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The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA1. As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities2. Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions3,4. Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel ß-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity.
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Bacterias , Bacteriófagos , Proteína 9 Asociada a CRISPR , Sistemas CRISPR-Cas , Bacterias/virología , Bacterias/genética , Bacterias/inmunología , Bacteriófagos/genética , Bacteriófagos/inmunología , Chryseobacterium/genética , Chryseobacterium/inmunología , Chryseobacterium/virología , Proteína 9 Asociada a CRISPR/química , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Sistemas CRISPR-Cas/inmunología , División del ADN , Sitios Genéticos/genética , Modelos Moleculares , Dominios ProteicosRESUMEN
The structure of solvated Li+ has a significant influence on the electrolyte/electrode interphase (EEI) components and desolvation energy barrier, which are two key factors in determining the Li+ diffusion kinetics in lithium metal batteries. Herein, the "solvent activity" concept is proposed to quantitatively describe the correlation between the electrolyte elements and the structure of solvated Li+. Through fitting the correlation of the electrode potential and solvent concentration, we suggest a "low-activity-solvent" electrolyte (LASE) system for deriving a stable inorganic-rich EEI. Nano LiF particles, as a model, were used to capture free solvent molecules for the formation of a LASE system. This advanced LASE not only exhibits outstanding antidendrite growth behavior but also delivers an impressive performance in Li/LiNi0.8Co0.1Mn0.1O2 cells (a capacity of 169 mAh g-1 after 250 cycles at 0.5 C).
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BACKGROUND: Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. METHODS: Our study utilized in vitro cell phenotype experiments to assess CCT6A's impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A's intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. RESULTS: CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD's aerobic glycolysis and progression. CONCLUSION: Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.
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Adenocarcinoma del Pulmón , Proliferación Celular , Chaperonina con TCP-1 , Progresión de la Enfermedad , Glucólisis , Hexoquinasa , Neoplasias Pulmonares , Factor de Transcripción STAT1 , Humanos , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genética , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Chaperonina con TCP-1/metabolismo , Regulación Neoplásica de la Expresión Génica , Hexoquinasa/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Invasividad Neoplásica , Transducción de Señal , Factor de Transcripción STAT1/metabolismoRESUMEN
Aqueous zinc ion batteries have been extensively researched due to their distinctive advantages such as low cost and high safety. Vanadium oxides are important cathode materials, however, poor cycle life caused by vanadium dissolution limits their application. Recent studies show that the lattice NH4 + in vanadium oxides can act as a pillar to enhance structural stability and play a crucial role in improving its cycling stability. Nevertheless, there is still a lack of research on the effect of the lattice NH4 + content on structural evolution and electrochemical performance. Herein, we synthesize vanadium oxides with different contents of lattice NH4 + by a one-step hydrothermal reaction. The vanadium oxides with lattice NH4 + exhibit high initial capacity, as well as good cycling stability and rate performance compared to bare vanadium oxide. Combined with electrochemical analyses, ex-situ structural characterizations, and in-situ X-ray diffraction tests, we reveal that the lattice NH4 + content plays a positive role in vanadium oxides' structural stability and cation diffusion kinetics. This work presents a direction for designing high-performance vanadium cathodes for aqueous zinc ion batteries.
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To achieve rapid enrichment of the targeted hydrogen-producing bacterial population and reconstruction of the microbial community in the biological hydrogen-producing reactor, the activated sludge underwent multiple pretreatments using micro-aeration, alkaline treatment, and heat treatment. The activated sludge obtained from the multiple pretreatments was inoculated into the continuous stirred tank reactor (CSTR) for continuous operations. The community structure alteration and hydrogen-producing capability of the activated sludge were analyzed throughout the operation of the reactor. We found that the primary phyla in the activated sludge population shifted to Proteobacteria, Firmicutes, and Bacteroidetes, which collectively accounted for 96.69% after undergoing several pretreatments. This suggests that the multiple pretreatments facilitated in achieving the selective enrichment of the fermentation hydrogen-producing microorganisms in the activated sludge. The CSTR start-up and continuous operation of the biological hydrogen production reactor resulted in the reactor entering a highly efficient hydrogen production stage at influent COD concentrations of 4000 mg/L and 5000 mg/L, with the highest hydrogen production rate reaching 8.19 L/d and 9.33 L/d, respectively. The main genus present during the efficient hydrogen production stage in the reactor was Ethanoligenens, accounting for up to 33% of the total population. Ethanoligenens exhibited autoaggregation capabilities and a superior capacity for hydrogen production, leading to its prevalence in the reactor and contribution to efficient hydrogen production. During high-efficiency hydrogen production, flora associated with hydrogen production exhibited up to 46.95% total relative abundance. In addition, redundancy analysis (RDA) indicated that effluent pH and COD influenced the distribution of the primary hydrogen-producing bacteria, including Ethanoligenens, Raoultella, and Pectinatus, as well as other low abundant hydrogen-producing bacteria in the activated sludge. The data indicates that the multiple pretreatments and reactor's operation has successfully enriched the hydrogen-producing genera and changed the community structure of microbial hydrogen production.
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Reactores Biológicos , Hidrógeno , Aguas del Alcantarillado , Hidrógeno/metabolismo , Reactores Biológicos/microbiología , Aguas del Alcantarillado/microbiología , Bacterias/metabolismo , Bacterias/genética , Eliminación de Residuos Líquidos/métodos , Fermentación , MicrobiotaRESUMEN
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.
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Factor Neurotrófico Derivado del Encéfalo , Región CA1 Hipocampal , Regulación hacia Abajo , Plasticidad Neuronal , Neuronas , Complicaciones Cognitivas Postoperatorias , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Ratones , Neuronas/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/etiología , Región CA1 Hipocampal/metabolismo , Masculino , Ratones Endogámicos C57BL , Potenciación a Largo Plazo , Ácido Glutámico/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatologíaRESUMEN
The lactation character of dairy goats is the most important characteristic, and milk protein is an important index to evaluate milk quality. Casein accounts for more than 80% of the total milk protein in goat milk and is the main component of milk protein. Using GMECs (goat mammary epithelial cells) as the research object, the CHECK2 vector of the CSN1S1 gene and the overexpression vector of pcDNA 3.1 were constructed, and the mimics of miR-2284b and the interfering RNA of CSN1S1 were synthesized. Using PCR, RT-qPCR, a dual luciferase activity detection system, EdU, CCK8, cell apoptosis detection and ELISA detection, we explored the regulatory mechanism and molecular mechanism of miR-2284b regulation of αs1-casein synthesis in GMECs. miR-2284b negatively regulates proliferation and apoptosis of GMECs and αs1-casein synthesis. Two new gene sequences of CSN1S1 were discovered. CSN1S1-1/-2 promoted the proliferation of GMECs and inhibited cell apoptosis. However, it had no effect on αs1-casein synthesis. MiR-2284b negatively regulates αs1-casein synthesis in GMECs by inhibiting the CSN1S1 gene. These results all indicated that miR-2284b could regulate αs1-casein synthesis, thus playing a theoretical guiding role in the future breeding process of dairy goats and accelerating the development of dairy goat breeding.
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Caseínas , MicroARNs , Femenino , Animales , Caseínas/genética , Caseínas/metabolismo , Proteínas de la Leche , Cabras/fisiología , Células Epiteliales/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Glándulas Mamarias Animales/metabolismoRESUMEN
Despite the great progress of current bacterially based biotherapeutics, their unsatisfying efficacy and underlying safety problems have limited their clinical application. Herein, inspired by probiotic Escherichia coli strain Nissle 1917, probiotic-derived outer membrane vesicles (OMVs) are found to serve as an effective therapeutic platform for the treatment of inflammatory bowel disease (IBD). To further enhance the therapeutic effect, the probiotic-derived OMV-encapsulating manganese dioxide nanozymes are constructed, named nanoprobiotics, which can adhere to inflamed colonic epithelium and eliminate intestinal excess reactive oxygen species in the murine IBD model. Moreover, combined with the anti-inflammatory medicine metformin, nanoprobiotics could further remold the pro-inflammatory microenvironment, improve the overall richness and diversity of the gut microbiota, and exhibit better therapeutic efficacy than commercial IBD chemotherapeutics. Importantly, insignificant overt systemic toxicity in this treatment was observed. By integrating cytokine storm calm with biotherapy, we develop a safe and effective bionanoplatform for the effective treatment of inflammation-mediated intestinal diseases.
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3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an eight-carbon monosaccharide found widely in bacterial lipopolysaccharides (LPSs) and capsule polysaccharides (CPSs). We developed an indirect method for the stereoselective synthesis of α-Kdo glycosides with a C3-p-tolylthio-substituted Kdo phosphite donor. The presence of the p-tolylthio group enhanced the reactivity, suppressed the formation of elimination by-products (2,3-enes), and provided complete α-stereocontrol. A variety of Kdo α-glycosides were synthesized by our method in excellent yields (up to 98 %). After glycosylation, the p-tolylthio group can be efficiently removed by free-radical reduction. Subsequently, the orthogonality of the phosphite donor and thioglycoside donor was demonstrated by the one-pot synthesis of a trisaccharide in Helicobacter pylori and Neisseria meningitidis LPS. Moreover, an efficient total synthesis route to the challenging 4,5-branched Kdo trisaccharide in LPSs from several A. baumannii strains was highlighted. To demonstrate the high reactivity of our approach further, the highly crowded 4,5,7,8-branched Kdo pentasaccharide was synthesized as a model molecule for the first time. Additionally, the reaction mechanism was investigated by DFT calculations.
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Glicósidos , Fosfitos , Oligosacáridos , Azúcares Ácidos , Lipopolisacáridos , TrisacáridosRESUMEN
A fully automated, closed-column chromatographic system with parallel multi-channel has been developed. This system is established with seven reagent reservoirs, one multi-channel syringe pump, eight 10-port valves, forty sample tubes, 40 columns, and a fraction collection tray. Four samples can be purified simultaneously at a time, and 40 samples can be purified in one batch. Each sample can be purified by an independent channel, avoiding cross-contamination. The sample tubes can be flipped upside down for automatic cleaning, which eliminates the residue of samples. Moreover, the fraction collection tray can collect up to 104 different target components. The key performance of the system has been investigated. The results show that the sample tubes are well-cleaned, the bubble does not affect the chemical behavior of columns, the consistency of the parallel channels is excellent and the blank of the system is negligible. The system was demonstrated by the purification of Sr from reference materials (BCR-2, JB-2, JB-3, and NIST SRM 987). The recoveries of Sr are better than 89.4% and the blank of the whole procedure is less than 200 pg. The Sr isotope values agree well with the reference values.
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China has diversified resources of indigenous cattle, which are classified into Northern, Central, and Southern groups according to their geographical distribution. Chaling cattle belong to Southern group. This breed is famous for the production of good quality meat with elite meat grades. To analyze the genetic diversity of Chaling cattle, 20 samples were sequenced using whole-genome resequencing technology, along with 138 published whole-genome sequencing data of Indian indicine cattle, Chinese indicine cattle, East Asian taurine cattle, Eurasian taurine cattle, and European taurine cattle as control. It was found that Chaling cattle originated from Chinese indicine cattle. The genetic diversity of Chaling cattle is higher than that of Indian indicine cattle, East Asian taurine cattle, Eurasian taurine cattle, and European taurine cattle, but lower than that of Chinese indicine cattle and Xiangxi cattle. Annotating the selection signals obtained by composite likelihood ratio, θπ, FST , π-ratio, and XP-EHH methods, several genes associated with immunity, heat tolerance, reproduction, growth, and meat quality showed strong selection signals. In general, this study provides a theoretical basis for analyzing the genetic mechanism of Chaling cattle with excellent adaptability, rough feeding tolerance, good immune performance, and good meat quality. This work lays a foundation for genetic breeding of Chaling cattle in future.
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Genoma , Polimorfismo de Nucleótido Simple , Bovinos , Animales , China , Secuenciación Completa del Genoma/veterinaria , ReproducciónRESUMEN
The BDS multipath delay error is highly related to the surrounding monitoring environment, which cannot be eliminated or mitigated by applying the double difference observation model. In the actual monitoring environment, due to the complexity of the BDS constellation, it is difficult for existing algorithms to consider GEO, IGSO, MEO and other different orbital types of satellites for real-time and efficient multipath error reduction. Therefore, we propose a novel BDS dual-frequency multipath error reduction method for real deformation monitoring for BDS considering various satellite orbit types. This method extracts the single error residual of each satellite based on the assumption of "zero mean" and divides the appropriate grid density of GEO and IGSO/MEO, respectively, to construct a dual-frequency multipath hemispherical map model suitable for BDS satellites with different orbital types. This method can realize the multipath error elimination of the observed values of different orbits and different frequencies. The results of simulation experiments and real deformation monitoring data demonstrate that this method can effectively eliminate low-frequency multipath delay errors in the observation domain and coordinate domain. After multipath correction, the precision of the horizontal coordinates and height coordinates are 1.7 mm and 4.6 mm. The precision of the horizontal coordinate and height coordinate is increased by 50% and 60%, respectively. The fixed rate of ambiguity increased by 5-7%.
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Patients with traumatic dental injuries commonly present in clinical practice with complex crown-root fractures. Prosthodontic treatment of such patients may be unsuccessful because of the violation of the supracrestal tissue attachment, making their management challenging. Minor tooth movement is an effective solution to extruding the residual root but may require referral to an orthodontist. The purpose of this technique was to present a digital orthodontic system including a 3-dimensional virtual patient technique, a computer-aided design and computer-aided manufacture (CAD-CAM) resin facial veneer-retained pontic, and a zirconia post as an orthodontic appliance for tooth extrusion in the esthetic zone. This veneered pontic may also serve as an interim prothesis. The appliance provides a precise design for the direction and extent of orthodontic extrusion.
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The integration of active cooling systems in super or hypersonic aircraft using endothermic hydrocarbon fuels is considered an effective way to relieve the thermal management issues caused by overheating. When the temperature of aviation kerosene exceeds 150 °C, the oxidation reaction of fuel is accelerated, forming insoluble deposits that could cause safety hazards. This work investigates the deposition characteristic as well as the morphology of the deposits formed by thermal-stressed Chinese RP-3 aviation kerosene. A microchannel heat transfer simulation device is used to simulate the heat transfer process of aviation kerosene under various conditions. The temperature distribution of the reaction tube was monitored by an infrared thermal camera. The properties and morphology of the deposition were analyzed by scanning electron microscopy and Raman spectroscopy. The mass of the deposits was measured using the temperature-programmed oxidation method. It is observed that the deposition of RP-3 is highly related to dissolved oxygen content (DOC) and temperature. When the outlet temperature increased to 527 °C, the fuel underwent violent cracking reactions, and the structure and morphology of deposition were significantly different from those caused by oxidation. Specifically, this study reveals that the structure of the deposits caused by short-to-medium term oxidation are dense, which is different from long-term oxidative deposits.
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Aviación , Queroseno , Hidrocarburos/química , Microscopía Electrónica de Rastreo , TemperaturaRESUMEN
Nanofluid-enhanced oil recovery (EOR) technology is an innovative approach to enhancing oil production in oilfields. It entails the dispersion of nanoparticles within a fluid, strategically utilizing the distinctive properties of these nanoparticles (NPs) to engage with reservoir rocks or crude oil, resulting in a significant enhancement of the oil recovery rate. Despite the notable advantages of nanofluid EOR technology over conventional oil recovery methods such as binary and ternary flooding, practical implementations continue to grapple with a range of pressing challenges. These challenges encompass concerns regarding the economic viability, stability, and adaptability of nanomaterials, which pose significant barriers to the widespread adoption of nanofluid EOR technology in the oil field. To tackle these challenges, addressing the current issues may involve selecting simpler and more readily available materials coupled with straightforward material modification techniques. This approach aims to more effectively meet the requirements of large-scale on-site applications. Within this framework, this review systematically explores commonly employed nanofluids in recent years, including inorganic nanofluids, organic nanofluids, and composite nanofluids. It categorizes the research advancements in optimizing modification techniques and provides a comprehensive overview of the mechanisms that underpin nanofluid EOR technology and its practical applications in oilfields. This comprehensive review aims to offer valuable references and serve as a solid foundation for subsequent research endeavors.
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The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of "Drying > Fixation > Rolling". The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (-)-epicatechin gallate, (-)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry.
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Camellia sinensis , Té , Té/metabolismo , Cafeína/análisis , Gusto , Percepción del Gusto , Metabolómica/métodos , Camellia sinensis/metabolismoRESUMEN
In situ combustion of heavy oil is currently the most suitable thermal method that meets energy consumption and carbon dioxide emission requirements for heavy oil recovery. The combustion catalyst needs to perform multiple roles for application; it should be capable of catalyzing heavy oil combustion at high temperatures, as well as be able to migrate in the geological formation for injection. In this work, a hyperbranched polymer composite nanometal fluid was used as the injection vector for a heavy oil in situ combustion catalyst, which enabled the catalyst to rapidly migrate to the surface of the oil phase in porous media and promoted heavy oil cracking deposition at high temperatures. Platinum (Pt) nanoparticles encapsulated with cetyl-hyperbranched poly(amide-amine) (CPAMAM), with high interfacial activity, were synthesized by a facile phase-transfer method; the resulting material is called Pt@CPAMAM. Pt@CPAMAM has good dispersion, and as an aqueous solution, it can reduce the interfacial tension between heavy oil and water. As a catalyst, it can improve the conversion rate during the pyrolysis of heavy oil in a nitrogen atmosphere. The catalyst structure designed in this study is closer to that exhibited in practical geological formation applications, making it a potential method for preparing catalysts for use in heavy oil in situ combustion to resolve the problem of catalyst migration in the geological formation.
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CD4+ CD8+ double-positive thymocytes give rise to both conventional TCRαß+ T cells and invariant natural killer T cells (iNKT cells), but these two kinds of cells display different characteristics. The molecular mechanism underlying iNKT cell lineage development and function acquisition remain to be elucidated. We show that the loss of chromatin assembly factor 1B (CHAF1b) maintains the normal development of conventional TCRαß+ T cells but severely impairs early development of iNKT cells. This dysregulation is accompanied by the impairment in chromatin activation and gene transcription at Vα14-Jα18 locus. Notably, ectopic expression of a Vα14-Jα18 TCR rescues Chaf1b-deficient iNKT cell developmental defects. Moreover, cytokine secretion and antitumor activity are substantially maintained in Vα14-Jα18 TCR transgene-rescued Chaf1b-deficient iNKT cells. Our study identifies CHAF1b as a critical factor that controls the early development but not function acquisition of iNKT cells via lineage- and stage-specific regulation.
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Factor 1 de Ensamblaje de la Cromatina/inmunología , Células T Asesinas Naturales/inmunología , Animales , Diferenciación Celular/inmunología , Línea Celular Tumoral , Linaje de la Célula/inmunología , Ensamble y Desensamble de Cromatina/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Timocitos/inmunologíaRESUMEN
A new method for measuring the time-dependent drive flux at the hohlraum center is proposed as a better alternative to conventional wall-based techniques. The drive flux here is obtained by simultaneous measurement of the reemitted flux and shock velocity from a three-layered "cakelike" sample. With these two independent observables, the influence induced by the uncertainty of the material parameters of the sample can be effectively decreased. The influence from the closure of the laser entrance hole, which was the main challenge in conventional wall-based techniques, was avoided through localized reemitted flux measurement, facilitating drive flux measurement throughout the entire time history. These studies pave a new way for probing the time-dependent drive flux, for both cylindrical hohlraums and novel hohlraums with six laser entrance holes.
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INTRODUCTION: Adipose tissue fibrosis is a typical feature of adipose tissue dysfunction in obese individuals, which is closely related to metabolic diseases. OBJECTIVE: To explore the effect and mechanism of Saponins from Panax japonicus (SPJ) on adipose tissue fibrosis in obese mice induced by high fat diet (HFD). MATERIALS AND METHODS: We established a HFD induced obese mice model. Then the obese mice were treated with 90 mg/kg SPJ by oral gavage for 10 weeks. The levels of adipose tissue fibrosis and molecules related to signalling pathways were measured. Then the effects of SPJ on TGFß1-induced fibrosis in 3T3-L1 differentiated adipocytes were evaluated. RESULTS: SPJ reduced body weight, fat accumulation, and improved glucose and lipid metabolism in obese mice. SPJ decreased collagen deposition and expressions of fibrotic genes in epididymal white adipose tissue (eWAT) of obese mice. SPJ decreased the levels of TGFß1 protein and pSmad2, and increased the expression of PPARγ and PGC1α, thus alleviating oxidative stress in eWAT. Consistently, SPJ inhibited TGFß1-induced fibrosis in 3T3-L1 differentiated adipocytes. CONCLUSIONS: SPJ may alleviate adipose tissue fibrosis and improve obesity by inhibiting TGFß1/Smad2 and activating PPARγ/PGC1α pathway. SPJ is expected to become an efficient medicine for treatment of obesity.