BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cas...BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.展开更多
Chinese yam(Dioscorea opposita Thunb.),as one of the medicinal and edible homologous plants,is rich in various nutrients and functional factors.In this study,Chinese yam fermented by Saccharomyces boulardii was perfor...Chinese yam(Dioscorea opposita Thunb.),as one of the medicinal and edible homologous plants,is rich in various nutrients and functional factors.In this study,Chinese yam fermented by Saccharomyces boulardii was performed to investigate its bioactive components and metabolic profile.And then,the main bioactive components and biological activities of fermented Chinese yam ethanol extract(FCYE)were evaluated.Results showed that there were 49 up-regulated metabolites and 52 down-regulated metabolites in fermented Chinese yam compared to unfermented Chinese yam.Besides,corresponding metabolic pathways analysis initially revealed that the distribution of bioactive substances was concentrated on alcoholsoluble small molecular substances.Ulteriorly,the total polyphenol content and the total flavonoid content in FCYE were significantly increased,and the corresponding antioxidant and immunomodulatory activities in vitro were also significantly enhanced.Our study provided a new reference for the comprehensive utilization of Chinese yam and laid a theoretical foundation for the development and application of natural probiotic-fermented products.展开更多
Objective Porphyromonas gingivalis(P.gingivalis)is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases,includin...Objective Porphyromonas gingivalis(P.gingivalis)is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases,including chronic kidney disease(CKD),but the roles and molecular mechanism of P.gingivalis in CKD pathogenesis are unclear.Methods In this study,an animal model of oral P.gingivalis administration and glomerular mesangial cells(GMCs)cocultured with M1-polarized macrophages and P.gingivalis supernatant were constructed.After seven weeks of P.gingivalis gavaged,peripheral blood was collected to detect the changes in renal function.By collecting the teeth and kidneys of mice,H&E staining and IHC were used to analyze the expression of periodontal inflammatory factors in mice,PAS staining was used to analyze glomerular lesions.The supernatant of macrophages was treated with 5%P.gingivalis supernatant.H&E staining,IHC,Western blot and RT-PCR were applied to analyze renal inflammatory factors,macrophage M1 polarization,NF-κB,NLRP3 and ferroptosis changes in vitro.Results We found that oral P.gingivalis administration induced CKD in mice.P.gingivalis supernatant induced macrophage polarization and inflammatory factor upregulation,which triggered the activation of the NF-κB/NLRP3 pathway and ferroptosis in GMCs.By inhibiting the NF-κB/NLRP3 pathway and ferroptosis in GMCs,cell viability and the inflammatory response were partially alleviated in vitro.Conclusion We demonstrated that P.gingivalis induced CKD in mice by triggering crosstalk between the NFκB/NLRP3 pathway and ferroptosis in GMCs.Overall,our study suggested that periodontitis can promote the pathogenesis of CKD in mice,which provides evidence of the importance of periodontitis therapy in the prevention and treatment of CKD.展开更多
Transformer-based stereo image super-resolution reconstruction(Stereo SR)methods have significantly improved image quality.However,existing methods have deficiencies in paying attention to detailed features and do not...Transformer-based stereo image super-resolution reconstruction(Stereo SR)methods have significantly improved image quality.However,existing methods have deficiencies in paying attention to detailed features and do not consider the offset of pixels along the epipolar lines in complementary views when integrating stereo information.To address these challenges,this paper introduces a novel epipolar line window attention stereo image super-resolution network(EWASSR).For detail feature restoration,we design a feature extractor based on Transformer and convolutional neural network(CNN),which consists of(shifted)window-based self-attention((S)W-MSA)and feature distillation and enhancement blocks(FDEB).This combination effectively solves the problem of global image perception and local feature attention and captures more discriminative high-frequency features of the image.Furthermore,to address the problem of offset of complementary pixels in stereo images,we propose an epipolar line window attention(EWA)mechanism,which divides windows along the epipolar direction to promote efficient matching of shifted pixels,even in pixel smooth areas.More accurate pixel matching can be achieved using adjacent pixels in the window as a reference.Extensive experiments demonstrate that our EWASSR can reconstruct more realistic detailed features.Comparative quantitative results show that in the experimental results of our EWASSR on the Middlebury and Flickr1024 data sets for 2×SR,compared with the recent network,the Peak signal-to-noise ratio(PSNR)increased by 0.37 dB and 0.34 dB,respectively.展开更多
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato...BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.展开更多
BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infe...BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.展开更多
De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephro...De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.展开更多
Cultivated strawberry(Fragaria×ananassa),a perennial herb belonging to the family Rosaceae,is a complex octoploid with high heterozygosity at most loci.However,there is no research on the haplotype of the octoplo...Cultivated strawberry(Fragaria×ananassa),a perennial herb belonging to the family Rosaceae,is a complex octoploid with high heterozygosity at most loci.However,there is no research on the haplotype of the octoploid strawberry genome.Here we aimed to obtain a high-quality genome of the cultivated strawberry cultivar,“Yanli”,using single molecule real-time sequencing and high-throughput chromosome conformation capture technology.The“Yanli”genome was 823 Mb in size,with a long terminal repeat assembly index of 14.99.The genome was phased into two haplotypes,Hap1(825 Mb with contig N50 of 26.70 Mb)and Hap2(808 Mb with contig N50 of 27.51 Mb).Using the combination of Hap1 and Hap2,we obtained for the first time a haplotype-resolved genome with 56 chromosomes for the cultivated octoploid strawberry.We identified a∼10 Mb inversion and translocation on chromosome 2-1.104957 and 102356 protein-coding genes were annotated in Hap1 and Hap2,respectively.Analysis of the genes related to the anthocyanin biosynthesis pathway revealed the structural diversity and complexity in the expression of the alleles in the octoploid F.×ananassa genome.In summary,we obtained a high-quality haplotype-resolved genome assembly of F.×ananassa,which will provide the foundation for investigating gene function and evolution of the genome of cultivated octoploid strawberry.展开更多
In recent years,microbial metabolomics,a new field that has attracted wide attention,provides a map of metabolic pathways and clarifies the interaction mechanism between microorganisms and hosts.Many microorganisms ar...In recent years,microbial metabolomics,a new field that has attracted wide attention,provides a map of metabolic pathways and clarifies the interaction mechanism between microorganisms and hosts.Many microorganisms are found in the human intestine,oral cavity,vagina,etc.Probiotics could maintain the good health of the host,while pathogens and an imbalance of bacterial flora lead to a series of diseases of the body and mind.Metabolomics is a science for qualitative and quantitative analysis of all metabolites in an organism or biological system,which could provide key information to understand the related metabolic pathways and associated changes.This approach analyzes the final products of cellular regulatory processes,the level of which can be regarded as the ultimate response of the biological system to genetic or environmental changes.Microbial metabolomics has been widely used in different research fields,such as microbial phenotypic classification,mutant screening,metabolic pathways,microbial metabolic engineering,fermentation engineering monitoring and optimization,microbial environmental pollution,and so on.However,there are only a few reviews on microbial metabolomics of probiotics and pathogens.This review summarizes the main methodologies,including sample preparation,identification of metabolites,data processing,and analysis.Recent applications in microbial metabolomics of probiotics and pathogens are also described.This paper first summarized the research progress and application of microbial metabolomics from two aspects:probiotics and pathogenic bacteria.Probiotics and pathogenic bacteria do not exist independently most of the time;hence,these were reviewed in the research field of coexistence of probiotics and pathogenic bacteria,which was subdivided into important microbial research fields closely related to human health,including the human gut,oral cavity,food,and nutrition-related microorganisms.Then,the main problems and trends associated with microbial metabolomics are discussed.展开更多
1. Objectives Ophiolites from the oceanic crust are important indicators for identifying tectonic suture zones. Recently, a continuous ophiolite belt was found near the Guola Mountain in the Nujiang tectonic belt. Due...1. Objectives Ophiolites from the oceanic crust are important indicators for identifying tectonic suture zones. Recently, a continuous ophiolite belt was found near the Guola Mountain in the Nujiang tectonic belt. Due to intensive hydrothermal alteration during tectonic evolution, clayey altered ophiolite with special engineering geological characteristics was formed, which has an extremely adverse impact on engineering stability. However, the adverse properties of clayey altered ophiolite are still not well understood in engineering practices(Zhang YS, et al., 2011).展开更多
MXenes are emerging transition metal carbides and nitrides-based 2D conductive materials.They have found wide applications in sensors due to their excellent valuable properties.This paper reviews the recent research s...MXenes are emerging transition metal carbides and nitrides-based 2D conductive materials.They have found wide applications in sensors due to their excellent valuable properties.This paper reviews the recent research status of MXene-based electrochemical(bio)sensors for detecting biomarkers,pesticides,and other aspects.The first part of this paper introduced the synthesis strategy and the effect of surface modification on various prop-erties of MXenes.The second part of this paper discussed the application of MXenes as electrode modifiers for detecting pesticides,environmental pollutants,and biomarkers such as glucose,hydrogen peroxide,etc.Hope this review will inspire more efforts toward research on MXene-based sensors to meet the growing requirements.展开更多
Leaves and f lowers are crucial for the growth and development of higher plants.In this study we identified a mutant with narrow leaf lets and early f lowering(nlef)in an ethyl methanesulfonate-mutagenized population ...Leaves and f lowers are crucial for the growth and development of higher plants.In this study we identified a mutant with narrow leaf lets and early f lowering(nlef)in an ethyl methanesulfonate-mutagenized population of woodland strawberry(Fragaria vesca)and aimed to identify the candidate gene.Genetic analysis revealed that a single recessive gene,nlef,controlled the mutant phenotype.We found that FvH4_1g25470,which encodes a putative DNA polymeraseαwith a polymerase and histidinol phosphatase domain(PHP),might be the candidate gene,using bulked segregant analysis with whole-genome sequencing,molecular markers,and cloning analyses.A splice donor site mutation(C to T)at the 5-end of the second intron led to an erroneous splice event that reduced the expression level of the full-length transcript of FvePHP in mutant plants.FvePHP was localized in the nucleus and was highly expressed in leaves.Silencing of FvePHP using the virus-induced gene silencing method resulted in partial developmental defects in strawberry leaves.Overexpression of the FvePHP gene can largely restore the mutant phenotype.The expression levels of FveSEP1,FveSEP3,FveAP1,FveFUL,and FveFT were higher in the mutants than those in‘Yellow Wonder’plants,probably contributing to the early f lowering phenotype in mutant plants.Our results indicate that mutation in FvePHP is associated with multiple developmental pathways.These results aid in understanding the role of DNA polymerase in strawberry development.展开更多
文摘BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.
基金supported by National Natural Science Foundation of China(32172211)the Natural Science Foundation of Henan Province for Outstanding Youth,China(202300410365)+2 种基金the National Key Research and Development Program of China(2022YFF1103300)the Program for Science and Technology Innovation Talents in Universities of Henan Province(22HASTIT037)the Technology Development(Cooperation)project of Zhengzhou University(20210442A,20210327A).
文摘Chinese yam(Dioscorea opposita Thunb.),as one of the medicinal and edible homologous plants,is rich in various nutrients and functional factors.In this study,Chinese yam fermented by Saccharomyces boulardii was performed to investigate its bioactive components and metabolic profile.And then,the main bioactive components and biological activities of fermented Chinese yam ethanol extract(FCYE)were evaluated.Results showed that there were 49 up-regulated metabolites and 52 down-regulated metabolites in fermented Chinese yam compared to unfermented Chinese yam.Besides,corresponding metabolic pathways analysis initially revealed that the distribution of bioactive substances was concentrated on alcoholsoluble small molecular substances.Ulteriorly,the total polyphenol content and the total flavonoid content in FCYE were significantly increased,and the corresponding antioxidant and immunomodulatory activities in vitro were also significantly enhanced.Our study provided a new reference for the comprehensive utilization of Chinese yam and laid a theoretical foundation for the development and application of natural probiotic-fermented products.
基金funded by the National Key Clinical Program on Orthodontics,the Nature Science Foundation of Shanghai(No.20ZR1443100 and No.21140904500)Shanghai Municipal Health Commission(No.202140504).
文摘Objective Porphyromonas gingivalis(P.gingivalis)is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases,including chronic kidney disease(CKD),but the roles and molecular mechanism of P.gingivalis in CKD pathogenesis are unclear.Methods In this study,an animal model of oral P.gingivalis administration and glomerular mesangial cells(GMCs)cocultured with M1-polarized macrophages and P.gingivalis supernatant were constructed.After seven weeks of P.gingivalis gavaged,peripheral blood was collected to detect the changes in renal function.By collecting the teeth and kidneys of mice,H&E staining and IHC were used to analyze the expression of periodontal inflammatory factors in mice,PAS staining was used to analyze glomerular lesions.The supernatant of macrophages was treated with 5%P.gingivalis supernatant.H&E staining,IHC,Western blot and RT-PCR were applied to analyze renal inflammatory factors,macrophage M1 polarization,NF-κB,NLRP3 and ferroptosis changes in vitro.Results We found that oral P.gingivalis administration induced CKD in mice.P.gingivalis supernatant induced macrophage polarization and inflammatory factor upregulation,which triggered the activation of the NF-κB/NLRP3 pathway and ferroptosis in GMCs.By inhibiting the NF-κB/NLRP3 pathway and ferroptosis in GMCs,cell viability and the inflammatory response were partially alleviated in vitro.Conclusion We demonstrated that P.gingivalis induced CKD in mice by triggering crosstalk between the NFκB/NLRP3 pathway and ferroptosis in GMCs.Overall,our study suggested that periodontitis can promote the pathogenesis of CKD in mice,which provides evidence of the importance of periodontitis therapy in the prevention and treatment of CKD.
基金This work was supported by Sichuan Science and Technology Program(2023YFG0262).
文摘Transformer-based stereo image super-resolution reconstruction(Stereo SR)methods have significantly improved image quality.However,existing methods have deficiencies in paying attention to detailed features and do not consider the offset of pixels along the epipolar lines in complementary views when integrating stereo information.To address these challenges,this paper introduces a novel epipolar line window attention stereo image super-resolution network(EWASSR).For detail feature restoration,we design a feature extractor based on Transformer and convolutional neural network(CNN),which consists of(shifted)window-based self-attention((S)W-MSA)and feature distillation and enhancement blocks(FDEB).This combination effectively solves the problem of global image perception and local feature attention and captures more discriminative high-frequency features of the image.Furthermore,to address the problem of offset of complementary pixels in stereo images,we propose an epipolar line window attention(EWA)mechanism,which divides windows along the epipolar direction to promote efficient matching of shifted pixels,even in pixel smooth areas.More accurate pixel matching can be achieved using adjacent pixels in the window as a reference.Extensive experiments demonstrate that our EWASSR can reconstruct more realistic detailed features.Comparative quantitative results show that in the experimental results of our EWASSR on the Middlebury and Flickr1024 data sets for 2×SR,compared with the recent network,the Peak signal-to-noise ratio(PSNR)increased by 0.37 dB and 0.34 dB,respectively.
文摘BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.
基金Supported by Collaborative Research Fund Scheme,University Grants Committee,No.C7154-20GFData Discovery for Health(D24H)Innovation and Technology Commission,AIR@InnoHK.
文摘BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.
基金financially supported by grants from the National Natural Science Foundation of China(82170873,81871095)the National Key R&D Program of China(2018YFC2000304)+1 种基金the Tsinghua Precision Medicine Foundation(10001020132)the Tsinghua University Spring Breeze Fund(20211080005)。
文摘De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.
基金This work was financially supported by National Natural Science Foundation of China(No.32130092,No.31872072)LiaoNing Revitalization Talents Pro-gram(No.XLYC1902069).
文摘Cultivated strawberry(Fragaria×ananassa),a perennial herb belonging to the family Rosaceae,is a complex octoploid with high heterozygosity at most loci.However,there is no research on the haplotype of the octoploid strawberry genome.Here we aimed to obtain a high-quality genome of the cultivated strawberry cultivar,“Yanli”,using single molecule real-time sequencing and high-throughput chromosome conformation capture technology.The“Yanli”genome was 823 Mb in size,with a long terminal repeat assembly index of 14.99.The genome was phased into two haplotypes,Hap1(825 Mb with contig N50 of 26.70 Mb)and Hap2(808 Mb with contig N50 of 27.51 Mb).Using the combination of Hap1 and Hap2,we obtained for the first time a haplotype-resolved genome with 56 chromosomes for the cultivated octoploid strawberry.We identified a∼10 Mb inversion and translocation on chromosome 2-1.104957 and 102356 protein-coding genes were annotated in Hap1 and Hap2,respectively.Analysis of the genes related to the anthocyanin biosynthesis pathway revealed the structural diversity and complexity in the expression of the alleles in the octoploid F.×ananassa genome.In summary,we obtained a high-quality haplotype-resolved genome assembly of F.×ananassa,which will provide the foundation for investigating gene function and evolution of the genome of cultivated octoploid strawberry.
基金This work was supported by the Science Foundation of Heilongjiang Administration of Traditional Chinese Medicine(No.ZHY18-021).
文摘In recent years,microbial metabolomics,a new field that has attracted wide attention,provides a map of metabolic pathways and clarifies the interaction mechanism between microorganisms and hosts.Many microorganisms are found in the human intestine,oral cavity,vagina,etc.Probiotics could maintain the good health of the host,while pathogens and an imbalance of bacterial flora lead to a series of diseases of the body and mind.Metabolomics is a science for qualitative and quantitative analysis of all metabolites in an organism or biological system,which could provide key information to understand the related metabolic pathways and associated changes.This approach analyzes the final products of cellular regulatory processes,the level of which can be regarded as the ultimate response of the biological system to genetic or environmental changes.Microbial metabolomics has been widely used in different research fields,such as microbial phenotypic classification,mutant screening,metabolic pathways,microbial metabolic engineering,fermentation engineering monitoring and optimization,microbial environmental pollution,and so on.However,there are only a few reviews on microbial metabolomics of probiotics and pathogens.This review summarizes the main methodologies,including sample preparation,identification of metabolites,data processing,and analysis.Recent applications in microbial metabolomics of probiotics and pathogens are also described.This paper first summarized the research progress and application of microbial metabolomics from two aspects:probiotics and pathogenic bacteria.Probiotics and pathogenic bacteria do not exist independently most of the time;hence,these were reviewed in the research field of coexistence of probiotics and pathogenic bacteria,which was subdivided into important microbial research fields closely related to human health,including the human gut,oral cavity,food,and nutrition-related microorganisms.Then,the main problems and trends associated with microbial metabolomics are discussed.
基金Supported by the National Natural Science Foundation of China (41941017)the Fundamental Research Funds for the Central Public Research Institutes (SK202109)。
文摘1. Objectives Ophiolites from the oceanic crust are important indicators for identifying tectonic suture zones. Recently, a continuous ophiolite belt was found near the Guola Mountain in the Nujiang tectonic belt. Due to intensive hydrothermal alteration during tectonic evolution, clayey altered ophiolite with special engineering geological characteristics was formed, which has an extremely adverse impact on engineering stability. However, the adverse properties of clayey altered ophiolite are still not well understood in engineering practices(Zhang YS, et al., 2011).
文摘MXenes are emerging transition metal carbides and nitrides-based 2D conductive materials.They have found wide applications in sensors due to their excellent valuable properties.This paper reviews the recent research status of MXene-based electrochemical(bio)sensors for detecting biomarkers,pesticides,and other aspects.The first part of this paper introduced the synthesis strategy and the effect of surface modification on various prop-erties of MXenes.The second part of this paper discussed the application of MXenes as electrode modifiers for detecting pesticides,environmental pollutants,and biomarkers such as glucose,hydrogen peroxide,etc.Hope this review will inspire more efforts toward research on MXene-based sensors to meet the growing requirements.
基金This work was finan-cially supported by Liao Ning Revitalization Talents Program(No.XLYC1902069).
文摘Leaves and f lowers are crucial for the growth and development of higher plants.In this study we identified a mutant with narrow leaf lets and early f lowering(nlef)in an ethyl methanesulfonate-mutagenized population of woodland strawberry(Fragaria vesca)and aimed to identify the candidate gene.Genetic analysis revealed that a single recessive gene,nlef,controlled the mutant phenotype.We found that FvH4_1g25470,which encodes a putative DNA polymeraseαwith a polymerase and histidinol phosphatase domain(PHP),might be the candidate gene,using bulked segregant analysis with whole-genome sequencing,molecular markers,and cloning analyses.A splice donor site mutation(C to T)at the 5-end of the second intron led to an erroneous splice event that reduced the expression level of the full-length transcript of FvePHP in mutant plants.FvePHP was localized in the nucleus and was highly expressed in leaves.Silencing of FvePHP using the virus-induced gene silencing method resulted in partial developmental defects in strawberry leaves.Overexpression of the FvePHP gene can largely restore the mutant phenotype.The expression levels of FveSEP1,FveSEP3,FveAP1,FveFUL,and FveFT were higher in the mutants than those in‘Yellow Wonder’plants,probably contributing to the early f lowering phenotype in mutant plants.Our results indicate that mutation in FvePHP is associated with multiple developmental pathways.These results aid in understanding the role of DNA polymerase in strawberry development.