ABSTRACT
The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionalized methoxypoly(ethylene glycol), which exhibit exceptional single-particle brightness and excellent free diffusion capability in the ECS of brain tissues. Tracking single RGNs in acute brain slices allowed us to dynamically map spatial organizational features and redox levels within the ECS of brain tissues in disease models. This provides a powerful super-resolution imaging method that offers a potential opportunity to study the dynamic changes in the ECS microenvironment and to understand the physiological and pathological roles of the ECS in vivo.
Subject(s)
Brain , Extracellular Space , Glutathione , Nanoparticles , Oxidation-Reduction , Brain/metabolism , Brain/diagnostic imaging , Animals , Extracellular Space/metabolism , Extracellular Space/chemistry , Glutathione/chemistry , Glutathione/metabolism , Nanoparticles/chemistry , Mice , Polyethylene Glycols/chemistryABSTRACT
Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.
Subject(s)
Endocytosis , Influenza A virus , Microtubules , Quantum Dots , Quantum Dots/chemistry , Microtubules/metabolism , Microtubules/virology , Humans , Influenza A virus/physiology , Virus Internalization , Animals , Dogs , Madin Darby Canine Kidney Cells , Actin Cytoskeleton/metabolismABSTRACT
In the last decades, 4-nitrophenol is regarded as one of highly toxic organic pollutants in industrial wastewater, which attracts great concern to earth sustainability. Herein, atomically dispersed ternary FeCoNb active sites were incorporated into nitrogen-doped honeycomb-like mesoporous carbon (termed FeCoNb/NHC) by a two-step pyrolysis strategy, whose morphology, structure and size were characterized by a set of techniques. Further, the catalytic activity and reusability of the as-prepared FeCoNb/NHC were rigorously examined by using 4-NP catalytic hydrogenation as a proof-of-concept model. The influence of the secondary pyrolysis temperature on the catalytic performance was investigated, combined by illuminating the catalytic mechanism. The resultant catalyst exhibited significantly enhanced catalytic features with a normalized rate constant (kapp) of 1.2 × 104 min-1g-1 and superior stability, surpassing the home-made catalysts in the control groups and earlier research. This study provides some constructive insights for preparation of high-efficiency and cost-effectiveness single-atom nanocatalysts in organic pollutants environmental remediation.
ABSTRACT
Nanozymes, nanostructured materials emulating natural enzyme activities, exhibit potential in catalyzing reactive oxygen species (ROS) production for cancer treatment. By facilitating oxidative reactions, elevating ROS levels, and influencing the tumor microenvironment (TME), nanozymes foster the eradication of cancer cells. Noteworthy are their superior stability, ease of preservation, and cost-effectiveness compared to natural enzymes, rendering them invaluable for medical applications. This comprehensive review intricately explores the interplay between ROS and tumor therapy, with a focused examination of metal-based nanozyme strategies mitigating tumor hypoxia. It provides nuanced insights into diverse catalytic processes, mechanisms, and surface modifications of various metal nanozymes, shedding light on their role in intra-tumoral ROS generation and applications in antioxidant therapy. The review concludes by delineating specific potential prospects and challenges associated with the burgeoning use of metal nanozymes in future tumor therapies.
Subject(s)
Neoplasms , Reactive Oxygen Species , Tumor Microenvironment , Humans , Reactive Oxygen Species/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Animals , Tumor Microenvironment/drug effects , Nanostructures/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Metals/chemistry , Tumor Hypoxia/drug effectsABSTRACT
Colorectal cancer (CRC) is the third most common cancer worldwide and the second most common cause of cancer death. Nanotherapies are able to selectively target the delivery of cancer therapeutics, thus improving overall antitumor efficiency and reducing conventional chemotherapy side effects. Mesoporous silica nanoparticles (MSNs) have attracted the attention of many researchers due to their remarkable advantages and biosafety. We offer insights into the recent advances of MSNs in CRC treatment and their potential clinical application value.
ABSTRACT
Background: The relationship between the intake of dietary fatty acids (FA) and bone mineral density (BMD) has been the subject of prior investigations. However, the outcomes of these studies remain contentious. The objective of this research is to examine the link between dietary FA consumption among adolescents and BMD. Methods: This study utilized high-quality data from the National Health and Nutrition Examination Survey database, spanning 2011 to 2018, to explore the association between dietary fatty acids and bone health indicators in adolescents, including BMD and bone mineral content (BMC). Analyses were performed using weighted multivariate linear regression models, incorporating detailed subgroup analysis. Results: The study included 3440 participants. Analysis demonstrated that intake of saturated fatty acids (SFA) was positively correlated with total BMD, left arm BMD, total BMC, and left arm BMC. Monounsaturated fatty acid (MUFA) intake was positively correlated with BMC across most body parts, though it showed no correlation with BMD. Intake of polyunsaturated fatty acids (PUFA) was significantly inversely correlated with both BMD and BMC in most body parts. Additionally, subgroup analysis indicated that variables such as sex, age, standing height, and race significantly influenced the correlation between FA intake and BMD. Conclusions: Our study indicates that dietary intake of SFA may benefit to BMD in adolescents, in contrast to PUFA and MUFA. Therefore, we recommend that adolescents maintain a balanced intake of SFA to promote optimal bone mass development while preserving metabolic health.
Subject(s)
Bone Density , Fatty Acids , Nutrition Surveys , Humans , Bone Density/drug effects , Adolescent , Female , Male , Child , Fatty Acids/administration & dosage , Young Adult , Dietary Fats/administration & dosage , Cross-Sectional StudiesABSTRACT
Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Polylactic Acid-Polyglycolic Acid Copolymer , Methicillin-Resistant Staphylococcus aureus/drug effects , Animals , Mice , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Microspheres , Photothermal Therapy , Pneumonia, Staphylococcal/therapy , Phage Therapy/methods , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Indocyanine Green/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Administration, Inhalation , Humans , Bacteriophages/chemistryABSTRACT
BACKGROUND AND AIMS: Video-assisted anal fistula treatment (VAAFT) is an innovative surgical approach enabling the direct visualization of the fistula tract structure. This study aims to assess the efficacy of VAAFT in comparison with that of traditional surgical methods and explore potential risk factors contributing to fistula recurrence to provide new recommendations for surgical selection. MATERIALS AND METHODS: Information was collected from 100 patients with complex anal fistula (CAF) in our hospital who underwent surgical treatment from January 2021 to January 2023. We compared the baseline information and surgical outcomes of two groups, analyzed the risk factors for fistula recurrence by using logistic regression analysis, and conducted further exploration by using the body mass index. RESULTS: Equal numbers of patients underwent VAAFT and traditional surgeries, and no significant differences in baseline information were observed. Patients who received VAAFT experienced less intraoperative bleeding (15.5 (14.0-20.0) vs. 32.0 (25.0-36.0)), shorter hospital stays (2.0 (2.0-2.5) vs. 3.0 (3.0-3.5)), reduced postoperative pain and wound discharge, but longer operative times (43.3 ± 6.9 vs. 35.0 (31.5-40.0)) compared with patients who underwent traditional surgeries. No significant differences in recurrence rates were found three and six months after operation (the p-values were 0.790 and 0.806, respectively). However, the Wexner scores of the VAAFT group were significantly low in the first follow-up (0 (0-1.0) vs. 2.0 (1.0-2.0)). Postoperative recurrence of fistulas may be associated with obesity (p-value = 0.040), especially in patients undergoing traditional surgeries (p-value = 0.036). CONCLUSION: VAAFT offers advantages, such as less pain, less trauma, and faster recovery, compared with traditional surgical treatment. Obese patients with CAF are prone to recurrence, and we recommend that they undergo VAAFT treatment rather than traditional surgeries.
Subject(s)
Obesity , Rectal Fistula , Recurrence , Video-Assisted Surgery , Humans , Rectal Fistula/surgery , Rectal Fistula/etiology , Obesity/complications , Obesity/surgery , Female , Male , Treatment Outcome , Middle Aged , Adult , Risk Factors , Body Mass Index , Operative Time , Length of StayABSTRACT
Membrane tension is an important physical parameter of describing cellular homeostasis, and it is widely used in the study of cellular processes involving membrane deformation and reorganization, such as cell migration, cell spreading, and cell division. Despite the importance of membrane tension, direct measurement remains difficult. In this work, we developed a ratiometric fluorescent probe sensitive to membrane tension by adjusting the carbon chain structure based on polarity-sensitive fluorophores. The probe is sensitive to changes in membrane tension after cells were subjected to physical or chemical stimuli, such as osmotic shock, lipid peroxidation, and mechanical stress. When the polarity of the plasma membrane increases (the green/red ratio decreases) and the membrane tension increases, the relative magnitude of the membrane tension can be quantitatively calculated by fluorescence ratio imaging. Thus, the probe proved to be an efficient and sensitive membrane tension probe.
Subject(s)
Cell Membrane , Fluorescent Dyes , Fluorescent Dyes/chemistry , Cell Membrane/metabolism , Humans , Optical Imaging/methods , Animals , Osmotic Pressure , Stress, MechanicalABSTRACT
Metropolitan integration development refers to the interconnection between cities and the coordinated development of various aspects such as economy, society, culture, and nature, which is the goal of metropolitan area development. With the Zhengzhou metropolitan area as the research area and based on nighttime light data from 2012 to 2021, we comprehensively used landscape index and landscape morphology spatial pattern analysis methods, systematically evaluated the integration process of the metropolitan area from the perspective of spatial expansion and spatial connection, analyzed the spatiotemporal variations of the landscape pattern of the metropolitan area, and revealed the spatiotemporal expansion and connection patterns of the metropolitan area. The results showed that the area of the Zhengzhou metropolitan area expanded year by year from 2012 to 2021, with the number of landscape patches continuously increasing, showing an agglomeration phenomenon. In the metropolitan area, there was a trend towards stability and multi-directional coordinated growth. The contribution of non-central cities to expansion increased annually, while the expansion patterns of various constituent cities gradually shifted from internal filling to external expansion. The connection scale within the metropolitan area had been expanding annually, with enhanced intercity connections. Intercity connection belts and channels for material and information exchange were emerging, and the integrated network of urban agglomeration connections was gradually forming. Metropolitan integration planning provided positive guidance for the development of metropolitan areas. We should fully leverage the driving effects of metropolitan areas, pay attention to the integration of Zhengzhou-Kaifeng and Zhengzhou-Xuchang, promote the formation of emerging growth poles in Xinxiang and Jiaozuo, as well as regional coordinated development, strengthen the network of policies, economy, transportation, information, etc., and form a diversified and integrated development situation.
Subject(s)
Cities , City Planning , Ecosystem , China , Spatio-Temporal Analysis , Urbanization , Environmental Monitoring/methods , Conservation of Natural Resources , LightABSTRACT
Cell membrane stiffness is critical for cellular function, with cholesterol and sphingomyelin as pivot contributors. Current methods for measuring membrane stiffness are often invasive, ex situ, and slow in process, prompting the need for innovative techniques. Here, we present a fluorescence resonance energy transfer (FRET)-based protein sensor designed to address these challenges. The sensor consists of two fluorescent units targeting sphingomyelin and cholesterol, connected by a linker that responds to the proximity of these lipids. In rigid membranes, cholesterol and sphingomyelin are in close proximity, leading to an increased FRET signal. We utilized this sensor in combination with confocal microscopy to explore changes in plasma membrane stiffness under various conditions, including differences in osmotic pressure, the presence of reactive oxygen species (ROS) and variations in substrate stiffness. Furthermore, we explored the impact of SARS-CoV-2 on membrane stiffness and the distribution of ACE2 after attachment to the cell membrane. This tool offers substantial potential for future investigations in the field of mechanobiology.
Subject(s)
Cell Membrane , Cholesterol , Fluorescence Resonance Energy Transfer , SARS-CoV-2 , Sphingomyelins , Fluorescence Resonance Energy Transfer/methods , Humans , Cell Membrane/metabolism , Cell Membrane/chemistry , Sphingomyelins/analysis , Sphingomyelins/metabolism , Cholesterol/analysis , Cholesterol/metabolism , Microscopy, Confocal/methods , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/analysis , COVID-19/virology , Angiotensin-Converting Enzyme 2/metabolism , Biosensing Techniques/methodsABSTRACT
Developing small-molecule photothermal agents (PTAs) with good near-infrared-II (NIR-II) response for deeper tissue penetration and minimizing damage to healthy tissues has attracted much attention in photothermal therapy (PTT). However, concentrating ultra-long excitation wavelengths and high photothermal conversion efficiencies (PCEs) into a single organic small molecule is still challenging due to the lack of suitable molecular structures. Here, six polymethine cyanine molecules based on the structure of indocyanine green are synthesized by increasing the conjugated structure of the two-terminal indole salts and the number of rigid methine units, and incorporating longer alkyl side chains into the indole salts. Ultimately, IC-1224 is obtained with an absorption wavelength of more than 1200 nm, which has a high PCE up to 83.2% in the NIR-II window and exhibits excellent PTT tumor ablation performance. This provides a high-performance NIR-II-responsive PTA, and offers further possibilities for the application of PTT in biomedical fields.
Subject(s)
Photothermal Therapy , Photothermal Therapy/methods , Animals , Mice , Humans , Carbocyanines/chemistry , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Cell Line, Tumor , Infrared Rays , Mice, Inbred BALB C , Phototherapy/methods , FemaleABSTRACT
Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.
Subject(s)
Glioblastoma , Nanoparticles , RNA, Small Interfering , Glioblastoma/therapy , Glioblastoma/pathology , Glioblastoma/metabolism , RNA, Small Interfering/chemistry , RNA, Small Interfering/metabolism , Humans , Nanoparticles/chemistry , Cell Line, Tumor , Animals , Protein Conformation , Brain Neoplasms/therapy , Brain Neoplasms/pathology , Mice , Blood-Brain Barrier/metabolism , Biomimetic Materials/chemistryABSTRACT
In vivo real-time qualitative and quantitative analysis is essential for the diagnosis and treatment of diseases such as tumors. Near-infrared-II (NIR-II, 1000-1700 nm) bioimaging is an emerging visualization modality based on fluorescent materials. The advantages of NIR-II region fluorescent materials in terms of reduced photon scattering and low tissue autofluorescence enable NIR-II bioimaging with high resolution and increasing depth of tissue penetration, and thus have great potential for in vivo qualitative and quantitative analysis. In this review, we first summarize recent advances in NIR-II imaging, including fluorescent probe selection, quantitative analysis strategies, and imaging. Then, we describe in detail representative applications to illustrate how NIR-II fluorescence imaging has become an important tool for in vivo quantitative analysis. Finally, we describe the future possibilities and challenges of NIR-II fluorescence imaging.
Subject(s)
Fluorescent Dyes , Optical Imaging , Fluorescent Dyes/chemistry , Optical Imaging/methods , Humans , Animals , Spectroscopy, Near-Infrared/methods , Neoplasms/diagnostic imaging , Infrared RaysABSTRACT
Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.
Subject(s)
Electrochemical Techniques , Luminescent Measurements , Nanotubes , Quantum Dots , Quantum Dots/chemistry , Humans , Electrochemical Techniques/methods , Nanotubes/chemistry , Luminescent Measurements/methods , HeLa Cells , Cell Membrane/metabolism , Cell Membrane/chemistry , Reactive Oxygen Species/metabolism , Reactive Oxygen Species/analysis , Carbon/chemistryABSTRACT
Background: Diabetes mellitus can occur after acute pancreatitis (AP), but the accurate quantitative methods to predict post-acute pancreatitis diabetes mellitus (PPDM-A) are lacking. This retrospective study aimed to establish a radiomics model based on contrast-enhanced computed tomography (CECT) for predicting PPDM-A. Methods: A total of 374 patients with first-episode AP were retrospectively enrolled from two tertiary referral centers. There were 224 patients in the training cohort, 56 in the internal validation cohort, and 94 in the external validation cohort, and there were 86, 22, and 27 patients with PPDM-A in these cohorts, respectively. The clinical characteristics were collected from the hospital information system. A total of 2,398 radiomics features, including shape-based features, first-order histogram features, high order textural features, and transformed features, were extracted from the arterial- and venous-phase CECT images. Intraclass correlation coefficients were used to assess the intraobserver reliability and interobserver agreement. Random forest-based recursive feature elimination, collinearity analysis, and least absolute shrinkage and selection operator (LASSO) were used for selecting the final features. Three classification methods [eXtreme Gradient Boosting (XGBoost), Adaptive Boosting, and Decision Tree] were used to build three models and performances of the three models were compared. Each of the three classification methods were used to establish the clinical model, radiomics model, and combined model for predicting PPDM-A, resulting in a total of nine classifiers. The predictive performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. Results: Eleven radiomics features were selected after a reproducibility test and dimensionality reduction. Among the three classification methods, the XGBoost classifier showed better and more consistent performances. The AUC of the XGBoost's radiomics model to predict PPDM-A in the training, internal, and external cohorts was good (0.964, 0.901, and 0.857, respectively). The AUC of the XGBoost's combined model to predict PPDM-A in the training, internal, and external cohorts was good (0.980, 0.901, and 0.882, respectively). The AUC of the XGBoost's clinical model to predict PPDM-A in the training, internal, and external cohorts did not perform well (0.685, 0.733, and 0.619, respectively). In the external validation cohort, the AUC of the XGBoost's radiomics model was significantly higher than that of the clinical model (0.857 vs. 0.619, P<0.001), but there was no significant difference between the combined and radiomics models (0.882 vs. 0.857, P=0.317). Conclusions: The radiomics model based on CECT performs well and can be used as an early quantitative method to predict the occurrence of PPDM-A.
ABSTRACT
The adsorption characteristics of ammonia nitrogen for constructed wetland were studied with ceramsite, quartz sand, and gravel. The material was characterized using scanning electron microscopy and a BET-specific surface area analyzer. It was found that the surface of ceramide was coarser than that of quartz sand and gravel, and the internal pores were more developed. The specific surface area of ceramide (18.97 m2·g-1) was higher than that of quartz sand and gravel. In the pure ammonia nitrogen solution and Grade I B standard for the wastewater treatment plant effluent ammonia nitrogen solution of the effluent from the simulated sewage plant, the adsorption capacity of the three substrates was as follows:ceramsite > gravel > quartz sand. The saturated adsorption capacity (63.55 m2·g-1) of ceramides was the highest in the mixed solution. The adsorption process of ammonia nitrogen by ceramides accorded with the pseudo-second-order kinetic model (R2 of 0.99 in the pure ammonia nitrogen solution and 0.98 in the mixed solution). The Freundlich and Langmuir models were used to fit the isothermal adsorption results in a pure ammonia nitrogen solution. It was found that the Freundlich model described the adsorption characteristics of the ceramics more accurately than the Langmuir model (R2=0.93), indicating that the adsorption of ammonia nitrogen by the ceramics was multilayer adsorption. In conclusion, the adsorption capacity of ceramide was strong, and the adsorption capacity of ceramide in the mixed solution was 31% higher than that in the pure ammonia nitrogen solution, which was suitable to be used as the matrix filler of constructed wetland.
ABSTRACT
Diabetes mellitus(DM) is a chronic endocrine disease characterized by hyperglycemia caused by carbohydrate or lipid metabolism disorders or insulin dysfunction. Hyperglycemia and long-term metabolic disorders in DM can damage tissues and organs throughout the body, leading to serious complications. Mitochondrial autophagy(mitophagy) is an important mitochondrial quality control process in cells and a special autophagy phenomenon, in which damaged or redundant mitochondria can be selectively removed by autophagic lysosome, which is crucial to maintain cell stability and survival under stress. Studies have confirmed that changes in autophagy play a role in the development and control of DM and its complications. Mitophagy has become a research hotspot in recent years and it is closely associated with the pathogenesis of a variety of diseases. Substantial evidence suggests that mitophagy plays a crucial role in regulating the metabolic homeostasis in the case of DM and its complications. Because the destructive great vessel complications and microvascular complications cause increased mortality, blindness, renal failure, and declined quality of life of DM patients, it is urgent to develop targeted therapies to intervene in DM and its complications. Traditional Chinese medicine(TCM), with a multi-component, multi-target, and multi-level action manner, can prevent the development of drug resistance and have significant therapeutic effects in the prevention and treatment of DM and its complications. Therefore, exploring the mechanisms of TCM in regulating mito-phagy may become a new method for treating DM and its complications. With focus on the roles and mechanisms of mitophagy in DM and its complications, this paper summarizes and prospects the research on the treatment of DM and its complications with TCM via re-gulating mitophagy, aiming to provide new ideas for the clinical practice.
Subject(s)
Diabetes Mellitus , Hyperglycemia , Humans , Mitophagy/physiology , Medicine, Chinese Traditional , Quality of Life , Diabetes Mellitus/drug therapy , Diabetes Mellitus/geneticsABSTRACT
The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However, whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdSxSe1-x quantum dots (QDs) in the nucleus by regulation of the glutathione (GSH) metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced 'supercells'.
ABSTRACT
Labeling the genome and envelope of a virus with multicolor quantum dots (QDs) simultaneously enables real-time monitoring of viral uncoating and genome release, contributing to our understanding of virus infection mechanisms. However, current labeling techniques require genetic modification, which alters the virus's composition and infectivity. To address this, we utilized the CRISPR/Cas13 system and a bioorthogonal metabolic method to label the Japanese encephalitis virus (JEV) genome and envelopes with different-colored QDs in situ. This technique allows one-step two-color labeling of the viral envelope and intraviral genome with QDs harnessing virus infection. In combination with single-virus tracking, we visualized JEV uncoating and genome release in real time near the endoplasmic reticulum of live cells. This labeling strategy allows for real-time visualization of uncoating and genome release at the single-virus level, and it is expected to advance the study of other viral infection mechanisms.