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1.
J Magn Reson Imaging ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606736

RESUMO

BACKGROUND: MRI features may be associated with adverse maternal outcome in patients with placenta accreta spectrum (PAS) disorders even with abdominal aortic balloon occlusion (AABO). PURPOSE: This study aimed to identify risk factors of MRI for association with adverse maternal outcome in patients with PAS disorders after AABO. STUDY TYPE: Retrospective. POPULATION: Clinical and MRI features of 80 patients were retrospectively reviewed from October 2016 to August 2021. A total of 40 patients had adverse maternal outcomes including intrapartum/peripartum bleeding >1000 mL and/or emergency hysterectomy after AABO. SEQUENCE: Half-Fourier acquisition single-shot turbo spin echo and gradient echo imaging True fast imaging with steady-state precession (True-FISP) at 1.5T MR scanner. ASSESSMENT: MRI features were evaluated by three radiologists and were tested for any association with adverse maternal outcome. STATISTICAL TESTS: Interobserver agreement was calculated with kappa (k) statistics. Association between MRI features and adverse maternal outcomes were evaluated by univariate and multivariate analyses. A nomogram was constructed based on the logistic regression. RESULTS: The interobserver agreement ranged from fair to substantial (k = 0.379-0.783). Multivariate analyses revealed that short cervical length (OR: 4.344), abnormal intraplacental vascularity (OR: 6.005), placental bulge (OR: 9.085), and myometrial interruption (OR: 9.550) were independent risk factors for adverse maternal outcomes. The combination of four risk factors together demonstrated the highest AUC of 0.851 (95% CI 0.769-0.933) with a sensitivity and specificity of 77.5% and 72.5%, respectively and then a nomogram composed of the above four risk factors was constructed to represent the probability of adverse maternal outcome. DATA CONCLUSION: The nomogram demonstrated the association between MRI features and patient's poor outcome after undergoing AABO and C-section delivery for PAS. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

2.
J Hematol Oncol ; 16(1): 1, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600307

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética
3.
Bioorg Med Chem Lett ; : 129148, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36690041

RESUMO

Novel indole-piperazine derivatives with a hydroxamic acid moiety were designed and synthesized as selective histone deacetylase 6 (HDAC6) inhibitors. In enzymatic assays, all compounds exhibited nanomolar IC50 values. N-hydroxy-4-((4-(7-methyl-1H-indole-3-carbonyl)piperazin-1-yl)methyl)benzamide, 9c, was the most potent HDAC6 inhibitor (IC50, 13.6 nM). In vitro, 9c induced neurite outgrowth of PC12 cells without producing toxic effects, better than Tubastatin A (Tub A). Additionally, 9c demonstrated blatant neuroprotective activity in PC12 cells against H2O2-induced oxidative damage. In western blot assay, 9c could increase the acetylation of α-tubulin in a dose-dependent manner.

4.
Phytomedicine ; 111: 154668, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36657316

RESUMO

BACKGROUND: Combination therapy with other antineoplastic agent is a favorable approach for targeting the molecules involved in sorafenib resistance. PURPOSE: In the present study, we determined whether tiliroside, a natural flavonoid glycoside isolated from oriental paperbush flower, could improve the sensitivity of hepatocellular carcinoma (HCC) cells to sorafenib. Furthermore, we investigated the mechanisms and identified the potential drug targets of tiliroside. METHODS: Synergy was performed using CalcuSyn. Transcriptomic studies were adopted to investigate whether tiliroside could induce ferroptosis and inhibit the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in HCC cells. Ferroptosis was analyzed using western blotting, flow cytometry, and transmission electron microscopy. Immunofluorescence, co-immunoprecipitation, and Nrf2 knockdown or overexpression were performed to confirm the involvement of Nrf2 in tiliroside-induced ferroptosis. Additionally, molecular docking and biolayer interferometry-based measurements were used to confirm the direct target of tiliroside. Finally, subcutaneous xenograft and orthotopic xenograft tumors in nude mice were used to assess the effects of tiliroside in vivo. RESULTS: Tiliroside significantly enhanced the anti-HCC activity of sorafenib without any discernible side effects. Moreover, the combination of tiliroside and sorafenib induced synergistic effects against HCC in vitro. The inhibitory effects of tiliroside on HCC were antagonized by N-acetylcysteine and the ferroptosis inhibitor liproxstatin-1. Studies on the mechanism of action revealed that tiliroside could directly bind to TANK-binding kinase 1 (TBK1) and inhibit its enzymatic activity. Inhibition of TBK1 by tiliroside decreased the phosphorylation of serine 349 on sequestosome-1 (p62) and the affinity of p62 for kelch like ECH-associated protein 1 (Keap1) and promoted Keap1-mediated Nrf2 ubiquitination and degradation. The downstream target proteins of Nrf2, including glutathione peroxidase 4, ferritin heavy chain 1, and glucose-6-phosphate dehydrogenase, demonstrated similar results to that of Nrf2 protein, inducing ferroptosis in tiliroside-treated HCC cells. We extended these findings in vivo and found that tiliroside inhibited the growth of HepG2 tumors in both subcutaneous xenograft and orthotopic xenograft tumor models of HCC. CONCLUSION: Our findings imply that tiliroside is a potent TBK1 inhibitor and a candidate natural anti-cancer product that could function as a sensitizer of sorafenib in HCC treatment by targeting TBK1 to induce ferroptosis.

5.
Neural Netw ; 160: 164-174, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36657330

RESUMO

Existing face super-resolution methods depend on deep convolutional networks (DCN) to recover high-quality reconstructed images. They either acquire information in a single space by designing complex models for direct reconstruction, or employ additional networks to extract multiple prior information to enhance the representation of features. However, existing methods are still challenging to perform well due to the inability to learn complete and uniform representations. To this end, we propose a self-attention learning network (SLNet) for three-stage face super-resolution, which fully explores the interdependence of low- and high-level spaces to achieve compensation of the information used for reconstruction. Firstly, SLNet uses a hierarchical feature learning framework to obtain shallow information in the low-level space. Then, the shallow information with cumulative errors due to DCN is improved under high-resolution (HR) supervision, while bringing an intermediate reconstruction result and a powerful intermediate benchmark. Finally, the improved feature representation is further enhanced in high-level space by a multi-scale context-aware encoder-decoder for facial reconstruction. The features in both spaces are explored progressively from coarse to fine reconstruction information. The experimental results show that SLNet has a competitive performance compared to the state-of-the-art methods.

6.
Environ Pollut ; 320: 121002, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608733

RESUMO

Heavy metal pollution of soils has become a serious environmental problem. Soil washing with degradable reagents is an effective remediation technique of heavy metal pollution, and the generated leachate must be appropriately treated before discharge. However, the existing methods usually have the problems of large consumption of regents, high cost, and secondary pollution. This study proposed a reagent-free electrochemical precipitation method to remove mixed heavy metal ions extracted from soils by citrate using inert electrodes (IrO2-Ta2O5/Ti anode and graphite cathode). The results showed that the low potential of cathode led to the electrodeposition of Cd; the local alkaline environment provided by electro-mediated water reduction caused the hydrolytic precipitation of Zn and Pb; and the precipitation of Fe washed out from Fe-rich soil resulted in the coprecipitation of As on cathode surface. These combined cathodic precipitation processes decreased the concentrations of toxic heavy metals by over 99.4% after 12 h of electrolysis at 26 mA cm-2. The electrodes exhibited high stability after multiple successive cycles of reuse. The concentrations of As, Zn, Pb and Cd in the leachate decreased to below the limits of industrial wastewater discharge in each cycle, and those in soils could be reduced by 53.8%, 58.8%, 25.5%, and 70.2% at the initial concentrations of 1549, 1016, 310 and 50 mg kg-1, respectively. The heavy metal removal rate increased with increasing current density in the range of 0-52 mA cm-2. This work provides an efficient and sustainable method for the remediation of site soils polluted by mixed heavy metals.

7.
Pattern Recognit ; 135: 109142, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36405881

RESUMO

The outbreak of the COVID-19 coronavirus epidemic has promoted the development of masked face recognition (MFR). Nevertheless, the performance of regular face recognition is severely compromised when the MFR accuracy is blindly pursued. More facts indicate that MFR should be regarded as a mask bias of face recognition rather than an independent task. To mitigate mask bias, we propose a novel Progressive Learning Loss (PLFace) that achieves a progressive training strategy for deep face recognition to learn balanced performance for masked/mask-free faces recognition based on margin losses. Particularly, our PLFace adaptively adjusts the relative importance of masked and mask-free samples during different training stages. In the early stage of training, PLFace mainly learns the feature representations of mask-free samples. At this time, the regular sample embeddings shrink to the prototype. In the later stage of training, PLFace converges on mask-free samples and further focuses on masked samples until the masked sample embeddings are also gathered in the center of the class. The entire training process emphasizes the paradigm that normal samples shrink first and masked samples gather afterward. Extensive experimental results on popular regular and masked face benchmarks demonstrate the superiority of our PLFace over state-of-the-art competitors.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 288: 122199, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36473293

RESUMO

The rotational spectrum of the binary adduct of formamide (HCONH2) with dimethyl sulfide (DMS) has been investigated employing cavity-based Fourier transform microwave spectroscopy combined with theoretical computations. Experimentally, only one isomer of the adduct was unambiguously observed and assigned according to the theoretically predicted spectroscopic parameters, and its rotational spectrum displays the hyperfine splittings associated with the 14N nuclear quadrupole coupling effect. The observed isomer exhibits Cs symmetry, such that the ∠CSC angle of the DMS subunit is bisected by the ab-plane of the HCONH2 moiety. The two moieties in the detected isomer are connected via one primary NH···S and two secondary CH···O hydrogen bonds. Quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI), natural bond orbital (NBO) and symmetry-adapted perturbation theory (SAPT) approaches were utilized for characterizing the intermolecular interactions occurring in the titled adduct. Additionally, the adduct of HCONH2 with dimethyl ether (DME) was also theoretically investigated to compare the difference in structure and energy characteristics between the NH···S and NH···O hydrogen bonds.

9.
Eur J Med Chem ; 246: 114940, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36462441

RESUMO

Bruton's tyrosine kinase (BTK) plays a crucial role in adaptive and immune responses by modulating B-cell, Fc, toll-like, and chemokine receptor signaling pathways. BTK inhibition is a promising therapeutic approach for the treatment of inflammatory and autoimmune diseases. The development of novel, highly selective, and less toxic BTK inhibitors may be beneficial for the treatment of autoimmune diseases with unmet medical needs. In this study, structure-based drug design was used to discover a series of novel, potent, and selective covalent BTK inhibitors with a 1,4,5,6,8-pentaazaacenaphthylen scaffold. Among them, compound 36R exhibited high kinase selectivity, long target occupancy time, appropriate pharmacokinetic properties, and dose-dependent efficacy in a rat model of collagen-induced arthritis. Therefore, 36R is a novel BTK inhibitor requiring further development for the treatment of autoimmune diseases.

10.
Front Aging Neurosci ; 14: 1017882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452439

RESUMO

Objective: The study aimed to examine the effects of hearing aids on cognitive function in middle-aged and older adults with hearing loss. Data sources and study selection: PubMed, Cochrane Library, and Embase were searched for studies published before 30 March 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) were included in the search. Restriction was set on neither types, severity, or the time of onset of hearing impairment nor cognitive or psychiatric statuses. Data extraction and synthesis: Two independent reviewers extracted data and assessed the study quality of RCTs. Cognitive function outcomes were descriptively summarized and converted to standardized mean difference (SMD) in the meta-analysis. Meta-analysis was conducted in RCTs. Sub-group analyses were conducted by cognitive statuses, psychiatric disorders, and cognitive domains. Results: A total of 15 studies met the inclusion criteria, including five RCTs (n = 339) and 10 NRSIs (n = 507). Groups were classified as subjects without dementia or with normal global cognition, subjects with AD or dementia, and subjects with depressive symptoms. For subjects without dementia, improvements were found in global cognition, executive function, and episodic memory. For subjects with depressive symptoms, improvements were found in immediate memory, global cognition, and executive function. No improvement was found in subjects with AD or dementia. In total, four RCTs were included in the meta-analysis. For subjects without dementia (SMD = 0.11, 95% confidence interval [CI]: -0.15-0.37) and those with AD, no significant effect was found (SMD = -0.19, 95% CI: -0.65-0.28). For subjects without dementia, no significant effect was found in language (SMD = 0.14, 95% CI: -0.30-0.59) or general executive function (SMD = -0.04, 95% CI: -0.46-0.38). Further sub-group analysis found no significant effect in executive function (SMD = -0.27, 95% CI: -0.72-0.18) or processing speed (SMD = -0.02, 95% CI: -0.49-0.44). Conclusion: Hearing aids might improve cognitive performance in domains such as executive function in subjects without dementia. The effects on subjects with depressive symptoms remained unclear. No improvement was found in subjects with AD or dementia. Long-term RCTs and well-matched comparison-group studies with large sample sizes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022349057.

11.
Front Microbiol ; 13: 1053153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36545194

RESUMO

With the widespread use of abamectin in agriculture, there is increasing urgency to assess the effects of abamectin on soil microorganisms. Here, we treated plant-soil microcosms with abamectin at concentrations of 0.1 and 1.0 mg/kg and quantified the impacts of abamectin on bulk and rhizosphere soil microbial communities by shotgun metagenomics after 7 and 21 days of exposure. Although abamectin was reported to be easily degradable, it altered the composition of the soil microbial communities, disrupted microbial interactions, and decreased community complexity and stability after 7 days of exposure. After treatment with abamectin at a concentration of 1.0 mg/kg, some opportunistic human diseases, and soil-borne pathogens like Ralstonia were enriched in the soil. However, most ecological functions in soil, particularly the metabolic capacities of microorganisms, recovered within 21 days after abamectin treatment. The horizontal and vertical gene transfer under abamectin treatments increased the levels of antibiotic resistance genes dissemination. Overall, our findings demonstrated the negative effects of abamectin on soil ecosystems in the short-term and highlight a possible long-term risk to public and soil ecosystem health associated with antibiotic resistance genes dissemination.

12.
J Med Chem ; 65(24): 16570-16588, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36480917

RESUMO

Fibroblast growth factor receptors (FGFRs) play key roles in promoting cancer cell proliferation, differentiation, and migration. However, acquired resistance to FGFR inhibitors has become an emerging challenge in long-term cancer therapies, especially for hepatocellular carcinoma (HCC). Gatekeeper (GK) mutations are the main mechanism of resistance. Herein, we describe the discovery of a series of reversible FGFR inhibitors, particularly for GK mutations with the 2-amino-7-sulfonyl-7H-pyrrolo[2,3-d]pyrimidine scaffold. Rational design, optimization, and pharmacokinetic screening provided representative compound 19 with potent FGFR inhibition in vitro, high bioavailability, and an acceptable half-life. GK mutation tolerance was supported by assays against FGFR4V550L and Ba/F3-TEL-FGFR4V550L cells. Moreover, compound 19 exhibited potent antitumor potency in HUH7 xenograft mouse models with no obvious toxicity observed. Compound 19 was identified as a potential candidate for overcoming GK mutations for HCC treatment.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Proliferação de Células , Mutação , Pirimidinas , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral
13.
Langmuir ; 38(50): 15729-15739, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36495271

RESUMO

Membrane separation is of great significance due to its unique performance in treating wastewater. However, the simultaneous treatment of oily emulsions and other complex pollutants in water remains challenging. Herein, we have proposed a simple strategy to prepare a multifunctional titanium dioxide/silver nanoparticles/polyacrylonitrile (TiO2/AgNPs/PAN) nanofibrous membrane. The experimental results showed that the combination of the hierarchical structure composed of PAN nanofibers and Ag/TiO2 nanoprotrusions contributed to the superhydrophilicity and superoleophobicity (UOCA = 153.3 ± 2.0°). Further, the nanofibrous membrane exhibited a rapid gravity-driven permeate flux (>1829.37 ± 83.51 L m-2 h-1) and an ultrahigh separation efficiency (>99.9%) for the surfactant-stabilized oil/water emulsions. Moreover, due to the synergistic effect between the PAN fibers and TiO2/Ag heterojunction, Rhodamine B dye in water can be removed quickly and efficiently (up to 97.67% in 90 min). More importantly, the obtained nanofibrous membrane exhibited ultrahigh stability in different harsh environments. The design of superoleophobic nanofiber membrane with a high separation efficiency and high photocatalytic activity has great potential for practical applications in the purification of oily wastewater.


Assuntos
Nanopartículas Metálicas , Nanofibras , Nanofibras/química , Corantes , Emulsões , Prata , Óleos/química , Bactérias
14.
Artigo em Inglês | MEDLINE | ID: mdl-36539666

RESUMO

The rhizosphere microbiome plays critical roles in plant growth and is an important interface for resource exchange between plants and the soil environment. Crops at various growing stages, especially the seedling stage, have strong shaping effects on the rhizosphere microbial community, and such community reconstruction will positively feed back to the plant growth. In the present study, we analyzed the variations of bacterial and fungal communities in the rhizosphere of four crop species: rice, soybean, maize, and wheat during successive cultivations (three repeats for the seedling stages) using 16S rRNA gene and internal transcribed spacer (ITS) high-throughput sequencing. We found that the relative abundances of specific microorganisms decreased after different cultivation times, e.g., Sphingomonas, Pseudomonas, Rhodanobacter, and Caulobacter, which have been reported as plant-growth beneficial bacteria. The relative abundances of potential plant pathogenic fungi Myrothecium and Ascochyta increased with the successive cultivation times. The co-occurrence network analysis showed that the bacterial and fungal communities under maize were much more stable than those under rice, soybean, and wheat. The present study explored the characteristics of bacteria and fungi in crop seedling rhizosphere and indicated that the characteristics of indigenous soil flora might determine the plant growth status. Further study will focus on the use of the critical microorganisms to control the growth and yield of specific crops.

15.
Molecules ; 27(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36558141

RESUMO

The construction of an N-C chiral axis for N-aryl indole derivatives is meaningful as they widely exist in functionalized molecules. This work provides a novel method for this purpose via amination of amino acid derivatives at the C2 position of the indole and chiral center induced chiral axis formation. The protocol of this transformation is easily accessible, not requiring metal or an organic chiral catalyst, endowing this method with great potential in the construction of axis chiral N-aryl indoles.


Assuntos
Indóis , Aminação , Indóis/química , Catálise
16.
Sensors (Basel) ; 22(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36560099

RESUMO

Wireless sensor networks (WSN) are widely used in various applications, such as environmental monitoring, healthcare, event detection, agriculture, disaster management, and so on. Due to their small size, sensors are limited power sources and are often deployed in special environments where frequent battery replacement is not feasible. Therefore, it is important to reduce the energy consumption of sensors and extend the network lifetime. An effective way to achieve this is clustering. This paper proposes a dual cluster-head energy-efficient algorithm (DCK-LEACH), which is based on K-means and Canopy optimization. Considering that the K-means algorithm is sensitive to the location of the initial clustering centers, this paper uses both the dynamic Canopy algorithm and K-means algorithm for clustering. For cluster-head election, this algorithm uses a hierarchy to minimize the cluster-head burden and balance the network load. The primary cluster-head is selected by two objectives: the node's residual energy and the distance from the node to the clustering center. The vice cluster-head is selected by the residual energy of the node, and the distance from the nodes to the base station. Simulator results show that DCK-LEACH significantly prolongs the energy-critical node lifetime and the network lifetime compared with existing protocols.


Assuntos
Redes de Comunicação de Computadores , Tecnologia sem Fio , Monitoramento Ambiental , Fenômenos Físicos , Algoritmos
17.
Future Med Chem ; 14(23): 1811-1830, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36484176

RESUMO

ATM, a member of the PIKK-like protein family, plays a central role in responding to DNA double-strand breaks and other lesions to protect the genome against DNA damage. Loss of ATM's kinase function has been shown to increase the sensitivity of most cells to ionizing radiation. Therefore, ATM is thought to be a promising target for chemotherapy as a radiotherapy sensitizer. The mechanism of ATM in cancer treatment and the development of its inhibitors have become research hotspots. Here we present an overview of research concerning ATM protein domains, functions and inhibitors, as well as perspectives and insights for future development of ATM-targeting agents.


Assuntos
Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinases , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Ligação a DNA , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Dano ao DNA
18.
Mol Divers ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369613

RESUMO

Kinase plays a significant role in various disease signaling pathways. Due to the highly conserved sequence of kinase family members, understanding the selectivity profile of kinase inhibitors remains a priority for drug discovery. Previous methods for kinase selectivity identification use biochemical assays, which are very useful but limited by the protein available. The lack of kinase selectivity can exert benefits but also can cause adverse effects. With the explosion of the dataset for kinase activities, current computational methods can achieve accuracy for large-scale selectivity predictions. Here, we present a multimodal multi-task deep neural network model for kinase selectivity prediction by calculating the fingerprint and physiochemical descriptors. With the multimodal inputs of structure and physiochemical properties information, the multi-task framework could accurately predict the kinome map for selectivity analysis. The proposed model displays better performance for kinase-target prediction based on system evaluations.

19.
Mol Inform ; : e2200039, 2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36372777

RESUMO

Improving screening efficiency is one of the most challenging tasks of virtual screening (VS). In this work, we propose an effective target-focused scoring criterion for VS and apply it to the screening of a specific target scaffold replacement library constructed by enumeration of suitable substitution fragments and R-groups of known ligands. This criterion is based on both ligand- and structure-based scoring methods, which includes feature maps, 3D shape similarity, and the pairwise distance information between proteins and ligands (FSDscore). It is precisely due to the hybrid advantages of ligand- and structure-based approaches that FSDscore performs far better on the validation dataset than other scoring methods. We apply FSDscore to the VS of different kinase targets, MERTK (Mer tyrosine kinase) and ABL1 (tyrosine-protein kinase ABL1) in order to avoid occasionality. Finally, a VS case study shows the potential and effectiveness of our scoring criterion in drug discovery and molecular dynamics simulation further verifies its powerful ability.

20.
Medicine (Baltimore) ; 101(46): e31732, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401401

RESUMO

BACKGROUND: Lipofibroadenoma is an extremely rare thymic tumor, and the anterior mediastinum is the most common site. CASE SUMMARY: A 21-year-old male was admitted with fever without obvious cause for 2 months. After admission, the patient's highest temperature was 38.3°C, accompanied by diarrhea. Physical examination showed coarse breath sounds in both lungs. Chest enhanced computed tomography (CT) showed a mass of mixed density shadow on the left side of the anterior mediastinum with a size of approximately 9.2 cm × 5 cm × 2.1 cm and a clear boundary mixed with a low fat density shadow. Mediastinal tumors were removed under general anesthesia by video-assisted thoracoscopic surgery. Macroscopically, a clear boundary was shown between the tumor and the remaining thymus. Microscopically, the tumor contained a large amount of mature adipose and fibrous tissue with scattered cord-like epithelial tissue and a small number of lymphocytes scattered in the stroma. The tumor lacked thymic bodies. The neoplastic epithelial cells were oval or polygonal and arranged in fissures, the nuclei were uniform in size and mild in shape, and mitosis was rare. Epithelial cells were positive for AE1/AE3 and CK19, lymphocytes were positive for CD3 and CD20, and fat and fibrous tissue were positive for S-100 and vimentin, respectively. The Ki67 labeling index was less than 5%. Based on histological features and immunophenotype, thymic lipofibroadenoma was diagnosed. The patient was followed up 1 year after the operation, and no recurrence or residual lesions were found on the X-ray re-examination. CONCLUSION: Lipofibroadenoma is a benign thymic tumor, and thymectomy is regarded as the best treatment. The biological behavior of thymic lipofibroadenoma is good, and the recurrence rate is low.


Assuntos
Neoplasias do Mediastino , Timoma , Neoplasias do Timo , Humanos , Masculino , Adulto Jovem , Adulto , Mediastino/patologia , Timoma/patologia , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Neoplasias do Timo/patologia , Timectomia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/patologia
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