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2.
Water Res ; 261: 122057, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38991246

RESUMEN

Wave-induced liquefaction is a geological hazard under the action of cyclic wave load on seabed. Liquefaction influences the suspended sediment concentration (SSC), which is essential for sediment dynamics and marine water quality. Till now, the identification of liquefaction state and the effect of liquefaction on SSC have not been sufficiently accounted for in the sediment model. In this study, we introduced a method for simulating the liquefaction-induced resuspension flux into an ocean model. We then simulated a storm north of the Yellow River Delta, China, and validated the results using observational data, including significant wave heights, water levels, excess pore water pressures, and SSCs. The liquefaction areas were mainly distributed in coastal zones with water depths less than 12 m, and the simulated maximum potential soil liquefaction depth was 1.39 m. The liquefaction-induced SSC was separated from the total SSC of both liquefaction- and shear-induced SSCs by the model, yielding a maximum liquefaction-induced SSC of 1.07 kg·m-3. The simulated maximum proportion of liquefaction-induced SSC was 26.2% in regions with water depths of 6-12 m, with a maximum significant wave height of 3.4 m along the 12 m depth contour. The erosion zone at water depths of 8-12 m was reproduced by the model. Within 52.5 h of the storm, the maximum erosion thickness along the 10 m depth contour was enhanced by 33.9%. The model is applicable in the prediction of liquefaction, and provides a new method to simulate the SSC and seabed erosion influenced by liquefaction. Model results show that liquefaction has significant effects on SSC and seabed erosion in the coastal area with depth of 6-12 m. The validity of this method is confined to certain conditions, including a fully saturated seabed exhibiting homogeneity and isotropic properties, small liquefaction depth, residual liquefaction dominating the development of pore pressures, no influence by structures, and the sediment composed of silt and mud that experiences frequent wave-induced liquefaction.

3.
Arch Virol ; 169(7): 143, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864946

RESUMEN

Potyvirus genomes are expressed as polyproteins that are autocatalytically cleaved to produce 10 to 12 multifunctional proteins, among which P1 is the most variable. It has long been hypothesized that P1 plays role(s) in host adaptation and host specificity. We tested this hypothesis using two phylogenetically distinct potyviruses: soybean mosaic virus (SMV), with a narrow host range, and clover yellow vein virus (ClYVV), with a broader host range. When the full-length P1 cistron of SMV-N was replaced with P1 from ClYVV-No.30, the chimera systemically infected only SMV-N-permissive hosts. Hence, there were no changes in the host range or host specificity of the chimeric viruses. Despite sharing only 20.3% amino acid sequence identity, predicted molecular models of P1 proteins from SMV-N and ClYVV-No.30 showed analogous topologies. These observations suggest that P1 of ClYVV-No.30 can functionally replace P1 of SMV-N. However, the P1 proteins of these two potyviruses are not determinants of host specificity and host range.


Asunto(s)
Especificidad del Huésped , Enfermedades de las Plantas , Potyvirus , Proteínas Virales , Potyvirus/genética , Potyvirus/fisiología , Enfermedades de las Plantas/virología , Proteínas Virales/genética , Proteínas Virales/metabolismo , Glycine max/virología , Nicotiana/virología , Filogenia
4.
PeerJ ; 12: e16692, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38406274

RESUMEN

Background: Acute superior mesenteric venous thrombosis (ASMVT) decreases junction-associated protein expression and intestinal epithelial cell numbers, leading to intestinal epithelial barrier disruption. Pyroptosis has also recently been found to be one of the important causes of mucosal barrier defects. However, the role and mechanism of pyroptosis in ASMVT are not fully understood. Methods: Differentially expressed microRNAs (miRNAs) in the intestinal tissues of ASMVT mice were detected by transcriptome sequencing (RNA-Seq). Gene expression levels were determined by RNA extraction and reverse transcription-quantitative PCR (RT-qPCR). Western blot and immunofluorescence staining analysis were used to analyze protein expression. H&E staining was used to observe the intestinal tissue structure. Cell Counting Kit-8 (CCK-8) and fluorescein isothiocyanate/propidine iodide (FITC/PI) were used to detect cell viability and apoptosis, respectively. Dual-luciferase reporter assays prove that miR-138-5p targets NLRP3. Results: miR-138-5p expression was downregulated in ASMVT-induced intestinal tissues. Inhibition of miR-138-5p promoted NLRP3-related pyroptosis and destroyed tight junctions between IEC-6 cells, ameliorating ASMVT injury. miR-138-5p targeted to downregulate NLRP3. Knockdown of NLRP3 reversed the inhibition of proliferation, apoptosis, and pyroptosis and the decrease in tight junction proteins caused by suppression of miR-138-5p; however, this effect was later inhibited by overexpressing HMGB1. miR-138-5p inhibited pyroptosis, promoted intestinal epithelial tight junctions and alleviated ASMVT injury-induced intestinal barrier disruption via the NLRP3/HMGB1 axis.


Asunto(s)
Proteína HMGB1 , Isquemia Mesentérica , MicroARNs , Trombosis , Animales , Ratones , Enfermedad Aguda , Proteína HMGB1/genética , Venas Mesentéricas/metabolismo , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética
5.
Arch Virol ; 169(3): 46, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38366035

RESUMEN

Ixeris denticulata is a perennial herbal plant with important medical and economic value. In this study, a novel rhabdovirus from I. denticulata with leaf curling and mottle symptoms was identified through next-generation sequencing and molecular cloning approaches. Based on the host species and properties of this virus, it was tentatively named "Ixeris denticulata-associated rhabdovirus" (IdaRV). IdaRV has a negative-sense RNA genome that is 12,705 nucleotides in length and has five open reading frames (ORFs) in the order 3'-nucleoprotein -phosphoprotein -movement protein -matrix protein -large RNA-dependent RNA polymerase-5'. Pairwise sequence comparisons showed that IdaRV had 42.2-53.0% sequence identity to members of the genera Cytorhabdovirus, Varicosavirus, Betanucleorhabdovirus, Gammanucleorhabdovirus, Dichorhavirus, and Alphanucleorhabdovirus in the subfamily Betarhabdovirinae. BLASTp searches indicated that putative products of ORF1, ORF2, ORF3, ORF4, and ORF5 of IdaRV are most closely related to those of rudbeckia virus 1 (RudV1, GenBank accession number ON185810), with 32.1%, 21.3%, 52.4%, 37.6%, and 57.1% amino acid sequence identity, respectively, at the protein level. Phylogenetic analysis showed that IdaRV forms a smaller branch with RudV1, which belongs to the genus Cytorhabdovirus. These results establish IdaRV as a novel rhabdovirus in the genus Cytorhabdovirus of the family Rhabdoviridae.


Asunto(s)
Asteraceae , Rhabdoviridae , Genoma Viral , Filogenia , Genómica , Sistemas de Lectura Abierta , ARN Viral/genética , ARN Viral/metabolismo
6.
Urology ; 187: 1-5, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38373576

RESUMEN

OBJECTIVE: To evaluate the clinical efficacy of a novel negative pressure ureteroscopic lithotripsy (NP-URL) compared to standard ureteroscopic lithotripsy (S-URL) for treating ureteral stones. METHODS: A total of 284 patients diagnosed with ureteral stones and who underwent ureteroscopic lithotripsy between December 2020 and May 2022 at our hospital were included in the study. Among them, 146 cases underwent NP-URL and 138 cases underwent S-URL. The negative pressure device used in NP-URL consists of a 5F ureteric catheter and a tee joint. We evaluated the operative duration, stone-free rate, incidence of postoperative complications, stone retropulsion rate, and adjunct procedure rate between the two groups. RESULTS: The mean operative duration was significantly shorter in the NP-URL group compared to the S-URL group (30.17 ± 5.84 minutes vs 34.84 ± 6.62 minutes; P<.05). Additionally, the NP-URL group had a lower incidence of postoperative fever (1.4% vs 8.7%; P<.05), reduced stone retropulsion rate (3.4% vs 11.6%; P<.05), and a statistically lower rate of adjunct procedures (5.5% vs 14.5%, P<.05). The NP-URL group also demonstrated a higher primary stone-free rate (91.8% vs 81.9%; P<.05). However, there was no significant difference in the final stone-free rate between the NP-URL and S-URL groups (P>.05). CONCLUSION: NP-URL potentially reduces operative duration, significantly decreases the incidence of postoperative complications, and achieves better primary stone-free rates compared to S-URL.


Asunto(s)
Litotricia , Tempo Operativo , Cálculos Ureterales , Ureteroscopía , Humanos , Cálculos Ureterales/terapia , Cálculos Ureterales/cirugía , Ureteroscopía/métodos , Masculino , Femenino , Litotricia/métodos , Litotricia/instrumentación , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
8.
J Sci Food Agric ; 104(10): 5834-5845, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38380967

RESUMEN

BACKGROUND: Hyaluronic acid liquid-core hydrogel beads (HA-LHB) is a good way for oral intake of HA. However, HA may affect the reaction-diffusion of sodium alginate (SA) and Ca2+ leading to poor mechanical properties, since HA is a polyanionic electrolyte having electrostatic effect and a certain spatial site-blocking effect. RESULTS: The mechanical properties of HA-LHB were modified from bathing solution, core solution and secondary calcium bath time. The mechanical properties varied with the SA structure and concentration in bathing solution, where SA with high G (guluronic acid) segment compounded with SA with high M (mannuronic acid) segment at a mass ratio of 7:3 with a 11 g kg-1 concentration showed the best mechanical properties. The secondary calcium bath can greatly improve the mechanical properties due to the tight network formed by bidirectional crosslinking, and 15 min reaction reached the plateau if Ca2+ is sufficient. And the mechanical properties were positively correlated with calcium lactate concentration only at <70 g kg-1 in core solution, but the diffusion of Ca2+ was hindered by the tight gel network at higher concentrations. Moreover, the mechanical properties can be maintained during heat treatment, due to the rearrangement of alginate network structure. CONCLUSION: Our results suggested that the problem of poor mechanical properties of LHB in the presence of high HA concentration can be avoided by process control, which may broaden the development of HA and popping boba market. © 2024 Society of Chemical Industry.


Asunto(s)
Alginatos , Calor , Ácido Hialurónico , Hidrogeles , Ácido Hialurónico/química , Hidrogeles/química , Alginatos/química , Microesferas , Lactatos , Compuestos de Calcio
9.
NPJ Precis Oncol ; 8(1): 43, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388726

RESUMEN

Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.

10.
Microbiol Spectr ; 12(2): e0243623, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38174936

RESUMEN

Fungiidae have shown increased thermal adaptability in coral reef ecosystems under global warming. This study analyzes the evolutionary divergence and microbial communities of Fungiidae in the Sanjiao Reef of the southern South China Sea and explores the impact of coral evolution radiation and microbial dynamics on the heat tolerance of Fungiidae. The results found that Cycloseris was an ancient branch of Fungiidae, dating back approximately 147.8953 Mya, and Fungiidae differentiated into two ancestral clades (clades I and II) before 107.0312 Ma. Fungiidae exhibited specific symbioses with the Cladocopium C27 sub-clade. Notably, the Cladocopium C1 sub-clade has a high relative abundance in clade I, whereas the heat-tolerant Cladocopium C40 and C3u sub-clades subdominante in clade II. Regarding bacterial communities, Cycloseris costulata, the earliest divergent species, had higher bacterial ß-diversity, while the latest divergent species, Lithophyllon scabra, displayed lower bacterial α-diversity and higher community stability. Beneficial bacteria dominante Fungiidae's bacterial community (54%). The co-occurrence network revealed that microbial networks in clade II exhibited lower complexity and greater resilience than those in clade I. Our study highlights that host evolutionary radiation and microbial communities shaped Fungiidae's thermal tolerance. The variability in subdominant Symbiodiniaceae populations may contribute to interspecific differences in thermal tolerance along the evolutionary branches of Fungiidae. The presence of abundant beneficial bacteria may further enhance the thermal ability of the Fungiidae. Furthermore, the later divergent species of Fungiidae have stronger heat tolerance, possibly driven by the increased regulation ability of the host on the bacterial community, greater microbial community stability, and interaction network resistance.IMPORTANCECoral reefs are facing significant threats due to global warming. The heat tolerance of coral holobionts depends on both the coral host and its microbiome. However, the association between coral evolutionary radiation and interspecific differences in microbial communities remains unclear. In this study, we investigated the role of evolutionary radiation and microbial community dynamics in shaping the thermal acclimation potential of Fungiidae in the Sanjiao Reef of the southern South China Sea. The study's results suggest that evolutionary radiation enhances the thermal tolerance of Fungiidae. Fungiidae species that have diverged more recently have exhibited a higher presence of heat-tolerant Symbiodiniaceae taxa, more stable bacterial communities, and a robust and resilient microbial interaction network, improving the thermal adaptability of Fungiidae. In summary, this study provides new insights into the thermal adaptation patterns of corals under global warming conditions.


Asunto(s)
Antozoos , Dinoflagelados , Microbiota , Animales , Antozoos/microbiología , Antozoos/fisiología , Arrecifes de Coral , Aclimatación , Bacterias , China , Dinoflagelados/fisiología
11.
AJNR Am J Neuroradiol ; 44(12): 1464-1470, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38081676

RESUMEN

BACKGROUND AND PURPOSE: Conventional MR imaging is not sufficient to discern the H3 K27-altered status of spinal cord diffuse midline glioma. This study aimed to develop a radiomics-based model based on preoperative T2WI to determine the H3 K27-altered status of spinal cord diffuse midline glioma. MATERIALS AND METHODS: Ninety-seven patients with confirmed spinal cord diffuse midline gliomas were retrospectively recruited and randomly assigned to the training (n = 67) and test (n = 30) sets. One hundred seven radiomics features were initially extracted from automatically-segmented tumors on T2WI, then 11 features selected by the Pearson correlation coefficient and the Kruskal-Wallis test were used to train and test a logistic regression model for predicting the H3 K27-altered status. Sensitivity analysis was performed using additional random splits of the training and test sets, as well as applying other classifiers for comparison. The performance of the model was evaluated through its accuracy, sensitivity, specificity, and area under the curve. Finally, a prospective set including 28 patients with spinal cord diffuse midline gliomas was used to validate the logistic regression model independently. RESULTS: The logistic regression model accurately predicted the H3 K27-altered status with accuracies of 0.833 and 0.786, sensitivities of 0.813 and 0.750, specificities of 0.857 and 0.833, and areas under the curve of 0.839 and 0.818 in the test and prospective sets, respectively. Sensitivity analysis confirmed the robustness of the model, with predictive accuracies of 0.767-0.833. CONCLUSIONS: Radiomics signatures based on preoperative T2WI could accurately predict the H3 K27-altered status of spinal cord diffuse midline glioma, providing potential benefits for clinical management.


Asunto(s)
Glioma , Humanos , Glioma/diagnóstico por imagen , Glioma/patología , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Estudios Retrospectivos , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología
12.
Sci Rep ; 13(1): 22972, 2023 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-38151518

RESUMEN

This study aims to evaluate the therapeutic efficacy of a novel double-sheath negative-pressure minimally invasive percutaneous nephrolithotomy (D-mPCNL) compared to conventional minimally invasive percutaneous nephrolithotomy (C-mPCNL) for large kidney stones. A total of 132 patients diagnosed with large kidney stones in our hospital were included in the study. Among them, sixty-eight patients underwent D-mPCNL, while sixty-four underwent C-mPCNL. Parameters such as operative duration, stone-free rate, incidence of postoperative complications, and the need for auxiliary procedures were evaluated between the two groups. Compared to the C-mPCNL group, the D-mPCNL group demonstrated a significantly shorter operative time (41.97 ± 8.24 min vs. 52.30 ± 13.72 min; P < 0.000), lower rates of auxiliary procedures (5.9% vs. 17.2%; P = 0.041), and lower fever rates (2.9% vs. 14.1%; P = 0.021). The group also had a significantly higher primary stone-free rate (85.3% vs. 70.3%; P = 0.038). However, there were no statistically significant advantages in terms of the final stone-free rate, hemoglobin drops, and stone composition in the D-mPCNL group (P > 0.05). D-mPCNL is a novel surgical method that is safe and effective, reducing operative time, improving stone-free efficiency, and decreasing postoperative complications.


Asunto(s)
Cálculos Renales , Nefrolitotomía Percutánea , Humanos , Nefrolitotomía Percutánea/efectos adversos , Nefrolitotomía Percutánea/métodos , Resultado del Tratamiento , Tiempo de Internación , Cálculos Renales/cirugía , Cálculos Renales/complicaciones , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología
13.
Clin Epigenetics ; 15(1): 175, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37919786

RESUMEN

BACKGROUND: Huazhuo Tiaozhi granule (HTG) is a herbal medicine formula widely used in clinical practice for hypolipidaemic effects. However, the molecular mechanisms underlying dyslipidaemia treatment have not been well elucidated. RESULTS: A significant reduction in the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) was observed in the serum of patients with dyslipidaemia after HTG treatment, without disruption in the levels of aspartate transaminase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine (Cr). The dyslipidaemia rat model was induced by a high-fat diet and treated with Xuezhikang (0.14 g/kg/d) or HTG (9.33 g crude herb/kg/day) by gavage for 8 weeks. Body weight and liver index were markedly decreased in dyslipidaemic rats after treatment with Xuezhikang or HTG. HTG administration markedly ameliorated hyperlipidaemia by decreasing the levels of TC and LDL-C in serum and hepatic lipid accumulation. In vitro, lipid accumulation in LO2 and HepG2 cells was alleviated by serum treatment with HTG. High lactylation was observed in 198 proteins, including lactylation of histone H2B (K6), H4 (K80). Deep sequencing of microRNAs showed that miR-155-5p was significantly downregulated. CONCLUSIONS: This study demonstrates that HTG is an effective and safe formula for treating dyslipidaemia, which promotes lactylation in hepatocytes, and the retardation of miR-155-5p biogenesis.


Asunto(s)
Hiperlipidemias , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratas , Animales , Histonas/metabolismo , LDL-Colesterol/metabolismo , Ratas Sprague-Dawley , Metilación de ADN , Hígado , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Dieta Alta en Grasa/efectos adversos
14.
ACS Appl Mater Interfaces ; 15(37): 43953-43962, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37682728

RESUMEN

The rational design of high-efficiency, low-cost electrocatalysts for electrochemical water oxidation in alkaline media remains a huge challenge. Herein, combined strategies of metal doping and vacancy engineering are employed to develop unique Mo-doped cobalt oxide nanosheet arrays. The Mo dopants exist in the form of high-valence Mo6+, and the doping amount has a significant effect on the structure morphology, which transforms from 1D nanowires/nanobelts to 2D nanosheets and finally 3D nanoflowers. In addition, the introduction of vast oxygen vacancies helps to modulate the electronic states and increase the electronic conductivity. The optimal catalyst MoCoO-3 exhibits greatly increased active sites and enhanced reaction kinetics. It gives a dramatically lower overpotential at 50 mA cm-2 (288 mV), much smaller than that of the undoped counterpart (418 mV) and comparable to those of the recently reported electrocatalysts. Density functional theory results further verify that the increased electronic conductivity and optimized adsorption energy toward oxygen evolution reaction intermediates are mainly responsible for the enhanced catalytic activity. Moreover, the assembled two-electrode electrolyzer (MoCoO-3||Pt/C) exhibits superior performance with the cell potential decreased by 233 mV to reach a current density of 50 mA cm-2 with respect to the benchmark counterpart catalysts (RuO2||Pt/C). This work might contribute to the rational design of effective, low-cost electrocatalyst materials by combining multiple strategies.

15.
Oncol Res ; 31(6): 917-927, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37744266

RESUMEN

Glioblastoma (GBM) is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy. Clarification of molecular mechanisms of GBM's characteristic invasive growth is urgently needed to improve the poor prognosis. Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor (CHRM3) were significantly higher in the recurrent samples than in the primary samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis, consistent with The Cancer Genome Atlas database. Knockdown of CHRM3 inhibited GBM cell growth and invasion. An assay of orthotopic GBM animal model in vivo indicated that inhibition of CHRM3 significantly suppressed GBM progression with prolonged survival time. Transcriptome analysis revealed that CHRM3 knockdown significantly reduced an array of classic factors involved in cancer invasive growth, including MMP1/MMP3/MMP10/MMP12 and CXCL1/CXCL5/CXCL8. Taken together, CHRM3 is a novel and vital factor of GBM progression via regulation of multiple oncogenic genes and may serve as a new biomarker for prognosis and therapy of GBM patients.


Asunto(s)
Glioblastoma , Animales , Humanos , Glioblastoma/genética , Pronóstico , Recurrencia Local de Neoplasia , Acetilcolina , Ciclo Celular , Receptor Muscarínico M3
17.
Nat Commun ; 14(1): 4062, 2023 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-37429858

RESUMEN

Temozolomide (TMZ) therapy offers minimal clinical benefits in patients with glioblastoma multiforme (GBM) with high EGFR activity, underscoring the need for effective combination therapy. Here, we show that tonicity-responsive enhancer binding protein (NFAT5) lysine methylation, is a determinant of TMZ response. Mechanistically, EGFR activation induces phosphorylated EZH2 (Ser21) binding and triggers NFAT5 methylation at K668. Methylation prevents NFAT5 cytoplasm interaction with E3 ligase TRAF6, thus blocks NFAT5 lysosomal degradation and cytosol localization restriction, which was mediated by TRAF6 induced K63-linked ubiquitination, resulting in NFAT5 protein stabilization, nuclear accumulation and activation. Methylated NFAT5 leads to the upregulation of MGMT, a transcriptional target of NFAT5, which is responsible for unfavorable TMZ response. Inhibition of NFAT5 K668 methylation improved TMZ efficacy in orthotopic xenografts and patient-derived xenografts (PDX) models. Notably, NFAT5 K668 methylation levels are elevated in TMZ-refractory specimens and confer poor prognosis. Our findings suggest targeting NFAT5 methylation is a promising therapeutic strategy to improve TMZ response in tumors with EGFR activation.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Temozolomida/farmacología , Temozolomida/uso terapéutico , Lisina , Metilación , Factor 6 Asociado a Receptor de TNF , Factores de Transcripción NFATC , Receptores ErbB/genética , Factores de Transcripción/genética
18.
J Clin Neurosci ; 113: 77-85, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37224612

RESUMEN

BACKGROUND: Syringo-subarachnoid shunt (SSS) is often considered a rescue procedure or a second-line treatment option for syringomyelia. However, the clinical efficacy of SSS in treating this condition remains controversial. OBJECTIVE: To evaluate the long-term outcome of the SSS and its relationship with the syrinx area, as well as to investigate the factors that influence the prognosis. METHODS: This retrospective study included twenty-seven consecutive patients who underwent SSS between 2014 and 2020. The study evaluated several independent variables such as age, sex, duration of progressive symptoms, morphological characteristics of the syrinx, changes in the syrinx area, and Chiari malformation. The long-term follow-up (>2 years) Japanese Orthopaedic Association (JOA) score was used to assess neurological function and outcome. Statistical analysis was performed using a stepwise logistic regression test. RESULTS: All patients were followed up for an average of 48.6 ± 14.8(26.8 to 78.0) months. Follow-up magnetic resonance imaging showed syrinx collapse to different degrees occurred in 96.3% (26 of 27) patients. The JOA score was improvedinonly6patients (22.2%), remained stable in 5 patients (18.5%),and deteriorated in 16 patients(59.3%).A logistic regression test showed that the tension syrinx (odds ratio 0.111) and early shunting intervention (odds ratio 0.138) were favorable independent prognostic factors. CONCLUSIONS: It is important to note that the shrinkage of the syrinx does not necessarily translate to an improvement in clinical outcomes. Therefore, the decision to perform SSS should be made with caution and considered as a last resort.


Asunto(s)
Malformación de Arnold-Chiari , Anomalías Cardiovasculares , Siringomielia , Humanos , Siringomielia/diagnóstico por imagen , Siringomielia/cirugía , Pronóstico , Estudios Retrospectivos , Derivaciones del Líquido Cefalorraquídeo/métodos , Malformación de Arnold-Chiari/complicaciones , Malformación de Arnold-Chiari/diagnóstico por imagen , Malformación de Arnold-Chiari/cirugía , Imagen por Resonancia Magnética/métodos , Resultado del Tratamiento
19.
Heliyon ; 9(4): e14627, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37064435

RESUMEN

Coronavirus disease 2019 (COVID-19) remains a public health emergency of international concern, and some countries still implement strict regional lockdowns. Further, the upcoming 2023 Asian Games and World University Games will implement a closed-loop management system. Quarantine can harm mental and physical health, to which adolescents are more vulnerable compared with adults. Previous studies indicated that light can affect our psychology and physiology, and adolescents were exposed to the artificial light environment in the evening during the lockdown. Thus, this study aimed to establish and assess appropriate residential light environments to mitigate the effects of lockdowns on sleep quality and fatigue in adolescents. The participants were 66 adolescents (12.15 ± 2.45 years of age) in a closed-loop management environment, who participated in a 28-day (7-day baseline, 21-day light intervention) randomized controlled trial of a light-emitting diode (LED) light intervention. The adolescents were exposed to different correlated color temperature (CCT) LED light environments (2000 K or 8000 K) for 1 h each evening. The results for self-reported daily sleep quality indicated that the low CCT LED light environment significantly improved sleep quality (p < 0.05), and the blood test results for serum urea and hemoglobin indicated that this environment also significantly reduced fatigue (p < 0.05) and moderately increased performance, compared to the high CCT LED light environment. These findings can serve as a springboard for further research that aims to develop interventions to reduce the effects of public health emergency lockdowns on mental and physical health in adolescents, and provide a reference for participants in the upcoming Asian Games and World University Games.

20.
RSC Adv ; 13(18): 12355-12360, 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37091597

RESUMEN

Accurate determination of gold in geological samples is an important prerequisite and guarantee for studying geological problems. There are many methods for digestion and enrichment of gold among which polyurethane foam (PUF) enrichment after aqua regia digestion is the most commonly used in the experiments. A new method to help the relief of gold from the PUF was put forward in this study, and it was applied to four certified reference materials (CRMs) together with three previously used methods, and the optimal extraction and enrichment conditions were determined through experiments. The four methods were compared by meta-analysis, and the thiourea liberation method was superior to the other three methods because of its simple operation and high accuracy. Out of consideration for the incomplete adsorption of gold in the solution by only one piece of PUF, repetitive adsorption of gold with a second and a third piece of PUF in the solution was proposed in this study. Results show that the gold content obtained by secondary and tertiary adsorption accounts for 11.03% of the total content, and the highest can reach 20.74%. When the third adsorption was carried out, the gold content in several samples was below the detection limit. Therefore, repeated adsorption of gold in the solution is necessary, and three times of adsorption is necessary.

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