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1.
Med Sci Monit ; 27: e927577, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386384

RESUMO

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a serious irreversible lung disease. The mechanism of immune checkpoint in idiopathic pulmonary fibrosis is still unknown. MATERIAL AND METHODS First, the expression levels of PD-1/PD-L1 on the surface of CD4+ T cells and the proportion of Treg cells in IPF or controls were detected by flow cytometry. Then, expression of TGF-ß in blood samples was detected with ELISA. Moreover, a co-culture system was composed of fibroblasts stimulated by TGF-ß and CD4+ T cells from healthy people. The proportions of Treg cells and PD-1 in the co-culture system were detected. In addition, we detected the proportion of Treg cells and the level of collagen-1 after adding PD-1 or PD-L1 protein antibody blocker to the co-culture system. RESULTS Flow cytometry revealed the upregulated expression of PD-1/PD-L1 in CD4+ T cells of IPF patients. PD-1 appears to inhibit the differentiation of CD4+ T cells into Treg cells. Co-culture of myofibroblasts and CD4+ T cells induced the generation of collagen-1 and reduced the proliferation of CD4+ T cells. When PD-1 was blocked, the inhibition of Treg cell differentiation was reversed, accompanied by decreased collagen-1 production. CONCLUSIONS This work identified the molecular mechanism of PD-1 in patients with IPF. It may provide a new perspective on the therapeutic effect of PD-1.

2.
Environ Pollut ; 273: 116448, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33486256

RESUMO

Emerging contaminants (ECs), a group of relatively low-concentration but high-toxicity pollutants in the environment, have attracted widespread attention in recent years. These trace pollutants can be enriched in organisms and finally transferred to human bodies, posing a potential hazard to public health. Biochar, a low-cost and high-efficiency adsorbent, has been used to treat ECs in water. However, due to certain limitations of pristine biochar, such as poor adsorption capacity, narrow adsorption range, and other shortcomings, it is necessary to modify biochar to improve its applications in water treatment for ECs. Currently, there are a lot of reports on the removal of ECs from water by modified biochar. These studies explored different modification methods to functionalize biochar with various physicochemical properties, which resulted in distinct adsorption effects, behaviors and mechanisms of modified biochar on different ECs. There is a need to systematically review and digest the knowledge on the adsorption of ECs on modified biochar. In this review, recent biochar modification methods used in ECs removal are firstly summarized, and the adsorption performance and mechanisms of modified biochar on typical ECs are then systematically reviewed. Finally, the main research directions and trends, as well as recommendations and suggestions for future development are pointed out.

3.
J Biomater Appl ; : 885328220988419, 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33487068

RESUMO

The multiple diagnosis and treatment mechanisms of chemotherapy combined with photothermal/photodynamic therapy have very large application prospects in the field of cancer treatment. Therefore, in order to achieve effective and safe antitumour treatment, it is necessary to design an intelligent responsive polymer nanoplatform as a drug delivery system. Herein, the thermosensitive poly-N-isopropylacrylamide (PNIPAM) nanogel particles were prepared by soap-free emulsion polymerization and loaded with a large amount of photosensitizer indocyanine green (ICG) and anticarcinogen 5-fluorouracil (5-Fu), which effectively to realize the cooperative chemotherapy and photothermal/photodynamic therapy for tumours. The 5-Fu@ICG-PNIPAM nanogels significantly improved the bioavailability of the drug and achieved controlled release. In addition, under near-infrared laser (NIR) irradiation at 808 nm, 5-Fu@ICG-PNIPAM nanogels generated lots of heat and reactive oxygen, which significantly enhanced cellular uptake and in vitro antitumour treatment effects. The results showed that 5-Fu@ICG-PNIPAM nanogels were effectively endocytosed by HeLa cells, which also enhanced the drug's entrance into the nucleus. Moreover, compared with alone chemotherapy or photothermal/photodynamic therapy, 5-Fu@ICG-PNIPAM nanogels significantly increased cytotoxicity under NIR irradiation, suggesting that chemotherapy and photothermal/photodynamic synergistic therapy had excellent antitumour properties. Therefore, this temperature-responsive nanogel platform probably has great application prospects in clinical antitumour treatment.

4.
Free Radic Biol Med ; 163: 356-368, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33385540

RESUMO

Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-α phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.

5.
J Agric Food Chem ; 69(2): 846-858, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33405917

RESUMO

Tan is a local fat-tail sheep that is famous for its great eating quality but with little attention to its meat metabolome. The aim of this study was to investigate Tan-lamb meat metabolome as well as the key rumen bacteria related to the beneficial compound deposition in the muscle using untargeted and targeted metabolomics under different feeding regimes: indoor feeding (F), artificial pasture grazing with indoor feeding (GF), and pure artificial pasture grazing (G). The untargeted metabolome was detected by ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Ruminal bacterial communities were detected by 16S rRNA sequencing. Using untargeted metabolomics, the main three altered metabolic pathways in the lamb, including amino acid, lipid, and nucleotide metabolisms, were found in the G group compared to the GF and F groups. Increased N-acetyl-l-aspartic acid, N-acetylaspartylglutamate, acetylcarnitine, and l-carnitine, but decreased carnosine and creatinine, were the main newly found G group-associated metabolites, which might contribute to the improved lamb meat functional quality. Compared to the F group, the G group feeding increased the contents of sweet amino acids (e.g., glycine, alanine, serine, and threonine) and umami amino acids (e.g., glutamic acid and aspartic acid) in the muscle, and G and GF groups increased the level of meat polyunsaturated fatty acid (PUFA), especially the concentration of n3 PUFA, and reduced n6/n3 in the muscle by targeted metabolomics. The abundance of ruminal Moryella was decreased, and Schwartzia and Anaeroplasma were increased in the G group, which were both strongly correlated with the n3 PUFA and other functional compounds in the muscle of lambs. In conclusion, artificial pasture grazing modified the meat amino acid and fatty acid composition as well as the related biological pathways through rescheduling the rumen bacterial community, which would be a better selection for production of healthier lamb meat products.

6.
Public Health Nutr ; : 1-23, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33472711

RESUMO

OBJECTIVE: We aimed to investigate whether dietary patterns were associated with the risk of type 2 diabetes (T2DM) or pre-diabetes in adults of rural area in Henan. DESIGN: Cross-sectional study. Principal component analysis was used to identify dietary patterns, while multivariate logistic regression analysis and restricted cubic spline regression models were used to analyze the association between dietary patterns and both pre-diabetes and T2DM. SETTING: Rural area of Henan province, China. PARTICIPANTS: A total of 38779 adults aged 18-79 years were recruited from the Henan rural cohort study as the subjects. RESULTS: The prevalence of pre-diabetes and T2DM in rural Henan was 6.8% and 9.4%, respectively. A total of three dietary patterns were assessed in the present study. Dietary patternⅠwith a high intake of red meat and white meat; dietary pattern Ⅱwith a high intake of grains, nuts, milk and eggs; and dietary pattern Ⅲ with a high intake of vegetables, staple food and fruits. The highest quintile (Q5) of pattern Ⅲ could reduce 32.7% risk of pre-diabetes. The Q5 of patternⅡshowed a 15.5% decreased risk of T2DM, in an U-shaped dose-response manner; meanwhile, the Q5 of pattern Ⅲ were significantly associated with reduced risks of T2DM (OR: 0.582, 95% CI: 0.497-0.682). CONCLUSIONS: Pattern Ⅲ is beneficial for reducing risk of pre-diabetes or T2DM. Though a higher consumption of "grains-nuts-egg" may associate with a reduced risk of T2DM, excessive intakes should be avoided. This study may provide a reference for the prevention of diabetes on dietary precautions.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119442, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33461141

RESUMO

In this work, the interaction between ferulic acid (FA) and pepsin was explored by UV-visible absorption spectroscopy, fluorescence spectroscopy, synchronous fluorescence, circular dichroism (CD) spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and molecular docking. The results of fluorescence revealed that FA had a strong ability to quench the intrinsic fluorescence of pepsin through a static quenching procedure. The binding constant and the number of binding sites were determined. Thermodynamic dates and docking information suggest that FA combine with pepsin is mainly driven via electrostatic force. It also requires synergistic drive of hydrophobic and hydrogen bonding. The consequences from UV-Vis, synchronous, CD and FT-IR spectra measurements manifested that the secondary structure of pepsin was changed and the microenvironments of certain amino acid residues was modulated by the binding of FA. FA induced conformational changes in pepsin. The ß-sheet, α-Helix, and Random fractions of pepsin increased and the ß-turn decreased with the treatment of FA. In addition, analysis of pepsin activity assay measurements confirmed that FA reduced enzymatic activity of pepsin within the investigated concentrations. This work studied the inhibitory effects and revealed mechanisms of the interaction between FA and pepsin in vitro, and suggested that FA could be a potential component to affect the structure and properties of digestive enzyme.

8.
Nano Lett ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464087

RESUMO

Phase transformation is an effective means to increase the ductility of a material. However, even for a commonly observed face-centered-cubic to hexagonal-close-packed (fcc-to-hcp) phase transformation, the underlying mechanisms are far from being settled. In fact, different transformation pathways have been proposed, especially with regard to nucleation of the hcp phase at the nanoscale. In CrCoNi, a so-called medium-entropy alloy, an fcc-to-hcp phase transformation has long been anticipated. Here, we report an in situ loading study with neutron diffraction, which revealed a bulk fcc-to-hcp phase transformation in CrCoNi at 15 K under tensile loading. By correlating deformation characteristics of the fcc phase with the development of the hcp phase, it is shown that the nucleation of the hcp phase was triggered by intrinsic stacking faults. The confirmation of a bulk phase transformation adds to the myriads of deformation mechanisms available in CrCoNi, which together underpin the unusually large ductility at low temperatures.

9.
J Orthop Sci ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33419627

RESUMO

BACKGROUND: The precise prediction of ideal lumbar lordosis (LL) has become increasingly important in clinical practice. The aim of this study was to explore the regulatory mechanisms of sagittal spinopelvic alignment and to predict ideal LL based on individual pelvic incidence (PI) and thoracic kyphosis (TK) parameters in asymptomatic adults. METHODS: A total of 233 asymptomatic subjects older than 18 years were consecutively enrolled in our study between April 2017 and December 2019. A full-spine, standing X-ray was performed for each subject. The following parameters were measured in the sagittal plane: the apex of lumbar lordosis (LLA), the distance between the plumb line of the lumbar apex (LAPL) and the gravity plumb line, the inflection point (IP), LL, the upper arc and lower arc of lumbar lordosis (LLUA and LLLA, respectively), PI and TK. Stepwise multiple linear regressions were conducted, and the statistical significance level was P < 0.05. RESULTS: Both PI and TK were two important predictive variables for LLA, LAPL, IP and LL. In addition, the LLUA was mainly explained by TK, while the LLLA was explained by PI. The corresponding predictive models are listed as follows: LLA = 17.110 - 0.040∗PI + 0.023∗TK (R2 = 0.380), LAPL = 31.296 + 0.467∗PI - 0.126∗TK (R2 = 0.309), IP = 10.437 + 0.091∗TK - 0.029∗PI (R2 = 0.227), LL = 2.035 + 0.618∗PI + 0.430∗TK (R2 = 0.595), LLUA = 0.893 + 0.418∗TK (R2 = 0.598), LLLA = 3.543 + 0.576∗PI (R2 = 0.433). CONCLUSION: The specific sagittal lumbar profile should be regulated by both pelvic and thoracic morphology. Such predictive models for lumbar parameters determined by individual PI and TK parameters have been established, which are meaningful for surgeons to better understand the regulatory mechanisms of sagittal spinopelvic alignment and reconstruct a satisfactory lumbar alignment.

10.
Pathogens ; 10(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450871

RESUMO

Antimicrobial resistance (AMR) in bovine respiratory disease (BRD) is an emerging concern that may threaten both animal and public health. Rapid and accurate detection of AMR is essential for prudent drug therapy selection during BRD outbreaks. This study aimed to develop a multiplex quantitative real-time polymerase chain reaction assay (qPCR) to provide culture-independent information regarding the phenotypic AMR status of BRD cases and an alternative to the gold-standard, culture-dependent test. Bovine clinical samples (297 lung and 111 nasal) collected in Nebraska were subjected to qPCR quantification of macrolide (MAC) and tetracycline (TET) resistance genes and gold-standard determinations of AMR of BRD pathogens. Receiver operating characteristic curve analysis was used to classify AMR based on the qPCR results. For lung tissues, the qPCR method showed good agreement with the gold-standard test for both MACs and TETs, with a sensitivity of 67-81% and a specificity higher than 80%. For nasal swabs, qPCR results passed validation criteria only for TET resistance detection, with a sensitivity of 88%, a specificity of 80% and moderate agreement. The culture-independent assay developed here provides the potential for more rapid AMR characterization of BRD cases directly from clinical samples at equivalent accuracy and higher time efficiency compared with the gold-standard, culture-based test.

11.
ACS Biomater Sci Eng ; 7(1): 311-321, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33455202

RESUMO

Intrauterine adhesions (IUA) often occur as a result of trauma to the basal layer after curettage, postpartum hemorrhage, or surgical miscarriage. Endometrial fibrosis is the primary pathological feature of IUA. The characteristic features of IUA include excessive deposition and reorganization of the extracellular matrix, replacing the normal endometrium. To prevent uterine fibrosis after injury, we prepared and evaluated a type of fibroblast suppressive hydrogel. Poly(ethylene glycol)-b-poly(l-phenylalanine) (PEBP) copolymers were successfully synthesized by ring opening polymerization of l-Phenylalanine N-carboxyanhydride, initiated by methoxy-poly(ethylene glycol)-amine. Injectable PEBP/PEG hydrogels were subsequently formed through π-π accumulations between PEBP macromolecules and hydrogen bonds among PEBP, PEG, and H2O molecules. PEBP/PEG hydrogel could suppress the proliferation of fibroblasts due to the action of l-Phe, released sustainably from PEBP/PEG gels. Lastly, the in vivo preventive effect of PEBP/PEG hydrogel on fibrosis was evaluated in a rat uterine curettage model. It was found that PEBP/PEG hydrogel suppressed uterine fibrosis caused by curettage and promoted embryo implantation in injured uterine by regulating the expression and interactions of transforming growth factor beta 1 (TGF-ß1) and Muc-4. PEBP/PEG hydrogels have the potential for application in uterine adhesion prevention owing to their fibrosis preventive and pregnancy promotiing effects on uterine tissue after injury.

12.
J Nanosci Nanotechnol ; 21(3): 1430-1438, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404405

RESUMO

Graphene oxide (GO) sheets attracted great attention as effectively antibacterial agents in water treatment and environmental remediation applications. In the study, the interaction of humic acid (HA) as the model of natural organic matter (NOM) with GO and their antibacterial activities against Escherichia coli (E. coli) was investigated. The interaction between GO and HA molecules was analyzed by isothermal titration calorimetry (ITC) and fluorescence spectroscopy analysis. The study demonstrated that GO reaction with HA was a spontaneously exothermic process, which enabled formation of stable and well dispersed GO-HA complex in aqueous solution. Both GO and GO-HA could significantly inhibit the growth of E. coli and present dose-dependent bactericidal property. GO and GO-HA showed more obvious antibacterial activity in saline solution than in LB broth. We suggest the surface wrinkles of GO and GO-HA could contribute to the firm wrapping of E. coli, which is the principle factor for the antibacterial activity of GO and GO-HA. Especially, GO-HA exhibit less surface wrinkles in comparison with GO, corresponding to its reduced antibacterial activity in saline solution.

13.
AAPS PharmSciTech ; 22(1): 15, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389269

RESUMO

The present study endeavored to develop orodispersible films (ODFs) containing 30 mg racecadotril for pediatric use, which focuses on improving the compliance of pediatric patients and reducing risk of choking. The challenge of this study is to prepare high drug loading ODFs with successful mechanical and physicochemical properties. Compatibilities between drug and different polymers (hydroxypropyl methylcellulose, HPMC; polyvinyl alcohol, PVA; low-substituted hydroxypropyl cellulose, L-HPC; pullulan, PU) were investigated to select stable and safe film-forming polymers. Afterwards, the study explored the maximum amount of racecadotril incorporated into PVA films and PU films. Subsequently, disintegrant (Lycoat RS720, 4-10%, w/w) and plasticizers (glycerol, 2-6%, w/w) were investigated to reduce disintegration time of PVA films and enhance the flexibility of PU films, respectively. Formulation characteristics (appearance, tensile strength, percent elongation, disintegration time, drug content, weight, thickness, pH value, moisture content, moisture uptake, and Q5min) of prepared ODFs were examined to obtain the optimal compositions of racecadotril ODFs. Differential scanning calorimetry (DSC) study, powder X-ray diffraction (XRD) study, Fourier transform infrared (FTIR) study, comparative in vitro dissolution study, and pharmacokinetic study in Beagle dogs of optimized racecadotril ODFs were then conducted. Eventually, ODFs containing 50% racecadotril, 38% PVA, 7% Lycoat RS720, 2% sucralose, 2% apricot, and 1% titanium dioxide could achieve desirable mechanical properties, disintegrating within a few seconds and releasing more than 85% drug within 5 min in four dissolution media. An in vivo study showed optimized racecadotril ODF and Hidrasec were bioequivalent in Beagle dogs. In summary, ODFs containing 30 mg racecadotril were successfully prepared by solvent casting method, and it was suitable for the administration to the pediatric patients.

14.
Int J Cancer ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403690

RESUMO

Pseudomyxoma peritonei (PMP) is a rare disorder with unique pathological and genetic changes. Although several studies have reported the clinical features and mutational changes of PMP that originates from the appendix, few studies on PMP originating from the ovary have been reported due to its extreme rarity. In order to characterize the somatic mutational landscape and to investigate the prognosis predicting factors of ovary-originating PMP, we examined 830 cases of PMP and identified 16 patients with PMP that originated from the ovary. Whole-exome sequencing (WES) was performed on 12 cases using formalin-fixed, paraffin-embedded (FFPE) tissue samples. We found that 25% (3/12) of the patients carried mutations in cancer driver genes, including TP53, ATM and SETD2, and 16.7% (2/12) of the patients carried mutations in cancer driver genes, including ATRX, EP300, FGFR2, KRAS, NOCR1 and RB1. The MUC16 (58.33%), BSN (41.67%), PCNT (41.67%), PPP2R5A (41.67%), PRSS36 (41.67%), PTPRK (41.67%) and SBF1 (41.67%) genes presented the highest mutational frequencies. The PI3K-Akt signaling pathway, human papillomavirus infection pathway, cell skeleton, cell adhesion, and extracellular matrix and membrane proteins were the major pathways or functions that were affected. Patients were followed up to 174 months (median: 48.26 months). The 5-year OS rate for all patients was 71.2% and the median OS was not reached. PTPRK mutations, presurgical CA199 level, completeness of cytoreduction (CCR) and peritoneal cancer index (PCI) were identified as potential predictive factors for patient survival. In conclusion, the mutational landscape for ovary-originating PMP was revealed and exhibited unique features distinct from appendix-originating PMP. PTPRK, CA199, CCR and PCI may predict patient survival.

15.
Hum Vaccin Immunother ; : 1-5, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33428528

RESUMO

Invasive meningococcal disease causes significant morbidity and mortality worldwide, with serogroup B being one of the predominant serogroups in Australia for many years. The South Australian (SA) State Government recently funded the introduction of a 4CMenB vaccination program for infants, children and adolescents. In addition to protecting against invasive meningococcal disease, emerging evidence suggests the 4CMenB vaccine may also be effective against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. The proposed project aims to evaluate the effectiveness of the SA 4CMenB vaccination program against invasive meningococcal disease and gonorrhoea through a combination of observational studies using routine surveillance and research data. The main methodological approaches involve an interrupted time series regression model, screening, and case-control analyses with different sets of controls to estimate vaccine impact and effectiveness. These analyses are designed to minimize potential biases inherent in all observational studies and to provide critical data on the effectiveness of the 4CMenB vaccine against two diseases of major global public health concern.

16.
Mol Biol Rep ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33439410

RESUMO

BAP31 is a ubiquitously expressed integral membrane protein of the endoplasmic reticulum. BAP31 is involved in various biological and molecular processes, including protein transport, viral processing, apoptosis signaling, MHC 1 antigen processing and presentation, mitochondria and ER calcium regulation, and proteasomal protein degradation. We employed a BAP31 interaction search using STRING and inBioMap™ protein-protein interaction networks, and the Metabolic Atlas, which revealed molecular and metabolic interactors involved in various pathways essential for cell growth, cell survival, and disease development. BAP31, as a chaperone and resident protein of the ER, was reported in the development of some central nervous system disorders and metabolic diseases about AD, ALS, and Liver disease. In addition, BAP31 is overexpressed in many cancers. Furthermore, research around BAP31 involvement in cancer has taken up a shape, focusing on its roles in cancer cell survival, disease prognosis, and targeted treatment. Here, we address published data on the Biological roles of BAP31 in both health and disease. We present an analytical description of BAP31 expression and functional implication in some human cancers and the impact of its expression and regulation while it models as a potential target in cancer therapy. Besides, a profound understanding of BAP31 is insightful of the gap between cancer development and neurodegeneration, thus generating novel ideas surrounding the link between the two different cell phenomena.

17.
Dev Comp Immunol ; 115: 103883, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33045274

RESUMO

Rare minnow (Gobiocypris rarus), a small cyprinid species that is highly sensitive to the grass carp reovirus (GCRV), is regarded as an ideal model to study the mechanisms of innate immunity in fish. In the present study, a TBK1 homologue from rare minnow (GrTBK1) was identified and its roles in defence against viral infection were investigated. Sequence analysis showed that GrTBK1 encoded a 727-amino acid peptide which shared 98% and 72% identity to the black carp (Mylopharyngodon piceus) and human (Homo sapiens) orthologues, respectively. The amino acid sequence analysis demonstrated that GrTBK1 contains a conserved Serine/Threonine protein kinases catalytic domain (S_TKc) at the N-terminus. Furthermore, cellular distribution proved that GrTBK1 was located in the cytoplasm region. Quantitative real-time PCR analysis revealed that GrTBK1 was ubiquitously expressed in all examined organs, but especially highly in liver. Temporal expression analysis in vivo showed that the expression levels of GrTBK1 were obviously up-regulated in response to GCRV infection. Meanwhile, qRT-PCR assay revealed that the levels of S7 RNA, an important segment of GCRV genome, were higher in the liver than in other tissues. This indicates that GrTBK1 might play a crucial role in responses to GCRV infection in fish. In addition, GrTBK1 activated several type I interferon (IFN) promoters and induced the expression of downstream type I IFN-stimulated genes (ISGs). Furthermore, GrTBK1 obviously phosphorylated the interferon regulatory factor 3 (IRF3). Furthermore, overexpression of GrTBK1 remarkably decreased the GCRV proliferation. In summary, we systematically characterized GrTBK1 and illustrated its role in the innate immune response to GCRV infections.

18.
J Environ Manage ; 277: 111394, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091787

RESUMO

The conservation and efficient use of water resources are directly related to the sustainable and high-quality development in China. This paper regards the pilot policy of water-saving society construction as a quasi-natural experiment, and employs a differences-in-differences approach to evaluate the effectiveness of urban water-saving policies and exploit its drive mechanism by using the panel data of 263 cities in China from 2001 to 2016. Findings show that the pilot policy of water-saving society construction can achieve better water-saving effects, which can not only promote the reduction of urban water consumption in intensity and total amount, but also improve the efficiency of water resources utilization. And this policy has brought long-term dynamic effects on the urban water resources conservation. Heterogeneous effects exist in different types of cities, that is, the water-saving performance is more significant in cities with sufficient water resources and in central China. Besides, this paper finds that the impact of this water-saving policy on urban water resource conservation is mainly through two channels such as water resources infrastructure investment and water resources pricing. These findings provide useful inspirations for local governments to take effective economic measures to manage water resources.


Assuntos
Conservação dos Recursos Hídricos , Água , China , Cidades , Conservação dos Recursos Naturais , Recursos Hídricos
19.
J Hazard Mater ; 402: 123527, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712359

RESUMO

The wide application of plastics led to the wide exposure of plasticizers to the environment. As a new environmental pollutant, plasticizers' toxicity researches were far from enough in fish. To further explore these mechanisms, we used two common plasticizers (Diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) expose to grass carp hepatocytes (L8824). The results showed that the mRNA levels of NOD2-RIP2-NF-κB signal pathway and its downstream inflammatory genes were significantly increased compared to those in control group. Then, the levels of mRNAs and proteins of apoptosis markers were changed, and hepatocytes apoptosis was induced. After DBP and DEHP exposure together, there were higher levels of inflammatory factors and the proportion of apoptotic cells. After NOD2 inhibitor treatment, the phenomena mentioned above were obviously alleviated. We conclude that DBP and DEHP exposure at least partially activated the NOD2-RIP2-NF-κB signal pathway in grass carp hepatocytes, and caused inflammation and apoptosis. In terms of hepatotoxicity, there was synergistic relationship between DBP and DEHP. In addition, we put forward new views on the use of plasticizers: select low toxicity plasticizers, then reduce the types of plasticizers used and reduce the high toxicity level of mixed plasticizers.

20.
J Proteomics ; 230: 103965, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32891891

RESUMO

The small proteins and short open reading frames encoded peptides (SEPs) are of fundamental importance because of their essential roles in biological processes. However, the annotation or identification of them is challenging, in part owing to the limitation of the traditional genome annotation pipeline and their inherent characteristics of low abundance and low molecular weight. To discover and characterize SEPs in Hep3B cell line, we developed an optimized peptidomic assay by combining different peptide extraction and separation methods. The organic solvent precipitation method in peptidomic showed promotion in the enrichment of low molecular proteins or peptides, and the data clearly showed a beneficial effect from the reduction of sample complexity, resulting in high-quality MS/MS spectra. Furthermore, different strategies exhibited good complementarity in improving the total amount of small proteins and their sequence coverage. In total, 1192 proteins within less than 100 amino acids were identified, including 271 newly discovered SEPs that been annotated in the OpenProt database and 147 SEPs of them encoded from ncRNA or lincRNA. Results in this work provide robust evidence to date that the human proteome is more complicated than previously appreciated, and this will be a benefit to discoveries of proteins without function annotation. SIGNIFICANCE: In this work, methods were optimized to identify SEPs in Hep3B. The organic solvent precipitation presents promotion in enrichment of low molecular proteins or peptides, and the data clearly showed a beneficial effect from the reduction of sample complexity, resulting in high quality MS/MS spectra. Different strategies exhibited good complementarity in improving total amount of small proteins and their sequence coverage. In total, 1192 proteins within less than 100 amino acids were identified, including 271 newly discovered SEPs that been annotated in the OpenProt database and 147 SEPs of them encoded from ncRNA or lincRNA. Furthermore, 22 SEPs generated from the uORF may has potential effect in translation control, and 149 newly identified SEPs have known functional domains or cross-species conservation. Results in this work present robust evidence for the coding potential of the ignored region of human genomes and may provide additional insights into tumor biology.

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