Prediction of potential geographic distributions is important for species protection and habitat restoration. Ulmus lamellosa is an endangered and endemic species in China for which conservation efforts are required. ...Prediction of potential geographic distributions is important for species protection and habitat restoration. Ulmus lamellosa is an endangered and endemic species in China for which conservation efforts are required. The maximum entropy （MaxEnt） model was used to predict the current and future geographic distribution （from 2030 to 2070） of U. lamellosa in China and discuss the reasons for changes in climatic suitability. The MaxEnt model provided a good fit to our data as confirmed by an AUC value of 0.948. The suitable areas for U. lamellosa were primarily projected in the northern part of China from 2030 to 2070, especially in Liaoning province. The variables ＂temperature seasonality＂, ＂precipitation of wettest month＂ and ＂precipitation of warmest quarter＂ were the most influential climatic variables in limiting the distribution of U. lamellosa. Our results clearly predict the future impacts of climate change on the geographic distribution of U. lamellosa and this can help prioritize design of localized conservation strategies in China.展开更多
Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncR...Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.展开更多
Understanding the signaling cascade that leads to the rapid memory and cognitive breakdown in Alzheimer’s disease is the key to finding a potential treatment method for the disease. Recently, Larson et al. connect th...Understanding the signaling cascade that leads to the rapid memory and cognitive breakdown in Alzheimer’s disease is the key to finding a potential treatment method for the disease. Recently, Larson et al. connect the roles of major proteins implicated in the disease progression and propose targeting of cellular prion protein (PrPc) as a way of someday rescuing synaptic plasticity in humans with Alzheimer’s, as it has been done on mice.展开更多
Despite substantial advancements in modern medicine,the management of hypertension remains a major challenge.Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases...Despite substantial advancements in modern medicine,the management of hypertension remains a major challenge.Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases,including hypertension.However,the antihypertensive mechanism of mesenchymal stem cells(MSCs)has not been extensively explored.This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis.Our previous study demonstrated that human induced pluripotent stem cellderived mesenchymal stem cells(hiPSC-MSCs)are functional and homogeneous sources for MSC-based therapy.After the injection of hiPSCMSCs,a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats(SHRs).Cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs.The injected hiPSC-MSCs accumulated adjacent to the splenic nerve,potentially contributing to the antihypertensive effects.Furthermore,the hiPSC-MSCs released abundant glutamate,which acts as a neuromodulator to activate the splenic sympathetic nerve.After inhibition of glutamate synthesis by siRNA,the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished.In addition,the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation(SND),underscoring the critical role of the splenic nerve.Moreover,activation of the splenic nerve resulted in increased release of norepinephrine(NE),which increased the number of choline acetyltransferase-positive(ChAT^(+))cells in the spleen and peripheral blood.Consequently,the acetylcholine(ACh)produced by elevated ChAT+cells could act as a vasodilator,lowering blood pressure and mitigating inflammation in end target organs.In summary,our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT+cells.The connection between blood pressure regulation and the splenic nerve may offer new insights into the treatment of hypertension.展开更多
To the Editor:Ovarian tissue cryopreservation(OTC)is now becoming more widely used clinically as a method of protecting female fertility.However,articles on its pregnancy outcomes are currently mixed.Evaluation of cur...To the Editor:Ovarian tissue cryopreservation(OTC)is now becoming more widely used clinically as a method of protecting female fertility.However,articles on its pregnancy outcomes are currently mixed.Evaluation of current evidence investigating pregnancy outcomes in patients undergoing OTC from population-based studies will facilitate to broaden the clinical application of OTC and provide a reference for better healthcare practices population-wide.展开更多
The isolation chip method(iChip)provides a novel approach for culturing previously uncultivable microorganisms;this method is currently limited by the user being unable to ensure single-cell loading within individual ...The isolation chip method(iChip)provides a novel approach for culturing previously uncultivable microorganisms;this method is currently limited by the user being unable to ensure single-cell loading within individual wells.To address this limitation,we integrated flow cytometry-based fluorescence-activated cell sorting with a modified iChip(FACS-iChip)to effectively mine microbial dark matter in soils.This method was used for paddy soils with the aim of mining uncultivable microorganisms and making preliminary comparisons between the cultured microorganisms and the bulk soil via 16S rRNA gene sequencing.Results showed that the FACS-iChip achieved a culture recovery rate of almost 40%and a culture retrieval rate of 25%.Although nearly 500 strains were cultured from 19 genera with 8 FACS-iChip plates,only six genera could be identified via 16S rRNA gene amplification.This result suggests that the FACS-iChip is capable of detecting strains in the currently dead spaces of PCR-based sequencing technology.We,therefore,conclude that the FACS-iChip system provides a highly efficient and readily available approach for microbial‘dark matter’mining.展开更多
RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I...RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUEcan generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced offtarget single-nucleotide variants (SNVs) is not fully appreciated. Therefore, to determine the off-target effects of RESCUE-mediatedediting, we employed transcription-wide sequencing on cells edited by RESCUE. The SNVs showed different off-target effects onmRNA, circRNA, lncRNA, and miRNA expression patterns and their interacting networks. Our results illustrate the transcriptionwide impact of RESCUE-induced off-target SNVs and highlight the need for careful characterization of the off-target impact by thisediting platform.展开更多
Tourism has become the primary leisure activity for modern people,and a scenic spot’s appeal to tourists is closely linked to the quality of supporting catering services within the area.Improving satisfaction with ca...Tourism has become the primary leisure activity for modern people,and a scenic spot’s appeal to tourists is closely linked to the quality of supporting catering services within the area.Improving satisfaction with catering services in these scenic spots has become a key factor in promoting the development of urban tourist destinations.Using Zhangzhou,a tourist city,as an example,this paper conducts an empirical study on the satisfaction of catering services in Zhangzhou’s scenic spots through IPA analysis.Firstly,based on the scale of relevant influencing factors affecting catering service satisfaction in Zhangzhou’s scenic spots,a field questionnaire survey has been conducted.Three main levels,five core elements,and 31 sub-indicators have been summarized to construct the evaluation system for catering service satisfaction in scenic spots.Through the analysis of IPA data and the examination of various indicators related to catering services in Zhangzhou’s scenic spots,we analyze the influencing factors affecting tourists’satisfaction with catering services.Meanwhile,we also introduce the 4Ps demand theory of catering service.Finally,based on the analysis and evaluation of IPA quadrant and the 4Ps demand theory,we initially construct the 4Ps improvement path.This will provide theoretical and practical references for enhancing the catering service satisfaction of tourists in scenic spots.展开更多
Background Thedysfunction ofthe immune system is one of the pathogeneses of endometriosis.Immune cells can not onlyaffect the microenvironmentof the endometrium by secreting cytokines and defensins but also promote an...Background Thedysfunction ofthe immune system is one of the pathogeneses of endometriosis.Immune cells can not onlyaffect the microenvironmentof the endometrium by secreting cytokines and defensins but also promote angiogenesis,growth and invasion of endometrial stromal cells.Result ATP is a key mediator in the immune mechanism of endometriosis and plays a crucial role in endometriosis.While ATP acts as a purinergic signaling molecule,it has a close relationship with the pain of endometriosis via activating ATP receptors,including P2X3,P2X4,P2X7 and P2Y receptors,after being activated by the immune system.Besides,ATP levels reflect the impairment of mitochondrial function in granulosa cells,which could lead to infertility.The modulation of ATP expression levels is controlled by ectonucleotidases.The content of ectonucleotidases is altered in endometriosis which may be emerging non-invasive biomarkers.Conclusion In the present review,we briefly introduce the relationship between the change of ATP level controlled by ectonucleotidases and endometriosis-associated infertility and pain,and illustrate our prospects for future research.展开更多
The original version of this article unfortunately contained a mistake.The presentation of Table 2 was incorrect.The corrected Table 2 is given below.The original article has been corrected.
基金supported by the Shanxi Natural Science Foundation(2015011069)the University Innovation program of Science and Technology of Shanxi Province(20161109)
文摘Prediction of potential geographic distributions is important for species protection and habitat restoration. Ulmus lamellosa is an endangered and endemic species in China for which conservation efforts are required. The maximum entropy （MaxEnt） model was used to predict the current and future geographic distribution （from 2030 to 2070） of U. lamellosa in China and discuss the reasons for changes in climatic suitability. The MaxEnt model provided a good fit to our data as confirmed by an AUC value of 0.948. The suitable areas for U. lamellosa were primarily projected in the northern part of China from 2030 to 2070, especially in Liaoning province. The variables ＂temperature seasonality＂, ＂precipitation of wettest month＂ and ＂precipitation of warmest quarter＂ were the most influential climatic variables in limiting the distribution of U. lamellosa. Our results clearly predict the future impacts of climate change on the geographic distribution of U. lamellosa and this can help prioritize design of localized conservation strategies in China.
基金This study was approved by the Medical Ethics Committee of Shenzhen University Health Science Center(protocol no.2016001).
文摘Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.
文摘Understanding the signaling cascade that leads to the rapid memory and cognitive breakdown in Alzheimer’s disease is the key to finding a potential treatment method for the disease. Recently, Larson et al. connect the roles of major proteins implicated in the disease progression and propose targeting of cellular prion protein (PrPc) as a way of someday rescuing synaptic plasticity in humans with Alzheimer’s, as it has been done on mice.
基金supported by the National Natural Science Foundation of China(82272164,82470367)the Natural Science Foundation of Guangdong Province(2019A1515010066,2021A1515011648,2024A1515013135)the Guangzhou Science,Technology and Innovation Commission(202002020004)。
文摘Despite substantial advancements in modern medicine,the management of hypertension remains a major challenge.Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases,including hypertension.However,the antihypertensive mechanism of mesenchymal stem cells(MSCs)has not been extensively explored.This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis.Our previous study demonstrated that human induced pluripotent stem cellderived mesenchymal stem cells(hiPSC-MSCs)are functional and homogeneous sources for MSC-based therapy.After the injection of hiPSCMSCs,a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats(SHRs).Cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs.The injected hiPSC-MSCs accumulated adjacent to the splenic nerve,potentially contributing to the antihypertensive effects.Furthermore,the hiPSC-MSCs released abundant glutamate,which acts as a neuromodulator to activate the splenic sympathetic nerve.After inhibition of glutamate synthesis by siRNA,the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished.In addition,the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation(SND),underscoring the critical role of the splenic nerve.Moreover,activation of the splenic nerve resulted in increased release of norepinephrine(NE),which increased the number of choline acetyltransferase-positive(ChAT^(+))cells in the spleen and peripheral blood.Consequently,the acetylcholine(ACh)produced by elevated ChAT+cells could act as a vasodilator,lowering blood pressure and mitigating inflammation in end target organs.In summary,our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT+cells.The connection between blood pressure regulation and the splenic nerve may offer new insights into the treatment of hypertension.
基金supported by a grant from the Beijing Municipal Natural Science Foundation(No.7222206).
文摘To the Editor:Ovarian tissue cryopreservation(OTC)is now becoming more widely used clinically as a method of protecting female fertility.However,articles on its pregnancy outcomes are currently mixed.Evaluation of current evidence investigating pregnancy outcomes in patients undergoing OTC from population-based studies will facilitate to broaden the clinical application of OTC and provide a reference for better healthcare practices population-wide.
基金This research was financially supported by the National Natural Science Foundation of China(41991334)the Zhejiang Provincial Natural Science Foundation of China(LD19D060001,LQ20C030006)the China Postdoctoral Science Foundation(2019M652097).
文摘The isolation chip method(iChip)provides a novel approach for culturing previously uncultivable microorganisms;this method is currently limited by the user being unable to ensure single-cell loading within individual wells.To address this limitation,we integrated flow cytometry-based fluorescence-activated cell sorting with a modified iChip(FACS-iChip)to effectively mine microbial dark matter in soils.This method was used for paddy soils with the aim of mining uncultivable microorganisms and making preliminary comparisons between the cultured microorganisms and the bulk soil via 16S rRNA gene sequencing.Results showed that the FACS-iChip achieved a culture recovery rate of almost 40%and a culture retrieval rate of 25%.Although nearly 500 strains were cultured from 19 genera with 8 FACS-iChip plates,only six genera could be identified via 16S rRNA gene amplification.This result suggests that the FACS-iChip is capable of detecting strains in the currently dead spaces of PCR-based sequencing technology.We,therefore,conclude that the FACS-iChip system provides a highly efficient and readily available approach for microbial‘dark matter’mining.
基金supported by grants from the Ministry of Agriculture of China(2016ZX08009003-006 and 2011ZX08006-001)the National Key Laboratory Open Fund Project(2020SKLAB6-24)+1 种基金the ZJU-Hangzhou Global Scientific and Technological Innovation Center,Zhejiang University(02020200-K02013008)the National Natural Science Foundation of China(32071347).
文摘RNA base editing is a promising tool in precise molecular therapy. Currently, there are two widely used RNA base editors, REPAIRand RESCUE. REPAIR only facilitates A-to-I conversions, while RESCUE performs both A-to-I and C-to-U conversions. Thus, RESCUEcan generate twice the number of mutations compared to REPAIR. However, transcription-wide impact due to RESCUE-induced offtarget single-nucleotide variants (SNVs) is not fully appreciated. Therefore, to determine the off-target effects of RESCUE-mediatedediting, we employed transcription-wide sequencing on cells edited by RESCUE. The SNVs showed different off-target effects onmRNA, circRNA, lncRNA, and miRNA expression patterns and their interacting networks. Our results illustrate the transcriptionwide impact of RESCUE-induced off-target SNVs and highlight the need for careful characterization of the off-target impact by thisediting platform.
基金Surpported by the National Social Science Foundation Western Project of China(19XJY010)。
文摘Tourism has become the primary leisure activity for modern people,and a scenic spot’s appeal to tourists is closely linked to the quality of supporting catering services within the area.Improving satisfaction with catering services in these scenic spots has become a key factor in promoting the development of urban tourist destinations.Using Zhangzhou,a tourist city,as an example,this paper conducts an empirical study on the satisfaction of catering services in Zhangzhou’s scenic spots through IPA analysis.Firstly,based on the scale of relevant influencing factors affecting catering service satisfaction in Zhangzhou’s scenic spots,a field questionnaire survey has been conducted.Three main levels,five core elements,and 31 sub-indicators have been summarized to construct the evaluation system for catering service satisfaction in scenic spots.Through the analysis of IPA data and the examination of various indicators related to catering services in Zhangzhou’s scenic spots,we analyze the influencing factors affecting tourists’satisfaction with catering services.Meanwhile,we also introduce the 4Ps demand theory of catering service.Finally,based on the analysis and evaluation of IPA quadrant and the 4Ps demand theory,we initially construct the 4Ps improvement path.This will provide theoretical and practical references for enhancing the catering service satisfaction of tourists in scenic spots.
基金supported by grants from the Beijing Municipal Natural Science Foundation(no.7222206).
文摘Background Thedysfunction ofthe immune system is one of the pathogeneses of endometriosis.Immune cells can not onlyaffect the microenvironmentof the endometrium by secreting cytokines and defensins but also promote angiogenesis,growth and invasion of endometrial stromal cells.Result ATP is a key mediator in the immune mechanism of endometriosis and plays a crucial role in endometriosis.While ATP acts as a purinergic signaling molecule,it has a close relationship with the pain of endometriosis via activating ATP receptors,including P2X3,P2X4,P2X7 and P2Y receptors,after being activated by the immune system.Besides,ATP levels reflect the impairment of mitochondrial function in granulosa cells,which could lead to infertility.The modulation of ATP expression levels is controlled by ectonucleotidases.The content of ectonucleotidases is altered in endometriosis which may be emerging non-invasive biomarkers.Conclusion In the present review,we briefly introduce the relationship between the change of ATP level controlled by ectonucleotidases and endometriosis-associated infertility and pain,and illustrate our prospects for future research.
文摘The original version of this article unfortunately contained a mistake.The presentation of Table 2 was incorrect.The corrected Table 2 is given below.The original article has been corrected.
