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1.
Clin Nutr ; 41(10): 2295-2307, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36096063

RESUMO

BACKGROUND AND AIMS: Dietary factors play an important role in promoting nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) development through regulation of metabolism and inflammation. However, so far there was no evidence regarding how dietary factors may influence different disease outcomes in the NAFLD to HCC progression. Our study aimed to comprehensively evaluate the role of dietary factors on the risk of progression from NAFLD to HCC. METHODS: A comprehensive literature research was conducted in PubMed, Web of Science and Embase databases to identify case-control and cohort studies published up to March 15, 2022 in English. We included studies investigating associations of food and beverage items (excluding alcohol), food groups, dietary patterns, and dietary habits with incidence risk of four main chronic liver diseases involved in the NAFLD-to-HCC progression (i.e., NAFLD, liver fibrosis, liver cirrhosis, and HCC). Three researchers independently performed the literature search, selected eligible articles, performed data abstraction and evaluated study quality. After evaluating adequacy and credibility of the associations reported for each dietary factor and each liver disease outcome, we summarized and evaluated the consistency of associations based on a priori determined criteria considering study design and the proportion of significant associations. RESULTS: There were 109 studies included in this review (47 on NAFLD, 1 on liver fibrosis, 6 on liver cirrhosis, and 55 on HCC). Consistent evidence suggested that higher dietary inflammatory potential was associated with increased risk of both NAFLD and HCC whereas Mediterranean diet was associated with lower risk of both diseases. Additionally, greater conformity to the Healthy Eating Index, Dietary Approaches to Stop Hypertension score, and Mediterranean Diet Score, and dietary patterns with high dietary antioxidant capacity reduced NAFLD risk. Some specific foods including soft drinks and red and/or processed meat were associated with increased NAFLD risk while total vegetables and spinach were associated with reduced NAFLD risk. Coffee and white meat consumption were inversely related to HCC risk. CONCLUSIONS: Dietary patterns or individual foods representing a more anti-inflammatory potential were associated with reduced risk of both NAFLD and HCC, which implied diet-induced inflammation may impact NAFLD progression towards HCC.

2.
Front Oncol ; 12: 929342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119532

RESUMO

Background: Research findings have revealed that combining anti-angiogenesis inhibitors with programmed death-1(PD-1) inhibitors can reverse the immunosuppressive tumor microenvironment and enhance the antitumor immune response. To explore the therapeutic options for breaking immune tolerance in microsatellite stability (MSS) or mismatch repair-proficiency (pMMR) advanced colorectal cancer (CRC), we assessed the efficacy, safety and predictors of the fruquintinib and PD-1 inhibitors combination in patients with MSS/pMMR advanced CRC in a real-world environment. Methods: We conducted a single-center retrospective study by collecting relevant data on patients with MSS/pMMR advanced CRC who received fruquintinib coupled with PD-1 inhibitors in the First Affiliated Hospital of Zhengzhou University between August 2019 and November 2021, focusing on progression-free survival. Results: We enrolled 110 eligible patients in this study between August 2019 and November 2021. At the deadline (January 20, 2022), 13 patients had objective responses. The objective response rate was 11.8% (13/110, 95% confidence interval [CI]: 6.4-18.2), the disease control rate was 70.0% (82/110, 95% CI: 60.9-78.2), and the progression-free survival was 5.4 months (95% CI: 4.0-6.8). Liver metastases (hazard ratio [HR]: 0.594, 95% CI: 0.363-0.973, P<0.05), alkaline phosphatase elevation (ALP>160U/L) (HR: 0.478, 95%CI: 0.241-0.948, P<0.05), fibrinogen elevation (FIB>4g/L) (HR: 0.517, 95% CI: 0.313-0.855, P<0.05), and an increase in the ALP level from the baseline after treatment (HR: 1.673, 95% CI: 1.040-2.690, P<0.05) were negative predictors of the progression-free survival. A total of 101 of 110 patients experienced treatment-related adverse events, including 14 who experienced grade 3 or above treatment-related adverse events, and no treatment-related deaths occurred. Hypertension was the most frequently encountered grade 3 treatment-related adverse event. Conclusion: Fruquintinib combined with PD-1 inhibitors has antitumor activity and manageable safety in treating patients with MSS/pMMR advanced CRC. Liver metastases, ALP level and FIB level might be a prediction of the patient response to this therapy.

3.
Sci Rep ; 12(1): 15517, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109550

RESUMO

Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.


Assuntos
COVID-19 , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Cricetinae , Humanos , Mesocricetus , Testes de Neutralização , SARS-CoV-2
4.
Med (N Y) ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-36044897

RESUMO

BACKGROUND: The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, in particular the newly emerged Omicron (B.1.1.529) variant and its BA.X lineages, has rendered ineffective a number of previously FDA emergency use authorized SARS-CoV-2 neutralizing antibody therapies. Furthermore, those approved antibodies with neutralizing activity against Omicron BA.1 are reportedly ineffective against the subset of Omicron subvariants that contain a R346K substitution, BA.1.1, and the more recently emergent BA.2, demonstrating the continued need for discovery and characterization of candidate therapeutic antibodies with the breadth and potency of neutralizing activity required to treat newly diagnosed COVID-19 linked to recently emerged variants of concern. METHODS: Following a campaign of antibody discovery based on the vaccination of Harbor H2L2 mice with defined SARS-CoV-2 spike domains, we have characterized the activity of a large collection of spike-binding antibodies and identified a lead neutralizing human IgG1 LALA antibody, STI-9167. FINDINGS: STI-9167 has potent, broad-spectrum neutralizing activity against the current SARS-COV-2 variants of concern and retained activity against each of the tested Omicron subvariants in both pseudotype and live virus neutralization assays. Furthermore, STI-9167 nAb administered intranasally or intravenously provided protection against weight loss and reduced virus lung titers to levels below the limit of quantitation in Omicron-infected K18-hACE2 transgenic mice. CONCLUSIONS: With this established activity profile, a cGMP cell line has been developed and used to produce cGMP drug product intended for intravenous or intranasal use in human clinical trials. FUNDING: Funded by CRIPT (no. 75N93021R00014), DARPA (HR0011-19-2-0020), and NCI Seronet (U54CA260560).

5.
Cell Rep Med ; 3(9): 100727, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35998626

RESUMO

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor-metabolite-diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Microbiota , Ácido 2-Aminoadípico , Adulto , Alanina , Aminoácidos/metabolismo , Asparagina/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Ácido Glutâmico , Histidina , Homosserina , Humanos , Lipídeos , Metionina , Prolina , Ácido Úrico
6.
Pharm Biol ; 60(1): 1237-1254, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35763552

RESUMO

CONTEXT: Hedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are used interchangeably in clinics to treat spleen-qi deficiency (SQD) symptom mainly including gastrointestinal dysfunction and decreased immunity, which has unknown differences in efficacy. OBJECTIVE: To investigate the differences between HRPCM and ARPCM on intervening gastrointestinal- and immune-function with SQD syndrome. MATERIALS AND METHODS: After the SQD model was established, the Sprague-Dawley (SD) rats were randomly divided into nine groups (n = 10): normal; model; Bu-Zhong-Yi-Qi Pills; 18.9, 12.6 and 6.3 g/kg dose groups of HRPCM and ARPCM. Gastrointestinal function including d-xylose, gastrin, amylase vasoactive intestinal peptide, motilin, pepsin, H+/K+-ATPase, Na+/K+-ATPase, sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2) and immune function including spleen and thymus index, blood routine, interleukin (IL)-2, IL-6, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), immunoglobulin (Ig) M, IgA, IgG and delayed-type hypersensitivity (DTH) were detected. Finally, the efficacy differences were analysed comprehensively by the fuzzy matter-element method. RESULTS: In regulating immune, the doses differences in efficacy between HRPCM and ARPCM showed in the high-dose (18.9 g/kg), but there were no differences in the middle- and low- dose (12.6 and 6.37 g/kg); the efficacy differences were primarily reflected in levels of IL-6, IFN-γ, TNF-α and IgM in serum, and the mRNA expression of IL-6 and IFN-γ in the spleen. In regulating gastrointestinal, the efficacy differences were primarily reflected in the levels of D-xylose, MTL, and GAS in serum, and the mRNA and protein expression of SGLT1 and GLUT2 in jejunum and ileum. DISCUSSION AND CONCLUSIONS: HRPCM is more effective than ARPCM on regulating gastrointestinal function and immune function with SQD syndrome. Therefore, we propose that HRPCM should be mainly used to treat SQD syndrome in the future.


Assuntos
Astrágalo (Planta) , Medicamentos de Ervas Chinesas , Adenosina Trifosfatases , Animais , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-6 , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Baço , Fator de Necrose Tumoral alfa/farmacologia , Xilose/farmacologia
7.
J Agric Food Chem ; 70(24): 7547-7565, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35687111

RESUMO

This study aimed to investigate the synergistic bactericidal activity and mechanism of dual-stage light-guided membrane and DNA-targeted photodynamic inactivation (PDI) by the combination of blue light (BL, 420 nm) and the food additive octyl gallate (OG) against Vibrio parahaemolyticus in planktonic and biofilm growth modes. While OG serves as an outstanding exogenous photosensitizer, the planktonic cells were not visibly detectable after the OG-mediated PDI treatment with 0.2 mM OG within 15 min (191.7 J/cm2), and its biofilm was nearly eradicated within 60 min (383.4 J/cm2). Gram-positive Staphylococcus aureus was more susceptible to the PDI than Gram-negative V. parahaemolyticus. The cellular wall and proteins, as well as DNA, were the vulnerable targets for PDI. The membrane integrity could be initially disrupted by OG bearing a hydrophilic head and a hydrophobic tail via transmembrane insertion. The enhancement of OG uptake due to the first-stage light-assisted photochemical internalization (PCI) promoted the accumulation of OG in cells. It further boosted the second-stage light irradiation of the photosensitizer-inducing massive cell death. Upon the second-stage BL irradiation, reactive oxygen species (ROS) generated through the OG-mediated PDI in situ could extensively deconstruct membranes, proteins, and DNA, as well as biofilms, while OG could be activated by BL to carry out photochemical reactions involving the formation of OG-bacterial membrane protein (BMP) covalent conjugates and the interactions with DNA. This dual-stage light-guided subcellular dual-targeted PDI strategy exhibits encouraging effects on the eradication of planktonic bacteria and sessile biofilms, which provides a new insight into the development of an ultraeffective antimicrobial and biofilm removing/reducing technique to improve microbiological safety in the food industry.


Assuntos
Fármacos Fotossensibilizantes , Plâncton , Bactérias , Biofilmes , DNA , Ácido Gálico/análogos & derivados , Fármacos Fotossensibilizantes/farmacologia
8.
Front Chem ; 10: 888285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646817

RESUMO

Gamma-ray irradiation, using the cobalt-60 isotope, is the most common radiation modality used for medical device and biopharmaceutical products sterilization. Although X-ray and electron-beam (e-beam) sterilization technologies are mature and have been in use for decades, impediments remain to switching to these sterilization modalities because of lack of data on the resulting radiation effects for the associated polymers, as well as a lack of education for manufacturers and regulators on the viability of these sterilization alternatives. For this study, the compatibility of ethylene vinyl acetate (EVA) multilayer films with different ionizing radiation sterilization (X-ray, e-beam, and gamma irradiation) is determined by measuring chemical and physical film properties using high performance liquid chromatography, differential scanning calorimetry, Fourier-Transform InfraRed spectroscopy (FTIR), surface energy measurement, and electron spin resonance techniques. The results indicate that the three irradiation modalities induce no differences in thermal properties in the investigated dose range. Gamma and X-Ray irradiations generate the same level of reactive species in the EVA multilayer film, whereas e-beam generates a reduced quantity of reactive species.

9.
Nat Commun ; 13(1): 2665, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562376

RESUMO

Pancreatic intraepithelial neoplasia (PanIN) is a precursor of pancreatic ductal adenocarcinoma (PDAC), which commonly occurs in the general populations with aging. Although most PanIN lesions (PanINs) harbor oncogenic KRAS mutations that initiate pancreatic tumorigenesis; PanINs rarely progress to PDAC. Critical factors that promote this progression, especially targetable ones, remain poorly defined. We show that peroxisome proliferator-activated receptor-delta (PPARδ), a lipid nuclear receptor, is upregulated in PanINs in humans and mice. Furthermore, PPARδ ligand activation by a high-fat diet or GW501516 (a highly selective, synthetic PPARδ ligand) in mutant KRASG12D (KRASmu) pancreatic epithelial cells strongly accelerates PanIN progression to PDAC. This PPARδ activation induces KRASmu pancreatic epithelial cells to secrete CCL2, which recruits immunosuppressive macrophages and myeloid-derived suppressor cells into pancreas via the CCL2/CCR2 axis to orchestrate an immunosuppressive tumor microenvironment and subsequently drive PanIN progression to PDAC. Our data identify PPARδ signaling as a potential molecular target to prevent PDAC development in subjects harboring PanINs.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , PPAR delta , Neoplasias Pancreáticas , Animais , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Humanos , Ligantes , Camundongos , PPAR delta/genética , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Microambiente Tumoral/genética
10.
Phys Chem Chem Phys ; 24(17): 10114-10123, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35416816

RESUMO

We investigate the low-lying electronic states and feasibility of direct laser cooling of AsH, SbH and BiH by means of the highly accurate ab initio and dynamical methods with the inclusion of the spin-orbit coupling effects. Twelve low-lying Ω states for each of them are computed using the internally contracted multireference configuration interaction method. Our computed spectroscopic constants are in excellent agreement with the available experimental data. The calculated spin-orbit matrix elements are large enough, and thus the intersystem crossings from the A3Π state and the transitions to the a1Δ2 state should be considered in laser cooling. We find that, from AsH to BiH, the location of the crossing point between the A3Π and 5Σ- states moves down towards the ground vibrational level of A3Π along with enhanced spin-orbit coupling effects, which increases the difficulty of laser cooling heavier hydrides. An empirical law of "crossing point shifting down" down a group in the periodic table is generalized, which may become a helpful caveat when cooling diatomic molecules containing heavier elements. By choosing specific spin-orbit states, we construct feasible laser cooling schemes for AsH and SbH based on the A3Π2 → X3Σ-1 transitions, which feature very large vibrational branching ratios R00 (AsH: 0.9662; SbH: 0.9248) and short radiative lifetimes (AsH: 914 ns; SbH: 883 ns). In particular, a constructed laser cooling scheme for AsH is able to scatter 1.24 × 104 photons, whereas that for SbH can scatter 8.60 × 103 photons, which are enough to cool AsH and SbH to the ultracold regime. The present work demonstrates the importance of intersystem crossings and spin-orbit couplings in molecular laser cooling.

11.
Front Med (Lausanne) ; 9: 813696, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425781

RESUMO

Purpose: This study is aimed to assess the efficacy of adalimumab in alleviating peripheral vascular leakage in pediatric chronic anterior uveitis patients, along with its ability to improve best-corrected visual acuity (BCVA) and inflammation parameters, its efficacy in reducing topical glucocorticosteroids (GCs) and systemic immunomodulatory therapy (IMT), and its safety profile. Methods: A self-controlled study of pediatric chronic anterior uveitis patients who presented with peripheral retinal vascular leakage on ultra-widefield fluorescein fundus angiography and underwent adalimumab treatment was conducted. The primary outcome was the extent of retinal vascular leakage at the 3- and 6-month follow-up visits. Secondary outcomes included BCVA, inflammation parameters (fresh keratic precipitates, anterior chamber cell, and vitreous cell grades), frequency of topical glucocorticosteroid eye drops, IMT load, and adverse effects at the 3- and 6-month follow-up visits. Results: Twenty patients with a mean age of 9.30 ± 3.26 years old were included. The mean follow-up period was 9.0 ± 3.0 months, with all patients followed up for at least 6 months. At the 3- and 6-month follow-ups, the peripheral vascular leakage score decreased significantly (2.87, 95% CI (2.14, 3.60), p < 0.001 for 3 months, 2.75, 95% CI (1.76, 3.73), p < 0.001 for 6 months). Alongside BCVA (p = 0.013 for 3 months, p = 0.005 for 6 months) was improved significantly, inflammatory parameters represented by fresh keratic precipitates, anterior chamber cell, and vitreous cell grades were improved significantly (p < 0.001, p < 0.001, for all parameters) and topical GC usage was significantly reduced (p < 0.001, p < 0.001) at 3 and 6 months. There was also a statistically significant reduction in systemic IMT load at 6 months (p < 0.001). Adverse events in the observation period included local redness around the injection site and mild upper respiratory symptoms. Conclusion: Adalimumab could effectively alleviate peripheral vascular leakage in pediatric patients with chronic anterior uveitis. It could also be helpful in improving BCVA and inflammation parameters and decreasing topical glucocorticosteroid eye drops and systemic IMT. Adalimumab is generally safe for pediatric uveitis.

12.
J Med Chem ; 65(6): 4709-4726, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35254067

RESUMO

Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC CP17, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFRL858R/T790M and EGFRdel19, reaching the lowest DC50 values among all reported EGFR-targeting PROTACs. Furthermore, CP17 exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFRL858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Quimera/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteólise , Purinas/farmacologia
13.
Nano Lett ; 22(7): 2867-2873, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35298183

RESUMO

Comprehending and controlling the stability of glasses is one of the most challenging issues in glass science. Here we explore the microscopic origin of the ultrastability of a Cu-Zr-Al metallic glass (MG). It is revealed that the ultrastable window (0.7-0.8 Tg) of MGs correlates with the enhanced degree of nanoscale-to-mesoscale structural/mechanical heterogeneity and the connection of stability-favored clusters. On one side, the increased fraction of stability-favored clusters promotes the formation of a stable percolating network through a critical percolation transition, which is essential to form ultrastable MG. On the other side, the enhanced heterogeneity arising from an increased distribution in local clusters may promote synergistically a more efficient and frustrated packing of amorphous structure, contributing to the ultrastability. The present work sheds new light on the stability of MGs and provides a step toward next-generation MGs with superior stability and performances.

14.
J Imaging ; 8(3)2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35324614

RESUMO

This paper proposes an objective glossiness index for objects in halftone color images. In the proposed index, we consider the characteristics of the human visual system (HVS) and associate the image's structure distortion and statistical information. According to the difference in the number of strategies adopted by the HVS in judging the difference between images, it is divided into single and multi-strategy modeling. In this study, we advocate multiple strategies to determine glossy or non-glossy quality. We assumed that HVS used different visual mechanisms to evaluate glossy and non-glossy objects. For non-glossy images, the image structure dominated, so the HVS tried to use structural information to judge distortion (a strategy based on structural distortion detection). For glossy images, the glossy appearance dominated; thus, the HVS tried to search for the glossiness difference (an appearance-based strategy). Herein, we present an index for glossiness assessment that attempts to explicitly model the structural dissimilarity and appearance distortion. We used the contrast sensitivity function to account for the mechanism of halftone images when viewed by the human eye. We estimated the structure distortion for the first strategy by using local luminance and contrast masking; meanwhile, local statistics changing in the spatial frequency components for skewness and standard deviation were used to estimate the appearance distortion for the second strategy. Experimental results showed that these two mixed-distortion measurement strategies performed well in consistency with the subjective ratings of glossiness in halftone color images.

15.
ACS Appl Mater Interfaces ; 14(11): 13942-13951, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35275490

RESUMO

The development of gas sensors based on two-dimensional (2D) layered materials has received lots of focus attributing to their excellent gas sensitivity. Here, a black phosphorus (BP) gas sensor device is fabricated based on high-quality few-layered BP microribbons using a facile route. Although BP is well known to oxidize in ambient conditions, energy dispersive spectroscopy (EDS) mapping manifests that the few-layered BP microribbons undergo slight oxidation and contamination during the grinding process. It is interesting that the surface and side of BP microribbons have nanoscale thin films and step-like nanoscale thin films, respectively, owing to the in-plane slip of the few-layered BP microribbons in the process of grinding, which are different from the conventional BP bulk crystals. The layered BP microribbon gas sensor demonstrated a high response to low-concentration NO2 and a very low limit of detection (LOD) of 0.4 ppb of NO2 under N2 and air conditions, which is the lowest LOD for NO2 detection reported so far. The mechanisms for excellently sensitive detection of NO2 for the BP microribbons have been investigated by first-principles calculations combined with experiment results, revealing that the sensitization mechanisms of the BP microribbon sensor are abundant nanoscale thin films, an optimum bandgap range with optimal carrier concentration, a hierarchical homojunction structure, and strong adsorption energy to NO2. In addition, the BP microribbon sensor demonstrated high selectivity to NO2, a low LOD under a high relative humidity, and good repeatability. The reported results of the BP sensor may provide great promise for improving the performance of other 2D material-based gas sensors and may expand sensing applications.

16.
Food Chem ; 382: 132311, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35149467

RESUMO

Biomacromolecules are used to encapsulate carotenoids, but their poor absorption-enhancing ability restricts their application. This study integrated dietary fatty acids (FAs) into the protein-based encapsulation of fucoxanthin (FUCO) due to its positive role in carotenoid absorption. The results showed that of the 14 tested FAs, only myristic, palmitic, stearic, oleic, linoleic, and docosahexaenoic acid obviously promoted FUCO absorption. FAs were employed for FUCO encapsulation using bovine serum albumin (BSA) to fabricate FUCO-FA-BSA systems, with an encapsulation efficiency of > 98%, a particle size ranging from 113.1 nm to 193.5 nm, and a Zeta-potential between -32.8 mV and -38.3 mV. Electron microscopy and Fourier transform infrared spectroscopy revealed complete FUCO encapsulation, while the FUCO-loading particles exhibited a "core-shell" structure. The retention rate of the encapsulated FUCO increased 2.16-4.06 times when heated at 80.0 °C for 200 min. These results suggested that FA-BSA complexes might provide a promising strategy for embedding carotenoids.


Assuntos
Ácidos Graxos , Xantofilas , Interações Hidrofóbicas e Hidrofílicas , Soroalbumina Bovina/química , Xantofilas/química
17.
Ying Yong Sheng Tai Xue Bao ; 33(1): 76-84, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35224928

RESUMO

Forest fuels are the basis of fire occurrences, while ground dead fuels are an important part of forest fuels. Undestanding the pyrolysis characteristics and gas emissions of forest fuels is of great significance to explore the effects of forest fire on atmospheric environment and carbon balance, as well as to prevent and combat forest fire. In this study, the thermogravimetric analysis and gas emission analysis were conducted on leaf litter of six tree species (Pinus sylvestris var. mongolica, Picea koraiensis, Fraxinus mandshurica, Juglans mandshurica, Quercus mongolica, Betula platyphylla) in Heilongjiang Province to explore the pyrolysis process and combustibility of forest fuels, to analyze their pyrolysis characteristics, pyrolysis kinetics characteristics, gas emission characteristics. A four-dimensional evaluation of their combustibility was conducted based on pyrolysis parameters. The results showed that the pyrolysis temperature of holocellulose in the leaves of those six tree species ranged in 143.31-180.48 ℃ at the beginning and 345.04-394.38 ℃ at the end, lignin pyrolysis temperature ranged in 345.04-394.38 ℃ at the beginning and 582.85-609.31 ℃ at the end. The pyrolysis of the six kinds of arbor blades during the pyrolysis process affected fuel ash content, quality and temperature of the total pyrolysis. The activation energies of two main pyrolysis stages of leaves of six tree species were 18.88-27.08 kJ·mol-1 and 13.25-27.54 kJ·mol-1, respectively, and the pre-exponential factors were 3.13-26.28 min-1 and 1.30-22.55 min-1. The holocellulose activation energy and pre-exponential factor of the pyrolysis stage for P. koraiensis, F. mandshurica, Q. mongolica, and B. platyphylla were greater than that of the lignin pyrolysis stage, while the opposite was true for P. sylvestris var. mongolica and J. mandshurica. The release amounts of CO and CO2 at the pyrolysis stage of the holocellulose was 535.16-880.11 mg·m-3 and 7004.97-10302.05 mg·m-3, and that at the pyrolysis stage of lignin was 240.31-1104.67 mg·m-3 and 20425.60-33946.68 mg·m-3, respectively. The release of CO and CO2 at the pyrolysis stage of healdellulose was less, but mass loss was greater than that at the pyrolysis stage of lignin. In the four-dimensional combustibility ranking of the six tree species leaves, B. platyphylla was the best ignitable, P. koraiensis was the most combustible, and P. sylvestris var. mongolica was the most sustainable and consumable. The ignitability was significantly positively correlated with pyrolysis kinetics parameters of the holocellulose, while the sustainability was negatively correlated with that of lignin.


Assuntos
Pinus , Árvores , China , Florestas , Pirólise
18.
Hum Gene Ther ; 33(5-6): 309-317, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35018832

RESUMO

Oncolytic virus therapy is a promising novel immunotherapy. In this report, we engineered a novel oncolytic influenza virus (IV) carrying an antihuman programmed cell death 1 (PD-1) monoclonal antibody utilizing reverse genetics. A reassortant chimeric IV, named rFlu-huPD1, was synthesized as follows: the heavy chain of the PD-1 antibody was encoded on the PB1 fragment, and the light chain of the PD-1 antibody was encoded on the polymerase acid protein fragment. rFlu-huPD1 antibodies were produced in infected ovalantoic eggs and could replicate to high titers. Moreover, selective cytotoxicity of rFlu-huPD1 was upregulated in multiple hepatocellular carcinoma (HCC) cell lines compared with a control, as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the activation of T cells in the spleen of tumor-bearing BALB/c mice treated with rFlu-huPD1 was observed, especially cytotoxic CD8+ T cell activation in vivo. In addition, in a patient-derived xenograft liver cancer mouse model, tumor growth was reduced and the overall survival of the mice was increased by intratumoral injections with rFlu-huPD1 compared with wild-type PR8 virus. Taken together, these findings provide evidence for the utility of a combination of oncolytic IVs expressing PD-1 inhibitors for use in HCC virotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia Viral Oncolítica , Vírus Oncolíticos , Orthomyxoviridae , Animais , Anticorpos Monoclonais/uso terapêutico , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Camundongos , Vírus Oncolíticos/genética , Receptor de Morte Celular Programada 1/genética
19.
Epigenetics ; : 1-16, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35030986

RESUMO

The role of DNA methylation and its interplay with gene expression in the susceptibility to pancreatic cancer (PanC) remains largely unexplored. To fill in this gap, we conducted an integrative two-phase epigenome-wide association study (EWAS) of PanC using genomic DNA from 44 cases and 556 controls (20 local controls and 536 public controls in the Framingham Heart Study) in phase 1 and 23 cases and 22 controls in phase 2. We validated the findings using pre-diagnostic blood samples from 13 cases and 26 controls in the Women's Health Initiative (WHI) Study. We further examined gene expression in peripheral leukocytes of 47 cases and 31 controls involved in the methylation study using RNA sequencing and performed bidirectional Mendelian randomization (MR) analysis using existing single nucleotide polymorphism (SNP) data. In phase 1, we identified 2776 significantly differentially methylated CpG sites (DMPs) and 154 significantly differentially methylated regions (DMRs). In phase 2, we validated six DMPs (in or near AIM2, DGKA, STK39, and TNFSF8) and three DMRs (in or near nc886, LY6G5C, and HLA-DPB1). The DMR near nc886 was further validated in the WHI samples (P = 6.69 × 10-5). MR analysis suggested that the CpG sites cg00308130 and cg16684184 for nc886 and cg16875057 for STK39 were causally related to PanC susceptibility and that PanC influenced methylation of cg15354065 for DGKA. This first integrative EWAS of PanC provides novel insights into the role of DNA methylation and its interplay with SNPs and gene expression in the disease susceptibility.

20.
HGG Adv ; 3(1): 100078, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35047863

RESUMO

Pancreatic cancer is a deadly disease that accounts for approximately 5% of cancer deaths worldwide, with a dismal 5-year survival rate of 10%. Known genetic risk factors explain only a modest proportion of the heritable risk of pancreatic cancer. We conducted a whole-exome case-control sequencing study in 1,591 pancreatic cancer cases and 2,134 cancer-free controls of European ancestry. In our gene-based analysis, ATM ranked first, with a genome-wide significant p value of 1 × 10-8. The odds ratio for protein-truncating variants in ATM was 24, which is substantially higher than prior estimates, although ours includes a broad 95% confidence interval (4.0-1000). SIK3 was the second highest ranking gene (p = 3.84 × 10-6, false discovery rate or FDR = 0.032). We observed nominally significant association signals in several genes of a priori interest, including BRCA2 (p = 4.3 × 10-4), STK11 (p = 0.003), PALB2 (p = 0.019), and TP53 (p = 0.037), and reported risk estimates for known pathogenic variants and variants of uncertain significance (VUS) in these genes. The rare variants in established susceptibility genes explain approximately 24% of log familial relative risk, which is comparable to the contribution from established common susceptibility variants (17%). In conclusion, this study provides new insights into the genetic susceptibility of pancreatic cancer, refining rare variant risk estimates in known pancreatic cancer susceptibility genes and identifying SIK3 as a novel candidate susceptibility gene. This study highlights the prominent importance of ATM truncating variants and the underappreciated role of VUS in pancreatic cancer etiology.

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