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The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti-PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti-PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification-dependent manner, thereby activating CD8+ T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy.
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Linfócitos T CD8-Positivos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteína Adaptadora de Sinalização NOD1 , Macrófagos Associados a Tumor , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Animais , Humanos , Camundongos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Linhagem Celular Tumoral , Imunoterapia/métodos , Masculino , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: Based on current knowledge, hepatocellular carcinoma (HCC) is a condition with numerous etiologies and risk factors. However, the pathogenesis of HCC remains unclear. AIM: To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of HCC. METHODS: The levels of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcylation in HCC cells and tissues were detected using western blot analysis. The effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic assays. The potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay. O-GlcNAcylation levels were altered via drug treatment and lentiviral infection, and western blot analysis was used to detect proteins involved in various pathways. RESULTS: Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells. O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral infection. An increase in the glycosylation level was linked to enhanced proliferation, invasiveness, clonogenicity, and metastatic potential of cancer cells. O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC cells. The levels of proteins involved in nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways, which are associated with endoplasmic reticulum stress, were altered. CONCLUSION: Senegenin lowers O-GlcNAcylation levels, decreases OGT expression, and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.
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Bone loss caused by long-duration spaceflight seriously affects the skeletal health of astronauts. There are many shortcomings in currently available treatments for weightlessness-induced bone loss. The aim of this study was to evaluate the preventive effect of Angelica dahuricae Radix (AR) on simulated microgravity-induced bone loss. Here, we established a hind limb unloading (HLU) mouse model and treated HLU mice with AR (2 g/kg) for 4 weeks. Results indicated that AR significantly inhibited simulated microgravity-induced bone loss. In addition, the components in AR were analyzed using UPLC-MS/MS; results showed that a total of 224 compounds were detected in AR, which mainly contained 7 classes of components. Moreover, the network pharmacological predictions suggested that active ingredients of AR might act on PTGS2 to prevent bone loss. These results elucidate the efficacy of AR in preventing microgravity-induced bone loss and its potential for use in protecting the bone health of astronauts.
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BACKGROUND: This study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. METHODS: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children's Hospital of Fujian Province in China. RESULTS: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation. CONCLUSIONS: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients.
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Doença da Deficiência de Ornitina Carbomoiltransferase , Humanos , Masculino , Feminino , China , Estudos Retrospectivos , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Lactente , Ornitina Carbamoiltransferase/genética , Pré-Escolar , Testes Genéticos , Mutação , FenótipoRESUMO
BACKGROUND: Respiratory disease is a predominantly observed problem in neonates. Moreover, the application of flexible bronchoscopy in newborns is gradually increasing. This study aimed to investigate the value of bronchoscopy in neonates respiratory abnormalities and evaluate the safety of bronchoscopy application. METHODS: Clinical data and outcomes of 56 neonates who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were assessed. RESULTS: A total of 56 neonates had a minimum weight of 1200 g at the time of bronchoscopy, while the minimum gestational age at birth was 26 + 1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were respiratory distress in 24 (42.9%), stridor in 22 (39.3%), pulmonary atelectasis in 10 (17.6%), feeding difficulty in 10 (17.6%), and difficult weaning from mechanical ventilation in 6 (10.7%) cases. A total of 13 types of abnormalities were detected in the respiratory tract. The most common abnormalities were laryngomalacia in 29 (59.2%), tracheobroncomalacia in 8 (16.3%), and vocal cord paralysis in 6 (12.2%) cases. Bronchoalveolar lavage was performed in 39 cases. Eight cases were diagnosed by bronchoscopy and then treated with surgery in the Thoracic Surgery/Otolaryngology Department; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, of whom none died. CONCLUSIONS: Flexible bronchoscopy could play an important role in diagnosing and identifying respiratory disorders in neonates and be safely used with few serious complications.
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Broncoscopia , Tecnologia de Fibra Óptica , Humanos , Broncoscopia/métodos , Recém-Nascido , Estudos Retrospectivos , Masculino , Feminino , Doenças Respiratórias/diagnósticoRESUMO
The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.
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Medicina Tradicional Chinesa , Estações do Ano , Humanos , Medicina Tradicional Chinesa/normas , ChinaRESUMO
Aroma is a key sensory factor in the flavor evaluation of pak choi (Brassica rapa L. ssp. chinensis var. Makino). The pak choi varieties Xiangqingcai (XQC) and Xiuhuajin (XHJ) have unique aroma characteristics, but the chemical profiles of these aromas are unknown. Here, the aroma profiles of three varieties of pak choi including XQC, XHJ, and Suzhouqing (CK, non-aromatic) were determined using gas chromatography-mass spectrometry (GC-MS) and relative odor activity values (rOAV). A total of 15 categories of 716 volatile metabolites were detected in the three pak choi varieties, with terpenoid metabolites identified as the major components, although in each sample the identity of the major terpenoid metabolite varied. There were 53 aroma components in XQC and 54 aroma components in XHJ with rOAV >1, which contribute to rice aroma and fishy odor of these varieties, respectively.
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In this study, a series of novel thieno [3, 2-b]pyridinone derivatives were designed and synthesized using a scaffold hopping strategy. Six compounds showed potent anti-mycobacterial activity (minimum inhibitory concentration (MIC) ≤ 1 µg/mL) against Mycobacterium tuberculosis (Mtb) UAlRa. Compound 6c displayed good activity against Mtb UAlRv (MIC = 0.5-1 µg/mL). Compounds 6c and 6i also showed activity against Mtb UAlRa in macrophages and exhibited low cytotoxicity against LO-2 cells. The selected compounds displayed a narrow antibacterial spectrum, with no activity against representative Gram-positive, Gram-negative bacteria, as well as fungi. Furthermore, compound 6c demonstrated favorable oral pharmacokinetic properties with a T1/2 value of 47.99 h and exhibited good in vivo activity in an acute mouse model of tuberculosis (TB). The target of compound 6c was identified as a NADH-dependent enoyl-acyl carrier protein reductase (InhA) by genome sequencing of spontaneously compound 6c-resistant Mtb mutants, indicating that compound 6c may not require activation and can directly target InhA. In vitro antimicrobial assays against a recombinant M. smegmatis overexpressing the Mtb-InhA, along with InhA inhibition assays, confirmed that InhA is the target of thieno [3, 2-b]pyridinone derivatives. Overall, this study identified thieno [3, 2-b]pyridinone scaffold as a novel chemotype that is promising for the development of anti-TB agents.
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Building carbon emissions (CE) have become the focus of the current topic, but there is still no mature typical building life cycle theory method from the perspective of building materials, and the research on the relationship between building durability and building life cycle is still insufficient. To this end, this study established a detailed calculation method for building carbon emissions (CE) and divided the building life cycle (BLC) into three stages: manufacturing, use, and demolition according to the result analysis. In addition, a durability improvement and carbon reduction scheme of "partition, resistance, and repair" is proposed, and the carbon emission reduction index of effectiveness index is proposed. The proposed method is applied to the case of residential buildings in Northwest China. The main conclusions are as follows: the CE of residential buildings are more dependent on the use stage. If the centralized heating system is adopted, the CE in the operation stage account for 80-90%. If the air conditioning refrigeration and heating system is adopted, the CE in the operation stage account for about 50%. Using the method of improving the durability of buildings to extend the service life of buildings is very significant for building carbon reduction (RC); the effectiveness index proposed in this paper includes key indicators such as total CE, service life, and building area. Compared with the traditional index, the effectiveness index is more accurate and comprehensive. CR is the focus of green building, but the impact of economy needs to be considered in practical engineering. In the future research, durability, CE, and economy need to be considered comprehensively for careful study.
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Magnesium chelatase (MgCh) plays a pivotal role in photosynthesis, catalyzing the insertion of magnesium into protoporphyrin IX (Proto IX), a key intermediate in chlorophyll (Chl) biosynthesis. MgCh is a heteromeric complex composed of the MgCh D subunit (CHLD), the MgCh H subunit (CHLH), and the MgCh I subunit (CHLI). The bright yellow leaves (byl) mutant was obtained through ethyl methanesulfonate (EMS) mutagenesis of the 'FT' Chinese cabbage (Brassica rapa L. ssp. pekinensis) doubled haploid line, whose Chl content, net photosynthetic rate (Pn), and non-photochemical quenching coefficient (NPQ) were decreased, and whose chloroplast development was incomplete. byl recovered to a light green phenotype under weak light conditions. Genetic analysis revealed that the bright yellow leaves phenotype of byl was caused by a single recessive nuclear gene. Using Mutmap sequencing and Kompetitive allele-specific PCR (KASP) identification, BraA01g010040.3.5C, encoding the CHLI subunit of MgCh, was identified as the candidate gene and named Brchli1. A nonsynonymous G-to-A mutation in the Brchli1 exon resulted in the substitution of aspartic acid with asparagine. Brchli1-silenced Chinese cabbage displayed bright yellow leaves with decreased Brchli1 expression. Transiently overexpressed Brchli1 in the byl mutant restored the green leaf phenotype and significantly increased relative Brchli1 expression levels. Both BrCHLI1 and its mutated variant were localized in chloroplasts. Yeast two-hybrid and luciferase complementation imaging assays demonstrated that BrCHLI1 interacted with both BrCHLD and itself. BrCHLI1 mutations did not affect its interaction with BrCHLD. Together, Brchli1 mutations impaired the function of MgCh, providing insights into the molecular mechanism of leaf coloration.
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Microalgae-based glycolate production through the photorespiratory pathway is considered an environmentally friendly approach. However, the potential for glycolate production is limited by photoautotrophic cultivation with low cell density and existing strains. In this study, a targeted knockout approach was used to disrupt the key photorespiration enzyme, Chlamydomonas reinhardtii hydroxypyruvate reductase 1 (CrHPR1), leading to a significant increase in glycolate production of 280.1 mg/L/OD750. The highest potency yield reached 2.1 g/L under optimized mixotrophic conditions, demonstrating the possibility of synchronizing cell growth with glycolate biosynthesis in microalgae. Furthermore, the hypothesis that the cell wall-deficient mutant facilitates glycolate excretion was proposed and validated by comparing the glycolate accumulation trends of various Chlamydomonas reinhardtii strains. This study will facilitate the development of microalgae-based biotechnology and shed lights on the continuous advancement of green biomanufacturing for industrial application.
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Chlamydomonas reinhardtii , Técnicas de Inativação de Genes , Glicolatos , Hidroxipiruvato Redutase , Microalgas , Chlamydomonas reinhardtii/metabolismo , Chlamydomonas reinhardtii/genética , Glicolatos/metabolismo , Microalgas/metabolismo , Microalgas/genética , Hidroxipiruvato Redutase/metabolismoRESUMO
Prenylation of amino acids is a critical step for synthesizing building blocks of prenylated alkaloid family natural products, where the corresponding prenyltransferase that catalyzes prenylation on free l-histidine (l-His) has not yet been identified. Here, we first discovered and characterized a prenyltransferase FunA from the antifungal agent fungerin pathway that efficiently performs C4-dimethylallylation on l-His. Crystal structure-guided engineering of the prenyl-binding pocket of FunA, a single M181A mutation, successfully converted it into a C4-geranyltransferase. Furthermore, FunA and its variant FunA-M181A show broad substrate promiscuity toward substrates that vary in substituents of the imidazole ring. Our work furthers our knowledge of free amino acid prenyltransferase and expands the arsenal of alkylation biocatalysts for imidazole-containing small molecules.
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Dimetilaliltranstransferase , Histidina , Histidina/química , Histidina/metabolismo , Dimetilaliltranstransferase/metabolismo , Dimetilaliltranstransferase/química , Dimetilaliltranstransferase/genética , Engenharia de Proteínas , Modelos Moleculares , Especificidade por Substrato , Imidazóis/química , Imidazóis/metabolismoRESUMO
Astaxanthin biosynthesis in Haematococcus pluvialis is driven by energy. However, the effect of the flagella-mediated energy-consuming movement process on astaxanthin accumulation has not been well studied. In this study, the profiles of astaxanthin and NADPH contents in combination with the photosynthetic parameters with or without flagella enabled by pH shock were characterized. The results demonstrated that there was no significant alteration in cell morphology, with the exception of the loss of flagella observed in the pH shock treatment group. In contrast, the astaxanthin content in the flagella removal groups was 62.9%, 62.8% and 91.1% higher than that of the control at 4, 8 and 12 h, respectively. Simultaneously, the increased Y(II) and decreased Y(NO) suggest that cells lacking the flagellar movement process may allocate more energy towards astaxanthin biosynthesis. This finding was verified by NADPH analysis, which revealed higher levels in flagella removal cells. These results provide preliminary insights into the underlying mechanism of astaxanthin accumulation enabled by energy reassignment in movement-lacking cells.
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The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus. IMPORTANCE: This study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.
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The multicut problem, also known as correlation clustering, is a classic combinatorial optimization problem that aims to optimize graph partitioning given only node (dis)similarities on edges. It serves as an elegant generalization for several graph partitioning problems and has found successful applications in various areas such as data mining and computer vision. However, the multicut problem with an exponentially large number of cycle constraints proves to be NP-hard, and existing solvers either suffer from exponential complexity or often give unsatisfactory solutions due to inflexible heuristics driven by hand-designed mechanisms. In this article, we propose a deep graph reinforcement learning method to solve the multicut problem within a combinatorial decision framework involving sequential edge contractions. The customized subgraph neural network adapts to the dynamically edge-contracted graph environment by extracting bilevel connected features from both contracted and original graphs. Our method can learn to infer feasible multicut solutions end-to-end toward optimization of the multicut objective in a data-driven manner. More specifically, by exploring the decision space adaptively, it implicitly gains heuristic knowledge from topological patterns of instances and thereby generates more targeted heuristics overcoming the short-sightedness inherent in the hand-designed ones. During testing, the learned heuristics iteratively contract graphs to construct high-quality solutions within polynomial time. Extensive experiments on synthetic and real-world multicut instances show the superiority of our method over existing combinatorial solvers, while also maintaining a certain level of out-of-distribution generalization ability.
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This work presents a new completion method that specifically designed for low-overlapping partial point cloud registration. Based on the assumption that the candidate partial point clouds to be registered belong to the same target, the proposed mutual prior based completion (MPC) method uses these candidate partial point clouds as completion reference for each other to extend their overlapping regions. Without relying on shape prior knowledge, MPC can work for different types of point clouds, such as object, room scene, and street view. The main challenge of this mutual reference approach is that partial clouds without spatial alignment cannot provide a reliable completion reference. Based on the mutual information maximization, a progressive completion structure is developed to achieve pose, feature representation and completion alignment between input point clouds. Experiments on public datasets show encouraging results. Especially for the low-overlapping cases, compared with the state-of-the-art (SOTA) models, the size of overlapping regions can be increased by about 15.0%, and the rotation and translation error can be reduced by 30.8% and 57.7% respectively.
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Resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure and cancer recurrence in non-small cell lung cancer (NSCLC). Approximately 30% of patients with EGFR-activating mutations exhibit primary resistance to EGFR-TKIs. However, the potential mechanisms of primary resistance to EGFR-TKIs remain poorly understood. Recent studies have shown that increased expression of programmed death ligand-1 (PD-L1) is associated with EGFR-TKIs resistance. Therefore, the present study aimed to investigate the mechanism of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma (LUAD) cells. We found that PD-L1 was associated with poor prognosis in patients with EGFR-mutant LUAD, while the combination of EGFR-TKIs with chemotherapy could improve its therapeutic efficacy. In vitro and in vivo experiments revealed that PD-L1 promoted the proliferation and autophagy and inhibited the apoptosis of LUAD cells. Mechanistic studies demonstrated that upregulation of PD-L1 was critical in inducing autophagy through the mitogen-activated protein kinase (MAPK) signaling pathway, which was beneficial for tumor progression and the development of gefitinib resistance. Furthermore, we found that gefitinib combined with pemetrexed could synergistically enhance antitumor efficacy in PD-L1-overexpression LUAD cells. Overall, our study demonstrated that PD-L1 contributed to primary resistance to EGFR-TKIs in EGFR-mutant LUAD cells, which may be mediated by inducing autophagy via the MAPK signaling pathway. These findings not only help improve the prognosis of patients with EGFR-mutant LUAD but also provide a reference for the research of other cancer types.
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Adenocarcinoma de Pulmão , Autofagia , Antígeno B7-H1 , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Sistema de Sinalização das MAP Quinases , Mutação , Inibidores de Proteínas Quinases , Humanos , Autofagia/efeitos dos fármacos , Autofagia/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Animais , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Linhagem Celular Tumoral , Mutação/genética , Camundongos , Camundongos Nus , Feminino , Masculino , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
The accurate identification of energetic heterocyclic compounds (EHCs) is of great significance in munition assessment, environmental monitoring, and biosafety but remains largely underexplored. Herein, a covalent organic frameworks-based fluorescence sensor array (COFx sensor array) for efficient screening of EHCs is reported. The topologies of the COFs were rationally designed by modulating the pore sizes and linkage strategies to achieve the simplified sensor array. Eighteen EHC representatives, including single-, dual-, and three-ring EHCs with multivariate substructures, were successfully discriminated ranging from 10 µM to 1 mM. The sensor array showed robust selectivity against a wide range of interferences. The quantitative structure-activity relationship (QSAR) analysis has been conducted for the mechanistic study of the sensor array. Three multiple linear regression models have been established using molecular descriptors to evaluate and predict Stern-Volmer coefficient values, achieving explicit correlation between EHC structures and the signal outputs of the sensor array. Five molecular descriptors are retained to reveal the governing factors of the sensor array resolution. The QSAR analysis facilitates the design and development of the COFx sensor array, offering a new approach for customized multivariate analysis.