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Scheuchzeria palustris, the only species in the Scheuchzeriaceae family, plays a crucial role in methane production and transportation, influencing the global carbon cycle and maintaining ecosystem stability. However, it is now threatened by human activities and global warming. In this study, we generated new organelle genomes for S. palustris, with the plastome (pt) measuring 158,573 bp and the mitogenome (mt) measuring 420,724 bp. We predicted 296 RNA editing sites in mt protein-coding genes (PCGs) and 142 in pt-PCGs. Notably, abundant RNA editing sites in pt-PCGs likely originated from horizontal gene transfer between the plastome and mitogenome. Additionally, we identified positive selection signals in four mt-PCGs (atp4, ccmB, nad3, and sdh4) and one pt-PCG (rps7), which may contribute to the adaptation of S. palustris to low-temperature and high-altitude environments. Furthermore, we identified 35 mitochondrial plastid DNA (MTPT) segments totaling 58,479 bp, attributed to dispersed repeats near most MTPT. Phylogenetic trees reconstructed from mt- and pt-PCGs showed topologies consistent with the APG IV system. However, the conflicting position of S. palustris can be explained by significant differences in the substitution rates of its mt- and pt-PCGs (p < .001). In conclusion, our study provides vital genomic resources to support future conservation efforts and explores the adaptation mechanisms of S. palustris.
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The regulation mechanism of bamboo height growth has always been one of the hotspots in developmental biology. In the preliminary work of this project, the function of LBD transcription factor regulating height growth was firstly studied. Here, a gene PheLBD12 regulating height growth was screened. PheLBD12-overexpressing transgenic rice had shorter internodes, less bioactive gibberellic acid (GA3), and were more sensitive to GA3 than wild-type (WT) plants, which implied that PheLBD12 involve in gibberellin (GA) pathway. The transcript levels of OsGA2ox3, that encoding GAs deactivated enzyme, was significantly enhanced in PheLBD12-overexpressing transgenic rice. The transcript levels of OsAP2-39, that directly regulating the expression of EUI1 to reduce GA levels, was also significantly enhanced in PheLBD12-overexpressing transgenic rice. Expectedly, yeast one-hybrid assays, Dual-luciferase reporter assay and EMSAs suggested that PheLBD12 directly interacted with the promoter of OsGA2ox3 and OsAP2-39. Together, our results reveal that PheLBD12 regulates plant height growth by modulating GA catabolism. Through the research of this topic, it enriches the research content of LBD transcription factors and it will theoretically enrich the research content of height growth regulation.
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Regulación de la Expresión Génica de las Plantas , Giberelinas , Oryza , Proteínas de Plantas , Factores de Transcripción , Giberelinas/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
At present, the power conversion efficiency (PCE) of perovskite solar cells (PSCs) has reached 26.1%. Polycrystalline perovskite films prepared by sequential deposition are often accompanied by excess PbI2. Although excess PbI2 can reduce the internal defects of the perovskites and promote charge transfer, excess PbI2 is unevenly distributed in the perovskites and easily decomposed into the composite center of charge. Therefore, the growth and distribution of PbI2 crystals can be regulated by introducing 4-fluoroaniline (4-FLA) as an additive into the precursor of PbI2. We observe that the presence of an amino group in 4-FLA leads to a reduction in the strength of van der Waals forces between PbI2 layer structures, thereby facilitating the uniform dispersion of excess PbI2 within the perovskites. Additionally, 4-FLA is restricted from being embedded in the PbI2 layer due to the steric hindrance of 4-FLA and the hydrogen bond interaction between nitrogen atoms and PbI2. Therefore, it leads to better dispersion of PbI2, resulting in better passivation and device efficiency. Based on the hydrophobicity of the benzene ring, the modified perovskite film shows excellent hydrophobicity. Ultimately, we achieved 21.63% PCE and 1.16V VOC. This provides an effective strategy for regulating excess PbI2 to achieve efficient and stable PSCs.
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Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.
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Harnessing the inexhaustible solar energy for water splitting is regarded one of the most promising strategies for hydrogen production. However, sluggish kinetics of oxygen evolution reaction (OER) and expensive photovoltaics have hindered commercial viability. Here, an adhesive-free electrodeposition process is developed for in-situ preparation of earth-abundant electrocatalysts on super-flat indium tin oxide (ITO) substrate. NiFe hydroxide exhibited prominent OER performance, achieving an ultra-low overpotential of 236 mV at 10 mA/cm2 in alkaline solution. With the superior OER activity, we achieved an unassisted solar water splitting by series connected perovskite solar cells (PSCs) of 2 cm2 aperture area with NiFe/ITO//Pt electrodes, yielding overall solar to hydrogen (STH) efficiency of 13.75 %. Furthermore, we upscaled the monolithic facility to utilize perovskite solar module for large-scale hydrogen production and maintained an approximate operating current of 20 mA. This creative strategy contributes to the decrease of industrial manufacturing expenses for perovskite-based photovoltaic-electrochemical (PV-EC) hydrogen production, further accelerating the conversion and utilization of carbon-free energy.
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BACKGROUND: Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant's pathogenicity and reveal a patient's genetic etiology. METHODS: The clinical data of a patient with HS who underwent genetic sequencing at the Children's Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. RESULTS: A novel variant (c.301-2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301-2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. CONCLUSION: We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.
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Espectrina , Esferocitosis Hereditaria , Humanos , Esferocitosis Hereditaria/genética , Espectrina/genética , Masculino , Femenino , Linaje , Mutación , Empalme del ARNRESUMEN
The SARS-CoV-2 pandemic has caused unprecedented worldwide infections from persistent mutant variants with various degrees of infectivity and virulence. The elusiveness of a highly penetrant, worldwide vaccination strategy suggests that the complete eradication of SARS-CoV-2 is unlikely. Even with the advent of new antiviral agents, the disease burden worldwide continues to exceed current preventative and therapeutic strategies. Greater interest has been placed towards the development of affordable,broadly effective antiviral therapeutics. Here, we report that the small branched-chain fatty acid Valproic acid (VPA), approved for maintenance of seizure and bipolar disorder, has a novel anti- coronavirus activity that can be augmented with the addition of a long-chain, polyunsaturated omega-3 fatty acid, Docosahexaenoic acid (DHA). An EMR-based epidemiological study of patients tested for COVID-19 demonstrated a correlation exists between a reduced infection rate in patients treated withVPA of up to 25%, as well as a decreased risk of emergency room visits, hospitalization, ICU admission,and use of mechanical ventilation. In vitro studies have demonstrated that VPA modifies gene expression in MRC5 cells. Interestingly, VPA correlates with the inhibition of several SARS-CoV2 interacting genes and the greater inhibition of alpha-coronavirus HCoV-229E (a "common cold" virus) and SARS-CoV2. The VPA-DHA combination activates pre-existing intracellular antiviral mechanisms normally repressed by coronaviruses. Gene expression profiles demonstrate subtle differences in overall gene expression between VPA-treated and VPA-DHA-treated cells. HCoV-229E infection caused an intensely different response with a marked induction of multiple intracellular inflammatory genes. Changes in gene expression took at least 24 hours to manifest and most likely why prior drug screens failed to identify any antiviral VPA activity despite in silico predictions. This report demonstrates an interaction between HDAC inhibition and the potent activation of cellular antiviral responses. A foundation now exists for a low-cost, highly effective antiviral strategy when supplemented with DHA.
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Antivirales , COVID-19 , SARS-CoV-2 , Ácido Valproico , Ácido Valproico/farmacología , Ácido Valproico/uso terapéutico , Humanos , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/efectos de los fármacos , Antivirales/uso terapéutico , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Índice de Severidad de la Enfermedad , Masculino , Femenino , Persona de Mediana EdadRESUMEN
High-value resources beyond oil extraction for the olive industry need to be developed due to increased olive production. Soluble dietary fibers (SDFs) and olive proteins (OPIs) are important components of olives. However, the commercial production process partially damages OPIs' emulsifying and foaming properties. Thus, the preparation of SDF-OPI complexes would help protect and even improve the emulsifying and foaming properties. The effects of pH and thermal-ultrasonic treatment on the complexation were explored, which showed that the SDF-OPI complexes prepared at pH 5 exhibited superior solubility (p < 0.05). SDF addition noticeably improved OPI thermal stability, emulsifying properties, and foaming properties. Moreover, the complexes prepared by thermal-ultrasonic treatment exhibited higher emulsion stability and lower emulsification activity than those prepared without thermal-ultrasonic treatment. In the acidic system, the electrostatic interaction was considered the main driving factor, assisted by the hydrophobic interaction. Additionally, after thermal-ultrasonic treatment, the covalent binding was observed by infrared spectroscopy. These results revealed the interaction mechanism between SDF and OPI, and the complexes significantly enhanced the functional properties of OPI. This study provides a reference for the high-value utilization of olives, thus broadening their potential uses in the food sector and beyond.
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OBJECTIVE: Powerful adjuvant strategies are required to improve the survival of patients with completely resected stage ΙΙΙA non-small cell lung cancer (NSCLC). We aimed to compare the efficacy of traditional Chinese medicine (TCM) treatment versus observation after adjuvant chemotherapy in these patients. METHODS: Eligible patients were randomized 1:1 to receive either oral decoctions based on Qi-Yin syndrome differentiation (TCM group) or observation (observation group). The intervention lasted for 12 months. The primary endpoint was 1-year disease-free survival (DFS). Secondary endpoints were DFS, quality of life, regulatory T cells (Tregs), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on the surface of Tregs in peripheral blood. We used EORTC QLQ-LC43 to evaluate quality of life. RESULTS: Between Apr 29, 2019, and Nov 11, 2021, 75 patients were randomly assigned to oral decoctions based on Qi-Yin syndrome differentiation (n = 38) or observation (n = 37). The full analysis set included 35 patients in the TCM group and 35 in the observation group. After a median follow-up of 24.2 months, oral decoctions based on Qi-Yin syndrome differentiation improved DFS compared with observation (HR 0.378, 95% CI: 0.157-0.912; P = .03). One-year DFS was 82.1% in the TCM group and 61.9% in the observation group (P = .06). Three months after randomization, scores of total health, role function, emotional function, and social function in the TCM group were higher than those in the observation group (P < .01 for all), scores of fatigue, pain, insomnia, appetite loss, constipation, cough, and chest pain were lower than those in the observation group (P < .05 for all); there was no significant difference in the proportion of Tregs between the TCM group and the observation group (P = .58); the proportion of CTLA-4+Tregs in the TCM group was lower than that in the observation group (P = .046). There were no adverse events that occurred in both groups. CONCLUSIONS: Oral decoctions based on Qi-Yin syndrome differentiation after adjuvant chemotherapy prolonged DFS, reduced the risk of disease recurrence and metastasis, improved quality of life, and down-regulated the proportion of CTLA-4+Tregs in completely resected stage ΙΙΙA NSCLC patients. TRIAL REGISTRATION: Chinese Clinical Trial Register, No. ChiCTR1800019396. Date of registration: 9 November 2018.
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Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Medicina Tradicional China , Calidad de Vida , Humanos , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Quimioterapia Adyuvante/métodos , Medicina Tradicional China/métodos , Anciano , Qi , Estadificación de Neoplasias , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: The excessive application of chemical fertilizers in the cultivation of Astragalus mongholicus Bunge results in a reduction in the quality of the medicinal plant and compromises the sustainable productivity of the soil. PGPB inoculant is a hot topic in ecological agriculture research. In the cultivation of Astragalus mongholicus, the screened nitrogen-fixing bacteria can promote plant growth, however, whether it can promote the accumulation of main bioactive components remains unknown. In this study, mixed inoculants containing 5 strains of growth promoting bacteria (Rhizobium T16 , Sinorhizobium T21 , Bacillus J1 , Bacillus G4 and Arthrobacter J2) were used in the field experiment. The metabolic substances in the root tissues of Astragalus mongholicus were identified during the harvest period by non-targeted metabolomics method, and the differential metabolites between groups were identified by statistical analysis. Meanwhile, high-throughput sequencing was performed to analyze the changes of rhizosphere soil and endophytic microbial community structure after mixed microbial treatment. RESULTS: The results of non-targeted metabolism indicated a significant increase in the levels of 26 metabolites after treatment including 13 flavonoids, 3 saponins and 10 other components. The contents of three plant hormones (abscisic acid, salicylic acid and spermidine) also increased after treatment, which presumed to play an important role in regulating plant growth and metabolism. Studies on endosphere and rhizosphere bacterial communities showed that Rhzobiaceae, Micromonosporaceae, and Hypomicrobiaceae in endophytic, and Oxalobactereae in rhizosphere were significantly increased after treatment. These findings suggest their potential importance in plant growth promotion and secondary metabolism regulation. CONCLUSIONS: This finding provides a basis for developing nitrogen-fixing bacteria fertilizer and improving the ecological planting efficiency of Astragalus mongholicus.
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Planta del Astrágalo , Microbiota , Raíces de Plantas , Rizosfera , Microbiología del Suelo , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Planta del Astrágalo/microbiología , Planta del Astrágalo/metabolismo , Bacterias Fijadoras de Nitrógeno/metabolismo , Bacterias Fijadoras de Nitrógeno/genética , Saponinas/metabolismo , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Metabolómica , Arthrobacter/metabolismo , Arthrobacter/genética , Endófitos/metabolismo , Endófitos/genética , Rhizobium/metabolismoRESUMEN
Ground ozone (O3) pollution has emerged as a prominent environmental concern in eastern cities of China, particularly during the summer and autumn seasons. However, a comprehensive investigation into the three-dimensional (3-D) evolution characteristics of O3 within complicated urban environments, especially in lake-land environment, is notably scarce. To enhance our understanding of the mechanisms underlying elevated O3 concentrations within a 3-D scale, this study employed an ozone lidar to delineate vertical ozone profiles in Changzhou, a typical city in China with complicated anthropogenic and biogenic emissions and complex land cover. The process analysis tool integrated into the Weather Research and Forecasting with Chemistry (WRF-Chem) model was further utilized to analyze the formation processes of O3. The results unveil a persistent O3 pollution episode lasting over 15 days in Changzhou during the study period, with multiple peaks exceeding 200 µg m⻳. Notably, O3 predominantly accumulated within the boundary layer, confined below 1.2 km. Both ground and vertical contributions to this pollution were mainly due to local chemical reactions, with a maximum near-surface contribution reaching 19 ppb h-1 and a vertical contribution of 10 ppb h-1 at the height of 900 ± 200 m. Furthermore, episodes of the enhanced O3 concentrations on August 9 and August 26, 2021, were influenced by external advection process. Our study also found that local circulation plays an important role in the accumulation of surface O3 during certain periods. There was a temperature difference between the surface of Lake Tai and the adjacent land, resulting in the formation of lake-land breezes that facilitate the transport of O3 from the lake surface to the terrestrial environment during pollution events. Our study emphasizes the necessity of reducing local pollutant emissions and implementing joint emission controls as the primary strategies for mitigating O3 pollution in Changzhou and the surrounding region.
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Contaminantes Atmosféricos , Contaminación del Aire , Monitoreo del Ambiente , Ozono , Ozono/análisis , China , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Estaciones del Año , Ciudades , Modelos QuímicosRESUMEN
OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.
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Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Supervivencia sin Progresión , China , Metástasis de la NeoplasiaRESUMEN
Elevated homocysteine (Hcy) levels have been recognized as significant risk factor for cardiovascular and cerebrovascular diseases, closely related to endothelial injury. While expression of Ciliary Neurotrophic Factor (CNTF) significantly increases during Hcy-induced vascular endothelial cell injury, the precise molecular pathways through which CNTF operates remain to be clarified. To induce vascular endothelial cell injury, human umbilical vein endothelial cells (HUVECs) were treated with Hcy. Cell viability and apoptosis in HUVECs were assessed using the CCK-8 assay and flow cytometry. Western blot analysis determined the expression levels of the JAK2-STAT3 pathway, inflammation-related factors (IL-1ß, NLRP3, ICAM-1, VCAM-1), and apoptosis-related factors (cleaved Caspase-3 and Bax). Immunofluorescence staining and western blotting were employed to examine CD31 and α-SMA expression. Knockdown of CNTF was achieved using lentiviral interference, and its effects on inflammation and cell injury were evaluated. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter analysis were conducted to investigate the interaction between the MAFK and CNTF promoters. Our results indicated that Hcy induced high expression of CNTF and activated the JAK2-STAT3 signaling pathway, thereby upregulating factors associated with inflammation and cell apoptosis. Inhibiting CNTF alleviated Hcy-induced inflammation and cell injury. MAFK was identified as a transcription factor promoting CNTF transcription, and its overexpression exacerbated inflammation and cell injury in Hcy-treated HUVECs through the CNTF-JAK2-STAT3 axis, which could be reversed by knocking down CNTF. Activation of MAFK leads to CNTF upregulation, which activates the JAK2-STAT3 signaling pathway, regulating inflammation and inducing injury in Hcy-exposed vascular endothelial cells. Targeting CNTF or its upstream regulator MAFK may represent potential therapeutic strategies for mitigating endothelial dysfunction associated with hyperhomocysteinemia and cardiovascular diseases.
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Apoptosis , Factor Neurotrófico Ciliar , Homocisteína , Células Endoteliales de la Vena Umbilical Humana , Inflamación , Janus Quinasa 2 , Factor de Transcripción STAT3 , Transducción de Señal , Janus Quinasa 2/metabolismo , Humanos , Factor de Transcripción STAT3/metabolismo , Homocisteína/farmacología , Homocisteína/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Inflamación/metabolismo , Inflamación/patología , Factor Neurotrófico Ciliar/metabolismo , Factor Neurotrófico Ciliar/genética , Apoptosis/efectos de los fármacos , Células Cultivadas , Supervivencia Celular/efectos de los fármacosRESUMEN
Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most prevalent mutation in non-small cell lung cancer (NSCLC), following the 19del and L858R mutations. The unique nature of the EGFR ex20ins mutation poses challenges for the effectiveness of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). As a result, chemotherapy remains the primary and more effective treatment approach. However, with advancements in time and technology, numerous experimental studies have revealed the potential of novel drugs and therapies to have stronger inhibitory effects on EGFR ex20ins mutations. In this comprehensive review, we provide an overview of the current treatment landscape, recent advancements, and the prospects for patients with advanced NSCLC characterized by EGFR ex20ins mutations.
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Background: Auditory-verbal training is essential for children with hearing challenges, and the gamification approach has become a promising direction for improving the rehabilitation experience and effect. However, the specific influence of the gamified training approach on participants at different rehabilitation stages has not been empirically studied, especially in the practical training effect caused by gamified interventions and the varying influence on children with different rehabilitation status. Objective: This article is thus intended to investigate the following research questions: (1) do the training performances of children at advanced rehabilitation stage differ before and after using the gamified training system? (2) Do the training performances of children at intermediate rehabilitation stage differ before and after using the gamified training system? (3) Do children enjoy the gamified training approach? Methods: For the purpose, a digital gamified auditory-verbal training system was originally developed, and a series of user experiments were organized. The training performance of 31 hearing-challenged children was assessed, and interviews with six professional therapists were conducted. Results: It can be found that generally the gamified training approach can effectively facilitate the training experience and help with the basic auditory memory and expression capabilities. Moreover, it is feasible to be applied in practical training due to the high customization of digital training contents, multimodal interactive training means, and highly enjoyable training experience. Conclusions: Regarding the specific influence, the gamified way can better improve the basic auditory-verbal performance of children at the intermediate stage since the focus is more on the ease of learning and adaption to the training system. While for children at the advanced rehabilitation stage, the precise training and professional training contents are more in demand, it is not easy to achieve quick improvements. These findings and conclusions can provide insights for further explorations and applications of the gamification approach in children's auditory-verbal rehabilitation. This study was approved by the Institutional Review Board (IRB) of Shanghai Jiao Tong University with the approval number H2022213P.
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BACKGROUND: Understanding the tooth anatomy is crucial for ensuring effective endodontic treatment. This study investigated the root canal morphology of the second mesiobuccal (MB2) canal in maxillary first molars (MFMs) in a Chinese population using cone-beam computed tomography (CBCT). METHODS: This study evaluated 486 MFMs with MB2 canals from 285 participants undergoing CBCT examination and determined the Vertucci's classification and position of the MB2 canal orifice. The prevalence of the MB2 canal was correlated with the sex, age, and tooth side. The correlations between the prevalence of the MB2 canal and sex and tooth side were assessed using the Fisher's exact test. The chi-square test was used for evaluating the correlation between the prevalence of the MB2 canal and age. RESULTS: The number of type II, III, IV, V, VI, VII, and other root canals in the MFMs was 30.9%, 0.6%, 65.0%, 1.2%, 1.2%, 0.4%, and 0.6%, respectively. Among the 201 cases with bilateral inclusion, 87.6% showed consistent canal configuration. Results of the first clear apparent position (FCAP) of the MB2 canals showed that 434, 44, and 3 teeth had FCAP at the upper, middle, and bottom one-third of the root, respectively. The FCAPs of the MB2 canal in the MFMs with types II, IV, and VI, as well as types III and V canals showed significant differences (p<0.05). The horizontal distance between the MB1 and MB2 canal orifices in the type II canals of MFMs was significantly lesser than those in the type IV canals of MFMs (p < 0.01). The longitudinal distance between the pulp chamber floor plane and MB2 canal orifice significantly correlated with age (p < 0.05). CONCLUSIONS: The morphology of the mesiobuccal root canal in the MFMs is complex. Complete understanding of the anatomical morphology of the root canal combined with the CBCT and dental operating microscope is necessary for the accurate detection of the MB2 canal and consequently improved success rate of root canal treatment. Our study findings can help endodontists improve endodontic treatment outcomes.
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Tomografía Computarizada de Haz Cónico , Cavidad Pulpar , Maxilar , Diente Molar , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Diente Molar/anatomía & histología , Diente Molar/diagnóstico por imagen , Masculino , Femenino , Adulto , Cavidad Pulpar/diagnóstico por imagen , Cavidad Pulpar/anatomía & histología , Persona de Mediana Edad , Maxilar/diagnóstico por imagen , Maxilar/anatomía & histología , China , Adolescente , Anciano , Adulto Joven , Pueblos del Este de AsiaRESUMEN
BACKGROUD: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia. METHODS: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER). RESULTS: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, AL was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P = 0.001 and P = 0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P = 0.029), the rPOSR increased significantly at 6 and 12 months (both P < 0.001), and the increase in rPOSR was greater with greater AL regression. CONCLUSIONS: Based on retinal function and structure follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation.
Asunto(s)
Miopía , Tomografía de Coherencia Óptica , Humanos , Miopía/fisiopatología , Miopía/terapia , Niño , Masculino , Femenino , Terapia por Luz de Baja Intensidad/métodos , Electrorretinografía , Sensibilidad de Contraste/fisiologíaRESUMEN
The two-step sequential deposition strategy has been widely recognized in promoting the research and application of perovskite solar cells, but the rapid reaction of organic salts with lead iodide inevitably affects the growth of perovskite crystals, accompanied by the generation of more defects. In this study, the regulation of crystal growth was achieved in a two-step deposition method by mixing 1-naphthylmethylammonium bromide (NMABr) with organic salts. The results show that the addition of NMABr effectively delays the aggregation and crystallization behavior of organic salts; thereby, the growth of the optimal crystal (001) orientation of perovskite is promoted. Based on this phenomenon of delaying the crystallization process of perovskite, the "slow-release effect assisted crystallization" is defined. Moreover, the incorporation of the Br element expands the band gap of perovskite and mitigates material defects as nonradiative recombination centers. Consequently, the power conversion efficiency (PCE) of the enhanced perovskite solar cells (PSCs) reaches 20.20%. It is noteworthy that the hydrophobic nature of the naphthalene moiety in NMABr can enhance the humidity resistance of PSCs, and the perovskite phase does not decompose for more than 3000 h (30-40% RH), enabling it to retain 90% of its initial efficiency even after exposure to a nitrogen environment for 1200 h.
RESUMEN
Tracer injection has long been recognized as a valuable tool for delineating tree hydraulics and assessing water transport pathways. Recently, isotope tracers have emerged as innovative instruments for investigating tree hydraulics, providing new insights into tree water dynamics. Nevertheless, there is a critical need for further research to comprehensively grasp water movement and distribution within trees. A previously introduced technique for analyzing the isotopic ratio of water in wet tissues, offering millimeter-scale resolution for visualizing tracer movement, faces challenges due to its underdeveloped sample preparation techniques. In this study, we introduced an H2 18O tracer into S. gracilistyla samples, exclusively comprising indeterminate roots, stems, and leaves, cultivated through hydroponics and grown within the current year. Our objective was to assess the axial distribution of the tracer in the xylem. Additionally, we devised a novel method for preparing frozen wet tissue samples, enhancing the repeatability and success rate of experiments. The results demonstrated that all frozen wet tissue samples exhibited an average water loss rate of less than 0.6%. Isotopic analysis of these samples unveiled a consistent decline in tracer concentration with increasing height in all Salix specimens, with three out of five samples revealing a significant isotope gradient. Our findings affirm the efficacy and practicality of combining isotopic labeling with freezing, stabilization, and preparation techniques. Looking ahead, our isotopic labeling and analysis methods are poised to transcend woody plants, finding extensive applications in plant physiology and ecohydrology.