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Incorporation of microbiome data has recently become important for prevention, diagnosis, and treatment of colorectal cancer, and several species of bacteria were shown to be associated with carcinogenesis. However, the role of commensal fungi in colon cancer remains poorly understood. Here, we report that mice lacking the c-type lectin Dectin-3 (Dectin-3-/- ) show increased tumorigenesis and Candida albicans burden upon chemical induction. Elevated C. albicans load triggered glycolysis in macrophages and interleukin-7 (IL-7) secretion. IL-7 induced IL-22 production in RORγt+ (group 3) innate lymphoid cells (ILC3s) via aryl hydrocarbon receptor and STAT3. Consistently, IL-22 frequency in tumor tissues of colon cancer patients positively correlated with fungal burden, indicating the relevance of this regulatory axis in human disease. These results establish a C. albicans-driven crosstalk between macrophages and innate lymphoid cells in the intestine and expand our understanding on how commensal mycobiota regulate host immunity and promote tumorigenesis.
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Neoplasias Colorrectales/metabolismo , Glucólisis , Interleucinas/metabolismo , Linfocitos/metabolismo , Macrófagos/metabolismo , Micobioma , Animales , Candida albicans/patogenicidad , Células Cultivadas , Neoplasias Colorrectales/microbiología , Humanos , Interleucina-7/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Ratones , Ratones Endogámicos C57BL , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Factor de Transcripción STAT3/metabolismo , Interleucina-22RESUMEN
SignificanceTraditional views indicate that the well-known layered LiCoO2 cathode delivers a typical solid-solution reaction upon delithiation. The problem is that "solid solution" is a vague concept, and the phase transition remains ambiguous. Here, we reveal a mechanism with the collective and quasi-continuous glide of CoO6 slabs in layered LiCoO2 through combining in situ XRD and ex situ STEM characterizations. Such a delithiation mechanism does not involve the nucleation-and-growth-type delithiation process and represents a completely different manner from the conventional two-phase or solid solution-phase transition processes. The lessons provide a different insight into understanding the working mechanism of layered oxide materials.
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The unstable solid electrolyte interface (SEI) formed by uncontrollable electrolyte degradation, which leads to dendrite growth and Coulombic efficiency decay, hinders the development of Li metal anodes. A controllable desolvation process is essential for the formation of stable SEI and improved lithium metal deposition behavior. Here, we show a functional artificial interface protective layer comprised of chondroitin sulfate-reduced graphene oxide (CrG), on which polar functional groups are distributed to effectively reduce the energy barrier for desolvation of Li+ and effectively alienate solvent molecules to avoid solvent involvement in SEI formation, thus promoting the formation of a LiF-rich SEI. Consequently, stable Coulombic efficiencies of 98.4% were achieved after 500 cycles in a Li//Cu cell. Moreover, the LiFePO4 full cells achieve steady circulation (470 cycles at 80%, 1 C) with a negative/positive electrode capacity ratio of 2.87. Our multifunctional artificial interface protective layer provides a new way to advance Li metal batteries.
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Designing cathode materials that effectively enhancing structural stability under high voltage is paramount for rationally enhancing energy density and safety of Na-ion batteries. This study introduces a novel P2-Na0.73K0.03Ni0.23Li0.1Mn0.67O2 (KLi-NaNMO) cathode through dual-site synergistic doping of K and Li in Na and transition metal (TM) layers. Combining theoretical and experimental studies, this study discovers that Li doping significantly strengthens the orbital overlap of Ni (3d) and O (2p) near the Fermi level, thereby regulates the phase transition and charge compensation processes with synchronized Ni and O redox. The introduction of K further adjusts the ratio of Nae and Naf sites at Na layer with enhanced structural stability and extended lattice space distance, enabling the suppression of TM dissolution, achieving a single-phase transition reaction even at a high voltage of 4.4 V, and improving reaction kinetics. Consequently, KLi-NaNMO exhibits a high capacity (105 and 120 mAh g-1 in the voltage of 2-4.2 V and 2-4.4 V at 0.1 C, respectively) and outstanding cycling performance over 300 cycles under 4.2 and 4.4 V. This work provides a dual-site doping strategy to employ synchronized TM and O redox with improved capacity and high structural stability via electronic and crystal structure modulation.
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It is generally accepted that the low-temperature environment typically augments electrolyte viscosity and impedes electrochemical kinetics, thereby diminishing battery performance. However, this prevailing notion, while valid in certain contexts, lacks universality, particularly regarding cycling stability. In this context, the Na-MoS2 batteries serve as a model to elucidate the impacts of low temperatures. By significantly suppressing the pulverization and amorphization of MoS2, the low-temperature milieu effectively mitigates the risk of micro-short circuits induced by the mass shuttling to the Na metal anode, thereby averting performance degradation by self-discharge. Upon cycling, the generated NaxMo3S4 intermediates only at low temperatures benefit the structural and electrochemical stabilizations to counteract the intrinsic performance degradation. The attenuation of kinetics at low temperatures facilitates the accumulation of Na2S, akin to a sustained-release agent within the electrode, steadily furnishing the capacity in long cycling. Moreover, the suppression of polysulfide dissolution and shuttling emerges as a pivotal factor contributing to the cycling stability at low-temperature. These findings provide a rewarding avenue toward understanding of the influence of low temperature on battery performance, as well as the design of practical electrodes and batteries for low-temperature applications.
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PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcriptionquantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Proliferación Celular , Neoplasias Colorrectales , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Regulación Neoplásica de la Expresión Génica , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Fluorodesoxiglucosa F18/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Femenino , Masculino , Línea Celular Tumoral , Persona de Mediana Edad , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , AncianoRESUMEN
BACKGROUND: Asthma's complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation. METHODS: High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining. RESULTS: A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs' viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774. CONCLUSION: The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma.
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Asma , Subunidad alfa del Factor 1 Inducible por Hipoxia , Miocitos del Músculo Liso , Proteína p53 Supresora de Tumor , Asma/metabolismo , Asma/patología , Asma/genética , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Células Cultivadas , Ratones Endogámicos BALB C , Apoptosis/fisiología , Proliferación Celular/fisiología , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Hipoxia/metabolismo , Hipoxia/patología , Modelos Animales de Enfermedad , Hipoxia de la Célula/fisiología , Femenino , Humanos , Movimiento Celular/fisiología , UbiquitinaciónRESUMEN
Cardiac fibrosis is an essential pathological process in pressure overload (PO)-induced heart failure. Recently, myocyte-fibroblast communication is proven to be critical in heart failure, in which, pathological growth of cardiomyocytes (CMs) may promote fibrosis via miRNAs-containing exosomes (Exos). Peli1 regulates the activation of NF-κB and AP-1, which has been demonstrated to engage in miRNA transcription in cardiomyocytes. Therefore, we hypothesized that Peli1 in CMs regulates the activation of cardiac fibroblasts (CFs) through an exosomal miRNA-mediated paracrine mechanism, thereby promoting cardiac fibrosis. We found that CM-conditional deletion of Peli1 improved PO-induced cardiac fibrosis. Moreover, Exos from mechanical stretch (MS)-induced WT CMs (WT MS-Exos) promote activation of CFs, Peli1-/- MS-Exos reversed it. Furthermore, miRNA microarray and qPCR analysis showed that miR-494-3p was increased in WT MS-Exos while being down regulated in Peli1-/- MS-Exos. Mechanistically, Peli1 promoted miR-494-3p expression via NF-κB/AP-1 in CMs, and then miR-494-3p induced CFs activation by inhibiting PTEN and amplifying the phosphorylation of AKT, SMAD2/3, and ERK. Collectively, our study suggests that CMs Peli1 contributes to myocardial fibrosis via CMs-derived miR-494-3p-enriched exosomes under PO, and provides a potential exosomal miRNA-based therapy for cardiac fibrosis.
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Comunicación Celular , Exosomas , Insuficiencia Cardíaca , Miocitos Cardíacos , Humanos , Exosomas/genética , Exosomas/metabolismo , Fibrosis/etiología , Fibrosis/genética , Fibrosis/metabolismo , Fibrosis/patología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , MicroARNs/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factor de Transcripción AP-1/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Cardiopatías/etiología , Cardiopatías/genética , Cardiopatías/metabolismo , Cardiopatías/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Comunicación Celular/genética , Comunicación Celular/fisiologíaRESUMEN
The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air â × Apu â) and Api (Apu â × Air â). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.
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Pectinidae , Factor 6 Asociado a Receptor de TNF , Humanos , Animales , Factor 6 Asociado a Receptor de TNF/metabolismo , Células HEK293 , Factor 2 Asociado a Receptor de TNF/metabolismo , Receptores del Factor de Necrosis Tumoral , Pectinidae/genética , Factor 4 Asociado a Receptor de TNF/metabolismoRESUMEN
Lithium (Li) metal is regarded as the most promising anode candidate for next-generation rechargeable storage systems due to its impeccable capacity and the lowest electrochemical potential. Nevertheless, the irregular dendritic Li, unstable interface, and infinite volume change, which are the intrinsic drawbacks rooted in Li metal, give a seriously negative effect on the practical commercialization for Li metal batteries. Among the numerous optimization strategies, designing a 3D framework with high specific surface area and sufficient space is a convincing way out to ameliorate the above issues. Due to the Li-free property of the 3D framework, a Li preloading process is necessary before the 3D framework that matches with the electrolyte and cathode. How to achieve homogeneous integration with Li and 3D framework is essential to determine the electrochemical performance of Li metal anode. Herein, this review overviews the recent general fabrication methods of 3D framework-based composite Li metal anode, including electrodeposition, molten Li infusion, and pressure-derived fabrication, with the focus on the underlying mechanism, design criteria, and interfacial optimization. These results can give specific perspectives for future Li metal batteries with thin thickness, low N/P ratio, lean electrolyte, and high energy density (>350 Wh Kg-1 ).
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2D materials have captured much recent research interest in a broad range of areas, including electronics, biology, sensors, energy storage, and others. In particular, preparing 2D nanosheets with high quality and high yield is crucial for the important applications in energy storage and conversion. Compared with other prevailing synthetic strategies, the electrochemical exfoliation of layered starting materials is regarded as one of the most promising and convenient methods for the large-scale production of uniform 2D nanosheets. Here, recent developments in electrochemical delamination are reviewed, including protocols, categories, principles, and operating conditions. State-of-the-art methods for obtaining 2D materials with small numbers of layers-including graphene, black phosphorene, transition metal dichalcogenides and MXene-are also summarized and discussed in detail. The applications of electrochemically exfoliated 2D materials in energy storage and conversion are systematically reviewed. Drawing upon current progress, perspectives on emerging trends, existing challenges, and future research directions of electrochemical delamination are also offered.
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The tumor necrosis factor receptor-related factor (TRAF) family has been reported to be involved in many immune pathways, such as TNFR, TLR, NLR, and RLR in animals. However, little is known about the roles of TRAF genes in the innate immune of Argopecten scallops. In this study, we first identified five TRAF genes, including TRAF2, TRAF3, TRAF4, TRAF6 and TRAF7, but not TRAF1 and TRAF5, from both the bay scallop A. irradians (Air) and the Peruvian scallop A. purpuratus (Apu). The phylogenetic analysis showed that the TRAF genes in Argopecten scallops (AiTRAF) belong to the branch of molluscan TRAF family, which lacks TRAF1 and TRAF5. Since TRAF6 is a key bridge factor in the tumor necrosis factor superfamily and plays an important role in innate and adaptive immunity, we cloned the ORFs of the TRAF6 gene in both A. irradians and A. purpuratus, as well as in two reciprocal hybrids (Aip for the hybrid Air × Apu and Api for the hybrid Apu × Air). Differences in conformational and post-translational modification resulted from the variation in amino acid sequences may cause differences in activity among them. Analysis of conserved motifs and protein structural domains revealed that AiTRAF contains typical structural domains similar to those of other mollusks and has the same conserved motifs. Tissue expression of TRAF in Argopecten scallops challenged by Vibrio anguillarum was examined by qRT-PCR. The results showed that AiTRAF were higher in gill and hepatopancreas. When challenged by Vibrio anguillarum, the expression of AiTRAF was significantly increased compared with the control group, indicating that AiTRAF may play an important role in the immunity of scallops. In addition, the expression of TRAF was higher in Api and Aip than in Air when challenged by Vibrio anguillarum, suggesting that TRAF may have contributed to the high resistance of Api and Aip to Vibrio anguillarum. The results of this study may provide new insights into the evolution and function of TRAF genes in bivalves and ultimately benefit scallop breeding.
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Pectinidae , Vibrio , Animales , Filogenia , Vibrio/fisiología , Secuencia de Aminoácidos , Pectinidae/genéticaRESUMEN
Vibrio bacteria are often fatal to aquatic organisms and selection of Vibrio-resistant strains is warranted for aquaculture animals. In this study, we found that hybrids between bay scallops and Peruvian scallops exhibited significantly higher resistance to Vibrio challenge, but little is available on its mechanism. Interferon induced protein 44 (IFI44), a member of the type I interferon (IFN) family, plays an important role in the IFN immune response in invertebrates, which may also participate in the resistance to Vibrio in scallops. To explore the roles of IFI44 genes in the resistance to Vibrio, they were identified and characterized in the bay scallop (designated as AiIFI44), the Peruvian scallop (designated as ApIFI44), and their reciprocal hybrids (designated as AipIFI44 and ApiIFI44, respectively). Their open reading frame (ORF) sequences were all 1434 bp, encoding 477 amino acids, but with large variations among the four genes. The AipIFI44 and ApiIFI44 exhibited higher similarity with ApIFI44 than with AiIFI44. All four genes have a TLDc structural domain with significant variations in sequences among them. Predicted differences in conformation and posttranslational modifications may lead to altered protein activity. We further demonstrated that the AiIFI44, AipIFI44 and ApiIFI44 expressed in all the tested tissues, with the highest expression in the gills and hepatopancreas. In response to Vibrio anguillarum challenge, the profile of mRNA expression of IFI44 gene differed among the bay scallops and the two hybrids. In the bay scallops, it increased at 6 h but dramatically decreased after 12-48 h. However, the mRNA expression of both AipIFI44 and ApiIFI44 decreased at 6 h but continuously increased thereafter and reached the highest value at 48 h. The results in the present study suggest the immune responds of IFI44 in scallops and it may be related to the higher resistance to Vibrio bacterial in hybrids.
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Pectinidae , Vibrio , Animales , Interferones/genética , Vibrio/fisiología , ARN Mensajero , FilogeniaRESUMEN
This work aims to provide a novel reference for future diagnosis and treatment of synovitis of the knee joint (SKJ) by analyzing the correlation of the TLR4/MyD88 axis with the degree of inflammatory response in SKJ patients. First, this study retrospectively analyzed the clinical data of 46 SKJ patients (research group, RG) treated in our hospital from January 2021 to December 2022 and 52 concurrent healthy controls (control group, CG). Concentrations of TLR4, MyD88 and inflammatory factors (IFs) in peripheral blood were measured, and differences in TLR4 and MyD88 between groups were observed to explore the diagnostic performance of the two for SKJ. Additionally, the correlation of TLR4 and MyD88 with IFs and Western Ontario Mac Master (WOMAC) scores in SKJ patients was discussed. Through the above experiment, we found that TLR4 and MyD88 presented higher mRNA levels in RG than in CG (P<0.05), both of which had excellent diagnostic efficiency for SKJ. Pearson correlation coefficients identified a positive correlation of TLR4 and MyD88 mRNA with IFs and WOMAC scores (P<0.05). Therefore, The TLR4/MyD88 axis is activated in SKJ patients and is strongly related to the intensification of inflammatory responses.
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Factor 88 de Diferenciación Mieloide , Sinovitis , Humanos , Factor 88 de Diferenciación Mieloide/genética , Estudios Retrospectivos , Receptor Toll-Like 4/genética , Proteínas Adaptadoras Transductoras de Señales , Articulación de la Rodilla , ARN MensajeroRESUMEN
T-2 toxin is the most potent and toxic mycotoxin, produced by various Fusarium species that can potentially affect human health, and widely exists in field crops and stored grain. In this work, an electrochemical aptasensor with nonenzymatic signal amplification strategy for the detection of T-2 toxin is presented, using noble metal nanocomposites and catalytic hairpin assembly as signal amplification strategy. Silver palladium nanoflowers and gold octahedron nanoparticles@graphene oxide nanocomposites are used for synergistic amplification of electrical signals. Simultaneously, the catalytic hairpin assembly strategy based on artificial molecular technology was introduced to further amplify the signal. Under optimal conditions, T-2 toxin was measured within a linear concentration range 1 × 10-2 ~ 1 × 104 pg·mL-1 with an extremely low detection limit of 6.71 fg·mL-1. The aptasensor exhibited high sensitivity, good selectivity, satisfactory stability, and excellent reproducibility. Moreover, this method had high accuracy in detecting T-2 toxin in beer sample. The encouraging results show the potential application in foodstuff analysis. A dual signal amplification electrochemical biosensor for the detection of T-2 toxins was constructed, through the signal amplification of noble metal nanomaterials and CHA strategy.
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Nanopartículas del Metal , Nanocompuestos , Toxina T-2 , Humanos , Reproducibilidad de los Resultados , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Límite de Detección , Nanocompuestos/químicaRESUMEN
As important pollinators, honey bees play a crucial role in both maintaining the ecological balance and providing products for humans. Although several versions of the western honey bee genome have already been published, its transcriptome information still needs to be refined. In this study, PacBio single-molecule sequencing technology was used to sequence the full-length transcriptome of mixed samples from many developmental time points and tissues of A. mellifera queens, workers and drones. A total of 116,535 transcripts corresponding to 30,045 genes were obtained. Of these, 92,477 transcripts were annotated. Compared to the annotated genes and transcripts on the reference genome, 18,915 gene loci and 96,176 transcripts were newly identified. From these transcripts, 136,554 alternative splicing (AS) events, 23,376 alternative polyadenylation (APA) sites and 21,813 lncRNAs were detected. In addition, based on the full-length transcripts, we identified many differentially expressed transcripts (DETs) between queen, worker and drone. Our results provide a complete set of reference transcripts for A. mellifera that dramatically expand our understanding of the complexity and diversity of the honey bee transcriptome.
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Secuenciación de Nucleótidos de Alto Rendimiento , Transcriptoma , Humanos , Abejas/genética , Animales , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Empalme Alternativo , Análisis de Secuencia de ARN , Anotación de Secuencia MolecularRESUMEN
Although lithium-sulfur batteries (LSBs) promise high theoretical energy density and potential cost effectiveness, their applications are severely impeded by the shuttling and sluggish redox kinetics of lithium polysulfides (LiPSs). In this context, a Co9 S8 @MoS2 heterostructure is sophisticatedly designed as an efficient catalytic host to boost the sulfur reduction reaction/evolution reaction (SRR/SER) kinetics and suppresses the LiPSs shuttling in LSBs. The results indicate that the electronic structure is manipulated in the Co9 S8 @MoS2 heterostructure, where the built-in electric fields (BIEFs) within the heterointerfaces enable the sufficient adsorption sites to accelerate the ionic diffusion/charge transfer kinetics for LiPSs redox, thus enhancing the sulfur conversion. By tuning the electronic structure, the metal d-band of Co9 S8 @MoS2 heterostructure plays an important role in adsorbing and catalyzing the conversion of LiPSs, thus promoting the reaction kinetics of the corresponding LSBs. This work unlocks the potential of heterostructures as promising catalysts to the design of high-energy and stabilized LSBs.
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OBJECTIVE: To evaluate the diagnostic performance of combined multiparametric 18F-fluorodeoxyglucose positron emission tomography (18FDG PET) with clinical characteristics in differentiating thymic epithelial tumors (TETs) from thymic lymphomas. PATIENTS AND METHODS: A total of 173 patients with 80 TETs and 93 thymic lymphomas who underwent 18F-FDG PET/CT before treatment were enrolled in this retrospective study. All patients were confirmed by pathology, and baseline characteristics and clinical data were also collected. The semi-parameters of 18F-FDG PET/CT, including lesion size, SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), TLG (total lesion glycolysis), MTV (metabolic tumor volume) and SUVR (tumor-to-normal liver standard uptake value ratio) were evaluated. The differential diagnostic efficacy was evaluated using the receiver operating characteristic (ROC) curve. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI), and Delong test were used to evaluate the improvement in diagnostic efficacy. The clinical efficacy was evaluated by decision curve analysis (DCA). RESULTS: Age, clinical symptoms, and metabolic parameters differed significantly between patients with TETs and thymic lymphomas. The ROC curve analysis of SUVR showed the highest differentiating diagnostic value (sensitivity = 0.763; specificity = 0.888; area under the curve [AUC] = 0.881). The combined diagnostics model of age, clinical symptoms and SUVR resulted in the highest AUC of 0.964 (sensitivity = 0.882, specificity = 0.963). Compared with SUVR, the diagnostic efficiency of the model was improved significantly. The DCA also confirmed the clinical efficacy of the model. CONCLUSIONS: The multiparameter diagnosis model based on 18F-FDG PET and clinical characteristics had excellent value in the differential diagnosis of TETs and thymic lymphomas.
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Linfoma , Neoplasias Glandulares y Epiteliales , Fluorodesoxiglucosa F18 , Humanos , Linfoma/diagnóstico por imagen , Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Curva ROC , Radiofármacos , Estudios Retrospectivos , Neoplasias del Timo , Carga TumoralRESUMEN
Simultaneous evolution of multiple enzyme properties remains challenging in protein engineering. A chimeric nitrilase (BaNITM0 ) with high activity towards isobutylsuccinonitrile (IBSN) was previously constructed for biosynthesis of pregabalin precursor (S)-3-cyano-5-methylhexanoic acid ((S)-CMHA). However, BaNITM0 also catalyzed the hydration of IBSN to produce by-product (S)-3-cyano-5-methylhexanoic amide. To obtain industrial nitrilase with vintage performance, we carried out engineering of BaNITM0 for simultaneous evolution of reaction specificity, enantioselectivity, and catalytic activity. The best variant V82L/M127I/C237S (BaNITM2 ) displayed higher enantioselectivity (E = 515), increased enzyme activity (5.4-fold) and reduced amide formation (from 15.8% to 1.9%) compared with BaNITM0 . Structure analysis and molecular dynamics simulations indicated that mutation M127I and C237S restricted the movement of E66 in the catalytic triad, resulting in decreased amide formation. Mutation V82L was incorporated to induce the reconstruction of the substrate binding region in the enzyme catalytic pocket, engendering the improvement of stereoselectivity. Enantio- and regio-selective hydrolysis of 150 g/L IBSN using 1.5 g/L Escherichia coli cells harboring BaNITM2 as biocatalyst afforded (S)-CMHA with >99.0% ee and 45.9% conversion, which highlighted the robustness of BaNITM2 for efficient manufacturing of pregabalin.
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Aminohidrolasas , Escherichia coli , Amidas , Aminohidrolasas/genética , Aminohidrolasas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Pregabalina/química , Especificidad por SustratoRESUMEN
BACKGROUND: The prognostic value of left ventricular (LV) mechanical dyssynchrony (MD) in patients with LV aneurysm (LVA) is unclear. This study aimed to investigate the long-term prognostic value of LVMD in LVA patients. METHODS: 92 consecutive patients who underwent 99mTc-sestamibi-gated SPECT myocardial perfusion imaging (GSPECT) were retrospectively analyzed and followed-up for a median of 63 months (range, 1-73 months). LV function and histogram bandwidth (BW) were analyzed by QGS software. LVMD was defined by ROC analysis. Cardiac death was defined as the primary endpoint, and the composite of cardiac deaths and severe or acute heart failure (MACE) as the secondary endpoint. RESULTS: The annual cardiac mortality rate of LVA patients with LVMD and treated by surgical therapy was significantly lower than those treated by medical therapy (2.40% vs. 6.40%, P < .05) but not annual MACE rate (6.61% vs. 10.06%, P > .05). In patients without LVMD, no significant difference in survival and MACE-free survival between medical and surgical treatment. In addition, the occurrence of LVMD is related to the worsen cardiac outcome in terms of MACE and cardiac death, independent of the treatment methods. BW was an independent predictor for MACE (HR 1.010, P < .01) and LVEF (HR .928, P < .05) was an independent predictor for cardiac death in all LVA patients. CONCLUSIONS: LVA patients with LVMD might be associated with high risk for cardiac death and surgical treatment might improve cardiac survival compared to medical therapy in these patients.