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NonSMC condensin I complex subunit D2 (NCAPD2) is a newly identified oncogene; however, the specific biological function and molecular mechanism of NCAPD2 in liver cancer progression remain unknown. In the present study, the aberrant expression of NCAPD2 in liver cancer was investigated using public tumor databases, including TNMplot, The Cancer Genome Atlas and the International Cancer Genome Consortium based on bioinformatics analyses, and it was validated using a clinical cohort. It was revealed that NCAPD2 was significantly upregulated in liver cancer tissues compared with in control liver tissues, and NCAPD2 served as an independent prognostic factor and predicted poor prognosis in liver cancer. In addition, the expression of NCAPD2 was positively correlated with the percentage of Ki67+ cells. Finally, singlecell sequencing data, geneset enrichment analyses and in vitro investigations, including cell proliferation assay, Transwell assay, wound healing assay, cell cycle experiments, cell apoptosis assay and western blotting, were carried out in human liver cancer cell lines to assess the biological mechanisms of NCAPD2 in patients with liver cancer. The results revealed that the upregulation of NCAPD2 enhanced tumor cell proliferation, invasion and cell cycle progression at the G2/Mphase transition, and inhibited apoptosis in liver cancer cells. Furthermore, NCAPD2 overexpression was closely associated with the phosphatidylinositol 3kinase (PI3K)Aktmammalian target of rapamycin (mTOR)/cMyc signaling pathway and epithelialmesenchymal transition (EMT) progression in HepG2 and Huh7 cells. In addition, upregulated NCAPD2 was shown to have adverse effects on overall survival and diseasespecific survival in liver cancer. In conclusion, the overexpression of NCAPD2 was shown to lead to cell cycle progression at the G2/Mphase transition, activation of the PI3KAktmTOR/cMyc signaling pathway and EMT progression in human liver cancer cells.
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Proliferación Celular , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Transducción de Señal/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Masculino , Femenino , Proliferación Celular/genética , Carcinogénesis/genética , Carcinogénesis/patología , Carcinogénesis/metabolismo , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Progresión de la Enfermedad , Línea Celular Tumoral , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Transición Epitelial-Mesenquimal/genética , Apoptosis/genética , Movimiento Celular/genética , PronósticoRESUMEN
Functional dyspepsia (FD) is a common digestive disease. Jianwei Xiaoshi (JWXS) tablet is composed of Radix Pseudostellariae (TZS), Pericarpium Citri Reticulatae (CP), Rhizoma Dioscoreae (SY), fired Hordei Fructus Germinatus (CMY) and Crataegi Fructus (SZ). It is a commonly used drug in the treatment of FD in China and has good therapeutic effects. However, there is very little research about the substance basis and action mechanism of JWXS tablet. In this research, ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and network pharmacology were used to explore the substance basis and action mechanism of the JWXS tablet. Finally, 19, 79, 22, 22 and 39 constituents were identified in the extracts of TZS, CP, SY, CMY and SZ, respectively. Based on these findings, a total of 104 ingredients were identified in JWXS tablet and 29 potentially absorbed ingredients were detected in rat plasma. The results of network pharmacology indicated that the inhibition of gastric acid secretion, the regulation of gastrointestinal motility, inflammation and immune response were the key approaches for treating FD with JWXS tablet. The material basis and potential action mechanism of JWXS tablet in treating FD were comprehensively clarified for the first time. This study will improve our understanding of JWXS tablet.
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Climate change has exacerbated the frequency and magnitude of extreme rainfall, which has led to the perpetuation of flooding as a hazard to humans and society. China has begun to consider introducing Flood drainage rights (FDR), a sustainable flood control measure, into non-engineering measures as a complement to engineering measures for flood control. FDR represent the right of regions to discharge regional floodwaters caused by extreme rainfall into the river, and are the primary means of controlling the amount of floodwaters from regions when regional flood capacity is exceeded. However, existing studies on quantitative FDR allocation still have limitations, and some previous methods have resulted in allocation schemes that are not entirely reasonable and fair because they do not comprehensively consider the influencing factors of FDR or the allocation method is unreasonable. This paper explores the impact of flooding on rural and agricultural areas. We incorporate the factors of agricultural economy and security and construct a system of the allocation indicators of FDR composed of five principles: Natural Environmental Endowment, General Economic and Social Development, Agricultural Economy and Security, Macro policy regulation, and Respect for Historical Background. Second, considering the influence of expert judgment and data of different time nodes on the allocation of FDR, we introduce the concepts of expert weight and time weight into the allocation model of FDR, and construct a new set of framework for the allocation of FDR, i.e., "[(expert weight + subjective weight)+(time weight + objective weight)]+decision making model ". To reduce the loss of information during the transformation of subjective judgments, we also introduced triangular fuzzy numbers for the transformation between expert judgments and numbers. Finally, we take the five provinces in the middle and lower reaches of the Yellow River as an example. Using the data from 2010 to 2021, we obtain the final allocation scheme (proportion) of FDR as Henan (33.26%) > Shaanxi (23.08%) > Inner Mongolia (21.31%) > Shanxi (14.44%) > Shandong (7.91%). On this basis, this paper utilizes sensitivity analysis and comparative validation to demonstrate the rationality and effectiveness of the method, and identifies several indicators that have a greater impact on the results of the allocation of FDR. FDR can form part of a set of integrated flood management system together with flood control projects, which greatly alleviates the drainage conflicts arising from flooding caused by extreme precipitation. Under extreme rainfall conditions, FDR improves drainage efficiency and minimizes the overall damage caused by flooding in the watershed. This study can contribute to the sustainable development of the watershed and provide a reference for the promotion and utilization of sustainable flood control measures.
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Toma de Decisiones , Inundaciones , Lluvia , Ríos , China , Cambio ClimáticoRESUMEN
An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1-6-linked ß-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.
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The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus's ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves.
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COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , China/epidemiología , Niño , Preescolar , Adulto , Adolescente , Persona de Mediana Edad , Adulto Joven , Genoma Viral/genética , Masculino , Femenino , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Epidemiología Molecular , Lactante , Anciano , Pandemias , FilogeniaRESUMEN
The positive contributions of carriers to aerobic granulation have been wildly appreciated. In this study, as a way resource utilization, the dredged sediment was thermally-treated to prepared as carriers to promote aerobic granular sludge (AGS) formation and stability. The system was started under low superficial gas velocity (SGV, 0.6 cm/s)for a lower energy consumption. Two sequencing batch reactors (SBR) labeled R1 (no added carriers) and R2 (carriers added), were used in the experiment. R2 had excellent performance of granulation time (shortened nearly 43%). The maximum mean particle size at the maturity stage of AGS in R2 (0.545 mm) was larger compared to R1 (0.296 mm). The sludge settling performance in R2 was better. The reactors exhibited high chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) removal rates. The total phosphorus (TP) removal rate in R2 was higher than R1 (almost 15% higher) on stage II (93-175d). R2 had a higher microbial abundance and dominant bacteria content. The relative abundance of dominant species was mainly affected by the carrier. However, the enrichment of dominant microorganisms and the evolution of subdominant species were more influenced by the increase of SGV. The results indicated that the addition of carriers induced the secretion of extracellular polymeric substances (EPS) by microorganisms and accelerated the rapid formation of initial microbial aggregates. This work provided a low-cost method and condition to enhance aerobic granulation, which may be helpful in optimizing wastewater treatment processes.
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Speech emotion recognition (SER) technology involves feature extraction and prediction models. However, recognition efficiency tends to decrease because of gender differences and the large number of extracted features. Consequently, this paper introduces a SER system based on gender. First, gender and emotion features are extracted from speech signals to develop gender recognition and emotion classification models. Second, according to gender differences, distinct emotion recognition models are established for male and female speakers. The gender of speakers is determined before executing the corresponding emotion model. Third, the accuracy of these emotion models is enhanced by utilizing an advanced differential evolution algorithm (ADE) to select optimal features. ADE incorporates new difference vectors, mutation operators, and position learning, which effectively balance global and local searches. A new position repairing method is proposed to address gender differences. Finally, experiments on four English datasets demonstrate that ADE is superior to comparison algorithms in recognition accuracy, recall, precision, F1-score, the number of used features and execution time. The findings highlight the significance of gender in refining emotion models, while mel-frequency cepstral coefficients are important factors in gender differences.
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Algoritmos , Emociones , Humanos , Emociones/fisiología , Femenino , Masculino , Habla , Factores Sexuales , Lenguaje , Software de Reconocimiento del HablaAsunto(s)
Nitratos , Percloratos , Tiocianatos , Humanos , Niño , Estudios Transversales , Femenino , Masculino , Nitratos/análisis , Estados Unidos , Adolescente , Hormonas Esteroides Gonadales/sangre , Contaminantes AmbientalesRESUMEN
Metabolic dysfunction-associated steatohepatitis (MASH) is regulated by complex interplay between the macrophages and surrounding cells in the liver. Here, we show that Atf3 regulates glucose-fatty acid cycle in macrophages attenuates hepatocyte steatosis, and fibrogenesis in hepatic stellate cells (HSCs). Overexpression of Atf3 in macrophages protects against the development of MASH in Western diet-fed mice, whereas Atf3 ablation has the opposite effect. Mechanistically, Atf3 improves the reduction of fatty acid oxidation induced by glucose via forkhead box O1 (FoxO1) and Cd36. Atf3 inhibits FoxO1 activity via blocking Hdac1-mediated FoxO1 deacetylation at K242, K245, and K262 and increases Zdhhc4/5-mediated CD36 palmitoylation at C3, C7, C464, and C466; furthermore, macrophage Atf3 decreases hepatocytes lipogenesis and HSCs activation via retinol binding protein 4 (Rbp4). Anti-Rbp4 can prevent MASH progression that is induced by Atf3 deficiency in macrophages. This study identifies Atf3 as a regulator of glucose-fatty acid cycle. Targeting macrophage Atf3 or Rbp4 may be a plausible therapeutic strategy for MASH.
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Factor de Transcripción Activador 3 , Macrófagos , Animales , Factor de Transcripción Activador 3/metabolismo , Factor de Transcripción Activador 3/genética , Ratones , Macrófagos/metabolismo , Hígado Graso/metabolismo , Hígado Graso/patología , Hígado Graso/etiología , Células Estrelladas Hepáticas/metabolismo , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Hígado/metabolismo , Hígado/patología , Hepatocitos/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genética , Lipogénesis , Humanos , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Reprogramación Celular , Ratones Endogámicos C57BL , Reprogramación MetabólicaRESUMEN
This was a single-arm, multicenter, open-label phase I trial. Lentiviral vectors (LV) carrying the ABCD1 gene (LV-ABCD1) was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy (CCALD), and multi-site injection was performed. The injection dose increased from 200 to 1600 µL (vector titer: 1×109 transduction units per mL (TU/mL)), and the average dose per kilogram body weight ranges from 8 to 63.6 µL/kg. The primary endpoint was safety, dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein. A total of 7 patients participated in this phase I study and were followed for 1 year. No injection-related serious adverse event or death occurred. Common adverse events associated with the injection were irritability (71%, 5/7) and fever (37.2-38.5 â, 57%, 4/7). Adverse events were mild and self-limited, or resolved within 3 d of symptomatic treatment. The maximal tolerable dose is 1600 µL. In 5 cases (83.3%, 5/6), no lentivirus associated antibodies were detected. The overall survival at 1-year was 100%. The ABCD1 protein expression was detected in neutrophils, monocytes and lymphocytes. This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo; even the maximal dose did not increase the risk of adverse events. Furthermore, the direct LV-ABCD1 injection displayed low immunogenicity. In addition, the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, registration number: ChiCTR1900026649).
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Miembro 1 de la Subfamilia D de Transportador de Casetes de Unión al ATP , Adrenoleucodistrofia , Terapia Genética , Vectores Genéticos , Lentivirus , Humanos , Adrenoleucodistrofia/terapia , Adrenoleucodistrofia/genética , Lentivirus/genética , Masculino , Miembro 1 de la Subfamilia D de Transportador de Casetes de Unión al ATP/genética , Niño , Vectores Genéticos/administración & dosificación , Femenino , Terapia Genética/métodos , Adolescente , Preescolar , Encéfalo/metabolismo , Encéfalo/patología , Resultado del TratamientoRESUMEN
Speech emotion recognition based on gender holds great importance for achieving more accurate, personalized, and empathetic interactions in technology, healthcare, psychology, and social sciences. In this paper, we present a novel gender-emotion model. First, gender and emotion features were extracted from voice signals to lay the foundation for our recognition model. Second, a genetic algorithm (GA) processed high-dimensional features, and the Fisher score was used for evaluation. Third, features were ranked by their importance, and the GA was improved through novel crossover and mutation methods based on feature importance, to improve the recognition accuracy. Finally, the proposed algorithm was compared with state-of-the-art algorithms on four common English datasets using support vector machines (SVM), and it demonstrated superior performance in accuracy, precision, recall, F1-score, the number of selected features, and running time. The proposed algorithm faced challenges in distinguishing between neutral, sad, and fearful emotions, due to subtle vocal differences, overlapping pitch and tone variability, and similar prosodic features. Notably, the primary features for gender-based differentiation mainly involved mel frequency cepstral coefficients (MFCC) and log MFCC.
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Small interference RNA (siRNA) is a class of short double-stranded RNA molecules that cause mRNA degradation through an RNA interference mechanism and is a promising therapeutic modality. RBD1016 is a siRNA drug in clinical development for the treatment of chronic Hepatitis B Virus (HBV) infection, which contains a conjugated with N-acetylglucosamine moiety that can facilitate its hepatic delivery. We aimed to construct a semi-mechanistic model of RBD1016 in pre-clinical animals, to elucidate the pharmacokinetic/pharmacodynamic (PK/PD) profiles in mice and PK profiles in monkeys, which can lay the foundation for potential future translation of RBD1016 PK and PD from the pre-clinical stage to the clinic stage. The proposed semi-mechanistic PK/PD model fitted PK and PD data in HBV transgenic mice well and described plasma and liver concentrations in the monkeys well. The simulation results showed that our model has a reasonable predictive ability for Hepatitis B surface antigen (HBsAg) levels after multiple dosing in mice. Further PK and PD data for RBD1016, including clinical data, will assist in refining the model presented here. Our current effort focused on model building for RBD1016, we anticipate that the model could apply to other GalNAc-siRNA drugs.
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OBJECTIVES: We sought to investigate the clinicopathologic features and differential diagnosis of plexiform fibrohistiocytic tumor (PFHT) and its pathogenesis. METHODS: Ten cases of PFHT were collected from Xi Jing Hospital, Fourth Military Medical University, from September 2008 to December 2022 for clinical data as well as microscopic and immunohistochemical observation. CCND1 gene amplification and break were assayed by fluorescence in situ hybridization (FISH). RESULTS: We report 10 cases of PFHT according to histologic classification. Seven cases were of histiocytoid type, and 3 had mucous degeneration in the nodules. One case was of fibroblastic type, which was mainly composed of fibroblast-like cells. Two cases were of mixed type. Immunohistochemically, the osteoclast-like multinucleated giant cells, histiocyte-like cells, and occasional spindle cells in the adjacent fascicles were reactive for CD68 (10/10), CD163 (5/8), CD10 (8/8), cyclin D1 (8/8), CDK4 (5/8), ß-catenin (4/6), MITF (2/6), and PGP9.5 (4/5). Vimentin (9/9) was strongly positive in tumor cells and peripheral fibroblast-like cells. The positive index of Ki-67 was 5% to 40%, with an average of 20%. The FISH analysis showed neither amplification nor break of the CCND1 gene. All cases underwent surgical resection, and patients were followed up for 9 months to 11 years. Only 2 cases recurred. CONCLUSIONS: Plexiform fibrohistiocytic tumor is a low-grade malignant soft tissue neoplasm. The diagnosis mainly depends on histopathologic and immunohistochemical markers. Cyclin D1 and CD10 expression has diagnostic value for the diagnosis and differential diagnosis of PFHT combined with its plexiform morphology. The overexpression of cyclin D1 suggests an involvement of cell cycle regulatory genes in the pathogenesis of PFHT.
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BACKGROUND: Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. METHODS: Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. RESULTS: From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1-77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6-14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3-83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3-4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5-1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. CONCLUSIONS: Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03781219.
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The cathode material Na4Fe3(PO4)2P2O7 (NFPP) has shown great potential for sodium-ion batteries (SIBs) due to its cost-effectiveness, prolonged cycle life, and high theoretical capacity. However, the practical large-scale production of NFPP is hindered by its poor intrinsic electron conductivity and the presence of a NaFePO4 impurity. In this study, we propose a mutually reinforcing approach involving Ti doping, mechanical nano treatment, and in situ carbon coating to produce Ti-NFPP via the solid-state methods of synthesis. Ti doping strengthens the covalent Fe-O interaction, hence accelerating the electron transfer and the redox reactions Fe2+/Fe3+. In situ carbon coating improves electrical conductivity and allows for accommodating the volumetric variation. Nanosized treatment promotes the uniform progression of solid-state reactions. The synthesized Na4Fe2.98Ti0.01(PO4)2P2O7 material (Ti-NFPP) exhibits promising electrochemical properties with an initial discharge specific capacity of 112.5 mA h g-1 at 0.1 C. A volumetric change of only 2.98% was observed during the de/sodiation process, indicating an enhanced reversibility of the crystal lattice. Moreover, it demonstrates exceptional cycling stability with a capacity retention rate of 97.2 mA h g-1 at 10 C over 5000 cycles. These findings offer a promising pathway for the large-scale production of Ti-NFPP in SIBs.
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Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.
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Nonaqueous Li - O2 battery (LOB) is considered one of the most promising energy storage system due to its ultrahigh theoretical specific capacity (3500 Wh kg-1). Introducing vacancies in CoMn2O4 catalysts is regarded as an effective strategy to enhance the electrochemical performances of LOB. However, the relation between vacancy types in CoMn2O4 and catalytic performances in the LOB remains ambiguous. Herein, ordered porous CoMn2O4 with oxygen and metal vacancies is obtained via solvothermal reaction followed by temperature-controlled calcination using polystyrene spheres as templates. The increase in treatment temperature reduces the content of oxygen vacancies while increasing that of the metal vacancies. Notably, experimental results and theoretical calculations show that oxygen vacancies in CoMn2O4 have a greater influence than metal vacancies in modulating the LiO2 adsorption during the reaction processes and reducing the overpotential. CoMn2O4 synthesized at 500 â (CoMnO-500) with higher oxygen vacancies exhibits stronger adsorption onto the LiO2, facilitating the formation of film-like Li2O2. Therefore, an LOB with the CoMnO-500 catalyst presents the lowest overpotential of 1.2 V and longest cycle lifespan of 286 cycles at a current density of 200 mA g-1. This study offers insights into the effect of CoMn2O4 vacancies on the formation pathway of Li2O2 discharge products.
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PTP1B, a promising target for insulin sensitizers in type 2 diabetes treatment, can be effectively degraded using proteolysis-targeting chimera (PROTAC). This approach offers potential for long-acting antidiabetic agents. We report potent bifunctional PROTACs targeting PTP1B through the E3 ubiquitin ligase cereblon. Western blot analysis showed significant PTP1B degradation by PROTACs at concentrations from 5 nM to 5 µM after 48 h. Evaluation of five highly potent PROTACs revealed compound 75 with a longer PEG linker (23 atoms), displaying remarkable degradation activity after 48 and 72 h, with DC50 values of 250 nM and 50 nM, respectively. Compound 75 induced selective degradation of PTP1B, requiring engagement with both the target protein and CRBN E3 ligase, in a ubiquitination and proteasome-dependent manner. It significantly reduced blood glucose AUC0-2h to 29% in an oral glucose tolerance test and activated the IRS-1/PI3K/Akt signaling pathway in HepG2 cells, showing promise for long-term antidiabetic therapy.
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Hipoglucemiantes , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteolisis , Animales , Humanos , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Descubrimiento de Drogas , Células Hep G2 , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/síntesis química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteolisis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
In this paper, a novel CeO2/Co3[Co(CN)6]2 (CeO2/PBACo-Co) composite was prepared with co-precipitation and utilized to activate peroxymonosulfate (PMS) to eliminate tetracycline hydrochloride (TCH). Catalyst screening showed that the composite with a CeO2:PBACo-Co mass ratio of 1:5 (namely, 0.2-CeO2/PBACo-Co) had the best performance. The degradation efficiency of TCH in 0.2-CeO2/PBACo-Co/Oxone system was investigated. The experimental results illustrated that 98% of 50 mg/L TCH and 48.5% of TOC were degraded by 50 mg/L 0.2-CeO2/PBACo-Co and 400 mg/L Oxone within 120 min at 25 °C and initial pH 5.3. Recycling studies showed that the elimination rate of TCH can still achieve 85.8% after five cycles, suggesting that 0.2-CeO2/PBACo-Co composite processes good reusability. Trapping experiments and EPR tests revealed that the reaction system produced multiple active species (1O2, O2â¢-, SO4â¢-, and â¢OH). We proposed the catalytic mechanism of 0.2-CeO2/PBACo-Co for PMS activation, which mainly involves the promoted Co3+/Co2+ cycle by Ce3+ donated electrons. These results indicate that CeO2/PBACo-Co composite is an effective catalyst for wastewater remediation.
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Cerio , Tetraciclina , Contaminantes Químicos del Agua , Cerio/química , Catálisis , Tetraciclina/química , Contaminantes Químicos del Agua/química , Cobalto/química , Peróxidos/química , Purificación del Agua/métodosRESUMEN
What is already known about this topic?: The inclusion of meningococcal vaccines in the National Immunization Program (NIP) over several years has significantly reduced the incidence of meningococcal meningitis in China to historic lows. Worldwide, there has been a diversification of meningococcal serogroups, leading to a shift in dominant serogroups in China from serogroup A to serogroups C and B, accompanied by a rise in reports of serogroups Y and W. What is added by this report?: An outbreak of serogroup Y Neisseria meningitidis (Nm) in a secondary vocational school involved a single confirmed severe case and 24 individuals with laboratory-confirmed Nm carriage. Epidemiological investigation revealed that the outbreak was localized to the classroom of the confirmed case. Prolonged close contact within a confined space was identified as a significant risk factor for Nm transmission. The genotype sequence identified was type 1655 (ST-1655), which is categorized under clonal complex 23 (CC-23) and bears resemblance to 8 previously confirmed cases of serogroup Y meningococcal meningitis within Guangdong Province. This suggests that serogroup Y infections continue to sporadically emerge and have become prevalent strains. What are the implications for public health practice?: This outbreak underscores the critical need to enhance surveillance of meningococcal serogroups and population carrier, and advocate for vaccination with MenY-containing vaccines.