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1.
Bioresour Technol ; 393: 130171, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086460

RESUMO

The study reports the economic and sustainable syntheses of a lignin-based porous carbon (LPC) for CO2 capture application. The pH values of hydrothermal solution affected the polymerization and aromatization of spheroidization, with morphological changes from blocky to microsphere. In addition, the reliable mechanisms of CO2 adsorption were proposed by combining experiments with Gaussian16 simulations based on DFT. The electrostatic attraction of oxygen-containing functional groups and the diffusivity resistance of CO2 in the pores are the key factors for the CO2 adsorption. ​The carboxyl groups have the strongest electrostatic attraction to CO2. LPC-pH 1 has the highest carboxyl group content, possessing a CO2 adsorption capacity of up to 5.10 mmol/g at 0℃, 1 bar. Furthermore, CO2 diffusion resistance became a main factor as the adsorption temperature increases. The innovative combination of quantum chemical calculations and microscopic properties provides a viable pathway for an insight into the future control of lignin-based carbon formation.


Assuntos
Dióxido de Carbono , Lignina , Dióxido de Carbono/química , Lignina/química , Adsorção , Porosidade , Microesferas , Concentração de Íons de Hidrogênio
2.
J Colloid Interface Sci ; 658: 90-99, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100979

RESUMO

The electrochemical properties of corn starch (CS)-based hydrothermal carbon microsphere (CMS) electrode materials for supercapacitor are closely related to their structures. Herein, cetyltrimethyl ammonium bromide (CTAB) was used as a soft template to form the corn starch (CS)-based carbon microspheres with radial hollow structure in the inner and middle layers by hydrothermal and sol-gel method. Due to the introduction of multi-layer hollow structure of carbon microsphere, more micropores were produced during CO2 activation, which increased the specific surface area and improved the capacitance performance. Compared to commercial activated carbon, the four different morphologies of corn starch CMS had better electrochemical performances. Consequently, the proposed CO2-(CTAB)-CS-CS exhibits a high discharge specific capacitance of 242.5F/g at 1 A/g in three-electrode system with 6 M KOH electrolyte, better than commercial activated carbon with 208.5F/g. Moreover, excellent stability is achieved for CO2-(CTAB)-CS-CS with approximately 97.14 % retention of the initial specific capacitance value after 10,000 cycles at a current density of 2 A/g, while the commercial activated carbon has 86.96 % retention. This implies that the corn starch-based multilayer hollow CMS could be a promising electrode material for high-performance supercapacitors.

3.
J Am Coll Cardiol ; 82(19): 1828-1838, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37914512

RESUMO

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peso Corporal , Constrição Patológica , Meios de Contraste , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Gadolínio , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Imagem de Perfusão do Miocárdio/métodos , Perfusão , Valor Preditivo dos Testes , Estudos Prospectivos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Vasodilatadores
4.
Biochem Pharmacol ; 218: 115903, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37918695

RESUMO

In critical care medicine, sepsis is a potentially fatal syndrome characterized by multi-organ dysfunction and eventual failure. Sepsis-induced cardiomyopathy (SIC) is characterized by decreased venstricular contractility. Serine incorporator 2 (Serinc2) is a protein involved in phosphatidylserine biosynthesis and membrane incorporation. It may also be a protective factor in septic lung injury. However, it is unknown whether Serinc2 influences SIC onset or progression. In the present study, we found that Serinc2 was downregulated in the cardiomyocytes of cecal ligation and puncture (CLP)-induced SIC and in neonatal rat cardiomyocytes (NRCMs) exposed to lipopolysaccharides (LPS). Serinc2 knockout (KO) exacerbated sepsis-induced myocardial inflammation, necroptosis, apoptosis, myocardial damage, and contractility impairment. Furthermore, the lack of Serinc2 in cardiomyocytes aggravated LPS-induced cardiomyopathic inflammation, necroptosis, and apoptosis. An adenovirus overexpressing Serinc2 inhibited the inflammatory response and favored cardiomyocyte survival. A mechanistic analysis revealed that Serinc2 deficiency exacerbated LPS-induced cardiac dysfunction by inhibiting the protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK-3ß) signaling pathway that regulates necrotic complex formation and apoptotic pathways in cardiomyopathy. The findings of the present work demonstrated that Serinc2 plays an essential role in SIC and is, therefore, promising as a prophylactic and therapeutic target for this condition.


Assuntos
Cardiomiopatias , Sepse , Ratos , Animais , Glicogênio Sintase Quinase 3 beta , Lipopolissacarídeos/toxicidade , Necroptose , Cardiomiopatias/genética , Apoptose , Sepse/complicações , Sepse/metabolismo , Inflamação
5.
J Inflamm Res ; 16: 5531-5543, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026251

RESUMO

Purpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach. Methods: Clinical data from 1274 patients with NP from 2014-2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas. Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p<0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas. Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.

6.
Endocrinology ; 164(12)2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37788569

RESUMO

Obesity is a process of fat accumulation due to the imbalance between energy intake and consumption. Long noncoding RNA (lncRNA) Hnscr is crucial for metabolic regulation, but its roles in lipid metabolism during obesity are still unknown. In this article, we found that the expression of Hnscr gradually decreased in adipose tissues of diet-induced obese mice. Furthermore, the deletion of Hnscr promoted an increase in body weight and adipose tissue weight by upregulating the expression of lipogenesis genes and downregulating lipolysis genes in inguinal white adipose tissue (iWAT) and brown adipose tissue. In vitro knockdown of Hnscr in adipocytes resulted in reduced lipolysis of adipocytes. Overexpression of Hnscr by adenovirus or drug mimics showed the opposite. Mechanistically, Hnscr regulated adipose lipid metabolism by mediating the cyclic adenosine monophosphate/protein kinase A signaling pathway. This study identifies the initial characterization of Hnscr as a critical modifier that regulates lipid metabolism, suggesting that lncRNA Hnscr is a potential target for treating obesity.


Assuntos
Metabolismo dos Lipídeos , RNA Longo não Codificante , Camundongos , Animais , Lipólise , RNA Longo não Codificante/metabolismo , Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL
7.
Polymers (Basel) ; 15(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37835935

RESUMO

CO2 flooding is a favorable technical means for the efficient development of low-permeability reservoirs, and it can also contribute to the realization of net-zero CO2 emissions. However, due to the unfavorable viscosity ratio and gravity overriding effect, CO2 channeling will inevitably occur, seriously affecting its storage and displacement effects. This paper conducts a systematic study on the application of polymer-assisted CO2 flooding in low-permeability reservoirs. Firstly, the polymer agent suitable for low-permeability reservoirs is optimized through the viscosity-increasing, rheological, and temperature- and salt-resistant properties of the solution. Then, the injectivity performance, resistance-increasing ability, and profile-improving effect of the polymer solution were evaluated through core experiments, and the optimum concentration was optimized. Finally, the enhanced oil recovery (EOR) effects of polymer-assisted and water-assisted CO2 flooding were compared. The results show that the temperature-resistant polymer surfactant (TRPS) has a certain viscosity-increasing performance, good temperature resistance performance, and can react with CO2 to increase the solution viscosity significantly. Meanwhile, TRPS has good injection performance and resistance-increasing effect. The resistance increasing factor (η and η') of TRPS-assisted CO2 flooding increases with increased permeability, the concentration of TRPS solution, and injection rounds. Considering η' and the profile improvement effect comprehensively, the application concentration of TRPS should be 1000 mg/L. The EOR effect of TRPS-assisted CO2 flooding is 8.21% higher than that of water-assisted CO2 flooding. The main effective period is in the first and second rounds, and the best injection round is three. The research content of this paper can provide data support for the field application of polymer-assisted CO2 flooding in low-permeability reservoirs.

8.
Nat Commun ; 14(1): 3494, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37311782

RESUMO

Large temperature difference is reported to be a risk factor for human health. However, little evidence has reported the effects of temperature fluctuation on sarcopenia, a senile disease characterized by loss of muscle mass and function. Here, we demonstrate that higher diurnal temperature range in humans has a positive correlation with the prevalence of sarcopenia. Fluctuated temperature exposure (10-25 °C) accelerates muscle atrophy and dampens exercise performance in mid-aged male mice. Interestingly, fluctuated temperature alters the microbiota composition with increased levels of Parabacteroides_distasonis, Duncaniella_dubosii and decreased levels of Candidatus_Amulumruptor, Roseburia, Eubacterium. Transplantation of fluctuated temperature-shaped microbiota replays the adverse effects on muscle function. Mechanically, we find that altered microbiota increases circulating aminoadipic acid, a lysine degradation product. Aminoadipic acid damages mitochondrial function through inhibiting mitophagy in vitro. And Eubacterium supplementation alleviates muscle atrophy and dysfunction induced by fluctuated temperature. Our results uncover the detrimental impact of fluctuated temperature on muscle function and provide a new clue for gut-muscle axis.


Assuntos
Microbioma Gastrointestinal , Microbiota , Sarcopenia , Humanos , Masculino , Animais , Camundongos , Pessoa de Meia-Idade , Temperatura , Atrofia Muscular , Eubacterium
9.
World J Surg Oncol ; 21(1): 158, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37221610

RESUMO

BACKGROUND: Multiple primary malignant tumors (MPMTs), usually associated with worse malignant behavior and prognosis comparing to a single primary tumor, and have recently been found to have an increasing incidence globally. However, the pathogenesis of MPMTs remains to be clarified. Here, we report a unique case of the coexistence of malignant melanoma (MM), papillary thyroid carcinoma (PTC), and clear-cell renal cell carcinoma (ccRCC) along with our perceptions on its pathogenesis. CASE PRESENTATION: The case reported is of a 59-year-old male patient with unilateral nasal obstruction as well as a renal occupying lesion. Positron emission tomography-computed tomography (PET-CT) revealed a palpable mass of 32 × 30 mm on the posterior and left walls of the nasopharynx. In addition, an isodense nodule was observed in the right superior renal pole, approximately 25 mm in diameter, as well as a slightly hypodense shadow in the right leaf of the thyroid, approximately 13 mm in diameter. Nasal endoscopy and magnetic resonance imaging (MRI) confirmed the existence of a nasopharyngeal neoplasm. Afterward, biopsies of the nasopharyngeal neoplasm, thyroid gland and kidney were performed, and the patient was diagnosed with MM, PTC, and ccRCC according to the pathological and immunohistochemical results. Moreover, mutation of BRAFV600E was detected in bilateral thyroid tissues, and amplification of both CCND1 and MYC oncogenes were detected in the nasopharyngeal melanoma. After chemotherapy, the patient is now in good overall condition. CONCLUSIONS: This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAFV600E might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Neoplasias Nasofaríngeas , Neoplasias Primárias Múltiplas , Neoplasias da Glândula Tireoide , Masculino , Humanos , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Câncer Papilífero da Tireoide , Mutação , Ciclina D1
10.
Food Funct ; 14(8): 3849-3862, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37013966

RESUMO

Doxorubicin (DOX) is used extensively in anticancer therapy, but its clinical application is limited due to its cardiotoxicity. Carnosic acid (CA) is a bioactive compound found in rosemary. It has been shown to reduce inflammation and reactive oxygen species. The purpose of this study was to investigate the potential cardioprotective effects of CA in response to DOX-induced cardiotoxicity. Here, C57BL/6 mice were administered an intraperitoneal injection of DOX (5 mg kg-1, ip) once a week for three consecutive weeks and treated with CA (40 mg kg-1, ig) for a three-week experimental period. For in vitro study, neonatal rat ventricular cardiomyocytes were used to validate the protective effects of CA (20 µM) in response to DOX-induced cardiotoxicity. CA markedly suppressed oxidative stress, apoptosis, and pyroptosis responses in the mouse hearts, eventually improving cardiac function. CA showed its antioxidant effect by activating nuclear factor erythroid 2-related factor (Nrf2) and its downstream heme oxygenase-1 (HO-1); CA also reduced oxidative stress by lowering the MDA and lipid ROS levels and raising the SOD and GSH-px levels. Additionally, CA treatment significantly increased Bcl-2 and inhibited Bax and Caspase-3 cleavage in DOX-induced cardiotoxicity. Moreover, CA suppressed the NOD-like receptor protein 3 (NLRP3) pathway to mitigate pyroptosis, as evidenced by lowered caspase1, interleukin-18, and interleukin-1ß. Consistently, the transfection of Nrf2-siRNA eliminated the protective effects of CA on cardiomyocytes. Altogether, our findings demonstrated that CA inhibited NLRP3 inflammasomes via activating the Nrf2-related cytoprotective system and protected the heart from oxidative damage, apoptosis, and pyroptosis, implying that the use of CA could be a potential therapeutic strategy in the prevention of DOX-associated myocardiopathy.


Assuntos
Cardiotoxicidade , Fator 2 Relacionado a NF-E2 , Camundongos , Ratos , Animais , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Camundongos Endogâmicos C57BL , Doxorrubicina/toxicidade , Estresse Oxidativo , Miócitos Cardíacos , Apoptose
11.
Clin Res Hepatol Gastroenterol ; 47(4): 102105, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36858278

RESUMO

BACKGROUND AND AIMS: Minimally invasive step-up interventions are now the standard treatment recommended by current guidelines for symptomatic pancreatic necrotic fluid collections (PNFC); however, it is controversial whether delayed treatment after four weeks should always be used in patients who have failed conservative treatment and whose condition has not improved or worsened. The aim of this meta-analysis was to evaluate the impacts of the different timing of interventions on the clinical outcomes and prognosis of patients with symptomatic PNEC requiring intervention. METHODS: We searched Embase, Cochrane Library, PubMed and Web of Science databases to identify comparative studies assessing the safety and efficacy of early and postponed interventions in treating symptomatic PNFC. PRIMARY OUTCOME: Mortality. Secondary outcomes included some major complications, need for further minimally invasive necrosectomy and length of hospital stay. RESULTS: This meta-analysis included ten studies (2 RCTs and 8 observational studies) with a total of 1178 symptomatic PNFC patients who required intervention. Pooled results showed that there was no significant difference between early minimally invasive intervention and postponed intervention in mortality(OR 1.41, 95%CI 0.93-2.12;p = 0.10) and the incidence of early and late complications, but the early intervention group had a significantly increased need for further minimally invasive necrosectomy compared with postponed intervention (OR 2.04,95%CI 1.04-4.03; p = 0.04). There was no increase in length of stay for patients who received early intervention compared to postponed drainage (MD 3.53, 95% CI -4.20, 11.27; p = 0.37). CONCLUSION: Intervention before four weeks should be considered for patients with PNFC complicated by persistent organ failure or infections, who have been treated conservatively to the maximum extent possible.


Assuntos
Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/cirurgia , Tempo de Internação , Drenagem/métodos , Necrose , Estudos Observacionais como Assunto
12.
Plant Biotechnol (Tokyo) ; 39(3): 251-257, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36349228

RESUMO

Codonopsis pilosula, a traditional Chinese medicinal and edible plant, contains several bioactive components. However, the biosynthetic mechanism is unclear because of the difficulties associated with functional gene analysis. Therefore, it is important to establish an efficient genetic transformation system for gene function analysis. In this study, we established a highly efficient Agrobacterium-mediated callus genetic transformation system for C. pilosula using stems as explants. After being pre-cultured for 3 days, the explants were infected with Agrobacterium tumefaciens strain GV3101 harboring pCAMBIA1381-35S::GUS at an OD600 value of 0.3 for 15 min, followed by co-cultivation on MS induction medium for 1 day and delayed cultivation on medium supplemented with 250 mg l-1 cefotaxime sodium for 12 days. The transformed calli were selected on screening medium supplemented with 250 mg l-1 cefotaxime sodium and 2.0 mg l-1 hygromycin and further confirmed by PCR amplification of the GUS gene and histochemical GUS assay. Based on the optimal protocol, the induction and transformation efficiency of calli reached a maximum of 91.07%. The establishment of a genetic transformation system for C. pilosula calli lays the foundation for the functional analysis of genes related to bioactive components through genetic engineering technology.

13.
RSC Adv ; 12(38): 24839-24848, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36128390

RESUMO

Water flooding increases the recovery factor of crude oil and has been proven to be an economical and viable technique for enhancing the oil recovery of oil fields. The process has been systematically studied previously, in which the oil was considered a substance of constant composition. However, the molecular selectivity during the water flooding process has rarely been addressed, especially for heavy oil. Herein, the properties and compositional changes of heavy oil have been investigated in a simulated water flooding process at 60 °C and 85 °C. The crude oil and produced oils from different water flooding stages were characterized by gas chromatography, gas chromatography-mass spectrometry, and Fourier transform ion cyclotron resonance mass spectrometry. The results show that with the increase in temperature, the content of resins in the produced oils from different water flooding stages decreases, and the content of asphaltenes increases slightly. The viscosity of the produced oils increases at low temperatures and decreases at high temperatures as the water cut increases. The composition of the produced oils from different water flooding stages is different. Compared with the no water cut and high water cut stages, the changes in the produced oils of the low water cut stages are significant at different temperatures. The molecular selectivity of heteroatoms is higher than that of hydrocarbons in the water flooding process. Water flooding preferentially extracts small-molecule low-carbon hydrocarbons and small-molecule heteroatoms with low condensation degrees. The compositional differences between the produced oils were characterized by the double bond equivalent versus carbon number distribution of the S, N, and O-containing compounds. This study can not only provide some explanations on the viscosity-forming mechanism of heavy oil but also explains the watered-out phenomena in the development of oilfields.

14.
Cell Mol Life Sci ; 79(7): 352, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676564

RESUMO

Immune checkpoint blockade therapy has drastically improved the prognosis of certain advanced-stage cancers. However, low response rates and immune-related adverse events remain important limitations. Here, we report that inhibiting ALG3, an a-1,3-mannosyltransferase involved in protein glycosylation in the endoplasmic reticulum (ER), can boost the response of tumors to immune checkpoint blockade therapy. Deleting N-linked glycosylation gene ALG3 in mouse cancer cells substantially attenuates their growth in mice in a manner depending on cytotoxic T cells. Furthermore, ALG3 inhibition or N-linked glycosylation inhibitor tunicamycin treatment synergizes with anti-PD1 therapy in suppressing tumor growth in mouse models of cancer. Mechanistically, we found that inhibiting ALG3 induced deficiencies of post-translational N-linked glycosylation modification and led to excessive lipid accumulation through sterol-regulated element-binding protein (SREBP1)-dependent lipogenesis in cancer cells. N-linked glycosylation deficiency-mediated lipid hyperperoxidation induced immunogenic ferroptosis of cancer cells and promoted a pro-inflammatory microenvironment, which boosted anti-tumor immune responses. In human subjects with cancer, elevated levels of ALG3 expression in tumor tissues are associated with poor patient survival. Taken together, we reveal an unappreciated role of ALG3 in regulating tumor immunogenicity and propose a potential therapeutic strategy for enhancing cancer immunotherapy.


Assuntos
Ferroptose , Manosiltransferases , Neoplasias , Animais , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Lipídeos , Manosiltransferases/genética , Manosiltransferases/metabolismo , Camundongos , Neoplasias/terapia
15.
Front Cell Dev Biol ; 9: 723103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650975

RESUMO

Background: Immune checkpoint inhibitors have been successfully used in a variety of tumors, however, the efficacy of immune checkpoint blockade therapy for patients with glioma is limited. In this study, we tried to clarify gene expression signatures related to the prognosis of gliomas and construct a signature to predict the survival of patients with gliomas. Methods: Calcium-related differential expressed genes (DEGs) between gliomas and normal brain tissues were comprehensively analyzed in two independent databases. Univariate, multivariate Cox regression analysis and proportional hazards model were used to identify the prognostic of calcium-related risk score signature. The CIBERSORT algorithm and association analysis were carried out to evaluate the relationship between calcium-related signature and characteristic clinical features, tumor-infiltrating immune cell signatures as well as immune checkpoint molecules in glioma. A nomogram model was developed for predicting the overall survival for patients with gliomas. Results: We found the intersection of 415 DEGs between gliomas and normal brain tissues, and identified that an eighteen calcium-related gene panel was significantly enriched in these DEGs. A calcium-related signature derived risk score was developed to divide patients into high- and low-risk groups. Low levels of calcium-related gene expression in high-risk score cases were accompanied with worse outcomes of patients. Calcium-related risk scores were significantly associated with characteristic clinical features, immune infiltrating signatures of tumor microenvironment, and exhausted T cell markers including programmed cell death 1 (PD-1), lymphocyte activating 3 (LAG3), and T cell membrane protein 3 (TIM-3), which contribute to an adverse therapeutic effect of immunotherapy. Calcium-related signature risk score was considered as an independent prognostic parameter to predict the of overall survival of patients with gliomas in nomogram model. Conclusion: Our study demonstrated that calcium signaling pathway is highly associated with immunosuppression of gliomas and overall survival of patients. Targeting the calcium signaling pathway might be a new strategy to reverse the immunosuppressive microenvironment of gliomas and improve the efficacy of glioma immunotherapy.

16.
J Am Coll Cardiol ; 76(13): 1536-1547, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32972530

RESUMO

BACKGROUND: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. OBJECTIVES: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. METHODS: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. RESULTS: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. CONCLUSIONS: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.


Assuntos
Técnicas de Imagem Cardíaca , Meios de Contraste , Doença da Artéria Coronariana/diagnóstico por imagem , Imageamento por Ressonância Magnética , Compostos Organometálicos , Idoso , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
17.
Waste Manag ; 114: 17-24, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707442

RESUMO

The gasification slag by acidification can leach abundant heavy metals. In this paper, the fate of heavy metals (Ni, Cd, and As) in the raw slag and the acidified slag that treated by HAc and HCl was systematically investigated combined with Density Functional Theory (DFT) calculations. The results show that the content of Ni and Cd is reduced with an increasing acid concentration and meets the regulatory standards by 7 M HAc and 3 M HCl, respectively. Most of Ni combined with gehlenite is released as gehlenite dissolves during acid treatment, whereas Cd in combination with gehlenite and iron compounds is hard to release at lower HAc concentrations. Unexpectedly, the content of As tends to elevate at a higher concentration of HAc, which is due to the increase in the content of Ca by new Ca-compound formation and the higher binding capacity of Ca to As according to DFT results. Additionally, if the acid-base ratio reaches about 2.0 by acid treatment, there would be a maximum leaching rate. It is recommended that acid concentration should be controlled to avoid a secondary risk of heavy metals.


Assuntos
Compostos de Ferro , Metais Pesados , Cádmio , Concentração de Íons de Hidrogênio
18.
Sensors (Basel) ; 20(11)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532071

RESUMO

Swarm robotics focuses on decentralised control of large numbers of simple robots with limited capabilities. Decentralised control in a swarm system requires a reliable communication link between the individuals that is able to provide linear and angular distances between the individuals-Range & Bearing. This study presents the development of an open-source, low-cost communication module which can be attached to miniature sized robots; e.g., Mona. In this study, we only focused on bearing estimation to mathematically model the bearings of neighbouring robots through systematic experiments using real robots. In addition, the model parameters were optimised using a genetic algorithm to provide a reliable and precise model that can be applied for all robots in a swarm. For further investigation and improvement of the system, an additional layer of optimisation on the hardware layout was implemented. The results from the optimisation suggested a new arrangement of the sensors with slight angular displacements on the developed board. The precision of bearing was significantly improved by optimising in both software level and re-arrangement of the sensors' positions on the hardware layout.

19.
J Basic Microbiol ; 60(1): 82-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31650621

RESUMO

Involvement of LaeA in various biological processes of filamentous fungi has been demonstrated. However, its role in Penicillium digitatum, the causal agent of citrus postharvest green mold, remains unclear. In this study, a ΔPdLaeA mutant was constructed using homologous recombination. The production of conidia by the ΔPdLaeA mutant was reduced by half compared with that of the wild-type strain. The sensitivity of the ΔPdLaeA mutant increased under alkaline conditions. The virulence assay revealed that PdLaeA was dispensable for the virulence of P. digitatum. Comparative transcriptome analysis revealed that the function loss of PdLaeA resulted in the reduced expression of several secondary metabolite gene clusters. In addition, expression of several key regulators of conidiation (BrlA, FlbA, FlbC, FlbD, and FluG) was also downregulated in the ΔPdLaeA mutant. In summary, the present work demonstrated that PdLaeA was involved in the regulation of SM biosynthesis, as well as the development and environmental adaptation of P. digitatum.


Assuntos
Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Penicillium/genética , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo , Citrus/microbiologia , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Família Multigênica/genética , Penicillium/crescimento & desenvolvimento , Penicillium/metabolismo , Penicillium/fisiologia , Deleção de Sequência , Esporos Fúngicos/genética , Esporos Fúngicos/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo , Esporos Fúngicos/fisiologia , Fatores de Transcrição/genética , Virulência/genética
20.
Int J Biol Macromol ; 138: 511-518, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31336119

RESUMO

Citrus grandis 'Tomentosa' (CGT) which is a region-famous medicinal and edible plant contains plentiful bioactive polysaccharides, however, its chemical structures and specific bioactivities still need to be further explored. In the present study, an acidic polysaccharide (CGTP-AP) was extracted and purified from the pulps of CGT. The structure elucidation and anti-cancer activity of CGTP-AP were investigated. Structure characterization indicated that CGTP-AP was a homogeneous heteropolysaccharide composed of arabinose, galactose and galacturonic acid in a molar ratio of 2.45:1:2.77, with an average molecular weight of 2721.68 kDa. Partial acid hydrolysis, methylation and NMR spectrometry revealed that the backbone of CGTP-AP mainly composed of (1 → 4)-α-D-galacturonan, while the branch principally consisted of (1 → 5)-α-L-Araf. In addition, CGTP-AP exhibited effective anti-proliferation against colon cancer cells LOVO and SW620 cells in dose- and time-dependent manners, with IC50 values of 5.55, 4.35 and 3.52 mg mL-1 after 24, 48 and 72 h, and 5.33, 3.63 and 2.97 mg mL-1 after 24, 48 and 72 h, respectively. This study indicated that CGTP-AP might be utilized as a promising food supplement for the patients of colon disorders.


Assuntos
Citrus/química , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Hidrólise , Espectroscopia de Ressonância Magnética , Metilação , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Relação Estrutura-Atividade
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