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1.
PLoS Pathog ; 19(11): e1011789, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37948454

RESUMEN

The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is strongly resistant to extracellular therapeutic and convalescent antibodies via an unknown mechanism. Here, we describe the antibody-mediated spike activation and syncytia formation on cells displaying the viral spike. We found that soluble antibodies against receptor binding motif (RBM) are capable of inducing the proteolytic processing of spike at both the S1/S2 and S2' cleavage sites, hence triggering ACE2-independent cell-cell fusion. Mechanistically, antibody-induced cell-cell fusion requires the shedding of S1 and exposure of the fusion peptide at the cell surface. By inhibiting S1/S2 proteolysis, we demonstrated that cell-cell fusion mediated by spike can be re-sensitized towards antibody neutralization in vitro. Lastly, we showed that cytopathic effect mediated by authentic SARS-CoV-2 infection remain unaffected by the addition of extracellular neutralization antibodies. Hence, these results unveil a novel mode of antibody evasion and provide insights for antibody selection and drug design strategies targeting the SARS-CoV-2 infected cells.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos , Membrana Celular , Glicoproteína de la Espiga del Coronavirus/genética
2.
Plant Physiol ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38875160

RESUMEN

Nine-carbon aldehydes and their relative alcohols (C9 aromas) are the main aroma compounds of cucumber (Cucumis sativus L.) fruits and provide a unique cucumber-like note. However, the key regulators of C9 aroma accumulation in cucumber fruit are poorly characterized. Based on C9 aroma dynamic analysis and transcriptome analysis during fruit development of two different cucumber inbred lines, Q16 and Q24, Lipoxygenase09 (CsLOX09) was identified as a candidate gene for C9 aroma accumulation. Additionally, Q24 with higher CsLOX09 expression accumulated more C9 aromas than Q16. To verify the function of CsLOX09, Cslox09 homozygote knockout lines were created. C9 aroma content decreased by 80.79%-99.16% in these mutants compared to the wild type. To further explore the reasons for the difference in CsLOX09 expression between Q16 and Q24 fruits, a co-expression network was constructed by integrating the C9 aroma-associated metabolism and transcriptomic data. Eighteen candidate transcription factors were highly correlated with the expression of CsLOX09. DNA binding with One Finger 1.8 (CsDof1.8) was confirmed to bind directly to the A/TAAAG motif of the CsLOX09 promoter through dual-luciferase, yeast one-hybrid, chromatin immunoprecipitation-qPCR and electrophoretic mobility shift assays. Furthermore, C9 aroma content and CsLOX09 expression were significantly increased in the CsDof1.8 overexpression lines. Overall, these data elucidate the metabolic regulation of C9 aromas in cucumber and provide a foundation for facilitating the regulation of flavor in cucumber breeding.

3.
Chemphyschem ; 25(1): e202300530, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-37867156

RESUMEN

Cr2 O3 was applied to study the modification of In2 O3 based catalysts for CO2 hydrogenation to methanol reaction. Combined with X-ray diffraction (XRD), scanning transmission electron microscopy (STEM), X-ray photoelectron spectroscopy (XPS), etc., the structure of the catalysts was characterized. The reaction performances for CO2 hydrogenation to methanol were evaluated on a stainless-steel fix-bed reactor. The results showed that solid solutions were formed for the Cr2 O3 promoted In2 O3 catalysts. The important role of electronic interaction between Cr2 O3 and In2 O3 was revealed in the hydrogenation reaction. In1.25 Cr0.75 O3 sample exhibited the highest methanol yield, which was 2.8 times higher than that of pure In2 O3 . No deactivation was observed for In1.25 Cr0.75 O3 sample during the 50 hours of reaction. The improved catalytic performance may be due to the formation of the solid solutions and the highest amount of oxygen vacancies.

4.
BMC Geriatr ; 24(1): 265, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500023

RESUMEN

BACKGROUND: Unhealthy behavior is an important factor threatening the health of older rural residents in China. We examine the effects of receiving pension on elderly rural residents' health behavior (namely conscious control of sugar, salt, and edible oil intake, as well as learning health or wellness knowledge), also including effect heterogeneity by income level and gender. METHODS: Using China Rural Revitalization Survey (CRRS) in 2020, we used the policy rule of the China's New Rural Pension Scheme that only those people who are over 60 years old can have access to pension as the natural experiment, and explore the causal effect of receiving pensions on the health behaviors by using regression discontinuity design method. RESULTS: Having access to pension can improve the health behavior of rural elderly residents, including increasing the probability of rural residents' conscious control of sugar (p < 0.1) and conscious control of salt intake (p < 0.1), which is still valid after a series of robustness tests. Heterogeneity analysis finds that access to pensions is more likely to improve the health behavior of low-income families and male rural elderly residents. CONCLUSIONS: The research has expanded the discussion on the correlation between the pension and the health of rural elderly residents, and the conclusion provides important policy implications for optimizing the rural elderly insurance system and leveraging pension to improve the health behavior of rural elderly residents.


Asunto(s)
Pensiones , Pobreza , Humanos , Masculino , Anciano , China/epidemiología , Población Rural , Conductas Relacionadas con la Salud , Azúcares
5.
BMC Anesthesiol ; 24(1): 96, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38459471

RESUMEN

BACKGROUND: Curative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection. METHODS: A total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded. RESULTS: Of the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction. CONCLUSION: Compared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I-III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events. TRIAL REGISTRATION: The study was retrospectively registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; registration number: ChiCTR2300069014 on 03/03/2023).


Asunto(s)
Anestésicos , Neoplasias Colorrectales , Hipotensión , Ketamina , Propofol , Humanos , Hipnóticos y Sedantes/efectos adversos , Estudios Prospectivos , Satisfacción del Paciente , Fentanilo/efectos adversos , Hipotensión/inducido químicamente , Hipotensión/epidemiología , Hipotensión/tratamiento farmacológico
6.
Food Microbiol ; 119: 104428, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38225058

RESUMEN

The glutamate decarboxylase (GAD) system is one of the acid-resistant systems of Listeria monocytogenes (L. monocytogenes), while the regulatory mechanism of GadT2/GadD2, which plays the major role in the GAD system for acid resistance, is not clear. The two-component system (TCS) is a signal transduction system that is also involved in regulating acid resistance in bacteria. By screening the TCSs of L. monocytogenes 10403S, we found that knocking out the TCS LisSR (encoded by lmo1021/lmo1022) led to a significant increase in the transcription and expression of the gadT2/gadD2 cluster. Subsequently, we constructed a complemental strain CΔliaSR. and a complemental strain with LiaS His157 to Ala, which was designated as CΔliaSRH157A. Survival assay, transcriptional and expression analysis and pathogenicity assay revealed that liaSR deletion significantly enhanced the acid resistance and pathogenicity of 10403S and significantly increased the gadT2/gadD2 transcription and expression. Mutating LiaS His157 to Ala significantly enhanced the acid resistance and pathogenicity of CΔliaSR and significantly increased the gadT2/gadD2 transcription and expression. The results suggest that the two-component system LiaSR mediates the acid resistance and pathogenicity in 10403S by inhibiting the gadT2/gadD2 cluster, and the key activation site of LiaS is His157. This study provides novel knowledge on the regulation of GAD system and the control of this foodborne pathogen.


Asunto(s)
Listeria monocytogenes , Listeria monocytogenes/metabolismo , Virulencia/genética , Ácidos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica
7.
Nano Lett ; 23(22): 10236-10242, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37906707

RESUMEN

Because of the lack of contact and spacer doping techniques for two-dimensional (2D) transistors, most high-performance 2D devices have been produced with nontypical structures that contain electrical gating in the contact regions. In the present study, we used chloroauric acid (HAuCl4) as a strong p-dopant for WSe2 monolayers used in transistors. The HAuCl4-doped devices exhibited a record-low contact resistance of 0.7 kΩ·µm under a doping concentration of 1.76 × 1013 cm-2. In addition, an extrinsic carrier diffusion phenomenon was discovered in the HAuCl4-WSe2 system. With a suitably designed spacer length for doping, a normally off, high-performance underlap top-gate device can be produced without the application of additional gating in the contact and spacer regions.

8.
Molecules ; 29(3)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38338426

RESUMEN

Bismuth vanadate (BVO) is regarded as an exceptional photoanode material for photoelectrochemical (PEC) water splitting, but it is restricted by the severe photocorrosion and slow water oxidation kinetics. Herein, a synergistic strategy combined with a Co3(HPO4)2(OH)2 (CoPH) cocatalyst and an Al2O3 (ALO) passivation layer was proposed for enhanced PEC performance. The CoPH/ALO/BVO photoanode exhibits an impressive photocurrent density of 4.9 mA cm-2 at 1.23 VRHE and an applied bias photon-to-current efficiency (ABPE) of 1.47% at 0.76 VRHE. This outstanding PEC performance can be ascribed to the suppressed surface charge recombination, facilitated interfacial charge transfer, and accelerated water oxidation kinetics with the introduction of the CoPH cocatalyst and ALO passivation layer. This work provides a novel and synergistic approach to design an efficient and stable photoanode for PEC applications by combining an oxygen evolution cocatalyst and a passivation layer.

9.
Molecules ; 29(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38792041

RESUMEN

Using silicon/reduced graphene oxide (Si/rGO) composites as lithium-ion battery (LIB) anodes can effectively buffer the volumetric expansion and shrinkage of Si. Herein, we designed and prepared Si/rGO-b with a sandwiched structure, formed by a duple combination of ammonia-modified silicon (m-Si) nanoparticles (NP) with graphene oxide (GO). In the first composite process of m-Si and GO, a core-shell structure of primal Si/rGO-b (p-Si/rGO-b) was formed. The amino groups on the m-Si surface can not only hybridize with the GO surface to fix the Si particles, but also form covalent chemical bonds with the remaining carboxyl groups of rGO to enhance the stability of the composite. During the electrochemical reaction, the oxygen on the m-Si surface reacts with lithium ions (Li+) to form Li2O, which is a component of the solid-electrolyte interphase (SEI) and is beneficial to buffering the volume expansion of Si. Then, the p-Si/rGO-b recombines with GO again to finally form a sandwiched structure of Si/rGO-b. Covalent chemical bonds are formed between the rGO layers to tightly fix the p-Si/rGO-b, and the conductive network formed by the reintroduced rGO improves the conductivity of the Si/rGO-b composite. When used as an electrode, the Si/rGO-b composite exhibits excellent cycling performance (operated stably for more than 800 cycles at a high-capacity retention rate of 82.4%) and a superior rate capability (300 mA h/g at 5 A/g). After cycling, tiny cracks formed in some areas of the electrode surface, with an expansion rate of only 27.4%. The duple combination of rGO and the unique sandwiched structure presented here demonstrate great effectiveness in improving the electrochemical performance of alloy-type anodes.

10.
J Integr Plant Biol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896078

RESUMEN

Phytohormones, epigenetic regulation and environmental factors regulate fruit ripening but their interplay during strawberry fruit ripening remains to be determined. In this study, bagged strawberry fruit exhibited delayed ripening compared with fruit grown in normal light, correlating with reduced abscisic acid (ABA) accumulation. Transcription of the key ABA catabolism gene, ABA 8'-hydroxylase FaCYP707A4, was induced in bagged fruit. With light exclusion whole genome DNA methylation levels were up-regulated, corresponding to a delayed ripening process, while DNA methylation levels in the promoter of FaCYP707A4 were suppressed, correlating with increases in transcript and decreased ABA content. Experiments indicated FaCRY1, a blue light receptor repressed in bagged fruit and FaAGO4, a key protein involved in RNA-directed DNA methylation, could bind to the promoter of FaCYP707A4. The interaction between FaCRY1 and FaAGO4, and an increased enrichment of FaAGO4 directed to the FaCYP707A4 promoter in fruit grown under light suggests FaCRY1 may influence FaAGO4 to modulate the DNA methylation status of the FaCYP707A4 promoter. Furthermore, transient overexpression of FaCRY1, or an increase in FaCRY1 transcription by blue light treatment, increases the methylation level of the FaCYP707A4 promoter, while transient RNA interference of FaCRY1 displayed opposite phenotypes. These findings reveal a mechanism by which DNA methylation influences ABA catabolism, and participates in light-mediated strawberry ripening.

11.
J Biol Chem ; 298(7): 102063, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35618020

RESUMEN

Tumor angiogenesis is closely associated with the metastasis and progression of non-small cell lung cancer (NSCLC), a highly vascularized solid tumor. However, novel therapeutics are lacking for the treatment of this cancer. Here, we developed a series of 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazol analogs (6a-6x) as tubulin colchicine-binding site inhibitors, aiming to find a novel promising drug candidate for NSCLC treatment. We first identified 2-(2-fluorophenyl)-3-(3,4,5-trimethoxybenzoyl)-5-(3-hydroxyazetidin-1-yl)-2H-1,2,3-triazole (6h) as a hit compound, which inhibited angiogenesis induced by NSCLC cells both in vivo and in vitro. In addition, our data showed that 6h could tightly bind to the colchicine-binding site of tubulin and inhibit tubulin polymerization. We also found that 6h could effectively induce G2/M cell cycle arrest of A549 and H460 cells, inhibit cell proliferation, and induce apoptosis. Furthermore, we showed 6h had the potential to inhibit the migration and invasion of NSCLC cells, two basic characteristics of tumor metastasis. Finally, we found 6h could effectively inhibit tumor progression in A549 xenograft mouse models with minimal toxicity. Taken together, these findings provide strong evidence for the development of 6h as a promising microtubule colchicine-binding site inhibitor for NSCLC treatment.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Colchicina/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Ratones , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéutico
12.
J Am Chem Soc ; 145(23): 12737-12744, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37253455

RESUMEN

In recent years, metal-free photoredox-catalyzed atom transfer radical polymerization (O-ATRP) has gained wide attention because of its advantages (e.g., no metal contamination and mild reaction conditions). However, this traditional one-photon excitation catalysis has thermodynamic limits. Most photocatalysts cannot effectively reduce the initiators and drive the polymerization under visible light. Herein, we investigate the two-photon excitation-catalyzed O-ATRP, in which the catalyst can absorb two photons to accumulate energy. Compared to one-photon excitation catalysis, this method not only has distinct advantages in the controllability, reaction rate, and catalyst loading but also can chemically reduce the various initiators (e.g., aryl halides) to initiate the polymerization. Density functional theory (DFT) calculation reveals that the two-photon excitation process reached a higher energy end state with stronger reduced ability via a thermodynamically more stable intermediate. We believe that this work will provide a new strategy for photoredox-catalyzed O-ATRP.

13.
J Neuroinflammation ; 20(1): 156, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37391774

RESUMEN

BACKGROUND: Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. METHODS: We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. RESULTS: We found that EPC-EXOs decreased the macrophages' pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P's effects on macrophage polarization and mouse motor behavior. CONCLUSION: Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs' role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.


Asunto(s)
Células Progenitoras Endoteliales , Exosomas , MicroARNs , Traumatismos de la Médula Espinal , Animales , Ratones , Ratones Endogámicos C57BL , Antiinflamatorios , Traumatismos de la Médula Espinal/terapia , Inflamación , Macrófagos , MicroARNs/genética
14.
Small ; 19(43): e2302914, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37357169

RESUMEN

Changes in atomic bonding configuration in carbon from sp3 to sp2 are known to exist in certain structural defects in diamond, such as twin boundaries, grain boundaries, and dislocations, which have a significant impact on many properties of diamond. In this work, the atomic structure of fivefold twinning in detonation synthesized ultra-dispersed diamonds is investigated using a combination of techniques, including spherical aberration-corrected high-resolution electron microscopy (HREM), HREM image simulations, and molecular mechanics (MM) calculations. The experimental HREM images reveal clearly that the fivefold twinning in diamond has two distinct structures. In addition to the concentric fivefold twins, where the core structure is the intersection of five {111} twinning boundaries, a new extended core structure with co-hybridization of bonding is identified and analyzed in fivefold twinning. The atomic structure forming these fivefold twinning boundaries and their respective core structures is proposed to involve both the tetrahedral sp3 and planar graphitic sp2 bonding configurations, in which a co-hybridized planar hexagon of carbon serves as a fundamental structural unit. The presence of this sp2 -bonded planar unit of hexagonal carbon rings in general grain boundaries is also discussed.

15.
J Virol ; 96(16): e0097122, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35916512

RESUMEN

The continuous antigenic variation of influenza A viruses remains a major hurdle for vaccine selection; however, the molecular determinants and mechanisms of antigenic change remain largely unknown. In this study, two escape mutants were generated by serial passages of the Eurasian avian-like H1N1 swine influenza virus (EA H1N1 SIV) A/swine/Henan/11/2005 (HeN11) in the presence of two neutralizing monoclonal antibodies (mAbs) against the hemagglutinin (HA) protein, which were designated HeN11-2B6-P5 and HeN11-4C7-P8, respectively. The HeN11-2B6-P5 mutant simultaneously harbored the N190D and I230M substitutions in HA, whereas HeN11-4C7-P8 harbored the M269R substitution in HA (H3 numbering). The effects of each of these substitutions on viral antigenicity were determined by measuring the neutralization and hemagglutination inhibition (HI) titers with mAbs and polyclonal sera raised against the representative viruses. The results indicate that residues 190 and 269 are key determinants of viral antigenic variation. In particular, the N190D mutation had the greatest antigenic impact, as determined by the HI assay. Further studies showed that both HeN11-2B6-P5 and HeN11-4C7-P8 maintained the receptor-binding specificity of the parent virus, although the single mutation N190D decreased the binding affinity for the human-type receptor. The replicative ability in vitro of HeN11-2B6-P5 was increased, whereas that of HeN11-4C7-P8 was decreased. These findings extend our understanding of the antigenic evolution of influenza viruses under immune pressure and provide insights into the functional effects of amino acid substitutions near the receptor-binding site and the interplay among receptor binding, viral replication, and antigenic drift. IMPORTANCE The antigenic changes that occur continually in the evolution of influenza A viruses remain a great challenge for the effective control of disease outbreaks. Here, we identified three amino acid substitutions (at positions 190, 230, and 269) in the HA of EA H1N1 SIVs that determine viral antigenicity and result in escape from neutralizing monoclonal antibodies. All three of these substitutions have emerged in nature. Of note, residues 190 and 230 have synergistic effects on receptor binding and antigenicity. Our findings provide a better understanding of the functional effects of amino acid substitutions in HA and their consequences for the antigenic drift of influenza viruses.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Evasión Inmune , Subtipo H1N1 del Virus de la Influenza A , Animales , Anticuerpos Monoclonales , Anticuerpos Neutralizantes/genética , Anticuerpos Antivirales , Deriva y Cambio Antigénico , Antígenos Virales/genética , Hemaglutininas , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/inmunología , Gripe Humana/virología , Mutación , Porcinos
16.
J Virol ; 96(9): e0195721, 2022 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-35412346

RESUMEN

African swine fever is a lethal hemorrhagic disease of pigs caused by African swine fever virus (ASFV), which greatly threatens the pig industry in many countries. Deletion of virulence-associated genes to develop live attenuated ASF vaccines is considered to be a promising strategy. A recent study has revealed that the A137R gene deletion results in ASFV attenuation, but the underlying mechanism remains unknown. To elucidate the mechanism of the A137R gene regulating ASFV virulence, an ASFV mutant with the A137R gene deleted (ASFV-ΔA137R) was generated based on the wild-type ASFV HLJ/2018 strain (ASFV-WT). Using transcriptome sequencing analysis, we found that ASFV-ΔA137R induced higher type I interferon (IFN) production in primary porcine alveolar macrophages (PAMs) than did ASFV-WT. Overexpression of the A137R protein (pA137R) inhibited the activation of IFN-ß or IFN-stimulated response element. Mechanistically, pA137R interacts with TANK-binding kinase 1 (TBK1) and promotes the autophagy-mediated lysosomal degradation of TBK1, which blocks the nuclear translocation of interferon regulator factor 3, leading to decreased type I IFN production. Taken together, our findings clarify that pA137R negatively regulates the cGAS-STING-mediated IFN-ß signaling pathway via the autophagy-mediated lysosomal degradation of TBK1, which highlights the involvement of pA137R regulating ASFV virulence. IMPORTANCE African swine fever (ASF) is a lethal viral disease of pigs caused by African swine fever virus (ASFV). No commercial vaccines and antiviral treatments are available for the prevention and control of the disease. Several virulence-associated genes of ASFV have been identified, but the underlying attenuation mechanisms are not clear. Compared with the virulent parental ASFV, the A137R gene-deleted ASFV mutant promoted the expression of type I interferon (IFN) in primary porcine alveolar macrophages. Further analysis indicated that the A137R protein negatively regulated the cGAS-STING-mediated IFN-ß signaling pathway through targeting TANK-binding kinase 1 (TBK1) for autophagy-mediated lysosomal degradation. This study not only facilitates the understanding of ASFV immunoevasion strategies, but also provides new clues to the development of live attenuated ASF vaccines.


Asunto(s)
Virus de la Fiebre Porcina Africana , Autofagia , Interferón beta , Proteínas Serina-Treonina Quinasas , Proteínas Virales , Fiebre Porcina Africana , Virus de la Fiebre Porcina Africana/genética , Animales , Interferón beta/metabolismo , Lisosomas/metabolismo , Macrófagos Alveolares/virología , Proteínas de la Membrana , Nucleotidiltransferasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Porcinos , Proteínas Virales/genética , Virulencia
17.
Chemistry ; 29(58): e202300433, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37526193

RESUMEN

A series of trimetallic cyanidometal-bridged compounds [Men Cp(dppe)FeII -(µ-NC)-RuII (MeOpy)4 -(µ-CN)-FeII (dppe)CpMen ] - [PF6 ]2 (N[PF6 ]2 , n=0, N =1; n=1, N=2; n=3, N=3; Cp=cyclopentadiene, dppe=1,2-bis(diphenylphosphino)ethane, MeOpy=4-methoxypyridine) and their one- and two-electron oxidized compounds N3+ and N4+ were synthesized and characterized. Meanwhile, a series of corresponding linear cyanido-bridged pentanuclear compounds [Men Cp(dppe)FeIII -(µ-NC)-RuII (MeOpy)4 -(µ-NC)-AgI -(µ-CN)-RuII (MeOpy)4 -(µ-CN)-FeIII (dppe)CpMen ][BF4 ]5 (M[BF4 ]5 , n=0, M=4; n=1, M=5; n=3, M=6) were also obtained and well characterized. The investigations suggest that in the trinuclear system there exists remote interaction between the two Fe centers, but no significant interactions exist across the central silver unit between the metals on the two sides of the silver center in the pentanuclear system. In both the trinuclear N4+ and the pentanuclear M5+ complexes, there exists the neighboring RuII →FeIII MM'CT transitions, and the MM'CT energy in the corresponding trinuclear system is higher than those in the pentanuclear system in which no remote metal-metal interaction occurs. Meanwhile, as the substituted methyl groups on the cyclopentadiene increases, the redox potential of the ruthenium in the trinuclear N4+ series increases, but that in the pentanuclear M5+ complexes decreases.

18.
Physiol Plant ; 175(1): e13853, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36628625

RESUMEN

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Malus , Malus/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Filogenia , Sequías , Proteínas de Arabidopsis/metabolismo
19.
J Chem Phys ; 158(13): 134702, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37031122

RESUMEN

Herein, a chiral charge transfer crystal that exhibits reversible phase transition between chiral space groups has been fabricated. When the phase switches from left-handed to right-handed chiral space group, more pronounced orbital angular momentum effects will be generated, where magneto-responsive optics are the opposite for chiral enantiomers. Moreover, circularly polarized light could enhance the chiral orbit of the crystal with the same spiral orientation to let spin have a better ability to resist external magnetic field. Thus, the magnetic field dependence of transmission and photoluminescence of chiral crystals are strongly dependent on the polarized state of incident light. Furthermore, by studying the coupling among spin, orbit, and circular photon, we obtained that the chiral orbit plays a key role in the coupling between the spin and circular photon. It is expected that this work could promote further exploration of organic chiral magneto-optical crystals in potential applications of sensing.

20.
Int Arch Occup Environ Health ; 96(8): 1101-1111, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37368145

RESUMEN

BACKGROUND: Volatile organic compounds (VOCs) are a broad class of chemicals, and previous studies showed that VOCs could increase the risk of central nervous system disorders. However, few studies have comprehensively explored their association with depression among general adults. OBJECTIVE: We aimed to explore the association between blood VOCs and depression risk based on a large cross-sectional study of the National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed data from 3449 American adults in the NHANES 2013-2016. Survey-weighted logistic regression model was used to explore the association of ten blood VOCs with depression. Subsequently, the relative importance of the selected VOCs was determined using the XGBoost model. The weighted quantile sum (WQS) regression model was used to explore the overall association of 10 blood VOCs with depression. Subgroup analyses were performed to identify high-risk populations. Finally, restricted cubic spline (RCS) analysis was utilized to explore the dose-response relationship between blood VOCs and the risk of depression. RESULTS: XGBoost Algorithm model identified blood 2,5-dimethylfuran was the most critical variable in depression. The logistic regression model showed that blood benzene, blood 2,5-dimethylfuran, and blood furan showed a positive correlation with depression. In subgroup analysis, we found that the effects of the above VOCs on depression existed among the female, young middle-aged, and overweight-obese population. Mixture VOCs exposure was positively associated with depression risk (OR = 2.089, 95% CI: 1.299-3.361), and 2,5-dimethylfuran had the largest weights in WQS regression. RCS displayed that blood benzene, blood 2,5-dimethylfuran, and blood furan were positively associated with depression. CONCLUSION: The results of this study indicated that VOCs exposure was associated with an increased prevalence of depression in U.S. adults. Women, young and middle-aged, and overweight-obese populations are more vulnerable to VOCs.


Asunto(s)
Exposición a Riesgos Ambientales , Compuestos Orgánicos Volátiles , Persona de Mediana Edad , Humanos , Adulto , Femenino , Estados Unidos/epidemiología , Encuestas Nutricionales , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Compuestos Orgánicos Volátiles/efectos adversos , Estudios Transversales , Benceno , Depresión/epidemiología , Sobrepeso , Obesidad/epidemiología
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