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1.
Membranes (Basel) ; 14(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38668109

RESUMO

Surface modification of membranes is essential for improving flux and resistance to contamination for membranes. This is of great significance for membrane distillation, which relies on the vapor pressure difference across the membrane as the driving force. In recent years, biomimetic mussel-inspired substances have become the research hotspots. Among them, dopamine serves as surface modifiers that would achieve highly desirable and effective membrane applications owing to their unique physicochemical properties, such as universal adhesion, enhanced hydrophilicity, tunable reducibility, and excellent thermal conductivity. The incorporation of a hydrophilic layer, along with the utilization of photothermal properties and post-functionalization capabilities in modified membranes, effectively addresses challenges such as low flux, contamination susceptibility, and temperature polarization during membrane distillation. However, to the best of our knowledge, there is still a lack of comprehensive and in-depth discussions. Therefore, this paper systematically compiles the modification method of dopamine on the membrane surface and summarizes its application and mechanism in membrane distillation for the first time. It is believed that this paper would provide a reference for dopamine-assisted membrane separation during production, and further promote its practical application.

2.
Int J Biol Macromol ; 267(Pt 1): 131453, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38588842

RESUMO

Enterovirus 71 (EV71) causes hand-foot-and-mouth disease (HFMD), neurological complications, and even fatalities in infants. Clinically, the increase of extracellular vesicles (EVs) in EV71 patients' serum was highly associated with the severity of HFMD. EV71 boosts EVs biogenesis in an endosomal sorting complex required for transport (ESCRT)-dependent manner to facilitate viral replication. Yet, the impact of EVs-derived from ESCRT-independent pathway on EV71 replication and pathogenesis is highly concerned. Here, we assessed the effects of EV71-induced EVs from ESCRT-independent pathway on viral replication and pathogenesis by GW4869, a neutral sphingomyelinase inhibitor. Detailly, in EV71-infected mice, blockade of the biogenesis of tissue-derived EVs in the presence of GW4869 restored body weight loss, attenuated clinical scores, and improved survival rates. Furthermore, GW4869 dampens EVs biogenesis to reduce viral load and pathogenesis in multiple tissues of EV71-infected mice. Consistently, GW4869 treatment in a human intestinal epithelial HT29 cells decreased the biogenesis of EVs, in which the progeny EV71 particle was cloaked, leading to the reduction of viral infection and replication. Collectively, GW4869 inhibits EV71-induced EVs in an ESCRT-independent pathway and ultimately suppresses EV71 replication and pathogenesis. Our study provides a novel strategy for the development of therapeutic agents in the treatment for EV71-associated HFMD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38597955

RESUMO

A nanomicrocapsule system was constructed through the polymerization of tannic acid (TA) and emulsifier OP-10 (OP-10), followed by the chelation of iron ions, to develop a safe and effective method for controlling Rhizoctonia solani in agriculture. The encapsulated active component is a rosin-based triazole derivative (RTD) previously synthesized by our research group (RTD@OP10-TA-Fe). The encapsulation efficiency of the nanomicrocapsules is 82.39%, with an effective compound loading capacity of 96.49%. Through the encapsulation of the RTD via nanomicrocapsules, we improved its water solubility, optimized its stability, and increased its adhesion to the leaf surface. Under acidic conditions (pH = 5.0), the release rate of nanomicrocapsules at 96 h is 96.31 ± 0.8%, which is 2.04 times higher than the release rate under normal conditions (pH = 7.0). Additionally, the results of in vitro and in vivo antifungal assays indicate that compared with the original compound, the nanomicrocapsules exhibit superior antifungal activity (EC50 values of RTD and RTD@OP10-TA-Fe are 1.237 and 0.860 mg/L, respectively). The results of field efficacy trials indicate that compared with RTD, RTD@OP10-TA-Fe exhibits a more prolonged period of effectiveness. Even after 3 weeks, the antifungal rate of RTD@OP10-TA-Fe remains at 40%, whereas RTD, owing to degradation, shows an antifungal rate of 11.11% during the same period. Furthermore, safety assessment results indicate that compared with the control, RTD@OP10-TA-Fe has almost no impact on the growth of rice seedlings and exhibits low toxicity to zebrafish. This study provides valuable insights into controlling R. solani and enhancing the compound performance.

4.
BMC Cancer ; 24(1): 429, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589800

RESUMO

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.


Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Adolescente , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Estudos Prospectivos , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/prevenção & controle , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Resposta Patológica Completa , Encéfalo/patologia
5.
World J Gastroenterol ; 30(9): 1237-1249, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577174

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Receptor ErbB-2 , Humanos , Feminino , Gencitabina , Desoxicitidina/uso terapêutico , Estudos Prospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Albuminas/uso terapêutico
6.
Pest Manag Sci ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38529554

RESUMO

BACKGROUND: To further develop potential natural fungicides, two series of new acrylopimaric acid triazole derivatives were synthesized, and their antifungal activities were tested and evaluated. RESULTS: In vitro antifungal activity results indicated that compound 5m exhibited significant inhibitory activity against Rhizoctonia solani with an half maximal effective concentration (EC50) value of 1.528 mg/L. Its antifungal effect was comparable to that of the commercially available fungicide fluconazole, epoxiconazole and propiconazole (EC50 values of 1.441, 0.815 and 1.173 mg/L). Subsequently, in vivo studies were conducted on compound 5m, which revealed its significant protective and curative effects against R. solani. In addition, physiological and biochemical studies showed that compound 5m could disrupt the morphology and ultrastructure of R. solani mycelium, increase cell membrane permeability, inhibit ergosterol synthesis, and enhance the activity of defense enzymes in rice plants. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies revealed that the molecular structure significantly influenced the binding of compound 5m to the receptor, thereby enhancing its antifungal activity. CONCLUSION: Compound 5m exhibits excellent antifungal activity against R. solani, making it a promising candidate fungicide for the prevention and control of R. solani. © 2024 Society of Chemical Industry.

7.
J Agric Food Chem ; 72(9): 4630-4638, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38407939

RESUMO

To investigate the potential application value of dehydroabietic acid, 27 novel dehydroabietyl-1,2,4-triazole-5-thioether-based derivatives were designed and characterized by IR, 1H NMR, 13C NMR, and LC-MS. Their antifungal activities were evaluated against five plant fungi, namely, Valsa mali, Colletotrichum orbiculare, Fusarium graminearum, Sclerotinia sclerotiorum, and Gaeumannomyces graminis; the results showed that compound 5h-1 (Co. 5h-1) exhibited a considerable inhibitory effect against V. mali. Moreover, in vivo experiments indicated that Co. 5h-1 had a certain protective effect on apple branches. The preliminary structure-activity relationship analysis suggested that the electron-withdrawing group on the benzyl group was significantly better than that of other substituent derivatives. Through electron microscopy analysis, it was found that Co. 5h-1 hindered the growth of mycelia, damaged their cell structure, and caused the large accumulation of reactive oxygen species (ROS). Preliminary research on the mode of action indicated that Co. 5h-1 could affect the activity of CAT by increasing the α-helix (0.790%), decreasing the ß-sheet (0.170%), which led to the accumulation of ROS. In addition, Co. 5h-1 also affected the activity of CYP51, hindered the biosynthesis of ergosterol, and increased cell membrane permeability. Overall, this above research proposed that Co. 5h-1 can be a novel leading structure for development of a fungicide agent.


Assuntos
Antifúngicos , Ascomicetos , Fungicidas Industriais , Resinas Vegetais , Antifúngicos/química , Proteção de Cultivos , Espécies Reativas de Oxigênio , Relação Estrutura-Atividade , Triazóis/farmacologia , Triazóis/química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química
8.
Food Chem ; 445: 138795, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38382257

RESUMO

The beany flavor of soy protein isolate (SPI) creates barriers to their application in food processing. This study investigated the effect of ultrasonic-thermal synergistic treatments, combined with vacuum degassing, on the removal of volatile compounds from SPI. The results revealed that ultrasonic-thermal synergistic treatments altered protein secondary structure and increased fluorescence intensity and surface hydrophobicity, which affected the flavor-binding ability of protein, resulting in reduced electronic nose sensor response values. At synergistic treatment (350 W, 120 ℃ and 150 s), the content of hexanal, (E)-2-hexenal, and 1-octen-3-ol reduced by 70.60 %, 95.60 % and 61.23 %. (E)-2-nonenal and 2-pentylfuran were not detected. Chemometric analysis indicated significant flavor differences between control and treated SPI. Furthermore, α-helix, ß-sheet, ß-turn, and surface hydrophobicity highly correlated with volatile compounds through correlation analysis, indicating that altered protein structure affected interactions with volatile compounds. The study reduced beany flavor and further expanded the range of applications of plant protein in food industry.


Assuntos
Aldeídos , Proteínas de Soja , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas , Proteínas de Soja/química , Quimiometria , Microextração em Fase Sólida/métodos , Ultrassom , Nariz Eletrônico , Compostos Orgânicos Voláteis/análise
9.
J Agric Food Chem ; 72(2): 973-982, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38166361

RESUMO

To develop new antioomycete agents against plant pathogens, two series of acrylopimaric acid triazole derivatives from rosin were synthesized. The in vitro antioomycete activity of these derivatives was evaluated and screened against Pseudoperonospora cubensisi, Plasmopara viticola, Phytophthora sojae, Phytophthora infestans, and Phytophthora capsici. Compound 5m showed the highest antioomycete activity against P. capsici, with a half-maximal effective concentration (EC50) value that was lower than that of the positive control metalaxyl (1.391 and 1.815 mg/L, respectively). Compound 5m demonstrated satisfactory protective and curative efficacy against P. capsici in pepper in in vivo antioomycete activity studies. Physiological and biochemical testing showed that the action mechanism of compound 5m on P. capsici involved altering the morphology and ultrastructure of the mycelium, increasing cell membrane permeability, inducing dysfunction of the nucleus and mitochondria, and ultimately causing cell necrosis. In addition, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) revealed the significance of the molecular structure and charge distribution in the interaction between compound 5m and its target. Collectively, these findings indicate that compound 5m has the potential as an antioomycete candidate.


Assuntos
Phytophthora infestans , Estrutura Molecular , Plantas , Alimentos , Relação Quantitativa Estrutura-Atividade , Doenças das Plantas
10.
Clin Rehabil ; 38(4): 478-496, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38043930

RESUMO

OBJECTIVE: To systematically evaluate the evidence relating to acupuncture on the sleep quality of patients with Parkinson's disease. DATA SOURCES: Six English-language (PubMed, Cochrane Library, EBSCOhost, Embase, OVID MEDLINE, and Web of Science) and four Chinese-language (China National Knowledge Infrastructure, SinoMed, China Scientific Journals Database, and Wanfang) databases were searched for pertinent studies published from database inception to 11 October 2023. METHODS: Two researchers independently screened eligible studies and extracted relevant data using custom data extraction tables. Methodological quality assessment of the included studies was performed using Cochrane Handbook 5.1.0. Meta-analysis was performed using Cochrane Review Manager version 5.4. RESULTS: Twenty-four studies (1701 participants) met inclusion criteria. The meta-analysis showed that acupuncture improved the Parkinson's Disease Sleep Scale, Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale, Hamilton Depression Scale, Self-Rating Depression Scale, and Parkinson's Disease Questionnaire 39 scores compared with controls (all P < 0.05). CONCLUSION: This review showed that acupuncture improved sleep quality, anxiety and depressive symptoms, and quality of life of patients with Parkinson's disease relative to controls.


Assuntos
Terapia por Acupuntura , Doença de Parkinson , Humanos , Qualidade do Sono , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Qualidade de Vida , Ansiedade
11.
J Colloid Interface Sci ; 658: 219-229, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38104404

RESUMO

The fabrics commonly used in architectural decorative materials pose significant fire hazards due to their flammability and rapid fire spread. Moreover, the traditional fire-alarm systems may fail to function properly in complex fire environments owing to power supply disruptions. In this study, we developed a low-cost and eco-friendly flame-retardant conductive fabric-based triboelectric nanogenerator (FCF-TENG) by integrating flame-retardant conductive nylon fabric and polytetrafluoroethylene soaked cotton fabric. This nanogenerator exhibits excellent flame-retardant properties and remarkable energy-harvesting capabilities. The nylon fabric, treated with layer-by-layer self-assembly method, possesses outstanding self-extinguishing capability and melt-dripping resistance. Additionally, the electrical performance of FCF-TENG significantly improves, with a 10-fold boost in conductivity, and the open-circuit voltage increases by 84% to 92 V. Besides, by incorporating the rectifier circuit, the FCF-TENG is capable of completely charging a 1 µF capacitor within 30 s. Furthermore, the FCF-TENG was successfully applied as a self-powered sensor in the fire-alarm system and served as a safety exit indicator for evacuees and fire rescue. This work presents an effective and innovative application of multifunctional smart textiles for energy harvesting and self-powered sensing.

12.
Int J Biol Macromol ; 260(Pt 2): 128940, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38143050

RESUMO

This study provides a novel strategy for preparing bio-based antibacterial emulsions stabilized by cellulose nanocrystals (CNCs). Antibacterial ε-polylysine (ε-PL) with a positive charge was introduced into the aqueous phase to modulate the interfacial behavior of CNCs via electrostatic interactions. Pickering emulsions containing ε-PL/CNCs (ε-PL 0.07-0.1 g/L) had significantly better stability, larger emulsion ratio, smaller emulsion droplet diameter, and superior antibacterial ability than emulsions stabilized by CNCs alone. This could be attributed to the formation of a CNC-dense layer at the interface in the continuous phase caused by a reduction of electrostatic repulsion after adding ε-PL. This was confirmed by zeta potential measurements, rheological properties, and bio-freezing scanning electron microscopy. In addition, cinnamaldehyde was introduced into the oil phase to further improve the antibacterial properties of the emulsion, thereby avoiding easy evaporation into water. Our findings provide an innovative solution for preparing bio-based antibacterial emulsions stabilized by ε-PL/CNCs, which will benefit the development of food, medicine, and cosmetic lotions.


Assuntos
Celulose , Nanopartículas , Celulose/química , Polilisina , Emulsões/química , Nanopartículas/química , Antibacterianos/farmacologia , Água/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-38127247

RESUMO

Uric acid is the final metabolite in humans. High level of uric acid chronically induces urate deposition, aggravates kidney damage, and concomitantly causes an increase in inflammatory factors. Alleviating acute inflammation and decreasing uric acid levels are the key points in the treatment of inflammatory diseases associated with high uric acid. However, a drug delivery system that combines anti-inflammatory and uric acid reduction functions at the same time remains a challenge to be settled. Here, we designed a nanocrystal-based co-delivery platform, IND Nplex, characterized by loading of indomethacin (IND) and uricase. Compared with free IND or uricase, IND Nplex possessed a better anti-inflammatory effect by restraining the release of inflammation-related factors in vitro. In addition, pharmacokinetic and biodistribution studies revealed that IND Nplex significantly prolonged the retention time in vivo and was more concentrated in the kidney. In acute gouty arthritis model rats, IND Nplex markedly relieved ankle joint swelling and mitigated synovial inflammation. In acute kidney injury model rats, IND Nplex indicated better biocompatibility and significant amelioration of renal fibrosis. Moreover, IND Nplex showed the effect of anti-inflammatory and improved renal function via determination of inflammatory factors and biochemical markers in the serum and kidney. In conclusion, these results indicate that IND Nplex exerts anti-inflammatory activity and uric acid-lowering effect and could become a promising candidate for the treatment of uric acid-related diseases. In this study, a stable neutral co-delivery platform (IND Nplex) was fabricated by using a co-delivery strategy, allowing for a combination of the anti-inflammation drug IND and the metabolic enzyme uricase. IND Nplex showed a good therapeutic effect on rats with acute gouty arthritis or acute kidney injury due to the dual effects of anti-inflammatory and uric acid lowering. This platform provided a novel strategy for high uric acid-related illnesses.

14.
Foods ; 12(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38137310

RESUMO

In this study, the structure of the anthocyanin fractions isolated from black rice (Oryza sativa L.) was modified by the enzyme catalysis method using caffeic acid as an acyl donor. At the same time, the effects of the acylation on the lipophilicity, antioxidant activity, and stability of black rice anthocyanins were comprehensively evaluated. The structural analyses of acylated derivatives based on ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, ultra-high-performance liquid chromatography-high-resolution mass spectrometry, and thermogravimetric analysis revealed that caffeic acid was efficiently grafted onto the anthocyanins of black rice through an acylated reaction, while the acylation binding site was on glucoside. When the mass ratios of anthocyanins to caffeic acid were 1:1, the A319/AVis-max value of acylated anthocyanins reached 6.37. Meanwhile, the lipophilicity of acylated derivatives was enhanced. The antioxidant capacity (DPPH and FRAP) and stability (thermal, pH, and light stability) were significantly increased. Overall, the study results provide deeper insights into controlling anthocyanin homeostasis in food processing, broadening the application of colored grain products.

15.
Anal Chem ; 95(45): 16639-16648, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37910128

RESUMO

The simultaneous detection of multiple antibiotic residues in food is of great significance for food safety. In this work, a novel dual-potential electrochemiluminescence (ECL) immunoassay was designed for the simultaneous detection of chloramphenicol and fluorfenicol residues in food. Ru@MOF was used as an anodic probe, and SnS2 QDs-PEI-Au-MoS2 was used as a cathodic probe. Notably, the coreactant for both luminophores was K2S2O8, avoiding interactions caused by different kinds of coreactants. Au nanoparticles functionalized with a nitrogen- and sulfur-doped graphene oxide-modified glassy carbon electrode to improve the electron transfer efficiency and provide a larger surface area for immobilization of antigen. The linear range for the detection of florfenicol was determined to be 0.1-1000 ng mL-1 with a detection limit of 0.03 ng mL-1, and the linear range for the detection of chloramphenicol was 0.01-1000 ng mL-1 with a detection limit of 3.2 pg mL-1 by recording the ECL responses at two different excitation potentials. The proposed immunoassay achieved a more stable recovery in the detection of actual samples and provided a new analytical method for the simultaneous detection of florfenicol and chloramphenicol residues with high sensitivity and specificity.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Cloranfenicol , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Ouro/química , Imunoensaio/métodos , Medições Luminescentes/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção
16.
Mol Divers ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910346

RESUMO

Tropomyosin receptor kinases (TRKs) are important broad-spectrum anticancer targets. The oncogenic rearrangement of the NTRK gene disrupts the extracellular structural domain and epitopes for therapeutic antibodies, making small-molecule inhibitors essential for treating NTRK fusion-driven tumors. In this work, several algorithms were used to construct descriptor-based and nondescriptor-based models, and the models were evaluated by outer 10-fold cross-validation. To find a model with good generalization ability, the dataset was partitioned by random and cluster-splitting methods to construct in- and cross-domain models, respectively. Among the 48 models built, the model with the combination of the deep neural network (DNN) algorithm and extended connectivity fingerprints 4 (ECFP4) descriptors achieved excellent performance in both dataset divisions. The results indicate that the DNN algorithm has a strong generalization prediction ability, and the richness of features plays a vital role in predicting unknown spatial molecules. Additionally, we combined the clustering results and decision tree models of fingerprint descriptors to perform structure-activity relationship analysis. It was found that nitrogen-containing aromatic heterocyclic and benzo heterocyclic structures play a crucial role in enhancing the activity of TRK inhibitors. Workflow for generating predictive models for TRK inhibitors.

17.
J Transl Med ; 21(1): 826, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978524

RESUMO

BACKGROUND: Protein palmitoylation, which is catalyzed by palmitoyl-transferase and de-palmitoyl-transferase, plays a crucial role in various biological processes. However, the landscape and dynamics of protein palmitoylation in human cancers are not well understood. METHODS: We utilized 23 palmitoyl-acyltransferases and seven de-palmitoyl-acyltransferases as palmitoylation-related genes for protein palmitoylation analysis. Multiple publicly available datasets were employed to conduct pan-cancer analysis, examining the transcriptome, genomic alterations, clinical outcomes, and correlation with c-Myc (Myc) for palmitoylation-related genes. Real-time quantitative PCR and immunoblotting were performed to assess the expression of palmitoylation-related genes and global protein palmitoylation levels in cancer cells treated with Myc depletion or small molecule inhibitors. Protein docking and drug sensitivity analyses were employed to predict small molecules that target palmitoylation-related genes. RESULTS: We identified associations between palmitoylation and cancer subtype, stage, and patient survival. We discovered that abnormal DNA methylation and oncogenic Myc-driven transcriptional regulation synergistically contribute to the dysregulation of palmitoylation-related genes. This dysregulation of palmitoylation was closely correlated with immune infiltration in the tumor microenvironment and the response to immunotherapy. Importantly, dysregulated palmitoylation was found to modulate canonical cancer-related pathways, thus influencing tumorigenesis. To support our findings, we performed a proof-of-concept experiment showing that depletion of Myc led to reduced expression of most palmitoylation-related genes, resulting in decreased global protein palmitoylation levels. Through mass spectrometry and enrichment analyses, we also identified palmitoyl-acyltransferases ZDHHC7 and ZDHHC23 as significant contributors to mTOR signaling, DNA repair, and immune pathways, highlighting their potential roles in tumorigenesis. Additionally, our study explored the potential of three small molecular (BI-2531, etoposide, and piperlongumine) to modulate palmitoylation by targeting the expression or activity of palmitoylation-related genes or enzymes. CONCLUSIONS: Overall, our findings underscore the critical role of dysregulated palmitoylation in tumorigenesis and the response to immunotherapy, mediated through classical cancer-related pathways and immune cell infiltration. Additionally, we propose that the aforementioned three small molecule hold promise as potential therapeutics for modulating palmitoylation, thereby offering novel avenues for cancer therapy.


Assuntos
Lipoilação , Neoplasias , Humanos , Lipoilação/fisiologia , Aciltransferases/genética , Aciltransferases/metabolismo , Carcinogênese/genética , Neoplasias/genética , Neoplasias/metabolismo , Transformação Celular Neoplásica , Microambiente Tumoral
18.
Ultrason Sonochem ; 101: 106675, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925914

RESUMO

This research explored the influences of ultrasonic and thermal treatments on the structure, functional properties, and beany flavor of soy protein isolate (SPI). In comparison with traditional thermal treatment, ultrasonic treatment effectively induced protein structural unfolding and exposure of hydrophobic groups, which reduced relative content of α-helix, increased relative content of ß-turn, ß-sheet and random coil, and improved the solubility, emulsifying and foaming properties of SPI. Both treatments significantly decreased the species and contents of flavor compounds, such as hexanal, (E)-2-nonenal, (Z)-2-heptenal and (E)-2-hexenal in SPI. The relative content of hexanal in the major beany flavor compound decreased from 11.69% to 6.13% and 5.99% at 350 W ultrasonic power and 150 s thermal treatment procedure, respectively. After ultrasonic treatment, structural changes in SPI were significantly correlated with functional properties but showed a weak correlation with flavor. Conversely, the opposite trend was observed for thermal treatment. Thus, using ultrasonic treatment to induce and stabilise the denatured state of proteins is feasible to improve the functional properties and beany flavor of SPI.


Assuntos
Proteínas de Soja , Ultrassom , Proteínas de Soja/química , Interações Hidrofóbicas e Hidrofílicas
19.
Foods ; 12(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37893620

RESUMO

Grains are an important part of a healthy diet, and provide most of the daily calories and nutrients [...].

20.
Nat Commun ; 14(1): 6666, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37863924

RESUMO

Highly effective and selective noble metal-free catalysts attract significant attention. Here, a single-atom iron catalyst is fabricated by saturated adsorption of trace iron onto zeolitic imidazolate framework-8 (ZIF-8) followed by pyrolysis. Its performance toward catalytic transfer hydrogenation of furfural is comparable to state-of-the-art catalysts and up to four orders higher than other Fe catalysts. Isotopic labeling experiments demonstrate an intermolecular hydride transfer mechanism. First principles simulations, spectroscopic calculations and experiments, and kinetic correlations reveal that the synthesis creates pyrrolic Fe(II)-plN3 as the active center whose flexibility manifested by being pulled out of the plane, enabled by defects, is crucial for collocating the reagents and allowing the chemistry to proceed. The catalyst catalyzes chemoselectively several substrates and possesses a unique trait whereby the chemistry is hindered for more acidic substrates than the hydrogen donors. This work paves the way toward noble-metal free single-atom catalysts for important chemical reactions.

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