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Magnetic two-dimensional (2D) materials are a unique class of quantum materials that can exhibit interesting magnetic phenomena, such as layer-dependent magnetism. The most significant barrier to 2D magnet discovery and study lies in our ability to exfoliate materials down to the monolayer limit. Therefore designing exfoliation methods that produce clean, monolayer sheets is crucial for the growth of 2D material research. In this work, we develop a facile chemical exfoliation method using lithium naphthalenide for obtaining 2D nanosheets of magnetic van der Waals material CrOCl. Using our optimized method, we obtain freestanding monolayers of CrOCl, with the thinnest measured height to date. We also provide magnetic characterization of bulk, intercalated intermediate, and nanosheet pellet CrOCl, showing that exfoliated nanosheets of CrOCl exhibit magnetic order. The results of this study highlight the tunability of the chemical exfoliation method, along with providing a simple method for obtaining 2D CrOCl.
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BACKGROUND AND PURPOSE: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). METHODS: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. RESULTS: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. CONCLUSION: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.
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Neoplasias Encefálicas , Irradiación Craneana , Neoplasias Pulmonares , Imagen por Resonancia Magnética , Terapia Recuperativa , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Anciano , Irradiación Craneana/métodos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Estudios Retrospectivos , Estadificación de Neoplasias , Adulto , Quimioradioterapia/métodosRESUMEN
Developing a dual-efficiency agent with antiresorptive and anabolic applications is a promising strategy for treating osteoporosis. This study reports the discovery of dual antiosteoporosis agents via a chemotype-assembly approach. Chemotype analysis identified 12 antiresorptive and 12 anabolic chemotypes and 7 dual-function chemotype-assembly rules. Based on these assembly rules, a dual-functional compound S24 was discovered. S24 exhibits osteoclastogenesis inhibition with an IC50 value of 10.28 µM and osteoblast differentiation stimulation at 10 µM. S24 derivatives were designed and synthesized based on the activity relationship of the chemotypes. This yielded a more active compound, S24-14, with an osteoclastogenesis inhibition IC50 value of 0.40 µM and osteoblast differentiation stimulation at 1.0 µM; compound S24-14 also suppressed bone loss in vivo. These results prove that S24-14 can be a potential lead for antiosteoporosis drug development.
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Lithium-sulfur (Li-S) batteries are widely regarded as one of the most promising next-generation high-energy-density energy storage devices. However, soluble lithium polysulfides (LiPSs) corrode Li metal and deteriorate the cycling stability of Li-S batteries. Understanding the reaction mechanism between LiPSs and Li metal anode is imperative. Herein, the reaction rate and products of LiPSs with Li metal anode, the composition and structure of the as-generated solid electrolyte interphase (SEI), and the mechanism of lithium nitrate (LiNO3) additives for inhibiting the corrosion reactions are systematically unveiled. Concretely, LiPSs react with Li metal anode more rapidly than Li salt and generate a Li2S-rich SEI. The Li2S-rich SEI is highly reactive with LiPSs, which exacerbates the formation of dendritic Li and the continuous corrosion of active Li. LiNO3 functions dominantly by modulating the solvation structure of LiPSs and inherently reducing the reactivity of LiPSs, rather than the conventional understanding of LiNO3 participating in the formation of SEI. This work reveals the reaction mechanism between LiPSs and Li metal anode and inspires rational regulating of the solvation structure of LiPSs for stabilizing Li metal anode in Li-S batteries.
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Recently, renewable bio-based materials have received more and more attention due to environmental issues such as global warming and ecosystem destruction. In the present work, a series of isosorbide-based bioelastomers poly(isosorbide carbonate-co-butanediol aliphatic esters)s (PICBAs) are synthesized by a facile and economical two-step melt polycondensation. Due to the slightly self-crosslinking reaction of isosorbide, PICBAs exhibit excellent tensile strength and self-healing ability, the mechanical properties of PICBAs can recover over 95% after 48 h under room temperature. In addition, PICBAs can stick different substances, such as glass, rubber, plastic, and stones, and show better adhesive performance than 3M commercially available double-sided tape. Consequently, isosorbide-based bioelastomers PICBAs are of great potential to be used as environmentally friendly pressure-sensitive adhesives (PSA) in the future.
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OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.
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Biotic stresses caused by bacterial and fungal pathogens damage crops; identifying treatments that enhance disease resistance provides important information for understanding plant defenses and sustainable agriculture. Salt stress affects crop yields worldwide; however, studies have focused on the toxic sodium ion, leaving the effects of the chloride ion unclear. In this study, we found that irrigation with a combination of chloride salts (MgCl2, CaCl2, and KCl) suppressed the cell death phenotype of the ceramide kinase mutant acd5. Chloride salt pre-irrigation also significantly limited the cell death caused by Pseudomonas syringae pv maculicola infection and inhibited the multiplication of this bacterial pathogen in a mechanism partially dependent on the salicylic acid pathway. Moreover, chloride salt pre-irrigation improved plant defenses against the fungal pathogen challenge, confining the lesion area caused by Botrytis cinerea infection. Furthermore, the growth of herbivorous larvae of Spodoptera exigua was retarded by feeding on chloride salt irrigated plants. Thus, our data suggest that treatment with Cl- increases broad spectrum resistance to biotic challenges.
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In situ polymerized solid-state electrolytes have attracted much attention due to high Li-ion conductivity, conformal interface contact, and low interface resistance, but are plagued by lithium dendrite, interface degradation, and inferior thermal stability, which thereby leads to limited lifespan and severe safety hazards for high-energy lithium metal batteries (LMBs). Herein, an in situ polymerized electrolyte is proposed by copolymerization of 1,3-dioxolane with 1,3,5-tri glycidyl isocyanurate (TGIC) as a cross-linking agent, which realizes a synergy of battery thermal safety and interface compatibility with Li anode. Functional TGIC enhances the electrolyte polymeric level. The unique carbon-formation mechanism facilitates flame retardancy and eliminates the battery fire risk. In the meantime, TGIC-derived inorganic-rich interphase inhibits interface side reactions and promotes uniform Li plating. Intrinsically safe LMBs with nonflammability and outstanding electrochemical performances under extreme temperatures (130 °C) are achieved. This functional polymer design shows a promising prospect for the development of safe LMBs.
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Operating a lithium-ion battery (LIB) in a wide temperature range is essential for ensuring a stable electricity supply amidst fluctuating temperatures caused by climate or terrain changes. Electrolyte plays a pivotal role in determining the temperature durability of batteries. However, specialized electrolytes designed for either low or high temperatures typically possess distinct features. Therefore, wide-temperature electrolytes (WTEs) are necessary as they encompass a combination of diverse properties, which complicates the clear instruction of WTE design. Here we represent an artificial intelligence (Al)-assisted workflow of WTE design through stepwise parameterizations and calculations. Linear mono-nitriles are identified as ideal wide-liquidus-range solvents that can "softly" solvate lithium ions by weak interactions. In addition, the explainable modules revealed the halogenoid similarity of cyanide as fluorine on the electrolyte properties (e.g. boiling point and dielectric constant). With the further introduction of an ether bond, 3-methoxypropionitrile (MPN) has been eventually determined as a main electrolyte solvent, enabling the battery operation from -60 to 120 °C. Particularly, a LiCoO2/Li cell using the proposed WTE can realize stable cycling with capacity retention reaching 72.3 % after 50 cycles under a high temperature of 100 °C.
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Accumulation of cadmium (Cd) in rice is not only harmful to the growth of plants but also poses a threat to human health. Exposure to Cd triggers unfolded protein response (UPR) within cells, a process that is still not completely understood. The study demonstrated that the lack of OsbZIP39, an essential endoplasmic reticulum (ER)-resident regulator of the UPR, resulted in decreased Cd intake and reduced Cd levels in the roots, stems, and grains of rice. Upon exposure to Cd stress, GFP-OsbZIP39 translocated from ER to nucleus, initiating UPR. Further investigation revealed that Cd treatment caused changes in sphingolipid levels in the membrane, influencing the localization and activation of OsbZIP39. Yeast one-hybrid and dual-LUC assays were conducted to validate the interaction between activated OsbZIP39 and the promoter of the defensin-like gene OsCAL2, resulting in an increase in its expression. Different variations were identified in the coding region of OsbZIP39, which may explain the varying levels of Cd accumulation observed in the indica and japonica subspecies. Under Cd treatment, OsbZIP39ind exhibited a more significant enhancement in the transcription of OsCAL2 compared to OsbZIP39jap. Our data suggest that OsbZIP39 positively regulates Cd uptake in rice, offering an encouraging objective for the cultivation of low-Cd rice.
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Cadmio , Estrés del Retículo Endoplásmico , Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , Oryza/metabolismo , Oryza/genética , Oryza/efectos de los fármacos , Cadmio/toxicidad , Cadmio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Defensinas/genética , Defensinas/metabolismo , Respuesta de Proteína Desplegada/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacosRESUMEN
The human brain is a dynamic system that shows frequency-specific features. Neuroimaging studies have shown that both healthy individuals and those with chronic pain disorders experience pain influenced by various processes that fluctuate over time. Primary dysmenorrhea (PDM) is a chronic visceral pain that disrupts the coordinated activity of brain's functional network. However, it remains unclear whether the dynamic interactions across the whole-brain network over time and their associations with neurobehavioral symptoms are dependent on the frequency bands in patients with PDM during the pain-free periovulation phase. In this study, we used an energy landscape analysis to examine the interactions over time across the large-scale network in a sample of 59 patients with PDM and 57 healthy controls (HCs) at different frequency bands. Compared with HCs, patients with PDM exhibit aberrant brain dynamics, with more significant differences in the slow-4 frequency band. Patients with PDM show more indirect neural transition counts due to an unstable intermediate state, whereas neurotypical brain activity frequently transitions between 2 major states. This data-driven approach further revealed that the brains of individuals with PDM have more abnormal brain dynamics than HCs. Our results suggested that unstable brain dynamics were associated with the strength of brain functional segregation and the Pain Catastrophizing Scale score. Our findings provide preliminary evidence that atypical dynamics in the functional network may serve as a potential key feature and biological marker of patients with PDM during the pain-free phase. PERSPECTIVE: We applied energy landscape analysis on brain-imaging data to identify relatively stable and dominant brain activity patterns for patients with PDM. More atypical brain dynamics were found in the slow-4 band and were related to the strength of functional segregation, providing new insights into the dysfunction brain dynamics.
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Thymocyte development requires precise control of PI3K-Akt signaling to promote proliferation and prevent leukemia and autoimmune disorders. Here, we show that ablating individual clusters of the miR-17â¼92 family has a negligible effect on thymocyte development, while deleting the entire family severely impairs thymocyte proliferation and reduces thymic cellularity, phenocopying genetic deletion of Dicer. Mechanistically, miR-17â¼92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17â¼92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17â¼92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR-17â¼92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17â¼92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17â¼92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17â¼92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases.
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Autoinmunidad , Leucemia , MicroARNs , Timocitos , MicroARNs/metabolismo , MicroARNs/genética , Animales , Timocitos/metabolismo , Timocitos/patología , Autoinmunidad/genética , Ratones , Leucemia/patología , Leucemia/genética , Proliferación Celular , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Diferenciación Celular/genética , Transducción de Señal , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Ratones Endogámicos C57BL , Receptores de Antígenos de Linfocitos T/metabolismo , Carcinogénesis/genética , Carcinogénesis/patología , Carcinogénesis/metabolismoRESUMEN
PURPOSE: To establish two nomograms to quantify the risk of lung metastasis (LM) in laryngeal carcinoma (LC) and predict the overall survival of LC patients with LM. METHODS: Totally 9515 LC patients diagnosed histologically from 2000 to 2019 were collected from the Surveillance, Epidemiology, and End Results database. The independent diagnostic factors for LM in LC patients and prognostic factors for LC patients with LM were identified by logistic and Cox regression analysis, respectively. Nomograms were established based on regression coefficients and evaluated by receiver operating characteristic curve, calibration curves, and decision curve analysis. RESULTS: Patients with supraglottis, higher pathological grade, higher N stage, and distant metastasis (bone, brain, or liver) were more likely to have LM (P < 0.05). Chemotherapy, surgery and radiotherapy were independent factors of the overall survival of LC patients with LM (P < 0.05). The area under curve of diagnostic nomogram were 0.834 and 0.816 in the training and validation cohort respectively. For the prognostic nomogram, the area under curves of 1-, 2-, and 3-years were 0.735, 0.734, and 0.709 in the training cohort and 0.705, 0.803, and 0.809 in the validation cohort. The calibration curves and decision curve analysis indicated good performance of the nomograms. CONCLUSION: Distant metastasis (bone, brain, or liver) and N stage should be considered for prediction of LM in LC patients. Chemotherapy is the most significant influencing prognostic factor improving the survival of LC patients with LM. Two nomograms may benefit for providing better precautionary measures and treatment decision.
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Neoplasias Laríngeas , Neoplasias Pulmonares , Nomogramas , Programa de VERF , Humanos , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/diagnóstico , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/diagnóstico , Persona de Mediana Edad , Pronóstico , Anciano , Estadificación de Neoplasias , Curva ROC , Adulto , Tasa de SupervivenciaRESUMEN
Background: Frailty has been one of the most serious global public health challenges we will ever face. Oxidative stress is associated with the pathogenesis of frailty, and may be accurately reflected by the oxidative balance score (OBS). However, there have been no studies examining the effect of OBS on frailty. Therefore, we aimed to explore the association between OBS and frailty and whether there was an interaction between the outcomes. Methods: 22 914 participants aged over 20 years taking part in the National Health and Nutrition Examination Survey (NHANES) in 2007-2018 were involved in the study. Sixteen dietary factors and four lifestyle factors were selected to score the OBS. A modified 36-item deficit cumulative frailty index (FI) was used to assess the degree of frailty. The association between OBS and frailty was analyzed using binary logistic regression. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations. Results: A negative association between OBS and the prevalence of frailty was found in this study. There was also an interaction between OBS and age in their association with frailty. High OBS was significantly and negatively associated with the prevalence of frailty in the 20-39 and 40-64 age groups. In addition, higher OBS combined with a population in the 20-39 age group resulted in a stronger negative association with frailty. Conclusion: High OBS was significantly associated with lower odds of frailty. An interaction existed between OBS and age. Individuals, especially in relatively young populations, are advised to increase OBS through greater intake of antioxidant nutrients and healthier lifestyles, thereby reducing the adverse effects of frailty.
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Fragilidad , Encuestas Nutricionales , Estrés Oxidativo , Humanos , Fragilidad/epidemiología , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Adulto Joven , Estudios Transversales , Estilo de Vida , Anciano de 80 o más Años , PrevalenciaRESUMEN
Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.
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Penfigoide Ampolloso , Pénfigo , Análisis de la Célula Individual , Humanos , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/genética , Penfigoide Ampolloso/patología , Pénfigo/inmunología , Pénfigo/genética , Pénfigo/patología , Análisis de la Célula Individual/métodos , Piel/inmunología , Piel/patología , Linfocitos T CD8-positivos/inmunología , Femenino , Masculino , Análisis de Secuencia de ARN , Linfocitos T CD4-Positivos/inmunología , Macrófagos/inmunología , Linfocitos B/inmunología , Anciano , Células Dendríticas/inmunología , Persona de Mediana EdadRESUMEN
The global rise in prediabetes and diabetes, with type 2 diabetes (T2DM) being predominant, highlights the association between T2DM and hypertriglyceridemia (HTG). Patients with both abnormal glucose levels and HTG require increased attention due to higher risks of complications and mortality. Therefore, this study aimed to find the key long non-coding RNA (lncRNA) of HTG in the abnormal glucose metabolism patients. We collected blood samples for RNA sequencing experiments and blood samples for validation in population. We have conducted RNA sequencing, weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR) in a 82-vs-82-sample-size population and insulin induced HepG2, RNA- Fluorescence in situ hybridization (FISH) and Cell Counting Kit-8 (CCK-8). We also explored lipid metabolism related transcription factor and the related protein expression and processed key lncRNA by both interference expression and overexpression, and the related consequences were rescued by its target mRNA. ENST00000540317.5 (LINC317.5) was lower in HTG with abnormal glucose metabolism and was found in both cytoplasm and nucleus in HepG2, inversely regulating the accumulation of TG and its target mRNA TKFC. Relative expression of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ) were decreasing, and SREBP-1c (sterol regulatory element-binding protein-1c) was increasing of the interference expression of LINC317.5. Interference expression of LINC317.5 significantly decreased the protein expression of ACADM and CPT1A, whereas increased the protein expression of FAS and ACC1. TKFC partly reduced the triglyceride (TG) accumulation of LINC317.5. In conclusion, we suggested LINC317.5-TKFC as a key for TG accumulation in the HepG2-insulin resistant (IR). These might provide information of non-invasive biomarkers for the HTG with abnormal glucose.
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Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent anthropogenic chemicals that are widely distributed in the environment and pose significant risks to human health. Foam fractionation has emerged as a promising method to recover PFOS/PFOA from water. However, PFOS/PFOA concentrations in wastewater are often inadequate to generate stable foams due to their high critical micelle concentrations and the addition of a cosurfactant is necessary. In this study, we developed whey soy protein (WSP) as a green frother and collector derived from soybean meal (SBM), which is an abundant and cost-effective agro-industrial residue. WSP exhibited excellent foaming properties across a wide pH range and demonstrated strong collection capabilities that enhanced the recovery of PFOS/PFOA. The mechanism underlying this collection ability was elucidated through various methods, revealing the involvement of electrostatic attraction, hydrophobic interaction, and hydrogen bonding. Furthermore, we designed a double plate internal to improve the enrichment of PFOS/PFOA by approximately 2.3 times while reducing water recovery. Under suitable conditions (WSP concentration: 300 mg/L, pH: 6.0, air flowrate: 300 mL/min), we achieved high recovery percentages of 94-98% and enrichment ratios of 7.5-12.8 for PFOS/PFOA concentrations ranging from 5 to 20 mg/L. This foam fractionation process holds great promise for the treatment of PFOS/PFOA and other per- and polyfluoroalkyl substances.
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Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Agua , Proteínas de Soja , Suero Lácteo/química , Proteína de Suero de Leche , Fluorocarburos/análisis , Caprilatos/análisis , Ácidos Alcanesulfónicos/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: The discovering of an osteoclast (OC) coupling active agent, capable of suppressing OC-mediated bone resorption while concurrently stimulating osteoblast (OB)-mediated bone formation, presents a promising strategy to overcome limitations associated with existing antiresorptive agents. However, there is a lack of research on active OC coupling agents. PURPOSE: This study aims to investigate the potential of Jiangu Formula (JGF) in inhibiting OCs while maintaining the OCOB coupling function. METHODS: The anti-osteoporosis efficacy of JGF was evaluated in osteoporosis models induced by ovariectomy in C57BL/6 mouse and SD rats. The effect of JGF on OCs was evaluated by detecting its capacity to inhibit OC differentiation and bone resorption in an in vitro osteoclastogenesis model induced by RANKL. The OCOB coupling activity of JGF was evaluated by measuring the secretion levels of OC-derived coupling factors, OB differentiation activity of MC3T3-E1 interfered with conditioned medium, and the effect of JGF on OC inhibition and OB differentiation in a C3H10T1/2-RAW264.7 co-culture system. The mechanism of JGF was studied by network pharmacology and validated using western blot, immunofluorescence (IF), and ELISA. Following that, the active ingredients of JGF were explored through a chemotype-assembly approach, activity evaluation, and LC-MS/MS analysis. RESULTS: JGF inhibited bone resorption in murine osteoporosis without compromising the OCOB coupling effect on bone formation. In vitro assays showed that JGF preserved the coupling effect of OC on OB differentiation by maintaining the secretion of OC-derived coupling factors. Network analysis predicted STAT3 as a key regulation point for JGF to exert anti-osteoporosis effect. Further validation assays confirmed that JGF upregulated p-STAT3(Ser727) and its regulatory factors IL-2 in RANKL-induced RAW264.7 cells. Moreover, 23 components in JGF with anti-OC activity identified by chemotype-assembly approach and verification experiments. Notably, six compounds, including ophiopogonin D, ginsenoside Re, ginsenoside Rf, ginsenoside Rg3, ginsenoside Ro, and ononin were identified as OC-coupling compounds. CONCLUSION: This study first reported JGF as an agent that suppresses bone loss without affecting bone formation. The potential coupling mechanism of JGF involves the upregulation of STAT3 by its regulators IL-2. Additionally, the chemotype-assembly approach elucidated the activity compounds present in JGF, offering a novel strategy for developing an anti-resorption agent that preserves bone formation.
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Resorción Ósea , Diferenciación Celular , Medicamentos Herbarios Chinos , Ratones Endogámicos C57BL , Osteoblastos , Osteoclastos , Osteoporosis , Ratas Sprague-Dawley , Animales , Osteoclastos/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Osteoporosis/tratamiento farmacológico , Osteoblastos/efectos de los fármacos , Femenino , Células RAW 264.7 , Diferenciación Celular/efectos de los fármacos , Resorción Ósea/tratamiento farmacológico , Ovariectomía , Ligando RANK , Ratas , Osteogénesis/efectos de los fármacos , Modelos Animales de Enfermedad , Factor de Transcripción STAT3/metabolismoRESUMEN
The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.