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1.
Plant Physiol ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39321167

RESUMEN

Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum (Lib.) De Bary is a devastating disease infecting hundreds of plant species. It also restricts the yield, quality, and safe production of rapeseed (Brassica napus) worldwide. However, the lack of resistance sources and genes to S. sclerotiorum has greatly restricted rapeseed SSR-resistance breeding. In this study, a previously identified GDSL motif-containing lipase gene, Brassica napus GDSL LIPASE-LIKE 1 (BnaC07.GLIP1), encoding a protein localized to the intercellular space, was characterized as functioning in plant immunity to S. sclerotiorum. The BnaC07.GLIP1 promoter is S. sclerotiorum-inducible and the expression of BnaC07.GLIP1 is substantially enhanced after S. sclerotiorum infection. Arabidopsis (Arabidopsis thaliana) heterologously expressing and rapeseed lines overexpressing BnaC07.GLIP1 showed enhanced resistance to S. sclerotiorum, whereas RNAi suppression and CRISPR/Cas9 knockout B. napus lines were hyper-susceptible to S. sclerotiorum. Moreover, BnaC07.GLIP1 affected the lipid composition and induced the production of phospholipid molecules, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidic acid, which were correlated with decreased levels of reactive oxygen species (ROS) and enhanced expression of defense-related genes. A B. napus bZIP44 transcription factor specifically binds the CGTCA motif of the BnaC07.GLIP1 promoter to positively regulate its expression. BnbZIP44 responded to S. sclerotiorum infection, and its heterologous expression inhibited ROS accumulation, thereby enhancing S. sclerotiorum resistance in Arabidopsis. Thus, BnaC07.GLIP1 functions downstream of BnbZIP44 and is involved in S. sclerotiorum resistance by modulating the production of phospholipid molecules and ROS homeostasis in B. napus, providing insights into the potential roles and functional mechanisms of BnaC07.GLIP1 in plant immunity and for improving rapeseed SSR disease-resistance breeding.

2.
Cell Rep ; 43(9): 114760, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39299236

RESUMEN

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level remains unexplored. In this study, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively chart the spatial cellular landscape of the human and rat CC under normal and disease conditions. We observe differences in the proportions of cell subtypes and marker genes between humans and rats. Based on the analysis of the fibroblast (FB) niche, we also find that the enrichment scores of mechanical force signaling vary across different regions and correlate with the spatial distribution of FB subtypes. In vitro, the soft and hard extracellular matrix (ECM) induces the differentiation of FBs into apolipoprotein (APO)+ FBs and cartilage oligomeric matrix protein (COMP)+ FBs, respectively. In summary, our study provides a cross-species and physiopathological transcriptomic atlas of the CC, contributing to a further understanding of the molecular anatomy and regulation of penile erection.


Asunto(s)
Pene , Análisis de la Célula Individual , Animales , Humanos , Masculino , Pene/metabolismo , Ratas , Matriz Extracelular/metabolismo , Transcriptoma/genética , Fibroblastos/metabolismo , Diferenciación Celular , Ratas Sprague-Dawley
3.
Diabetes Metab Syndr Obes ; 17: 3087-3102, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193547

RESUMEN

Purpose: The purpose of this study is to develop and validate a clinical prediction model for diagnosing Metabolic Syndrome (MetS) based on indicators associated with its occurrence. Patients and Methods: This study included a total of 26,637 individuals who underwent health examinations at the Jiaxing First Hospital Health Examination Center from January 19, 2022, to December 31, 2022. They were randomly divided into training (n = 18645) and validation (n = 7992) sets in a 7:3 ratio. Firstly, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was employed for variable selection. Subsequently, a multifactor Logistic regression analysis was conducted to establish the predictive model, accompanied by nomograms. Thirdly, model validation was performed using Receiver Operating Characteristic (ROC) curves, Harrell's concordance index (C-index), calibration plots, and Decision Curve Analysis (DCA), followed by internal validation. Results: In this study, six predictive indicators were selected, including Body Mass Index, Triglycerides, Blood Pressure, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Fasting Blood Glucose. The model demonstrated excellent predictive performance, with an AUC of 0.978 (0.976-0.980) for the training set and 0.977 (0.974-0.980) for the validation set in the nomogram. Calibration curves indicated that the model possessed good calibration ability (Training set: Emax 0.081, Eavg 0.005, P = 0.580; Validation set: Emax 0.062, Eavg 0.007, P = 0.829). Furthermore, decision curve analysis suggested that applying the nomogram for diagnosis is more beneficial when the threshold probability of MetS is less than 89%, compared to either treating-all or treating-none at all. Conclusion: We developed and validated a nomogram based on MetS risk factors, which can effectively predict the occurrence of MetS. The proposed nomogram demonstrates significant discriminative ability and clinical applicability. It can be utilized to identify variables and risk factors for diagnosing MetS at an early stage.

4.
Gene ; 930: 148864, 2024 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-39151674

RESUMEN

The NYN domain gene family consists of genes that encode ribonucleases that are characterized by a newly identified NYN domain. Members of the family were widely distributed in all life kingdoms and play a crucial role in various RNA regulation processes, although the wide genome overview of the NYN domain gene family is not yet available in any species. Rapeseed (Brassica napus L.), a polyploid model species, is an important oilseed crop. Here, the phylogenetic analysis of these BnaNYNs revealed five distinct groups strongly supported by gene structure, conserved domains, and conserved motifs. The survey of the expansion of the gene family showed that the birth of BnaNYNs is explained by various duplication events. Furthermore, tissue-specific expression analysis, protein-protein interaction prediction, and cis-element prediction suggested a role for BnaNYNs in plant growth and development. Interestingly, the data showed that three tandem duplicated BnaNYNs (TDBs) exhibited distinct expression patterns from those other BnaNYNs and had a high similarity in protein sequence level. Furthermore, the analysis of one of these TDBs, BnaNYN57, showed that overexpression of BnaNYN57 in Arabidopsis thaliana and B. napus accelerated plant growth and significantly increased silique length, while RNA interference resulted in the opposite growth pattern. It suggesting a key role for the TDBs in processes related to plant growth and development.


Asunto(s)
Brassica napus , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Filogenia , Proteínas de Plantas , Brassica napus/genética , Brassica napus/crecimiento & desarrollo , Brassica napus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Ribonucleasas/genética , Ribonucleasas/metabolismo , Desarrollo de la Planta/genética , Duplicación de Gen , Dominios Proteicos
5.
J Fungi (Basel) ; 10(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39194865

RESUMEN

Fruits and vegetables play an important role in people's dietary health and economic development [...].

6.
Microb Biotechnol ; 17(7): e14522, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39016683

RESUMEN

As a Gram-negative anaerobic bacterium, Akkermansia muciniphila (AKK) participates in the immune response in many cancers. Our study focused on the factors and molecular mechanisms of AKK affecting immune escape in lung adenocarcinoma (LUAD). We cultured AKK bacteria, prepared AKK outer membrane protein Amuc_1100 and constructed a subcutaneous graft tumour mouse model. A549, NCI-H1395 cells and mice were respectively treated with inactivated AKK, Amuc_1100, Ruxolitinib (JAK inhibitor) and RO8191 (JAK activator). CD8+ T cells that penetrated the membrane were counted in the Transwell assay. The toxicity of CD8+ T cells was evaluated by lactate dehydrogenase assay. Western blot was applied to determine JAK/STAT-related protein and PD-L1 expression, whilst CCL5, granzyme B and INF-γ expression were assessed through enzyme-linked immunosorbent assay (ELISA). The proportion of tumour-infiltrating CD8+ T cells and the levels of granzyme B and INF-γ were determined by flow cytometry. AKK markedly accelerated A549 and NCI-H1395 recruiting CD8+ T cells and enhanced CD8+ T cell toxicity. Amuc_1100 purified from AKK exerted the same promoting effects. Besides, Amuc_1100 dramatically suppressed PD-L1, p-STAT and p-JAK expression and enhanced CCL5, granzyme B and INF-γ expression. Treatment with Ruxolitinib accelerated A549 and NCI-H1395 cells recruiting CD8+ T cells, enhanced CD8+ T cell toxicity, CCL5, granzyme B and INF-γ expression, and inhibited PD-L1 expression. In contrast, the RO8191 treatment slowed down the changes induced by Amuc_1100. Animal experiments showed that Amuc_1100 was found to increase the number of tumour-infiltrating CD8+ T cells, increase the levels of granzyme B and INF-γ and significantly inhibit the expression of PD-L1, p-STAT and p-JAK, which exerted an antitumour effect in vivo. In conclusion, through inhibiting the JAK/STAT signalling pathway, AKK outer membrane protein facilitated the recruitment of CD8+ T cells in LUAD and suppressed the immune escape of cells.


Asunto(s)
Adenocarcinoma del Pulmón , Akkermansia , Proteínas de la Membrana Bacteriana Externa , Linfocitos T CD8-positivos , Quinasas Janus , Transducción de Señal , Linfocitos T CD8-positivos/inmunología , Animales , Ratones , Humanos , Quinasas Janus/metabolismo , Adenocarcinoma del Pulmón/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de la Membrana Bacteriana Externa/inmunología , Neoplasias Pulmonares/inmunología , Línea Celular Tumoral , Factores de Transcripción STAT/metabolismo , Modelos Animales de Enfermedad
7.
Oncol Rep ; 52(4)2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39054954

RESUMEN

Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation­PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6­adenosine­methyltransferase non­catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.


Asunto(s)
Apoptosis , Proliferación Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Metiltransferasas , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Apoptosis/genética , Proliferación Celular/genética , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Línea Celular Tumoral , Animales , Activación Transcripcional , Ratones , Regiones Promotoras Genéticas , Anciano , Regulación hacia Abajo , Metilación de ADN
8.
Front Plant Sci ; 15: 1429011, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081522

RESUMEN

The epitranscriptomic mark N 6-methyladenosine (m6A) is the most common type of messenger RNA (mRNA) post-transcriptional modification in eukaryotes. With the discovery of the demethylase FTO (FAT MASS AND OBESITY-ASSOCIATED PROTEIN) in Homo Sapiens, this modification has been proven to be dynamically reversible. With technological advances, research on m6A modification in plants also rapidly developed. m6A modification is widely distributed in plants, which is usually enriched near the stop codons and 3'-UTRs, and has conserved modification sequences. The related proteins of m6A modification mainly consist of three components: methyltransferases (writers), demethylases (erasers), and reading proteins (readers). m6A modification mainly regulates the growth and development of plants by modulating the RNA metabolic processes and playing an important role in their responses to environmental signals. In this review, we briefly outline the development of m6A modification detection techniques; comparatively analyze the distribution characteristics of m6A in plants; summarize the methyltransferases, demethylases, and binding proteins related to m6A; elaborate on how m6A modification functions in plant growth, development, and response to environmental signals; and provide a summary and outlook on the research of m6A in plants.

9.
Adv Sci (Weinh) ; 11(33): e2404397, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38946685

RESUMEN

Extraction of U(VI) in water is of great significance in energy and environmental fields. However, the traditional methods usually fail due to the indispensable extra addition of catalyst, adsorbent, precipitant, or sacrificial agents, which may lead to enhanced extraction costs and secondary pollution. Here, a new efficient uranium extraction strategy is proposed based on triboelectricity without adding a catalyst or other additives. It is found only under the friction between the microbubbles (generated under ultrasonication) and the water flow, that reactive oxygen species (ROS) can largely be generated, which thus contributes to the solidification of U(VI) from water. In addition, the magnetic field can affect the phase of the product. Under mechanical stirring, the product contains (UO2)O2·2H2O, while which contains UO2(OH)2 and (UO2)O2·4H2O under the magnetic stirring. Quenching experiments are also carried out to explore the influence of environmental factors. Most importantly, it shows great potential in the extraction of U(VI) from seawater. This work proposes a catalyst-free and light-free strategy toward the solidification of U(VI) from water, which avoids the secondary pollution of the catalyst to the environment and is low-cost, and has great potential in the real application.

10.
BMC Pulm Med ; 24(1): 302, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926685

RESUMEN

BACKGROUND: This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission. METHODS: This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell's C-index, calibration plots, DCA, and K-M curve. RESULT: Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836-0.881), 0.773 (0.746-0.799), 0.736 (0.701-0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723-0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model's good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P < 0.0001). CONCLUSION: The nomogram can provide valuable guidance for clinical practitioners to early predict the probability of RF occurrence in AECOPD patients, take relevant measures, prevent RF, and improve patient outcomes.


Asunto(s)
Unidades de Cuidados Intensivos , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Unidades de Cuidados Intensivos/estadística & datos numéricos , Persona de Mediana Edad , Bases de Datos Factuales , Curva ROC , Medición de Riesgo/métodos , Anciano de 80 o más Años , Nomogramas , Factores de Riesgo , Enfermedad Pulmonar Obstructiva Crónica
11.
Exp Neurol ; 378: 114819, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38763355

RESUMEN

BACKGROUND: Both glymphatic system dysfunction and inflammatory response aggravate neurological dysfunction after subarachnoid hemorrhage (SAH). Studies have shown that ß-hydroxybutyrate (BHB) may mitigate painful diabetic neuropathy (PDN) by upregulating SNTA1 expression and reinstating AQP4 polarity. However, the potential of BHB to ameliorate glymphatic system function and inflammatory response in SAH mice remains uncertain. METHODS: The SAH models were constructed by injection of arterial blood into cisterna Magana. Three groups of C57 mice were randomly assigned: Sham, SAH, and BHB. All mice were subjected to neurological function assessment, western blot, immunofluorescence double staining, and RNA-seq. Glymphatic system function was examined with tracer and immunofluorescence double staining, and the differential genes were examined with RNA-seq. In addition, the expression of related inflammation was detected. RESULTS: Compared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice. CONCLUSION: The study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.


Asunto(s)
Ácido 3-Hidroxibutírico , Sistema Glinfático , Ratones Endogámicos C57BL , Hemorragia Subaracnoidea , Animales , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/metabolismo , Hemorragia Subaracnoidea/tratamiento farmacológico , Ratones , Sistema Glinfático/efectos de los fármacos , Sistema Glinfático/metabolismo , Masculino , Ácido 3-Hidroxibutírico/farmacología , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/etiología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/metabolismo
12.
Adv Mater ; 36(31): e2312856, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38775656

RESUMEN

Antiferroelectric ceramics, via the electric-field-induced antiferroelectric (AFE)-ferroelectric (FE) phase transitions, show great promise for high-energy-density capacitors. Yet, currently, only 70-80% energy release is found during a charge-discharge cycle. Here, for PbZrO3-based oxides, geometric nonlinear theory of martensitic phase transitions is applied (first used to guide supercompatible shape-memory alloys) to predict the reversibility of the AFE-FE transition by using density-functional theory to assess AFE/FE interfacial lattice-mismatch strain that assures ultralow electric hysteresis and extended fatigue lifetime. A good correlation of mismatch strain with electric hysteresis, hence, with energy efficiency of AFE capacitors is observed. Guided by theory, high-throughput material search is conducted and AFE compositions with a near-perfect charge-discharge energy efficiency (98.2%), i.e., near-zero hysteresis are discovered. And the fatigue life of the capacitor reaches 79.5 million charge-discharge cycles, a factor of 80 enhancement over AFE ceramics with large electric hysteresis.

13.
Heliyon ; 10(9): e30281, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38726150

RESUMEN

Background: The most serious manifestation of pulmonary cryptococcosis is complicated with cryptococcal meningitis, while its clinical manifestations lack specificity with delayed diagnosis and high mortality. The early prediction of this complication can assist doctors to carry out clinical interventions in time, thus improving the cure rate. This study aimed to construct a nomogram to predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis through a scoring system. Methods: The clinical data of 525 patients with pulmonary cryptococcosis were retrospectively analyzed, including 317 cases (60.38 %) with cryptococcal meningitis and 208 cases (39.62 %) without cryptococcal meningitis. The risk factors of cryptococcal meningitis were screened by univariate analysis, LASSO regression analysis and multivariate logistic regression analysis. Then the risk factors were incorporated into the nomogram scoring system to establish a prediction model. The model was validated by receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve. Results: Fourteen risk factors for cryptococcal meningitis in patients with pulmonary cryptococcosis were screened out by statistical method, including 6 clinical manifestations (fever, headache, nausea, psychiatric symptoms, tuberculosis, hematologic malignancy) and 8 clinical indicators (neutrophils, lymphocytes, glutamic oxaloacetic transaminase, T cells, helper T cells, killer T cells, NK cells and B cells). The AUC value was 0.978 (CI 96.2 %∼98.9 %), indicating the nomogram was well verified. Conclusion: The nomogram scoring system constructed in this study can accurately predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis, which may provide a reference for clinical diagnosis and treatment of patients with cryptococcal meningitis.

14.
Int J Cancer ; 155(4): 766-775, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38594805

RESUMEN

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.


Asunto(s)
Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Inmunoterapia , Inestabilidad de Microsatélites , Nomogramas , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/inmunología , Femenino , Masculino , Pronóstico , Persona de Mediana Edad , Reparación de la Incompatibilidad de ADN/genética , Inmunoterapia/métodos , Anciano , Inmunohistoquímica , Adulto , Biomarcadores de Tumor/genética
15.
Respir Investig ; 62(4): 541-550, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38643536

RESUMEN

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. At present, the definitive pathology of PAH has not been elucidated and its effective treatment remains lacking. Despite PAHs having multiple pathogeneses, the cancer-like characteristics of cells have been considered the main reason for PAH progression. RECENT FINDINGS: p53 protein, an important tumor suppressor, regulates a multitude of gene expressions to maintain normal cellular functions and suppress the progression of malignant tumors. Recently, p53 has been found to exert multiple biological effects on cardiovascular diseases. Since PAH shares similar metabolic features with cancer cells, the regulatory roles of p53 in PAH are mainly the induction of cell cycle, inhibition of cell proliferation, and promotion of apoptosis. SUMMARY: This paper summarized the advanced findings on the molecular mechanisms and regulatory functions of p53 in PAH, aiming to reveal the potential therapeutic targets for PAH.


Asunto(s)
Apoptosis , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/fisiología , Proteína p53 Supresora de Tumor/metabolismo , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/genética , Proliferación Celular , Ciclo Celular , Animales , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Terapia Molecular Dirigida , Progresión de la Enfermedad , Expresión Génica
16.
J Biochem Mol Toxicol ; 38(4): e23707, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38622979

RESUMEN

Heart failure remains a global threaten to public health, cardiac fibrosis being a crucial event during the development and progression of heart failure. Reportedly, M2 macrophages might affect endothelial cell (ECs) and fibroblast proliferation and functions through paracrine signaling, participating in myocardial fibrosis. In this study, differentially expressed paracrine factors between M0/1 and M2 macrophages were analyzed and the expression of TNFSF13 was most significant in M2 macrophages. Culture medium (CM) of M2 (M2 CM) coculture to ECs and cardiac fibroblasts (CFbs) significantly promoted the cell proliferation of ECs and CFbs, respectively, and elevated α-smooth muscle actin (α-SMA), collagen I, and vimentin levels within both cell lines; moreover, M2 CM-induced changes in ECs and CFbs were partially abolished by TNFSF13 knockdown in M2 macrophages. Lastly, the NF-κB and Akt signaling pathways were proved to participate in TNFSF13-mediated M2 CM effects on ECs and CFbs. In conclusion, TNFSF13, a paracrine factor upregulated in M2 macrophages, could mediate the promotive effects of M2 CM on EC and CFb proliferation and fibrogenic alterations.


Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Humanos , Cardiomiopatías/metabolismo , Células Endoteliales/metabolismo , Fibroblastos/metabolismo , Macrófagos/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo
17.
Gastroenterol Rep (Oxf) ; 12: goae011, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38566849

RESUMEN

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

18.
Front Plant Sci ; 15: 1342359, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567131

RESUMEN

Introduction: An important strategy to combat yield loss challenge is the development of varieties with increased tolerance to drought to maintain production. Improvement of crop yield under drought stress is critical to global food security. Methods: In this study, we performed multiomics analysis in a collection of 119 diverse rapeseed (Brassica napus L.) varieties to dissect the genetic control of agronomic traits in two watering regimes [well-watered (WW) and drought stress (DS)] for 3 years. In the DS treatment, irrigation continued till the 50% pod development stage, whereas in the WW condition, it was performed throughout the whole growing season. Results: The results of the genome-wide association study (GWAS) using 52,157 single-nucleotide polymorphisms (SNPs) revealed 1,281 SNPs associated with traits. Six stable SNPs showed sequence variation for flowering time between the two irrigation conditions across years. Three novel SNPs on chromosome C04 for plant weight were located within drought tolerance-related gene ABCG16, and their pleiotropically effects on seed weight per plant and seed yield were characterized. We identified the C02 peak as a novel signal for flowering time, harboring 52.77% of the associated SNPs. The 288-kbps LD decay distance analysis revealed 2,232 candidate genes (CGs) associated with traits. The CGs BIG1-D, CAND1, DRG3, PUP10, and PUP21 were involved in phytohormone signaling and pollen development with significant effects on seed number, seed weight, and grain yield in drought conditions. By integrating GWAS and RNA-seq, 215 promising CGs were associated with developmental process, reproductive processes, cell wall organization, and response to stress. GWAS and differentially expressed genes (DEGs) of leaf and seed in the yield contrasting accessions identified BIG1-D, CAND1, and DRG3 genes for yield variation. Discussion: The results of our study provide insights into the genetic control of drought tolerance and the improvement of marker-assisted selection (MAS) for breeding high-yield and drought-tolerant varieties.

19.
Langmuir ; 40(18): 9688-9701, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38654502

RESUMEN

Rubidium (Rb) and cesium (Cs) have important applications in highly technical fields. Salt lakes contain huge reserves of Rb and Cs with industrial significance, which can be utilized after extraction. In this study, a composite magnetic adsorbent (Fe3O4@ZIF-8@AMP, AMP = ammonium phosphomolybdate) was prepared and its adsorption properties for Rb+ and Cs+ were studied in simulated and practical brine. The structure of the adsorbent was characterized by SEM, XRD, N2 adsorption-desorption, FT-IR, and vibrating sample magnetometer (VSM). The adsorbent had good adsorption affinity for Rb+ and Cs+. The Langmuir model and pseudo-second-order dynamics described the adsorbing isotherm and kinetic dates, respectively. The adsorption capacity and adsorption rate of Fe3O4@ZIF-8@AMP were increased by 1.86- and 2.5-fold compared with those of powdered crystal AMP, owing to the large specific surface area and high dispersibility of the adsorbent in the solution. The adsorbent was rapidly separated from the solution within 17 s using an applied magnetic field owing to the good magnetic properties. The composite adsorbent selectively adsorbed Rb+ and Cs+ from the practical brine even in the presence of a large number of coexisting ions. The promising adsorbent can be used to extract Rb+ and Cs+ from aqueous solutions.

20.
J Colloid Interface Sci ; 667: 575-584, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38657541

RESUMEN

Energy and environmental issues make the generation of H2O2 and the separation of U(VI) from water very important topics. In this work, we disclosed a low-cost, high-efficiency method for separating U(VI) from water based on the naturally formed catalyst (red volcanic stone powders, RVSP) of Ca(Al2Si2O8)/Fe2O3 heterojunction through a piezocatalytic pathway induced by ultrasonication. The charges were found to be elevatedly separated due to the formation of the heterojunction. It is found that under ultrasonication, charges were effectively separated and then reacted with water to form H2O2 with a high yield of 196.7 µmol·g-1 in 4 h, which further solidifies U(VI) to form a solid of UO2O2. The removal rate of U(VI) in water reached 96 % (50 ppm) within 150 min. Furthermore, the results calculated by VASP show that the cyclic variation of the conduction bands under a cyclic force field facilitates the charge separation, and thus may promote piezocatalysis. Most importantly, the application study in real seawater indicates that U(VI) piezocatalysis based on natural minerals has great potential. This work presents a comprehensive investigation of U(VI) piezocatalysis by Ca(Al2Si2O8)/Fe2O3 and provides a new idea for piezocatalytic extraction of uranium.

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