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1.
Pharmgenomics Pers Med ; 14: 1505-1515, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34848996

RESUMO

Purpose: Granulysin (GNLY) is a cytotoxic granule that has been reported to have various antimicrobial activities. We evaluated the association between a missense variant in GNLY (rs11127) and treatment efficacy of pegylated interferon-alpha (PegIFNα) or nucleos(t)ide analogs (NUCs) in patients with chronic hepatitis B (CHB). Patients and Methods: We included a total of 1823 patients with hepatitis B e antigen (HBeAg)-positive CHB (954 patients treated with PegIFNα and 869 patients treated with NUCs) in four Phase IV multicenter randomized controlled trials. The association of the GNLY rs11127 genotype with the combined response (CR), defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA level <2000 IU/mL was evaluated. A polygenic score (PGS) was constructed to evaluate the cumulative effect of multiple single-nucleotide polymorphisms (SNPs), including rs11127 and several other SNPs, STAT4 rs7574865, CFB rs12614, and CD55 rs28371597, which were reported to be associated with CR. Results: GNLY rs11127 was significantly associated with CR in patients treated with PegIFNα. The CR rate in patients with the rs11127 CC genotype was higher than that with the CT or TT genotype (40.98% vs 30.34% or 27.09%, P = 0.003). Furthermore, a PGS integrating GNLY rs11127 and three other SNPs was significantly associated with CR in PegIFNα-treated patients (P < 0.001). However, no significant correlation was found between GNLY rs11127 and CR in NUCs-treated patients. Conclusion: GNLY rs11127 is an independent biomarker for predicting the response to PegIFNα therapy in HBeAg-positive CHB patients. Furthermore, the PGS, including GNLY rs11127, provides new insights for individualized treatment in clinical practice.

2.
Front Immunol ; 12: 728190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659214

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear. Therefore, effective and low side-effect therapies for SLE are lacking. Recently, mesenchymal stem cell (MSC) therapy for autoimmune diseases, particularly SLE, has gained increasing attention. This therapy can improve the signs and symptoms of refractory SLE by promoting the proliferation of Th2 and Treg cells and inhibiting the activity of Th1, Th17, and B cells, etc. However, MSC therapy is also reported ineffective in some patients with SLE, which may be related to MSC- or patient-derived factors. Therefore, the therapeutic effects of MSCs should be further confirmed. This review summarizes the status of MSC therapy in refractory SLE treatment and potential reasons for the ineffectiveness of MSC therapy from three perspectives. We propose various MSC modification methods that may be beneficial in enhancing the immunosuppression of MSCs in SLE. However, their safety and protective effects in patients with SLE still need to be confirmed by further experimental and clinical evidence.

3.
Appl Opt ; 60(25): 7574-7580, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613223

RESUMO

Three types of alumina surface irradiated by laser are simulated in this study to investigate stray light ablation. Results indicate that temperature fields of triangular and rectangular microstructures exhibit the "head effect," while overall still exhibit Gaussian distributions. For the stress, there is a notable difference between the microstructure surface and the ideal surface. The most stress concentration occurs at the corners on the microstructure surface termed as the "bottom effect." The maximum tensile stress of a triangular microstructure appears below the midline of the slope. The location of the maximum tensile stress on the triangle first shifts down and then up. The inflection point is 0.9 µm in height of the triangle.

4.
Chem Sci ; 12(38): 12719-12725, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34703558

RESUMO

Anticoagulant therapeutics are a mainstay of modern surgery and of clotting disorder management such as venous thrombosis, yet performance and supply limitations exist for the most widely used agent - heparin. Herein we report the first synthesis, characterization, and performance of sulfated poly-amido-saccharides (sulPASs) as heparin mimetics. sulPASs inhibit the intrinsic pathway of coagulation, specifically FXa and FXIa, as revealed by ex vivo human plasma clotting assays and serine protease inhibition assays. sulPASs activity positively correlates with molecular weight and degree of sulfation. Importantly, sulPASs are not degraded by heparanases and are non-hemolytic. In addition, their activity is reversed by protamine sulfate, unlike small molecule anticoagulants. In an in vivo murine model, sulPASs extend clotting time in a dose dependent manner with bleeding risk comparable to heparin. These findings support continued development of synthetic anticoagulants to address the clinical risks and shortages associated with heparin.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34705658

RESUMO

Seeking good correspondences between two images is a fundamental and challenging problem in the remote sensing (RS) community, and it is a critical prerequisite in a wide range of feature-based visual tasks. In this article, we propose a flexible and general deep state learning network for both rigid and nonrigid feature matching, which provides a mechanism to change the state of matches into latent canonical forms, thereby weakening the degree of randomness in matching patterns. Different from the current conventional strategies (i.e., imposing a global geometric constraint or designing additional handcrafted descriptor), the proposed StateNet is designed to perform alternating two steps: 1) recalibrates matchwise feature responses in the spatial domain and 2) leverages the spatially local correlation across two sets of feature points for transformation update. For this purpose, our network contains two novel operations: adaptive dual-aggregation convolution (ADAConv) and point rendering layer (PRL). These two operations are differentiable, so our network can be inserted into the existing classification architecture to reduce the cost of establishing reliable correspondences. To demonstrate the robustness and universality of our approach, extensive experiments on various real image pairs for feature matching are conducted. Experiments reveal the superiority of our StateNet significantly over the state-of-the-art alternatives.

7.
Front Mol Biosci ; 8: 693651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490347

RESUMO

C1ORF112 is an evolutionarily conserved gene across vertebrates. Over the last decade, studies have suggested that C1ORF112 may play a role in tumorigenesis. Using The Cancer Genome Atlas datasets, we explored the role of C1ORF112 across various tumor types in this study. In most tumor types, C1ORF112 expression was increased in tumor tissues compared to corresponding non-tumor tissues. In patients with certain tumor types, higher C1ORF112 expression was correlated with shorter overall survival, disease-free survival, and progression-free survival. Further analyses of C1ORF112 genetic alteration data showed that C1ORF112 amplification and mutations may have an impact on liver hepatocellular carcinoma and uterine corpus endometrial carcinoma prognosis. In cancers including lower grade glioma and adrenocortical carcinoma, C1ORF112 expression was linked to cancer-associated fibroblast infiltration. Gene Ontology analysis showed that C1ORF112 was co-expressed with genes involved in biological processes such as cell cycle and mitotic regulation. The protein interaction network demonstrated that C1ORF112 physically interacted with RAD51, DMC1, and FIGNL1, which have well characterized functions in DNA repair and cell cycle regulation. This pan-cancer study revealed the prognostic value and oncogenic role of C1ORF112 across multiple tumor types.

8.
Org Lett ; 23(16): 6246-6251, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34351170

RESUMO

Sodium tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate (NaBArF) catalyzes the [2 + 2] cycloaddition of 1,4-disubstituted cyclopenta-1,3-dien-2-yl esters with nitrsobenzene in toluene, affording two isolable regioisomers of 6-oxa-7-azabicyclo[3.2.0] heptanes, which thermally rearrange into the same 4-aminocyclopent-1-en-3-ones. In the case of 4-substituted cyclopenta-1,3-dien-2-yl esters, their initial [2 + 2] cycloaddition intermediates undergo a rapid ring expansion to afford six-membered piperidone derivatives efficiently.

9.
BMC Plant Biol ; 21(1): 394, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418959

RESUMO

BACKGROUND: To understand the mechanism of glucosinolates (GSs) accumulation in the specific organs, combined analysis of physiological change and transcriptome sequencing were applied in the current study. Taking Chinese kale as material, seeds and silique walls were divided into different stages based on the development of the embryo in seeds and then subjected to GS analysis and transcriptome sequencing. RESULTS: The main GS in seeds of Chinese kale were glucoiberin and gluconapin and their content changed with the development of the seed. During the transition of the embryo from torpedo- to the early cotyledonary-embryo stage, the accumulation of GS in the seed was accompanied by the salient decline of GS in the corresponding silique wall. Thus, the seed and corresponding silique wall at these two stages were subjected to transcriptomic sequencing analysis. 135 genes related to GS metabolism were identified, of which 24 genes were transcription factors, 81 genes were related to biosynthetic pathway, 25 genes encoded catabolic enzymes, and 5 genes matched with transporters. The expression of GS biosynthetic genes was detected both in seeds and silique walls. The high expression of FMOGS-OX and AOP2, which is related to the production of gluconapin by side modification, was noted in seeds at both stages. Interestingly, the expression of GS biosynthetic genes was higher in the silique wall compared with that in the seed albeit lower content of GS existed in the silique wall than in the seed. Combined with the higher expression of transporter genes GTRs in silique walls than in seeds, it was proposed that the transportation of GS from the silique wall to the seed is an important source for seed GS accumulation. In addition, genes related to GS degradation expressed abundantly in the seed at the early cotyledonary-embryo stage indicating its potential role in balancing seed GS content. CONCLUSIONS: Two stages including the torpedo-embryo and the early cotyledonary-embryo stage were identified as crucial in GS accumulation during seed development. Moreover, we confirmed the transportation of GS from the silique wall to the seed and proposed possible sidechain modification of GS biosynthesis may exist during seed formation.


Assuntos
Brassica/genética , Brassica/metabolismo , Glucosinolatos/genética , Glucosinolatos/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/genética , Sementes/metabolismo , Parede Celular/genética , Parede Celular/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo
10.
J Hepatocell Carcinoma ; 8: 951-961, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34430511

RESUMO

Introduction: Genome-wide association studies identified susceptibility loci in the major histocompatibility complex region for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the causal variants underlying HBV-related HCC pathogenesis remain elusive. Methods: With a total of 1,161 HBV-related HCC cases and 1,353 chronic HBV carriers without HCC, we imputed human leukocyte antigen (HLA) variants based on a Chinese HLA reference panel and evaluated the associations of these variants with the risk of HBV-related HCC. Conditional analyses were used to identify independent signals associated with the risk of HBV-related HCC (P false-discovery rate (FDR) <0.20). A total of 14,930 variants within the MHC region were genotyped or imputed. Results: We identified two variants, rs114401688 (P = 1.05 × 10-6, PFDR = 2.43 × 10-3) and rs115126566 (P = 9.04 × 10-5, PFDR = 1.77 × 10-1), that are independently associated with the risk of HBV-related HCC. Single nucleotide polymorphism (SNP) rs114401688 is in linkage disequilibrium with a previously reported SNP rs9275319. In the current study, we found that its association with HCC could be explained by HLA-DQB1*04 and HLA-DRB1*04. SNP rs115126566 is a novel risk variant and may function by regulating transcriptions of HLA-DPA1/DPB1 through enhancer-mediated mechanisms. HLA zygosity analysis showed that homozygosity at HLA-DQB1 gene is suggestively associated with a higher risk of HCC (P = 0.10) and the risk was more pronounced in the older age group (age ≥50, P = 0.03). Discussion: Our findings further the understanding of the genetic basis for HBV-related HCC predisposition in chronic HBV carriers.

11.
Elife ; 102021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34223818

RESUMO

We describe MIP-1 and MIP-2, novel paralogous C. elegans germ granule components that interact with the intrinsically disordered MEG-3 protein. These proteins promote P granule condensation, form granules independently of MEG-3 in the postembryonic germ line, and balance each other in regulating P granule growth and localization. MIP-1 and MIP-2 each contain two LOTUS domains and intrinsically disordered regions and form homo- and heterodimers. They bind and anchor the Vasa homolog GLH-1 within P granules and are jointly required for coalescence of MEG-3, GLH-1, and PGL proteins. Animals lacking MIP-1 and MIP-2 show temperature-sensitive embryonic lethality, sterility, and mortal germ lines. Germline phenotypes include defects in stem cell self-renewal, meiotic progression, and gamete differentiation. We propose that these proteins serve as scaffolds and organizing centers for ribonucleoprotein networks within P granules that help recruit and balance essential RNA processing machinery to regulate key developmental transitions in the germ line.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Células Germinativas/fisiologia , Animais , Caenorhabditis elegans/embriologia , Proteínas de Caenorhabditis elegans/genética , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Regulação da Expressão Gênica/fisiologia
12.
J Colloid Interface Sci ; 601: 338-345, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34087594

RESUMO

Development of high-performance, economic, and stable non-noble metal catalysts is a still formidable challenge in hydrogen evolution reaction (HER) that must be overcome to alleviate the energy and environmental crisis. Herein, we designed and fabricated N-doped carbon nanoframes encapsulated by CoP nanoparticles (CoP-NCN). The 3D porous structure of the ZIF-67-derived N-doped carbon shortened the charge and mass transport pathways, contributing to enhanced electrocatalytic performance. Moreover, the synergistic effects of excellent conductivity, abundant mesopores, and high-activity CoP nanoparticles led to remarkable electrocatalytic activity toward HER with an extremely low overpotential of 120 mV at 10 mA cm-2 and long-term stability. We further indicate that the fantastic HER catalytic ability of CoP-NCN is attributed to the good conductivity and the abundant active sites. The present study provides a promising avenue toward the design of cost-effective HER electrocatalysts.


Assuntos
Hidrogênio , Nanopartículas , Carbono , Catálise , Porosidade
13.
PLoS Genet ; 17(6): e1009600, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34166401

RESUMO

Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second increases STA-2 levels in the nucleus, modifies the nucleolus, and, potentially as a consequence of a host surveillance mechanism, causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/imunologia , Enterotoxinas/genética , Hypocreales/patogenicidade , Imunidade Inata , Fatores de Transcrição STAT/genética , Esporos Fúngicos/patogenicidade , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/imunologia , Coevolução Biológica , Transporte Biológico , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Proteínas de Caenorhabditis elegans/imunologia , Enterotoxinas/metabolismo , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Hypocreales/crescimento & desenvolvimento , Longevidade/genética , Longevidade/imunologia , Fatores de Transcrição STAT/imunologia , Transdução de Sinais , Esporos Fúngicos/crescimento & desenvolvimento , Vesículas Transportadoras/metabolismo , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
14.
Blood ; 138(13): 1182-1193, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33945603

RESUMO

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.

15.
Cell Death Dis ; 12(5): 449, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953166

RESUMO

Sex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells, drives cancer stem cells (CSCs) properties, fuels tumor initiation, and contributes to tumor aggressiveness. Our previous study has demonstrated the oncogenic role of SOX2 in colorectal cancer (CRC). In this study, we sought to elucidate the underlying mechanisms. Cell function experiments were performed to detect chemoresistance, proliferation, stemness, migration, and invasion in vitro. Chromatin immunoprecipitation, co-immunoprecipitation, luciferase reporter assay, and immunofluorescence were performed to explore the regulation of ABCC2, ß-catenin, and Beclin1 by SOX2. The carcinogenic role of SOX2-ß-catenin/Beclin1-ABCC2 axis in vivo was analyzed by CRC tissues and xenograft models. Here, we reported that SOX2 sustained chemoresistance by transcriptional activation of ABCC2 expression. Suppressing either ß-catenin or autophagy signaling curbed SOX2-driven chemoresistance, stemness, and epithelial-mesenchymal transition (EMT). Mechanistically, SOX2 combined with ß-catenin and increased its nuclear expression and transcriptional activity. Transcriptional activation of Beclin1 expression by SOX2 consequently activating autophagy and inducing malignant phenotype. Furthermore, overexpression of ß-catenin or Beclin1 facilitated ABCC2 expression. The clinical analyses showed that high expression of ABCC2 and Beclin1 were positively correlated with SOX2 and were associated with poor prognosis in CRC patients. Finally, xenograft models revealed that inhibition of SOX2 expression and autophagy restrained tumor growth and chemoresistance in vivo. Conclusively, we demonstrated a novel mechanism by which the SOX2-ß-catenin/Beclin1/autophagy signaling axis regulates chemoresistance, stemness, and EMT in CRC. Our findings provide novel insights into CRC carcinogenesis and may help develop potential therapeutic candidates for CRC.


Assuntos
Proteína Beclina-1/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , beta Catenina/metabolismo , Animais , Autofagia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Feminino , Células HEK293 , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia
16.
Nat Protoc ; 16(1): 327-351, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33277630

RESUMO

Using siRNAs to genetically manipulate immune cells is important to both basic immunological studies and therapeutic applications. However, siRNA delivery is challenging because primary immune cells are often sensitive to the delivery materials and generate immune responses. We have recently developed an amphiphilic dendrimer that is able to deliver siRNA to a variety of cells, including primary immune cells. We provide here a protocol for the synthesis of this dendrimer, as well as siRNA delivery to immune cells such as primary T and B cells, natural killer cells, macrophages, and primary microglia. The dendrimer synthesis entails straightforward click coupling followed by an amidation reaction, and the siRNA delivery protocol requires simple mixing of the siRNA and dendrimer in buffer, with subsequent application to the primary immune cells to achieve effective and functional siRNA delivery. This dendrimer-mediated siRNA delivery largely outperforms the standard electroporation technique, opening a new avenue for functional and therapeutic studies of the immune system. The whole protocol encompasses the dendrimer synthesis, which takes 10 days; the primary immune cell preparation, which takes 3-10 d, depending on the tissue source and cell type; the dendrimer-mediated siRNA delivery; and subsequent functional assays, which take an additional 3-6 d.


Assuntos
Linfócitos B/metabolismo , Dendrímeros/química , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Linfócitos T/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Química Click , Dendrímeros/síntese química , Humanos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética
17.
Cell Chem Biol ; 28(4): 567-582.e4, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33378651

RESUMO

The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and glycan-binding proteins (GBPs) are integral to macrophage function and may contribute to macrophage diversity, little is known about the factors governing their expression. Here, we provide a resource for characterizing the N-/O-glycomes of various murine peritoneal macrophage sub-populations, demonstrating that glycosylation primarily reflects developmental origin and, to a lesser degree, cellular polarization. Furthermore, comparative analysis of GBP-coding genes in resident and elicited macrophages indicated that GBP expression is consistent with specialized macrophage functions and correlates with specific types of displayed glycans. An integrated, semi-quantitative approach was used to confirm distinct expression patterns of glycans and their binding proteins across different macrophages. The data suggest that regulation of glycan-protein complexes may be central to macrophage residence and recruitment.


Assuntos
Proteínas de Transporte/genética , Glicômica , Macrófagos/metabolismo , Polissacarídeos/genética , Animais , Proteínas de Transporte/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/metabolismo
18.
Philos Trans A Math Phys Eng Sci ; 378(2169): 20190189, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32114914

RESUMO

With the escalation of heterogeneous data traffic, the research on optical wireless communication (OWC) has attracted much attention, owing to its advantages such as wide spectrum, low power consumption and high security. Ubiquitous optical devices, e.g. light-emitting diodes (LEDs) and cameras, are employed to support optical wireless links. Since the distribution of these optical devices is usually dense, multiple-input-multiple-output (MIMO) can be naturally adopted to attain spatial diversity gain or spatial multiplexing gain. As the scale of OWC networks enlarges, optical MIMO can also collaborate with network-level operations, like user/AP grouping, to enhance the network throughput. Since OWC is preferred for short-range communications and is sensitive to the directions/rotations of transceivers, optical MIMO links vary frequently and sharply in outdoor scenarios when considering the mobility of optical devices, raising new challenges to network design. In this work, we present an overview of optical MIMO techniques, as well as the cooperation of MIMO and user/AP grouping in OWC networks. In consideration of the challenges for outdoor OWC, key technologies are then proposed to facilitate the adoption of optical MIMO in outdoor scenarios, especially in vehicular ad hoc networks. Lastly, future applications of MIMO in OWC networks are discussed. This article is part of the theme issue 'Optical wireless communication'.

19.
Cell Death Dis ; 11(3): 173, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144236

RESUMO

Growing evidence indicates that a small number of cancer cells express stem cell markers and possess stem cell-like properties that promote malignant progression. Sex-determining region Y-box2 (SOX2) is a stem cell transcription factor essential for maintaining the properties of cancer stem cell (CSC). As CSC properties have been associated with angiogenesis and vasculogenic mimicry (VM), we aimed to comprehensively investigate whether SOX2 regulates CSC properties, angiogenesis, and VM in colorectal carcinoma (CRC) and its potential mechanism in this study. For this study, sphere formation assay, flow cytometry, cell survival analysis, tube formation, 3D culture, immunoblot, mouse model, and luciferase reporter assay were performed in vivo and in vitro. Expressions of SOX2 and miR-450a-5p in CRC tissue samples were examined through immunohistochemistry. First, the expression of SOX2 was not only associated with poor differentiation and prognosis but also promoted angiogenesis and VM. Knockdown of SOX2 ceased stemness properties, angiogenesis, and VM, along with decreased expression of CD133, CD31, and VE-cadherin as observed in functional experiments. Downregulation of SOX2 was found to inhibit tumorigenesis in vivo. Second, miR-450a-5p suppressed the expression of SOX2 by targeting its 3'UTR region directly and hence restrained SOX2-induced CSC properties, angiogenesis, and VM. Moreover, SOX2 overexpression preserved the miR-450a-5p-induced inhibition of CRC properties, angiogenesis, and VM. Finally, clinical samples exhibited a negative correlation between miR-450a-5p and SOX2. Patients with higher SOX2 and lower miR-450a-5p expressions had a poorer prognosis than patients with inverse expressions. Conclusively, we elucidated a unique mechanism of miR-450a-5p-SOX2 axis in the regulation of stemness, angiogenesis, and VM, which may act as a potential therapeutic practice in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Regulação para Baixo/genética , Humanos , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/patologia
20.
Sci Adv ; 6(3): eaay8230, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31998845

RESUMO

Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate for clinical translation due to low activity, inadequate pharmacokinetics, or toxicity. We synthesized a structurally diverse library and used integrated computational and experimental studies to discover mechanisms governing ligand-receptor interaction and to design potent drug leads PY109 and PY108, which display physiochemical drug-likeness properties, desirable pharmacokinetic profiles, and low toxicity. In a murine model of dextran sulfate sodium-induced colitis, orally administered compounds increase interleukin-22 (IL-22) production and accelerate mucosal healing by modulating mucosal adaptive and innate lymphoid cells. AHR and IL-22 pathway induction was confirmed using RNA sequencing and characterization of the lymphocyte protein-protein interaction network. Significant induction of IL-22 was also observed using human T cells from patients with IBD. Our findings support rationally designed AHR agonists for IBD therapy.


Assuntos
Desenho de Fármacos , Imunomodulação/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Cicatrização/efeitos dos fármacos , Cicatrização/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Colite/etiologia , Colite/metabolismo , Colite/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Estabilidade de Medicamentos , Expressão Gênica , Humanos , Interleucinas/biossíntese , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Ligantes , Linfócitos/imunologia , Camundongos , Modelos Moleculares , Conformação Molecular , Receptores de Hidrocarboneto Arílico/química , Regeneração , Relação Estrutura-Atividade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Cicatrização/genética
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