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1.
Cell ; 187(3): 764-781.e14, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38306985

RESUMEN

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.


Asunto(s)
Metabolómica , Embarazo , Animales , Femenino , Humanos , Embarazo/metabolismo , Corticosterona/metabolismo , Metaboloma/fisiología , Placenta/metabolismo , Preeclampsia , Primates/metabolismo
2.
Cell ; 186(10): 2078-2091.e18, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37172562

RESUMEN

Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely unknown due to prohibitions on human embryo research and limitations of available model systems. Here, we establish a three-dimensional (3D) prolonged in vitro culture (pIVC) system supporting cynomolgus monkey embryo development from 7 to 25 days post-fertilization. Through single-cell multi-omics analyses, we demonstrate that pIVC embryos form three germ layers, including primordial germ cells, and establish proper DNA methylation and chromatin accessibility through advanced gastrulation stages. In addition, pIVC embryo immunofluorescence confirms neural crest formation, NT closure, and neural progenitor regionalization. Finally, we demonstrate that the transcriptional profiles and morphogenetics of pIVC embryos resemble key features of similarly staged in vivo cynomolgus and human embryos. This work therefore describes a system to study non-human primate embryogenesis through advanced gastrulation and early neurulation.


Asunto(s)
Defectos del Tubo Neural , Neurulación , Técnicas de Cultivo de Tejidos , Animales , Humanos , Blastocisto , Embrión de Mamíferos , Desarrollo Embrionario , Macaca fascicularis , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/patología , Técnicas de Cultivo de Tejidos/métodos
3.
Nature ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385027

RESUMEN

Behavioural time scale plasticity (BTSP) is non-Hebbian plasticity induced by integrating presynaptic and postsynaptic components separated by a behaviourally relevant time scale (seconds)1. BTSP in hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms that enable synapse-specific plasticity on a behavioural time scale are unknown. Here we show that BTSP can be induced in a single dendritic spine using two-photon glutamate uncaging paired with postsynaptic current injection temporally separated by a behavioural time scale. Using an improved Ca2+/calmodulin-dependent kinase II (CaMKII) sensor, we did not detect CaMKII activation during this BTSP induction. Instead, we observed dendritic, delayed and stochastic CaMKII activation (DDSC) associated with Ca2+ influx and plateau potentials 10-100 s after BTSP induction. DDSC required both presynaptic and postsynaptic activity, which suggests that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 15-30 s after the BTSP protocol inhibited synaptic potentiation, which indicated that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca2+ release facilitated both DDSC and BTSP. Thus, our study suggests that non-synapse-specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP.

4.
Nature ; 612(7941): 732-738, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36517595

RESUMEN

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.


Asunto(s)
Gastrulación , Macaca fascicularis , Organogénesis , Análisis de la Célula Individual , Animales , Humanos , Ratones , Gastrulación/genética , Macaca fascicularis/embriología , Macaca fascicularis/genética , Organogénesis/genética , Cuerpos Embrioides , Perfilación de la Expresión Génica , Línea Primitiva/citología , Línea Primitiva/embriología , Tubo Neural/citología , Tubo Neural/embriología , Cresta Neural/citología , Cresta Neural/embriología , Vía de Señalización Hippo , Mesodermo/citología , Mesodermo/embriología , Células Madre
5.
J Immunol ; 213(7): 1008-1022, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39194407

RESUMEN

The functions of the natural dsRNA sensors TLR3 (TRIF) and RIG-I (MAVS) are crucial during viral challenge and have not been accurately clarified in adaptive immune responses to rotavirus (RV) infection. In this study, we found that RV infection caused severe pathological damage to the small intestine of TLR3-/- and TRIF-/- mice. Our data found that dendritic cells from TLR3-/- and TRIF-/- mice had impaired Ag presentation to the RV and attenuated initiation of T cells upon viral infection. These attenuated functions resulted in impaired CD4+ T and CD8+ T function in mice lacking TLR3-TRIF signaling postinfection. Additionally, attenuated proliferative capacity of T cells from TLR3-/- and TRIF-/- mice was observed. Subsequently, we observed a significant reduction in the absolute number of memory T cells in the spleen and mesenteric lymph node (MLN) of TRIF-/- recipient mice following RV infection in a bone marrow chimeric model. Furthermore, there was reduced migration of type 2 classical dendritic cells from the intestine to MLNs after RV infection in TLR3-/- and TRIF-/- mice. Notably, RV infection resulted in attenuated killing of spleen and MLN tissues in TRIF-/- and MAVS-/- mice. Finally, we demonstrated that RV infection promoted apoptosis of CD8+ T cells in TRIF-/- and TLR3-/-MAVS-/- mice. Taken together, our findings highlight an important mechanism of TLR3 signaling through TRIF in mucosal T cell responses to RV and lay the foundation for the development of a novel vaccine.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas Adaptadoras del Transporte Vesicular , Células Dendríticas , Ratones Noqueados , Infecciones por Rotavirus , Rotavirus , Transducción de Señal , Receptor Toll-Like 3 , Animales , Receptor Toll-Like 3/inmunología , Ratones , Infecciones por Rotavirus/inmunología , Transducción de Señal/inmunología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/inmunología , Rotavirus/inmunología , Células Dendríticas/inmunología , Ratones Endogámicos C57BL , Mucosa Intestinal/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunidad Mucosa , Presentación de Antígeno/inmunología
6.
Chem Soc Rev ; 53(4): 2056-2098, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38214051

RESUMEN

Global warming has become a growing concern over decades, prompting numerous research endeavours to reduce the carbon dioxide (CO2) emission, the major greenhouse gas (GHG). However, the contribution of other non-CO2 GHGs including methane (CH4), nitrous oxide (N2O), fluorocarbons, perfluorinated gases, etc. should not be overlooked, due to their high global warming potential and environmental hazards. In order to reduce the emission of non-CO2 GHGs, advanced separation technologies with high efficiency and low energy consumption such as adsorptive separation or membrane separation are highly desirable. Advanced porous materials (APMs) including metal-organic frameworks (MOFs), covalent organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs), porous organic polymers (POPs), etc. have been developed to boost the adsorptive and membrane separation, due to their tunable pore structure and surface functionality. This review summarizes the progress of APM adsorbents and membranes for non-CO2 GHG separation. The material design and fabrication strategies, along with the molecular-level separation mechanisms are discussed. Besides, the state-of-the-art separation performance and challenges of various APM materials towards each type of non-CO2 GHG are analyzed, offering insightful guidance for future research. Moreover, practical industrial challenges and opportunities from the aspect of engineering are also discussed, to facilitate the industrial implementation of APMs for non-CO2 GHG separation.

7.
Nano Lett ; 24(15): 4580-4587, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38573804

RESUMEN

Photon upconverison has attracted a substantial amount of interest in diverse fields due to its characteristic anti-Stokes emissions. However, obtaining intense emission under low-power laser irradiation has remained a challenge. Here we report a mechanistic design of activator-sensitizer alloyed nanoparticles to achieve bright upconversion under weak infrared irradiation. This design allows a nearest sensitizer-activator separation to facilitate efficient energy transfer that results in remarkably enhanced upconversion (>2 orders of magnitude) under 0.26 W cm-2 irradiation compared to that of the Er sublattice, and the upconversion quantum yield also shows a 20-fold increase. Interestingly, the alloyed nanoparticles exhibit a gradual change in emission color with an increase in Yb3+ content, and moreover, their emission colors can be dynamically controlled by simply modulating the excitation laser power and pulse widths. Such alloyed nanoparticles show great promise for application in a near-infrared photodetector.

8.
BMC Genomics ; 25(1): 620, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898399

RESUMEN

BACKGROUND: Soybean mosaic disease caused by soybean mosaic virus (SMV) is one of the most devastating and widespread diseases in soybean producing areas worldwide. The WRKY transcription factors (TFs) are widely involved in plant development and stress responses. However, the roles of the GmWRKY TFs in resistance to SMV are largely unclear. RESULTS: Here, 185 GmWRKYs were characterized in soybean (Glycine max), among which 60 GmWRKY genes were differentially expressed during SMV infection according to the transcriptome data. The transcriptome data and RT-qPCR results showed that the expression of GmWRKY164 decreased after imidazole treatment and had higher expression levels in the incompatible combination between soybean cultivar variety Jidou 7 and SMV strain N3. Remarkably, the silencing of GmWRKY164 reduced callose deposition and enhanced virus spread during SMV infection. In addition, the transcript levels of the GmGSL7c were dramatically lower upon the silencing of GmWRKY164. Furthermore, EMSA and ChIP-qPCR revealed that GmWRKY164 can directly bind to the promoter of GmGSL7c, which contains the W-box element. CONCLUSION: Our findings suggest that GmWRKY164 plays a positive role in resistance to SMV infection by regulating the expression of GmGSL7c, resulting in the deposition of callose and the inhibition of viral movement, which provides guidance for future studies in understanding virus-resistance mechanisms in soybean.


Asunto(s)
Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Glycine max , Enfermedades de las Plantas , Proteínas de Plantas , Potyvirus , Factores de Transcripción , Glycine max/virología , Glycine max/genética , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/virología , Enfermedades de las Plantas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Potyvirus/fisiología , Potyvirus/patogenicidad , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiones Promotoras Genéticas
9.
J Am Chem Soc ; 146(28): 19303-19309, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38970779

RESUMEN

Sulfur hexafluoride (SF6) is extensively employed in the power industry. However, its emissions significantly contribute to the greenhouse effect. The direct recovery of high purity SF6 from industrial waste gases would benefit its sustainable use, yet this represents a considerable challenge. Herein, we report the enrichment of SF6 from SF6/N2 mixtures via adsorptive separation in a stable Co(II)-pyrazolate MOF BUT-53 (BUT: Beijing University of Technology), which features dynamic molecular traps. BUT-53 exhibits an excellent SF6 adsorption uptake of 2.82 mmol/g at 0.1 bar and 298 K, as well as an unprecedented SF6/N2 (10:90) selectivity of 2485. Besides, the remarkable SF6/N2 selectivity of BUT-53 enables recovery of high purity (>99.9%) SF6 from a low concentration (10%) mixture through a breakthrough experiment. The excellent SF6/N2 separation efficiency was also well maintained under humid conditions (RH = 90%) over multiple cycles. Molecular simulation, single-crystal diffraction, and adsorption kinetics studies elucidate the associated adsorption mechanism and water tolerance.

10.
Chembiochem ; : e202400691, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39436752

RESUMEN

Panepoxydone is a natural NF-кB inhibitor isolated from basidiomycetes belonging to the genus Panus and Lentinus. It is biosynthesized from prenylhydroquinone through successive hydroxylation, epoxidation, and reduction reactions. In this study, we establish an efficient precursor-directed biosynthesis strategy for the structural expansion of panepoxydone based on its biosynthetic pathway. Supplementation of the panepoxydone-producing strain, Panus rudis, with various prenylhydroquinone analogues enabled the production of fourteen previously undescribed panepoxydone derivatives, panepoxyquinoid A-N (2-14). The obtained panepoxydone derivatives together with their parental molecules were evaluated for their inhibitory activity on LPS-induced NO production in RAW 264.7 cells. Compounds 1, 5-6, 10-11, and 14-15 displayed significant suppressive effects on LPS-induced NO production with IC50 values ranging from 4.3 to 30.1 µM.

11.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34849567

RESUMEN

MOTIVATION: Understanding chemical-gene interactions (CGIs) is crucial for screening drugs. Wet experiments are usually costly and laborious, which limits relevant studies to a small scale. On the contrary, computational studies enable efficient in-silico exploration. For the CGI prediction problem, a common method is to perform systematic analyses on a heterogeneous network involving various biomedical entities. Recently, graph neural networks become popular in the field of relation prediction. However, the inherent heterogeneous complexity of biological interaction networks and the massive amount of data pose enormous challenges. This paper aims to develop a data-driven model that is capable of learning latent information from the interaction network and making correct predictions. RESULTS: We developed BioNet, a deep biological networkmodel with a graph encoder-decoder architecture. The graph encoder utilizes graph convolution to learn latent information embedded in complex interactions among chemicals, genes, diseases and biological pathways. The learning process is featured by two consecutive steps. Then, embedded information learnt by the encoder is then employed to make multi-type interaction predictions between chemicals and genes with a tensor decomposition decoder based on the RESCAL algorithm. BioNet includes 79 325 entities as nodes, and 34 005 501 relations as edges. To train such a massive deep graph model, BioNet introduces a parallel training algorithm utilizing multiple Graphics Processing Unit (GPUs). The evaluation experiments indicated that BioNet exhibits outstanding prediction performance with a best area under Receiver Operating Characteristic (ROC) curve of 0.952, which significantly surpasses state-of-theart methods. For further validation, top predicted CGIs of cancer and COVID-19 by BioNet were verified by external curated data and published literature.


Asunto(s)
Biología Computacional , Simulación por Computador , Modelos Biológicos , Redes Neurales de la Computación
12.
Scand J Immunol ; 99(5): e13362, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38605563

RESUMEN

T cells contribute to the pathogenesis of atherosclerosis. However, the presence and function of granulocyte-macrophage-colony-stimulating factor (GM-CSF)-producing T helper (ThGM) cells in atherosclerosis development is unknown. This study aims to characterize the phenotype and function of ThGM cells in experimental atherosclerosis. Atherosclerosis was induced by feeding apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet. Aortic ThGM cells were detected and sorted by flow cytometry. The effect of oxidized low-density lipoprotein (oxLDL) on ThGM cells and the impact of ThGM cells on macrophages were evaluated by flow cytometry, quantitative RT-PCR, oxLDL binding/uptake assay, immunoblotting and foam cell formation assay. We found that GM-CSF+IFN-γ- ThGM cells existed in atherosclerotic aortas. Live ThGM cells were enriched in aortic CD4+CCR6-CCR8-CXCR3-CCR10+ T cells. Aortic ThGM cells triggered the expression of interleukin-1ß (IL-1ß), tumour necrosis factor (TNF), interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2) in macrophages. Besides, aortic ThGM cells expressed higher CD69 than other T cells and bound to oxLDL. oxLDL suppressed the cytokine expression in ThGM cells probably via inhibiting the signal transducer and activator of transcription 5 (STAT5) signalling. Furthermore, oxLDL alleviated the effect of ThGM cells on inducing macrophages to produce pro-inflammatory cytokines and generate foam cells. The nuclear receptor subfamily 4 group A (NR4A) members NR4A1 and NR4A2 were involved in the suppressive effect of oxLDL on ThGM cells. Collectively, oxLDL suppressed the supportive effect of ThGM cells on pro-atherosclerotic macrophages.


Asunto(s)
Aterosclerosis , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Lipoproteínas LDL , Macrófagos , Linfocitos T Colaboradores-Inductores , Animales , Ratones , Aterosclerosis/genética , Citocinas/metabolismo , Células Espumosas/patología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Interleucina-6/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo
13.
Anal Biochem ; 685: 115388, 2024 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-37967783

RESUMEN

The retrospective detection of organophosphorus nerve agents (OPNAs) exposure has been achieved by the off-site analysis of OPNA-human serum albumin (HSA) adducts using mass spectrometry-based detection approaches. However, few specific methods are accessible for on-site detection. To address this, a novel immunofluorescence microfluidic chip (IFMC) testing system combining europium chelated microparticle (EuCM) with self-driven microfluidic chip assay has been established to unambiguously determine soman (GD) and VX exposure within 20 min, respectively. The detection system was based on the principle of indirect competitive enzyme-linked immunosorbent assay. The specific monoclonal antibodies that respectively recognized the phosphonylated tyrosine 411 of GD-HSA and VX-HSA adducts were labeled by EuCM to capture corresponding adducts in the exposed samples. The phosphonylated peptides in the test line and goat-anti-rabbit antibody in the control line were utilized to bind the EuCM-labeled antibodies for signal exhibition. The developed IFMC chip could discriminatively detect exposed HSA adducts with high specificity, demonstrating a low limit of detection at exposure concentrations of 0.5 × 10-6 mol/L VX and 1.0 × 10-6 mol/L GD. The exposed serum samples can be qualitatively detected following an additional pretreatment procedure. This is a novel rapid detection system capable of discriminating GD and VX exposure, providing an alternative method for rapidly identifying OPNA exposure.


Asunto(s)
Soman , Animales , Humanos , Conejos , Soman/metabolismo , Europio , Microfluídica , Estudios Retrospectivos , Albúmina Sérica Humana , Técnica del Anticuerpo Fluorescente
14.
Theor Appl Genet ; 137(8): 178, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976061

RESUMEN

KEY MESSAGE: Three QTLs associated with low-temperature tolerance were identified by genome-wide association analysis, and 15 candidate genes were identified by haplotype analysis and gene expression analyses. Low temperature is a critical factor affecting the geographical distribution, growth, development, and yield of soybeans, with cold stress during seed germination leading to substantial productivity loss. In this study, an association panel comprising 260 soybean accessions was evaluated for four germination traits and four cold tolerance index traits, revealing extensive variation in cold tolerance. Genome-wide association study (GWAS) identified 10 quantitative trait nucleotides (QTNs) associated with cold tolerance, utilizing 30,799 single nucleotide polymorphisms (SNPs) and four GWAS models. Linkage disequilibrium (LD) analysis positioned these QTNs within three cold-tolerance quantitative trait loci (QTL) and, with QTL19-1, was positioned by three multi-locus models, underscoring its importance as a key QTL. Integrative haplotype analysis, supplemented by transcriptome analysis, uncovered 15 candidate genes. The haplotypes within the genes Glyma.18G044200, Glyma.18G044300, Glyma.18G044900, Glyma.18G045100, Glyma.19G222500, and Glyma.19G222600 exhibited significant phenotypic variations, with differential expression in materials with varying cold tolerance. The QTNs and candidate genes identified in this study offer substantial potential for marker-assisted selection and gene editing in breeding cold-tolerant soybeans, providing valuable insights into the genetic mechanisms underlying cold tolerance during soybean germination.


Asunto(s)
Frío , Germinación , Glycine max , Haplotipos , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Glycine max/genética , Glycine max/crecimiento & desarrollo , Germinación/genética , Estudio de Asociación del Genoma Completo , Fenotipo , Estudios de Asociación Genética , Mapeo Cromosómico/métodos , Genes de Plantas
15.
Fish Shellfish Immunol ; : 109986, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39461397

RESUMEN

Largemouth bass virus (LMBV) is an infectious pathogen that causes high mortality rates in largemouth bass, and outbreaks of this virus can significantly harm the aquaculture industry. Currently, no vaccine has been developed that can effectively prevent the transmission of LMBV. In this study, we constructed a recombinant Lactobacillus plantarum (L. plantarum) strain capable of expressing the MCP gene of LMBV and displaying this protein on its surface; then, we evaluated the immunoprotective effect of this recombinant bacterium on largemouth bass. Western blotting, immunofluorescence, and flow cytometry confirmed that MCP was successfully expressed and anchored on the surfaces of NC8 cells. Immunization of largemouth bass with NC8-pSIP409-pgsA'-MCP via the oral feeding route induced CD4, CD8, IL-1ß, and IL-6 gene expression. In addition, NC8-pSIP409-pgsA'-MCP at different CFUs increased the survival of largemouth bass after LMBV infection; in particular, NC8-pSIP409-pgsA'-MCP (109 CFU) resulted in approximately 30% survival. NC8-pSIP409-pgsA'-MCP immunization alleviated the pathological changes in the liver and spleen, exerting a more advantageous protective effect. These data suggest that the recombinant L. plantarum strain NC8-pSIP409-pgsA'-MCP can increase the resistance of largemouth bass to LMBV infection and that this strain is a promising candidate oral vaccine for the prevention of LMBV infection.

16.
Appl Microbiol Biotechnol ; 108(1): 467, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292268

RESUMEN

Epigenetic regulation plays a central role in the regulation of a number of cellular processes such as proliferation, differentiation, cell cycle, and apoptosis. In particular, small molecule epigenetic modulators are key elements that can effectively influence gene expression by precisely regulating the epigenetic state of cells. To identify useful small-molecule regulators that enhance the expression of recombinant proteins in Chinese hamster ovary (CHO) cells, we examined a novel dual-HDAC/LSD1 inhibitor I-4 as a supplement for recombinant CHO cells. Treatment with 2 µM I-4 was most effective in increasing monoclonal antibody production. Despite cell cycle arrest at the G1/G0 phase, which inhibits cell growth, the addition of the inhibitor at 2 µM to monoclonal antibody-expressing CHO cell cultures resulted in a 1.94-fold increase in the maximal monoclonal antibody titer and a 2.43-fold increase in specific monoclonal antibody production. In addition, I-4 significantly increased the messenger RNA levels of the monoclonal antibody and histone H3 acetylation and methylation levels. We also investigated the effect on HDAC-related isoforms and found that interference with the HDAC5 gene increased the monoclonal antibody titer by 1.64-fold. The results of this work provide an effective method of using epigenetic regulatory strategies to enhance the expression of recombinant proteins in CHO cells. KEY POINTS: • HDAC/LSD1 dual-target small molecule inhibitor can increase the expression level of recombinant monoclonal antibodies in CHO cells. • By affecting the acetylation and methylation levels of histones in CHO cells and downregulating HDAC5, the production of recombinant monoclonal antibodies increased. • It provides an effective pathway for applying epigenetic regulation strategies to enhance the expression of recombinant proteins.


Asunto(s)
Anticuerpos Monoclonales , Cricetulus , Epigénesis Genética , Proteínas Recombinantes , Células CHO , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Epigénesis Genética/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histonas/metabolismo , Histonas/genética , Acetilación , Cricetinae , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Metilación
17.
BMC Ophthalmol ; 24(1): 231, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822280

RESUMEN

BACKGROUND: The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. METHODS: A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. RESULTS: Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). CONCLUSION: In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.


Asunto(s)
Presión Intraocular , Facoemulsificación , Agudeza Visual , Vitrectomía , Cuerpo Vítreo , Humanos , Vitrectomía/métodos , Facoemulsificación/métodos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Cuerpo Vítreo/cirugía , Presión Intraocular/fisiología , Cápsula Posterior del Cristalino/cirugía , Anciano de 80 o más Años
18.
Luminescence ; 39(3): e4712, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38481369

RESUMEN

In this study, a novel fluorescent chemosensor 1 based on chromone-3-carboxaldehyde Schiff base was synthesized and featured through nuclear magnetic resonance (NMR) and mass spectra. Spectroscopic investigation indicated that the fluorescent sensor showed high selectivity toward Zn2+ over other metal ions and that the detection limit of 1 could reach 10-7  M. These indicated that 1 acted as a highly selective and sensitive fluorescence chemosensor for Zn2+ .


Asunto(s)
Colorantes Fluorescentes , Bases de Schiff , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes/química , Bases de Schiff/química , Cromonas , Zinc
19.
J Insect Sci ; 24(4)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39023176

RESUMEN

Tephritis angustipennis (Diptera: Tephritidae) and Campiglossa loewiana (Diptera: Tephritidae) are phytophagous pests in China. Their damage has significantly impacted the collection and cultivation of germplasm resources of native Asteraceae plants. However, the genetic characteristics and structure of their population are unclear. This study focused on the highly damaging species of T. angustipennis and C. loewiana collected from the three-river source region (TRSR). We amplified the mitochondrial cytochrome C oxidase subunit I (mtCOI) gene sequences of these pests collected from this area and compared them with COI sequences from GenBank. We also analyzed their genetic diversity and structure. In T. angustipennis, 5 haplotypes were identified from 5 geographic locations; the genetic differentiation between France population FRPY (from Nylandia, Uusimaa) and China populations GLJZ (from Dehe Longwa Village, Maqin County), GLDR (from Zhique Village, Dari County), and GLMQ (from Rijin Village, Maqin County) was the strongest. GLJZ exhibited strong genetic differentiation from GLDR and GLMQ, with relatively low gene flow. For C. loewiana, 11 haplotypes were identified from 5 geographic locations; the genetic differentiation between the Chinese population GLMQ-YY (from Yangyu Forest Farm, Maqin County) and Finnish population FDNL (from Nylandia, Uusimaa) was the strongest, with relatively low gene flow, possibly due to geographical barriers in the Qinghai-Tibet plateau. Only 1 haplotype was identified across GLDR, GLMQ, and GLBM. High gene flow between distant locations indicates that human activities or wind dispersal may facilitate the dispersal of fruit flies and across different geographic. Geostatistical analysis suggested a recent population expansion of these 2 species in TRSR. Our findings provide technical references for identifying pests in the TRSR region and theoretical support for managing resistance, monitoring pest occurrences, analyzing environmental adaptability, and formulating biological control strategies for Tephritidae pests on Asteraceae plants.


Asunto(s)
Código de Barras del ADN Taxonómico , Complejo IV de Transporte de Electrones , Variación Genética , Tephritidae , Animales , Tephritidae/genética , China , Complejo IV de Transporte de Electrones/genética , Haplotipos , Filogenia , Proteínas de Insectos/genética
20.
J Craniofac Surg ; 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39437000

RESUMEN

BACKGROUND: At present, conventional operations are weak for pain relief and restoring the carpal joint function in the treatment of avascular necrosis of the lunate bone. CASE REPORT: Mirror image 3-dimensional (3D)-printing technology has rarely been reported for the treatment of lunate bone necrosis, The use of mirror 3D-printed lunar bone replacement and bone cement technology in the treatment of stage IIIb lunar bone necrosis has been rarely reported in previous literature. Personalized customized 3D-printed prostheses have become an effective solution for solving many complex cases, and the flexible application of bone cement technology can also achieve satisfactory clinical results. The authors report 3 patients who underwent mirror printing of lunar bone prostheses based on healthy side lunar bone computed tomography data, 3D printing of lunar bone prostheses replacement through small incisions, and intraoperative selection of alternative bone cement technology based on actual conditions. CONCLUSION: Mirror image 3D printing relieved the pain and resulted in satisfactory functional recovery for stage IIIb lunate bone necrosis.

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