Ubiquitin-specific protease 54 regulates GLUT1-mediated aerobic glycolysis to inhibit lung adenocarcinoma progression by modifying p53 degradation.

Lung adenocarcinoma (LUAD) is one of the most prevalent types of cancer. Ubiquitination is crucial in modulating cell proliferation and aerobic glycolysis in cancer. The frequency of TP53 mutations in LUAD is approximately 50%. Currently, therapeutic targets for wild-type (WT) p53-expressing LUAD are limited. In the present study, we systemically explored the expression of ubiquitin-specific protease genes using public datasets. Then, we focused on ubiquitin-specific protease 54 (USP54), and explored its prognostic significance in LUAD patients using public datasets, analyses, and an independent cohort from our center. We found that the expression of USP54 was lower in LUAD tissues compared with that in the paracancerous tissues. Low USP54 expression levels were linked to a malignant phenotype and worse survival in patients with LUAD. The results of functional experiments revealed that up-regulation of USP54 suppressed LUAD cell proliferation in vivo and in vitro. USP54 directly interacted with p53 protein and the levels of ubiquitinated p53 were inversely related to USP54 levels, consistent with a role of USP54 in deubiquitinating p53 in p53-WT LUAD cells. Moreover, up-regulation of the USP54 expression inhibited aerobic glycolysis in LUAD cells. Importantly, we confirmed that USP54 inhibited aerobic glycolysis and the growth of tumor cells by a p53-mediated decrease in glucose transporter 1 (GLUT1) expression in p53-WT LUAD cells. Altogether, we determined a novel mechanism of survival in the p53-WT LUAD cells to endure the malnourished tumor microenvironment and provided insights into the role of USP54 in the adaptation of p53-WT LUAD cells to metabolic stress.

Squalene Epoxidase: Its Regulations and Links with Cancers.

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate-cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate-cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.

Systemic Analyses of Cuproptosis-Related lncRNAs in Pancreatic Adenocarcinoma, with a Focus on the Molecular Mechanism of LINC00853.

Pancreatic cancer (PC) is a deadly malignant digestive tumor with poor prognoses and a lack of effective treatment options. Cuproptosis, a recently identified copper-dependent programmed cell death type, has been implicated in multiple cancers. Long non-coding RNAs (lncRNAs) are also linked to the progression of PC. However, the role and prognostic values of cuproptosis-related lncRNAs in pancreatic adenocarcinoma (PAAD) remain unclear. In this study, we systemically analyzed the differential expressions and prognostic values of 672 cuproptosis-related lncRNAs in PAAD. Based on this, a prognostic signature including four lncRNAs (LINC00853, AC099850.3, AC010719.1, and AC006504.7) was constructed and was able to divide PAAD patients into high- and low-risk groups with significantly different prognoses. Next, we focused on lncRNA LINC00853. The differential expressions of LINC00853 between normal tissue and PAAD samples were validated by qRT-PCR. LINC00853 was knocked down by siRNA in PC cell lines BxPC-3 and PANC-1 and the oncogenic role of LINC00853 was validated by CCK8, colony formation, and EdU assays. Subsequently, LINC00853 knockdown cells were subjected to tumor xenograft tests and exhibited decreased tumor growth in nude mice. Mechanistically, knockdown of LINC00853 significantly reduced cellular glycolysis and enhanced cellular mitochondrial respiration levels in PC cells. Moreover, knockdown of LINC00853 decreased the protein level of a glycolytic kinase PFKFB3. Finally, glycolysis tests and functional tests using LINC00853 and HA-PFKFB3 indicated that the effects of LINC00853 on glycolysis and cell proliferation were mediated by PFKFB3. In conclusion, our systemic analyses have highlighted the important roles of cuproptosis-related lncRNAs in PAAD while the prognostic signature based on them showed excellent performance in PAAD patients and is expected to provide clinical guidance for individualized treatment. In addition, our findings provide a novel mechanism by which the LINC00853-PFKFB3 axis critically regulates aerobic glycolysis and cell proliferation in PC cells.

Enhanced Ammonia Decomposition by Tuning the Support Properties of Ni/GdxCe1-xO2-δ at 600 °C.

Ammonia decomposition is a promising method to produce high-purity hydrogen. However, this process typically requires precious metals (such as Ru, Pt, etc.) as catalysts to ensure high efficiency at relatively low temperatures. In this study, we propose using several Ni/GdxCe1-xO2-δ catalysts to improve ammonia decomposition performance by adjusting the support properties. We also investigate the underlying mechanism for this enhanced performance. Our results show that Ni/Ce0.8Gd0.2O2-δ at 600 °C can achieve nearly complete ammonia decomposition, resulting in a hydrogen production rate of 2008.9 mmol.g-1.h-1 with minimal decrease over 150 h. Density functional theory calculations reveal that the recombinative desorption of nitrogen is the rate-limiting step of ammonia decomposition over Ni. Our characterizations indicate that Ni/Ce0.8Gd0.2O2-δ exhibits a high concentration of oxygen vacancies, highly dispersed Ni on the surface, and abundant strong basic sites. These properties significantly enhance the associative desorption of N and strengthen the metal support interactions, resulting in high catalytic activity and stability. We anticipate that the mechanism could be applied to designing additional catalysts with high ammonia decomposition performance at relatively low temperatures.

Functional exercise capacity in sedentary college students / Capacidade de exercício físico funcional em estudantes universitários sedentários / Capacidad de ejercicio físico funcional en estudiantes universitarios sedentarios

ABSTRACT Introduction The functional training method has been widely adopted as core training by national and foreign sports teams, due to the good results achieved in improving physical fitness and sports skills. However, there are still gaps about its intervention in sedentary students. Objective Explore the effect of physical function training on exercise capacity in sedentary college students. Methods Volunteer students randomly assigned to experimental and control groups were selected from 120 non-sport majors. Before the formal experiment, the physical indicators of the two groups of college students were measured and recorded. After the experiment, the physical indicators of the two groups of college students were measured and recorded again, and these data were statistically analyzed and discussed. Results After 12 weeks of training under the prescribed intervention protocol, the test scores of the two groups of subjects in functional movement screening were elevated. It is concluded that there is no significant difference between traditional physical training and functional training on height, weight and body mass index of sedentary college students. Conclusion Functional training can improve the physical quality of college students, improve their ability to exercise and play an active role in preventing sports injuries, representing no statistical difference for those who practice it sporadically. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O método de treinamento funcional tem sido vastamente adotado como treinamento principal por equipes esportivas nacionais e estrangeiras, devido aos bons resultados alcançados na melhoria da aptidão física e das habilidades esportivas. Contudo, ainda há lacunas sobre a sua intervenção em estudantes sedentários. Objetivo Explorar o efeito do treinamento da função física na capacidade de exercício físico em estudantes universitários sedentários. Métodos Foram selecionados entre 120 disciplinas não esportivas, alunos voluntários designados aleatoriamente para grupos experimental e controle. Antes do experimento formal, os indicadores físicos dos dois grupos de estudantes universitários foram mensurados e registrados. Após o experimento, os indicadores físicos dos dois grupos de estudantes universitários foram medidos e registrados novamente, sendo esses dados analisados estatisticamente e discutidos. Resultados Após 12 semanas de treinamento sob o protocolo de intervenção prescrito, os resultados dos testes dos dois grupos de sujeitos em triagem de movimento funcional foram elevados. Conclui-se que não há diferença significativa entre o treinamento físico tradicional e o treinamento funcional sobre a altura, peso e índice de massa corporal dos estudantes universitários sedentários. Conclusão O treinamento funcional pode melhorar a qualidade física dos estudantes universitários, melhorar sua capacidade de exercício físico e desempenhar um papel ativo na prevenção de lesões esportivas, não representando diferenças estatísticas para aqueles que o praticam esporadicamente. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El método de entrenamiento funcional ha sido ampliamente adoptado como entrenamiento principal por equipos deportivos nacionales y extranjeros, debido a los buenos resultados obtenidos en la mejora de la forma física y las habilidades deportivas. Sin embargo, aún existen lagunas sobre su intervención en estudiantes sedentarios. Objetivo Explorar el efecto del entrenamiento de la función física sobre la capacidad de ejercicio en estudiantes universitarios sedentarios. Métodos Se seleccionaron estudiantes voluntarios asignados aleatoriamente a los grupos experimental y de control entre 120 sujetos no deportistas. Antes del experimento formal, se midieron y registraron los indicadores físicos de los dos grupos de estudiantes universitarios. Tras el experimento, se volvieron a medir y registrar los indicadores físicos de los dos grupos de universitarios, y estos datos se analizaron y discutieron estadísticamente. Resultados Tras 12 semanas de entrenamiento según el protocolo de intervención prescrito, las puntuaciones de los dos grupos de sujetos en las pruebas de detección de movimientos funcionales fueron elevadas. Se concluye que no hay diferencias significativas entre el entrenamiento físico tradicional y el entrenamiento funcional sobre la altura, el peso y el índice de masa corporal de los estudiantes universitarios sedentarios. Conclusión El entrenamiento funcional puede mejorar la calidad física de los estudiantes universitarios, mejorar su capacidad de ejercicio y desempeñar un papel activo en la prevención de lesiones deportivas, sin representar ninguna diferencia estadística para los que lo practican esporádicamente. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review.

Thyroid Hürthle cell carcinoma, known as thyroid eosinophilic carcinoma, is a rare pathological type of differentiated thyroid cancer (DTC), representing 3-4% of all thyroid cancers. However, given the high risk of invasion and metastasis, thyroid Hürthle cell carcinoma has a relatively poor prognosis. Traditional treatment methods have limited effects on patients with metastatic thyroid cancers. Developing a valuable therapy for advanced thyroid carcinomas is an unfilled need, and immunotherapy could represent another choice for these tumors. We herein reported the case of a patient with recurrent advanced thyroid Hürthle cell cancer and positive programmed death-ligand 1 (PD-L1) expression, who suffered tumor progression after re-surgery, radiotherapy, and targeted therapy. It is encouraging that PD-1 inhibitors in combination with GM-CSF and stereotactic body irradiation (SBRT) on metastatic disease have a significant anti-tumor effect.

Survival Analysis of Radiation Therapy in Ovarian Cancer: A SEER Database Analysis.

RESULTS: A total of 20031 ovarian cancer patients were included, with 291 (1.45%) patients who received radiotherapy. The median overall survival (OS) in patients who received radiotherapy was shorter than which in patients without radiotherapy (23 vs. 75 months, P < 0.001). The Elderly, nonepithelial pathology, advanced American Joint Committee on Cancer (AJCC) stage, elevated level of CA125, and receiving radiotherapy were risk predictors to survival in both multivariable analyses before and after PSM. Among 11872 patients with III/IV stage, the radiotherapy group also showed a significantly worse prognosis (median OS: 19 vs. 44 months in patients without radiotherapy, P < 0.001). Consistent results were observed in stratification analyses on pathology and stage among patients with III/IV stage. CONCLUSIONS: For patients with ovarian cancer, radiotherapy was associated with a poor prognosis regardless of pathology or stage. Considering this is a retrospective study, future studies concerning radiotherapy combination with other new agents in ovarian cancer are needed.

Highly Active AuCu-Based Catalysts for Acetylene Hydrochlorination Prepared Using Organic Aqua Regia.

Development of a sustainable process for designing and synthesising an active and stable catalyst for hydrochlorination of acetylene is challenging, yet crucial, for industrial vinyl chloride monomer (VCM) production. Herein, direct synthesis of bimetallic AuCu catalysts using organic aqua regia (OAR) preparation methods was investigated. In comparison with conventional aqua regia (AR), bimetallic AuCu catalysts synthesised from OAR exhibit enhanced activity and stability. After careful characterisation of the catalyst samples using X-ray diffraction patterns (XRD), Scanning transmission electron microscopy (STEM), X-ray photoelectron spectroscopy (XPS), and Temperature-programmed desorption (TPD), this observation was justified for the following reasons: 1) the existence of sulphur and nitrogen atoms stabilised the cationic Au active sites, and 2) OAR helped to sustain the function of the Cu promotor by stabilising it. Advanced understanding on the importance of promoter stability has unveiled new perspectives for this research area.

Design strategies for the development of a Pd-based acetylene hydrochlorination catalyst: improvement of catalyst stability by nitrogen-containing ligands.

Acetylene hydrochlorination is an attractive chemical reaction for the manufacture of polyvinyl chloride (PVC), and the development efforts are focused on the search for non-mercury catalyst systems. Supported Pd-based catalysts have relatively high activity in the catalytic hydrochlorination of acetylene but are still deactivated rather quickly. Herein, we demonstrated that the atomically dispersed (NH4)2PdCl4 complex, distributed on activated carbon, enabled the highly active and stable production of the vinyl chloride monomer (VCM) through acetylene hydrochlorination under low temperature conditions. We found that the presence of nitrogen-containing ligands in the structure of the active center could remarkably improve the stability of the Pd-based catalysts when compared with the case of the conventional PdCl2 catalyst. Further analyses via X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and temperature-programmed reduction (TPR) show that the variations in the Pd dispersion, chemical state and reduction property are caused by the nitrogen-containing ligands. Temperature-programmed desorption (TPD) characterizations illustrated that the N-containing ligands over the (NH4)2PdCl4/AC catalyst might enhance the adsorption of HCl. These findings suggest that in addition to strategies that target the doping modification of support materials, optimization of the structure of the active center complexes provides a new path for the design of highly active and stable Pd-based catalysts.

Insight into the dispersion behavior of 1-butyl-3-methylimiazolium chloride confined in nanoscale pores of carbon materials.

It is important to understand the behaviour of ionic liquids (ILs) in nanoscale pores, as application of supported ionic liquid phase (SILP) materials has attracted much attention. The main intention of this investigation is to study the dispersion performance of ionic liquid on activated carbons with different surface oxygen groups. Several active carbons with diverse oxygenated surface groups were obtained by oxidation and reduction methods. All samples were impregnated with [Bmim]Cl at different loadings. The blocked porosity of ionic liquid on SILP materials mainly depends on the amount of ionic liquid and surface oxygen content. In addition, stability of the supported IL in water was tested by analyzing the leached amount of IL. We found that the supported IL is not easily leached from the interface of carbon with low amount of surface oxygen. This may be due to the high free π-electron density of oxygen-free supports, forming more CH-π bonds with H atoms at the C2 position of the acidic cation. In addition, we propose that dispersion of ionic liquid in the pores depends on the density of surface free π-electrons of carbon materials.

[Studies on the chemical constituents of Epimedium brevicornum].

OBJECTIVE: To study the chemical constituents of Epimedium breviconum. METHODS: Compounds were purificated with various chromatographic techniques such as silica vacuum liquid chromatography and Sephadex LH-20 column chromatography. Their structures were elucidated by physico-chemical methods and spectral analysis. RESULTS: Ten compounds were obtained and indentified as (7R, 8S) 4,9-dihydroxyl-3,3'-dimethyoxyl-7, 8-dihydrobenzofunan-1'-propanolneolignan-9'-O-alpha-L-rhamnopyranoside (1), (7R, 8S, 8' R) 4, 4', 8', 9-tetrahydroxyl-3, 3'-dimethyoxyl-7, 9'-monoepoxylignan (2), (+)-cycloolivil (3), (3, 5, 7, 4')-tetrahydroxyl-8-isopentene group flavonoids-3-O-alpha-L-rhamnopyranoside (4), beta-sitosterol (5), p-hydroxybenzaldehyde (6), succinic acid (7) and p-hydroxyphenethyl (8). CONCLUSIONS: Compound 1 is isolated from this genus for the first time. Compounds 2,3,5 -8 are isolated from the plant for the first time.

[Determination of 5-hydroxymethyl furfuraldehyde in different processed products of polygonatum].

OBJECTIVE: By finding the changing regularity of 5-Hydroxymethyl furfuraldehyde (5-HMF) content in Polygonatum for different time, this provides basis for the technology of processing Polygonatum and quality standards of its prepared pieces. METHODS: The testing solution was acquired by ultrasonic extraction, HPLC was used to determine the contents. The chromatographic conditions: Agilent HC-C18 column (5 microm, 250 mm x 4.6 mm). The mobile phase: methanol-water (15:85) at the flow rate of 1 ml/min. The determination wave length was 284 nm. RESULTS: All kinds of processed Polygonatum had 5-Hydroxymethyl furfuraldethyde in different degrees, contents in Polygonatum kept relatively stable before 30 hours, but contents rose rapidly after 30 hours, contents decreased as continuing heating. CONCLUSION: The result can provide useful references to quality control and standard porcessing condition of Polygonatum.