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Zygotic genome activation (ZGA), the first transcription event following fertilization, kickstarts the embryonic program that takes over the control of early development from the maternal products. How ZGA occurs, especially in mammals, is poorly understood due to the limited amount of research materials. With the rapid development of single-cell and low-input technologies, remarkable progress made in the past decade has unveiled dramatic transitions of the epigenomes, transcriptomes, proteomes, and metabolomes associated with ZGA. Moreover, functional investigations are yielding insights into the key regulators of ZGA, among which two major classes of players are emerging: licensors and specifiers. Licensors would control the permission of transcription and its timing during ZGA. Accumulating evidence suggests that such licensors of ZGA include regulators of the transcription apparatus and nuclear gatekeepers. Specifiers would instruct the activation of specific genes during ZGA. These specifiers include key transcription factors present at this stage, often facilitated by epigenetic regulators. Based on data primarily from mammals but also results from other species, we discuss in this review how recent research sheds light on the molecular regulation of ZGA and its executors, including the licensors and specifiers.
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van der Waals (vdW) superlattices, comprising different 2D materials aligned alternately by weak interlayer interactions, offer versatile structures for the fabrication of novel semiconductor devices. Despite their potential, the precise control of optoelectronic properties with interlayer interactions remains challenging. Here, we investigate the discrepancies between the SnS/TiS2 superlattice (SnTiS3) and its subsystems by comprehensive characterization and DFT calculations. The disappearance of certain Raman modes suggests that the interactions alter the SnS subsystem structure. Specifically, such structural changes transform the band structure from indirect to direct band gap, causing a strong PL emission (â¼2.18 eV) in SnTiS3. In addition, the modulation of the optoelectronic properties ultimately leads to the unique phenomenon of thermally activated photoluminescence. This phenomenon is attributed to the inhibition of charge transfer induced by tunable intralayer strains. Our findings extend the understanding of the mechanism of interlayer interactions in van der Waals superlattices and provide insights into the design of high-temperature optoelectronic devices.
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BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.
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Apoptosis , Subtipo H3N2 del Virus de la Influenza A , Melatonina , Enfermedad Pulmonar Obstructiva Crónica , Animales , Melatonina/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/virología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Ratones , Apoptosis/efectos de los fármacos , Células RAW 264.7 , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/inmunología , Ratones Endogámicos C57BL , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Progresión de la Enfermedad , Polaridad Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologíaRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that is highly aggressive with a poor prognosis. There is no standard treatment for BPDCN. Although conventional chemotherapies are usually sensitive in the initial therapy, relapse and drug resistance are inevitable within a short duration. Targeted therapies have enlightened new prospects for the treatment of BPDCN, especially for those in a frail state and intolerable to standard chemotherapies or hematopoietic stem cell transplantation. Here, we report an 82-year-old man diagnosed with cutaneous-limited BPDCN. Considering the old age and limited involvement of the tumor, we reduced the dosage of venetoclax. His skin lesions subsided significantly after 1 cycle of azacytidine (100 mg d1-7) combined with reduced doses of venetoclax (200 mg d1-14). The reduction in the dose of venetoclax avoided severe myelosuppression while achieving satisfactory outcomes. The patient received 2 cycles of therapy with no skin lesions re-occurred for 7 months before relapsing.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Neoplasias Hematológicas , Trastornos Mieloproliferativos , Neoplasias Cutáneas , Sulfonamidas , Masculino , Humanos , Anciano de 80 o más Años , Azacitidina/uso terapéutico , Células Dendríticas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Hematológicas/terapia , Trastornos Mieloproliferativos/patologíaRESUMEN
A more practical model for plasmonic core@shell-satellite antenna-reactor photocatalysts is promoted. In contrast to the mainstream view, total light absorption in the Pt nanoparticle (NP) reactors can be further improved by 70% after coating a 10-nm-thick high refractive index TiO2 shell on the large Ag antenna as a result of more Pt NPs undergoing high absorption enhancement. The enhancement effect is maximized at the electric quadrupole (EQ) resonance. Considering the high refractive index of the TiO2 coating and the embedding of the Pt NPs, the underlying physics is addressed within classical electrodynamics, making a necessary supplement to the conventional plasmonic near-field enhancement mechanism. These findings provide a general strategy for developing novel, to the best of our knowledge, visible light photocatalysts made of transition metals directly.
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Water scarcity presents a pressing global challenge, necessitating innovative solutions, such as the collection of water from the air using conical structures. However, current research primarily focuses on mist collection rather than on nanoscale clusters of water molecules. Under standard atmospheric conditions, water vapor predominantly exists as imperceptible clusters. Therefore, it is crucial to investigate the interactions between these water molecule clusters and conical structures, particularly regarding whether the conical shape induces Laplace pressure difference on the adhering cluster formations. To gain deeper insights and determine optimal droplet collection structures, we conducted molecular dynamics simulations to investigate interactions between water molecule clusters and conical structures. Our investigations focused on studying the interactions between conical structures and water molecule clusters with varying densities, as well as the impact of surface energies on the collection of water by these conical structures. Notably, our simulations unveiled the significant roles played by van der Waals forces and Laplace pressure in the process of collecting water molecule clusters. Furthermore, our simulations revealed that Janus conical structures, featuring two distinct surface energy regions, played a crucial role in promoting the aggregation of water molecules, resulting in the formation of larger droplets. This aggregation was driven by surface tension gradients, which arise from the contrasting wetting properties in different regions of the Janus structure. As a consequence, under the influence of gravitational forces, these larger droplets could eventually detach from the structure. Through the combined effects of surface tension gradients and gravitational forces, Janus conical structures offer a promising avenue for enhancing the collection efficiency of water from the air. Our research sheds light on the fundamental mechanisms governing water molecule cluster-based water collection and provides valuable insights for the design of more efficient and effective water collection systems.
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Background: Sepsis has become one of the main factors inducing the development of acute lung injury (ALI) in clinical practice. Currently, inhibiting the activation of NLRP3 mediated pyroptosis is the target of multiple drugs in the treatment of sepsis induced ALI. This study aimed to explore the effects of METTL14 on the pyroptosis in the sepsis induced ALI progression.Methods: LPS-stimulated A549 cells and cecal ligation and puncture (CLP)-treated mice were used to establish the ALI model in vitro and in vivo. Then, the cell viability was measured by CCK-8 assay. ELISA kits were used to determine the IL-18 and IL-1ß contents. Pyroptosis rate was tested by flow cytometry. M6A dot blot was conducted to analyze the global m6A levels and MeRIP assay was performed to detect the m6A levels of NLRP3. The relationship between METTL14 and NLRP3 was confirmed by RIP and dual-luciferase report assays.Results: The global m6A levels were significantly increased in the LPS-stimulated A549 cells and CLP-treated mice. METTL14 knockdown decreased the cell viability, IL-18 and IL-1ß contents, and pyroptosis rate of the LPS-stimulated A549 cells. Furthermore, the increase of pyroptosis-related proteins in LPS-stimulated A549 cells was significantly decreased after METTL14 knockdown. Additionally, METTL14 knockdown decreased the m6A and mRNA levels of NLRP3, and NLRP3 overexpression reversed the effects of METTL14 knockdown on the pyroptosis in the LPS-stimulated A549 cells. In CLP-treated mice, METTL14 knockdown relieved the injury and decreased the IL-18 and IL-1ß contents in the lung tissues, serum and bronchoalveolar lavage fluid.Conclusion: This study demonstrated that METTL14 knockdown inhibited the pyroptosis in the sepsis-induced ALI progression through decreasing the NLRP3 levels dependent on m6A methylation modification.
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Lesión Pulmonar Aguda , Sepsis , Animales , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Interleucina-18/efectos adversos , Lipopolisacáridos/efectos adversos , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Sepsis/complicacionesRESUMEN
A chemoenzymatic strategy has been implemented to synthesize nitriles from benzyl amines under mild conditions. Aldoxime dehydratase (Oxd) plays a decisive role to convert aldoximes into corresponding nitriles. However, natural Oxds commonly exhibit extremely low catalytic capacity toward benzaldehyde oximes. Here, we engineered the OxdF1 from Pseudomonas putida F1 to enhance its catalytic efficiency toward benzaldehyde oximes by a semi-rational design strategy. The protein structure-based CAVER analysis indicates that M29, A147, F306, and L318 are located adjacent to the substrate tunnel entrance of OxdF1, which were responsible for the transportation of substrate into the active site. After two rounds of mutagenesis, the maximum activities of the mutants L318F and L318F/F306Y were 2.6 and 2.8 U/mg respectively, which were significantly higher than the wild OxdF1 of 0.7 U/mg. Meanwhile, the lipase type B from Candida antarctica was functionally expressed in Escherichia coli cells to selectively oxidize benzyl amines to aldoximes using urea-hydrogen peroxide adduct (UHP) as an oxidant in ethyl acetate. To merge the oxidation and dehydration reactions, a reductive extraction solution was added to remove the residue UHP, which is critical to eliminate its inhibition on the Oxd activity. Consequently, nine benzyl amines were efficiently converted into corresponding nitriles by the chemoenzymatic sequence.
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Benzaldehídos , Nitrilos , Nitrilos/metabolismo , Oximas/químicaRESUMEN
Nitriles are of significant interest in the flavor and fragrance industries with potential application in cosmetics due to their higher stability than analogous aldehydes. However, the traditional methods to prepare nitriles need toxic reagents and hash conditions. This work aimed to develop a chemoenzymatic strategy to synthesize nitriles from natural aldehydes with aldoxime as the intermediate. A non-classical aldoxime dehydratase (Oxd) was discovered from the fungus Aspergillus ibericus (OxdAsp) to catalyze the dehydration of aldoximes to corresponding nitriles under mild conditions. The amino acid sequence of OxdAsp exhibits an approximately 20% identity with bacterial Oxds. OxdAsp contains a heme prosthetic group bound with the axial H287 in the catalytic pocket. The structure models of OxdAsp with substrates suggest that its catalytic triad is Y138-R141-E192, which is different from the classically bacterial Oxds of His-Arg-Ser/Thr. The catalytic mechanism of OxdAsp was proposed based on the mutagenesis of key residues. The hydroxyl group of the substrate is fixed by E192 to increase its basicity. Y138 acts as a general acid-based catalyst, and its phenolic proton is polarized by the adjacent R141. The protonated Y138 would donate a proton to the hydroxyl group of the substrate and eliminate a water molecule from aldoxime to produce nitrile. The recombinant OxdAsp can efficiently dehydrate citronellal oxime and cinnamaldoxime to citronellyl nitrile and cinnamonitrile in aqueous media, which are applied as fragrance ingredients in the food and cosmetic fields. KEY POINTS: ⢠A novel aldoxime dehydratase from the Aspergillus genus was first characterized as a heme-binding protein. ⢠The catalytic mechanism was predicted based on the molecular interactions of the catalytic pocket with the substrate. ⢠A chemoenzymatic strategy was developed to synthesize nitriles from natural aldehydes with aldoxime as the intermediate.
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Bacterias , Protones , Bacterias/metabolismo , Hidroliasas/metabolismo , Nitrilos/metabolismo , AldehídosRESUMEN
The advance in nursing care for stoma patients is a challenging issue, which will influence the life quality. The quality of life is a major issue in the recovery of stoma patients. The evidence of experimental nursing has not been explored enough. A systematic search and a meta-analysis were performed for the studies of experimental nursing interventions versus routine warming interventions on patients with a stoma. The comparisons between nursing interventions were performed to find which kind of intervention will be superior in improving life quality. After a restricted selection, 10 studies, 460 subjects with experimental nursing intervention, and 478 controls with the routine nursing intervention were enrolled in a variety of causes of the stoma. The focused outcome was the quality of life. The meta-analysis was performed by Review Manager 5.4. Among the stoma patients, the meta-analysis favours the experimental nursing intervention group with higher scores of life quality when compared to the routine nursing intervention group. The meta-analysis results were with positive mean differences, significant tests for overall effect, and significant heterogeneities in the random-effects model. The experimental nursing intervention showed higher positive effects on the quality of life when compared to routine nursing intervention for stoma patients. Experimental nursing intervention might be an option for stoma nursing practitioners to improve stoma care.
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Calidad de Vida , Estomas Quirúrgicos , HumanosRESUMEN
By rational design and parameter engineering of the TiO2-Pt core-satellite construction, visible light absorption in small Pt nanoparticles (NPs) can be enhanced by nearly 100 times. The TiO2 microsphere support works as the optical antenna, giving rise to superior performance compared to conventional plasmonic nanoantennas. A crucial step is to bury the Pt NPs completely in the high refractive index TiO2 microsphere, because light absorption in the Pt NP approximately scales with the fourth power of the refractive index of its surrounding media. The proposed evaluation factor for light absorption enhancement in the Pt NPs at different positions is proved to be valid and useful. The physics modeling of the buried Pt NPs corresponds to the general case in practice where the surface of the TiO2 microsphere is naturally rough or a thin TiO2 coating is subsequently added. These results offer new avenues for directly transforming dielectric supported nonplasmonic catalytic transition metals into visible light photocatalysts.
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BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Nomogramas , PronósticoRESUMEN
Adipogenesis is a multi-step process orchestrated by activation of numerous TFs, whose cooperation and regulatory network remain elusive. Activating transcription factor 4 (ATF4) is critical for adipogenesis, yet its regulatory network is unclarified. Here, we mapped genome-wide ATF4 binding landscape and its regulatory network by Chip-seq and RNA-seq and found ATF4 directly modulated transcription of genes enriching in fat cell differentiation. Motifs of TFs especially CTCF were found from ATF4 binding sites, suggesting a direct role of ATF4 in regulating adipogenesis associated with CTCF and other TFs. Deletion of CTCF attenuated adipogenesis while overexpression enhanced adipocyte differentiation, indicating CTCF is indispensable for adipogenesis. Intriguingly, combined analysis of Chip-seq data of these two TFs showed that ATF4 co-localized with CTCF in the promoters of key adipogenic genes including Cebpd and PPARg and co-regulated their transactivation. Moreover, ATF4 directly regulated CTCF expression and interacted with CTCF in differentiated 3T3-L1 cells. In vivo, downregulation of ATF4 suppressed the expression of CTCF, Cebpd, and PPARg, leading to reduced adipose tissue expansion in refeeding mice. Consistently, mRNA expression of ATF4 and CTCF was positively correlated with each other in human subcutaneous adipose tissue and inversely associated with BMI, indicating a possible involvement of these two TFs in adipose development. Taken together, our data propose for the first time that ATF4 and CTCF work cooperatively to control adipogenesis and adipose development via orchestrating transcription of adipogenic genes. Our findings reveal novel therapeutic targets in obesity treatment.
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Factor de Transcripción Activador 4/metabolismo , Adipogénesis , Factor de Unión a CCCTC/metabolismo , Factor de Transcripción Activador 4/genética , Adipocitos/metabolismo , Adipogénesis/genética , Animales , Diferenciación Celular/genética , Humanos , Ratones , PPAR gamma/genética , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease with varying clinical courses and responses to treatment. To improve the prognosis of patients, it is necessary to understand such heterogeneity. METHODS: We used single-sample gene set enrichment analysis to classify 35 MIBC cases into immunity-high and immunity-low groups. Bioinformatics analyses were conducted to compare the differences between these groups. Eventually, single-cell mass cytometry (CyTOF) was used to compare the characteristics of the immune microenvironment between the patients in the two groups. RESULTS: Compared with patients in the immunity-low group, patients in the immunity-high group had a higher number of tumor-infiltrating immune cells and greater enrichment of gene sets associated with antitumor immune activity. Furthermore, positive immune response-related pathways were more enriched in the immunity-high group. We identified 26 immune cell subsets, including cytotoxic T cells (Tcs), helper T cells (Ths), regulatory T cells (Tregs), B cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs) using CyTOF. Furthermore, there was a higher proportion of CD45+ lymphocytes and enrichment of one Tc subset in the immunity-high group. Additionally, M2 macrophages were highly enriched in the immunity-low group. Finally, there was higher expression of PD-1 and Tim-3 on Tregs as well as a higher proportion of PD-1+ Tregs in the immunity-low group than in the immunity-high group. CONCLUSION: In summary, the immune microenvironments of the immunity-high and immunity-low groups of patients with MIBC are heterogeneous. Specifically, immune suppression was observed in the immune microenvironment of the patients in the immunity-low group.
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Citometría de Flujo , Músculos/patología , Microambiente Tumoral/inmunología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunofenotipificación , Terapia de Inmunosupresión , Invasividad Neoplásica , Microambiente Tumoral/genéticaRESUMEN
A novel micro matrix solid phase dispersion method was successfully used for the extraction of quaternary alkaloids in Phellodendri chinensis cortex. The elution of target compounds was accomplished with sodium hexanesulfonate as the eluent solvent. A neutral ion pair was formed between ion-pairing reagent and positively charged alkaloids in this process, which was beneficial for selectively extraction of polar alkaloids. Several parameters were optimized and the optimal conditions were listed as follows: silica gel as the sorbent, silica to sample mass ratio of 1:1, the grinding time of 1 min. The exhaustive elution of targets was achieved by 200 µL methanol/water (9:1) containing 150 mM sodium hexane sulfonate at pH 4.5. The method validation covered linearity, recovery, precision of intraday and interday, limits of detection, limits of quantitation, and repeatability. This established method was rapid, simple, environmentally friendly, and highly sensitive.
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Berberina , Medicamentos Herbarios Chinos/química , Quinolizinas , Extracción en Fase Sólida/métodos , Berberina/análisis , Berberina/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Límite de Detección , Modelos Lineales , Phellodendron/química , Plantas Medicinales/química , Quinolizinas/análisis , Quinolizinas/aislamiento & purificación , Reproducibilidad de los ResultadosRESUMEN
KEY MESSAGE: An InDel marker closely linked with a major and stable quantitative trait locus (QTL) on chromosome 4BS, QSnpa.cau-4B, controlling spike number per unit area will benefit wheat yield improvement. Spike number per unit area (SNPA) is an essential yield-related trait, and analyzing its genetic basis is important for cultivar improvement in wheat (Triticum aestivum L.). In this study, we used the F2 population derived from a cross between two wheat accessions displaying significant differences in SNPA to perform quantitative trait locus (QTL) analysis. Through bulked segregant analysis, a major and stable QTL that explained 18.11-82.11% of the phenotypic variation was identified on chromosome 4BS. The QTL interval was validated using F4:5 and F6:7 families and narrowed it to a 24.91-38.36 Mb region of chromosome 4BS according to the 'Chinese Spring' reference genome sequence. In this region, variations in 16 genes caused amino acid changes and three genes were present in only one parent. Among these, we annotated a gene orthologous to TB1 in maize (Zea mays), namely TraesCS4B01G042700, which carried a 44-bp deletion in its promoter in the higher-SNPA parent. An InDel marker based on the insertion/deletion polymorphism was designed and used to diagnose the allelic distribution within a natural population. The frequency of the 44-bp deletion allele associated with higher SNPA was relatively low (13.24%), implying that this favorable allele has not been widely utilized and could be valuable for wheat yield improvement. In summary, we identified a major and stable QTL for SNPA and developed a diagnostic marker for the more-spiked trait, which will be beneficial for molecular-assisted breeding in wheat.
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Cromosomas de las Plantas , Genes de Plantas , Sitios de Carácter Cuantitativo , Triticum/genética , Alelos , Mapeo Cromosómico , Cruzamientos Genéticos , Ligamiento Genético , Marcadores Genéticos , Fenotipo , FitomejoramientoRESUMEN
BACKGROUND: Renal tumors are highly heterogeneous, and identification of tumor heterogeneity is an urgent clinical need for effective treatment. Mass cytometry (MC) can be used to perform high-dimensional single-cell proteomics analysis of heterogeneous samples via cytometry by time-of-flight (CyTOF), in order to achieve more accurate observation and classification of phenotypes within a cell population. This study aimed to develop a high-dimensional MC method for the detection and analysis of heterogeneity in renal tumors. MATERIALS AND METHODS: We collected tissue samples from 8 patients with different types of renal tumors. Single-cell suspensions were prepared and stained using a panel of 28 immune cell-centric antibodies and a panel of 21 stem-like cell-centric antibodies. The stained cells were detected using CyTOF. RESULT: Renal tumors were divided into 25 immune cell subsets (4 CD4+ T cells, 7 CD8+ T cells, 1 B cells, 8 macrophages, 1 dendritic cells, 2 natural killer (NK) cells, 1 granulocyte, and 1 other subset) and 7 stem-like cells subsets (based on positivity of vimentin, CD326, CD34, CD90, CD13, CD44, and CD47). Different types of renal tumors have different cell subsets with significantly different characteristics. CONCLUSION: High-dimensional single-cell proteomics analysis using MC aids in the discovery and analysis of renal tumors heterogeneity. Additionally, it can be used to accurately classify the immune cell population and analyze the expression of stem cell-related markers in renal tumors. Our findings provide a valuable resource for deciphering tumor heterogeneity and might improve the clinical management of patients with renal tumors.
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Neoplasias Renales/inmunología , Neoplasias Renales/patología , Análisis de la Célula Individual/métodos , Antígenos CD/análisis , Antígenos CD/metabolismo , Linfocitos B/inmunología , Linfocitos B/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Granulocitos/inmunología , Granulocitos/patología , Humanos , Inmunofenotipificación/métodos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Células Madre Neoplásicas/patología , Proteómica/métodosRESUMEN
A new bile acid tauro-16ß-hydroxy-12α-sulfate-5ß-cholenoic acid (1), along with six known ones (2-7), was isolated from the snake bile. Its planar structure and relative configuration were elucidated based on extensive spectroscopic analyses. Moreover, compound 2 showed inhibitory effect on NO production in RAW 264.7 macrophages at non-cytotoxic concentration (20 µM) with inhibitory rate of 69.7%. [Formula: see text].
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Bilis , Medicina Tradicional China , Ácidos y Sales Biliares , Estructura MolecularRESUMEN
Endoplasmic reticulum-associated degradation (ERAD) employs membrane-bound ubiquitin ligases and the translocation-driving ATPase p97 to retrotranslocate misfolded proteins for proteasomal degradation. How retrotranslocated polypeptides bearing exposed hydrophobic motifs or transmembrane domains (TMDs) avoid aggregation before reaching the proteasome is unclear. Here we identify a ubiquitin ligase-associated multiprotein complex comprising Bag6, Ubl4A, and Trc35, which chaperones retrotranslocated polypeptides en route to the proteasome to improve ERAD efficiency. In vitro, Bag6, the central component of the complex, contains a chaperone-like activity capable of maintaining an aggregation-prone substrate in an unfolded yet soluble state. The physiological importance of this holdase activity is underscored by observations that ERAD substrates accumulate in detergent-insoluble aggregates in cells depleted of Bag6, or of Trc35, a cofactor that keeps Bag6 outside the nucleus for engagement in ERAD. Our results reveal a ubiquitin ligase-associated holdase that maintains polypeptide solubility to enhance protein quality control in mammalian cells.
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Retículo Endoplásmico/metabolismo , Chaperonas Moleculares/metabolismo , Péptidos/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Células HEK293 , Humanos , Chaperonas Moleculares/genética , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Proteínas de Unión al ARN/metabolismo , Solubilidad , Proteínas Virales/metabolismoRESUMEN
The quantification of three alkaloids is important because quantitative study is a means of assessing the reliability of the experimental method, and three alkaloids of peimine, peiminine, and peimisine are main active ingredients in Chinese Pharmacopoeia 2015. An effective method based on the matrix solid-phase dispersion microextraction was developed for the extraction of alkaloid compounds in Fritillariae Thunbergii Bulbus. Target analytes were analyzed by capillary electrophoresis coupled with quadrupole time-of-flight mass spectrometry. The optimized experimental condition was that 50 mg Fritillariae Thunbergii Bulbus was blended homogeneously with 10 mg citric acid for 5 min. Two hundred microliters of water acidized by 1 mol/L hydrochloric acid (pH = 4.5) was selected to elute tested alkaloids. The results demonstrated that the investigated method had low limits of detection (1.32-1.59 ng/mL), good recoveries (86.63-98.12%), and reproducibility (relative standard deviations of peak areas < 0.87%). The proposed matrix solid-phase dispersion microextraction coupled with capillary electrophoresis combined with quadrupole time-of-flight mass spectrometry was successfully applied for the extraction of alkaloids in plants.