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1.
Arthritis Res Ther ; 24(1): 102, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35526024

RESUMO

OBJECTIVE: Aortic valve involvement is not uncommon in patients with Takayasu arteritis (TAK) and leading to poor prognosis. The aim of our study was to explore the risk factors of aortic valve involvement and to evaluate the prognosis in TAK patients with aortic valve involvement. METHOD: In this retrospective study, 172 TAK patients were divided into groups with or without aortic valve involvement to identify the risk factors. Patients who underwent aortic valve surgical treatment were followed up to assess cumulative incidence of postoperative adverse events. RESULTS: A total of 92 TAK patients (53.49%) had aortic valvular lesion. The infiltration of inflammatory cells was found in surgical specimens of aortic valve. Numano type IIb, elevated high-sensitivity C-reactive protein (hs-CRP) level, and dilation of ascending aorta and aortic root were statistically associated with aortic valvular lesion in TAK patients (OR [95%CI] 6.853 [1.685-27.875], p=0.007; 4.896 [1.646-14.561], p=0.004; 4.509 [1.517-13.403], p=0.007; 9.340 [2.188-39.875], p=0.003). The 1-, 5-, and 7-year cumulative incidence of postoperative adverse events were 14.7%, 14.7%, and 31.8%, respectively. Surgical methods (p=0.024, hazard ratio (HR) 0.082) and postoperatively anti-inflammatory therapy (p=0.036, HR 0.144) were identified as potential predictors of postoperative adverse events. CONCLUSIONS: Regularly echocardiogram screening is suggested in patients with Numano type IIb and aggressive treatment should be performed early in TAK patients. As for TAK patients with aortic valve surgery, aortic root replacement seems to be the preferred option and regular anti-inflammatory therapy may reduce the occurrence of adverse events of them.


Assuntos
Insuficiência da Valva Aórtica , Arterite de Takayasu , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/cirurgia
2.
Int J Mol Sci ; 23(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35562879

RESUMO

Fucan sulfate I (FSI) from the sea cucumber Holothuria fuscopunctata was purified and its structure was clarified based on a bottom-up strategy. The unambiguous structures of a series of oligosaccharides including disaccharides, trisaccharides, and tetrasaccharides, which were released from mild acid hydrolysis of FSI, were identified by one-dimensional (1D)/two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. All the glycosidic bonds in these oligosaccharides were presented as α1,3 linkages confirmed by correlated signals from their 1H-1H ROESY and 1H-13C HMBC spectra. The structural sequence of these oligosaccharides formed by Fuc2S4S, Fuc2S, and non-sulfated ones (Fuc0S), along with the general structural information of FSI, indicated that the structure of FSI could be elucidated as: [-L-Fuc2S4S-α1,3-L-Fuc(2S)-α1,3-L-Fuc2S-α1,3-L-Fuc0S-α1,3-1-]n. Moreover, the L-Fuc0S-α1,3-L-Fuc2S4S linkage in FSI was susceptible to be cleaved by mild acid hydrolysis. The antioxidant activity assays in vitro showed that FSI and the depolymerized product (dFSI') had potent activities for superoxide radical scavenging activity with IC50 of 65.71 and 83.72 µg/mL, respectively, while there was no scavenging effect on DPPH, hydroxyl and ABTS radicals.

3.
Clin Rheumatol ; 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35438374

RESUMO

OBJECTIVES: It has been known that aorta, subclavian, and extracranial arteries are commonly involved in Takayasu arteritis (TA). However, the involvement of intracranial artery in TA has not been well explored. The purpose of this study was to describe the clinical characteristics of intracranial artery lesions in TA patients and identify associated risk factors. METHODS: A total of 160 patients diagnosed with TA at Beijing Anzhen Hospital from November 2012 to November 2019 were retrospectively enrolled in this study and assigned to different groups according to the presence or absence of intracranial artery lesions. RESULTS: Our data showed that 20% of the enrolled 160 patients developed intracranial artery lesions and the right internal carotid artery (ICA) was the most common involved artery (53%). The average age of patients with intracranial artery lesions was significantly older compared to that of patients without intracranial artery involvement (43.56 ± 11.40 vs 36.41 ± 12.22, p = 0.003). In addition, more patients in the intracranial artery group had concomitant disease histories of stroke and/or hypertension (p = 0.010, 0.033). Chest tightness, chest pain, palpitation, coronary artery lesions, and extracranial segment lesions of ICA were more commonly observed in patients with intracranial artery lesions (p < 0.001, 0.017, 0.015, < 0.001, 0.003). Furthermore, we discovered that patients with coronary artery involvement, extracranial segment lesions of ICA, and higher Vasculitis Damage Index (VDI) score had an increased risk of developing intracranial artery lesions (p = 0.013, 0.019, 0.019). CONCLUSION: Our study showed that the intracranial artery disease was common in TA and was associated with coronary artery lesions, extracranial segment lesions of ICA, and higher VDI score. Key Points • Intracranial artery disease in TA patients had advanced age and higher triglyceride level. • Besides coronary artery lesions, intracranial artery disease in TA patients was associated with the extracranial segment lesions of ICA and higher VDI score.

4.
Diabetes Metab Syndr Obes ; 15: 1165-1171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464260

RESUMO

Purpose: To establish a high-glucose (HG) stressed cell model and study the expression of main components of the Dll4/Notch-VEGF signaling pathway under high-glucose stimulation. Methods: A model of HG-conditioned cells (human umbilical vein endothelial cells, HUVECs) was first established, and then the expression of Dll4, Notch1, Notch4 and VEGF in HG-stressed cells with or without Notch pathway blockage was analyzed by RT-PCR and Western blot. To observe cell migration, we also evaluated the Transwell assay. Results: HUVECs stimulated with 30mmol/L HG was selected as a cell model. RT-PCR and Western blot results showed that HG stimulation induced the expression of Dll4, Notch1 and VEGF and downregulated Notch4. The expressions were reversed after Notch pathway blockage; meanwhile, the blockage of Notch pathway inhibited cell migration under HG condition. Conclusion: The function of Notch4 in responses to HG stimulation deserves further researching. Combination therapy by blocking Dll4/Notch and VEGF pathways may provide us with a new way for anti-neovascularization.

5.
Mol Nutr Food Res ; : e2100826, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35384292

RESUMO

SCOPE: Quercetin (QU) is one of the most abundant flavonoids in plants and has attracted the attention of researchers because of its remarkable antirheumatoid arthritis (RA) effects and extremely low adverse reactions. However, the underlying mechanism needs further study. METHODS AND RESULTS: Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) reveal the obvious inhibitory effects of QU on Th17 cell differentiation in arthritic mice. More importantly, QU markedly limits the development of Th17 cell polarization, which is virtually compromised by the treatment with peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662 and knockdown of PPARγ. Additionally, molecular dynamics simulation and immunofluorescence exhibit QU directly binds to PPARγ and increases PPARγ nuclear translocation. Besides, QU confers its moderation effect on suppressor of cytokine signaling protein (SOCS3)/signal transducer and activator of transcription 3 (STAT3) axis partially depending on PPARγ. Furthermore, coimmunoprecipitation shows QU redistributes the corepressor silencing mediator for retinoid and thyroid-hormone receptors (SMRT) from PPARγ to STAT3. Finally, the inhibition of Th17 response and the antiarthritic effect of QU are nullified by GW9662 treatment in arthritic mice. CONCLUSION: QU targets PPARγ and consequently inhibits Th17 cell differentiation by dual inhibitory activity of STAT3 to exert antiarthritic effect. The findings facilitate its development and put forth a stage for uncovering the mechanism of other naturally occurring compounds with chemical structures similar to QU.

6.
BMC Microbiol ; 22(1): 104, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35421928

RESUMO

BACKGROUND: Bacterial floc formation plays a central role in the activated sludge (AS) process. The formation of AS flocs has long been known to require exopolysaccharide biosynthesis. We had demonstrated that both expolysaccharides and PEP-CTERM (a short C-terminal domain includes a near-invariant motif Pro-Glu-Pro (PEP)) proteins were required for floc-forming in Zoogloea resiniphila MMB, a dominant AS bacterium. However, the PEP-CTERM proteins are not encoded in the genome of AS bacterium Shinella zoogloeoides ATCC 19623 (formerly known as Zoogloea ramigera I-16-M) and other sequenced AS bacteria strains. The mechanism underlying floc formation of Shinella and related AS bacteria remained largely unclear. RESULTS: In this study, we have sequenced and annotated the complete genome of S. zoogloeoides ATCC 19623 (aka I-16-M), previously isolated in USA and treated as the neotype for the AS floc-forming bacterium Zoogloea ramigera I-16-M, and another AS strain XJ20 isolated in China. Mariner transposon mutagenesis had been conducted to isolate floc-forming-deficient mutants in the strain ATCC 19623 as previously performed by using Tn5 transposon three decades ago. The transposon insertional sites of multiple mutants were mapped to the gene cluster for bacterial cellulose synthesis (bcs) and secretion, and the role played by these genes in floc-formation had been further confirmed by genetic complementation. Interestingly, the restriction map of this bcs locus-flanking region was highly similar to that of the previously identified DNA fragment required for floc-formation in 1980s. Cellulase treatment abolished the floc-forming phenotype of S. zoogloeoides ATCC 19623 but not that of Z. resiniphila MMB strain. The FTIR spectral analyses revealed that the samples extracted from S. zoogloeoides ATCC 19623 were cellulose polymer. CONCLUSION: Our results indicated that we have largely reproduced and completed the unfinished pioneering work on AS floc-formation mechanism, demonstrating that the floc-formation and flocculating capability of Shinella were mediated by extracellular cellulose polymers.


Assuntos
Rhizobiaceae , Esgotos , Celulose , Esgotos/microbiologia , Zoogloea
7.
Environ Pollut ; 305: 119325, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35439598

RESUMO

The Nanfei River was one of dominant inflowing rivers of the fifth largest freshwater Chaohu Lake in China, which had been subjected to increasing nutrients and contaminants from population expansion, rapid industrialization and agricultural intensification in recent decades. In present study, surface sediment from the Nanfei River was collected to investigate the anthropogenic impact on distribution and bioavailability of heavy metals. Possible Cd sources along the river were constrained by using Cd isotope signatures and labile concentrations of heavy metals in sediment were determined through the DGT technique for risk assessment. Results showed that Cd in river sediment showed greatest enrichment (EF 0.8-9.4), indicating massive pollution from anthropogenic activities. Among the various possible Cd source materials, urban road dust, industrial soil and chicken manure, displayed higher Cd abundance and enrichment that might contribute to Cd accumulation in river sediment. Cadmium isotopic composition in river sediment was ranged from -0.21 ± 0.01‰ to 0.13 ± 0.03‰, whereas yielded relative variation from -0.31 ± 0.02‰ to 0.23 ± 0.01‰ in source materials. Accordingly, Cd sources along the river were constrained, i.e. traffic and industrial activities in the upper and middle reaches whereas agricultural activities in the lower reaches. Furthermore, the evaluation on ecological risk of heavy metals in sediment on basis of SQGs and DGT-labile concentrations demonstrated that Pb and Zn might pose higher risk on aquatic species. The present study confirmed that Cd isotopes were promising source tracer in environmental studies.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Cádmio , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Isótopos , Metais Pesados/análise , Medição de Risco , Rios , Poluentes Químicos da Água/análise
8.
Environ Pollut ; 304: 119232, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35364188

RESUMO

Combining biochar with irrigation management to alter the microbial community is a sustainable method for remediating soils contaminated by heavy metals. However, studies on how these treatments promote Cr(VI) reduction are limited, and the corresponding microbial mechanisms are unclear. Therefore, we conducted a pot experiment to explore the responses of soil microbial communities to combined biochar amendment and irrigation management strategies and their involvement in Cr transformation in paddy soils. Six treatments were established using varying concentrations of biochar (0, 1, and 2% [w/w]) combined with two irrigation management strategies (continuous flooding [CF] and dry-wet alternation [DWA]). The results showed that the combined biochar addition and irrigation management strategy significantly altered soil pH, redox potential, organic matter content, and Fe(II) and sulfide concentrations. In addition, the Cr(VI) concentration under CF irrigation management was conspicuously lower (48.2-54.4%) than that under DWA irrigation management. Biochar amendment also resulted in a substantial reduction (8.8-27.4%) in Cr(VI) concentration. Moreover, the changes in soil physicochemical properties remarkably affected the soil microbial community. The microbial diversity and abundance significantly increased with biochar amendment. Furthermore, the combined biochar amendment and CF strategy stimulated the growth of Geobacter- and Anaeromyxobacter-related Fe(III)-reducing bacteria, Gallionella-related Fe(II)-oxidizing bacteria, and Desulfovibro- and Clostridium-related sulfate-reducing bacteria, which simultaneously facilitated the generation of Fe(II) and sulfide, thereby enhancing Cr(VI) reduction. Consequently, our results suggest that the effectively increased abundance of Fe-reducing/oxidizing bacteria and sulfate-reducing bacteria via combined CF irrigation management and biochar addition may be a key factor in reducing Cr(VI) in paddy soil. The keystone genera responsible for Cr(VI) reduction were Geobacter, Anaeromyxobacter, Gallionella, Desulfovibro, and Clostridium. This study provides novel insights into the coupling mechanism of the Fe/S/Cr transformation mediated by Fe-reducing/oxidizing bacteria and sulfate-reducing bacteria.


Assuntos
Geobacter , Microbiota , Oryza , Poluentes do Solo , Bactérias , Carvão Vegetal/química , Compostos Férricos , Compostos Ferrosos , Oxirredução , Solo/química , Poluentes do Solo/análise , Sulfatos , Sulfetos
9.
Parasit Vectors ; 15(1): 141, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449112

RESUMO

BACKGROUND: Microsporidia are a group of intracellular parasitic eukaryotes, serious pathogens that cause widespread infection in humans, vertebrates, and invertebrates. Because microsporidia have a thick spore wall structure, the in vitro transformation, cell culture, and genetic operation technology of microsporidia are far behind that of other parasites. METHODS: In this study, according to an analysis of the life-cycle of microsporidia, Nosema bombycis, and different electro-transformation conditions, the transduction efficiency of introducing foreign genes into N. bombycis was systematically determined. RESULTS: We analyzed the direct electro-transformation of foreign genes into germinating N. bombycis using reporters under the regulation of different characteristic promoters. Furthermore, we systematically determined the efficiency of electro-transformation into N. bombycis under different electro-transformation conditions and different developmental stages through an analysis of the whole life-cycle of N. bombycis. These results revealed that foreign genes could be effectively introduced through a perforation voltage of 100 V pulsed for 15 ms during the period of N. bombycis sporeplasm proliferation. CONCLUSIONS: We present an effective method for electro-transformation of a plasmid encoding a fluorescent protein into N. bombycis, which provides new insight for establishing genetic modifications and potential applications in these intracellular parasites.


Assuntos
Bombyx , Nosema , Animais , Bombyx/metabolismo , Eletroporação , Humanos , Nosema/metabolismo , Esporos Fúngicos/genética , Esporos Fúngicos/metabolismo
10.
Virol Sin ; 37(1): 19-29, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35234619

RESUMO

After dengue virus (DENV) infection, antibody-dependent enhancement (ADE) is easy to occur when the neutralizing antibody (NAb) gradually decreases to a sub-neutralizing concentration. In this cohort surveillance, we utilized sera samples collected from dengue fever patients at different convalescent phases in Jinghong City, to investigate the dynamic change rule of DENV-specific antibodies, and to analyze the risk of ADE caused by secondary infection with heterologous serotypes DENVs. For baseline serosurvey, 191 four-year and 99 six-year sera samples during convalescence were collected in 2017 and 2019, respectively. The positive rate of DENV-specific immunoglobulin G was 98.4% in 2017, which significantly decreased to 82.8% in 2019. The geometric mean titer (GMT) of NAb decreased from 1:155.35 to 1:46.66. Among 290 overall samples, 73 paired consecutive samples were used for follow-up serosurvey. In four-year sera, the GMTs of NAb against DENV-3 and cross-reactive antibodies against DENV-1, DENV-2 and DENV-4 were 1:167.70, 1:13.80, 1:18.54 and 1:45.26, respectively, which decreased to 1:53.18, 1:10.30, 1:14.60 and 1:8.17 in six-year sera. In age-stratified analysis, due to the increasing number of ADE positive samples from 2017 to 2019 in 31-40 and 51-60 years groups, the risk of ADE in DENV-4 infection was positively associated with the extension of convalescent phase, and the odd ratio was higher than other groups. With the recovery period lengthened, the risk of secondary infection with DENV-1 and DENV-2 was reduced. Our results offer essential experimental data for risk prediction of severe dengue in hyper-endemic dengue areas, and provide crucial scientific insight for the development of effective dengue vaccines.


Assuntos
Vírus da Dengue , Dengue , Dengue Grave , Anticorpos Neutralizantes , Anticorpos Antivirais , China/epidemiologia , Humanos , Estudos Soroepidemiológicos
11.
J Healthc Eng ; 2022: 7339930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251574

RESUMO

This paper proposes a representation learning framework HE-LSTM model for heterogeneous temporal events, which can automatically adapt to the multiscale sampling frequency of multisource heterogeneous data. The proposed model also demonstrates its superiority over other typical approaches on real data sets. A controlled study is performed according to computerized randomization, with 38 patients in each of the two groups. The study group has a higher resuscitation success rate and patient satisfaction than the conventional group (P < 0.05), and the time from the first consultation to the completion of the first ECG, the time from the completion of the ECG to the activation of the path lab, and the time from the emergency admission to the balloon dilation were significantly shorter in the study group than in the conventional group (P < 0.05). The emergency care process reengineering intervention helps patients with acute myocardial infarction to be treated quickly and effectively, thus improving their resuscitation success rate and satisfaction rate, and is worthy to be caused in the clinic and widely applied.


Assuntos
Aprendizado Profundo , Serviços Médicos de Emergência , Infarto do Miocárdio , Eletrocardiografia , Humanos , Infarto do Miocárdio/terapia , Encaminhamento e Consulta , Fatores de Tempo
12.
Oncogene ; 41(17): 2480-2491, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35314790

RESUMO

The tumor microenvironment (TME) was usually studied in tumor tissue and in relation to only tumor progression, with little involved in occurrence, recurrence and metastasis of tumor. Thus, a new concept "peritumor microenvironment (PME)" was proposed in the proteomic characterization of peritumor liver tissues in human hepatocellular carcinoma (HCC). The PME for occurrence (PME-O) and progression (PME-P) were almost totally different at proteome composition and function. Proteins for occurrence and progression rarely overlapped and crossed. Immunity played a central role in PME-O, whereas inflammation, angiogenesis and metabolism were critical in PME-P. Proteome profiling identified three PME subtypes with different features of HCC. Thymidine phosphorylase (TYMP) was validated as an antiangiogenic target in an orthotopic HCC mouse model. Overall, the proteomic characterization of the PME revealed that the entire processes of HCC occurrence and progression differ substantially. These findings could enable advances in cancer biology, diagnostics and therapeutics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Proteoma/metabolismo , Proteômica , Microambiente Tumoral
13.
Huan Jing Ke Xue ; 43(3): 1159-1169, 2022 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-35258180

RESUMO

In order to explore the chemical composition and source profiles of atmospheric particulate matter in winter in the northern area of Handan, a heavily polluted city in the southern part of North China, PM1 and PM2.5 samples were collected and analyzed from November 23 to December 12, 2020. During the observation period, the daily average ρ(PM1)and ρ(PM2.5) were 114.53 µg·m-3 and 124.25 µg·m-3, respectively, and the ratio of PM1/PM2.5 was 83.3%-95.3%, which was significantly higher than those of other cities in the Beijing-Tianjin-Hebei region, indicating that air pollution of fine particulate matter, especially sub-micron particulate matter, was more serious in Handan. Compared with that during clean days, SNA (SO42-, NO3-, and NH4+) in PM1 increased by 14.5% during heavy pollution, and SNA in PM2.5 increased by 15.2%; the nitrogen oxidation rate (NOR) in particular increased by three times on heavy pollution days. With the deepening of pollution, the proportion of secondary organic carbon (SOC) in PM1 and PM2.5 increased by 22.0% and 12.5%, respectively. SOC tended to accumulate in small particles, whereas the proportion of primary organic carbon (POC) and elemental carbon (EC) in PM1 decreased by 15.4% and 6.6%, and the POC and EC in PM2.5 decreased by 8.2% and 4.3%, respectively. The above results indicated that secondary formation played an important role in the heavy pollution of particulate matter. With the aggravation of air pollution, the liquid water content of the particles increased, and both the sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) increased, indicating that the aqueous phase chemical reaction made an important contribution to the formation of secondary inorganics. With the deepening of pollution, inorganic elements were on the rise; Se, As, Pb, and Zn were highly enriched in inorganic elements. The results of principal component analysis (PCA) showed that secondary formation, industrial emissions, vehicle exhaust, and biomass burning emissions were the main sources of particulate pollutants. The results of potential source contribution factor analysis (PSCF) showed that the high value areas of SO42-, NO3-, EC, OC, and inorganic elements were mainly from the north and southwest directions of the observation area.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano , Emissões de Veículos/análise
14.
Cell Death Dis ; 13(2): 130, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136014

RESUMO

Although there are many studies on the relationship between genetic polymorphisms and the incidence of diseases, mechanisms are rarely known. We report the mechanism by which signal transducer and activator of transcription 4 (stat4) rs7574865 promotes the occurrence and progression of hepatocellular carcinoma (HCC). We found that the GG genotype at stat4 rs7574865 was a risk genotype, and STAT4 levels in serum and peritumoral tissue from HCC patients with the GG genotype were significantly higher than those found in TT or TG carriers. Furthermore, HCC patients with the GG genotype or elevated STAT4 levels had poor prognoses. In vitro experiments demonstrated that STAT4 silencing promoted apoptosis and inhibited the invasion and migration of HepG2 and L02 cells. Proteomic analysis of HCC peritumors identified 273 proteins related to STAT4, of which CYP2E1 activity and FGL2 content exhibited the highest positive correlation. The relationship between CYP2E1 and FGL2 was also confirmed in cyp2e1-/- mice and in CYP2E1 inhibitor-treated mice. In conclusion, this study elucidates the mechanism by which the stat4 rs7574865 polymorphism promotes the occurrence and progression of HCC via the Stat4/CYP2E1/FGL2 pathway.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Fator de Transcrição STAT4 , Animais , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Fibrinogênio/metabolismo , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Camundongos , Polimorfismo de Nucleotídeo Único , Proteômica , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/metabolismo
15.
Sci Total Environ ; 826: 154021, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35202691

RESUMO

Crop productivity maximization while minimizing carbon emissions is of critical importance for achieving sustainable agriculture. Socio-economic and ecological benefits should be taken together under the circumstance of stagnant farming profitability and climatic variability. The effectiveness of various mulching strategies in rain-fed semiarid areas has been confirmed, but scarce the comprehensive evaluations of the conventional and new mulching strategies in terms of yield, economic benefit, and carbon footprint based on life cycle assessment (LCA) have been conducted. Hence, a two-year field experiment was conducted on maize (Zea mays L.) crop to explore the effects of four mulching strategies (PM: plastic-film mulching, SM: maize straw mulching, BM: biodegradable-film mulching, and NM: no mulching) on the yield, net return, greenhouse gas (GHG) emissions, and carbon footprint (CF). The results revealed that PM and BM significantly increased maize yield by 11.3-13.3% and 9.4-10.6%. PM marginally raised the net return by 2.0-2.4% whereas BM slightly reduced it by 4.6-8.8% relative to NM. Unexpectedly, the yield and net return were the lowest under SM, and intensified N2O emissions, GWPdirect, and yield-scaled GWPdirect were observed. When the GHGs using LCA concept and SOC sequestration rate were considered, the lowest net GWP (1804.1-1836.4 kg CO2-eq ha-1) and CF (148.9-119.9kg CO2-eq t-1) were observed in the SM treatment due to the boost of soil organic carbon (SOC) sequestration. Conversely, PM and BM significantly increased the net GWP and CF compared to NM. When the tradeoffs between the high production, high net return and low net GWP were assessed by an integrated evaluation framework, the NM was recommended as an efficient low-carbon agricultural practice in the rain-fed semiarid areas.


Assuntos
Pegada de Carbono , Zea mays , Agricultura/métodos , Carbono , Dióxido de Carbono , China , Fertilizantes/análise , Solo
16.
J Transl Med ; 20(1): 88, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35164791

RESUMO

The effect of the cytochrome P450 oxidoreductase (POR) rs10954732 (G > A) polymorphism on hepatocellular carcinoma (HCC) susceptibility is unknown. Here we found that A allele carriers showed a 69% decrease in susceptibility to HCC with overall survival (OS) prolonged to 199%, accompanied by lower activity for cytochrome P450 2E1. A total of 222 differentially expressed proteins were mainly enriched in neutrophil and T cell activation and involved in the immune and inflammatory responses, constituting the altered immune tumor microenvironment related with A allele by proteomics analysis. Hepsin (HPN) showed significant down-regulation in HCC and up-regulation in A allele carriers. A lower HPN level was associated with increased susceptibility to HCC and a worse prognosis. Moreover, HPN is a potential independent prognostic biomarker for HCC and is strongly associated with clinicopathological features, tumor-infiltrating status of immune cells both in our discovery cohort and database surveys. Our findings provide a new potential mechanism by which HPN may play an important role in the susceptibility of rs10954732 A allele carriers to HCC and their prognosis through tumor immune infiltration, thus offering potential insights for future studies on tumor immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/metabolismo , Sistema Enzimático do Citocromo P-450 , Humanos , Neoplasias Hepáticas/metabolismo , Prognóstico , Proteômica , Serina Endopeptidases , Microambiente Tumoral/genética
17.
Nat Commun ; 13(1): 823, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35145088

RESUMO

Buffalo is an important livestock species. Here, we present a comprehensive metagenomic survey of the microbial communities along the buffalo digestive tract. We analysed 695 samples covering eight different sites in three compartments (four-chambered stomach, intestine, and rectum). We mapped ~85% of the raw sequence reads to 4,960 strain-level metagenome-assembled genomes (MAGs) and 3,255 species-level MAGs, 90% of which appear to correspond to new species. In addition, we annotated over 5.8 million nonredundant proteins from the MAGs. In comparison with the rumen microbiome of cattle, the buffalo microbiota seems to present greater potential for fibre degradation and less potential for methane production. Our catalogue of microbial genomes and the encoded proteins provides insights into microbial functions and interactions at distinct sites along the buffalo digestive tract.


Assuntos
Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Metagenoma , Animais , Bactérias/genética , Bovinos , DNA Bacteriano , Fibras na Dieta/metabolismo , Fezes/microbiologia , Feminino , Genoma Microbiano , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Metagenômica , Filogenia , RNA Ribossômico 16S/genética , Rúmen/microbiologia
18.
Nat Commun ; 13(1): 231, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017553

RESUMO

Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8+ T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.


Assuntos
Butirofilinas/genética , Butirofilinas/metabolismo , Interleucina-17/metabolismo , Linfócitos T/metabolismo , Evasão Tumoral/fisiologia , Animais , Linfócitos T CD8-Positivos/imunologia , Antígeno CTLA-4 , Feminino , Expressão Gênica , Células HEK293 , Humanos , Imunoterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias , Linfócitos T Citotóxicos/imunologia , Microambiente Tumoral
19.
Hepatol Int ; 16(1): 183-194, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35037228

RESUMO

BACKGROUND: No reports exist regarding the prevalence of different Na levels and their relationship with 90-day prognosis in hospitalized patients with acute-on-chronic liver disease (AoCLD) in China. Therefore, the benefit of hyponatremia correction in AoCLD patients remains unclear. METHODS: We prospectively collected the data of 3970 patients with AoCLD from the CATCH-LIFE cohort in China. The prevalence of different Na levels (≤ 120; 120-135; 135-145; > 145) and their relationship with 90-day prognosis were analyzed. For hyponatremic patients, we measured Na levels on days 4 and 7 and compared their characteristics, based on whether hyponatremia was corrected. RESULTS: A total of 3880 patients were involved; 712 of those developed adverse outcomes within 90 days. There were 80 (2.06%) hypernatremic, 28 (0.72%) severe hyponatremic, and 813 (20.95%) mild hyponatremic patients at admission. After adjusting for all confounding factors, the risk of 90-day adverse outcomes decreased by 5% (odds ratio [OR] 0.95; 95% confidence interval [CI] 0.93-0.97; p < 0.001), 24% (OR 0.76; 95% CI 0.70-0.84; p < 0.001), and 42% (OR 0.58; 95% CI 0.49-0.70; p < 0.001) as Na level increased by 1, 5, and 10 mmol/L, respectively. Noncorrection of hyponatremia on days 4 and 7 was associated with 2.05-fold (hazard ratio [HR], 2.05; 95% CI, 1.50-2.79; p < 0.001) and 1.46-fold (HR 1.46; 95% CI 1.05-2.02; p = 0.028) higher risk of adverse outcomes. CONCLUSIONS: Hyponatremia was an independent risk factor for a poor 90-day prognosis in patients with AoCLD. Failure to correct hyponatremia in a week after admission was often associated with increased mortality. (ClinicalTrials.gov number: NCT02457637, NCT03641872). CLINICAL TRIAL NUMBERS: This study is registered at Shanghai www.clinicaltrials.org (NCT02457637 and NCT03641872).


Assuntos
Hiponatremia , Hepatopatias , China/epidemiologia , Humanos , Hiponatremia/epidemiologia , Prevalência , Prognóstico , Estudos Prospectivos , Sódio
20.
Nanoscale ; 14(3): 653-662, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35018953

RESUMO

The external quantum efficiency of a high-Al content (>0.6) AlGaN deep-ultraviolet (DUV) light-emitting diode is typically below 1% in the sub-250 nm wavelength range. One of the main reasons for this low efficiency is the fundamental properties of high-Al content AlGaN comprising the transverse-magnetic (TM)-dominant emission and low light extraction due to the total internal reflection (TIR). This work demonstrates a truncated pyramid nanostructure with fine-tuned multiple facets in an (AlN)8/(GaN)2 digital alloy to achieve highly efficient DUV emission at 234 nm. By applying nanoimprint lithography, dry and wet etching, a hexagonal truncated pyramid nanohole structure is fabricated featuring multiple crystal facets of (0001), (10-13), and (20-21) planes. These fine-tuned multiple facets act as reflecting mirrors that can effectively modulate the light propagation and extraction patterns to overcome the TIR via multiple reflections and enhanced scattering. Consequently, significant light extraction enhancements of 5.6 times and 1.1 times for TM and transverse-electric emissions are achieved in the truncated pyramid nanohole structure, respectively. The total luminous intensity of this unique nanostructure is greatly increased by 191% compared to that of a conventional planar structure. The truncated pyramid AlN/GaN nanostructure with fine-tuned multiple facets used in this work provides a promising approach for realizing highly efficient sub-250 nm DUV light-emitting devices.

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