The adequacy of language education largely depends on the favorable and unfavorable emotions that teachers and students experience throughout the education process.Simply said,emotional factors play a key role in impr...The adequacy of language education largely depends on the favorable and unfavorable emotions that teachers and students experience throughout the education process.Simply said,emotional factors play a key role in improving the quality of language teaching and learning.Furthermore,these emotional factors also promote the well-being of language teachers and learners and place them in a suitable mental condition.In view of the favorable impact of emotional factors on the mental health of language teachers and learners,many educational scholars around the world have studied these factors,their background,and their pedagogical consequences.Nonetheless,the majority of previous studies have employed traditional research methods in assessing these variables and their influences on language teachers’and learners’mental health.Because of the complex and dynamic quality of emotional factors,traditional research approaches often fail to evaluate these factors and their dynamic,non-linear connections with teachers’and learners’mental health and well-being.Accordingly,some novel research approaches are required to measure the dynamicity and complexity of emotional factors in language education settings.To address this call,the current state-of-the-art conceptual article seeks to provide new insights for investigating emotional factors and their potential impact on language teachers’and learners’mental states.This study also intends to offer a comprehensive list of emerging methods that take into account the complex and dynamic nature of emotional variables.Finally,the study outlines the potential implications of this review for educational researchers.展开更多
Background: Traditional treatment of axillary odour is the surgical removal of skin and subcutaneous tissue along the edge of the axillary hair in a fusiform shape, which requires the restriction of upper limb activit...Background: Traditional treatment of axillary odour is the surgical removal of skin and subcutaneous tissue along the edge of the axillary hair in a fusiform shape, which requires the restriction of upper limb activity, has large scars and a high recurrence rate. Minimally invasive methods have developed in recent years. The subcutaneous trimming method with small incision reduces the incision compared to traditional incision, but still requires skin incision, which does not achieve true, minimally invasive treatment. Simple negative pressure suction is difficult to destroy the sweat glands and sebaceous glands in the dermis layer. Thus, we hypothesized that combination of three minimally invasive methods might be more effective. Objective: To explore the clinical effect of combined treatment of axillary osmidrosis by three minimally invasive methods of microwave, scraping & suction and scratching. Methods: From October 2015 to October 2020, 80 patients with underarm odor were enrolled and lacal swelling anesthetic was applied. Microwave was used to treat sweat glands and sebaceous glands in the dermis following the pores. The curettage-aspiration was used to scrape and suck the apocrine sweat glands in the subcutaneous fat layer and the junction between the subcutaneous fat and dermis. To achieve the purpose of minimally invasive and thorough treatment of underarm odor, the spoon scraped the remaining sweat gland tissue. Results: Among 80 patients on 160 sides, all cases (100.00%) were cured on 160 sides at 1 month post-operative follow-up, 75 cases (93.75%) were cured on 150 sides, 5 cases (6.25%) on 5 sides were ineffective at 6-month post-operative follow-up, 74 cases (92.50%) were cured on 148 sides, 6 cases (7.50%) on 5 sides were ineffective at 1-year post-operative follow-up. Complications occurred in 5 cases (6.25%) after operation: 2 cases (2.50%) with skin necrosis on 3 sides, 1 case (1.25%) with uneven skin on 2 sides, 1 case (1.25%) with axillary abscess on 2 sides, and 1 case (1.25%) with keloids on 2 sides. Conclusion: The combination of three minimally invasive methods of microwave, scraping & suction and scratching to treat underarm odor is simple operation, has high cure rate, quick postoperative recovery, and few complications. It is an effective method for minimally invasive and thorough treatment of underarm odor in clinic.展开更多
Chronic hepatitis B virus(HBV)infection can lead to advanced liver pathology.Here,we establish a transgenic murine model expressing a basic core promoter(BCP)-mutated HBV genome.Unlike previous studies on the wild-typ...Chronic hepatitis B virus(HBV)infection can lead to advanced liver pathology.Here,we establish a transgenic murine model expressing a basic core promoter(BCP)-mutated HBV genome.Unlike previous studies on the wild-type virus,the BCP-mutated HBV transgenic mice manifest chronic liver injury that culminates in cirrhosis and tumor development with age.Notably,agonistic anti-Fas treatment induces fulminant hepatitis in these mice even at a negligible dose.As the BCP mutant exhibits a striking increase in HBV core protein(HBc)expression,we posit that HBc is actively involved in hepatocellular injury.Accordingly,HBc interferes with Fis1-stimulated mitochondrial recruitment of Tre-2/Bub2/Cdc16 domain family member 15(TBC1D15).HBc may also inhibit multiple Rab GTPase-activating proteins,including Rab7-specific TBC1D15 and TBC1D5,by binding to their conserved catalytic domain.In cells under mitochondrial stress,HBc thus perturbs mitochondrial dynamics and prevents the recycling of damaged mitochondria.Moreover,sustained HBc expression causes lysosomal consumption via Rab7 hyperactivation,which further hampers late-stage autophagy and substantially increases apoptotic cell death.Finally,we show that adenovirally expressed HBc in a mouse model is directly cytopathic and causes profound liver injury,independent of antigen-specific immune clearance.These findings reveal an unexpected cytopathic role of HBc,making it a pivotal target for HBV-associated liver disease treatment.The BCP-mutated HBV transgenic mice also provide a valuable model for understanding chronic hepatitis B progression and for the assessment of therapeutic strategies.展开更多
The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importanc...The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future epidemics.Host non-coding RNAs(ncRNAs)display aberrations in the context of COVID-19.Specifically,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease progression.In this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long COVID.Furthermore,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment response.In addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel treatments.Through an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.展开更多
Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five ...Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five kinds of systematic quality characteristics,nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing.Then,from simplex to the multivariate system,the digital process capability diagnosis strategy was proposed by multivariate C_(pk)integrated Bootstrap-t.The C_(pk)of Ginkgo Folium extracts,granules,and tablets were discovered,which was 0.59,0.42,and 0.78,respectively,indicating a relatively weak process capability,especially in granulating.Furthermore,the quality traceability was discovered from unit to end-to-end analysis,which decreased from 2.17 to 1.73.This further proved that attention should be paid to granulating to improve the quality characteristic.In conclusion,this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.展开更多
Direct reprogramming of a variety of somatic cells with the transcription factors Oct4(also called Pou5f1),Sox2 with either Klf4 and Myc or Lin28 and Nanog generates the induced pluripotent stem cells(iPSCs)with marke...Direct reprogramming of a variety of somatic cells with the transcription factors Oct4(also called Pou5f1),Sox2 with either Klf4 and Myc or Lin28 and Nanog generates the induced pluripotent stem cells(iPSCs)with marker similarity to embryonic stem cells.However,the difference between iPSCs derived from different origins is unclear.In this study,we hypothesized that reprogrammed cells retain a“memory”of their origins and possess additional potential of related tissue differentiation.We reprogrammed primary mouse astrocytes via ectopic retroviral expression of OCT3/4,Sox2,Klf4 and Myc and found the iPSCs from mouse astrocytes expressed stem cell markers and formed teratomas in SCID mice containing derivatives of all three germ layers similar to mouse embryonic stem cells besides semblable morphologies.To test our hypothesis,we compared embryonic bodies(EBs)formation and neuronal differentiation between iPSCs from mouse embryonic fibroblasts(MEFsiPSCs)and iPSCs from mouse astrocytes(mAsiPSCs).We found that mAsiPSCs grew slower and possessed more potential for neuronal differentiation compared to MEFsiPSCs.Our results suggest that mAsiPSCs retain a“memory”of the central nervous system,which confers additional potential upon neuronal differentiation.展开更多
Colorectal cancer(CRC)is one of the most frequently occurring malignancy tumors with a high morbidity additionally,CRC patients may develop liver metastasis,which is the major cause of death.Despite significant advanc...Colorectal cancer(CRC)is one of the most frequently occurring malignancy tumors with a high morbidity additionally,CRC patients may develop liver metastasis,which is the major cause of death.Despite significant advances in diagnostic and therapeutic techniques,the survival rate of colorectal liver metastasis(CRLM)patients remains very low.CRLM,as a complex cascade reaction process involving multiple factors and procedures,has complex and diverse molecular mechanisms.In this review,we summarize the mechanisms/pathophysiology,diagnosis,treatment of CRLM.We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM,further improving the prognosis of CRLM patients.展开更多
Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPS...Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPSCs,reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.Methods:Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors(TFs)Foxg1,Sox2,and Brn2.The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.Results:Astrocyte-derived induced NPCs(AiNPCs)share high similarities,including the expression of NPC-specific genes,DNA methylation patterns,the ability to proliferate and differentiate,with the wild type NPCs.The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes.Interestingly,additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation,respectively.Conclusions:Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs.Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases.展开更多
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The...Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 is respiratory dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor expressed on cell membranes. Patients with Alzheimer’s disease (AD) are more susceptible to SARS-CoV-2 infection and prone to severe clinical outcomes. Recent studies have revealed some common risk fac-tors for AD and COVID-19. An understanding of the association between COVID-19 and AD and the potential related mechanisms may lead to the development of novel approaches to treating both diseases. In the present review, we first summarize the mechanisms by which SARS-CoV-2 invades the central nervous system (CNS) and then discuss the associations and potential shared key factors between COVID-19 and AD, with a focus on the ACE2 receptor, apolipo-protein E (APOE) genotype, age, and neuroinflammation.展开更多
Ecological semiotics belongs to the field of culture,and biological semiotics refers to biology.There are both similarities and differences between ecological semiotics(ecosemiotics)and biological semiotics(biosemioti...Ecological semiotics belongs to the field of culture,and biological semiotics refers to biology.There are both similarities and differences between ecological semiotics(ecosemiotics)and biological semiotics(biosemiotics)."Co-existence and co-prosperity"are the highest true meaning of human beings and nature.Faced with the increasingly serious ecological crisis,human beings,as the only semiotic animal that can reflect on sign activities,are ultimately responsible for other species and the entire ecological community.展开更多
基金supported by Nanjing Normal University’s New Liberal Arts Research and Reform Project in 2021.
文摘The adequacy of language education largely depends on the favorable and unfavorable emotions that teachers and students experience throughout the education process.Simply said,emotional factors play a key role in improving the quality of language teaching and learning.Furthermore,these emotional factors also promote the well-being of language teachers and learners and place them in a suitable mental condition.In view of the favorable impact of emotional factors on the mental health of language teachers and learners,many educational scholars around the world have studied these factors,their background,and their pedagogical consequences.Nonetheless,the majority of previous studies have employed traditional research methods in assessing these variables and their influences on language teachers’and learners’mental health.Because of the complex and dynamic quality of emotional factors,traditional research approaches often fail to evaluate these factors and their dynamic,non-linear connections with teachers’and learners’mental health and well-being.Accordingly,some novel research approaches are required to measure the dynamicity and complexity of emotional factors in language education settings.To address this call,the current state-of-the-art conceptual article seeks to provide new insights for investigating emotional factors and their potential impact on language teachers’and learners’mental states.This study also intends to offer a comprehensive list of emerging methods that take into account the complex and dynamic nature of emotional variables.Finally,the study outlines the potential implications of this review for educational researchers.
基金supported by the National Natural Science Foundation of China(21978325 and 22122807)Outstanding Youth Fund of the National Natural Science Foundation of China(22122807)+1 种基金Outstanding Youth Fund of Shandong Provincial Natural Science Foundation(ZR2020YQ17)Natural Science Foundation of Shandong Province(ZR2020KB006)。
文摘Background: Traditional treatment of axillary odour is the surgical removal of skin and subcutaneous tissue along the edge of the axillary hair in a fusiform shape, which requires the restriction of upper limb activity, has large scars and a high recurrence rate. Minimally invasive methods have developed in recent years. The subcutaneous trimming method with small incision reduces the incision compared to traditional incision, but still requires skin incision, which does not achieve true, minimally invasive treatment. Simple negative pressure suction is difficult to destroy the sweat glands and sebaceous glands in the dermis layer. Thus, we hypothesized that combination of three minimally invasive methods might be more effective. Objective: To explore the clinical effect of combined treatment of axillary osmidrosis by three minimally invasive methods of microwave, scraping & suction and scratching. Methods: From October 2015 to October 2020, 80 patients with underarm odor were enrolled and lacal swelling anesthetic was applied. Microwave was used to treat sweat glands and sebaceous glands in the dermis following the pores. The curettage-aspiration was used to scrape and suck the apocrine sweat glands in the subcutaneous fat layer and the junction between the subcutaneous fat and dermis. To achieve the purpose of minimally invasive and thorough treatment of underarm odor, the spoon scraped the remaining sweat gland tissue. Results: Among 80 patients on 160 sides, all cases (100.00%) were cured on 160 sides at 1 month post-operative follow-up, 75 cases (93.75%) were cured on 150 sides, 5 cases (6.25%) on 5 sides were ineffective at 6-month post-operative follow-up, 74 cases (92.50%) were cured on 148 sides, 6 cases (7.50%) on 5 sides were ineffective at 1-year post-operative follow-up. Complications occurred in 5 cases (6.25%) after operation: 2 cases (2.50%) with skin necrosis on 3 sides, 1 case (1.25%) with uneven skin on 2 sides, 1 case (1.25%) with axillary abscess on 2 sides, and 1 case (1.25%) with keloids on 2 sides. Conclusion: The combination of three minimally invasive methods of microwave, scraping & suction and scratching to treat underarm odor is simple operation, has high cure rate, quick postoperative recovery, and few complications. It is an effective method for minimally invasive and thorough treatment of underarm odor in clinic.
基金supported by the Shanghai Municipal Science and Technology Major Project(ZD2021CY001)the National Natural Science Foundation of China(82372233,82072279,81871647,and 82205055)the Innovation Fund for Medical Sciences from Chinese Academy of Medical Sciences(2019-I2M-5-040).
文摘Chronic hepatitis B virus(HBV)infection can lead to advanced liver pathology.Here,we establish a transgenic murine model expressing a basic core promoter(BCP)-mutated HBV genome.Unlike previous studies on the wild-type virus,the BCP-mutated HBV transgenic mice manifest chronic liver injury that culminates in cirrhosis and tumor development with age.Notably,agonistic anti-Fas treatment induces fulminant hepatitis in these mice even at a negligible dose.As the BCP mutant exhibits a striking increase in HBV core protein(HBc)expression,we posit that HBc is actively involved in hepatocellular injury.Accordingly,HBc interferes with Fis1-stimulated mitochondrial recruitment of Tre-2/Bub2/Cdc16 domain family member 15(TBC1D15).HBc may also inhibit multiple Rab GTPase-activating proteins,including Rab7-specific TBC1D15 and TBC1D5,by binding to their conserved catalytic domain.In cells under mitochondrial stress,HBc thus perturbs mitochondrial dynamics and prevents the recycling of damaged mitochondria.Moreover,sustained HBc expression causes lysosomal consumption via Rab7 hyperactivation,which further hampers late-stage autophagy and substantially increases apoptotic cell death.Finally,we show that adenovirally expressed HBc in a mouse model is directly cytopathic and causes profound liver injury,independent of antigen-specific immune clearance.These findings reveal an unexpected cytopathic role of HBc,making it a pivotal target for HBV-associated liver disease treatment.The BCP-mutated HBV transgenic mice also provide a valuable model for understanding chronic hepatitis B progression and for the assessment of therapeutic strategies.
基金supported by the National Programs for Brain Science and Brain-like Intelligence Technology of China(nos.2021ZD0200800 and 2021ZD0200700)National Key Research and Development Program(no.2021YFC0863700)+1 种基金Natural Science Foundation of Beijing Municipality of China(M23013)the National Natural Science Foundation of China(nos.82288101 and 82171514)。
文摘The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future epidemics.Host non-coding RNAs(ncRNAs)display aberrations in the context of COVID-19.Specifically,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease progression.In this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long COVID.Furthermore,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment response.In addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel treatments.Through an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.
基金co-National Outstanding Youth Science Fund Project of National Natural Science Foundation of China(Grant No.82022073,China)Major scientific and technological R&D projects in Jiangxi Province(Grant No.20203ABC28W018,China)National Key Research and Development Program of China(Grant No.2018YFC1706900,China)。
文摘Smart manufacturing still remains critical challenges for pharmaceutical manufacturing.Here,an original data-driven engineering framework was proposed to tackle the challenges.Firstly,from sporadic indicators to five kinds of systematic quality characteristics,nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing.Then,from simplex to the multivariate system,the digital process capability diagnosis strategy was proposed by multivariate C_(pk)integrated Bootstrap-t.The C_(pk)of Ginkgo Folium extracts,granules,and tablets were discovered,which was 0.59,0.42,and 0.78,respectively,indicating a relatively weak process capability,especially in granulating.Furthermore,the quality traceability was discovered from unit to end-to-end analysis,which decreased from 2.17 to 1.73.This further proved that attention should be paid to granulating to improve the quality characteristic.In conclusion,this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.
基金the National Institutes of Health:R01 NS 41858-01,R01 NS 061642-01,R21 MH 083525-01,P01 NS043985,and P20 RR15635-01(JZ)the State of Nebraska,DHHS-LB606(JZ),Stem Cell-2010-10(SD)National Natural Science Foundation of China(Grant No.81028007)(JZ).
文摘Direct reprogramming of a variety of somatic cells with the transcription factors Oct4(also called Pou5f1),Sox2 with either Klf4 and Myc or Lin28 and Nanog generates the induced pluripotent stem cells(iPSCs)with marker similarity to embryonic stem cells.However,the difference between iPSCs derived from different origins is unclear.In this study,we hypothesized that reprogrammed cells retain a“memory”of their origins and possess additional potential of related tissue differentiation.We reprogrammed primary mouse astrocytes via ectopic retroviral expression of OCT3/4,Sox2,Klf4 and Myc and found the iPSCs from mouse astrocytes expressed stem cell markers and formed teratomas in SCID mice containing derivatives of all three germ layers similar to mouse embryonic stem cells besides semblable morphologies.To test our hypothesis,we compared embryonic bodies(EBs)formation and neuronal differentiation between iPSCs from mouse embryonic fibroblasts(MEFsiPSCs)and iPSCs from mouse astrocytes(mAsiPSCs).We found that mAsiPSCs grew slower and possessed more potential for neuronal differentiation compared to MEFsiPSCs.Our results suggest that mAsiPSCs retain a“memory”of the central nervous system,which confers additional potential upon neuronal differentiation.
基金the Natural Science Foundation of China(81773293,81873640,81970569,82000756)the Key Project of Science and Technology Program of Hunan Provincial Science and Technology Department(2015GK3117,2017WK2063).
文摘Colorectal cancer(CRC)is one of the most frequently occurring malignancy tumors with a high morbidity additionally,CRC patients may develop liver metastasis,which is the major cause of death.Despite significant advances in diagnostic and therapeutic techniques,the survival rate of colorectal liver metastasis(CRLM)patients remains very low.CRLM,as a complex cascade reaction process involving multiple factors and procedures,has complex and diverse molecular mechanisms.In this review,we summarize the mechanisms/pathophysiology,diagnosis,treatment of CRLM.We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM,further improving the prognosis of CRLM patients.
基金This work was supported in part by research grants from the National Basic Research Program of China(973 ProgramGrant No.2014CB965001 to JZ)Innovative Research Groups of the National Natural Science Foundation of China(#81221001 to JZ)+2 种基金Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China(#81329002 to JZ)the National Institutes of Health:2R56NS041858-15A1(JZ),1R01NS097195-01(JZ),and R03 NS094071-01(YH)the State of Nebraska,DHHS-LB606 Stem Cell 2009-10 to JZ.
文摘Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPSCs,reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.Methods:Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors(TFs)Foxg1,Sox2,and Brn2.The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.Results:Astrocyte-derived induced NPCs(AiNPCs)share high similarities,including the expression of NPC-specific genes,DNA methylation patterns,the ability to proliferate and differentiate,with the wild type NPCs.The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes.Interestingly,additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation,respectively.Conclusions:Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs.Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases.
基金the National Natural Science Foundation of China(81671181)the Project funded by China Postdoctoral Science Foundation(2022M710848).
文摘Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), is a life-threatening disease, especially in elderly individuals and those with comorbidities. The predominant clinical manifestation of COVID-19 is respiratory dysfunction, while neurological presentations are increasingly being recognized. SARS-CoV-2 invades host cells primarily via attachment of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor expressed on cell membranes. Patients with Alzheimer’s disease (AD) are more susceptible to SARS-CoV-2 infection and prone to severe clinical outcomes. Recent studies have revealed some common risk fac-tors for AD and COVID-19. An understanding of the association between COVID-19 and AD and the potential related mechanisms may lead to the development of novel approaches to treating both diseases. In the present review, we first summarize the mechanisms by which SARS-CoV-2 invades the central nervous system (CNS) and then discuss the associations and potential shared key factors between COVID-19 and AD, with a focus on the ACE2 receptor, apolipo-protein E (APOE) genotype, age, and neuroinflammation.
文摘Ecological semiotics belongs to the field of culture,and biological semiotics refers to biology.There are both similarities and differences between ecological semiotics(ecosemiotics)and biological semiotics(biosemiotics)."Co-existence and co-prosperity"are the highest true meaning of human beings and nature.Faced with the increasingly serious ecological crisis,human beings,as the only semiotic animal that can reflect on sign activities,are ultimately responsible for other species and the entire ecological community.