Astrocytes have important neurosupportive functions in the brain that are altered in neurodegenerative diseases by unresolved mechanisms.We showed previously that astrocytes cultured from mice transgenic for human P30...Astrocytes have important neurosupportive functions in the brain that are altered in neurodegenerative diseases by unresolved mechanisms.We showed previously that astrocytes cultured from mice transgenic for human P301S-tau(P301S-mice)recapitulate the deficit in production and secretion of thrombospondin1 found in symptomatic P301S mouse brains,causing both reduced synapse formation and survival of cultured neurons.To further characterize how P301S-derived astrocytes differ from controls,we have compared the astrocyte-conditioned media of cultured astrocytes from postnatal day 7/8 P301S mice(P301S-astrocyte-conditioned media)versus controls(C57-astrocyte-conditioned media)using label-free liquid chromatography-mass spectrometry.We verified that thrombospondin1 secretion was significantly reduced in the P301S-astrocyte-conditioned media versus C57-astrocyte-conditioned media,demonstrating the robustness of the analysis.The most notable distinction was that~57%of the P301S-astrocyte-conditioned media-enriched proteins were cytoplasmic proteins linked to cellular metabolism that are not predicted to be secreted via classical or non-classical secretion pathways,whereas~88%of C57-astrocyte-conditioned media-enriched proteins comprised classically secreted proteins enriched in extracellular matrix components.These differences are associated with the finding that P301S-derived cultured astrocytes were smaller and in vivo appeared less mature in the cortex of P301S mice.The unconventional secretion pathway that P301S-astrocyte-conditioned media display shares similarities with several amyloid-β-exposed astrocyte-conditioned media,indicating that stimuli induced by tau and amyloid-βmay induce a common adverse response pathway.Altogether,members of this adverse pathway may serve as a potential set of biomarkers to aid the clinical diagnosis of Alzheimer’s disease and other tauopathies,while the list of reduced neurosupportive factors could indicate new approaches to enhance neuronal survival by factor supplementation in tauopathies.展开更多
BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicat...BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.展开更多
Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction d...Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.展开更多
BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in pati...BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.展开更多
Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic...Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.展开更多
BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs...BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs exhibit dynamic secretion patterns during lactation,influenced by maternal genetics and environ-mental factors.Their direct and indirect antimicrobial properties have garnered significant research interest.However,a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial,viral,and protozoal pathogens.METHODS A systematic search of PubMed,Scopus,Web of Science,and Cochrane Library focused on studies investigating natural and synthetic HMOs,their secretion dynamics,and antimicrobial properties.Studies involving human,animal,and in vitro models were included.Data on HMO composition,temporal secretion patterns,and mechanisms of antimicrobial action were extracted.Quality assess-ment was performed using validated tools appropriate for study design.RESULTS A total of 44 studies were included,encompassing human,animal,and in vitro research.HMOs exhibited dynamic secretion patterns,with 2′-fucosyllactose(2′-FL)and lacto-N-tetraose peaking in early lactation and declining over time,while 3-fucosyllactose(3-FL)increased during later stages.HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition,biofilm disruption,and enzymatic activity impairment.Synthetic HMOs,including bioengineered 2′-FL and 3-FL,were structurally and functionally comparable to natural HMOs,effectively inhibiting pathogens such as Pseudomonas aeruginosa,Escherichia coli,and Campylobacter jejuni.Additionally,HMOs exhibited synergistic effects with antibiotics,enhancing their efficacy against resistant pathogens.CONCLUSION HMOs are vital in antimicrobial defense,supporting infant health by targeting various pathogens.Both natural and synthetic HMOs hold significant potential for therapeutic applications,particularly in infant nutrition and as adjuncts to antibiotics.Further research,including clinical trials,is essential to address gaps in knowledge,validate findings,and explore the broader applicability of HMOs in improving maternal and neonatal health.展开更多
Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.H...Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.展开更多
High-risk human papillomavirus(HPV)replication requires deregulation of host DNA damage response(DDR)and inflammatory pathways.DNA topoisomerase 2β(Top2β)was previously shown to promote HPV replication.We investigat...High-risk human papillomavirus(HPV)replication requires deregulation of host DNA damage response(DDR)and inflammatory pathways.DNA topoisomerase 2β(Top2β)was previously shown to promote HPV replication.We investigated whether its paralog Top2α protein acts similarly to the virus.Elevated levels of Top2α are consistently observed in cervical intraepithelial lesions and the related carcinomas,as well as in HPV-positive cell lines.Silencing Top2α with shRNA severely suppresses HPV genome maintenance and amplification,but in a DDR-independent manner.Instead,Top2α facilitates secretion of interleukin(IL)-6 and IL-8,which are necessary for HPV replication.Mechanistically,this manipulation is regulated by toll-like receptor 4(TLR4).Top2α binds to the TLR4 promoter to transcriptionally induce TLR4 expression.Blockade of TLR4 signaling by the specific inhibitor TAK-242 significantly reduces the secreted IL-6/IL-8 levels and HPV replication.Overall,our results reveal a novel role of Top2α to shape the inflammatory microenvironment that benefits HPV replication,making it a promising therapeutic target for HPV-associated diseases.展开更多
The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies h...The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies have documented the residues of ARGs in soils and crops,but little is known about who drives the proliferation of ARGs in farming systems and what their underlying mechanisms are.Herein,we explored the occurrence and proliferating behavior of ARGs in soil-crop environments in terms of root secretions and plant volatiles.This review highlighted that plant root secretions and volatile organic compounds(VOCs)served as key substances mediating the development of antibiotic resistance in the soil-crop system.Still,there is controversy here as to plant root secretions promote the ARGs proliferation or inhibit.Some studies indicated that root secretions can suppress the colonization of ARGs,mainly attributed by the production of bluntedmetabolic enzymes and blocking of cellular exocytosis systems.Whereas the others have evidenced that root secretions can promote ARGs proliferation,primarily by altering the structure of microbial communities to influence species interactions and thus indirectly affect the proliferation of ARGs.Also,VOCs can act as molecular signals to convey antibiotic resistance information to their neighbors,which in turn drive the up-regulation of ARGs expression.Even so,the mechanism by which VOC-driven antibiotic resistance acquisition and proliferation need to be further probed.Overall,this review contributed to the development of products and technologies to impede the ARGs proliferation in agricultural environment.展开更多
The oral secretions of insect herbivores are complex mixtures of organic and inorganic solutes and enzymes that are deposited onto plant tissues during the feeding process.Some specific components of insect oral secre...The oral secretions of insect herbivores are complex mixtures of organic and inorganic solutes and enzymes that are deposited onto plant tissues during the feeding process.Some specific components of insect oral secretions have been shown to confer important functions in mediating plant–insect interactions at the molecular level.In this review,we examined the biochemical studies of insect oral secretions to summarize the current knowledge of their compositions.We then moved beyond the functional studies of components of oral secretions,and focused on the literature that pinpointed specific molecular targets of these compounds.Finally,we highlighted the investigations of oral secretion components in the context of insect physiology,which shed light on the potential evolutionary trajectory of these multi-functional molecules.展开更多
Outer-surface functionalized solid-state nanochannels have emerged as a new powerful tool for labelfree and sensitive detection of biotargets,owing to the unique advantages,such as the target's size is not limited...Outer-surface functionalized solid-state nanochannels have emerged as a new powerful tool for labelfree and sensitive detection of biotargets,owing to the unique advantages,such as the target's size is not limited by the nanochannel size,probes on the outer surface are easier to modify and characterize.Despite the advancements,the current outer-surface functionalized nanochannels can only achieve single target detection,which is insufficient for understanding disease pathogenesis and clinical diagnosis.Herein,we develop an ordered mesoporous carbon-silicon/anodic aluminum oxide hybrid membrane(MCS/AAO)with outer surface probes for in situ detecting living cells released secretions with a wide size range(from nano-scale to micron-scale).Due to asymmetric nanochannel structure and charge distribution,the hybrid membrane exhibits cation selectivity and a high ionic current rectification value of 29.21.By taking advantage of this mechanism,different cell secretions can be selectively and sensitively detected through replacing the modified aptamers on the outer surface of hybrid membrane.ATP(adenosine triphosphate),VEGF(vascular endothelial growth factor),and HepG2-MVs(micro vesicles)are chosen as model secretions representing different sizes.The detection limits are 0.64 fmol/L for ATP,3.31fg/m L for VEGF,and 5.37×10^(4) particles/m L for HepG2-MVs,which was over 10-fold higher than that of commercial assay kits.In addition,the prepared hybrid membrane has exceptional mechanical stability,the detection interface could be regenerated at least 5 times.This work provides a promising platform for in situ detection of cell secretions with different types and sizes by one sensing device and facilitates the clinical diagnosis of secretion-related diseases.展开更多
Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were f...Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were found toxic to mice with the intraperitoneal LD 50 of 11 5?mg/kg,18 8?mg/kg,and 264?mg/kg,respectively.No acute lethal toxicities were observed for the skin secretions of Rana nigromaculata,Rana guentheri and Rana limnocharis in a dose up to 500?mg/kg.The lethal toxicities of the skin secretions of T verrucosus and B maxima to mice are in the same grade as those of Viperidae snake venoms.The toxic components in T verrucosus and B maxima skin secretions are the proteins with molecular weights ranging from 3 to 60?kDa.All the skin secretions had both proteolytic activity and trypsin inhibitory activity.The skin secretions from T verrucosus , B maxima and B andrewsi also displayed wide spectrum antimicrobial activity.On the other hand,the skin secretions from B andrewsi and B maxima showed cytotoxicity on human cancer cells.All the six samples had not significant effects on mammalian blood coagulation system.Phospholipase A 2 activity was only found in the skin secretions of T verrucosus .None of these skin secretions showed acetylcholine esterase activity.展开更多
基金MGS from the Alzheimer Society(#384,AS-PG-17-026,Alzheimer’s Research UK(ART-PG2011-20 and ARUK-EXT2015B-2)the BBSRC(BB/T509085/1)+1 种基金The Fondation Recherche Alzheimer(G112606)the Scholl Foundation,and to MGS and AMT from the National Center for the Replacement,Refinement,&Reduction of Animals in Research(NC3R)(#NC/L000741/1).
文摘Astrocytes have important neurosupportive functions in the brain that are altered in neurodegenerative diseases by unresolved mechanisms.We showed previously that astrocytes cultured from mice transgenic for human P301S-tau(P301S-mice)recapitulate the deficit in production and secretion of thrombospondin1 found in symptomatic P301S mouse brains,causing both reduced synapse formation and survival of cultured neurons.To further characterize how P301S-derived astrocytes differ from controls,we have compared the astrocyte-conditioned media of cultured astrocytes from postnatal day 7/8 P301S mice(P301S-astrocyte-conditioned media)versus controls(C57-astrocyte-conditioned media)using label-free liquid chromatography-mass spectrometry.We verified that thrombospondin1 secretion was significantly reduced in the P301S-astrocyte-conditioned media versus C57-astrocyte-conditioned media,demonstrating the robustness of the analysis.The most notable distinction was that~57%of the P301S-astrocyte-conditioned media-enriched proteins were cytoplasmic proteins linked to cellular metabolism that are not predicted to be secreted via classical or non-classical secretion pathways,whereas~88%of C57-astrocyte-conditioned media-enriched proteins comprised classically secreted proteins enriched in extracellular matrix components.These differences are associated with the finding that P301S-derived cultured astrocytes were smaller and in vivo appeared less mature in the cortex of P301S mice.The unconventional secretion pathway that P301S-astrocyte-conditioned media display shares similarities with several amyloid-β-exposed astrocyte-conditioned media,indicating that stimuli induced by tau and amyloid-βmay induce a common adverse response pathway.Altogether,members of this adverse pathway may serve as a potential set of biomarkers to aid the clinical diagnosis of Alzheimer’s disease and other tauopathies,while the list of reduced neurosupportive factors could indicate new approaches to enhance neuronal survival by factor supplementation in tauopathies.
文摘BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.
基金supported by the National Natural Science Foundation of China(81673680)the Fundamental Research Funds for the Central Public Welfare Research Institutes(YZX-202306).
文摘Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.
基金Supported by National Natural Science Foundation of China(General Program),No.82073909Four‘Batches’Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province,No.2023XM022The Shanxi Provincial Central Leading Local Science and Technology Development Fund Project,No.YDZJSX2022A059 and No.YDZJSX20231A059。
文摘BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.
基金supported by the National Natural Science Foundation of China(32401919)the Department of Science and Technology of Henan Province(242102111126).
文摘Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.
文摘BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs exhibit dynamic secretion patterns during lactation,influenced by maternal genetics and environ-mental factors.Their direct and indirect antimicrobial properties have garnered significant research interest.However,a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial,viral,and protozoal pathogens.METHODS A systematic search of PubMed,Scopus,Web of Science,and Cochrane Library focused on studies investigating natural and synthetic HMOs,their secretion dynamics,and antimicrobial properties.Studies involving human,animal,and in vitro models were included.Data on HMO composition,temporal secretion patterns,and mechanisms of antimicrobial action were extracted.Quality assess-ment was performed using validated tools appropriate for study design.RESULTS A total of 44 studies were included,encompassing human,animal,and in vitro research.HMOs exhibited dynamic secretion patterns,with 2′-fucosyllactose(2′-FL)and lacto-N-tetraose peaking in early lactation and declining over time,while 3-fucosyllactose(3-FL)increased during later stages.HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition,biofilm disruption,and enzymatic activity impairment.Synthetic HMOs,including bioengineered 2′-FL and 3-FL,were structurally and functionally comparable to natural HMOs,effectively inhibiting pathogens such as Pseudomonas aeruginosa,Escherichia coli,and Campylobacter jejuni.Additionally,HMOs exhibited synergistic effects with antibiotics,enhancing their efficacy against resistant pathogens.CONCLUSION HMOs are vital in antimicrobial defense,supporting infant health by targeting various pathogens.Both natural and synthetic HMOs hold significant potential for therapeutic applications,particularly in infant nutrition and as adjuncts to antibiotics.Further research,including clinical trials,is essential to address gaps in knowledge,validate findings,and explore the broader applicability of HMOs in improving maternal and neonatal health.
基金the financial support from the National Key Research and Development Program of China(No.2023YFD1701100)the National Natural Science Foundation of China(No.32072450)+2 种基金the National Science Fund for Distinguished Young Scholars of Guangdong Province(No.2021B1515020107)the Opening Foundation of Hubei Key Laboratory of Novel Reactor and Green Chemical Technology(No.NRG202306)the Opening Foundation of Guangdong Province Key Laboratory of Microbial Signals and Disease Control(No.MSDC2023-19)。
文摘Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.
基金supported by CQMU Program for Youth Innovation in Future Medicine(172020320220090 W0072)to S.H.Chongqing Yuzhong District Basic Research and Frontier Exploration Project(20210128)to S.H.+1 种基金Natural Science Program of Chongqing Science and Technology Commission(2024NSCQ-KJFZZDX)to S.H.National Natural Science foundation of China(NSFC)Young Scientists Fund(82300970).
文摘High-risk human papillomavirus(HPV)replication requires deregulation of host DNA damage response(DDR)and inflammatory pathways.DNA topoisomerase 2β(Top2β)was previously shown to promote HPV replication.We investigated whether its paralog Top2α protein acts similarly to the virus.Elevated levels of Top2α are consistently observed in cervical intraepithelial lesions and the related carcinomas,as well as in HPV-positive cell lines.Silencing Top2α with shRNA severely suppresses HPV genome maintenance and amplification,but in a DDR-independent manner.Instead,Top2α facilitates secretion of interleukin(IL)-6 and IL-8,which are necessary for HPV replication.Mechanistically,this manipulation is regulated by toll-like receptor 4(TLR4).Top2α binds to the TLR4 promoter to transcriptionally induce TLR4 expression.Blockade of TLR4 signaling by the specific inhibitor TAK-242 significantly reduces the secreted IL-6/IL-8 levels and HPV replication.Overall,our results reveal a novel role of Top2α to shape the inflammatory microenvironment that benefits HPV replication,making it a promising therapeutic target for HPV-associated diseases.
基金supported by the Youth innovation Program of Chinese Academy of Agricultural Sciences(No.Y2023QC32)the foundation of Tianjin Natural Science Foundation(No.22JCQNJC01460)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(Agro-Environmental Protection Institute,Ministry of Agricultural and Rural Affairs)and the Youth Talent Project of Agro-Environmental Protection Institute,Ministry of Agricultural and Rural Affairs(Xu Yan).
文摘The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies have documented the residues of ARGs in soils and crops,but little is known about who drives the proliferation of ARGs in farming systems and what their underlying mechanisms are.Herein,we explored the occurrence and proliferating behavior of ARGs in soil-crop environments in terms of root secretions and plant volatiles.This review highlighted that plant root secretions and volatile organic compounds(VOCs)served as key substances mediating the development of antibiotic resistance in the soil-crop system.Still,there is controversy here as to plant root secretions promote the ARGs proliferation or inhibit.Some studies indicated that root secretions can suppress the colonization of ARGs,mainly attributed by the production of bluntedmetabolic enzymes and blocking of cellular exocytosis systems.Whereas the others have evidenced that root secretions can promote ARGs proliferation,primarily by altering the structure of microbial communities to influence species interactions and thus indirectly affect the proliferation of ARGs.Also,VOCs can act as molecular signals to convey antibiotic resistance information to their neighbors,which in turn drive the up-regulation of ARGs expression.Even so,the mechanism by which VOC-driven antibiotic resistance acquisition and proliferation need to be further probed.Overall,this review contributed to the development of products and technologies to impede the ARGs proliferation in agricultural environment.
基金received financial support from the Shenzhen Science and Technology Program,China(KQTD20180411143628272)the special funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District,China(PT202101-02)。
文摘The oral secretions of insect herbivores are complex mixtures of organic and inorganic solutes and enzymes that are deposited onto plant tissues during the feeding process.Some specific components of insect oral secretions have been shown to confer important functions in mediating plant–insect interactions at the molecular level.In this review,we examined the biochemical studies of insect oral secretions to summarize the current knowledge of their compositions.We then moved beyond the functional studies of components of oral secretions,and focused on the literature that pinpointed specific molecular targets of these compounds.Finally,we highlighted the investigations of oral secretion components in the context of insect physiology,which shed light on the potential evolutionary trajectory of these multi-functional molecules.
基金supported by National Natural Science Foundation of China(Nos.22374019,22174016)Start-up Research Fund of Southeast University(No.RF1028624037)。
文摘Outer-surface functionalized solid-state nanochannels have emerged as a new powerful tool for labelfree and sensitive detection of biotargets,owing to the unique advantages,such as the target's size is not limited by the nanochannel size,probes on the outer surface are easier to modify and characterize.Despite the advancements,the current outer-surface functionalized nanochannels can only achieve single target detection,which is insufficient for understanding disease pathogenesis and clinical diagnosis.Herein,we develop an ordered mesoporous carbon-silicon/anodic aluminum oxide hybrid membrane(MCS/AAO)with outer surface probes for in situ detecting living cells released secretions with a wide size range(from nano-scale to micron-scale).Due to asymmetric nanochannel structure and charge distribution,the hybrid membrane exhibits cation selectivity and a high ionic current rectification value of 29.21.By taking advantage of this mechanism,different cell secretions can be selectively and sensitively detected through replacing the modified aptamers on the outer surface of hybrid membrane.ATP(adenosine triphosphate),VEGF(vascular endothelial growth factor),and HepG2-MVs(micro vesicles)are chosen as model secretions representing different sizes.The detection limits are 0.64 fmol/L for ATP,3.31fg/m L for VEGF,and 5.37×10^(4) particles/m L for HepG2-MVs,which was over 10-fold higher than that of commercial assay kits.In addition,the prepared hybrid membrane has exceptional mechanical stability,the detection interface could be regenerated at least 5 times.This work provides a promising platform for in situ detection of cell secretions with different types and sizes by one sensing device and facilitates the clinical diagnosis of secretion-related diseases.
文摘Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were found toxic to mice with the intraperitoneal LD 50 of 11 5?mg/kg,18 8?mg/kg,and 264?mg/kg,respectively.No acute lethal toxicities were observed for the skin secretions of Rana nigromaculata,Rana guentheri and Rana limnocharis in a dose up to 500?mg/kg.The lethal toxicities of the skin secretions of T verrucosus and B maxima to mice are in the same grade as those of Viperidae snake venoms.The toxic components in T verrucosus and B maxima skin secretions are the proteins with molecular weights ranging from 3 to 60?kDa.All the skin secretions had both proteolytic activity and trypsin inhibitory activity.The skin secretions from T verrucosus , B maxima and B andrewsi also displayed wide spectrum antimicrobial activity.On the other hand,the skin secretions from B andrewsi and B maxima showed cytotoxicity on human cancer cells.All the six samples had not significant effects on mammalian blood coagulation system.Phospholipase A 2 activity was only found in the skin secretions of T verrucosus .None of these skin secretions showed acetylcholine esterase activity.
