Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due t...Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis.Here,we investigate the pathological mechanism and propose a potential treatment method for HO.Immunofluorescence assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)mice.Single-cell RNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon cells.Single-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during HO.Moreover,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO.These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.展开更多
Objective:Applying Traditional Chinese Medicine(TCM)network pharmacology and molecular docking technology to explore the mechanism of anti-coronary virus pneumonia(Corona Virus Disease 2019,COVID-19)of Compound Qinlan...Objective:Applying Traditional Chinese Medicine(TCM)network pharmacology and molecular docking technology to explore the mechanism of anti-coronary virus pneumonia(Corona Virus Disease 2019,COVID-19)of Compound Qinlan oral liquid.Methods:Traditional Chinese Medicines Integrated Database(TCMID),Traditional Chinese Medicine Systems Pharmacology(TCMSP),OMIM,GeneCards,String and others online databases were used for building a series of networks,and selecting the core targets and analyzing the signal pathways.Finally,Discovery Studio 2016 software was used to conduct molecular docking of the main compounds(Chinese Medicine Legal Quality Control Compound)of Compound Qinlan oral liquid with key targets ACE2,3CLpro,etc.Results:the results showed that Compound Qinlan oral liquid has specific effects in lung,heart and stomach diseases.The Compound Qinlan oral liquid compound-pneumonia target network contained 98 compounds and 184 corresponding targets,and the core targets involved INS,TP53,IL6,VEGFA,ALB and JUN.GO(GeneOntology)function enrichment analysis yielded 653 GO entries,and KEGG(KyotoEncyclopedia of Genes and Genomes)enrichment screening yielded 112 related pathways,including hypoxia inducible factor-1(HIF-1)and Toll-like receptor(TLRs)signaling pathway related to pneumonia,as well as Influenza A signaling pathway and Hepatitis B signaling pathway related to microbial infection.The results of molecular docking show that Isochlorogenic acid C,Baicalein,etc have good binding capacity with ACE2,3CLpro,AKT1 and other proteins.Conclusion:In this paper,we preliminarily explored the potential therapeutic mechanism for Compound Qinlan oral liquid to against coronavirus pneumonia(COVID-19)and predicted the active ingredients.We hope that the results will help to further study on the active ingredients and mechanism of Compound Qinlan oral liquid for anti-COVID-19.展开更多
In June 2023,the 2022 global mpox(monkeypox)outbreak began to affect Guangdong Province,one of the first regions in China's Mainland to report mpox cases.By July 10,2023,93 mpox cases had been reported in Guangdon...In June 2023,the 2022 global mpox(monkeypox)outbreak began to affect Guangdong Province,one of the first regions in China's Mainland to report mpox cases.By July 10,2023,93 mpox cases had been reported in Guangdong Province.This study describes the epidemiological characteristics of these patients by collecting and analyzing data on demographics,sexual behavior,medical history,travel history,clinical symptoms,and diagnostic pathways and processes.The 93 mpox cases were all men aged 20-48 years,95.70%were men who have sex with men(MSM),and 48.39%were HIV-positive.A few cases were married(to women)or living with children.The rash was present in almost all cases(98.91%),with the most common sites being the genital and perianal areas(70.33%).Intimate sexual contact was suspected to be the main route of infection,with a median incubation period of 8.5 days(IQR 5.0–11.8).The number of cases increased rapidly,and most patients had no history of international travel,suggesting sustained community transmission within the MSM population in Guangdong Province.In addition,93.55%of cases were detected by medical institutions,and more than half of these patients had two or more hospital visits before being diagnosed as an mpox case,indicating that clinicians need further training to increase their sensitivity to mpox.Targeted interventions should prioritize MSM while remaining vigilant for transmission to other populations,such as women and children.展开更多
Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell...Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues,we systematically evaluate the interactions between the host and calcium phosphate(CaP)USNCs at the organism level.Combining single-cell mass cytometry,and magnetic luminex assay results,we identify dynamic immune responses to CaP USNCs at the single cell resolution.The innate immune is initially activated and followed by adaptive immune activation,as evidenced by dynamic immune cells proportions.Furthermore,using Nano Genome Atlas of multi-tissues,we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney.Moreover,based on the immunological response profiles,histological evaluation of major organs and local tissue,and a body-wide transcriptomics,we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection.Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.展开更多
Introduction:With the large-scale roll-out of the coronavirus disease 2019(COVID-19)booster vaccination effort(a vaccine dose given 6 months after completing primary vaccination)in China,we explore when and how China ...Introduction:With the large-scale roll-out of the coronavirus disease 2019(COVID-19)booster vaccination effort(a vaccine dose given 6 months after completing primary vaccination)in China,we explore when and how China could lift non-pharmacological interventions(NPIs)against COVID-19 in 2022.Methods:Using a modified susceptible-infectiousrecovered(SIR)mathematical model,we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province,China.Results:If the number of people entering from overseas recovers to 20%of the number in 2019,the epidemic in 2022 could be controlled at a low level by a containment(215 local cases)or suppression strategy(1,397 local cases).A mitigation strategy would lead to 21,722 local cases.A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong’s medical system.With 50%or 100%recovery of the 2019 level of travelers from overseas,the epidemic could also be controlled with containment or suppression,but enormous resources,including more hotel rooms for border quarantine,will be required.However,coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases.Discussion:With booster vaccinations,the number of travelers from overseas could increase slightly in 2022,but a suppression strategy would need to be maintained to ensure a controllable epidemic.展开更多
基金supported by the National Key R&D Program of China(2017YFA0104900)the National Natural Science Foundation of China(31830029,81501937 and 81522029)the Fundamental Research Funds for the Central Universities(K20200099).
文摘Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily life.Current therapies fail to promote functional tissue repair largely due to our limited understanding of HO pathogenesis.Here,we investigate the pathological mechanism and propose a potential treatment method for HO.Immunofluorescence assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)mice.Single-cell RNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon cells.Single-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during HO.Moreover,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of HO.These findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.
基金the Key Science and Technology Research Projects of Tibet Autonomous Region of China(XZ201801-GA-16)Special funds for guiding local scientific and technological development by the central government(2018ZYYD002).
文摘Objective:Applying Traditional Chinese Medicine(TCM)network pharmacology and molecular docking technology to explore the mechanism of anti-coronary virus pneumonia(Corona Virus Disease 2019,COVID-19)of Compound Qinlan oral liquid.Methods:Traditional Chinese Medicines Integrated Database(TCMID),Traditional Chinese Medicine Systems Pharmacology(TCMSP),OMIM,GeneCards,String and others online databases were used for building a series of networks,and selecting the core targets and analyzing the signal pathways.Finally,Discovery Studio 2016 software was used to conduct molecular docking of the main compounds(Chinese Medicine Legal Quality Control Compound)of Compound Qinlan oral liquid with key targets ACE2,3CLpro,etc.Results:the results showed that Compound Qinlan oral liquid has specific effects in lung,heart and stomach diseases.The Compound Qinlan oral liquid compound-pneumonia target network contained 98 compounds and 184 corresponding targets,and the core targets involved INS,TP53,IL6,VEGFA,ALB and JUN.GO(GeneOntology)function enrichment analysis yielded 653 GO entries,and KEGG(KyotoEncyclopedia of Genes and Genomes)enrichment screening yielded 112 related pathways,including hypoxia inducible factor-1(HIF-1)and Toll-like receptor(TLRs)signaling pathway related to pneumonia,as well as Influenza A signaling pathway and Hepatitis B signaling pathway related to microbial infection.The results of molecular docking show that Isochlorogenic acid C,Baicalein,etc have good binding capacity with ACE2,3CLpro,AKT1 and other proteins.Conclusion:In this paper,we preliminarily explored the potential therapeutic mechanism for Compound Qinlan oral liquid to against coronavirus pneumonia(COVID-19)and predicted the active ingredients.We hope that the results will help to further study on the active ingredients and mechanism of Compound Qinlan oral liquid for anti-COVID-19.
文摘In June 2023,the 2022 global mpox(monkeypox)outbreak began to affect Guangdong Province,one of the first regions in China's Mainland to report mpox cases.By July 10,2023,93 mpox cases had been reported in Guangdong Province.This study describes the epidemiological characteristics of these patients by collecting and analyzing data on demographics,sexual behavior,medical history,travel history,clinical symptoms,and diagnostic pathways and processes.The 93 mpox cases were all men aged 20-48 years,95.70%were men who have sex with men(MSM),and 48.39%were HIV-positive.A few cases were married(to women)or living with children.The rash was present in almost all cases(98.91%),with the most common sites being the genital and perianal areas(70.33%).Intimate sexual contact was suspected to be the main route of infection,with a median incubation period of 8.5 days(IQR 5.0–11.8).The number of cases increased rapidly,and most patients had no history of international travel,suggesting sustained community transmission within the MSM population in Guangdong Province.In addition,93.55%of cases were detected by medical institutions,and more than half of these patients had two or more hospital visits before being diagnosed as an mpox case,indicating that clinicians need further training to increase their sensitivity to mpox.Targeted interventions should prioritize MSM while remaining vigilant for transmission to other populations,such as women and children.
基金the National Key Research and Development Program of China(2018YFC1105100)NSFC grants(T2121004,81972099,82072463,81871764)+1 种基金Zhejiang Provincial Natural Science Foundation of China(LZ22H060002,LR20H060001)Fundamental Research Funds for the Central Universities.
文摘Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues,we systematically evaluate the interactions between the host and calcium phosphate(CaP)USNCs at the organism level.Combining single-cell mass cytometry,and magnetic luminex assay results,we identify dynamic immune responses to CaP USNCs at the single cell resolution.The innate immune is initially activated and followed by adaptive immune activation,as evidenced by dynamic immune cells proportions.Furthermore,using Nano Genome Atlas of multi-tissues,we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney.Moreover,based on the immunological response profiles,histological evaluation of major organs and local tissue,and a body-wide transcriptomics,we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection.Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.
基金Supported by National Key Research and Development Program of China(2021YFC2301604)Chinese Postdoctoral Science Foundation(2020T130020ZX)+1 种基金the Science and Technology Program of Guangzhou(202102021285)Innovation and Development Project of China Meteorological Administration(CXFZ2021J045).
文摘Introduction:With the large-scale roll-out of the coronavirus disease 2019(COVID-19)booster vaccination effort(a vaccine dose given 6 months after completing primary vaccination)in China,we explore when and how China could lift non-pharmacological interventions(NPIs)against COVID-19 in 2022.Methods:Using a modified susceptible-infectiousrecovered(SIR)mathematical model,we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province,China.Results:If the number of people entering from overseas recovers to 20%of the number in 2019,the epidemic in 2022 could be controlled at a low level by a containment(215 local cases)or suppression strategy(1,397 local cases).A mitigation strategy would lead to 21,722 local cases.A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong’s medical system.With 50%or 100%recovery of the 2019 level of travelers from overseas,the epidemic could also be controlled with containment or suppression,but enormous resources,including more hotel rooms for border quarantine,will be required.However,coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases.Discussion:With booster vaccinations,the number of travelers from overseas could increase slightly in 2022,but a suppression strategy would need to be maintained to ensure a controllable epidemic.
