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1.
Heliyon ; 10(12): e32998, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988566

RESUMO

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatment of tumors.

2.
Cell Chem Biol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38986618

RESUMO

RNA molecules undergo dynamic chemical modifications in response to various external or cellular stimuli. Some of those modifications have been demonstrated to post-transcriptionally modulate the RNA transcription, localization, stability, translation, and degradation, ultimately tuning the fate decisions and function of mammalian cells, particularly T cells. As a crucial part of adaptive immunity, T cells play fundamental roles in defending against infections and tumor cells. Recent findings have illuminated the importance of RNA modifications in modulating T cell survival, proliferation, differentiation, and functional activities. Therefore, understanding the epi-transcriptomic control of T cell biology enables a potential avenue for manipulating T cell immunity. This review aims to elucidate the physiological and pathological roles of internal RNA modifications in T cell development, differentiation, and functionality drawn from current literature, with the goal of inspiring new insights for future investigations and providing novel prospects for T cell-based immunotherapy.

3.
Angew Chem Int Ed Engl ; : e202412179, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990010

RESUMO

Here, we report a strategy enabling triple switchable chemo-, regio-, and stereodivergence in newly developed palladium-catalyzed cycloadditions of allenes. An asymmetric pseudo-stereodivergent cycloaddition of allenes bearing a primary leaving group at the α-position, where a dynamic kinetic asymmetric hydroalkoxylation of racemic unactivated allenes was the enantio-determining step, is realized, providing four stereoisomers [(Z,R), (Z,S), (E,S), and (E,R)] containing a di-substituted alkene scaffold and a stereogenic center. By tuning reaction conditions, a mechanistically distinctive cycloaddition is uncovered selectively with the same set of substrates. By switching the position of the leaving group of allenes, a cycloaddition involving an intermolecular O-attack is disclosed. Diverse mechanisms of the cycloaddition reactions of allenes enable rapid access to structurally and stereochemically diverse 3,4-dihydro-2H-1,4-benzoxazines in high efficiency and selectivity.

4.
Cancer Med ; 13(14): e7416, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39046433

RESUMO

INTRODUCTION: In this study, we aimed to evaluate the predictive value of circulating lymphocyte subsets and inflammatory indexes in response to neoadjuvant chemoradiotherapy (NCRT) in patients with rectal mucinous adenocarcinomas (MACs). METHODS: Rectal MAC patients who underwent NCRT and curative resection at Fujian Medical University Union Hospital's Department of Colorectal Surgery between 2016 and 2020 were included in the study. Patients were categorized into good and poor response groups based on their pathological response to NCRT. An independent risk factor-based nomogram model was constructed by utilizing multivariate logistic regression analysis. Additionally, the extreme gradient boosting (XGB) algorithm was applied to build a machine learning (ML)-based predictive model. Feature importance was quantified using the Shapley additive explanations method. RESULTS: Out of the 283 participants involved in this research, 190 (67.1%) experienced an unfavorable outcome. To identify the independent risk factors, logistic regression analysis was performed, considering variables such as tumor length, pretreatment clinical T stage, PNI, and Th/Tc ratio. Subsequently, a nomogram model was constructed, achieving a C-index of 0.756. The ML model exhibited higher prediction accuracy than the nomogram model, achieving an AUROC of 0.824 in the training set and 0.762 in the tuning set. The top five important parameters of the ML model were identified as the Th/Tc ratio, neutrophil to lymphocyte, Th lymphocytes, Gross type, and T lymphocytes. CONCLUSION: Radiochemotherapy sensitivity is markedly influenced by systemic inflammation and lymphocyte-mediated immune responses in rectal MAC patients. Our ML model integrating clinical characteristics, circulating lymphocyte subsets, and inflammatory indexes is a potential assessment tool that can provide a reference for individualized treatment for rectal MAC patients.


Assuntos
Adenocarcinoma Mucinoso , Aprendizado de Máquina , Terapia Neoadjuvante , Nomogramas , Neoplasias Retais , Humanos , Masculino , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/imunologia , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/imunologia , Subpopulações de Linfócitos/imunologia , Idoso , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Quimiorradioterapia/métodos , Fatores de Risco , Adulto , Inflamação , Quimiorradioterapia Adjuvante/métodos
5.
Microbiome ; 12(1): 134, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039555

RESUMO

BACKGROUND: Understanding the interactions and dynamics of microbiotas within biological wastewater treatment systems is essential for ensuring their stability and long-term sustainability. In this study, we developed a systematic framework employing multi-omics and Hi-C sequencing to extensively investigate prokaryotic and phage communities within a hybrid biofilm and activated sludge system. RESULTS: We uncovered distinct distribution patterns, metabolic capabilities, and activities of functional prokaryotes through the analysis of 454 reconstructed prokaryotic genomes. Additionally, we reconstructed a phage catalog comprising 18,645 viral operational taxonomic units (vOTUs) with high length and contiguity using hybrid assembly, and a distinct distribution of phages was depicted between activated sludge (AS) and biofilm. Importantly, 1340 host-phage pairs were established using Hi-C and conventional in silico methods, unveiling the host-determined phage prevalence. The majority of predicted hosts were found to be involved in various crucial metabolic processes, highlighting the potential vital roles of phages in influencing substance metabolism within this system. Moreover, auxiliary metabolic genes (AMGs) related to various categories (e.g., carbohydrate degradation, sulfur metabolism, transporter) were predicted. Subsequent activity analysis emphasized their potential ability to mediate host metabolism during infection. We also profiled the temporal dynamics of phages and their associated hosts using 13-month time-series metagenomic data, further demonstrating their tight interactions. Notably, we observed lineage-specific infection patterns, such as potentially host abundance- or phage/host ratio-driven phage population changes. CONCLUSIONS: The insights gained from this research contribute to the growing body of knowledge surrounding interactions and dynamics of host-phage and pave the way for further exploration and potential applications in the field of microbial ecology. Video Abstract.


Assuntos
Bactérias , Bacteriófagos , Esgotos , Águas Residuárias , Bacteriófagos/genética , Bacteriófagos/classificação , Bacteriófagos/fisiologia , Bacteriófagos/isolamento & purificação , Esgotos/virologia , Esgotos/microbiologia , Águas Residuárias/virologia , Águas Residuárias/microbiologia , Bactérias/virologia , Bactérias/genética , Bactérias/classificação , Biofilmes , Metagenômica , Purificação da Água/métodos , Microbiota
6.
Mil Med Res ; 11(1): 48, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034405

RESUMO

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.


Assuntos
Modelos Animais de Doenças , Células-Tronco Mesenquimais , Mucosa Olfatória , Doença de Parkinson , Fator de Crescimento Transformador beta1 , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Células-Tronco Mesenquimais/métodos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Recuperação de Função Fisiológica , Fator de Crescimento Transformador beta1/metabolismo
7.
Sci Total Environ ; 947: 174538, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977090

RESUMO

Arsenic (As) is recognized as a potent environmental contaminant associated with bladder carcinogenesis. However, its molecular mechanism remains unclear. Metabolic reprogramming is one of the hallmarks of cancer and is as a central feature of malignancy. Here, we performed the study of cross-talk between the mammalian target of rapamycin complex 1 (mTORC1)/ Hypoxia-inducible factor 1 alpha (HIF-1α) pathway and aerobic glycolysis in promoting the proliferation and migration of bladder epithelial cells treated by arsenic in vivo and in vitro. We demonstrated that arsenite promoted N-methyl-N-nitrosourea (MNU)-induced tumor formation in the bladder of rats and the malignant behavior of human ureteral epithelial (SV-HUC-1) cell. We found that arsenite positively regulated the mTORC1/HIF-1α pathway through glucose transporter protein 1 (GLUT1), which involved in the malignant progression of bladder epithelial cells relying on glycolysis. In addition, pyruvate kinase M2 (PKM2) increased by arsenite reduced the protein expressions of succinate dehydrogenase (SDH) and fumarate hydratase (FH), leading to the accumulation of tumor metabolites of succinate and fumarate. Moreover, heat shock protein (HSP)90, functioning as a chaperone protein, stabilized PKM2 and thereby regulated the proliferation and aerobic glycolysis in arsenite treated SV-HUC-1 cells. Taken together, these results provide new insights into mTORC1/HIF-1α and PKM2 networks as critical molecular targets that contribute to the arsenic-induced malignant progression of bladder epithelial cells.

8.
Biotechnol Adv ; 75: 108404, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002783

RESUMO

Two-component systems (TCSs) are prevalent signaling pathways in bacteria. These systems mediate phosphotransfer between histidine kinase and a response regulator, facilitating responses to diverse physical, chemical, and biological stimuli. Advancements in synthetic and structural biology have repurposed TCSs for applications in monitoring heavy metals, disease-associated biomarkers, and the production of bioproducts. However, the utility of many TCS biosensors is hindered by undesired performance due to the lack of effective engineering methods. Here, we briefly discuss the architectures and regulatory mechanisms of TCSs. We also summarize the recent advancements in TCS engineering by experimental or computational-based methods to fine-tune the biosensor functional parameters, such as response curve and specificity. Engineered TCSs have great potential in the medical, environmental, and biorefinery fields, demonstrating a crucial role in a wide area of biotechnology.

9.
J Orthop Surg Res ; 19(1): 410, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014468

RESUMO

BACKGROUND: The minimally invasive approach for the treatment of displaced scapular neck or body fractures has the advantages of less trauma and minimal muscle dissection. In clinical practice, the minimally invasive approach combined with an anatomical locking plate has been used to treat scapular body fractures. In addition, we have made minor modifications to the minimally invasive approach. However, the biomechanical study about the approach combined with an anatomical locking plate in treating scapular body fractures was limited. METHODS: Finite element analysis (FEA) was used to conduct the biomechanical comparison between the anatomical locking plate (AP model) and reconstructive plate (RP model) in the treatment of scapular body fractures through the modified minimally invasive approach. A healthy male volunteer with no history of scapula or systemic diseases was recruited. High-resolution computed tomography images of his right scapula were obtained. Two scapula models were constructed and analyzed by the software of Mimics 21.0, Geomagic Wrap 2021, SolidWorks 2021, and ANSYS Workbench 2022, respectively. RESULTS: Through static structural analysis, in terms of equivalent von Mises stress, equivalent elastic strain, and total deformation, the AP model exhibited superior safety characteristics, enhanced flexibility, and anticipated stability compared with the RP model. This was evidenced by lower maximum stress, lower maximum strain and displacement. CONCLUSION: The minimally invasive approach combined with an anatomical locking plate for scapular body fractures had better biomechanical stability. The study provided a biomechanical basis to guide the clinical treatment of scapular body fractures.


Assuntos
Placas Ósseas , Análise de Elementos Finitos , Fixação Interna de Fraturas , Fraturas Ósseas , Procedimentos Cirúrgicos Minimamente Invasivos , Escápula , Humanos , Escápula/lesões , Escápula/cirurgia , Escápula/diagnóstico por imagem , Masculino , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fenômenos Biomecânicos , Adulto , Tomografia Computadorizada por Raios X
10.
Cancer Lett ; 598: 217113, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009068

RESUMO

Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths. According to clinical diagnosis and treatment, liver metastasis occurs in approximately 50 % of CRC patients, indicating a poor prognosis. The unique immune tolerance of the liver fosters an immunosuppressive tumor microenvironment (TME). In the context of tumors, numerous membrane and secreted proteins have been linked to tumor immune evasion as immunomodulatory molecules, but much remains unknown about how these proteins contribute to immune evasion in colorectal cancer liver metastasis (CRLM). This article reviews recently discovered membrane and secreted proteins with roles as both immunostimulatory and immunosuppressive molecules within the TME that influence immune evasion in CRC primary and metastatic lesions, particularly their mechanisms in promoting CRLM. This article also addresses screening strategies for identifying proteins involved in immune evasion in CRLM and provides insights into potential protein targets for treating CRLM.

11.
Adv Mater ; : e2313547, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011781

RESUMO

The straightforward synthesis of noble-metal-nanoparticle-decorated ordered mesoporous transition metal oxides remains a great challenge due to the difficulty of balancing the interactions between precursors and templates. Herein, a solvent-pair-enabled multicomponent coassembly (SPEMC) strategy is developed for straightforward synthesis of noble-metal-nanoparticle-decorated nitrogen-doped ordered mesoporous tungsten oxide (abbreviated as NM/N-mWO3, NM = Pt, Rh, Pd). The amphiphilic poly(ethylene oxide)-block-polystyrene (PEO-b-PS) copolymers coassemble with ammonium metatungstate (AMT) clusters and different kinds of hydrophilic noble metal precursors without phase separation. SPEMC synthesis requires no direct interaction between PEO-b-PS and AMT, thus the assembly equilibriums between noble metal precursors and PEO-b-PS can be readily controlled. The obtained NM/N-mWO3 nanocomposites possess ordered mesopores, abundant oxygen vacancies, and metal-metal oxide interfaces. As a result, the Pt/N-mWO3 sensors exhibit superior ammonia sensing performances with high sensitivity, an ultralow limit of detection (51.2 ppb), good selectivity, and long-term stability. Spectroscopic analysis reveals that ammonia is oxidized stepwise to NO, NO2 -, and NO3 - during the sensing process. Moreover, a portable wireless module based on Pt/N-mWO3 sensor can recognize ppm-level concentration of ammonia, which lays a solid foundation for its application in various fields.

12.
Methods Mol Biol ; 2814: 107-118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954201

RESUMO

A given protein can perform numerous roles in a cell with its participation in protein complexes and distinct localization within the cell playing a critical role in its diverse functions. Thus, the ability to artificially dimerize proteins and recruit proteins to specific locations in a cell has become a powerful tool for the investigation of protein function and the understanding of cell biology. Here, we discuss two systems that have been used to activate signal transduction pathways, a chemically inducible dimerization (CID) and a light-inducible (LI) system to control signaling and cytoskeletal regulation in a spatial and temporal manner.


Assuntos
Optogenética , Multimerização Proteica , Transdução de Sinais , Optogenética/métodos , Humanos , Animais , Luz , Transporte Proteico
13.
Nat Cell Biol ; 26(7): 1062-1076, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38951708

RESUMO

Ras has been extensively studied as a promoter of cell proliferation, whereas few studies have explored its role in migration. To investigate the direct and immediate effects of Ras activity on cell motility or polarity, we focused on RasGAPs, C2GAPB in Dictyostelium amoebae and RASAL3 in HL-60 neutrophils and macrophages. In both cellular systems, optically recruiting the respective RasGAP to the cell front extinguished pre-existing protrusions and changed migration direction. However, when these respective RasGAPs were recruited uniformly to the membrane, cells polarized and moved more rapidly, whereas targeting to the back exaggerated these effects. These unexpected outcomes of attenuating Ras activity naturally had strong, context-dependent consequences for chemotaxis. The RasGAP-mediated polarization depended critically on myosin II activity and commenced with contraction at the cell rear, followed by sustained mTORC2-dependent actin polymerization at the front. These experimental results were captured by computational simulations in which Ras levels control front- and back-promoting feedback loops. The discovery that inhibiting Ras activity can produce counterintuitive effects on cell migration has important implications for future drug-design strategies targeting oncogenic Ras.


Assuntos
Actomiosina , Movimento Celular , Polaridade Celular , Dictyostelium , Proteínas ras , Dictyostelium/metabolismo , Dictyostelium/genética , Células HL-60 , Actomiosina/metabolismo , Humanos , Proteínas ras/metabolismo , Proteínas ras/genética , Macrófagos/metabolismo , Miosina Tipo II/metabolismo , Miosina Tipo II/genética , Neutrófilos/metabolismo , Proteínas Ativadoras de ras GTPase/metabolismo , Proteínas Ativadoras de ras GTPase/genética , Animais , Quimiotaxia , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Actinas/metabolismo , Simulação por Computador , Camundongos , Transdução de Sinais
14.
Artigo em Inglês | MEDLINE | ID: mdl-39003438

RESUMO

PURPOSE: Differentiating pulmonary lymphoma from lung infections using CT images is challenging. Existing deep neural network-based lung CT classification models rely on 2D slices, lacking comprehensive information and requiring manual selection. 3D models that involve chunking compromise image information and struggle with parameter reduction, limiting performance. These limitations must be addressed to improve accuracy and practicality. METHODS: We propose a transformer sequential feature encoding structure to integrate multi-level information from complete CT images, inspired by the clinical practice of using a sequence of cross-sectional slices for diagnosis. We incorporate position encoding and cross-level long-range information fusion modules into the feature extraction CNN network for cross-sectional slices, ensuring high-precision feature extraction. RESULTS: We conducted comprehensive experiments on a dataset of 124 patients, with respective sizes of 64, 20 and 40 for training, validation and testing. The results of ablation experiments and comparative experiments demonstrated the effectiveness of our approach. Our method outperforms existing state-of-the-art methods in the 3D CT image classification problem of distinguishing between lung infections and pulmonary lymphoma, achieving an accuracy of 0.875, AUC of 0.953 and F1 score of 0.889. CONCLUSION: The experiments verified that our proposed position-enhanced transformer-based sequential feature encoding model is capable of effectively performing high-precision feature extraction and contextual feature fusion in the lungs. It enhances the ability of a standalone CNN network or transformer to extract features, thereby improving the classification performance. The source code is accessible at https://github.com/imchuyu/PTSFE .

15.
J Med Virol ; 96(6): e29719, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873911

RESUMO

This study aimed to determine the timing patterns of the initial respiratory syncytial virus (RSV) infection and to identify the factors influencing disease severity in infants of varying health status. A retrospective study was conducted at the Affiliated Children's Hospital of Chongqing Medical University from 2012 to 2022. The timing of the first RSV infection was estimated in infants with differing health status using correlation analysis, considering their birth time. Logistic regression was utilized to identify factors influencing severe RSV infection in these infants. RSV detection primarily occurred in the winter and spring. Epidemic season and peak timing of RSV were not significantly affected by health status or the COVID-19 pandemic. A strong positive correlation was observed between the age at RSV infection and the interval from birth to the RSV peak season. Infants born during the RSV epidemic season exhibited a higher likelihood of infection within the first 2 months postbirth. In contrast, those born outside the RSV epidemic season were more susceptible to infection during the subsequent peak. Notably, infants with pre-existing health conditions contracted RSV at an earlier age compared to their healthy counterparts. Among healthy infants, severe RSV infection was associated with sex, age, and timing of infection. For infants with underlying conditions, severe RSV infection was primarily related to age and timing of infection. The initial timing of RSV infection in infants varied depending on their health status. Young age and infection timing during the RSV epidemic season were significant risk factors for severe RSV infection. These findings provide a theoretical basis for optimizing immunization strategies for infants with diverse health conditions.


Assuntos
Infecções por Vírus Respiratório Sincicial , Estações do Ano , Índice de Gravidade de Doença , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Lactente , Masculino , Feminino , Estudos Retrospectivos , Recém-Nascido , Vírus Sincicial Respiratório Humano , Hospitalização/estatística & dados numéricos , Fatores de Risco , COVID-19/epidemiologia , Nível de Saúde , China/epidemiologia , Fatores de Tempo
16.
Front Genet ; 15: 1408688, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873109

RESUMO

N4-acetylcysteine (ac4C) is a chemical modification in mRNAs that alters the structure and function of mRNA by adding an acetyl group to the N4 position of cytosine. Researchers have shown that ac4C is closely associated with the occurrence and development of various cancers. Therefore, accurate prediction of ac4C modification sites on human mRNA is crucial for revealing its role in diseases and developing new diagnostic and therapeutic strategies. However, existing deep learning models still have limitations in prediction accuracy and generalization ability, which restrict their effectiveness in handling complex biological sequence data. This paper introduces a deep learning-based model, STM-ac4C, for predicting ac4C modification sites on human mRNA. The model combines the advantages of selective kernel convolution, temporal convolutional networks, and multi-head self-attention mechanisms to effectively extract and integrate multi-level features of RNA sequences, thereby achieving high-precision prediction of ac4C sites. On the independent test dataset, STM-ac4C showed improvements of 1.81%, 3.5%, and 0.37% in accuracy, Matthews correlation coefficient, and area under the curve, respectively, compared to the existing state-of-the-art technologies. Moreover, its performance on additional balanced and imbalanced datasets also confirmed the model's robustness and generalization ability. Various experimental results indicate that STM-ac4C outperforms existing methods in predictive performance. In summary, STM-ac4C excels in predicting ac4C modification sites on human mRNA, providing a powerful new tool for a deeper understanding of the biological significance of mRNA modifications and cancer treatment. Additionally, the model reveals key sequence features that influence the prediction of ac4C sites through sequence region impact analysis, offering new perspectives for future research. The source code and experimental data are available at https://github.com/ymy12341/STM-ac4C.

17.
Heliyon ; 10(11): e31807, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882330

RESUMO

The Smartphone Distraction Scale (SDS) is a novel assessment scale for smartphone distraction; it comprises 16 items that cover attention impulsiveness, online vigilance, multitasking, and emotion regulation. This study aimed to investigate the validity and reliability of the SDS in college students in China. After translating and culturally adapting the original version of the SDS into Chinese, the scale was tested on a sample of 1302 college students.The validity and reliability were assessed utilizing SPSS 25.0, AMOS 25.0 and Mplus 8.3. Parallel analysis, Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were performed for the validity analysis. Criterion-related validity for the SDS was tested by correlation analysis with the mobile phone addiction scale (MPAI). The reliability analysis was tested by Cronbach's alpha coefficients and intraclass correlation coefficients (ICC). EFA and parallel analysis revealed a three-factor structure. The EFA identified factor loadings on three factors (14 items), explaining a total variance of 60.73 %. The CFA model fit was good (χ2/df = 4.644, RMSEA = 0.047, GFI = 0.930, CFI = 0.955, SRMR = 0.047), and the multigroup confirmatory factor analysis indicated measurement invariance for gender. Both convergent and discriminant validity were established. The criterion-related validity was established based on a significant correlation (r = 0.758) with the MPAI. The Cronbach's alpha coefficient was 0.916, and the split-half reliability was 0.769, demonstrating a satisfactory internal consistency. The score of ICC was 0.907, demonstrating the stability of the SDS. Based on these data, the Chinese version of the SDS demonstrated satisfactory validity and reliability in a sample of college students.

18.
J Colloid Interface Sci ; 674: 345-352, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38941928

RESUMO

Aqueous zinc batteries (AZBs) with the advantages of safety, low cost, and sustainability are promising candidates for large-scale energy storage devices. However, the issues of interface side reactions and dendrite growth at the zinc metal anode (ZMA) significantly harm the cycling lifespan of AZBs. In this study, we designed a nano-molecular sieve additive, fullerenol (C60(OH)n), which possesses a surface rich in hydroxyl groups that can be uniformly dispersed in the aqueous solution, and captures free water in the electrolyte, thereby suppressing the occurrence of interfacial corrosion. Besides, fullerenol can be further reduced to fullerene (C60) on the surface of ZMA, holding a unique self-smoothing effect that can inhibit the growth of dendritic Zn. With the synergistic action of these two effects, the fullerenol-contained electrolyte (FE) enables dendrite-free ZMAs. The Zn-Ti half-cell using FE exhibits stable cycling over 2500 times at 5 mA cm-2 with an average Coulombic efficiency as high as 99.8 %. Additionally, the Zn-NaV3O8 cell using this electrolyte displays a capacity retention rate of 100 % after 1000 cycles at -20 °C. This work provides important insights into the molecular design of multifunctional electrolyte additives.

19.
ACS Nano ; 18(26): 17162-17174, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38902594

RESUMO

Although in vitro neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks. Analysis of synaptic delay and signal speed between cells enabled us to establish a communication connectivity model. We anticipate that our discoveries of the dynamic changes in communication across the neuronal network will provide a valuable tool for future studies in understanding health and disease as well as in developing effective platforms for evaluating therapies.


Assuntos
Ouro , Microeletrodos , Rede Nervosa , Neurônios , Ouro/química , Animais , Neurônios/fisiologia , Rede Nervosa/fisiologia , Comunicação Celular , Ratos , Células Cultivadas
20.
Ultrason Sonochem ; 107: 106933, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38865900

RESUMO

Extraction of anthocyanins from Lycium ruthenicum Murr. (L. ruthenicum) is a notable challenge in food production, requiring methods that balance efficiency and safety. In this study, we conducted a comparative analysis the extraction of anthocyanins by natural air drying (NAD), vacuum freeze drying (VFD), hot air drying (HAD), and vacuum microwave drying (MVD) combined with ultrasonic-assisted enzymolysis extraction (UAEE). The results demonstrated that the extraction yield and antioxidant activity of anthocyanins were significantly higher in VFD. This phenomenon can be attributed to the modification of raw material's microstructure, leading to an increased extraction yield of specific anthocyanins such as Cyanidin-3-galactoside, Delphinidin chloride, Cyanidin, and Petunidin. According to the pretreatment results, the extraction process of anthocyanins was further optimized. The highest yield (3.16 g/100 g) was obtained in following conditions: 0.24 % pectinase, 48 °C, solid:liquid = 1:21, and 21 min ultrasonic time. This study improves the commercial value and potential application of L. ruthenicum in food industry.


Assuntos
Antocianinas , Dessecação , Lycium , Antocianinas/isolamento & purificação , Antocianinas/química , Lycium/química , Dessecação/métodos , Ondas Ultrassônicas , Fracionamento Químico/métodos , Antioxidantes/isolamento & purificação , Antioxidantes/química , Poligalacturonase , Micro-Ondas
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