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The construction of supported Ir-based catalysts can effectively reduce the amount of Ir and generate a synergistic effect that enhances the oxygen evolution reaction (OER) activity and stability, making it one of the effective solutions for optimizing acidic OER catalysts. However, most reported metal oxide supports suffer from poor acid resistance and low electrical conductivity, which are critical for the OER process. Herein, we synthesized a nanosheet-like defected 1T phase-rich MoBxS2-x via a molten salt calcination process, during which the 1T phase was formed, and B was intercalated into MoS2 to protect the 1T phase structure during annealing procedure. After the wet refluxing process, IrOx clusters were uniformly deposited on the surface of MoBxS2-x to form IrOx@MoBxS2-x, which exhibited an overpotential of 168 mV at a current density of 10 mA cm-2 with an Ir loading amount of 25.8 wt %. By comparing the OER performance of IrOx@MoBxS2-x, IrOx@MoS2(Calcinated), and IrOx@MoS2, it is demonstrated that calcination and B intercalation of MoS2 can significantly increase acidic OER performance. This work digs into the application of 1T-MoS2 as an OER catalyst support, providing strategies for the phase and morphology control of 1T-MoS2.
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OBJECTIVE: To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city. METHODS: A total of 210 RhD- samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population. Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene. Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene, and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype. RESULTS: Among 210 RhD- specimens, 128 cases (60.38%) had RHD gene deletion. 27 cases had partial exons of RHD, including 2 cases with RHD*DVI.3/RHD*01N.01, 24 cases with RHD*01N.04/RHD*01N.01, and 1 case with RHD-CE(2-10)/RHD*01N.01. 55 cases had retained all of 10 exons, including 4 cases with RHD*01/RHD*01N.01, 6 cases with RHD*15/RHD*01N.01, 1 case with RHD*01W.72/RHD*01N.01, 1 case with RHD*15/RHD*01EL.01, 39 cases with RHD*01EL.01/RHD*01N.01, and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G>A mutation loci. CONCLUSION: There is polymorphism in the molecular mechanism of RhD- D gene in Wuhu blood donor population, among which RHD*01EL.01 and RHD*15 are the main variants in this region. The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.
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Doadores de Sangue , Éxons , Genótipo , Sistema do Grupo Sanguíneo Rh-Hr , Humanos , Sistema do Grupo Sanguíneo Rh-Hr/genética , Fenótipo , Povo Asiático/genética , AlelosRESUMO
Two-photon photodynamic therapy (TP-PDT) has become a major cancer treatment due to its larger tissue penetration depth, good spatial selectivity, and less damage to normal cells. In this contribution, a series of novel photosensitizer molecules (Ir-2, Ir-2-1â¼Ir-2-4) have been designed based on the experimentally demonstrated photosensitizer [Ir(ppy)2(osip)] (PF6) by fine tuning the π-conjugated structure and introducing different nitrogen-heterocyclic substituents. The electronic structures, one- and two-photon absorption spectra, triplet excited state lifetime, solvation-free energy, and photosensitizing performance were evaluated by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results suggested that the molecule Ir-2, incorporating thiophene as the π-connecting group, exhibits a higher probability of triplet state formation, enhanced two-photon absorption cross-section, and prolonged triplet state lifetime. Furthermore, the four designed nitrogen-heterocyclic complexes Ir-2-1â¼Ir-2-4 demonstrate favorable photosensitizing properties, with two-photon absorption cross-sections reaching up to 110 GM and triplet excited state lifetimes exceeding 1000 µs for Ir-2-4.
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Irídio , Nitrogênio , Fotoquimioterapia , Fótons , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Irídio/química , Irídio/farmacologia , Nitrogênio/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Teoria da Densidade Funcional , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Piridinas/química , Piridinas/farmacologia , Piridinas/síntese química , Estrutura MolecularRESUMO
PURPOSE: This study aims to assess the diagnostic efficacy of Korean Thyroid imaging reporting and data system (K-TIRADS), S-Detect software and contrast-enhanced ultrasound (CEUS) when employed individually, as well as their combined application, for the evaluation of thyroid nodules, with the objective of identifying the optimal method for diagnosing thyroid nodules. METHODS: Two hundred and sixty eight cases pathologically proven of thyroid nodules were retrospectively enrolled. Each nodule was classified according to K-TIRADS. S-Detect software was utilized for intelligent analysis. CEUS was employed to acquire contrast-enhanced features. RESULTS: The area under curve (AUC) values for diagnosing benign and malignant thyroid nodules using K-TIRADS alone, S-Detect software alone, CEUS alone, the combined application of K-TIRADS and CEUS, the combined application of S-Detect software and CEUS were 0.668, 0.668, 0.719, 0.741, and 0.759, respectively (p < 0.001). The sensitivity rate of S-Detect software was 89.9% (p < 0.001). It was the highest of the five diagnostic methods above. CONCLUSION: The utilization of S-Detect software can be served as a powerful tool for early screening. Notably, the combined utilization of S-Detect software with CEUS demonstrates superior diagnostic performance compared to employing K-TIRADS, S-Detect software, CEUS used individually, as well as the combined application of K-TIRADS with CEUS.
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The photophysical properties and luminescent mechanism of a series of tripod-type Cu(I) complexes in solution and solids were comprehensively investigated through theoretical simulations. From a microscopic perspective, the experimental phenomenon is explained: (1) The intrinsic reason for the quenching of complex 1 in solution was attributed to the significant nonradiative transition caused by structural deformation; (2) In the solid, the reduced ΔEST for complex 2 effectively facilitate reverse intersystem crossing (RISC) and improves its luminescence efficiency; (3) The enhanced performance of complex 3 in solution is attributed to that its stronger steric hindrance is advantageous to decrease not only the ΔEST but also the reorganization energy through intramolecular weak interactions. Based on complex 3, the tert-butyl substituted isomeric complex 4 was designed. Complex 4 further amplifies the advantages of 3 to further promote the RISC to make full use of excitons. Meanwhile, it has an emission wavelength of 462.6 nm, which makes it an excellent candidate for high-efficiency deep-blue TADF materials. This study provides valuable information for obtaining efficient blue phosphorescence and TADF dual-channel luminescent materials.
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OBJECTIVES: This study aims to investigate the feasibility and safety of combined anesthesia with spontaneous breathing in the operation of intertrochanteric fracture of femur in the elderly. PATIENTS AND METHODS: Between January 2020 and January 2023, a total of 141 elderly patients (45 males, 96 females; mean age: 72.5±6.8 years; range, 65 to 87 years) who underwent proximal femoral nail anti-rotation (PFNA) surgery for intertrochanteric fracture of femur were included in this single-blind, prospective, randomized-controlled study. The patients were randomly divided into three groups. Group A (experimental group) was a general anesthesia with laryngeal mask airway (LMA) group preserving spontaneous breathing, Group B (control group 1) was a general anesthesia with LMA group for mechanical ventilation, and Group C (control group 2) was a tracheal intubation anesthesia group for mechanical ventilation. The differences of related indexes among the three groups were compared. RESULTS: The mean onset time of anesthesia (6.23±1.45 vs. 12.78±2.78 vs. 13.73±2.43 min), postoperative recovery time of consciousness (8.13±0.83 vs. 11.34±0.89 vs. 12.45±0.86 min), and postoperative complete awakening time (10.45±2.34 vs. 18.87±2.56 vs. 19.62±2.93 min) were significantly shorter in Group A than in Groups B and C (p<0.05). The duration of analgesic effect was longer in Group A than in Groups B and C (p<0.05). After anesthesia, the Ramsay Sedation Scale and Visual Analog Scale (VAS) scores were significantly lower in Group A than the other groups (p<0.05). The mean Mini-Mental State Examination (MMS) scores were significantly higher in Group A than in Groups B and C (p<0.05). Hemodynamic parameters showed that blood pressure, heart rate, cardiac output, and cardiac index (CI) levels were significantly higher in Group A than the other groups (p<0.05). CONCLUSION: Our study results indicate that combined anesthesia preserving spontaneous breathing is safe and feasible in the operation of intertrochanteric fracture of femur in the elderly, with faster anesthesia recovery than the mechanical ventilation group.
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Anestesia Geral , Fraturas do Quadril , Máscaras Laríngeas , Respiração Artificial , Humanos , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Fraturas do Quadril/cirurgia , Anestesia Geral/métodos , Estudos Prospectivos , Método Simples-Cego , Respiração Artificial/métodos , Respiração , Estudos de Viabilidade , Intubação Intratraqueal/métodosRESUMO
OBJECTIVE: To investigate the nutritional content of edible medicinal materials in mountainous areas of Guizhou Province and compare the comprehensive nutritional value of different varieties. METHODS: A total of 15 kinds of edible herbs were collected from Guizhou Province. According to the national standard, direct drying method, Kjeldahl nitrogen determination method, Soxhlet extraction method, high performance liquid chromatography, inductively coupled plasma mass spectrometry and other detection method were used to determine the content of general nutrients, fat soluble vitamins, minerals and ash. According to the weight ranking of nutritional indexes in principal component analysis and membership function analysis, the quality of 9 kinds of food and drug substances and 6 kinds of Chinese medicinal materials were evaluated and ranked. RESULTS: The eigenvalues of the first 4 principal components were greater than 1, and the cumulative contribution rate was 82.32%. Compared with membership function analysis, the top 5 in comprehensive evaluation were Eucommia, Epimedium and honeysuckle, all of which were food and drug substances. The contents of calcium(851.69 mg/100 g), phosphorus(270.22 mg/100 g) and potassium(1446.48 mg/100 g) were the highest. The contents of carotene(21 963.87 µg/100 g) and vitamin E(57.82 mg/100 g) were the highest in the fat-soluble vitamins of Herbimedium. The contents of various indexes of honeysuckle were relatively high. CONCLUSION: Food and pharmaceutical substances have both medicinal value and nutritional value, and the overall nutritional benefit is higher than that of Chinese medicinal materials.
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Valor Nutritivo , China , Plantas Medicinais/química , Plantas Comestíveis/química , Análise de Alimentos , Fósforo/análise , Altitude , Medicamentos de Ervas Chinesas/análise , Minerais/análiseRESUMO
Carbon dioxide corrosion is a pervasive issue in pipelines and the petroleum industry, posing substantial risks to equipment safety and longevity. Accurate prediction of corrosion rates and severity is essential for effective material selection and equipment maintenance. This paper begins by addressing the limitations of traditional corrosion prediction methods and explores the application of machine learning algorithms in CO2 corrosion prediction. Conventional models often fail to capture the complex interactions among multiple factors, resulting in suboptimal prediction accuracy, limited adaptability, and poor generalization. To overcome these limitations, this study systematically organized and analyzed the data, performed a correlation analysis of the data features, and examined the factors influencing corrosion. Subsequently, prediction models were developed using six algorithms: Random Forest (RF), K-Nearest Neighbors (KNN), Gradient Boosting Decision Tree (GBDT), Support Vector Machine (SVM), XGBoost, and LightGBM. The results revealed that SVM exhibited the lowest performance on both training and test sets, while RF achieved the best results with R2 values of 0.92 for the training set and 0.88 for the test set. In the classification of corrosion severity, RF, LightGBM, SVM, and KNN were utilized, with RF demonstrating superior performance, achieving an accuracy of 99% and an F1-score of 0.99. This study highlights that machine learning algorithms, particularly Random Forest, offer substantial potential for predicting and classifying CO2 corrosion. These algorithms provide innovative approaches and valuable insights for practical applications, enhancing predictive accuracy and operational efficiency in corrosion management.
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In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.
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Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C18 column (2.1 × 50 mm, 1.7 µm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2 mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).
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Iridoides , Espectrometria de Massa com Cromatografia Líquida , Espectrometria de Massas em Tandem , Animais , Ratos , Iridoides/farmacocinética , Iridoides/sangue , Iridoides/química , Limite de Detecção , Modelos Lineares , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodosRESUMO
The nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed substitution reaction plays a pivotal role in the biosynthesis of nucleotide compounds. However, industrial applications are hindered by the low activity of NAMPTs. In this study, a novel dual-channel protein engineering strategy was developed to increase NAMPT activity by enhancing substrate accessibility. The best mutant (CpNAMPTY13G+Y15S+F76P) with a remarkable 5-fold increase in enzyme activity was obtained. By utilizing CpNAMPTY13G+Y15S+F76P as a biocatalyst, the accumulation of ß-nicotinamide mononucleotide reached as high as 19.94 g L-1 within 3 h with an impressive substrate conversion rate of 99.8%. Further analysis revealed that the newly generated substrate channel, formed through crack propagation, facilitated substrate binding and enhanced byproduct tolerance. In addition, three NAMPTs from different sources were designed based on the dual-channel protein engineering strategy, and the corresponding dual-channel mutants with improved enzyme activity were obtained, which proved the effectiveness and practicability of the approach.
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The use of CAR-T cells in treating solid tumors frequently faces significant challenges, mainly due to the heterogeneity of tumor antigens. This study assessed the efficacy of an acidity-targeting transition-aided universal chimeric antigen receptor T (ATT-CAR-T) cell strategy, which is facilitated by an acidity-targeted transition. Specifically, the EGFRvIII peptide was attached to the N-terminus of a pH-low insertion peptide. Triggered by the acidic conditions of the tumor microenvironment, this peptide alters its structure and selectively integrates into the membrane of solid tumor cells. The acidity-targeted transition component effectively relocated the EGFRvIII peptide across various tumor cell membranes; thus, allowing the direct destruction of these cells by EGFRvIII-specific CAR-T cells. This method was efficient even when endogenous antigens were absent. In vivo tests showed marked antigen modification within the acidic tumor microenvironment using this component. Integrating this component with CAR-T cell therapy showed high effectiveness in combating solid tumors. These results highlight the capability of ATT-CAR-T cell therapy to address the challenges presented by tumor heterogeneity and expand the utility of CAR-T cell therapy in the treatment of solid tumors.
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Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Microambiente Tumoral , Receptores de Antígenos Quiméricos/imunologia , Humanos , Animais , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Neoplasias/imunologia , Camundongos , Receptores ErbB/metabolismo , Linfócitos T/imunologia , FemininoRESUMO
Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.
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Anticorpos Biespecíficos , Complexo CD3 , Proteínas Proto-Oncogênicas p21(ras) , Linfócitos T , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/imunologia , Humanos , Animais , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/imunologia , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Camundongos , Complexo CD3/imunologia , Complexo CD3/metabolismo , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/genética , FemininoRESUMO
BACKGROUND: The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid ß-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression. METHODS: Distribution of lipids in GBC was described by LC-MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5' and 3' rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex. RESULTS: Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N6-methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination. CONCLUSIONS: LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients.
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Carnitina/análogos & derivados , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/genética , Hibridização in Situ Fluorescente , RNA , Lipídeos , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
Bile acids (BAs) constitute essential components of cholesterol metabolites that are synthesized in the liver, stored in the gallbladder, and excreted into the intestine through the biliary system. They play a crucial role in nutrient absorption, lipid and glucose regulation, and the maintenance of metabolic homeostasis. In additional, BAs have demonstrated the ability to attenuate disease progression such as diabetes, metabolic disorders, heart disease, and respiratory ailments. Intriguingly, recent research has offered exciting evidence to unveil their potential antitumor properties against various cancer cell types including tamoxifen-resistant breast cancer, oral squamous cell carcinoma, cholangiocarcinoma, gastric cancer, colon cancer, hepatocellular carcinoma, prostate cancer, gallbladder cancer, neuroblastoma, and others. Up to date, multiple laboratories have synthesized novel BA derivatives to develop potential drug candidates. These derivatives have exhibited the capacity to induce cell death in individual cancer cell types and display promising anti-tumor activities. This review extensively elucidates the anticancer activity of natural BAs and synthetic derivatives in cancer cells, their associated signaling pathways, and therapeutic strategies. Understanding of BAs and their derivatives activities and action mechanisms will evidently assist anticancer drug discovery and devise novel treatment.
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It is important to develop materials with environmental stability and long device shelf life for use in organic field-effect transistors (OFETs). The microscopic, molecular-level nature of the organic layer in OFETs is not yet well understood. The stability of geometric and electronic structures and the regulation of the external electric field (EEF) on the charge transport properties of four typical homogeneous organic semiconductors (OSCs) were investigated by density functional theory (DFT). The results showed that under the EEF, the structural changes in single-bond linked oligomers were more sensitive and complex than those of condensed molecules, and there were non-monotonic changes in their reorganization energy (λ) during charge transport under an EEF consisting of decreases and then increases (Series D). The change in λ under an EEF can be preliminarily and qualitatively determined by the change in the frontier molecular orbitals (FMOs) - the number of C-atoms with nonbonding characteristics. For single-bonded molecules, the transfer integral is basically unchanged under a low EEF, but it will greatly change at a high EEF. Because the structure and properties of the molecule will greatly change under different EEFs, the effect of an EEF should be fully considered when determining the intrinsic mobility of OSCs, which could cause a deviation 0.3-20 times in mobility. According to detailed calculations, one heterogeneous oligomer, TH-BTz, was designed. Its λ can be greatly reduced under an EEF, and the change in the energy level of FMOs can be adjusted to different degrees. This study provides a reasonable idea for verification of the experimental mobility value and also provides guidance for the directional design of stable high-mobility OSCs.
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In the process of developing tight oil and gas reservoirs, multistage fractured horizontal wells (NFHWs) can greatly increase the production rate, and the optimal design of its fracturing parameters is also an important means to further increase the production rate. Accurate production prediction is essential for the formulation of effective development strategies and development plans before and during project execution. In this study, a novel workflow incorporating machine learning (ML) and particle swarm optimization algorithms (PSO) is proposed to predict the production rate of multi-stage fractured horizontal wells in tight reservoirs and optimize the fracturing parameters. The researchers conducted 10,000 numerical simulation experiments to build a complete training and validation dataset, based on which five machine learning production prediction models were developed. As input variables for yield prediction, eight key factors affecting yield were selected. The results of the study show that among the five models, the random forest (RF) model best establishes the mapping relationship between feature variables and yield. After verifying the validity of the Random Forest-based yield prediction model, the researchers combined it with the particle swarm optimization algorithm to determine the optimal combination of fracturing parameters under the condition of maximizing the net present value. A hybrid model, called ML-PSO, is proposed to overcome the limitations of current production forecasting studies, which are difficult to maximize economic returns and optimize the fracturing scheme based on operator preferences (e.g., target NPV). The designed workflow can not only accurately and efficiently predict the production of multi-stage fractured horizontal wells in real-time, but also be used as a parameter selection tool to optimize the fracture design. This study promotes data-driven decision-making for oil and gas development, and its tight reservoir production forecasts provide the basis for accurate forecasting models for the oil and gas industry.
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Background: The present systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of music on pain management in preterm neonates during painful procedures. Methods: The PubMed, Embase, Web of Science, EBSCO and Cochrane Library databases were searched to identify relevant articles published from their inception to September 2023. The study search strategy and all other processes were implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Four RCTs that satisfied the inclusion criteria were included in this meta-analysis. The music group had significantly lower Premature Infant Pain Profile (PIPP) scores during (RR = -1.21; 95% CI = -2.02--0.40, p = 0.0032) and after painful procedures (RR = -0.65; 95% CI = -1.06--0.23, p = 0.002). The music group showed fewer changes in PIPP scores after invasive operations than did the control group (RR = -2.06; 95% CI -3.16--0.96; p = 0.0002). Moreover, our results showed that music improved oxygen saturation during (RR = 3.04, 95% CI = 1.64-4.44, p < 0.0001) and after painful procedures (RR = 3.50, 95% CI = 2.11-4.90, p < 0.00001). However, the change in peak heart rate during and after painful procedures was not statistically significant (RR = -12.14; 95% CI = -29.70-5.41 p = 0.18; RR = -10.41; 95% CI = -22.72-1.90 p = 0.10). Conclusion: In conclusion, this systematic review demonstrated that music interventions are effective for relieving procedural pain in preterm infants. Our results indicate that music can reduce stress levels and improve blood oxygen saturation. Due to the current limitations, large-scale, prospective RCTs should be performed to validate the present results.
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Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human cancer. However, knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely limited. Here, by taking advantage of in situ Hi-C, RNA-sequencing, and chromatin immunoprecipitation sequencing (ChIP-seq), we investigated structural reorganization and functional changes in chromosomal compartments, topologically associated domains (TADs), and CCCTC binding factor (CTCF)-mediated loops in gallbladder cancer (GBC) tissues and cell lines. We observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression changes. Increased inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal controls. Furthermore, the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial-mesenchymal transition activation were enriched in cancer compared with their control counterparts. Cancer-specific enhancer-promoter loops, which contain multiple transcription factor binding motifs, acted as a central element to regulate aberrant gene expression. Depletion of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene expressions. Collectively, our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.
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BACKGROUND: Rational prediction of the probability of decannulation in tracheotomy patients is of great importance to clinicians and patients' families. This study aimed to develop a prediction model for decannulation in tracheotomized patients with neurological injury using routine clinical data and blood tests. METHODS: We developed a prediction model based on 186 tracheotomized patients, and data were collected from January 2018 to March 2021. The least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for the decannulation risk model. The performance of the prediction model was evaluated in terms of discrimination, calibration, and clinical utility using measures such as C-index, calibration plot, and decision curve analysis (DCA). Internal validation was performed through bootstrapping validation. RESULTS: A total of 66.13% (123/186) of patients were decannulated. Predictors included in the prediction nomogram were age, gender, subtype of neurological injury, Glasgow Coma Scale (GCS) score, swallowing function, duration of tracheotomy, procalcitonin (PCT) level, white blood cell (WBC) count, and serum albumin (ALB) level. The predictive model showed good discrimination, with a C-index of 0.755 (95% confidence interval: 0.68-0.83). Internal validation also confirmed a satisfactory C-index of 0.690. The DCA indicated that the nomogram added substantial value in predicting decannulation risk for patients with threshold probabilities falling between >21% and <98% compared to the existing scheme. CONCLUSIONS: This predictive model serves as a valuable instrument for clinicians to quantitatively assess the probability of decannulation in patients with neurological injury, aiding in informed decision-making and patient management.