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1.
Proc Natl Acad Sci U S A ; 120(45): e2205463120, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37917793

RESUMEN

Zero-knowledge proof (ZKP) is a fundamental cryptographic primitive that allows a prover to convince a verifier of the validity of a statement without leaking any further information. As an efficient variant of ZKP, noninteractive zero-knowledge proof (NIZKP) adopting the Fiat-Shamir heuristic is essential to a wide spectrum of applications, such as federated learning, blockchain, and social networks. However, the heuristic is typically built upon the random oracle model that makes ideal assumptions about hash functions, which does not hold in reality and thus undermines the security of the protocol. Here, we present a quantum solution to the problem. Instead of resorting to a random oracle model, we implement a quantum randomness service. This service generates random numbers certified by the loophole-free Bell test and delivers them with postquantum cryptography (PQC) authentication. By employing this service, we conceive and implement NIZKP of the three-coloring problem. By bridging together three prominent research themes, quantum nonlocality, PQC, and ZKP, we anticipate this work to inspire more innovative applications that combine quantum information science and the cryptography field.

2.
Anal Chem ; 96(2): 904-909, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38158374

RESUMEN

Analyzing coeluting impurities with similar masses in synthetic oligonucleotides by liquid chromatography-mass spectrometry (LC-MS) poses challenges due to inadequate separation in either dimension. Herein, we present a direct method employing fully resolved isotopic envelopes, enabled by high resolution mass spectrometry (HRMS), to identify and quantify isobaric impurity ions resulting from the deletion or addition of a uracil (U) or cytosine (C) nucleotide from or to the full-length sequence. These impurities may each encompass multiple sequence variants arising from various deletion or addition sites. The method utilizes a full or targeted MS analysis to measure accurate isotopic distributions that are chemical formula dependent but nucleotide sequence independent. This characteristic enables the quantification of isobaric impurity ions involving sequence variants, a capability typically unavailable in sequence-dependent MS/MS methods. Notably, this approach does not rely on standard curves to determine isobaric impurity compositions in test samples; instead, it utilizes the individual isotopic distributions measured for each impurity standard. Moreover, in cases where specific impurity standards are unavailable, the measured isotopic distributions can be adequately replaced with the theoretical distributions (calculated based on chemical formulas of standards) adjusted using experiment-specific correction factors. In summary, this streamlined approach overcomes the limitations of LC-MS analysis for coeluting isobaric impurity ions, offering a promising solution for the in-depth profiling of complex impurity mixtures in synthetic oligonucleotide therapeutics.


Asunto(s)
Oligonucleótidos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Oligonucleótidos/química , Cromatografía Líquida con Espectrometría de Masas , Peso Molecular , Contaminación de Medicamentos , Cromatografía Líquida de Alta Presión/métodos
3.
Phys Rev Lett ; 132(20): 203801, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38829094

RESUMEN

Non-Hermitian systems can exhibit unique quantum phases without any Hermitian counterparts. For example, the latest theoretical studies predict a new surprising phenomenon that bulk bands can localize and dissipate prominently at the system boundary, which is dubbed the non-Hermitian edge burst effect. Here we realize a one-dimensional non-Hermitian Su-Schrieffer-Heeger lattice with bulk translation symmetry implemented with a photonic quantum walk. Employing time-resolved single-photon detection to characterize the chiral motion and boundary localization of bulk bands, we determine experimentally that the dynamics underlying the non-Hermitian edge burst effect is due to the interplay of non-Hermitian skin effect and imaginary band gap closing. This new non-Hermitian physical effect deepens our understanding of quantum dynamics in open quantum systems.

4.
Phys Rev Lett ; 132(19): 196402, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38804933

RESUMEN

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

5.
Anal Bioanal Chem ; 416(13): 3127-3137, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580890

RESUMEN

Monoclonal antibodies (mAbs) represent the largest class of therapeutic protein drug products. mAb glycosylation produces a heterogeneous, analytically challenging distribution of glycoforms that typically should be adequately characterized because glycosylation-based product quality attributes (PQAs) can impact product quality, immunogenicity, and efficacy. In this study, two products were compared using a panel of analytical methods. Two high-resolution mass spectrometry (HRMS) workflows were used to analyze N-glycans, while nuclear magnetic resonance (NMR) was used to generate monosaccharide fingerprints. These state-of-the-art techniques were compared to conventional analysis using hydrophilic interaction chromatography (HILIC) coupled with fluorescence detection (FLD). The advantages and disadvantages of each method are discussed along with a comparison of the identified glycan distributions. The results demonstrated agreement across all methods for major glycoforms, demonstrating how confidence in glycan characterization is increased by combining orthogonal analytical methodologies. The full panel of methods used represents a diverse toolbox that can be selected from based on the needs for a specific product or analysis.


Asunto(s)
Anticuerpos Monoclonales , Interacciones Hidrofóbicas e Hidrofílicas , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Polisacáridos , Glicosilación , Anticuerpos Monoclonales/química , Polisacáridos/análisis , Polisacáridos/química , Espectrometría de Masas/métodos , Espectroscopía de Resonancia Magnética/métodos , Cromatografía Liquida/métodos
6.
J Sci Food Agric ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591367

RESUMEN

BACKGROUND: Goat milk is considered a nutritionally superior resource, owing to its advantageous nutritional attributes. Nevertheless, it is susceptible to spoilage and the persistence of pathogens. Electron beam irradiation stands as a promising non-thermal processing technique capable of prolonging shelf life with minimal residue and a high degree of automation. RESULTS: The effects of electron beam irradiation (2, 3, 5, and 7 kGy) on microorganisms, physicochemical properties, and protein structure of goat milk compared with conventional pasteurized goat milk (PGM) was evaluated. It was found that a 2 kGy electron beam irradiation reduces the total microbial count of goat milk by 6-logs, and the irradiated goat milk protein secondary structure showed a significant decrease in ɑ-helix content. Low irradiation doses led to microaggregation and crosslinking. In contrast, high doses (≥ 5 kGy) slightly disrupted the aggregates and decreased the particle size, disrupting the microscopic surface structure of goat milk, verified by scanning electron microscopy and confocal laser scanning microscopy. CONCLUSION: The irradiation of goat milk with a 2 kGy electron beam may effectively inactivate harmful microorganisms in the milk and maintain/or improve the physicochemical quality and protein structure of goat milk compared to thermal pasteurization. © 2024 Society of Chemical Industry.

7.
Opt Lett ; 48(19): 5053-5056, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37773383

RESUMEN

The shape from polarization is a noncontact 3D imaging method that shows great potential, but its application is limited by the monocular camera system and surface integration algorithm. This Letter proposes a novel, to the best of our knowledge, method that employs deep neural networks to enhance multi-target 3D reconstruction, making a significant advancement in the field. By constructing the relationship between targets' blur, distance, and clarity, the proposed method provides accurate spatial information while mitigating inaccuracies arising from the continuous model. Experiments show that the constructed neural network can help improve the multi-target 3D reconstruction quality compared with conventional methods.

8.
Environ Sci Technol ; 57(48): 20421-20430, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37971949

RESUMEN

A flow-through anode has demonstrated high efficiency for micropollutant abatement in water purification. In addition to developing novel electrode materials, a rational design of its porous structure is crucial to achieve high electrooxidation kinetics while sustaining a low cost for flow-through operation. However, our knowledge of the relationship between the pore structure and its performance is still incomplete. Therefore, we systematically explore the effect of pore size (with a median from 4.7 to 49.4 µm) on the flow-through anode efficiency. Results showed that when the pore size was <26.7 µm, the electrooxidation kinetics was insignificantly improved, but the permeability declined dramatically. Traditional empirical evidence from hydrodynamic modeling and electrochemical tests indicated that a flow-through anode with a smaller pore size (e.g., 4.7 µm) had a high mass transfer capability and large electroactive area. However, this did not further accelerate the micropollutant removal. Combining an overpotential distribution model and an imprinting method has revealed that the reactivity of a flow-through anode is related to the catalytically active volume/sites. The rapid overpotential decay as a function of depth in the anode would offset the merits arising from a small pore size. Herein, we demonstrate an optimal pore size distribution (∼20 µm) of typical flow-through anodes to maximize the process performance at a low energy cost, providing insights into the design of advanced flow-through anodes in water purification applications.


Asunto(s)
Purificación del Agua , Dominio Catalítico , Electrodos , Purificación del Agua/métodos , Porosidad , Permeabilidad
9.
Exp Cell Res ; 416(2): 113154, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35421368

RESUMEN

Gastric cancer is a type of serious malignant tumors all around the world. TCGA data showed that the expression of TRIM65 (E3 ubiquitin ligase) was enhanced in the gastric cancer tissues. The role of TRIM65 in the tumorigenesis of gastric cancer remains unclear. In this study, we successfully established TRIM65-knockdown gastric cancer cells. Next, CCK-8, colony formation assays and transwell assays were performed to detect the cell proliferation and invasion. The results showed that suppression of TRIM65 inhibited the proliferation and invasion of gastric cancer cells. Interestingly, the Western blot assay confirmed that downregulation of TRIM65 increased the level of PPM1A and decreased the level of p-TBK1 in gastric cancer cells. Mechanistically, immunoprecipitation assay revealed that knockdown of TRIM65 inhibited the ubiquitin degradation of PPM1A. In rescue experiments, suppression of PPM1A promoted the proliferation and invasion of gastric cancer cells transfected with sh-TRIM65. Therefore, our results suggested that knockdown of TRIM65 inhibited the proliferation and invasion of gastric cancer cells by suppressing the ubiquitin degradation of PPM1A and phosphorylation of TBK1.


Asunto(s)
Proteína Fosfatasa 2C , Neoplasias Gástricas , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica/genética , Proteína Fosfatasa 2C/metabolismo , Neoplasias Gástricas/genética , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
10.
Nature ; 549(7670): 70-73, 2017 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-28825708

RESUMEN

An arbitrary unknown quantum state cannot be measured precisely or replicated perfectly. However, quantum teleportation enables unknown quantum states to be transferred reliably from one object to another over long distances, without physical travelling of the object itself. Long-distance teleportation is a fundamental element of protocols such as large-scale quantum networks and distributed quantum computation. But the distances over which transmission was achieved in previous teleportation experiments, which used optical fibres and terrestrial free-space channels, were limited to about 100 kilometres, owing to the photon loss of these channels. To realize a global-scale 'quantum internet' the range of quantum teleportation needs to be greatly extended. A promising way of doing so involves using satellite platforms and space-based links, which can connect two remote points on Earth with greatly reduced channel loss because most of the propagation path of the photons is in empty space. Here we report quantum teleportation of independent single-photon qubits from a ground observatory to a low-Earth-orbit satellite, through an uplink channel, over distances of up to 1,400 kilometres. To optimize the efficiency of the link and to counter the atmospheric turbulence in the uplink, we use a compact ultra-bright source of entangled photons, a narrow beam divergence and high-bandwidth and high-accuracy acquiring, pointing and tracking. We demonstrate successful quantum teleportation of six input states in mutually unbiased bases with an average fidelity of 0.80 ± 0.01, well above the optimal state-estimation fidelity on a single copy of a qubit (the classical limit). Our demonstration of a ground-to-satellite uplink for reliable and ultra-long-distance quantum teleportation is an essential step towards a global-scale quantum internet.

11.
JAMA ; 329(24): 2135-2144, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37367978

RESUMEN

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.


Asunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Activador de Tejido Plasminógeno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Cerebral/inducido químicamente , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento , Quimioterapia Combinada , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Administración Intravenosa , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Estudios de Seguimiento , Anciano , Recuperación de la Función
12.
Opt Express ; 30(7): 11684-11692, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35473107

RESUMEN

Quantum interference plays an essential role in understanding the concepts of quantum physics. Moreover, the interference of photons is indispensable for large-scale quantum information processing. With the development of quantum networks, interference of photons transmitted through long-distance fiber channels has been widely implemented. However, quantum interference of photons using free-space channels is still scarce, mainly due to atmospheric turbulence. Here, we report an experimental demonstration of Hong-Ou-Mandel interference with photons transmitted by free-space channels. Two typical photon sources, i.e., correlated photon pairs generated in spontaneous parametric down conversion (SPDC) process and weak coherent states, are employed. A visibility of 0.744 ± 0.013 is observed by interfering with two photons generated in the SPDC process, exceeding the classical limit of 0.5. Our results demonstrate that the quantum property of photons remains even after transmission through unstable free-space channels, indicating the feasibility and potential application of free-space-based quantum interference in quantum information processing.

13.
Microb Pathog ; 162: 105152, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34742892

RESUMEN

Hypervirulent Klebsiella pneumoniae (hvKp) has been globally disseminated recently, especially in Asia. The purpose of this study was to identify the molecular characteristics, clinical manifestations, and clinical risk factors of hvKp infections among patients in a large teaching hospital. A retrospective study was conducted in 123 patients infected with K. pneumoniae at the Affiliated Hospital of Southwest Medical University (Luzhou, China) from October 2016 to November 2018. An isolate that positive for both PCR amplification of aerobactin gene and Galleria mellonella infection model was defined as hvKp. Overall, 43.1% (53/123) of K. pneumoniae isolates were hvKp. String tests were performed on all isolates, and MLSTs of all hvKp were conducted. The K1 ST23 isolates were the dominant clone of hvKp (35.8%). Univariate analysis revealed the following risk factors for hvKp: hepatic abscess (OR = 41.818 [95% CI, 5.379-335.086]), bacteremia (OR = 19.94 [95% CI, 5.565-71.446]), metastatic spread (OR = 19.938 [95% CI, 6.344-62.654]), CRP (OR = 1.008 [95% CI, 1.001-1.015]), nitroimidazole treatment (OR = 7.907 [95% CI, 1.652-37.843]), diabetes (OR = 3.067 [95% CI, 1.38-6.817]), and admission to positive culture interval (OR = 3.636 [95% CI, 1.524-8.678]). Moreover, Multivariate analysis implicated hepatic abscess (OR = 74.332 [95% CI, 3.121-1769.588]), bacteremia (OR = 28.388 [95% CI, 3.039-264.200]), and metastatic spread (OR = 19.391 [95% CI, 3.633-103.498]) as independent risk factors for hvKp infections. Thirteen of twenty-one tested antibiotics were founded resistant to non-hvKp, which is significantly greater than hvKp. Importantly, the ESBL-hvKp and MDR-hvKp were responsible for 7.5% and 15.1% in the hvKp group, respectively.


Asunto(s)
Infecciones por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , China/epidemiología , Hospitales de Enseñanza , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Estudios Retrospectivos , Factores de Riesgo , Virulencia
14.
Molecules ; 27(15)2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35897851

RESUMEN

Among nitrogen-containing cationic electrolytes, diallyl quaternary ammonium salt is a typical monomer with the highest positive charge density, which has attracted the most attention, especially in the research on homopolymers and copolymers of dimethyl diallyl ammonium chloride (DMDAAC), which occupy a very unique and important position. In order to improve the lipophilicity of substituted diallyl ammonium chloride monomers under the premise of high cationic charge density, the simplest, most direct, and most efficient structure design strategy was selected in this paper. Only one of the substituents on DMDAAC quaternary ammonium nitrogen was modified by alkyl; the substituents were propyl and amyl groups, and their corresponding monomers were methyl propyl diallyl ammonium chloride (MPDAAC) and methyl amyl diallyl ammonium chloride (MADAAC), respectively. The effect of substituent structure on the homopolymerization activity of methyl alkyl diallyl ammonium chloride was illustrated by quantum chemical calculation and homopolymerization rate determination experiments via ammonium persulfate (APS) as the initiator system. The results of quantum chemistry simulation showed that, with the finite increase in substituted alkyl chain length, the numerical values of the bond length and the charge distribution of methyl alkyl diallyl ammonium chloride monomer changed little, with the activation energy of the reactions in the following order: DMDAAC < MPDAAC < MADAAC. The polymerization activities measured by the dilatometer method were in the order DMDAAC > MPDAAC > MADAAC. The activation energies Ea of homopolymerization were 96.70 kJ/mol, 97.25 kJ/mol, and 100.23 kJ/mol, and the rate equation of homopolymerization of each monomer was obtained. After analyzing and comparing these results, it could be easily found that the electronic effect of substituent was not obvious, whereas the effect of the steric hindrance was dominant. The above studies have laid a good foundation for an understanding of the polymerization activity of methyl alkyl diallyl ammonium chloride monomers and the possibility of preparation and application of these polymers with high molecular weight.


Asunto(s)
Compuestos de Amonio , Polímeros , Cloruro de Amonio/farmacología , Nitrógeno , Polimerizacion , Polímeros/química
15.
Biochem Biophys Res Commun ; 548: 60-66, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33631675

RESUMEN

Repeated and long-term oxaliplatin therapy leads to drug resistance and severe adverse events, which limit its clinical use. These difficulties highlight the importance of identifying potent and specific drug combinations to enhance the antitumor effects of oxaliplatin. The farnesoid X receptor (FXR) deficiency in colorectal cancer (CRC) suggests that restoring FXR function might be a promising strategy for CRC treatment. A drug combination study showed that the GW4064 acted synergistically with oxaliplatin in colon cancer cells. The combination of oxaliplatin plus GW4064 inhibited cell growth and colony formation, induced apoptosis and pyroptosis in vitro, and slowed tumor growth in vivo. Mechanistically, GW4064 enhanced the chemosensitivity of cells to oxaliplatin by inducing BAX/caspase-3/GSDME-mediated pyroptosis. Furthermore, the combination of oxaliplatin and GW4064 synergistically inhibited STAT3 signaling by restoring SHP expression. Our study revealed that GW4064 could enhance the antitumor effects of oxaliplatin against CRC, which provides a novel therapeutic strategy based on a combinational approach for CRC treatment.


Asunto(s)
Neoplasias Colorrectales/patología , Isoxazoles/farmacología , Oxaliplatino/farmacología , Piroptosis/efectos de los fármacos , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/ultraestructura , Sinergismo Farmacológico , Humanos , Inflamasomas/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Estrógenos/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo
16.
FASEB J ; 34(8): 11168-11184, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32638441

RESUMEN

Macrophages in lung, including resident alveolar macrophages (AMs) and interstitial macrophages (IMs), and monocyte-derived macrophages, play important roles in pulmonary fibrosis (PF), but mechanisms underlying their differential regulation remain unclear. Recombination signal-binding protein Jκ (RBP-J)-mediated Notch signaling regulates macrophage development and phenotype. Here, using bleomycin-induced fibrosis model combined with myeloid-specific RBP-J disruption (RBP-JcKO ) mouse, we investigated the role of Notch signaling in macrophages during PF. Compared with the control, RBP-JcKO mice exhibited alleviated lung fibrosis as manifested by reduced collagen deposition and inflammation, and decreased TGF-ß production. FACS analysis suggested that decreased Ly6clo MHCIIhi AMs might make the major contribution to attenuated fibrogenesis in RBP-JcKO mice, probably by reduced inflammatory factor release and enhanced matrix metalloproteinases expression. Using clodronate-mediated macrophage depletion in RBP-JckO mice, we demonstrated that embryonic-derived AMs play negligible role in lung fibrosis, which was further supported by adoptive transfer experiments. Moreover, on CCR2 knockout background, the effect of RBP-J deficiency on fibrogenesis was not elicited, suggesting that Notch regulated monocyte-derived AMs. Co-culture experiment showed that monocyte-derived AMs from RBP-JcKO mice exhibit reduced myofibroblast activation due to decreased TGF-ß secretion. In conclusion, monocyte-derived Ly6clo MHCIIhi AMs, which are regulated by RBP-J-mediated Notch signaling, play an essential role in lung fibrosis.


Asunto(s)
Antígenos de Histocompatibilidad Clase II/metabolismo , Macrófagos Alveolares/metabolismo , Monocitos/metabolismo , Fibrosis Pulmonar/metabolismo , Receptores Notch/metabolismo , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Secreciones Corporales/metabolismo , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Inflamación/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Miofibroblastos/metabolismo
17.
World J Surg Oncol ; 19(1): 314, 2021 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-34702278

RESUMEN

BACKGROUND: The immune infiltration of patients with colon cancer (CC) is closely associated with RNA-binding proteins (RBPs). However, immune-associated RBPs (IARBPs) in CC remain unexplored. METHODS: The data were downloaded from The Cancer Genome Atlas (TCGA) and the patients were divided into four immune subgroups by single sample gene set enrichment analysis (ssGSEA), in which weighted gene correlation network analysis (WGCNA) identified modules of co-expressed genes correlated with immune infiltration. Univariate (UCR) and multivariate Cox regression (MCR) analyses were applied to screen survival-associated IARBPs. Then, a prognostic signature was performed on TCGA dataset. Risk model was constructed based on the TCGA dataset. Based on the median risk score, CC patients were subdivided into low- and high-risk groups. Furthermore, the accuracy and prognostic value of this signature were validated by using Kaplan-Meier (K-M) curve, receiver operating characteristic (ROC). We further validated the findings in Gene Expression Omnibus (GEO) database. Finally, we evaluated the association between gene expression level and drug sensitivity. RESULTS: Based on the infiltration of immune cells, the TCGA patients were divided into four subgroups. In total, we identified 25 IARBPs, after differential expression and WGCNA analysis. Subsequently, two IARBP signatures (FBXO17 and PPARGC1A) were identified to be significantly associated with the overall survival (OS) of CC patients. K-M survival analysis revealed that the low-risk group correlated with prolonged OS. The prognostic signature was an independent prognostic factor and reflects the immune status of CC patients. Finally, FBXO17 was related with drug sensitivity of bleomycin, gemcitabine, and lenvatinib. PPARGC1A was related to drug sensitivity of dabrafenib, vemurafenib, and trametinib. CONCLUSION: A novel two immune-associated RBPs that was established that may be useful in predicting survival and individualized treatment.


Asunto(s)
Biomarcadores de Tumor , Neoplasias del Colon , Biomarcadores de Tumor/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Proteínas de Unión al ARN
18.
Trends Biochem Sci ; 41(11): 954-969, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27663237

RESUMEN

Lipidomics is a newly emerged discipline that studies cellular lipids on a large scale based on analytical chemistry principles and technological tools, particularly mass spectrometry. Recently, techniques have greatly advanced and novel applications of lipidomics in the biomedical sciences have emerged. This review provides a timely update on these aspects. After briefly introducing the lipidomics discipline, we compare mass spectrometry-based techniques for analysis of lipids and summarize very recent applications of lipidomics in health and disease. Finally, we discuss the status of the field, future directions, and advantages and limitations of the field.


Asunto(s)
Investigación Biomédica/métodos , Lípidos/química , Extracción Líquido-Líquido/métodos , Espectrometría de Masas/métodos , Investigación Biomédica/instrumentación , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/metabolismo , Cromatografía Liquida/métodos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/metabolismo , Humanos , Metabolismo de los Lípidos , Espectrometría de Masas/instrumentación , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/metabolismo , Obesidad/diagnóstico , Obesidad/metabolismo , Solventes/química
19.
J Virol ; 93(22)2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31484750

RESUMEN

Human norovirus (HuNoV) is a leading cause of acute gastroenteritis in both developed and developing countries. Studies of HuNoV host cell interactions are limited by the lack of a simple, robust cell culture system. Due to their diverse HuNoV-like biological features, including histo-blood group antigen (HBGA) binding, rhesus enteric caliciviruses (ReCVs) are viable surrogate models for HuNoVs. In addition, several ReCV strains can be propagated to high titers in standard nonhuman primate cell lines while causing lytic infection and cell death. To identify the ReCV entry receptor, we performed CRISPR/Cas9 library screening in Vero cells, which identified the coxsackievirus and adenovirus receptor (CAR) as a candidate ReCV entry receptor. We showed that short interfering RNA, anti-human CAR (hCAR) monoclonal antibody RmcB treatment, and recombinant hCAR ectodomain blocked ReCV replication in LLC-MK2 cells. CRISPR/Cas9-targeted knockout of CAR in LLC-MK2 and Vero cells made these cell lines resistant to ReCV infection, and susceptibility to infection could be restored by transient expression of CAR. CHO cells do not express CAR or HBGAs and are resistant to ReCV infection. Recombinant CHO cells stably expressing hCAR or the type B HBGA alone did not support ReCV infection. However, CHO cells expressing both hCAR and the type B HBGA were susceptible to ReCV infection. In summary, we have demonstrated that CAR is required for ReCV infection and most likely is a functional ReCV receptor, but HBGAs are also necessary for infection.IMPORTANCE Because of the lack of a simple and robust human norovirus (HuNoV) cell culture system surrogate, caliciviruses still represent valuable research tools for norovirus research. Due to their remarkable biological similarities to HuNoVs, including the utilization of HBGAs as putative attachment receptors, we used rhesus enteric caliciviruses (ReCVs) to study enteric calicivirus host cell interactions. Using CRISPR/Cas9 library screening and functional assays, we identified and validated the coxsackievirus and adenovirus receptor (CAR) as a functional proteinaceous receptor for ReCVs. Our work demonstrated that CAR and HBGAs both are necessary to convert a nonsusceptible cell line to being susceptible to ReCV infection. Follow-up studies to evaluate the involvement of CAR in HuNoV infections are ongoing.


Asunto(s)
Infecciones por Caliciviridae/metabolismo , Receptores Virales/metabolismo , Replicación Viral/fisiología , Infecciones por Adenoviridae/metabolismo , Animales , Células CHO , Caliciviridae/metabolismo , Chlorocebus aethiops , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus/genética , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus/metabolismo , Infecciones por Coxsackievirus/metabolismo , Cricetulus , Gastroenteritis/virología , Intestino Delgado/inmunología , Macaca mulatta/inmunología , Modelos Biológicos , Norovirus/fisiología , Virus ARN/metabolismo , Receptores Virales/genética , Receptores Virales/fisiología , Células Vero , Acoplamiento Viral
20.
Opt Express ; 28(24): 36600-36610, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33379750

RESUMEN

Satellite-based quantum communication is a promising approach for realizing global-scale quantum networks. For free-space quantum channel, single-mode fiber coupling is particularly important for improving the signal-to-noise ratio of daylight quantum key distribution (QKD) and compatibility with standard fiber-based QKD. However, achieving a highly efficient and stable single-mode coupling efficiency under strong atmospheric turbulence remains experimentally challenging. Here, we develop a single-mode receiver with an adaptive optics (AO) system based on a modal version of the stochastic parallel gradient descent (M-SPGD) algorithm and test its performance over an 8 km urban terrestrial free-space channel. Under strong atmospheric turbulence, the M-SPGD AO system obtains an improvement of about 3.7 dB in the single-mode fiber coupling efficiency and a significant suppression of fluctuation, which can find its applications in free-space long-range quantum communications.

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