Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and s...Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR–insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.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
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
Microbial resistance to antibiotics is a global problem that threatens the lives of millions of people and affects several sectors, including aquaculture. The aim of the present study is to contribute to the monitorin...Microbial resistance to antibiotics is a global problem that threatens the lives of millions of people and affects several sectors, including aquaculture. The aim of the present study is to contribute to the monitoring of multi-resistant enterobacterial strains circulating in fish ponds in the Sud-Comoé region of south-eastern Côte d’Ivoire, more specifically in the Aboisso and Tiapoum departments. To this end, 20 samples of Tilapia fish (Oreochromis niloticus) and 60 samples of farm water were collected from 5 fish farms in the Sud-Comoé region. Microbiological analyses were based on the isolation and identification of enterobacteria on Mac Conkey + Ceftazidime medium. These analyses resulted in the isolation of 73 strains of enterobacteria, including 58 from fish and 15 from fish pond water samples. Antibiotic sensitivity tests carried out on enterobacteria isolated from water and fish samples showed high levels of resistance (100%) to the beta-lactam family (Amoxicilin + clavulanic acid, Ceftazidime). Klebsiella pneumoniae and Enterobacter spp. showed resistance to Ciprofloxacins (100%) and (25%) respectively. The study also showed that strains of Enterobacteriaceae were resistant to all 3 families of antibiotics, notably Beta-lactams, Fluoro-quinolones and Aminosides. The presence of multi-resistant Enterobacteriaceae in fish and pond water samples represents a public health risk.展开更多
The authors regret to report a mistake in the text and an associated change necessary to section 3.6 of the paper.On page 1766 in the right-hand column,line 4,the heading of subsection 3.6“GmWRKY40 represses the expr...The authors regret to report a mistake in the text and an associated change necessary to section 3.6 of the paper.On page 1766 in the right-hand column,line 4,the heading of subsection 3.6“GmWRKY40 represses the expression of PR genes”should be changed to“GmWRKY40 promotes the expression of PR genes”.The authors would like to apologize for any inconvenience caused.展开更多
Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enter...Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.展开更多
The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the c...The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.展开更多
To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Po...To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.展开更多
The increase and spread of bacterial resistance to extended-spectrum beta-lactam antibiotics are reported in many infections and are a real public health problem worldwide. Drug pressure is a factor that favors the em...The increase and spread of bacterial resistance to extended-spectrum beta-lactam antibiotics are reported in many infections and are a real public health problem worldwide. Drug pressure is a factor that favors the emergence of a population of better adapted bacteria. However, there is no literature highlighting the genetic diversity and evolutionary structure of E. coli and K. pneumoniae in an environment with high selection pressure in Côte d’Ivoire. The objective of this study was to evaluate the genetic diversity of E. coli and K. pneumoniae strains circulating at the HKB Hospital in Abobo and at the Daloa Regional Hospital and its impact on the dissemination of extended spectrum beta-lactam resistance genes. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. From genomic DNA extracts, ESBL resistance genes were amplified by PCR and sequenced, in addition to genetic typing by ERIC-PCR. The data obtained were submitted to genetic and bioinformatics analyses. The results have shown a genetic diversity important in E. coli and K. pneumoniae with diversity indexs (SID) ranging from 0.5 to 0.77. The genetic structure of the bacterial species studied has shown a clonal distribution of strains with clones expressing TEM-9 and CTX-M-15 variants. Also, this clonal structure was correlated with the spread of resistance genes in E. coli and K. pneumoniae. The spread of resistant clones is a factor that might limit the fight against antibiotic resistance.展开更多
Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment fai...Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.展开更多
Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to...Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses;hence,this study aimed to engineer SMV resistance in soybean using this system.Specifically,multiple sgRNAs were designed to target positive-and/or negative-sense strands of the SMV HC-Pro gene.Subsequently,the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans.After inoculation with SMV,39.02%,35.77%,and 18.70%of T_(1)plants were confirmed to be highly resistant(HR),resistant(R),and mildly resistant(MR)to SMV,respectively,whereas only 6.50%were identified as susceptible(S).Additionally,qRT-PCR and DAS-ELISA showed that,both at 15 and 30 d post-inoculation(dpi),SMV accumulation significantly decreased or was even undetectable in HR and R plants,followed by MR and S plants.Additionally,the expression level of the CasRx gene varied in almost all T_(1)plants with different resistance level,both at 15 and 30 dpi.Furthermore,when SMV resistance was evaluated in the T_(2)generation,the results were similar to those recorded for the T_(1)generation.These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity.展开更多
Turnip mosaic virus(TuMV)is a devastating potyvirus pathogen that infects a wide variety of both cultivated and wild Brassicaceae plants.We urgently need more information and understanding of TuMV pathogenesis and the...Turnip mosaic virus(TuMV)is a devastating potyvirus pathogen that infects a wide variety of both cultivated and wild Brassicaceae plants.We urgently need more information and understanding of TuMV pathogenesis and the host responses involved in disease development in cruciferous crops.TuMV displays great versatility in viral pathogenesis,especially in its replication and intercellular movement.Moreover,in the coevolutionary arms races between TuMV and its hosts,the virus has evolved to co-opt host factors to facilitate its infection and counter host defense responses.This review mainly focuses on recent advances in understanding the viral factors that contribute to the TuMV infection cycle and the host resistance mechanism in Brassica.Finally,we propose some future research directions on TuMV pathogenesis and control strategies to design durable TuMV-resistant Brassica crops.展开更多
This comprehensive review examines the structural,mechanical,electronic,and thermodynamic properties of Mg-Li-Al alloys,focusing on their corrosion resistance and mechanical performance enhancement.Utilizing first-pri...This comprehensive review examines the structural,mechanical,electronic,and thermodynamic properties of Mg-Li-Al alloys,focusing on their corrosion resistance and mechanical performance enhancement.Utilizing first-principles calculations based on Density Functional Theory(DFT)and the quasi-harmonic approximation(QHA),the combined properties of the Mg-Li-Al phase are explored,revealing superior incompressibility,shear resistance,and stiffness compared to individual elements.The review highlights the brittleness of the alloy,supported by B/G ratios,Cauchy pressures,and Poisson’s ratios.Electronic structure analysis shows metallic behavior with varied covalent bonding characteristics,while Mulliken population analysis emphasizes significant electron transfer within the alloy.This paper also studied thermodynamic properties,including Debye temperature,heat capacity,enthalpy,free energy,and entropy,which are precisely examined,highlighting the Mg-Li-Al phase sensitive to thermal conductivity and thermal performance potential.Phonon density of states(PHDOS)confirms dynamic stability,while anisotropic sound velocities reveal elastic anisotropies.This comprehensive review not only consolidates the current understanding of the Mg-Li-Al alloy’s properties but also proposes innovative strategies for enhancing corrosion resistance.Among these strategies is the introduction of a corrosion barrier akin to the Mg-Li-Al network,which holds promise for advancing both the applications and performance of these alloys.This review serves as a crucial foundation for future research aimed at optimizing alloy design and processing methods.展开更多
Airport pavement engineers are required to maintain pavement skid resistance at a satisfactory level to minimize the likelihood of runway excursions.Runway overruns and skidding along rapid exit taxiways are the two m...Airport pavement engineers are required to maintain pavement skid resistance at a satisfactory level to minimize the likelihood of runway excursions.Runway overruns and skidding along rapid exit taxiways are the two most frequently encountered forms of runway excursion accidents.Currently only empirical statistical models based on historical accident data are available to predict the risks of runway excursions.All such models fail to account for the impacts of pavement skid resistance properties.Mechanistic solutions of the tire-fluid-pavement interaction problem are now available,and the impacts of pavement skid resistance properties on runway excursion accidents can now be quantitatively evaluated.This paper presents a state-of-the-art review of recent research developments on the topic.It highlights the Concept of Pavement Skid Resistance State which provides(i)a logical theoretical framework for mechanistic representation of tire-pavement skid resistance,and(ii)an approach for modeling of the physical process of aircraft skidding and hydroplaning.Next,runway excursion risk prediction models are presented for risk evaluation of aircraft hydroplaning,runway overruns,and rapid exit taxiway excursions.Also examined in detail mechanistically is the effectiveness of pavement grooving in reducing the risks of runway excursions.The review clearly confirms the capability of mechanistic approach in analyzing runway excursions for the purpose of enhancing safe aircraft operations on airport runways.展开更多
Ultra-deep reservoirs play an important role at present in fossil energy exploitation.Due to the related high temperature,high pressure,and high formation fracture pressure,however,methods for oil well stimulation do ...Ultra-deep reservoirs play an important role at present in fossil energy exploitation.Due to the related high temperature,high pressure,and high formation fracture pressure,however,methods for oil well stimulation do not produce satisfactory results when conventional fracturing fluids with a low pumping rate are used.In response to the above problem,a fracturing fluid with a density of 1.2~1.4 g/cm^(3)was developed by using Potassium formatted,hydroxypropyl guanidine gum and zirconium crosslinking agents.The fracturing fluid was tested and its ability to maintain a viscosity of 100 mPa.s over more than 60 min was verified under a shear rate of 1701/s and at a temperature of 175℃.This fluid has good sand-carrying performances,a low viscosity after breaking the rubber,and the residue content is less than 200 mg/L.Compared with ordinary reconstruction fluid,it can increase the density by 30%~40%and reduce the wellhead pressure of 8000 m level reconstruction wells.Moreover,the new fracturing fluid can significantly mitigate safety risks.展开更多
To study the anti-explosion protection effect of polyurea coating on reinforced concrete box girder,two segmental girder specimens were made at a scale of 1:3,numbered as G(without polyurea coating)and PCG(with polyur...To study the anti-explosion protection effect of polyurea coating on reinforced concrete box girder,two segmental girder specimens were made at a scale of 1:3,numbered as G(without polyurea coating)and PCG(with polyurea coating).The failure characteristics and dynamic responses of the specimens were compared through conducting explosion tests.The reliability of the numerical simulation using LS-DYNA software was verified by the test results.The effects of different scaled distances,reinforcement ratios,concrete strengths,coating thicknesses and ranges of polyurea were studied.The results show that the polyurea coating can effectively enhance the anti-explosion performance of the girder.The top plate of middle chamber in specimen G forms an elliptical penetrating hole,while that in specimen PCG only shows a very slight local dent.The peak vertical displacement and residual displacement of PCG decrease by 74.8% and 73.7%,respectively,compared with those of specimen G.For the TNT explosion with small equivalent,the polyurea coating has a more significant protective effect on reducing the size of fracture.With the increase of TNT equivalent,the protective effect of polyurea on reducing girder displacement becomes more significant.The optimal reinforcement ratio,concrete strength,thickness and range of polyurea coating were also drawn.展开更多
基金supported by the Major Research Program of the National Natural Science Foundation of China(Subproject No.81991503)the Youth Research Program of the National Natural Science Foundation of China(No.82201069)+1 种基金the Innovative Talent Promotion Plan of Shaanxi Province-Research Fund for Young Star of Science and Technology(No.2021KJXX-24,No.2022KJXX-100)Basic and Applied Basic Research Fund of Guangdong Province(No.2023A1515012126).
文摘Periodontitis is a critical risk factor for the occurrence and development of diabetes.Porphyromonas gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of P.gingivalis in IR remain unclear.In the present study,clinical samples were analysed to determine the statistical correlation between P.gingivalis and IR occurrence.Through culturing of hepatocytes,myocytes,and adipocytes,and feeding mice P.gingivalis orally,the functional correlation between P.gingivalis and IR occurrence was further studied both in vitro and in vivo.Clinical data suggested that the amount of P.gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score.In vitro studies suggested that coculture with P.gingivalis decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and adipocytes.Mice fed P.gingivalis tended to undergo IR.P.gingivalis was detectable in the liver,skeletal muscle,and adipose tissue of experimental mice.The distribution sites of gingipain coincided with the downregulation of INSR.Gingipain proteolysed the functional insulin-binding region of INSR.Coculture with P.gingivalis significantly decreased the INSR–insulin binding ability.Knocking out gingipain from P.gingivalis alleviated the negative effects of P.gingivalis on IR in vivo.Taken together,these findings indicate that distantly migrated P.gingivalis may directly proteolytically degrade INSR through gingipain,thereby leading to IR.The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.
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Microbial resistance to antibiotics is a global problem that threatens the lives of millions of people and affects several sectors, including aquaculture. The aim of the present study is to contribute to the monitoring of multi-resistant enterobacterial strains circulating in fish ponds in the Sud-Comoé region of south-eastern Côte d’Ivoire, more specifically in the Aboisso and Tiapoum departments. To this end, 20 samples of Tilapia fish (Oreochromis niloticus) and 60 samples of farm water were collected from 5 fish farms in the Sud-Comoé region. Microbiological analyses were based on the isolation and identification of enterobacteria on Mac Conkey + Ceftazidime medium. These analyses resulted in the isolation of 73 strains of enterobacteria, including 58 from fish and 15 from fish pond water samples. Antibiotic sensitivity tests carried out on enterobacteria isolated from water and fish samples showed high levels of resistance (100%) to the beta-lactam family (Amoxicilin + clavulanic acid, Ceftazidime). Klebsiella pneumoniae and Enterobacter spp. showed resistance to Ciprofloxacins (100%) and (25%) respectively. The study also showed that strains of Enterobacteriaceae were resistant to all 3 families of antibiotics, notably Beta-lactams, Fluoro-quinolones and Aminosides. The presence of multi-resistant Enterobacteriaceae in fish and pond water samples represents a public health risk.
文摘The authors regret to report a mistake in the text and an associated change necessary to section 3.6 of the paper.On page 1766 in the right-hand column,line 4,the heading of subsection 3.6“GmWRKY40 represses the expression of PR genes”should be changed to“GmWRKY40 promotes the expression of PR genes”.The authors would like to apologize for any inconvenience caused.
基金supported by the National Key Research and Development Program of China(2022YFF0710505)The Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001)the Talents Introduction Projects of Hebei Agricultural University,China(YJ201945)。
文摘Oxazolidinones are highly effective antimicrobial agents for the treatment of serious infections caused by Gram-positive organisms,including methicillin-resistant Staphylococcus aureus(MRSA),vancomycin-resistant enterococci(VRE),multidrug-resistant(MDR)pneumococci and MDR mycobacteria(Brenciani et al.2022).However,the emergence and prevalence of acquired oxazolidinone resistance genes.
基金supported by the National Natural Science Foundation of China(No.81703001)the Natural Science Foundation of Hebei Province(No.H2021406021),Hebei Province Medical Science Research Project(Nos.20210247,20221335)Hebei Province Government-Funded Clinical Medical Outstanding Talents Project,Chengde Medical University Scientific Research Major Projects(No.KY2020005).
文摘The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.
基金supported by the National Natural Science Foundation of China(31770164)Jiangsu Province’s Innovation Program(JSSCTD202142).
文摘To fight against invasion by pathogens,plants have evolved an elaborate innate immune system,of which the nucleotide-binding domain leucine-rich repeat-containing receptor(NLR)acts as the sensor and immune executor.Potyviruses,comprising one of the largest genera of plant viruses,cause severe crop yield losses worldwide.Inherited crop resistance to potyviruses can be used in breeding and plant transgenesis to control disease development.This review summarizes achievements in mapping and cloning NLR genes conferring dominant resistance against potyvirus in the families Fabaceae,Solanaceae,Brassicaceae,and Cucurbitaceae.It compares mechanisms of potyviral protein recognition and downstream signaling employed by NLRs and discusses strategies for exploiting NLRs to better control diseases caused by potyviruses.
文摘The increase and spread of bacterial resistance to extended-spectrum beta-lactam antibiotics are reported in many infections and are a real public health problem worldwide. Drug pressure is a factor that favors the emergence of a population of better adapted bacteria. However, there is no literature highlighting the genetic diversity and evolutionary structure of E. coli and K. pneumoniae in an environment with high selection pressure in Côte d’Ivoire. The objective of this study was to evaluate the genetic diversity of E. coli and K. pneumoniae strains circulating at the HKB Hospital in Abobo and at the Daloa Regional Hospital and its impact on the dissemination of extended spectrum beta-lactam resistance genes. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. From genomic DNA extracts, ESBL resistance genes were amplified by PCR and sequenced, in addition to genetic typing by ERIC-PCR. The data obtained were submitted to genetic and bioinformatics analyses. The results have shown a genetic diversity important in E. coli and K. pneumoniae with diversity indexs (SID) ranging from 0.5 to 0.77. The genetic structure of the bacterial species studied has shown a clonal distribution of strains with clones expressing TEM-9 and CTX-M-15 variants. Also, this clonal structure was correlated with the spread of resistance genes in E. coli and K. pneumoniae. The spread of resistant clones is a factor that might limit the fight against antibiotic resistance.
基金supported by the National Natural Science Foundation of China(Nos.81872255,62141109)the Leading-Edge Technology Programme of Jiangsu Natural Science Foundation:BK20212021.
文摘Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.
基金supported by grants from National Natural Science Foundation of China(32001571)R&D Program of Beijing Municipal Education Commission(KM202212448003,KM202312448004)+4 种基金Science and Technology Innovation Project of Beijing Vocational College of Agriculture(XY-YF-22-02)Zhongshan Biological Breeding Laboratory(ZSBBL-KY2023-03)China Agriculture Research System of MOF and MARA(CARS-04)Jiangsu Collaborative Innovation Center for Modern Crop Production(JCICMCP)Collaborative Innovation Center for Modern Crop Production co-sponsored by Province and Ministry(CIC-MCP).
文摘Soybean mosaic virus(SMV),an RNA virus,is the most common and destructive pathogenic virus in soybean fields.The newly developed CRISPR/Cas immune system has provided a novel strategy for improving plant resistance to viruses;hence,this study aimed to engineer SMV resistance in soybean using this system.Specifically,multiple sgRNAs were designed to target positive-and/or negative-sense strands of the SMV HC-Pro gene.Subsequently,the corresponding CRISPR/CasRx vectors were constructed and transformed into soybeans.After inoculation with SMV,39.02%,35.77%,and 18.70%of T_(1)plants were confirmed to be highly resistant(HR),resistant(R),and mildly resistant(MR)to SMV,respectively,whereas only 6.50%were identified as susceptible(S).Additionally,qRT-PCR and DAS-ELISA showed that,both at 15 and 30 d post-inoculation(dpi),SMV accumulation significantly decreased or was even undetectable in HR and R plants,followed by MR and S plants.Additionally,the expression level of the CasRx gene varied in almost all T_(1)plants with different resistance level,both at 15 and 30 dpi.Furthermore,when SMV resistance was evaluated in the T_(2)generation,the results were similar to those recorded for the T_(1)generation.These findings provide new insights into the application of the CRISPR/CasRx system for soybean improvement and offer a promising alternative strategy for breeding for resistance to biotic stress that will contribute to the development of SMV-immune soybean germplasm to accelerate progress towards greater soybean crop productivity.
基金supported by a grant from Chinese Agriculture Research System of MOF and MARA (Grant No.CARS-24-C-04)Zhejiang Provincial Natural Science Foundation (Grant No.LZ24C140001)+1 种基金National Natural Science Foundation of China (Grant Nos.32370144,32070165)the K.C.Wong Magna Fund in Ningbo University。
文摘Turnip mosaic virus(TuMV)is a devastating potyvirus pathogen that infects a wide variety of both cultivated and wild Brassicaceae plants.We urgently need more information and understanding of TuMV pathogenesis and the host responses involved in disease development in cruciferous crops.TuMV displays great versatility in viral pathogenesis,especially in its replication and intercellular movement.Moreover,in the coevolutionary arms races between TuMV and its hosts,the virus has evolved to co-opt host factors to facilitate its infection and counter host defense responses.This review mainly focuses on recent advances in understanding the viral factors that contribute to the TuMV infection cycle and the host resistance mechanism in Brassica.Finally,we propose some future research directions on TuMV pathogenesis and control strategies to design durable TuMV-resistant Brassica crops.
文摘This comprehensive review examines the structural,mechanical,electronic,and thermodynamic properties of Mg-Li-Al alloys,focusing on their corrosion resistance and mechanical performance enhancement.Utilizing first-principles calculations based on Density Functional Theory(DFT)and the quasi-harmonic approximation(QHA),the combined properties of the Mg-Li-Al phase are explored,revealing superior incompressibility,shear resistance,and stiffness compared to individual elements.The review highlights the brittleness of the alloy,supported by B/G ratios,Cauchy pressures,and Poisson’s ratios.Electronic structure analysis shows metallic behavior with varied covalent bonding characteristics,while Mulliken population analysis emphasizes significant electron transfer within the alloy.This paper also studied thermodynamic properties,including Debye temperature,heat capacity,enthalpy,free energy,and entropy,which are precisely examined,highlighting the Mg-Li-Al phase sensitive to thermal conductivity and thermal performance potential.Phonon density of states(PHDOS)confirms dynamic stability,while anisotropic sound velocities reveal elastic anisotropies.This comprehensive review not only consolidates the current understanding of the Mg-Li-Al alloy’s properties but also proposes innovative strategies for enhancing corrosion resistance.Among these strategies is the introduction of a corrosion barrier akin to the Mg-Li-Al network,which holds promise for advancing both the applications and performance of these alloys.This review serves as a crucial foundation for future research aimed at optimizing alloy design and processing methods.
文摘Airport pavement engineers are required to maintain pavement skid resistance at a satisfactory level to minimize the likelihood of runway excursions.Runway overruns and skidding along rapid exit taxiways are the two most frequently encountered forms of runway excursion accidents.Currently only empirical statistical models based on historical accident data are available to predict the risks of runway excursions.All such models fail to account for the impacts of pavement skid resistance properties.Mechanistic solutions of the tire-fluid-pavement interaction problem are now available,and the impacts of pavement skid resistance properties on runway excursion accidents can now be quantitatively evaluated.This paper presents a state-of-the-art review of recent research developments on the topic.It highlights the Concept of Pavement Skid Resistance State which provides(i)a logical theoretical framework for mechanistic representation of tire-pavement skid resistance,and(ii)an approach for modeling of the physical process of aircraft skidding and hydroplaning.Next,runway excursion risk prediction models are presented for risk evaluation of aircraft hydroplaning,runway overruns,and rapid exit taxiway excursions.Also examined in detail mechanistically is the effectiveness of pavement grooving in reducing the risks of runway excursions.The review clearly confirms the capability of mechanistic approach in analyzing runway excursions for the purpose of enhancing safe aircraft operations on airport runways.
文摘Ultra-deep reservoirs play an important role at present in fossil energy exploitation.Due to the related high temperature,high pressure,and high formation fracture pressure,however,methods for oil well stimulation do not produce satisfactory results when conventional fracturing fluids with a low pumping rate are used.In response to the above problem,a fracturing fluid with a density of 1.2~1.4 g/cm^(3)was developed by using Potassium formatted,hydroxypropyl guanidine gum and zirconium crosslinking agents.The fracturing fluid was tested and its ability to maintain a viscosity of 100 mPa.s over more than 60 min was verified under a shear rate of 1701/s and at a temperature of 175℃.This fluid has good sand-carrying performances,a low viscosity after breaking the rubber,and the residue content is less than 200 mg/L.Compared with ordinary reconstruction fluid,it can increase the density by 30%~40%and reduce the wellhead pressure of 8000 m level reconstruction wells.Moreover,the new fracturing fluid can significantly mitigate safety risks.
基金the Natural Science Foundation of Jiangsu Province(Grant No.BK20200494)China Postdoctoral Science Foundation(Grant No.2021M701725)+3 种基金Jiangsu Postdoctoral Research Funding Program(Grant No.2021K522C)Fundamental Research Funds for the Central Universities(Grant No.30919011246)National Natural Science Foundation of China(Grant No.52278188)Natural Science Foundation of Jiangsu Province(Grant No.BK20211196)。
文摘To study the anti-explosion protection effect of polyurea coating on reinforced concrete box girder,two segmental girder specimens were made at a scale of 1:3,numbered as G(without polyurea coating)and PCG(with polyurea coating).The failure characteristics and dynamic responses of the specimens were compared through conducting explosion tests.The reliability of the numerical simulation using LS-DYNA software was verified by the test results.The effects of different scaled distances,reinforcement ratios,concrete strengths,coating thicknesses and ranges of polyurea were studied.The results show that the polyurea coating can effectively enhance the anti-explosion performance of the girder.The top plate of middle chamber in specimen G forms an elliptical penetrating hole,while that in specimen PCG only shows a very slight local dent.The peak vertical displacement and residual displacement of PCG decrease by 74.8% and 73.7%,respectively,compared with those of specimen G.For the TNT explosion with small equivalent,the polyurea coating has a more significant protective effect on reducing the size of fracture.With the increase of TNT equivalent,the protective effect of polyurea on reducing girder displacement becomes more significant.The optimal reinforcement ratio,concrete strength,thickness and range of polyurea coating were also drawn.