ABSTRACT
Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.
Subject(s)
Cisplatin , Drug Resistance, Neoplasm , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gene Expression Regulation, Neoplastic , Kruppel-Like Transcription Factors , Neural Cell Adhesion Molecule L1 , Humans , Cisplatin/pharmacology , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/metabolism , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/genetics , Neural Cell Adhesion Molecule L1/metabolism , Neural Cell Adhesion Molecule L1/genetics , Cell Line, Tumor , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasm Metastasis , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitination/drug effects , Mice , Cell Proliferation/drug effects , Tripartite Motif Proteins , DNA-Binding Proteins , Nuclear ProteinsABSTRACT
In this work, cyano contained g-C3N4 comodified by In2S3 and polypyrrole (C≡NâCN/IS/Ppy) materials are synthesized for the photocatalytic production of H2O2 and photocatalysis-self-Fenton reaction for highly efficient degradation of metronidazole. The results from UV-vis spectrophotometry, surface photovoltage, and Kelvin probe measurements reveal the promoted transport and separation efficiency of photoinduced charges after the introduction of In2S3 and Ppy in the heterojunction. The existence of a built-in electric field accelerates the photoinduced charge separation and preserves the stronger oxidation ability of holes at the valence band of C≡NâCN. Linear sweep voltammetry measurements, zeta potential analyzations, nitroblue tetrazolium determination, and other measurements show that Ppy improves the conversion ratio of â¢O2 - to H2O2 and the utilization ratio of â¢O2 -, as well as suppresses decomposition of H2O2. Accordingly, the H2O2 evolution rate produced via a two-step single-electron reduction reaction reaches almost 895 µmol L-1 h-1, a value 80% and 7.2-fold higher than those obtained with C≡NâCN/IS and C≡NâCN, respectively. The metronidazole removal rate obtained via photocatalysis-self-Fenton reaction attains 83.7% within 120 minutes, a value much higher than that recorded by the traditional Fenton method. Overall, the proposed synthesis materials and route look promising for the H2O2 production and organic pollutants degradation.
ABSTRACT
Despite the challenges associated with the synthesis of flexible metal-covalent organic frameworks (MCOFs), these offer the unique advantage of maximizing the atomic utilization efficiency. However, the construction of flexible MCOFs with flexible building units or linkages has rarely been reported. In this study, novel flexible MCOFs are constructed using flexible building blocks and copper clusters with hydrazone linkages. The heterometallic frameworks (Cu, Co) are prepared through the hydrazone linkage coordination method and evaluated as catalysts for the oxygen evolution reaction (OER). Owing to the spatial separation and functional cooperation of the heterometallic MCOF catalysts, the as-synthesized MCOFs exhibited outstanding catalytic activities with an overpotential of 268.8 mV at 10 mA cm-2 for the OER in 1 M KOH, which is superior to those of the reported covalent organic frameworks (COFs)-based OER catalysts. Theoretical calculations further elucidated the synergistic effect of heterometallic active sites within the linkages and frameworks, contributing to the enhanced OER activity. This study thus introduces a novel approach to the fundamental design of flexible MCOF catalysts for the OER, emphasizing their enhanced atomic utilization efficiency.
ABSTRACT
Serious water contamination induced by massive discharge of cadmium(II) ions is becoming an emergent environmental issue due to high toxicity and bioaccumulation; thus, it is extremely urgent to develop functional materials for effectively treating with Cd2+ from wastewater. Benefiting from abundant binding sites, simple preparation process, and adjustable structure, UiO-66-type metal-organic frameworks (MOFs) had emerged as promising candidates in heavy metal adsorption. Herein, monolithic UiO-66-(COOH)2-functionalized cellulose fiber (UCLF) adsorbents were simply fabricated by incorporating MOFs into cellulose membranes through physical blending and self-entanglement. A two-dimensional structure was facilely constructed by cellulose fibers from sustainable biomass agricultural waste, providing a support platform for the integration of eco-friendly UiO-66-(COOH)2 synthesized with lower temperature and toxicity solvent. Structure characterization and bath experiments were performed to determine operational conditions for the maximization of adsorption capacity, thereby bringing out an excellent adsorption capacity of 96.10 mg/g. UCLF adsorbent holding 10 wt % loadings of UiO-66-(COOH)2 (UCLF-2) exhibited higher adsorption capacity toward Cd2+ as compared to other related adsorbents. Based on kinetics, isotherms, and thermodynamics, the adsorption behavior was spontaneous, exothermic, as well as monolayer chemisorption. Coordination and electrostatic attraction were perhaps mechanisms involved in the adsorption process, deeply unveiled by the effects of adsorbate solution pH and X-ray photoelectron spectroscopy. Moreover, UCLF-2 adsorbent with good mechanical strength offered a structural guarantee for the successful implementation of practical applications. This study manifested the feasibility of UCLF adsorbents used for Cd2+ adsorption and unveiled a novel strategy to shape MOF materials for wastewater decontamination.
ABSTRACT
BACKGROUND AND OBJECTIVES: B(A) phenotype is usually formed by nucleotide mutations in the ABO*B.01 allele, with their products exhibiting glycosyltransferases (GTs) A and B overlapping functionality. We herein report a B(A) allele found in a Chinese family. MATERIALS AND METHODS: The entire ABO genes of the probands, including flanking regulatory regions, were sequenced through PacBio third-generation long-read single-molecule real-time sequencing. 3D molecular models of the wild-type and mutant GTB were generated using the DynaMut web server. The effect of the mutation on the enzyme function was predicted by PROVEAN and PolyPhen2. The predictions of stability changes were performed using DynaMut and SNPeffect. RESULTS: Based on serological and sequencing features, we concluded the two probands as possible cases of the B(A) phenotype. Crystallization analysis showed that Thr266 substitution does not disrupt the hydrogen bonds. However, some changes in interatomic contacts, such as loss of ionic interactions and hydrophobic contacts, and addition of weak hydrogen bonds, may have affected protein stability to some extent. This mutation was predicted to have a benign effect on enzyme function and slightly reduce protein stability. CONCLUSION: The probands had the same novel B(A) allele with a c.797T>C (p.Met266Thr) mutation on the ABO*B.01 backbone.
Subject(s)
Glycosyltransferases , Mutation, Missense , Humans , Phenotype , Mutation , Glycosyltransferases/chemistry , Glycosyltransferases/genetics , Alleles , China , ABO Blood-Group System/genetics , GenotypeABSTRACT
Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients' poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Tumor Microenvironment , Carcinoma, Squamous Cell/genetics , Lung Neoplasms/genetics , Lung , Prognosis , Kallikreins/geneticsABSTRACT
A novel iridium (III) complex bearing boron dipyrromethene (Bodipy) as the light-harvesting antenna has been synthesized and is firstly employed as photosensitizer to assemble a dye-sensitized NiO photocathode. The assembled photocathode exhibits significantly improved photoelectrochemical (PEC) performance. Integrating the prepared photocathode with hybridization chain reaction (HCR)--based signal amplification strategy, a cathodic PEC biosensor is proposed for the detection of microRNA-133a (miRNA-133a). In the presence of the target, HCR is triggered to form long duplex concatamers on the photocathode, which allows numerous manganese porphyrins (MnPP) to bind in the dsDNA groove. With the help of H2O2, MnPP with peroxidase-like activity catalyzes 4--chloro-1-naphthol (4-CN) to produce benzo--4--chlorohexadienone (4-CD) precipitate on the electrode, leading to a significant decrease of photocurrent signal. The decreased photocurrent correlates linearly with the target concentration from 0.1 fM to 1 nM with a detection limit of 66.2 aM (S/N = 3). The proposed PEC strategy exhibits delightful selectivity, reproducibility and stability.
Subject(s)
Hydrogen Peroxide , Iridium , Reproducibility of Results , Electrochemical Techniques , Limit of DetectionABSTRACT
An efficient PEC biosensor is proposed for ATP detection based on exciton energy transfer from CdTe quantum dots (CdTe QDs) to Au nanoparticles (AuNPs), integrating CRISPR/Cas12a trans-cleavage activity and specific recognition of ZIF-67 to ATP. Exciton energy transfer between CdTe QDs and AuNPs system is firstly constructed as photoelectrochemical (PEC) sensing substrate. Then, the activator DNAs, used to activate CRISPR/Cas12a, are absorbed on the surface of ZIF-67. In the presence of ATP, the activator DNAs are released due to more efficient adsorption of ZIF-67 to ATP. The released activator DNA activates trans-cleavage activity of CRISPR/Cas12a to degrade ssDNA on the electrode, leading to the recovery of photocurrent due to the interrupted energy transfer. Benefiting from the specific recognition of ZIF-67 to ATP and CRISPR/Cas12a-modulated amplification strategy, the sensor is endowed with excellent specificity and high sensitivity.
Subject(s)
Adenosine Triphosphate , Biosensing Techniques , CRISPR-Cas Systems , Cadmium Compounds , Electrochemical Techniques , Gold , Metal Nanoparticles , Quantum Dots , Biosensing Techniques/methods , Adenosine Triphosphate/analysis , Adenosine Triphosphate/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Cadmium Compounds/chemistry , Quantum Dots/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Tellurium/chemistry , Imidazoles/chemistry , CRISPR-Associated Proteins/chemistry , Limit of Detection , Zeolites/chemistry , Endodeoxyribonucleases/chemistry , Metal-Organic Frameworks/chemistry , Photochemical Processes , Bacterial Proteins/chemistry , Bacterial Proteins/geneticsABSTRACT
A renewable electrochemical screen-printed electrode (SPE) is proposed based on magnetic bamboo-like nitrogen-carbon (N-C) nanotubes loaded with nickel-cobalt alloy (NiCo) nanoparticles (NiCo@N-CNTs) for the determination of ractopamine (RAC). During the preparation of NiCo@N-CNTs, Co-MOF-67 (ZIF-67) was firstly synthesized, and then blended with dicyandiamide and nickel acetate, followed by a one-step pyrolysis procedure to prepare NiCo@N-doped carbon nanotubes. The surface morphology, structure, and chemical composition of NiCo@N-CNTs were characterized by SEM, TEM, XRD, XPS, and EDS. The electrocatalytic and electrochemical behavior of NiCo@N-CNTs were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that NiCo@N-CNTs possessed remarkable conductivity and electrocatalysis to the oxidation of ractopamine (RAC). By using screen-printed electrode (SPE), NiCo@N-CNTs, and a designed base support, a magnetic RAC sensor (NiCo@N-CNTs/SPE) was successfully constructed. It presented a detection linear range of 0.05-80 µM with a detection limit of 12 nM (S/N = 3). It also exhibited good sensitivity, reproducibility, and practicability in spiked real pork samples. Since the adhesion of NiCo/N-CNTs on SPE was controlled by magnet, the NiCo@N-CNTs was easily detached from the SPE surface by magnetism and thus displayed excellent renewability. This work broadened insights into portable devices for on-site and real-time analysis.
ABSTRACT
Background: This study aimed to determine whether the hemodynamics of patients with right ventricle outflow tract obstructive congenital heart disease (RVOTO-CHD) improve after corrective surgery by changing the ventilation mode. Methods: Patients with RVOTO-CHD who underwent corrective surgery were enrolled in this study. Echocardiography and advanced hemodynamic monitoring were performed using the pulse indicator continuous cardiac output (PiCCO) technology in the pressure-regulated volume control (PRVC) mode, followed with switching to the pressure support ventilation (PSV) mode and neurally adjusted ventilatory assist (NAVA) mode in random order. Results: Overall, 31 patients were enrolled in this study from April 2021 to October 2021. Notably, changing the ventilation mode from PRVC to a spontaneous mode (PSV or NAVA) led to better cardiac function outcomes, including right ventricular cardiac index (PRVC: 3.19 ± 1.07 L/min/ m 2 vs. PSV: 3.45 ± 1.32 L/min/ m 2 vs. NAVA: 3.82 ± 1.03 L/min/ m 2 , p < 0.05) and right ventricle contractility (tricuspid annular peak systolic velocity) (PRVC: 6.58 ± 1.40 cm/s vs. PSV: 7.03 ± 1.33 cm/s vs. NAVA: 7.94 ± 1.50 cm/s, p < 0.05), as detected via echocardiography. Moreover, in the NAVA mode, PiCCO-derived cardiac index (PRVC: 2.92 ± 0.54 L/min/ m 2 vs. PSV: 3.04 ± 0.56 L/min/ m 2 vs. NAVA: 3.20 ± 0.62 L/min/ m 2 , p < 0.05), stroke volume index (PRVC: 20.38 ± 3.97 mL/ m 2 vs. PSV: 21.23 ± 4.33 mL/ m 2 vs. NAVA: 22.00 ± 4.33 mL/ m 2 , p < 0.05), and global end diastolic index (PRVC: 295.74 ± 78.39 mL/ m 2 vs. PSV: 307.26 ± 91.18 mL/ m 2 vs. NAVA: 323.74 ± 102.87 mL/ m 2 , p < 0.05) improved, whereas extravascular lung water index significantly reduced (PRVC: 16.42 ± 7.90 mL/kg vs. PSV: 15.42 ± 5.50 mL/kg vs. NAVA: 14.4 ± 4.19 mL/kg, p < 0.05). Furthermore, peak inspiratory pressure, mean airway pressure, driving pressure, and compliance of the respiratory system improved in the NAVA mode. No deaths were reported in this study. Conclusions: We found that utilizing spontaneous ventilator modes, especially the NAVA mode, after corrective surgery in patients with RVOTO-CHD may improve their right heart hemodynamics and respiratory mechanics. However, further randomized controlled trials are required to verify the advantages of spontaneous ventilation modes in such patients. Clinical Trial Registration: NCT04825054.
ABSTRACT
An enhancement effect for the activation of CRISPR/Cas12a (CRISPR = clustered regularly interspaced short palindromic repeats; Cas = CRISPR-associated) was discovered. That was, a hairpin model with dangling 5' end complementary to crRNA (CRISPR RNA) greatly improved the activity of CRISPR/Cas12a after extention of two random sequences. But, the corresponding intact hairpin without PAM (protospacer adjacent motif) or suboptimal PAM sequences was completely inactive to CRISPR/Cas12a because of the superhigh stability of intact hairpin. According to the finding, a CRISPR/Cas12a-based strategy coupled with a signal reported system was designed for transcription factors detection. By using mono-labeled ssDNA (single-stranded DNA) as reporter and two newly synthesized N-C (nitrogen-doped carbon) nanosheets as scavenger to eliminate the fluorescent background, the strategy realized the detection of NF-ĸB p50 (p50 subunit of nuclear factor kappa-B) with a linear detection range of 0.8 - 2000.0 pM and a LOD of 0.5 pM. The discovery of "enhancement and inactivation effect" not only deepened insight into CRISPR/Cas12a but also broadened the practical application of CRISPR/Cas systems for the molecular detection and disease diagnostics.
Subject(s)
CRISPR-Cas Systems , Transcription Factors , DNA, Single-Stranded , RNASubject(s)
Alleles , Rh-Hr Blood-Group System , Humans , Rh-Hr Blood-Group System/genetics , Female , Sequence Deletion , MaleSubject(s)
ABO Blood-Group System , Humans , Alleles , Exons , Phenotype , ABO Blood-Group System/genetics , GenotypeABSTRACT
Objective: This study is dedicated to revealing the potential mechanism of Qin Run Hua Jie (QRHJ) decoction in Interstitial pneumonia (IP) treatment. Methods: The TCMSP database predicted the chemical components and targets of QRHJ decoction, and the IP-related genes were from the Genecards database. Cytoscape software was used to establish the interaction network. R package clusterProfiler was utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The molecular docking analysis of target proteins and the corresponding active pharmaceutical ingredients in the core position of the interaction network was conducted. Then, molecular dynamics (MD) simulations of a potential active substance and its key targets were performed. The binding efficiency of EGFR and luteolin, HIF1A and diosgenin was detected by cellular thermal shift assay (CETSA), and protein expression was measured by Western blot. CCK-8 was used to detect cell activity. Results: A total of 153 active ingredients, 127 targets and 362 IP-related genes were obtained. KEGG enrichment analysis identified IP-related signaling pathways including HIF-1 signaling pathway and TNF signaling pathway. The two key components luteolin and diosgenin stably bound to the key targets EGFR and HIF1A. Cell experiments further showed that EGFR and luteolin, HIF1A and diosgenin bound to exert anti-fibrotic effects. Conclusion: As an active ingredient of QRHJ decoction, luteolin and diosgenin may exert therapeutic effect on IP through binding to the key target EGFR and HIF1A. This work initially revealed the key molecular mechanism of QRHJ decoction in IP treatment and offered theoretical evidence.
ABSTRACT
Multifunctional single-atom catalysts (SACs) have been extensively investigated as outstanding signal amplifiers in bioanalysis field. Herein, a type of Fe single-atom catalysts with Fe-nitrogen coordination sites in nitrogen-doped carbon (Fe-N/C SACs) was synthesized and demonstrated to possess both catalase and peroxidase-like activity. Utilizing Fe-N/C SACs as dual signal amplifier, an efficient bipolar electrode (BPE)-based electrochemiluminescence (ECL) immunoassay was presented for determination of prostate-specific antigen (PSA). The cathode pole of the BPE-ECL platform modified with Fe-N/C SACs is served as the sensing side and luminol at the anode as signal output side. Fe-N/C SACs could catalyze decomposition of H2O2 via their high catalase-like activity and then increase the Faraday current, which can boost the ECL of luminol due to the electroneutrality in a closed BPE system. Meanwhile, in the presence of the target, glucose oxidase (GOx)-Au NPs-Ab2 was introduced through specific immunoreaction, which catalyzes the formation of H2O2. Subsequently, Fe-N/C SACs with peroxidase-like activity catalyze the reaction of H2O2 and 4-chloro-1-naphthol (4-CN) to generate insoluble precipitates, which hinders electron transfer and then inhibits the ECL at the anode. Thus, dual signal amplification of Fe-N/C SACs was achieved by increasing the initial ECL and inhibiting the ECL in the presence of target. The assay exhibits sensitive detection of PSA linearly from 1.0 pg/mL to 100 ng/mL with a detection limit of 0.62 pg/mL. The work demonstrated a new ECL enhancement strategy of SACs via BPE system and expands the application of SACs in bioanalysis field.
Subject(s)
Biosensing Techniques , Electrochemical Techniques , Electrodes , Hydrogen Peroxide , Iron , Limit of Detection , Luminescent Measurements , Luminol , Prostate-Specific Antigen , Catalysis , Luminescent Measurements/methods , Electrochemical Techniques/methods , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Humans , Luminol/chemistry , Prostate-Specific Antigen/analysis , Prostate-Specific Antigen/blood , Iron/chemistry , Glucose Oxidase/chemistry , Immunoassay/methods , Gold/chemistry , Peroxidase/chemistry , Metal Nanoparticles/chemistry , Nitrogen/chemistry , Carbon/chemistry , NaphtholsABSTRACT
Transforming growth factor (TGF)-ß is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-ß can stimulate diverse cellular responses and is particularly critical to embryonic development, wound healing, tissue homeostasis, and immune homeostasis in health. The dysfunction of TGF-ß can play key roles in many diseases, and numerous targeted therapies have been developed to rectify its pathogenic activity. In the past decades, a large number of studies on TGF-ß signaling have been carried out, covering a broad spectrum of topics in health, disease, and therapeutics. Thus, a comprehensive overview of TGF-ß signaling is required for a general picture of the studies in this field. In this review, we retrace the research history of TGF-ß and introduce the molecular mechanisms regarding its biosynthesis, activation, and signal transduction. We also provide deep insights into the functions of TGF-ß signaling in physiological conditions as well as in pathological processes. TGF-ß-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted. Through the summary of previous knowledge and recent updates, this review aims to provide a systematic understanding of TGF-ß signaling and to attract more attention and interest to this research area.
Subject(s)
Signal Transduction , Transforming Growth Factor beta , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , CytokinesABSTRACT
Juglans sigillata Dode is one of the important tree species in southwest China, and it has significant economic and ecological value. However, there is still a lack of effective methods to identify the functional genes of J. sigillata. By verifying the model plant tobacco, the pTRV2::JsPDS vector was able to cause photobleaching. This study showed that photobleaching occurred 24 and 30 d after the silencing vector was infected with aseptic seedlings and fruits of J. sigillata, respectively. When the OD600 was 0.6, and the injection dose was 500 µL, the gene silencing efficiency of aseptic seedlings was the highest at 16.7 %, significantly better than other treatments. Moreover, when the OD600 was 0.8, and the injection dose was 500 µL, the gene silencing efficiency in the walnut fruit was the highest (20 %). In addition, the VIGS system was successfully used to silence JsFLS2 and JsFLS4 genes in J. sigillata. This study also showed that the flavonol content and gene expression in the treatment group were decreased compared to the control group. In addition, the proteins transcribed and translated from the JsFLS4 gene may have higher catalytic activity for dihydroquercetin. The above results indicate that the TRV-mediated VIGS system can be an ideal tool for studying J. sigillata gene function.
Subject(s)
Juglans , Plant Viruses , Juglans/genetics , Gene Silencing , Phenotype , Fruit , Nicotiana , Seedlings/genetics , Gene Expression Regulation, Plant , Plant Viruses/geneticsABSTRACT
Histones are the main components of chromatin, functioning as an instructive scaffold to maintain chromosome structure and regulate gene expression. The dysregulation of histone modification is associated with various pathological processes, especially cancer initiation and development, and histone methylation plays a critical role. However, the specific mechanisms and potential therapeutic targets of histone methylation in cancer are not elucidated. Lys-specific demethylase 1A (LSD1) was the first identified demethylase that specifically removes methyl groups from histone 3 at lysine 4 or lysine 9, acting as a repressor or activator of gene expression. Recent studies have shown that LSD1 promotes cancer progression in multiple epigenetic regulation or non-epigenetic manners. Notably, LSD1 dysfunction is correlated with repressive cancer immunity. Many LSD1 inhibitors have been developed and clinical trials are exploring their efficacy in monotherapy, or combined with other therapies. In this review, we summarize the oncogenic mechanisms of LSD1 and the current applications of LSD1 inhibitors. We highlight that LSD1 is a promising target for cancer treatment. This review will provide the latest theoretical references for further understanding the research progress of oncology and epigenetics, deepening the updated appreciation of epigenetics in cancer.
Subject(s)
Epigenesis, Genetic , Histone Demethylases , Neoplasms , Histone Demethylases/metabolism , Histone Demethylases/antagonists & inhibitors , Histone Demethylases/genetics , Humans , Neoplasms/genetics , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Neoplasms/enzymology , Gene Expression Regulation, Neoplastic , Histones/metabolism , Histones/genetics , Molecular Targeted Therapy , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Animals , Enzyme Inhibitors/therapeutic use , Enzyme Inhibitors/pharmacologyABSTRACT
BACKGROUND: Plastic bronchitis (PB) can occur in patients who have undergone congenital heart surgery (CHS). This study aimed to investigate the clinical features of PB in children after CHS. METHODS: We conducted a retrospective cohort study using the electronic medical record system. The study population consisted of children diagnosed with PB after bronchoscopy in the cardiac intensive care unit after CHS from May 2016 to October 2021. RESULTS: A total of 68 children after CHS were finally included in the study (32 in the airway abnormalities group and 36 in the right ventricular dysfunction group). All children were examined and treated with fiberoptic bronchoscopy. Pathogens were detected in the bronchoalveolar lavage fluid of 41 children, including 32 cases in the airway abnormalities group and 9 cases in the right ventricular dysfunction group. All patients were treated with antibiotics, corticosteroids (intravenous or oral), and budesonide inhalation suspension. Children with right ventricular dysfunction underwent pharmacological treatment such as reducing pulmonary arterial pressure. Clinical symptoms improved in 64 children, two of whom were treated with veno-arterial extracorporeal membrane oxygenation (ECMO) due to recurrent PB and disease progression. CONCLUSIONS: Children with airway abnormalities or right ventricular dysfunction after CHS should be alerted to the development of PB. Pharmacological treatment such as anti-infection, corticosteroids, or improvement of right ventricular function is the basis of PB treatment, while fiberoptic bronchoscopy is an essential tool for the diagnosis and treatment of PB. ECMO assistance is a vital salvage treatment for recurrent critically ill PB patients.
Subject(s)
Bronchitis , Heart Defects, Congenital , Ventricular Dysfunction, Right , Child , Humans , Retrospective Studies , Bronchitis/diagnosis , Bronchitis/drug therapy , Bronchitis/etiology , Bronchoscopy , Adrenal Cortex Hormones , Heart Defects, Congenital/surgeryABSTRACT
A practical synthetic method for the synthesis of vinyl sulfonyl fluorides through copper-promoted direct fluorosulfonylation has been developed. The reaction of the vinylboronic acids with DABSO and then NFSI is performed under mild reaction conditions. This transformation efficiently affords aryl or alkyl vinyl sulfonyl fluorides with good reaction yields, exclusive E-configuration, broad substrate scope, excellent compatibility, and operational simplicity.