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Liquid manipulation using tubular actuators finds diverse applications ranging from microfluidics, printing, liquid transfer to micro-reactors. Achieving flexible and simple regulation of manipulated liquid droplets during transport is crucial for the tubular liquid actuators to perform complex and multiple functions, yet it remains challenging. Here, a facile tubular actuator for directional transport of various liquid droplets under the control of an externally applied magnetic field is presented. The surfaces of the actuator can be engineered with submillimeter-sized through-hole pores, which enables the liquid droplet to be easily modulated in the transport process. Furthermore, the liquid actuator with featured through-hole pores is expanded to function as a switch in an integrated external electric circuit by magnetically controlling the motion of a conductive liquid droplet. This work develops a strategy for regulating liquid droplets in the tubular actuation systems, which may inspire ideas for designing functional liquid actuators with potential applications in microfluidics, microchemical reaction, liquid switch, and liquid robotics.
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BACKGROUND: Sarcopenia is a common cause of disability in the aging population, and managing sarcopenia is an important step in building intrinsic capacity and promoting healthy aging. A growing body of evidence suggests that sleep deprivation may be a mediator of the development of sarcopenia. The purpose of this study was to explore the longitudinal association between sleep duration and possible sarcopenia using data from a national sample. METHODS: Two waves of data from the CHARLS database for 2011 and 2015 were used in this study. All possible sarcopenia participants met the Asia Working Group for Sarcopenia 2019 (AWGS 2019) diagnostic criteria. Sleep duration was assessed using a self-report questionnaire, and sleep duration was categorized as short (≤ 6 h), medium (6-8 h), or long (> 8 h) based on previous studies. Longitudinal associations between sleep duration and possible sarcopenia will be calculated by univariate and multifactorial logistic regression analyses and expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 5654 individuals participated in the follow-up study, with a prevalence of possible sarcopenia of 53.72% (578) in the short sleep duration group, 38.29% (412) in the medium sleep duration group, and 7.99% (86) in the long sleep duration group. According to the crude model of the second-wave follow-up study, short sleep durations were significantly more strongly associated with possible sarcopenia than were medium and long sleep durations (OR: 1.35, 95% CI: 1.17-1.55, P = 0.000). The association between short sleep duration and possible sarcopenia was maintained even after adjustment for covariates such as age, gender, residence, education level, BMI, smoking status, alcohol consumption and comorbidities (OR: 1.18, 95% CI: 1.02-1.36, P = 0.029). In the subgroup analysis, short sleep duration was associated with low grip strength (OR: 1.20, 95% CI: 1.02-1.41, P = 0.031). CONCLUSIONS: Sleep deprivation may be closely associated with the development of possible sarcopenia in middle-aged and elderly people, which provides new insights and ideas for sarcopenia intervention, and further studies are needed to reveal the underlying mechanisms involved.
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Sarcopenia , Sueño , Humanos , Sarcopenia/epidemiología , Sarcopenia/diagnóstico , Sarcopenia/fisiopatología , Masculino , Femenino , Estudios Longitudinales , China/epidemiología , Anciano , Persona de Mediana Edad , Sueño/fisiología , Factores de Tiempo , Prevalencia , Duración del Sueño , Pueblos del Este de AsiaRESUMEN
Ocular neurodegenerative diseases like glaucoma lead to progressive retinal ganglion cell (RGC) loss, causing irreversible vision impairment. Neuroprotection is needed to preserve RGCs across debilitating conditions. Nerve growth factor (NGF) protein therapy shows efficacy, but struggles with limited bioavailability and a short half-life. Here we explore a novel approach to address this deficiency by utilizing circular RNA (circRNA)-based therapy. We show that circRNAs exhibit an exceptional capacity for prolonged protein expression and circRNA-expressed NGF protects cells from glucose deprivation. In a mouse optic nerve crush model, lipid nanoparticle (LNP)-formulated circNGF administered intravitreally protects RGCs and axons from injury-induced degeneration. It also significantly outperforms NGF protein therapy without detectable retinal toxicity. Furthermore, single-cell transcriptomics revealed LNP-circNGF's multifaceted therapeutic effects, enhancing genes related to visual perception while reducing trauma-associated changes. This study signifies the promise of circRNA-based therapies for treating ocular neurodegenerative diseases and provides an innovative intervention platform for other ocular diseases.
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Background: In order to lessen the burden of Alzheimer's disease (AD), timely and efficient management and intervention methods for mild cognitive impairment (MCI) are crucial. MCI is seen as a transitional stage between normal aging and dementia. Although sarcopenia is an important risk factor for MCI, it is unclear what factors mediates and regulates the brain-muscle communication. Our objective was to investigate the indirect moderating effects of sleep duration and leisure activity on depressive symptoms, sarcopenia and MCI. Method: Panel data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) database was used in this investigation. we used Bootstrap sampling to determine the relationship between sleep duration, leisure activity, depressive symptoms, sarcopenia, and MCI in mediation and indirect moderation models. The outcome measurements were odds ratio (OR) and confidence interval (CI). Result: After adjusting for confounding variables, we discovered that sarcopenia and its traits, such as handgrip strength, gait speed, standing test, and muscle mass, were significantly correlated with MCI. Second, the results implied that depressive symptoms played a role in modulating the link between physical function, muscle strength, and MCI. This moderating effect was impacted by short sleep duration and moderate to high levels of leisure activities. Conclusion: We discovered that MCI was highly correlated not only with physical function and muscle strength but also with depressed symptoms, which acted as a partially mediating factor in this connection. Handgrip strength, gait speed, and standing test mediated the correction of MCI caused by depression symptoms. Importantly, leisure activities and sleep duration had indirect moderating effects on the above associations, and future management policies should take these factors into account.
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Global population growth and industrialization have exacerbated the nonrenewable energy crises and environmental issues, thereby stimulating an enormous demand for producing environmentally friendly materials. Typically, biomass-based aerogels (BAs), which are mainly composed of biomass materials, show great application prospects in various fields because of their exceptional properties such as biocompatibility, degradability, and renewability. To improve the performance of BAs to meet the usage requirements of different scenarios, a large number of innovative works in the past few decades have emphasized the importance of micro-structural design in regulating macroscopic functions. Inspired by the ubiquitous random or regularly arranged structures of materials in nature ranging from micro to meso and macro scales, constructing different microstructures often corresponds to completely different functions even with similar biomolecular compositions. This review focuses on the preparation process, design concepts, regulation methods, and the synergistic combination of chemical compositions and microstructures of BAs with different porous structures from the perspective of gel skeleton and pore structure. It not only comprehensively introduces the effect of various microstructures on the physical properties of BAs, but also analyzes their potential applications in the corresponding fields of thermal management, water treatment, atmospheric water harvesting, CO2 absorption, energy storage and conversion, electromagnetic interference (EMI) shielding, biological applications, etc. Finally, we provide our perspectives regarding the challenges and future opportunities of BAs. Overall, our goal is to provide researchers with a thorough understanding of the relationship between the microstructures and properties of BAs, supported by a comprehensive analysis of the available data.
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Flexible light-emitting fibers and fabrics serve to bridge human-machine interactions. The desire for practical applications and the commercialization of flexible light-emitting fibers has accelerated structural progress and improvements. This review focuses on the structural design of light-emitting fibers and fabrics, starting with a summary of design principles, emission mechanisms, and structural evolution of coaxial structured light-emitting fibers. Subsequently, we explore recent advances in the helical structure design strategies that boost the mechanical sensitivity of light-emitting fibers. Following that, we analyze continuous preparation processes and the development of large-area intelligent light-emitting fabrics based on interwoven structures. Examples based on stiff and rigid inorganic-based light-emitting diodes integrated into flexible systems are also presented. Finally, we discuss the current challenges and future opportunities for light-emitting applications in the field of wearable and smart devices.
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Abnormal lipid droplets (LDs) are known to be intimately bound with the occurrence and development of cancer, allowing LDs to be critical biomarkers for cancers. Aggregation-induced emission luminogens (AIEgens), with efficient reactive oxygen species (ROS) production performance, are prime photosensitizers (PSs) for photodynamic therapy (PDT) with imaging. Therefore, the development of dual-functional fluorescent probes with aggregation-induced emission (AIE) characteristics that enable both simultaneous LD monitoring and imaging-guided PDT is essential for concurrent cancer diagnosis and treatment. Herein, we reported the development of a novel LD-targeting fluorescent probe (TDTI) with AIE performance, which was expected to realize the integration of cancer diagnosis through LD visualization and cancer treatment via PDT. We demonstrated that TDTI, with typical AIE characteristics and excellent photostability, could target LDs with high specificity, which enables the dynamic tracking of LDs in living cells, specific imaging of LDs in zebrafish, and the differentiation of cancer cells from normal cells for cancer diagnosis. Meanwhile, TDTI exhibited fast ROS generation ability (achieving equilibrium within 60 s) under white light irradiation (10 mW/cm2). The cell apoptosis assay revealed that TDTI effectively induced growth inhibition and apoptosis of HeLa cells. Further, the results of PDT in vivo indicated that TDTI had a good antitumor effect on the tumor-bearing mice model. Collectively, these results highlight the potential utility of the dual-functional fluorescent probe TDTI in the integrated diagnosis and treatment of cancer.
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Neoplasias , Fotoquimioterapia , Humanos , Animales , Ratones , Células HeLa , Colorantes Fluorescentes , Gotas Lipídicas/metabolismo , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Pez Cebra/metabolismo , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológicoRESUMEN
Absent, small, or homeotic1-like (ASH1L) is a histone lysine methyltransferase that generally functions as a transcriptional activator in controlling cell fate. So far, its physiological relevance in bone homeostasis and osteoclast differentiation remains elusive. Here, by conditional deleting Ash1l in osteoclast progenitors of mice, we found ASH1L deficiency resulted in osteoporosis and potentiation of osteoclastogenesis in vivo and in vitro. Mechanistically, ASH1L binds the promoter of the Src homology 3 and cysteine-rich domain 2 (Stac2) and increases the gene's transcription via histone 3 lysine 4 (H3K4) trimethylation modification, thus augmenting the STAC2's protection against receptor activator of nuclear factor kB ligand (RANKL)-initiated inflammation during osteoclast formation. Collectively, we demonstrate the first piece of evidence to prove ASH1L as a critical checkpoint during osteoclastogenesis. The work sheds new light on our understanding about the biological function of ASH1L in bone homeostasis, therefore providing a valuable therapeutic target for the treatment of osteoporosis or inflammatory bone diseases.
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N-Metiltransferasa de Histona-Lisina , Osteoclastos , Osteogénesis , Animales , Ratones , Resorción Ósea/metabolismo , Resorción Ósea/patología , Diferenciación Celular , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Osteoporosis/patología , Osteoporosis/genética , Ligando RANK/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genéticaRESUMEN
Proteasome-mediated degradation of chromatin-bound NF-κB is critical in terminating the transcription of pro-inflammatory genes and can be triggered by Set9-mediated lysine methylation of the RelA subunit. However, the E3 ligase targeting methylated RelA remains unknown. Here, we find that two structurally similar substrate-recognizing components of Cullin-RING E3 ligases, WSB1 and WSB2, can recognize chromatin-bound methylated RelA for polyubiquitination and proteasomal degradation. We showed that WSB1/2 negatively regulated a subset of NF-κB target genes via associating with chromatin where they targeted methylated RelA for ubiquitination, facilitating the termination of NF-κB-dependent transcription. WSB1/2 specifically interacted with methylated lysines (K) 314 and 315 of RelA via their N-terminal WD-40 repeat (WDR) domains, thereby promoting ubiquitination of RelA. Computational modeling further revealed that a conserved aspartic acid (D) at position 158 within the WDR domain of WSB2 coordinates K314/K315 of RelA, with a higher affinity when either of the lysines is methylated. Mutation of D158 abolished WSB2's ability to bind to and promote ubiquitination of methylated RelA. Together, our study identifies a novel function and the underlying mechanism for WSB1/2 in degrading chromatin-bound methylated RelA and preventing sustained NF-κB activation, providing potential new targets for therapeutic intervention of NF-κB-mediated inflammatory diseases.
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Cromatina , Complejo de la Endopetidasa Proteasomal , Factor de Transcripción ReIA , Ubiquitinación , Humanos , Cromatina/metabolismo , Células HEK293 , Lisina/metabolismo , Metilación , FN-kappa B/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Unión Proteica , Proteolisis , Factor de Transcripción ReIA/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
What is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.
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Cancer cells need a greater supply of glucose mainly due to their aerobic glycolysis, known as the Warburg effect. Glucose transport by glucose transporter 1 (GLUT1) is the rate-limiting step for glucose uptake, making it a potential cancer therapeutic target. However, GLUT1 is widely expressed and performs crucial functions in a variety of cells, and its indiscriminate inhibition will cause serious side effects. In this study, we designed and synthesized a photocaged GLUT1 inhibitor WZB117-PPG to suppress the growth of cancer cells in a spatiotemporally controllable manner. WZB117-PPG exhibited remarkable photolysis efficiency and substantial cytotoxicity toward cancer cells under visible light illumination with minimal side effects, ensuring its safety as a potential cancer therapy. Furthermore, our quantitative proteomics data delineated a comprehensive portrait of responses in cancer cells under glucose deprivation, underlining the mechanism of cell death via necrosis rather than apoptosis. We reason that our study provides a potentially reliable cancer treatment strategy and can be used as a spatiotemporally controllable trigger for studying nutrient deprivation-related stress responses.
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Glucosa , Hidroxibenzoatos , Neoplasias , Glucosa/metabolismo , Transportador de Glucosa de Tipo 1/genética , Preparaciones de Acción Retardada , Línea Celular Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
KEY MESSAGE: The new stripe rust resistance gene Yr4EL in tetraploid Th. elongatum was identified and transferred into common wheat via 4EL translocation lines. Tetraploid Thinopyrum elongatum is a valuable genetic resource for improving the resistance of wheat to diseases such as stripe rust, powdery mildew, and Fusarium head blight. We previously reported that chromosome 4E of the 4E (4D) substitution line carries all-stage stripe rust resistance genes. To optimize the utility of these genes in wheat breeding programs, we developed translocation lines by inducing chromosomal structural changes through 60Co-γ irradiation and developing monosomic substitution lines. In total, 53 plants with different 4E chromosomal structural changes were identified. Three homozygous translocation lines (T4DS·4EL, T5AL·4EL, and T3BL·4EL) and an addition translocation line (T5DS·4EL) were confirmed by the genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), FISH-painting, and wheat 55 K SNP array analyses. These four translocation lines, which contained chromosome arm 4EL, exhibited high stripe rust resistance. Thus, a resistance gene (tentatively named Yr4EL) was localized to the chromosome arm 4EL of tetraploid Th. elongatum. For the application of marker-assisted selection (MAS), 32 simple sequence repeat (SSR) markers were developed, showing specific amplification on the chromosome arm 4EL and co-segregation with Yr4EL. Furthermore, the 4DS·4EL line could be selected as a good pre-breeding line that better agronomic traits than other translocation lines. We transferred Yr4EL into three wheat cultivars SM482, CM42, and SM51, and their progenies were all resistant to stripe rust, which can be used in future wheat resistance breeding programs.
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Basidiomycota , Triticum , Triticum/genética , Hibridación Fluorescente in Situ , Fitomejoramiento , Tetraploidía , Poaceae/genéticaRESUMEN
BACKGROUND & AIMS: Metabolic reprogramming is essential for the activation and functions of macrophages, including bacterial killing and cytokine production. Bromodomain-containing protein 4 (BRD4) has emerged as a critical regulator of innate immune response. However, the potential role of BRD4 in the metabolic reprogramming of macrophage activation upon Helicobacter pylori infection remains unclear. METHODS: Bone marrow-derived macrophages (BMDMs) from wild-type (WT) and Brd4-myeloid deletion conditional knockout (Brd4-CKO) mice were infected with H pylori. RNA sequencing was performed to evaluate the differential gene expression between WT and Brd4-deficient BMDMs upon infection. An in vivo model of H pylori infection using WT and Brd4-CKO mice was used to confirm the role of BRD4 in innate immune response to infection. RESULTS: Depletion of Brd4 in BMDMs showed impaired H pylori-induced glycolysis. In addition, H pylori-induced expression of glycolytic genes, including Slc2a1 and Hk2, was decreased in Brd4-deficient BMDMs. BRD4 was recruited to the promoters of Slc2a1 and Hk2 via hypoxia-inducible factor-1α, facilitating their expression. BRD4-mediated glycolysis stabilized H pylori-induced nitric oxide synthase (Nos2) messenger RNA to produce nitric oxide. The NO-mediated killing of H pylori decreased in Brd4-deficient BMDMs, which was rescued by pyruvate. Furthermore, Brd4-CKO mice infected with H pylori showed reduced gastric inflammation and increased H pylori colonization with reduced inducible NO synthase expression in gastric macrophages. CONCLUSIONS: Our study identified BRD4 as a key regulator of hypoxia-inducible factor-1α-dependent glycolysis and macrophage activation. Furthermore, we show a novel regulatory role of BRD4 in innate immunity through glycolysis to stabilize Nos2 messenger RNA for NO production to eliminate H pylori infection.
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Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Infecciones por Helicobacter/microbiología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Helicobacter pylori/metabolismo , Macrófagos/metabolismo , Óxido Nítrico Sintasa/metabolismo , ARN Mensajero/metabolismo , Glucólisis , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
Self-organization by the directed migration of components within a system is an important process in many applications, such as the unidirectional migration of motor proteins for transporting items to specific sites in a cell. This manuscript describes a class of functional polymeric molecules that have a set of instructions written by specific chemical moieties. These instructions allow the functional polymeric molecules to be used for autonomous synthesis of particles: particles with both functional core-shell structure and customizable shapes are fabricated for the first time. The functional polymeric molecules direct the large-scale migration of the liquid molecules to specific sites for forming the required customized structure of the particle, thus overcoming previous challenges of fabricating this class of particles. This first synthesis of this class of particles enables the development of novel applications: the concept of shape specificity for targeting sites. Both the basic structural properties (core-shell structure and customizable shape) are used in the specific applications of targeted drug delivery and imaging. The secure physical fit due to the complementary shapes enables the particles to remain locked in position for the targeting. Polymeric molecules are first shown to be highly capable of being encoded with instructions for autonomous synthesis of structured materials.
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Background: Ovarian cancer is considered the leading cause of cancer-related deaths among all gynecological malignancies and a significant reason for mortality in women. This cohort study aimed to explore the survival trends of malignant ovarian tumors (MOT), cancer antigen 125 (CA125) level, and clinicopathological prognostic factors of MOT by histological subtype. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 41,411 MOT cases diagnosed between January 2005 and December 2014 were extracted. According to the histological classification of MOT, four categories were included: epithelial ovarian carcinoma (EOC), malignant ovarian germ cell tumors (MOGCTs), malignant ovarian sex cord-stromal tumors (MOSCSTs) and ovarian neuroendocrine tumors (ONTs). We analyzed disease-specific survival (DS) and overall survival (OS) among the four categories, and their histological subtypes. Kaplan-Meier method was used to estimate survival curves, and log-rank test was used to evaluate differences between curves. Univariate and multivariate Cox proportional hazards models were applied to evaluate the prognostic impact of MOT. Results: Significant predictors related to improved OS were younger age, low grade, early FIGO stage and localized SEER stage, while positive/elevated CA125 level was a risk factor. For MOGCT and MOSCST, 3-, 5- and 10-year DS rate estimates were all >80%, followed by ONT around 70%. Malignant epithelial cancer showed low DS rate at 3-year (70.7%), 5-year (58.7%), and 10-year (47.3%). Conclusions: EOC patients had the worst outcome, whereas MOGCT cases had the most favorable survival. Positive/elevated CA125 level led to poor prognosis. Furthermore, younger age, low grade, early FIGO stage and localized SEER stage were significant predictors for improved OS.
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MOTIVATION: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. METHODS: A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). RESULTS: Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. CONCLUSION: Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test.
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Óxido Nítrico , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/genética , Biopsia , Área Bajo la Curva , ArgininaRESUMEN
Liquid transportation is fundamentally important in microfluidics, water collection, biosensing, and printing, and has attracted enormous research interest in the past decades. However, despite substantial progress, it remains a big challenge to achieve the controlled transport of viscous liquids (>100 mPa s) commonly existing in daily life and the chemical industry. Inspired by the gastrointestinal peristalsis of mammalians that can efficiently transport viscous chyme (viscosity up to 2000 mPa s) by the synergistic combination of contraction driving force and lubrication, here, the design and construction of double-layered tubular hydrogel actuators for directional transport of highly viscous liquids ranging from ≈1000 mPa s to >80 000 mPa s under the control of an applied 808 nm laser, which is attributed to the cooperation of outer layer contraction and water film lubrication of the inner layer, is reported. It is demonstrated that the actuators are capable of transporting polymerizing liquid whose viscosity significantly increases to ≈11 182 mPa s in 2 h. This work paves a new avenue toward directional transport of highly viscous liquids, which not only expands the research scope of liquid transportation, but will spur the design of new liquid actuators with potential applications in viscous-liquid-based microfluidics, artificial blood vessels, and soft robots.
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Background: Systemic lupus erythematosus (SLE) is characterized by poor regulation of the immune response leading to chronic inflammation and multiple organ dysfunction. Glucocorticoid (GC) is currently one of the main treatments. However, a high dose or prolonged use of GC may result in glucocorticoid-induced osteoporosis (GIOP). Jiedu Quyu Ziyin decoction (JP) is effective in treating SLE and previous clinical studies have proved that JP can prevent and treat SLE steroid osteoporosis (SLE-GIOP). We aim to examine JPs main mechanism on SLE-GIOP through network pharmacology and molecular docking. Methods: TCMSP and TCMID databases were used to screen potential active compounds and targets of JP. The SLE-GIOP targets are collected from GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. R software was used to obtain the cross-targets of JP and SLE-GIOP and to perform GO and KEGG enrichment analysis. Cytoscape software was used to make the Chinese Medicines-Active Ingredient-Intersection Targets network diagram. STRING database construct protein-protein interaction network and obtain the core targets. Auto Dock Tools and Pymol software were used for docking. Results: Fifty eight targets overlapped between JP and SLE-GIOP were suggested as potential targets of JP in the treatment of SLE-GIOP. Network topology analysis identified five core targets. GO enrichment analysis was obtained 1,968 items, and the top 10 biological process, closeness centrality, and molecular function were displayed. A total of 154 signaling pathways were obtained by KEGG enrichment analysis, and the top 30 signaling pathways were displayed. JP was well bound by MAPK1, TP53, and MYC according to the molecular docking results. Conclusion: We investigated the potential targets and signaling pathways of JP against SLE-GIOP in this study. It shows that JP is most likely to achieve the purpose of treating SLE-GIOP by promoting the proliferation and differentiation of osteoblasts. A solid theoretical foundation will be provided for the future study of clinical and experimental topics.
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Medicamentos Herbarios Chinos , Lupus Eritematoso Sistémico , Osteoporosis , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Glucocorticoides , Lupus Eritematoso Sistémico/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
RUNX3 is a transcription factor with regulatory roles in cell proliferation and development. While largely characterized as a tumor suppressor, RUNX3 can also be oncogenic in certain cancers. Many factors account for the tumor suppressor function of RUNX3, which is reflected by its ability to suppress cancer cell proliferation after expression-restoration, and its inactivation in cancer cells. Ubiquitination and proteasomal degradation represent a major mechanism for the inactivation of RUNX3 and the suppression of cancer cell proliferation. On the one hand, RUNX3 has been shown to facilitate the ubiquitination and proteasomal degradation of oncogenic proteins. On the other hand, RUNX3 can be inactivated through the ubiquitin-proteasome system. This review encapsulates two facets of RUNX3 in cancer: how RUNX3 suppresses cell proliferation by facilitating the ubiquitination and proteasomal degradation of oncogenic proteins, and how RUNX3 is degraded itself through interacting RNA-, protein-, and pathogen-mediated ubiquitination and proteasomal degradation.
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Neoplasias , Complejo de la Endopetidasa Proteasomal , Humanos , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina/metabolismo , Ubiquitinación , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismoRESUMEN
A novel electromagnetic induction low temperature thermal desorption treatment (EMI LTTD) for petroleum hydrocarbons contaminated soil was introduced in this work. The removal rate of total petroleum hydrocarbons (TPH) under various factors, the morphology changes of soils as well as removal mechanism were investigated. Results suggested that increasing the heating temperature significantly increased the removal rate of TPH. At the beginning of 20 min, most of hydrocarbons (93.44-96.91 wt%) was removed with the temperature ranged from 200 °C to 300 °C. Besides, the initial contaminants concentration, particle size and thickness of soil slightly influenced the removal rate of TPH. Desorption kinetic study demonstrated that first-order model was well-described for desorption behavior. Response surface methodology analysis showed the temperature of 216 °C, the residence time of 21 min and the moisture content of 18% was an optimum condition recommended for potentially practical application. Under this condition, the results for the composition of hydrocarbons based on carbon number fractions indicated that the fractions of C10â¼C16, C17â¼C22 still existed in soil, while C23â¼C28 was not detected after EMI LTTD treatment. Proposed mechanism was both hydrocarbons removed by evaporation at any temperature, while parts of heavy hydrocarbons was cracked within the soil close to induction medium, resulting in re-adsorption of light hydrocarbons. A buckwheat germination and growth test indicated that soil treated by EMI LTTD was potential in reutilization for planting.