Epilepsy is one of the most prevalent and severe neurological disorders,and it is inadequately controlled with currently available medications.While cinnabar(mercury(II)sulfide)—a traditional Chinese medicine—has hi...Epilepsy is one of the most prevalent and severe neurological disorders,and it is inadequately controlled with currently available medications.While cinnabar(mercury(II)sulfide)—a traditional Chinese medicine—has historical application in epilepsy treatment,its therapeutic efficacy and underlying mechanisms are unclear.In this study,we find that cinnabar exerts model-dependent antiseizure efficacy in mice.Specifically,it significantly attenuates acute seizures,enhances the termination of diazepam-resistant status epilepticus,and reduces spontaneous seizures in the kainic acid(KA)-induced seizure model.Conversely,no therapeutic effect was found in the maximal electroshock-,pentylenetetrazole-,or kindling-induced seizure model.Fiber photometry revealed that cinnabar normalizes KA-induced hippocampal neurotransmission imbalances by simultaneously decreasing glutamate hyperactivity andγ-aminobutyric acid hypoactivity.Furthermore,cinnabar has neuroprotective effects and alleviates comorbid anxiety-like behaviors,while showing no alterations in motor function.Our findings suggest cinnabar's potential as a therapeutic agent for seizure management,via a mechanism associated with the reversal of the hippocampal excitatory/inhibitory imbalance.展开更多
DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical world.In analogy with the biological world,the DEL world can evolv...DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical world.In analogy with the biological world,the DEL world can evolve by using a chemical central dogma,wherein DNA replicates using the PCR reactions to amplify the genetic codes,DNA sequencing transcripts the genetic information,and DNA-compatible synthesis translates into chemical phenotypes.Importantly,DNA-compatible synthesis is the key to expanding the DEL chemical space.Besides,the evolution-driven selection system pushes the chemicals to evolve under the selective pressure,i.e.,desired selection strategies.In this perspective,we summarized recent advances in expanding DEL synthetic toolbox and panning strategies,which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.展开更多
Photoelectrochemical(PEC)water splitting is regarded as a promising way for solar hydrogen production,while the fast development of photovoltaic-electrolysis(PV-EC)has pushed PEC research into an embarrassed situation...Photoelectrochemical(PEC)water splitting is regarded as a promising way for solar hydrogen production,while the fast development of photovoltaic-electrolysis(PV-EC)has pushed PEC research into an embarrassed situation.In this paper,a comparison of PEC and PV-EC in terms of efficiency,cost,and stability is conducted and briefly discussed.It is suggested that the PEC should target on high solar-to-hydrogen efficiency based on cheap semiconductors in order to maintain its role in the technological race of sustainable hydrogen production.展开更多
基金supported by the National Natural Science Foundation of China(82204353,82330116)the Zhejiang Provincial Natural Science Foundation of China(LD24H310001,LY24H310002)+1 种基金the Research Project of Zhejiang Chinese Medical University(2023JKZDZC08)the Jinhua Municipal Science and Technology Projects(2023-3-118).
文摘Epilepsy is one of the most prevalent and severe neurological disorders,and it is inadequately controlled with currently available medications.While cinnabar(mercury(II)sulfide)—a traditional Chinese medicine—has historical application in epilepsy treatment,its therapeutic efficacy and underlying mechanisms are unclear.In this study,we find that cinnabar exerts model-dependent antiseizure efficacy in mice.Specifically,it significantly attenuates acute seizures,enhances the termination of diazepam-resistant status epilepticus,and reduces spontaneous seizures in the kainic acid(KA)-induced seizure model.Conversely,no therapeutic effect was found in the maximal electroshock-,pentylenetetrazole-,or kindling-induced seizure model.Fiber photometry revealed that cinnabar normalizes KA-induced hippocampal neurotransmission imbalances by simultaneously decreasing glutamate hyperactivity andγ-aminobutyric acid hypoactivity.Furthermore,cinnabar has neuroprotective effects and alleviates comorbid anxiety-like behaviors,while showing no alterations in motor function.Our findings suggest cinnabar's potential as a therapeutic agent for seizure management,via a mechanism associated with the reversal of the hippocampal excitatory/inhibitory imbalance.
基金Financial support was provided by the National Natural Science Foundation of China(grant numbers 22177073,21977070,21907085,and U19A2011)the Natural Science Foundation of Shanghai,China(grant numbers 21ZR1442900 and 23ZR1437600)+2 种基金the Natural Science Foundation of Zhejiang Province,China(grant number LY22H300001)Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal SystemShanghai Key Laboratory of Orthopedic Implants(grant number KFKT202207,China)for financial support.
文摘DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical world.In analogy with the biological world,the DEL world can evolve by using a chemical central dogma,wherein DNA replicates using the PCR reactions to amplify the genetic codes,DNA sequencing transcripts the genetic information,and DNA-compatible synthesis translates into chemical phenotypes.Importantly,DNA-compatible synthesis is the key to expanding the DEL chemical space.Besides,the evolution-driven selection system pushes the chemicals to evolve under the selective pressure,i.e.,desired selection strategies.In this perspective,we summarized recent advances in expanding DEL synthetic toolbox and panning strategies,which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.
基金This work was supported by the Australian Research Council through its Discovery Programs,DECRA and Laureate Fellowship。
文摘Photoelectrochemical(PEC)water splitting is regarded as a promising way for solar hydrogen production,while the fast development of photovoltaic-electrolysis(PV-EC)has pushed PEC research into an embarrassed situation.In this paper,a comparison of PEC and PV-EC in terms of efficiency,cost,and stability is conducted and briefly discussed.It is suggested that the PEC should target on high solar-to-hydrogen efficiency based on cheap semiconductors in order to maintain its role in the technological race of sustainable hydrogen production.
