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Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.
Assuntos
Hominidae , Tecnologia , Humanos , Animais , Ásia Oriental , China , ÁfricaRESUMO
Borneol, camphor, and bornyl acetate are highly promising monoterpenoids widely used in medicine, flavor, food, and chemical applications. Bornyl diphosphate (BPP) serves as a common precursor for the biosynthesis of these monoterpenoids. Although bornyl diphosphate synthase (BPPS) that catalyzes the cyclization of geranyl diphosphate (GPP) to BPP has been identified in multiple plants, the enzyme responsible for the hydrolysis of BPP to produce borneol has not been reported. Here, we conducted in vitro and in vivo functional characterization to identify the Nudix hydrolase WvNUDX24 from W. villosa, which specifically catalyzes the hydrolysis of BPP to generate bornyl phosphate (BP), and then BP forms borneol under the action of phosphatase. Subcellular localization experiments indicated that the hydrolysis of BPP likely occurs in the cytoplasm. Furthermore, site-directed mutagenesis experiments revealed that four critical residues (R84, S96, P98, and G99) for the hydrolysis activity of WvNUDX24. Additionally, the functional identification of phosphatidic acid phosphatase (PAP) demonstrated that WvPAP5 and WvPAP10 were able to hydrolyze geranylgeranyl diphosphate (GGPP) and farnesyl diphosphate (FPP) to generate geranylgeranyl phosphate (GGP) and farnesyl phosphate (FP), respectively, but could not hydrolyze BPP, GPP, and neryl diphosphate (NPP) to produce corresponding monophosphate products. These findings highlight the essential role of WvNUDX24 in the first step of BPP hydrolysis to produce borneol and provide genetic elements for the production of BPP-related terpenoids through plant metabolic engineering and synthetic biology.
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Canfanos , Nudix Hidrolases , Proteínas de Plantas , Pirofosfatases , Pirofosfatases/metabolismo , Pirofosfatases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Canfanos/metabolismo , Brassicaceae/genética , Brassicaceae/enzimologia , Brassicaceae/metabolismo , Fosfatos de Poli-Isoprenil/metabolismoRESUMO
Salicylic acid (SA) is known to enhance salt tolerance in plants. However, the mechanism of SA-mediated response to high salinity in halophyte remains unclear. Using electrophysiological and molecular biological methods, we investigated the role of SA in response to high salinity in mangrove species, Kandelia obovata, a typical halophyte. Exposure of K. obovata roots to high salinity resulted in a rapid increase in endogenous SA produced by phenylalanine ammonia lyase pathway. The application of exogenous SA improved the salt tolerance of K. obovata, which depended on the NADPH oxidase-mediated H2O2. Exogenous SA and H2O2 increased Na+ efflux and reduced K+ loss by regulating the transcription levels of Na+ and K+ transport-related genes, thus reducing the Na+/K+ ratio in the salt-treated K. obovata roots. In addition, exogenous SA-enhanced antioxidant enzyme activity and its transcripts, and the expressions of four genes related to AsA-GSH cycle as well, then alleviated oxidative damages in the salt-treated K. obovata roots. However, the above effects of SA could be reversed by diphenyleneiodonium chloride (the NADPH oxidase inhibitor) and paclobutrazol (a SA biosynthesis inhibitor). Collectively, our results demonstrated that SA-induced salt tolerance of K. obovata depends on NADPH oxidase-generated H2O2 that affects Na+/K+ and redox homeostasis in response to high salinity.
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Homeostase , Peróxido de Hidrogênio , NADPH Oxidases , Oxirredução , Raízes de Plantas , Potássio , Ácido Salicílico , Tolerância ao Sal , Sódio , Peróxido de Hidrogênio/metabolismo , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologia , Potássio/metabolismo , Tolerância ao Sal/genética , Sódio/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Plantas Tolerantes a Sal/fisiologia , Regulação da Expressão Gênica de Plantas , Rhizophoraceae/fisiologia , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Mangroves grow in tropical/subtropical intertidal habitats with extremely high salt tolerance. Trehalose and trehalose-6-phosphate (T6P) have an alleviating function against abiotic stress. However, the roles of trehalose in the salt tolerance of salt-secreting mangrove Avicennia marina is not documented. Here, we found that trehalose was significantly accumulated in A. marina under salt treatment. Furthermore, exogenous trehalose can enhance salt tolerance by promoting the Na+ efflux from leaf salt gland and root to reduce the Na+ content in root and leaf. Subsequently, eighteen trehalose-6-phosphate synthase (AmTPS) and 11 trehalose-6-phosphate phosphatase (AmTPP) genes were identified from A. marina genome. Abscisic acid (ABA) responsive elements were predicted in AmTPS and AmTPP promoters by cis-acting elements analysis. We further identified AmTPS9A, as an important positive regulator, that increased the salt tolerance of AmTPS9A-overexpressing Arabidopsis thaliana by altering the expressions of ion transport genes and mediating Na+ efflux from the roots of transgenic A. thaliana under NaCl treatments. In addition, we also found that ABA could promote the accumulation of trehalose, and the application of exogenous trehalose significantly promoted the biosynthesis of ABA in both roots and leaves of A. marina. Ultimately, we confirmed that AmABF2 directly binds to the AmTPS9A promoter in vitro and in vivo. Taken together, we speculated that there was a positive feedback loop between trehalose and ABA in regulating the salt tolerance of A. marina. These findings provide new understanding to the salt tolerance of A. marina in adapting to high saline environment at trehalose and ABA aspects.
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UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1-induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism-associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC-associated UHMK1 mutation induced NCOA3-S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho-NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1-activated de novo purine synthesis pathway significantly promotes GC development.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Coativador 3 de Receptor Nuclear/metabolismo , Nucleotídeos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias Gástricas/genética , Animais , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Coativador 3 de Receptor Nuclear/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Estômago/patologia , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
Recent years have witnessed rapid progress in the field of epitranscriptomics. Functional interpretation of the epitranscriptome relies on sequencing technologies that determine the location and stoichiometry of various RNA modifications. However, contradictory results have been reported among studies, bringing the biological impacts of certain RNA modifications into doubt. Here, we develop a synthetic RNA library resembling the endogenous transcriptome but without any RNA modification. By incorporating this modification-free RNA library into established mapping techniques as a negative control, we reveal abundant false positives resulting from sequence bias or RNA structure. After calibration, precise and quantitative mapping expands the understanding of two representative modification types, N6-methyladenosine (m6A) and 5-methylcytosine (m5C). We propose that this approach provides a systematic solution for the calibration of various RNA-modification mappings and holds great promise in epitranscriptomic studies.
Assuntos
Epigênese Genética , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA/genética , Transcriptoma , Calibragem , Regulação da Expressão Gênica , Células HeLa , HumanosRESUMO
Wurfbainia longiligularis and Wurfbainia villosa are both rich in volatile terpenoids and are 2 primary plant sources of Fructus Amomi used for curing gastrointestinal diseases. Metabolomic profiling has demonstrated that bornyl diphosphate (BPP)-related terpenoids are more abundant in the W. villosa seeds and have a wider tissue distribution in W. longiligularis. To explore the genetic mechanisms underlying the volatile terpenoid divergence, a high-quality chromosome-level genome of W. longiligularis (2.29 Gb, contig N50 of 80.39 Mb) was assembled. Functional characterization of 17 terpene synthases (WlTPSs) revealed that WlBPPS, along with WlTPS 24/26/28 with bornyl diphosphate synthase (BPPS) activity, contributes to the wider tissue distribution of BPP-related terpenoids in W. longiligularis compared to W. villosa. Furthermore, transgenic Nicotiana tabacum showed that the GCN4-motif element positively regulates seed expression of WvBPPS and thus promotes the enrichment of BPP-related terpenoids in W. villosa seeds. Systematic identification and analysis of candidate TPS in 29 monocot plants from 16 families indicated that substantial expansion of TPS-a and TPS-b subfamily genes in Zingiberaceae may have driven increased diversity and production of volatile terpenoids. Evolutionary analysis and functional identification of BPPS genes showed that BPP-related terpenoids may be distributed only in the Zingiberaceae of monocot plants. This research provides valuable genomic resources for breeding and improving Fructus Amomi with medicinal and edible value and sheds light on the evolution of terpenoid biosynthesis in Zingiberaceae.
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Alquil e Aril Transferases , Terpenos , Humanos , Terpenos/metabolismo , Difosfatos , Melhoramento Vegetal , Frutas/genética , Frutas/metabolismo , Plantas/metabolismo , Alquil e Aril Transferases/genéticaRESUMO
Brassinosteroid (BR) has been shown to modulate plant tolerance to various stresses. S-nitrosoglutathione reductase (GSNOR) is involved in the plant response to environment stress by fine-turning the level of nitric oxide (NO). However, whether GSNOR is involved in BR-regulated Na+ /K+ homeostasis to improve the salt tolerance in halophyte is unknown. Here, we firstly reported that high salinity increases the expression of BR-biosynthesis genes and the endogenous levels of BR in mangrove Kandelia obovata. Then, salt-induced BR triggers the activities and gene expressions of GSNOR and antioxidant enzymes, thereafter decrease the levels of malondialdehyde, hydrogen peroxide. Subsequently, BR-mediated GSNOR negatively regulates NO contributions to the reduction of reactive oxygen species generation and induction of the gene expression related to Na+ and K+ transport, leading to the decrease of Na+ /K+ ratio in the roots of K. obovata. Finally, the applications of exogenous BR, NO scavenger, BR biosynthetic inhibitor and GSNOR inhibitor further confirm the function of BR. Taken together, our result provides insight into the mechanism of BR in the response of mangrove K. obovata to high salinity via GSNOR and NO signaling pathway by reducing oxidative damage and modulating Na+ /K+ homeostasis.
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Óxido Nítrico , Rhizophoraceae , Óxido Nítrico/metabolismo , Oxirredutases/metabolismo , Brassinosteroides/farmacologia , Brassinosteroides/metabolismo , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Tolerância ao Sal , Transdução de SinaisRESUMO
Sorption to activated carbon is a common approach to reducing environmental risks of waterborne perfluorooctanoic acid (PFOA), while effective and flexible approaches to PFOA sorption are needed. Variations in temperature or the use of electrokinetic phenomena (electroosmosis and electromigration) in the presence of external DC electric fields have been shown to alter the contaminant sorption of contaminants. Their role in PFOA sorption, however, remains unclear. Here, we investigated the joint effects of DC electric fields and the temperature on the sorption of PFOA on activated carbon. Temperature-dependent batch and column sorption experiments were performed in the presence and absence of DC fields, and the results were evaluated by using different kinetic sorption models. We found an emerging interplay of DC and temperature on PFOA sorption, which was linked via the liquid viscosity (η) of the electrolyte. For instance, the combined presence of a DC field and low temperature increased the PFOA loading up to 38% in 48 h relative to DC-free controls. We further developed a model that allowed us to predict temperature- and DC field strength-dependent electrokinetic benefits on the drivers of PFOA sorption kinetics (i.e., intraparticle diffusivity and the film mass transfer coefficient). Our insights may give rise to future DC- and temperature-driven applications for PFOA sorption, for instance, in response to fluctuating PFOA concentrations in contaminated water streams.
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Fluorocarbonos , Poluentes Químicos da Água , Temperatura , Carvão Vegetal , Adsorção , Fluorocarbonos/análise , Caprilatos , Cinética , Poluentes Químicos da Água/análiseRESUMO
GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.
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DNA Helicases , RNA Helicases , Humanos , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas com Motivo de Reconhecimento de RNA , Regiões 5' não Traduzidas , Corpos de Inclusão Intranuclear , Ribossomos , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
BACKGROUND INFORMATION: Persistent myelin debris can inhibit axonal regeneration, thereby hindering remyelination. Effective removal of myelin debris is essential to eliminate the interference of myelin debris in oligodendrocyte progenitor cell (OPC) activation, recruitment to demyelinating sites and/or differentiation into mature oligodendrocytes (OLs). In addition to microglia, it has been reported that astrocytic phagocytosis of myelin debris is a feature of early demyelination. RESULTS: In the present study, astrocytes effectively phagocytized myelin debris in vitro and in vivo. On the 5th day after injecting myelin debris into the brain, astrocytes were enriched in the area injected with myelin debris compared with microglia, and their ability to engulf myelin debris was stronger than that of microglia. When exposed to myelin debris, astrocytes phagocytizing myelin debris triggered self-apoptosis, accompanied by the activation of NF-κB, down-regulation of Nrf2, and the increase of ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF). However, the activation of astrocytic NF-κB did not influence the inflammatory cytokines IL-1ß, IL-6, and TNF-α, and the anti-inflammatory factor IL-10. The proliferation of astrocytes and mobilization of OPCs in the subventricular zone were elevated on the 5th day after intracerebral injection of myelin debris. CONCLUSIONS: The results suggested that myelin phagocytosis of astrocytes should help improve the microenvironment and promote myelin regeneration by increasing CNTF and bFGF within the central nervous system. SIGNIFICANCE: However, the molecular interaction of astrocytes acting as phagocytes remains to be further explored. Therefore, an improvement of astrocytes to phagocytize myelin debris may be a promising treatment measure to prevent demyelination and promote remyelination in MS and other diseases with prominent myelin injury.
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Doenças Desmielinizantes , Bainha de Mielina , Humanos , Bainha de Mielina/metabolismo , Astrócitos/metabolismo , Doenças Desmielinizantes/metabolismo , Fator Neurotrófico Ciliar/metabolismo , NF-kappa B/metabolismo , Fagocitose , Oligodendroglia/metabolismoRESUMO
Asthenospermia is a predominant cause of male infertility, and antioxidant supplements can be effective in treating asthenospermia. We demonstrate the antioxidant potential of traditional Chinese medicine, the Yishenhuoxue (YSHX) formula, in treating polyglycosides of Tripterygium wilfordii (GTW)-induced asthenospermia in rats. Fifty male rats were randomly divided into the normal, model, and treatment groups. HE staining was used to evaluate the improvement of spermatogenic function of rats, and TBA reaction, qRT-PCR, Western Blot and other methods were used to determine the changes of oxidative stress indicators and to evaluate the improvement of antioxidant capacity of rats by YSHX. Comparison with the model group showed significant improvement in pathological damage caused by GTW to seminiferous tubules. MDA and NO content in rat testes decreased, especially in middle- and high-dosage groups. No significant changes were observed in SOD and CAT activity or mRNA expression. GSH-Px activity and GSH mRNA expression were significantly higher in the low-dosage group than in the model group. Compared to the model group, GR activity was significantly lower in the middle and high dosage groups, while the mRNA expression was higher. The PKC-beta level increased, while p-ERK1/2, NF-κB, and the ratio of p-ERK1/2*(ERK1/2)-1 decreased significantly in the treatment groups. Therefore, YSHX can alleviate GTW-induced testicular damage, enhance GSH-Px activity, regulate GSH redox cycling, and mitigate oxidative stress injury. Furthermore, YSHX can promote PKC-beta expression and inhibit the phosphorylation of ERK1/2 and NF-κB. Using YSHX may be an effective way to increase sperm motility via the PKC-ERK1/2-NF-ĸB axis.
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Antioxidantes , Astenozoospermia , Medicamentos de Ervas Chinesas , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Masculino , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Astenozoospermia/tratamento farmacológico , Astenozoospermia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ratos , NF-kappa B/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Tripterygium/química , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Phthalate esters (PAEs) have become one of the most concerned emerging organic pollutants in the world, due to the toxicity to human health, and hard to remove it efficiently. In this study, the degradation performance of DBP and DEHP in the soil by water bath heating activated sodium persulfate (PS) method under different factors were studied, in which the degradation rate of DBP and DEHP were improved with the increasing of temperature, PS concentration and water/soil ratio, and higher diffusion efficiency treatments methods, due to the improved mass transfer from organic phase to aqueous media. However, the degradation rate of DEHP was much lower than that of DBP, because DEHP in the soil was more difficult to contact with SO4â¢- for reaction on soil surface, and the degradation rate of PAEs in soil was significantly lower than that in water. Redundancy analysis of degradation rate of DBP and DEHP in water demonstrated that the key factors that determine the degradation rate is time for DBP, and cosolvent dosage for DEHP, indicating that the solubility and diffusion rate of PAEs from soil to aqueous are predominance function. This study provides comprehensive scenes in PAEs degradation with persulfate oxidation activated by thermal in soil, reveal the difference of degradation between DBP and DEHP is structure-dependent. So that we provide fundamental understanding and theoretical operation for subsequent filed treatment of various structural emerging pollutants PAEs contaminated soil with thermal activated persulfate.
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Oxirredução , Ácidos Ftálicos , Poluentes do Solo , Solo , Sulfatos , Sulfatos/química , Ácidos Ftálicos/química , Poluentes do Solo/química , Solo/química , Ésteres/química , Compostos de Sódio/química , Temperatura AltaRESUMO
BACKGROUND: Esophageal cancer, a global health concern, impacts predominantly men, particularly in Eastern Asia. Lymph node metastasis (LNM) significantly influences prognosis, and current imaging methods exhibit limitations in accurate detection. The integration of radiomics, an artificial intelligence (AI) driven approach in medical imaging, offers a transformative potential. This meta-analysis evaluates existing evidence on the accuracy of radiomics models for predicting LNM in esophageal cancer. METHODS: We conducted a systematic review following PRISMA 2020 guidelines, searching Embase, PubMed, and Web of Science for English-language studies up to November 16, 2023. Inclusion criteria focused on preoperatively diagnosed esophageal cancer patients with radiomics predicting LNM before treatment. Exclusion criteria were applied, including non-English studies and those lacking sufficient data or separate validation cohorts. Data extraction encompassed study characteristics and radiomics technical details. Quality assessment employed modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) tools. Statistical analysis involved random-effects models for pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Heterogeneity and publication bias were assessed using Deek's test and funnel plots. Analysis was performed using Stata version 17.0 and meta-DiSc. RESULTS: Out of 426 initially identified citations, nine studies met inclusion criteria, encompassing 719 patients. These retrospective studies utilized CT, PET, and MRI imaging modalities, predominantly conducted in China. Two studies employed deep learning-based radiomics. Quality assessment revealed acceptable QUADAS-2 scores. RQS scores ranged from 9 to 14, averaging 12.78. The diagnostic meta-analysis yielded a pooled sensitivity, specificity, and AUC of 0.72, 0.76, and 0.74, respectively, representing fair diagnostic performance. Meta-regression identified the use of combined models as a significant contributor to heterogeneity (p-value = 0.05). Other factors, such as sample size (> 75) and least absolute shrinkage and selection operator (LASSO) usage for feature extraction, showed potential influence but lacked statistical significance (0.05 < p-value < 0.10). Publication bias was not statistically significant. CONCLUSION: Radiomics shows potential for predicting LNM in esophageal cancer, with a moderate diagnostic performance. Standardized approaches, ongoing research, and prospective validation studies are crucial for realizing its clinical applicability.
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Neoplasias Esofágicas , Metástase Linfática , Humanos , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Metástase Linfática/diagnóstico por imagem , Sensibilidade e Especificidade , Inteligência Artificial , RadiômicaRESUMO
Heart rate is a key vital sign that can be used to understand an individual's health condition. Recently, remote sensing techniques, especially acoustic-based sensing, have received increasing attention for their ability to non-invasively detect heart rate via commercial mobile devices such as smartphones and smart speakers. However, due to signal interference, existing methods have primarily focused on monitoring a single user and required a large separation between them when monitoring multiple people. These limitations hinder many common use cases such as couples sharing the same bed or two or more people located in close proximity. In this paper, we present an approach that can minimize interference and thereby enable simultaneous heart rate monitoring of multiple individuals in close proximity using a commonly available smart speaker prototype. Our user study, conducted under various real-life scenarios, demonstrates the system's accuracy in sensing two users' heart rates when they are seated next to each other with a median error of 0.66 beats per minute (bpm). Moreover, the system can successfully monitor up to four people in close proximity.
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Determinação da Frequência Cardíaca , Telemetria , Humanos , Frequência Cardíaca , Acústica , Computadores de MãoRESUMO
The treatment of immunomodulation in multiple sclerosis (MS) can alleviate the severity and relapses. However, it cannot improve the neurological disability of patients due to a lack of myelin protection and regeneration. Therefore, remyelinating therapies may be one of the feasible strategies that can prevent axonal degeneration and restore neurological disability. Natural product icariin (ICA) is a flavonol compound extracted from epimedium flavonoids, which has neuroprotective effects in several models of neurological diseases. Here, we attempt to explore whether ICA has the potential to treat demyelination and its possible mechanisms of action using lipopolysaccharide-treated BV2 microglia, primary microglia, bone marrow-derived macrophages, and cuprizone-induced demyelination model. The indicators of oxidative stress and inflammatory response were evaluated using commercial kits. The results showed that ICA significantly reduced the levels of oxidative intermediates nitric oxide, hydrogen peroxide, malondialdehyde, and inflammatory cytokines TNF-α, IL-1ß, and increased the levels of antioxidants superoxide dismutase, catalase, glutathione peroxidase, and anti-inflammatory cytokines IL-10 and TGF-ß in vitro cell experiments. In vivo demyelination model, ICA significantly alleviated the behavioral abnormalities and enhanced the integrated optical density/mm2 of Black Gold II and myelin basic protein myelin staining, accompanied by the inhibition of oxidative stress/inflammatory response. Immunohistochemical staining showed that ICA significantly induced the expression of nuclear factor erythroid derived 2/heme oxygenase-1 (Nrf2/HO-1) and inhibited the expression of toll-like receptor 4/ nuclear factor kappa B (TLR4/NF-κB), which are two key signaling pathways in antioxidant and anti-inflammatory processes. Our results strongly suggest that ICA may be used as a potential agent to treat demyelination via regulating Nrf2/HO-1-mediated antioxidative stress and TLR4/NF-κB-mediated inflammatory responses.
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Antioxidantes , Doenças Desmielinizantes , Flavonoides , Humanos , Antioxidantes/farmacologia , Cuprizona/farmacologia , Receptor 4 Toll-Like , NF-kappa B , Fator 2 Relacionado a NF-E2 , Anti-Inflamatórios/farmacologia , Citocinas , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológicoRESUMO
PURPOSE: The removal of small foreign bodies embedded within the deep soft tissues of the maxillofacial region is a complex and challenging task for maxillofacial surgeons. The purpose of this study was to explore the efficacy of the combination of intraoperative CT and surgical navigation for the removal of small foreign objects in the maxillofacial region. METHODS: A serial case study was conducted involving all consecutive patients who underwent surgical removal of small foreign bodies in the maxillofacial region. The combination of intraoperative CT and a surgical navigation system was used at a single medical institution from January 2018 to December 2022. Comprehensive data, including patient demographics, characteristics of the foreign bodies, previous surgical interventions, duration of the surgical procedure, and removal success rate were collected for this study. Relevant data were recorded into Microsoft Excel sheet and analyzed using SPSS version 22.0. RESULTS: Nine patients (6 males and 3 females) were included in this study, with an average age of 37 years. Each patient had previously undergone an unsuccessful removal attempt utilizing conventional surgical methods based on preoperative CT imaging or C-arm guidance at a local healthcare facility. Four patients also experienced unsuccessful attempts with preoperative CT image-based navigation systems. However, by employing the combined approach of intraoperative CT and surgical navigation, the foreign bodies were successfully removed in all 9 patients. The mean duration of the surgical procedure was 59 min, and the average size of the foreign bodies was approximately 26 mm³. Postoperative follow-up exceeding 6 months revealed no complications. CONCLUSION: The combined use of a surgical navigation system and intraoperative CT represents a potent and effective strategy for the precise localization and subsequent removal of small foreign bodies from the soft tissue structures of the maxillofacial region. This integrative approach appears to increase the success rate of surgical interventions in such cases.
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Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.
Assuntos
Dopamina , Ketamina , Humanos , Animais , Camundongos , Dopamina/metabolismo , Dopamina/farmacologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Ketamina/metabolismo , Ketamina/farmacologia , Larva , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologiaRESUMO
Slow release of emerging contaminants limits their accessibility from soil to pore water, constraining the treatment efficiency of physio-chemical treatment sites. DC fields mobilize organic contaminants and influence their interactions with geo-matrices such as zeolites. Poor knowledge, however, exists on the joint application of heating and electrokinetic approaches on perfluorooctanoic acid (PFOA) transport in porous media. Here, we investigated electrokinetic PFOA transport in zeolite-filled percolation columns at varying temperatures. Variations of pseudo-second-order kinetic constants (kPSO) were correlated to the liquid viscosity variations (η) and elctroosmotic flow velocities (vEOF). Applying DC fields and elevated temperature significantly (>37%) decreased PFOA sorption to zeolite. A good correlation between η, vEOF, and kPSO was found and used to develop an approach interlinking the three parameters to predict the joint effects of DC fields and temperature on PFOA sorption kinetics. These findings may give rise to future applications for better tailoring PFOA transport in environmental biotechnology.
Assuntos
Caprilatos , Fluorocarbonos , Zeolitas , Caprilatos/química , Fluorocarbonos/química , Adsorção , Zeolitas/química , Cinética , Modelos QuímicosRESUMO
Objective: To investigate the relationship between the DNA methylation state of NRG1 promoter and its expression changes, and to analyze the clinical significance of its regulatory mechanism of DNA methylation in cervical carcinoma. Methods: This was a retrospective study. One-hundred and twenty patients from the Department of Gynecology of Cangzhou People's Hospital from September 2017 to September 2019 were selected, including 40 cases of cervical SCC, 40 cases of high grade squamous intraepithelial lesions(HSIL) and 40 cases of control cervical tissues. RT-qPCR, immunohistochemistry and DNA methylation-specific PCR(MSP) were used to detect the mRNA and protein expression of NRG1 and DNA methylation status in different tissue types. Results: Immunohistochemical results showed that the positive protein expression rate of NRG1 gene in the SCC group was lower than that in both HSIL and Control groups. RT-qPCR results showed that the mRNA gene of NRG1 gradually decreased in expression with the increase of cervical tissue lesions, with a statistically significant difference. Similarly, it also found that the mRNA expression level of NRG1 in the SCC group was independent of patients' age (p>0.05), but significantly correlated with tumor pathological staging, surgical pathology staging and lymphatic metastasis (p<0.05). Furthermore, methylation-specific PCR results revealed a significantly higher DNA methylation rate of NRG1 gene in the SCC group than in both HSIL and Control groups, with a statistically significant difference. Moreover, the methylation degree of NRG1 gene in SCC tissues was negatively correlated with its mRNA expression (p<0.05). Conclusions: Abnormal DNA hypermethylation of NRG1 gene inhibits the expression of mRNA and protein in the progression of cervical tissue from normal to cancerous state, which is involved in the occurrence and development of cervical carcinoma.