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Promoter methylation is one of the most studied epigenetic modifications and it is highly relevant to the onset and progression of thyroid carcinoma (THCA). This study investigates the promoter methylation and expression pattern of intercellular adhesion molecule 5 (ICAM5) in THCA. CpG islands with aberrant methylation pattern in THCA, and the expression profiles of the corresponding genes in THCA, were analyzed using bioinformatics. ICAM5 was suggested to have a hypermethylation status, and it was highly expressed in THCA tissues and cells. Its overexpression promoted proliferation, mobility, and tumorigenic activity of THCA cells. As for the downstream signaling, ICAM5 was found to activate the MAPK/ERK and MAPK/JNK signaling pathways. Either inhibition of ERK or JNK blocked the oncogenic effects of ICAM5. DNA methyltransferases 1 (DNMT1) and DNMT3a were found to induce promoter hypermethylation of ICAM5 in THCA cells. Knockdown of DNMT1 or DNMT3a decreased the ICAM5 expression and suppressed malignant properties of THCA cells in vitro and in vivo, which were, however, restored by further artificial ICAM5 overexpression. Collectively, this study reveals that DNMT1 and DNMT3a mediates promoter hypermethylation and transcription activation of ICAM5 in THCA, which promotes malignant progression of THCA through the MAPK signaling pathway.
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DNA (Citosina-5-)-Metiltransferases , Neoplasias da Glândula Tireoide , Humanos , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Ativação Transcricional , Metilação de DNA , Neoplasias da Glândula Tireoide/genética , Proteínas do Tecido Nervoso/genética , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismoRESUMO
Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform. Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.
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Glioblastoma , Ribonucleoproteínas Nucleares Heterogêneas , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Proteína cdc42 de Ligação ao GTP , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Humanos , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Linhagem Celular Tumoral , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Redes Reguladoras de Genes , Regulação Neoplásica da Expressão Gênica , Splicing de RNA , Neurônios/metabolismo , Neurônios/patologiaRESUMO
BACKGROUND: Delta-like ligand 3 (DLL3) is highly expressed on the cell surface of small cell lung cancer (SCLC), one of the most lethal malignancies, but minimally or not in normal tissues, making it an attractive target for SCLC. However, none of the DLL3-targeting antibody-drug conjugates (ADCs) have been approved for SCLC therapy yet. We developed DB-1314, the new anti-DLL3 ADC composed of a novel humanized anti-DLL3 monoclonal antibody (DB131401) conjugated with eight molecules of P1021 (topoisomerase I inhibitor), and described its preclinical profiles. METHODS: The binding epitope for DB131401 and Rovalpituzumab was tested by biolayer interferometry. The binding affinity and specificity of DB-1314 to DLL3 and other homologous proteins were respectively measured by surface plasmon resonance and enzyme-linked immunosorbent assay. Internalization, bystander effects, and antibody-dependent cell-mediated cytotoxicity (ADCC) were assessed by respective assay. DLL3 was quantified by antibodies bound per cell assay and immunohistochemistry. In vitro and in vivo growth inhibition studies were evaluated in SCLC cell lines, and cell line/patient-derived xenograft models. The safety profile was measured in cynomolgus monkeys. RESULTS: DB-1314 induces potent, durable, and dose-dependent antitumor effects in cells in vitro and in cell/patient-derived xenograft models in vivo. The killing activity of DB-1314 mechanically arises from P1021-induced DNA damage, whereby P1021 is delivered and released within tumor cells through DLL3-specific binding and efficient internalization. Bystander effects and ADCC also contribute to the antitumor activity of DB-1314. DB-1314 displays favorable pharmacokinetic and toxicokinetic profiles in rats and cynomolgus monkeys; besides, DB-1314 is well-tolerated at a dose of up to 60 mg/kg in monkeys. CONCLUSIONS: These results suggest that DB-1314 may be a candidate ADC targeting DLL3 for the treatment of DLL3-positive SCLC, supporting further evaluation in the clinical setting.
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Imunoconjugados , Neoplasias Pulmonares , Proteínas de Membrana , Carcinoma de Pequenas Células do Pulmão , Inibidores da Topoisomerase I , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase I/uso terapêutico , Linhagem Celular Tumoral , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Proteínas de Membrana/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Macaca fascicularis , Ensaios Antitumorais Modelo de Xenoenxerto , Ratos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Camundongos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/farmacologia , BenzodiazepinonasRESUMO
IgNAR exhibits significant promise in the fields of cancer and anti-virus biotherapies. Notably, the variable regions of IgNAR (VNAR) possess comparable antigen binding affinity with much smaller molecular weight (â¼12 kDa) compared to IgNAR. Antigen specific VNAR screening is a changeling work, which limits its application in medicine and therapy fields. Though phage display is a powerful tool for VNAR screening, it has a lot of drawbacks, such as small library coverage, low expression levels, unstable target protein, complicating and time-consuming procedures. Here we report VANR screening with next generation sequencing (NGS) could effectively overcome the limitations of phage display, and we successfully identified approximately 3000 BAFF-specific VNARs in Chiloscyllium plagiosum vaccinated with the BAFF antigen. The results of modelling and molecular dynamics simulation and ELISA assay demonstrated that one out of the top five abundant specific VNARs exhibited higher binding affinity to the BAFF antigen than those obtained through phage display screening. Our data indicates NGS would be an alternative way for VNAR screening with plenty of advantages.
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Sequenciamento de Nucleotídeos em Larga Escala , Tubarões , Tubarões/imunologia , Tubarões/genética , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Antígenos/imunologia , Antígenos/genética , Doenças dos Peixes/imunologiaRESUMO
Zinc(II) ions (Zn2g) play crucial roles in the growth, propagation, and metabolism of animals, plants, and humans. Abnormal concentrations of Zn2+ in the environment and living organisms pose potential risks to environmental protection and human health. Therefore, it is imperative to develop rapid, reliable and in-situ detection methods for Zn2+ in both environmental and biological contexts. Furthermore, effective analytical methods are required for diagnosing diseases and understanding physiological metabolic mechanisms associated with Zn2+ concentration levels. Organic small-molecule fluorescent probes offer advantages such as fast, reliable, convenient, non-destructive detection capabilities and have significant application potential in Zn2+ detection and bioimaging; thus garnering extensive attention. Over the past two years alone, various organic small-molecule probes for Zn2+ based on different detection mechanisms and fluorophores have been rapidly developed. However, these probes still exhibit several limitations that need further resolution. In light of this context, we provide a comprehensive summary of the detection mechanisms, performance characteristics, and application scope of Zn2+ fluorescence probes since year 2022 while highlighting their advantages. We also propose solutions to address existing issues with these probes and outline future directions for their advancement. This review aims to serve as a valuable reference source offering insights into the development of advanced organic small-molecule-based fluorescence probes specifically designed for detecting Zn2+.
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OBJECTIVES: The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA. METHODS: We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow-up 1 year after the procedure. The primary endpoint was the 1-year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention). RESULTS: A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well-balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57-1.69], p < 0.001), The reduction in 1-year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11-0.99]; log-rank p = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001). CONCLUSIONS: The combination of ELCA and DCB is a safe and effective treatment strategy for in-stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long-term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.
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Angioplastia Coronária com Balão , Reestenose Coronária , Lasers de Excimer , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Reestenose Coronária/terapia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Idoso , Lasers de Excimer/uso terapêutico , Angioplastia Coronária com Balão/instrumentação , Resultado do Tratamento , Estudos Retrospectivos , Stents Farmacológicos , Tomografia de Coerência Óptica , Terapia Combinada , Angioplastia com Balão a LaserRESUMO
Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.
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Antozoários , Caenorhabditis elegans , Sesquiterpenos , Animais , Antozoários/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Caenorhabditis elegans/efeitos dos fármacos , Cristalografia por Raios X , Doença de Alzheimer/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Estrutura MolecularRESUMO
Background: Post-auricular injection of lidocaine and methylprednisolone sodium succinate is a commonly used treatment for outpatient patients with tinnitus, but it is invasive, painful and has uncertain efficacy. We need to try to replace it with more non-invasive and effective treatments. The 2014 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery recommend the use of cognitive behavioral therapy (CBT) to treat tinnitus. Some clinical doctors have also attempted sound therapy for tinnitus. It is unclear whether sound therapy combined with CBT y is more effective than local injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus. Objective: To evaluate the efficacy and influencing factors of refined sound therapy combined with CBT in the treatment of tinnitus and compare it with post-auricular injection of lidocaine and methylprednisolone sodium succinate. Methods: We recruited 100 patients with tinnitus; ultimately, 81 patients completed the experiment and underwent follow-up. Patients were randomly assigned to either the treatment group (refined sound therapy combined with CBT) or the control group (post-auricular injections of lidocaine and methylprednisolone sodium succinate). Data was collected from 49 patients in the treatment group and 32 patients in the control group. Pre- and post-treatment data were collected using the Self-Rating Depression Scale (SDS), Hamilton Anxiety Rating Scale (HAM-A), Visual Analogue Score (VAS), Tinnitus loudness and Tinnitus Handicap Inventory (THI) score. Comparisons between groups were performed using the chi-square test, Fisher's exact test, or Wilcoxon rank-sum test. All tests were two-sided and considered statistically significant with P < .05. Results: The THI, SDS and HAM-A scores in the treatment group decreased significantly. In the control group, there was a significant reduction in THI scores, but not in SDS and HAM-A scores. In addition, tinnitus loudness and VAS scores were significantly decreased in the 2 groups. There was a significant difference in the reduction of THI, SDS, HAM-A and VAS scores between the 2 groups; the treatment group showed a greater reduction. However, there was no significant difference in the reduction of tinnitus loudness. There was no statistical difference in the reduction of THI scores, SDS scores, VAS scores and tinnitus loudness in different frequency groups, but there was a statistical difference in the reduction of HAM-A scores. There was no statistical difference in the reduction of THI scores, SDS scores, HAM-A scores, VAS scores and tinnitus loudness between patients with and without hearing loss. Conclusions: (1) This new combination is more effective than post-auricular injection of lidocaine and methylprednisolone sodium succinate in treating tinnitus and improving psychological symptoms. The latter had no effect on improving psychological indicators. (2) With this combination, patients with different tinnitus frequencies experienced different improvements in anxiety. (3) Low-frequency tinnitus seems have been more likely to cause sound adaptation. (4) The improvement in tinnitus and anxiety was the same regardless of whether or not there was hearing loss.
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Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.
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Magnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.
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BACKGROUND: The objective of this investigation was to examine the impact of enzymatic hydrolysis of arabinoxylan (AX) on frozen dough quality under subfreezing conditions. The dough was subjected to freezing at -40 °C for 2 h and then stored at -9, -12, and -18 °C for 15 days. The water loss, freezable water content, water migration, and microstructure of the dough were measured. RESULTS: The dough containing 0.8% cellulase enzymatically hydrolyzed AX (CAX) required the shortest duration when traversing the maximum ice-crystal formation zone (6.5 min). The dough with xylanase enzymatically hydrolyzed AX (XAX) demonstrated a faster freezing rate than the dough with CAX. The inclusion of both XAX and CAX in the dough resulted in the lowest freezable water loss and reduced freezable water content and free-water content levels, whereas the inclusion of xylanase-cellulase combined with enzymatically hydrolyzed AX resulted in higher free-water content levels. The textural properties of the subfreezing temperature dough were not significantly different from the dough stored at -18 °C and sometimes even approached or surpassed the quality observed in the control group rather than the dough stored at -18 °C. In addition, the gluten network structure remains well preserved in XAX- and CAX-containing doughs with minimal starch damage. CONCLUSION: The enzymatic hydrolysis of AX from wheat bran can be used as a useful additive to improve the quality of frozen dough. © 2024 Society of Chemical Industry.
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Farinha , Congelamento , Triticum , Xilanos , Xilanos/química , Xilanos/metabolismo , Hidrólise , Farinha/análise , Triticum/química , Triticum/metabolismo , Água/química , Celulase/química , Celulase/metabolismo , Endo-1,4-beta-Xilanases/química , Endo-1,4-beta-Xilanases/metabolismo , Pão/análise , Manipulação de Alimentos/métodosRESUMO
Band structure of a semiconducting film critically determines the charge separation and transport efficiency. In antimony selenosulfide (Sb2(S,Se)3) solar cells, the hydrothermal method has achieved control of band gap width of Sb2(S,Se)3 thin film through tuning the atomic ratio of S/Se, resulting in an efficiency breakthrough towards 10 %. However, the obtained band structure exhibits an unfavorable gradient distribution in terms of carrier transport, which seriously impedes the device efficiency improvement. To solve this problem, here we develop a strategy by intentionally regulating hydrothermal temperature to control the chemical reaction kinetics between S and Se sources with Sb source. This approach enables the control over vertical distribution of S/Se atomic ratio in Sb2(S,Se)3 films, forming a favorable band structure which is conducive to carrier transport. Meanwhile, the adjusted element distribution not only ensures the uniformity of grain structure, but also increases the Se content of the films and suppress sulfur vacancy defects. Ultimately, the device delivers a high efficiency of 10.55 %, which is among the highest reported efficiency of Sb2(S,Se)3 solar cells. This study provides an effective strategy towards manipulating the element distribution in mixed-anion compound films prepared by solution-based method to optimize their optical and electrical properties.
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block2 is an open source framework to implement and perform density matrix renormalization group and matrix product state algorithms. Out-of-the-box it supports the eigenstate, time-dependent, response, and finite-temperature algorithms. In addition, it carries special optimizations for ab initio electronic structure Hamiltonians and implements many quantum chemistry extensions to the density matrix renormalization group, such as dynamical correlation theories. The code is designed with an emphasis on flexibility, extensibility, and efficiency and to support integration with external numerical packages. Here, we explain the design principles and currently supported features and present numerical examples in a range of applications.
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In this paper, an event-driven wireless sensor node is proposed and demonstrated. The primary design objective is to devise a wireless sensor node with miniaturization, integration, and high-accuracy recognition ability. The proposed wireless sensor node integrates two vibration-threshold-triggered energy harvesters that sense and power a threshold voltage control circuit for power management, a microcontroller unit (MCU) for system control, a one-dimensional convolutional neural network (1D-CNN) environment data analysis and vibration events distribution, and a radio frequency (RF) digital baseband transmitter with IEEE 802.15.4-/.6 protocols. The dimensions of the wireless sensor node are 4 × 2 × 1 cm3. Finally, the proposed wireless sensor node was fabricated and tested. The alarming time for detecting the vibration event is less than 6 s. The measured recognition accuracy of three events (knock, shake, and heat) is over 97.5%. The experimental results showed that the proposed integrated wireless sensor node is very suitable for wireless environmental monitoring systems.
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Combined large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) is extremely rare, with only a few reports available in the literature. An accurate diagnosis is difficult to make due to the overlapping clinical features between LCNEC and SCLC, and a standardized treatment option is lacking. A 53-year-old female patient was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) due to symptoms of dyspnea and phlegm, with blood in the sputum. Computed tomography revealed a 52×32×26-mm irregular soft-tissue mass in the left upper lung. Pathological examination of the biopsy specimen showed a poorly differentiated neuroendocrine carcinoma with compression injury, consistent with a mixed type of large and small cell carcinoma. The patient was administered chemotherapy, radiotherapy and targeted therapy, and as of October 2023, the patient had a survival period of 29 months. LCNEC combined with SCLC is a sporadic tumor with a high potential for malignancy. Multidisciplinary treatment and close follow-up are recommended. The multidisciplinary treatment strategy used in the present study is expected to help inform future therapeutic decisions.
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BACKGROUND: Healthy diets and physical exercise, two modifiable lifestyle factors, are protective against depression in older adults. This study aimed to investigate whether physical exercise may influence the associations of dietary habits with depression in Chinese community-dwelling older adults. METHODS: In the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey, 12,708 community-dwelling older adults aged ≥65 years were included for analyses. Older adults' dietary habits (including daily intake of food components such as fruits, vegetables, animal oil, and so on) and physical exercise were assessed. Depression was evaluated via the 10 item Center for Epidemiologic Studies Depression (CES-D-10) scale. The influences of physical exercise on the associations of dietary habits with depression were estimated using logistic regression models adjusted for confounders. RESULTS: Older adults who took physical exercise had a significantly decreased probability of depression (adjusted OR = 0.73, p < 0.001). As for dietary habits, the intake of fruits, vegetables, eggs, nut products, mushrooms or algae, and vitamins were inversely associated with the prevalence of depression (adjusted ORs = 0.61-0.81; p-values: from <0.001 to 0.025), while animal oil was positively associated with it (adjusted OR = 1.52, p < 0.001). When stratified by physical exercise, older adults who ate fruits or vegetables had consistent decreased risk of depression, no matter whether they took physical exercise or not (adjusted ORs = 0.52-0.70), while the intake of eggs, nut products, and vitamins were inversely associated, and animal oil was consistently positively associated with depression only in older adults who did not take physical exercise (adjusted ORs = 0.79, 0.68, 0.63, and 1.67, respectively). CONCLUSIONS: Physical exercise may conceal the potential protective effects of some healthy dietary habits in terms of depression and counteract the detrimental effects of the unhealthy habits. Some dietary habits may be considered as alternative protective measures for depression in community-dwelling older adults when physical exercise cannot be performed.
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Depressão , Vida Independente , Animais , Estudos Transversais , Depressão/epidemiologia , Dieta , Exercício Físico , Verduras , Vitaminas , Comportamento Alimentar , ChinaRESUMO
By virtue of its narrow pulse width and high peak power, the femtosecond pulsed laser can achieve high-precision material modification, material additive or subtractive, and other forms of processing. With additional good material adaptability and process compatibility, femtosecond laser-induced application has achieved significant progress in flexible electronics in recent years. These advancements in the femtosecond laser fabrication of flexible electronic devices are comprehensively summarized here. This review first briefly introduces the physical mechanism and characteristics of the femtosecond laser fabrication of various electronic microdevices. It then focuses on effective methods of improving processing efficiency, resolution, and size. It further highlights the typical progress of applications, including flexible energy storage devices, nanogenerators, flexible sensors, and detectors, etc. Finally, it discusses the development tendency of ultrashort pulse laser processing. This review should facilitate the precision manufacturing of flexible electronics using a femtosecond laser.
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Introduction: The ratio of Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) is a crucial indicator for diabetes diagnosis. Methods: This study utilizes the Copula function to model and fit the non-linear correlation among fasting blood glucose (Glu), glycosylated hemoglobin (HbA1C), and TG/HDL-C in patients with diabetes. The Copula function chosen for this study includes the two-dimensional Archimedes and Elliptical distribution family, as well as the multidimensional Vine Copula function, for fitting the data. The evaluation of the fitting effect is performed using the mean absolute error (MAE) and mean square error (MSE). Results: The results indicate that the Clayton Copula exhibits the highest effectiveness in fitting the pairwise relationship between Glu and TG/HDL-C, as well as HbA1C and TG/HDL-C, displaying the smallest fitting error. Additionally, the Vine Copula function produces a satisfactory fit for the relationship among all three indicators. Compared to linear analysis methods, the Copula function more accurately depicts the correlation among these three types of indicators. Discussion: Moreover, our findings indicate a stronger correlation in the lower tail between Glu and HbA1C, as well as TG/HDL-C, suggesting that the Copula function provides greater accuracy and applicability in depicting the relationship among these indicators. As a result, it can offer a more precise auxiliary diagnosis and serve as a valuable reference in clinical judgment.
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Glicemia , Diabetes Mellitus , Humanos , Hemoglobinas Glicadas , Diabetes Mellitus/diagnóstico , Triglicerídeos , HDL-ColesterolRESUMO
The nature of semantic representation has long been a key question in linguistic research. The Embodied Cognition theory challenges the traditional view of language representation, stating that semantic information stems from the sensory-motor cortex, which is activated automatically during semantic processing. However, most of the evidence comes from monolingual studies; it remains unclear whether second-language (L2) comprehension involves different semantic representations or mirrors the pattern seen in first-language (L1) processing. Therefore, the present study investigated the role of the sensory-motor system in language processing via making Electroencephalography (EEG) recordings during the processing of L1 and L2 action verbs. The results showed that L1 (Chinese) action verbs generated higher mu-event-related desynchronization (ERD) than L1 abstract verbs in the early processing stage (250 ms after verb presentation), and the same phenomenon was also observed for L2 (English). The results also indicated that language modulated the processing of action verbs, with L1 action verbs eliciting stronger ERD than L2 action verbs. These results demonstrate that the sensory-motor cortex plays a crucial role in comprehending both L1 and L2 action verbs.
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A novel biomass-based magnetic nanoparticle (Fe3O4-P-CMC/PAMAM) was synthesized by crosslinking carboxymethyl chitosan (CMC) and poly(amidoamine) (PAMAM), followed by phosphorylation with the incorporation of magnetic ferric oxide nanoparticles. The characterization results verified the successful functionalization and structural integrity of the adsorbents with a surface area of ca. 43 m2/g. Batch adsorption experiments revealed that the adsorbent exhibited a maximum adsorption capacity of 1513.47 mg·g-1 for U(VI) at pH 5.5 and 298.15 K, with Fe3O4-P-CMC/G1.5-2 showing the highest affinity among the series. The adsorption kinetics adhered to a pseudo-second-order model (R2 = 0.99, qe,exp = 463.81 mg·g-1, k2 = 2.15×10-2 g·mg-1·min-1), indicating a chemically driven process. Thermodynamic analysis suggested that the adsorption was endothermic and spontaneous (ΔH° = 14.71 kJ·mol-1, ΔG° = -50.63 kJ·mol-1, 298. 15 K), with increasing adsorption capacity at higher temperatures. The adsorbent demonstrated significant selectivity for U(VI) in the presence of competing cations, with Fe3O4-P-CMC/G1.5-2 showing a high selectivity coefficient. The performed desorption and reusability tests indicated that the adsorbent could be effectively regenerated using 1M HCl, maintaining its adsorption capacity after five cycles. XPS analysis highlighted the role of phosphonate and amino groups in the complexation with uranyl ions, and validated the existence of bimodal U4f peaks at 380.1 eV and 390.1 eV belonging to U 4f7/2 and U 4f5/2. The results of this study underscore the promise of the developed adsorbent as an effective and selective material for the treatment of uranium-contaminated wastewater.