Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparamet...Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.展开更多
In recent years,there has been a significant acceleration in the thinning,calving and retreat of the Pine Island Ice Shelf(PIIS).The basal channels,results of enhanced basal melting,have the potential to significantly...In recent years,there has been a significant acceleration in the thinning,calving and retreat of the Pine Island Ice Shelf(PIIS).The basal channels,results of enhanced basal melting,have the potential to significantly impact the stability of the PIIS.In this study,we used a variety of remote sensing data,including Landsat,REMA DEM,ICESat-1 and ICESat-2 satellite altimetry observations,and Ice Bridge airborne measurements,to study the spatiotemporal changes in the basal channels from 2003 to 2020 and basal melt rate from 2010 to 2017 of the PIIS under the Eulerian framework.We found that the basal channels are highly developed in the PIIS,with a total length exceeding 450 km.Most of the basal channels are ocean-sourced or groundingline-sourced basal channels,caused by the rapid melting under the ice shelf or near the groundingline.A raised seabed prevented warm water intrusion into the eastern branch of the PIIS,resulting in a lower basal melt rate in that area.In contrast,a deepsea trough facilitates warm seawater into the mainstream and the western branch of the PIIS,resulting in a higher basal melt rate in the main-stream,and the surface elevation changes above the basal channels of the mainstream and western branch are more significant.The El Ni?o event in 2015–2016 possibly slowed down the basal melting of the PIIS by modulating wind field,surface sea temperature and depth seawater temperature.Ocean and atmospheric changes were driven by El Ni?o,which can further explain and confirm the changes in the basal melting of the PIIS.展开更多
Multispecies forests have received increased scientific attention,driven by the hypothesis that biodiversity improves ecological resilience.However,a greater species diversity presents challenges for forest management...Multispecies forests have received increased scientific attention,driven by the hypothesis that biodiversity improves ecological resilience.However,a greater species diversity presents challenges for forest management and research.Our study aims to develop basal area growth models for tree species cohorts.The analysis is based on a dataset of 423 permanent plots(2,500 m^(2))located in temperate forests in Durango,Mexico.First,we define tree species cohorts based on individual and neighborhood-based variables using a combination of principal component and cluster analyses.Then,we estimate the basal area increment of each cohort through the generalized additive model to describe the effect of tree size,competition,stand density and site quality.The principal component and cluster analyses assign a total of 37 tree species to eight cohorts that differed primarily with regard to the distribution of tree size and vertical position within the community.The generalized additive models provide satisfactory estimates of tree growth for the species cohorts,explaining between 19 and 53 percent of the total variation of basal area increment,and highlight the following results:i)most cohorts show a"rise-and-fall"effect of tree size on tree growth;ii)surprisingly,the competition index"basal area of larger trees"had showed a positive effect in four of the eight cohorts;iii)stand density had a negative effect on basal area increment,though the effect was minor in medium-and high-density stands,and iv)basal area growth was positively correlated with site quality except for an oak cohort.The developed species cohorts and growth models provide insight into their particular ecological features and growth patterns that may support the development of sustainable management strategies for temperate multispecies forests.展开更多
Objective:To evaluate the efficacy and safety of different basal insulins in the treatment of type 2 diabetes mellitus(T2DM).Methods:The current research progress on different basal insulins was evaluated,with efficac...Objective:To evaluate the efficacy and safety of different basal insulins in the treatment of type 2 diabetes mellitus(T2DM).Methods:The current research progress on different basal insulins was evaluated,with efficacy indicators including fasting plasma glucose(FPG)and glycated hemoglobin(HbAic),and safety indicators focusing mainly on weight change and the incidence of hypoglycemia.Results:Several different basal insulins showed similar metabolic control effects in terms of fasting plasma glucose and glycated hemoglobin.However,the risk of hypoglycemia was lower with insulin glargine 300(Glar-300),insulin degludec 100(Deg-100),and insulin degludec 200(Deg-200)compared to insulin glargine 100(Glar-100).Additionally,Glar-300 had the least impact on weight.Conclusion:For the treatment of T2DM,different basal insulins have similar therapeutic effects,but there are differences in the incidence of hypoglycemic events and their impact on weight.Rational insulin selection and dosage adjustments should be made based on the different patient groups.展开更多
Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-...Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.展开更多
BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural...BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE: To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING: This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS: The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS: MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES: S100 protein and mRNA expression. RESULTS: MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION: MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.展开更多
Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studie...Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.展开更多
The basal channel is a detailed morphological feature of the ice shelf caused by uneven basal melting.This kind of specifically morphology is widely distributed in polar ice shelves.It is an important research object ...The basal channel is a detailed morphological feature of the ice shelf caused by uneven basal melting.This kind of specifically morphology is widely distributed in polar ice shelves.It is an important research object of sea-ice interaction and plays a vital role in studying the relationship between the ice sheet/ice shelf and global warming.In this paper,high-resolution remote sensing image and ice penetration data were combined to extract the basal channel of the Pine Island Ice Shelf.The depth variation of Pine Island Ice Shelf in the recent 20 years was analyzed and discussed by using ICESat-1,ICESat-2,and IceBridge data.Combined with relevant marine meteorological elements(sea surface temperature,surface melting days,circumpolar deep water and wind)to analyze the basal channel changes,the redistribution of ocean heat is considered to be the most important factor affecting the evolution and development of the basal channel.展开更多
BACKGROUND Basal cell carcinoma(BCC)is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential.It ideally affects sun-exposed skin of older patients with more ...BACKGROUND Basal cell carcinoma(BCC)is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential.It ideally affects sun-exposed skin of older patients with more propensity for the facial region.AIM To evaluate the different clinicopathological characteristics of the facial BCC and the efficacy and safety of diode laser for the treatment of these lesions.METHODS We retrospectively reviewed facial BCC lesions of<1.5 cm in diameter and subjected them to diode laser ablation during the period from September 2016 to August 2021 at Al-Ramadi Teaching Hospital,Ramadi City,Iraq.Data matching the age,gender,duration,site,and clinical and histological types were registered for every subject.The functional and aesthetic outcomes and complications following diode laser ablation for each patient were also recorded.RESULTS Of 67 patients with facial BCC,there was 65.67%from the age group≥60 years and 58.21%males.The mean duration of the lesions was 5.15±1.836 mo.The most involved location was the nose(29.85%).About half of the cases belong to the noduloulcerative type.Solid histological type comprises 40.3%of the cases,while the least was keratotic(13.4%).Moreover,65.2%of the solid cases were from the age group≤60 years and 38.6%of the adenoid type from the age group>60 years(P value=0.007).Excellent aesthetic and functional outcomes were reported in all cases after 6 mo of follow-up.Few complications were reported after diode laser ablation.CONCLUSION Facial BCC was mostly seen in the elderly and men.The mean duration was 5.15 mo.The nose was the commonest involved site.Noduloulcerative lesions were seen in approximately half of the lesions.The age of the patients determined the histological type of the lesion(solid type was mostly seen in the age group≤60 years,while,adenoid in the age group>60 years).Diode laser ablation showed excellent functional and aesthetic outcomes following a 6-mo follow-up.展开更多
文摘Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.
基金The National Natural Science Foundation of China under contract Nos 41941010 and 42006184the Fundamental Research Funds for the Central Universities under contract No.2042022kf1068。
文摘In recent years,there has been a significant acceleration in the thinning,calving and retreat of the Pine Island Ice Shelf(PIIS).The basal channels,results of enhanced basal melting,have the potential to significantly impact the stability of the PIIS.In this study,we used a variety of remote sensing data,including Landsat,REMA DEM,ICESat-1 and ICESat-2 satellite altimetry observations,and Ice Bridge airborne measurements,to study the spatiotemporal changes in the basal channels from 2003 to 2020 and basal melt rate from 2010 to 2017 of the PIIS under the Eulerian framework.We found that the basal channels are highly developed in the PIIS,with a total length exceeding 450 km.Most of the basal channels are ocean-sourced or groundingline-sourced basal channels,caused by the rapid melting under the ice shelf or near the groundingline.A raised seabed prevented warm water intrusion into the eastern branch of the PIIS,resulting in a lower basal melt rate in that area.In contrast,a deepsea trough facilitates warm seawater into the mainstream and the western branch of the PIIS,resulting in a higher basal melt rate in the main-stream,and the surface elevation changes above the basal channels of the mainstream and western branch are more significant.The El Ni?o event in 2015–2016 possibly slowed down the basal melting of the PIIS by modulating wind field,surface sea temperature and depth seawater temperature.Ocean and atmospheric changes were driven by El Ni?o,which can further explain and confirm the changes in the basal melting of the PIIS.
基金The National Forestry Commission of Mexico and The Mexican National Council for Science and Technology(CONAFOR-CONACYT-115900)。
文摘Multispecies forests have received increased scientific attention,driven by the hypothesis that biodiversity improves ecological resilience.However,a greater species diversity presents challenges for forest management and research.Our study aims to develop basal area growth models for tree species cohorts.The analysis is based on a dataset of 423 permanent plots(2,500 m^(2))located in temperate forests in Durango,Mexico.First,we define tree species cohorts based on individual and neighborhood-based variables using a combination of principal component and cluster analyses.Then,we estimate the basal area increment of each cohort through the generalized additive model to describe the effect of tree size,competition,stand density and site quality.The principal component and cluster analyses assign a total of 37 tree species to eight cohorts that differed primarily with regard to the distribution of tree size and vertical position within the community.The generalized additive models provide satisfactory estimates of tree growth for the species cohorts,explaining between 19 and 53 percent of the total variation of basal area increment,and highlight the following results:i)most cohorts show a"rise-and-fall"effect of tree size on tree growth;ii)surprisingly,the competition index"basal area of larger trees"had showed a positive effect in four of the eight cohorts;iii)stand density had a negative effect on basal area increment,though the effect was minor in medium-and high-density stands,and iv)basal area growth was positively correlated with site quality except for an oak cohort.The developed species cohorts and growth models provide insight into their particular ecological features and growth patterns that may support the development of sustainable management strategies for temperate multispecies forests.
基金Health Research Project of the Kunming Municipal Health Commission(Project No.2022-03-06-015)。
文摘Objective:To evaluate the efficacy and safety of different basal insulins in the treatment of type 2 diabetes mellitus(T2DM).Methods:The current research progress on different basal insulins was evaluated,with efficacy indicators including fasting plasma glucose(FPG)and glycated hemoglobin(HbAic),and safety indicators focusing mainly on weight change and the incidence of hypoglycemia.Results:Several different basal insulins showed similar metabolic control effects in terms of fasting plasma glucose and glycated hemoglobin.However,the risk of hypoglycemia was lower with insulin glargine 300(Glar-300),insulin degludec 100(Deg-100),and insulin degludec 200(Deg-200)compared to insulin glargine 100(Glar-100).Additionally,Glar-300 had the least impact on weight.Conclusion:For the treatment of T2DM,different basal insulins have similar therapeutic effects,but there are differences in the incidence of hypoglycemic events and their impact on weight.Rational insulin selection and dosage adjustments should be made based on the different patient groups.
文摘Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.
基金the National High-Tech Research & Development Program of China, No. 2006AA02A128the National Natural Science Foundation of China, No. 30670667
文摘BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE: To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING: This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS: The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS: MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES: S100 protein and mRNA expression. RESULTS: MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION: MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.
基金supported by Technological Innovation 2030-Major Projects of Brain Science and Brain-like Research(Grant No.:2022zD0206200)the Natural Science Foundation of China(Grant Nos.:31872796,82030108 to W.Yang,32071102 to P.Yu)+3 种基金the National Major Special Project on New Drug Innovation of China(Grant No.:2018ZX09711001-004-005)the key research and development program of Ningxia Hui Autonomous Region(Grant No.:2019BFH02003)Fundamental Research Funds for the Central Universities of China(Grant No.:2016QNA7002 to P.Yu)Zhejiang Provincial Natural Science Foundation(Grant No.:LR16H090001 to W.Yang).
文摘Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.
基金The National Natural Science Foundation of China under contract Nos 41941010 and 42006184the Fundamental Research Funds for the Central Universities under contract No.2042022kf1068the Independent Scientific Research Project of the State Key Laboratory of Information Engineering in Surveying,Mapping and Remote Sensing.
文摘The basal channel is a detailed morphological feature of the ice shelf caused by uneven basal melting.This kind of specifically morphology is widely distributed in polar ice shelves.It is an important research object of sea-ice interaction and plays a vital role in studying the relationship between the ice sheet/ice shelf and global warming.In this paper,high-resolution remote sensing image and ice penetration data were combined to extract the basal channel of the Pine Island Ice Shelf.The depth variation of Pine Island Ice Shelf in the recent 20 years was analyzed and discussed by using ICESat-1,ICESat-2,and IceBridge data.Combined with relevant marine meteorological elements(sea surface temperature,surface melting days,circumpolar deep water and wind)to analyze the basal channel changes,the redistribution of ocean heat is considered to be the most important factor affecting the evolution and development of the basal channel.
文摘BACKGROUND Basal cell carcinoma(BCC)is a slow-growing malignant tumor characterized by local invasiveness but an exceptionally rare metastatic potential.It ideally affects sun-exposed skin of older patients with more propensity for the facial region.AIM To evaluate the different clinicopathological characteristics of the facial BCC and the efficacy and safety of diode laser for the treatment of these lesions.METHODS We retrospectively reviewed facial BCC lesions of<1.5 cm in diameter and subjected them to diode laser ablation during the period from September 2016 to August 2021 at Al-Ramadi Teaching Hospital,Ramadi City,Iraq.Data matching the age,gender,duration,site,and clinical and histological types were registered for every subject.The functional and aesthetic outcomes and complications following diode laser ablation for each patient were also recorded.RESULTS Of 67 patients with facial BCC,there was 65.67%from the age group≥60 years and 58.21%males.The mean duration of the lesions was 5.15±1.836 mo.The most involved location was the nose(29.85%).About half of the cases belong to the noduloulcerative type.Solid histological type comprises 40.3%of the cases,while the least was keratotic(13.4%).Moreover,65.2%of the solid cases were from the age group≤60 years and 38.6%of the adenoid type from the age group>60 years(P value=0.007).Excellent aesthetic and functional outcomes were reported in all cases after 6 mo of follow-up.Few complications were reported after diode laser ablation.CONCLUSION Facial BCC was mostly seen in the elderly and men.The mean duration was 5.15 mo.The nose was the commonest involved site.Noduloulcerative lesions were seen in approximately half of the lesions.The age of the patients determined the histological type of the lesion(solid type was mostly seen in the age group≤60 years,while,adenoid in the age group>60 years).Diode laser ablation showed excellent functional and aesthetic outcomes following a 6-mo follow-up.