniline(PANI)nanoparticles are synthesized via heterogeneous precipitation and in-situ polymerization.The obtained PANI-TiO_(2)-ATP one-di-mensional(1D)nanostructures can intertwine into three-dimensional(3D)conductive network,which favors energy dissipation.The min-imum reflection loss(RL_(min))of the PANI-TiO_(2)-ATP coating(20wt%)reaches-49.36 dB at 9.53 GHz,and the effective absorption band-width(EAB)can reach 6.53 GHz with a thickness of 2.1 mm.The excellent MA properties are attributed to interfacial polarization,mul-tiple loss mechanisms,and good impedance matching induced by the synergistic effect of PANI-TiO_(2)nanoparticle shells and ATP nanor-ods.In addition,salt spray and Tafel polarization curve tests reveal that the PANI-TiO_(2)-ATP coating shows outstanding corrosion resist-ance performance.This study provides a low-cost and high-efficiency strategy for constructing 1D nanonetwork composites for MA and corrosion resistance applications using natural porous ATP nanorods as carriers.展开更多
BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatm...BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.展开更多
Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection ...Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to neurodegeneration.Interestingly,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.展开更多
The rapid development of industrialization requires the advancement of multifunctional coatings.In this study,successful self-assembly of iron porphyrin on BP nanosheets resulted in the synthesis of IBP nanosheets wit...The rapid development of industrialization requires the advancement of multifunctional coatings.In this study,successful self-assembly of iron porphyrin on BP nanosheets resulted in the synthesis of IBP nanosheets with a sandwich structure.Characterization tests including SEM,XPS,SPM,and XRD confirmed the successful preparation of IBP nanosheets with robust structural stability and antioxidation.Subsequently,a water-based epoxy resin(WEP)coating containing IBP nanosheets was prepared.Test results revealed that the composite coating containing 0.4 wt.%IBP nanosheets exhibited outstanding anti-corrosion,wear-resistant,and flame-retardant properties.After 42 days of immersion in a 3.5 wt.%NaCl solution,the Rct value of the 4-IBP/WEP coating was 1.79×10^(9)Ωcm^(2),surpassing the Pure WEP coating by more than 3 orders of magnitude.Additionally,the peak heat release rate(PHRR)and wear rate of the 4-IBP/WEP coating decreased by 19.29%and 90.97%compared to the Pure WEP coating.This research presents a novel idea for the utilization of BP nanosheets in multifunctional coatings.展开更多
This study addresses the challenge of real-time resistivity gradient measurement in the Czochralski(CZ)silicon production process.Due to the inability to directly measure this parameter,we propose a Long Short-Term Me...This study addresses the challenge of real-time resistivity gradient measurement in the Czochralski(CZ)silicon production process.Due to the inability to directly measure this parameter,we propose a Long Short-Term Memory soft-sensing model based on Convolutional Neural Network(CNN)and attention mechanism(CNN-ALSTM)that enhances traditional LSTM by integrating CNN and attention mechanism to overcome time lag variations during silicon pulling.The CNN module extracts spatial features from multi-source sensor data,while the attention-enhanced LSTM(ALSTM)dynamically adjusts historical parameter weights,enabling accurate resistivity gradient prediction.Experiments with real production data show that CNN-ALSTM outperforms SVR,FNN,RNN,XGBoost,and GRU,improving prediction accuracy by 11.76%,16.67%,21.05%,30.23%,and 9.09%,respectively.This soft-sensing approach enhances real-time monitoring and optimization of monocrystalline silicon growth.展开更多
Magnesium alloy is a promising biodegradable metal material for hard tissue engineering.However,its high corrosion rate limits its application.In our previous study,we biomimetically deposited a calcium carbonate coat...Magnesium alloy is a promising biodegradable metal material for hard tissue engineering.However,its high corrosion rate limits its application.In our previous study,we biomimetically deposited a calcium carbonate coating on the surface of magnesium alloy using siloxane induction.This calcium carbonate coating demonstrated excellent in vitro biocompatibility and provided partial protection for the magnesium alloy substrate.In this study,we further enhanced the corrosion resistance of the calcium carbonate coating by treating it with stearic acid and its derivative,sodium stearate.Electrochemical corrosion tests revealed that the sodium stearate-treated calcium carbonate coating reduced the corrosion rate by two orders of magnitude.Additionally,in vitro biocompatibility assessments showed that while the biocompatibility of the sodium stearate-treated coating was slightly reduced,it remained acceptable compared to the magnesium substrate.This study builds on our previous work and offers a promising reinforcement strategy for degradable magnesium alloys in medical applications.展开更多
Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in th...Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.展开更多
Emerging new races of wheat stem rust(Puccinia graminis f.sp.tritici)are threatening global wheat(Triticum aestivum L.)production.Host resistance is the most effective and environmentally friendly method of controllin...Emerging new races of wheat stem rust(Puccinia graminis f.sp.tritici)are threatening global wheat(Triticum aestivum L.)production.Host resistance is the most effective and environmentally friendly method of controlling stem rust.The stem rust resistance gene Sr59 was previously identified within a T2DS 2RL wheat-rye whole arm translocation,providing broad-spectrum resistance to various stem rust races.Seedling evaluation,molecular marker analysis,and cytogenetic studies identified wheat-rye introgression line#284 containing a new translocation chromosome T2BL 2BS-2RL.This line has demonstrated broad-spectrum resistance to stem rust at the seedling stage.Seedling evaluation and cytogenetic analysis of three backcross populations between the line#284 and the adapted cultivars SLU-Elite,Navruz,and Linkert confirmed that Sr59 is located within the short distal 2RL translocation.This study aimed physical mapping of Sr59 in the 2RL introgression segment and develop a robust molecular marker for marker-assisted selection.Using genotyping-by-sequencing(GBS),GBS-derived SNPs were aligned with full-length annotated rye nucleotide-binding leucine-rich repeat(NLR)genes in the parental lines CS ph1b,SLU238,SLU-Elite,Navruz,and Linkert,as well as in 33 BC4F5progeny.Four NLR genes were identified on the 2R chromosome,with Chr2R_NLR_60 being tightly linked to the Sr59resistance gene.In-silico functional enrichment analysis of the translocated 2RL region(25,681,915 bp)identified 223 genes,with seven candidate genes associated with plant disease resistance and three linked to agronomic performance,contributing to oxidative stress response,protein kinase activity,and cellular homeostasis.These findings facilitate a better understanding of the genetic basis of stem rust resistance provided by Sr59.展开更多
In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reverse...In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.展开更多
基金Funded by the Natural Science Foundation of Jiangsu Province(No.BK20220626)the National Natural Science Foundation of China(No.52078068)+2 种基金Science and Technology Innovation Foundation of NIT(No.KCTD006)Jiangsu Marine Structure Service Performance Improvement Engineering Research CenterKey Laboratory of Jiangsu"Marine Floating Wind Power Technology and Equipment"。
文摘We investigated the effects of fly ash(FA)content on the mechanical properties of recycled aggregate concrete(RAC)and its regeneration potential under freeze and thaw(F-T)cycles.The physical properties of second-generation recycled concrete aggregates(RCA)were used to analyze the regeneration potential of RAC after F-T cycles.Scanning electron microscopy was used to study the interfacial transition zone microstructure of RAC after F-T cycles.Results showed that adding 20%FA to RAC significantly enhanced its mechanical properties and frost resistance.Before the F-T cycles,the compressive strength of RAC with 20%FA reached 48.3 MPa,exceeding research strength target of 40 MPa.A majority of second-generation RCA with FA had been verified to attain class Ⅲ,which enabled their practical application in non-structural projects such as backfill trenches and road pavement.However,the second-generation RCA with 20%FA can achieve class Ⅱ,making it ideal for 40 MPa structural concrete.
基金supported by the Original Exploratory Program of the National Natural Science Foundation of China(No.52450012)。
文摘TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing TiB_(2)coatings have disadvantages such as high equipment costs,complicated processes,and highly toxic gas emissions.This paper proposes an environmentally friendly method,which requires inexpensive equipment and simple processing,for preparing TiB_(2)coating on molybdenum via electrophoretic deposition within Na3AlF6-based molten salts.The produced TiB_(2)layer had an approximate thickness of 60μm and exhibited high density,outstanding hardness(38.2 GPa)and robust adhesion strength(51 N).Additionally,high-temperature oxidation experiments revealed that,at900℃,the TiB_(2)coating provided effective protection to the molybdenum substrate against oxidation for 3 h.This result indicates that the TiB_(2)coating prepared on molybdenum using molten salt electrophoretic deposition possesses good high-temperature oxidation resistance.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金National Natural Science Foundation of China(52071126)Natural Science Foundation of Tianjin City,China(22JCQNJC01240)+2 种基金Central Guidance on Local Science and Technology Development Fund of Hebei Province(226Z1009G)Special Funds for Science and Technology Innovation in Hebei(2022X19)Anhui Provincial Natural Science Foundation(2308085ME135)。
文摘Co-based alloy coating was prepared on Zr alloy using laser melting and cladding technique to study the difference in the high-temperature oxidation behavior between pure metal Co coatings and Co-T800 alloy coatings,as well as the wear resistance of the coatings.Besides,the effect of changing the laser melting process on the coatings was also investigated.The oxidation mass gain at 800–1200℃and the high-temperature oxidation behavior during high-temperature treatment for 1 h of two coated Zr alloy samples were studied.Results show that the Co coating and the Co-T800 coating have better resistance against high-temperature oxidation.After oxidizing at 1000℃for 1 h,the thickness of the oxide layer of the uncoated sample was 241.0μm,whereas that of the sample with Co-based coating is only 11.8–35.5μm.The friction wear test shows that the depth of the abrasion mark of the coated sample is only 1/2 of that of the substrate,indicating that the hardness and wear resistance of the Zr substrate are greatly improved.The disadvantage of Co-based coatings is the inferior corrosion resistance in 3.5wt%NaCl solution.
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
文摘In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powders were fabricated to improve the wear and corrosion behavior of 1Cr18Ni9Ti steel blades in high speed mixers.Microstructure evolution,phases,element distribution,microhardness,wear and corrosion behavior of the laser alloyed layers were investigated.Results indicated that high Mn steel matrix composites with undissolved W_(2)C,WC and other in-situ formed carbides were formed by LSA with Mn+W_(2)C and Mn+NiWC while SiC totally dissolved into the high Mn matrix when adding Mn+SiC.Ni as the binding phase in Ni-WC powder decreased the crack sensitivity of the alloyed layer as compared with the addition of W_(2)C powder.An improvement in average microhardness was achieved in the matrix in specimen A,B and C,with the value of 615,602 and 277 HV_(0.5),while that of the substrate was 212 HV_(0.5).The increase of microhardness,wear and corrosion resistance is highly corelated to microstructure,formed phases,type and content of carbides,micro-hardness and toughness of the alloyed layers.
基金Supported by the National Natural Science Foundation of China,No.82270594the Independent Exploration and Innovation Project of Central South University,No.2024ZZTS0966.
文摘BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori(H.pylori)infection.The antibiotic resistance spectrum of H.pylori varies in different regions.We investigated the current status of antibiotic resistance of H.pylori in Hunan Province and analyzed the factors related to such resistance to provide strategies for the accurate clinical treatment of H.pylori infection.AIM To understand the antibiotic resistance of H.pylori in Hunan Province and provide guidance for the clinical treatment of H.pylori infection.METHODS This study selected patients who underwent gastroscopy in five hospitals in Hunan Province from April 2022 to April 2023.The sensitivity of H.pylori to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline was detected using the Agar dilution method.RESULTS H.pylori strains from a total of 566 patients were isolated and identified.The resistance rates of H.pylori strains to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline were 49.2%,37.8%,76.1%,2.3%,1.4%,and 0.7%,respectively.The resistance rates to clarithromycin,levofloxacin,and metronidazole were high in the four regions of Hunan Province,and the overall resistance rates in central Hunan Province were higher than those in other regions.The resistance rates of H.pylori strains to clarithromycin and levofloxacin were significantly different among the different age groups(P<0.05),with the elderly group having a higher resistance rate than the young group.The resistance rate of H.pylori strains to clarithromycin was greater in patients with atrophic gastritis,and the resistance rate to levofloxacin was the lowest in patients with peptic ulcers.CONCLUSION The resistance rate of H.pylori to amoxicillin,clarithromycin,and metronidazole is high in Hunan Province.Age,stomach disease,and H.pylori reinfection may affect the antibiotic resistance of H.pylori.
基金financially supported by National Natural Science Foundation of China(32301800,32301923 and 32072053)Wheat Industrial Technology System of Shandong Province(SDAIT-01-01)Key Research and Development Project of Shandong Province(2022LZG002-4,2023LZGC009-4-4).
文摘Powdery mildew negatively impacts wheat yield and quality.Emmer wheat(Triticum dicoccum),an ancestral species of common wheat,is a gene donor for wheat improvement.Cultivated emmer accession H1-707 exhibited all-stage resistance to powdery mildew over consecutive years.Genetic analysis of H1-707 at the seedling stage revealed a dominant monogenic inheritance pattern,and the underlying gene was designated Pm71.By employing bulked segregant exome sequencing(BSE-Seq)and using 2000 F2:3 families,Pm71 was fine mapped to a 336-kb interval on chromosome arm 6AS by referencing to the durum cv.Svevo RefSeq 1.0.Collinearity analysis revealed high homology in the candidate interval between Svevo and six Triticum species.Among six high-confidence genes annotated within this interval,TRITD6Av1G005050 encoding a GDSL esterase/lipase was identified as a key candidate for Pm71.
基金supported by the National Key Re-search and Development Program of China(No.2022YFB4002100)the National Natural Science Foundation of China(No.52271136)the Natural Science Foundation of Shaanxi Province(Nos.2019TD-020 and 2021JC-06).
文摘Proton exchange membrane water electrolysis(PEMWE)is one of the most promising strategies to pro-duce green hydrogen energy,and it is crucial to exploit highly conductive and good corrosion-resistant coatings on bipolar plates(BPs),one of the core components in PEMWE cells.In this work,NbN coatings are deposited on Ti BPs by magnetron sputtering to improve the corrosion resistance and conductivity,for which the critical process parameters,such as the working pressure,partial nitrogen pressure and de-position temperature are well optimized.It is found that the compact microstructure,highly conductive δ-NbN and uniform nanoparticles play a dominant role in the synergistic improvement of the corrosion resistance and electrical conductivity of NbN coatings.The optimized NbN coatings exhibit excellent cor-rosion resistance with the low corrosion current density of 1.1×10^(-8) A cm^(-2),a high potential value of-0.005 V vs.SCE and a low ICR value of 15.8 mΩcm2@1.5 MPa.Accordingly,NbN coatings can be a promising candidate for the development of the low-cost and high-anti-corrosion Ti BPs of PEMWE.
基金Supported by the Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,Brazil,No.0932204294929829 and No.7414780530977345the Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil,No.5763023359532159,No.6472982965854452,and No.7340128440641417+2 种基金the Scientific Initiation Scholarship Programme(PIBIC)of Bahia State Research Support Foundation,FAPESB,Brazil,No.19.573.301.5418the PERMANECER Programme of Pro-Rectory of Student Assistance at Federal University of Bahia,No.R8EZ-4V4W-6LQX-5LC8the CNPq Research Productivity Fellow,No.4357511882624145.
文摘Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.
基金supported by the National Natural Science Foundation of China (Nos.52100182 and 52300204)the the Science and Technology Innovation Program of Hunan Province (No.2023RC3122).
文摘Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.
基金support from the National Key Research and Development Program of China(No.2021YFB3701503)the Key Research and Development Program of Ningbo,China(No.2023Z107)+1 种基金the Jiangsu Key R&D program,China(No.BE2019072)the special project of Gansu regional science and technology cooperation,China(No.20JR10 QA579).
文摘Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods embedded with TiO_(2)and polyaniline(PANI)nanoparticles are synthesized via heterogeneous precipitation and in-situ polymerization.The obtained PANI-TiO_(2)-ATP one-di-mensional(1D)nanostructures can intertwine into three-dimensional(3D)conductive network,which favors energy dissipation.The min-imum reflection loss(RL_(min))of the PANI-TiO_(2)-ATP coating(20wt%)reaches-49.36 dB at 9.53 GHz,and the effective absorption band-width(EAB)can reach 6.53 GHz with a thickness of 2.1 mm.The excellent MA properties are attributed to interfacial polarization,mul-tiple loss mechanisms,and good impedance matching induced by the synergistic effect of PANI-TiO_(2)nanoparticle shells and ATP nanor-ods.In addition,salt spray and Tafel polarization curve tests reveal that the PANI-TiO_(2)-ATP coating shows outstanding corrosion resist-ance performance.This study provides a low-cost and high-efficiency strategy for constructing 1D nanonetwork composites for MA and corrosion resistance applications using natural porous ATP nanorods as carriers.
文摘BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.
基金supported by a grant of the Deutsche Forschungsgemeinschaft(DFGCRC1177 and joint DFG/ANR grant)(to CB)a fellowship of the Deutscher Akademischer Austauschdienst(DAAD)(to TNMP)。
文摘Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron demise.The entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to neurodegeneration.Interestingly,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.
基金supports from the Science and Technology Program of Guangzhou(No.2024A04J3710)the National Natural Science Foundation of China(No.22268025).
文摘The rapid development of industrialization requires the advancement of multifunctional coatings.In this study,successful self-assembly of iron porphyrin on BP nanosheets resulted in the synthesis of IBP nanosheets with a sandwich structure.Characterization tests including SEM,XPS,SPM,and XRD confirmed the successful preparation of IBP nanosheets with robust structural stability and antioxidation.Subsequently,a water-based epoxy resin(WEP)coating containing IBP nanosheets was prepared.Test results revealed that the composite coating containing 0.4 wt.%IBP nanosheets exhibited outstanding anti-corrosion,wear-resistant,and flame-retardant properties.After 42 days of immersion in a 3.5 wt.%NaCl solution,the Rct value of the 4-IBP/WEP coating was 1.79×10^(9)Ωcm^(2),surpassing the Pure WEP coating by more than 3 orders of magnitude.Additionally,the peak heat release rate(PHRR)and wear rate of the 4-IBP/WEP coating decreased by 19.29%and 90.97%compared to the Pure WEP coating.This research presents a novel idea for the utilization of BP nanosheets in multifunctional coatings.
文摘This study addresses the challenge of real-time resistivity gradient measurement in the Czochralski(CZ)silicon production process.Due to the inability to directly measure this parameter,we propose a Long Short-Term Memory soft-sensing model based on Convolutional Neural Network(CNN)and attention mechanism(CNN-ALSTM)that enhances traditional LSTM by integrating CNN and attention mechanism to overcome time lag variations during silicon pulling.The CNN module extracts spatial features from multi-source sensor data,while the attention-enhanced LSTM(ALSTM)dynamically adjusts historical parameter weights,enabling accurate resistivity gradient prediction.Experiments with real production data show that CNN-ALSTM outperforms SVR,FNN,RNN,XGBoost,and GRU,improving prediction accuracy by 11.76%,16.67%,21.05%,30.23%,and 9.09%,respectively.This soft-sensing approach enhances real-time monitoring and optimization of monocrystalline silicon growth.
基金supported by the National Natural Science Foundation of China(No.52205310)the TUA research funding,UmeåUniversity/Region Västerbotten,Sweden(RV-937838)+1 种基金the Kempe foundation(JCSMK22-0122)the Natural Science Foundation of Shandong Province(No.ZR2021QE263).
文摘Magnesium alloy is a promising biodegradable metal material for hard tissue engineering.However,its high corrosion rate limits its application.In our previous study,we biomimetically deposited a calcium carbonate coating on the surface of magnesium alloy using siloxane induction.This calcium carbonate coating demonstrated excellent in vitro biocompatibility and provided partial protection for the magnesium alloy substrate.In this study,we further enhanced the corrosion resistance of the calcium carbonate coating by treating it with stearic acid and its derivative,sodium stearate.Electrochemical corrosion tests revealed that the sodium stearate-treated calcium carbonate coating reduced the corrosion rate by two orders of magnitude.Additionally,in vitro biocompatibility assessments showed that while the biocompatibility of the sodium stearate-treated coating was slightly reduced,it remained acceptable compared to the magnesium substrate.This study builds on our previous work and offers a promising reinforcement strategy for degradable magnesium alloys in medical applications.
基金supported by the National Natural Science Foundation of China(Grant No.:82272749)the Natural Science Foundation of Liaoning Province,China(Grant No.:2022-MS-190).
文摘Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.
基金the financial support from FORMAS(2018-01029)the Swedish Institute(01132-2022)for supporting Ivan Motsnyi’s visit and research at Swedish University of Agricultural Sciences。
文摘Emerging new races of wheat stem rust(Puccinia graminis f.sp.tritici)are threatening global wheat(Triticum aestivum L.)production.Host resistance is the most effective and environmentally friendly method of controlling stem rust.The stem rust resistance gene Sr59 was previously identified within a T2DS 2RL wheat-rye whole arm translocation,providing broad-spectrum resistance to various stem rust races.Seedling evaluation,molecular marker analysis,and cytogenetic studies identified wheat-rye introgression line#284 containing a new translocation chromosome T2BL 2BS-2RL.This line has demonstrated broad-spectrum resistance to stem rust at the seedling stage.Seedling evaluation and cytogenetic analysis of three backcross populations between the line#284 and the adapted cultivars SLU-Elite,Navruz,and Linkert confirmed that Sr59 is located within the short distal 2RL translocation.This study aimed physical mapping of Sr59 in the 2RL introgression segment and develop a robust molecular marker for marker-assisted selection.Using genotyping-by-sequencing(GBS),GBS-derived SNPs were aligned with full-length annotated rye nucleotide-binding leucine-rich repeat(NLR)genes in the parental lines CS ph1b,SLU238,SLU-Elite,Navruz,and Linkert,as well as in 33 BC4F5progeny.Four NLR genes were identified on the 2R chromosome,with Chr2R_NLR_60 being tightly linked to the Sr59resistance gene.In-silico functional enrichment analysis of the translocated 2RL region(25,681,915 bp)identified 223 genes,with seven candidate genes associated with plant disease resistance and three linked to agronomic performance,contributing to oxidative stress response,protein kinase activity,and cellular homeostasis.These findings facilitate a better understanding of the genetic basis of stem rust resistance provided by Sr59.
基金supported by the National Natural Science Foundation of China(Grant Nos.82172728,82370096).
文摘In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.
