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Break-induced replication (BIR) is a pathway of homology-directed repair that repairs one-ended DNA breaks, such as those formed at broken replication forks or uncapped telomeres. In contrast to conventional S phase DNA synthesis, BIR proceeds by a migrating D-loop and results in conservative synthesis of the nascent strands. DNA polymerase delta (Pol δ) initiates BIR; however, it is not known whether synthesis of the invading strand switches to a different polymerase or how the complementary strand is synthesized. By using alleles of the replicative DNA polymerases that are permissive for ribonucleotide incorporation, thus generating a signature of their action in the genome that can be identified by hydrolytic end sequencing, we show that Pol δ replicates both the invading and the complementary strand during BIR. In support of this conclusion, we show that depletion of Pol δ from cells reduces BIR, whereas depletion of Pol ε has no effect.
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Quebras de DNA , DNA Polimerase III/metabolismo , Replicação do DNA , DNA Fúngico/biossíntese , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , DNA Ligase Dependente de ATP/genética , DNA Ligase Dependente de ATP/metabolismo , DNA Polimerase I/genética , DNA Polimerase I/metabolismo , DNA Polimerase II/genética , DNA Polimerase II/metabolismo , DNA Polimerase III/genética , DNA Fúngico/genética , Células HEK293 , Células HeLa , Humanos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
Leucine-rich glioma-inactivated protein 1 (LGI1), a secretory protein in the brain, plays a critical role in myelination; dysfunction of this protein leads to hypomyelination and white matter abnormalities (WMAs). Here, we hypothesized that LGI1 may regulate myelination through binding to an unidentified receptor on the membrane of oligodendrocytes (OLs). To search for this hypothetic receptor, we analyzed LGI1 binding proteins through LGI1-3 × FLAG affinity chromatography with mouse brain lysates followed by mass spectrometry. An OL-specific membrane protein, the oligodendrocytic myelin paranodal and inner loop protein (OPALIN), was identified. Conditional knockout (cKO) of OPALIN in the OL lineage caused hypomyelination and WMAs, phenocopying LGI1 deficiency in mice. Biochemical analysis revealed the downregulation of Sox10 and Olig2, transcription factors critical for OL differentiation, further confirming the impaired OL maturation in Opalin cKO mice. Moreover, virus-mediated re-expression of OPALIN successfully restored myelination in Opalin cKO mice. In contrast, re-expression of LGI1-unbound OPALIN_K23A/D26A failed to reverse the hypomyelination phenotype. In conclusion, our study demonstrated that OPALIN on the OL membrane serves as an LGI1 receptor, highlighting the importance of the LGI1/OPALIN complex in orchestrating OL differentiation and myelination.
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Diferenciação Celular , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos Knockout , Oligodendroglia , Animais , Oligodendroglia/metabolismo , Oligodendroglia/citologia , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Bainha de Mielina/metabolismo , Proteínas da Mielina/metabolismo , Proteínas da Mielina/genéticaRESUMO
Tumor metastasis is the major cause of breast cancer morbidity and mortality. It has been reported that the F-box protein FBXO3 functions as an E3 ubiquitin ligase in regulating various biological processes, including host autoimmune, antiviral innate immunity, and inflammatory response. However, the role of FBXO3 in tumor metastasis remains elusive. We have previously shown that ΔNp63α is a common inhibitory target in oncogene-induced cell motility and tumor metastasis. In this study, we show that FBXO3 plays a vital role in PI3K-mediated breast cancer metastasis independent of its E3 ligase activity and ΔNp63α in breast cancer cells and in mouse. FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis. Mechanistically, FBXO3 disrupts the interaction between USP4 and aspartyl aminopeptidase (DNPEP), thereby protecting USP4 from DNPEP-mediated degradation. Furthermore, p110αH1047R facilitates the phosphorylation and stabilization of FBXO3 in an ERK1-dependent manner. Knockdown of either FBXO3 or USP4 leads to significant inhibition of PI3K-induced breast cancer metastasis. Clinically, elevated expression of p110α/FBXO3/USP4/Twist1 is associated with poor overall survival (OS) and recurrence-free survival (RFS) of breast cancer patients. Taken together, this study reveals that the FBXO3-USP4-Twist1 axis is pivotal in PI3K-mediated breast tumor metastasis and that FBXO3/USP4 may be potential therapeutic targets for breast cancer treatment.
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Neoplasias da Mama , Melanoma , Neoplasias Cutâneas , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , UbiquitinaçãoRESUMO
As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.
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Actinidia , Resistência à Seca , Actinidia/genética , Actinidia/fisiologia , Resistência à Seca/genética , Frutas/genética , Frutas/fisiologia , Genótipo , Análise Multivariada , Raízes de Plantas/fisiologia , Raízes de Plantas/genética , Estresse Fisiológico/genéticaRESUMO
The utilization of high-throughput sequencing (HTS) for B-cell receptor (BCR) immune repertoire analysis has become widespread in the fields of adaptive immunity and antibody drug development. However, the sheer volume of sequences generated by these experiments presents a challenge in data processing. Specifically, multiple sequence alignment (MSA), a critical aspect of BCR analysis, remains inadequate for handling massive BCR sequencing data and lacks the ability to provide immunoglobulin-specific information. To address this gap, we introduce Abalign, a standalone program specifically designed for ultrafast MSA of BCR/antibody sequences. Benchmark tests demonstrate that Abalign achieves comparable or even better accuracy than state-of-the-art MSA tools, and shows remarkable advantages in terms of speed and memory consumption, reducing the time required for high-throughput analysis from weeks to hours. In addition to its alignment capabilities, Abalign offers a broad range of BCR analysis features, including extracting BCRs, constructing lineage trees, assigning VJ genes, analyzing clonotypes, profiling mutations, and comparing BCR immune repertoires. With its user-friendly graphic interface, Abalign can be easily run on personal computers instead of computing clusters. Overall, Abalign is an easy-to-use and effective tool that enables researchers to analyze massive BCR/antibody sequences, leading to new discoveries in the field of immunoinformatics. The software is freely available at http://cao.labshare.cn/abalign/.
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Anticorpos , Software , Alinhamento de Sequência , Anticorpos/genética , Imunidade Adaptativa , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Receptores de Antígenos de Linfócitos B/genéticaRESUMO
Manganese/nickel-based layered transition metal oxides have caught the attention of studies as promising cathodes for sodium-ion batteries (SIBs). It is reported that utilizing both cationic and anionic redox reactions is a promising method for higher energy density cathodes. However, the anionic redox reaction comes at the expense of irreversible oxygen release. Hence, a Li-Mg cosubstituted P2-Na0.67Li0.07Mg0.07Ni0.28Mn0.58O2 material with a honeycomb-ordered superstructure was designed. The Ni3+/Ni4+ redox couple and the anionic redox reaction are proven to have a competitive relationship. Density functional theory calculations reveal the effect of O 2p nonbonding states from Li and prove that Mg-O bonds can stabilize the Ni-O eg states. In situ electrochemical impedance spectroscopy measurements and galvanostatic charging/discharging derived dV/dQ, representing resistance changes with time, are obtained to reveal the mechanism of the anionic redox reaction. This study presents the effect and mechanism of the O 2p nonbonding state and Mg-O bonds of manganese/nickel-based layered oxides.
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Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.
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Linfócitos T CD8-Positivos , Endometriose , Fator de Transcrição STAT1 , Células Estromais , Endometriose/imunologia , Endometriose/patologia , Endometriose/metabolismo , Feminino , Linfócitos T CD8-Positivos/imunologia , Humanos , Animais , Camundongos , Células Estromais/imunologia , Células Estromais/metabolismo , Fator de Transcrição STAT1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Endométrio/imunologia , Endométrio/patologia , Modelos Animais de Doenças , Transdução de Sinais , Camundongos Nus , Adulto , Proteína Quinase CDC2/metabolismo , Técnicas de Cocultura , Citocinas/metabolismoRESUMO
Protein-ligand docking is an essential method in computer-aided drug design and structural bioinformatics. It can be used to identify active compounds and reveal molecular mechanisms of biological processes. A successful docking usually requires thorough conformation sampling and scoring, which are computationally expensive and difficult. Recent studies demonstrated that it can be beneficial to docking with the guidance of existing similar co-crystal structures. In this work, we developed a protein-ligand docking method, named FitDock, which fits initial conformation to the given template using a hierarchical multi-feature alignment approach, subsequently explores the possible conformations and finally outputs refined docking poses. In our comprehensive benchmark tests, FitDock showed 40%-60% improvement in terms of docking success rate and an order of magnitude faster over popular docking methods, if template structures exist (> 0.5 ligand similarity). FitDock has been implemented in a user-friendly program, which could serve as a convenient tool for drug design and molecular mechanism exploration. It is now freely available for academic users at http://cao.labshare.cn/fitdock/.
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Desenho de Fármacos , Proteínas , Sítios de Ligação , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Proteínas/químicaRESUMO
Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant-pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.
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Basidiomycota , Dendrobium , Micorrizas , Orchidaceae , Simbiose , Dendrobium/genética , Sementes , Micorrizas/fisiologia , Basidiomycota/fisiologia , Orchidaceae/genética , FilogeniaRESUMO
Transforming growth factor-ß (TGF-ß) signaling plays a critical role in promoting epithelial-to-mesenchymal transition (EMT), cell migration, invasion, and tumor metastasis. ΔNp63α, the major isoform of p63 protein expressed in epithelial cells, is a key transcriptional regulator of cell adhesion program and functions as a critical metastasis suppressor. It has been documented that the expression of ΔNp63α is tightly controlled by oncogenic signaling and is frequently reduced in advanced cancers. However, whether TGF-ß signaling regulates ΔNp63α expression in promoting metastasis is largely unclear. In this study, we demonstrate that activation of TGF-ß signaling leads to stabilization of E3 ubiquitin ligase FBXO3, which, in turn, targets ΔNp63α for proteasomal degradation in a Smad-independent but Erk-dependent manner. Knockdown of FBXO3 or restoration of ΔNp63α expression effectively rescues TGF-ß-induced EMT, cell motility, and tumor metastasis in vitro and in vivo. Furthermore, clinical analyses reveal a significant correlation among TGF-ß receptor I (TßRI), FBXO3, and p63 protein expression and that high expression of TßRI/FBXO3 and low expression of p63 are associated with poor recurrence-free survival (RFS). Together, these results demonstrate that FBXO3 facilitates ΔNp63α degradation to empower TGF-ß signaling in promoting tumor metastasis and that the TßRI-FBXO3-ΔNp63α axis is critically important in breast cancer development and clinical prognosis. This study suggests that FBXO3 may be a potential therapeutic target for advanced breast cancer treatment.
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Neoplasias da Mama/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Células HEK293 , Células HaCaT , Humanos , Metástase Neoplásica/patologia , Isoformas de Proteínas , Proteínas Supressoras de Tumor/metabolismoRESUMO
The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.
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p53, a tumor suppressor protein, has a vital role in the regulation of the cell cycle, apoptosis, and DNA damage repair. The degradation of p53 is predominantly controlled by the murine double minute 2 (MDM2) protein, a ubiquitin E3 ligase. The overexpression or amplification of MDM2 is commonly observed in various human cancers bearing wild-type p53 alleles, leading to the rapid degradation of the p53 protein and the attenuation of p53 tumor suppression functions. Thus, a major effort in p53-based cancer therapy has been to research MDM2 antagonists that specifically stabilize and activate p53, leading to the suppression of tumor growth. However, despite numerous efforts to develop MDM2 antagonists, to date they have failed to reach clinical use, largely because of the cytotoxicity associated with these small molecules. This study used our newly designed structure-based virtual screening approach on a commercial compound library to identify a novel compound, CGMA-Q18, which directly binds to MDM2, leading to the activation of p53, the induction of apoptosis, and cell cycle arrest in cancer cells. Notably, CGMA-Q18 significantly inhibited tumor xenograft growth in nude mice without observable toxicity. These findings highlight our useful virtual screening protocol and CGMA-Q18 as a putative MDM2 antagonist.
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Flat bands in 2D twisted materials are key to the realization of correlation-related exotic phenomena. However, a flat band often was achieved in the large system with a very small twist angle, which enormously increases the computational and experimental complexity. In this work, we proposed group-V twisted bilayer materials, including P, As, and Sb in the ß phase with large twist angles. The band structure of twisted bilayer materials up to 2524 atoms has been investigated by a deep learning method DeepH, which significantly reduces the computational time. Our results show that the bandgap and the flat bandwidth of twisted bilayer ß-P, ß-As, and ß-Sb reduce gradually with the decreasing of twist angle, and the ultra-flat band with bandwidth approaching 0 eV is achieved. Interestingly, we found that a twist angle of 9.43° is sufficient to achieve the band flatness for ß-As comparable to that of twist bilayer graphene at the magic angle of 1.08°. Moreover, we also find that the bandgap reduces with decreasing interlayer distance while the flat band is still preserved, which suggests interlayer distance as an effective routine to tune the bandgap of flat band systems. Our research provides a feasible platform for exploring physical phenomena related to flat bands in twisted layered 2D materials.
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OBJECTIVE: By observing the differences in sleep parameters between portable sleep monitoring (PM) and polysomnography (PSG) in children, we aimed to investigate the diagnostic value and feasibility of PM in children with suspected obstructive sleep apnea (OSA). STUDY DESIGN: This prospective study enrolled consecutive children (aged 3-14 years) with suspected OSA in Shenzhen Children's Hospital. They had PSG and PM in the sleep laboratory. Clinical parameters of the two sleep monitoring methods were compared. RESULTS: A total of 58 children participated. They were classified into two groups according to age: 28 children aged 3 to 5 years and 30 children aged 6 to 14 years. No significant differences were observed in apnea-hypopnea index (AHI), lowest oxygen saturation (LSaO2), and mean oxygen saturation (MSaO2) between PM and PSG, but the sleep efficiency with PM was significantly higher (3-5 years age: 92.2 ± 11.3% vs 85.2 ± 14.3%, 6-14 years age: 93.2 ± 14.5% vs 84.8 ± 16.3%, both P < 0.05) than the sleep efficiency with PSG. Pearson correlation analysis indicated a strong correlation between AHI, LSaO2, MSaO2, and sleep efficiency measured by PSG and PM. Receiver operating characteristic curve (ROC) analysis showed that PM was a reliable diagnostic tool for OSA. PM has high sensitivity (3-5 years age: 95.8%, 6-14 years age: 96.3%) and low specificity (3-5 years age: 25.0%, 6-14 years age: 33.3%) for OSA in children. Thus, there is a low rate of missed diagnoses, but there is some inaccuracy in excluding children who do not have OSA. CONCLUSION: The results showed that PM has a good correlation with the various parameters of PSG. PM may be a reliable tool for diagnosing moderate and severe OSA in children, especially those who cannot cooperate with PSG or who have limited access to PSG.
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Apneia Obstrutiva do Sono , Sono , Criança , Humanos , Adulto , Idoso de 80 Anos ou mais , Idoso , Polissonografia/métodos , Estudos Prospectivos , Apneia Obstrutiva do Sono/diagnóstico , Curva ROCRESUMO
Protein-ligand blind docking is a powerful method for exploring the binding sites of receptors and the corresponding binding poses of ligands. It has seen wide applications in pharmaceutical and biological researches. Previously, we proposed a blind docking server, CB-Dock, which has been under heavy use (over 200 submissions per day) by researchers worldwide since 2019. Here, we substantially improved the docking method by combining CB-Dock with our template-based docking engine to enhance the accuracy in binding site identification and binding pose prediction. In the benchmark tests, it yielded the success rate of â¼85% for binding pose prediction (RMSD < 2.0 Å), which outperformed original CB-Dock and most popular blind docking tools. This updated docking server, named CB-Dock2, reconfigured the input and output web interfaces, together with a highly automatic docking pipeline, making it a particularly efficient and easy-to-use tool for the bioinformatics and cheminformatics communities. The web server is freely available at https://cadd.labshare.cn/cb-dock2/.
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Algoritmos , Proteínas , Sítios de Ligação , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Proteínas/química , Software , Proteínas Ativadoras de GTPase/química , Fatores de Troca do Nucleotídeo Guanina/químicaRESUMO
Pif1 family 5' â 3' DNA helicases are important for replication fork progression and genome stability. The budding yeast Saccharomyces cerevisiae encodes two Pif1 family helicases, Rrm3 and Pif1, both of which are multi-functional. Here we describe novel functions for Rrm3 in promoting mutation avoidance during DNA replication. We show that loss of RRM3 results in elevated spontaneous mutations made by DNA polymerases Pols ϵ and δ, which are subject to DNA mismatch repair. The absence of RRM3 also causes higher mutagenesis by the fourth B-family DNA polymerase Pol ζ. By genome-wide analysis, we show that the mutational consequences due to loss of RRM3 vary depending on the genomic locus. Rrm3 promotes the accuracy of DNA replication by Pols ϵ and δ across the genome, and it is particularly important for preventing Pol ζ-dependent mutagenesis at tRNA genes. In addition, mutation avoidance by Rrm3 depends on its helicase activity, and Pif1 serves as a backup for Rrm3 in suppressing mutagenesis. We present evidence that the sole human Pif1 family helicase in human cells likely also promotes replication fidelity, suggesting that a role for Pif1 family helicases in mutation avoidance may be evolutionarily conserved, a possible underlying mechanism for its potential tumor-suppressor function.
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DNA Helicases , Replicação do DNA , Humanos , Células Cultivadas , Sequência Conservada , DNA Helicases/genética , DNA Helicases/metabolismo , Replicação do DNA/genética , Mutação , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
PURPOSE: Generative AI will become an integral part of education in future. The potential of this technology in different disciplines should be identified to promote effective adoption. This study evaluated the performance of ChatGPT in tutorial and case-based learning questions in physiology and biochemistry for medical undergraduates. Our study mainly focused on the performance of GPT-3.5 version while a subgroup was comparatively assessed on GPT-3.5 and GPT-4 performances. MATERIALS AND METHODS: Answers were generated in GPT-3.5 for 44 modified essay questions (MEQs) in physiology and 43 MEQs in biochemistry. Each answer was graded by two independent examiners. Subsequently, a subset of 15 questions from each subject were selected to represent different score categories of the GPT-3.5 answers; responses were generated in GPT-4, and graded. RESULTS: The mean score for physiology answers was 74.7 (SD 25.96). GPT-3.5 demonstrated a statistically significant (p = .009) superior performance in lower-order questions of Bloom's taxonomy in comparison to higher-order questions. Deficiencies in the application of physiological principles in clinical context were noted as a drawback. Scores in biochemistry were relatively lower with a mean score of 59.3 (SD 26.9) for GPT-3.5. There was no statistically significant difference in the scores for higher and lower-order questions of Bloom's taxonomy. The deficiencies highlighted were lack of in-depth explanations and precision. The subset of questions where the GPT-4 and GPT-3.5 were compared demonstrated a better overall performance in GPT-4 responses in both subjects. This difference between the GPT-3.5 and GPT-4 performance was statistically significant in biochemistry but not in physiology. CONCLUSIONS: The differences in performance across the two versions, GPT-3.5 and GPT-4 across the disciplines are noteworthy. Educators and students should understand the strengths and limitations of this technology in different fields to effectively integrate this technology into teaching and learning.
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Bioquímica , Educação de Graduação em Medicina , Avaliação Educacional , Fisiologia , Humanos , Educação de Graduação em Medicina/métodos , Bioquímica/educação , Fisiologia/educação , Avaliação Educacional/métodos , Estudantes de Medicina/psicologia , Instrução por Computador/métodos , Aprendizagem Baseada em Problemas/métodos , AprendizagemRESUMO
Singapore, located strategically at the meeting point of the Malacca Strait and the South China Sea, has established itself as a global financial and economic hub. Despite its small geographical size, Singapore is home to over 5 million people from diverse cultural backgrounds. The city-state's medical education landscape has evolved significantly over the past century. Originally, Singapore had only one undergraduate medical school, the NUS Yong Loo Lin School of Medicine, established in 1905. Over time, this institution has grown into Singapore's largest and oldest medical school. NUS Medicine's vision centres on developing highly competent, values-driven, and inspired healthcare professionals to transform the practice of medicine and improve health worldwide. A curriculum overhaul in 2020 introduced new educational components to prepare future healthcare professionals for the challenges of Singapore's resilient healthcare system. This includes proficiency in integrated care, collaboration across disciplines, and leveraging AI and data science in clinical decision-making. The introduction of a common curriculum in August 2023 for Medicine, Nursing, Dentistry, and Pharmacy undergraduates further aligns with Singapore's 'Healthier SG' vision, ensuring that graduates are well-equipped to meet the evolving needs of the healthcare landscape. The common curriculum aims to address professional hierarchies and foster interprofessional collaboration among students from diverse academic backgrounds. By promoting frequent interaction and a team-oriented mindset, the curriculum seeks to instil a collective approach to healthcare, emphasising the importance of interprofessional practice in achieving the broader goals of healthcare delivery. This paper describes the reforms that took place and how the challenges were mitigated in a research-intensive top-ranked academic medical institution. This strategic alignment of medical education with national healthcare priorities underscores NUS Medicine's commitment to transforming medical practice and improving health outcomes in Singapore and beyond.
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In the current study, a rapid online extraction combined with high-performance liquid chromatography (HPLC) antioxidant analysis approach was developed to explore the antioxidant ingredients in three different parts of Polygonum Chinense. A total of 22 chromatographic peaks were found, among which 8 components were found for the first time. And among these 22 peaks, 19 of them were demonstrated as antioxidants. Furthermo, all three parts from Polygonum Chinense exhibited antioxidant activity (13.19, 3.89, and 19.85 mg CE/g extract, for the leaf, stem, and flower, respectively) and the antioxidant activity values of the leaf and flower were more than 3 times that of the stem. The leaf, flower, and stem of Polygonum Chinense had 17, 13, and 15 antioxidant components, respectively. Among them, neochlorogenic acid (2) and quercetin-3-O-malonylglucoside (18) were considered as the main antioxidants in the leaf of Polygonum Chinense. In terms of flower, geraniin (10) and quercetin-3-O-malonylglucoside (18) were proved as the major antioxidants. This is the first report on the antioxidant components from different parts of Polygonum Chinense. It provides foundational scientific data for the continued exploration of chemical and pharmacological study of Polygonum Chinense, beneficial for the future product development and quality evaluation improvement of Polygonum Chinense.
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The construction of large-diameter shield tunnels underwater involves complex variations in water and earth load outside the tunnel segment, as well as intricate mechanical responses. This study analyzes the variation laws of external loads, axial forces, and bending moments acting on the segment ring during the shield assembly and removal from the shield tail. It accomplishes this through the establishment of an on-site monitoring system based on the Internet of Things (IoT) and proposes a Bayesian-genetic algorithm model to estimate the water and earth pressure. The fluctuation section exhibits a peak load twice as high as that in the stable section. These variations are influenced by Jack thrust, shield shell force, and grouting pressure. The peak load observed in the fluctuation section is twice as high as the load observed in the stable section. During the shield tail removal process, the internal forces undergo significant fluctuations due to changes in both load and boundary conditions, and the peak value of the axial force during the fluctuation section is eight times higher than that during the stable section, while the peak value of the bending moment during the fluctuation section is five times higher than that during the stable section. The earth and water pressure calculated using the inversion analysis method, which relies on the measured internal forces, closely matches the actual measured values. The results demonstrate that the accuracy of the water and earth pressure obtained through inversion analysis is twice as high as that obtained using the full coverage pressure method. These results can serve as a valuable reference for similar projects.