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1.
J Med Virol ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36661039

RESUMO

Mpox is caused by the mpox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Animal hosts, such as African rodents, mice, prairie, dogs, and non-human primates, play important roles in the development and transmission of outbreaks. Laboratory animal infection experiments have demonstrated that some animals are susceptible to mpox virus. This review summarizes the current progress on the animal hosts for mpox virus. The surveillance of mpox virus in animal hosts will provide important insights into virus tracing, analysis of mutation evolutionary patterns, transmission mechanisms, and development of control measures. This article is protected by copyright. All rights reserved.

2.
ACS Appl Mater Interfaces ; 15(1): 479-493, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36583377

RESUMO

Since most current studies have focused on exploring how phagocyte internalization of drug-loaded nanovesicles by macrophages would affect the function and therapeutic effects of infiltrated neutrophils or monocytes, research has evaluated the specificity of the inhaled nanovesicles for targeting various phagocytes subpopulations. In this study, liposomes with various charges (including neutral (L1), anionic (L2), and cationic at inflammatory sites (L3)) were constructed to investigate how particle charge determined their interactions with key phagocytes (including macrophages and neutrophils) in acute lung injury (ALI) models and to establish correlations with their biofate and overall anti-inflammatory effect. Our results clearly indicated that neutrophils were capable of rapidly sequestering L3 with a 3.2-fold increase in the cellular liposome distribution, compared to that in AMs, while 70.5% of L2 were preferentially uptaken by alveolar macrophages (AMs). Furthermore, both AMs and the infiltrated neutrophils performed as the potential vesicles for the inhaled liposomes to prolong their lung retention in ALI models, whereas AMs function as sweepers to recognize and process liposomes in the healthy lung. Finally, inhaled roflumilast-loaded macrophage or neutrophil preferential liposomes (L2 or L3) exhibited optimal anti-inflammatory effect because of the decreased AMs phagocytic capacity or the prolonged circulation times of neutrophils. Such findings will be beneficial in exploiting a potential pathway to specifically manipulate lung phagocyte functions in lung inflammatory diseases where these cells play crucial roles.


Assuntos
Lesão Pulmonar Aguda , Pneumopatias , Pneumonia , Humanos , Neutrófilos , Lipossomos/metabolismo , Pulmão/metabolismo , Macrófagos/metabolismo , Pneumonia/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo
3.
Chemistry ; 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464909

RESUMO

Dehydratase (DH), a domain located at polyketide synthase (PKS) modules, commonly catalyzes the dehydration of ß-hydroxy to an α,ß-unsaturated acyl intermediate. As a unique bifunctional dehydratase, AmbDH3 (the DH domain of module 3 of the ambruticin PKS) is verified to be responsible for both dehydration and the following pyran-forming cyclization. Besides, in vitro studies showed that its catalytic efficiency varies with different chiral substrates. However, the detailed molecular mechanism of AmbDH3 remains unclear. In this work, the structural rationale for the substrate specificity (2R/2S- and 6R/6S-substrates) in AmbDH3 was elucidated and the complete reaction pathways including dehydration and cyclization were presented. Both MD simulations and binding free energy calculations indicated AmbDH3 had a stronger preference for 2R-substrates (2R6R-2, 2R6S-3) than 2S-substrates (2S6R-1), and residue H51 and G61 around the catalytic pocket were emphasized by forming stable hydrogen bonds with 2R-substrates. In addition, AmbDH3's mild tolerance at C6 was explained by comparison of substrate conformation and hydrogen bond network in 6S- and 6R-substrate systems. The QM/MM results supported a consecutive one-base dehydration and cyclization mechanism for 2R6S-3 substrate with the energy barrier of 25.2 kcal mol-1 and 24.5 kcal mol-1, respectively. Our computational results uncover the substrate recognition and catalytic process of the first bifunctional dehydratase-cyclase AmbDH3, which will shed light on the application of multifunctional DH domains in PKSs for diverse natural product analogs and benefit the chemoenzymatic synthesis of stereoselective pyran-containing products.

4.
Sci Rep ; 12(1): 22288, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566295

RESUMO

Cluster of differentiation 31 (CD31), phalloidin and alpha smooth muscle actin (α-SMA) have been widely applied to label the cerebral blood vessels in the past years. Although CD31 is mainly used as endothelial marker in determining the cerebral capillaries, it seems likely that its labeling efficiency is closely correlated with the antibodies from the polyclonal or monoclonal one, as well as the conditions of blood vessels. In order to test this phenomenon, we compared the labeling characteristics of goat polyclonal anti-CD31 (gP-CD31) and mouse monoclonal anti-CD31 (mM-CD31) with those of phalloidin and α-SMA on the rat brain in health and ischemia/reperfusion (I/R) with the middle cerebral artery occlusion. By multiple immunofluorescence staining, it was found that gP-CD31 labeling expressed extensively on the cerebral capillaries forming the vascular networks on the normal and ischemic regions, but mM-CD31 labeling mainly presented on the capillaries in the ischemic region. In contrast to the vascular labeling with gP-CD31, phalloidin and α-SMA were mainly expressed on the wall of cortical penetrating arteries, and less on that of capillaries. By three-dimensional reconstruction analysis, it was clearly shown that gP-CD31 labeling was mainly located on the lumen side of vascular wall and was surrounded by phalloidin labeling and α-SMA labeling. These results indicate that gP-CD31 is more sensitive than mM-CD31 for labeling the cerebral vasculature, and is highly compatible with phalloidin and α-SMA for evaluating the cerebral vascular networks under the physiological and pathological conditions.


Assuntos
Actinas , Isquemia Encefálica , Artérias Cerebrais , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Animais , Camundongos , Ratos , Actinas/metabolismo , Faloidina/metabolismo , Isquemia Encefálica/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Artérias Cerebrais/metabolismo
5.
Sci Adv ; 8(51): eade0838, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36542721

RESUMO

DNA and proteins fold in three dimensions (3D) to enable functions that sustain life. Emulation of such folding schemes for functional materials can unleash enormous potential in advancing a wide range of technologies, especially in robotics, medicine, and telecommunication. Here, we report a microfolding strategy that enables formation of 3D morphable microelectronic systems integrated with various functional materials, including monocrystalline silicon, metallic nanomembranes, and polymers. By predesigning folding hosts and configuring folding pathways, 3D microelectronic systems in freestanding forms can transform across various complex configurations with modulated functionalities. Nearly all transitional states of 3D microelectronic systems achieved via the microfolding assembly can be easily accessed and modulated in situ, offering functional versatility and adaptability. Advanced morphable microelectronic systems including a reconfigurable microantenna for customizable telecommunication, a 3D vibration sensor for hand-tremor monitoring, and a bloomable robot for cardiac mapping demonstrate broad utility of these assembly schemes to realize advanced functionalities.

6.
J Adv Res ; 42: 163-176, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36513411

RESUMO

INTRODUCTION: Mature seeds deteriorate gradually and die eventually during long-term storage. Controlled deterioration is often used to accelerate the seed deterioration rate to assess the seed vigor and physiological quality of seed lots. OBJECTIVES: Although it is well known that the process of seed deterioration produced by controlled deterioration is distinct from that caused by long-term storage, the differences in transcriptional levels have not been reported. Clarifying the mechanism of seed deterioration is critical for identifying, conserving and utilizing germplasm resources. METHODS: Tobacco (Nicotiana tabacum L.) seeds were studied thoroughly using transcriptome, small RNA, and degradome sequencing after long-term storage (LS) and controlled deterioration (CD). Co-expression trend analysis identified transcripts involved in tobacco seed deterioration, while phylogenetic analysis helped to uncover comparable targets in rice (Oryza sativa L.) for further verification and utilization. RESULTS: In LS and CD, a total of 2,112 genes and 164 miRNAs were differentially expressed, including 20 interaction miRNA-mRNA pairs with contrasting expression. Transcriptional multiomics found that the main causes of LS were plant hormone signal transduction and protein processing in the endoplasmic reticulum, whereas the primary cause of CD was nucleotide excision repair dysfunction. The homeostatic balance of RNA degradation and the spliceosome occurred in both modes of seed deterioration. Additionally, co-expression trend analysis identified two coherent pairs, nta-miR160b-NtARF18 and nta-miR396c-NtMBD10, as being significant in LS and CD, respectively. For utilization, rice homologous targets OsARF18 and OsMBD707 were verified to play similar roles in LS and CD, respectively. CONCLUSION: This study demonstrated the transcriptional mechanism of tobacco and key genes in seed deterioration. And the application of key genes in rice also verified the feasibility of the multiomics method, guiding the identification of candidate genes to precisely delay seed deterioration in other species of seed research.


Assuntos
MicroRNAs , Oryza , Oryza/genética , Oryza/metabolismo , Tabaco/genética , Tabaco/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Sementes/genética , MicroRNAs/metabolismo
7.
Zhongguo Zhen Jiu ; 42(12): 1385-93, 2022 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-36484192

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain behavior, synovial inflammatory response and demyelination of saphenous nerve in the rats modeled with knee osteoarthritis (KOA) and explore the effect mechanism of EA for reliving allodynia. METHODS: Eighty-four male SD rats were randomly divided into a control group, a model group and an EA group, 28 rats in each one. Intra-articular injection of sodium monoiodoacetate (MIA) was administered in right knee joint of each rat in the model group and the EA group to establish the KOA model. In the EA group, separately, on day 5, 7 and 9 after modeling, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave (2 Hz/15 Hz), 1 mA in current intensity, for 30 min in one intervention, once a day, and 3 interventions were required. On the 9th day after modeling, the weight-bearing rate was calculated for the affected limbs of the rats in each group, the synovial morphological changes were observed using HE and Masson staining, flow cytometry was adopted to detect the synovial immunocyte counts, and MSD multi-spot assay was used to detected the synovial inflammatory cytokine content. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was observed in each group and the ultrastructure of the saphenous nerve was observed under transmission electron microscopy. RESULTS: On the 9th day after modeling, compared with the control group, the weight-bearing rate of the affected limb was reduced (P<0.01), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis occurred in the affected limb; the counts of synovial CD11b+ cells and M1 macrophages (CD11b+CD86+) were increased (P<0.01), the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, IL-10 and IL-13 in the synovial tissue were elevated (P<0.01, P<0.05) for the rats of the model group. Compared with the model group, the weight-bearing rate of the affected limb was increased (P<0.05), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis were mitigated, the counts of CD11b+ cells and M1 macrophages (CD11b+CD86+) in the synovial tissue, and the contents of TNF-α and IL-6 were reduced (P<0.01, P<0.05) in the EA group. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was reduced in the model group when compared with the control group (P<0.01), and it was increased in the EA group when compared with the model group (P<0.05). Besides, in the model group, obviously, the myelin sheath structure was destroyed, the myelin layer was disintegrated and loosened, the axon was extruded or the layer thicken and cracked. Compared with the model group, the injury of saphenous nerve was alleviated remarkably in the EA group. CONCLUSION: The intervention with EA may attenuate the synovial inflammatory response and the injury of saphenous nerve in the affected limb of the rat with KOA, so that the spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage are relieved.


Assuntos
Citocinas , Fator de Necrose Tumoral alfa , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Hiperplasia , Dor/etiologia
8.
Org Biomol Chem ; 20(46): 9127-9131, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36377719

RESUMO

An Fe-catalyzed unprotected hydroxylamine mediated Heck-type coupling between sulfinic acids and alkenes for the regioselective synthesis of (E)-vinyl sulfones has been developed. Mechanism studies indicated for the first time that a radical process may be involved and that hydroxylamines play multiple roles, including those of a mild oxidant and an in situ base. It was found for the first time that this transformation not only realizes C-S bond construction promoted by unprotected hydroxylamines, but also provides a practical and complementary method for the preparation of structurally important (E)-vinyl sulfones.


Assuntos
Hidroxilaminas , Ferro , Hidroxilaminas/química , Ferro/química , Catálise , Sulfonas/química
9.
Metabolites ; 12(11)2022 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-36355094

RESUMO

Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK).

10.
Foods ; 11(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36429314

RESUMO

Until now, Streptoverticillium mobaraense transglutaminase (TG) is the only commercialized TG, but limited information is known about its selection tendency on crosslinking sites at the protein level, restricting its application in the food industry. Here, four recombinant Bacillus TGs were stable in a broad range of pH (5.0-9.0) and temperatures (<50 °C), exhibiting their maximum activity at 50-60 °C and pH 6.0-7.0. Among them, TG of B. cereus (BCETG) demonstrated the maximal specific activity of 177 U/mg. A structural analysis indicated that the Ala147-Ala156 region in the substrate tunnel of BCETG played a vital role in catalytic activity. Furthermore, bovine serum albumin, as well as nearly all protein ingredients in soy protein isolate and whey protein, could be cross-linked by BCETG, and the internal crosslinking paths of three protein substrates were elucidated. This study demonstrated Bacillus TGs are a candidate for protein crosslinking and provided their crosslinking mechanism at the protein level for applications in food processing.

11.
J Agric Food Chem ; 70(43): 13922-13934, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36264009

RESUMO

The malonyl-CoA:ACP transacylase (MAT) domain is responsible for the selection and incorporation of malonyl building blocks in the biosynthesis of polyunsaturated fatty acids (PUFAs) in eukaryotic microalgae (Schizochytrium) and marine bacteria (Moritella marina, Photobacterium profundum, and Shewanella). Elucidation of the structural basis underlying the substrate specificity and catalytic mechanism of the MAT will help to improve the yield and quality of PUFAs. Here, a methodology guided by molecular dynamics simulations was carried out to identify and mutate specificity-conferring residues within the MAT domain of Schizochytrium. Combining mutagenesis, cell-free protein synthesis, and in vitro biochemical assay, we dissected nearby interactions and molecular mechanisms relevant for binding and catalysis and found that the reorientation of the Ser154 Cß-Oγ bond establishes distinctive proton-transfer chains (His153-Ser154 and Asn235-His153-Ser154) for catalysis. Gln66 can be replaced by tyrosine to shorten the distance between His153 (Nε2) and Ser154 (Oγ), which facilitates a faster proton-transfer rate, allowing better use of acyl substrates than the wild type. Furthermore, we screened a mutant that displayed an 18.4% increase in PUFA accumulation. These findings provide important insights into the study of MAT through protein engineering and will benefit dissecting the molecular mechanisms of other PUFA-related catalytic domains.


Assuntos
Malonil Coenzima A , Estramenópilas , Malonil Coenzima A/metabolismo , Prótons , Proteína de Transporte de Acila S-Maloniltransferase/metabolismo , Aciltransferases/metabolismo , Estramenópilas/metabolismo , Ácidos Graxos Insaturados/metabolismo
12.
Front Mol Biosci ; 9: 1004036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225258

RESUMO

The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry through associating with ACE2 on host cells. Intracellular trafficking and palmitoylation of S protein are required for its function. The short cytoplasmic tail of S protein plays a key role in the intracellular trafficking, which contains the binding site for the host trafficking proteins such as COPI, COPII and SNX27. This cytoplasmic tail also contains the palmitoylation sites of S protein. Protein palmitoylation modification of S protein could be catalyzed by a family of zinc finger DHHC domain-containing protein palmitoyltransferases (ZDHHCs). The intracellular trafficking and membrane location facilitate surface expression of S protein and assembly of progeny virions. In this review, we summarize the function of S protein cytoplasmic tail in transportation and localization. S protein relies on intracellular trafficking pathways and palmitoylation modification to facilitate the life cycle of SARS-CoV-2, meanwhile it could interfere with the host transport pathways. The interplay between S protein and intracellular trafficking proteins could partially explain the acute symptoms or Long-COVID complications in multiple organs of COVID-19 patients.

13.
J Agric Food Chem ; 70(41): 13186-13199, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36194761

RESUMO

This study investigated the influence of chitosan oligosaccharides (COSs) on a thioacetamide-induced hepatic encephalopathy (HE) Wistar rat model. COS treatment statistically reduced the false neurotransmitters and blood ammonia in HE rats, along with the suppression of oxidative stress and inflammation. The disbalanced gut microbiota was detected in HE rats by 16S rDNA sequencing, but the abundance alterations of some intestinal bacteria at either the phylum or genus level were at least partly restored by COS treatment. According to metabolomics analysis of rat feces, six metabolism pathways with the greatest response to HE were screened, several of which were remarkably reversed by COS. The altered metabolites might serve as a bridge for the alleviated HE rats treated with COS and the enhanced intestinal bacterial structure. This study provides novel guidance to develop novel food or dietary supplements to improve HE diseases due to the potential beneficial effect of COS on gut-liver axis.


Assuntos
Quitosana , Microbioma Gastrointestinal , Encefalopatia Hepática , Animais , Ratos , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/metabolismo , Encefalopatia Hepática/microbiologia , Quitosana/farmacologia , Amônia/farmacologia , Tioacetamida , Ratos Wistar , DNA Ribossômico , Oligossacarídeos/farmacologia
14.
Front Pharmacol ; 13: 1015510, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249804

RESUMO

There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical issue. We performed a comprehensive analysis of published data and real-world data. First, we conducted analyses of the published trials to show the landscape of efficacy and safety in the treatments of left-sided RAS WT mCRC. Then, we initiated a multicenter real-world study as the validation dataset. This study included six published randomized controlled trials (RCTs) and a total of 1925 patients. The double-drug regimen plus cetuximab/panitumumab (D + C/P) achieved the longest overall survival (OS) in patients with left-sided mCRC (HR = 0.74, 95%CI: 0.57-0.98), while triple-drug regimen with bevacizumab (T + B, HR = 1.1, 95%CI: 0.63-2.0), compared with double-drug with bevacizumab (D + B). The D + C/P had the highest overall response rate (ORR) in patients with left-sided mCRC (OR = 1.8, 95%CI: 0.89-3.8), while T + B (OR = 1.8, 95%CI: 0.70-4.8), compared with D + B. The multicenter real-world cohort showed the double-drug regimen plus cetuximab had longer progression-free survival (PFS) in left-sided mCRC patients than the triple-drug regimen with bevacizumab. The safety analysis showed the incidence of the adverse events (grade≥3) in the triple-drug therapy plus bevacizumab was higher than that in the double-drug therapy plus cetuximab/panitumumab. This work demonstrates the ranking of three regimens for therapeutic efficacy and safety in patients with left-sided RAS WT mCRC. The double-drug regimen plus cetuximab/panitumumab appears more effective and safer than double-drug and triple-drug based regimens with bevacizumab. Further trials and cohort analyses on this topic would increase confidence in these results.

15.
Bioprocess Biosyst Eng ; 45(10): 1705-1717, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36063213

RESUMO

As a promising feedstock, alkali-extracted xylan from lignocellulosic biomass is desired for producing xylose, which can be used for renewable biofuels production. In this study, an efficient pathway has been established for low-cost and high-yield production of xylose by hydrolysis of alkali-extracted xylan from agricultural wastes using an endo-1,4-xylanase (XYLA) from Bacillus safensis TCCC 111022 and a ß-xylosidase (XYLO) from B. pumilus TCCC 11573. The optimum activities of recombinant XYLA (rXYLA) and XYLO (rXYLO) were 60 â„ƒ and pH 8.0, and 30 â„ƒ and pH 7.0, respectively. They were stable over a broad pH range (pH 6.0-11.0 and 7.0-10.0). rXYLO showed a relatively high xylose tolerance up to 100 mM. Furthermore, the yield of xylose from wheat straw, rice straw, corn stover, corncob and sugarcane bagasse by rXYLA and rXYLO was 63.77%, 71.76%, 68.55%, 53.81%, and 58.58%, respectively. This study demonstrated a strategy to produce xylose from agricultural wastes by integrating alkali-extracted xylan and enzymatic hydrolysis.


Assuntos
Bacillus , Saccharum , Xilosidases , Álcalis , Bacillus/metabolismo , Biocombustíveis , Celulose , Endo-1,4-beta-Xilanases/metabolismo , Hidrólise , Saccharum/metabolismo , Xilanos , Xilose/metabolismo , Xilosidases/metabolismo
16.
Front Immunol ; 13: 951529, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159831

RESUMO

Background: Immunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified. Methods: In this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models. Results: The 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis. Conclusion: In conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Axitinibe , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Docetaxel , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Prognóstico , Vimblastina
17.
Front Immunol ; 13: 1005586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172361

RESUMO

Alphaviruses contain many human and animal pathogens, such as CHIKV, SINV, and VEEV. Accumulating evidence indicates that innate immunity plays an important role in response to alphaviruses infection. In parallel, alphaviruses have evolved many strategies to evade host antiviral innate immunity. In the current review, we focus on the underlying mechanisms employed by alphaviruses to evade cGAS-STING, IFN, transcriptional host shutoff, translational host shutoff, and RNAi. Dissecting the detailed antiviral immune evasion mechanisms by alphaviruses will enhance our understanding of the pathogenesis of alphaviruses and may provide more effective strategies to control alphaviruses infection.


Assuntos
Infecções por Alphavirus , Alphavirus , Animais , Antivirais , Humanos , Evasão da Resposta Imune , Nucleotidiltransferases
18.
Artigo em Inglês | MEDLINE | ID: mdl-36170396

RESUMO

Multiple-view (MV) representations enabling multi-perspective exploration of large and complex data are often employed on 2D displays. The technique also shows great potential in addressing complex analytic tasks in immersive visualization. However, although useful, the design space of MV representations in immersive visualization lacks in deep exploration. In this paper, we propose a new perspective to this line of research, by examining the effects of view layout for MV representations on situated analytics. Specifically, we disentangle situated analytics in perspectives of situatedness regarding spatial relationship between visual representations and physical referents, and analytics regarding cross-view data analysis including filtering, refocusing, and connecting tasks. Through an in-depth analysis of existing layout paradigms, we summarize design trade-offs for achieving high situatedness and effective analytics simultaneously. We then distill a list of design requirements for a desired layout that balances situatedness and analytics, and develop a prototype system with an automatic layout adaptation method to fulfill the requirements. The method mainly includes a cylindrical paradigm for egocentric reference frame, and a force-directed method for proper view-view, view-user, and view-referent proximities and high view visibility. We conducted a formal user study that compares layouts by our method with linked and embedded layouts. Quantitative results show that participants finished filtering- and connecting-centered tasks significantly faster with our layouts, and user feedback confirms high usability of the prototype system.

19.
J Control Release ; 350: 435-447, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36030991

RESUMO

The cross-talk between hyperproliferative keratinocytes and activated immune cells is responsible for the progression of psoriasis. The strategy to alleviate psoriasis through inhibiting the abnormal proliferation of keratinocytes remains challenging due to limited therapeutic effects and low skin penetration of drugs. Herein we designed an ultrasound-triggered phase-transition nanodroplet that could produce cavitation to enhance skin penetration and effectively generate reactive oxygen species (ROS) to induce keratinocyte apoptosis for psoriasis treatment. After ultrasound stimulation, the perfluoro-n-pentane (PFP) liquid core of the nanodroplets vaporized, and the Haematoporphyrin monomethyl ether (HMME) encapsulated in the nanodroplets generated plenty of intracellular ROS which caused the apoptosis of HaCat cells through inducing mitochondrial dysfunction. In addition, the blank nanodroplets successfully inhibited the secretion of IL-6 and TNF-α from macrophages and dendritic cells in vitro due to the anti-inflammatory effect of POPG. For the skin penetration test, the phase-transition nanodroplets could effectively accumulate in the epidermis of the skin and generate intracellular ROS. The in-vivo anti-psoriasis experiment demonstrated that the phase-transition nanodroplets relieved the symptoms of psoriasis lesion and inhibited epidermal hyperplasia through induction of cell apoptosis under ultrasound irritation. Meanwhile, the inflammatory cytokines in the skin lesion almost decreased to the normal baseline level after SDT. Collectively, this study demonstrated a new strategy to inhibit keratinocyte hyperproliferation for psoriasis management based on sonodynamic responded nanodroplets.


Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Anti-Inflamatórios/uso terapêutico , Éteres/farmacologia , Éteres/uso terapêutico , Humanos , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Interleucina-6 , Queratinócitos , Psoríase/tratamento farmacológico , Psoríase/patologia , Espécies Reativas de Oxigênio
20.
Physiol Mol Biol Plants ; 28(6): 1175-1190, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35910447

RESUMO

Zinc oxide nano particles (ZnO NPs) have been employed as a novel strategy to regulate plant tolerance and alleviate heavy metal stress, but our scanty knowledge regarding the systematic role of ZnO NPs to ameliorate chromium (Cr) stress especially in rice necessitates an in-depth investigation. An experiment was performed to evaluate the effect of different concentrations of ZnO NPs (e.g., 0, 25, 50, 100 mg/L) in ameliorating the Cr toxicity and accumulation in rice seedlings in hydroponic system. Our results demonstrated that Cr (100 µM) severely inhibited the rice seedling growth, whereas exogenous treatment of ZnO NPs significantly alleviated Cr toxicity stress and promoted the plant growth. Moreover, application of ZnO NPs significantly augmented the germination energy, germination percentage, germination index, and vigor index. In addition, biomass accumulation, antioxidants (SOD, CAT, POD), nutrient acquisition (Zn, Fe) was also improved in ZnO NPs-treated plants, while the lipid peroxidation (MDA, H2O2), electrolyte leakage as well as Cr uptake and in-planta accumulation was significantly decreased. The burgeoning effects were more apparent at ZnO NPs (100 mg/L) suggesting the optimum treatment to ameliorate Cr induced oxidative stress in rice plants. Furthermore, the treatment of ZnO NPs (100 mg/L) reduced the level of endogenous abscisic acid (ABA) and stimulated the growth regulator hormones such as brassinosteroids (BRs) possibly linked with enhanced phytochelatins (PCs) levels. The ultrastructure analysis at cellular level of rice revealed that the application of 100 mg/L ZnO NPs protected the chloroplast integrity and other cell organells via improvement in plant ionomics, antioxidant activities and down regulating Cr induced oxidative stress in rice plants. Conclusively, observations of the current study will be helpful in developing stratigies to decrease Cr contamination in food chain by employing ZnO NPs and to mitigate the drastic effects of Cr in plants for the sustainable crop growth.

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