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1.
Anal Chem ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826297

RESUMO

Precise evaluation of breast tumor malignancy based on tissue calcifications has important practical value in the disease diagnosis, as well as the understanding of tumor development. Traditional X-ray mammography provides the overall morphologies of the calcifications but lacks intrinsic chemical information. In contrast, spontaneous Raman spectroscopy offers detailed chemical analysis but lacks the spatial profiles. Here, we applied hyperspectral stimulated Raman scattering (SRS) microscopy to extract both the chemical and morphological features of the microcalcifications, based on the spectral and spatial domain analysis. A total of 211 calcification sites from 23 patients were imaged with SRS, and the results were analyzed with a support vector machine (SVM) based classification algorithm. With optimized combinations of chemical and geometrical features of microcalcifications, we were able to reach a precision of 98.21% and recall of 100.00% for classifying benign and malignant cases, significantly improved from the pure spectroscopy or imaging based methods. Our findings may provide a rapid means to accurately evaluate breast tumor malignancy based on fresh tissue biopsies.

2.
Environ Pollut ; 279: 116925, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33744636

RESUMO

Numerous pieces of evidence documented the importance of gut microbiota in regulating human health and evaluating the toxicity of environmental pollutants, which are closely related to the host health in various aspects, including nutrition, energy translation, metabolism, pathogen resistance, and immune function. A variety of environmental factors can disrupt gut microbiota and their functions, and inevitably cause immune diseases, obesity and diabetes. However, deciphering the inner mechanisms involved in the functional interaction of gut microbes with host health is still needed extensive investigations. This review focused on the essential roles of intestinal microbes in host-related diseases and highlighted the development and applications of germ-free (GF) animal models, mainly zebrafish. Moreover, the generation, immunity characters, advantages and challenges of GF zebrafish models were also summarized. Importantly, the composition and isolation of zebrafish gut bacteria for further application and toxicity evaluation of aquatic environmental pollutants were also discussed. In conclusion, GF zebrafish play irreplaceable roles in understanding the potential functions and responses of customized microbiota towards human and environmental health implications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33682046

RESUMO

PURPOSE: The aim of the study is to identify a reliable gene panel to predict the prognosis of HNSCC patients by integrated genomic analysis. METHODS: Co-expression gene networks were constructed by WGCNA using GSE113282 gene expression profile. The biological functional investigation was performed by GO and KEGG function enrichment analysis. The hub gene module was screened by PPI. The prognostic gene panel was established by Lasso regression analysis, and further progression-free survival (PFS) analysis was validated by Kaplan-Meier survival analysis using GSE102995 data. RESULTS: We identified 195 genes associated with the overall survival (OS) status (correlation coefficients: - 0.42, and p value: 2e-05) by WGCNA. These genes were enriched in immune-related cytokines and pathways analyzed by GO and KEGG. Among the 195 genes, the module (42 genes) with the highest score was screened by PPI. A novel seven-gene predictive panel (CD19, CD40LG, CD5, CXCR6, FPR2, NCAM1, and SELL) was established by Lasso regression analysis, and the area under ROC curve (AUC) for 3-year OS status was 0.8298 and 0.7571, respectively, in the training set and the test set. The PFS time of the low-risk patients was significantly longer than the high-risk patients (p < 0.0001; log-rank test) by further validation using GSE102995 data. CONCLUSION: The seven-gene panel may serve as a reliable predictive tool for HNSCC patients treated with platinum-based radio (chemo) therapy, and may be potential therapeutic targets for HNSCC patients.

4.
J Ethnopharmacol ; 274: 114072, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33781876

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The ancient Chinese herbal formula Longdan Xiegan Tang (LXT, also called Gentiana Longdancao Decoction to Drain the Liver) treats insulin resistance- and inflammation-associated liver injuries in clinical practice. AIM OF THE STUDY: To investigate the molecular mechanisms underlying LXT-elicited improvement of the liver injuries. MATERIALS AND METHODS: Male rats were co-treated with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) for eight weeks. Blood parameters were determined enzymatically or by ELISA. Gene/protein expression was analyzed by Real-Time PCR, Western blot and/or immunohistochemistry. RESULTS: LXT attenuated olanzapine-induced liver injury manifested by hyperactivities of plasma alanine aminotransferase and aspartate aminostransferase, hyperbilirubinemia and hypoalbuminemia. Furthermore, LXT improved hepatic insulin resistance that was indicated by hyperinsulinemia, the increased HOMA-IR index, and hepatic over-phosphorylation of Ser307 in insulin receptor substrate (IRS)1, Ser731 in IRS2, Tyr607 in phosphoinositide 3-kinase p85α and Ser473 in AKT at baseline. Mechanistically, LXT inhibited olanzapine-triggered hepatic over-phosphorylation of both IκB kinase (IKK)α/ß and nuclear factor (NF)κB p65 proteins, and mRNA overexpression of tumor necrosis factor α, interleukin 6, interleukin 1ß and CD68. More importantly, LXT restored the decreases in angiotensin-converting enzyme 2 (ACE2) protein level, and its downstream targets Ang (1-7) content and Mas receptor expression. CONCLUSIONS: The present results demonstrate that LXT attenuates liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1-7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated liver injuries.

5.
Theranostics ; 11(7): 3074-3088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537075

RESUMO

Gout is a common metabolic disease with growing burden, caused by monosodium urate (MSU) microcrystal deposition. In situ and chemical-specific histological identification of MSU is crucial in the diagnosis and management of gout, yet it remains inaccessible for current histological methods. Methods: Stimulated Raman scattering (SRS) microscopy was utilized to image MSU based on its fingerprint Raman spectra. We first tested SRS for the diagnosis capability of gout and the differentiation power from pseudogout with rat models of acute gout arthritis, calcium pyrophosphate deposition disease (CPDD) and comorbidity. Then, human synovial fluid and surgical specimens (n=120) were were imaged with SRS to obtain the histopathology of MSU and collagen fibers. Finally, quantitative SRS analysis was performed in gout tissue of different physiological phases (n=120) to correlate with traditional histopathology including H&E and immunohistochemistry staining. Results: We demonstrated that SRS is capable of early diagnosis of gout, rapid detection of MSU in synovial fluid and fresh unprocessed surgical tissues, and accurate differentiation of gout from pseudogout in various pathophysiological conditions. Furthermore, quantitative SRS analysis revealed the optical characteristics of MSU deposition at different pathophysiological stages, which were found to matched well with corresponding immunofluorescence histochemistry features. Conclusion: Our work demonstrated the potential of SRS microscopy for rapid intraoperative diagnosis of gout and may facilitate future fundamental researches of MSU-based diseases.

6.
Transpl Int ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606319

RESUMO

Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1 pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.

7.
Sensors (Basel) ; 21(4)2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33562275

RESUMO

Image semantic segmentation has been applied more and more widely in the fields of satellite remote sensing, medical treatment, intelligent transportation, and virtual reality. However, in the medical field, the study of cerebral vessel and cranial nerve segmentation based on true-color medical images is in urgent need and has good research and development prospects. We have extended the current state-of-the-art semantic-segmentation network DeepLabv3+ and used it as the basic framework. First, the feature distillation block (FDB) was introduced into the encoder structure to refine the extracted features. In addition, the atrous spatial pyramid pooling (ASPP) module was added to the decoder structure to enhance the retention of feature and boundary information. The proposed model was trained by fine tuning and optimizing the relevant parameters. Experimental results show that the encoder structure has better performance in feature refinement processing, improving target boundary segmentation precision, and retaining more feature information. Our method has a segmentation accuracy of 75.73%, which is 3% better than DeepLabv3+.

8.
Sensors (Basel) ; 21(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546245

RESUMO

By detecting the defect location in high-resolution insulator images collected by unmanned aerial vehicle (UAV) in various environments, the occurrence of power failure can be timely detected and the caused economic loss can be reduced. However, the accuracies of existing detection methods are greatly limited by the complex background interference and small target detection. To solve this problem, two deep learning methods based on Faster R-CNN (faster region-based convolutional neural network) are proposed in this paper, namely Exact R-CNN (exact region-based convolutional neural network) and CME-CNN (cascade the mask extraction and exact region-based convolutional neural network). Firstly, we proposed an Exact R-CNN based on a series of advanced techniques including FPN (feature pyramid network), cascade regression, and GIoU (generalized intersection over union). RoI Align (region of interest align) is introduced to replace RoI pooling (region of interest pooling) to address the misalignment problem, and the depthwise separable convolution and linear bottleneck are introduced to reduce the computational burden. Secondly, a new pipeline is innovatively proposed to improve the performance of insulator defect detection, namely CME-CNN. In our proposed CME-CNN, an insulator mask image is firstly generated to eliminate the complex background by using an encoder-decoder mask extraction network, and then the Exact R-CNN is used to detect the insulator defects. The experimental results show that our proposed method can effectively detect insulator defects, and its accuracy is better than the examined mainstream target detection algorithms.

9.
Sci Total Environ ; 770: 145321, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33515886

RESUMO

The conversion of lignocellulosic biomass to bioethanol is a potential approach to alleviate the energy crisis and environmental deterioration. To improve the conversion efficiency of bioethanol from wheat straw (WS), the optimization of subcritical water pretreatment and high solid hydrolysis were investigated in this study. Response surface methodology (RSM) accompanied with glucose concentration after enzymatic hydrolysis as a more reasonable response value was applied for the pretreatment optimization, and the optimum conditions were obtained as 220.51 °C of extraction temperature, 22.01 min of extraction time and 2.50% (w/v) of substrate loading. After pretreatment, the hemicellulose decreased by 18.37%, and the cellulose and lignin increased by 25.92% and 8.81%, respectively, which were consistent with the destroyed microstructure and raised crystallinity. The high efficiency of separate hydrolysis and fermentation (SHF) was verified by five commercial cellulases, and yields of hydrolysis and fermentation were 77.85-89.59% and 93.34-96.18%, respectively. Based on the high solid (15%) hydrolysis and fermentation, the ethanol concentration was significantly improved to 37.00 g/L. Interestingly, 64.47% of lignin was accumulated in the solid residue after enzymatic hydrolysis and it did not affect the efficiency of SHF, which further suggested that subcritical water mainly affected the structure of WS rather than the removal of lignin. Therefore, subcritical water pretreatment combined with high solid hydrolysis is a more effective solution for bioethanol conversion, which is also a promising strategy to utilize all components of lignocellulosic biomass.


Assuntos
Triticum , Água , Biomassa , Fermentação , Hidrólise , Lignina/metabolismo , Triticum/metabolismo
10.
J Hazard Mater ; 412: 125175, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33516115

RESUMO

The preparation of fast, highly responsive and reliable gas sensing devices for the detection of acetone gas is considered to be a key challenge for the development of accurate disease diagnosis systems through exhaled respiratory gases. In the paper, yolk shell Sb2O3/WO3 is synthesized and its gas sensing performance was studied by static test system. Special, the maximum response value of 1:1 Sb2O3/WO3 yolk-shell (WO3-1 YSL) sensor to 100 ppm acetone can reach as high as 50.0 at 200 â„ƒ. And it also exhibits excellent response/recover time (4 s/5 s), low detection limit (2 ppm) and superior selectivity towards acetone. More importantly, in mixed selective gas test, the sensor shows high selectivity towards acetone. And the mechanism is analyzed by ex-situ XPS. The excellent gas-sensing performance can be attributed to unique yolk-shell structure, which facilitates the rapid transport of charge carriers from the surface to the bulk and provides more active sites for gas adsorption and desorption; the heterojunction between of Sb2O3 and WO3, which promotes oxygen pre-adsorption on the surface and increasing the interfacial potential; the increased oxygen vacancies which allowing more chemisorbed oxygen to form.

11.
J Hazard Mater ; 403: 123604, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32781281

RESUMO

The toxicity of Cr(VI) was widely investigated, but the defense mechanism against Cr(III) in bacteria are seldom reported. Here, we found that Cr(III) inhibited bacterial growth and induced reactive oxygen species (ROS). After exposure to Cr(III), loss of sodA not only led to the excessive generation of ROS, but also enhanced the level of lipid peroxidation and reduced the GSH level, indicating that the deficiency of Mn-SOD decreased the bacterial resistance ability against Cr(III). The adverse effects of oxidative stress caused by Cr(III) could be recovered by the rescue of Mn-SOD in the sodA-deficient strain. Besides the oxidative stress, Cr(III) could cause the bacterial morphology variation, which was distinct between the wild-type and the sodA-deficient strains due to the differential expressions of Z-ring division genes. Moreover, Mn-SOD might prevent Cr(III) from oxidation on the bacterial surface by combining with Cr(III). Taken together, our results indicated that the Mn-SOD played a vital role in regulating the stress resistance, expression of cell division-related genes, bacterial morphology, and chemistry valence state of Cr. Our findings firstly provided a more in-depth understanding of Cr(III) toxicity and bacterial defense mechanism against Cr(III).

12.
ACS Biomater Sci Eng ; 7(1): 166-179, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33372514

RESUMO

Tumor microenvironment (TME), with complex composition, plays a vital role in the occurrence, development, and metastasis of tumors. TME becomes an important obstacle to the accessibility of nanotherapy, thus indicating the need to improve the functional design to overcome this challenge. In this study, we generate an intelligent nano-drug-delivery system (DOX@PssP-Hh NPs) with dual environmental response, which involves heparanase (HPSE) in TME and glutathione (GSH) in tumor cells. The nanosystem consists of a nanoskeleton formed by self-assembly of mPEG-ss-PEI and α-CD (PssP), chemotherapy drug doxorubicin (DOX) for enhancing antitumor efficacy, together with hyaluronidase (HAase), which is designed to degrade extracellular matrix to increase drug penetration, and an outer shell of heparin. Through the process of "responsive disintegration-remodeling tumor microenvironment-enhancing drug penetration-inducing oxidative stress", the semi-rotaxaneself-assembled nanomicelles were constructed to achieve the progressive function. DOX@PssP-Hh NPs with the size of 81.85 ± 1.85 nm exhibited satisfactory cytotoxicity (IC50 = 0.80 ± 0.33 µg/mL). With the disulfide bond-mediated GSH depletion and DOX-mediated reactive oxygen species (ROS) production, treatment with DOX@PssP-Hh NPs prominently reduced glutathione peroxidase 4 (GPX4) level and would lead to enhanced oxidative stresses. Hyaluronic acid (HA), collagen I, and α-smooth muscle actin (α-SMA) were significantly reduced for TME remodulation. Moreover, the antitumor effect in vivo implied that DOX@PssP-Hh NPs could inhibit tumor growth effectively and reduce tumor interstitial fluid pressure (IFP) evidently. In conclusion, DOX@PssP-Hh NPs improved the penetration of drugs and exhibited enhanced antitumor efficacy.

13.
Elife ; 92020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33315013

RESUMO

Endothelial cells (ECs) are widely heterogenous depending on tissue and vascular localization. Jambusaria et al. recently demonstrated that ECs in various tissues surprisingly possess mRNA signatures of their underlying parenchyma. The mechanism underlying this observation remains unexplained, and could include mRNA contamination during cell isolation, in vivo mRNA paracrine transfer from parenchymal cells to ECs, or cell-autonomous expression of these mRNAs in ECs. Here, we use a combination of bulk RNASeq, single-cell RNASeq datasets, in situ mRNA hybridization, and most importantly ATAC-Seq of FACS-isolated nuclei, to show that cardiac ECs actively express cardiomyocyte myofibril (CMF) genes and have open chromatin at CMF gene promoters. These open chromatin sites are enriched for sites targeted by cardiac transcription factors, and closed upon expansion of ECs in culture. Together, these data demonstrate unambiguously that the expression of CMF genes in ECs is cell-autonomous, and not simply a result of technical contamination or paracrine transfers of mRNAs, and indicate that local cues in the heart in vivo unexpectedly maintain fully open chromatin in ECs at genes previously thought limited to cardiomyocytes.


Assuntos
Cromatina/metabolismo , Células Endoteliais/metabolismo , Transcriptoma , Animais , Cromatina/genética , Coração , Camundongos , Miócitos Cardíacos/metabolismo , Miofibrilas/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-33315562

RESUMO

The crowd counting is challenging for deep networks due to several factors. For instance, the networks can not efficiently analyze the perspective information of arbitrary scenes, and they are naturally inefficient to handle the scale variations. In this work, we deliver a simple yet efficient multi-column network, which integrates the perspective analysis method with the counting network. The proposed method explicitly excavates the perspective information and drives the counting network to analyze the scenes. More concretely, we explore the perspective information from the estimated density maps and quantify the perspective space into several separate scenes. We then embed the perspective analysis into the multi-column framework with a recurrent connection. Therefore, the proposed network matches various scales with the different receptive fields efficiently. Secondly, we share the parameters of the branches with various receptive fields. This strategy drives the convolutional kernels to be sensitive to the instances with various scales. Furthermore, to improve the evaluation accuracy of the column with a large receptive field, we propose a transform dilated convolution. The transform dilated convolution breaks the fixed sampling structure of the deep network. Moreover, it needs no extra parameters and training, and the offsets are constrained in a local region, which is designed for the congested scenes. The proposed method achieves state-of-the-art performance on five datasets (ShanghaiTech, UCF CC 50, WorldEXPO10, UCSD, and TRANCOS).

15.
J Oral Pathol Med ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33220105

RESUMO

BACKGROUND: Overexpression of long noncoding RNAs (lncRNAs) reveals the abnormal pathological processes in many human cancers. KRT16P3, a novel overexpressed lncRNA in tongue squamous cell carcinoma (TSCC), was identified by previous lncRNA microarrays. However, the role of KRT16P3 in TSCC is not clear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of KRT16P3 in TSCC tissues and cells. Next, the relationships between KRT16P3 and the clinical significance of TSCC patients were analyzed. Additionally, Cell Counting Kit-8, 5-Bromo-2-deoxyUridine (BrdU) incorporation assay, cell colony formation assay, flow cytometry cell apoptosis analysis, scratch wound healing assay, transwell invasion assay were used to explore the biological function of KRT16P3. Western blot and qRT-PCR were used to determine the expression of epithelial-mesenchymal transition (EMT) markers. The pathway changes after KRT16P3 knockdown were detected by western blot. RESULTS: We found KRT16P3 expression is significantly upregulated in TSCC tissues and positively associated with advanced clinicopathological features of TSCC patients, and it may serve as a poor prognostic factor. Functionally, KRT16P3 knockdown inhibits proliferation, migration, invasion, and promotes apoptosis of TSCC cells. Furthermore, we also revealed that KRT16P3 knockdown supresses EMT and JAK2/STAT3 signaling pathway. CONCLUSION: Our results validated that KRT16P3 can modulate the malignant progression, EMT process, and JAK2/STAT3 signaling pathway of TSCC, which might also serve as a novel prognostic biomarker and an attractive target for TSCC patients.

16.
Life Sci ; : 118743, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188837

RESUMO

AIM: Karyopherin α4 (KPNA4, importin α3) has been verified to be an oncogene in many cancers. However, its role in papillary thyroid cancer (PTC), the most frequent endocrine malignancy, is still unclear. MATERIALS AND METHODS: KPNA4 expression was analyzed in PTC tissues and cells. The effects of KPNA4 on the proliferation, invasion, and apoptosis of PTC cells were evaluated after overexpression or downregulation of KPNA4. The influence of KPNA4 on NF-κB activation was evaluated by nuclear NF-κB p65 expression and NF-κB-luciferase reporter assays. Moreover, we also explored whether KPNA4 was regulated by miR-548b-3p. Additionally, the roles of miR-548b-3p and KPNA4 were explored in a xenograft mouse model. KEY FINDINGS: KPNA4 expression was increased in PTC tissues and cells, and its expression was significantly related to patients' clinicopathologic features and overall survival. Overexpression of KPNA4 significantly promoted PTC cell proliferation and invasion, enhanced nuclear p65 expression and augmented NF-κB luciferase activity. However, KPNA4 silencing showed opposite effects on the above indexes, and induced apoptosis of PTC cells. KPNA4 was a target of miR-548b-3p, which was downregulated in PTC and inhibited proliferation and invasion, but promoted apoptosis of PTC cells. KPNA4 overexpression abrogated the suppression of miR-548b-3p on the malignant phenotypes of PTC cells. Both miR-548b-3p overexpression and KPNA4 downregulation inhibited tumor growth and Ki-67 expression, elevated numbers of Tunel-positive cells, and deceased nuclear p65 expression in mouse tumor tissues. SIGNIFICANCE: KPNA4 was negatively regulated by miR-548b-3p and promoted the development of PTC via activating the NF-κB pathway.

17.
Proc Natl Acad Sci U S A ; 117(48): 30433-30440, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33199635

RESUMO

Two-component systems (TCS), which typically consist of a membrane-embedded histidine kinase and a cytoplasmic response regulator, are the dominant signaling proteins for transduction of environmental stimuli into cellular response pathways in prokaryotic cells. HptRSA is a recently identified TCS consisting of the G6P-associated sensor protein (HptA), transmembrane histidine kinase (HptS), and cytoplasmic effector (HptR). HptRSA mediates glucose-6-phosphate (G6P) uptake to support Staphylococcus aureus growth and multiplication within various host cells. How the mechanism by which HptRSA perceives G6P and triggers a downstream response has remained elusive. Here, we solved the HptA structures in apo and G6P-bound states. G6P binding in the cleft between two HptA domains caused a conformational closing movement. The solved structures of HptA in complex with the periplasmic domain of HptS showed that HptA interacts with HptS through both constitutive and switchable interfaces. The G6P-free form of HptA binds to the membrane-distal side of the HptS periplasmic domain (HptSp), resulting in a parallel conformation of the HptSp protomer pair. However, once HptA associates with G6P, its intramolecular domain closure switches the HptA-HptSp contact region into the membrane-proximal domain, which causes rotation and closure of the C termini of each HptSp protomer. Through biochemical and growth assays of HptA and HptS mutant variants, we proposed a distinct mechanism of interface switch-mediated signaling transduction. Our results provide mechanistic insights into bacterial nutrient sensing and expand our understanding of the activation modes by which TCS communicates external signals.

18.
Food Chem ; : 128340, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33069536

RESUMO

The inhibition effect of urea on ovalbumin (OVA) glycation was investigated, and the mechanism was evaluated through the changes in protein structure as well as glycation sites and average degree of substitution per peptide molecule (DSP) by conventional spectrometry and liquid chromatography-high resolution mass spectrometry (LC-HRMS). A urea concentration of 3 M was chosen as the optimum condition. Ultraviolet and fluorescence spectra suggested that both glycation and urea treatment could unfold the OVA, but urea inhibited the glycation-induced protein unfolding. Circular dichroism spectra showed that urea treatment could increase the ß-sheet content and reduce the α-helix content of OVA. LC-HRMS indicated that the number of glycation sites was reduced from 15 to 3, and DSP values decreased with urea treatment. In conclusion, urea could significantly inhibit the OVA-glucose glycation, and the sites competition as well as structure unfolding inhibition resulted from urea could be the main factors.

19.
PLoS Pathog ; 16(10): e1009035, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33108395

RESUMO

The tumor suppressor p53 as an innate antiviral regulator contributes to restricting Japanese encephalitis virus (JEV) replication, but the mechanism is still unclear. The interferon-induced transmembrane protein 3 (IFITM3) is an intrinsic barrier to a range of virus infection, whether IFITM3 is responsible for the p53-mediated anti-JEV response remains elusive. Here, we found that IFITM3 significantly inhibited JEV replication in a protein-palmitoylation-dependent manner and incorporated into JEV virions to diminish the infectivity of progeny viruses. Palmitoylation was also indispensible for keeping IFITM3 from lysosomal degradation to maintain its protein stability. p53 up-regulated IFITM3 expression at the protein level via enhancing IFITM3 palmitoylation. Screening of palmitoyltransferases revealed that zinc finger DHHC domain-containing protein 1 (ZDHHC1) was transcriptionally up-regulated by p53, and consequently ZDHHC1 interacted with IFITM3 to promote its palmitoylation and stability. Knockdown of IFITM3 significantly impaired the inhibitory role of ZDHHC1 on JEV replication. Meanwhile, knockdown of either ZDHHC1 or IFITM3 expression also compromised the p53-mediated anti-JEV effect. Interestingly, JEV reduced p53 expression to impair ZDHHC1 mediated IFITM3 palmitoylation for viral evasion. Our data suggest the existence of a previously unrecognized p53-ZDHHC1-IFITM3 regulatory pathway with an essential role in restricting JEV infection and provide a novel insight into JEV-host interaction.

20.
J Chin Polit Sci ; : 1-25, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32952389

RESUMO

By employing discourse-historical approach and corpus linguistics, this paper examines media reports to analyze the Chinese official discourse in the context of the COVID-19 outbreak. The results demonstrate that a paradox of globalism and nationalism has been simultaneously reflected when reporting the global pandemic. Based on a polarizing discursive construction of positive "self" and negative "others," on many occasions, the globalist and nationalist arguments have been closely intertwined and complement each other to reinforce the legitimacy of the ruling party at home and the international reputation of China under the leadership of the ruling party.

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