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Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental-stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation, with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes.
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Metilação de DNA , Células Germinativas/metabolismo , Transcriptoma , Movimento Celular , Cromossomos Humanos X , Análise por Conglomerados , Embrião de Mamíferos/metabolismo , Feminino , Histonas/metabolismo , Humanos , Masculino , Análise de Componente Principal , Fatores de Transcrição SOX/metabolismoRESUMO
The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.
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Parede Celular , Etilenos , Regulação da Expressão Gênica de Plantas , Glucosiltransferases , Oryza , Proteínas de Plantas , Raízes de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Parede Celular/metabolismo , Etilenos/metabolismo , Glucosiltransferases/metabolismo , Glucosiltransferases/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Glucanos/metabolismo , Xilanos/metabolismo , Celulose/metabolismoRESUMO
Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics. Using network embedding in the Poincaré disk, the hierarchy depths of chromatin from CRC and T-ALL patients were found to be significantly shallower compared to their normal controls. A reverse trend of change in chromatin structure was observed during early embryo development. We found tissue-specific conservation of hierarchy order in chromatin contact networks. Our findings reveal the top-down hierarchy of chromatin organization, which is significantly attenuated in cancer.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Genoma , Cromatina , Diferenciação CelularRESUMO
The interactome networks at the DNA, RNA, and protein levels are crucial for cellular functions, and the diverse variations of these networks are heavily involved in the establishment of different cell states. We have developed a diffusion-based method, Hi-C to geometry (CTG), to obtain reliable geometric information on the chromatin from Hi-C data. CTG produces a consistent and reproducible framework for the 3D genomic structure and provides a reliable and quantitative understanding of the alterations of genomic structures under different cellular conditions. The genomic structure yielded by CTG serves as an architectural blueprint of the dynamic gene regulatory network, based on which cell-specific correspondence between gene-gene and corresponding protein-protein physical interactions, as well as transcription correlation, is revealed. We also find that gene fusion events are significantly enriched between genes of short CTG distances and are thus close in 3D space. These findings indicate that 3D chromatin structure is at least partially correlated with downstream processes such as transcription, gene regulation, and even regulatory networking through affecting protein-protein interactions.
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Cromatina , Redes Reguladoras de Genes , Cromatina/genética , Regulação da Expressão Gênica , Cromossomos , DNARESUMO
The perception of facial expression plays a crucial role in social communication, and it is known to be influenced by various facial cues. Previous studies have reported both positive and negative biases toward overweight individuals. It is unclear whether facial cues, such as facial weight, bias facial expression perception. Combining psychophysics and event-related potential technology, the current study adopted a cross-adaptation paradigm to examine this issue. The psychophysical results of Experiments 1A and 1B revealed a bidirectional cross-adaptation effect between overweight and angry faces. Adapting to overweight faces decreased the likelihood of perceiving ambiguous emotional expressions as angry compared to adapting to normal-weight faces. Likewise, exposure to angry faces subsequently caused normal-weight faces to appear thinner. These findings were corroborated by bidirectional event-related potential results, showing that adaptation to overweight faces relative to normal-weight faces modulated the event-related potential responses of emotionally ambiguous facial expression (Experiment 2A); vice versa, adaptation to angry faces relative to neutral faces modulated the event-related potential responses of ambiguous faces in facial weight (Experiment 2B). Our study provides direct evidence associating overweight faces with facial expression, suggesting at least partly common neural substrates for the perception of overweight and angry faces.
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Expressão Facial , Preconceito de Peso , Humanos , Sobrepeso , Ira/fisiologia , Potenciais Evocados/fisiologia , Emoções/fisiologiaRESUMO
RNA-RNA association and phase separation appear to be essential for the assembly of stress granules and underlie RNA foci formation in repeat expansion disorders. RNA molecules are found to play a significant role in gene-regulatory functions via condensate formation among themselves or with RNA-binding proteins. The interplay between driven versus spontaneous processes is likely to be an important factor for controlling the formation of RNA-mediated biomolecular condensate. However, the sequence-specific interactions and molecular mechanisms that drive the spontaneous RNA-RNA association and help to form RNA-mediated phase-separated condensate remain unclear. With microseconds-long atomistic molecular simulations here, we report how essential aspects of RNA chains, namely, base composition, metal ion binding, and hydration properties, contribute to the association of the series of simplest biologically relevant homopolymeric and heteropolymeric short RNA chains. We show that spontaneous processes make the key contributions governed by the sequence-intrinsic properties of RNA chains, where the definite roles of base-specific hydrogen bonding and stacking interactions are prominent in the association of the RNA chains. Purine versus pyrimidine contents of RNA chains can directly influence the association properties of RNA chains by modulating hydrogen bonding and base stacking interactions. This study determines the impact of ionic environment in sequence-specific spontaneous association of short RNA chains, hydration features, and base-specific interactions of Na+, K+, and Mg2+ ions with RNA chains.
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This article comprehensively elucidates the discovery of Krebs von den Lungen-6 (KL-6), its structural features, functional mechanisms, and the current research status in various respiratory system diseases. Discovered in 1985, KL-6 was initially considered a tumor marker, but its elevated levels in interstitial lung disease (ILD) led to its recognition as a relevant serum marker for ILD. KL-6 is primarily produced by type 2 alveolar epithelial cell regeneration. Over the past 30 years since the discovery of KL-6, the number of related research papers has steadily increased annually. Following the coronavirus disease 2019 (COVID-19) pandemic, there has been a sudden surge in relevant literature. Despite KL-6's potential as a biomarker, its value in the diagnosis, treatment, and prognosis varies across different respiratory diseases, including ILD, idiopathic pulmonary fibrosis (IPF), COVID-19, and lung cancer. Therefore, as an important serum biomarker in respiratory system diseases, the value of KL-6 still requires further investigation.
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Biomarcadores , COVID-19 , Mucina-1 , Humanos , Mucina-1/sangue , COVID-19/epidemiologia , Biomarcadores/sangue , SARS-CoV-2 , Doenças Respiratórias/diagnóstico , Doenças Pulmonares Intersticiais/diagnósticoRESUMO
Identifying the active phase with the highest activity, which is long-believed to be a steady state of the catalyst, is the basis of rational design of heterogeneous catalysis. In this work, we performed detailed in situ investigations, successfully capturing the instantaneous structure-activity change in oscillating Pd nanocatalysts during methane oxidation, which reveals an unprecedented oscillatory active state. Combining in situ quantitative environmental transmission electron microscopy and highly sensitive online mass spectrometry, we identified two distinct phases for the reaction: one where the Pd nanoparticles refill with oxygen, and the other, a period of abrupt pumping of oxygen and boosted methane oxidation within about 1 s. It is the rapid reduction process that shows the highest activity for total oxidation of methane, not a PdO or Pd steady state under the conditions applied here (methane:oxygen = 5:1). This observation challenges the traditional understanding of the active phase and requires a completely different strategy for catalyst optimization.
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Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.
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Cromatina , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Humanos , Cromatina/genética , Cromatina/metabolismo , Histonas/metabolismo , Histonas/genética , Redes Reguladoras de Genes , Variações do Número de Cópias de DNARESUMO
Covering: up to the end of 2023Type I CRISPR-Cas systems are widely distributed, found in over 40% of bacteria and 80% of archaea. Among genome-sequenced actinomycetes (particularly Streptomyces spp.), 45.54% possess type I CRISPR-Cas systems. In comparison to widely used CRISPR systems like Cas9 or Cas12a, these endogenous CRISPR-Cas systems have significant advantages, including better compatibility, wide distribution, and ease of operation (since no exogenous Cas gene delivery is needed). Furthermore, type I CRISPR-Cas systems can simultaneously edit and regulate genes by adjusting the crRNA spacer length. Meanwhile, most actinomycetes are recalcitrant to genetic manipulation, hindering the discovery and engineering of natural products (NPs). The endogenous type I CRISPR-Cas systems in actinomycetes may offer a promising alternative to overcome these barriers. This review summarizes the challenges and recent advances in CRISPR-based genome engineering technologies for actinomycetes. It also presents and discusses how to establish and develop genome editing tools based on type I CRISPR-Cas systems in actinomycetes, with the aim of their future application in gene editing and the discovery of NPs in actinomycetes.
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Actinobacteria , Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Actinobacteria/genética , Genoma BacterianoRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. METHODS: The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. RESULTS: SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. CONCLUSIONS: SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidor de Serinopeptidase do Tipo Kazal 5 , Humanos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Células HEK293 , Lipopolissacarídeos , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Inibidor de Serinopeptidase do Tipo Kazal 5/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
In contemporary medical practice, general anesthesia plays an essential role in pediatric surgical procedures. While modern anesthetic protocols have demonstrated safety and efficacy across various pathological conditions, concerns persist regarding the potential neurotoxic effects associated with early exposure to general anesthesia. Current research primarily examines the neurocognitive developmental impacts, with limited focus on neurobehavioral developmental disorders. This review presents a comprehensive analysis of clinical trial results related to five critical neurobehavioral developmental disorders: fine motor disability, attention-deficit-hyperactivity disorder (ADHD), impulse control disorders (ICDs), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, the review synthesizes insights from basic research on the potential toxicological mechanisms of general anesthetic agents that could influence clinical neurobehavioral changes. These findings provide valuable guidance for the prudent and safe utilization of anesthetic agents in pediatric patients.
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To meet increasing requirement for innovative energy storage and conversion technology, it is urgent to prepare effective, affordable, and long-term stable oxygen electrocatalysts to replace precious metal-based counterparts. Herein, a two-step pyrolysis strategy is developed for controlled synthesis of Fe2O3 and Mn3O4 anchored on carbon nanotubes/nanosheets (Fe2O3-Mn3O4-CNTs/NSs). The typical catalyst has a high half-wave potential (E1/2 = 0.87 V) for oxygen reduction reaction (ORR), accompanied with a smaller overpotential (η10 = 290 mV) for oxygen evolution reaction (OER), showing substantial improvement in the ORR and OER performances. As well, density functional theory calculations are performed to illustrate the catalytic mechanism, where the in situ generated Fe2O3 directly correlates to the reduced energy barrier, rather than Mn3O4. The Fe2O3-Mn3O4-CNTs/NSs-based Zn-air battery exhibits a high-power density (153 mW cm-2) and satisfyingly long durability (1650 charge/discharge cycles/550 h). This work provides a new reference for preparation of highly reversible oxygen conversion catalysts.
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The development of capable of simultaneously modulating the sluggish electrochemical kinetics, shuttle effect, and lithium dendrite growth is a promising strategy for the commercialization of lithium-sulfur batteries. Consequently, an elaborate preparation method is employed to create a host material consisting of multi-channel carbon microspheres (MCM) containing highly dispersed heterostructure Fe3O4-FeTe nanoparticles. The Fe3O4-FeTe@MCM exhibits a spontaneous built-in electric field (BIEF) and possesses both lithophilic and sulfophilic sites, rendering it an appropriate host material for both positive and negative electrodes. Experimental and theoretical results reveal that the existence of spontaneous BIEF leads to interfacial charge redistribution, resulting in moderate polysulfide adsorption which facilitates the transfer of polysulfides and diffusion of electrons at heterogeneous interfaces. Furthermore, the reduced conversion energy barriers enhanced the catalytic activity of Fe3O4-FeTe@MCM for expediting the bidirectional sulfur conversion. Moreover, regulated Li deposition behavior is realized because of its high conductivity and remarkable lithiophilicity. Consequently, the battery exhibited long-term stability for 500 cycles with 0.06% capacity decay per cycle at 5 C, and a large areal capacity of 7.3 mAh cm-2 (sulfur loading: 9.73 mg cm-2) at 0.1 C. This study provides a novel strategy for the rational fabrication of heterostructure hosts for practical Li-S batteries.
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SUMMARY: Limited by spatial resolution and visual contrast, bone scintigraphy interpretation is susceptible to subjective factors, which considerably affects the accuracy and repeatability of lesion detection and anatomical localization. In this work, we design and implement an end-to-end multi-task deep learning model to perform automatic lesion detection and anatomical localization in whole-body bone scintigraphy. A total of 617 whole-body bone scintigraphy cases including anterior and posterior views were retrospectively analyzed. The proposed semi-supervised model consists of two task flows. The first one, the lesion segmentation flow, received image patches and was trained in a supervised way. The other one, skeleton segmentation flow, was trained on as few as five labeled images in conjunction with the multi-atlas approach, in a semi-supervised way. The two flows joint in their encoder layers so each flow can capture more generalized distribution of the sample space and extract more abstract deep features. The experimental results show that the architecture achieved the highest precision in the finest bone segmentation task in both anterior and posterior images of whole-body scintigraphy. Such an end-to-end approach with very few manual annotation requirement would be suitable for algorithm deployment. Moreover, the proposed approach reliably balances unsupervised labels construction and supervised learning, providing useful insight for weakly labeled image analysis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Aprendizado Profundo , Estudos Retrospectivos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Cintilografia , Aprendizado de Máquina SupervisionadoRESUMO
Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.
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Aminoácidos , Proliferação de Células , Fluoretos , Músculo Liso Vascular , Ratos Sprague-Dawley , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos dos fármacos , Fluoretos/farmacologia , Linhagem Celular , Aminoácidos/metabolismo , Proliferação de Células/efeitos dos fármacos , Ratos , Movimento Celular/efeitos dos fármacos , Masculino , Aorta/patologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Metabolômica , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Redes Reguladoras de Genes/efeitos dos fármacosRESUMO
BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Humanos , Masculino , Feminino , Terapia Neoadjuvante/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Taxa de Sobrevida , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esofagectomia/mortalidade , Prognóstico , Seguimentos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Resposta Patológica CompletaRESUMO
BACKGROUND: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy. PATIENTS AND METHODS: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection. RESULTS: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40). CONCLUSION: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival.
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Underwater wireless optical communication (UWOC) has been widely studied as a key technology for ocean exploration and exploitation. However, current UWOC systems neglect semantic information of transmitted symbols, leading to unnecessary consumption of communication resources for transmitting non-essential data. In this paper, we propose and demonstrate a deep-learning-based underwater wireless optical semantic communication (UWOSC) system for image transmission. By utilizing a deep residual convolutional neural network, the semantic information can be extracted and mapped into the transmitted symbols. Moreover, we design a channel model based on long short-term memory network and employ a two-phase training strategy to ensure that the system matches the underwater channel. To evaluate the performance of the proposed UWOSC system, we conduct a series of experiments on an emulated UWOC experimental platform, in which the effects of different turbidity channel environments and bandwidth compression ratios are investigated. Experimental results show that the UWOSC system exhibits superior performance compared to the conventional communication schemes, particularly in challenging channel environments and low bandwidth compression ratios.
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BACKGROUND: Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. METHODS: This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. RESULTS: During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear < 0.0001). CONCLUSIONS: In this study, there is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. Besides, a higher AIP was significantly associated with an increased risk of diabetes mortality, which only found in women older than 65 years. AIP was associated with all-cause mortality in a U-shape. This association could be explained by the finding that higher AIP predicted a higher risk of death from diabetes, and that lower AIP predicted a higher risk of death from non-diabetes causes.
We used a large national database and a prospective cohort study with a long follow-up period. Higher AIP was significantly associated with an increased risk of diabetes mortality, only in women older than 65 years. There is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. AIP was associated with all-cause mortality in a U-shape. This finding suggest that controlling AIP levels may have a positive effect on reducing diabetes mortality.