RESUMEN
Efficient and precise targeted insertion holds great promise but remains challenging in plant genome editing. An efficient nonhomologous end-joining-mediated targeted insertion method was recently developed by combining clustered regularly interspaced short palindromic repeat (CRISPR)/Streptococcus pyogenes CRISPR-associated nuclease 9 (SpCas9) gene editing with phosphorothioate modified double-stranded oligodeoxynucleotides (dsODNs). Yet, this approach often leads to imprecise insertions with no control over the insertion direction. Here, we compared the influence of chemical protection of dsODNs on efficiency of targeted insertion. We observed that CRISPR/SpCas9 frequently induced staggered cleavages with 1-nucleotide 5' overhangs; we also evaluated the effect of donor end structures on the direction and precision of targeted insertions. We demonstrate that chemically protected dsODNs with 1-nucleotide 5' overhangs significantly improved the precision and direction control of target insertions in all tested CRISPR targeted sites. We applied this method to endogenous gene tagging in green foxtail (Setaria viridis) and engineering of cis-regulatory elements for disease resistance in rice (Oryza sativa). We directionally inserted 2 distinct transcription activator-like effector binding elements into the promoter region of a recessive rice bacterial blight resistance gene with up to 24.4% efficiency. The resulting rice lines harboring heritable insertions exhibited strong resistance to infection by the pathogen Xanthomonas oryzae pv. oryzae in an inducible and strain-specific manner.
Asunto(s)
Oligonucleótidos , Oryza , Edición Génica/métodos , Plantas/genética , Secuencias Reguladoras de Ácidos Nucleicos , Genoma de Planta , Oryza/genética , Oryza/microbiologíaRESUMEN
Global warming and energy crises have motivated the development of renewable energy and its energy carriers. Green hydrogen is the most promising renewable energy carrier and will be fundamental to future energy conversion and storage systems. Solid Oxide Electrolysis Cells (SOECs) are a promising green hydrogen production technology featuring high electrical efficiency, no noble metal catalyst usage, and reversible operation. This review provides a timely summary of the latest SOEC progress, covering developments at various levels, from cells to stacks to systems. Cell/stack components, configurations, advanced electrode material/fabrication, and novel characterization methods are discussed. Electrochemical and durable performance for each cell/stack configuration is reviewed, focusing on degradation mechanisms and associated mitigation strategies. SOEC system integration with renewable energy and downstream users is outlined, showing flexibility, robustness, scalability, viability, and energy efficiency. Challenges of cost and durability are expected to be overcome by innovation in material, fabrication, production, integration, and operation. Overall, this comprehensive review identifies the SOEC commercialization bottleneck, encourages further technology development, and envisions a future green hydrogen society with net-zero carbon emissions.
RESUMEN
Schistosomiasis is a zoonotic parasitic disease. Schistosoma japonicum eggs deposited in the liver tissue induce egg granuloma formation and liver fibrosis, seriously threatening human health. Natural killer (NK) cells kill activated hepatic stellate cells (HSCs) or induce HSC apoptosis and inhibit the progression of liver fibrosis. However, the function of NK cells in liver fibrosis caused by S. japonicum infection is significantly inhibited. The mechanism of this inhibition remains unclear. Twenty mice were percutaneously infected with S. japonicum cercariae. Before infection and 2, 4, 6, and 8 weeks after infection, five mice were euthanized and dissected at each time point. Hepatic NK cells were isolated and transcriptome sequenced. The sequencing results showed that Tigit expression was high at 4-6 weeks post infection. This phenomenon was verified by reverse transcription quantitative PCR (RT-qPCR) and flow cytometry. NK cells derived from Tigit-/- and wild-type (WT) mice were co-cultured with HSCs. It was found that Tigit-/- NK cells induced apoptosis in a higher proportion of HSCs than WT NK cells. Schistosomiasis infection models of Tigit-/- and WT mice were established. The proportion and killing activity of hepatic NK cells were significantly higher in Tigit-/- mice than in WT mice. The degree of liver fibrosis in Tigit-/- mice was significantly lower than that in WT mice. NK cells were isolated from Tigit-/- and WT mice and injected via the tail vein into WT mice infected with S. japonicum. The degree of liver fibrosis in mice that received NK cell infusion reduced significantly, but there was no significant difference between mice that received NK cells from Tigit-/- and WT mice, respectively. Our findings indicate that Tigit knockout enhanced the function of NK cells and reduced the degree of liver fibrosis in schistosomiasis, thus providing a novel strategy for treating hepatic fibrosis induced by schistosomiasis.
Asunto(s)
Receptores Inmunológicos , Schistosoma japonicum , Esquistosomiasis Japónica , Esquistosomiasis , Animales , Ratones , Células Asesinas Naturales/metabolismo , Hígado/patología , Cirrosis Hepática/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Esquistosomiasis/patologíaRESUMEN
Global climate change is accompanied by carbon dioxide (CO2) enrichment and high temperature (HT) stress; however, how plants adapt to the combined environments and the underlying mechanisms remain largely unclear. In this study, we show that elevated CO2 alleviated plant sensitivity to HT stress, with significantly increased apoplastic glucose (Glc) levels in tomato (Solanum lycopersicum) leaves. Exogenous Glc treatment enhanced tomato resilience to HT stress under ambient CO2 conditions. Cell-based biolayer interferometry, subcellular localization, and Split-luciferase assays revealed that Glc bound to the tomato regulator of G protein signaling 1 (RGS1) and induced RGS1 endocytosis and thereby RGS1-G protein α subunit (GPA1) dissociation in a concentration-dependent manner. Using rgs1 and gpa1 mutants, we found that RGS1 negatively regulated thermotolerance and was required for elevated CO2-Glc-induced thermotolerance. GPA1 positively regulated the elevated CO2-Glc-induced thermotolerance. A combined transcriptome and chlorophyll fluorescence parameter analysis further revealed that GPA1 integrated photosynthesis- and photoprotection-related mechanisms to regulate thermotolerance. These results demonstrate that Glc-RGS1-GPA1 signaling plays a crucial role in the elevated CO2-induced thermotolerance in tomato. This information enhances our understanding of the Glc-G protein signaling function in stress resilience in response to global climate change and will be helpful for genetic engineering approaches to improve plant resilience.
Asunto(s)
Dióxido de Carbono , Glucosa , Transducción de Señal , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/fisiología , Solanum lycopersicum/metabolismo , Dióxido de Carbono/metabolismo , Glucosa/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Calor , Regulación de la Expresión Génica de las Plantas , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/genética , Fotosíntesis , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Proteínas RGS/metabolismo , Proteínas RGS/genética , Termotolerancia/fisiologíaRESUMEN
Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal-tension glaucoma. These detrimental effects were potentially mediated by accelerated RGC senescence through Caveolin-1 upregulation and by the induction of mitochondrial dysfunction. In mouse models of high-tension glaucoma, Sirt6 level was decreased after IOP elevation. Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons, whereas partial or RGC-specific Sirt6 deletion accelerated RGC loss. Importantly, therapeutically targeting Sirt6 with pharmacological activator or AAV2-mediated gene delivery ameliorated high IOP-induced RGC degeneration. Together, our studies reveal a critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma, setting the stage for further exploration of Sirt6 activation as a potential therapy for glaucoma.
Asunto(s)
Envejecimiento , Modelos Animales de Enfermedad , Glaucoma , Nervio Óptico , Células Ganglionares de la Retina , Sirtuinas , Animales , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Ratones , Sirtuinas/metabolismo , Sirtuinas/genética , Glaucoma/metabolismo , Glaucoma/genética , Glaucoma/patología , Glaucoma/etiología , Nervio Óptico/metabolismo , Nervio Óptico/patología , Envejecimiento/metabolismo , Envejecimiento/genética , Presión Intraocular , Humanos , Axones/metabolismo , Axones/patología , Ratones Noqueados , Degeneración Nerviosa/metabolismoRESUMEN
Sodium-ion batteries (SIBs) are experiencing a large-scale renaissance to supplement or replace expensive lithium-ion batteries (LIBs) and low energy density lead-acid batteries in electrical energy storage systems and other applications. In this case, layered oxide materials have become one of the most popular cathode candidates for SIBs because of their low cost and comparatively facile synthesis method. However, the intrinsic shortcomings of layered oxide cathodes, which severely limit their commercialization process, urgently need to be addressed. In this review, inherent challenges associated with layered oxide cathodes for SIBs, such as their irreversible multiphase transition, poor air stability, and low energy density, are systematically summarized and discussed, together with strategies to overcome these dilemmas through bulk phase modulation, surface/interface modification, functional structure manipulation, and cationic and anionic redox optimization. Emphasis is placed on investigating variations in the chemical composition and structural configuration of layered oxide cathodes and how they affect the electrochemical behavior of the cathodes to illustrate how these issues can be addressed. The summary of failure mechanisms and corresponding modification strategies of layered oxide cathodes presented herein provides a valuable reference for scientific and practical issues related to the development of SIBs.
RESUMEN
O3-type layered oxides have been extensively studied as cathode materials for sodium-ion batteries due to their high reversible capacity and high initial sodium content, but they suffer from complex phase transitions and an unstable structure during sodium intercalation/deintercalation. Herein, we synthesize a high-entropy O3-type layered transition metal oxide, NaNi0.3Cu0.05Fe0.1Mn0.3Mg0.05Ti0.2O2 (NCFMMT), by simultaneously doping Cu, Mg, and Ti into its transition metal layers, which greatly increase structural entropy, thereby reducing formation energy and enhancing structural stability. The high-entropy NCFMMT cathode exhibits significantly improved cycling stability (capacity retention of 81.4% at 1C after 250 cycles and 86.8% at 5C after 500 cycles) compared to pristine NaNi0.3Fe0.4Mn0.3O2 (71% after 100 cycles at 1C), as well as remarkable air stability. Finally, the NCFMMT//hard carbon full-cell batteries deliver a high initial capacity of 103 mAh g-1 at 1C, with 83.8 mAh g-1 maintained after 300 cycles (capacity retention of 81.4%).
RESUMEN
BACKGROUND: Surgical site infection (SSI) is a common and costly complication in spinal surgery. Identifying risk factors and preventive strategies is crucial for reducing SSIs. GPT-4 has evolved from a simple text-based tool to a sophisticated multimodal data expert, invaluable for clinicians. This study explored GPT-4's applications in SSI management across various clinical scenarios. METHODS: GPT-4 was employed in various clinical scenarios related to SSIs in spinal surgery. Researchers designed specific questions for GPT-4 to generate tailored responses. Six evaluators assessed these responses for logic and accuracy using a 5-point Likert scale. Inter-rater consistency was measured with Fleiss' kappa, and radar charts visualized GPT-4's performance. RESULTS: The inter-rater consistency, measured by Fleiss' kappa, ranged from 0.62 to 0.83. The overall average scores for logic and accuracy were 24.27±0.4 and 24.46±0.25 on 5-point Likert scale. Radar charts showed GPT-4's consistently high performance across various criteria. GPT-4 demonstrated high proficiency in creating personalized treatment plans tailored to diverse clinical patient records and offered interactive patient education. It significantly improved SSI management strategies, infection prediction models, and identified emerging research trends. However, it had limitations in fine-tuning antibiotic treatments and customizing patient education materials. CONCLUSIONS: GPT-4 represents a significant advancement in managing SSIs in spinal surgery, promoting patient-centered care and precision medicine. Despite some limitations in antibiotic customization and patient education, GPT-4's continuous learning, attention to data privacy and security, collaboration with healthcare professionals, and patient acceptance of AI recommendations suggest its potential to revolutionize SSI management, requiring further development and clinical integration.
RESUMEN
The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis patients, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in fine needle aspiration (FNA) washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) was computed to evaluate HA's clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than those in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC = 0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in FNA washouts from PTC patients were significantly higher than those in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than those in nonmetastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from nonmetastatic LNs. HA levels in serum and FNA washout exhibited a potential significance for PTC diagnosis and an indicator for LN metastasis in patients with PTC.
Asunto(s)
Carcinoma Papilar , Ácido Hialurónico , Metástasis Linfática , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Ácido Hialurónico/sangre , Ácido Hialurónico/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/diagnóstico , Adulto , Carcinoma Papilar/metabolismo , Carcinoma Papilar/diagnóstico , Línea Celular Tumoral , Carcinoma/metabolismo , Carcinoma/diagnóstico , Carcinoma/patología , Ganglios Linfáticos/patología , Ganglios Linfáticos/metabolismo , Enfermedad de Hashimoto/metabolismo , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/patología , Enfermedad de Hashimoto/diagnóstico , Biopsia con Aguja Fina , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/sangre , Proliferación CelularRESUMEN
Irritable bowel syndrome (IBS), which is characterized by chronic abdominal pain, has a high global prevalence. The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS-like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro-Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma-aminobutyric acid-producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC-LHA GABAergic pathway. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5-hydroxytryptamine (5-HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS-like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS-like symptoms. The chemogenetic activation of ACC-LHA GABAergic neurons elicited anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC-LHA GABAergic neurons alleviated anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC-LHA GABAergic pathway in modulating anxiety-like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS-like symptoms.
RESUMEN
Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10. Behavioral tests and single-nucleus RNA sequencing (snRNA-seq) of the PFC were conducted from PNDs 31 to 37. Mechanistic exploration included clustering analysis, identification of differentially expressed genes (DEGs), enrichment analyses, single-cell trajectory analysis, and genome-wide association studies (GWAS). Sevoflurane anesthesia resulted in sociability and cognition impairments in mice. Novel specific marker genes identified 8 distinct cell types in the PFC. Most DEGs between the control and sevoflurane groups were unique to specific cell types. Re-defining 15 glutamatergic neuron subclusters based on layer identity revealed their altered expression profiles. Notably, sevoflurane disrupted the trajectory from oligodendrocyte precursor cells (OPCs) to oligodendrocytes (OLs). Validation of disease-relevant candidate genes across the main cell types demonstrated their association with social dysfunction and working memory impairment. Behavioral results and snRNA-seq collectively elucidated the cellular atlas in the PFC of young male mice, providing a foundation for further mechanistic studies on developmental neurotoxicity induced by anesthesia.
Asunto(s)
Anestésicos por Inhalación , Corteza Prefrontal , Sevoflurano , Animales , Sevoflurano/toxicidad , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratones , Anestésicos por Inhalación/toxicidad , Masculino , Animales Recién Nacidos , Femenino , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits. METHODS: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining. RESULTS: We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-ß and the activation of its downstream pathways through interaction with PDGFR-ß. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance. CONCLUSIONS: Our findings establish the miR-15b/PDZK1/PDGFR-ß axis as a promising therapeutic target and a novel predictor for ccRCC patients' response to sunitinib treatment.
Asunto(s)
Carcinoma de Células Renales , Resistencia a Antineoplásicos , Neoplasias Renales , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Sunitinib , Sunitinib/farmacología , Sunitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Humanos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Animales , Resistencia a Antineoplásicos/genética , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , MicroARNs/genética , Transducción de Señal/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Ratones Desnudos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismoRESUMEN
Lung cancer poses a significant threat globally, especially in China. This puts higher demands on the treatment methods and drugs for lung cancer. Natural plants provide valuable resources for the development of anti-cancer drugs. Hederagenin (Hed) is a triterpenoid compound extracted from ivy leaves and has anti-tumor activity against multifarious cancers, including lung cancer. However, the regulatory mechanism of Hed in lung cancer remains unclear. In this study, we used Hed to treat lung cancer cells, and observed the effect of Hed on cell proliferation (including CCK-8 and colony formation experiments), apoptosis (including flow cytometry and apoptosis gene detection (BAX and Bcl-2)). The results showed that Hed induced lung cancer cell death (inhibiting proliferation and promoting apoptosis). Next, we performed bioinformatics analysis of the expression profile GSE186218 and found that Hed treatment significantly increased the expression of CHAC1 gene. CHAC1 is a ferroptosis-inducing gene. RT-qPCR detection of lung cancer clinical tissues and related cell lines also showed that CHAC1 was lowly expressed in lung cancer. Therefore, we knocked down and overexpressed CHAC1 in lung cancer cells, respectively. Subsequently, cell phenotype experiments showed that down-regulating CHAC1 expression inhibited lung cancer cell death (promoting proliferation and inhibiting apoptosis); on the contrary, up-regulating CHAC1 expression promoted lung cancer cell death. To further verify that Hed exerts anti-tumor effects in lung cancer by promoting CHAC1 expression, we performed functional rescue experiments. The results showed that down-regulating CHAC1 expression reversed the promoting effect of Hed on lung cancer cell death. Mechanistically, in vitro and in vivo experiments jointly demonstrated that Hed exerts anti-cancer effects by promoting CHAC1-induced ferroptosis. In summary, our study further enriches the regulatory mechanism of Hed in lung cancer.
Asunto(s)
Proliferación Celular , Ferroptosis , Neoplasias Pulmonares , Ácido Oleanólico , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células A549 , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. RESULTS: Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. CONCLUSIONS: This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut.
Asunto(s)
Arachis , Ralstonia solanacearum , Arachis/genética , Arachis/microbiología , Transcriptoma , Ralstonia solanacearum/fisiología , Fitomejoramiento , Resistencia a la Enfermedad/genética , Glutatión/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiologíaRESUMEN
Developing low-cost and highly efficient bifunctional catalysts for both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) is a challenging problem in electrochemical overall water splitting. Here, iron, tungsten dual-doped nickel sulfide catalyst (Fe/W-Ni3S2) is synthesized on the nickel foam, and it exhibits excellent OER and HER performance. As a result, the water electrolyze based on Fe/W-Ni3S2 bifunctional catalyst illustrates 10 mA cm-2 at 1.69 V (without iR-compensation) and highly durable overall water splitting over 100 h tested under 500 mA cm-2. Experimental results and DFT calculations indicate that the synergistic interaction between Fe doping and Ni vacancy induced by W leaching during the in situ oxidation process can maximize exposed OER active sites on the reconstructed NiOOH species for accelerating OER kinetics, while the Fe/W dual-doping optimizes the electronic structure of Fe/W-Ni3S2 and the binding strength of intermediates for boosting HER. This study unlocks the different promoting mechanisms of incorporating Fe and W for boosting the OER and HER activity of Ni3S2 for water splitting, which provides significant guidance for designing high-performance bifunctional catalysts for overall water splitting.
RESUMEN
ASFV is a large DNA virus that is highly pathogenic in domestic pigs. How this virus is sensed by the innate immune system as well as why it is so virulent remains enigmatic. In this study, we show that the ASFV genome contains AT-rich regions that are recognized by the DNA-directed RNA polymerase III (Pol-III), leading to viral RNA sensor RIG-I-mediated innate immune responses. We further show that ASFV protein I267L inhibits RNA Pol-III-RIG-I-mediated innate antiviral responses. I267L interacts with the E3 ubiquitin ligase Riplet, disrupts Riplet-RIG-I interaction and impairs Riplet-mediated K63-polyubiquitination and activation of RIG-I. I267L-deficient ASFV induces higher levels of interferon-ß, and displays compromised replication both in primary macrophages and pigs compared with wild-type ASFV. Furthermore, I267L-deficiency attenuates the virulence and pathogenesis of ASFV in pigs. These findings suggest that ASFV I267L is an important virulence factor by impairing innate immune responses mediated by the RNA Pol-III-RIG-I axis.
Asunto(s)
Virus de la Fiebre Porcina Africana/patogenicidad , Inmunidad Innata/inmunología , Factores de Virulencia/inmunología , Virulencia/inmunología , Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/inmunología , Animales , ARN Polimerasa III/inmunología , Receptores de Superficie Celular/inmunología , PorcinosRESUMEN
Increasing studies suggest that the biased retention of stress-related transcription factors (TFs) after whole-genome duplications (WGDs) could rewire gene transcriptional networks, facilitating plant adaptation to challenging environments. However, the role of posttranscriptional factors (e.g. RNA-binding proteins, RBPs) following WGDs has been largely ignored. Uncovering thousands of RBPs in 21 representative angiosperm species, we integrate genomic, transcriptomic, regulatomic, and paleotemperature datasets to unravel their evolutionary trajectories and roles in adapting to challenging environments. We reveal functional enrichments of RBP genes in stress responses and identify their convergent retention across diverse angiosperms from independent WGDs, coinciding with global cooling periods. Numerous RBP duplicates derived from WGDs are then identified as cold-induced. A significant overlap of 29 orthogroups between WGD-derived and cold-induced RBP genes across diverse angiosperms highlights a correlation between WGD and cold stress. Notably, we unveil an orthogroup (Glycine-rich RNA-binding Proteins 7/8, GRP7/8) and relevant TF duplicates (CCA1/LHY, RVE4/8, CBF2/4, etc.), co-retained in different angiosperms post-WGDs. Finally, we illustrate their roles in rewiring circadian and cold-regulatory networks at both transcriptional and posttranscriptional levels during global cooling. Altogether, we underline the adaptive evolution of RBPs in angiosperms after WGDs during global cooling, improving our understanding of plants surviving periods of environmental turmoil.
Asunto(s)
Magnoliopsida , Magnoliopsida/genética , Filogenia , Evolución Molecular , Genoma de Planta , Duplicación de Gen , Plantas/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
Hand, foot, and mouth disease is a serious public health problem, and the main pathogen is enterovirus 71 (EV71). Its capsid assembly mechanism including capsid protein processing has been widely studied. Full and empty capsids have different immunological efficacy. Therefore, tracking full/empty capsid ratio throughout the EV71 production process is important to ensure consistent product quality and proper dosing response. The analysis of full/empty capsid ratio of intact virus has been widely reported as well. A variety of techniques have been employed to evaluate the full/empty capsid ratios. However, there has not been a rapid, reproducible, and robust assay to determine the full/empty capsid ratios of final and in-process products. In this study, a novel assay based on capillary zone electrophoresis was established. The separation of full and empty species could be achieved within 10 min and the ratio of peak areas was used to calculate the full/empty capsid ratio directly. The results showed good reproducibility and linearity for the determination of full/empty capsid ratios.
Asunto(s)
Enterovirus Humano A , Enterovirus Humano A/metabolismo , Reproducibilidad de los Resultados , Proteínas de la Cápside , Cápside/metabolismo , Procesamiento Proteico-PostraduccionalRESUMEN
BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.
Asunto(s)
Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Dieta Mediterránea , Grasa Intraabdominal , Estado Prediabético , Factores Protectores , Conducta de Reducción del Riesgo , Humanos , Estado Prediabético/epidemiología , Estado Prediabético/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Grasa Intraabdominal/fisiopatología , Anciano , Factores de Riesgo , Medición de Riesgo , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/prevención & control , Factores de Tiempo , Incidencia , Adiposidad , Reino Unido/epidemiología , Adulto , Dieta Saludable , Ejercicio Físico , Estilo de Vida Saludable , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Obesidad Abdominal/fisiopatología , Estudios ProspectivosRESUMEN
PURPOSE: To compare the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer patients. METHODS: Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT within 2 weeks, and surgical treatment was performed within 10 days after PET. RESULTS: Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [18F]FDG and [68 Ga]Ga-FAPI-04 lymph node high metabolism were staged as FIGO IIIC1r, and concurrent chemoradiation therapy (CCRT) was performed. [18F]FDG and [68 Ga]Ga-FAPI-04 had equivalent detection ability on primary tumors, with a positive detection rate of 96.0%. The accuracy of T staging using [18F]FDG and [68 Ga]Ga-FAPI-04 was relatively 50% and 55.0%. Elevated and underrated staging was due to misdiagnosis of either vaginal infiltration or tumor size. In terms of lymph node metastasis detection, the specificity of [68 Ga]Ga-FAPI-04 was 100% (95% CI, 84.6% ~ 100.0%), which was significantly higher than [18F]FDG (59.1% (95% CI, 36.4% ~ 79.3%)) (p = 0.004). CONCLUSION: [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT demonstrated an equivalent detection ability on cervical cancer primary tumors. However, [68 Ga]Ga-FAPI-04 PET/MR's diagnostic value in lymph node metastasis was significantly higher than [18F]FDG PET/CT. [68 Ga]Ga-FAPI-04 PET/MR has the potential for more accurate treatment planning, thus clarifying fertility preservation indications for early-stage young patients.