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BACKGROUND: Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. METHODS: We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. RESULTS: Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. DISSCUSSION: Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.
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Based on the heterogeneous composite design of C3N4 and TiO2, composite photocatalysts of C3N4@TiO2 (with varied molar ratios of C3N4 to TiO2) were synthesized by a water bath method to degrade RhB in wastewater. The composition, morphology, structure, and photocatalytic properties of the materials were assessed through a variety of characterization techniques. The results show that TiO2 nanoparticles are uniformly coated on two-dimensional g-C3N4 nanosheets, forming relatively dense heterostructures within the C3N4@TiO2 composite. Due to the synergistic effect derived from the heterogeneous component and appropriate proportion of C3N4 and TiO2, the light absorption range is extended, and the separation/transport performance of photon-generated carrier is improved. As a result, TCNT-3 (where the molar ratio of C3N4 to TiO2 is 1:1) presents remarkable photocatalytic performance, the degradation rate of which for 60 min is 99.8%, and the reaction rate constant is calculated to be 0.0872 min-1. Moreover, the degradation efficiency remains 94.4% after 5 cycles, indicating the superior cycle stability.
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The Nipah virus (NiV) and the Hendra virus (HeV) are highly pathogenic zoonotic diseases that can cause fatal infections in humans and animals. Early detection is critical for the control of NiV and HeV infections. We present the development of two antigen-detection ELISAs (AgELISAs) using the henipavirus-receptor EphrinB2 and monoclonal antibodies (mAbs) to detect NiV and HeV. The NiV AgELISA detected only NiV, whereas the NiV/HeV AgELISA detected both NiV and HeV. The diagnostic specificities of the NiV AgELISA and the NiV/HeV AgELISA were 100% and 97.8%, respectively. Both assays were specific for henipaviruses and showed no cross-reactivity with other viruses. The AgELISAs detected NiV antigen in experimental pig nasal wash samples taken at 4 days post-infection. With the combination of both AgELISAs, NiV can be differentiated from HeV. Complementing other henipavirus detection methods, these two newly developed AgELISAs can rapidly detect NiV and HeV in a large number of samples and are suitable for use in remote areas where other tests are not available.
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Anticuerpos Monoclonales , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Efrina-B2 , Virus Hendra , Infecciones por Henipavirus , Virus Nipah , Virus Hendra/inmunología , Animales , Virus Nipah/inmunología , Anticuerpos Monoclonales/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Efrina-B2/metabolismo , Efrina-B2/inmunología , Infecciones por Henipavirus/diagnóstico , Infecciones por Henipavirus/virología , Infecciones por Henipavirus/inmunología , Anticuerpos Antivirales/inmunología , Porcinos , Humanos , Sensibilidad y Especificidad , Receptores Virales/metabolismo , Antígenos Virales/inmunologíaRESUMEN
The frequent occurrence of major public health emergencies (MPHEs) significantly challenges national security, economic stability, social operation and the safety of people's lives and property worldwide. Consequently, enhancing the emergency management of MPHEs is critically urgent. This paper constructs a game model involving local government, social organisations, and the public for MPHE management, exploring strategy combinations and influencing factors across various scenarios. Several results were obtained. (1) Local government, social organisations, and the public each have positive and negative strategy choices based on cost-benefit analysis, leading to eight different strategy combinations. Furthermore, all three take positive strategies as the optimal way to achieve the game equilibrium. (2) The transformation of strategy combinations is primarily influenced by the cost-benefit gap and the strategic decisions of local government. (3) Altering a subject's initial strategy value doesn't change its final choice but impacts the time to achieve a stable strategy equilibrium. The severity of local government punishments on social organisations influences their strategic choices and the time to optimal strategy, whereas rewards to the public or social organisations only affect the time to achieve this strategy. The findings of this study can not only help improve the collaborative governance system of MPHEs but also provide scientific guidance on how governments can manage MPHEs.
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Wolfiporia cocos is a medicinal mushroom used in China. It biosynthesizes pachymic acid (PA), a main therapeutic triterpene associated with therapies. Nowadays, the unknown PA biosynthesis leads to difficulties in increasing its content in W. cocos. Herein, we report sequencing, assembling, and characterization of the genome and several transcriptomes of W. cocos. Sequence mining determined candidate genes that encode lanosterol synthase, sterol O-acyltransferase, and sterol C-24 methyltransferase likely involved in the steps from lanosterol to PA. Gene cluster analysis identified four CYP450 cDNAs likely involved in the biosynthesis of PA, namely WcCYP64-1, WcCYP64-2, WcCYP52, and WcCYP_FUM15, which were subjected to both overexpression and silencing in mycelia. The overexpression of each of WcCYP64-1, WcCYP52 and WcCYP_FUM15 increased the content of PA, 16α-hydroxytrametenolic acid, eburicoic acid, and tumulosic acid, while the silencing of each gene either significantly or slightly decreased the contents of these four compounds, indicating their involvement in the PA biosynthesis. In addition, different temperatures affected the expression of these genes and the formation of PA. By contrast, the overexpression and silencing of WcCYP64-2 did not alter the formation of these compounds. Taken together, these findings determine more potential steps in the biosynthetic pathway of PA for metabolic engineering.
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Vías Biosintéticas , Sistema Enzimático del Citocromo P-450 , Triterpenos , Wolfiporia , Triterpenos/metabolismo , Wolfiporia/genética , Wolfiporia/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Vías Biosintéticas/genética , Regulación Fúngica de la Expresión Génica , Transcriptoma , Transferasas IntramolecularesRESUMEN
Background: Low-dose colchicine has been shown to lower major adverse cardiovascular events (MACE) among those with cardiovascular disease (CVD). It remains unclear how long a CVD patient needs to live to potentially benefit from colchicine. Our study aimed to determine the time to benefit (TTB) of colchicine in individuals with CVD. Methods: Literature searches were performed in PubMed for the cardiovascular outcome trial of colchicine in patients with CVD until October 12, 2023. The primary outcome measured was MACE. Reconstructed individual participant data (IPD) and the stratified Cox proportional hazards model were used to calculate the hazard ratio (HR) and 95 % confidence interval (CI) to estimate the efficacy of colchicine, and Weibull survival curves were fitted to estimate TTB for specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.01). Results: Four trials randomizing 11,594 adults aged between 59.8 and 66.5 years were included (follow-up duration: 12-28.6 months). Compared with placebo, colchicine reduced the risk of MACE (HR 0.68, 95 % CI: 0.60 to 0.78) but had no impact on cardiovascular and all-cause mortality. A TTB of 11.0 months (95 % CI: 0.59 to 21.3) was estimated to be needed to prevent 1 MACE in 100-colchicine-treated patients. The TTB for acute coronary syndrome was similar compared to stable coronary artery disease (10.7 vs. 11.2 months for ARR = 0.010). Conclusions: By using reconstructed IPD, this pooled analysis demonstrated that colchicine was associated with reduced nonfatal MACE, and the TTB was approximately 11.0 months to prevent 1 MACE per 100 patients.
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The latest developments in deep learning have demonstrated the importance of CT medical imaging for the classification of pulmonary nodules. However, challenges remain in fully leveraging the relevant medical annotations of pulmonary nodules and distinguishing between the benign and malignant labels of adjacent nodules. Therefore, this paper proposes the Nodule-CLIP model, which deeply mines the potential relationship between CT images, complex attributes of lung nodules, and benign and malignant attributes of lung nodules through a comparative learning method, and optimizes the model in the image feature extraction network by using its similarities and differences to improve its ability to distinguish similar lung nodules. Firstly, we segment the 3D lung nodule information by U-Net to reduce the interference caused by the background of lung nodules and focus on the lung nodule images. Secondly, the image features, class features, and complex attribute features are aligned by contrastive learning and loss function in Nodule-CLIP to achieve lung nodule image optimization and improve classification ability. A series of testing and ablation experiments were conducted on the public dataset LIDC-IDRI, and the final benign and malignant classification rate was 90.6%, and the recall rate was 92.81%. The experimental results show the advantages of this method in terms of lung nodule classification as well as interpretability.
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Neoplasias Pulmonares , Nódulo Pulmonar Solitario , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Aprendizaje Profundo , Pulmón/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Bases de Datos FactualesRESUMEN
Signal peptide peptidase (SPP) and its homologs, signal peptide peptidase-like (SPPL) proteases, are members of the GxGD-type aspartyl protease family, which is widespread in plants and animals and is a class of transmembrane proteins with significant biological functions. SPP/SPPLs have been identified; however, the functions of SPP/SPPL in rapeseed (Brassica napus L.) have not been reported. In this study, 26 SPP/SPPLs were identified in rapeseed and categorized into three groups: SPP, SPPL2, and SPPL3. These members mainly contained the Peptidase_A22 and PA domains, which were distributed on 17 out of 19 chromosomes. Evolutionary analyses indicated that BnaSPP/SPPLs evolved with a large number of whole-genome duplication (WGD) events and strong purifying selection. Members are widely expressed and play a key role in the growth and development of rapeseed. The regulation of rapeseed pollen fertility by the BnaSPPL4 gene was further validated through experiments based on bioinformatics analysis, concluding that BnaSPPL4 silencing causes male sterility. Cytological observation showed that male infertility caused by loss of BnaSPPL4 gene function occurs late in the mononucleate stage due to microspore dysplasia.
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Brassica napus , Brassica rapa , Infertilidad Masculina , Animales , Humanos , Masculino , Brassica napus/genética , Ácido Aspártico Endopeptidasas , Fertilidad/genética , Péptido HidrolasasRESUMEN
STUDY OBJECTIVES: This study investigated the impact of APAP therapy on vascular behavior and its potential to lower cardiovascular risk in patients with OSA, as well as differentiating APAP therapy heterogeneity. METHODS: All participants were diagnosed with OSA by portable monitoring, and pulse wave parameters and cardiac risk composite parameter index (CRI) were obtained by photoplethysmography before and after APAP. Clustering analysis of pulse wave parameters before APAP in the high-risk population was performed using k-means clustering. Linear regression was used to assess the associations of changes in CRI and pulse wave parameters with clinical characteristics. RESULTS: Eighty-two patients with OSA underwent APAP therapy. The CRI after APAP was significantly lower than before APAP (0.38± 0.33 and 0.58 ± 0.31, respectively; p < 0.001). All pulse wave parameters (except irregular pulse) were significantly different (p < 0.001) in patients with OSA and in the high-risk responders group after versus before APAP. The differences in pulse wave parameters after versus before APAP were not significant in the high-risk non-responders group, except for RCRD and pulse rate variability. Four clusters were obtained from the clustering analysis of pulse wave parameters before APAP in the high-risk responders group. CONCLUSIONS: APAP reduces the CRI in patients with OSA by altering vascular behavior. Overnight photoplethysmography monitoring of pulse wave parameters can be used to assess whether patients with OSA will benefit from APAP.
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AIM: This meta-analysis aimed to assess the precision of Sonazoid contrast-enhanced ultrasound (CEUS) to distinguish hepatocellular carcinoma (HCC) from focal liver lesions (FLLs). MATERIAL AND METHODS: The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched and checked for studies using Sonazoid CEUS to characterize HCC. A comprehensive meta-analysis was conducted, involving data pooling, subgroup analyses, meta-regression, and investigation of publication bias. RESULTS: The meta-analysis included fourteen studies. The overall diagnostic accuracy for characterizing HCC was as follows (all ranges show the 95% confidence interval): pooled sensitivity of 0.87 (0.80-0.92), pooled specificity of 0.95 (0.91-0.97), and a diagnostic odds ratio of 121 (61-241). The overall weighted area under the curve was 0.97 (0.95-0.98). The pooled sensitivity, specificity, and diagnostic odds ratio for Sonazoid and Sonovue were 0.75 (0.63- 0.84), 0.97 (0.86-0.99), 82 (15-445); and 0.64 (0.51-0.76), 0.98 (0.91-0.99), 72 (17-311), respectively. The sources of heterogeneity were identified as the study location, prevailing risk factor, reference diagnosis standard, criteria of Sonazoid CUES, and the proportion of cases of HCC. We observed no potential publication bias. CONCLUSION: Sonazoid CEUS is efficient to distinguish HCC from FLLs, with good sensitivity and specificity. It is comparable to Sonovue CEUS to diagnose HCC.
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Carcinoma Hepatocelular , Medios de Contraste , Hierro , Neoplasias Hepáticas , Óxidos , Ultrasonografía , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Diagnóstico Diferencial , Compuestos Férricos , Aumento de la Imagen/métodos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ultrasonografía/métodosRESUMEN
STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.
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Síndrome de las Piernas Inquietas , Humanos , Femenino , Masculino , Polisomnografía , Síndrome de las Piernas Inquietas/epidemiología , Sueño , Pierna , China , Proteínas Nucleares , Proteína-Arginina N-MetiltransferasasRESUMEN
OBJECTIVE: This study aimed to assess the clinical efficacy of Daiwenjiu ointment in the treatment of cervical spondylosis with cold dampness obstruction nerve root type. METHODS: A retrospective analysis was conducted on a cohort of 110 patients diagnosed with cervical spondylotic radiculopathy. Based on the treatment method, the patients were divided into two groups. The control group received electroacupuncture treatment, while the observation group received a combination of Daiwenjiu ointment and electroacupuncture treatment. The outcome measures included Japanese Orthopedic Association (JOA) scores for cervical spine function, Simplified McGill Pain Questionnaire (SF-MPQ) scores, and changes in serum inflammatory factors TNF-α and IL-1ß. RESULTS: Following treatment, the JOA score in the observation group increased from 9.45 ± 1.35 to 14.82 ± 1.29 after treatment, indicating better recovery of cervical spine function compared to the control group (p < 0.001). The SF-MPQ score in the observation group decreased to 18.25 ± 3.80 after treatment, while it remained at 30.20 ± 4.30 in the control group. This difference between the groups was statistically significant (p < 0.001). Furthermore, the observation group demonstrated a significant decrease in serum levels of TNF-α and IL-1ß after treatment compared to the control group (p < 0.001). CONCLUSION: Daiwenjiu ointment exhibits significant therapeutic effects in patients with cold dampness obstruction nerve root type cervical spondylosis. It effectively improves cervical function, reduces pain, and downregulates inflammatory cytokine levels.
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Entity alignment refers to discovering the entity pairs with the same realistic meaning in different knowledge graphs. This technology is of great significance for completing and fusing knowledge graphs. Recently, methods based on knowledge representation learning have achieved remarkable achievements in entity alignment. However, most existing approaches do not mine hidden information in the knowledge graph as much as possible. This paper suggests SCMEA, a novel cross-lingual entity alignment framework based on multi-aspect information fusion and bidirectional contrastive learning. SCMEA initially adopts diverse representation learning models to embed multi-aspect information of entities and integrates them into a unified embedding space with an adaptive weighted mechanism to overcome the missing information and the problem of different-aspect information are not uniform. Then, we propose a stacked relation-entity co-enhanced model to further improve the representations of entities, wherein relation representation is modeled using an Entity Collector with Global Entity Attention. Finally, a combined loss function based on improved bidirectional contrastive learning is introduced to optimize model parameters and entity representation, effectively mitigating the hubness problem and accelerating model convergence. We conduct extensive experiments to evaluate the alignment performance of SCMEA. The overall experimental results, ablation studies, and analysis performed on five cross-lingual datasets demonstrate that our model achieves varying degrees of performance improvement and verifies the effectiveness and robustness of the model.
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Conocimiento , AprendizajeRESUMEN
BACKGROUND: Several in silico studies have determined that quercetin, a plant flavonol, could bind with strong affinity and low free energy to SARS-CoV-2 proteins involved in viral entry and replication, suggesting it could block infection of human cells by the virus. In the present study, we examined the ex vivo ability of quercetin to inhibit of SARS-CoV-2 replication and explored the mechanisms of this inhibition. METHODS: Green monkey kidney Vero E6 cells and in human colon carcinoma Caco-2 cells were infected with SARS-CoV-2 and incubated in presence of quercetin; the amount of replicated viral RNA was measured in spent media by RT-qPCR. Since the formation of syncytia is a mechanism of SARS-CoV-2 propagation, a syncytialization model was set up using human embryonic kidney HEK293 co-expressing SARS-CoV-2 Spike (S) protein and human angiotensin converting enzyme 2 (ACE2), [HEK293(S + ACE2) cells], to assess the effect of quercetin on this cytopathic event by microscopic imaging and protein immunoblotting. RESULTS: Quercetin inhibited SARS-CoV-2 replication in Vero E6 cells and Caco-2 cells in a concentration-dependent manner with a half inhibitory concentration (IC50) of 166.6 and 145.2 µM, respectively. It also inhibited syncytialization of HEK293(S + ACE2) cells with an IC50 of 156.7 µM. Spike and ACE2 co-expression was associated with decreased expression, increased proteolytic processing of the S protein, and diminished production of the fusogenic S2' fragment of S. Furin, a proposed protease for this processing, was inhibited by quercetin in vitro with an IC50 of 116 µM. CONCLUSION: These findings suggest that at low 3-digit micromolar concentrations of quercetin could impair SARS-CoV-2 infection of human cells partly by blocking the fusion process that promotes its propagation.
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COVID-19 , Humanos , Chlorocebus aethiops , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2/genética , Quercetina/farmacología , Proteínas Virales/metabolismo , Células CACO-2 , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células HEK293 , Células Gigantes/patología , Unión ProteicaRESUMEN
Nucleic acids, including DNA and RNA, have been considered as powerful and functional biomaterials owing to their programmable structure, good biocompatibility, and ease of synthesis. However, traditional nucleic acid-based probes have always suffered from inherent limitations, including restricted cell internalization efficiency and structural instability. In recent years, DNA nanotechnology has shown great promise for the applications of bioimaging and drug delivery. The attractive superiorities of DNA nanostructures, such as precise geometries, spatial addressability, and improved biostability, have enabled them to be a novel category of nucleic acid delivery systems for biomedical applications. In this review, we introduce the development of DNA nanotechnology, and highlight recent advances of DNA nanostructure-based delivery systems for cellular imaging and therapeutic applications. Finally, we propose the challenges as well as opportunities for the future development of DNA nanotechnology in biomedical research.
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Nanoestructuras , Ácidos Nucleicos , Nanotecnología/métodos , ADN/genética , ADN/química , Nanoestructuras/química , Sistemas de Liberación de MedicamentosRESUMEN
Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform based on biocompatible fluorocarbon modified chitosan (FCS) is developed to achieve highly efficient non-invasive delivery of biomacromolecules including antibodies and antigens. The formed nanocomplexes exhibits effective transdermal penetration ability via both intercellular and transappendageal routes. Non-invasive transdermal delivery of immune checkpoint blockade antibodies induces stronger immune responses for melanoma in female mice and reduces systemic toxicity compared to intravenous injection. Moreover, transdermal delivery of a SARS-CoV-2 vaccine in female mice results in comparable humoral immunity as well as improved cellular immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Additionally, FCS-based protein delivery systems demonstrate transdermal ability for rabbit and porcine skins. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of bio-therapeutics.
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Quitosano , Melanoma , Vacunas Virales , Porcinos , Femenino , Humanos , Animales , Ratones , Conejos , Melanoma/tratamiento farmacológico , Vacunas contra la COVID-19 , Inmunoterapia , Sistemas de Liberación de MedicamentosRESUMEN
Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients' prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG.
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Apoptosis , Glioma , Humanos , Reproducibilidad de los Resultados , Muerte Celular , Glioma/genética , Glioma/terapia , InmunoterapiaRESUMEN
Most fresh bananas belong to the Cavendish and Gros Michel subgroups. Here, we report chromosome-scale genome assemblies of Cavendish (1.48 Gb) and Gros Michel (1.33 Gb), defining three subgenomes, Ban, Dh and Ze, with Musa acuminata ssp. banksii, malaccensis and zebrina as their major ancestral contributors, respectively. The insertion of repeat sequences in the Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 RGA2 (resistance gene analog 2) promoter was identified in most diploid and triploid bananas. We found that the receptor-like protein (RLP) locus, including Foc race 1-resistant genes, is absent in the Gros Michel Ze subgenome. We identified two NAP (NAC-like, activated by apetala3/pistillata) transcription factor homologs specifically and highly expressed in fruit that directly bind to the promoters of many fruit ripening genes and may be key regulators of fruit ripening. Our genome data should facilitate the breeding and super-domestication of bananas.
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Fusarium , Musa , Musa/genética , Fusarium/genética , Triploidía , Fitomejoramiento , Factores de Transcripción/genética , Enfermedades de las Plantas/genéticaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Qi-zhi-wei-tong granule (QZWT) significantly reduced the major gastrointestinal and psychological symptoms of functional dyspepsia. AIM OF THE STUDY: We aimed to explore the therapeutic effect of QZWT treated chronic non-atrophic gastritis (CNAG) and to elucidate its potential mechanism. MATERIALS AND METHODS: The composition of QZWT was analysed by UPLC-Q/TOF-MS. The CNAG mice model was established by chronic restraint stress (CRS) in combination with iodoacetamide (IAA). Morphological staining was utilized to reveal the impact of QZWT on stomach and gut integrity. RTâqPCR and ELISA were used to measure proinflammatory cytokines in the stomach, colon tissues and serum of CNAG mice. Next-generation sequencing of 16 S rDNA was applied to analyse the gut microbiota community of faecal samples. Finally, we investigated the faecal bile acid composition using GCâMS. RESULTS: Twenty-one of the compounds from QZWT were successfully identified by UPLC-Q/TOF-MS analysis. QZWT enhanced gastric and intestinal integrity and suppressed inflammatory responses in CNAG mice. Moreover, QZWT treatment reshaped the gut microbiota structure by increasing the levels of the Akkermansia genus and decreasing the populations of the Desulfovibrio genus in CNAG mice. The alteration of gut microbiota was associated with gut bacteria BA metabolism. In addition, QZWT reduced BAs and especially decreased conjugated BAs in CNAG mice. Spearman's correlation analysis further confirmed the links between the changes in the gut microbiota and CNAG indices. CONCLUSIONS: QZWT can effectively inhibited gastrointestinal inflammatory responses of CNAG symptoms in mice; these effects may be closely related to restoring the balance of the gut microbiota and regulating BA metabolism to protect the gastric mucosa. This study provides a scientific reference for the pathogenesis of CNAG and the mechanism of QZWT treatment.
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Gastritis , Microbioma Gastrointestinal , Animales , Ratones , Qi , Metabolismo de los Lípidos , Ácidos y Sales Biliares , Gastritis/tratamiento farmacológicoRESUMEN
Necrotrophic fungal plant pathogens employ cell death-inducing proteins (CDIPs) to facilitate infection. However, the specific CDIPs and their mechanisms in pathogenic processes of Sclerotinia sclerotiorum, a necrotrophic pathogen that causes disease in many economically important crop species, have not yet been clearly defined. This study found that S. sclerotiorum secretes SsXyl2, a glycosyl hydrolase family 11 xylanase, at the late stage of hyphal infection. SsXyl2 targets the apoplast of host plants to induce cell death independent of xylanase activity. Targeted disruption of SsXyl2 leads to serious impairment of virulence, which can be recovered by a catalytically impaired SsXyl2 variant, thus supporting the critical role of cell death-inducing activity of SsXyl2 in establishing successful colonization of S. sclerotiorum. Remarkably, infection by S. sclerotiorum induces the accumulation of Nicotiana benthamiana hypersensitive-induced reaction protein 2 (NbHIR2). NbHIR2 interacts with SsXyl2 at the plasma membrane and promotes its localization to the cell membrane and cell death-inducing activity. Furthermore, gene-edited mutants of NbHIR2 displayed increased resistance to the wild-type strain of S. sclerotiorum, but not to the SsXyl2-deletion strain. Hence, SsXyl2 acts as a CDIP that manipulates host cell physiology by interacting with hypersensitive induced reaction protein to facilitate colonization by S. sclerotiorum. These findings provide valuable insights into the pathogenic mechanisms of CDIPs in necrotrophic pathogens and lead to a more promising approach for breeding resistant crops against S. sclerotiorum.