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1.
Front Chem ; 12: 1380551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572069

RESUMO

Nitrobenzene (NB) is one of the major organic pollutants that has seriously endangered human health and the environment even in trace amounts. Therefore, it is of great significance to detect trace NB efficiently and sensitively. Herein, a porphyrinic metal-organic framework (MOF) of Mn-PCN-222 (PCN, porous coordination network) was first synthesized by the coordination between Zr6 cluster and tetrakis (4-carboxyphenyl)-porphyrin-Mn (Ⅲ) (MnTCPPCl) ligand. To regulate its structure and the electrochemical properties, a phenyl group was inserted in each branched chain of TCPP to form the TCBPP organic ligand. Then, we used Zr6 clusters and manganese metalloporphyrin (MnTCBPPCl) to synthesize a new porphyrin-based MOF (Mn-CPM-99, CPM, crystalline porous material). Due to the extended chains of TCPP, the rod-shaped structure of Mn-PCN-222 was switched to concave quadrangular bipyramid of Mn-CPM-99. Mn-CPM-99 exhibited higher porosity, larger specific surface area, better electrochemical performances than those of Mn-PCN-222. By using modular assembly technique, Mn-CPM-99 film was sequentially assembled on the surface of indium-tin-oxide (ITO) to prepare an electrochemical sensor (Mn-CPM-99/ITO). The proposed sensor showed excellent electrochemical reduction of NB and displayed three linear response ranges in the wide concentration ranges. The obtained low limit of detection (LOD, 1.3 nM), high sensitivity and selectivity, and good reproducibility of the sensor for NB detection fully illustrate that Mn-CPM-99 is an excellent candidate for electrochemical sensor interface material. Moreover, the sensor was successfully applied to the detection of NB in lake water and vegetable samples showing satisfactory recovery of 98.9%-101.8%.

2.
Structure ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38582077

RESUMO

PI3Kα is a lipid kinase that phosphorylates PIP2 and generates PIP3. The hyperactive PI3Kα mutation, H1047R, accounts for about 14% of breast cancer, making it a highly attractive target for drug discovery. Here, we report the cryo-EM structures of PI3KαH1047R bound to two different allosteric inhibitors QR-7909 and QR-8557 at a global resolution of 2.7 Å and 3.0 Å, respectively. The structures reveal two distinct binding pockets on the opposite sides of the activation loop. Structural and MD simulation analyses show that the allosteric binding of QR-7909 and QR-8557 inhibit PI3KαH1047R hyper-activity by reducing the fluctuation and mobility of the activation loop. Our work provides a strong rational basis for a further optimization and development of highly selective drug candidates to treat PI3KαH1047R-driven cancers.

3.
Food Chem X ; 21: 101107, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38292684

RESUMO

Grapefruit (Citrus × paradisi Macf.) peel, a by-product of the citrus-processing industry, possesses an important economic value due to the richness of bioactive compounds. In this study, boron-linked covalent organic frameworks integrated with molecularly imprinted polymers (CMIPs) were developed via a facile one-pot bulk polymerization approach for the selective extraction of naringenin from grapefruit peel extract. The obtained CMIPs possessed a three-dimensional network structure with uniform pore size distribution, large surface areas (476 m2/g), and high crystallinity. Benefiting from the hybrid functional monomer APTES-MAA, the acylamino group can coordinate with the boronate ligands of the boroxine-based framework to form B-N bands, facilitating the integration of imprinted cavities with the aromatic skeleton. The composite materials exhibited a high adsorption capacity of 153.65 mg/g, and a short adsorption equilibrium time of 30 min for naringenin, together with favorable selectivity towards other flavonoid analogues. Additionally, the CMIPs captured the template molecules through π-π* interaction and hydrogen bonding, as verified by FT-IR and XPS. Furthermore, they had good performance when employed to enrich naringenin in grapefruit peels extract compared with the common adsorbent materials including AB-8, D101, cationic exchange resin, and active carbon. This research highlights the potential of CMIPs composite materials as a promising alternative adsorbent for naringenin extraction from grapefruit peel.

4.
J Gastroenterol Hepatol ; 39(1): 121-132, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037531

RESUMO

BACKGROUND: Gastric cancer (GC) is a common malignancy with high incidence and mortality, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the molecular mechanism of circTMEM87A in GC malignant progression is uncertain. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of circTMEM87A, miR-1276, and solute carrier family 7 membrane 11 (SLC7A11). Western blot was applied to detect protein expression levels of EMT-related proteins (vimentin and E-cadherin) and SLC7A11. Cell counting kit-8 assay (CCK8) and thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) were performed to assess cell proliferation. Apoptosis was investigated using flow cytometry. Transwell assay and wound healing assay were carried out to examine the migration of MKN-7 and AGS cells. The Cellular ROS Assay Kit, Iron Assay Kit, and GSH/GSSG Ratio Detection Assay Kit were utilized to monitor lipid ROS level, iron level, and GSH/GSSG ratio, respectively. The interaction between miR-1276 and circTMEM87A or SLC7A11 was investigated using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft mouse model was constructed to explore the function of circTMEM87A in tumor formation in vivo. RESULTS: CircTMEM87A and SLC7A11 were upregulated, while miR-1276 was downregulated in GC tissues and cells. Knockdown of circTMEM87A suppressed the proliferation and migration and promoted apoptosis and ferroptosis of GC cells. CircTMEM87A served as a sponge for miR-1276, and miR-1276 inhibitor relieved the circTMEM87A knockdown-induced effects on GC cell phenotypes. Similarly, SLC7A11, a downstream gene of miR-1276, rescued miR-1276 overexpression-induced effects on GC cell function. Furthermore, circTMEM87A knockdown inhibited GC cell tumor phenotypes in vivo. CONCLUSION: CircTMEM87A promoted the proliferation and migration and inhibited apoptosis and ferroptosis of GC cells by increasing SLC7A11 expression through binding to miR-1276.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/genética , Dissulfeto de Glutationa , Espécies Reativas de Oxigênio , Carcinogênese/genética , Transformação Celular Neoplásica , Proliferação de Células/genética , Modelos Animais de Doenças , Ferro , MicroRNAs/genética , Linhagem Celular Tumoral , Sistema y+ de Transporte de Aminoácidos/genética
5.
Immun Ageing ; 20(1): 66, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990246

RESUMO

BACKGROUND: CircZBTB46 has been identified as being associated with the risk of coronary artery disease (CAD) and has the potential to be a diagnostic biomarker for CAD. However, the specific function and detailed mechanism of circZBTB46 in CAD are still unknown. METHODS: The expression levels and properties of circRNAs were examined using qRT‒PCR, RNA FISH, and subcellular localization analysis. ApoE-/- mice fed a high-fat diet were used to establish an atherosclerosis model. HE, Masson, and Oil Red O staining were used to analyze the morphological features of the plaque. CCK-8, Transwell, and wound healing assays, and flow cytometric analysis were used to evaluate cell proliferation, migration, and apoptosis. RNA pull-down, silver staining, mass spectrometry analysis, and RNA-binding protein immunoprecipitation (RIP) were performed to identify the interacting proteins of circZBTB46. RESULTS: CircZBTB46 is highly conserved and is significantly upregulated in atherosclerotic lesions. Functional studies revealed that knockdown of circZBTB46 significantly decreased the atherosclerotic plaque area, attenuating the progression of atherosclerosis. In addition, silencing circZBTB46 inhibited cell proliferation and migration and induced apoptosis. Mechanistically, circZBTB46 physically interacted with hnRNPA2B1 and suppressed its degradation, thereby regulating cell functions and the formation of aortic atherosclerotic plaques. Additionally, circZBTB46 was identified as a functional mediator of PTEN-dependent regulation of the AKT/mTOR signaling pathway and thus affected cell proliferation and migration and induced apoptosis. CONCLUSION: Our study provides the first direct evidence that circZBTB46 functions as an important regulatory molecule for CAD progression by interacting with hnRNPA2B1 and regulating the PTEN/AKT/mTOR pathway.

6.
PeerJ ; 11: e16477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025763

RESUMO

Aim: To create a prognosis model based on mRNA-based stem index (mRNAsi) for evaluating the prognostic outcomes of colon adenocarcinoma (COAD). Background: Generation of heterogeneous COAD cells could be promoted by the self-renewal and differentiation potential of cancer stem cells (CSCs). Biomarkers contributing to the development of COAD stem cells remained to be discovered. Objective: To develop and validate an mRNAsi-based risk model for estimating the prognostic outcomes of patients suffering from COAD. Methods: Samples were collected from Rectal Adenocarcinoma (TCGA-READ) PanCancer Atlas datasets, The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD), and the GSE87211 dataset. MRNAsi was calculated by one-class logistic regression (OCLR) algorithm. Under the criterion of correlation greater than 0.4, genes related to mRNAsi were screened and clustered. Meanwhile, differentially expressed genes (DEGs) between molecular subtypes were identified to establish a risk model. According to the median risk score value for immunotherapy and results from immune cell infiltration and clinicopathological analyses, clusters and patients were divided into high-RiskScore and low-RiskScore groups. Cell apoptosis and viability were detected by flow cytometer and Cell Counting Kit-8 (CCK-8) assay, respectively. Results: A negative correlation between mRNAsi and clinical stages was observed. Three clusters of patients (C1, C2, and C3) were defined based on a total of 165 survival-related mRNAsi genes. Specifically, C1 patients had greater immune cell infiltration and a poorer prognosis. A 5-mRNAsi-gene signature (HEYL, FSTL3, FABP4, ADAM8, and EBF4) served as a prediction index for COAD prognosis. High-RiskScore patients had a poorer prognosis and higher level of immune cell infiltration. In addition, the five genes in the signature all showed a high expression in COAD cells. Knocking down HEYL promoted COAD cell apoptosis and inhibited viability. Conclusion: Our mRNAsi risk model could better predict the prognosis of COAD patients.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/genética , Adenocarcinoma/genética , Prognóstico , Algoritmos , Proteínas de Membrana , Proteínas ADAM
7.
Acta Psychol (Amst) ; 240: 104042, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37783184

RESUMO

Given that there is limited evidence concerning the psychometric properties of DASS-21 when applied to primary school students, the present study undertook a comprehensive exploration of the psychometric evidence supporting the use of the DASS-21 within this demographic. The research comprised three studies. In Study 1, the basic psychometric properties of internal consistency and construct validity were examined. A total of 3138 primary school students from three provinces in mainland China participated. The internal reliability of the overall scale was 0.93, and for all the subscales, it was higher than 0.80. Construct validity was partially supported. Both exploratory and confirmatory factor analyses upheld the factorial validity of the original three-factor structure. While convergent validity was established, the results showed unsatisfactory discriminant validity. The bifactor model showed that DASS-21 raw scores predominantly indicated the general factor, evidenced by the high explained common variance and omega-hierarchical values. However, the contributions from the three specific factors were minimal, with their omega hierarchical values all below 0.15. In Study 2, a longitudinal design was adopted, tracking 1366 primary school students from Southwest China over a three-month interval. The results further confirmed that the DASS-21 exhibited scalar time-invariance. The latent mean analysis showed that there were no statistically significant differences in the latent means of depression, anxiety, and stress between Time 1 and Time 2. In Study 3, which included 364 college students and 483 enterprise workers, the results demonstrated that the DASS-21 had measurement invariance across different populations. The latent mean analysis further confirmed that, in terms of the latent mean of all three subscales, both college students and enterprise workers had significantly higher scores than primary school students. Overall, the findings indicated that the DASS-21 is a suitable tool for screening schoolchildren for general psychological distress, but it is not suitable for discerning distinct negative mood state disorders.


Assuntos
Ansiedade , Depressão , Escalas de Graduação Psiquiátrica , Estresse Psicológico , Criança , Humanos , Ansiedade/diagnóstico , Estudos Transversais , Depressão/diagnóstico , População do Leste Asiático , Psicometria , Reprodutibilidade dos Testes , Estresse Psicológico/diagnóstico , Inquéritos e Questionários , Estudos Longitudinais
8.
Ear Nose Throat J ; : 1455613231182678, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37381665

RESUMO

Alveolar rhabdomyosarcoma is a rare pediatric malignant tumor with a poor prognosis, and it is exceedingly rare for this tumor to manifest on the skin of the nasal dorsum. Therefore, timely and accurate treatment can improve the survival rate of patients. We reported a case of a 4 year-old child with acinar rhabdomyosarcoma of the nasal dorsum, and the patient was cured by surgery and postoperative chemotherapy without recurrence. This case report contributes to the understanding of this rare tumor.

9.
BMC Med Genomics ; 16(1): 131, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316908

RESUMO

BACKGROUND: Recent studies suggest that classical coronary risk factors play a significant role in the pathogenesis of coronary artery disease. Our study aims to explore the interaction of circRNA with classical coronary risk factors in coronary atherosclerotic disease. METHOD: Combined analysis of RNA sequencing results from coronary segments and peripheral blood mononuclear cells of patients with coronary atherosclerotic disease was employed to identify critical circRNAs. Competing endogenous RNA networks were constructed by miRanda-3.3a and TargetScan7.0. The relative expression quantity of circRNA in peripheral blood mononuclear cells was determined by qRT-PCR in a large cohort including 256 patients and 49 controls. Spearman's correlation test, receiver operating characteristic curve analysis, multivariable logistic regression analysis, one-way analysis of variance, and crossover analysis were performed. RESULTS: A total of 34 circRNAs were entered into our study, hsa_circRPRD1A, hsa_circHERPUD2, hsa_circLMBR1, and hsa_circDHTKD1 were selected for further investigation. A circRNA-miRNA-mRNA network is composed of 20 microRNAs and 66 mRNAs. The expression of hsa_circRPRD1A (P = 0.004) and hsa_circHERPUD2 (P = 0.003) were significantly down-regulated in patients with coronary artery disease compared to controls. The area under the curve of hsa_circRPRD1A and hsa_circHERPUD2 is 0.689 and 0.662, respectively. Univariate and multivariable logistic regression analyses identified hsa_circRPRD1A (OR = 0.613, 95%CI:0.380-0.987, P = 0.044) as a protective factor for coronary artery disease. Based on the additive model, crossover analysis demonstrated that there was an antagonistic interaction between the expression of hsa_circHERPUD2 and alcohol consumption in subjects with coronary artery disease. CONCLUSION: Our findings imply that hsa_circRPRD1A and hsa_circHERPUD2 could be used as biomarkers for the diagnosis of coronary artery disease and provide epidemiological support for the interactions between circRNAs and classical coronary risk factors.


Assuntos
Doença da Artéria Coronariana , MicroRNAs , Humanos , Doença da Artéria Coronariana/genética , RNA Circular , Leucócitos Mononucleares , RNA Mensageiro , Fatores de Risco
10.
Eur J Pharmacol ; 951: 175761, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37169142

RESUMO

The modification of N6-methyladenosine (m6A) modification is implicated in human diseases. However, considerable uncertainty is associated with the regulatory mechanisms of m6A circRNAs in coronary artery disease (CAD), which require further clarification. In this study, m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) was conducted to investigate m6A-modified circRNAs in human coronary artery smooth muscle cells (HCASMCs) and to identify potential biomarkers for CAD. A total of 830 and 331 up- and down-regulated m6A peaks, (corresponding to 463 and 243 up- and down-regulated circRNAs, respectively), were identified in HCASMCs in a pathological condition. Functional analysis suggested that these circRNAs appeared to participate in intracellular protein, histone deacetylase complex, ATP-dependent activity, autophagy, and AMPK signaling pathway. Four candidate circRNAs were selected for further evaluation in HCASMCs and human samples. The results suggested that hsa_circHECTD1 and hsa_circZBTB46 were significantly increased in patients with CAD (p-value = 0.039 and p-value = 0.014) and may act as potential diagnostic biomarkers of CAD. Furthermore, statistical results showed that hsa_circHECTD1 and hsa_circSEC62 were positively correlated with triglyceride (TG) (r = 0.213, p-value = 0.014) and Gensini Score (used to quantify the severity of CAD) (r = 0.349, p-value <0.001), respectively. Logistic regression revealed that hsa_circZBTB46 was strongly correlated with the incidence of CAD, and the synergistic effects of circRNAs and hypertension enhanced the risk of CAD. These results show that hsa_circHECTD1 and hsa_circZBTB46 may be new targets for further studies, and this study enhances our understanding of the effects of m6A-circRNAs on the pathogenesis of CAD.


Assuntos
Doença da Artéria Coronariana , RNA Circular , Humanos , RNA Circular/genética , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/diagnóstico , Transdução de Sinais/genética , Fatores de Risco , Biomarcadores
11.
Comput Med Imaging Graph ; 107: 102245, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37245416

RESUMO

Automatic segmentation of vertebral bodies (VBs) and intervertebral discs (IVDs) in 3D magnetic resonance (MR) images is vital in diagnosing and treating spinal diseases. However, segmenting the VBs and IVDs simultaneously is not trivial. Moreover, problems exist, including blurry segmentation caused by anisotropy resolution, high computational cost, inter-class similarity and intra-class variability, and data imbalances. We proposed a two-stage algorithm, named semi-supervised hybrid spine network (SSHSNet), to address these problems by achieving accurate simultaneous VB and IVD segmentation. In the first stage, we constructed a 2D semi-supervised DeepLabv3+ by using cross pseudo supervision to obtain intra-slice features and coarse segmentation. In the second stage, a 3D full-resolution patch-based DeepLabv3+ was built. This model can be used to extract inter-slice information and combine the coarse segmentation and intra-slice features provided from the first stage. Moreover, a cross tri-attention module was applied to compensate for the loss of inter-slice and intra-slice information separately generated from 2D and 3D networks, thereby improving feature representation ability and achieving satisfactory segmentation results. The proposed SSHSNet was validated on a publicly available spine MR image dataset, and remarkable segmentation performance was achieved. Moreover, results show that the proposed method has great potential in dealing with the data imbalance problem. Based on previous reports, few studies have incorporated a semi-supervised learning strategy with a cross attention mechanism for spine segmentation. Therefore, the proposed method may provide a useful tool for spine segmentation and aid clinically in spinal disease diagnoses and treatments. Codes are publicly available at: https://github.com/Meiyan88/SSHSNet.


Assuntos
Imageamento por Ressonância Magnética , Coluna Vertebral , Coluna Vertebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Algoritmos , Aprendizado de Máquina Supervisionado , Processamento de Imagem Assistida por Computador/métodos
12.
Med Image Anal ; 88: 102842, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37247468

RESUMO

Imaging genetics is a crucial tool that is applied to explore potentially disease-related biomarkers, particularly for neurodegenerative diseases (NDs). With the development of imaging technology, the association analysis between multimodal imaging data and genetic data is gradually being concerned by a wide range of imaging genetics studies. However, multimodal data are fused first and then correlated with genetic data in traditional methods, which leads to an incomplete exploration of their common and complementary information. In addition, the inaccurate formulation in the complex relationships between imaging and genetic data and information loss caused by missing multimodal data are still open problems in imaging genetics studies. Therefore, in this study, a deep multimodality-disentangled association analysis network (DMAAN) is proposed to solve the aforementioned issues and detect the disease-related biomarkers of NDs simultaneously. First, the imaging data are nonlinearly projected into a latent space and imaging representations can be achieved. The imaging representations are further disentangled into common and specific parts by using a multimodal-disentangled module. Second, the genetic data are encoded to achieve genetic representations, and then, the achieved genetic representations are nonlinearly mapped to the common and specific imaging representations to build nonlinear associations between imaging and genetic data through an association analysis module. Moreover, modality mask vectors are synchronously synthesized to integrate the genetic and imaging data, which helps the following disease diagnosis. Finally, the proposed method achieves reasonable diagnosis performance via a disease diagnosis module and utilizes the label information to detect the disease-related modality-shared and modality-specific biomarkers. Furthermore, the genetic representation can be used to impute the missing multimodal data with our learning strategy. Two publicly available datasets with different NDs are used to demonstrate the effectiveness of the proposed DMAAN. The experimental results show that the proposed DMAAN can identify the disease-related biomarkers, which suggests the proposed DMAAN may provide new insights into the pathological mechanism and early diagnosis of NDs. The codes are publicly available at https://github.com/Meiyan88/DMAAN.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/genética , Doença de Alzheimer/genética , Neuroimagem/métodos , Imagem Multimodal/métodos , Biomarcadores
13.
Laryngoscope Investig Otolaryngol ; 8(2): 508-517, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37090880

RESUMO

Objective: To explore whether narrow-band imaging (NBI) endoscopy is accurate in the diagnosis of malignant transformation of vocal cord leukoplakia. Methods: The PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect data on studies reporting the use of NBI endoscopy as a diagnostic test for diagnosing vocal cord leukoplakia from January 2015 to December 2021. Study design, analysis method, and extraction results were performed according to the PRISMA guidelines. The sensitivity, specificity, pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) were used to summarize the performance metrics of the meta-analysis. Risk of bias data and the quality of the included studies was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). Results: Nine studies were finally included in the analysis. The results of the meta-analysis showed that the pooled sensitivity and specificity of NBI endoscopy for diagnosing leukoplakia lesions were 0.76 (95% CI: 0.72-0.8) and 0.93 (95% CI: 0.91-0.95), respectively. The PLR and NLR were 10.09 (95% CI: 6.53-15.59) and 0.22 (95% CI: 0.13-0.38), respectively. The comprehensive diagnostic odds ratio (DOR) was 54.96 (95% CI: 24.32-124.17), and the area under the curve was 0.9584. The eight articles had a low risk of bias risk and one article was unclear. Conclusion: NBI likely has good accuracy for diagnosing malignant transformation of vocal cord leukoplakia. However, multicenter studies and large samples are still needed.

14.
Ear Nose Throat J ; : 1455613231162222, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36927171

RESUMO

Atypical Ramsay-Hunt syndrome is caused by varicella zoster viruses (VZV), without herpes, herpes is not around the ear, or posterior cranial nerve palsy is the first clinical manifestation. In this case, a 60-year-old male patient with VZV invades the branches of the vagus nerve alone. The initial symptoms were in the pharynx and larynx, which presented as mucosal ulcers and voice disorders. The ear symptoms were only otalgia and auricular herpes, without deafness, tinnitus, or peripheral facial palsy. Herpes and ulcers healed with medication, but voice disorders caused by vocal cord paralysis did not return. Voice correction treatment has been implemented to help restore the movement and closure of the vocal cords, with ultimately good results. After voice correction treatment, the patient recovered without residual nerve palsy complications. Voice correction treatment has been shown to be potentially effective and promising in shortening the recovery period and improving the recovery rate for vocal cord paralysis caused by viral infection.

15.
ACS Med Chem Lett ; 14(3): 297-304, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36923916

RESUMO

Selective CDK2 inhibitors have the potential to provide effective therapeutics for CDK2-dependent cancers and for combating drug resistance due to high cyclin E1 (CCNE1) expression intrinsically or CCNE1 amplification induced by treatment of CDK4/6 inhibitors. Generative models that take advantage of deep learning are being increasingly integrated into early drug discovery for hit identification and lead optimization. Here we report the discovery of a highly potent and selective macrocyclic CDK2 inhibitor QR-6401 (23) accelerated by the application of generative models and structure-based drug design (SBDD). QR-6401 (23) demonstrated robust antitumor efficacy in an OVCAR3 ovarian cancer xenograft model via oral administration.

16.
Pest Manag Sci ; 79(7): 2539-2555, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36864521

RESUMO

BACKGROUND: Natural products play a significant role in the development of novel bactericide candidates. Caesalpinia pulcherrima, a traditional medicine, had anti-inflammatory, antimicrobial, and antifeedant activities, therefore the previous bioassay results of C. pulcherrima implied that its main active ingredients may have potential to be used as botanical bactericides. RESULTS: Bio-guided isolation of C. pulcherrima was conducted to obtain 11 novel cassane diterpenoids (capulchemins A-K) and 10 known sesquiterpenes. Their structures were established by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. Capulchemins A-F possess a rare aromatic C ring, while capulchemin K with a 15,16-degradative carbon skeleton represents a rare group of cassane diterpenes. Capulchemin A exhibited remarkable antibacterial activity against four phytopathogenic bacteria, particularly against Pseudomonas syringae pv. actinidae and Bacillus cereus, with minimal inhibitory concentration values of 3.13 µM. Meanwhile, capulchemin A showed significant control effect on kiwifruit canker in vivo. Further investigation of its mechanism of antibacterial activity revealed that compound 1 was closely related to destroy cell membrane to cause cell death. Additionally, some of those cassane diterpenoids showed potential antifeedant against Mythimna separate walker and Plutella xylostella. Consequently, capulchemin A could have the potential to be used as a template for the development for new eco-friendly NP-based bactericides. CONCLUSION: These data contribute to a better understanding of the antibacterial activity of cassane diterpenes. Cassane diterpenes have been discovered to be leading to broad application prospects in the development as novel botanical bactericides. © 2023 Society of Chemical Industry.


Assuntos
Antibacterianos , Caesalpinia , Diterpenos , Extratos Vegetais , Animais , Antibacterianos/farmacologia , Caesalpinia/química , Diterpenos/farmacologia , Diterpenos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mariposas , Sementes/química , Extratos Vegetais/farmacologia
17.
Aquat Toxicol ; 257: 106466, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36871483

RESUMO

This research aimed to evaluate the protective mechanism of alpha-lipoic acid (α-LA) on the food-borne aflatoxin B1 (AFB1) exposure-induced liver toxicity and physiological dysfunction in the northern snakehead (Channa argus). 480 fish (9.24±0.01 g) were randomly assigned to four treatment groups and fed with four experimental diets for 56 d including the control group (CON), AFB1 group (200 ppb AFB1), 600 α-LA group (600 ppm α-LA+200 ppb AFB1), and 900 α-LA group (900 ppm α-LA+200 ppb AFB1). The results revealed that 600 and 900 ppm α-LA attenuated AFB1-induced growth inhibition and immunosuppression in northern snakehead. 600 ppm α-LA significantly decreased the serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase levels, and AFB1 bioaccumulation, and attenuated the changes of hepatic histopathological and ultrastructure induced by AFB1. Moreover, 600 and 900 ppm α-LA significantly up-regulated phase I metabolism genes (cytochrome P450-1a, 1b, and 3a) mRNA expression, inhibited the levels of malondialdehyde, 8­hydroxy-2 deoxyguanosine and reactive oxygen species in the liver. Notably, 600 ppm α-LA significantly up-regulated the expression levels of nuclear factor E2 related factor 2 and its related downstream antioxidant molecules (heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1, etc.), increased the phase II detoxification enzyme-related molecules (glutathione-S-transferase and glutathione), antioxidant parameters (catalase and superoxide dismutase, etc.), and the expressions of Nrf2 and Ho-1 protein in the presence of AFB1 exposure. Furthermore, 600 and 900 ppm α-LA significantly reduced the characteristic indices of AFB1-induced endoplasmic reticulum stress (glucose-regulated protein 78 and inositol requiring enzyme 1, etc.), apoptosis (caspase-3 and cytochrome c, etc.) and inflammation (nuclear factor kappa B and tumor necrosis factor α, etc.), while increased the B-cell lymphoma-2 and inhibitor of κBα in the liver after being exposed to AFB1. To summarize, the above results indicate that dietary α-LA could modulate the Nrf2 signaling pathway to ameliorate AFB1-induced growth inhibition, liver toxicity, and physiological dysfunction in northern snakehead. Although the concentration of α-LA increased to 900 ppm from 600 ppm, the protective effects of the 900 ppm α-LA do not show an advantage over the 600 ppm α-LA, and even show inferiority in some respects. So that the recommended concentration of α-LA is 600 ppm. The present study provides the theoretical foundation for developing α-LA as the prevention and treatment of AFB1-induced liver toxicity in aquatic animals.


Assuntos
Ácido Tióctico , Poluentes Químicos da Água , Animais , Aflatoxina B1/toxicidade , Aflatoxina B1/metabolismo , Antioxidantes/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Fígado , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ácido Tióctico/farmacologia , Ácido Tióctico/metabolismo , Poluentes Químicos da Água/toxicidade
18.
Nanoscale ; 15(6): 2642-2649, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36651807

RESUMO

Lanthanide-doped upconversion nanoparticle (UCNP)-based nanocomposites can address the intrinsic limitations associated with UCNPs and bestow new functions on UCNPs, which can facilitate the development and application of UCNPs. However, the fabrication of UCNP-based composites typically suffers from complex operations, long-drawn-out procedures, and even loss or damage of UCNPs. Herein, we report a tandem fabrication strategy for the preparation of UCNP-based nanocomposites, in which protons, confined in the non-aqueous polar solvent, can produce ligand-free UCNPs for the direct fabrication of a composite without further treatment. Our studies show that the confined protons can be generated by diverse materials and can yield different types of ligand-free nanomaterials for desired composites. This versatile strategy enables a simple but scalable fabrication of UCNP-based nanocomposites, and can be extended to other nanomaterial-based composites. These findings should provide a platform for constructing multifunctional UCNP-based materials, and benefit potential applications of UCNPs in varied fields.

19.
Ear Nose Throat J ; 102(8): NP379-NP382, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33975449

RESUMO

Central retinal artery occlusion (CRAO) is an ophthalmic emergency and has poor visual prognosis. It is commonly found in elderly people and very rare in child. We reported an 8-year-old girl who suffered from acute sinusitis, periorbital swelling, and the visual acuity of her right eye was only light perception. She was diagnosed with CRAO, SPOA (subperiosteal orbital abscess), and acute sinusitis. Emergency treatments including surgery, antibiotics, glucocorticoids, intraocular-pressure-lowering drugs, and vasodilators were taken immediately in order to save the eyesight. The visual acuity of the right eye returned to 20/400. Conclusions: Severe intraorbital complications of acute sinusitis can lead to CRAO. Timely drainage, strong antibiotics, and glucocorticoids are the most effective methods for the treatments.


Assuntos
Celulite Orbitária , Doenças Orbitárias , Oclusão da Artéria Retiniana , Sinusite , Humanos , Criança , Feminino , Idoso , Abscesso/etiologia , Abscesso/cirurgia , Glucocorticoides , Celulite Orbitária/etiologia , Sinusite/tratamento farmacológico , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/tratamento farmacológico , Doença Aguda , Antibacterianos/uso terapêutico , Doenças Orbitárias/etiologia , Doenças Orbitárias/cirurgia
20.
IEEE Trans Image Process ; 31: 6951-6963, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36322494

RESUMO

Visible-infrared person re-identification (VI-ReID) task aims to retrieve the same person between visible and infrared images. VI-ReID is challenging as the images captured by different spectra present large cross-modality discrepancy. Many methods adopt a two-stream network and design additional constraint conditions to extract shared features for different modalities. However, the interaction between the feature extraction processes of different modalities is rarely considered. In this paper, a partially interactive collaboration method is proposed to exploit the complementary information of different modalities to reduce the modality gap for VI-ReID. Specifically, the proposed method is achieved in a partially interactive-shared architecture: collaborative shallow layers and shared deep layers. The collaborative shallow layers consider the interaction between modality-specific features of different modalities, encouraging the feature extraction processes of different modalities constrain each other to enhance feature representations. The shared deep layers further embed the modality-specific features to a common space to endow them the same identity discriminability. To ensure the interactive collaborative learning implement effectively, the conventional loss and collaborative loss are utilized jointly to train the whole network. Extensive experiments on two publicly available VI-ReID datasets verify the superiority of the proposed PIC method. Specifically, the proposed method achieves a rank-1 accuracy of 83.6% and 57.5% on RegDB and SYSU-MM01 datasets, respectively.

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