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1.
Acta Pharmacol Sin ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538718

RESUMO

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

2.
Plant Biotechnol J ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497586

RESUMO

Adzuki bean (Vigna angularis) is an important legume crop cultivated in over 30 countries worldwide. We developed a high-quality chromosome-level reference genome of adzuki bean cultivar Jingnong6 by combining PacBio Sequel long-read sequencing with short-read and Hi-C technologies. The assembled genome covers 97.8% of the adzuki bean genome with a contig N50 of approximately 16 Mb and a total of 32 738 protein-coding genes. We also generated a comprehensive genome variation map of adzuki bean by whole-genome resequencing (WGRS) of 322 diverse adzuki beans accessions including both wild and cultivated. Furthermore, we have conducted comparative genomics and a genome-wide association study (GWAS) on key agricultural traits to investigate the evolution and domestication. GWAS identified several candidate genes, including VaCycA3;1, VaHB15, VaANR1 and VaBm, that exhibited significant associations with domestication traits. Furthermore, we conducted functional analyses on the roles of VaANR1 and VaBm in regulating seed coat colour. We provided evidence for the highest genetic diversity of wild adzuki (Vigna angularis var. nipponensis) in China with the presence of the most original wild adzuki bean, and the occurrence of domestication process facilitating transition from wild to cultigen. The present study elucidates the genetic basis of adzuki bean domestication traits and provides crucial genomic resources to support future breeding efforts in adzuki bean.

3.
Sci Total Environ ; 918: 170773, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38336054

RESUMO

Cadmium (Cd) exposure is known to enhance breast cancer (BC) progression. Cd promotes epithelial-mesenchymal transition (EMT) in BC cells, facilitating BC cell aggressiveness and invasion, but the underlying molecular mechanisms are unclear. Hence, transgenic MMTV-Erbb2 mice (6 weeks) were orally administered Cd (3.6 mg/L, approximately equal to 19.64 µΜ) for 23 weeks, and BC cells (BT474 cells) were exposed to Cd (0, 0.1, 1 or 10 µΜ) for 72 h to investigate the effect of Cd exposure on EMT in BC cells. Chronic Cd exposure dramatically expedited tumor metastasis to multiple organs; decreased E-cadherin density; and increased Vimentin, N-cadherin, ZEB1, and Twist density in the tumor tissues of MMTV-Erbb2 mice. Notably, transcriptomic analysis of BC tumors revealed cytochrome P450 1B1 (CYP1B1) as a key factor that regulates EMT progression in Cd-treated MMTV-Erbb2 mice. Moreover, Cd increased CYP1B1 expression in MMTV-Erbb2 mouse BC tumors and in BT474 cells, and CYP1B1 inhibition decreased Cd-induced BC cell malignancy and EMT in BT474 cells. Importantly, the promotion of EMT by CYP1B1 in Cd-treated BC cells was presumably controlled by glutamine metabolism. This study offers novel perspectives into the effect of environmental Cd exposure on driving BC progression and metastasis, and this study provides important guidance for comprehensively assessing the ecological and health risks of Cd.


Assuntos
Cádmio , Neoplasias , Camundongos , Animais , Cádmio/farmacologia , Linhagem Celular Tumoral , Glutamina/metabolismo , Glutamina/farmacologia , Reprogramação Metabólica , Transição Epitelial-Mesenquimal , Caderinas/genética , Caderinas/metabolismo , Caderinas/farmacologia
4.
Front Aging Neurosci ; 16: 1335550, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298610

RESUMO

Non-motor symptoms are prevalent among individuals with Parkinson's disease (PD) and seriously affect patient quality of life, even more so than motor symptoms. In the past decade, an increasing number of studies have investigated non-motor symptoms in PD. The present study aimed to comprehensively analyze the global literature, trends, and hotspots of research investigating non-motor symptoms in PD through bibliometric methods. Studies addressing non-motor symptoms in the Web of Science Core Collection (WoSCC), published between January 2013 and December 2022, were retrieved. Bibliometric methods, including the R package "Bibliometrix," VOS viewer, and CiteSpace software, were used to investigate and visualize parameters, including yearly publications, country/region, institution, and authors, to collate and quantify information. Analysis of keywords and co-cited references explored trends and hotspots. There was a significant increase in the number of publications addressing the non-motor symptoms of PD, with a total of 3,521 articles retrieved. The United States was ranked first in terms of publications (n = 763) and citations (n = 11,269), maintaining its leadership position among all countries. King's College London (United Kingdom) was the most active institution among all publications (n = 133) and K Ray Chaudhuri was the author with the most publications (n = 131). Parkinsonism & Related Disorders published the most articles, while Movement Disorders was the most cited journal. Reference explosions have shown that early diagnosis, biomarkers, novel magnetic resonance imaging techniques, and deep brain stimulation have become research "hotspots" in recent years. Keyword clustering revealed that alpha-synuclein is the largest cluster for PD. The keyword heatmap revealed that non-motor symptoms appeared most frequently (n = 1,104), followed by quality of life (n = 502), dementia (n = 403), and depression (n = 397). Results of the present study provide an objective, comprehensive, and systematic analysis of these publications, and identifies trends and "hot" developments in this field of research. This work will inform investigators worldwide to help them conduct further research and develop new therapies.

5.
Diabetes Metab Syndr Obes ; 16: 4025-4042, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089431

RESUMO

Introduction: Adjusting internal organs and dredging channel electroacupuncture has a definite effect on type 2 diabetes, but the specific mechanism still needs to be further clarified. This study aims to investigate the effects of electroacupuncture on the gut microbiota and bile acids in db/db mice after the intervention of "adjusting internal organs and dredging channel" and further explore its mechanism of action in treating T2DM. Methods: We used db/db mice as the animal model and db/m mice from the same litter as the blank control group, a total of 4 weeks of intervention were conducted. We evaluated the effectiveness of the "adjusting internal organs and dredging channel" treatment by detecting indicators related to glucose and lipid- metabolism. Detect changes in the gut microbiota of mice in each group using 16SrDNA sequencing technology. The content of bile acids in mouse feces was determined using liquid chromatography mass spectrometry, and the correlation analysis between different bile acids and differential bacterial communities was performed. The expression levels of TGR5 and GLP-1 proteins were measured using the Western blot method. Results: Adjusting internal organs and dredging channel electroacupuncture can improve blood glucose levels in db/db mice, increase the abundance of Firmicutes and Actinobacteria, and increase the content of fecal bile acid pool heavy CA and UDCA. At the same time, it also increased the content of TGR5/GLP1 in the small intestine. Conclusion: Adjusting internal organs and dredging channel electroacupuncture can improve the disorder of glucose and lipid metabolism in db/db mice, regulate the abundance and colony composition of intestinal microbiota in mice, and regulate bile acid metabolism in mice. The interaction between bile acid and intestinal microbiota can also be observed; Mutual influence may play a role in regulating blood sugar together.

6.
Sci Data ; 10(1): 768, 2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925542

RESUMO

Neosalanx taihuensis is widely distributed in freshwater and brackish water areas in China. Due to its high commercial value, it has been artificially introduced into many lakes and reservoirs, showing strong ecological adaptability. Here, a gap-free chromosome-level reference genome was constructed by combining short reads, PacBio HiFi long reads, Nanopore ultralong reads and Hi-C data. The reference genome of N. taihuensis was 397.29 Mb with a contig N50 of 15.61 Mb. The assembled sequences were anchored to 28 chromosomes. Furthermore, 20,024 protein-coding genes and 98.16% of the predicted genes were annotated in publicly available biological databases. This high-quality gap-free assembled genome will provide an essential reference for studying the evolution and ecological adaptability of N. taihuensis.


Assuntos
Cromossomos , Peixes , Genoma , China , Anotação de Sequência Molecular , Filogenia , Animais
7.
Handb Exp Pharmacol ; 281: 103-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37735301

RESUMO

Glia are integral components of neural networks and are crucial in both physiological functions and pathological processes of the brain. Many brain diseases involve glial abnormalities, including inflammatory changes, mitochondrial damage, calcium signaling disturbance, hemichannel opening, and loss of glutamate transporters. Induced pluripotent stem cell (iPSC)-derived glia provide opportunities to study the contributions of glia in human brain diseases. These cells have been used for human disease modeling as well as generating new therapies. This chapter introduces glial involvement in brain diseases, then summarizes different methods of generating iPSC-derived glia disease models of these cells. Finally, strategies for treating disease using iPSC-derived glia are discussed. The goal of this chapter is to provide an overview and shed light on the applications of iPSC-derived glia in brain disease research and treatment.


Assuntos
Encefalopatias , Células-Tronco Pluripotentes Induzidas , Humanos , Encéfalo , Células-Tronco Pluripotentes Induzidas/fisiologia , Neuroglia
8.
Sci Total Environ ; 905: 167039, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37716689

RESUMO

Cadmium (Cd), a predominant environmental pollutant, is a canonical toxicant that acts on the kidneys. However, the nephrotoxic effect and underlying mechanism activated by chronic exposure to Cd remain unclear. In the present study, male mice (C57BL/6J, 8 weeks) were treated with 0.6 mg/L cadmium chloride (CdCl2) administered orally for 6 months, and tubular epithelial cells (TCMK-1 cells) were treated with low-dose (1, 2, and 3 µM) CdCl2 for 72 h (h). Our study results revealed that environmental Cd exposure triggered ferroptosis and renal dysfunction. Spatially resolved metabolomics enabled delineation of metabolic profiles and visualization of the disruption to glutathione homeostasis related to ferroptosis in mouse kidneys. Multiomics analysis revealed that chronic Cd exposure induced glutathione redox imbalance that depended on STEAP3-driven lysosomal iron overload. In particular, glutathione metabolic reprogramming linked to ferroptosis emerged as a metabolic hallmark in the blood of Cd-exposed workers. In conclusion, this study provides the first evidence indicating that chronic Cd exposure triggers ferroptosis and renal dysfunction that depend on STEAP3-mediated glutathione redox imbalance, greatly increasing our understanding of the metabolic reprogramming induced by Cd exposure in the kidneys and providing novel clues linking chronic Cd exposure to nephrotoxicity.


Assuntos
Ferroptose , Nefropatias , Humanos , Masculino , Camundongos , Animais , Cádmio/toxicidade , Cádmio/metabolismo , Camundongos Endogâmicos C57BL , Oxirredução , Nefropatias/induzido quimicamente , Glutationa/metabolismo
9.
Sci Data ; 10(1): 360, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280262

RESUMO

The Chinese tapertail anchovy, Coilia nasus, is a socioeconomically important anadromous fish that migrates from near ocean waters to freshwater to spawn every spring. The analysis of genomic architecture and information of C. nasus were hindered by the previously released versions of reference genomes with gaps. Here, we report the assembly of a chromosome-level gap-free genome of C. nasus by incorporating high-coverage and accurate long-read sequence data with multiple assembly strategies. All 24 chromosomes were assembled without gaps, representing the highest completeness and assembly quality. We assembled the genome with a size of 851.67 Mb and used BUSCO to estimate the completeness of the assembly as 92.5%. Using a combination of de novo prediction, protein homology and RNA-seq annotation, 21,900 genes were functionally annotated, representing 99.68% of the total predicted protein-coding genes. The availability of gap-free reference genomes for C. nasus will provide the opportunity for understanding genome structure and function, and will also lay a solid foundation for further management and conservation of this important species.


Assuntos
Peixes , Genômica , Animais , Peixes/genética , Genoma , Cromossomos , Anotação de Sequência Molecular
10.
Materials (Basel) ; 16(12)2023 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-37374639

RESUMO

This paper used poly (aryl ether ketone) (PAEK) resin with a low melting temperature to prepare laminate via the compression-molding process for continuous-carbon-fiber-reinforced composites (CCF-PAEK). Then, poly (ether ether ketone) (PEEK), or a short-carbon-fiber-reinforced poly (ether ether ketone) (SCF-PEEK) with a high melting temperature, was injected to prepare the overmolding composites. The shear strength of short beams was used to characterize the interface bonding strength of composites. The results showed that the interface properties of the composite were affected by the interface temperature, which was adjusted by mold temperature. PAEK and PEEK formed a better interfacial bonding at higher interface temperatures. The shear strength of the SCF-PEEK/CCF-PAEK short beam was 77 MPa when the mold temperature was 220 °C and 85 MPa when the mold temperature was raised to 260 °C. The melting temperature did not significantly affect the shear strength of SCF-PEEK/CCF-PAEK short beams. For the melting temperature increasing from 380 °C to 420 °C, the shear strength of the SCF-PEEK/CCF-PAEK short beam ranged from 83 MPa to 87 MPa. The microstructure and failure morphology of the composite was observed using an optical microscope. A molecular dynamics model was established to simulate the adhesion of PAEK and PEEK at different mold temperatures. The interfacial bonding energy and diffusion coefficient agreed with the experimental results.

11.
Sci Data ; 9(1): 765, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36513679

RESUMO

In recent years, conservation efforts have increased for rare and endangered aquatic wildlife, especially cetaceans. However, the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri), which has a wide distribution in China, has received far less attention and protection. As an endangered small cetacean, the lack of a chromosomal-level reference for the East Asian finless porpoise limits our understanding of its population genetics and conservation biology. To address this issue, we combined PacBio HiFi long reads and Hi-C sequencing data to generate a gapless genome of the East Asian finless porpoise that is approximately 2.5 Gb in size over its 21 autosomes and two sex chromosomes (X and Y). A total of 22,814 protein-coding genes were predicted where ~97.31% were functionally annotated. This high-quality genome assembly of East Asian finless porpoise will not only provide new resources for the comparative genomics of cetaceans and conservation biology of threatened species, but also lay a foundation for more speciation, ecology, and evolutionary studies. Measurement(s) Neophocaena asiaeorientalis sunameri • Gapless genome assembly • sequence annotation Technology Type(s) MGISEQ. 2000 • PacBio HiFi Sequencing • Hi-C Sample Characteristic - Organism Neophocaena asiaeorientalis sunameri Sample Characteristic - Environment seawater Sample Characteristic - Location Yellow Sea near Lianyungang City, Jiangsu Province, China.


Assuntos
Genoma , Toninhas , Animais , China , Espécies em Perigo de Extinção , Toninhas/genética
12.
Medicine (Baltimore) ; 101(50): e32182, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36550879

RESUMO

BACKGROUND: To provide evidence, this review evaluated the methodological quality, risk of bias, and reporting quality of SRs/MAs in the treatment of Facial Spasm with acupuncture. METHODS: Systematic reviews and Meta analyses (SRs/MAs) of acupuncture for Facial Spasm were retrieved from 8 databases from inception to October 1, 2022. Two reviewers independently screened the literature and extracted the data, then used Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Bias Risk in Systematic Review (ROBIS), and Preferred Report Item for Systematic review and Meta-analysis (PRISMA), Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to assess methodological quality, risk of bias, quality of reporting, and quality of evidence. RESULTS: A total of 8 SRs/meta-analyses were included. All the SRs were published between 2012-2022. Based on AMSTAR-2, 8 SRs were rated critically low quality. By using the ROBIS tool, 6 SRs were rated low-risk bias. With the PRISMA-A checklist, we found 2 out of 8 SRs were found adequately reported over 70%. With the GRADE system, no high-quality evidence was found, and only two outcomes provided moderate-quality evidence. Among the downgraded factors, the risk of bias within the original trials was ranked first, followed by publication bias, inconsistency, and imprecision. CONCLUSION: Acupuncture is a promising complementary treatment for HFS. However, due to the low quality of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.


Assuntos
Terapia por Acupuntura , Humanos , Viés , Lista de Checagem , Projetos de Pesquisa , Espasmo , Revisões Sistemáticas como Assunto
13.
Diabetes Metab Syndr Obes ; 15: 2265-2276, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936053

RESUMO

Introduction: The study objective was to investigate the effects of electroacupuncture performed at the he-sea and front-mu acupoints on the intestinal microflora and intestinal barrier in db/db mice and to explore the related mechanism in type 2 diabetes mellitus. Methods: Db/m mice in the normal control group (NOC), electroacupuncture group (EA), metformin group (MET) and T2DM group (T2DM) were used as model controls, and db/db mice were used in all three groups, with 8 mice in each group. The treatment period was 2 weeks. Fasting blood glucose (FBG) and triglyceride (TG) levels were measured. Lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immune sorbent assay (ELISA). The ileal tissue was stained with hematoxylin-eosin staining (H&E), and histopathological changes were observed under a light microscope. Illumina sequencing was used to analyze the V4 region of the 16S rRNA gene to evaluate the effect of EA on the intestinal flora. Results: Our results suggest that EA treatment can reduce the expression of diabetes-related markers, with an effect similar to that of metformin. After EA intervention, the abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes increased, while the abundances of Bacteroidetes and Eubacterium decreased. In addition, the serum levels of LPS and TNF-α in the electroacupuncture group were downregulated, and ileal tissue damage was alleviated under an electron microscope. Conclusion: EA combined with acupoints can restore the intestinal flora structure, decrease the blood LPS level, reduce levels of inflammation, maintain the integrity of the intestinal barrier, and play a therapeutic role in the treatment of T2DM, mainly by increasing the abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes and decreasing the abundances of Bacteroidetes and Eubacterium.

14.
Polymers (Basel) ; 14(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35808723

RESUMO

The ablation mechanism and performance of carbon fiber (CF)-reinforced poly aryl ether ketone (PAEK) thermoplastic composites were studied in this paper. The results show that the ablation damaged area is controlled by the irradiation energy, while the mass loss rate is controlled by the irradiation power density. In the ablation center, the PAEK resin and CFs underwent decomposition and sublimation in an anaerobic environment. In the transition zone, the resin experienced decomposition and remelting in an aerobic environment, and massive char leaves were present in the cross section. In the heat-affected zone, only remelting of the resin was observed. The fusion and decomposition of the resin caused delamination and pores in the composites. Moreover, oxygen appeared crucial to the ablation morphology of CFs. In an aerobic environment, a regular cross section formed, while in an anaerobic environment, a cortex-core structure formed. The cortex-core structure of CF inside the ablation pit was caused by the inhomogeneity of fibers along the radial direction and the residual carbon layer generated by resin decomposition in an anoxic environment. The description of the ablation mechanism presented in this study broadens our understanding of damage evolution in thermoplastic composites subjected to high-energy CW laser irradiation.

15.
Mol Ecol Resour ; 22(8): 3049-3067, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35661414

RESUMO

As a medicinal herbal plant, Entada phaseoloides has high levels of secondary metabolites, particularly triterpenoid saponins, which are important resources for scientific research and medical applications. However, the lack of a reference genome for this genus has limited research on its evolution and utilization of its medicinal potential. In this study, we report a chromosome-scale genome assembly for E. phaseoloides using Illumina, Nanopore long reads and high-throughput chromosome conformation capture technology. The assembled reference genome is 456.18 Mb (scaffold N50 = 30.9 Mb; contig N50 = 6.34 Mb) with 95.71% of the sequences anchored onto 14 pseudochromosomes. E. phaseoloides was estimated to have diverged from the Leguminosae lineage at ~72.0 million years ago. With the integration of transcriptomic and metabolomic data, gene expression patterns and metabolite profiling of E. phaseoloides were determined in different tissues. The pattern of gene expression and metabolic profile of the kernel were distinct from those of other tissues. Furthermore, the evolution of certain gene families involved in the biosynthesis of triterpenoid saponins and terpenes was analysed and offers new insights into the formation of these two metabolites. Four CYP genes, one UGT gene and related transcription factors were identified as candidate genes contributing to regulation of triterpenoid saponin biosynthesis. As the first high-quality assembled reference genome in the genus Entada, it will not only provide new information for the evolutionary study of this genus and conservation biology of E. phaseoloides but also lay a foundation for the formation and utilization of secondary metabolites in medicinal plants.


Assuntos
Fabaceae , Plantas Medicinais , Saponinas , Triterpenos , Cromossomos , Evolução Molecular , Fabaceae/genética , Fabaceae/metabolismo , Filogenia , Plantas Medicinais/genética , Saponinas/genética , Fatores de Transcrição/genética , Triterpenos/metabolismo
16.
Stem Cell Res Ther ; 13(1): 285, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35765112

RESUMO

Aging causes astrocyte morphological degeneration and functional deficiency, which impairs neuronal functions. Until now, whether age-induced neuronal deficiency could be alleviated by engraftment of glial progenitor cell (GPC) derived astrocytes remained unknown. In the current study, GPCs were generated from embryonic cortical neural stem cells in vitro and transplanted into the brains of aged mice. Their integration and intervention effects in the aged brain were examined 12 months after transplantation. Results indicated that these in-vitro-generated GPC-derived astrocytes possessed normal functional properties. After transplantation they could migrate, differentiate, achieve long-term integration, and maintain much younger morphology in the aged brain. Additionally, these GPC-derived astrocytes established endfeet expressing aquaporin-4 (AQP4) and ameliorate AQP4 polarization in the aged neocortex. More importantly, age-dependent sensory response degeneration was reversed by GPC transplantation. This work demonstrates that rejuvenation of the astrocyte niche is a promising treatment to prevent age-induced degradation of neuronal and behavioral functions.


Assuntos
Células-Tronco Neurais , Neuroglia , Animais , Astrócitos/metabolismo , Camundongos , Neurônios , Transplante de Células-Tronco
17.
J Hazard Mater ; 435: 128942, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35468398

RESUMO

Metabolic disorders induced by arsenic exposure have attracted great public concern. However, it remains unclear whether hypothalamus-based central regulation mechanisms are involved in this process. Here, we exposed mice to 100 µg/L arsenic in drinking water and established a chronic arsenic exposure model. Our study revealed that chronic arsenic exposure caused metabolic disorders in mice including impaired glucose metabolism and decreased energy expenditure. Arsenic exposure also impaired glucose sensing and the activation of proopiomelanocortin (POMC) neurons in the hypothalamus. In particular, arsenic exposure damaged the plasticity of hypothalamic astrocytic process. Further research revealed that arsenic exposure inhibited the expression of sex-determining region Y-Box 2 (SOX2), which decreased the expression level of insulin receptors (INSRs) and the phosphorylation of AKT. The conditional deletion of astrocytic SOX2 exacerbated arsenic-induced effects on metabolic disorders, the impairment of hypothalamic astrocytic processes, and the inhibition of INSR/AKT signaling. Furthermore, the arsenic-induced impairment of astrocytic processes and inhibitory effects on INSR/AKT signaling were reversed by SOX2 overexpression in primary hypothalamic astrocytes. Together, we demonstrated here that chronic arsenic exposure caused metabolic disorders by impairing SOX2-modulated hypothalamic astrocytic process plasticity in mice. Our study provides evidence of novel central regulatory mechanisms underlying arsenic-induced metabolic disorders and emphasizes the crucial role of SOX2 in regulating the process plasticity of adult astrocytes.


Assuntos
Arsênio , Doenças Metabólicas , Animais , Arsênio/metabolismo , Arsênio/toxicidade , Hipotálamo/metabolismo , Doenças Metabólicas/metabolismo , Camundongos , Pró-Opiomelanocortina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
18.
RSC Adv ; 12(7): 4234-4239, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35425439

RESUMO

To obtain high thermostable materials for flexible display substrates, a series of copoly(benzimidazole imide)s was prepared using 5-amine-2-(4-aminobenzene)-1-phenyl-benzimidazole (N-PhPABZ) and 6(5)-amino-2-(4-aminobenzene)-benzimidazole (PABZ). Incorporating N-phenyl groups effectively healed the brittleness of the poly(benzimidazole imide)s (PBIIs) derived from pyromellitic dianhydride (PMDA), and the resultant homo- and copoly(benzimidazole imide)s displayed an outstandingly high glass transition temperature (T g > 450 °C) and a low coefficient of thermal expansion (CTE < 10 ppm K-1). Furthermore, the influence of removing intermolecular hydrogen bonds on the properties of these poly(benzimidazole imide)s was systematically analyzed. These data provide a feasible method to prepare superheat-resistant poly(benzimidazole imide)s without H-bonding.

19.
Chemosphere ; 289: 133205, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34890624

RESUMO

Herein, we obtained porous hollow carboxyl-polysulfone (PH-CPSF) microspheres through non-solvent-induced phase separation (NIPS) method and simple modification, used as highly efficient adsorbents for removing cationic dyes from sewage. The resulting PH-CPSF microspheres possess a hollow core and sponge-like shell structure, with high surface area, durable chemical inertness and structural stability. The as-synthesized PH-CPSF microspheres deliver a desirable adsorption effect after deprotonation treatment, with an adsorption capacity reaching up to 154.5 mg g-1 at 25 °C (pH = 7) of methylene blue (MB). The inter-molecular interactions between MB and the surface of the PH-CPSF, including π-π interaction, hydrogen bonding, strong charge attraction and weak charge attraction endow the adsorption ability of the PH-CPSF. The pseudo-second-order kinetic model pronounces in the adsorption behavior, and the adsorption equilibrium data is fitted to the Langmuir model. Moreover, PH-CPSF microspheres can also be used as adsorption fillers for large-scale water purification, and a removal rate of 94.0% for MB can be achieved under a flow rate of 8000 L m-3 h-1. The reusability of 95.3% removal effect for PH-CPSF microspheres after 20 consecutive cycles can be attained by a simple regeneration treatment. The adsorption efficiency of the PH-CPSF microspheres was evaluated by variety of cationic and anionic dyes, with high adsorption capacity toward cationic dyes (100%) and less than 10% toward anionic dyes. These results manifest that PH-CPSF microspheres are a potential adsorbent with long-term purification capabilities, which are expected to be used in small and large-scale sewage treatment.


Assuntos
Corantes , Poluentes Químicos da Água , Adsorção , Microesferas , Polímeros , Porosidade , Sulfonas
20.
Front Public Health ; 9: 771508, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881219

RESUMO

Background: With the global popularity of communication devices such as mobile phones, there are increasing concerns regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on the brain, one of the most important organs sensitive to RF-EMR exposure at 1,800 MHz. However, the effects of RF-EMR exposure on neuronal cells are unclear. Neurite outgrowth plays a critical role in brain development, therefore, determining the effects of 1,800 MHz RF-EMR exposure on neurite outgrowth is important for exploring its effects on brain development. Objectives: We aimed to investigate the effects of 1,800 MHz RF-EMR exposure for 48 h on neurite outgrowth in neuronal cells and to explore the associated role of the Rap1 signaling pathway. Material and Methods: Primary hippocampal neurons from C57BL/6 mice and Neuro2a cells were exposed to 1,800 MHz RF-EMR at a specific absorption rate (SAR) value of 4 W/kg for 48 h. CCK-8 assays were used to determine the cell viability after 24, 48, and 72 h of irradiation. Neurite outgrowth of primary hippocampal neurons (DIV 2) and Neuro2a cells was observed with a 20 × optical microscope and recognized by ImageJ software. Rap1a and Rap1b gene expressions were detected by real-time quantitative PCR. Rap1, Rap1a, Rap1b, Rap1GAP, and p-MEK1/2 protein expressions were detected by western blot. Rap1-GTP expression was detected by immunoprecipitation. The role of Rap1-GTP was assessed by transfecting a constitutively active mutant plasmid (Rap1-Gly_Val-GFP) into Neuro2a cells. Results: Exposure to 1,800 MHz RF-EMR for 24, 48, and 72 h at 4 W/kg did not influence cell viability. The neurite length, primary and secondary neurite numbers, and branch points of primary mouse hippocampal neurons were significantly impaired by 48-h RF-EMR exposure. The neurite-bearing cell percentage and neurite length of Neuro2a cells were also inhibited by 48-h RF-EMR exposure. Rap1 activity was inhibited by 48-h RF-EMR with no detectable alteration in either gene or protein expression of Rap1. The protein expression of Rap1GAP increased after 48-h RF-EMR exposure, while the expression of p-MEK1/2 protein decreased. Overexpression of constitutively active Rap1 reversed the decrease in Rap1-GTP and the neurite outgrowth impairment in Neuro2a cells induced by 1,800 MHz RF-EMR exposure for 48 h. Conclusion: Rap1 activity and related signaling pathways are involved in the disturbance of neurite outgrowth induced by 48-h 1,800 MHz RF-EMR exposure. The effects of RF-EMR exposure on neuronal development in infants and children deserve greater focus.


Assuntos
Hipocampo , Neurônios , Animais , Radiação Eletromagnética , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/farmacologia , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Crescimento Neuronal , Neurônios/metabolismo , Neurônios/efeitos da radiação
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