ABSTRACT
Autophagy-related protein 7 (ATG7) is an essential autophagy effector enzyme. Although it is well known that autophagy plays crucial roles in the infections with various viruses including influenza A virus (IAV), function and underlying mechanism of ATG7 in infection and pathogenesis of IAV remain poorly understood. Here, in vitro studies showed that ATG7 had profound effects on replication of IAV. Depletion of ATG7 markedly attenuated the replication of IAV, whereas overexpression of ATG7 facilitated the viral replication. ATG7 conditional knockout mice were further employed and exhibited significantly resistant to viral infections, as evidenced by a lower degree of tissue injury, slower body weight loss, and better survival, than the wild type animals challenged with either IAV (RNA virus) or pseudorabies virus (DNA virus). Interestingly, we found that ATG7 promoted the replication of IAV in autophagy-dependent and -independent manners, as inhibition of autophagy failed to completely block the upregulation of IAV replication by ATG7. To determine the autophagy-independent mechanism, transcriptome analysis was utilized and demonstrated that ATG7 restrained the production of interferons (IFNs). Loss of ATG7 obviously enhanced the expression of type I and III IFNs in ATG7-depleted cells and mice, whereas overexpression of ATG7 impaired the interferon response to IAV infection. Consistently, our experiments demonstrated that ATG7 significantly suppressed IRF3 activation during the IAV infection. Furthermore, we identified long noncoding RNA (lncRNA) GAPLINC as a critical regulator involved in the promotion of IAV replication by ATG7. Importantly, both inactivation of IRF3 and inhibition of IFN response caused by ATG7 were mediated through control over GAPLINC expression, suggesting that GAPLINC contributes to the suppression of antiviral immunity by ATG7. Together, these results uncover an autophagy-independent mechanism by which ATG7 suppresses host innate immunity and establish a critical role for ATG7/GAPLINC/IRF3 axis in regulating IAV infection and pathogenesis.
Subject(s)
Influenza A virus , Influenza, Human , Virus Diseases , Animals , Humans , Mice , Immunity, Innate , Interferons , Virus ReplicationABSTRACT
Physiological root resorption is a common occurrence during the development of deciduous teeth in children. Previous research has shown that the regulation of the inflammatory microenvironment through autophagy in DDPSCs is a significant factor in this process. However, it remains unclear why there are variations in the autophagic status of DDPSCs at different stages of physiological root resorption. To address this gap in knowledge, this study examines the relationship between the circadian clock of DDPSCs, the autophagic status, and the periodicity of masticatory behavior. Samples were collected from deciduous teeth at various stages of physiological root resorption, and DDPSCs were isolated and cultured for analysis. The results indicate that the circadian rhythm of important autophagy genes, such as Beclin-1 and LC3, and the clock gene REV-ERBα in DDPSCs, disappears under mechanical stress. Additionally, the study found that REV-ERBα can regulate Beclin-1 and LC3. Evidence suggests that mechanical stress is a trigger for the regulation of autophagy via REV-ERBα. Overall, this study highlights the importance of mechanical stress in regulating autophagy of DDPSCs via REV-ERBα, which affects the formation of the inflammatory microenvironment and plays a critical role in physiological root resorption in deciduous teeth.
Subject(s)
Circadian Clocks , Root Resorption , Child , Humans , Root Resorption/genetics , Beclin-1/genetics , Circadian Rhythm/genetics , Stem Cells , Tooth, DeciduousABSTRACT
Filamentous temperature-sensitive Z (FtsZ) is a tubulin-like GTPase that is highly conserved in bacteria and plants. It polymerizes into a ring at the division site of bacteria and chloroplasts and serves as the scaffold protein of the division complex. While a single FtsZ is present in bacteria and cyanobacteria, there are two subfamilies, FtsZ1 and FtsZ2 in the green lineage, and FtsZA and FtsZB in red algae. In Arabidopsis thaliana, the C-terminal motifs of AtFtsZ1 (Z1C) and AtFtsZ2-1 (Z2C) display distinct functions in the regulation of chloroplast division. Z1C exhibits weak membrane-binding activity, whereas Z2C engages in the interaction with the membrane protein AtARC6. Here, we provide evidence revealing the distinct traits of the C-terminal motifs of FtsZ1 and FtsZ2 throughout the plant evolutionary process. In a range of plant species, the C-terminal motifs of FtsZ1 exhibit diverse membrane-binding properties critical for regulating chloroplast division. In chlorophytes, the C-terminal motifs of FtsZ1 and FtsZ2 exhibit both membrane-binding and protein interaction functions, which are similar to those of cyanobacterial FtsZ and red algal FtsZA. During the transition from algae to land plants, the functions of the C-terminal motifs of FtsZ1 and FtsZ2 exhibit differentiation. FtsZ1 lost the function of interacting with ARC6 in land plants, and the membrane-binding activity of FtsZ2 was lost in ferns. Our findings reveal the functional differentiation of the C-terminal motifs of FtsZs during plant evolution, which is critical for chloroplast division.
Subject(s)
Arabidopsis Proteins , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Amino Acid Motifs , Arabidopsis/genetics , Arabidopsis/metabolism , Evolution, Molecular , Chloroplasts/metabolism , Biological EvolutionABSTRACT
Supramolecular chemistry combines the strength of molecular assembly via various molecular interactions. Hydrogen bonding facilitated self-assembly with the advantages of directionality, specificity, reversibility, and strength is a promising approach for constructing advanced supramolecules. There are still some challenges in hydrogen bonding based supramolecular polymers, such as complexity originating from tautomerism of the molecular building modules, the assembly process, and structure versatility of building blocks. In this review, examples are selected to give insights into multiple hydrogen bonding driven emerging supramolecular architectures. We focus on chiral supramolecular assemblies, multiple hydrogen bonding modules as stimuli responsive sources, interpenetrating polymer networks, multiple hydrogen bonding assisted organic frameworks, supramolecular adhesives, energy dissipators, and quantitative analysis of nano-adhesion. The applications in biomedical materials are focused with detailed examples including drug design evolution for myotonic dystrophy, molecular assembly for advanced drug delivery, an indicator displacement strategy for DNA detection, tissue engineering, and self-assembly complexes as gene delivery vectors for gene transfection. In addition, insights into the current challenges and future perspectives of this field to propel the development of multiple hydrogen bonding facilitated supramolecular materials are proposed.
Subject(s)
Biocompatible Materials , Polymers , Hydrogen Bonding , Polymers/chemistryABSTRACT
Controllable ring-opening of polycyclic aromatic hydrocarbons plays a crucial role in various chemical and biological processes. However, breaking down aromatic covalent C-C bonds is exceptionally challenging due to their high stability and strong aromaticity. This study presents a seminal report on the precise and highly selective on-surface ring-opening of the seven-membered ring within the aromatic azulene moieties under mild conditions. The chemical structures of the resulting products were identified using bond-resolved scanning probe microscopy. Furthermore, through density functional theory calculations, we uncovered the mechanism behind the ring-opening process and elucidated its chemical driving force. The key to achieving this ring-opening process lies in manipulating the local aromaticity of the aromatic azulene moiety through strain-induced internal ring rearrangement and cyclodehydrogenation. By precisely controlling these factors, we successfully triggered the desired ring-opening reaction. Our findings not only provide valuable insights into the ring-opening process of polycyclic aromatic hydrocarbons but also open up new possibilities for the manipulation and reconstruction of these important chemical structures.
ABSTRACT
Perigonadal adipose tissue is a homogeneous white adipose tissue (WAT) in adult male mice without any brown adipose tissue (BAT). However, there are congenital differences in the gonads between male and female mice. Whether heterogeneity existed in perigonadal adipose tissues (ATs) in female mice remains unknown. This study reported a perigonadal brown-like AT located between abdominal lymph nodes and the uterine cervix in female mice, termed lymph node-cervical adipose tissue (LNCAT). Its counterpart, lymph node-prostatic adipose tissue (LNPAT), exhibited white phenotype in adult virgin male mice. When exposed to cold, LNCAT/LNPAT increased uncoupling protein 1 (UCP1) expression via activation of tyrosine hydroxylase (TH), in which abdominal lymph nodes were involved. Interestingly, the UCP1 expression in LNCAT/LNPAT varied under different reproductive stages. The UCP1 expression in LNCAT was upregulated at early pregnancy, declined at midlate pregnancy, and reverted in weaning dams. Mating behavior stimulated LNPAT browning in male mice. We found that androgen but not estrogen or progesterone inhibited UCP1 expression in LNCAT. Androgen administration reversed the castration-induced LNPAT browning. Our results identified a perigonadal brown-like AT in female mice and characterized its UCP1 expression patterns under various conditions.NEW & NOTEWORTHY A novel perigonadal brown-like AT (LNCAT) of female mice was identified. Abdominal lymph nodes were involved in cold-induced browning in this newly discovered adipose tissue. The UCP1 expression in LNCAT/LNPAT was also related to ages, sexes, and reproductive stages, in which androgen acted as an inhibitor role.
Subject(s)
Adipose Tissue, Brown , Cervix Uteri , Lymph Nodes , Prostate , Uncoupling Protein 1 , Animals , Male , Female , Mice , Lymph Nodes/metabolism , Uncoupling Protein 1/metabolism , Uncoupling Protein 1/genetics , Adipose Tissue, Brown/metabolism , Cervix Uteri/metabolism , Prostate/metabolism , Pregnancy , Adipose Tissue, White/metabolism , Mice, Inbred C57BL , Adipose Tissue/metabolism , Androgens/pharmacology , Androgens/metabolism , Sexual Behavior, Animal/physiologyABSTRACT
The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Podocytes , Mice , Animals , Podocytes/metabolism , Diabetes Mellitus, Experimental/complications , Sleep Deprivation/complications , Sleep Deprivation/metabolism , Proteinuria/genetics , Proteinuria/metabolism , Diabetic Nephropathies/genetics , Diabetic Nephropathies/complications , Mice, Knockout , AutophagyABSTRACT
Peritoneal fibrosis (PF) is particularly common in individuals undergoing peritoneal dialysis (PD). Fibrosis of the parenchymal tissue typically progresses slowly. Therefore, preventing and reducing the advancement of fibrosis is crucial for effective patient treatment. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), primarily used to treat and improve renal anemia. Recent studies have found that HIF-1α possesses antioxidant activity and exerts a certain protective effect in ischemic heart disease and spinal cord injury, while it can also delay the progression of pulmonary and renal fibrosis. This study establishes the mice model through intraperitoneal injection of 4.25 % peritoneal dialysate fluid (PDF) and explores the therapeutic effects of Roxadustat by inducing TGF-ß1-mediated epithelial-mesenchymal transition (EMT) in Met-5A cells. The aim is to investigate the protective role and mechanisms of Roxadustat against PD-related PF. We observed thicker peritoneal tissue and reduced permeability in animals with PD-related PF samples. This was accompanied by heightened inflammation, which Roxadustat alleviated by lowering the levels of inflammatory cytokines (IL-6, TNF-α). Furthermore, Roxadustat inhibited EMT in PF mice and TGF-ß1-induced Met-5A cells, as evidenced by decreased expression of fibrotic markers, such as fibronectin, collagen I, and α-SMA, alongside an elevation in the expression of the epithelial marker, E-cadherin. Roxadustat also significantly decreased the expression of TGF-ß1 and the phosphorylation of p-Smad2 and p-Smad3. In conclusion, Roxadustat ameliorates peritoneal fibrosis through the TGF-ß/Smad pathway.
Subject(s)
Kidney Diseases , Peritoneal Fibrosis , Humans , Mice , Animals , Peritoneal Fibrosis/drug therapy , Peritoneal Fibrosis/pathology , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism , Peritoneum/pathology , Fibrosis , Epithelial-Mesenchymal Transition , Kidney Diseases/pathologyABSTRACT
BACKGROUND: The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. RESULTS: In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. CONCLUSION: A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.
Subject(s)
Calmodulin , Flowers , Fruit , Passiflora , Phylogeny , Plant Proteins , Passiflora/genetics , Passiflora/growth & development , Flowers/genetics , Flowers/growth & development , Flowers/metabolism , Fruit/genetics , Fruit/growth & development , Fruit/metabolism , Calmodulin/genetics , Calmodulin/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Genome, Plant , Genes, Plant , Gene Expression ProfilingABSTRACT
Radiation resistance in breast cancer resulting in residual lesions or recurrence is a significant cause to radiotherapy failure. Cancer-associated fibroblasts (CAFs) and radiotherapy-induced senescent CAFs can further lead to radiation resistance and tumor immunosuppressive microenvironment. Here, an engineering cancer-cell-biomimetic nanoplatform is constructed for dual-targeted clearance of CAFs as well as senescent CAFs. The nanoplatform is prepared by 4T1 cell membrane vesicles chimerized with FAP single-chain fragment variable as the biomimetic shell for targeting of CAFs and senescent CAFs, and PLGA nanoparticles (NPs) co-encapsulated with nintedanib and ABT-263 as the core for clearance of CAFs and senescent CAFs, which are noted as FAP-CAR-CM@PLGA-AB NPs. It is evidenced that FAP-CAR-CM@PLGA-AB NPs directly suppressed the tumor-promoting effect of senescent CAFs. It also exhibits prolonged blood circulation and enhanced tumor accumulation, dual-cleared CAFs and senescent CAFs, improved radiation resistance in both acquired and patient-derived radioresistant tumor cells, and effective antitumor effect with the tumor suppression rate of 86.7%. In addition, FAP-CAR-CM@PLGA-AB NPs reverse the tumor immunosuppressive microenvironment and enhance systemic antitumor immunity. The biomimetic system for dual-targeted clearance of CAFs and senescent CAFs provides a potential strategy for enhancing the radio-sensitization of breast cancer.
Subject(s)
Breast Neoplasms , Cancer-Associated Fibroblasts , Cellular Senescence , Nanoparticles , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Female , Nanoparticles/chemistry , Humans , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/drug effects , Animals , Cell Line, Tumor , Cellular Senescence/drug effects , Radiation Tolerance/drug effects , Mice , Biomimetics/methods , Tumor Microenvironment/drug effects , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistryABSTRACT
Copper-based nanozymes exhibit excellent antitumor activity but are easily inactivated due to the disturbance of proteins or other macromolecules with sulfhydryl. A tumor microenvironment-responsive CuMnO@Fe3O4 (CMF) core-shell nanozyme for highly efficient tumor theranostics is developed. A platelet-derived growth factor receptor-ß-recognizing cyclic peptide (PDGFB) target is conjugated to the surface of CMF to fabricate a tumor-specific nanozyme (PCMF). The core-shell nanostructure significantly avoids the oxidation and inactivation of copper-based nanozyme, promoting the antitumor activity of PCMF. The weak acid- and GSH-activated T1 and T2 relaxation rate of PCMF contributes to T1 and T2 dual contrast imaging at the tumor site. In addition, the PCMF disintegrates and produces some metal ions that possess Fenton catalytic activity (i.e., Cu+, Mn2+, and Fe2+) under TME. This process significantly depletes GSH, accelerates Fenton and Fenton-like reactions, enhances cellular reactive oxygen species (ROS) levels, and induces cancer cell apoptosis and ferroptosis. PCMF also exhibits photothermal functions, so it can be used in combined photothermal therapy, ferroptosis therapy, and chemodynamic therapy, improving anticancer activity. This work provides insights into the design of an exquisite nanostructure for high-sensitive and tumor-specific theranostics.
Subject(s)
Nanostructures , Neoplasms , Humans , Precision Medicine , Copper , Tumor Microenvironment , Magnetic Resonance Imaging , Neoplasms/diagnostic imaging , Neoplasms/therapy , Hydrogen Peroxide , Cell Line, TumorABSTRACT
Plants possess the remarkable ability to integrate the circadian clock with various signalling pathways, enabling them to quickly detect and react to both external and internal stress signals. However, the interplay between the circadian clock and biological processes in orchestrating responses to environmental stresses remains poorly understood. TOC1, a core component of the plant circadian clock, plays a vital role in maintaining circadian rhythmicity and participating in plant defences. Here, our study reveals a direct interaction between TOC1 and the promoter region of MYB44, a key gene involved in plant defence. TOC1 rhythmically represses MYB44 expression, thereby ensuring elevated MYB44 expression at dawn to help the plant in coping with lowest temperatures during diurnal cycles. Additionally, both TOC1 and MYB44 can be induced by cold stress in an Abscisic acid (ABA)-dependent and independent manner. TOC1 demonstrates a rapid induction in response to lower temperatures compared to ABA treatment, suggesting timely flexible regulation of TOC1-MYB44 regulatory module by the circadian clock in ensuring a proper response to diverse stresses and maintaining a balance between normal physiological processes and energy-consuming stress responses. Our study elucidates the role of TOC1 in effectively modulating expression of MYB44, providing insights into the regulatory network connecting the circadian clock, ABA signalling, and stress-responsive genes.
Subject(s)
Abscisic Acid , Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Signal Transduction , Stress, Physiological , Transcription Factors , Arabidopsis/genetics , Arabidopsis/physiology , Arabidopsis/metabolism , Abscisic Acid/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Stress, Physiological/genetics , Promoter Regions, Genetic/genetics , Circadian Clocks/geneticsABSTRACT
BACKGROUND: Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes. RESULTS: A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 (p = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively (p < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005-2.804) and MACEs (HR 2.064, 95% CI 1.386-3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM). CONCLUSION: Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status.
Subject(s)
Biomarkers , Blood Glucose , ST Elevation Myocardial Infarction , Humans , Male , Female , Middle Aged , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/therapy , Blood Glucose/metabolism , Aged , China/epidemiology , Time Factors , Risk Factors , Risk Assessment , Biomarkers/blood , Cause of Death , Incidence , Retrospective Studies , Treatment OutcomeABSTRACT
Regulatory T cells (Tregs), a subset of CD4+ T cells, are indispensable in maintaining immune self-tolerance and have been utilized in various diseases. Treg-derived extracellular vesicles (Treg-EVs) have been discovered to play an important role in the mechanism of Treg functions. As cell-derived membranous particles, EVs carry multiple bioactive substances that possess tremendous potential for theranostics. Treg-EVs are involved in numerous physiological and pathological processes, carrying proteins and miRNAs inherited from the parental cells. To comprehensively understand the function of Treg-EVs, here we reviewed the classification of Treg-EVs, the active molecules in Treg-EVs, their various applications in diseases, and the existing challenges for Treg-EVs based theranostics. This Review aims to clarify the feasibility and potential of Treg-EVs in diseases and theranostics, facilitating further research and application of Treg-EVs.
Subject(s)
Extracellular Vesicles , T-Lymphocytes, Regulatory , T-Lymphocytes, Regulatory/immunology , Extracellular Vesicles/metabolism , Extracellular Vesicles/immunology , Humans , Animals , Theranostic Nanomedicine/methods , MicroRNAs/genetics , Precision Medicine/methodsABSTRACT
It is known that the abnormal expression of specific cellular miRNAs is closely related to cell apoptosis, and so monitoring the level change of these miRNAs can in principle be used to evaluate the process of apoptosis stimulated by drugs. Towards this goal, here we construct an ultrasensitive electrochemiluminescence (ECL) nanoplatform via the target miRNA-triggered immobilization of spherical nucleic acid enzymes (SNAzymes) onto tetrahedral DNA nanostructures on the electrode surface, which catalyzes the luminol-H2O2 reaction to output an ECL signal. This enables the sensitive and specific detection of two apoptosis-related miRNAs, miR-21 and miR-133a, with a detection limit of 33 aM. Furthermore, we employed the developed ECL nanoplatform to monitor the levels of these two miRNAs inside cancer cells stimulated by DOX, showing that the level of miR-21 decreases, while that of miR-133a increases in the early apoptotic cells. This difference highlights the distinct roles of the two target miRNAs, where miR-21 promotes the early apoptosis of cancer cells, whereas miR-133a suppresses it, providing new insight into cell physiological processes.
Subject(s)
Apoptosis , Electrochemical Techniques , Limit of Detection , Luminescent Measurements , Luminol , MicroRNAs , MicroRNAs/analysis , Humans , Apoptosis/drug effects , Luminescent Measurements/methods , Electrochemical Techniques/methods , Luminol/chemistry , Hydrogen Peroxide/chemistry , Biosensing Techniques/methods , Doxorubicin/pharmacology , Doxorubicin/chemistry , Nanostructures/chemistry , DNA/chemistry , DNA/genetics , Electrodes , HeLa Cells , Cell Line, Tumor , Enzymes, Immobilized/chemistry , Immobilized Nucleic Acids/chemistry , Immobilized Nucleic Acids/geneticsABSTRACT
Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (â¢O2-, â¢OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.
ABSTRACT
MOF-based materials, as bifunctional catalysts for electrocatalytic water splitting, play an important role in the application and development of clean fuel hydrogen energy. This study presents a series of novel 3D Co-based MOFs with layered networks, including [Co(4,4'-bipy)0.5(aip)(CH3OH)·H2O]n (Co-MOF 1), [Co2(1,3'-bit)(aip)2(CH3OH)·H2O]n (Co-MOF 2), [Co(4,4'-bipb)(aip)]n (Co-MOF 3), and [Co2(4,4'-bipe)(aip)2·1.5H2O]n (Co-MOF 4). Their single-crystal structures of Co-MOFs 1-4 are characterized and analyzed before being applied in alkaline solutions for water decomposition (OER and HER). The electrocatalytic tests indicate that Co-MOFs 1-4 exhibit a good performance. Notably, Co-MOF 4 exhibits great behavior which has low overpotentials of 94 and 188 mV (OER) as well as 185 and 352 mV (HER) at the currents of 10 and 100 mA cm-2, respectively. In comparison with Co-MOFs 1-3, Co-MOF 4 has the lowest Tafel slopes, highest ECSA, and smallest resistance. The immanent qualities, such as distinct interwoven long chain layered structure, unsaturated coordination modes, and synergistic catalytic qualities among Co ions, contribute to explaining the results. The fundamentals provide valuable information for the investigation of innovative MOF-based bifunctional electrocatalysts for overall water splitting.
ABSTRACT
Two two-dimensional (2D) layered metal-organic frameworks (MOFs), namely, {[Yb(L)(H2O)2NO3]·2H2O}n (Yb-MOF) and [Er(L)(H2O)3Cl]n (Er-MOF) (H2L = 5-((6H-purin-6-yl)amino)isophthalic acid), were constructed by a solvothermal method and characterized. The catalytic performance study showed that the Yb-MOF could efficiently catalyze the oxidation of sulfides to sulfoxides under 15 W light-emitting diode (LED) blue light irradiation. Electron paramagnetic resonance spectroscopy and free-radical trapping experiments demonstrated that the photocatalytic reaction process involved â¢O2-, and the corresponding mechanism was proposed. Moreover, Er-MOF exhibited good catalytic efficiency and excellent substrate tolerance in the cycloaddition reaction of CO2, and the reaction conditions were mild. After 5 cycles, the catalytic activities of two MOFs did not significantly decrease, and the framework structures remained unchanged. Therefore, the Yb-MOF and Er-MOF were considered efficient and stable heterogeneous catalysts.
ABSTRACT
Converting CO2 to valuable chemicals and fuels is a viable method to establish a carbon-neutral energy cycle in the environment. Metal-organic frameworks (MOFs), characterized by dispersed active sites, high porosity, etc., have displayed a great application prospect in the electrochemical/chemical CO2 reduction reaction (CO2RR) process. Herein, we proposed a one-step production to establish a series of pillar-layered porous MOFs, [Co2(L)(bimb)]n (MOF 1) and [Co4(L)2(bidpe)2]n (MOF 2) [H4L = 5'-(4-carboxyphenyl)-(1,1':2',1â³-terphenyl)-4,4',4â³-tricarboxylic, bimb = 1,4-bis(imidazol-1-yl)-butane, bidpe = 4'-bis(imidazolyl) diphenyl ether], for preferential conversion of CO2 via ligand adjustment and increase of active sites' density. According to single-crystal X-ray diffraction studies, [Co2(L)(bimb)]n exhibits pillar-layered binuclear 3D frameworks with a 2,4,6-linked 3-nodes new topology structure, while [Co4(L)2(bidpe)2]n displays pillar-layered tetranuclear interspersed networks with a 4,6-linked 2-nodes fsc topology structure through a ligand adjustment strategy. Meanwhile, the pillar-layered structure of the MOFs with abundant active sites is conducive to mass diffusion and benefits the conversion of CO2. MOFs 1-2 exhibit good electrocatalytic activity for CO2RR in 0.5 M KHCO3 solution. Especially, the current density of MOF 2 generated at -0.90 V (vs. RHE) reaches -81.6 mA·cm-2, which is 3.1 times higher than that under an Ar atmosphere. In addition, MOFs 1-2 can be used as a heterogeneous catalyst for chemical conversion of CO2. The results are expected to provide inspiration for rational design to develop stable and high-efficiency MOF-based electrocatalysts for CO2RR.
ABSTRACT
In line with the "healthy aging" principle, we aim to assess the exposure map and health risks of environmental chemicals in the elderly. Blood samples from 918 elderly individuals in Wuhan, China, were analyzed using the combined gas/liquid-mass spectrometry technology to detect levels of 118 environmental chemicals. Cluster analysis identified exposure profiles, while risk indexes and bioanalytical equivalence percentages were calculated using EPA's ToxCast database. The detection rates for 87 compounds exceeded 70%. DEHP, DiBP, naphthalene, phenanthrene, DnBP, pyrene, anthracene, permethrin, fluoranthene, and PFOS showed the highest concentrations. Fat-soluble pollutants varied across lifestyles. In cluster 2, which was characterized by higher concentrations of fat-soluble substances, the proportion of smokers or drinkers was higher than that of nonsmokers or nondrinkers. Pesticides emerged as the most active environmental chemicals in peroxisome proliferator-activated receptor gamma antagonist, thyroid hormone receptor (TR) antagonist, TR agonist, and androgen receptor (AR) agonist activity assays. Additionally, PAEs and polycyclic aromatic hydrocarbons played significant roles as active contaminants for the corresponding targets of AR antagonists and estrogen receptor alpha. We proposed a list of priority pollutants linked to endocrine-disrupting toxic effects in the elderly, which may provide the groundwork for further research into environmental etiology.