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1.
Molecules ; 24(22)2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31717579

RESUMO

The dried seeds of Aesculus chinensis Bge. var. chekiangensis (Hu et Fang) Fang, called "Suo Luo Zi", have been used in traditional Chinese medicine. Nevertheless, most studies have been focused on components of less polarity fractions. In this research, twelve indoles, including six new indole glycosides (1-6) as well as six known analogs were isolated from the polar portion which has been seldom studied. This is the first description of N-glucosylated indoles obtained from the genus of Aesculus. Structures of the new compounds (1-6) were elucidated based on comprehensive interpretation of HRESIMS, 1D and 2D NMR. Additionally, the neuroprotective activities of the N-glucosylated indoles were evaluated for the first time indicating that compounds 1-5 and 9-10 exhibited moderate neuroprotective activities. Further cytotoxicity tests of isolates 1-10 on three human tumor cell lines suggested that none of these compounds were cytotoxic (IC50 > 50 µM).

2.
J Phys Chem Lett ; 10(22): 7100-7106, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31682127

RESUMO

The underlying hole-transfer mechanism in high-efficiency OSC bulk heterojunctions based on acceptor-donor-acceptor (A-D-A) nonfullerene acceptors (NFAs) remains unclear. Herein, we study the hole-transfer process between copolymer donor J91 and five A-D-A NFAs with different highest occupied molecular orbital energy offsets (ΔEH) (0.05-0.42 eV) via ultrafast optical spectroscopies. Transient absorption spectra reveal a rapid hole-transfer rate with small ΔEH, suggesting that a large energy offset is not required to overcome the exciton binding energy. Capacitance-frequency spectra and time-resolved photoluminescence spectra confirm the delocalization of an A-D-A-structured acceptor exciton with weak binding energy. Relative to the hole-transfer rate, hole-transfer efficiency is the key factor affecting device performance. We propose that holes primarily stem from weakly bound acceptor exciton dissociation, revealing a new insight into the hole-transfer process in A-D-A NFA-based OSCs.

3.
Zootaxa ; 4651(2): zootaxa.4651.2.3, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31716909

RESUMO

A new sciaenid fish, Johnius taiwanensis, is described from the southeast coast of mainland China from Zhejiang to Guangdong, Hong Kong, and west coast of Taiwan. Johnius taiwanensis sp. nov. can be distinguished from other Johnius species by having a grayish dorsal half of body divided by a clear line from a whitish ventral half, and a black spot at the dorsal half of pectoral-fin axil, appearing as a distinct dot at the most dorsal point of the pectoral-fin base. First dorsal fin black tipped, other fins pale to dusky but never darkly pigmented. The species lacks distinctly enlarged teeth on upper and lower jaws. Body scales ctenoid, moderately large, with five or six rows between first dorsal-fin origin and lateral line. It is one of the most abundant sciaenids found in the shallow coastal waters (20 m) of southeast mainland China and the west coast of Taiwan. It has often been misidentified as J. macrorhynus in the region. Phylogenetic analysis from all 27 sciaenid species found in Chinese waters based on the complete COI and 16S rRNA gene sequences confirmed that the genus Johnius is monophyletic and J. taiwanensis is placed as a sister species of J. trewavasae. Acoustic analysis has shown that J. taiwanensis produces a unique sound among fishes in Taiwan coastal waters.


Assuntos
Peixes , Animais , China , Peixes/genética , Hong Kong , Filogenia , RNA Ribossômico 16S , Taiwan
4.
J Environ Pathol Toxicol Oncol ; 38(3): 217-227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679309

RESUMO

BACKGROUND: Natural active components have been reported to serve as adjuvant medications in the clinical practice of cancer therapeutics. However, the antineoplastic roles of atractylenolide III (ATL) are rarely reported. In the present study, we assessed the functions of ATL combined with docetaxel in gastric cancer cells. METHODS: Cell viability and cytotoxic activity were evaluated using CCK-8 and LDH-based cytotoxicity assays, respectively. Protein expression levels were measured by western blotting analysis. Annexin V-FITC/PI staining was used to evaluate cell apoptosis using flow cytometry. RESULTS: AGS and SGC-7901 cell viability was significantly inhibited in ATL combined with docetaxel group compared with docetaxel treatment alone. The levels of LDH, apoptosis rate, and the ratio of BAX to Bcl-2 were significantly elevated in combination treatment group compared to docetaxel treatment alone. Intriguingly, docetaxel combined with ATL resulted in a significant decrease in FGFR1, FGFR2, and FGFR4 protein expression compared with docetaxel treatment alone. Knockout of FGFR1, -2, and -4 exhibited a similar role of medications to inhibit growth and induce apoptosis in AGS and SGC-7901 cells. CONCLUSIONS: ATL and docetaxel treatment performed the synergistic effects on the inhibition of growth and induction of apoptosis in gastric cancer cells, and the underlying mechanism was mediated, at least partially, through the inhibition of FGFR1, -2, and -4.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Lactonas/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias Gástricas/tratamento farmacológico
5.
Nat Commun ; 10(1): 4597, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601812

RESUMO

While high sulfur loading has been pursued as a key parameter to build realistic high-energy lithium-sulfur batteries, less attention has been paid to the cathode porosity, which is much higher in sulfur/carbon composite cathodes than in traditional lithium-ion battery electrodes. For high-energy lithium-sulfur batteries, a dense electrode with low porosity is desired to minimize electrolyte intake, parasitic weight, and cost. Here we report the profound impact on the discharge polarization, reversible capacity, and cell cycling life of lithium-sulfur batteries by decreasing cathode porosities from 70 to 40%. According to the developed mechanism-based analytical model, we demonstrate that sulfur utilization is limited by the solubility of lithium-polysulfides and further conversion from lithium-polysulfides to Li2S is limited by the electronically accessible surface area of the carbon matrix. Finally, we predict an optimized cathode porosity to maximize the cell level volumetric energy density without sacrificing the sulfur utilization.

6.
Nat Commun ; 10(1): 4854, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649240

RESUMO

Nanocrystallization is a well-known strategy to dramatically tune the properties of materials; however, the grain-size effect of graphene at the nanometer scale remains unknown experimentally because of the lack of nanocrystalline samples. Here we report an ultrafast growth of graphene films within a few seconds by quenching a hot metal foil in liquid carbon source. Using Pt foil and ethanol as examples, four kinds of nanocrystalline graphene films with average grain size of ~3.6, 5.8, 8.0, and 10.3 nm are synthesized. It is found that the effect of grain boundary becomes more pronounced at the nanometer scale. In comparison with pristine graphene, the 3.6 nm-grained film retains high strength (101 GPa) and Young's modulus (576 GPa), whereas the electrical conductivity is declined by over 100 times, showing semiconducting behavior with a bandgap of ~50 meV. This liquid-phase precursor quenching method opens possibilities for ultrafast synthesis of typical graphene materials and other two-dimensional nanocrystalline materials.

7.
J Sex Med ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585805

RESUMO

INTRODUCTION: Modulating tissue-resident stem and progenitor cells with a non-invasive, mechanobiological intervention is an optimal approach for tissue regeneration. Stem cell antigen-1 (Sca-1) has been identified as a stem cell marker within many organs but never within the penis. AIM: To localize and isolate penile stem/progenitor cells (PSPCs) and to evaluate cellular differentiation after exposure to induction medium and microenergy acoustic pulse (MAP) therapy. METHODS: Six male Sprague-Dawley rats were used to isolate PSPCs. Isolation was followed by stem cell characterization and differentiation assays. The PSPCs were then treated with MAP (0.033 mJ/mm2, 1 Hz) at various dosages (25, 50, 100, and 200 pulses) and for different durations (1, 2, 4, 6, or 8 hours) in vitro. MAIN OUTCOME MEASURE: The PSPCs (Sca-1-positive cells) were isolated using the magnetic-activated cell sorting system. PSPC cellular differentiation was assessed after induction with induction medium and with MAP in vitro. Wnt/ß-catenin signaling was also assayed. RESULTS: The PSPCs were successfully localized within the penile subtunic and perisinusoidal spaces, and they were successfully isolated using magnetic-activated cell sorting. The stemness of the cells was confirmed by stem cell marker characterization and by multiple differentiation into smooth muscle cells, endothelial cells, adipocytes, and neurons. MAP-induced PSPCs differentiated into smooth muscle cells by activating the Wnt/ß-catenin signaling pathway in a time- and dosage-dependent manner. CLINICAL IMPLICATIONS: By modulating resident PSPCs, MAP may have utility in the treatment of erectile dysfunction (ED). STRENGTHS & LIMITATIONS: This study provides solid evidence in support of microenergy therapies, including both MAP and low-intensity extracorporeal shock wave therapy, for the treatment of ED. Additional studies are needed and should include additional stem cells markers. Furthermore, studies exploring the underling mechanisms for PSPC activation and differentiation are required. CONCLUSION: PSPCs were successfully identified, localized, and isolated. Additionally, MAP provoked PSPCs to differentiate into smooth muscle cells via the Wnt/ß-catenin signaling pathway. As such, MAP provides a novel method for activating endogenous tissue-resident stem/progenitor cells and might facilitate stem cell regenerative therapy targeting ED. Peng D, Yuan H, Liu T, et al. Smooth Muscle Differentiation of Penile Stem/Progenitor Cells Induced by Microenergy Acoustic Pulses In Vitro. J Sex Med 2019; XX:XXX-XXX.

8.
Soft Matter ; 15(40): 7992-7995, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31502625

RESUMO

Azobenzene based inorganic salts containing lithium, sodium or potassium cations were prepared and the behaviors of reversible light modulated ionic conductivity were observed based on photoisomerizations of azobenzene salts in aqueous solutions. The highest ionic conductivity was observed in the solution of potassium ionized azobenzene, assisted by the unique formation of a network-like aggregated morphology.

9.
Adv Mater ; 31(43): e1902978, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31502709

RESUMO

Contamination is a major concern in surface and interface technologies. Given that graphene is a 2D monolayer material with an extremely large surface area, surface contamination may seriously degrade its intrinsic properties and strongly hinder its applicability in surface and interfacial regions. However, large-scale and facile treatment methods for producing clean graphene films that preserve its excellent properties have not yet been achieved. Herein, an efficient postgrowth treatment method for selectively removing surface contamination to achieve a large-area superclean graphene surface is reported. The as-obtained superclean graphene, with surface cleanness exceeding 99%, can be transferred to dielectric substrates with significantly reduced polymer residues, yielding ultrahigh carrier mobility of 500 000 cm2 V-1 s-1 and low contact resistance of 118 Ω µm. The successful removal of contamination is enabled by the strong adhesive force of the activated-carbon-based lint roller on graphene contaminants.

10.
J Fish Biol ; 95(5): 1286-1297, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31469430

RESUMO

We used the cytochrome oxidase subunit I (coI) gene DNA to barcode 117 endemic Gulf and cosmopolitan Indo-West Pacific fish species belonging to 54 families and 13 orders. Novel DNA barcodes were provided for 18 fish species (Trachinocephalus sp., Nematalosa sp., Herklotsichthys lossei, Upeneus doriae, Trachurus indicus, Apogonichthyoides taeniatus, Verulux cypselurus, Favonigobius sp., Suezichthus gracilis, Sillago sp., Brachirus orientalis, Pegusa sp., Lepidotrigla bispinosa, Lepidotrigla sp., Grammoplites suppositus, Hippichthys sp., Paramonacanthus sp. and Triacanthus sp.). The species delimitation analysis, conducted with Poisson tree processes- Bayesian PTP (PTP-bPTP) and nucleotide-divergence-threshold (NDT) models), found 137 and 119 entities respectively. Overall, NDT method, neighbour-joining species tree and the prior taxonomic assessment provided similar results. Among the 54 families considered, only 10 (Ariommatidae, Ephippidae, Leiognathidae, Nemipteridae, Plotosidae, Pomacanthidae, Pomacentridae, Priacanthidae and Rachycentridae) showed the occurrence of molecular diagnostic pure characters. The DNA barcoding database developed during this study will help ichthyologists to identify and resolve the taxonomic ambiguities they may encounter with the fishes occurring in The Gulf and throughout the region.

11.
Neurourol Urodyn ; 38(8): 2140-2150, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31452249

RESUMO

AIM: To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism. METHODS: The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033 mJ/mm2 , 3 Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax-7, Int-7α, H3P, and EdU expression. Meanwhile, pelvic floor muscle-derived stem cells (MDSCs) were harvested through magnetic-activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation. RESULTS: Obesity reduced EdU-label-retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP-activated protein kinase (AMPK) /Wnt/ß-catenin signaling pathways by MAP is the potential mechanism. CONCLUSIONS: MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK-AMPK and Wnt/ß-catenin signaling pathway.

12.
Chem Biol Drug Des ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31444845

RESUMO

Neuropeptide Y4 receptor has the most significant effect on body weight and fat mass in its physiological functions, and the activation of Y4 receptor has explicit role on losing weight. The Y4 receptor has been successfully applied in the development of anti-obesity agent, thus representing a potential therapeutic target for obesity treatment. Here, we reported the first discovery of small molecule agonists targeting Y4 receptor: three Y4 receptor models with active and inactive conformations were built, each model was submitted following structure-based virtual screening, and finally six hits were identified as Y4 receptor agonists. These results confirm the reliability of the constructed Y4 receptor models and the proposed computational strategy for investigating novel Y4 receptor agonists. These new small molecule Y4 receptor agonists will contribute to the further development of Y4 agonists as potential therapeutics and functional probes.

13.
Sci Adv ; 5(8): eaaw8337, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31448331

RESUMO

Directly incorporating heteroatoms into the hexagonal lattice of graphene during growth has been widely used to tune its electrical properties with superior doping stability, uniformity, and scalability. However the introduction of scattering centers limits this technique because of reduced carrier mobilities and conductivities of the resulting material. Here, we demonstrate a rapid growth of graphitic nitrogen cluster-doped monolayer graphene single crystals on Cu foil with remarkable carrier mobility of 13,000 cm2 V-1 s-1 and a greatly reduced sheet resistance of only 130 ohms square-1. The exceedingly large carrier mobility with high n-doping level was realized by (i) incorporation of nitrogen-terminated carbon clusters to suppress the carrier scattering and (ii) elimination of all defective pyridinic nitrogen centers by oxygen etching. Our study opens up an avenue for the growth of high-mobility/conductivity doped graphene with tunable work functions for scalable graphene-based electronic and device applications.

14.
Chin J Integr Med ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418133

RESUMO

OBJECTIVE: To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia. METHODS: We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia. RESULTS: Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AME) of generation of neurons (AME-GN) was validated successfully in vivo. Newborn neurons increased in BJC treatment group (P<0.05). The expression of VEGF and MMP-9 decreased in the compound treatment groups compared with the I/R model group (P<0.05). CONCLUSIONS: AME demonstrates effectiveness of our pioneering approach to the discovery of therapeutic target. The novel approach for AM discovery in an effort to identify therapeutic targets holds the promise of accelerating elucidation of underlying pharmacological mechanisms in cerebral ischemia.

15.
J Sep Sci ; 42(16): 2592-2601, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31161707

RESUMO

A rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for simultaneous determination of puerarin, daidzin, daidzein, 3'-hydroxy puerarin, and genistein in rat plasma after oral administration of Puerariae lobatae radix extract. The method of protein precipitation with acetonitrile was used for sample preparation. Chromatographic separation was achieved on a C18 column with the mobile phases of acetonitrile/water containing 0.1% formic acid. The analytes were detected by mass spectrometer with an electrospray ionization source operating in the negative ion mode. The linearity, precision, accuracy, dilution reliability, recovery, matrix effects, and stability of the method were within acceptable ranges. The developed method was successfully used to compare the pharmacokinetic characteristics of five analytes in normal and type 2 diabetics rats after oral administration of Puerariae lobatae radix extract. Several pharmacokinetic alterations were observed and this might be caused by the pathological state of type 2 diabetes.

16.
Sci Adv ; 5(5): eaaw4466, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31149638

RESUMO

The tight coupling between cerebral blood flow and neural activity is a key feature of normal brain function and forms the basis of functional hyperemia. The mechanisms coupling neural activity to vascular responses, however, remain elusive despite decades of research. Recent studies have shown that cerebral functional hyperemia begins in capillaries, and red blood cells (RBCs) act as autonomous regulators of brain capillary perfusion. RBCs then respond to local changes of oxygen tension (PO2) and regulate their capillary velocity. Using ex vivo microfluidics and in vivo two-photon microscopy, we examined RBC capillary velocity as a function of PO2 and showed that deoxygenated hemoglobin and band 3 interactions on RBC membrane are the molecular switch that responds to local PO2 changes and controls RBC capillary velocity. Capillary hyperemia can be controlled by manipulating RBC properties independent of the neurovascular unit, providing an effective strategy to treat or prevent impaired functional hyperemia.

17.
J Am Chem Soc ; 141(19): 7670-7674, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31058498

RESUMO

Chemical vapor deposition (CVD) enables the large-scale growth of high-quality graphene film and exhibits considerable potential for the industrial production of graphene. However, CVD-grown graphene film contains surface contamination, which in turn hinders its potential applications, for example, in electrical and optoelectronic devices and in graphene-membrane-based applications. To solve this issue, we demonstrated a modified gas-phase reaction to achieve the large-scale growth of contamination-free graphene film, i.e., superclean graphene, using a metal-containing molecule, copper(II) acetate, Cu(OAc)2, as the carbon source. During high-temperature CVD, the Cu-containing carbon source significantly increased the Cu content in the gas phase, which in turn suppressed the formation of contamination on the graphene surface by ensuring sufficient decomposition of the carbon feedstock. The as-received graphene with a surface cleanness of about 99% showed enhanced optical and electrical properties. This study opens a new avenue for improving graphene quality with respect to surface cleanness and provides new insight into the mechanism of graphene growth through the gas-phase reaction pathway.

18.
Nat Commun ; 10(1): 1912, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015405

RESUMO

Impurities produced during the synthesis process of a material pose detrimental impacts upon the intrinsic properties and device performances of the as-obtained product. This effect is especially pronounced in graphene, where surface contamination has long been a critical, unresolved issue, given graphene's two-dimensionality. Here we report the origins of surface contamination of graphene, which is primarily rooted in chemical vapour deposition production at elevated temperatures, rather than during transfer and storage. In turn, we demonstrate a design of Cu substrate architecture towards the scalable production of super-clean graphene (>99% clean regions). The readily available, super-clean graphene sheets contribute to an enhancement in the optical transparency and thermal conductivity, an exceptionally lower-level of electrical contact resistance and intrinsically hydrophilic nature. This work not only opens up frontiers for graphene growth but also provides exciting opportunities for the utilization of as-obtained super-clean graphene films for advanced applications.

19.
Mater Sci Eng C Mater Biol Appl ; 98: 545-549, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30813057

RESUMO

This study reports magnetic targeting guided magnetic (MR)/photoacoustic (PA) dual-modal imaging by core/shell Fe3O4/Au nanoparticles. In this work, MR imaging provides time-dependent tumor location, and PA imaging reveals high resolution vasculatures inside the tumor. It is noted that the synthesized Fe3O4/Au nanoparticles exhibited higher r2 value up to 329 mM-1 s-1 than previously reported T2 contrast agents. Furthermore, the Fe3O4/Au NPs are applied as a promising candidate for in vivo MR/PA imaging of tumors by intravenously injection into LNCaP tumor-beared mice. The MR/PA imaging results show a significantly enhanced MR/PA images in the tumor site. The prepared core/shell Fe3O4/Au nanoparticles will be widely applicable in multi-modal imaging.


Assuntos
Óxido Ferroso-Férrico/química , Ouro/química , Magnetismo , Nanopartículas Metálicas/química , Imagem Multimodal , Técnicas Fotoacústicas , Imagem por Ressonância Magnética , Nanopartículas Metálicas/ultraestrutura
20.
Immunity ; 50(4): 1043-1053.e5, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30902636

RESUMO

Human Vγ9Vδ2 T cells respond to microbial infections and malignancy by sensing diphosphate-containing metabolites called phosphoantigens, which bind to the intracellular domain of butyrophilin 3A1, triggering extracellular interactions with the Vγ9Vδ2 T cell receptor (TCR). Here, we examined the molecular basis of this "inside-out" triggering mechanism. Crystal structures of intracellular butyrophilin 3A proteins alone or in complex with the potent microbial phosphoantigen HMBPP or a synthetic analog revealed key features of phosphoantigens and butyrophilins required for γδ T cell activation. Analyses with chemical probes and molecular dynamic simulations demonstrated that dimerized intracellular proteins cooperate in sensing HMBPP to enhance the efficiency of γδ T cell activation. HMBPP binding to butyrophilin doubled the binding force between a γδ T cell and a target cell during "outside" signaling, as measured by single-cell force microscopy. Our findings provide insight into the "inside-out" triggering of Vγ9Vδ2 T cell activation by phosphoantigen-bound butyrophilin, facilitating immunotherapeutic drug design.


Assuntos
Antígenos CD/química , Butirofilinas/química , Ativação Linfocitária , Organofosfatos/metabolismo , Subpopulações de Linfócitos T/imunologia , Antígenos CD/metabolismo , Sítios de Ligação , Butirofilinas/metabolismo , Cristalografia por Raios X , Dimerização , Desenho de Drogas , Humanos , Ligações de Hidrogênio , Imunoterapia , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Conformação Proteica , Domínios Proteicos , Isoformas de Proteínas/química , Processamento de Proteína Pós-Traducional , Receptores de Antígenos de Linfócitos T gama-delta , Análise de Célula Única , Relação Estrutura-Atividade , Subpopulações de Linfócitos T/metabolismo
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