Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 268
Filtrar
1.
J Virol ; 98(3): e0168623, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38376196

RESUMO

The porcine reproductive and respiratory syndrome virus (PRRSV) can lead to severe reproductive problems in sows, pneumonia in weaned piglets, and increased mortality, significantly negatively impacting the economy. Post-translational changes are essential for the host-dependent replication and long-term infection of PRRSV. Uncertainty surrounds the function of the ubiquitin network in PRRSV infection. Here, we screened 10 deubiquitinating enzyme inhibitors and found that the ubiquitin-specific proteinase 1 (USP1) inhibitor ML323 significantly inhibited PRRSV replication in vitro. Importantly, we found that USP1 interacts with nonstructural protein 1ß (Nsp1ß) and deubiquitinates its K48 to increase protein stability, thereby improving PRRSV replication and viral titer. Among them, lysine at position 45 is essential for Nsp1ß protein stability. In addition, deficiency of USP1 significantly reduced viral replication. Moreover, ML323 loses antagonism to PRRSV rSD16-K45R. This study reveals the mechanism by which PRRSV recruits the host factor USP1 to promote viral replication, providing a new target for PRRSV defense.IMPORTANCEDeubiquitinating enzymes are critical factors in regulating host innate immunity. The porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1ß (Nsp1ß) is essential for producing viral subgenomic mRNA and controlling the host immune system. The host inhibits PRRSV proliferation by ubiquitinating Nsp1ß, and conversely, PRRSV recruits the host protein ubiquitin-specific proteinase 1 (USP1) to remove this restriction. Our results demonstrate the binding of USP1 to Nsp1ß, revealing a balance of antagonism between PRRSV and the host. Our research identifies a brand-new PRRSV escape mechanism from the immune response.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Animais , Feminino , Endopeptidases/genética , Peptídeo Hidrolases/metabolismo , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Suínos , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral
2.
Small ; 20(4): e2305877, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37718437

RESUMO

The precise design of low-cost, efficient, and definite electrocatalysts is the key to sustainable renewable energy. The urea oxidation reaction (UOR) offers a promising alternative to the oxygen evolution reaction for energy-saving hydrogen generation. In this study, by tuning the lattice expansion, a series of M-FeNi layered double hydroxides (M-FeNi LDHs, M: Mo, Mn, V) with excellent UOR performance are synthesized. The hydrolytic transformation of Fe-MIL-88A is assisted by urea, Ni2+ and high-valence metals, to form a hollow M-FeNi LDH. Owing to the large atomic radius of the high-valence metal, lattice expansion is induced, and the electronic structure of the FeNi-LDH is regulated. Doping with high-valence metal is more favorable for the formation of the high-valence active species, NiOOH, for the UOR. Moreover, the hollow spindle structure promoted mass transport. Thus, the optimal Mo-FeNi LDH showed outstanding UOR electrocatalytic activity, with 1.32 V at 10 mA cm-2 . Remarkably, the Pt/C||Mo-FeNi LDH catalyst required a cell voltage of 1.38 V at 10 mA·cm-2 in urea-assisted water electrolysis. This study suggests a new direction for constructing nanostructures and modulating electronic structures, which is expected to ultimately lead to the development of a class of auxiliary electrocatalysts.

3.
Phys Rev Lett ; 132(1): 014002, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38242657

RESUMO

Multicomponent droplets are pertinent to diverse applications ranging from 3D printing to fabrication of electronic devices to medical diagnostics and are typically inherent with the occurrence of the phase transition in the manifestation of evaporation and solidification. Indeed, the versatile transformations and fascinating morphologies of the droplets have been identified, which primarily arise from the evaporation-induced flow. Here, we report the self-lifting behavior of a frozen binary droplet, resulting in a nearly doubling in height, in a fashion that defies against the gravitational effect. This counterintuitive observation is attributed to an internal solutal Marangoni flow up to 1 mm/s, which is driven by the enriched solute concentration locally in the vicinity of the solidification front. Moreover, we perform theoretical analysis by incorporating the propagation of solidification front, and the calculated spatiotemporal evolution of droplet shape agrees with experiments excellently. The effects of several key physical parameters on self-lifting are elucidated quantitatively, providing guidance to control the self-lifting. These results will further advance our understanding of underlying physicochemical hydrodynamics in the multicomponent liquid systems subjected to heat transfer and phase change, consequently shedding light on the relevant technological applications.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38713298

RESUMO

PURPOSE: The unsatisfactory efficacy of PD-L1 antibodies in glioblastoma (GBM) is largely due to the temporal and spatial heterogeneity of PD-L1 expression. Molecular imaging can enhance understanding of the tumor immune microenvironment and guide immunotherapy. However, highly sensitive imaging agents capable of effectively visualizing PD-L1 heterogeneity are limited. This study introduces a novel PET tracer, offering improved imaging of PD-L1 heterogeneity in GBM xenografts, with a comparative analysis to [18F]AlF-NOTA-WL12. METHODS: [18F]AlF-NOTA-PCP2 was synthesized with high purity and its affinity for PD-L1 was characterized using surface plasmon resonance (SPR) and cell binding assays. Its specificity for PD-L1 was evaluated both in vitro using various cell lines and in vivo with GBM xenograft models in NOD/SCID mice. PET/CT imaging was conducted to evaluate the tracer's biodistribution, pharmacokinetics, and ability to quantify tumoral spatial heterogeneity of PD-L1 expression. A focused comparative analysis between [18F]AlF-NOTA-PCP2 and [18F]AlF-NOTA-WL12 was conducted, examining binding affinity, biodistribution, pharmacokinetics, and imaging effectiveness in GBM xenografts. Additionally, human radiation dosimetry estimates compared the safety profiles of both tracers. RESULTS: [18F]AlF-NOTA-PCP2 demonstrated high radiochemical purity (> 95%) and a strong affinity for PD-L1, comparable to [18F]AlF-NOTA-WL12. In vitro and in vivo studies confirmed its specificity for PD-L1, with increased uptake in PD-L1 expressing cells and tumors. Toxicological profiles indicated no significant abnormalities in serum biochemical indicators or major organ tissues. MicroPET/CT imaging showed [18F]AlF-NOTA-PCP2's effectiveness in visualizing PD-L1 expression levels and spatial heterogeneity in GBM xenografts. Comparative studies revealed [18F]AlF-NOTA-PCP2's improved pharmacokinetic properties, including higher tumor-to-blood ratios and lower nonspecific liver uptake, as well as reduced radiation exposure compared to [18F]AlF-NOTA-WL12. CONCLUSION: [18F]AlF-NOTA-PCP2 distinguishes itself as an exceptionally sensitive PET/CT tracer, adept at non-invasively and accurately quantifying PD-L1 expression and its spatial heterogeneity in tumors, especially in GBM. Its favorable pharmacokinetic properties, safety profile, and high affinity for PD-L1 highlight its potential for enhancing the precision of cancer immunotherapy and guiding individualized treatment strategies. While promising, its clinical translation, especially in brain imaging, necessitates further validation in clinical trials.

5.
Mol Pharm ; 21(3): 1515-1525, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38291578

RESUMO

Immune checkpoint inhibitors (ICIs) are a powerful treatment modality for various types of cancer. The effectiveness of ICIs is intimately connected to the binding status of antibodies to receptors. However, validated means to accurately evaluate target specificity and predict antibody efficacy in vivo are lacking. A novel peptide-based probe called Al[18F]F-NOTA-PCP1 was developed and validated for its specificity to PD-L1 in A549, U87MG, GL261, and GL261-iPDL1 cell lines, as well as in xenograft models. Then the probe was used in PET/CT scans to determine the binding status of PD-L1 antibodies (atezolizumab, avelumab, and durvalumab) in U87MG xenograft model mice. Moreover, Al[18F]F-NOTA-PCP1 was used to evaluate the impact of different treatment times and doses. Al[18F]F-NOTA-PCP1 PET/CT can be used to evaluate the interaction between PD-L1 and antibodies to determine the effectiveness of immunotherapy. By quantifying target engagement, the probe has the potential to predict the efficacy of immunotherapy and optimize the dose and treatment schedules for PD-L1 immunotherapy. This imaging agent could be a valuable tool in guiding personalized treatment strategies and improving cancer patient outcomes.


Assuntos
Compostos Heterocíclicos com 1 Anel , Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Peptídeos
6.
Drug Resist Updat ; 71: 101005, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37647746

RESUMO

AIMS: Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer. METHODS: The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo. RESULTS: CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells. CONCLUSIONS: Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Animais , Camundongos , Neoplasias Pancreáticas/tratamento farmacológico , Cardiotoxicidade , Membrana Celular , Resistência a Múltiplos Medicamentos , Neoplasias Pancreáticas
7.
BMC Med Educ ; 24(1): 404, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605290

RESUMO

OBJECTIVE: The present study aims to explore the influencing factors of the scientific fitness literacy of nurses and provide a strategic basis for literacy improvement. METHODS: A questionnaire on the influencing factors of scientific fitness literacy of nurses was designed by the group conducting the present study; the questionnaire was based on the socioecology model and the questionnaire preparation method. The general data questionnaire and the questionnaire on the influencing factors of scientific fitness literacy of nurses were adopted to investigate nurses in tertiary hospitals in order to analyze and discuss the influencing factors of their scientific fitness literacy. RESULTS: (1) The questionnaire on the influencing factors of the scientific fitness literacy of nurses comprised five dimensions and 36 items. The overall item-content validity index was 0.833-1.000, the scale-content validity index was 0.974, and the overall Cronbach's α coefficient was 0.955; (2) the results of the pairwise Pearson correlation analysis showed that all five dimensions were positively correlated with the scientific fitness literacy of nurses; and (3) the results of the multiple linear regression analysis revealed that five dimensions, as well as the existence of exercise habits in daily life, had a significant impact on the scientific fitness literacy of nurses (P < 0.001). CONCLUSION: The factors influencing the scientific fitness literacy of nurses involved all levels of the socioecological system. The methods of improving the awareness of the scientific fitness of nurses and providing opportunities for scientific fitness activities via the hospital played a critical role in literacy improvement. However, the lack of professional guidance and an atmosphere promoting scientific fitness might hinder literacy improvement.


Assuntos
Letramento em Saúde , Humanos , Reprodutibilidade dos Testes , Letramento em Saúde/métodos , Centros de Atenção Terciária , Inquéritos e Questionários
8.
J Environ Manage ; 365: 121497, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38897077

RESUMO

Water diversion can effectively alleviate water resource shortages and improve water environmental conditions, while also causing unknown ecological consequences, in particular, the assembly mechanism of zooplankton communities in the affected areas will become more complex after long-term water transfer. Taking Nansi Lake, the second largest impounded lake along the eastern route of China's South to North Water Diversion Project (SNWDP), as an example, the composition and diversity of zooplankton communities in the lake area and estuaries during the water diversion period (WDP) and non-water diversion period (NWDP) were studied. The potential assembly process of zooplankton communities was further explored, and the stability of communities in different regions during different periods was compared. The related results indicated that the changes in water quality conditions induced by water diversion had a relatively weak impact on the zooplankton communities. In the assembly mechanism of zooplankton communities, stochastic process played a more important role during both WDP or NWDP, and the proportion of deterministic process was relatively higher during NWDP, which may be related to the greater role of total nitrogen (TN) in the assembly of the zooplankton communities. The network analysis and cohesion calculation results showed that the stability of the zooplankton communities in the lake area sites was higher than that in the estuary sites, and the stability during NWDP was higher than that during WDP. In sum, the stability of zooplankton communities displayed a degree of change affected by water diversion activities, but the community assembly was not significantly influenced by the water quality fluctuations after about relatively long-term water diversion. This study provides an in-depth understanding of the ecological effects of water diversion on the biological communities in the affected lake, which is beneficial to the management and regulation of long-term water diversion projects.

9.
Small ; 19(11): e2207044, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36642802

RESUMO

Precise design of low-cost, efficient and definite electrocatalysts is the key to sustainable renewable energy. Herein, this work develops a targeted-anchored and subsequent spontaneous-redox strategy to synthesize nickel-iron layered double hydroxide (LDH) nanosheets anchored with monodispersed platinum (Pt) sites (Pt@LDH). Intermediate metal-organic frameworks (MOF)/LDH heterostructure not only provides numerous confine points to guarantee the stability of Pt sites, but also excites the spontaneous reduction for PtII . Electronic structure, charge transfer ability and reaction kinetics of Pt@LDH can be effectively facilitated by the monodispersed Pt moieties. As a result, the optimized Pt@LDH that with the 5% ultra-low content Pt exhibits the significant increment in electrochemical water splitting performance in alkaline media, which only afford low overpotentials of 58 mV at 10 mA cm-2 for hydrogen evolution reaction (HER) and 239 mV at 10 mA cm-2 for oxygen evolution reaction (OER), respectively. In a real device, Pt@LDH can drive an overall water-splitting at low cell voltage of 1.49 V at 10 mA cm-2 , which can be superior to most reported similar LDH-based catalysts. Moreover, the versatility of the method is extended to other MOF precursors and noble metals for the design of ultrathin LDH supported monodispersed noble metal electrocatalysts promoting research interest in material design.

10.
Microb Pathog ; 176: 106001, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36682670

RESUMO

The zoonotic pathogen avian influenza A H5N8 causes enormous economic losses in the poultry industry and poses a serious threat to the public health. Here, we report the first systematic review and meta-analysis of the worldwide prevalence of birds. We filtered 45 eligible articles from seven databases. A random-effects model was used to analyze the prevalence of H5N8 in birds. The pooled prevalence of H5N8 in birds was 1.6%. In the regions, Africa has the highest prevalence (8.0%). Based on the source, village (8.3%) was the highest. In the sample type, the highest prevalence was organs (79.7%). In seasons, the highest prevalence was autumn (28.1%). The largest prevalence in the sampling time was during 2019 or later (7.0%). Furthermore, geographical factors also were associated with the prevalence. Therefore, we recommend site-specific prevention and control tools for this strain in birds and enhance the surveillance to reduce the spread of H5N8.


Assuntos
Vírus da Influenza A Subtipo H5N8 , Influenza Aviária , Influenza Humana , Animais , Humanos , Influenza Aviária/epidemiologia , Animais Selvagens , Prevalência , Aves , Influenza Humana/epidemiologia , Filogenia , Surtos de Doenças/veterinária
11.
Physiol Plant ; 175(6): e14117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148215

RESUMO

Nonstructural carbohydrates (NSC, including soluble sugars and starch) are essential for supporting growth and survival of woody plants, and play multifunctional roles in various ecophysiological processes that are being rapidly changed by climate warming. However, it still remains unclear whether there is a consistent response pattern of NSC dynamics in woody plants to climate warming across organ types and species taxa. Here, based on a compiled database of 52 woody plant species worldwide, we conducted a meta-analysis to investigate the effects of experimental warming on NSC dynamics. Our results indicated that the responses of NSC dynamics to warming were primarily driven by the fluctuations of starch, while soluble sugars did not undergo significant changes. The effects of warming on NSC shifted from negative to positive with the extension of warming duration, while the negative warming effects on NSC became more pronounced as warming magnitude increased. Overall, our study showed the divergent responses of NSC and its components in different organs of woody plants to experimental warming, suggesting a potentially changed carbon (C) balance in woody plants in future global warming. Thus, our findings highlight that predicting future changes in plant functions and terrestrial C cycle requires a mechanism understanding of how NSC is linked to a specific global change driver.


Assuntos
Carboidratos , Plantas , Carboidratos/química , Amido , Madeira , Açúcares
12.
Nephrology (Carlton) ; 28(3): 196-207, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36576135

RESUMO

BACKGROUND: Renal tubular injury is the main feature of diabetic nephropathy (DN). We intend to investigate the function and related mechanisms of lncRNA SOX2 overlapping transcript (SOX2OT) in high glucose (HG)-induced oxidative stress and apoptosis of renal tubular epithelial cells (RTECs). METHODS: To construct diabetes models, the human kidney-2 (HK-2) cells were treated with HG (30 mM), and mice were injected with streptozotocin. The levels of intracellular and mitochondrial reactive oxygen species (ROS) were assessed by dihydroethidium staining and MitoSox staining. The cell apoptosis was assessed by flow cytometry and TUNEL staining. Levels of serum creatinine, blood urea nitrogen (BUN), Urinary ACR, and oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected by relevant kits. In addition, fluorescence in situ hybridization staining, RNA-pull down, RNA immunoprecipitation (RIP), co-immunoprecipitation (co-IP), dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) were also executed. RESULTS: Levels of SOX2OT and silent information regulator 1 (SIRT1) were down-regulated in HG-cultured HK-2 cells. Overexpressing SOX2OT reduced intracellular and mitochondrial ROS levels and cell apoptosis in vitro. Moreover, SOX2OT overexpression also reduced serum creatinine, BUN, urinary ACR, 8-OHdG, renal tubular injury markers KIM1 and NGAL, ROS levels, and cell apoptosis in vivo. In addition, SOX2OT promoted SIRT1 expression by suppressing its ubiquitination. Besides, interference with SIRT1 reversed the inhibitory effect of SOX2OT overexpression on HG-induced oxidative stress and apoptosis. Forkhead box A2 (Foxa2) levels were up-regulated in HG-cultured HK-2 cells. Foxa2 could bind to the SOX2OT promoter and suppress its expression. Furthermore, interfering with SOX2OT reversed the inhibitory effect of Foxa2 interference on HG-induced oxidative stress and apoptosis. CONCLUSION: Foxa2-mediated SOX2OT up-regulation reduced oxidative stress and apoptosis of RTECs by promoting SIRT1 expression, thus alleviating the progression of DN.


Assuntos
Nefropatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Sirtuína 1 , Animais , Humanos , Camundongos , Apoptose , Creatinina , Diabetes Mellitus , Nefropatias Diabéticas/metabolismo , Células Epiteliais/metabolismo , Glucose/farmacologia , Hibridização in Situ Fluorescente , MicroRNAs/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , RNA Longo não Codificante/genética , Sirtuína 1/metabolismo , Regulação para Cima
13.
Phytother Res ; 37(12): 5787-5802, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37580045

RESUMO

Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.


Assuntos
Diabetes Mellitus Experimental , Ferroptose , Doenças do Sistema Nervoso Periférico , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Sirtuína 1/metabolismo , Células de Schwann , Glucose/metabolismo
14.
Chem Biodivers ; 20(7): e202300753, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37269045

RESUMO

Chemical investigation of the deep-sea-derived fungus Hypocrea sp. ZEN14 afforded a new 3α-hydroxy steroidal lactone, hyposterolactone A (1) and 25 known secondary metabolites (2-26). The structure of the new compound was established by detailed spectroscopic analysis, electronic circular dichroism (ECD) calculation as well as a J-based configuration analysis. Compound 10 showed potent cytotoxicity against Huh7 and Jurkat cells with IC50 values of 1.4 µM and 6.7 µM, respectively.


Assuntos
Hypocrea , Trichoderma , Humanos , Lactonas/farmacologia , Esteroides/farmacologia , Estrutura Molecular , Dicroísmo Circular
15.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37511165

RESUMO

The affinity of peptides is a crucial factor in studying peptide-protein interactions. Despite the development of various techniques to evaluate peptide-receptor affinity, the results may not always reflect the actual affinity of the peptides accurately. The current study provides a free tool to assess the actual peptide affinity based on virtual docking data. This study employed a dataset that combined actual peptide affinity information (active and inactive) and virtual peptide-receptor docking data, and different machine learning algorithms were utilized. Compared with the other algorithms, the random forest (RF) algorithm showed the best performance and was used in building three RF models using different numbers of significant features (four, three, and two). Further analysis revealed that the four-feature RF model achieved the highest Accuracy of 0.714 in classifying an independent unknown peptide dataset designed with the PEDV spike protein, and it also revealed overfitting problems in the other models. This four-feature RF model was used to evaluate peptide affinity by constructing the relationship between the actual affinity and the virtual docking scores of peptides to their receptors.


Assuntos
Algoritmos , Algoritmo Florestas Aleatórias , Peptídeos , Aprendizado de Máquina
16.
Mol Med ; 28(1): 55, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562651

RESUMO

BACKGROUND: The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). METHODS: A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests. RESULTS: The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. CONCLUSIONS: In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.


Assuntos
Neoplasias Nasofaríngeas , Fosfatidilinositol 3-Quinases , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética
17.
Inorg Chem ; 61(28): 10774-10780, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35796528

RESUMO

HIV-1 reverse transcriptase (RT) inhibitors are fundamental to the discovery and development of anti-HIV drugs. Their main target is RT, and only a tiny number of them can bind to viral RNA. In this paper, five new Zn(II) porphyrin compounds were developed with different characters. ZnTPP4 has both the appearance and the functions of a scorpion with a rigid tail and stinger to selectively hunt HIV-1 TAR RNA based on the molecular recognition of hydrogen bonds, a fierce chelicera to bite RNA by metal coordination, mighty pedipalps to grasp the bound RNA by supramolecular inclusion, and a broad body maintaining the configuration of each functional area so that they can cooperate with each other and providing accommodation space for the bound RNA. This tetrafunctional Zn(II) porphyrin is relatively nontoxic to normal cells and can produce sensitive responses for RNA. Moreover, this work offers practical construction methodologies for medication of AIDS and other diseases closely related to RT like EBOV and SARS-CoV-2.


Assuntos
COVID-19 , HIV-1 , Metaloporfirinas , Inibidores da Transcriptase Reversa , Transcriptase Reversa do HIV/antagonistas & inibidores , Humanos , Metaloporfirinas/farmacologia , RNA Viral , Inibidores da Transcriptase Reversa/química , Inibidores da Transcriptase Reversa/farmacologia , SARS-CoV-2
18.
Inorg Chem ; 61(8): 3553-3562, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35148476

RESUMO

High storage capacity, high separation selectivity, and high structure stability are essential for an idea gas adsorbent. However, it is not easy to achieve all three at the same time, even for the promising metal-organic framework (MOF) adsorbents. We demonstrate herein that robust [Sc3O]-organic frameworks could be regulated by a micropore combination strategy for high-performance acetylene adsorption. Under the same solvent system with formic acid as a modulator, similar tritopic ligands extend [Sc3O(COO)6] trigonal-prismatic clusters to generate SNNU-5-Sc and SNNU-150-Sc adsorbents. Notably, the two Sc-MOFs can keep their architectures over 24 h in water at different pH values (2-12) or at 90 °C. Modulated by the linker symmetry, the final stacking metal-organic polyhedral cages produce open window sizes of about 10 Å for SNNU-5-Sc and 5 Å + 7 Å for SNNU-150-Sc. Due to such micropore combinations, SNNU-5-Sc exhibits a top-level C2H2 uptake of 211.2 cm3 g-1 (1 atm and 273 K) and SNNU-150-Sc shows high C2H2/CH4, C2H2/C2H4, and C2H2/CO2 selectivities of 80.65, 4.03, and 8.19, respectively, under ambient conditions. Dynamic breakthrough curves obtained on a fixed-bed column and grand canonical Monte Carlo (GCMC) simulations further support their prominent acetylene storage and purification performance. High framework stability, storage capacity, and separation selectivity make SNNU-5-Sc and SNNU-150-Sc ideal acetylene adsorbents in practical applications.

19.
Cell Mol Biol (Noisy-le-grand) ; 68(9): 63-67, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36905273

RESUMO

The purpose of this experiment was to observe the biological effect and mechanism of miR-10b on cervical cancer (CC) rats. For this purpose, the rat model of CC was established and divided into three groups (Inhibitors/ Mimics/Control). The miR-10b transfection efficiency was analyzed via RT-PCR in cervical tissues in each group. The content of CD3+, CD4+, and CD8+ was detected. The levels of IL-8, TNF-ß, IL-6, (CAT, SOD, and MDA were determined via ELISA, and the apoptosis of cervical tissues was detected usingTUNEL assay. The expressions of Caspase-3, Bcl-2, and the mTOR/P70S6K pathway genes and proteins were detected by qRT-PCR and Western blotting. Results showed that miR-10b was significantly increased in the Mimics group and decreased in the Inhibitors group. The content of IL-8, TNF-ß, IL-6, CAT and MDA was raised, while that of SOD notably declined in the Inhibitors group. There were remarkably more apoptotic cells in the Mimics group, dominated by gliocytes, and fewer apoptotic cells in the Inhibitors group, with increased content of CD3+, CD4+ and CD8+. The Bcl-2, mTOR, and P70S6K mRNA expressions in the Inhibitors group were up-regulated than those in the other two groups, and the Caspase-3 gene in the Mimics group was increased and close to that in the control group. In the Mimics group, the mTOR and P70S6K protein were remarkably lower than those in the Inhibitors group. In conclusion, miR-10b can inhibit the occurrence and development of CC in rats by suppressing mTOR/P70S6K signaling, reducing the level of inflammation and oxidative stress, and increasing the level of immune factors.


Assuntos
MicroRNAs , Transdução de Sinais , Neoplasias do Colo do Útero , Animais , Feminino , Ratos , Apoptose/genética , Caspase 3/metabolismo , Interleucina-6/farmacologia , Interleucina-8 , Linfotoxina-alfa/farmacologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/farmacologia , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
Int J Hyperthermia ; 39(1): 379-389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35188057

RESUMO

PURPOSE: Thermal ablation (TA) is a minimally invasive treatment method for symptomatic benign thyroid nodules (BTNs). This study aimed to evaluate the value of TA by comparing the efficacy, safety, and patient satisfaction with conventional/open thyroidectomy (ConT) and endoscopic thyroidectomy (ET) for symptomatic BTNs. METHODS: Patients with symptomatic BTNs who underwent ConT, ET, or TA therapy between January 2018 and January 2020 were included. Pre-operation data of the two comparisons (TA vs. ConT and TA vs. ET) was balanced using propensity score matching. The technique efficacy (volume reduction ratio ≥50%), nodule disappearance, and regrowth rate were calculated after ablation. The operation and hospitalization time, medical cost, complications, post-operative symptoms, and cosmetic scores were recorded and compared. Patient satisfaction was evaluated using a telephone survey. RESULTS: After a median 19-month follow-up (range, 12-36 months), the technique efficacy rate, nodule disappearance, and regrowth rate were 93.2% (119/129), 6.8% (10/129), and 0.8% (1/129), respectively. Operation time, hospitalization time, and medical costs were less for patients in the TA group than for patients in the ConT and ET groups (all p < 0.001). The incidence of complications, post-operative symptoms, cosmetic scores, and overall satisfaction were not significantly different among groups (all p > 0.05). Post-operative hypothyroidism was less frequent in the TA group than in the ConT and ET groups (all p < 0.05). CONCLUSIONS: Compared to ConT and ET, TA has comparable efficacy, safety, and patient satisfaction and exhibits greater protection of thyroid function for the treatment of symptomatic BTNs.


Assuntos
Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Humanos , Satisfação do Paciente , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa