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V-Ce/Ti catalysts were prepared for the removal of naphthalene and NOx in the flue gas. The adverse effects of NH3 and NO on the naphthalene degradation were weakened on V-Ce/Ti, resulting in a decrease of only 2.5 % in COx selectivity. The formation of high molecular weight byproducts was also reduced. Besides the acid sites on the catalysts, Ce introduced new Brønsted basic sites, which could also adsorb and degrade naphthalene into naphthol effectively. With the separated active sites for naphthalene degradation and NO removal, the reaction between NH3 and the intermediates during the naphthalene degradation was also inhibited, decreasing the formation and accumulation of phthalimide. The oxidation of the intermediates was promoted by active V5+ introduced by Ce, inhibiting the transformation of the intermediates to higher molecular weight byproducts. Nearly 100 % conversion of naphthalene and NO, as well as 40.1 % of the COx selectivity were obtained on V-Ce/Ti.
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A series of V-xCe/Ti catalysts was prepared by a step impregnation method with gradual increased Ce amount. Compared to the commercial V-W/Ti catalysts, the V-xCe/Ti catalysts exhibited considerably higher COx selectivity during the oxidation of naphthalene (Nap), and less intermediates or by-products were detected both in gas phase and on the surface of the catalysts. Through a series of characterizations, it was found that abundance of weak basic sites in the form of OH was introduced by Ce, as well as the oxygen vacancies caused by the redox cycle of V4++Ce4+âV5++Ce3+. The weak basic sites introduced by Ce could greatly enhance the Nap adsorption, and the Nap adsorbed was quickly converted to naphthol on Ce-OH. Furthermore, V existed at a high valence with the interaction of V and Ce, and the oxygen vacancies also increased the Oads and OOH. It improved the redox ability and the regeneration of Ce-OH on V-xCe/Ti catalysts. The intermediates could be further oxidized, and the Ce-OH consumed in the reaction could recover quickly. Therefore, almost 100% Nap conversion and a high COx selectivity was observed in the V-xCe/Ti catalysts system.
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Naftalenos , Oxidación-Reducción , Naftalenos/química , Catálisis , AdsorciónRESUMEN
Background: Exposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators. Methods: Data from the National Health and Nutrition Examination Survey 2017-2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin. Results: The current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction. Conclusion: The association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures.
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Cálculos Biliares , Insulina , Encuestas Nutricionales , Ácidos Ftálicos , Humanos , Femenino , Masculino , Adulto , Insulina/metabolismo , Persona de Mediana Edad , Cálculos Biliares/inducido químicamente , Estados Unidos/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Teorema de BayesRESUMEN
COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of COPD includes sustained airway inflammation and the eventual destruction of lung tissue structure. While multiple risk factors are implicated in the disease's progression, the underlying mechanisms remain largely elusive. The perpetuation of inflammation is pivotal to the advancement of COPD, emphasising the importance of investigating these self-sustaining mechanisms for a deeper understanding of the pathogenesis. Autoimmune responses constitute a critical mechanism in maintaining inflammation, with burgeoning evidence pointing to their central role in COPD progression; yet, the intricacies of these mechanisms remain inadequately defined. This review elaborates on the evidence supporting the presence of autoimmune processes in COPD and examines the potential mechanisms through which autoimmune responses may drive the chronic inflammation characteristic of the disease. Moreover, we attempt to interpret the clinical manifestations of COPD through autoimmunity.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Autoinmunidad , Pulmón/patología , Factores de Riesgo , InflamaciónRESUMEN
Purpose: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. Methods: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models. Results: Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus. Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia. Conclusion: Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage.
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Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.
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Carpas , Evolución Molecular , Animales , Poliploidía , Genoma/genética , Epigénesis Genética , Genoma de PlantaRESUMEN
Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial-mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients' poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.
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Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Neoplasias Pancreáticas/genética , Proliferación Celular/genética , Glucólisis/genética , Regulación Neoplásica de la Expresión Génica , Transición Epitelial-Mesenquimal/genética , Movimiento Celular/genética , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Neoplasias PancreáticasRESUMEN
BACKGROUND: Neutrophils consume a large amount of energy when performing their functions. Compared with other white blood cells, neutrophils contain few mitochondria and mainly rely on glycolysis and gluconeogenesis to produce ATP. The inflammatory site is hypoxic and nutrient poor. Our aim is to study the role of abnormal adenosine metabolism of neutrophils in the asthmatic airway inflammation microenvironment. METHOD: In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene-knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5'-(α, ß-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect. RESULT: PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic knockdownof CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C-C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis. CONCLUSION: Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.
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Asma , Neutrófilos , Animales , Ratones , Neutrófilos/metabolismo , Aspergillus fumigatus/metabolismo , Adenosina/metabolismo , Asma/terapia , Citocinas/metabolismo , Inflamación , Quimiocinas/metabolismo , Líquido del Lavado Bronquioalveolar , Extractos Vegetales , Remodelación de las Vías Aéreas (Respiratorias)RESUMEN
Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro-inflammatory cytokines secretion, while overwhelmed pyroptosis contributes to organ dysfunction and pathological inflammatory response. Caffeic acid (CA) and ferulic acid (FA) are both well-known antioxidant and anti-inflammatory phenolic acids, which resemble in chemical structure. Here we found that CA, but not FA, protects macrophages from both Nigericin-induced canonical and cytosolic lipopolysaccharide (LPS)-induced non-canonical pyroptosis and alleviates LPS-induced mice sepsis. It significantly improved the survival of pyroptotic cells and LPS-challenged mice and blocked proinflammatory cytokine secretion. The anti-pyroptotic effect of CA is independent of its regulations in cellular lipid peroxidation, mitochondrial function, or pyroptosis-associated gene transcription. Instead, CA arrests pyroptosis by directly associating with gasdermin D (GSDMD) and blocking its processing, resulting in reduced N-GSDMD pore construction and less cellular content release. In LPS-induced septic mice, CA inhibits GSDMD activation in peritoneal macrophages and reduces the serum levels of interleukin-1ß and tumor necrosis factor-α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis-associated disease.
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RING finger protein-7 (RNF7) functions as a positive regulator in the progression of multiple malignancies. However, the underlying mechanism by which RNF7 contributes to pancreatic cancer (PC) is lacking. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the level of RNF7expression in PC cell lines and tissues. The role of RNF7 in PC tumorigenesis was analyzed by Cell Counting Kit-8 (CCK-8). 5-Ethynyl-20-deoxyuridine (EdU), wound-healing/Transwell assays, as well as a subcutaneous tumorigenesis model were constructed to assess the role of RNF7 in PC cells. The association between RNF7 and PI3K/Akt signaling were assessed by western blot and further confirmed by rescue experiments. The PC patients with upregulated expression of RNF7 had poor survival. Overexpression of RNF7 significantly facilitated PC proliferative and migrative and invasive properties in vitro and vivo; however, knockdown of RNF7exhibited the opposite results. Mechanistically, RNF7 promoted PANC-1 and SW1990 cell growth through impacting the activation of the PI3K/Akt signaling pathway. Our data demonstrated that RNF7 promoted PC tumorigenesis via activating the PI3K/Akt signaling pathway and might be regarded as one of the potential therapies to PC.
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Neoplasias Pancreáticas , Proteínas Proto-Oncogénicas c-akt , Ubiquitina-Proteína Ligasas , Humanos , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias PancreáticasRESUMEN
It has been always attractive to design a sustainable bio-derived adsorbent based on industrial waste lignin for removing organic dyes from water. However, existing adsorbent strategies often lead to the difficulties in adsorbent separation and recycling. Herein, we report a novel magnetically recyclable bio-adsorbent of Mg(OH)2/Fe3O4/PEI functionalized enzymatic lignin (EL) composite (EL-PEI@Fe3O4-Mg) for removing Congo red (CR) by Mannish reaction and hydrolysis-precipitation. The Mg(OH)2 and PEI functionalized EL on the surface act as active sites for the removal of CR, while the Fe3O4 allows for the easy separation under the help of a magnet. As-obtained EL-PEI@Fe3O4-Mg forms flower-like spheres and has a relatively lager surface area of 24.8 m2 g-1 which is 6 times that of EL. The EL-PEI@Fe3O4-Mg exhibits a relatively high CR adsorption capacity of 74.7 mg g-1 which is 15 times that of EL when initial concentration is around 100 mg L-1. And it can be easily separated from water by applying an external magnetic field. Moreover, EL-PEI@Fe3O4-Mg shows an excellent anti-interference capability according to the results of pH values and salt ions influences. Importantly, EL-PEI@Fe3O4-Mg possesses a good reusability and a removal efficiency of 92 % for CR remains after five consecutive cycles. It is illustrated that electrostatic attraction, π-π interaction and hydrogen binding are primary mechanisms for the removal of CR onto EL-PEI@Fe3O4-Mg. This work provides a novel sustainable strategy for the development of highly efficient, easy separable, recyclability bio-derived adsorbents for removing organic dyes, boosting the efficient utilization of industrial waste lignin.
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Rojo Congo , Contaminantes Químicos del Agua , Rojo Congo/química , Lignina , Residuos Industriales , Contaminantes Químicos del Agua/química , Agua/química , Colorantes , Adsorción , Concentración de Iones de Hidrógeno , CinéticaRESUMEN
Background: Senescence is thought to be an imperative effect on the development of cancer. However, few studies pay an attention to the senescence-associated genes in pancreatic cancer (PC). The prognostic value of senescence-related genes (SRGs) and their involvement in tumor microenvironment (TME) in the PC remain obscure. The aim of this research was to investigate the prognostic role of senescence-associated genes and their affection in TME in PC. Methods: The transcriptome and clinical information of PC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Two SRG-mediated molecular clusters were comprehensively identified. In total, data from the 285 PC patients were randomly used to develop a senescence-associated gene signature in the training set and verified in the validation set. Immune microenvironment analysis pertained to senescence-related genes was performed. Results: A SRG_score including five senescence-associated genes was established to separate PC patients into two risk groups. High-risk patients had worse overall survival than low-risk patients. The result of the multivariate Cox regression analysis identified the risk score and stage as independent prognostic factors for PC patients. Receiver operating characteristic curve (ROC) analysis confirmed the credible predictive ability of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.746 at 1 year, 0.781 at 3 years, and 0.868 at 5 years in the training set and 0.653 at 1 year, 0.755 at 3 years, and 0.785 at 5 years in the validation set. Moreover, the SRG_score was associated with TME, tumor mutation burden (TMB), and chemotherapeutic drug sensitivity. Conclusions: This study found that the novel SRG_score could be an independent prognostic target for PC patients. Senescence-associated genes had a vital impact on the immune microenvironment and the treatment of PC patients.
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Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Pronóstico , Neoplasias Pancreáticas/genética , Nomogramas , Neoplasias PancreáticasRESUMEN
The discovery of the robust antidepressant actions of ketamine is regarded as one of the greatest advancements in depression treatment in the past 60 years. Recent findings have provided strong evidence for the presence of bidirectional communication networks between the gastrointestinal tract and the brain in depression. Moreover, increasing evidence supports the antidepressant role of ketamine in regulating the gut microbiome and microbiota-derived molecules; however, the mechanisms underpinning such effects are still ambiguous. This review summarizes the current understanding of the anti-depressant mechanisms of ketamine and its metabolites regarding the bidirectional regulation by microbiota-gut-brain axis. We review the relationship between gut microbiota and the antidepressant mechanisms of ketamine, and discuss the role of stress response, brain-derived neurotrophic factor (BDNF)-mediated neurogenesis, anti-inflammatory effect and neurotransmitters.
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Microbioma Gastrointestinal , Ketamina , Antiinflamatorios/farmacología , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Ketamina/farmacología , Ketamina/uso terapéuticoRESUMEN
Major histocompatibility complex class II (MHC II) is an essential immune regulatory molecule that plays an important role in antigen presentation and T-cell development. Abnormal MHC II expression can lead to immunodeficiency, clinically termed as type II bare lymphocyte syndrome (BLS), which usually results from mutations in the MHC II transactivator (CIITA) and other coactivators. Here, we present a new paradigm for MHC II deficiency in mice that involves a spontaneous point mutation on H2-Aa. A significantly reduced population of CD4+ T cells was observed in mice obtained from the long-term homozygous breeding of autophagy-related gene microtubule-associated protein 1 light chain 3 ß (Map1lc3b, Lc3b) knockout mice; this phenotype was not attributed to the original knocked-out gene. MHC II expression was generally reduced, together with a marked deficiency of H2-Aa in the immune cells of these mice. Using cDNA and DNA sequencing, a spontaneous H2-Aa point mutation that led to false pre-mRNA splicing, deletion of eight bases in the mRNA, and protein frameshift was identified in these mice. These findings led to the discovery of a new type of spontaneous MHC II deficiency and provided a new paradigm to explain type II BLS in mice.
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Antígenos de Histocompatibilidad Clase II , Mutación Puntual , Animales , Linfocitos T CD4-Positivos , Ratones , Ratones Noqueados , Inmunodeficiencia Combinada Grave , Linfocitos TRESUMEN
BACKGROUND: For evaluating pericapsular nerve group (PENG) block's analgesic effect on elderly patients suffering from femoral neck fracture undergoing hip arthroplasty to provide a basis for optimizing perioperative analgesia in hip arthroplasty. METHODS: Forty-eight patients undergoing hip arthroplasty with spinal anesthesia for femoral neck fracture in our hospital were chosen in this study. Based on the random number table method, patients were categorized into the following two groups (n = 24 per group): the hip peripheral nerve group block group (PE group) and the iliac fascia block group (FI group). The fascia iliaca compartment block was used in the FI group, whereas the pericapsular nerve group block in the PE group. When placed in the position for spinal anesthesia (T4), we measured dynamic and static visual analog scale (VAS) scores as well as analgesic satisfaction before blockade (T0), along with at 10 min (T1), 20 min (T2), and 30 min postblockade (T3). Sufentanil dosage and effective analgesic pump press number at 6 h (T5), 12 h (T6), 24 h (T7), and 48 h (T8) postoperatively were recorded. In the meantime, the development of related complications was also recorded. RESULTS: Compared with T0, patients in both groups achieved lower static VAS scores at T1-T4 (P < 0.05) and lower dynamic VAS scores at T2-T4 of the FI group (P < 0.05). Relative to the FI group, both static and dynamic VAS scores at T1-T4 were obviously lower in the PE group (P < 0.05), along with increased dynamic analgesic satisfaction (P < 0.05). Weakness of the quadriceps was observed in seven patients in the FI groups (P < 0.05). No delirium, hematoma, puncture site infection, or nerve injury occurred in either group. CONCLUSION: The pericapsular nerve group block can provide safe and effective analgesia for elderly patients during the perioperative period of hip arthroplasty, with rapid onset, good analgesic effect, high patient satisfaction, and low complication rate, and is worthy of widespread application. The trial is registered with ChiCTR2100046785.
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Artroplastia de Reemplazo de Cadera , Fracturas del Cuello Femoral , Anciano , Analgésicos/uso terapéutico , Fracturas del Cuello Femoral/complicaciones , Fracturas del Cuello Femoral/cirugía , Nervio Femoral , Humanos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & controlRESUMEN
BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.
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COVID-19 , SARS-CoV-2 , Adulto , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , China , Humanos , Inmunogenicidad Vacunal , Inmunoglobulina G , Pandemias/prevención & control , Glicoproteína de la Espiga del Coronavirus , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
This research is aimed at evaluating the effects of leucine supplementation on muscle fibers growth and development of blunt snout bream through a feeding trial and a primary muscle cells treatment. An 8-week trial with diets containing 1.61% leucine (LL) or 2.15% leucine (HL) was conducted in blunt snout bream (mean initial weight = 56.56 ± 0.83 g). Results demonstrated that the specific gain rate and the condition factor of fish in the HL group were the highest. The essential amino acids content of fish fed HL diets was significantly higher than that fed LL diets. The texture (hardness, springiness, resilience, and chewiness), the small-sized fiber ratio, fibers density, and sarcomere lengths in fish all obtained the highest in the HL group. Additionally, the proteins expression related with the activation of the AMPK pathway (p-Ampk, Ampk, p-Ampk/Ampk, and Sirt1) and the expression of genes (myogenin (myog), myogenic regulatory factor 4 (mrf4) and myoblast determination protein (myod), and protein (Pax7) related to muscle fiber formation were significantly upregulated with increasing level of dietary leucine. In vitro, the muscle cells were treated with 0, 40 and 160 mg/L leucine for 24 h. The results showed that treated with 40 mg/L leucine significantly raised the protein expressions of BCKDHA, Ampk, p-Ampk, p-Ampk/Ampk, Sirt1, and Pax7 and the gene expressions of myog, mrf4, and myogenic factor 5 (myf5) in muscle cells. In summary, leucine supplementation promoted muscle fibers growth and development, which may be related to the activation of BCKDH and AMPK.
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Abstract@#With the increasing attention paid to preschool physical activity in recent years, physical activity load assessment of preschool children has evolved with the development of theory and the wide application of microelectronic technology. In this paper, relevant literature from PubMed, Web of Science, and CNKI database were collected and analyzed, aiming to provide review and updates on physical activity load assessment in preschoolers. Given the characteristics of children s physical activities, effective measurement methods should be chosen and integrated from these tools, to improve the accuracy and effectiveness of children s physical activity load assessment.
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As a member of the dibenzyl isoquinoline alkaloid family, cepharathine is an alkaloid from the traditional Chinese medicine cepharathine, which is mainly used for treatment of leukopenia and other diseases. Recent studies of the inhibitory effect of cepharathine against SARS-CoV-2 have attracted widespread attention and aroused heated discussion. As the original discoverer of the anti-SARS-CoV-2 activity of cepharanthine, here we briefly summarize the discovery of cepharanthine and review important progress in relevant studies concerning the discovery and validation of anti-SARS-CoV-2 activity of cepharathine, its antiviral mechanisms and clinical trials of its applications in COVID-19 therapy.
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Humanos , Antivirales/uso terapéutico , Bencilisoquinolinas/uso terapéutico , COVID-19 , SARS-CoV-2RESUMEN
BACKGROUND: ArfGAP with GTPase domain, Ankyrin repeat and PH domain 2 Antisense 1 (AGAP2-AS1) is a promising long noncoding RNA that may possess prognostic value for different types of tumors. The objective of this meta-analysis is to evaluate the prognostic value of long noncoding RNA AGAP2-AS1 in cancer patients. METHODS: A systematic literature search of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, CNKI, Weipu, and Wanfang electronic databases were carried out in this meta-analysis. Synthetic hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were obtained to determine the prognostic and clinicopathological significance of AGAP2-AS1 expression in tumors. RESULTS: The final meta-analysis included 10 studies that contained 948 patients. The pooled results provided evidence that AGAP2-AS1 overexpression predicted reduced overall survival (OS) (HRâ=â1.77, 95% CI: 1.49-2.09, Pâ<â.00001), disease-free survival (HRâ=â1.84, 95% CI: 1.40-2.41, Pâ<â.0001), and progression-free survival (HRâ=â1.84, 95% CI: 1.01-3.33, Pâ=â.04) and for various cancers. Additionally, the AGAP2-AS1 overexpression was concerned with lymph node metastasis (positive vs negative, ORâ=â2.95, 95% CI: 1.96-4.45, Pâ<â.00001), advanced tumor node metastasis stage (III/IV vs I/II, ORâ=â3.73, 95% CI: 2.71-5.13, Pâ<â.00001), and tumor size (larger vs smaller, ORâ=â2.28, 95% CI: 1.24-4.18, Pâ=â.008). Besides, data from gene expression profiling interactive analysis dataset verified the results in our meta-analysis. The results showed that the expression level of AGAP2-AS1 was higher in most tumor tissues than in the corresponding normal tissues and was linked to poor OS and disease-free survival. CONCLUSIONS: Our results indicated that AGAP2-AS1 overexpression was closely correlated with shorter OS in multiple cancer types, suggesting that AGAP2-AS1 might function as a promising predictor for clinical outcomes in cancer.