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1.
Angew Chem Int Ed Engl ; : e202400143, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698663

RESUMEN

The chemistry of quinone methides formed in situ has been flourishing in recent years. In sharp contrast, the development and utilization of biphenyl quinone methides are rare. Herein, we achieved a remote stereocontrolled 1,12-conjugate addition of biphenyl quinone methides formed in situ for the first time. In the presence of a suitable chiral phosphoric acid, alkynyl biphenyl quinone methides were generated from α-[4-(4-hydroxyphenyl)phenyl]propargyl alcohols, followed by enantioselective 1,12-conjugate addition with indole-2-carboxylates. The strategy enabled the additional alcohols to serve as efficient allenylation reagents, providing a practical access to a broad range of axially chiral allenes bearing (1,1'-biphenyl)-4-ol unit that are previously less accessible. Combined with control experiments, density functional theory calculations shed light on the reaction mechanism, indicating that enantioselectivity originates from the nucleophilic addition of alkynyl biphenyl quinone methides. Notably, not only the presence of biphenyl quinone methides as versatile intermediates was confirmed but also organocatalytic enantioselective 1,12-addition was established for the first time. This work enriched the family of quinone methides and provided a new platform for the remote stereocontrolled transformation of such versatile intermediates.

3.
Circ Res ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38629274

RESUMEN

BACKGROUND: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood. METHODS: We generated NR4A3-/- mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification. RNA-seq was performed to determine the transcriptional profile of NR4A3-/- vascular smooth muscle cells under ß-glycerophosphate treatment. We integrated CUT&Tag analysis and RNA-seq data to further investigate the gene regulatory mechanisms of NR4A3 in arterial calcification and target genes regulated by histone lactylation. RESULTS: NR4A3 expression was upregulated in calcified aortic tissues from chronic kidney disease mice, 1,25(OH)2VitD3 overload-induced mice, and human calcified aorta. NR4A3 deficiency preserved the vascular smooth muscle cell contractile phenotype, inhibited osteoblast differentiation-related gene expression, and reduced calcium deposition in the vasculature. Further, NR4A3 deficiency lowered the glycolytic rate and lactate production during the calcification process and decreased histone lactylation. Mechanistic studies further showed that NR4A3 enhanced glycolysis activity by directly binding to the promoter regions of the 2 glycolysis genes ALDOA and PFKL and driving their transcriptional initiation. Furthermore, histone lactylation promoted medial calcification both in vivo and in vitro. NR4A3 deficiency inhibited the transcription activation and expression of Phospho1 (phosphatase orphan 1). Consistently, pharmacological inhibition of Phospho1-attenuated calcium deposition in NR4A3-overexpressed vascular smooth muscle cells, whereas overexpression of Phospho1 reversed the anticalcific effect of NR4A3 deficiency in vascular smooth muscle cells. CONCLUSIONS: Taken together, our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification.

4.
J Microencapsul ; 41(3): 190-203, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38602138

RESUMEN

AIMS: To develop Antarctic krill oil emulsions with casein and whey protein concentrate (WPC) and study their physicochemical properties and storage stability. METHODS: Emulsions were prepared by homogenisation and ultrasonication. The properties of the emulsions were investigated via ultraviolet ray spectroscopy, dynamic light scattering, confocal laser scanning microscope, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, Fourier transform infra-red spectrometer, and fluorescence spectrum. Shelf life was predicted by the Arrhenius model. RESULTS: Casein- and WPC-krill oil emulsions were well formed; the mean particle diameters were less than 128.19 ± 0.64 nm and 158 ± 1.56 nm, the polymer dispersity indices were less than 0.26 ± 0.01 and 0.27 ± 0.01, and the zeta potential were around -46.88 ± 5.02 mV and -33.51 ± 2.68 mV, respectively. Shelf life was predicted to be 32.67 ± 1.55 days and 29.62 ± 0.65 days (40 °C), 27.69 ± 1.15 days and 23.58 ± 0.14 days (50 °C), 24.02 ± 0.15 days and 20.1 ± 0.08 days (60 °C). CONCLUSION: The prepared krill oil emulsions have great potential to become a new krill oil supplement.


Asunto(s)
Caseínas , Euphausiacea , Animales , Emulsiones/química , Proteína de Suero de Leche/química , Aceites
5.
J Environ Manage ; 357: 120783, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38579475

RESUMEN

The rapid development of the economy and society is causing an increase in the amount of municipal solid waste (MSW) produced by people's daily lives. With the strong support of the Chinese government, incineration power generation has steadily become the primary method of treating MSW, accounting for 79.86%. However, burning produces a significant amount of municipal solid waste incineration fly ash (MSWI-FA), which contains heavy metals, soluble chlorine salts, and dioxins. China's MSWI-FA yield increased by 8.23% annually to 7.80 million tons in 2022. Besides, the eastern region, especially the southeastern coastal region, has the highest yield of MSWI-FA. There are certain similarities in the chemical characteristics of MSWI-FA samples from Northeast, North, East, and South China. Zn and CaO have the largest amounts of metals and oxides, respectively. The Cl content is about 20 wt%. This study provides an overview of the techniques used in the thermal treatment method, solidification and stabilization, and separation and extraction of MSWI-FA and compares their benefits and drawbacks. In addition, the industrial applications and standard requirements of landfill treatment and resource utilization of MSWI-FA in China are analyzed. It is discovered that China's resource utilization of MSWI-FA is insufficient through the study on the fly ash disposal procedures at a few MSW incineration facilities located in the economically developed Guangdong Province and the traditional industrial city of Tianjin. Finally, the prospects for the disposal of MSWI-FA were discussed.


Asunto(s)
Metales Pesados , Eliminación de Residuos , Humanos , Ceniza del Carbón/química , Residuos Sólidos/análisis , Material Particulado/análisis , Carbono/análisis , Incineración , Metales Pesados/análisis , China
6.
J Imaging Inform Med ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653912

RESUMEN

Biomedical image segmentation is essential in clinical practices, offering critical insights for accurate diagnosis and strategic treatment approaches. Nowadays, self-attention-based networks have achieved competitive performance in both natural language processing and computer vision, but the computational cost has reduced their popularity in practical applications. The recent study of Convolutional Neural Network (CNN) explores linear functions within modified CNN layer demonstrating pure CNN-based networks can still achieve competitive results against Vision Transformer (ViT) in biomedical image segmentation, with fewer parameters. The modified CNN, i.e., Depthwise CNN, however, leaves the features cleaved off in the channel dimension and prevents the extraction of features in the perspective of channel interaction. To effectively further explore the feature learning power of modified CNN with biomedical image segmentation, we design a lightweight multi-convolutional multi-scale convolutional network block (MSConvNeXt) for U-shape symmetrical network. Specifically, a network block consisting of a depthwise CNN, a deformable CNN, and a dilated CNN is proposed to capture semantic feature information effectively while with low computational cost. Furthermore, channel shuffling operation is proposed to dynamically promote an efficient feature fusion among the feature maps. The network block hereby is properly deployed within U-shape symmetrical encoder-decoder style network, named TriConvUNeXt. The proposed network is validated on a public benchmark dataset with a comprehensive evaluation in both computational cost and segmentation performance against 13 baseline methods. Specifically, TriConvUNeXt achieves 1% higher than UNet and TransUNet in Dice-Coefficient while 81% and 97% lower in computational cost. The implementation of TriConvUNeXt is made publicly accessible via  https://github.com/ziyangwang007/TriConvUNeXt .

7.
J Med Chem ; 67(8): 6726-6737, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38570733

RESUMEN

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.


Asunto(s)
Quinasas Ciclina-Dependientes , Ratones Endogámicos BALB C , Animales , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Humanos , Ratones , Masculino , Simulación del Acoplamiento Molecular , Diseño de Fármacos , Distribución Tisular , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Radiofármacos/química , Radiofármacos/farmacocinética , Línea Celular Tumoral
8.
Eur J Drug Metab Pharmacokinet ; 49(3): 295-316, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38635015

RESUMEN

Because of their high specificity, high affinity, and targeting, antibody drugs have been widely used in the treatment of many diseases and have become the most favored new drugs for research in the world. However, some antibody drugs (such as small-molecule antibody fragments) have a short half-life and need to be administered frequently, and are often associated with injection-site reactions and local toxicities during use. Increasing attention has been paid to the development of antibody drugs that are long-acting and have fewer side effects. This paper reviews existing strategies to achieve long-acting antibody drugs, including modification of the drug structure, the application of drug delivery systems, and changing their administration route. Among these, microspheres have been studied extensively regarding their excellent tolerance at the injection site, controllable loading and release of drugs, and good material safety. Subcutaneous injection is favored by most patients because it can be quickly self-administered. Subcutaneous injection of microspheres is expected to become the focus of developing long-lasting antibody drug strategies in the near future.


Asunto(s)
Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Microesferas , Humanos , Sistemas de Liberación de Medicamentos/métodos , Animales , Inyecciones Subcutáneas , Anticuerpos/administración & dosificación , Semivida , Vías de Administración de Medicamentos , Liberación de Fármacos
9.
Biomimetics (Basel) ; 9(4)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38667237

RESUMEN

In this paper, we proposed a miniature quadrupedal piezoelectric robot with a mass of 1.8 g and a body length of 4.6 cm. The robot adopts a novel spatial parallel mechanism as its transmission. Each leg of the robot has two degrees of freedom (DOFs): swing and lift. The trajectory necessary for walking is achieved by the appropriate phasing of these two DOFs. A new manufacturing method for piezoelectric actuators was developed. During the stacking process, discrete patterned PZT pieces are used to avoid dielectric failure caused by laser cutting. Copper-clad FR-4 is used as the solder pad instead of copper foil, making the connection between the pad and the actuator more reliable. The lift powertrain of the robot was modeled and the link length of the powertrain was optimized based on the model. The maximum output force of each leg can reach 26 mN under optimized design parameters, which is 1.38 times the required force for successful walking. The frequency response of the powertrain was measured and fitted to the second-order system, which enabled increased leg amplitudes near the powertrain resonance of approximately 70 Hz with adjusted drive signals. The maximum speed of the robot without load reached 48.66 cm/s (10.58 body lengths per second) and the payload capacity can reach 5.5 g (3.05 times its mass) near the powertrain resonance.

10.
J Sci Food Agric ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38483173

RESUMEN

BACKGROUND: The accurate recognition and early warning for plant diseases and pests are a prerequisite of intelligent prevention and control for plant diseases and pests. As a result of the phenotype similarity of the hazarded plant after plant diseases and pests occur, as well as the interference of the external environment, traditional deep learning models often face the overfitting problem in phenotype recognition of plant diseases and pests, which leads to not only the slow convergence speed of the network, but also low recognition accuracy. RESULTS: Motivated by the above problems, the present study proposes a deep learning model EResNet-support vector machine (SVM) to alleviate the overfitting for the recognition and classification of plant diseases and pests. First, the feature extraction capability of the model is improved by increasing feature extraction layers in the convolutional neural network. Second, the order-reduced modules are embedded and a sparsely activated function is introduced to reduce model complexity and alleviate overfitting. Finally, a classifier fused by SVM and fully connected layers are introduced to transforms the original non-linear classification problem into a linear classification problem in high-dimensional space to further alleviate the overfitting and improve the recognition accuracy of plant diseases and pests. The ablation experiments further demonstrate that the fused structure can effectively alleviate the overfitting and improve the recognition accuracy. The experimental recognition results for typical plant diseases and pests show that the proposed EResNet-SVM model has 99.30% test accuracy for eight conditions (seven plant diseases and one normal), which is 5.90% higher than the original ResNet18. Compared with the classic AlexNet, GoogLeNet, Xception, SqueezeNet and DenseNet201 models, the accuracy of the EResNet-SVM model has improved by 5.10%, 7%, 8.10%, 6.20% and 1.90%, respectively. The testing accuracy of the EResNet-SVM model for 6 insect pests is 100%, which is 3.90% higher than that of the original ResNet18 model. CONCLUSION: This research provides not only useful references for alleviating the overfitting problem in deep learning, but also a theoretical and technical support for the intelligent detection and control of plant diseases and pests. © 2024 Society of Chemical Industry.

11.
ACS Appl Mater Interfaces ; 16(13): 16809-16819, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38502907

RESUMEN

Polymers/polymer matrix composites possessing low dielectric constants (low-k polymer dielectrics) contribute to the advance of electronics, for instance, microprocessor chips, mobile phone antennas, and data communication terminals. However, the intrinsic long-chain structural characteristic results in poor thermal conductivities, which draw heat accumulation and undermine the outstanding low-k performance of polymers. Herein, multisource free-volume effects that combine two novel kinds of extra free volume with the known in-cage free volume of polyhedral oligomeric silsesquioxanes (POSSs) are discussed to reduce the capacity for dielectric constant reduction. The multisource free-volume effects of POSSs are associated with the thermal conductive network formed by the hexagonal boron nitride (BN) in the polymer matrix. The results show a decent balance between low-k performance (dielectric constant is 2.08 at 1 MHz and 1.98 at 10 GHz) and thermal conductivity (0.555 W m-1 K-1, 4.91 times the matrix). The results provide a new idea to maximize the free-volume effects of POSSs to optimize dielectric properties together with other desired performances for the dielectrics.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38511513

RESUMEN

Significance: As an essential procedure, wound care comes with acute pain, which is short but high in intensity, causing patients to fear and affecting subsequent treatment. Nitrous oxide (N2O) is used to relieve pain related to wound care; however, evidence regarding its application is conflicting. Thus, this systematic review and meta-analysis was performed to evaluate the efficacy of N2O in wound care-related pain. Recent Advances: Randomized controlled trials that investigated the effect of N2O in adults undergoing wound care were systematically searched from PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov up to February 2023. The primary outcome was the pain score. Secondary outcomes included patients' satisfaction and side effects. Critical Issues: Through screening the 265 identified articles, seven and six studies were finally included in the systematic review and meta-analysis, respectively. Pooled analysis suggested that there was no significant difference in reducing wound care-related pain between the N2O group and the control group (mean difference [MD], -0.02, 95% confidence interval [CI], -1.46, 1.42; p = 0.98, I2 = 96%). Subgroup analyses indicated that there was a significant difference in favor of N2O for burns, not for ulcers, and N2O was superior to oxygen and similar to topical or intravenous anesthesia. There was no significant difference in patients' satisfaction or the incidence of side effects between groups. Future Directions: This review suggests that N2O might be effective for pain management in patients undergoing wound care. Caution must be taken when interpreting these results due to the high risk of biased methods in the included studies.

13.
Ying Yong Sheng Tai Xue Bao ; 35(1): 237-246, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38511461

RESUMEN

Building a scientific and reasonable ecological network is the key for optimizing the pattern of territorial development and protection, and is of great significance for ensuring regional ecological security and promoting the virtuous cycle of ecosystems. In previous studies, nodal attack method (destruction of ecological source area) was often used in the "robustness" evaluation of ecological networks. Actually, the ecological corridor is more fragile than the source area, and thus the nodal attack method is not reasonable. In this study, taking Jiuquan City as the research area, based on the circuit model to construct the ecological network, we carried out the topology optimization of ecological network by using three strategies (random edge increase, node degree and priority edge increase with low node intermedium number) in complex network theory. We compared and analyzed the "robustness" of ecological network before and after optimization by constructing edge attack strategy, and selected the best network optimization strategy. The results showed that 65 ecological source areas were identified in Jiuquan City, with a total area of 20275.15 km2, and that grassland accounted for 89.5% of the source area. We identified 179 ecological corridors with a total length of 6387.16 km, 158 ecological barrier points with a total area of 1385.5 km2. The unused land accounted for 92.2% of the total barrier points area. We identified 63 ecological pinch points, mainly concentrated in the source edge and corridor intersection. Among them, the spatial distribution of 11 barrier points and pinch points was consistent, which was the key area to be repaired in ecological network optimization. The three optimization strategies had significantly improved the stability of ecological network in Jiuquan City. The relative size of the maximum connected subgraph and the edge connected rate of the ecological network of the optimization strategy of adding edges according to degree were all the most stable under random attack mode and deliberate attack mode, which was the best optimization scheme for ecological network in Jiuquan City.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Ciudades , China , Ecología
14.
Sleep Biol Rhythms ; 22(1): 103-111, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38476857

RESUMEN

The 8-item Youth Self-rated Insomnia Scale (YSIS) was developed to assess insomnia severity in the past month among youths. The YSIS has satisfactory psychometric properties in the general adolescent population. This study examined psychometric properties of the YSIS in a large sample of adolescent psychiatric patients. A total of 536 patients aged 10-19 years were consecutively recruited from the outpatient department of Shandong Mental Health Center between December 2021 and March 2022. Patients completed a structured questionnaire consisting of the YSIS scale and questions about sleep duration, nightmares, psychiatric history, depression, psychiatric and sleep medications, and demographics. Patients were diagnosed following the ICD-10 criteria. Of the participants, the mean age was 15.30 years (SD = 1.95), 61.0% were female, 60.9% were diagnosed with mood disorders, 65.7% were on antidepressants, and 49.0% were on anxiolytics or hypnotics. The mean YSIS score was 22.6 (SD = 8.07). Coefficient omega was 0.84. Exploratory factor analysis revealed one factor and two correlated residuals. The YSIS scores were significantly correlated with depression scores (r = 0.68) and significantly increased with sleep onset latency, short sleep duration, nightmare frequency, and sleep medication use. The YSIS demonstrated satisfactory internal consistency reliability, construct validity, and criteria-related validity in adolescent psychiatric patients. The YSIS appears to be a reliable and valid scale for measuring insomnia severity in adolescent psychiatric patients.

15.
Curr Pharm Des ; 30(3): 215-229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38532341

RESUMEN

BACKGROUND: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.


Asunto(s)
Medicamentos Herbarios Chinos , Psoriasis , Animales , Ratones , Farmacología en Red , Simulación del Acoplamiento Molecular , Piel , Inflamación , Medicina Tradicional China
16.
Sci Rep ; 14(1): 7548, 2024 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555283

RESUMEN

The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein-protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the 'EA anti-RV target-pathway network' was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1ß (IL-1ß), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1ß-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS → TRP), 220 (CYS → TYR), and 220 (CYS → PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR → TYR), 136 (THR → PHE), and 136 (THR → TRP). The Δaffinity of TNF-α was highest in 150 (VAL → TRP), 18 (ALA → GLU), and 144 (PHE → GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways.


Asunto(s)
Medicamentos Herbarios Chinos , Rotavirus , Factor de Necrosis Tumoral alfa , Ácido Elágico/farmacología , Interleucina-4 , Resonancia por Plasmón de Superficie , Receptor Toll-Like 4 , Factor de Crecimiento Epidérmico , Farmacología en Red , Simulación del Acoplamiento Molecular , Biología Computacional , Albúminas
17.
Cell Death Dis ; 15(3): 196, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459004

RESUMEN

Cancer metabolism mainly includes carbohydrate, amino acid and lipid metabolism, each of which can be reprogrammed. These processes interact with each other to adapt to the complicated microenvironment. Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation, which is morphologically different from apoptosis, necrosis, necroptosis, pyroptosis, autophagy-dependent cell death and cuprotosis. Cancer metabolism plays opposite roles in ferroptosis. On the one hand, carbohydrate metabolism can produce NADPH to maintain GPX4 and FSP1 function, and amino acid metabolism can provide substrates for synthesizing GPX4; on the other hand, lipid metabolism might synthesize PUFAs to trigger ferroptosis. The mechanisms through which cancer metabolism affects ferroptosis have been investigated extensively for a long time; however, some mechanisms have not yet been elucidated. In this review, we summarize the interaction between cancer metabolism and ferroptosis. Importantly, we were most concerned with how these targets can be utilized in cancer therapy.


Asunto(s)
Ferroptosis , Neoplasias , Humanos , Neoplasias/genética , Apoptosis , Necrosis , Peroxidación de Lípido , Aminoácidos , Microambiente Tumoral
18.
Gen Psychiatr ; 37(1): e101387, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38390240
19.
Mol Carcinog ; 63(4): 701-713, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38411346

RESUMEN

Thyroid cancer (TC) is one of the most common endocrine tumors worldwide. Sciellin (SCEL) is involved in various disease processes, including burn wound healing and neutrophil extracellular traps (NETs); it is highly expressed in TC. However, its biological impact on TC and related mechanisms remain unclear. This study aimed to investigate the effect of SCEL on the function of human TC cell lines B-CPAP and OCUT-2C (cancer cell lines with BRAF V600E mutations). Analyses of data sets and clinical samples revealed enhanced expression of SCEL in TC than in adjacent normal tissue. SCEL knockout suppresses proliferation and cell cycle progression in TC cells, and these results were reversed by the upregulated SCEL expression in TC. SCEL knockout inhibited tumor development in xenograft mouse models. Western blot (WB) demonstrated that the expression of p-JAK2 and p-STAT3 was reduced in SCEL-knockdown TC. These results suggest that SCEL plays a key role in TC progression through the JAK2-STAT3 pathway. Therefore, SCEL can be considered a potential diagnostic biomarker and therapeutic target for TC.


Asunto(s)
Neoplasias de la Tiroides , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo , Transducción de Señal , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología
20.
Int J Mol Sci ; 25(4)2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38397108

RESUMEN

The conifer Taxodium hybrid 'Zhongshanshan' (T. hybrid 'Zhongshanshan') is characterized by rapid growth, strong stress resistance, and high ornamental value and has significant potential for use in afforestation, landscaping, and wood production. The main method of propagating T. hybrid 'Zhongshanshan' is tender branch cutting, but the cutting rooting abilities of different T. hybrid 'Zhongshanshan' clones differ significantly. To explore the causes of rooting ability differences at a molecular level, we analyzed the transcriptome data of cutting base and root tissues of T. hybrid 'Zhongshanshan 149' with a rooting rate of less than 5% and T. hybrid 'Zhongshanshan 118' with rooting rate greater than 60%, at the developmental time points in this study. The results indicated that differentially expressed genes between the two clones were mainly associated with copper ion binding, peroxidase, and oxidoreductase activity, response to oxidative stress, phenylpropanoid and flavonoid biosynthesis, and plant hormone signal transduction, among others. The expression pattern of ThAP2 was different throughout the development of the adventitive roots of the two clone cuttings. Therefore, this gene was selected for further study. It was shown that ThAP2 was a nuclear-localized transcription factor and demonstrated a positive feedback effect on rooting in transgenic Nicotiana benthamiana cuttings. Thus, the results of this study explain the molecular mechanism of cutting rooting and provide candidate gene resources for developing genetic breeding strategies for optimizing superior clones of T. hybrid 'Zhongshanshan'.


Asunto(s)
Taxodium , Taxodium/genética , Fitomejoramiento , Transcriptoma , Reguladores del Crecimiento de las Plantas/metabolismo , Regulación de la Expresión Génica , Raíces de Plantas/metabolismo
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