Cellular mechanotransduction characterized by the transformation of mechanical stimuli into biochemical signals,represents a pivotal and complex process underpinning a multitude of cellular functionalities.This proces...Cellular mechanotransduction characterized by the transformation of mechanical stimuli into biochemical signals,represents a pivotal and complex process underpinning a multitude of cellular functionalities.This process is integral to diverse biological phenomena,including embryonic development,cell migration,tissue regeneration,and disease pathology,particularly in the context of cancer metastasis and cardiovascular diseases.Despite the profound biological and clinical significance of mechanotransduction,our understanding of this complex process remains incomplete.The recent development of advanced optical techniques enables in-situ force measurement and subcellular manipulation from the outer cell membrane to the organelles inside a cell.In this review,we delved into the current state-of-the-art techniques utilized to probe cellular mechanobiology,their principles,applications,and limitations.We mainly examined optical methodologies to quantitatively measure the mechanical properties of cells during intracellular transport,cell adhesion,and migration.We provided an introductory overview of various conventional and optical-based techniques for probing cellular mechanics.These techniques have provided into the dynamics of mechanobiology,their potential to unravel mechanistic intricacies and implications for therapeutic intervention.展开更多
Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders,such as Alzheimer’s disease(AD),which can be induced by an excess of reactive oxygen speci...Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders,such as Alzheimer’s disease(AD),which can be induced by an excess of reactive oxygen species(ROS).As an antioxidant,hydrogen gas(H_(2))has the potential to mitigate AD by scavenging highly harmful ROS such as·OH.However,conventional administration methods of H_(2) face significant challenges in controlling H_(2) release on demand and fail to achieve effective accumulation at lesion sites.Herein,we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared(NIR)light-driven photocatalytic H_(2) evolution in situ.The nanoreactors are constructed by biocompatible crosslinked vesicles(CVs)encapsulating ascorbic acid and two photosensitizers,chlorophyll a(Chla)and indoline dye(Ind).In addition,platinum nanoparticles(Pt NPs)serve as photocatalysts and upconversion nanoparticles(UCNP)act as light-harvesting antennas in the nanoreacting system,and both attach to the surface of CVs.Under NIR irradiation,the nanoreactors release H_(2) in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model.Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.展开更多
The ongoing outbreak of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)pandemic has posed significant challenges in early viral diagnosis.Hence,it is urgently desirable to develop a rapid,inexpensive,and s...The ongoing outbreak of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)pandemic has posed significant challenges in early viral diagnosis.Hence,it is urgently desirable to develop a rapid,inexpensive,and sensitive method to aid point-of-care SARS-CoV-2 detection.In this work,we report a highly sequence-specific biosensor based on nanocomposites with aggregationinduced emission luminogens(AIEgen)-labeled oligonucleotide probes on graphene oxide nanosheets(AIEgen@GO)for one step-detection of SARS-CoV-2-specific nucleic acid sequences(Orf1ab or N genes).A dual“turn-on”mechanism based on AIEgen@GO was established for viral nucleic acids detection.Here,the first-stage fluorescence recovery was due to dissociation of the AIEgen from GO surface in the presence of target viral nucleic acid,and the second-stage enhancement of AIEbased fluorescent signal was due to the formation of a nucleic acid duplex to restrict the intramolecular rotation of the AIEgen.Furthermore,the feasibility of our platform for diagnostic application was demonstrated by detecting SARS-CoV-2 virus plasmids containing both Orf1ab and N genes with rapid detection around 1 h and good sensitivity at pM level without amplification.Our platform shows great promise in assisting the initial rapid detection of the SARS-CoV-2 nucleic acid sequence before utilizing quantitative reverse transcription-polymerase chain reaction for second confirmation.展开更多
Adoptive T-cell therapy(ACT)is a promising therapeutic approach based on the concept of potent T-cell mediated immunity against the tumor.The outcome of antigen-specific T-cells responses relies on the interaction bet...Adoptive T-cell therapy(ACT)is a promising therapeutic approach based on the concept of potent T-cell mediated immunity against the tumor.The outcome of antigen-specific T-cells responses relies on the interaction between T-cells and antigen-presenting cells,which provides signals for generating different T-cell phenotypes with different roles in tumor removal.However,such interaction is often not optimal in vivo and results in low therapeutic efficacy.To reach the full potential of the T-cell response,current research put effort into developing dynamic biomaterials as artificial antigen-presenting cells to study and regulate the T-cell activity for controlling T-cell fate.In this perspective,we provide(1)an overview of ACT and general T-cells behaviors,(2)explore the insight on how biomaterials can be used for studying and regulating T-cell behaviors,(3)and discuss conceptual gaps in knowledge for biomaterials-based immunotherapy.展开更多
基金the funding from Start-up Fundings of Ocean University of China(862401013154 and 862401013155)Laboratory for Marine Drugs and Bioproducts Qingdao Marine Science and Technology Center(LMDBCXRC202401 and LMDBCXRC202402)+1 种基金Taishan Scholar Youth Expert Program of Shandong Province(tsqn202306102 and tsqn202312105)Shandong Provincial Overseas Excellent Young Scholar Program(2024HWYQ-042 and 2024HWYQ-043)for supporting this work.
文摘Cellular mechanotransduction characterized by the transformation of mechanical stimuli into biochemical signals,represents a pivotal and complex process underpinning a multitude of cellular functionalities.This process is integral to diverse biological phenomena,including embryonic development,cell migration,tissue regeneration,and disease pathology,particularly in the context of cancer metastasis and cardiovascular diseases.Despite the profound biological and clinical significance of mechanotransduction,our understanding of this complex process remains incomplete.The recent development of advanced optical techniques enables in-situ force measurement and subcellular manipulation from the outer cell membrane to the organelles inside a cell.In this review,we delved into the current state-of-the-art techniques utilized to probe cellular mechanobiology,their principles,applications,and limitations.We mainly examined optical methodologies to quantitatively measure the mechanical properties of cells during intracellular transport,cell adhesion,and migration.We provided an introductory overview of various conventional and optical-based techniques for probing cellular mechanics.These techniques have provided into the dynamics of mechanobiology,their potential to unravel mechanistic intricacies and implications for therapeutic intervention.
基金supported by the Shenzhen Science and Technology Program-Basic Research Scheme(JCYJ20220531090808020)the Research Grants Council(RGC)of Hong Kong Collaborative Research Grant(C5005-23W and C5078-21E)+7 种基金the Research Grants Council(RGC)of Hong Kong General Research Grant(PolyU 15217621 and PolyU 15216622)the Guangdong-Hong Kong Technology Cooperation Funding Scheme(GHP/032/20SZ and SGDX20201103095404018)the Hong Kong Polytechnic University Shenzhen Institute Bai Cheng Bai Yuan Fund(I2022A002)PolyU Internal Fund(1-YWB4,1-WZ4E,1-CD8M,1-WZ4E,1-CEB1,1-YWDU,1-CE2J and 1-W02C)the funding from the Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center(No.:LMDBCXRC202401 and LMDBCXRC202402)Shandong Provincial Overseas Excellent Young Scholar Program(2024HWYQ-042 and 2024HWYQ-043)Taishan Scholar Youth Expert Program of Shandong Province(tsqn202306102 and tsqn202312105)supporting this worksupported by the University Research Facility in Life Sciences of the Hong Kong Polytechnic University.
文摘Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders,such as Alzheimer’s disease(AD),which can be induced by an excess of reactive oxygen species(ROS).As an antioxidant,hydrogen gas(H_(2))has the potential to mitigate AD by scavenging highly harmful ROS such as·OH.However,conventional administration methods of H_(2) face significant challenges in controlling H_(2) release on demand and fail to achieve effective accumulation at lesion sites.Herein,we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared(NIR)light-driven photocatalytic H_(2) evolution in situ.The nanoreactors are constructed by biocompatible crosslinked vesicles(CVs)encapsulating ascorbic acid and two photosensitizers,chlorophyll a(Chla)and indoline dye(Ind).In addition,platinum nanoparticles(Pt NPs)serve as photocatalysts and upconversion nanoparticles(UCNP)act as light-harvesting antennas in the nanoreacting system,and both attach to the surface of CVs.Under NIR irradiation,the nanoreactors release H_(2) in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model.Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.
基金Shenzhen-Hong Kong-Macao Science and Technology Plan Project,Grant/Award Number:SGDX2020110309260000Research Grants Council(RGC)Collaborative Research Fund,Grant/Award Number:C5110-20GF+2 种基金Research Grants Council(RGC)General Research Fund,Grant/Award Numbers:PolyU 15214619,PolyU 15210818Hong Kong Polytechnic University Internal Fund,Grant/Award Numbers:1-ZE1E,1-ZVVQNational Natural Science Foundation of China,Grant/Award Number:31771077。
文摘The ongoing outbreak of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)pandemic has posed significant challenges in early viral diagnosis.Hence,it is urgently desirable to develop a rapid,inexpensive,and sensitive method to aid point-of-care SARS-CoV-2 detection.In this work,we report a highly sequence-specific biosensor based on nanocomposites with aggregationinduced emission luminogens(AIEgen)-labeled oligonucleotide probes on graphene oxide nanosheets(AIEgen@GO)for one step-detection of SARS-CoV-2-specific nucleic acid sequences(Orf1ab or N genes).A dual“turn-on”mechanism based on AIEgen@GO was established for viral nucleic acids detection.Here,the first-stage fluorescence recovery was due to dissociation of the AIEgen from GO surface in the presence of target viral nucleic acid,and the second-stage enhancement of AIEbased fluorescent signal was due to the formation of a nucleic acid duplex to restrict the intramolecular rotation of the AIEgen.Furthermore,the feasibility of our platform for diagnostic application was demonstrated by detecting SARS-CoV-2 virus plasmids containing both Orf1ab and N genes with rapid detection around 1 h and good sensitivity at pM level without amplification.Our platform shows great promise in assisting the initial rapid detection of the SARS-CoV-2 nucleic acid sequence before utilizing quantitative reverse transcription-polymerase chain reaction for second confirmation.
基金the start-up funding(A0033912)from the Department of Biomedical EngineeringStart-up Fund for RAPs under the Strategic Hiring Scheme(0035876)the Hong Kong Polytechnic University(University Grant Council),for supporting this work.
文摘Adoptive T-cell therapy(ACT)is a promising therapeutic approach based on the concept of potent T-cell mediated immunity against the tumor.The outcome of antigen-specific T-cells responses relies on the interaction between T-cells and antigen-presenting cells,which provides signals for generating different T-cell phenotypes with different roles in tumor removal.However,such interaction is often not optimal in vivo and results in low therapeutic efficacy.To reach the full potential of the T-cell response,current research put effort into developing dynamic biomaterials as artificial antigen-presenting cells to study and regulate the T-cell activity for controlling T-cell fate.In this perspective,we provide(1)an overview of ACT and general T-cells behaviors,(2)explore the insight on how biomaterials can be used for studying and regulating T-cell behaviors,(3)and discuss conceptual gaps in knowledge for biomaterials-based immunotherapy.
