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Large-scale genomic projects and ancient DNA innovations have ushered in a new paradigm for exploring human evolutionary history. However, the genetic legacy of spatiotemporally diverse ancient Eurasians within Chinese paternal lineages remains unresolved. Here, we report an integrated Y-chromosome genomic database encompassing 15,563 individuals from both modern and ancient Eurasians, including 919 newly reported individuals, to investigate the Chinese paternal genomic diversity. The high-resolution, time-stamped phylogeny reveals multiple diversification events and extensive expansions in the early and middle Neolithic. We identify four major ancient population movements, each associated with technological innovations that have shaped the Chinese paternal landscape. First, the expansion of early East Asians and millet farmers from the Yellow River Basin predominantly carrying O2/D subclades significantly influenced the formation of the Sino-Tibetan people and facilitated the permanent settlement of the Tibetan Plateau. Second, the dispersal of rice farmers from the Yangtze River Valley carrying O1 and certain O2 sublineages reshapes the genetic makeup of southern Han Chinese, as well as the Tai-Kadai, Austronesian, Hmong-Mien, and Austroasiatic people. Third, the Neolithic Siberian Q/C paternal lineages originated and proliferated among hunter-gatherers on the Mongolian Plateau and the Amur River Basin, leaving a significant imprint on the gene pools of northern China. Fourth, the J/G/R paternal lineages derived from western Eurasia, which were initially spread by Yamnaya-related steppe pastoralists, maintain their presence primarily in northwestern China. Overall, our research provides comprehensive genetic evidence elucidating the significant impact of interactions with culturally distinct ancient Eurasians on the patterns of paternal diversity in modern Chinese populations.
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Povo Asiático , Cromossomos Humanos Y , Migração Humana , Humanos , China , Povo Asiático/genética , Masculino , Cromossomos Humanos Y/genética , DNA Antigo/análise , Herança Paterna , Filogenia , População do Leste AsiáticoRESUMO
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant disease with a poor prognosis. We previously found that p62 presented a marked nuclear-cytoplasmic translocation in ESCC cells as compared that in normal esophageal epithelial cells, but its effects on ESCC cells remain unclear. This study aims to clarify the impacts of different cellular localization of p62 on the function of ESCC cells and the underlying molecular mechanisms. We here demonstrated that cytoplasmic p62 enhances the migration and invasion abilities of esophageal cancer cells, whereas nuclear p62 has no effect. We further explored the interaction protein of p62 by using GST pull-down experiment and identified EPLIN as a potential protein interacting with p62. In addition, reducing EPLIN expression significantly inhibited the migration and invasion of ESCC cells, which were rescued when EPLIN expression was restored after the p62 knockdown. At a molecular level, p62 in cytoplasm positively regulated the expression of EPLIN via enhancing its protein stability. Data from the TCGA and GEO database displayed a significant up-regulation of EPLIN mRNA expression in ESCC tissues compared with corresponding paired esophageal epithelial samples. Our findings present evidence that the nuclear-cytoplasmic translocation of p62 protein contributes to an aggressive malignancy phenotype, providing candidate molecular biomarkers and potential molecular targets for the diagnosis and treatment of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Citoplasma/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/genética , Invasividade Neoplásica/genética , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismoRESUMO
Tandem mass tags (TMT) are widely used in proteomics to simultaneously quantify multiple samples in a single experiment. The tags can be easily added to the primary amines of peptides/proteins through chemical reactions. In addition to amines, TMT reagents also partially react with the hydroxyl groups of serine, threonine, and tyrosine residues under alkaline conditions, which significantly compromises the analytical sensitivity and precision. Under alkaline conditions, reducing the TMT molar excess can partially mitigate overlabeling of histidine-free peptides, but has a limited effect on peptides containing histidine and hydroxyl groups. Here, we present a method under acidic conditions to suppress overlabeling while efficiently labeling amines, using only one-fifth of the TMT amount recommended by the manufacturer. In a deep-scale analysis of a yeast/human two-proteome sample, we systematically evaluated our method against the manufacturer's method and a previously reported TMT-reduced method. Our method reduced overlabeled peptides by 9-fold and 6-fold, respectively, resulting in the substantial enhancement in peptide/protein identification rates. More importantly, the quantitative accuracy and precision were improved as overlabeling was reduced, endowing our method with greater statistical power to detect 42% and 12% more statistically significant yeast proteins compared to the standard and TMT-reduced methods, respectively. Mass spectrometric data have been deposited in the ProteomeXchange Consortium via the iProX partner repository with the data set identifier PXD047052.
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Aminas , Proteoma , Proteômica , Espectrometria de Massas em Tandem , Proteoma/análise , Proteoma/química , Proteômica/métodos , Humanos , Aminas/química , Espectrometria de Massas em Tandem/métodos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Peptídeos/química , Peptídeos/análise , Análise Custo-Benefício , Proteínas de Saccharomyces cerevisiae/análise , Proteínas de Saccharomyces cerevisiae/química , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. RESULTS: Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. CONCLUSIONS: Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine.
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Genética Populacional , Haplótipos , Polimorfismo de Nucleotídeo Único , Humanos , China , Genômica , Evolução Molecular , Frequência do Gene , Povo Asiático/genética , Genoma HumanoRESUMO
INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low- and high-score groups, and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p = 0.011). A smaller final infarct size and a higher diffusion-weighted imaging-based Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p < 0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.
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Enteritis poses a significant threat to fish farming, characterized by symptoms of intestinal and hepatic inflammation, physiological dysfunction, and dysbiosis. Focused on the leopard coral grouper (Plectropomus leopardus) with an enteritis outbreak on a South China Sea farm, our prior scrutiny did not find any abnormalities in feeding or conventional water quality factors, nor were any specific pathogen infections related to enteritis identified. This study further elucidates their intestinal flora alterations, host responses, and their interactions to uncover the underlying pathogenetic mechanisms and facilitate effective prevention and management strategies. Enteritis-affected fish exhibited substantial differences in intestinal flora compared to control fish (P = 0.001). Notably, norank_f_Alcaligenaceae, which has a negative impact on fish health, predominated in enteritis-affected fish (91.76 %), while the probiotic genus Lactococcus dominated in controls (93.90 %). Additionally, certain genera with pathogenesis potentials like Achromobacter, Sphingomonas, and Streptococcus were more abundant in diseased fish, whereas Enterococcus and Clostridium_sensu_stricto with probiotic potentials were enriched in control fish. At the transcriptomic level, strong inflammatory responses, accompanied by impaired metabolic functions, tissue damage, and iron death signaling activation were observed in the intestines and liver during enteritis. Furthermore, correlation analysis highlighted that potential pathogen groups were positively associated with inflammation and tissue damage genes while presenting negatively correlated with metabolic function-related genes. In conclusion, dysbiosis in the intestinal microbiome, particularly an aberrantly high abundance of Alcaligenaceae with pathogenic potential may be the main trigger for this enteritis outbreak. Alcaligenaceae alongside Achromobacter, Sphingomonas, and Streptococcus emerged as biomarkers for enteritis, whereas some species of Lactococcus, Clostridium_sensu_stricto, and Enterococcus showed promise as probiotics to alleviate enteritis symptoms. These findings enhance our understanding of enteritis pathogenesis, highlight intestinal microbiota shifts in leopard coral grouper, and propose biomarkers for monitoring, probiotic selection, and enteritis management.
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Enterite , Doenças dos Peixes , Microbioma Gastrointestinal , Animais , Enterite/veterinária , Enterite/imunologia , Enterite/microbiologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Perciformes/imunologia , China , Expressão GênicaRESUMO
The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag2O2-CDs) with high photothermal conversion efficiency viain situoxidation process. The prepared Ag2O2-CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag2O2-CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag2O2into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag2O2-CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag2O2-CDs could be served as a potential antibacterial agent for clinical applications.
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Antibacterianos , Carbono , Pontos Quânticos , Compostos de Prata , Carbono/química , Pontos Quânticos/química , Antibacterianos/farmacologia , Antibacterianos/química , Compostos de Prata/química , Compostos de Prata/farmacologia , Óxidos/química , Óxidos/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Prata/química , Prata/farmacologia , Testes de Sensibilidade Microbiana , Escherichia coli/efeitos dos fármacosRESUMO
BACKGROUND: Undertreatment of ovarian cancer is common among older women. We aimed to evaluate the treatment modalities offered to older patients and their impact on overall survival (OS). METHODS: The study identified 5,055 patients with high-grade serous ovarian cancer and 3584 patients with advanced stage (IIIC + IV) disease from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2017. We performed comparisons of OS and ovarian cancer-specific survival (OCSS) across age groups using a Cox proportional hazards model. RESULTS: Very elderly patients (≥ 75 years old) received treatment with significantly less surgical complexity, such as no lymphadenectomy (59.7% vs. 48.6%; p < 0.001) and a lower rate of optimal debulking surgery (44.0% vs. 52.7%; p < 0.001), as well as lower rates of chemotherapy (78.2% vs. 89.4%; P<0.001) and standard treatment (70.6% vs. 85%; p < 0.001). High proportions of both very elderly and elderly patients received neoadjuvant chemotherapy (NACT), with no significant difference (38.7% vs. 36.2%; P = 0.212). Patients aged ≥ 75 years had significantly worse OS and OCSS. CONCLUSION: With increasing age, the survival rate of women with ovarian cancer decreases significantly. Noticeably fewer ovarian cancer patients aged over 75 years receive standard treatments, and more very elderly patients are treated with NACT.
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Neoplasias Ovarianas , Idoso , Humanos , Feminino , Estadiamento de Neoplasias , Quimioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Terapia NeoadjuvanteRESUMO
This paper presents the test results for high-performance and high-uniformity waveguide silicon-based germanium (Ge) photodetectors (PDs) for the O band and C band. Both wafer-scale and chip-scale test results are provided. The fabricated lateral p-i-n (LPIN) PDs exhibit a responsivity of 0.97 A/W at a bias of -2V, a bandwidth of 60 GHz, and a no-return-to-zero (NRZ) eye diagram rate of 53.125 Gb/s. Additionally, an average dark current of 22.4 nA was obtained in the vertical p-i-n (VPIN) PDs at -2V by optimizing the doping process. The device can reach an average responsivity of 0.9 A/W in the O band. The standard deviation in a wafer with a dark current and responsivity is as low as 7.77 nA and 0.03 A/W at -2V, respectively.
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OBJECTIVE: This study aimed to evaluate the role of receptor-interacting protein kinase-3 (RIPK3) in the diagnosis, estimation of disease severity, and prognosis of premature infants with necrotising enterocolitis (NEC). METHODS: RIPK3, lactic acid (LA), and C-reactive protein (CRP) levels were measured in the peripheral blood of 108 premature infants between 2019 and 2023, including 24 with stage II NEC, 18 with stage III NEC and 66 controls. Diagnostic values of the indicators for NEC were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: Plasma RIPK3 and LA levels upon NEC suspicion in neonates with stage III NEC were 32.37 ± 16.20 ng/mL. The ROC curve for the combination of RIPK3, LA, CRP for NEC diagnosis were 0.925. The time to full enteral feeding (FEFt) after recovery from NEC was different between two expression groups of plasma RIPK3 (RIPK3 < 20.06 ng/mL and RIPK3 ≥ 20.06 ng/mL). CONCLUSION: Plasma RIPK3 can be used as a promising marker for the diagnosis and estimation of disease severity of premature infants with NEC and for the guidance on proper feeding strategies after recovery from NEC.
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Biomarcadores , Enterocolite Necrosante , Recém-Nascido Prematuro , Proteína Serina-Treonina Quinases de Interação com Receptores , Humanos , Enterocolite Necrosante/sangue , Enterocolite Necrosante/diagnóstico , Recém-Nascido , Proteína Serina-Treonina Quinases de Interação com Receptores/sangue , Biomarcadores/sangue , Masculino , Feminino , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Prognóstico , Curva ROC , Índice de Gravidade de Doença , Doenças do Prematuro/sangue , Doenças do Prematuro/diagnóstico , Estudos de Casos e Controles , Ácido Láctico/sangueRESUMO
AIM: To summarize existing studies that focused on improving hospitalized patient safety through patient and family engagement interventions to identify priorities and gaps. DESIGN: A scoping review. METHODS: Eight databases and citations of important reviews were searched on 30 September 2022. Two researchers independently screened the records. Then, two researchers extracted the data and cross-checked. The results were synthesized narratively, and a comparison was performed for studies from China and those from other countries. RESULTS: Ninety-eight studies were included. The results indicated that patient and family engagement interventions were applied to decrease the incidence of patient safety incidents, and to improve the healthcare providers' and patients' knowledge, attitude or practice of patient safety. Most studies only engaged patients and families at the direct care level, and the engagement strategies at the organization and health system levels were insufficient. For stakeholders, many studies failed to consider patients' perspectives in intervention design and report taking staff training as a supportive strategy. Healthcare providers, especially nurses, were the main implementers of current interventions. Certain differences were observed between studies from China and those from other countries in the above aspects. CONCLUSIONS: International interest in engaging patient and family for patient safety is growing. Future studies should enhance the patient and family engagement as a partner in various patient safety at the direct care level, and further explore the engagement at the organization and health system levels. RELEVANCE TO CLINICAL PRACTICE: Nurses, as the main formal caregivers for patients, should promote patient and family engagement in patient safety, especially at direct care level. Nurse should also incorporate the perspectives of patients in the design and implementation of interventions. REPORTING METHOD: PRISMA-ScR Checklist.
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Família , Segurança do Paciente , Feminino , Humanos , Masculino , China , Família/psicologia , Hospitalização , Participação do Paciente/métodos , Segurança do Paciente/normasRESUMO
The ability to rapidly provide examinees with detailed and effective diagnostic information is a critical topic in psychology. Knowing what diagnostic criteria the examinees have met enables the practitioner to seek the solution to help them in a timely manner, and this can be achieved by cognitive diagnostic computerized adaptive testing (CD-CAT). However, the pervasive challenge of replenishing items in the CD-CAT item bank limits its practical application. Online calibration is a means to address item replenishment, but in CD-CAT, most existing online calibration methods that jointly calibrate the Q-matrix and item parameters of the new items are developed only for dichotomous responses and are time-consuming. Notably, previous studies pay no attention to polytomously scored items that are frequently observed in testing, even though they can offer additional evidence for the examinees' diagnosis. To fill this gap, we propose a SCAD-based method (SCAD-EM) to calibrate the Q-matrix and item parameters of the new items with polytomous response data in order to promote the application of CD-CAT in practice. The performance of the SCAD-EM was investigated in two comprehensive simulation studies and compared against the revised single-item estimation method (SIE-BIC). Results indicated that the SCAD-EM produces a higher calibration accuracy for the category-level Q-matrix and is computationally more efficient across all conditions, but it produces a lower calibration accuracy for the item-level Q-matrix. An empirical study further demonstrated the utility of the SCAD-EM and the SIE-BIC methods in calibrating new items with a real dataset. The advantages of the proposed method, its limitations, and possible future research directions are offered at the end.
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Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.
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Diabetes Mellitus Tipo 2 , Fator 1-alfa Nuclear de Hepatócito , Células Secretoras de Insulina , Humanos , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Células Secretoras de Insulina/metabolismo , MutaçãoRESUMO
Inflammatory bowel disease (IBD) is a group of diseases characterized by refractory and chronic inflammation of the bowel, which can be treated with biologics in clinical practice. Anti-tumor necrosis factor α (TNF-α) agents, which are among the most widely used biologics, alleviate the inflammatory activity in a variety of ways. Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa, which could cause chronic inflammation and even induce gastric cancer. However, it has been suggested that H. pylori has a potential protective role in IBD patients. Yet there has been limited research on the mechanisms of the effect of H. pylori infection in IBD patients, and whether there is an interaction between H. pylori and anti-TNF-α agents. This review aims to summarize the possible mechanisms of H. pylori and anti-TNF-α agents in the development and treatment of IBD, and to explore the possible interaction between H. pylori infection and anti-TNF-α agents.
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In situ cyclized polyacrylonitrile (CPAN) is developed to replace n-type metal oxide semiconductors (TiO2 or SnO2) as an electron selective layer (ESL) for highly efficient and stable n-i-p perovskite solar cells (PSCs). The CPAN layer is fabricated via facile in situ cyclization reaction of polyacrylonitrile (PAN) coated on a conducting glass substrate. The CPAN layer is robust and insoluble in common solvents, and possesses n-type semiconductor properties with a high electron mobility of 4.13×10-3â cm2 V-1 s-1. With the CPAN as an ESL, the PSC affords a power conversion efficiency (PCE) of 23.12 %, which is the highest for the n-i-p PSCs with organic ESLs. Moreover, the device with the CPAN layer holds superior operational stability, maintaining over 90 % of their initial efficiency after 500â h continuous light soaking. These results confirm that the CPAN layer would be a desirable low-cost and efficient ESL for n-i-p PSCs and other photoelectronic devices with high performance and stability.
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BACKGROUND: With the advent of proline-based reporter isobaric Tandem Mass Tag (TMTpro) reagents, the sample multiplexing capacity of tandem mass tags (TMTs) has been expanded, and up to 18 samples can be quantified in a multiplexed manner. Like classic TMT reagents, TMTpro reagents contain a tertiary amine group, which markedly enhances their reactivity toward hydroxyl groups and results in O-acylation of serine, threonine and tyrosine residues. This overlabeling significantly compromises proteome analysis in terms of depth and precision. In particular, the reactivity of hydroxyl-containing residues can be dramatically enhanced when coexisting with a histidine in the same peptides, leading to a severe systematic bias against the analysis of these peptides. Although some protocols using a reduced molar excess of TMT under alkaline conditions can alleviate overlabeling of histidine-free peptides to some extent, they have a limited effect on histidyl- and hydroxyl-containing peptides. RESULTS: Here, we report a novel TMTpro labeling method that overcomes detrimental overlabeling while providing high labeling efficiency of amines. Additionally, our method is cost-effective, as it requires only half the amount of TMTpro reagents recommended by the reagent manufacturer. In a deep-scale analysis of a yeast/human two-proteome model sample, we compared our method with a typical alkaline labeling method using a reduced molar excess of TMTpro. Even at a depth of over 10,000 proteins, our method detected 23.7% more unique peptides and 8.7% more protein groups compared to the alkaline labeling method. Moreover, our method significantly improved the quantitative precision due to the reduced variability in labeling and increased protein sequence coverage. This substantially enhanced the statistical power of our method for detecting differentially abundant proteins, providing an average of 13% more yeast proteins that reached statistical significance. SIGNIFCANCE: We presented a novel TMTpro labeling method that overcomes the detrimental O-acylation and thus significantly improves the depth and quantitative precision for proteome analysis.
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Proteoma , Espectrometria de Massas em Tandem , Humanos , Proteoma/análise , Espectrometria de Massas em Tandem/métodos , Proteômica/métodos , Peptídeos/química , Aminas , AcilaçãoRESUMO
Metastatic hepatocellular carcinoma (HCC) is an aggressive disease which usually have a poor prognosis. Early mortality and risk factors in patients with metastatic HCC are poorly understood. Our study sought to identify associated risk factors and develop the nomograms for predicting early death in metastatic HCC patients. The patients diagnosed with metastatic HCC were chosen from the surveillance, epidemiology, and end results database between 2010 and 2015. To identify significant independent risk factors for early death, both univariate and multivariate logistic regression models were used. We constructed a pragmatic nomogram and then evaluated by using receiver operating characteristic curves, calibration plots, and decision curve analysis. The prediction model included 2587 patients with metastatic HCC. Among them, 1550 experienced early death (died within 3 months of initial diagnosis) and 1437 died from cancer-specific causes. Multivariate logistic regression analysis found that grade, surgery, radiation, chemotherapy, alpha-fetoprotein levels, and lung metastasis were independent risk factors for both all-cause early death and cancer-specific early death. In addition, bone metastasis were independent risk factors for all-cause early death, T-stage and brain metastasis were also independent risk factors for cancer-specific early death. Then we used the relevant risk factors to developed the practical nomograms of all-cause and cancer-specific early deaths. The nomograms demonstrated good predictive power and clinical utility under receiver operating characteristic curves and decision curve analysis. We developed 2 novel comprehensive nomograms to predict early death among metastatic HCC patients. Nomograms may help oncologists develop better treatment strategies and implementation of individualized treatment plans.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Nomogramas , Estudos de Coortes , AgressãoRESUMO
Objective: This study aimed to explore disulfidptosis-related clusters of triple-negative breast cancer (TNBC) and build a reliable disulfidptosis-related gene signature for forecasting TNBC prognosis. Methods: The disulfidptosis-related clusters of TNBC were identified based on public datasets, and a comparative analysis was conducted to assess their differences in the overall survival (OS) and immune cell infiltration. Morever, the differentially expressed genes (DEGs) between clusters were recognized. Then, the prognostic DEGs were then chosen. A prognostic signature was constructed by the prognostic DEGs, followed by nomogram construction, drug sensitivity, immune correlation, immunotherapy response prediction, and cluster association analyses. Results: Two disulfidptosis-related clusters of TNBC were identified, which had different OS and macrophage infiltration. Moreover, 235 DEGs were identified between two clusters. A prognostic signature was then constructed by five prognostic DEGs including HLA-DQA2, CCL13, GBP1, LAMP3, and SLC7A11. This signature was highly valuable in predicting prognosis. A nomogram was built by risk score and AJCC stage, which could forecast OS accurately. Moreover, patients with high-risk scores exhibited greater sensitivity to chemotherapy drugs such as lapatinib and had a lower immunotherapy response. Conclusions: Two TNBC clusters linked to disulfidptosis were identified, with different OS and immune cell infiltration. Moreover, a five-disulfidptosis-related gene signature may be a powerful prognostic biomarker for TNBC.
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Objective: Childhood sexual abuse (CSA) can have a negative impact on women's psychological, emotional and social functioning. The purpose of this study was to explore the relationship between CSA and depressive symptoms in female college students, as well as the mediating roles of negative core schema and experiential avoidance. Methods: 515 female college students responded to the Sexual Abuse subscale of the Childhood Trauma Questionnaire, the Depression subscale of the Depression Anxiety Stress Scale, the Brief Core Schema Scales, and the Acceptance and Action Questionnaire - II. The structural equation modeling was used for the mediation analysis. Results: There was a significant positive correlation between CSA and depressive symptoms in female college students. The theoretical model was well fitted, χ2/df = 3.422, RMSEA = 0.069, CFI = 0.929, TLI = 0.919. The negative core schema played a mediating role between CSA and depressive symptoms. Experiential avoidance played a mediating role between CSA and depressive symptoms. The negative core schema and experiential avoidance played a serial mediating role between CSA and depressive symptoms. Conclusion: These results deepen our understanding of the relationship between CSA and depressive symptoms in female college students, and provide theoretical guidance for the prevention of depression in female college students. Attention should be paid to female college students who have experienced CSA, to eliminate the adverse influence of negative core schema on these students. Meanwhile, we should teach female college students to accept themselves as they are, and thereby reduce their use of experiential avoidance strategies.
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Forced-choice (FC) measures have been widely used in many personality or attitude tests as an alternative to rating scales, which employ comparative rather than absolute judgments. Several response biases, such as social desirability, response styles, and acquiescence bias, can be reduced effectively. Another type of data linked with comparative judgments is response time (RT), which contains potential information concerning respondents' decision-making process. It would be challenging but exciting to combine RT into FC measures better to reveal respondents' behaviors or preferences in personality measurement. Given this situation, this study aims to propose a new item response theory (IRT) model that incorporates RT into FC measures to improve personality assessment. Simulation studies show that the proposed model can effectively improve the estimation accuracy of personality traits with the ancillary information contained in RT. Also, an application on a real data set reveals that the proposed model estimates similar but different parameter values compared with the conventional Thurstonian IRT model. The RT information can explain these differences.