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Climate change is a new disrupter to global fisheries systems and their governance frameworks. It poses a pressing management challenge, particularly in China, which is renowned as the world's largest fishing country and seafood producer. As climate change continues to intensify in the region and climate awareness grows within the country's national policy, the need to understand China's fisheries' resilience to the escalating climate crisis becomes paramount. In this study, we conduct an interdisciplinary analysis to assess the vulnerability and risk of China's marine capture fisheries in response to climate change. This study employs a spatially explicit, indicator-based approach with a coupled social-ecological framework, focusing on 67 species and 11 coastal regions. By integrating diverse sets of climatic, ecological, economic, societal, and governance indicators and information, we elucidate the factors that could hinder climate adaptation, including a limited understanding of fish early life stages, uncertainty in seafood production, unequal allocation and accessibility of resources, and inadequate consideration of inclusive governance and adaptive management. Our results show that species, which have managed to survive the stress of overfishing, demonstrate a remarkable ability to adapt to climate change. However, collapsing stocks such as large yellow croaker face a high risk due to the synergistic effects of inherent biological traits and external management interventions. We emphasize the imperative to build institutional, scientific, and social capacity to support fisheries adaptation. The scientific insights provided by this study can inform fisheries management decisions and promote the operationalization of climate-resilient fisheries in China and other regions.
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Conservação dos Recursos Naturais , Pesqueiros , Animais , Mudança Climática , Meio Social , China , Ecossistema , PeixesRESUMO
Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.
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Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog , Larva , Metamorfose Biológica , Desenvolvimento Muscular , Mytilus , Transdução de Sinais , Animais , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Mytilus/crescimento & desenvolvimento , Mytilus/metabolismo , Alcaloides de Veratrum/farmacologia , Músculos/metabolismoRESUMO
Liver can sense the nutrient status and send signals to other organs to regulate overall metabolic homoeostasis. Herein, we demonstrate that ketone bodies act as signals released from the liver that specifically determine the distribution of excess lipid in epididymal white adipose tissue (eWAT) when exposed to a ketogenic diet (KD). An acute KD can immediately result in excess lipid deposition in the liver. Subsequently, the liver sends the ketone body ß-hydroxybutyrate (BHB) to regulate white adipose expansion, including adipogenesis and lipogenesis, to alleviate hepatic lipid accumulation. When ketone bodies are depleted by deleting 3-hydroxy-3-methylglutaryl-CoA synthase 2 gene in the liver, the enhanced lipid deposition in eWAT but not in inguinal white adipose tissue is preferentially blocked, while lipid accumulation in liver is not alleviated. Mechanistically, ketone body BHB can significantly decrease lysine acetylation of peroxisome proliferator-activated receptor gamma in eWAT, causing enhanced activity of peroxisome proliferator-activated receptor gamma, the key adipogenic transcription factor. These observations suggest that the liver senses metabolic stress first and sends a corresponding signal, that is, ketone body BHB, to specifically promote eWAT expansion to adapt to metabolic challenges.
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Tecido Adiposo Branco , Dieta Cetogênica , Fígado Gorduroso , Corpos Cetônicos , Humanos , Tecido Adiposo Branco/metabolismo , Fígado Gorduroso/metabolismo , Corpos Cetônicos/metabolismo , Lipídeos , Fígado/metabolismo , PPAR gama/metabolismoRESUMO
BACKGROUND: Although network analysis studies of psychiatric syndromes have increased in recent years, most have emphasized centrality symptoms and robust edges. Broadening the focus to include bridge symptoms within a systematic review could help to elucidate symptoms having the strongest links in network models of psychiatric syndromes. We conducted this systematic review and statistical evaluation of network analyses on depressive and anxiety symptoms to identify the most central symptoms and bridge symptoms, as well as the most robust edge indices of networks. METHODS: A systematic literature search was performed in PubMed, PsycINFO, Web of Science, and EMBASE databases from their inception to May 25, 2022. To determine the most influential symptoms and connections, we analyzed centrality and bridge centrality rankings and aggregated the most robust symptom connections into a summary network. After determining the most central symptoms and bridge symptoms across network models, heterogeneity across studies was examined using linear logistic regression. RESULTS: Thirty-three studies with 78,721 participants were included in this systematic review. Seventeen studies with 23 cross-sectional networks based on the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder (GAD-7) assessments of clinical and community samples were examined using centrality scores. Twelve cross-sectional networks based on the PHQ and GAD-7 assessments were examined using bridge centrality scores. We found substantial variability between study samples and network features. 'Sad mood', 'Uncontrollable worry', and 'Worrying too much' were the most central symptoms, while 'Sad mood', 'Restlessness', and 'Motor disturbance' were the most frequent bridge centrality symptoms. In addition, the connection between 'Sleep' and 'Fatigue' was the most frequent edge for the depressive and anxiety symptoms network model. CONCLUSION: Central symptoms, bridge symptoms and robust edges identified in this systematic review can be viewed as potential intervention targets. We also identified gaps in the literature and future directions for network analysis of comorbid depression and anxiety.
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Ansiedade , Depressão , Feminino , Humanos , Masculino , Ansiedade/complicações , Ansiedade/terapia , Transtornos de Ansiedade , Estudos Transversais , Depressão/complicações , Depressão/terapiaRESUMO
Effective visual search is essential for daily life, and attention orientation as well as inhibition of return play a significant role in visual search. Researches have established the involvement of dorsolateral prefrontal cortex in cognitive control during selective attention. However, neural evidence regarding dorsolateral prefrontal cortex modulates inhibition of return in visual search is still insufficient. In this study, we employed event-related functional magnetic resonance imaging and dynamic causal modeling to develop modulation models for two types of visual search tasks. In the region of interest analyses, we found that the right dorsolateral prefrontal cortex and temporoparietal junction were selectively activated in the main effect of search type. Dynamic causal modeling results indicated that temporoparietal junction received sensory inputs and only dorsolateral prefrontal cortex âtemporoparietal junction connection was modulated in serial search. Such neural modulation presents a significant positive correlation with behavioral reaction time. Furthermore, theta burst stimulation via transcranial magnetic stimulation was utilized to modulate the dorsolateral prefrontal cortex region, resulting in the disappearance of the inhibition of return effect during serial search after receiving continuous theta burst stimulation. Our findings provide a new line of causal evidence that the top-down modulation by dorsolateral prefrontal cortex influences the inhibition of return effect during serial search possibly through the retention of inhibitory tagging via working memory storage.
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Córtex Pré-Frontal Dorsolateral , Córtex Pré-Frontal , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Imageamento por Ressonância Magnética , Estimulação Magnética Transcraniana/métodos , Tempo de Reação/fisiologiaRESUMO
BACKGROUND: Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. METHODS: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. RESULTS: In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). CONCLUSION: This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.
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BACKGROUND: The potential benefits of drug combination synergy in cancer medicine are significant, yet the risks must be carefully managed due to the possibility of increased toxicity. Although artificial intelligence applications have demonstrated notable success in predicting drug combination synergy, several key challenges persist: (1) Existing models often predict average synergy values across a restricted range of testing dosages, neglecting crucial dose amounts and the mechanisms of action of the drugs involved. (2) Many graph-based models rely on static protein-protein interactions, failing to adapt to dynamic and higher-order relationships. These limitations constrain the applicability of current methods. RESULTS: We introduce SAFER, a Sub-hypergraph Attention-based graph model, addressing these issues by incorporating complex relationships among biological knowledge networks and considering dosing effects on subject-specific networks. SAFER outperformed previous models on the benchmark and the independent test set. The analysis of subgraph attention weight for the lung cancer cell line highlighted JAK-STAT signaling pathway, PRDM12, ZNF781, and CDC5L that have been implicated in lung fibrosis. CONCLUSIONS: SAFER presents an interpretable framework designed to identify drug-responsive signals. Tailored for comprehending dose effects on subject-specific molecular contexts, our model uniquely captures dose-level drug combination responses. This capability unlocks previously inaccessible avenues of investigation compared to earlier models. Furthermore, the SAFER framework can be leveraged by future inquiries to investigate molecular networks that uniquely characterize individual patients and can be applied to prioritize personalized effective treatment based on safe dose combinations.
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Redes Neurais de Computação , Humanos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Relação Dose-Resposta a Droga , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologiaRESUMO
Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Eferocitose , Análise da Expressão Gênica de Célula Única , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Macrófagos/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Proteínas de Ligação a DNA/genética , Fatores de Transcrição de Domínio TEA , Profilinas/genéticaRESUMO
BACKGROUND: The mediator complex subunits (MED) constitutes a multiprotein complex, with each subunit intricately involved in crucial aspects of plant growth, development, and responses to stress. Nevertheless, scant reports pertain to the VunMED gene within the context of asparagus bean (Vigna unguiculata ssp. sesquipedialis). Establishing the identification and exploring the responsiveness of VunMED to cold stress forms a robust foundation for the cultivation of cold-tolerant asparagus bean cultivars. RESULTS: Within this study, a comprehensive genome-wide identification of VunMED genes was executed in the asparagus bean cultivar 'Ningjiang3', resulting in the discovery of 36 distinct VunMED genes. A phylogenetic analysis encompassing 232 MED genes from diverse species, including Arabidopsis, tomatoes, soybeans, mung beans, cowpeas, and asparagus beans, underscored the highly conserved nature of MED gene sequences. Throughout evolutionary processes, each VunMED gene underwent purification and neutral selection, with the exception of VunMED19a. Notably, VunMED9/10b/12/13/17/23 exhibited structural variations discernible across four cowpea species. Divergent patterns of temporal and spatial expression were evident among VunMED genes, with a prominent role attributed to most genes during early fruit development. Additionally, an analysis of promoter cis-acting elements was performed, followed by qRT-PCR assessments on roots, stems, and leaves to gauge relative expression after exposure to cold stress and subsequent recovery. Both treatments induced transcriptional alterations in VunMED genes, with particularly pronounced effects observed in root-based genes following cold stress. Elucidating the interrelationships between subunits involved a preliminary understanding facilitated by correlation and principal component analyses. CONCLUSIONS: This study elucidates the pivotal contribution of VunMED genes to the growth, development, and response to cold stress in asparagus beans. Furthermore, it offers a valuable point of reference regarding the individual roles of MED subunits.
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Fabaceae , Vigna , Vigna/genética , Filogenia , Resposta ao Choque Frio , Complexo Mediador/genética , Fabaceae/genéticaRESUMO
Nature uses compact but functionalized biosynthetic fragments as building blocks to generate complex natural products. To leverage this strategy for the discovery of natural products with new scaffolds, we performed genome mining to identify biosynthetic gene clusters (BGCs) in fungi that embed genes that can synthesize targeted fragments. The three-enzyme pathway that biosynthesizes the strained dityrosine cyclophane in the herquline A pathway was used to identify a large number of potential BGCs that may use the cyclophane as a fragment. Characterization of a conserved BGC from fungal strains led to the isolation of octacyclin A, an octacyclic natural product with an unprecedented structure, including two hetero-[3.3.1]bicycles and a combination of fused, bridged, and macrocyclic rings. Biosynthetic steps leading to octacyclin A were fully elucidated using pathway reconstitution and enzymatic assays, unveiling intriguing chemical logic and new enzymatic reactions in building the octacyclic core. Our work demonstrates the potential utility of fragment-guided genome mining in expanding natural product chemical space.
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Two-dimensional (2D) zeolite, with a high aspect ratio, has more open skeletons and accessible active sites than its three-dimensional (3D) counterpart. However, traditional methods of obtaining 2D zeolites often cause structural damage and widespread skeleton defects, hindering efficient selectivity in molecular separation. In this study, we present, for the first time, a direct epitaxial synthesis of 2D zeolite (Epi-MWW) guided by hexagonal boron nitride (h-BN) with a coincidence matching of site lattices to MWW zeolite. The as-grown Epi-MWW zeolite possesses a high crystallinity and intact hexagonal 2D morphology, with an average thickness of 10 nm and an aspect ratio of over 50. Thanks to its excellent molecular accessibility, the diffusion time constants of o-xylene (OX) and p-xylene (PX) are as 12 and 133 times higher than those of conventional MCM-22, respectively; the PX/OX selectivity of Epi-MWW is 7.4 times better than MCM-22 as calculated by the ideal adsorbed solution theory.
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Pyridoxal 5'-phosphate (PLP)-dependent enzymes are the most versatile biocatalysts for synthesizing nonproteinogenic amino acids. α,α-Disubstituted quaternary amino acids, such as 1-aminocyclopentane-1-carboxylic acid (cycloleucine), are useful building blocks for pharmaceuticals. In this study, starting with the biosynthesis of fusarilin A, we discovered a family of PLP-dependent enzymes that can facilitate tandem carbon-carbon forming steps to catalyze an overall [3 + 2]-annulation. In the first step, the cycloleucine synthases use SAM as the latent electrophile and an in situ-generated enamine as the nucleophile for γ-substitution. Whereas previously characterized γ-replacement enzymes protonate the resulting α-carbon and release the acyclic amino acid, cycloleucine synthases can catalyze an additional, intramolecular aldol or Mannich reaction with the nucleophilic α-carbon to form the substituted cyclopentane. Overall, the net [3 + 2]-annulation reaction can lead to 2-hydroxy or 2-aminocycloleucine products. These studies further expand the biocatalytic scope of PLP-dependent enzymes.
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Fosfato de Piridoxal , Fosfato de Piridoxal/metabolismo , Fosfato de Piridoxal/química , Biocatálise , Estrutura Molecular , Ciclopentanos/química , Ciclopentanos/metabolismoRESUMO
It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.
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Carcinogênese , Neoplasias , Humanos , Transformação Celular Neoplásica/genética , Morte Celular , Nutrientes , Oxigênio , ApoptoseRESUMO
BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.
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Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , RNA Circular , Receptor IGF Tipo 1 , Transdução de Sinais , Humanos , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Acrilamidas/farmacologia , RNA Circular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Compostos de Anilina/farmacologia , Linhagem Celular Tumoral , Animais , Camundongos , Apoptose , Movimento Celular/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Feminino , Indóis , PirimidinasRESUMO
OBJECTIVE: To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Studies on ICG imaging use in patients with LAGC on NAC are rare. METHODS: Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. RESULTS: Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs 38.3, P < 0.001). The ICG fluorescence guidance significantly decreased the LN noncompliance rates (33.9% vs 55.1%, P = 0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN noncompliance rate ( P < 0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response ( P < 0.05) but not in those who did not ( P > 0.05). Surgical outcomes were comparable between the groups ( P > 0.05). CONCLUSIONS: ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.
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Adenocarcinoma , Gastrectomia , Verde de Indocianina , Laparoscopia , Excisão de Linfonodo , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Verde de Indocianina/administração & dosagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Excisão de Linfonodo/métodos , Masculino , Laparoscopia/métodos , Feminino , Pessoa de Meia-Idade , Gastrectomia/métodos , Idoso , Adenocarcinoma/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Corantes/administração & dosagem , Adulto , Resultado do Tratamento , Estadiamento de Neoplasias , Quimioterapia AdjuvanteRESUMO
Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/genética , Fosfofrutoquinase-1 , Fígado , Glicólise , Proliferação de Células , Proteases Específicas de Ubiquitina , Linhagem Celular Tumoral , Ubiquitina TiolesteraseRESUMO
BACKGROUND: To provide a preoperative prediction model for lymph node metastasis in pancreatic cancer patients and provide molecular information of key radiomic features. METHODS: Two cohorts comprising 151 and 54 pancreatic cancer patients were included in the analysis. Radiomic features from the tumor region of interests were extracted by using PyRadiomics software. We used a framework that incorporated 10 machine learning algorithms and generated 77 combinations to construct radiomics-based models for lymph node metastasis prediction. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to determine the relationships between gene expression levels and radiomic features. Molecular pathways enrichment analysis was performed to uncover the underlying molecular features. RESULTS: Patients in the in-house cohort (mean age, 61.3 years ± 9.6 [SD]; 91 men [60%]) were separated into training (n = 105, 70%) and validation (n = 46, 30%) cohorts. A total of 1,239 features were extracted and subjected to machine learning algorithms. The 77 radiomic models showed moderate performance for predicting lymph node metastasis, and the combination of the StepGBM and Enet algorithms had the best performance in the training (AUC = 0.84, 95% CI = 0.77-0.91) and validation (AUC = 0.85, 95% CI = 0.73-0.98) cohorts. We determined that 15 features were core variables for lymph node metastasis. Proliferation-related processes may respond to the main molecular alterations underlying these features. CONCLUSIONS: Machine learning-based radiomics could predict the status of lymph node metastasis in pancreatic cancer, which is associated with proliferation-related alterations.
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Metástase Linfática , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Masculino , Metástase Linfática/patologia , Feminino , Genômica , Aprendizado de Máquina , Anotação de Sequência Molecular , Regulação Neoplásica da Expressão Gênica , Estudos de Coortes , Idoso , Algoritmos , Redes Reguladoras de Genes , Curva ROC , Reprodutibilidade dos Testes , RadiômicaRESUMO
A distributed optical fiber magnetic field sensor based on a polarization-sensitive optical frequency domain reflectometer (POFDR) is proposed. It extracts the accumulated Faraday rotation by combining the Stokes vectors and the backward Mueller matrices from the measured states of polarization (SOPs) and obtains the magnetic field component. This method avoids adjusting the input polarization during the magnetic field sensing process. It overcomes the drawback of the conventional POFDR scheme, which requires at least two sets of different input SOPs for each sensing. Finally, the aforementioned effectiveness has been experimentally verified by using a single-mode sensing fiber. The results show that the sensor has good repeatability and linearity. The measurement error of the magnetic field sensor is 19.4â mT. The measured magnetic field variations agree with the applied ones with similarities higher than 0.98.
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Nonlinear sum frequency generation (SFG) and difference frequency generation (DFG) are fundamental methods to obtain new light sources for various applications. However, most of the on-chip SFG and DFG are based on conventional resonators, lacking robustness against fabrication defects. Here, we demonstrate topologically protected SFG and DFG in a second-order topological photonic system. The mechanism is based on the nonlinear interaction between three high-Q corner modes inside dual topological band gaps. The frequency matching condition for SFG and DFG is precisely satisfied by designing a valley-photonic-crystal-like topological system, which provides more freedoms to tune the corner modes. The topological SFG and DFG are achieved with high conversion efficiency, and the underlying topological physics is revealed. This work opens up avenues toward topologically protected nonlinear frequency conversion, and can find applications in the fields of on-chip single-photon detections and optical quantum memories with robustness against defects.
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A design of a heterogeneous integrated optical fiber with side nickel core (SNCF) has been proposed and demonstrated for distributed fiber-optic magnetic field sensing. Experimental results show that magnetic properties of nickel can be preserved well after the high temperature drawing process. The functionality of the SNCF has been well verified, with the sensitivity for DC magnetic field being up to -2.42 µÎµ/mT (below 8â mT). Besides, the SNCF finally presents magnetostriction saturation under a certain magnetic field, which agrees with the simulation. The proposed direct thermal drawing method to produce metal-heterogeneous integrated optical fiber paves the way for a simple and scalable means of incorporating metallic materials into fibers, as well as providing a promising candidate for long-distance distributed magnetic field sensing.