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BACKGROUND: Long non-coding RNA (lncRNA) is a class of single-stranded RNA biomolecules involving over 200 nucleotides and does not encode proteins. Research on lncRNA has become a hot spot for the past few years. DNM3OS (Dynamin 3 Opposite Strand), which has been clearly identified as a regulatory lncRNA, exerts an integral role in the pathophysiology of multiple human diseases. OBJECTIVE: The current review study summarizes the pathogenic mechanism of DNM3OS in various pathophysiological processes, aiming to reveal its important value as a therapeutic drug target for related human diseases and provide a new way for targeted therapy. METHODS: Through systematic retrieval and in-depth study of relevant articles in PubMed, this article analyzes and summarizes the pathogenic roles and molecular mechanisms in pathophysiological processes of long non-coding RNA DNM3OS. RESULTS: DNM3OS exerts an important regulatory role in the occurrence and development of bone diseases, neoplastic diseases, fibrotic diseases, inflammatory diseases, and many other diseases. CONCLUSION: DNM3OS is a potential new biomarker and therapeutic target for the treatment of a series of diseases, consisting of bone diseases, neoplastic diseases, fibrotic diseases, and inflammatory diseases.
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Neoplasias , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Inflamación/metabolismo , Enfermedades Óseas/genética , Enfermedades Óseas/metabolismo , Fibrosis , AnimalesRESUMEN
NLRP3 plays a role in the development of autoinflammatory diseases. NLRP3, ASC, and Caspases 1 or 8 make up the NLRP3 inflammasome, which is an important part of innate immune system. The NLRP3 inflammasome-mediated inflammatory cytokines may also participate in metabolic disorders, such as diabetes, hyperlipidemia, atherosclerosis, non-alcoholic fatty liver disease, and gout. Hence, an overview of the NLRP3 regulation in these metabolic diseases and the potential drugs targeting NLRP3 is the focus of this review.
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Polluted environments often contain large amounts of toxic metals, such as cadmium, which pose a major threat to ecosystems and public health. Contamination by cadmium and its compounds is often observed in areas surrounding zinc mining sites and electroplating factories, and the control of cadmium pollution is essential for environmental safety and health. In this study, a highly efficient and straightforward separation strategy for K4Fe(CN)6@Fe3O4 nanocomposites is successfully developed to capture the Cd ions in the water environment. Batch adsorption experiments revealed that K4Fe(CN)6@Fe3O4 exhibited a high cadmium removal rate (greater than 98â¯%) at a pH level of 6.0 and solid-liquid ratio of 1.0â¯g/L at room temperature (298â¯K). Kinetic analysis revealed that the adsorption process followed a pseudo-second-order model and cadmium was rapidly removed in the first 10â¯min, with chemisorption dominating the capture of Cd2+ by K4Fe(CN)6@Fe3O4. Adsorption isotherms revealed a heterogeneous adsorption behavior, with a maximum adsorption capacity of 40.78â¯mg/g. The intrinsic adsorption of Cd2+ by K4Fe(CN)6@Fe3O4 occurring primarily through electrostatic interaction and ion exchange. In addition, K4Fe(CN)6@Fe3O4 exhibited an excellent regeneration capacity. Therefore, integrating Fe3O4 into the metal cyanide not only provided the composite material with excellent chemical stability and selective adsorption sites for Cd2+, but also facilitated subsequent sorbent collection and recovery. Overall, this study presents a simple and feasible approach for integrating Fe3O4 into potassium ferrocyanide frameworks for efficient cadmium removal from contaminated water.
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Cadmio , Ferrocianuros , Contaminantes Químicos del Agua , Cadmio/química , Cadmio/análisis , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Adsorción , Ferrocianuros/química , Cinética , Purificación del Agua/métodos , Concentración de Iones de Hidrógeno , Nanocompuestos/químicaRESUMEN
Total saponins from Panax japonicus (TSPJ) have many beneficial physiological activities, particularly in alleviating the damages of aging and abnormal lipid metabolism. This work used mice models to investigate if TSPJ reduced obesity and regulated metabolic functions via the intestinal microbiota, the disturbance of which has been shown to cause aging-related diseases. The results showed that TSPJ significantly reduced the weight and blood lipid level of aging mice. Further analyses showed that TSPJ significantly inhibited adipogenesis, changed the composition of the intestinal flora, and protected the integrity of the intestinal barrier. It was inferred from the accumulated experimental data that TSPJ helped to combat obesity in aging mice by regulating the intestinal microbiota and promoting microbial metabolism.
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Envejecimiento , Microbioma Gastrointestinal , Panax , Saponinas , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Saponinas/farmacología , Saponinas/uso terapéutico , Panax/química , Ratones , Envejecimiento/efectos de los fármacos , Masculino , Obesidad/metabolismo , Obesidad/microbiología , Metabolismo de los Lípidos/efectos de los fármacos , Trastornos del Metabolismo de los Lípidos/tratamiento farmacológico , Trastornos del Metabolismo de los Lípidos/metabolismo , Adipogénesis/efectos de los fármacos , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Aging affects lipid metabolism and can cause obesity as it is closely related to the disorder of many lipogenic regulatory factors. LncRNAs have been recognized as pivotal regulators across diverse biological processes, but their effects on lipogenesis in aging remain to be further studied. In this work, using RNA sequencing (RNA-Seq), we found that the expression of lncRNA AI504432 was significantly upregulated in the eWAT (epididymal white adipose tissue) of aging mice, and the knockdown of AI504432 notably reduced the expression of several adipogenic genes (e.g., Cebp/α, Srebp-1c, Fasn, Acaca, and Scd1) in senescent adipocytes. The bioinformatics investigation revealed that AI504432 possessed a binding site for miR-1a-3p, and the discovery was verified by the luciferase reporter assay. The expression of Fasn was increased upon the inhibition of miR-1a-3p but restored upon the simultaneous silencing of AI504432. Taken together, our results suggested that AI504432 controlled lipogenesis through the miR-1a-3p/Fasn signaling pathway. The findings may inspire new therapeutic approaches to target imbalanced lipid homeostasis due to aging.
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Adipocitos , Senescencia Celular , Acido Graso Sintasa Tipo I , Lipogénesis , MicroARNs , ARN Largo no Codificante , Regulación hacia Arriba , Animales , MicroARNs/metabolismo , MicroARNs/genética , Lipogénesis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Adipocitos/metabolismo , Acido Graso Sintasa Tipo I/metabolismo , Acido Graso Sintasa Tipo I/genética , Regulación hacia Arriba/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Envejecimiento/metabolismo , Envejecimiento/genéticaRESUMEN
The poor machinability of halide perovskite crystals severely hampered their practical applications. Here a high-throughput growth method is reported for armored perovskite single-crystal fibers (SCFs). The mold-embedded melt growth (MEG) method provides each SCF with a capillary quartz shell, thus guaranteeing their integrality when cutting and polishing. Hundreds of perovskite SCFs, exemplified by CsPbBr3, CsPbCl3, and CsPbBr2.5I0.5, with customized dimensions (inner diameters of 150-1000 µm and length of several centimeters), are grown in one batch, with all the SCFs bearing homogeneity in shape, orientation, and optical/electronic properties. Versatile assembly protocols are proposed to directly integrate the SCFs into arrays. The assembled array detectors demonstrated low-level dark currents (< 1 nA) with negligible drift, low detection limit (< 44.84 nGy s-1), and high sensitivity (61147 µC Gy-1 cm-2). Moreover, the SCFs as isolated pixels are free of signal crosstalk while showing uniform X-ray photocurrents, which is in favor of high spatial resolution X-ray imaging. As both MEG and the assembly of SCFs involve none sophisticated processes limiting the scalable fabrication, the strategy is considered to meet the preconditions of high-throughput productions.
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The environmental implications of antibiotics have drawn widespread attention. Numerous monomer-based bismuth oxide halide catalysts have been extensively studied to remove tetracycline (TC) from aquatic environments. Integrating bismuth oxide halide composites with In-based metal organic framework (NH2-MIL-68(In)) might potentially serve as a novel strategy. By meticulously adjusting Cl and I within the composite bismuth halide oxide (B-x), a suite of purpose built heterojunctions (NMB-x) were synthesized, which were engineered to facilitate the efficient photodegradation of TC in simulated and actual aquatic environments. The incorporation of Z-scheme heterojunctions yielded a significant enhancement in photocatalytic responsiveness and charge carrier separation. Notably, NMB-0.3 demonstrated remarkable TC removal efficiency of 88.52 ± 3.05%, which is 3.74 times of B-0.3 within 90 min. The apparent quantum yield was also increased from 8.97% (B-0.3) to 19.68% (NMB-0.3). The removal of TC from natural water bodies was also assessed. Moreover, the photocatalyst concentration, assessed using response surface method, was found to show influential factors on TC removal. In addition, density functional theory (DFT) simulations were employed to identify vulnerable sites within TC. Intermediates and pathways in the photodegradation of TC have also been inferred. Furthermore, a comprehensive environmental toxicity assessment of representative intermediates demonstrated that these intermediates exhibited significantly reduced environmental toxicity compared to TC. This study provides a new approach to the design strategy of efficient and environmentally friendly MOF-based photocatalysts.
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Bismuto , Estructuras Metalorgánicas , Fotólisis , Tetraciclina , Contaminantes Químicos del Agua , Estructuras Metalorgánicas/química , Tetraciclina/química , Catálisis , Bismuto/química , Contaminantes Químicos del Agua/química , Antibacterianos/químicaRESUMEN
BACKGROUND: Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear. METHODS: Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation. RESULTS: Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1. CONCLUSION: In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.
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Glucemia , Diabetes Mellitus Experimental , Células Endoteliales de la Vena Umbilical Humana , Canales Iónicos , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo III , Estrés Oxidativo , Animales , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Diabetes Mellitus Experimental/metabolismo , Canales Iónicos/metabolismo , Canales Iónicos/genética , Glucemia/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Mecanotransducción Celular , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/deficiencia , Células Cultivadas , Proliferación Celular , Apoptosis , Masculino , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/fisiopatología , Angiopatías Diabéticas/patología , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/etiología , Movimiento Celular , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Aorta Torácica/metabolismo , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Ratones , Estreptozocina , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Endotelio Vascular/patología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genéticaRESUMEN
The intensification of the aging population is often accompanied by an increase in agerelated diseases, which impair the quality of life of the elderly. The characteristic feature of aging is progressive physiological decline, which is the largest cause of human pathology and death worldwide. However, natural aging interacts in exceptionally complex ways within and between organs, but its underlying mechanisms are still poorly understood. Long non-coding RNA (lncRNA) is a type of noncoding RNA that exceeds 200 nucleotides in length and does not possess protein-coding ability. It plays a crucial role in the occurrence and development of diseases. ANRIL, also known as CDKN2B-AS1, is an antisense ncRNA located at the INK4 site. It can play a crucial role in agerelated disease progression by regulating single nucleotide polymorphism, histone modifications, or post-transcriptional modifications (such as RNA stability and microRNA), such as cardiovascular disease, diabetes, tumor, arthritis, and osteoporosis. Therefore, a deeper understanding of the molecular mechanisms of lncRNA ANRIL in age-related diseases will help provide new diagnostic and therapeutic targets for clinical practice.
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Sulfadimidine (SM2) is an N-substituted derivative of p-aminobenzenesulfonyl structure. This study aimed to analyze the metabolism of SM2 in carp (Cyprinus carpio). The carps were fed with SM2 at a dose of 200 mg/(kg · bw) and then killed. The blood, muscle, liver, kidney, gill, other guts, and carp aquaculture water samples were collected. The UHPLC-Q-Exactive Plus Orbitrap-MS was adopted for determining the metabolites of SM2 in the aforementioned samples. Twelve metabolites, which were divided into metabolites in vivo and metabolites in vitro, were identified using Compound Discoverer software. The metabolic pathways in vivo of SM2 in carp included acetylation, hydroxylation, glucoside conjugation, glycine conjugation, carboxylation, glucuronide conjugation, reduction, and methylation. The metabolic pathways in vitro included oxidation and acetylation. This study clarified the metabolites and metabolic pathways of SM2 in carp and provided a reference for further pharmacodynamic evaluation and use in aquaculture.
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Carpas , Carpas/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Redes y Vías Metabólicas , Sulfonamidas/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Espectrometría de Masas/métodosRESUMEN
Introduction: The Tibetan antelope (Pantholops hodgsonii) is a remarkable mammal thriving in the extreme Qinghai-Tibet Plateau conditions. Despite the availability of its genome sequence, limitations in the scaffold-level assembly have hindered a comprehensive understanding of its genomics. Moreover, comparative analyses with other Bovidae species are lacking, along with insights into genome rearrangements in the Tibetan antelope. Methods: Addressing these gaps, we present a multifaceted approach by refining the Tibetan Antelope genome through linkage disequilibrium analysis with data from 15 newly sequenced samples. Results: The scaffold N50 of the refined reference is 3.2 Mbp, surpassing the previous version by 1.15-fold. Our annotation analysis resulted in 50,750 genes, encompassing 29,324 novel genes not previously study. Comparative analyses reveal 182 unique rearrangements within the scaffolds, contributing to our understanding of evolutionary dynamics and species-specific adaptations. Furthermore, by conducting detailed genomic comparisons and reconstructing rearrangements, we have successfully pioneered the reconstruction of the X-chromosome in the Tibetan antelope. Discussion: This effort enhances our comprehension of the genomic landscape of this species.
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ETHNOPHARMACOLOGICAL RELEVANCE: Hawthorn leaves are a combination of the dried leaves of the Rosaceae plants, i.e., Crataegus pinnatifida Bge. or Crataegus pinnatifida Bge. var. major N. E. Br., is primarily cultivated in East Asia, North America, and Europe. hawthorn leaf flavonoids (HLF) are the main part of extraction. The HLF have demonstrated potential in preventing hypertension, inflammation, hyperlipidemia, and atherosclerosis. However, the potential pharmacological mechanism behind its anti-atherosclerotic effect has yet to be explored. AIM OF THE STUDY: The in vivo and in vitro effects of HLF on lipid-mediated foam cell formation were investigated, with a specific focus on the levels of secreted phospholipase A2 type IIA (sPLA2-II A) in macrophage cells. MATERIALS AND METHODS: The primary constituents of HLF were analyzed using ultra-high performance liquid chromatography and liquid chromatography-tandem mass spectrometry. In vivo, HLF, at concentrations of 5 mg/kg, 20 mg/kg, and 40 mg/kg, were administered to apolipoprotein E knockout mice (ApoE-/-) fed by high-fat diet (HFD) for 16 weeks. Aorta and serum samples were collected to identify lesion areas and lipids through mass spectrometry analysis to dissect the pathological process. RAW264.7 cells were incubated with oxidized low-density lipoprotein (ox-LDL) alone, or ox-LDL combined with different doses of HLF (100, 50, and 25 µg/ml), or ox-LDL plus 24-h sPLA2-IIA inhibitors, for cell biology analysis. Lipids and inflammatory cytokines were detected using biochemical analyzers and ELISA, while plaque size and collagen content of plaque were assessed by HE and the Masson staining of the aorta. The lipid deposition in macrophages was observed by Oil Red O staining. The expression of sPLA2-IIA and SCAP-SREBP2-LDLR was determined by RT-qPCR and Western blot analysis. RESULTS: The chemical profile of HLF was studied using UPLC-Q-TOF-MS/MS, allowing the tentative identification of 20 compounds, comprising 1 phenolic acid, 9 flavonols and 10 flavones, including isovitexin, vitexin-4â³-O-glucoside, quercetin-3-O-robibioside, rutin, vitexin-2â³-O-rhamnoside, quercetin, etc. HLF decreased total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels in ApoE-/- mice (P < 0.05), reduced ox-LDL uptake, inhibited level of inflammatory factors, such as IL-6, IL-8, TNF-α, and IL-1êµ (P < 0.001), and alleviated aortic plaques with a thicker fibrous cap. HLF effectively attenuated foam cell formation in ox-LDL-treated RAW264.7 macrophages, and reduced levels of intracellular TC, free cholesterol (FC), cholesteryl ester (CE), IL-6, TNF-α, and IL-1ß (P < 0.001). In both in vivo and in vitro experiments, HLF significantly downregulated the expression of sPLA2-IIA, SCAP, SREBP2, LDLR, HMGCR, and LOX-1 (P < 0.05). Furthermore, sPLA2-IIA inhibitor effectively mitigated inflammatory release in RAW264.7 macrophages and regulated SCAP-SREBP2-LDLR signaling pathway by inhibiting sPLA2-IIA secretion (P < 0.05). CONCLUSION: HLF exerted a protective effect against atherosclerosis through inhibiting sPLA2-IIA to diminish SCAP-SREBP2-LDLR signaling pathway, to reduce LDL uptake caused foam cell formation, and to slow down the progression of atherosclerosis in mice.
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Aterosclerosis , Crataegus , Fosfolipasas A2 Secretoras , Placa Aterosclerótica , Ratones , Animales , Crataegus/química , Quercetina/uso terapéutico , Fosfolipasas A2 Secretoras/metabolismo , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Espectrometría de Masas en Tándem , Aterosclerosis/metabolismo , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/metabolismo , Macrófagos/metabolismo , Flavonoides/uso terapéutico , Lipoproteínas LDL/metabolismo , Transducción de Señal , Colesterol/metabolismo , Ratones Noqueados , Apolipoproteínas E/genéticaRESUMEN
Purpose: To analyze changes in survival outcomes in patients with ovarian clear cell carcinoma (OCCC) treated consecutively over a 16-year period using a population-based cohort. Methods: We conducted a retrospective analysis of OCCC from 2000 to 2015 using data from the Surveillance, Epidemiology, and End Results (SEER) program. The ovarian cancer-specific survival (OCSS) and overall survival (OS) were analyzed according to the year of diagnosis. Joinpoint Regression Program, Kaplan-Meier analysis, and multivariate Cox regression analyses were used for statistical analysis. Results: We included 4257 patients in the analysis. The analysis of annual percentage change in OCSS (P=0.014) and OS (P=0.006) showed that patients diagnosed in later years had significantly better outcomes compared to those diagnosed in early years. The results of the multivariate Cox regression analyses showed that the year of diagnosis was the independent prognostic factor associated with OCSS (P=0.004) and had a borderline effect on OS (P=0.060). Regarding the SEER staging, the OCSS (P=0.017) and OS (P=0.004) of patients with distant stage showed a significant trend toward increased, while no significant trends were found in the survival of patients with localized or regional stage diseases. Similar trends were found in those aged <65 years or those treated with surgery and chemotherapy. However, no statistically significant changes in the survival rate were found in those aged ≥65 years or those receiving surgery alone regardless of SEER stage during the study period. Conclusions: Our study observed a significant increase in the survival outcomes in OCCC from 2000 to 2015, and patients aged <65 years and those with distant stage experienced a greater improvement in survival.
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Recent scientific studies have highlighted the importance of long-chain noncoding RNAs (lncRNAs) in a variety of metabolic diseases, but the specific functions and mechanisms of lncRNAs in aberrant lipid synthesis associated with aging are unknown. In this work, we inspected the effects of lncRNAs on the lipid metabolism in aging mice, as substantial evidence suggests that aging disturbs lipid metabolism. The results revealed that the expression of lncRNA Gm15232 was significantly elevated in the epididymal white adipose tissue of aging mice compared to adult mice. This upregulation of Gm15232 functioned as a competitive endogenous RNA by inhibiting the expression of miR-192-3p, and the ensuing downregulation of miR-192-3p increased the expression of the glucocorticoid receptor gene, which ultimately stimulated fat synthesis. The upregulation of Gm15232 thus increased lipogenesis through this mechanism. This study reveals a potential target for the treatment of age-related abnormalities of lipid metabolism.
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Lipogénesis , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Regulación hacia Abajo , Lipogénesis/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Envejecimiento/genética , Envejecimiento/metabolismoRESUMEN
As shallow coal reserves continue to deplete rapidly, deep mining has become an unavoidable course of action. In the process of deep coal mining, affected by blasting, mining, and excavation, the coal-rock interface often encounters the action of compression-shear composite load. The interface crack directly affects the stability of the coal-rock structure. Uniaxial compression experiments have been conducted on rock and coal-like material with pre-existing interfacial oblique cracks to study the crack propagation criterion of the rock and coal-like material interface. An image acquisition system is used to record the surface speckle field of the whole process of specimen failure. The strain fields and stress intensity factor of the sample at different times are obtained by digital image correlation. At the same time, the stress field near the crack tip is calculated. The results show that with the increase of loading, two strains of localization bands are formed on the surface of the specimen. One of the strain-localized bands starts at the lower tip of the prefabricated crack and propagates along the vertical interface. The other starts at the upper tip of the prefabricated damage and propagates along the interface direction. It can be seen that the lower tip of the prefabricated crack enters into the crack fracture process zone earlier than the upper tip. The strain localization band narrows gradually with the load increase, and then macro cracks appear. The initiation of two tips is suitable for different fracture criteria. The lower tip is dominated by the maximum circumferential tensile stress, and the upper tip is dominated by shear stress. The specimens eventually fracture along the interface. The evolution of the strain field during the failure process of rock and coal-like material can reflect the generation and propagation of the crack.
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Telomeres undergo shortening with each cell division, serving as biomarkers of human aging, which is characterized by short telomeres and restricted telomerase expression in adult tissues. Contrarily, mice, featuring their longer telomeres and widespread telomerase activity, present limitations as models for understanding telomere-related human biology and diseases. To bridge this gap, we engineered a mouse strain with a humanized mTert gene, hmTert, wherein specific non-coding sequences were replaced with their human counterparts. The hmTert gene, encoding the wildtype mTert protein, was repressed in adult tissues beyond the gonads and thymus, closely resembling the regulatory pattern of the human TERT gene. Remarkably, the hmTert gene rescued telomere dysfunction in late generations of mTert-knockout mice. Through successive intercrosses of Terth/- mice, telomere length progressively declined, stabilizing below 10-kb. Terth/h mice achieved a human-like average telomere length of 10-12 kb, contrasting with the 50-kb length in wildtype C57BL/6J mice. Despite shortened telomeres, Terth/h mice maintained normal body weight and cell homeostasis in highly proliferative tissues. Notably, colonocyte proliferation decreased significantly in Terth/h mice during dextran sodium sulfate-induced ulcerative colitis-like pathology, suggesting limitations on cellular renewal due to short telomeres. Our findings underscore the genetic determination of telomere homeostasis in mice by the Tert gene. These mice, exhibiting humanized telomere homeostasis, serve as a valuable model for exploring fundamental questions related to human aging and cancer.
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Telomerase activation is a crucial step in melanomagenesis, often occurring because of ultraviolet radiation (UVR)-induced mutations at the telomerase gene (TERT) promoter and rendering TERT transcription in response to the activated Raf-MAP kinase pathway by BRAFV600E mutation. Due to the excessively long telomeres in mice, this process does not occur during melanomagenesis in mouse models. To investigate the impact of telomere dysfunction on melanomagenesis, BrafV600E was induced in generations 1 and 4 (G1 and G4) of Tert-/- mice. Our findings revealed that, regardless of UVR exposure, melanoma development was delayed in G4 mice, which had shorter telomeres compared to G1 and wild-type C57BL/6J (G0) mice. Moreover, many G4 tumors displayed an accumulation of excessive DNA damage, as evidenced by increased γH2A.X staining. Tumors from UVR-exposed mice exhibited elevated p53 protein expression. Cultured tumor cells isolated from G4 mice displayed abundant chromosomal fusions and rearrangements, indicative of telomere dysfunction in these cells. Additionally, tumor cells derived from UVB-exposed mice exhibited constitutively elevated expression of mutant p53 proteins, suggesting that p53 was a target of UVB-induced mutagenesis. Taken together, our findings suggest that telomere dysfunction hampers melanomagenesis, and targeting telomere crisis-mediated genomic instability may hold promise for the prevention and treatment of melanoma.
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Melanoma , Proteínas Proto-Oncogénicas B-raf , Telomerasa , Animales , Ratones , Melanoma/genética , Melanoma/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Telomerasa/genética , Telomerasa/metabolismo , Telómero/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Rayos Ultravioleta/efectos adversosRESUMEN
Metals are rarely found as free ions in natural and anthropogenic environments, but they are often associated with organic matter and minerals. Under the context of circular economy, metals should be recycled, yet they are difficult to extract for their complex forms in real situations. Based on the protocols of review methodology and the analysis of VOS viewer, there are few reviews on the properties of metal-organic complexes, decomplexation methods, the effect of coexisting ions, the pH influence, and metal recovery methods for the increasingly complicated metal-organic complexes wastewater. Conventional treatment methods such as flocculation, adsorption, biological degradation, and ion exchange fail to decompose metal-organic complexes completely without causing secondary pollution in wastewater. To enhance comprehension of the behavior and morphology exhibited by metal-organic complexes within aqueous solutions, we presented the molecular structure and properties of metal-organic complexes, the decomplexation mechanisms that encompassed both radical and non-radical oxidizing species, including hydroxyl radical (OH), sulfate radical (SOË4-), superoxide radical (OË2-), hydrogen peroxide (H2O2), ozone (O3), and singlet oxygen (1O2). More importantly, we reviewed novel aspects that have not been covered by previous reviews considering the impact of operational parameters and coexisting ions. Finally, the potential avenues and challenges were proposed for future research.
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Carotenoids in tomatoes confer significant health benefits to humans but with the disadvantage of the carotenoids from raw tomatoes not being easily absorbed for utilization. Thus, this study aimed to investigate the effects of different cooking processes on carotenoid release and human gut microbiota composition during in vitro simulated gastrointestinal digestion of tomatoes. The results showed that stir-frying significantly increased the release of lycopene and ß-carotene during gastrointestinal digestion, with boiling being the second most effective treatment. The boiling-treated tomatoes enhanced the carotenoid release during in vitro fermentation. Gut microbiota analysis revealed that the digestion of the raw and boiled tomatoes promoted the growth of potentially beneficial microbiota while reducing the ratio of Firmicutes/Bacteroides, which potentially helps prevent obesity. Boiling treatment significantly reduced the growth of Peptostreptococcus and was negatively correlated with carotenoid release. Overall, the boiling-treated tomatoes were more effective than the raw or stir-fried tomatoes in terms of both colon health benefits and carotenoid release.
Asunto(s)
Microbioma Gastrointestinal , Solanum lycopersicum , Humanos , Fermentación , Carotenoides/metabolismo , DigestiónRESUMEN
In order to separate the colloidal in high-turbidity water, a kind of magnetic composite (Fe3O4/HBPN) was prepared via the functional assembly of Fe3O4 and an amino-terminal hyperbranched polymer (HBPN). The physical and chemical characteristics of Fe3O4@HBPN were investigated by different means. The Fourier Transform infrared spectroscopy (FTIR) spectra showed that the characteristic absorption peaks positioned at 1110 cm-1, 1468 cm-1, 1570 cm-1 and 1641 cm-1 were ascribed to C-N, H-N-C, N-H and C=O bonds, respectively. The shape and size of Fe3O4/HBPN showed a different and uneven distribution; the particles clumped together and were coated with an oil-like film. Energy-dispersive spectroscopy (EDS) displayed that the main elements of Fe3O4/HBPN were C, N, O, and Fe. The superparamagnetic properties and good magnetic response were revealed by vibrating sample magnetometer (VSM) analysis. The characteristic diffraction peaks of Fe3O4/HBPN were observed at 2θ = 30.01 (220), 35.70 (311), 43.01 (400), 56.82 (511), and 62.32 (440), which indicated that the intrinsic phase of magnetite remained. The zeta potential measurement indicated that the surface charge of Fe3O4/HBPN was positive in the pH range 4-10. The mass loss of Fe3O4/HBPN in thermogravimetric analysis (TGA) proved thermal decomposition. The -C-NH2 or -C-NH perssad of HBPN were linked and loaded with Fe3O4 particles by the N-O bonds. When the Fe3O4/HBPN dosage was 2.5 mg/L, pH = 4-5, the kaolin concentration of 1.0 g/L and the magnetic field of 3800 G were the preferred reaction conditions. In addition, a removal efficiency of at least 86% was reached for the actual water treatment. Fe3O4/HBPN was recycled after the first application and reused five times. The recycling efficiency and removal efficiency both showed no significant difference five times (p > 0.05), and the values were between 84.8% and 86.9%.