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Heavy metal sediment pollution has become an increasingly serious problem associated with industrial development, so extensive studies have been conducted concerning their removal. Biochar has recently shown good potential for in-situ remediation of heavy metal-contaminated sediments. The heavy metal adsorption capacity of inexpensive biochar can be improved by loading it with metal oxides. In this study, manganese-modified biochar (MBC) was prepared by KMnO4-modified waste-activated sludge biochar and applied to immobilize Pb and Cd in sediments. Its effects on the sediment microbial community were also investigated. The Results showed that manganese modification of the biochar made it more conducive to the adsorption of heavy metals, owing to its higher specific surface area and graphitization structure, more active sites and oxygen-containing groups, and the presence of Mn2O3 crystal structure on the surface. The maximum adsorption capacities of this material for Pb2+ and Cd2+ in solution were 176.9 mg/g and 44.0 mg/g, respectively. The application of MBC to the remediation of heavy metal-contaminated sediments transformed Pb and Cd in the sediments from exchangeable to residual state. The F4 content of Pb in the sediments increased from 40.52%-42.36% to 49.11%-51.14% after application of 1% MBC, and to 63.94%-64.49% after application of 5% MBC. Correspondingly, the F1 content of Pb in the sediments decreased from 29.09%-30.68% to 17.43%-17.69% after the application of 5% MBC. Furthermore, MBC efficiently enriched the microbial biodiversity and affected the microbial population structure within 60 days. The relative abundance of uncultured f Symbiobacteraceae and Fonticella communities significantly increased after incubation. The results may provide empirical support for the combination of metal oxides and biochar for the remediation of heavy metal-contaminated sediments.
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Reconfiguration of in situ heterojunction composites without interfacial resistance by substitution of homologous anions for the formation of gradient work function differences inducing the formation of built-in electric field is an effective strategy to enhance the charge separation efficiency. Herein, Te2-/ZnIn2S4-VS (Te2-/ZIS-VS) in situ heterojunction was synthesized by substitution of Te2- ions for S2- in ultrathin ZIS containing S vacancies, which can significantly promote photogenerated charge separation, surface electron enrichment, and CO2 adsorption/activation. The presence of S vacancies and adjacent Te2-/S2- double anions, the double active sites constructed by defect engineering promote the desorption of *CO molecules while inhibiting the protonation toward *CHO, which was more favorable for selective CO2 photoreduction to CO. The experimental results showed that the CO yield of Te2-/ZIS-VS was significantly increased to 672.1 µmol g-1 h-1 compared with pristine ZIS (54.3 µmol g-1 h-1) and the CO selectivity was close to 83 %. Notably, the life cycle assessment (LCA) of Te2-/Znln2S4 nanosheets with S-vacancy was performed. The evaluation results showed that most of the 17 impact categories showed low overall impact values and were environmentally friendly. Based on the results of this LCA, suggestions were put forward to further optimize the product to reduce carbon emissions.
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BACKGROUND AND PURPOSE: Oxidative stress plays a critical role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The small molecule ULK1 agonist, BL-918, demonstrated neuroprotective effects in other central nervous system diseases; however, its role in SAH has not yet been explored. This study aimed to evaluate whether BL-918 could provide neuroprotective effects in rats following SAH. METHODS: An SAH model was established in Sprague-Dawley rats using endovascular perforation. BL-918 was administered intraperitoneally after SAH, while the ULK1 inhibitor SBI was given intraperitoneally prior to SAH modeling. PINK1 siRNA was administered into the lateral ventricle before SAH induction. The neuroprotective effects and mechanisms of BL-918 were assessed through SAH grading, brain water content measurement, blood-brain barrier permeability, neurobehavioral tests, Western blot, immunofluorescence, TUNEL staining, DHE staining, and transmission electron microscopy (TEM). RESULTS: After SAH, the expression levels of p-ULK1, PINK1, Parkin, and LC3â ¡ increased, peaking at 24 h post-SAH. BL-918 treatment improved neurological function in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Western blot analysis revealed that BL-918 increased the expression of p-ULK1, PINK1, Parkin, LC3â ¡, Bcl-xl, and Bcl-2 while inhibiting the expression of Bax and Cleaved Caspase-3. Oxidative stress-related indicators showed that BL-918 alleviated oxidative stress. Immunofluorescence and TEM results demonstrated that BL-918 promoted mitophagy and preserved mitochondrial morphology. Furthermore, the positive effects of BL-918 were reversed by SBI and PINK1 siRNA, respectively. CONCLUSION: BL-918 improved both short-term and long-term neurological impairments in rats after SAH and reduced oxidative stress by promoting mitophagy, at least partially through the ULK1/PINK1/Parkin signaling pathway.
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The efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) -2.13 kg/m2, 95% credible interval (CrI) [-2.7, -1.57]), waist circumference (MD -1.34 cm, 95% CrI [-2.33, -0.35]), total cholesterol (MD -6.55 mg/dL, 95% CrI [-10.61, -2.45]), triglycerides (MD -3.71 mg/dL, 95% CrI [-5.76, -1.67]), leptin (MD -3.99 ng/mL, 95% CrI [-4.68, -3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD -1.21 mg/L, 95% CrI [-1.45, -0.97]). Synbiotics were effective in reducing BMI-z score (MD -0.07, 95% CrI [-0.10, -0.04]) and LDL-C (MD -1.54 mg/dL, 95% CrI [-1.98, -1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings.
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Aim: Physical exercise is essential for the physical and mental health of visually impaired people, but they often face challenges such as inaccurate movements, lack of rhythm and difficulty in mastering postures during exercise. This project introduces an assistive device based on a multi-channel interaction design strategy to improve the accuracy of yoga practice for the visually impaired and to enable their independent exercise.Methods: The system uses a 1:1 model combined with an output interaction model. The effectiveness was verified through controlled experiments with unassisted exercise as the control group and yoga-assisted exercise as the experimental group. Improvements in yoga accuracy and product usability were verified using the Assisted Accuracy Scale and the SUS Scale, respectively.Results: The results showed that the multi-channel interaction design significantly improved the accuracy and usability of yoga exercises and enhanced the ability of visually impaired people to exercise independently.Conclusion: Through this project, we hope to replicate this design strategy to help more visually impaired individuals independently perform effective physical exercise at home, in a gym, or in an outdoor space, thereby improving their quality of life and overall health.
A yoga assistive device called E-YOGA, which improves the accuracy of yoga for the visually impaired through augmented interactive technology, thereby enhancing the ability of the visually impaired to exercise on their own.By participating in sports activities, visually impaired people can improve their health, living ability, body system and organ function.Regular physical activity is essential for visually impaired people, not only to build strength and endurance, but also for simple daily activities that require a lot of energy.
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BACKGROUND AND PURPOSE: Following subarachnoid hemorrhage (SAH), excessive activation of oxidative stress and cell apoptosis plays a critical role in early brain injury (EBI). Peroxiredoxin-5 (Prdx5), predominantly expressed in neuronal mitochondria, acts as an antioxidant. However, the role of Prdx5 in EBI after SAH remains unclear. This study aims to elucidate the antioxidative stress and anti-apoptotic effects of Prdx5 in rats following SAH. METHODS: In this study, an SAH model was established in Sprague-Dawley rats using endovascular perforation. Recombinant Prdx5 (rPrdx5) was administered intranasally to upregulate Prdx5 expression after SAH in rats. Prdx5 small interfering RNA (Prdx5 siRNA) was administered prior to SAH modelling. The neuroprotective effects of Prdx5 were validated through SAH grading, brain water content, blood-brain barrier permeability, neurobehavioral tests, immunofluorescence, TUNEL staining, and Western blotting. RESULTS: The expression levels of endogenous Prdx5 significantly decreased after SAH. Treatment with rPrdx5 improved both short-term and long-term behaviour in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Measurements of oxidative stress-related indicators, including MDA, SOD, GSH-Px and GSH/GSSG, confirmed that Prdx5 can alleviate oxidative stress in rats after SAH. Western blot analysis showed that rPrdx5 significantly increased the expression of Bcl-XL and Bcl-2 and reduced the expression of Bax and Cleaved Caspase-3, thereby exerting anti-apoptotic effects. Additionally, Prdx5 siRNA reversed the neuroprotective effects of rPrdx5, exacerbated neuronal damage and blood-brain barrier permeability, and increased levels of oxidative stress and apoptosis. CONCLUSION: In conclusion, our study demonstrated that specifically upregulating the expression of Prdx5 can reduce oxidative stress and apoptosis in rats after SAH, while also improving both short-term and long-term neurological impairments. Prdx5 is primarily expressed in the mitochondria of neuronal cells and is a crucial target for reducing ROS after SAH. rPrdx5 treatment may offer a promising therapeutic approach for clinical SAH patients.
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Apoptose , Barreira Hematoencefálica , Lesões Encefálicas , Estresse Oxidativo , Peroxirredoxinas , Ratos Sprague-Dawley , Hemorragia Subaracnóidea , Animais , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/complicações , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Peroxirredoxinas/metabolismo , Masculino , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas/metabolismo , Ratos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologiaRESUMO
Reducing voltage losses while maintaining high photocurrents is the holy grail of current research on non-fullerene acceptor (NFA) based organic solar cell. Recent focus lies in understanding the various fundamental mechanisms in organic blends with minimal energy offsets - particularly the relationship between ionization energy offset (ΔIE) and free charge generation. Here, we quantitatively probe this relationship in multiple NFA-based blends by mixing Y-series NFAs with PM6 of different molecular weights, covering a broad power conversion efficiency (PCE) range: from 15% down to 1%. Spectroelectrochemistry reveals that a ΔIE of more than 0.3 eV is necessary for efficient photocurrent generation. Bias-dependent time-delayed collection experiments reveal a very pronounced field-dependence of free charge generation for small ΔIE blends, which is mirrored by a strong and simultaneous field-dependence of the quantified photoluminescence from the NFA local singlet exciton (LE). We find that the decay of singlet excitons is the primary competition to free charge generation in low-offset NFA-based organic solar cells, with neither noticeable losses from charge-transfer (CT) decay nor evidence for LE-CT hybridization. In agreement with this conclusion, transient absorption spectroscopy consistently reveals that a smaller ΔIE slows the NFA exciton dissociation into free charges, albeit restorable by an electric field. Our experimental data align with Marcus theory calculations, supported by density functional theory simulations, for zero-field free charge generation and exciton decay efficiencies. We conclude that efficient photocurrent generation generally requires that the CT state is located below the LE, but that this restriction is lifted in systems with a small reorganization energy for charge transfer.
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All-small molecule (ASMs) solar cells have great potential to actualize the commercialization of organic photovoltaics owing to their higher solubility, lesser batch-to-batch variety and simpler synthesis routes compared to the blend systems that utilize conjugated polymers. However, the efficiencies of the ASMs are slightly lacking behind the polymer: small molecule bulk-heterojunctions. To address this discrepancy, we compare an ASM blend ZR1:Y6 with a polymer:small molecule blend PM7:Y6, sharing the same non-fullerene acceptor (NFA). Our analyses reveal similar energetic offset between the exciton singlet state and charge transfer state (ΔES1-CT) in ZR1:Y6 and PM7:Y6. In comparison to the latter, surprisingly, the ZR1:Y6 has noticeably a stronger field-dependency of charge generation. Low charge carrier mobilities of ZR1:Y6 measured, using space charge limited current measurements, entail a viable explanation for suppressed charge dissociation. Less crystalline and more intermixed domains as observed in the ZR1:Y6 system compared to polymer:Y6 blends, makes it difficult for NFA to form a continuous pathway for electron transport, which reduces the charge carrier mobility.
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Introduction: Endometriosis (EMs) is characterized by ectopic growth of active endometrial tissue outside the uterus. The Luoshi Neiyi prescription (LSNYP) has been extensively used for treating EMs in China. However, data on the active chemical components of LSNYP are insufficient, and its pharmacological mechanism in EMs treatment remains unclear. This study aimed to explore the potential mechanism of LSNYP for EMs through network pharmacology based on the components absorbed into the blood. Methods: Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze blood components, and a series of network pharmacology strategies were utilized to predict targets of these components and EMs. Protein-protein interaction (PPI) network analysis, component-target-disease network construction, gene ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Additionally, molecular docking, molecular dynamics simulations, and in vitro and in vivo experiments were conducted to validate the HIF1A/EZH2/ANTXR2 pathway associated with hypoxic pathology in EMs. Results: Thirty-four absorbed components suitable for network pharmacology analysis were identified, and core targets, such as interleukin 6, EGFR, HIF1A, and EZH2, were founded. Enrichment results indicated that treatment of EMs with LSNYP may involve the regulation of hypoxia and inflammatory-related signaling pathways and response to oxidative stress and transcription factor activity. Experimental results demonstrated that LSNYP could decrease the expression of HIF1A, ANTXR2, YAP1, CD44, and ß-catenin, and increased EZH2 expression in ectopic endometrial stromal cells and endometriotic tissues. Molecular docking and molecular dynamics simulations manifested that there was stable combinatorial activity between core components and key targets of the HIF1A/EZH2/ANTXR2 pathway. Conclusion: LSNYP may exert pharmacological effects on EMs via the HIF1A/EZH2/ANTXR2 pathway; hence, it is a natural herb-related therapy for EMs.
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PURPOSE: Ovarian metastasis of gastric cancer (GC), commonly referred to as Krukenberg tumors, leads to a poor prognosis. However, the cause of metastasis remains unknown. Here, we present an integrated single-cell RNA sequencing (scRNA-Seq) analysis of the immunological microenvironment of two paired clinical specimens with ovarian metastasis of GC. METHODS: scRNA-Seq was performed to determine the immunological microenvironment in ovarian metastasis of gastric cancer. CellChat was employed to analyze cell-cell communications across different cell types. Functional enrichment analysis was done by enrichKEGG in clusterProfiler. GEPIA2 was used to assess the influence of certain genes and gene signatures on prognosis. RESULTS: The ovarian metastasis tissues exhibit a heterogenous immunological microenvironment compared to the primary tumors. Exhaustion of T and B cells is observed in the ovarian metastasis tissues. Compared to the paired adjacent non-tumoral and primary tumors, the ratio of endothelial cells and fibroblasts is high in the ovarian metastasis tissues. Compared to primary ovarian cancers, we identify a specific group of tumor-associated fibroblasts with MFAP4 and CAPNS1 expression in the ovarian metastatic tissues of GC. We further define metastasis-related-endothelial and metastasis-related-fibroblast signatures and indicate that patients with these high signature scores have a poor prognosis. In addition, the ovarian metastasis tissue has a lower level of intercellular communications compared to the primary tumor. CONCLUSION: Our findings reveal the immunological microenvironment of ovarian metastasis of gastric cancer and will promote the discovery of new therapeutic strategies for ovarian metastasis in gastric cancer.
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Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Análise de Célula Única , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Feminino , Microambiente Tumoral/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Transcriptoma/genética , PrognósticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMS) is a common gynecological disease that causes dysmenorrhea, chronic pelvic pain and infertility. Luoshi Neiyi Prescription (LSNYP), a traditional Chinese medicine (TCM) formula, is used to relieve EMS in the clinic. AIMS: This study aimed to examine the active components of LSNYP and the possible mechanism involved in its treatment of EMS. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to identify the chemical components of LSNYP. Human primary ectopic endometrial stromal cells (ecESCs) and eutopic endometrial stromal cells (euESCs) were isolated, and the expression levels of hypoxia inducible factor 1A (HIF1A), enhancer of zeste homolog 2 (EZH2) and steroidogenic factor 1 (SF-1) were detected by immunofluorescence and qPCR. Cobalt chloride (CoCl2) was utilized to construct an in vitro hypoxic environment, and lentiviruses were engineered to downregulate HIF1A and EZH2 and upregulate EZH2. Subsequently, the expression levels of HIF1A, EZH2, and SF-1 were measured using qPCR or western blotting. The binding of EZH2 to the SF-1 locus in ESCs was examined via ChIP. Furthermore, the effects of LSNYP on the HIF1A/EZH2/SF-1 pathway were evaluated both in vitro and in vivo. RESULTS: A total of 185 components were identified in LSNYP. The protein and gene expression levels of HIF1A and SF-1 were increased, whereas those of EZH2 were decreased in ecESCs. After treating euESCs with 50 µmol L-1 CoCl2 for 24 h, cell viability and estradiol (E2) production were enhanced. Hypoxia decreased EZH2 protein expression, while si-HIF1A increased it. SF-1 was increased when EZH2 was downregulated in normal and hypoxic environments, whereas the overexpression of EZH2 led to a decrease in SF-1 expression. ChIP revealed that hypoxia reduced EZH2 binding to the SF-1 locus in euESCs. In vitro, LSNYP-containing serum decreased E2 and prostaglandin E2 (PGE2) production, inhibited cell proliferation and invasion, and reduced the expression of HIF1A, SF-1, steroidogenic acute regulatory protein (StAR), and aromatase cytochrome P450 (P450arom). In vivo, LSNYP suppressed inflammation and adhesion and inhibited the HIF1A/EZH2/SF-1 pathway in endometriotic tissues. CONCLUSIONS: LSNYP may exert pharmacological effects on EMS by inhibiting E2 synthesis and inflammation through regulation of the HIF1A/EZH2/SF-1 pathway. These results suggest that LSNYP may be a promising candidate for the treatment of EMS.
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Medicamentos de Ervas Chinesas , Endometriose , Proteína Potenciadora do Homólogo 2 de Zeste , Estradiol , Subunidade alfa do Fator 1 Induzível por Hipóxia , Adulto , Animais , Feminino , Humanos , Camundongos , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Estradiol/biossíntese , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator Esteroidogênico 1/genética , Fator Esteroidogênico 1/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismoRESUMO
Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.
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Numerous penguins can propagate pathogens with antibiotic resistance genes (ARGs) into Antarctica. However, the effects of penguin dissemination on the lake ARGs still have received little attention via guano deposition. Here, we have profiled ARGs in ornithogenic sediments subject to penguin guano (OLS) and nonornithogenic sediments (NOLS) from 16 lakes across Antarctica. A total of 191 ARGs were detected in all sediment samples, with a much higher abundance and diversity in OLS than in NOLS. Surprisingly, highly diverse and abundant ARGs were found in the OLS with a detection frequency of >40% and an absolute abundance of (2.34 × 109)-(4.98 × 109) copies g-1, comparable to those in coastal estuarine sediments and pig farms. The strong correlations of identified resistance genes with penguin guano input amount, environmental factors, mobile genetic elements, and bacterial community, in conjunction with network and redundancy analyses, all indicated that penguins were responsible for the dissemination and high enrichment of ARGs in lake sediments via the guano deposition, which might greatly outweigh local human-activity effects. Our results revealed that ARGs could be carried into lakes across the Antarctica through penguin migration, food chains, and guano deposition, which were closely connected with the widespread pollution of ARGs at the global scale.
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Resistência Microbiana a Medicamentos , Lagos , Spheniscidae , Lagos/microbiologia , Animais , Spheniscidae/genética , Regiões Antárticas , Resistência Microbiana a Medicamentos/genética , Sedimentos Geológicos/microbiologia , Genes BacterianosRESUMO
OBJECTIVE: In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. METHODS: This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People's Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. RESULTS: 702 EEC patients with stage I and grade 1-2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). CONCLUSIONS: LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Invasividade Neoplásica , Estadiamento de Neoplasias , Humanos , Feminino , Estudos Retrospectivos , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Pessoa de Meia-Idade , Prognóstico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/terapia , Taxa de Sobrevida , Seguimentos , China/epidemiologia , Histerectomia/estatística & dados numéricos , Histerectomia/métodos , Gradação de Tumores , Idoso , Metástase Linfática , Vasos Linfáticos/patologia , Adulto , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , População do Leste AsiáticoRESUMO
As the fields of photonics and information technology develop, a lot of novel applications based on VO2 material, such as optoelectronic computing and information encryption, have been developed. While the performance of these devices was not only closely associated with the VO2 phase transition properties but also depended on their dimensional characteristics. In the current study, we conducted the dimension-controlled vanadium dioxide (VO2) film growth, resulting in the epitaxial 2-dimensional (2D) VO2 film and well-distributed 3-dimensional (3D) VO2 crystal film deposition, respectively. It was revealed that, unlike the 2D film, the pronounced localized surface plasmon resonance dominated the near-infrared spectrum across the phase transition for the 3D VO2 film due to the naturally formed meta-surface structure, which showed a transmittance valley in the infrared spectrum after metallization. Based on this distinct infrared spectrum feature in the 3D VO2 film, we proposed an optoelectronic logic gate controlled by the input voltage and the probing Vis/IR light. By detecting the transmittance states of the probing light with different wavelengths, we achieved multistate encoding functions and demonstrated the information encryption application. This new conception device also showed great potential for some other applications such as optoelectronic coupled computing, information encryption, and optical near-field sensing computing.
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The factors driving glioma progression remain poorly understood. Here, the epigenetic regulator TRIM24 is identified as a driver of glioma progression, where TRIM24 overexpression promotes HRasV12 anaplastic astrocytoma (AA) progression into epithelioid GBM (Ep-GBM)-like tumors. Co-transfection of TRIM24 with HRasV12 also induces Ep-GBM-like transformation of human neural stem cells (hNSCs) with tumor protein p53 gene (TP53) knockdown. Furthermore, TRIM24 is highly expressed in clinical Ep-GBM specimens. Using single-cell RNA-sequencing (scRNA-Seq), the authors show that TRIM24 overexpression impacts both intratumoral heterogeneity and the tumor microenvironment. Mechanically, HRasV12 activates phosphorylated adaptor for RNA export (PHAX) and upregulates U3 small nucleolar RNAs (U3 snoRNAs) to recruit Ku-dependent DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Overexpressed TRIM24 is also recruited by PHAX to U3 snoRNAs, thereby facilitating DNA-PKcs phosphorylation of TRIM24 at S767/768 residues. Phosphorylated TRIM24 induces epigenome and transcription factor network reprogramming and promotes Ep-GBM-like transformation. Targeting DNA-PKcs with the small molecule inhibitor NU7441 synergizes with temozolomide to reduce Ep-GBM tumorigenicity and prolong animal survival. These findings provide new insights into the epigenetic regulation of Ep-GBM-like transformation and suggest a potential therapeutic strategy for patients with Ep-GBM.
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Progressão da Doença , Glioma , Mutação , RNA Nucleolar Pequeno , Animais , Humanos , Camundongos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteínas de Transporte , Linhagem Celular Tumoral , Modelos Animais de Doenças , Proteína Quinase Ativada por DNA/genética , Proteína Quinase Ativada por DNA/metabolismo , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Mutação/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas ras/metabolismo , Proteínas ras/genética , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismoRESUMO
Lithium metal batteries (LMBs), with high energy densities, are strong contenders for the next generation of energy storage systems. Nevertheless, the unregulated growth of lithium dendrites and the unstable solid electrolyte interphase (SEI) significantly hamper their cycling efficiency and raise serious safety concerns, rendering LMBs unfeasible for real-world implementation. Covalent organic frameworks (COFs) and their derivatives have emerged as multifunctional materials with significant potential for addressing the inherent problems of the anode electrode of the lithium metal. This potential stems from their abundant metal-affine functional groups, internal channels, and widely tunable architecture. The original COFs, their derivatives, and COF-based composites can effectively guide the uniform deposition of lithium ions by enhancing conductivity, transport efficiency, and mechanical strength, thereby mitigating the issue of lithium dendrite growth. This review provides a comprehensive analysis of COF-based and derived materials employed for mitigating the challenges posed by lithium dendrites in LMB. Additionally, we present prospects and recommendations for the design and engineering of materials and architectures that can render LMBs feasible for practical applications.
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Bifunctional conjugates targeting PD-L1/PARP7 were designed, synthesized, and evaluated for the first time. Compounds B3 and C6 showed potent activity against PD-1/PD-L1 interaction (IC50 = 0.426 and 0.342 µM, respectively) and PARP7 (IC50 = 2.50 and 7.05 nM, respectively). They also displayed excellent binding affinity with hPD-L1, approximately 100-200-fold better than that of hPD-1. Both compounds restored T-cell function, leading to the increase of IFN-γ secretion. In the coculture assay, B3 and C6 enhanced the killing activity of MDA-MB-231 cells by Jurkat T cells in a concentration-dependent manner. Furthermore, B3 and C6 displayed significant in vivo antitumor efficacy in a melanoma B16-F10 tumor mouse model, more than 5.3-fold better than BMS-1 (a PD-L1 inhibitor) and RBN-2397 (a PARP7i clinical candidate) at the dose of 25 mg/kg, without observable side effects. These results provide valuable insight and understanding for developing bifunctional conjugates for potential anticancer therapy.
Assuntos
Antineoplásicos , Antígeno B7-H1 , Imunoterapia , Humanos , Animais , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Feminino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Melanoma Experimental/terapiaRESUMO
Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.