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Background: As a heterogeneous malignancy, breast cancer (BRCA) shows high incidence and mortality. Discovering novel molecular markers and developing reliable prognostic models may improve the survival of BCRA. Methods: The RNA-seq data of BRCA patients were collected from the training set The Cancer Genome Atlas (TCGA)-BRCA and validation set GSE20685 in the Gene Expression Omnibus (GEO) databases. The "GSVA" R package was used to calculate the glycolysis score for each patient, based on which all the patients were divided into different glycolysis groups. The "limma" package was employed to perform differentially expression genes (DEGs) analysis. Key signature genes were selected by performing un/multivariate and least absolute shrinkage and selection operator (LASSO) C regression and used to develop a RiskScore model. The ESTIMATE and MCP-Counter algorithms were used for quantifying immune infiltration level. The functions of the genes were validated using Western blot, colony formation, transwell and wound-healing assay. Results: The glycolysis score and prognostic analysis showed that high glycolysis score was related to tumorigenesis pathway and a poor prognosis in BRCA as overactive glycolysis inhibited the normal functions of immune cells. Subsequently, we screened five key prognostic genes using the LASSO Cox regression analysis and used them to establish a RiskScore with a high classification efficiency. Based on the results of the RiskScore, it was found that patients in the high-risk group had significantly unfavorable immune infiltration and prognostic outcomes. A nomogram integrating the RiskScore could well predict the prognosis for BRCA patients. Knockdown of PSCA suppressed cell proliferation, invasion and migration of BRCA cells. Conclusion: This study developed a glycolysis-related signature with five genes to distinguish between high-risk and low-risk BRCA patients. A nomogram developed on the basis of the RiskScore was reliable to predict BRCA survival. Our model provided clinical guidance for the treatment of BRCA patients.
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Neoplasias da Mama , Glicólise , Humanos , Glicólise/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Perfilação da Expressão GênicaRESUMO
The increasing global phenomenon of soil salinization has prompted heightened interest in the physiological ecology of plant salt and alkali tolerance. Halostachys caspica belonging to Amaranthaceae, an exceptionally salt-tolerant halophyte, is widely distributed in the arid and saline-alkali regions of Xinjiang, in Northwest China. Soil salinization and alkalinization frequently co-occur in nature, but very few studies focus on the interactive effects of various salt and alkali stress on plants. In this study, the impacts on the H. caspica seed germination, germination recovery and seedling growth were investigated under the salt and alkali stress. The results showed that the seed germination percentage was not significantly reduced at low salinity at pH 5.30-9.60, but decreased with elevated salt concentration and pH. Immediately after, salt was removed, ungerminated seeds under high salt concentration treatment exhibited a higher recovery germination percentage, indicating seed germination of H. caspica was inhibited under the condition of high salt-alkali stress. Stepwise regression analysis indicated that, at the same salt concentrations, alkaline salts exerted a more severe inhibition on seed germination, compared to neutral salts. The detrimental effects of salinity or high pH alone were less serious than their combination. Salt concentration, pH value, and their interactions had inhibitory effects on seed germination, with salinity being the decisive factor, while pH played a secondary role in salt-alkali mixed stress.
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Álcalis , Amaranthaceae , Germinação , Plantas Tolerantes a Sal , Sementes , Germinação/efeitos dos fármacos , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Amaranthaceae/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Salinidade , Estresse Fisiológico , Cloreto de Sódio/farmacologia , Estresse Salino , Tolerância ao SalRESUMO
Photocatalytic coupling of methane to ethane and ethylene (C2 compounds) offers a promising approach to utilizing the abundant methane resource. However, the state-of-the-art photocatalysts usually suffer from very limited C2 formation rates. Here, we report our discovery that the anatase TiO2 nanocrystals mainly exposing {101} facets, which are generally considered less active in photocatalysis, demonstrate surprisingly better performances than those exposing the high-energy {001} facet. The palladium co-catalyst plays a pivotal role and the Pd2+ site on co-catalyst accounts for the selective C2 formation. We unveil that the anatase {101} facet favors the formation of hydroxyl radicals in aqueous phase near the surface, where they activate methane molecules into methyl radicals, and the Pd2+ site participates in facilitating the adsorption and coupling of methyl radicals. This work provides a strategy to design efficient nanocatalysts for selective photocatalytic methane coupling by reaction-space separation to optimize heterogeneous-homogeneous reactions at solid-liquid interfaces.
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Microcystin-LR (MC-LR) and sodium nitrite (NaNO2) co-exist in the environment and are hepatotoxic. The liver has the function of lipid metabolism, but the impacts and mechanisms of MC-LR and NaNO2 on liver lipid metabolism are unclear. Therefore, we established a chronic exposure model of Balb/c mice and used LO2 cells for in vitro verification to investigate the effects and mechanisms of liver lipid metabolism caused by MC-LR and NaNO2. The results showed that after 6 months of exposure to MC-LR and NaNO2, the lipid droplets content was increased, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were raised in the liver (P < 0.05). Moreover, MC-LR and NaNO2 synergistically induced hepatic oxidative stress by decreasing total superoxide dismutase (T-SOD) activity and glutathione (GSH) levels and increasing malondialdehyde (MDA) content levels. In addition, the levels of Nrf2, HO-1, NQO1 and P-AMPK was decreased and Keap1 was increased in the Nrf2/HO-1 pathway. The key factors of lipid metabolism, SREBP-1c, FASN and ACC, were up-regulated in the liver. More importantly, there was a combined effect on lipid deposition of MC-LR and NaNO2 co-exposure. In vitro experiments, MC-LR and NaNO2-induced lipid deposition and changes in lipid metabolism-related changes were mitigated after activation of the Nrf2/HO-1 signaling pathway by the Nrf2 activator tertiary butylhydroquinone (TBHQ). Additionally, TBHQ alleviated the rise of reactive oxygen species (ROS) in LO2 cells induced by MC-LR and NaNO2. Overall, our findings indicated that MC-LR and NaNO2 can cause abnormal liver lipid metabolism, and the combined effects were observed after MC-LR and NaNO2 co-exposure. The Nrf2/HO-1 signal pathway may be a potential target for prevention and control of liver toxicity caused by MC-LR and NaNO2.
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Metabolismo dos Lipídeos , Fígado , Toxinas Marinhas , Camundongos Endogâmicos BALB C , Microcistinas , Nitrito de Sódio , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Microcistinas/toxicidade , Fígado/metabolismo , Fígado/efeitos dos fármacos , Camundongos , Nitrito de Sódio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Masculino , Linhagem CelularRESUMO
Microcystins (MCs) and nitrites are coexisted in the environment and have reproductive toxicity. The combined toxic effect and mechanism of MCs and nitrite on spermatogenesis remain largely unclear. In the present study, co-exposure to microcystin-leucine arginine (MC-LR) and sodium nitrite (NaNO2) aggravated testicular damage of Balb/c mice and mitochondrial impairment of spermatogonia, Sertoli cells, and sperm. Furthermore, MC-LR and NaNO2 reduced sperm density with a synergistic effect. In addition, MC-LR and NaNO2 synergistically induced oxidative stress in the reproductive system by decreasing superoxide dismutase (SOD) activity and glutathione (GSH) levels and increasing levels of mitochondrial reactive oxygen species (mtROS) and reactive oxygen species (ROS). More importantly, mitoquidone mesylate (MitoQ), an inhibitor of mtROS, blocked MC-LR and NaNO2-induced spermatogonia and Sertoli cell apoptosis by inhibiting high expression of Bax, Fadd, Caspase-8, and cleaved-Caspase-3. On the other hand, MitoQ suppressed pyroptosis of Sertoli cells by inhibiting the expression of NLRP3, N-GSDMD, and cleaved-Caspase-1. Additionally, MitoQ alleviated co-exposure-induced sperm density reduction and organ index disorders in F1 generation mice. Together, co-exposure of MC-LR and NaNO2 can enhance spermatogenic disorders by mitochondrial oxidative impairment-mediated germ cell death. This study emphasizes the potential risks of MC-LR and NaNO2 on reproduction in realistic environments and highlights new insights into the cause and treatment of spermatogenic disorders.
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Apoptose , Camundongos Endogâmicos BALB C , Microcistinas , Piroptose , Espécies Reativas de Oxigênio , Espermatogênese , Microcistinas/toxicidade , Animais , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Piroptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Espermatozoides/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Nitrito de Sódio , Toxinas Marinhas , Espermatogônias/efeitos dos fármacos , Espermatogônias/metabolismoRESUMO
Marine toxins produced by marine organisms threaten human health and impose a heavy public health burden on coastal countries. Lately, there has been an emergence of marine toxins in regions that were previously unaffected, and it is believed that climate change may be a significant factor. This paper systematically summarizes the impact of climate change on the risk of marine toxins in terms of changes in seawater conditions. From our findings, climate change can cause ocean warming, acidification, stratification, and sea-level rise. These climatic events can alter the surface temperature, salinity, pH, and nutrient conditions of seawater, which may promote the growth of various algae and bacteria, facilitating the production of marine toxins. On the other hand, climate change may expand the living ranges of marine organisms (such as algae, bacteria, and fish), thereby exacerbating the production and spread of marine toxins. In addition, the sources, distribution, and toxicity of ciguatoxin, tetrodotoxin, cyclic imines, and microcystin were described to improve public awareness of these emerging marine toxins. Looking ahead, developing interdisciplinary cooperation, strengthening monitoring of emerging marine toxins, and exploring more novel approaches are essential to better address the risks of marine toxins posed by climate change. Altogether, the interrelationships between climate, marine ecology, and marine toxins were analyzed in this study, providing a theoretical basis for preventing and managing future health risks from marine toxins.
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Mudança Climática , Toxinas Marinhas , Água do Mar , Água do Mar/química , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Humanos , Animais , Organismos Aquáticos/efeitos dos fármacos , Medição de Risco , Monitoramento AmbientalRESUMO
Microcystin-LR (MC-LR) is a reproductive toxin produced by cyanobacteria in the aquatic environment and can be ingested by humans through drinking water and the food chain, posing a threat to human reproductive health. However, the toxic mechanisms and prospective interventions for MC-LR-induced ovarian dysfunction at environmental doses are unknown. The mulberry fruit is a traditional natural product of plant origin, with various pharmacological effects, such as antioxidant and anti-inflammatory effects. Here, mice were exposed to MC-LR (10, 100 µg/L) in drinking water for 90 days, during which mice were gavage 600 mg/kg/week of mulberry fruit extract (MFE). It was found that MC-LR can accumulate in mouse ovaries, causing sexual hormone disturbance, inflammatory infiltration, and ovarian pathological damage. Results from RNA-seq were shown that CCL2, a chemokine associated with inflammatory response, was significantly increased in mouse ovary after MC-LR exposure. Further investigation revealed that MC-LR exposure aggravates apoptosis of granulosa cells via the CCL2-CCR10 axis-mediated Jak/Stat pathway. Importantly, MFE can significantly ameliorate these ovarian dysfunction phenotypes by inhibiting the activation of the CCL2-CCR10 axis. This study broadened new insights into the ovarian toxicity of MC-LR and clarified the pharmacological effects of mulberry fruit on ovarian function protection.
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Toxinas Marinhas , Microcistinas , Morus , Animais , Feminino , Microcistinas/toxicidade , Camundongos , Morus/química , Ovário/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Extratos Vegetais/farmacologia , Células da Granulosa/efeitos dos fármacosRESUMO
Topological photonics provide a promising way to realize more robust optical devices against some defects and environmental perturbations. Quantum logic gates are fundamental units of quantum computers, which are widely used in future quantum information processing. Thus, constructing robust universal quantum logic gates is an important way forward to practical quantum computing. However, the most important problem to be solved is how to construct the quantum-logic-gate-required 2 × 2 beam splitter with topological protection. Here, the experimental realization of the topologically protected contradirectional coupler is reported, which can be employed to realize the quantum logic gates, including control-NOT and Hadamard gates, on the silicon photonic platform. These quantum gates not only have high experimental fidelities but also exhibit a certain degree of tolerances against certain types of defects. This work paves the way for the development of practical optical quantum computations and signal processing.
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OBJECTIVE: This study aimed to overcome the growing antibiotic resistance. Moreover, the new series of emodin alkyl azoles were synthesized. METHOD: The novel emodin alkyl azoles were synthesized using commercial emodin and azoles by alkylation. The NMR and HRMS spectra were employed to confirm the structures of novel prepared compounds. The in vitro antibacterial and antifungal activities of the prepared emodin compounds were studied by the 96-well plate method. The binding behavior between emodin 4-nitro imidazole compound 3c and S. aureus DNA was researched using an ultraviolet-visible spectrophotometer. Furthermore, fluorescence spectrometry was used to explore the interaction with human serum albumin (HSA). RESULTS: The in vitro antimicrobial results displayed that compound 3c gave relatively strong activities with MIC values of 4-16 µg/mL. Notably, this compound exhibited 2-fold more potent activity against S. aureus (MIC = 4 µg/mL) and E. coli (MIC = 8 µg/mL) strains than clinical drug Chloromycin (MIC = 8 and 16 µg/mL). The UV-vis absorption spectroscopy showed that 4-nitro imidazole emodin 3c could form the 3c-DNA complex by intercalating into S. aureus DNA, inhibiting antimicrobial activities. The simulation results displayed that the emodin 3c and DNA complex were formed by hydrogen bonds. The spectral experiment demonstrated that compound 3c could be transported by human serum albumin (HSA) via hydrogen bonds. The molecular simulation found that the hydroxyl group and the nitroimidazole ring of the emodin compound showed an important role in transportation behavior. CONCLUSION: This work may supply useful directions for the exploration of novel antimicrobial agents.
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Azóis , Emodina , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Albumina Sérica Humana , Staphylococcus aureus , Emodina/farmacologia , Emodina/química , Emodina/síntese química , Emodina/análogos & derivados , Humanos , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Azóis/química , Azóis/farmacologia , Azóis/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , DNA/metabolismo , DNA/química , Relação Estrutura-Atividade , Estrutura Molecular , DNA Bacteriano/efeitos dos fármacos , DNA Bacteriano/metabolismoRESUMO
Objective: To explore the correlation between 5 dimensions of personality, physical activity (PA), and bone mineral density (BMD) among college students. Methods: A total of 705 undergraduates (329 males and 376 females) from a sports university were recruited. Based on their sports training experience, the participants were divided into 6 major sports groups, including ball sports, skilled sports, competitive sports, track and field, leisure sports, and no sports. Students with professional sports training (ie, athletes) were categorized into ballgame, skilled, competitive, and track and field groups, while the rest (non-athletes) were placed in leisure and no sports groups. Ten-Item Personality Inventory in China (TIPI-C), or the 5-factor model of personality, was used to measure the 5 personality dimensions of openness, conscientiousness, extraversion, agreeableness, and neuroticism of the participants. Their daily level was measured with GT3X+ triaxial accelerometers over 7 continuous days. Then, parameter thresholds were established and the participants' PA was categorized as light (LPA), moderate (MPA), and vigorous (VPA). The bone mineral density (BMD) of arms, legs, and the total body was measured using dual-energy X-ray absorptiometry. The mediation effect of PA and that of the 5-factor model of personality were tested using PROCESS and Sobel tests. The correlation between the 5 personality dimensions, PA, and BMD was explored, with PA and the 5 personality dimensions as mediator variables. A comparison of PA and BMD was conducted across the 6 major sports groups. The correlation between PA of different intensities and BMD was also analyzed using Spearman's correlation. Results: Although there were 90 potential relationships between PA, the 5 personality dimensions, and BMD, only 3 were significant. When conscientiousness was used as an independent variable and MPA, as a mediating variable, statistically significant differences in PROCESS results were reported (P<0.01), with MPA mediating 17.3% of arm BMD, 19.4% of leg BMD, and 19.1% of total body BMD. Among male students, there was no significant difference in LPA among the 6 groups, but significant differences in MPA and VPA (P<0.05). Among female students, significant differences in LPA, MPA, and VPA were observed in all 6 groups and the differences between MPA and VPA were especially prominent (P<0.05). For both males and females, the differences in arm, leg, and total body BMD across the 6 groups were statistically significant (P<0.05), with these differences being more pronounced in females. There was no correlation between LPA and BMD in either sex. MPA and VPA were positively correlated with BMD, with MPA correlating with arm, leg, and total body BMD (males, Spearman's correlation [rs]: 0.11-0.14, P<0.05; females, rs: 0.20-0.23, P<0.01). VPA correlated with arm, leg, and total body BMD (males, rs: 0.11-0.23, P<0.05; females, rs: 0.26-0.30, P<0.01). Conclusion: MPA is associated with BMD in college students scoring high in the conscientiousness dimension of personality. In addition, there is a weak positive correlation between both MPA and VPA and BMD levels, with these associations being more pronounced in females.
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Densidade Óssea , Exercício Físico , Humanos , Masculino , Feminino , Estudos Transversais , Absorciometria de Fóton/métodos , Estudantes , PersonalidadeRESUMO
Topological photonics provides a new degree of freedom to robustly control electromagnetic fields. To date, most of established topological states in photonics have been employed in Euclidean space. Motivated by unique properties of hyperbolic lattices, which are regular tessellations in non-Euclidean space with a constant negative curvature, the boundary-dominated hyperbolic topological states have been proposed. However, limited by highly crowded boundary resonators and complicated site couplings, the hyperbolic topological insulator has only been experimentally constructed in electric circuits. How to achieve hyperbolic photonic topological insulators is still an open question. Here, we report the experimental realization of hyperbolic photonic topological insulators using coupled ring resonators on silicon chips. Boundary-dominated one-way edge states with pseudospin-dependent propagation directions have been observed. Furthermore, the robustness of edge states in hyperbolic photonic topological insulators is also verified. Our findings have potential applications in the field of designing high-efficient topological photonic devices with enhanced boundary responses.
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Polychlorinated biphenyls (PCBs) are a class of endocrine-disrupting chemicals (EDCs) widely present in the environment. PCBs have been of concern due to their anti/estrogen-like effects, which make them more toxic to the female reproductive system. However, there is still a lack of systematic reviews on the reproductive toxicity of PCBs in females, so the adverse effects and mechanisms of PCBs on the female reproductive system were summarized in this paper. Our findings showed that PCBs are positively associated with lower pregnancy rate, hormone disruption, miscarriage and various reproductive diseases in women. In animal experiments, PCBs can damage the structure and function of the ovaries, uterus and oviducts. Also, PCBs could produce epigenetic effects and be transferred to the offspring through the maternal placenta, causing development retardation, malformation and death of embryos, and damage to organs of multiple generations. Furthermore, the mechanisms of PCBs-induced female reproductive toxicity mainly include receptor-mediated hormone disorders, oxidative stress, apoptosis, autophagy, and epigenetic modifications. Finally, we also present some directions for future research on the reproductive toxicity of PCBs. This detailed information provided a valuable reference for fully understanding the reproductive toxicity of PCBs.
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Poluentes Ambientais , Bifenilos Policlorados , Gravidez , Animais , Feminino , Humanos , Bifenilos Policlorados/toxicidade , Bifenilos Policlorados/análise , Revisões Sistemáticas como Assunto , Reprodução , Estrogênios , Ovário , Poluentes Ambientais/análiseRESUMO
Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria, which is widely distributed in eutrophic water bodies and has multi-organ toxicity. Previous cytotoxicity studies have mostly elucidated the effects of MC-LR on intracellular-related factors, proteins, and DNA at the molecular level. However, there have been few studies on the adverse effects of MC-LR on cell ultrastructure and function. Therefore, research on the cytotoxicity of MC-LR in recent years was collected and summarized. It was found that MC-LR can induce a series of cytotoxic effects, including decreased cell viability, induced autophagy, apoptosis and necrosis, altered cell cycle, altered cell morphology, abnormal cell migration and invasion as well as leading to genetic damage. The above cytotoxic effects were related to the damage of various ultrastructure and functions such as cell membranes and mitochondria. Furthermore, MC-LR can disrupt cell ultrastructure and function by inducing oxidative stress and inhibiting protein phosphatase activity. In addition, the combined toxic effects of MC-LR and other environmental pollutants were investigated. This review explored the toxic targets of MC-LR at the subcellular level, which will provide new ideas for the prevention and treatment of multi-organ toxicity caused by MC-LR.
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Toxinas Marinhas , Microcistinas , Microcistinas/toxicidade , Apoptose , Estresse OxidativoRESUMO
BACKGROUND: Programmed cell death (PCD) has been widely investigated in various human diseases. The present study aimed to identify a novel PCD-related genetic signature in cervical squamous cell carcinoma (CESC) to provide clues for survival, immunotherapy and drug sensitization prediction. METHODS: Single-sample gene set enrichment analysis (ssGSEA) was used to quantify the PCD score and assess the distribution of PCD in clinicopathological characteristics in The Cancer Genome Atlas (TCGA)-CESC samples. Then, the ConsensusClusterPlus method was used to identify molecular subtypes in the TCGA-CESC database. Genomic mutation analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment, as well as tumor microenvironment (TME) infiltration analysis, were performed for each molecular subtype group. Finally, a prognostic model by Uni-Cox and least absolute shrinkage and selection operator-Cox analysis was established based on differentially expressed genes from molecular subtypes. ESTIMATE (i.e. Estimation of STromal and Immune cells in MAlignantTumours using Expression data) and ssGSEA were performed to assess the correlation between the model and TME. Drug sensitization prediction was carried out with the oncoPredict package. RESULTS: Preliminary analysis indicated that PCD had a potential association clinical characteristics of the TCGA-CESC cohort, and PCD-related genes mutated in 289 (70.59%) CESC patients. Next, four groups of CESC molecular typing were clustered based on 63 significantly prognostic PCD-related genes. Among four subtypes, C1 group displayed the worst prognosis combined with over expressed PCD genes and enriched cell cycle-related pathways. C4 group exhibited the best prognosis accompanied with high degree of immune infiltration. Finally, a five-gene (SERPINE1, TNF, CA9, CX3CL1 and JAK3) prognostic model was constructed. Patients in the high-risk group displayed unfavorable survival. Immune infiltration analysis found that the low-risk group had significantly higher levels of immune cell infiltration such as T cells, Macrophages_M1, relative to the high-risk group, and were significantly enriched in apoptosis-associated pathways, which predicted a higher level of immunity. Drug sensitivity correlation analysis revealed that the high-risk group was resistant to conventional chemotherapeutic drugs and sensitive to the Food and Drug Administration-approved drugs BI.2536_1086 and SCH772984_1564. CONCLUSIONS: In the present study, we first found that PCD-related gene expression patterns were correlated with clinical features of CESC patients, which predicts the feasibility of subsequent mining of prognostic features based on these genes. The five-PCD-associated-gene prognostic model showed good assessment ability in predicting patient prognosis, immune response and drug-sensitive response, and provided guidance for the elucidation of the mechanism by which PCD affects CESC, as well as for the clinical targeting of drugs.
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Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Estados Unidos , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Prognóstico , Apoptose , Biomarcadores , Microambiente Tumoral/genéticaRESUMO
This study found that the level of neuroepithelial cell-transforming gene 1 protein (NET1) was significantly increased in a mouse cardiac fibrosis model. Moreover, the expression level of NET1 was increased in cardiac fibrosis induced by TGF-ß1, suggesting that NET1 was involved in the pathological process of cardiac fibrosis. Overexpression of NET1 promoted ß-catenin expression in the nucleus and significantly increased the proliferation and migration of cardiac fibroblasts. NET1 may form a complex with ß-catenin through GSK3ß. Knockdown of ß-catenin alleviated the effects of NET1 overexpression on collagen production and cell migration. In the heart of NET1 knockout mice, NET1 knockout can reduce the expression of ß-catenin, α-SMA, and collagen content induced by MI. In conclusion, NET1 may regulate the activation of Wnt/ß-catenin and TGF/Smads signaling pathway, promote collagen synthesis in fibroblasts, and participate in cardiac fibrosis. Thus, NET1 may be a potential therapeutic target in cardiac fibrosis.
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BACKGROUND: Community-acquired pneumonia (CAP) patients usually present with parapneumonic pleural effusion (PPE), which complicates the treatment of pneumonia. This study aims to investigate the clinical characteristics and risk factors of elderly CAP patients hospitalised with PPE. METHODS: The clinical data of 132 elderly patients with CAP were retrospectively analysed. A total of 54 patients with PPE (PPE group) and 78 patients without PPE (NPPE group) were included in this study. Clinical data, laboratory examinations, treatments and other relevant indicators were collected. Univariate analysis and multivariate logistic regression analysis will be used to explore the possible risk factors for PPE. RESULTS: The proportion of PPE in elderly patients with CAP was 40.9%. PPE patients were significantly more likely to be older, have comorbid neurological diseases, experience chest tightness, and have a lasting fever (P < 0.05). In contrast to NPPE patients, the total number of lymphocytes, serum albumin and blood sodium levels in the PPE group were significantly lower (P < 0.05). The blood D-dimer, C-reactive protein and CURB-65 score of PPE patients were significantly higher (P < 0.05) than those of NPPE patients. Multivariate logistic regression identified chest tightness (OR = 3.964, 95% CI: 1.254-12.537, P = 0.019), long duration of fever (OR = 1.108, 95%CI: 1.009-1.217, P = 0.03), low serum albumin (OR = 0.876, 95%CI: 0.790- 0.971, P = 0.012) or low blood sodium (OR = 0.896, 95%CI: 0.828-0.969, P = 0.006) as independently associated with the development of parapneumonic pleural effusion in the elderly. CONCLUSION: This study has identified several clinical factors, such as chest tightness, long duration of fever, low serum albumin, and low blood sodium, as risk factors for the development of pleural effusion in elderly patients with CAP. Early identification and prompt management of these patients can prevent inappropriate treatment and reduce morbidity and mortality.
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Infecções Comunitárias Adquiridas , Derrame Pleural , Pneumonia , Idoso , Humanos , Estudos Retrospectivos , Derrame Pleural/epidemiologia , Fatores de Risco , Infecções Comunitárias Adquiridas/epidemiologia , Febre/epidemiologia , Pneumonia/complicações , Pneumonia/epidemiologia , Albumina Sérica , SódioRESUMO
Cow's milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.
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Microbioma Gastrointestinal , Hipersensibilidade a Leite , Criança , Feminino , Animais , Bovinos , Humanos , Lactente , Pré-Escolar , Leite Humano , Oligossacarídeos , Suplementos Nutricionais , Metaboloma , Fórmulas Infantis/químicaRESUMO
PURPOSE: To systematically assess the quality of radiomics research in giant cell tumor of bone (GCTB) and to test the feasibility of analysis at the level of radiomics feature. METHODS: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang Data to identify articles of GCTB radiomics until 31 July 2022. The studies were assessed by radiomics quality score (RQS), transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement, checklist for artificial intelligence in medical imaging (CLAIM), and modified quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The radiomic features selected for model development were documented. RESULTS: Nine articles were included. The average of the ideal percentage of RQS, the TRIPOD adherence rate and the CLAIM adherence rate were 26%, 56%, and 57%, respectively. The risk of bias and applicability concerns were mainly related to the index test. The shortness in external validation and open science were repeatedly emphasized. In GCTB radiomics models, the gray level co-occurrence matrix features (40%), first order features (28%), and gray-level run-length matrix features (18%) were most selected features out of all reported features. However, none of the individual feature has appeared repeatably in multiple studies. It is not possible to meta-analyze radiomics features at present. CONCLUSION: The quality of GCTB radiomics studies is suboptimal. The reporting of individual radiomics feature data is encouraged. The analysis at the level of radiomics feature has potential to generate more practicable evidence for translating radiomics into clinical application.
Assuntos
Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Humanos , Inteligência Artificial , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Diagnóstico por Imagem , Biomarcadores , Neoplasias Ósseas/diagnóstico por imagemRESUMO
Endocrine disrupting chemicals (EDCs) are increasingly concerned substance endangering human health and environment. However, there is no unified standard for identifying chemicals as EDCs, which is also controversial internationally. In this review, the procedures for EDC identification in different organizations/countries were described. Importantly, three aspects to be considered in identifying chemical substances as EDCs were summarized, which were mechanistic data, animal experiments, and epidemiological information. The relationships between them were also discussed. To elaborate more clearly on these three aspects of evidence, scientific data on some chemicals including bisphenol A, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane and perchlorate were collected and evaluated. Altogether, the above three chemicals were assessed for interfering with hormones and elaborated their health hazards from macroscopic to microscopic. This review is helpful for standardizing the identification procedure of EDCs.
Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Animais , Humanos , HormôniosRESUMO
Integrated quantum photonic circuit is a promising platform for the realization of quantum information processing in the future. To achieve the large-scale quantum photonic circuits, the applied quantum logic gates should be as small as possible for the high-density integration on chips. Here, we report the implementation of super-compact universal quantum logic gates on silicon chips by the method of inverse design. In particular, the fabricated controlled-NOT gate and Hadamard gate are both nearly a vacuum wavelength, being the smallest optical quantum gates reported up to now. We further design the quantum circuit by cascading these fundamental gates to perform arbitrary quantum processing, where the corresponding size is about several orders smaller than that of previous quantum photonic circuits. Our study paves the way for the realization of large-scale quantum photonic chips with integrated sources and can have important applications in the field of quantum information processes.