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Assembling titanium carbide (Ti3C2Tx) MXene nanosheets into macroscopic films presents challenges, including voids, low orientation degree, and weak interfacial interactions, which reduce mechanical performance. We demonstrate an ultrastrong macroscopic MXene film using liquid metal (LM) and bacterial cellulose (BC) to sequentially bridge MXene nanosheets (an LBM film), achieving a tensile strength of 908.4 megapascals. A layer-by-layer approach using repeated cycles of blade coating improves the orientation degree to 0.935 in the LBM film, while a LM with good deformability reduces voids into porosity of 5.4%. The interfacial interactions are enhanced by the hydrogen bonding from BC and the coordination bonding with LM, which improves the stress-transfer efficiency. Sequential bridging provides an avenue for assembling other two-dimensional nanosheets into high-performance materials.
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BACKGROUND: Glioma is the most common primary brain tumor with high mortality and disability rates. Recent studies have highlighted the significant prognostic consequences of subtyping molecular pathological markers using tumor samples, such as IDH, 1p/19q, and TERT. However, the relative importance of individual markers or marker combinations in affecting patient survival remains unclear. Moreover, the high cost and reliance on postoperative tumor samples hinder the widespread use of these molecular markers in clinical practice, particularly during the preoperative period. We aim to identify the most prominent molecular biomarker combination that affects patient survival and develop a preoperative MRI-based predictive model and clinical scoring system for this combination. METHODS: A cohort dataset of 2,879 patients was compiled for survival risk stratification. In a subset of 238 patients, recursive partitioning analysis (RPA) was applied to create a survival subgroup framework based on molecular markers. We then collected MRI data and applied Visually Accessible Rembrandt Images (VASARI) features to construct predictive models and clinical scoring systems. RESULTS: The RPA delineated four survival groups primarily defined by the status of IDH and TERT mutations. Predictive models incorporating VASARI features and clinical data achieved AUC values of 0.85 for IDH and 0.82 for TERT mutations. Nomogram-based scoring systems were also formulated to facilitate clinical application. CONCLUSIONS: The combination of IDH-TERT mutation status alone can identify the most distinct survival differences in glioma patients. The predictive model based on preoperative MRI features, supported by clinical assessments, offers a reliable method for early molecular mutation prediction and constitutes a valuable scoring tool for clinicians in guiding treatment strategies.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Imageamento por Ressonância Magnética , Telomerase , Humanos , Glioma/genética , Glioma/mortalidade , Glioma/diagnóstico por imagem , Glioma/patologia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Isocitrato Desidrogenase/genética , Pessoa de Meia-Idade , Telomerase/genética , Mutação , Adulto , Nomogramas , Prognóstico , IdosoRESUMO
Despite their potential as conversion-type energy storage technologies, the performance of static lithium-bromide (SLB) batteries has remained stagnant for decades. Progress has been hindered by the intrinsic liquid-liquid redox mode and single-electron transfer of these batteries. Here, we developed a high-performance SLB battery based on the active bromine salt cathode and the two-electron transfer chemistry with a Br-/Br+ redox couple by electrolyte tailoring. The introduction of NO3- improved the reversible single-electron transition of Br-, and more impressively, the coordinated Cl- anions activated the Br+ conversion to provide an additional electron transfer. A voltage plateau was observed at 3.8 V, and the discharge capacity and energy density were increased by 142 and 159% compared to the one-electron reaction benchmark. This two-step conversion mechanism exhibited excellent stability, with the battery functioning for 1000 cycles. These performances already approach the state of the art of currently established Li-halogen batteries. We consider the established two-electron redox mechanism highly exemplary for diversified halogen batteries.
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Pomegranate are often treated with preservatives during storage. This study investigated the effects of storage and food processing on the residual behavior of the five commonly used preservatives (prochloraz, thiophanate-methyl, pyrimethanil, imazalil, and difenoconazole) and their metabolites in pomegranate and its products. The LOQs for all target compounds were 0.001 mg kg-1. The residue levels of five preservatives in the calyx was highest, followed by the peel, stalk, septum, umbilicus, and seed. For the migration ability, the five preservatives from pomegranate peel to seed was negatively correlated with their octanol/water partition coefficients. The processing factors of each procedures of juice, wine, vinegar, and pectin processing were <1. Nevertheless, the PF values in drying peel during the overall process ranged from 1.26 to 4.09. Hence, it is worth noting that consumption of pomegranate essential oil and drying peel may pose a potential risk to the health of consumers.
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Conservantes de Alimentos , Armazenamento de Alimentos , Frutas , Punica granatum , Punica granatum/química , Punica granatum/metabolismo , Conservantes de Alimentos/química , Conservantes de Alimentos/análise , Conservantes de Alimentos/metabolismo , Frutas/química , Frutas/metabolismo , Manipulação de AlimentosRESUMO
A large amount of lithium-ion storage in Si-based anodes promises high energy density yet also results in large volume expansion, causing impaired cyclability and conductivity. Instead of restricting pulverization of Si-based particles, herein, we disclose that single-walled carbon nanotubes (SWNTs) can take advantage of volume expansion and induce interfacial reactions that stabilize the pulverized Si-based clusters in situ. Operando Raman spectroscopy and density functional theory calculations reveal that the volume expansion by the lithiation of Si-based particles generates â¼14% tensile strains in SWNTs, which, in turn, strengthens the chemical interaction between Li and C. This chemomechanical coupling effect facilitates the transformation of sp2-C at the defect of SWNTs to Li-C bonds with sp3 hybridization, which also initiates the formation of new Si-C chemical bonds at the interface. Along with this process, SWNTs can also induce in situ reconstruction of the 3D architecture of the anode, forming mechanically strengthened networks with high electrical and ionic conductivities. As such, with the addition of only 1 wt % of SWNTs, graphite/SiOx composite anodes can deliver practical performance well surpassing that of commercial graphite anodes. These findings enrich our understanding of strain-induced interfacial reactions, providing a general principle for mitigating the degradation of alloying or conversion-reaction-based electrodes.
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Conventional metal sulfide (SnS2) gas-sensitive sensing materials still have insufficient surface area and slow response/recovery times. To increase its gas-sensing performance, MoS2nanoflower was produced hydrothermally and mechanically combined with SnS2nanoplate. Extensive characterization results show that MoS2was effectively integrated into SnS2. Four different concentrations of SnS2-MoS2composites were evaluated for their NO2gas sensitization capabilities. Among them, SnS2-15% MoS2at 170 °C demonstrated the greatest response values to NO2, 7.3 for 1 ppm NO2, which is about three times greater than the SnS2sensor at 170 °C (2.58). The creation of pn junctions following compositing with SnS2was determined to be the primary reason for the composite's faster recovery time, while the heterojunction allowed for the rapid separation of hole-electron pairs. Because the MoS2surface has multiple vacancy defects, the adsorption energy of these vacancies is significantly higher than that of other places, resulting in increased NO2adsorption. Furthermore, MoS2can serve as active adsorption sites for SnS2micrometer sheets during gas sensing. This study may help to build new NO2gas sensors.
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The brain network of speech fluency has not yet been investigated via a study with a large and homogenous sample. This study analysed multimodal imaging data from 115 patients with low-grade glioma to explore the brain network of speech fluency. We applied voxel-based lesion-symptom mapping to identify domain-specific regions and white matter pathways associated with speech fluency. Direct cortical stimulation validated the domain-specific regions intra-operatively. We then performed connectivity-behaviour analysis with the aim of identifying connections that significantly correlated with speech fluency. Voxel-based lesion-symptom mapping analysis showed that damage to domain-specific regions (the middle frontal gyrus, the precentral gyrus, the orbital part of inferior frontal gyrus and the insula) and white matter pathways (corticospinal fasciculus, internal capsule, arcuate fasciculus, uncinate fasciculus, frontal aslant tract) are associated with reduced speech fluency. Furthermore, we identified connections emanating from these domain-specific regions that exhibited significant correlations with speech fluency. These findings illuminate the interaction between domain-specific regions and 17 domain-general regions-encompassing the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and rolandic operculum, superior temporal gyrus, temporal pole, inferior temporal pole, middle cingulate gyrus, supramarginal gyrus, fusiform gyrus, inferior parietal lobe, as well as subcortical structures such as thalamus-implicating their collective role in supporting fluent speech. Our detailed mapping of the speech fluency network offers a strategic foundation for clinicians to safeguard language function during the surgical intervention for brain tumours.
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In this Letter, the CH3NH3PbBr3 nanocrystals (NCs) are embedded into the interstices of the fluorine (polyvinyl fluoride/polyvinylidene fluoride, PVF/PVDF) matrix on polyethylene terephthalate (PET) substrate to introduce new advantages, such as being flexible and waterproof, while maintaining the high optical performance of perovskites. The sample's photoluminescence (PL) spectra under 325â nm laser is a green emission peaked at 537â nm with full width at half maximum (FWHM) of about 21.2â nm and a fast PL decay time. As a color converter, it shows high optical absorption and can transform light from solar-blind ultraviolet to a blue region into a green region in air, water, and bending conditions. While excited by a 270â nm ultraviolet light-emitting diode (LED), the system's observed -3â dB bandwidth with the color converter is near 4.4â MHz in air and water conditions with well-eye diagrams at a data rate of 30â Mbps. Finally, we demonstrate an audio transmission application with an ultraviolet light source, a color conversion layer, and a low-cost silicon-based photodetector.
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Pesticides play vital roles in controlling pests and boosting crop yields. Imidacloprid is widely used all over the world and may form in agricultural products. The presence of pesticide residues in apples raises serious health concerns. Understanding the residual fate of imidacloprid is critical for food safety and human health. In this study, the dissipation behavior, metabolism, household processing and risk assessment of imidacloprid and its metabolites in apple were investigated from filed to products. Field experiment results suggested that the half-lives of imidacloprid at 5 times the recommended dosage was 1.5 times that of the standard dosage. And the final residues of imidacloprid were less than the established maximum residue limits (MRLs). Clarification and simmering had little effect on the reduction the residues of imidacloprid and its metabolites. The calculated processing factors were lower than 1 for imidacloprid and its metabolites, implying that the residual ratios of imidacloprid and its metabolites in each steps of the food processing were reduced. The risk quotients were <1 for all Chinese people, indicating that acceptable risks associated with dietary exposure to imidacloprid in apple. However, the higher risks were observed in young people than adults, and females faced higher risks than males. Given high residue levels in pomace, imidacloprid and its metabolites should be further studied in commercial byproducts.
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Inseticidas , Malus , Neonicotinoides , Nitrocompostos , Resíduos de Praguicidas , Malus/química , Malus/metabolismo , Neonicotinoides/metabolismo , Neonicotinoides/análise , Nitrocompostos/análise , Nitrocompostos/metabolismo , Medição de Risco , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/metabolismo , Inseticidas/análise , Inseticidas/metabolismo , Humanos , Contaminação de Alimentos/análise , Exposição Dietética/análise , China , Feminino , Imidazóis/metabolismo , Imidazóis/análise , Imidazóis/químicaAssuntos
Adenocarcinoma de Pulmão , Anticorpos Monoclonais Humanizados , Antígeno CTLA-4 , Neoplasias Pulmonares , Receptor de Morte Celular Programada 1 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento , Imunoterapia/métodos , Masculino , Resistencia a Medicamentos Antineoplásicos , Pessoa de Meia-Idade , Feminino , Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , IdosoRESUMO
PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.
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Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Humanos , Interferon-alfa/uso terapêutico , Soroconversão , Hepatite B Crônica/tratamento farmacológico , Vacinas contra Hepatite B/uso terapêutico , Citocinas , Anticorpos Anti-Hepatite B , Vacinação , Imunidade , Antígenos E da Hepatite B , Antivirais/uso terapêutico , Polietilenoglicóis/uso terapêuticoRESUMO
Epilepsy, a chronic neuropsychiatric brain disorder characterized with recurrent seizures, is closely associated with abnormal neural communications within the brain. Despite that the phase-amplitude coupling (PAC) has been suggested to offer a new way to observe neural interactions during epilepsy, however, few studies pay attention to alterations of the epileptic functional brain network based on PAC, especially on the [Formula: see text] PAC. Therefore, we use scalp electroencephalography (EEG) data of epileptic patients and the [Formula: see text] PAC modulation index (MI) to construct functional brain networks to examine variations of neural interactions during different epileptic phases. Statistically, the findings show that between-channel MI values in the post-ictal period significantly increase compared to that in the pre-ictal period, and the between-channel MI value has a close association with the information of phase and amplitude provided by the channels. Importantly, in both the phase-amplitude and amplitude-phase functional brain networks, the average node degree is remarkably higher in the post-ictal period than that in the pre-ictal period, whereas the characteristic path length in the ictal and post-ictal periods is significantly lower than that in the pre-ictal period. Besides, the average betweenness centrality in the post-ictal period is remarkably higher than that in the ictal period. Interestingly, the positive correlations between within-channel MI values and between-channel MI values can be observed during the pre-ictal, ictal and post-ictal periods. These findings suggest that the [Formula: see text] PAC-based functional brain network may provide a novel perspective to understanding alterations of neural interactions during the epileptic evolution, and may contribute to effectively controlling the spread of epileptic seizures.
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Encéfalo , Eletroencefalografia , Epilepsia , Processamento de Sinais Assistido por Computador , Humanos , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Encéfalo/fisiopatologia , Adulto , Masculino , Feminino , Adulto Jovem , Adolescente , Rede Nervosa/fisiopatologia , Pessoa de Meia-Idade , CriançaRESUMO
AIM: Myocarditis is a recognized safety concern following COVID-19 mRNA vaccination. However, there is limited research quantifying the risk associated with the third dose or comparing the risk between the three doses. The US Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that monitors rare adverse events after US-licensed vaccination. However, studies analyzing VAERS data have often faced criticism for underreporting cases and lacking a control group to assess the increase in baseline risk. METHODS: The temporal association between myocarditis onset and COVID-19 vaccination was studied. To overcome limitations, a novel modified self-controlled case series method was employed, explicitly modeling the case reporting process in VAERS data. RESULTS: We found an increased risk of myocarditis during the 1- to 3-day period following the second and third doses of both the BNT162b2 vaccine and the mRNA-1273 vaccine. Following the second dose, the relative incidence (RI) was 4.89 (95% confidence interval (CI), 2.39-10.08) for the BNT162b2 vaccine and 2.86 (95% CI: 1.18-7.03) for the mRNA-1273 vaccine. Similarly, following the third dose, the RI was 9.04 (95% CI: 2.79-40.99) for the BNT162b2 vaccine and 4.71 (95% CI: 1.42-19.09) for the mRNA-1273 vaccine. No significant increase in risk was observed during other periods. Notably, our analysis also identified a similar increased risk of myocarditis among individuals aged below 30. CONCLUSIONS: These findings raise safety concerns regarding COVID-19 mRNA vaccines, provide insights into the quantification of myocarditis risk at different postvaccination periods, and offer a novel approach to interpreting passive surveillance system data.
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Vacinas contra COVID-19 , COVID-19 , Miocardite , Humanos , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas de mRNA , Miocardite/epidemiologia , Miocardite/etiologia , Projetos de Pesquisa , Estados Unidos/epidemiologiaRESUMO
Sonic hedgehog (SHH) and heat shock protein 90ß (HSP90ß) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90ß is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90ß ubiquitylation through deubiquitylase USP31, thus preventing HSP90ß degradation and promoting hepatic lipid synthesis. HSP90ß significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90ß axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90ß-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.
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MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteínas de Choque Térmico/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Camundongos Endogâmicos C57BLRESUMO
To evaluate the prediction model comprised of patients' laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case-control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030-0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768-71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006-0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040-0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138-13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.
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BACKGROUND: Extent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival. METHODS: Patients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm3 decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm3 and postoperative (post-OP) TV > 4.6 cm3 showed worse OS (P= 0.0117) CONCLUSIONS: It showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Estudos Retrospectivos , Monitorização Intraoperatória/métodos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
In contrast to the well-defined biological feedback loops controlling glucose, the mechanisms by which the body responds to changes in fatty acid availability are less clearly defined. Growth differentiating factor 15 (GDF15) suppresses the consumption of diets high in fat but is paradoxically increased in obese mice fed a high-fat diet. Given this interrelationship, we investigated whether diets high in fat could directly increase GDF15 independently of obesity. We found that fatty acids increase GDF15 levels dose dependently, with the greatest response observed with linolenic acid. GDF15 mRNA expression was modestly increased in the gastrointestinal tract; however, kidney GDF15 mRNA was â¼1,000-fold higher and was increased by more than threefold, with subsequent RNAscope analysis showing elevated expression within the cortex and outer medulla. Treatment of wild-type mice with linolenic acid reduced food intake and body mass; however, this effect disappeared in mice lacking the GDF15 receptor GFRAL. An equal caloric load of glucose did not suppress food intake or reduce body mass in either wild-type or GFRAL-knockout mice. These data indicate that fatty acids such as linolenic acid increase GDF15 and suppress food intake through a mechanism requiring GFRAL. These data suggest that a primary physiological function of GDF15 may be as a fatty acid sensor designed to protect cells from fatty acid overload. ARTICLE HIGHLIGHTS: The mechanisms by which the body responds to changes in fatty acid availability are less clearly defined. We investigated whether diets high in fat could directly increase growth differentiating factor 15 (GDF15) independently of obesity. Fatty acids increase GDF15 and reduce food intake through a GFRAL signaling axis. GDF15 is a sensor of fatty acids that may have important implications for explaining increased satiety after consumption of diets high in fat.
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Ingestão de Alimentos , Obesidade , Animais , Camundongos , Ácidos Graxos , Glucose/metabolismo , Ácidos Linolênicos/farmacologia , Camundongos Knockout , Obesidade/metabolismo , RNA MensageiroRESUMO
The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS33) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.
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Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.
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Hepatite B Crônica , Hepatite B , Humanos , Vacinas contra Hepatite B , Antígenos de Superfície da Hepatite B , Estudos Retrospectivos , Soroconversão , Anticorpos Anti-Hepatite B , Hepatite B/prevenção & controleRESUMO
In tonal languages, which are spoken by nearly one-third of the world's population, speakers precisely control the tension of vocal folds in the larynx to modulate pitch in order to distinguish words with completely different meanings. The specific pitch trajectories for a given tonal language are called lexical tones. Here, we used high-density direct cortical recordings to determine the neural basis of lexical tone production in native Mandarin-speaking participants. We found that instead of a tone category-selective coding, local populations in the bilateral laryngeal motor cortex (LMC) encode articulatory kinematic information to generate the pitch dynamics of lexical tones. Using a computational model of tone production, we discovered two distinct patterns of population activity in LMC commanding pitch rising and lowering. Finally, we showed that direct electrocortical stimulation of different local populations in LMC evoked pitch rising and lowering during tone production, respectively. Together, these results reveal the neural basis of vocal pitch control of lexical tones in tonal languages.