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1.
Bioorg Chem ; 133: 106377, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36731294

RESUMO

Cannabinoid receptors (CBs), including CB1 and CB2, are the key components of a lipid signaling endocannabinoid system (ECS). Development of synthetic cannabinoids has been attractive to modulate ECS functions. CB1 and CB2 are structurally closely related subtypes but with distinct functions. While most efforts focus on the development of selective ligands for single subtype to circumvent the undesired off-target effect, Yin-Yang ligands with opposite pharmacological activities simultaneously on two subtypes, offer unique therapeutic potential. Herein we report the development of a new Yin-Yang ligand which functions as an antagonist for CB1 and concurrently an agonist for CB2. We found that in the pyrazole-cored scaffold, the arm of N1-phenyl group could be a switch, modification of which yielded various ligands with distinct activities. As such, the ortho-morpholine substitution exerted the desired Yin-Yang bifunctionality which, based on the docking study and molecular dynamic simulation, was proposed to be resulted from the hydrogen bonding with S173 and S285 in CB1 and CB2, respectively. Our results demonstrated the feasibility of structure guided ligand evolution for challenging Yin-Yang ligand.

2.
Adv Mater ; : e2211165, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36708103

RESUMO

Atmospheric water is ubiquitous on Earth and extensively participates in the natural water cycle through evaporation and condensation. This process involves tremendous energy exchange with the environment, but very little of the energy has so far been harnessed. The recently emerged hydrovoltaic technology, especially moisture-induced electricity, has shown great potential in harvesting energy from atmospheric water and gives birth to moisture energy harvesting devices. The device performance, especially the long-term operational capacity, has been significantly enhanced over the past few years. Further development, however, requires in-depth understanding of mechanisms, innovative materials, and ingenious system designs. In this review, beginning with describing the basic properties of water, we discuss the key aspects of the water-hygroscopic material interactions and mechanisms of power generation. We then summarize the current material systems and advances in promising material development. Aiming at the chief bottlenecks of limited operational time, we list advanced system designs that are helpful to improve device performance. Especially, the synergistic effect of moisture adsorption and water evaporation on material and system levels to accomplish sustained electricity generation is discussed. Finally, we analyze the remaining challenges and suggest future directions for developing this promising technology. This article is protected by copyright. All rights reserved.

3.
Int Immunopharmacol ; 116: 109739, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36706590

RESUMO

Dendritic cells (DCs) play pivotal roles in immune responses. The differentiation and function of DCs are regulated by environmental metabolites. Putrescine is ubiquitous in various metabolic microenvironments and its immunoregulation has been of increasing interest. However, the mechanisms associated with its DC-induced immunoregulation remain unclear. In this study, we found putrescine promoted induction of immature bone marrow derived DCs (BMDCs), along with the increased phagocytosis and migration, and altered cytokine secretion in immature BMDCs. Transcriptomic profiles indicated significantly impaired inflammatory-related pathways, elevated oxidative phosphorylation, and decreased p-STAT3 (Tyr705) expression. Additionally, putrescine performed minor influence on the lipopolysaccharide (LPS)-induced maturation of BMDCs but significantly impaired LPS-induced DC-elicited allogeneic T-cell proliferation as well as the cytokine secretion. Furthermore, molecular docking and dynamics on the conjugation between putrescine and STAT3 revealed that putrescine could be stably bound to the hydrophilic cavity in STAT3 and performed significant influence on the Tyr705 phosphorylation. CUT&Tag analysis uncovered altered motifs, downregulated IFN-γ response, and upregulated p53 pathway in Putrescine group compared with Control group. In summary, our results demonstrated for the first time that putrescine might accelerate the differentiation of BMDCs by inhibiting the phosphorylation of STAT3 at Tyr705. Given that both DCs and putrescine have ubiquitous and distinct roles in various immune responses and pathogeneses, our findings may provide more insights into polyamine immunoregulation on DCs, as well as distinct strategies in the clinical utilization of DCs by targeting polyamines.

4.
Microbiome ; 11(1): 6, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631833

RESUMO

BACKGROUND: The economic and environmental value of honeybees has been severely challenged in recent years by the collapse of their colonies worldwide, often caused by outbreaks of infectious diseases. However, our understanding of the diversity, prevalence, and transmission of honeybee viruses is largely obscure due to a lack of large-scale and longitudinal genomic surveillance on a global scale. RESULTS: We report the meta-transcriptomic sequencing of nearly 2000 samples of the two most important economic and widely maintained honeybee species, as well as an associated ectoparasite mite, collected across China during 2016-2019. We document the natural diversity and evolution of honeybee viruses in China, providing evidence that multiple viruses commonly co-circulate within individual bee colonies. We also expanded the genomic data for 12 important honeybee viruses and revealed novel genetic variants and lineages associated with China. We identified more than 23 novel viruses from the honeybee and mite viromes, with some exhibiting ongoing replication in their respective hosts. Together, these data provide additional support to the idea that mites are an important reservoir and spill-over host for honeybee viruses. CONCLUSIONS: Our data show that honeybee viruses are more widespread, prevalent, and genetically diverse than previously realized. The information provided is important in mitigating viral infectious diseases in honeybees, in turn helping to maintain sustainable productive agriculture on a global scale. Video Abstract.


Assuntos
Doenças Transmissíveis , Varroidae , Vírus , Abelhas , Animais , Prevalência , Genômica , China/epidemiologia
5.
Dalton Trans ; 52(5): 1413-1424, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36644791

RESUMO

Co-precipitation of Ni0.8Co0.1Mn0.1(OH)2 (NCM811) and Mg-doped (0.25 wt% and 0.5 wt%) NCM811 precursors is carried out from concentrated metal sulphate solutions. In this paper, the aim is to study the role of magnesium dopant in the co-precipitation step of NCM811, the cathode active material and further the Li-ion battery cell performance. Based on the results, magnesium was fully co-precipitated in the NCM811 precursors, as expected from thermodynamic calculations. The presence of magnesium in these precursors was also confirmed by several characterization methods and magnesium was evenly distributed in the sample. It was observed that tapped density decreased and surface area increased with an expected increase in Mg content. Surprisingly, Mg doping did not improve the cyclability of coin cells, due to the stable crystal structure of NCM811. However, a slight improvement in cyclability was seen in pouch cells after 1000 cycles. A washing effect was clearly seen in lattice parameters and washing also decreased the capacity retention after 62 cycles for all samples.

6.
Biomacromolecules ; 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36642871

RESUMO

At-home tooth whitening solutions with good efficacy and biosafety are highly desirable to meet the ever-growing demand for aesthetic dentistry. As a promising alternative to the classic peroxide bleaching that may damage tooth enamel and gums, piezocatalysis has been recently proposed to realize non-destructive whitening by toothbrushing with piezoelectrical particles. However, traditional particles either pose potential threats to human health or exhibit low piezoresponse to weak mechanical stimuli in the toothbrushing. Here, biocompatible and biodegradable polylactide particles constructed from interlocking crystalline lamellae have been hierarchically designed as next-generation whitening materials with ultra-high piezocatalytic activity and biosafety. By simultaneously controlling the chain conformation within lamellae and the porosity of such unique lamellae network at the nano- and microscales, the particles possessing unprecedented piezoelectricity have been successfully prepared due to the markedly increased dipole alignment, mechanical deformability, and specific surface area. The piezoelectric output can reach as high as 18.8 V, nearly 50 times higher than that of common solid polylactide particles. Consequently, their piezocatalytic effect can be readily activated by a toothbrush to rapidly clean the teeth stained with black tea and coffee, without causing detectable enamel damage. Furthermore, these particles have no cytotoxicity. This work presents a paradigm for achieving high piezoelectric activity in polylactide, which enables its practical application in tooth whitening.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 203-207, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647668

RESUMO

Terahertz waves, the electromagnetic waves in the range of 0.1 to 10 THz, has the advantages of being damage-free, causing no ionizing radiation injury, and being capable of recognizing the fingerprint spectrum of molecular characteristics, thus holding encouraging prospects for wide applications in the field of biomedicine. Terahertz spectrum can be used to identify and characterize biological structures of different levels, from biomolecules such as proteins to cells and tissues, through the spectral signals and/or restored images of the samples. Herein, we summarized the current stomatogical application of and research progress in terahertz spectroscopy and imaging in dentistry, reported the latest research findings, strengths and limitations from three perspectives, tooth anatomical structure, the extent of caries progression, and oral soft tissue, and suggested possible directions for future exploration.


Assuntos
Medicina Bucal , Espectroscopia Terahertz , Espectroscopia Terahertz/métodos , Proteínas/química , Tecnologia
8.
Sci Total Environ ; 858(Pt 3): 159659, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36302416

RESUMO

Urban vegetation affects urban microclimate and maintains biodiversity, which is vital to the social-ecological system. However, there is a lack of research on quantitatively identifying urbanization stage impact on vegetation dynamics, and the stage difference in the response of vegetation dynamics to urbanization characteristics is not clear. In this study, taking Changsha City as an example, we explored the response of vegetation dynamics to urbanization, and identified the impact stages of urbanization on vegetation dynamics as well as their social-ecological characteristics. The results showed that the vegetation dynamics in Changsha City presented spatial pattern of "increase-decrease-increase" from downtown to outside in the past 20 years. The population density, GDP density and construction land proportion firstly inhibited vegetation growth, and then promoted it, with the turning points of 141.58 million yuan/km2, 1205 person/km2, and 19.80 %, respectively. Then, the urbanization impact on vegetation dynamics was quantitatively divided into three stages according to the vegetation change speed, and in different stages, urbanization impacts on vegetation dynamics were compared. This study illustrated the typical stage feature of the urbanization impact on vegetation dynamics.


Assuntos
Urbanização , Humanos , China
9.
Int J Appl Earth Obs Geoinf ; 116: 103160, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36570490

RESUMO

Globally, the COVID-19 pandemic has induced a mental health crisis. Social media data offer a unique opportunity to track the mental health signals of a given population and quantify their negativity towards COVID-19. To date, however, we know little about how negative sentiments differ across countries and how these relate to the shifting policy landscape experienced through the pandemic. Using 2.1 billion individual-level geotagged tweets posted between 1 February 2020 and 31 March 2021, we track, monitor and map the shifts in negativity across 217 countries and unpack its relationship with COVID-19 policies. Findings reveal that there are important geographic, demographic, and socioeconomic disparities of negativity across continents, different levels of a nation's income, population density, and the level of COVID-19 infection. Countries with more stringent policies were associated with lower levels of negativity, a relationship that weakened in later phases of the pandemic. This study provides the first global and multilingual evaluation of the public's real-time mental health signals to COVID-19 at a large spatial and temporal scale. We offer an empirical framework to monitor mental health signals globally, helping international authorizations, including the United Nations and World Health Organization, to design smart country-specific mental health initiatives in response to the ongoing pandemic and future public emergencies.

10.
J Colloid Interface Sci ; 633: 923-931, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36509036

RESUMO

Aqueous zinc-ion batteries (AZIBs) are regarded as attractive candidates for next-generation energy storage devices. Among various cathode materials, V2O5·nH2O (VOH) possesses a high theoretical capacity but poor cycle stability due to the susceptibility of its open structure to damage by the quick shuttling of Zn2+. Herein, the structural stability of VOH is directly improved by wrapping polyaniline (PANI) on the VOH nanobelts (VOH@PANI). As a cathode material for AZIBs, the VOH nanobelts@PANI core-shell structures exhibit an outstanding cycle stability of 98% after 2000 cycles at 2 A g-1. The improved conductivity and additional energy storage contribution of the PANI endow VOH@PANI with a specific capacity as high as 440 mAh g-1 at 0.1 A g-1, substantially higher than pure VOH (291 mAh g-1). At the same time, high energy and power densities of 349 Wh kg-1 and 3347 W kg-1 are achieved. This work not only demonstrates that p-type doped PANI coatings on VOH can boost the Zn2+ storage of VOH, but also provides a novel method to enhance cathode materials for high electrochemical performance.

11.
Phys Chem Chem Phys ; 25(3): 1616-1626, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36541178

RESUMO

Thermoelectric (TE) materials have attracted great attention in solving the problems in the waste heat field, while low figure of merit and poor material stability drastically limit their practical applications. In this work, a two-dimensional (2D) Sc2Si2Te6 monolayer was systematically explored as a promising TE material via ab initio methods. The results reveal that the Sc2Si2Te6 monolayer possesses an indirect band gap with a rhombohedral crystal phase and exhibits excellent dynamic stability. The lower electronic/lattice thermal conductivity and higher electron carrier mobility result in good n-type power factor parameters between 6.24 × 1010 and 1.5 × 1011 W m-1 s-1 K-2 from 300 to 700 K. Such combined merits of low thermal conductivity and high power factor parameters endow the Sc2Si2Te6 monolayer with superior thermoelectric properties with figure of merit (ZT) values of 1.41 and 3.81 at 300 K and 700 K, respectively. This study presented here can shed light on the future design of various 2D materials for thermoelectric applications.

12.
Colloids Surf B Biointerfaces ; 222: 113117, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36586238

RESUMO

Photodynamic therapy (PDT) has many exceptional advantages in cancer treatment, such as minor trauma, low toxicity side effects, and strong adaptability, effectively overcoming some obstacles of traditional therapy and providing more revolutionary opportunities for curing cancer. Chlorin e6 (Ce6) exhibits excellent singlet oxygen generation and conversion efficiency under near-infrared laser irradiation and is a promising PDT photosensitizer. However, its hydrophobicity, short half-life and lack of tumor specificity limit its in vivo anticancer application. Therefore, this work has designed and prepared a multifunctional nanoplatform, Ce6/FeOOH@BSA, to efficiently deliver Ce6. Nanoparticles exhibit excellent dispersion and stability in deionized water, PBS and DMEM, and the blood half-life is 3.98 ± 0.31 h. The nanoplatform demonstrates effective tumor targeting and accumulation, overcoming the obstacles of the biological application of Ce6. Iron ions can exert a chemodynamic therapy (CDT) effect by reacting with overexpressed H2O2 in the tumor to generate toxic hydroxyl radicals (·OH). Moreover, FeOOH nanoparticles effectively promote glutathione (GSH) consumption in tumor cells, which is conducive to accumulating reactive oxygen species (ROS). In brief, Ce6/FeOOH@BSA nanoparticles realize the targeted delivery of Ce6 and mediate synergistic PDT/CDT against tumors, broadening the biomedical application of nanomaterials.

13.
J Med Genet ; 59(9): 840-849, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/genética , Proteína C9orf72/genética , Estudos de Coortes , Predisposição Genética para Doença , Humanos , Mutação/genética , Superóxido Dismutase-1/genética
14.
Analyst ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472862

RESUMO

Curcumin is a dietary spice and coloring agent widely used in food and herbal medicine. Herein, we visualized the distribution of curcumin in fresh Curcuma longa (turmeric) root sections using the state-of-the-art vacuum-ultraviolet (VUV, 118 nm) single photon-postionization mass spectrometric imaging method. Compared with other mass spectrometric imaging methods, the proposed method does not require any sample pre-treatment. The proposed approach could be more conducive to in situ detection of small molecules. The mass spectroscopic imaging (MSI) images of curcumin sections with a lateral resolution of 100 µm indicated that the concentrations of curcumin decreased from the phloem to the xylem of the root. We also show MS imaging of curcumin in the turmeric root at different maturity periods, revealing the transformation of this endogenous species. The result of quantitative analysis indicates that the total curcumin content of the mature turmeric root is estimated to be 3.43%, which is consistent with the previous report that the content of curcumin in the turmeric root is estimated between 3% and 5%. The report indicated that the proposed method of VUV single photon postionization MSI can be used to explore the metabolic process of plants, which is critical for herbal farming, harvest, and its ingredient extraction.

15.
Curr Psychol ; : 1-10, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36468160

RESUMO

Using a convenience sample of adolescents (N = 1609; 63.5% female; M age = 16.54), this study explored whether EI predicted adolescent life satisfaction and whether friendship quality and optimism mediated this relationship during the COVID-19 pandemic. The structural equation modeling revealed that EI predicted adolescent life satisfaction, friendship quality, and optimism, friendship quality partially mediated the relationship between EI and life satisfaction, and optimism partially mediated the relationship between EI and friendship quality. These findings prove that psychological or educative approaches focused on EI could increase life satisfaction in adolescents during difficult times such as COVID-19, but EI may be linked with life satisfaction via friendship quality only. Training in optimism approaches and friendship quality enhancement programs could also effectively promote life satisfaction.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36527562

RESUMO

Deep geological disposal of high-level radioactive waste is a feasible method for solving the problem of spent fuel storage in China. High-level radioactive waste releases heat during the decay process, which increases the temperature of the surrounding rock in the repository, resulting in a significant increase in radon concentration. In this study, the surrounding rock (granite) of a high-level radioactive waste repository was taken as the research object and, based on the similarity principle, an orthogonal test designed. Similar materials of uranium-containing granite were prepared in the laboratory and the physical and mechanical properties and cumulative radon concentration of granite samples assessed under different temperatures (25, 50, 100, 150, and 200 °C). The results showed that, with increased temperature, the compressive and tensile strengths of samples gradually increased and their pore volume gradually decreased. After heat treatment, the longitudinal wave velocity and thermal conductivity of samples decreased linearly with increased temperature. The radon exhalation rate first increased and then decreased, with the rate reaching a maximum at 100 °C. The radon exhalation rate of single-sided and double-sided samples was 0.00914 and 0.00460 Bq·m-2·s-1, respectively. When the temperature was 25-100 °C, the dominant stage was pore water. The radon exhalation rates of samples were positively correlated with compressive and tensile strengths and negatively correlated with pore volume, longitudinal wave velocity, and thermal conductivity. The temperature of 100-200 °C was range of the dominant stage of pore structure. The conclusions obtained in this study can provide theoretical support for radon reduction and radon control of granite in high temperature environments.

17.
Diagnostics (Basel) ; 12(12)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36553135

RESUMO

Serous ovarian cancer is the most common type of ovarian epithelial cancer and usually has a poor prognosis. The objective of this study was to construct an individualized prognostic model for predicting overall survival in serous ovarian cancer. Based on the relative expression orderings (Ea > Eb/Ea ≤ Eb) of gene pairs closely associated with serous ovarian prognosis, we tried constructing a potential individualized qualitative biomarker by the greedy algorithm and evaluated the performance in independent validation datasets. We constructed a prognostic biomarker consisting of 20 gene pairs (SOV-P20). The overall survival between high- and low-risk groups stratified by SOV-P20 was statistically significantly different in the training and independent validation datasets from other platforms (p < 0.05, Wilcoxon test). The average area under the curve (AUC) values of the training and three validation datasets were 0.756, 0.590, 0.630, and 0.680, respectively. The distribution of most immune cells between high- and low-risk groups was quite different (p < 0.001, Wilcoxon test). The low-risk patients tended to show significantly better tumor response to chemotherapy than the high-risk patients (p < 0.05, Fisher's exact test). SOV-P20 achieved the highest mean index of concordance (C-index) (0.624) compared with the other seven existing prognostic signatures (ranging from 0.511 to 0.619). SOV-P20 is a promising prognostic biomarker for serous ovarian cancer, which will be applicable for clinical predictive risk assessment.

18.
Macromol Rapid Commun ; : e2200926, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36527198

RESUMO

To enhance the proton conductivity of sulfonated poly(ether ether ketone) (SPEEK), proton-conducting groups are required to be covalently connected to SPEEK and form proton-conducting channels. Herein, SPEEK fully grafted with segments containing multiple, flexible propanesulfonic acid groups (MS-SPEEK-102) is successfully prepared. Compared with SPEEK, MS-SPEEK-102 exhibits a higher proton conductivity of 8.3 × 10-2  S cm-1 at 80 °C with 98% relative humidity, and consequently a greater power density of 0.530 W cm-2 at 60 °C. These can be ascribed to the increased number of sulfonic acid groups, and ample, uninterrupted proton-conducting channels constructed by the movement of the maximum content, flexible side-chain segments. This approach offers an idea for obtaining a proton exchange membrane with good proton conductivity based on SPEEK.

19.
Front Cell Infect Microbiol ; 12: 1007950, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425786

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive tumors with rapid progression and poor prognosis. Human papillomavirus (HPV) infection has been identified as one of the most important carcinogens for HNSCC. As an early event in HNSCC, infection with HPV leads to altered immune profiles in the tumor microenvironment (TME). The TME plays a key role in the progression and transformation of HNSCC. However, the TME in HNSCC is a complex and heterogeneous mix of tumor cells, fibroblasts, different types of infiltrating immune cells, and extracellular matrix. Biomarkers relevant to the TME, and the biological role of these biomarkers, remain poorly understood. To this end, we performed comprehensive analysis of the RNA sequencing (RNA-Seq) data from tumor tissue of 502 patients with HNSCC and healthy tissue of 44 control samples. In total, we identified 4,237 differentially expressed genes, including 2,062 upregulated and 2,175 downregulated genes. Further in-depth bioinformatic analysis suggested 19 HNSCC tumor tissue-specific genes. In the subsequent analysis, we focused on the biomarker candidates shown to be significantly associated with unfavorable patient survival: ITGA5, PLAU, PLAUR, SERPINE1, TGFB1, and VEGFC. We found that the expression of these genes was negatively regulated by DNA methylation. Strikingly, all of these potential biomarkers are profoundly involved in the activation of the epithelial-mesenchymal transition (EMT) pathway in HNSCCs. In addition, these targets were found to be positively correlated with the immune invasion levels of CD4+ T cells, macrophages, neutrophils, and dendritic cells, but negatively correlated with B-cell infiltration and CD8+ T-cell invasion. Notably, our data showed that the expression levels of ITGA5, PLAU, PLAUR, SERPINE1, and TGFB1 were significantly overexpressed in HPV-positive HNSCCs compared to normal controls, indicating the potential role of these biomarkers as transformation and/or malignant progression markers for HNSCCs in patients with HPV infection. Taken together, the results of our study propose ITGA5, PLAU, PLAUR, SERPINE1, and TGFB1 as potential prognostic biomarkers for HNSCCs, which might be involved in the HPV-related TME remodeling of HNSCC. Our findings provide important implications for the development and/or improvement of patient stratification and customized immunotherapies in HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Microambiente Tumoral/genética , Infecções por Papillomavirus/genética , Biologia Computacional , Papillomaviridae/genética , Prognóstico
20.
J Biol Chem ; : 102699, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36379254

RESUMO

Unlike most flaviviruses transmitted by arthropods, Tembusu virus (TMUV) is still active during winter and causes outbreaks in some areas, indicating vector-independent spread of the virus. Gastrointestinal transmission might be one of the possible routes of vector-free transmission, which also means that the virus has to interact with more intestinal bacteria. Here, we found evidence that TMUV indeed can transmit through the digestive tract. Interestingly, using an established TMUV disease model by oral gavage combined with an antibiotic treatment, we revealed that a decrease in intestinal bacteria significantly reduced local TMUV proliferation in the intestine, revealing that the bacterial microbiome is important in TMUV infection. We found that lipopolysaccharide (LPS) present in the outer membrane of Gram-negative bacteria enhanced TMUV proliferation by promoting its attachment. Toll-like receptor 4 (TLR4), a cell surface receptor, can transmit signal from LPS. We confirmed co-localization of TLR4 with TMUV envelope (E) protein as well as their interaction in infected cells. Coherently, TMUV infection of susceptible cells was inhibited by an anti-TLR4 antibody, purified soluble TLR4 protein, and knockdown of TLR4 expression. LPS-enhanced TMUV proliferation could also be blocked by a TLR4 inhibitor. Meanwhile, pre-treatment of duck primary cells with TMUV significantly impaired LPS-induced IL6 production. Collectively, our study provides first insights into vector-free transmission mechanisms of flaviviruses.

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