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Microplastics negatively impact soil health and productivity. Organic fertilizers constitute significant contributors of microplastics in agricultural soils. Nevertheless, comprehensive data on the diversity of microplastics in long-term fertilized soils remain unavailable. In this study, we assessed the presence of microplastics in soils subjected to application of three different organic fertilizers (pig manure, chicken manure, and sludge composts) over 12 years, and evaluated the potential ecological risks posed by microplastic accumulation. The average microplastic abundance in soil was 368.88 ± 207.97 (range: 90-910) items/kg. Microplastic abundance differed among fertilization treatments, with substantial increases of 16.67%, 71.67%, and 61.43% upon low to high application of the three treatments, respectively. Overall, the microplastics predominantly comprised fibers (70.94%) and fragments (25.25%), of which a substantial proportion constituted light-colored microplastics (transparent and white). The size of microplastics was mainly concentrated in the 1-2 mm range (39.96%), with rayon, polypropylene, polyester, and polyethylene being identified as the major types. The risk assessment indices of the three treatments were 229.38, 257.64, and 175.89, respectively, and were all classified as level 4 (high risk). The microplastic diversity integrated index and principal component analysis revealed that microplastics were uniformly distributed throughout the 0-20 cm soil depth consequent to tillage activity. Together, these findings provide a comprehensive assessment of microplastic pollution in long-term fertilized soils and serve as a scientific basis for reducing microplastic contamination in agricultural soils.
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BACKGROUND: Talent transfer (TT) program is an appropriate approach to address the talent gap evident in specific sports activities, while little is known about the injury characteristics of snowboarding athletes involved in the TT program. OBJECTIVE: To determine the epidemiology of injuries among snowboarders involved in the TT program. METHODS: A total of 244 athletes who were not previously engaged in winter sports were selected for training in snowboarding that lasted for 109 days. The injuries and at-risk exposures (A-Es) data were recorded by physicians. Injury rates (IRs), incidence rate ratios (IRRs), and injury proportion ratios (IPRs) were calculated and compared by sex and age groups. RESULTS: The overall and time loss (TL) IR were 32.4/1000 A-Es and 12.2/1000 A-Es respectively. The overall and non-time loss (NTL) IRR were higher for female athletes than for male athletes. Additionally, the overall IRR and TL-IRR for female athletes were higher in those athletes who aged ≤15 years old. Over 93% of TL injuries resulted in participation restriction time of ≤7 days (male athletes, 93.94%; female athletes, 94.10%). Trunk (28.43%), knee joints (21.33%), and hand/wrist (16.53%) were found as the common sites of injury in both female and male athletes. The most frequent type of injury was contusion (male athletes: 53.00%, female athletes: 59.10%) resulted from ground/apparatus contact (male athletes: 75.10%, female athletes: 75.20%). CONCLUSION: The risk injury among snowboarding athletes involved in the TT program during the first snow season training was found noticeable, especially for younger female athletes. The high incidence of ground/apparatus contact-related injuries suggested the necessity of specifically designed training programs and braces for snowboarding athletes involved in the TT program.
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Atletas , Traumatismos en Atletas , Esquí , Humanos , Femenino , Masculino , Estudios Prospectivos , Traumatismos en Atletas/epidemiología , Adolescente , Adulto , Esquí/lesiones , Adulto Joven , Incidencia , Factores de RiesgoRESUMEN
Rehmannia glutinosa Libosch, Achyranthes bidentata Bl. (A. bidentata), Dioscorea opposita Thunb, and Chrysanthemum morifolium Ramat (C. morifolium) are known as the 'Four Huaiqing Chinese Medicine' in China, which are used as materials for functional foods. In this paper, the constituents of Four Huaiqing Chinese Medicine were identified by UPLC-Q-TOF-MS/MS, and flavones and aromatic compounds are mainly responsible for these herbs. Moreover, C. morifolium exhibited the most significant effect in cobalt chloride-induced HUVECs injury, which could decrease cell apoptosis and the overproduction of ROS, lactic dehydrogenase (LD) and pyruvic acid, and increase the migration capacity of cells. Meanwhile, A. bidentata exhibited the most significant effect in isoproterenol-induced H9C2 cell injury, which could decrease the levels of ROS overproduction, BNP, NO, LD and pyruvic acid. Western blot revealed that C. morifolium and A. bidentata also could decrease the levels of bax/bcl-2 ratio, cleaved caspase-3, cytochrome c, HIF-1É, GLUT1, HKII and PFKFB3, respectively.
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Introduction: Acetyl-CoA synthetase 2 (ACSS2), one of the enzymes that catalyze the conversion of acetate to acetyl-CoA, has been proved to be an oncogene in various cancers. However, the function of ACSS2 is still largely a black box in melanoma. Methods: The ACSS2 expression was detected in melanoma cells and melanocytes at both protein and mRNA levels. Cell viability, apoptosis, migration and invasion were investigated after ACSS2 knockdown. RNA sequencing (RNA-Seq) technology was employed to identify differentially expressed genes caused by ACSS2 knockdown, which were then verified by immunoblotting analysis. Animal experiments were further performed to investigate the influence of ACSS2 on tumor growth and metastasis in vivo. Results: Firstly, we found that ACSS2 was upregulated in most melanoma cell lines compared with melanocytes. In addition, ACSS2 knockdown dramatically suppressed melanoma cell migration and invasion, whereas promoted cell apoptosis in response to endoplasmic reticulum (ER) stress. Furthermore, tumor growth and metastasis were dramatically suppressed by ACSS2 knockdown in vivo. RNA-Seq suggested that the Hippo pathway was activated by ACSS2 knockdown, which was forwardly confirmed by Western blotting and rescue experiments. Taken together, we demonstrated that ACSS2 enables melanoma cell survival and tumor metastasis via the regulation of the Hippo pathway. Discussion: In summary, this study demonstrated that ACSS2 may promote the growth and metastasis of melanoma by negatively regulating the Hippo pathway. Targeting ACSS2 may be a promising target for melanoma treatment.
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Melanoma, arising from the malignant transformation of melanocytes, stands as the most lethal type of skin cancer. While significant strides have been made in targeted therapy and immunotherapy, substantially enhancing therapeutic efficacy, the prognosis for melanoma patients remains unoptimistic. SIRT7, a nuclear-localized deacetylase, plays a pivotal role in maintaining cellular homeostasis and adapting to external stressors in melanoma, with its activity closely tied to intracellular nicotinamide adenine dinucleotide (NAD+). However, its involvement in adaptive resistance to targeted therapy remains unclear. Herein, we unveil that up-regulated SIRT7 promotes mitochondrial biogenesis to render the adaptive resistance to MAPK inhibition in melanoma. Initially, we observed a significant increase of SIRT7 expression in publicly available datasets following targeted therapy within a short duration. In consistent, we found elevated SIRT7 expression in melanoma cells subjected to BRAF or MEK inhibitors in vitro. The up-regulation of SIRT7 expression was also confirmed in xenograft tumors in mice after targeted therapy in vivo. Furthermore, we proved that SIRT7 deficiency led to decreased cell viability upon prolonged exposure to BRAF or MEK inhibitors, accompanied by an increase in cell apoptosis. Mechanistically, SIRT7 deficiency restrained the upregulation of genes associated with mitochondrial biogenesis and intracellular ATP levels in response to targeted therapy treatment in melanoma cells. Ultimately, we proved that SIRT7 deficieny could sensitize BRAF-mutant melanoma cells to MAPK inhibition targeted therapy in vivo. In conclusion, our findings underscore the role of SIRT7 in fostering adaptive resistance to targeted therapy through the facilitation of mitochondrial biogenesis. Targeting SIRT7 emerges as a promising strategy to overcome MAPK inhibitor adaptive resistance in melanoma.
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Resistencia a Antineoplásicos , Melanoma , Biogénesis de Organelos , Inhibidores de Proteínas Quinasas , Sirtuinas , Melanoma/metabolismo , Melanoma/patología , Melanoma/genética , Melanoma/tratamiento farmacológico , Humanos , Sirtuinas/metabolismo , Sirtuinas/genética , Animales , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Inhibidores de Proteínas Quinasas/farmacología , Ratones , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/tratamiento farmacológico , Ratones Desnudos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidoresRESUMEN
Extensive microbial interactions occur within insect hosts. However, the interactions between the Huanglongbing (HLB) pathogen and endosymbiotic bacteria within the Asian citrus psyllid (ACP, Diaphorina citri Kuwayama) in wild populations remain elusive. Thus, this study aimed to detect the infection rates of HLB in the ACP across five localities in China, with a widespread prevalence in Ruijin (RJ, 58%), Huidong (HD, 28%), and Lingui (LG, 15%) populations. Next, microbial communities of RJ and LG populations collected from citrus were analyzed via 16S rRNA amplicon sequencing. The results revealed a markedly higher microbial diversity in the RJ population compared to the LG population. Moreover, the PCoA analysis identified significant differences in microbial communities between the two populations. Considering that the inter-population differences of Bray-Curtis dissimilarity in the RJ population exceeded those between populations, separate analyses were performed. Our findings indicated an increased abundance of Enterobacteriaceae in individuals infected with HLB in both populations. Random forest analysis also identified Enterobacteriaceae as a crucial indicator of HLB infection. Furthermore, the phylogenetic analysis suggested a potential regulatory role of ASV4017 in Enterobacteriaceae for ACP, suggesting its possible attractant activity. This research contributes to expanding the understanding of microbial communities associated with HLB infection, holding significant implications for HLB prevention and treatment.
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Enterobacteriaceae , Hemípteros , Filogenia , Enfermedades de las Plantas , ARN Ribosómico 16S , Animales , Hemípteros/microbiología , Enterobacteriaceae/genética , Enterobacteriaceae/clasificación , Enterobacteriaceae/patogenicidad , ARN Ribosómico 16S/genética , Enfermedades de las Plantas/microbiología , China/epidemiología , Citrus/microbiología , MicrobiotaRESUMEN
Cholangiocarcinoma (CCA), an exceptionally aggressive malignancy originating from the epithelium of the bile duct, poses a formidable challenge in cancer research and clinical management. Currently, attention is focused on exploring the oncogenic role and prognostic implications associated with Bmi1 in the context of CCA. In our study, we assessed the correlation of Bmi1 and Foxn2 expression across all types of CCA and evaluated their prognostic significance. Our results demonstrated that Bmi1 exhibits significantly upregulated expression in CCA tissues, while Foxn2 expression shows an inverse pattern. Simultaneously, the high expression of Bmi1, coupled with the low expression of Foxn2, indicates an unfavorable prognosis. Through in vitro and in vivo experiments, we confirmed the crucial role of Foxn2 in the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of CCA. Mechanistically, Bmi1 promotes the ubiquitination of histone H2A (H2AUb), leading to chromatin opening attenuation and a decrease in Foxn2 expression, ultimately driving CCA progression. Additionally, we described the potential value of Bmi1 and H2AUb inhibitors in treating CCA through in vitro experiments and orthotopic models. This study is of significant importance in deepening our understanding of the interaction between Bmi1 and Foxn2 in CCA and has the potential to advance the development of precision therapies for CCA.
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Neoplasias de los Conductos Biliares , Proliferación Celular , Colangiocarcinoma , Progresión de la Enfermedad , Factores de Transcripción Forkhead , Regulación Neoplásica de la Expresión Génica , Histonas , Complejo Represivo Polycomb 1 , Ubiquitinación , Animales , Femenino , Humanos , Ratones , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Línea Celular Tumoral , Colangiocarcinoma/patología , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Transición Epitelial-Mesenquimal , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Histonas/metabolismo , Ratones Desnudos , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 1/genética , Pronóstico , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.
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Actinidia , Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Simulación del Acoplamiento Molecular , Farmacología en Red , Extractos Vegetales , Hojas de la Planta , Actinidia/química , Hojas de la Planta/química , Animales , Ratones , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Masculino , Cromatografía Líquida de Alta Presión/métodos , Transducción de Señal/efectos de los fármacosRESUMEN
One fundamental problem in deep learning is understanding the excellent performance of deep Neural Networks (NNs) in practice. An explanation for the superiority of NNs is that they can realize a large family of complicated functions, i.e., they have powerful expressivity. The expressivity of a Neural Network with Piecewise Linear activations (PLNN) can be quantified by the maximal number of linear regions it can separate its input space into. In this paper, we provide several mathematical results needed for studying the linear regions of Convolutional Neural Networks with Piecewise Linear activations (PLCNNs), and use them to derive the maximal and average numbers of linear regions for one-layer PLCNNs. Furthermore, we obtain upper and lower bounds for the number of linear regions of multi-layer PLCNNs. Our results suggest that deeper PLCNNs have more powerful expressivity than shallow PLCNNs, while PLCNNs have more expressivity than fully-connected PLNNs per parameter, in terms of the number of linear regions.
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Pyrogenic carbon and magnetite (Fe3O4) were mixed together for the activation of hydrogen peroxide (H2O2), aiming to enhance the oxidation of refractory pollutants in a sustainable way. The experimental results indicated that the straw-derived carbon obtained by pyrolysis at 500-800 °C was efficient on coactivation of H2O2, and the most efficient one was that prepared at 700 °C (C700) featured with abundant defects. Specifically, the reaction rate constant (kobs) for removal of an antibiotic ciprofloxacin in the coactivation system (C700/Fe3O4/H2O2) is 12.5 times that in the magnetite-catalyzed system (Fe3O4/H2O2). The faster pollutant oxidation is attributed to the sustainable production of â¢OH in the coactivation process, in which the carbon facilitated decomposition of H2O2 and regeneration of Fe(II). Besides the enhanced H2O2 utilization in the coactivation process, the leaching of iron was controlled within the concentration limit in drinking water (0.3 mg·L-1) set by the World Health Organization.
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Calreticulin (CRT), a damage-associated molecular pattern molecule, is reported to translocate from the endoplasmic reticulum to the membrane in melanocytes under oxidative stress. To investigate the potential role of CRT in the pathogenesis of vitiligo, we analyzed the correlation between CRT and ROS in serum and lesions of vitiligo, detected CRT and protein kinase RNA-like endoplasmic reticulum kinase (PERK) expression in vitiligo lesions, and studied the production of CRT and mediators of unfolded protein response (UPR) pathway and then tested the chemotactic migration of CD8+ T cells or CD11c+ CD86+ cells. Initially, we verified the overexpression of CRT in perilesional epidermis that was positively correlated with the disease severity of vitiligo. Furthermore, the PERK branch of UPR was confirmed to be responsible for the overexpression and membranal translocation of CRT in melanocytes under oxidative stress. We also found that oxidative stress-induced membranal translocation of CRT promoted the activation and migration of CD8+ T cells in vitiligo. In addition, dendritic cells from patients with vitiligo were also prone to maturation with the coincubation of melanocytes harboring membranal CRT. CRT could be induced on the membrane of melanocytes through UPR and might play a role in oxidative stress-triggered CD8+ T-cell response in vitiligo.
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Autoinmunidad , Linfocitos T CD8-positivos , Calreticulina , Melanocitos , Estrés Oxidativo , Respuesta de Proteína Desplegada , Vitíligo , Vitíligo/inmunología , Vitíligo/metabolismo , Vitíligo/patología , Humanos , Melanocitos/metabolismo , Melanocitos/inmunología , Estrés Oxidativo/inmunología , Calreticulina/metabolismo , Respuesta de Proteína Desplegada/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Masculino , Adulto , eIF-2 Quinasa/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Adulto Joven , Membrana Celular/metabolismo , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patologíaRESUMEN
BACKGROUND: Tumor cells frequently suffer from endoplasmic reticulum (ER) stress. Previous studies have extensively elucidated the role of tumorous unfolded protein response in melanoma cells, whereas the effect on tumor immunology and the underlying mechanism remain elusive. METHODS: Bioinformatics, biochemical assays and pre-clinical mice model were employed to demonstrate the role of tumorous inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in anti-tumor immunity and the underlying mechanism. RESULTS: We firstly found that IRE1α signaling activation was positively associated with the feature of tumor-infiltrating lymphocytes. Then, pharmacological ER stress induction by HA15 exerted prominent anti-tumor effect in immunocompetent mice and was highly dependent on CD8+T cells, paralleled with the reshape of immune cells in tumor microenvironment via tumorous IRE1α-XBP1 signal. Subsequently, tumorous IRE1α facilitated the expression and secretion of multiple chemokines and cytokines via XBP1-NF-κB axis, leading to increased infiltration and anti-tumor capacity of CD8+T cells. Ultimately, pharmacological induction of tumorous ER stress by HA15 brought potentiated therapeutic effect along with anti-PD-1 antibody on melanoma in vivo. CONCLUSIONS: Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy by regulating chemokines and cytokines via XBP1-NF-κB axis. The combination of ER stress inducer and anti-PD-1 antibody could be promising for increasing the efficacy of melanoma immunotherapy.
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Melanoma , Animales , Ratones , Linfocitos T CD8-positivos/patología , Quimiocinas , Citocinas , Endorribonucleasas , Melanoma/patología , FN-kappa B , Proteínas Serina-Treonina Quinasas/metabolismo , Linfocitos T/metabolismo , Microambiente TumoralRESUMEN
OBJECTIVES: Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. METHODS: Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (nâ¯=â¯9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. RESULTS: MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (pâ¯<â¯0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1ß and Nuclear Transcription Factor-κB (NF-κB) (pâ¯<â¯0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (pâ¯<â¯0.05). CONCLUSION: NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.
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Infecciones por Virus de Epstein-Barr , Exosomas , MicroARNs , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Exosomas/genética , Exosomas/metabolismo , Exosomas/patología , Infecciones por Virus de Epstein-Barr/genética , Línea Celular Tumoral , Proliferación Celular , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Regulación Neoplásica de la Expresión Génica , Proteínas que Contienen Bromodominio , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismoRESUMEN
Financial technology provides strong support for the low-carbon transformation of energy through digital technology. There is limited research on the relationship between financial technology and low-carbon transformation of energy, and the information transmission and connection between the two entities are still unclear. Therefore, this paper innovatively conducts in-depth research on the spatial effect between financial technology and low-carbon transformation of energy and further analyzes the intermediary role of green finance in it. Firstly, the spatial Durbin model and spatial intermediary effect model between financial technology and low-carbon transformation of energy are constructed. Then, based on the Moran coefficient, the spatial effects of low-carbon transformation in financial technology and energy were analyzed. Finally, an empirical study was conducted using the panel data of China's provinces from 2011 to 2020. The results show that financial technology can effectively promote the energy transformation, and financial technology and the degree of low-carbon transformation of energy have significant spatial effects. From the perspective of intermediary effect, financial technology can effectively improve the green finance structure and promote low-carbon transformation of energy. From the perspective of spatial intermediary effect, while promoting the development of green finance in the local area, financial technology will also suppress the development of green finance in surrounding areas, thereby inhibiting the low-carbon transformation of energy in the surrounding areas. Therefore, China should strengthen the development of financial science and technology, guide the transformation of traditional finance, improve the coverage of green finance, and realize the low-carbon transformation of national energy.
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Carbono , Tecnología , China , Investigación Empírica , Desarrollo EconómicoRESUMEN
Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.
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Clean energy development has played a pivotal role in economic transformation. Based on the panel data of 30 provinces in China from 2006 to 2021, the spatial Dubin model was used to empirically investigate the impact of clean energy development on green economic growth. Furthermore, this research selected industrial structure optimization as the mediating variable to analyze the mediating effect between clean energy development and green economic growth. The results are as follows. Firstly, there is a positive spatial correlation for green economic development, in which the level of green economic development in a region can be influenced by neighboring regions. Secondly, there is a significant positive relationship between clean energy development and green economic growth, in which the clean energy development has a positive impact on green economic growth. Thirdly, the mediating effect analysis demonstrates that the clean energy development can influence green economic growth through industrial structure optimization. Based on the findings in this paper, several suggestions are proposed. China should formulate a unified national strategy for green economy by coordinating and balancing regional differences, develop the clean energy industry to promote green economic growth, and pay attention to the intermediary effect of industrial structure to promote green economic growth.
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Desarrollo Económico , Industrias , ChinaRESUMEN
Understanding and controlling carrier dynamics in two-dimensional (2D) van der Waals heterostructures through strain are crucial for their flexible applications. Here, femtosecond transient absorption spectroscopy is employed to elucidate the interlayer electron transfer and relaxation dynamics under external tensile strains in a WSe2/MoS2 heterostructure. The results show that a modest â¼1% tensile strain can significantly alter the lifetimes of electron transfer and nonradiative electron-hole recombination by >30%. Ab initio non-adiabatic molecular dynamics simulations suggest that tensile strain weakens the electron-phonon coupling, thereby suppressing the transfer and recombination dynamics. Theoretical predictions indicate that strain-induced energy difference increases along the electron transfer path could contribute to the prolongation of the transfer lifetime. A subpicosecond decay process, related to hot-electron cooling, remains almost unaffected by strain. This study demonstrates the potential of tuning interlayer carrier dynamics through external strains, offering insights into flexible optoelectronic device design with 2D materials.
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Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis by acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed the increased level of AGEs in the serum and skin of psoriasis patients, but the role of AGEs in psoriatic inflammation has not been well investigated. In the present study, we initially detected abnormal accumulation of AGEs in epidermal keratinocytes of psoriatic lesions collected from psoriasis patients. Furthermore, AGEs promoted the proliferation of keratinocytes via upregulated Keratin 17 (K17)-mediated p27KIP1 inhibition followed by accelerated cell cycle progression. More importantly, AGEs facilitated the production of interleukin-36 alpha (IL-36α) in keratinocytes, which could enhance T helper 17 (Th17) immune response. In addition, the induction of both K17 and IL-36α by AGEs in keratinocytes was dependent on the activation of signal transducer and activator of transcription 1/3 (STAT1/3) signaling pathways. At last, the effects of AGEs on keratinocytes were mediated by the receptor for AGEs (RAGE). Taken together, these findings support that AGEs potentiate the innate immune function of keratinocytes, which contributes to the formation of psoriatic inflammation. Our study implicates AGEs as a potential pathogenic link between psoriasis and cardiometabolic comorbidities.
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Enfermedades Cardiovasculares , Psoriasis , Humanos , Piel/patología , Queratinocitos , Inflamación/metabolismo , Inmunidad , Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/farmacología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patologíaRESUMEN
Melanoma is the most lethal skin cancer originating from the malignant transformation of epidermal melanocyte. The dysregulation of cellular metabolism is a hallmark of cancer, including in melanoma. Aberrant branched-chain amino acids (BCAA) metabolism and related enzymes has been greatly implicated in the progression of multiple types of cancer, whereas remains far from understood in melanoma. Herein, we reported that the critical BCAA metabolism enzyme branched-chain amino acid transaminase 2 (BCAT2) is an oncogenic factor in melanoma by activating lipogenesis via the epigenetic regulation of fatty acid synthase (FASN) and ATP-citrate lyase (ACLY) expressions. Firstly, we found that BCAT2 expression was prominently increased in melanoma, and highly associated with clinical stage. Then, it was proved that the deficiency of BCAT2 led to impaired tumor cell proliferation, invasion and migration in vitro, and tumor growth and metastasis in vivo. Further, RNA sequencing technology and a panel of biochemical assays demonstrated that BCAT2 regulated de novo lipogenesis via the regulation of the expressions of both FASN and ACLY. Mechanistically, the inhibition of BCAT2 suppressed the generation of intracellular acetyl-CoA, mitigating P300-dependent histone acetylation at the promoter of FASN and ACLY, and thereby their transcription. Ultimately, zinc finger E-box binding homeobox 1 (ZEB1) was identified as the upstream transcriptional factor responsible for BCAT2 up-regulation in melanoma. Our results demonstrate that BCAT2 promotes melanoma progression by epigenetically regulating FASN and ACLY expressions via P300-dependent histone acetylation. Targeting BCAT2 could be exploited as a promising strategy to restrain tumor progression in melanoma.
Asunto(s)
Melanoma , Proteínas Gestacionales , Humanos , Lipogénesis/genética , ATP Citrato (pro-S)-Liasa/genética , ATP Citrato (pro-S)-Liasa/metabolismo , Histonas/metabolismo , Epigénesis Genética , Melanoma/genética , Transaminasas/genética , Proteínas Gestacionales/genética , Proteínas Gestacionales/metabolismo , Antígenos de Histocompatibilidad Menor/metabolismo , Acido Graso Sintasa Tipo I/genéticaRESUMEN
Actinidia arguta leaves (AAL) are an excellent source of bioactive components for the food industry and possess many functional properties. However, the hypoglycemic effect and mechanism of AAL remain unclear. The aim of this work was to investigate the potential hypoglycemic effect of AAL and explore its possible mechanism using 16S rRNA sequencing and serum metabolomics in diabetic mice induced by high-fat feeding in combination with streptozotocin injection. A total of 25 flavonoids from AAL were isolated and characterized, and the contents of the extract from the AAL ranged from 0.14 mg/g DW to 8.97 mg/g DW. The compound quercetin (2) had the highest content of 8.97 ± 0.09 mg/g DW, and the compound kaempferol-3-O-(2'-O-D-glucopyl)-ß-D-rutinoside (12) had the lowest content of 0.14 ± 0.01 mg/g DW. In vivo experimental studies showed that AAL reduced blood glucose and cholesterol levels, improved insulin sensitivity, and ameliorated oxidative stress and liver and kidney pathological damage. In addition, gut microbiota analysis found that AAL significantly reduced the F/B ratio, enriched the beneficial bacteria Bacteroides and Bifidobacterium, and inhibited the harmful bacteria Lactobacillus and Desulfovibrio, thereby playing an active role in intestinal imbalance. In addition, metabolomics analysis showed that AAL could improve amino acid metabolism and arachidonic acid metabolism, thereby exerting a hypoglycemic effect. This study confirmed that AAL can alleviate type 2 diabetes mellitus (T2DM) by regulating intestinal flora and interfering with related metabolic pathways, providing a scientific basis for its use as a dietary supplement and for further exploration of the mechanism of AAL against T2DM.