Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandin...Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive.Here,we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell(MSC)function and regeneration.Interestingly,replenishment of cell aggregates-derived extracellular vesicles(CA-EVs)rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5.Importantly,in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice,suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration.Collectively,our findings provide insights into Golgi regulation in stem cell senescence and bone aging,which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.展开更多
Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies(PTT and PDT).Herein,Bi2...Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies(PTT and PDT).Herein,Bi2Se3@AIPH nanoparticles(NPs)are facilely developed to overcome these problems.Through a one-step method,free radical generator(AIPH)and phase transition material(lauric acid,LA,44-46°C)are encapsulated in hollow bismuth selenide nanoparticles(Bi2Se3 NPs).Under a single 808-nm laser irradiation at the tumor area,hyperthermia produced by Bi2Se3 not only directly leads to cell death,but also promotes AIPH release by melting LA and triggers free radical generation,which could further eradicate tumor cells in hypoxic environments.Moreover,Bi2Se3 with high X-ray attenuation coefficient endows the NPs with high computed tomography(CT)imaging capability,which is important for treating area determination.The results exhibit that Bi2Se3@AIPH NPs possesses 31.2%photothermal conversion efficiency for enhanced PTT,ideal free radical generation for oxygen-independent PDT,and 37.77 HU mL mg?1 X-ray attenuation coefficient for CT imaging with high quality.Most importantly,the tumor growth inhibition rate by synergistic PTT,PDT,and following immunotherapy is 99.6%,and even one tumor disappears completely,which demonstrates excellent cascaded synergistic effect of Bi2Se3@AIPH NPs for the tumor therapy.展开更多
BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The d...BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.展开更多
The detection of bacterial pathogen such as Staphylococcus aureus(S.aureus) is essential for the regulation of food hygiene and disease diagnosis.Herein,we developed a simple one-step fluorescence resonance energy tra...The detection of bacterial pathogen such as Staphylococcus aureus(S.aureus) is essential for the regulation of food hygiene and disease diagnosis.Herein,we developed a simple one-step fluorescence resonance energy transfer(FRET)-based sensor for specific and sensitive detection of S.aureus in food and serum samples,in which aptamer-modified quantum dots(aptamer-QDs) was employed as the energy donor and antibiotic of teicoplanin functionalized-gold nanoparticles(Teico-AuNPs) was chosen as the energy acceptor.Within 1 h,the FRET-based sensor showed a linear range of from 10 cfu/mL to 5 × 10^(8) cfu/mL,with the low limit of detection(LOD,2 cfu/mL) for S.aureus in buffer.When further applied to assay S.aureus in real samples,the FRET-based sensor showed good recoveries ranging from 84.5% to 110.0%,with relative standard derivations(RSDs) of 0.01%-0.44% and a LOD of 100 cfu/mL in milk,orange juice and human serum.展开更多
BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized...BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized.AIM To examine the association of serum HBsAg concentrations with HBV DNA levels and hepatic function parameters in patients with CHB.METHODS A total of 110 individuals with CHB admitted to Kunming Third People’s Hospital between January 2023 and January 2025 were enrolled as the observation group,whereas 70 age-and sex-matched healthy individuals served as the control group.Fasting peripheral venous blood(5 mL)was collected from all participants.Serum HBsAg and HBV DNA levels(in the observation group),along with hepatic function markers,including total bilirubin(TBIL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were measured in both groups.Pearson correlation analysis was used to assess the association between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels in patients with CHB.Receiver operating characteristic(ROC)curve analysis was conducted to determine optimal cutoff values of HBsAg for predicting high viral load(HBV DNA≥10^(5) IU/mL)and significant liver injury(ALT≥2×upper limit of normal[ULN]).RESULTS HBsAg levels differed significantly across CHB phases:Immune tolerance(IT)phase(4.62±1.51 lgIU/mL),immune clearance(IC)phase(3.84±1.16 lgIU/mL),low replication(LR)phase(2.99±0.66 lgIU/mL),and HBV e antigen-negative hepatitis(ENH)phase(3.40±0.69 lgIU/mL).Corresponding HBV DNA levels were highest in the IT phase(7.41±1.83 log copies/mL),followed by the IC phase(6.03±1.92 log copies/mL),ENH phase(3.89±1.23 log copies/mL),and LR phase(2.55±1.00 log copies/mL).All hepatic function parameters in patients with CHB were significantly elevated compared to the healthy controls.Pearson correlation analysis showed significant positive associations between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels.ROC analysis revealed that an HBsAg cutoff>4.09 lgIU/mL predicted HBV DNA≥105 IU/mL(high viral load)with 88.57%sensitivity,78.67%specificity,and an area under the curve(AUC)of 0.868(P<0.001),while a cutoff>4.07 lgIU/mL predicted ALT≥2×ULN(significant liver injury)with 69.70%sensitivity,90.91%specificity,and an AUC of 0.821(P<0.001).CONCLUSION Serum HBsAg,a noninvasive serological marker,holds significant clinical value in CHB management by aiding in the stratification of viral burden and the prediction of hepatic impairment.展开更多
Periodontitis is a prevalent and progressive detrimental disease characterized by chronic inflammation,and the immunopathological mechanisms are not yet fully understood.Mesenchymal stem cells(MSCs)play crucial roles ...Periodontitis is a prevalent and progressive detrimental disease characterized by chronic inflammation,and the immunopathological mechanisms are not yet fully understood.Mesenchymal stem cells(MSCs)play crucial roles as immunoregulators and maintain tissue homeostasis and regeneration,but their in vivo function in immunopathology and periodontal tissue deterioration is still unclear.Here,we utilized multiple transgenic mouse models to specifically mark,ablate and modulate Gli1^(+)cells,a critical and representative subset of MSCs in the periodontium,to explore their specific role in periodontal immunopathology.We revealed that Gli1^(+)cells,upon challenge with an inflammatory microenvironment,significantly induce rapid trafficking and aberrant activation of neutrophils,thus exacerbating alveolar bone destruction.Mechanistically,extracellular vesicles(EVs)released by Gli1^(+)cells act as crucial immune regulators in periodontal tissue,mediating the recruitment and activation of neutrophils through increased neutrophil generation of reactive oxygen species and stimulation of nuclear factor kappa-B signaling.Furthermore,we discovered that CXC motif chemokine ligand 1(CXCL1)is exposed on the surface of EVs derived from inflammation-challenged Gli1^(+)cells to prime aberrant neutrophils via the CXCL1-CXC motif chemokine receptor 2(CXCR2)axis.Importantly,specific inhibition of EV release from Gli1^(+)cells or pharmacological therapy with GANT61 ameliorates periodontal inflammation and alveolar bone loss.Collectively,our findings identify previously unrecognized roles of Gli1^(+)cells in orchestrating infiltration and promoting aberrant activation of neutrophils under inflammation,which provides pathological insights and potential therapeutic targets for periodontitis.展开更多
基金supported by grants from the National Natural Science Foundation of China(81930025,82201013,82371020,82370949,82100992)the Young Science and Technology Rising Star Project of Shaanxi Province(2023KJXX-027)the China Postdoctoral Science Foundation(BX20230485).
文摘Healthy aging is a common goal for humanity and society,and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration.However,the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive.Here,we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell(MSC)function and regeneration.Interestingly,replenishment of cell aggregates-derived extracellular vesicles(CA-EVs)rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5.Importantly,in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice,suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration.Collectively,our findings provide insights into Golgi regulation in stem cell senescence and bone aging,which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.
基金supported by the National Natural Science Foundation of China(Nos.51433004 and 51773096)Natural Science Foundation of Tianjin(No.17JCZDJC33500)PCSIRT(IRT1257).
文摘Inconvenient dual-laser irradiation and tumor hypoxic environment as well as limited judgment of treating region have impeded the development of combined photothermal and photodynamic therapies(PTT and PDT).Herein,Bi2Se3@AIPH nanoparticles(NPs)are facilely developed to overcome these problems.Through a one-step method,free radical generator(AIPH)and phase transition material(lauric acid,LA,44-46°C)are encapsulated in hollow bismuth selenide nanoparticles(Bi2Se3 NPs).Under a single 808-nm laser irradiation at the tumor area,hyperthermia produced by Bi2Se3 not only directly leads to cell death,but also promotes AIPH release by melting LA and triggers free radical generation,which could further eradicate tumor cells in hypoxic environments.Moreover,Bi2Se3 with high X-ray attenuation coefficient endows the NPs with high computed tomography(CT)imaging capability,which is important for treating area determination.The results exhibit that Bi2Se3@AIPH NPs possesses 31.2%photothermal conversion efficiency for enhanced PTT,ideal free radical generation for oxygen-independent PDT,and 37.77 HU mL mg?1 X-ray attenuation coefficient for CT imaging with high quality.Most importantly,the tumor growth inhibition rate by synergistic PTT,PDT,and following immunotherapy is 99.6%,and even one tumor disappears completely,which demonstrates excellent cascaded synergistic effect of Bi2Se3@AIPH NPs for the tumor therapy.
基金Supported by the Shanghai Municipal Commission of Health and Family Planning,No.PKJ2018-Y05.
文摘BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.
基金supported by the National Natural Science Foundation of China (Nos.21974110,21575118,21976145 and 31672605)Natural Science Foundation Project of Chongqing (No.CSTC2019jcyj-msxmX0406)。
文摘The detection of bacterial pathogen such as Staphylococcus aureus(S.aureus) is essential for the regulation of food hygiene and disease diagnosis.Herein,we developed a simple one-step fluorescence resonance energy transfer(FRET)-based sensor for specific and sensitive detection of S.aureus in food and serum samples,in which aptamer-modified quantum dots(aptamer-QDs) was employed as the energy donor and antibiotic of teicoplanin functionalized-gold nanoparticles(Teico-AuNPs) was chosen as the energy acceptor.Within 1 h,the FRET-based sensor showed a linear range of from 10 cfu/mL to 5 × 10^(8) cfu/mL,with the low limit of detection(LOD,2 cfu/mL) for S.aureus in buffer.When further applied to assay S.aureus in real samples,the FRET-based sensor showed good recoveries ranging from 84.5% to 110.0%,with relative standard derivations(RSDs) of 0.01%-0.44% and a LOD of 100 cfu/mL in milk,orange juice and human serum.
文摘BACKGROUND The relationship between hepatitis B surface antigen(HBsAg)concentrations,hepatitis B virus(HBV)DNA levels,and hepatic function in individuals with chronic hepatitis B(CHB)remains incompletely characterized.AIM To examine the association of serum HBsAg concentrations with HBV DNA levels and hepatic function parameters in patients with CHB.METHODS A total of 110 individuals with CHB admitted to Kunming Third People’s Hospital between January 2023 and January 2025 were enrolled as the observation group,whereas 70 age-and sex-matched healthy individuals served as the control group.Fasting peripheral venous blood(5 mL)was collected from all participants.Serum HBsAg and HBV DNA levels(in the observation group),along with hepatic function markers,including total bilirubin(TBIL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were measured in both groups.Pearson correlation analysis was used to assess the association between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels in patients with CHB.Receiver operating characteristic(ROC)curve analysis was conducted to determine optimal cutoff values of HBsAg for predicting high viral load(HBV DNA≥10^(5) IU/mL)and significant liver injury(ALT≥2×upper limit of normal[ULN]).RESULTS HBsAg levels differed significantly across CHB phases:Immune tolerance(IT)phase(4.62±1.51 lgIU/mL),immune clearance(IC)phase(3.84±1.16 lgIU/mL),low replication(LR)phase(2.99±0.66 lgIU/mL),and HBV e antigen-negative hepatitis(ENH)phase(3.40±0.69 lgIU/mL).Corresponding HBV DNA levels were highest in the IT phase(7.41±1.83 log copies/mL),followed by the IC phase(6.03±1.92 log copies/mL),ENH phase(3.89±1.23 log copies/mL),and LR phase(2.55±1.00 log copies/mL).All hepatic function parameters in patients with CHB were significantly elevated compared to the healthy controls.Pearson correlation analysis showed significant positive associations between serum HBsAg levels and HBV DNA,TBIL,AST,and ALT levels.ROC analysis revealed that an HBsAg cutoff>4.09 lgIU/mL predicted HBV DNA≥105 IU/mL(high viral load)with 88.57%sensitivity,78.67%specificity,and an area under the curve(AUC)of 0.868(P<0.001),while a cutoff>4.07 lgIU/mL predicted ALT≥2×ULN(significant liver injury)with 69.70%sensitivity,90.91%specificity,and an AUC of 0.821(P<0.001).CONCLUSION Serum HBsAg,a noninvasive serological marker,holds significant clinical value in CHB management by aiding in the stratification of viral burden and the prediction of hepatic impairment.
基金supported by grants from the National Key Research and Development Program of China(2022YFA1104400)the National Natural Science Foundation of China(82401201,82370949,82371020,82100969,and 82100992)+3 种基金the Young Science and Technology Rising Star Project of Shaanxi Province(2024ZC-KJXX-122)the China Postdoctoral Science Foundation(BX20230485)the“Rapid Response”Research Projects(2023KXKT017 and 2023KXKT090)the Shaanxi Provincial Health Research and Innovation Platform Construction Plan(2024PT-04).
文摘Periodontitis is a prevalent and progressive detrimental disease characterized by chronic inflammation,and the immunopathological mechanisms are not yet fully understood.Mesenchymal stem cells(MSCs)play crucial roles as immunoregulators and maintain tissue homeostasis and regeneration,but their in vivo function in immunopathology and periodontal tissue deterioration is still unclear.Here,we utilized multiple transgenic mouse models to specifically mark,ablate and modulate Gli1^(+)cells,a critical and representative subset of MSCs in the periodontium,to explore their specific role in periodontal immunopathology.We revealed that Gli1^(+)cells,upon challenge with an inflammatory microenvironment,significantly induce rapid trafficking and aberrant activation of neutrophils,thus exacerbating alveolar bone destruction.Mechanistically,extracellular vesicles(EVs)released by Gli1^(+)cells act as crucial immune regulators in periodontal tissue,mediating the recruitment and activation of neutrophils through increased neutrophil generation of reactive oxygen species and stimulation of nuclear factor kappa-B signaling.Furthermore,we discovered that CXC motif chemokine ligand 1(CXCL1)is exposed on the surface of EVs derived from inflammation-challenged Gli1^(+)cells to prime aberrant neutrophils via the CXCL1-CXC motif chemokine receptor 2(CXCR2)axis.Importantly,specific inhibition of EV release from Gli1^(+)cells or pharmacological therapy with GANT61 ameliorates periodontal inflammation and alveolar bone loss.Collectively,our findings identify previously unrecognized roles of Gli1^(+)cells in orchestrating infiltration and promoting aberrant activation of neutrophils under inflammation,which provides pathological insights and potential therapeutic targets for periodontitis.
