In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cere...In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.展开更多
Precision medicine calls for advanced theranostics that integrate controllable diagnostic and therapeutic capabilities into one platform for disease treatment in the early stage.Phototheranostics such as fluorescence ...Precision medicine calls for advanced theranostics that integrate controllable diagnostic and therapeutic capabilities into one platform for disease treatment in the early stage.Phototheranostics such as fluorescence imaging(FLI),photoacoustic imaging(PAI),photodynamic therapy(PDT),and photothermal therapy(PTT)have attracted considerable attention in recent years,which mainly employ different excited-state energy dissipation pathways of a chromophore.According to the Jablonski diagram,FLI is related to the radiative process,PAI and PTT are derived from the nonradiative thermal deactivation,and PDT originates from the triplet state energy,in which these processes are usually competitive.Therefore,it is critically important to precisely tune the photophysical energy transformation processes to realize certain diagnosis and treatment properties in optimal state for boosting biomedical applications.Currently,there are mainly two strategies including chemical structure and aggregate behavior changes that relate to the regulation of excited state energy dissipation.In this review,we will discuss the recent advances of smart molecular probes that the photophysical properties can be regulated by external triggers and their applications in biomedical fields.We will summarize the development of activatable phototheranostic molecular probes in response to stimuli such as reactive oxygen species,pH,light,hypoxia,enzyme and gas.The assembly and disassembly of molecular aggregates that greatly affect the photophysical energy transformation processes will also be highlighted.This review aims to provide valuable insights into the development of more accurate diagnostic and therapeutic systems,thereby advancing the emerging field of smart medicine.展开更多
New ionization and detection techniques in mass spectrometry have been successfully applied for efficient analyses of complex biological systems. It is, however, still difficult to trace structural changes of a specif...New ionization and detection techniques in mass spectrometry have been successfully applied for efficient analyses of complex biological systems. It is, however, still difficult to trace structural changes of a specific molecular species in such systems. In the present study, a molecular probe strategy in combination with tandem electrospray ionization mass spectrometry has been examined using synthetic deuterium-labeled phosphatidylcholine hydroperoxide (PC-OOH/D3) and ethyl-labeled phosphatidylcholine having docosahexaenoic acid side chain (DHA-PC/Et). Administration of a mixture of PC-OOH/D3 and DHA-PC/Et to human blood and human skin surface, followed by extraction and analysis with collision-induced tandem electrospray ionization mass spectrometry demonstrated that metabolites of both molecular probes can be detected simultaneously with strict selectivity. The present method is also found to be useful in tracing chemical changes of the unstable docosahexaenoyl group on the surface of processed fish. The activity of phospholipase A2 can also be assessed using a phospholipid molecular probe with a linoleoyl and a deuteriomethyl group via selective detection of the lyso-phospholipid product by mass spectrometry. The advantage of the present method is that no chromatographic separation is required and analysis can be performed under strictly the same condition for different molecular probes, affording multiple data by one experiment. The present strategy may be useful for tracing time-dependent phenomena in dynamic phospholipid biochemistry, and can be widely used for any biological and food systems.展开更多
Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy.Nonetheless,the optimization of the catal...Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy.Nonetheless,the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes.Herein,we reported a self-amplifying fluorescent molecular probe,Bis-HTPICG,for photodynamic therapy(PDT)and subsequent PDT-induced immunoreaction.The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO),a crucial enzyme secreted by neutrophils at inflammation sites.Upon exposure to laser irradiation,Bis-HTP-ICG showed a high PDT efficacy,inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion.The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis,instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG,neutrophils and MPO.Meanwhile,PDT efficiently incites immunogenic cell death(ICD)in tumor cells,initiating an anti-tumor immune response including dendritic cells(DCs)maturation,T cell proliferation and reprogramming of tumor-associated neutrophils(TANs).This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.展开更多
Morphological imaging techniques are very limited in their ability to evaluate the early efficacy of tumor therapies,with the limitation of being more reflective and lagging.Many of the newer therapies are cytostatic,...Morphological imaging techniques are very limited in their ability to evaluate the early efficacy of tumor therapies,with the limitation of being more reflective and lagging.Many of the newer therapies are cytostatic,and tumor necrosis or lack of tumor progression is associated with a good response to treatment even in the absence of tumor shrinkage;therefore,there is an increasing need to develop techniques for the assessment of tumor efficacy.Magnetic resonance imaging(MRI),with the help of a variety of contrast mechanisms and probes,provides excellent soft-tissue imaging,high-quality anatomical signals as well as reflecting certain functional states of the tumor and molecular biological information.It can be used to differentiate between cancer and normal tissue,to noninvasively monitor tumor growth,and to identify changes in the tumor and its microenvironment in response to treatment.This review will discuss the role of magnetic resonance imaging in the assessment of tumor efficacy,with a focus on presenting research advances in magnetic resonance molecular imaging and its probes in the assessment of tumor efficacy.展开更多
Labelling and identification of proliferating cells is important for the study of physiological or pathological processes in high-content screening (HCS) assays. Here we describe ethynyl deoxyuridine (EdU) as a biomar...Labelling and identification of proliferating cells is important for the study of physiological or pathological processes in high-content screening (HCS) assays. Here we describe ethynyl deoxyuridine (EdU) as a biomarker for the assessment of cell proliferation and clearly demonstrate the feasibility of the EdU-labelling method for use in HCS assays. EdU detection is highly robust, reproducible, technically simple, and well suited for automated segmentation, which provides an excellent al- ternative for setting up multiplexed HCS assays of siRNA, miRNA and small-molecule libraries.展开更多
Macrophage is a kind of immune cell and performs multiple functions including pathogen phagocytosis,antigen presentation and tissue remodeling.To fulfll their functionally distinct roles,macrophages undergo polarizati...Macrophage is a kind of immune cell and performs multiple functions including pathogen phagocytosis,antigen presentation and tissue remodeling.To fulfll their functionally distinct roles,macrophages undergo polarization towards a spectrum of phenotypes,particularly the classically activated(M1)and alternatively activated(M2)subtypes.However,the binary M1/M2 phenotype fails to capture the complexity of macrophages subpopulations in vivo.Hence,it is crucial to employ spatiotemporal imaging techniques to visualize macrophage phenotypes and polarization,enabling the monitoring of disease progression and assessment of therapeutic responses to drug candidates.This review begins by discussing the origin,function and diversity of macrophage under physiological and pathological conditions.Subsequently,we summarize the identifed macrophage phenotypes and their specifc biomarkers.In addition,we present the imaging probes locating the lesions by visualizing macrophages with specifc phenotype in vivo.Finally,we discuss the challenges and prospects associated with monitoring immune microenvironment and disease progression through imaging of macrophage phenotypes.展开更多
Acute kidney injury(AKI),a prevalent and complex clinical condition associated with elevated risks of morbidity and mortality,necessitates the meticulous detection and monitoring of kidney damage globally.Biomedicine ...Acute kidney injury(AKI),a prevalent and complex clinical condition associated with elevated risks of morbidity and mortality,necessitates the meticulous detection and monitoring of kidney damage globally.Biomedicine has shown keen interest in molecular probes and detectors for AKI due to their sensitivity,rapidity,and cost-effectiveness.Bioimaging technologies play a significant role in identifying and quantifying AKI indicators,enhancing diagnostic approaches,and potentially refining clinical therapies for immediate injury control.Molecular probes serve as valuable tools for drug screening,uncovering renoprotective components,signaling pathways,and the nephrotoxic effects of drugs.This review comprehensively summarizes the latest advancements in molecular probes,emphasizing their exceptional efficacy in various characteristics,including renal cleanability,multichannel detection capability,near-infrared-II responsiveness,and reactivity toward reactive oxygen species.These probes offer enhanced benefits for assessing kidney damage and evaluating the therapeutic effects of medications while simultaneously reducing toxic effects.Additionally,the review delves into future potentials and challenges in this field,aiming to inspire the development and enhancement of molecular bioimaging for the early diagnosis and treatment of kidney diseases.展开更多
A summer-autumn (1994) molecular epidemiological study of enteric adenoviruses (EAds) in stool specimens collected in Wuhan area was conducted by using Digoxigenin-labelled DNA probes specific to EAd40, and EAd41, res...A summer-autumn (1994) molecular epidemiological study of enteric adenoviruses (EAds) in stool specimens collected in Wuhan area was conducted by using Digoxigenin-labelled DNA probes specific to EAd40, and EAd41, respectively.44 of 602 specimens were positive, among which 23 cases were identified as EAd40, 14 were EAd41, infection and 7 were dual infection. The ratio of males to females for the positive specimens was 1. 44. The infection rate of EAd40 and EAd41 each displayed no marked difference in seasons (summer and autumn) and similar age distribution was found between them. All of the two types of EAds in-fections predominated in patients with diarrhea under 3 years old- The results indicated that the Digoxigenin probe could detect DNA quantities as low as 1 pgwith satis factory specificity and the technique can be used for both clinical and ex-perimental purposes.展开更多
The properties of one-photon absorption（OPA）, emission and two-photon absorption（TPA） of a di-2-picolylaminebased zinc ion sensor are investigated by employing the density functional theory in combination with res...The properties of one-photon absorption（OPA）, emission and two-photon absorption（TPA） of a di-2-picolylaminebased zinc ion sensor are investigated by employing the density functional theory in combination with response functions.The responsive mechanism is explored. It is found that the calculated OPA and TPA properties are quite consistent with experimental data. Because the intra-molecular charge transfer（ICT） increases upon zinc ion binding, the TPA intensity is enhanced dramatically. According to the model sensor, we design a series of zinc ion probes which differ by conjugation center, acceptor and donor moieties. The properties of OPA, emission and TPA of the designed molecules are calculated at the same computational level. Our results demonstrate that the OPA and emission wavelengths of the designed probes have large red-shifts after zinc ions have been bound. Comparing with the model sensor, the TPA intensities of the designed probes are enhanced significantly and the absorption positions are red-shifted to longer wavelength range. Furthermore, the TPA intensity can be improved greatly upon zinc ion binding due to the increased ICT mechanism. These compounds are potential excellent candidates for two-photon fluorescent zinc ion probes.展开更多
During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognize...During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognized.At present,^18F-fluorodeoxyglucose（^18F-FDG） is the most broadly used PET probe.However,^18F-FDG also suffers many limitations.Thus,scientists and clinicians are greatly interested in exploring and developing new PET imaging probes with high affinity and specificity.In this review,we briefly summarize the representative PET probes beyond ^18F-FDG that are available for patients imaging in three major clinical areas（oncology,neurology and cardiology）,and we also discuss the feasibility and trends in developing new PET probes for personalized medicine.展开更多
Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast ca...Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.展开更多
中药化学生物学(traditional Chinese medicine chemical biology,TCMCB)作为21世纪中医药现代化进程中形成的重要学科方向,其研究模式通过整合现代化学与生物学等技术手段,构建了具有鲜明中医药特色的研究体系。该学科方向立足中医药理...中药化学生物学(traditional Chinese medicine chemical biology,TCMCB)作为21世纪中医药现代化进程中形成的重要学科方向,其研究模式通过整合现代化学与生物学等技术手段,构建了具有鲜明中医药特色的研究体系。该学科方向立足中医药理论,聚焦以中药活性成分为分子探针的研究策略,通过识别作用靶点,系统解析中药成分调控的复杂生物学机制。当前,TCMCB主要通过有机合成化学实现中药活性分子结构优化与探针制备,借助化学蛋白质组学完成靶点识别,结合结构生物学解析分子互作模式,并整合分子药理学与临床医学验证其生物学调控机制,形成了多维度揭示中药药效物质基础及其药理作用规律的方法学体系。研究成果为中药复杂而独特的作用机制解析提供了分子层面的科学证据,进而有效推动了中药质量标准制定、中医临床精准用药以及中医药的现代化与国际化推广。值得强调的是,TCMCB不仅推动了传统中医药理论的现代科学诠释,更通过发现新型生物靶点与作用机制为现代生命科学提供了独特的观察视角,特别是在复杂疾病系统调控机制研究方面展现出显著优势。该文通过系统梳理TCMCB领域近十年的研究概况,重点探讨其方法论对中医药现代化研究的推动作用,同时TCMCB也将着力构建具有自主知识产权的技术体系,持续为中医药理论创新发展提供原动力,并为生命科学研究和新药研发开辟可借鉴的范式。展开更多
Protein folding involves the aminoacid sequence to come forth and form an energy minimized structure.Recently molecular crowding leading to increase in viscosity is said to be one of the major concerns affecting prote...Protein folding involves the aminoacid sequence to come forth and form an energy minimized structure.Recently molecular crowding leading to increase in viscosity is said to be one of the major concerns affecting protein folding.Many external fluorescent probes are used to detect such increases in viscosity.Since most of the protein sequences contain L-Phe and L-Trp,in this study we have used these aminoacids as probes to detect changes in viscosity.This study will help to advance the knowledge on molecular crowding effects in protein folding.展开更多
The modernization and internationalization of traditional Chinese medicine(TCM)have long been constrained by the"black box"problem of its complex compositional system and unclear mechanisms of action.Target ...The modernization and internationalization of traditional Chinese medicine(TCM)have long been constrained by the"black box"problem of its complex compositional system and unclear mechanisms of action.Target discovery,as a core step in revealing drug action principles,is key to promoting TCM's transition from"empirical medicine"to"precision medicine".In recent years,the rapid development of chemical biology technologies has provided powerful tools to address this challenge.This article focuses on the latest progress in applying chemical biology strategies,such as molecular probes,click chemistry,fluorescent labeling,and photo-crosslinking microarrays,in TCM target identification research.Combined with typical case studies like Sapanone A and Eupalinolide B,it elaborates on how these cutting-edge technologies can precisely identify the direct targets of active TCM components,thereby achieving comprehensive mechanism analysis from cells and animals to clinical samples.Furthermore,this article prospectively discusses novel"supramolecular drugs"formed by the self-assembly of TCM components at the nanoscale and their unique biological effects.It also preliminarily constructs a modern scientific interpretation framework for TCM theories like"property-flavor-channel tropism"and"processing theory",centered around target distribution and regulation.Finally,this article proposes that"chemical biology of TCM,"as a key driver to discover original drug targets derived from TCM theory,is posited to offer a novel paradigm for innovative drug discovery and to contribute significantly to the modernization and scientific elucidation of TCM theory.展开更多
Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine(TCM),substantially advancing research and de...Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine(TCM),substantially advancing research and development efforts.Spectrum-effect correlation analysis,affinity ultrafiltration,high-content screening(HCS)imaging,and cell membrane chromatography(CMC)have emerged as essential tools,effectively linking TCM chemical constituents to their biological effects,thereby enabling efficient active ingredient screening.Additionally,molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms,enhancing understanding of its therapeutic potential.Computer-aided techniques facilitate TCM active ingredient identification,optimizing the screening process for efficiency and cost-effectiveness.Molecular probe technology,as an emerging methodology,enables precise and rapid screening for novel therapeutic drug discovery.Ongoing technological advancement in this field indicates promising future developments,potentially leading to more effective and targeted TCM-based therapies.展开更多
In this paper the results of dynamic NMR studies on ethylmethylamino-tertiary-butyl-phenylborane (EMABPB) with or without light are reported. The NMR data were recorded on a Bruker 400 MHz NMR equipped with our custom...In this paper the results of dynamic NMR studies on ethylmethylamino-tertiary-butyl-phenylborane (EMABPB) with or without light are reported. The NMR data were recorded on a Bruker 400 MHz NMR equipped with our custom-made optical probe and with our custom-made 450 watts (W) monochromatic light sources. The molecular photochemistry including twisted intramolecular charge-transfer-excited-state (TICT) of the EMABPB in several solvents has been investigated. These results indicate that the aminoborane demonstrates multiple configurations in CD3Cl and CD2Cl2 resulting in the shifts of the signals of the alkyl groups on the nitrogen and boron. This indicates that there are some time-dependent changes at constant temperature over the irradiation interval. At ﹣60°C and the presence of light (λ = 265 nm), we observed a large change in the populations of the two sites, and this by itself indicates a modification in the rotation around the boron nitrogen bond in the excited state. By considering the existence of the TICT state, many important energy technologies may be developed with higher efficiency by controlling the back-electron transfer processes.展开更多
基金supported by the National Natural Science Foundation of China,No.81730050(to WH).
文摘In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.
基金supported by the NSFC(82172081 and 52103168)the Science and Technology Program of Tianjin,China(21JCZDJC00970 and 22JCQNJC01640)Tianjin Key Medical Discipline(Specialty)Construction Project,and the Fundamental Research Funds for the Central Universities(63243137).
文摘Precision medicine calls for advanced theranostics that integrate controllable diagnostic and therapeutic capabilities into one platform for disease treatment in the early stage.Phototheranostics such as fluorescence imaging(FLI),photoacoustic imaging(PAI),photodynamic therapy(PDT),and photothermal therapy(PTT)have attracted considerable attention in recent years,which mainly employ different excited-state energy dissipation pathways of a chromophore.According to the Jablonski diagram,FLI is related to the radiative process,PAI and PTT are derived from the nonradiative thermal deactivation,and PDT originates from the triplet state energy,in which these processes are usually competitive.Therefore,it is critically important to precisely tune the photophysical energy transformation processes to realize certain diagnosis and treatment properties in optimal state for boosting biomedical applications.Currently,there are mainly two strategies including chemical structure and aggregate behavior changes that relate to the regulation of excited state energy dissipation.In this review,we will discuss the recent advances of smart molecular probes that the photophysical properties can be regulated by external triggers and their applications in biomedical fields.We will summarize the development of activatable phototheranostic molecular probes in response to stimuli such as reactive oxygen species,pH,light,hypoxia,enzyme and gas.The assembly and disassembly of molecular aggregates that greatly affect the photophysical energy transformation processes will also be highlighted.This review aims to provide valuable insights into the development of more accurate diagnostic and therapeutic systems,thereby advancing the emerging field of smart medicine.
文摘New ionization and detection techniques in mass spectrometry have been successfully applied for efficient analyses of complex biological systems. It is, however, still difficult to trace structural changes of a specific molecular species in such systems. In the present study, a molecular probe strategy in combination with tandem electrospray ionization mass spectrometry has been examined using synthetic deuterium-labeled phosphatidylcholine hydroperoxide (PC-OOH/D3) and ethyl-labeled phosphatidylcholine having docosahexaenoic acid side chain (DHA-PC/Et). Administration of a mixture of PC-OOH/D3 and DHA-PC/Et to human blood and human skin surface, followed by extraction and analysis with collision-induced tandem electrospray ionization mass spectrometry demonstrated that metabolites of both molecular probes can be detected simultaneously with strict selectivity. The present method is also found to be useful in tracing chemical changes of the unstable docosahexaenoyl group on the surface of processed fish. The activity of phospholipase A2 can also be assessed using a phospholipid molecular probe with a linoleoyl and a deuteriomethyl group via selective detection of the lyso-phospholipid product by mass spectrometry. The advantage of the present method is that no chromatographic separation is required and analysis can be performed under strictly the same condition for different molecular probes, affording multiple data by one experiment. The present strategy may be useful for tracing time-dependent phenomena in dynamic phospholipid biochemistry, and can be widely used for any biological and food systems.
基金supported by the Key Areas Research and Development Program of Guangzhou(202007020006)the National Natural Science Foundation of China(51933011,31971296,82102194,82302360)+1 种基金the Science and Technology Projects of Guangzhou(2023A03J0215)the Guangdong Basic Research Center of Excellence for Functional Molecular Engineering。
文摘Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy.Nonetheless,the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes.Herein,we reported a self-amplifying fluorescent molecular probe,Bis-HTPICG,for photodynamic therapy(PDT)and subsequent PDT-induced immunoreaction.The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO),a crucial enzyme secreted by neutrophils at inflammation sites.Upon exposure to laser irradiation,Bis-HTP-ICG showed a high PDT efficacy,inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion.The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis,instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG,neutrophils and MPO.Meanwhile,PDT efficiently incites immunogenic cell death(ICD)in tumor cells,initiating an anti-tumor immune response including dendritic cells(DCs)maturation,T cell proliferation and reprogramming of tumor-associated neutrophils(TANs).This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.
基金supported by the National Natural Science Foundation of China(Grants 82272137,82272055)National Key Research and Development Project(Grant 2022YFB3804500)+2 种基金Shanghai Municipal Commission of Health and Family Planning Project(Grant 20204Y0032)Shanghai Sailing Program(Grant 21YF1436600)the Fundamental Research Funds for the Central Universities(Grant 22120220585).
文摘Morphological imaging techniques are very limited in their ability to evaluate the early efficacy of tumor therapies,with the limitation of being more reflective and lagging.Many of the newer therapies are cytostatic,and tumor necrosis or lack of tumor progression is associated with a good response to treatment even in the absence of tumor shrinkage;therefore,there is an increasing need to develop techniques for the assessment of tumor efficacy.Magnetic resonance imaging(MRI),with the help of a variety of contrast mechanisms and probes,provides excellent soft-tissue imaging,high-quality anatomical signals as well as reflecting certain functional states of the tumor and molecular biological information.It can be used to differentiate between cancer and normal tissue,to noninvasively monitor tumor growth,and to identify changes in the tumor and its microenvironment in response to treatment.This review will discuss the role of magnetic resonance imaging in the assessment of tumor efficacy,with a focus on presenting research advances in magnetic resonance molecular imaging and its probes in the assessment of tumor efficacy.
基金supported by the National Natural Science Foundation of China (30870535 and 90913017) (B. Zhang) Introduced Innovative R&D Team Program of Guangdong Province (Gene Silencing Technology and Therapeutics)
文摘Labelling and identification of proliferating cells is important for the study of physiological or pathological processes in high-content screening (HCS) assays. Here we describe ethynyl deoxyuridine (EdU) as a biomarker for the assessment of cell proliferation and clearly demonstrate the feasibility of the EdU-labelling method for use in HCS assays. EdU detection is highly robust, reproducible, technically simple, and well suited for automated segmentation, which provides an excellent al- ternative for setting up multiplexed HCS assays of siRNA, miRNA and small-molecule libraries.
基金the National Natural Science Foundation of China(Nos.92159304,82227806)the National Science Fund for Distinguished Young Scholars(No.82025019)the Shanghai Municipal Health Commission Project(202040106).
文摘Macrophage is a kind of immune cell and performs multiple functions including pathogen phagocytosis,antigen presentation and tissue remodeling.To fulfll their functionally distinct roles,macrophages undergo polarization towards a spectrum of phenotypes,particularly the classically activated(M1)and alternatively activated(M2)subtypes.However,the binary M1/M2 phenotype fails to capture the complexity of macrophages subpopulations in vivo.Hence,it is crucial to employ spatiotemporal imaging techniques to visualize macrophage phenotypes and polarization,enabling the monitoring of disease progression and assessment of therapeutic responses to drug candidates.This review begins by discussing the origin,function and diversity of macrophage under physiological and pathological conditions.Subsequently,we summarize the identifed macrophage phenotypes and their specifc biomarkers.In addition,we present the imaging probes locating the lesions by visualizing macrophages with specifc phenotype in vivo.Finally,we discuss the challenges and prospects associated with monitoring immune microenvironment and disease progression through imaging of macrophage phenotypes.
基金supported by grants from the National Natural Science Foundation of China(21775166)China Postdoctoral Science Foundation(2023TQ0380)+3 种基金Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province(BK20180026)China Postdoctoral Science Foundation(2023TQ0380)Postdoctoral Fellowship Program of CPSF(GZB20230867)Jiangsu Excellent Postdoctoral Program(2023ZB388)。
文摘Acute kidney injury(AKI),a prevalent and complex clinical condition associated with elevated risks of morbidity and mortality,necessitates the meticulous detection and monitoring of kidney damage globally.Biomedicine has shown keen interest in molecular probes and detectors for AKI due to their sensitivity,rapidity,and cost-effectiveness.Bioimaging technologies play a significant role in identifying and quantifying AKI indicators,enhancing diagnostic approaches,and potentially refining clinical therapies for immediate injury control.Molecular probes serve as valuable tools for drug screening,uncovering renoprotective components,signaling pathways,and the nephrotoxic effects of drugs.This review comprehensively summarizes the latest advancements in molecular probes,emphasizing their exceptional efficacy in various characteristics,including renal cleanability,multichannel detection capability,near-infrared-II responsiveness,and reactivity toward reactive oxygen species.These probes offer enhanced benefits for assessing kidney damage and evaluating the therapeutic effects of medications while simultaneously reducing toxic effects.Additionally,the review delves into future potentials and challenges in this field,aiming to inspire the development and enhancement of molecular bioimaging for the early diagnosis and treatment of kidney diseases.
文摘A summer-autumn (1994) molecular epidemiological study of enteric adenoviruses (EAds) in stool specimens collected in Wuhan area was conducted by using Digoxigenin-labelled DNA probes specific to EAd40, and EAd41, respectively.44 of 602 specimens were positive, among which 23 cases were identified as EAd40, 14 were EAd41, infection and 7 were dual infection. The ratio of males to females for the positive specimens was 1. 44. The infection rate of EAd40 and EAd41 each displayed no marked difference in seasons (summer and autumn) and similar age distribution was found between them. All of the two types of EAds in-fections predominated in patients with diarrhea under 3 years old- The results indicated that the Digoxigenin probe could detect DNA quantities as low as 1 pgwith satis factory specificity and the technique can be used for both clinical and ex-perimental purposes.
基金Project supported by the Shandong Provincial Natural Science Foundation,China(Grant No.ZR2014AM026)the National Natural Science Foundation of China(Grant Nos.11374195 and 11404193)the Taishan Scholar Project of Shandong Province,China
文摘The properties of one-photon absorption（OPA）, emission and two-photon absorption（TPA） of a di-2-picolylaminebased zinc ion sensor are investigated by employing the density functional theory in combination with response functions.The responsive mechanism is explored. It is found that the calculated OPA and TPA properties are quite consistent with experimental data. Because the intra-molecular charge transfer（ICT） increases upon zinc ion binding, the TPA intensity is enhanced dramatically. According to the model sensor, we design a series of zinc ion probes which differ by conjugation center, acceptor and donor moieties. The properties of OPA, emission and TPA of the designed molecules are calculated at the same computational level. Our results demonstrate that the OPA and emission wavelengths of the designed probes have large red-shifts after zinc ions have been bound. Comparing with the model sensor, the TPA intensities of the designed probes are enhanced significantly and the absorption positions are red-shifted to longer wavelength range. Furthermore, the TPA intensity can be improved greatly upon zinc ion binding due to the increased ICT mechanism. These compounds are potential excellent candidates for two-photon fluorescent zinc ion probes.
文摘During the past several decades,positron emission tomography（PET） has been one of the rapidly growing areas of medical imaging;particularly,its applications in routine oncological practice have been widely recognized.At present,^18F-fluorodeoxyglucose（^18F-FDG） is the most broadly used PET probe.However,^18F-FDG also suffers many limitations.Thus,scientists and clinicians are greatly interested in exploring and developing new PET imaging probes with high affinity and specificity.In this review,we briefly summarize the representative PET probes beyond ^18F-FDG that are available for patients imaging in three major clinical areas（oncology,neurology and cardiology）,and we also discuss the feasibility and trends in developing new PET probes for personalized medicine.
基金supported by National Natural Science Foundation of China(Grant No.81202795)China Postdoctoral Science Foundation(Grant No.2015M571271)
文摘Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.
文摘中药化学生物学(traditional Chinese medicine chemical biology,TCMCB)作为21世纪中医药现代化进程中形成的重要学科方向,其研究模式通过整合现代化学与生物学等技术手段,构建了具有鲜明中医药特色的研究体系。该学科方向立足中医药理论,聚焦以中药活性成分为分子探针的研究策略,通过识别作用靶点,系统解析中药成分调控的复杂生物学机制。当前,TCMCB主要通过有机合成化学实现中药活性分子结构优化与探针制备,借助化学蛋白质组学完成靶点识别,结合结构生物学解析分子互作模式,并整合分子药理学与临床医学验证其生物学调控机制,形成了多维度揭示中药药效物质基础及其药理作用规律的方法学体系。研究成果为中药复杂而独特的作用机制解析提供了分子层面的科学证据,进而有效推动了中药质量标准制定、中医临床精准用药以及中医药的现代化与国际化推广。值得强调的是,TCMCB不仅推动了传统中医药理论的现代科学诠释,更通过发现新型生物靶点与作用机制为现代生命科学提供了独特的观察视角,特别是在复杂疾病系统调控机制研究方面展现出显著优势。该文通过系统梳理TCMCB领域近十年的研究概况,重点探讨其方法论对中医药现代化研究的推动作用,同时TCMCB也将着力构建具有自主知识产权的技术体系,持续为中医药理论创新发展提供原动力,并为生命科学研究和新药研发开辟可借鉴的范式。
文摘Protein folding involves the aminoacid sequence to come forth and form an energy minimized structure.Recently molecular crowding leading to increase in viscosity is said to be one of the major concerns affecting protein folding.Many external fluorescent probes are used to detect such increases in viscosity.Since most of the protein sequences contain L-Phe and L-Trp,in this study we have used these aminoacids as probes to detect changes in viscosity.This study will help to advance the knowledge on molecular crowding effects in protein folding.
基金supported by the Natural Science Foundation of Shandong Province(No.ZR2023ZD25)the Taishan Scholars Project in Shandong Province(Nos.tstp20230633 and tsqn202408246).
文摘The modernization and internationalization of traditional Chinese medicine(TCM)have long been constrained by the"black box"problem of its complex compositional system and unclear mechanisms of action.Target discovery,as a core step in revealing drug action principles,is key to promoting TCM's transition from"empirical medicine"to"precision medicine".In recent years,the rapid development of chemical biology technologies has provided powerful tools to address this challenge.This article focuses on the latest progress in applying chemical biology strategies,such as molecular probes,click chemistry,fluorescent labeling,and photo-crosslinking microarrays,in TCM target identification research.Combined with typical case studies like Sapanone A and Eupalinolide B,it elaborates on how these cutting-edge technologies can precisely identify the direct targets of active TCM components,thereby achieving comprehensive mechanism analysis from cells and animals to clinical samples.Furthermore,this article prospectively discusses novel"supramolecular drugs"formed by the self-assembly of TCM components at the nanoscale and their unique biological effects.It also preliminarily constructs a modern scientific interpretation framework for TCM theories like"property-flavor-channel tropism"and"processing theory",centered around target distribution and regulation.Finally,this article proposes that"chemical biology of TCM,"as a key driver to discover original drug targets derived from TCM theory,is posited to offer a novel paradigm for innovative drug discovery and to contribute significantly to the modernization and scientific elucidation of TCM theory.
基金supported by the National Natural Science Foundation of China (Nos. 22175078, 52373287, 82404846, and 22467002)the Natural Science Foundation of Jiangsu Province of China (No. BK20241597)the Fundamental Research Funds for the Central Universities (No. 2632024TD05)
文摘Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine(TCM),substantially advancing research and development efforts.Spectrum-effect correlation analysis,affinity ultrafiltration,high-content screening(HCS)imaging,and cell membrane chromatography(CMC)have emerged as essential tools,effectively linking TCM chemical constituents to their biological effects,thereby enabling efficient active ingredient screening.Additionally,molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms,enhancing understanding of its therapeutic potential.Computer-aided techniques facilitate TCM active ingredient identification,optimizing the screening process for efficiency and cost-effectiveness.Molecular probe technology,as an emerging methodology,enables precise and rapid screening for novel therapeutic drug discovery.Ongoing technological advancement in this field indicates promising future developments,potentially leading to more effective and targeted TCM-based therapies.
文摘In this paper the results of dynamic NMR studies on ethylmethylamino-tertiary-butyl-phenylborane (EMABPB) with or without light are reported. The NMR data were recorded on a Bruker 400 MHz NMR equipped with our custom-made optical probe and with our custom-made 450 watts (W) monochromatic light sources. The molecular photochemistry including twisted intramolecular charge-transfer-excited-state (TICT) of the EMABPB in several solvents has been investigated. These results indicate that the aminoborane demonstrates multiple configurations in CD3Cl and CD2Cl2 resulting in the shifts of the signals of the alkyl groups on the nitrogen and boron. This indicates that there are some time-dependent changes at constant temperature over the irradiation interval. At ﹣60°C and the presence of light (λ = 265 nm), we observed a large change in the populations of the two sites, and this by itself indicates a modification in the rotation around the boron nitrogen bond in the excited state. By considering the existence of the TICT state, many important energy technologies may be developed with higher efficiency by controlling the back-electron transfer processes.
