Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)an...Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.展开更多
Poor permeation of drugs and“immune-cold”tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment.Here,light-activated penetrable na...Poor permeation of drugs and“immune-cold”tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment.Here,light-activated penetrable nanoparticles(PEGVAL&DOX&ICG@RNPs)for co-delivery of the chemotherapeutic drug doxorubicin(DOX),the photosensitizer agent indocyanine green(ICG),and the angiotensin II receptor blockers valsartan(VAL)were developed to achieve deep drug penetration and synergistic photo-chemo-immunotherapy of solid tumor.Studies showed that under the first-wave of laser irradiation,the polyethylene glycol(PEG)hydrophilic layer as an“inert”surface could detach from the nanoparticles,release VAL and expose the arginine-rich peptide modified-cores that can facilitate deep drug penetration via a transcytosis pathway.When exposed to the second-wave of laser irradiation,the synergistic chemo-photo-immunotherapy can be achieved.As expected,in 4T1 tumorbearing mice,PEG-VAL&DOX&ICG@RNPs treatment could effectively inhibit the growth of tumors,down-regulateα-smooth muscle actin expression level of cancer-associated fibroblasts cells in tumors,induce dendritic cells(DCs)maturation,and promote intratumoral infiltration of cytotoxic T lymphocytes.Moreover,combination therapy by PEG-VAL&DOX&ICG@RNPs and anti-PD-1 monoclonal antibody can elicit memory T cell response for preventing tumor recurrence and metastasis in vivo.This work provides a promising delivery strategy to overcome the current limitations of nanomedicine for achieving more effective therapeutic index of“immune-cold”solid tumor treatment.展开更多
Recently,exploiting a novel supramolecular fabrication pathway have drawn great attention.To this endeavor,we firstly designed and reported an original light-activated platform based on the internal-driven forces of m...Recently,exploiting a novel supramolecular fabrication pathway have drawn great attention.To this endeavor,we firstly designed and reported an original light-activated platform based on the internal-driven forces of macrocyclic host by hiring the pillar[5]arene as the host molecule(H)and phenazine derivatives acting as an energetic guest molecule(G).Surprisingly,after adding the H solution into G system,the intensive fluorescence emission of the G molecule rapidly decreased under the irradiation of the UV-light(254 nm)until absolutely quenching.Delightfully,different from the traditional supramolecular host-guest interaction,the fluorescent emission of G molecule could be recovered after irradiating under the nature light.In view of this interesting observations,the interaction mechanism was carefully investigated by a series of characterizations.Those results suggested that the G molecule was easily threaded into the macrocyclic cavity(H)under the internal-driven forces induced by the UV-light irradiation,forming a 1:1 host-guest complex.Moreover,taking advantage of this especial feature,the light-activated platform of host-guest complex was further applied for ink-free light-driven printing materials,exhibiting great potential in the real application.展开更多
Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal contr...Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.展开更多
In light, the photosynthetic reactions of redox in thylakoids release protons which drive CF<sub>0</sub>-CF<sub>1</sub> complex to energize ATP formation, while the oxidation of water by PSII a...In light, the photosynthetic reactions of redox in thylakoids release protons which drive CF<sub>0</sub>-CF<sub>1</sub> complex to energize ATP formation, while the oxidation of water by PSII and that of PQH<sub>2</sub> by PSI are linked by cytochrome CF<sub>0</sub>. The unsolved problem is how these protons are diffused to ATP synthetase from the pumping sites. About展开更多
Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and proteins.Rec...Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and proteins.Recently,other types of molecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of applications.Herein,we provide a concise review of using various forms of molecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding mechanisms,and/or providing a handle to trigger a conformational process of interest with light.The applications discussed here cover a wide range of topics,ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function.展开更多
基金supported by the National Natural Science Foundation of China(22278241)the National Key R&D Program of China(2018YFA0901700)+1 种基金a grant from the Institute Guo Qiang,Tsinghua University(2021GQG1016)Department of Chemical Engineering-iBHE Joint Cooperation Fund.
文摘Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.
基金We acknowledge financial support from National Natural Science Foundation of China(Nos.82172089,22178270 and 22078246)the Fundamental Research Funds for the Central Universities(No.2019PT320028)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-058).
文摘Poor permeation of drugs and“immune-cold”tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment.Here,light-activated penetrable nanoparticles(PEGVAL&DOX&ICG@RNPs)for co-delivery of the chemotherapeutic drug doxorubicin(DOX),the photosensitizer agent indocyanine green(ICG),and the angiotensin II receptor blockers valsartan(VAL)were developed to achieve deep drug penetration and synergistic photo-chemo-immunotherapy of solid tumor.Studies showed that under the first-wave of laser irradiation,the polyethylene glycol(PEG)hydrophilic layer as an“inert”surface could detach from the nanoparticles,release VAL and expose the arginine-rich peptide modified-cores that can facilitate deep drug penetration via a transcytosis pathway.When exposed to the second-wave of laser irradiation,the synergistic chemo-photo-immunotherapy can be achieved.As expected,in 4T1 tumorbearing mice,PEG-VAL&DOX&ICG@RNPs treatment could effectively inhibit the growth of tumors,down-regulateα-smooth muscle actin expression level of cancer-associated fibroblasts cells in tumors,induce dendritic cells(DCs)maturation,and promote intratumoral infiltration of cytotoxic T lymphocytes.Moreover,combination therapy by PEG-VAL&DOX&ICG@RNPs and anti-PD-1 monoclonal antibody can elicit memory T cell response for preventing tumor recurrence and metastasis in vivo.This work provides a promising delivery strategy to overcome the current limitations of nanomedicine for achieving more effective therapeutic index of“immune-cold”solid tumor treatment.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.22165027,22061039,22001214)Gansu Province Innovation Star(No.2021CXZX-183).
文摘Recently,exploiting a novel supramolecular fabrication pathway have drawn great attention.To this endeavor,we firstly designed and reported an original light-activated platform based on the internal-driven forces of macrocyclic host by hiring the pillar[5]arene as the host molecule(H)and phenazine derivatives acting as an energetic guest molecule(G).Surprisingly,after adding the H solution into G system,the intensive fluorescence emission of the G molecule rapidly decreased under the irradiation of the UV-light(254 nm)until absolutely quenching.Delightfully,different from the traditional supramolecular host-guest interaction,the fluorescent emission of G molecule could be recovered after irradiating under the nature light.In view of this interesting observations,the interaction mechanism was carefully investigated by a series of characterizations.Those results suggested that the G molecule was easily threaded into the macrocyclic cavity(H)under the internal-driven forces induced by the UV-light irradiation,forming a 1:1 host-guest complex.Moreover,taking advantage of this especial feature,the light-activated platform of host-guest complex was further applied for ink-free light-driven printing materials,exhibiting great potential in the real application.
基金supported in part by NIH NS059622,NS073636,DOD CDMRP W81XWH-12-1-0562,Merit Review Award I01 BX002356 from the U.SDepartment of Veterans Affairs,Craig H Neilsen Foundation 296749+1 种基金Indiana Spinal Cord and Brain Injury Research Foundation(ISCBIRF)019919Mari Hulman George Endowment Funds
文摘Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer＇s disease and Parkinson＇s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.
基金Project supported by the National Natural Science Foundation of China
文摘In light, the photosynthetic reactions of redox in thylakoids release protons which drive CF<sub>0</sub>-CF<sub>1</sub> complex to energize ATP formation, while the oxidation of water by PSII and that of PQH<sub>2</sub> by PSI are linked by cytochrome CF<sub>0</sub>. The unsolved problem is how these protons are diffused to ATP synthetase from the pumping sites. About
基金supported by the National Institutes of Health(GM-065978,AG-039253)
文摘Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and proteins.Recently,other types of molecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of applications.Herein,we provide a concise review of using various forms of molecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding mechanisms,and/or providing a handle to trigger a conformational process of interest with light.The applications discussed here cover a wide range of topics,ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function.
