We described a new species, Microhyla beilunensis sp. nov., from Zhejiang Province of China. Phylogenetic analyses based on the mitochondrial 12 S, 16 S and CO1 gene sequences suggested that the new taxon was distinct...We described a new species, Microhyla beilunensis sp. nov., from Zhejiang Province of China. Phylogenetic analyses based on the mitochondrial 12 S, 16 S and CO1 gene sequences suggested that the new taxon was distinctly separated from its congeners and closed to M. mixtura and M. okinavensis. Morphologically, the new species could be identified from its congeners except M. mixtura by several characters：（1） rudimentary webs on toe base;（2） absence of disks and dorsal median longitudinal grooves on finger tips;（3） presence of disks and dorsal median longitudinal grooves on toe tips. As well, the new species could be identified from topotype M. mixtura by the combination of characters：（1） apart from the stripes, bar-shaped and oval-shaped patterns, the rounded spots present on the dorsum of body and legs;（2） the outer metacarpal tubercles prominently larger than the inner one;（3） of males, the ratios of HW, IND, UEW and LAW to SVL of the new species were significantly larger than those of M. mixtura（P 〈 0.01）, and the ratios of SL, IOD, LAHL, HLL, TL, TFL and FL to SVL of the new species were significantly less than those of M. mixtura（P 〈 0.05）.展开更多
Diabetic retinopathy(DR)is the leading cause of blindness among the working-age population.Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%,there are c...Diabetic retinopathy(DR)is the leading cause of blindness among the working-age population.Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%,there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-wellcontrolled diabetic patients(GW-DR).In this study,we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period.The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline,all of whom consistently maintained hemoglobin A1c(HbA1c)levels below 7%without experiencing hypoglycemia.Within this cohort of 71 individuals,21 subsequently experienced new-onset GW-DR,resulting in an incidence rate of 29.6%.In the validation cohort,we also observed a significant GW-DR incidence rate of 17.9%.Employing targeted metabolomics,we investigated the metabolic characteristics of serum in GW-DR,revealing a significant association between lower levels of ethanolamine and GW-DR risk.This association was corroborated in the validation cohort,exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c,with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts,respectively.Furthermore,in a streptozotocin(STZ)-induced diabetic rat model,ethanolamine attenuated diabetic retinal inflammation,accompanied by suppression of microglial diacylglycerol(DAG)-dependent protein kinase C(PKC)pathway activation.In conclusion,we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.展开更多
Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intrica...Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD progression.Herein,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of AD.In this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβhitchhiking.In vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB crossing.The engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.展开更多
Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC...Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.展开更多
Gestational diabetes mellitus(GDM)is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes,but its pathogenesis has not been clearly elucidated.Investigations of the d...Gestational diabetes mellitus(GDM)is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes,but its pathogenesis has not been clearly elucidated.Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression.Therefore,in the present study,we analysed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance throughout the three trimesters.We found that the variation trends of 38 metabolites were significantly changed during GDM development.Specifically,longitudinal analyses revealed that cysteine(Cys)levels significantly decreased over the course of GDM progression.Further study showed that Cys alleviated GDM in female mice at gestational day 14.5,possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis.Taken together,these findings suggest that the Cys metabolism pathway might play a crucial role in GDM and Cys supplementation represents a potential new treatment strategy for GDM patients.展开更多
Understanding the fundamental charge carrier dynamics is of great significance for photodetectors with both high speed and high responsivity.Devices based on two-dimensional(2D)transition metal dichalcogenides can exh...Understanding the fundamental charge carrier dynamics is of great significance for photodetectors with both high speed and high responsivity.Devices based on two-dimensional(2D)transition metal dichalcogenides can exhibit picosecond photoresponse speed.However,2D materials naturally have low absorption,and when increasing thickness to gain higher responsivity,the response time usually slows to nanoseconds,limiting their photodetection performance.Here,by taking time-resolved photocurrent measurements,we demonstrated that graphene/MoTe_(2) van der Waals heterojunctions realize a fast 10 ps photoresponse time owing to the reduced average photocurrent drift time in the heterojunction,which is fundamentally distinct from traditional Dirac semimetal photodetectors such as graphene or Cd_(3)As_(2) and implies a photodetection bandwidth as wide as 100 GHz.Furthermore,we found that an additional charge carrier transport channel provided by graphene can ef-fectively decrease the photocurrent recombination loss to the entire device,preserving a high responsivity in the near-infrared region.Our study provides a deeper understanding of the ultrafast electrical response in van der Waals heterojunctions and offers a promising approach for the realization of photodetectors with both high responsivity and ultrafast electrical response.展开更多
基金supported by National Key Programme of Research and Development, Ministry of Science and Technology (2017YFC0505202)National Natural Sciences Foundation of China (NSFC31471964 and 31201702)+1 种基金Important Research Project of Chinese Academy of Sciences (KJZG-EW-L13)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA19050201)
文摘We described a new species, Microhyla beilunensis sp. nov., from Zhejiang Province of China. Phylogenetic analyses based on the mitochondrial 12 S, 16 S and CO1 gene sequences suggested that the new taxon was distinctly separated from its congeners and closed to M. mixtura and M. okinavensis. Morphologically, the new species could be identified from its congeners except M. mixtura by several characters：（1） rudimentary webs on toe base;（2） absence of disks and dorsal median longitudinal grooves on finger tips;（3） presence of disks and dorsal median longitudinal grooves on toe tips. As well, the new species could be identified from topotype M. mixtura by the combination of characters：（1） apart from the stripes, bar-shaped and oval-shaped patterns, the rounded spots present on the dorsum of body and legs;（2） the outer metacarpal tubercles prominently larger than the inner one;（3） of males, the ratios of HW, IND, UEW and LAW to SVL of the new species were significantly larger than those of M. mixtura（P 〈 0.01）, and the ratios of SL, IOD, LAHL, HLL, TL, TFL and FL to SVL of the new species were significantly less than those of M. mixtura（P 〈 0.05）.
基金supported by the Key R&D project of the National Ministry of Science and Technology(2023YFA1801100)the Major Research Plan of the National Natural Science Foundation of China(92357307 and 92057106)+1 种基金the National Natural Science Foundation of China(32171177 and 81870610)Shanghai Jiaotong University-Gaofeng Clinical Medicine Grant。
文摘Diabetic retinopathy(DR)is the leading cause of blindness among the working-age population.Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%,there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-wellcontrolled diabetic patients(GW-DR).In this study,we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period.The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline,all of whom consistently maintained hemoglobin A1c(HbA1c)levels below 7%without experiencing hypoglycemia.Within this cohort of 71 individuals,21 subsequently experienced new-onset GW-DR,resulting in an incidence rate of 29.6%.In the validation cohort,we also observed a significant GW-DR incidence rate of 17.9%.Employing targeted metabolomics,we investigated the metabolic characteristics of serum in GW-DR,revealing a significant association between lower levels of ethanolamine and GW-DR risk.This association was corroborated in the validation cohort,exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c,with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts,respectively.Furthermore,in a streptozotocin(STZ)-induced diabetic rat model,ethanolamine attenuated diabetic retinal inflammation,accompanied by suppression of microglial diacylglycerol(DAG)-dependent protein kinase C(PKC)pathway activation.In conclusion,we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.
基金the Research and Development Program of Science and Technology Department of Sichuan Province(2022JDJQ0050)111 Project(B18035)the Fundamental of Research Funds for the Central Universities.
文摘Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD progression.Herein,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of AD.In this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβhitchhiking.In vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB crossing.The engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.
基金the National Natural Science Foundation of China(No.82102769)the 111 Project(No.B18035,China)the Fundamental of Research Funds for the Central Universities and Beijing Natural Science Foundation(No.L212054,China).
文摘Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.
基金supported by grants from the National Natural Science Foundation of China(81870610)Shanghai Science and Technology Commission Foundation(21Y11904800 and 23ZR1451500)+1 种基金the Clinical Research Plan of SHDC(SHDC2020CR3065B)the National Key Research and Development Program of China(2021YFC2501600 and 2021YFC2501601).
文摘Gestational diabetes mellitus(GDM)is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes,but its pathogenesis has not been clearly elucidated.Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression.Therefore,in the present study,we analysed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance throughout the three trimesters.We found that the variation trends of 38 metabolites were significantly changed during GDM development.Specifically,longitudinal analyses revealed that cysteine(Cys)levels significantly decreased over the course of GDM progression.Further study showed that Cys alleviated GDM in female mice at gestational day 14.5,possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis.Taken together,these findings suggest that the Cys metabolism pathway might play a crucial role in GDM and Cys supplementation represents a potential new treatment strategy for GDM patients.
基金This work was supported by the National Natural Science Foundation of China(Grants No.52022029,91850116,51772084,and U19A2090)the Sino-German Center for Research Promotion(Grant No.GZ1390)the Hunan Provincial Natural Science Foundation of China(Grants No.2018RS3051 and 2019XK2001)。
文摘Understanding the fundamental charge carrier dynamics is of great significance for photodetectors with both high speed and high responsivity.Devices based on two-dimensional(2D)transition metal dichalcogenides can exhibit picosecond photoresponse speed.However,2D materials naturally have low absorption,and when increasing thickness to gain higher responsivity,the response time usually slows to nanoseconds,limiting their photodetection performance.Here,by taking time-resolved photocurrent measurements,we demonstrated that graphene/MoTe_(2) van der Waals heterojunctions realize a fast 10 ps photoresponse time owing to the reduced average photocurrent drift time in the heterojunction,which is fundamentally distinct from traditional Dirac semimetal photodetectors such as graphene or Cd_(3)As_(2) and implies a photodetection bandwidth as wide as 100 GHz.Furthermore,we found that an additional charge carrier transport channel provided by graphene can ef-fectively decrease the photocurrent recombination loss to the entire device,preserving a high responsivity in the near-infrared region.Our study provides a deeper understanding of the ultrafast electrical response in van der Waals heterojunctions and offers a promising approach for the realization of photodetectors with both high responsivity and ultrafast electrical response.
