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1.
J Virol ; 98(5): e0157323, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38572974

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-ß). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and production, and inhibited the RIG-I-like receptor (RLR) signaling pathway through selectively interacting with mitochondrial antiviral-signaling protein (MAVS). MAVS439-466 region and MAVS Lys461 were essential for the physical association between MAVS and ORF7b, and the inhibition of the RLR signaling pathway by ORF7b. MAVSK461/K63 ubiquitination was essential for the RLR signaling regulated by the MAVS-ORF7b complex. ORF7b interfered with the recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) and the activation of the RLR signaling pathway by MAVS. Furthermore, interfering peptides targeting the ORF7b complex reversed the ORF7b-suppressed MAVS-RLR signaling pathway. The most potent interfering peptide V disrupts the formation of ORF7b tetramers, reverses the levels of the ORF7b-inhibited physical association between MAVS and TRAF6, leading to the suppression of viral growth and infection. Overall, this study provides a mechanism for the suppression of innate immunity by SARS-CoV-2 infection and the mechanism-based approach via interfering peptides to potentially prevent SARS-CoV-2 infection.IMPORTANCEThe pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and continues to be a threat to public health. It is imperative to understand the biology of SARS-CoV-2 infection and find approaches to prevent SARS-CoV-2 infection and ameliorate COVID-19. Multiple SARS-CoV-2 proteins are known to function on the innate immune response, but the underlying mechanism remains unknown. This study shows that ORF7b inhibits the RIG-I-like receptor (RLR) signaling pathway through the physical association between ORF7b and mitochondrial antiviral-signaling protein (MAVS), impairing the K63-linked MAVS polyubiquitination and its recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) to MAVS. The most potent interfering peptide V targeting the ORF7b-MAVS complex may reverse the suppression of the MAVS-mediated RLR signaling pathway by ORF7b and prevent viral infection and production. This study may provide new insights into the pathogenic mechanism of SARS-CoV-2 and a strategy to develop new drugs to prevent SARS-CoV-2 infection.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , COVID-19 , Proteína DEAD-box 58 , SARS-CoV-2 , Transdução de Sinais , Fator 6 Associado a Receptor de TNF , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Proteína DEAD-box 58/metabolismo , Células HEK293 , COVID-19/virologia , COVID-19/imunologia , COVID-19/metabolismo , Ubiquitinação , Receptores Imunológicos/metabolismo , Animais , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Interferon beta/metabolismo , Apoptose , Imunidade Inata , Fator de Necrose Tumoral alfa/metabolismo
2.
Transl Oncol ; 44: 101954, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38608405

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

3.
Anal Methods ; 16(16): 2472-2477, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38606501

RESUMO

Sialic acids are a family of monosaccharides that share a nine-carbon backbone and a carboxyl group. A recent derivatization method based on 3-nitrophenylhydrazine (3-NPH) provides a mild chemical labeling technique for biomolecules containing carbonyl or carboxyl groups. In this study, we utilized 3-NPH to label sialic acids via a two-step derivatization process. The derivatized species can produce a common reporter ion corresponding to C1-C3 with two labels, and a fragment differentiating between Neu5Ac, Neu5Gc, and KDN. This method is compatible with O-acetylated sialic acids and provides high sensitivity to Neu5Gc and KDN, and since the utilization of dual labeling significantly enhances the hydrophobicity of derivatives, it can effectively mitigate matrix effects when combined with parallel reaction monitoring technology. Negative-ion tandem mass spectrometry (MS/MS) analysis reveals a distinctive fragmentation profile for the 4-O-acetylated species, while the other sialic acids yield similar MS/MS spectra with a high abundance of reporter ions. Using the reporter ion as a transition, this analytical strategy is effective for analyzing complex biological samples. For example, it was successfully employed to quantify sialic acids in the intestinal tissues of several carp species, demonstrating its potential in sialylation research.


Assuntos
Fenil-Hidrazinas , Ácidos Siálicos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Animais , Ácidos Siálicos/química , Ácidos Siálicos/análise , Fenil-Hidrazinas/química , Cromatografia Líquida/métodos , Acetilação , Espectrometria de Massa com Cromatografia Líquida
4.
J Exp Psychol Hum Percept Perform ; 50(5): 479-497, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38546626

RESUMO

How compound words are processed remains a central question in research on Chinese reading. The Chinese reading model assumes that all possible words sharing characters are activated during word processing and these activated words compete for a winner (Li & Pollatsek, 2020). The present studies aimed to examine whether embedded component words compete with whole compound words in Chinese reading. In Study 1, we analyzed two existing lexical decision databases and revealed inhibitory effects of component-word frequency and facilitative effects of character frequency on the first components. In Study 2, we conducted two factorial experiments to further examine the effects of first component-word frequency, with character frequencies controlled. The results consistently indicated significant inhibitory effects of component-word frequency. Collectively, these findings support the theoretical proposition that both component words and compound words are activated and engage in competition during word processing. This provides a new approach to compound word processing in Chinese reading and a possible solution to mixed results of character frequency effects reported in the literature. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Reconhecimento Visual de Modelos , Processamento de Texto , Humanos , China , Leitura
5.
J Proteomics ; 297: 105128, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382841

RESUMO

Investigating site-specific protein phosphorylation remains a challenging task. The present study introduces a two-step chemical derivatization method for accurate identification of phosphopeptides. Methylamine neutralizes carboxyl groups, thus reducing the adsorption of non-phosphorylated peptides during enrichment, while dimethylamine offers a cost-effective reagent for stable isotope labeling of phosphorylation sites. The derivatization improves the mass spectra obtained through liquid chromatography-tandem mass spectrometry. The product ions at m/z 58.07 and 64.10 Da, resulting from dimethylamine-d0 and dimethylamine-d6 labeled phosphorylation sites respectively, can serve as report ions. Derivatized phosphopeptides from casein demonstrate enhanced ionization and formation of product ions, yielding a significant increase in the number of identifiable peptides. When using the parallel reaction monitoring technique, it is possible to distinguish isomeric phosphopeptides with the same amino acid sequence but different phosphorylation sites. By employing a proteomic software and screening the report ions, we identified 29 endogenous phosphopeptides in 10 µL of human saliva with high reliability. These findings indicate that the two-step derivatization strategy has great potential in site-specific phosphorylation and large-scale phosphoproteomics research. SIGNIFICANCE: There is a significant need to improve the accuracy of identifying phosphoproteins and phosphopeptides and analyzing them quantitatively. Several chemical derivatization techniques have been developed to label phosphorylation sites, thus enabling the identification and relative quantification of phosphopeptides. Nevertheless, these methods have limitations, such as incomplete conversion or the need for costly isotopic reagents. Building upon previous contributions, our study moves the field forward due to high efficiency in site-specific labeling, cost-effectiveness, improved sensitivity, and comprehensive product ion coverage. Using the two-step derivatization approach, we successfully identified 29 endogenous phosphopeptides in 10 µL of human saliva with high reliability. The outcomes underscore the possibility of the method for site-specific phosphorylation and large-scale phosphoproteomics investigations.


Assuntos
Fosfopeptídeos , Proteômica , Humanos , Fosfopeptídeos/análise , Marcação por Isótopo/métodos , Proteômica/métodos , Reprodutibilidade dos Testes , Indicadores e Reagentes , Fosforilação , Íons , Dimetilaminas
6.
Microbiol Spectr ; 12(4): e0341023, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38376366

RESUMO

The nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer's stability, a circular bivalent form, cb-N-Apt17, was designed and evaluated. Our findings demonstrated that cb-N-Apt17 exhibited improved stability, enhanced binding affinity, and superior inhibition of N protein LLPS; thus, it has the potential inhibition ability on viral replication. These results provide valuable evidence supporting the potential of cb-N-Apt17 as a promising candidate for the development of antiviral therapies against COVID-19.IMPORTANCEVariants of SARS-CoV-2 pose a significant challenge to currently available COVID-19 vaccines and therapies due to the rapid epitope changes observed in the viral spike protein. However, the nucleocapsid (N) protein of SARS-CoV-2, a highly conserved structural protein, offers promising potential as a target for inhibiting viral replication. The N protein forms complexes with genomic RNA, interacts with other viral structural proteins during virion assembly, and plays a critical role in evading host innate immunity by impairing interferon production during viral infection. In this investigation, we discovered a single-stranded DNA aptamer, designated as N-Apt17, exhibiting remarkable affinity and specificity for the N protein. Notably, N-Apt17 disrupts the liquid-liquid phase separation (LLPS) of the N protein. To enhance the stability and molecular recognition capabilities of N-Apt17, we designed a circular bivalent DNA aptamer termed cb-N-Apt17. In both in vivo and in vitro experiments, cb-N-Apt17 exhibited increased stability, enhanced binding affinity, and superior LLPS disrupting ability. Thus, our study provides essential proof-of-principle evidence supporting the further development of cb-N-Apt17 as a therapeutic candidate for COVID-19.


Assuntos
COVID-19 , Proteínas do Nucleocapsídeo , Humanos , SARS-CoV-2/genética , DNA de Cadeia Simples/farmacologia , Vacinas contra COVID-19 , Antivirais/farmacologia
7.
iScience ; 27(1): 108726, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38235327

RESUMO

The tight coupling between electricity and gas has put the US New England region at constant risk of electricity price spikes due to a shortage of gas supplies, especially in the wake of limited natural gas supply in 2022. Here, we investigate the electricity-gas price couplings in the six states in New England from 2006 to 2022. We found that the price coupling in New England has been high and consistent in the past five years across all states, despite varying levels of gas-fired power generation. Additionally, we anticipate it will remain high even with increasing renewables by 2030. Furthermore, the price coupling exhibits an asymmetrical influence with electricity prices closely tracking gas prices, while gas prices are weakly affected by electricity price variations. Our findings also suggest that promoting electricity-gas cooperations could potentially mitigate the asymmetrical influence and electricity price spikes in New England.

8.
J Med Virol ; 95(11): e29182, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37909805

RESUMO

INTRODUCTION: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. METHODS: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. RESULTS: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). CONCLUSIONS: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções Comunitárias Adquiridas , Pneumonia Viral , Pneumonia , Criança , Humanos , Feminino , Lactente , Adenovírus Humanos/genética , Proteômica , Fatores de Risco
9.
Pancreatology ; 23(8): 949-956, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37968184

RESUMO

BACKGROUND: Hypertriglyceridemia (HTG) is frequently observed in non-HTG-induced acute pancreatitis (AP), such as in the early stage of acute biliary pancreatitis (ABP). There is overlap in the etiologies of ABP, HTG-AP, and biliary-hypertriglyceridemia acute pancreatitis (BHAP), which may be perplexing for clinicians. METHODS: We retrospectively analyzed 394 AP patients. The patients were divided into three groups based on etiology. We analyzed the differences among the three groups of patients in terms of general information, laboratory parameters, and prognosis. RESULTS: The mean age of patients in the ABP group was significantly higher than that in the HTG-AP and BHAP groups (p < 0.001). Females made up a greater percentage of the ABP group, whereas males made up the majority in the HTG-AP and BHAP groups. The ABP group had the highest PCT, AMS, LPS, ALT, AST, GGT, TBIL, DBIL, APACHE II, and BISAP scores. TG and BMI were highest in the HTG-AP group. AST and GGT levels were substantially greater in BHAP patients than those in HTG-AP. The BHAP group had the greatest incidence of organ failure, systemic complications, and local complications. CONCLUSION: ABP usually develops in people aged 50-59 years. HTG-AP primarily affects people aged 30-39 years. However, the peak incidence age of BHAP falls between the two aforementioned age groups (40-49 years). We also found that patients with BHAP seem to be in an intermediate state in terms of some biochemical markers and demographic characteristics. Furthermore, BHAP may have the worst clinical outcomes compared with HTG-AP and ABP.


Assuntos
Hipertrigliceridemia , Pancreatite , Masculino , Feminino , Humanos , Pancreatite/complicações , Pancreatite/epidemiologia , Estudos Retrospectivos , Doença Aguda , Triglicerídeos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/epidemiologia
10.
J Interv Med ; 6(3): 107-110, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37846332

RESUMO

Recently, interventional ablation techniques have gained prominence in tumor treatment guidelines and complement traditional approaches, such as surgery, chemotherapy, and radiotherapy. Conventional ablation techniques, such as microwave, radiofrequency, and cryoablation, have been used; however, they have certain limitations, including the risk of damaging surrounding normal tissues and the heat sink effect caused by tumor blood flow.1 Irreversible electroporation (IRE), an ablation technology independent of thermal energy, is a promising alternative.2 Clinical studies have demonstrated IRE's efficacy in treating tumors, such as pancreatic and liver tumors.3 Recent research has shown that IRE can elicit specific anti-tumor immune responses in the body.5 IRE also plays a crucial role in eliminating residual tumor cells postoperatively and preventing tumor recurrence.

11.
J Am Chem Soc ; 145(43): 23832-23841, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850961

RESUMO

Norepinephrine (NE) is a key neurotransmitter in the central and sympathetic nervous systems, whose content fluctuates dynamically and rapidly in various brain regions during different physiological and pathophysiological processes. However, it remains a great challenge to directly visualize and precisely quantify the transient NE dynamics in living systems with high accuracy, specificity, sensitivity, and, in particular, high temporal resolution. Herein, we developed a series of small-molecular probes that can specifically detect NE through a sequential nucleophilic substitution-cyclization reaction, accompanied by a ratiometric near-infrared fluorescence response, within an impressively short time down to 60 ms, which is 3 orders of magnitude faster than that of present small-molecular probes. A unique water-promoted intermolecular proton transfer mechanism is disclosed, which dramatically boosted the recognition kinetics by ∼680 times. Benefiting from these excellent features, we quantitatively imaged the transient endogenous NE dynamics under external stimuli at the single living neuron level and further revealed the close correlations between NE fluctuations and Parkinson's disease pathology at the level of acute brain slices and live mouse brains in vivo.


Assuntos
Encéfalo , Norepinefrina , Animais , Camundongos , Encéfalo/diagnóstico por imagem , Sondas Moleculares , Imagem Óptica , Neurônios
12.
Chin J Traumatol ; 26(6): 351-356, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37838578

RESUMO

PURPOSE: As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy. METHODS: This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses. RESULTS: Difficult laryngoscopy was indicated in 49 patients (CL grade Ⅲ - Ⅳ) and easy laryngoscopy in 453 patients (CL grade Ⅰ - Ⅱ). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups. CONCLUSION: Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.


Assuntos
Laringoscopia , Língua , Humanos , Adolescente , Estudos Prospectivos , Língua/diagnóstico por imagem , Sistema Respiratório , Ultrassonografia
13.
Sleep Breath ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884785

RESUMO

BACKGROUND: Numerous individuals opt for napping to achieve adequate rest, and several studies have linked napping to various health conditions. Consequently, we aimed to investigate the potential effect of napping on the development of deep vein thrombosis (DVT). METHODS: We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) meta-analyses for napping in individuals included in the UK Biobank as the exposure and a GWAS for DVT from the individuals included in the FinnGen Biobank as the outcome. The two-sample MR research approach was utilized to explore the causative link between napping and DVT. Single nucleotide polymorphisms (SNPs) data strongly related to napping were found and used as instrumental factors. Inverse variance weighting (IVW), weighted median and MR-Egger regression, and weighted mode approaches were four statistical techniques. RESULTS: There were 86 SNPs in all that were discovered to be strongly related to napping (P < 5 × 10-8, linkage disequilibrium r2 < 0.1). Consistent association between napping and DVT (IVW: odds ratio (OR) 0.508, 95% confidence interval (CI) 0.280-0.921; MR-Egger regression: OR 0.988, 95% CI 0.118-8.303; weighted median estimates: OR 0.419, 95% CI 0.181-0.974; weighted mode: OR 0.442, 95% CI 0.080-2.427) suggested that napping correlated with decreased risk of DVT. There was no evidence that genetic pleiotropy affected the link between napping and DVT (MR-Egger intercept - 6.7 × 10-3; P = 0.525). CONCLUSION: The results of the Mendelian randomization study suggested a potential causal relationship between napping and a reduced incidence of DVT.

14.
Nature ; 623(7988): 752-756, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37853128

RESUMO

Subduction related to the ancient supercontinent cycle is poorly constrained by mantle samples. Sublithospheric diamond crystallization records the release of melts from subducting oceanic lithosphere at 300-700 km depths1,2 and is especially suited to tracking the timing and effects of deep mantle processes on supercontinents. Here we show that four isotope systems (Rb-Sr, Sm-Nd, U-Pb and Re-Os) applied to Fe-sulfide and CaSiO3 inclusions within 13 sublithospheric diamonds from Juína (Brazil) and Kankan (Guinea) give broadly overlapping crystallization ages from around 450 to 650 million years ago. The intracratonic location of the diamond deposits on Gondwana and the ages, initial isotopic ratios, and trace element content of the inclusions indicate formation from a peri-Gondwanan subduction system. Preservation of these Neoproterozoic-Palaeozoic sublithospheric diamonds beneath Gondwana until its Cretaceous breakup, coupled with majorite geobarometry3,4, suggests that they accreted to and were retained in the lithospheric keel for more than 300 Myr during supercontinent migration. We propose that this process of lithosphere growth-with diamonds attached to the supercontinent keel by the diapiric uprise of depleted buoyant material and pieces of slab crust-could have enhanced supercontinent stability.

15.
Sci Data ; 10(1): 646, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37736750

RESUMO

Efficient electricity market operations and cost-effective electricity generations are fundamental to a low-carbon energy future. The Western Electricity Coordinating Council (WECC) and Northeast Power Coordinating Council (NPCC) systems were built to provide efficient electrical grid simulation solutions for their respective U.S. regions. Data reuse for electricity economic studies remains a challenge due to the lack of credible and realistic economic data. This paper delivers a comprehensive dataset containing generator aggregations, generator costs, transmission limits, load distributions, and electricity prices for the WECC and NPCC systems based on real-world grid operation data at year 2020, including power plant geographic locations, generation profiles, regional power flow interchanges, and load distributions in both regions. The electricity price from the developed dataset is simulated based on the other items in the dataset, and we show that the variation of the simulated electricity price reasonably aligns with the real-world electricity price in both the WECC and NPCC regions. Overall, the developed dataset is of interest for various electricity market and economic studies, such as the economic dispatch and locational marginal price (LMP) analysis.

16.
Cell Signal ; 112: 110908, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37769891

RESUMO

Growth arrest-specific gene 7 (Gas7) was involved in various cellular functions, although its specific roles and molecular mechanisms in hepatocellular carcinoma (HCC) remained unclear. So the current study was to investigate the role of Gas7 in HCC. Our findings revealed that Gas7 was downregulated in various HCC cell lines and low Gas7 expression was associated with decreased overall survival in patients with HCC. Additionally, our functional assays showed that Gas7 inhibited cell proliferation and migration, induced cell cycle arrest, apoptosis, and autophagy, and enhanced oxaliplatin sensitivity by inhibiting the PI3K/Akt signaling pathway. We also observed that transcription factorSp1 was responsible for inhibiting Gas7. These findings provide insights into the role and elucidated a potential mechanism of Gas7 in HCC progression and metastasis. It was also observed that the Sp1/Gas7/PI3K/Akt axis was critical for malignant phenotype and oxaliplatin sensitivity in HCC. Therefore, Gas7 can be considered as a prognostic predictor and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
17.
J Virol ; 97(10): e0101423, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37712705

RESUMO

IMPORTANCE: Adenoviruses are widely used in gene therapy and vaccine delivery. Due to the high prevalence of human adenoviruses (HAdVs), the pre-existing immunity against HAdVs in humans is common, which limits the wide and repetitive use of HAdV vectors. In contrast, the pre-existing immunity against simian adenoviruses (SAdVs) is low in humans. Therefore, we performed epidemiological investigations of SAdVs in simians and found that the SAdV prevalence was as high as 33.9%. The whole-genome sequencing and sequence analysis showed SAdV diversity and possible cross species transmission. One isolate with low level of pre-existing neutralizing antibodies in humans was used to construct replication-deficient SAdV vectors with E4orf6 substitution and E1/E3 deletion. Interestingly, we found that the E3 region plays a critical role in its replication in human cells, but the absence of this region could be compensated for by the E4orf6 from HAdV-5 and the E1 expression intrinsic to HEK293 cells.


Assuntos
Adenovirus dos Símios , Terapia Genética , Vetores Genéticos , Vacinas , Animais , Humanos , Adenovírus Humanos/genética , Adenovirus dos Símios/genética , Vetores Genéticos/genética , Células HEK293 , Macaca/genética
19.
Int J Biol Macromol ; 253(Pt 3): 126935, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37722638

RESUMO

Soybean meal, excessively used in place of fish meal (FM) in aquaculture, has a detrimental impact on fish. In this study, the nanopeptide CI20, which was created by conjugating antimicrobial peptide gcIFN-20H and CMCS, were evaluated the feeding effect in mandarin fish (Siniperca chuatsi). Compared with the control group, 150 mg/kg C-I20-fed fish showed the second highest growth performance with no significant changes in body composition. C-I20-fed fish showed more goblet cells and thicker mucin after feeding. The 150 mg/kg CI20 diet boosted the antioxidant capacity, immunity, and digestive enzymes. After Aeromonas hydrophila and infection spleen and kidney necrosis virus infection, the survival rates in the 150 mg/kg CI20 group were highest. Meanwhile, many tissues in the 150 mg/kg CI20 group had significantly lower pathogen loads than the other groups. Treatment with 150 mg/kg CI20 was effective in increasing antioxidant capacity and immunity. The minimum tissue lesions were observed in the 150 mg/kg CI20 group. The goblet cell number and mucin thickness were significantly increased by CI20 treatment after infection. The study results herein showed that a reasonable dietary concentration of CI20 feed promoted growth performance and disease resistances in fish, suggesting a prospective nano antimicrobial peptide for the aquaculture.


Assuntos
Resistência à Doença , Doenças dos Peixes , Animais , Antioxidantes/farmacologia , Estudos Prospectivos , Peixes , Dieta , Mucinas , Doenças dos Peixes/tratamento farmacológico , Ração Animal/análise
20.
Geriatr Gerontol Int ; 23(11): 779-787, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37721114

RESUMO

AIM: Aging decreases muscle mass and bone mineral density (BMD), especially in older women. It has been reported that rowing and inulin intake positively affect muscle and bone, respectively. We examined the synergistic effect of rowing and functional food intake, including inulin, on lean body mass, BMD, and physical function parameters in older Japanese women. METHODS: Fifty women aged 65-79 years were divided into four groups with or without inulin intake and rowing. The interventions were carried out for 12 weeks in each group. We assessed lean body mass and BMD using dual-energy X-ray absorptiometry at baseline and after the intervention and examined the changes in the values in each group. RESULTS: Lean body mass in all groups decreased, and the change in lean body mass in the group with rowing and inulin intake was significantly smaller than that in the group without them (-0.05 ± 0.61; -0.83 ± 0.59 kg; P = 0.030). The BMD in the three intervention groups increased after the 12-week intervention. The change in BMD in each of the three intervention groups showed significant differences compared with the control group (Rowing + Inulin: P = 0.03; Rowing + No inulin: P = 0.01; No rowing + Inulin: P < 0.01). CONCLUSIONS: Rowing and the intake of functional foods, including inulin, synergistically prevented a decrease in lean body mass. These factors, individually and additively, might increase BMD in older Japanese women. Geriatr Gerontol Int 2023; 23: 779-787.


Assuntos
Densidade Óssea , Exercício Físico , Alimento Funcional , Idoso , Feminino , Humanos , Absorciometria de Fóton , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , População do Leste Asiático , Inulina/administração & dosagem , Músculos
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