The rising flexible and intelligent electronics greatly facilitate the noninvasive and timely tracking of physiological information in telemedicine healthcare.Meticulously building bionic-sensitive moieties is vital f...The rising flexible and intelligent electronics greatly facilitate the noninvasive and timely tracking of physiological information in telemedicine healthcare.Meticulously building bionic-sensitive moieties is vital for designing efficient electronic skin with advanced cognitive functionalities to pluralistically capture external stimuli.However,realistic mimesis,both in the skin’s three-dimensional interlocked hierarchical structures and synchronous encoding multistimuli information capacities,remains a challenging yet vital need for simplifying the design of flexible logic circuits.Herein,we construct an artificial epidermal device by in situ growing Cu_(3)(HHTP)_(2) particles onto the hollow spherical Ti_(3)C_(2)T_(x) surface,aiming to concurrently emulate the spinous and granular layers of the skin’s epidermis.The bionic Ti_(3)C_(2)T_(x)@Cu_(3)(HHTP)_(2) exhibits independent NO_(2) and pressure response,as well as novel functionalities such as acoustic signature perception and Morse code-encrypted message communication.Ultimately,a wearable alarming system with a mobile application terminal is self-developed by integrating the bimodular senor into flexible printed circuits.This system can assess risk factors related with asthmatic,such as stimulation of external NO_(2) gas,abnormal expiratory behavior and exertion degrees of fingers,achieving a recognition accuracy of 97.6%as assisted by a machine learning algorithm.Our work provides a feasible routine to develop intelligent multifunctional healthcare equipment for burgeoning transformative telemedicine diagnosis.展开更多
The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory...The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.展开更多
Achieving highly regioselective synthesis in organic chemistry is challenging due to the uncontrollable orientation between reacting partners.External electric fields(EEFs)can influence the reactivity and selectivity ...Achieving highly regioselective synthesis in organic chemistry is challenging due to the uncontrollable orientation between reacting partners.External electric fields(EEFs)can influence the reactivity and selectivity of the substrate by causing directional adsorption.However,scalable and efficient techniques for using EEFs as“smart catalysts”have been lacking,hindering their application.In this study,we present a novel method for modifying the regioselectivity of quinoxaline-2(1H)-ones by functionalizing their C7-position using the electric double layer(EDL)theory.This approach led to moderate to good yields of the corresponding C7-thiocyanation products.DFT calculations and control experiments demonstrated that EEFs could reverse the regioselectivity of quinoxaline-2(1H)-ones,allowing the C7-thiocyanation to proceed via a radical reaction mechanism.Additionally,the resulting 7-thiocyano-1-methylquinoxaline-2(1H)-ones exhibited promising AIE properties.Our work showcases a promising strategy for achieving highly regioselective functionalization by aligning the electric field with the desired reaction/bond axis.展开更多
Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of...Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of paramount importance in unraveling the intricacies of pathological mechanisms and advancing the development of disease diagnosis.We herein introduce NFCOP,a state-of-the-art near-infrared(NIR)turn-on fluorescence(FL)probe that has been meticulously designed for highly sensitive,swift and selective imaging of CO.The NFCOP response occurred rapidly with CO,within just 10 s,and the calculated detection limit for CO was determined to be 0.32μmol/L.Further investigations conducted at the cellular level and in vivo demonstrated that NFCOP possesses high sensitivity and selectivity for imaging CO.展开更多
Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assemb...Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.展开更多
Cisplatin, carboplatin, and oxaliplatin are well-known firstline antineoplastic drugs that have been approved worldwide. Recently, the successful integration of chemotherapy and immunotherapy in clinical trials has hi...Cisplatin, carboplatin, and oxaliplatin are well-known firstline antineoplastic drugs that have been approved worldwide. Recently, the successful integration of chemotherapy and immunotherapy in clinical trials has highlighted the immunogenic potential [1].展开更多
Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processe...Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processes in plants by labeling specific molecular or cellular structures with fluorescent probes. However, tissue scattering and phytochrome interference have been obstacles for conventional fluorescence imaging of plants in the ultraviolet and visible spectrum, resulting in unsatisfactory imaging quality. Fortunately, advances in near-infrared(NIR) fluorescence imaging technology(650-900 nm) offer superior spatial-temporal resolution and reduced tissue scattering, which is sure to improve plant imaging quality. In this review, we summarize recent progress in the development of NIR fluorescence imaging probes and their applications for in vivo plant imaging and the identification of plant-related biomolecules. We hope this review provides a new perspective for plant science research and highlights NIR fluorescence imaging as a powerful tool for analyzing plant physiology, adaptive mechanisms, and coping with environmental stress in the near future.展开更多
Modifying the electrodes of electrochemical sensors is critical to enhance sensitivity,selectivity,and stability,ultimately improving both their effectiveness and performance.In this paper,recent advancements in elect...Modifying the electrodes of electrochemical sensors is critical to enhance sensitivity,selectivity,and stability,ultimately improving both their effectiveness and performance.In this paper,recent advancements in electrochemical sensors are reviewed,focusing on the utilization of layered double hydroxides(LDHs).The first section explores the advantageous and disadvantageous aspects of electrochemical sensing.Benefits include rapid response,ease of operation,and cost-effectiveness,while drawbacks concern the potential instability of prolonged use,susceptibility to interference,and the risk of biomolecule inactivation.Following this,the second section delves into the synthesis,constituents,and structure of LDHs.Moreover,after introducing the chemical mechanisms and functions of LDHs in electrochemical sensors,we concentrate on diverse modifying materials of LDHs and their different performances.Finally,the applications of LDHs in electrochemical sensing across different fields are discussed.This review aims to facilitate the continued advancement for applying LDHs in electrochemical sensors,as well as inspire the evolution of electrochemical sensing technology.展开更多
The induction of regulated cell death(RCD)through photo/ultrasound sensiti-zation therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors.Aggregation-induced emission...The induction of regulated cell death(RCD)through photo/ultrasound sensiti-zation therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors.Aggregation-induced emission(AIE)therapeutic agents generate reactive oxygen species through photo/ultrasound activation,which can synergize with RCD inducers or directly induce RCD,ultimately resulting in the death of tumor cells.The presented comprehensive review delves into recent advancements in AIE therapeutic agents designed to trigger RCD or synergize with RCD inducers,encompassing apoptosis,necroptosis,pyroptosis,immunogenic cell death,autophagy,ferroptosis,and cuproptosis.Additionally,the intricate regula-tory mechanisms through which activatory-AIE therapeutics influence distinct RCD pathways are examined.A forward-looking perspective on future developments and pertinent challenges within this exciting realm is presented,anticipating the con-tinued evolution of activatable AIE therapeutics as a transformative approach to enhance tumor therapy.展开更多
Microbial biofilm-related infections present a significant global health challenge,posing a major threat to public health systems[1].Biofilms,complex structures formed by the aggregation of microorganisms,are commonly...Microbial biofilm-related infections present a significant global health challenge,posing a major threat to public health systems[1].Biofilms,complex structures formed by the aggregation of microorganisms,are commonly found on medical devices,human tissue surfaces,and in natural environments[2].These biofilms exhibit high levels of antibiotic resistance and survival stability,rendering traditional antibiotic treatments ineffective in eradicating infections[3].展开更多
Polarity is a critical microenvironmental factor of the plasma membrane,which can offer valuable insights into various biological processes.Herein,we proposed a novel strategy for the construction of fluorescent agent...Polarity is a critical microenvironmental factor of the plasma membrane,which can offer valuable insights into various biological processes.Herein,we proposed a novel strategy for the construction of fluorescent agents to measure plasma membrane polarity by conjoining twisted intramolecular charge transfer(TICT)modulation and charge number control.It is shown that compounds with a stronger TICT tendency are more sensitive to polarity shifts due to the number of dialkylated amino groups present(from 1 to 3),and the molecules with two or more charged centers remain in the plasma membrane.Therefore,we developed two fluorescent agents with high polarity sensitivity,excellent turn-on ratios,and superior ability,to target the plasma membrane.In the wash-free fluorescence imaging and fluorescence lifetime tests,our designed agent could detect plasma membrane polarity with high precision,allowing effective distinction between cancer cells and normal cells based on their differences in plasma membrane polarity.Moreover,both fluorescence and fluorescence lifetime changes of the plasma membrane in the ferroptosis model established by Sorafenib confirmed an increase in plasma membrane polarity during cell ferroptosis.展开更多
Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area.The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cance...Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area.The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs,such as poor localization at the tumor site,high drug doses and toxicity,recurrence,and poor immune response.However,inadequate biocompatibility restricts their potential in clinical translation.Therefore,advanced nanomaterials with high biocompat-ibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines.Intrinsic properties of nanoscale covalent organic frameworks(nCOFs),such as suitable size,modular pore geometry and porosity,and straightforward post-synthetic modification via simple organic transformations,make them incredibly attractive for future nanomedicines.The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery.This review summarizes recently published applications of COFs in drug delivery,photo-immuno therapy,sonodynamic therapy,photothermal therapy,chemotherapy,pyroptosis,and combination therapy.Herein we mainly focused on modifications of COFs to enhance their biocompatibility,efficacy and potential clinical translation.This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nano-medicines and will help in the rapid development of cancer drug carriers and theranostics.展开更多
Ferroptosis, a recently identified form of non-apoptotic programmed cell death, has attracted significant attention in the field of cancer therapy due to its unique mechanism of cell death. To meet the demands of ferr...Ferroptosis, a recently identified form of non-apoptotic programmed cell death, has attracted significant attention in the field of cancer therapy due to its unique mechanism of cell death. To meet the demands of ferroptosis-mediated cancer treatment, several small molecule-based drugs have been reported for the implementation of ferroptosis. However, some cancer cells are inherently resistant to these drugs, and the lack of selectivity of these drugs against cancer cells can limit their clinical application. Recent advancements in light-mediated biomedical techniques offer a promising alternative for the development of ferroptotic therapy, that is photo-controlled activation of ferroptosis. In this review, we systematically summarize the current strategies for photo-controlled ferroptosis activation and detail analysis of the underlying mechanisms of those photo-controlled ferroptotic therapies. Finally, we discuss the challenges associated with photo-activated ferroptosis and provide an outlook on the future developments in ferroptotic cancer therapy.展开更多
Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vi...Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vivo difficult.We therefore synthesized a novel Pt(Ⅱ)metallacycle(Pt1110)that can be activated with a 980 nm laser for photodiagnosis/treatment in deep tissue.We found that Pt1110 significantly improved photothermal conversion(95%improvement)and ^(1)O_(2) generation(ΦΔ75%increase)compared to the ligand itself 1 and was well capable of light-induced sterilization under safe laser irradiation(0.72 W/cm^(2)).In addition,Pt1110 has little to no toxicity to cells.After incorporated into liposome,Pt1110 NPs was effective in wound healing in infection and keratitis models upon laser irradiation,which was accurately observed by NIR-Ⅱfluorescence imaging.This novel metal-coordinated supramolecular material has a potential to become a universal platform for phototherapy in deep tissue.展开更多
COVID-19,caused by SARS-CoV-2,has resulted in serious economic and health burdens.Current treatments remain inadequate to extinguish the epidemic,and efficient therapeutic approaches for COVID-19 are urgently being so...COVID-19,caused by SARS-CoV-2,has resulted in serious economic and health burdens.Current treatments remain inadequate to extinguish the epidemic,and efficient therapeutic approaches for COVID-19 are urgently being sought.Interestingly,accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in patients.In addition,recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection,providing new insight into COVID-19 treatment.Most literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 patients.To fill this gap,this review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms.Next,advances in nanotechnology-based strategies for promoting homeostasis restoration are summarized.Finally,we discuss the challenges and prospects of using nanomaterials for COVID-19 management.This review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.展开更多
COVID-19,a highly contagious respiratory infection caused by the SARS-Co V-2 virus,was first identified in December 2019 and has rapidly expanded to become a global pandemic[1].From then on,millions of people were inf...COVID-19,a highly contagious respiratory infection caused by the SARS-Co V-2 virus,was first identified in December 2019 and has rapidly expanded to become a global pandemic[1].From then on,millions of people were infected,while the exact number of infections is difficult to determine,as not all people who are infected with the virus get tested,and some may not show any symptoms,and the number is rising as the pandemic continues.The sickness is characterized by fever,cough.展开更多
Functional dyes go beyond traditional color applications and offer distinctive properties and functionalities,making them suitable for a wide range of industrial applications such as healthcare,agriculture,textiles,an...Functional dyes go beyond traditional color applications and offer distinctive properties and functionalities,making them suitable for a wide range of industrial applications such as healthcare,agriculture,textiles,and electronics.Functional dyes can serve as fluorescent probes in medical research,photosensitizers in cancer therapy,pesticide markers in agriculture,antimicrobial agents on textiles,and charge transport materials in electronics.The ongoing research into new functional dyes reflects the interest of industries in identifying novel applications for these materials.展开更多
An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfor...An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.展开更多
The pathological origin of Alzheimer’s disease(AD)is still shrouded in mystery,despite intensive worldwide research efforts.The selective visualization ofβ-amyloid(Aβ),the most abundant proteinaceous deposit in AD,...The pathological origin of Alzheimer’s disease(AD)is still shrouded in mystery,despite intensive worldwide research efforts.The selective visualization ofβ-amyloid(Aβ),the most abundant proteinaceous deposit in AD,is pivotal to reveal AD pathology.To date,several small-molecule fluorophores for Aβspecies have been developed,with increasing binding affinities.In the current work,two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ_(1-42) fibrils-while concurrently preventing poor aqueous solubility-via biannulate donor motifs in D-π-A dyes.An unprecedented sub-nanomolar affinity was found(K_(d)=0.62±0.33 nM)and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo.These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.展开更多
The nucleolus,the locus of ribosome biogenesis,was found to be the predominant intracellular target of a new fluorescent probe,V-P1.In solution,the probe demonstrated both a selectivity to RNA G-quadruplexes and a sen...The nucleolus,the locus of ribosome biogenesis,was found to be the predominant intracellular target of a new fluorescent probe,V-P1.In solution,the probe demonstrated both a selectivity to RNA G-quadruplexes and a sensitivity to the viscosity,while G-quadruplex binding did not disturb the viscosity sensing.In cells,confocal and fluorescence lifetime imaging,combined with digestion and competition experiments,lent support to the hypothesis of an RNA-based G-quadruplex as the intracellular target,postulated to be nucleolar ribosomal RNA(rRNA).The probe demonstrated a high sensitivity to viscosity in both the cytoplasm and the nuclear compartment and was used to precisely interrogate the viscosity changes resulting from diverse stimuli,such as temperature,monensin treatment,and etoposide-induced apoptosis.Owing to the putative rRNA G-quadruplex binding in vitro and in vivo,and further combined with a relatively low degree of toxicity,the dye enabled the interrogation of cytoplasm and intranuclear viscosity changes under diverse conditions and found applications in studying the influence and significance of cytoplasm and intranuclear viscosity as well as in gaining insight into the native secondary structure of rRNA in nucleoli.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.U22A20184,52250077,and 52272080)the Jilin Province Natural Science Foundation of China(No.20220201093GX)+2 种基金the Fundamental Research Funds for the Central Universitiessupported by the National Research Foundation of Korea(2018R1A3B1052702 to JSK)the Starting growth Technological R&D Program(TIPS Program,No.S3201803,2021,MW)funded by the Ministry of SMEs and Startups(MSS,Korea).
文摘The rising flexible and intelligent electronics greatly facilitate the noninvasive and timely tracking of physiological information in telemedicine healthcare.Meticulously building bionic-sensitive moieties is vital for designing efficient electronic skin with advanced cognitive functionalities to pluralistically capture external stimuli.However,realistic mimesis,both in the skin’s three-dimensional interlocked hierarchical structures and synchronous encoding multistimuli information capacities,remains a challenging yet vital need for simplifying the design of flexible logic circuits.Herein,we construct an artificial epidermal device by in situ growing Cu_(3)(HHTP)_(2) particles onto the hollow spherical Ti_(3)C_(2)T_(x) surface,aiming to concurrently emulate the spinous and granular layers of the skin’s epidermis.The bionic Ti_(3)C_(2)T_(x)@Cu_(3)(HHTP)_(2) exhibits independent NO_(2) and pressure response,as well as novel functionalities such as acoustic signature perception and Morse code-encrypted message communication.Ultimately,a wearable alarming system with a mobile application terminal is self-developed by integrating the bimodular senor into flexible printed circuits.This system can assess risk factors related with asthmatic,such as stimulation of external NO_(2) gas,abnormal expiratory behavior and exertion degrees of fingers,achieving a recognition accuracy of 97.6%as assisted by a machine learning algorithm.Our work provides a feasible routine to develop intelligent multifunctional healthcare equipment for burgeoning transformative telemedicine diagnosis.
基金supported by the National Research Foundation of Korea(CRI project no.2018R1A3B1052702 and 2019M3E5D1A01068998,J.S.K.)Basic Science Research Program(2020R1A6A3A01100551,M.W.and 2020R1A6A3A01100558,S.K.)funded by the Ministry of EducationKorea University Grant。
文摘The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.
基金supported by the National Natural Science Foundation of China(21172200,21302172)the Basic Research Training Project of Zhengzhou University(JC2020053021)supported by the National Research Foundation of Korea(CRI Project No.2018R1A3B1052702 for Jong Seung Kim)。
文摘Achieving highly regioselective synthesis in organic chemistry is challenging due to the uncontrollable orientation between reacting partners.External electric fields(EEFs)can influence the reactivity and selectivity of the substrate by causing directional adsorption.However,scalable and efficient techniques for using EEFs as“smart catalysts”have been lacking,hindering their application.In this study,we present a novel method for modifying the regioselectivity of quinoxaline-2(1H)-ones by functionalizing their C7-position using the electric double layer(EDL)theory.This approach led to moderate to good yields of the corresponding C7-thiocyanation products.DFT calculations and control experiments demonstrated that EEFs could reverse the regioselectivity of quinoxaline-2(1H)-ones,allowing the C7-thiocyanation to proceed via a radical reaction mechanism.Additionally,the resulting 7-thiocyano-1-methylquinoxaline-2(1H)-ones exhibited promising AIE properties.Our work showcases a promising strategy for achieving highly regioselective functionalization by aligning the electric field with the desired reaction/bond axis.
基金supported by the National Key R&D Programs(No.2021YFA0910001)the Shenzhen Science and Technology Program(Nos.JCYJ20210324115804013,JCYJ2022081810160716,JCYJ20220531093604009)+2 种基金the Specific Research Assistant Funding Program of Chinese Academy of Sciences(No.E35902)the National Natural Science Foundation of China(Nos.22005343,32000982)the Guangdong Provincial Key Area R&D Program(No.2020B1111540001).
文摘Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of paramount importance in unraveling the intricacies of pathological mechanisms and advancing the development of disease diagnosis.We herein introduce NFCOP,a state-of-the-art near-infrared(NIR)turn-on fluorescence(FL)probe that has been meticulously designed for highly sensitive,swift and selective imaging of CO.The NFCOP response occurred rapidly with CO,within just 10 s,and the calculated detection limit for CO was determined to be 0.32μmol/L.Further investigations conducted at the cellular level and in vivo demonstrated that NFCOP possesses high sensitivity and selectivity for imaging CO.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.RS-2023-00208427,2021R1I1A1A01046207,2021R1A2C2005418,2022R1A2C2005943,and 2022M3H4A1A03076638)supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.RS-2023-00271399 and RS-2023-00275654)+1 种基金supported by a Korea University Grant and KIST intramural programHAADF-STEM was conducted with the support of the Seoul center in Korea Basic Science Institute(KBSI).
文摘Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.
文摘Cisplatin, carboplatin, and oxaliplatin are well-known firstline antineoplastic drugs that have been approved worldwide. Recently, the successful integration of chemotherapy and immunotherapy in clinical trials has highlighted the immunogenic potential [1].
基金supported by the National Natural Science Foundation of China(U20A2038,22022404,21977036,22074050)the CRI Project of National Research Foundation of Republic of Korea(2018R1A3B1052702)+1 种基金Department of Biotechnology,New Delhi,India,for prestigious DBT-Ramalingaswami fellowship(BT/RLF/Re-entry/59/2018)Science&Engineering Research Board,New Delhi(CRG/2021/002476)。
文摘Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processes in plants by labeling specific molecular or cellular structures with fluorescent probes. However, tissue scattering and phytochrome interference have been obstacles for conventional fluorescence imaging of plants in the ultraviolet and visible spectrum, resulting in unsatisfactory imaging quality. Fortunately, advances in near-infrared(NIR) fluorescence imaging technology(650-900 nm) offer superior spatial-temporal resolution and reduced tissue scattering, which is sure to improve plant imaging quality. In this review, we summarize recent progress in the development of NIR fluorescence imaging probes and their applications for in vivo plant imaging and the identification of plant-related biomolecules. We hope this review provides a new perspective for plant science research and highlights NIR fluorescence imaging as a powerful tool for analyzing plant physiology, adaptive mechanisms, and coping with environmental stress in the near future.
基金supported by the National Natural Science Foundation of China(82170998 and 61874049)the Jilin Province College Student Innovation Project and the Fundamental Research Funds for the Central Universities+1 种基金the National Research Foundation of Korea(2018R1A3B1052702 to Kim)the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(RS-202300208427 to Kang H)。
文摘Modifying the electrodes of electrochemical sensors is critical to enhance sensitivity,selectivity,and stability,ultimately improving both their effectiveness and performance.In this paper,recent advancements in electrochemical sensors are reviewed,focusing on the utilization of layered double hydroxides(LDHs).The first section explores the advantageous and disadvantageous aspects of electrochemical sensing.Benefits include rapid response,ease of operation,and cost-effectiveness,while drawbacks concern the potential instability of prolonged use,susceptibility to interference,and the risk of biomolecule inactivation.Following this,the second section delves into the synthesis,constituents,and structure of LDHs.Moreover,after introducing the chemical mechanisms and functions of LDHs in electrochemical sensors,we concentrate on diverse modifying materials of LDHs and their different performances.Finally,the applications of LDHs in electrochemical sensing across different fields are discussed.This review aims to facilitate the continued advancement for applying LDHs in electrochemical sensors,as well as inspire the evolution of electrochemical sensing technology.
基金National Natural Science Foundation of China,Grant/Award Numbers:22067019,22367023Yunnan Provincial Science and Technology Department-Yunnan University Joint Special Project,Grant/Award Number:202201BF070001-001+2 种基金Postgraduate Research Innovation Foundation of Yunnan University,Grant/Award Number:KC-22222295National Research Foundation of Korea,Grant/Award Number:2018R1A3B1052702 J.S.KChina Scholarship Council,Grant/Award Number:201907030009。
文摘The induction of regulated cell death(RCD)through photo/ultrasound sensiti-zation therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors.Aggregation-induced emission(AIE)therapeutic agents generate reactive oxygen species through photo/ultrasound activation,which can synergize with RCD inducers or directly induce RCD,ultimately resulting in the death of tumor cells.The presented comprehensive review delves into recent advancements in AIE therapeutic agents designed to trigger RCD or synergize with RCD inducers,encompassing apoptosis,necroptosis,pyroptosis,immunogenic cell death,autophagy,ferroptosis,and cuproptosis.Additionally,the intricate regula-tory mechanisms through which activatory-AIE therapeutics influence distinct RCD pathways are examined.A forward-looking perspective on future developments and pertinent challenges within this exciting realm is presented,anticipating the con-tinued evolution of activatable AIE therapeutics as a transformative approach to enhance tumor therapy.
文摘Microbial biofilm-related infections present a significant global health challenge,posing a major threat to public health systems[1].Biofilms,complex structures formed by the aggregation of microorganisms,are commonly found on medical devices,human tissue surfaces,and in natural environments[2].These biofilms exhibit high levels of antibiotic resistance and survival stability,rendering traditional antibiotic treatments ineffective in eradicating infections[3].
基金support of this work by the National Natural Science Foundation of China(grant nos.22067019 and 22367023)Yunnan Provincial Science and Technology Department-Yunnan University Joint Special Project(grant no.202201BF070001-001)+5 种基金the Postgraduate Research Innovation Foundation of Yunnan University(grant no.KC-22222295)the Scientific Research Foundation Project of Yunnan Provincial Department of Education(grant no.2022Y028)the National Research Foundation of Korea(CRIproject no.2018R1A3B1052702,J.S.K)L.Yu thanks the China Scholarship Council(CSCgrant no.2021907030009).
文摘Polarity is a critical microenvironmental factor of the plasma membrane,which can offer valuable insights into various biological processes.Herein,we proposed a novel strategy for the construction of fluorescent agents to measure plasma membrane polarity by conjoining twisted intramolecular charge transfer(TICT)modulation and charge number control.It is shown that compounds with a stronger TICT tendency are more sensitive to polarity shifts due to the number of dialkylated amino groups present(from 1 to 3),and the molecules with two or more charged centers remain in the plasma membrane.Therefore,we developed two fluorescent agents with high polarity sensitivity,excellent turn-on ratios,and superior ability,to target the plasma membrane.In the wash-free fluorescence imaging and fluorescence lifetime tests,our designed agent could detect plasma membrane polarity with high precision,allowing effective distinction between cancer cells and normal cells based on their differences in plasma membrane polarity.Moreover,both fluorescence and fluorescence lifetime changes of the plasma membrane in the ferroptosis model established by Sorafenib confirmed an increase in plasma membrane polarity during cell ferroptosis.
基金National Research Foundation of Korea CRI project(Grant No.2018R1A3B1052702 and 2019M3E5D1A01068998,J.S.K.and NRF-2021R1A2B03002487,S.-G.C.)Basic Science Research Programs(2022R1C1C2007637,SK)of the NRF KoreaThis work was also supported by the Korea University Grant(PJ).
文摘Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area.The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs,such as poor localization at the tumor site,high drug doses and toxicity,recurrence,and poor immune response.However,inadequate biocompatibility restricts their potential in clinical translation.Therefore,advanced nanomaterials with high biocompat-ibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines.Intrinsic properties of nanoscale covalent organic frameworks(nCOFs),such as suitable size,modular pore geometry and porosity,and straightforward post-synthetic modification via simple organic transformations,make them incredibly attractive for future nanomedicines.The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery.This review summarizes recently published applications of COFs in drug delivery,photo-immuno therapy,sonodynamic therapy,photothermal therapy,chemotherapy,pyroptosis,and combination therapy.Herein we mainly focused on modifications of COFs to enhance their biocompatibility,efficacy and potential clinical translation.This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nano-medicines and will help in the rapid development of cancer drug carriers and theranostics.
基金financial support received from the National Research Foundation of Korea(CRI project no.2018R1A3B1052702,J.S.K)L.Y.thanks the China Scholarship Fund(CSC number 201907030009).
文摘Ferroptosis, a recently identified form of non-apoptotic programmed cell death, has attracted significant attention in the field of cancer therapy due to its unique mechanism of cell death. To meet the demands of ferroptosis-mediated cancer treatment, several small molecule-based drugs have been reported for the implementation of ferroptosis. However, some cancer cells are inherently resistant to these drugs, and the lack of selectivity of these drugs against cancer cells can limit their clinical application. Recent advancements in light-mediated biomedical techniques offer a promising alternative for the development of ferroptotic therapy, that is photo-controlled activation of ferroptosis. In this review, we systematically summarize the current strategies for photo-controlled ferroptosis activation and detail analysis of the underlying mechanisms of those photo-controlled ferroptotic therapies. Finally, we discuss the challenges associated with photo-activated ferroptosis and provide an outlook on the future developments in ferroptotic cancer therapy.
基金supported by National Natural Science Foundation of China(22022404,22074050,21904103)the Fundamental Research Funds for the Central Universities(CCNU22QN007)+4 种基金the Open Research Fund of State Key Laboratory of Chemo/Biosensing and Chemometrics(2021005)the Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules Hubei University(KLSAOFM2111)the Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education,Jianghan University(JDGD-202209)the Open Project Program of Key Laboratory for Analytical Science of Food Safety and Biology,Ministry of Education(FS2202)supported by the CRI project of National Research Foundation of Republic of Korea(2018R1A3B1052702,JSK)。
文摘Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vivo difficult.We therefore synthesized a novel Pt(Ⅱ)metallacycle(Pt1110)that can be activated with a 980 nm laser for photodiagnosis/treatment in deep tissue.We found that Pt1110 significantly improved photothermal conversion(95%improvement)and ^(1)O_(2) generation(ΦΔ75%increase)compared to the ligand itself 1 and was well capable of light-induced sterilization under safe laser irradiation(0.72 W/cm^(2)).In addition,Pt1110 has little to no toxicity to cells.After incorporated into liposome,Pt1110 NPs was effective in wound healing in infection and keratitis models upon laser irradiation,which was accurately observed by NIR-Ⅱfluorescence imaging.This novel metal-coordinated supramolecular material has a potential to become a universal platform for phototherapy in deep tissue.
基金financially supported by the National Natural Science Foundation of China(No.92168106,China)the key project for clinical innovation of Third Military Medical University(No.CX2019LC107,China)the National Research Foundation of Korea(CRI project No.2018R1A3B1052702,Korea)。
文摘COVID-19,caused by SARS-CoV-2,has resulted in serious economic and health burdens.Current treatments remain inadequate to extinguish the epidemic,and efficient therapeutic approaches for COVID-19 are urgently being sought.Interestingly,accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in patients.In addition,recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection,providing new insight into COVID-19 treatment.Most literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 patients.To fill this gap,this review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms.Next,advances in nanotechnology-based strategies for promoting homeostasis restoration are summarized.Finally,we discuss the challenges and prospects of using nanomaterials for COVID-19 management.This review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.
文摘COVID-19,a highly contagious respiratory infection caused by the SARS-Co V-2 virus,was first identified in December 2019 and has rapidly expanded to become a global pandemic[1].From then on,millions of people were infected,while the exact number of infections is difficult to determine,as not all people who are infected with the virus get tested,and some may not show any symptoms,and the number is rising as the pandemic continues.The sickness is characterized by fever,cough.
文摘Functional dyes go beyond traditional color applications and offer distinctive properties and functionalities,making them suitable for a wide range of industrial applications such as healthcare,agriculture,textiles,and electronics.Functional dyes can serve as fluorescent probes in medical research,photosensitizers in cancer therapy,pesticide markers in agriculture,antimicrobial agents on textiles,and charge transport materials in electronics.The ongoing research into new functional dyes reflects the interest of industries in identifying novel applications for these materials.
基金supported by the National Natural Science Foundation of China(Grant No.11904239,Y.W.W)the Creative Research Initiative of National Research Foundation of Korea(NRF)(CRI project No.2018R1A3B1052702,J.S.K.)+1 种基金Initial support for the work in Austin came from the National Institutes of Health(CA 68682 to J.L.S.)with subsequent funding from the Robert A.Welch Foundation(F-0018 to J.L.S.)supported by Brain Pool Program through the funded by the Ministry of Science and ICT(Grant No.2020H1D3A1A02080172,M.L.).
文摘An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.
基金This research was supported by the National Research Foundation of Korea(CRI project no.2018R1A3B1052702,NRF-2019M3E5D1A01068998,J.S.Kim)the Korea University Graduate School Junior Fellow Research Grant(J.An)+3 种基金the National Research Council of Science&Technology(NST)granted by the Ministry of Science,ICT&Future Planning(MSIP)(No.CRC-15-04-KIST)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)and Korea Dementia Research Center(KDRC)the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea(No.HI20C1234)P.V.acknowledges support from Interne Fondsen KU Leuven/Internal Funds KU Leuven(STG/19/029).
文摘The pathological origin of Alzheimer’s disease(AD)is still shrouded in mystery,despite intensive worldwide research efforts.The selective visualization ofβ-amyloid(Aβ),the most abundant proteinaceous deposit in AD,is pivotal to reveal AD pathology.To date,several small-molecule fluorophores for Aβspecies have been developed,with increasing binding affinities.In the current work,two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ_(1-42) fibrils-while concurrently preventing poor aqueous solubility-via biannulate donor motifs in D-π-A dyes.An unprecedented sub-nanomolar affinity was found(K_(d)=0.62±0.33 nM)and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo.These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.
基金supported by CRI project(no.2018R1A3B1052702J.S.K.)from the National Research Foundation of Korea(NRF)+3 种基金by the China Scholarship Fund(CSC no.201907030009L.Y.)by the Interne Fondsen KU Leuven/Internal Funds KU Leuven(STG/19/029P.V.).
文摘The nucleolus,the locus of ribosome biogenesis,was found to be the predominant intracellular target of a new fluorescent probe,V-P1.In solution,the probe demonstrated both a selectivity to RNA G-quadruplexes and a sensitivity to the viscosity,while G-quadruplex binding did not disturb the viscosity sensing.In cells,confocal and fluorescence lifetime imaging,combined with digestion and competition experiments,lent support to the hypothesis of an RNA-based G-quadruplex as the intracellular target,postulated to be nucleolar ribosomal RNA(rRNA).The probe demonstrated a high sensitivity to viscosity in both the cytoplasm and the nuclear compartment and was used to precisely interrogate the viscosity changes resulting from diverse stimuli,such as temperature,monensin treatment,and etoposide-induced apoptosis.Owing to the putative rRNA G-quadruplex binding in vitro and in vivo,and further combined with a relatively low degree of toxicity,the dye enabled the interrogation of cytoplasm and intranuclear viscosity changes under diverse conditions and found applications in studying the influence and significance of cytoplasm and intranuclear viscosity as well as in gaining insight into the native secondary structure of rRNA in nucleoli.
