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Alzheimer's disease (AD) poses a global health threat, progressively robbing patients of their memory and cognitive abilities. While it is recognized that meaningful social contact can alleviate the symptoms of dementia in AD patients, the precise mechanisms by which social stimulation mitigates AD symptoms remain poorly understood. We found that social interaction with novel mice, also known as novel social, simulated meaningful socializing. Therefore, we developed the multiple novel social (MNS) stimulation paradigm to train AD model mice and found that MNS effectively alleviated cognitive deficits in AD mice. This discovery not only opens up a new avenue for investigating the relationship between social stimulation and Alzheimer's disease but also lays the groundwork for delving into the underlying mechanisms, thereby providing crucial theoretical support for developing novel strategies to treat Alzheimer's disease. Key features ⢠Designing a new social stimulation method to simulate meaningful social interactions in daily life. ⢠The MNS stimulation protocol spans 14 days, with one novel mouse introduced to the subject mice each day. ⢠The subjects were 2.5-month-old FAD4T mice, simulating patients with mild cognitive impairment (MCI). ⢠Results of behavioral tests confirm the efficacy of MNS in reducing cognitive deficits in the AD model. This protocol is used in: J Neurosci (2024), DOI: 10.1523/JNEUROSCI.1689-23.2024.
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BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.
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Transtorno Autístico , Encéfalo , Cognição , Comportamento Problema , Humanos , Feminino , Masculino , Criança , Encéfalo/crescimento & desenvolvimento , Adolescente , Cognição/fisiologia , Conflito Familiar , Mães , Adulto , Gravidez , Adulto Jovem , Gravidez na Adolescência , Fatores SexuaisRESUMO
The Kinesin Family Member C1 (KIFC1) is highly expressed in a variety of tumors. Since it is linked with tumorigenesis and progression, KIFC1 has emerged as a promising candidate for targeted chemotherapies. Thus, this study aims to find out the association between KIFC1 and lung cancer. The original data were assessed from The Cancer Genome Atlas and Gene Expression Omnibus databases. Compared to normal lung tissues, both mRNA and protein levels of KIFC1 were significantly increased in lung cancer tissues. The upregulation of KIFC1 was significantly correlated with sex, pathological stage, and TMN stage. Survival analysis revealed that increased KIFC1 expression was associated with poor overall survival, first-progression survival and post-progression survival in lung cancer. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, we observed that KIFC1 upregulation was linked to enrichment of the cell cycle and TP53 signaling pathway. Additionally, the overexpression of KIFC1 was positively correlated with TP53 mutations in lung cancer. Based on real-world cohort results, western blotting and RT-qPCR showed high-KIFC1 expression in lung cancer, which may be related to the malignancy of lung cancer. Finally, experiments in vitro showed that KIFC1 inhibitor could significantly inhibit the proliferation and invasion of lung cancer cells. In conclusion, KIFC1 is a poor prognostic biomarker, and patients with high-KIFC1 levels may benefit from targeted therapy.
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Neoplasias Pulmonares , Humanos , Prognóstico , Neoplasias Pulmonares/genética , Análise de Sobrevida , Regulação para Cima , Biomarcadores , Proteína Supressora de Tumor p53/genéticaRESUMO
As the most common form of dementia in the world, Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive and behavioral impairment. According to previous researches, abundant social connections shield against dementia. However, it is still unclear how exactly social interactions benefit cognitive abilities in people with AD and how this process is used to increase their general cognitive performance. In this study, we found that single novel social (SNS) stimulation promoted c-Fos expression and increased the protein levels of mature ADAM10/17 and sAPPα in the ventral hippocampus (vHPC) of wild-type (WT) mice, which are hippocampal dorsal CA2 (dCA2) neuron activity and vHPC NMDAR dependent. Additionally, we discovered that SNS caused similar changes in an AD model, FAD4T mice, and these alterations could be reversed by α-secretase inhibitor. Furthermore, we also found that multiple novel social (MNS) stimulation improved synaptic plasticity and memory impairments in both male and female FAD4T mice, accompanied by α-secretase activation and Aß reduction. These findings provide insight into the process underpinning how social interaction helps AD patients who are experiencing cognitive decline, and we also imply that novel social interaction and activation of the α-secretase may be preventative and therapeutic in the early stages of AD.
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Doença de Alzheimer , Humanos , Masculino , Camundongos , Feminino , Animais , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Camundongos Transgênicos , Transtornos da Memória/metabolismo , Hipocampo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de DoençasRESUMO
The application of sericin hydrogels is limited mainly due to their poor mechanical strength, tendency to be brittle and inconvenient sterilization. To address these challenges, a sericin hydrogel exhibiting outstanding physical and chemical properties along with cytocompatibility was prepared through crosslinking genipin with degraded sericin extracted from fibroin deficient silkworm cocoons by the high temperature and pressure method. Our reported sericin hydrogels possess good elasticity, injectability, and robust behaviors. The 8% sericin hydrogel can smoothly pass through a 16 G needle. While the 12% sericin hydrogel remains intact until its compression ratio reaches 70%, accompanied by a compression strength of 674 kPa. 12% sericin hydrogel produce a maximum stretch of 740%, with breaking strength and tensile modulus of 375 kPa and 477 kPa respectively. Besides that, the hydrogel system demonstrated remarkable cell-adhesive capabilities, effectively promoting cell attachment and, proliferation. Moreover, the swelling and degradation behaviors of the hydrogels are pH responsiveness. Sericin hydrogel releases drugs in a sustained manner. Furthermore, this study addresses the challenge of sterilizing sericin hydrogels (sterilization will inevitably lead to the destruction of their structures). In addition, it challenges the prior notion that sericin extracted under high temperature and pressure is difficult to directly cross-linked into a stable hydrogel. This developed hydrogel system in this study holds promise to be a new multifunctional platform expanding the application area scope of sericin.
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Diabetic wounds are serious complications caused by diabetes mellitus (DM), which are further exacerbated by angiogenesis disorders and prolonged inflammation. Injectable platelet-rich fibrin (i-PRF) is rich in growth factors (GFs) and has been used for the repair and regeneration of diabetic wounds; however, direct application of i-PRF has certain disadvantages, including the instability of the bioactive molecules. Sericin hydrogel, fabricated by silkworm-derived sericin, is a biocompatible material that has anti-inflammatory and healing-promoting properties. Therefore, in this study, we developed a novel hydrogel (named sericin/i-PRF hydrogel) using a simple one-step activation method. The in vitro studies showed that the rapid injectability of the sericin/i-PRF hydrogel allows it to adapt to the irregular shape of the wounds. Additionally, sericin hydrogel could prolong the release of i-PRF-derived bioactive GFs in the sericin/i-PRF hydrogel. Furthermore, sericin/i-PRF hydrogel effectively repaired diabetic wounds, promoted angiogenesis, and reduced inflammation levels in the diabetic wounds of nude mice. These results demonstrate that the sericin/i-PRF hydrogel is a promising agent for diabetic wound healing.
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Diabetes Mellitus , Fibrina Rica em Plaquetas , Sericinas , Camundongos , Animais , Fibrina Rica em Plaquetas/metabolismo , Hidrogéis/metabolismo , Sericinas/farmacologia , Sericinas/uso terapêutico , Sericinas/metabolismo , Camundongos Nus , Diabetes Mellitus/metabolismo , Cicatrização , Inflamação/metabolismoRESUMO
Time pressure affects multiple cognitive processes but how it affects attention capture remains unclear. Two experiments were carried out in the present study to assess whether time pressure prevents attention from capturing by salient distractors and explore the underlying neural mechanisms using functional near-infrared spectroscopy. The results of behavioral tests showed that the singleton effect decreased (Experiment 2) or even disappeared (Experiment 1) when the subject was under time pressure. Neuroimaging data showed that under time pressure, a salient distractor elicited greater activation in the left middle frontal gyrus/inferior frontal gyrus and bilateral superior parietal lobule, brain areas that are thought to be involved in cognitive inhibition and control of spatial attentional shifts. These findings suggest that the reduction or disappearance of the singleton effect under time pressure results from enhanced inhibition of and/or accelerated disengagement from salient distractors.
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Atenção , Encéfalo , Estresse Psicológico , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Espectroscopia de Luz Próxima ao Infravermelho , Estresse Psicológico/diagnóstico por imagem , Neuroimagem , Encéfalo/diagnóstico por imagem , Fatores de TempoRESUMO
Whereas increasing evidences demonstrate that miR-297 contributes to the tumour development and progression, the role of miR-297 and its underlying molecular mechanisms in hepatocellular carcinoma (HCC) was still unclear. Here, we reported that the expression of miR-297 increased significantly in hepG2 cells after the treatment of the conditioned medium of human amniotic epithelial cells(hAECs) which can inhibit the proliferation and migration of hepG2. And the overexpression of miR-297 inhibits the cell proliferation, migration and invasion of HCC cell lines in vitro and suppressed the tumorigenesis of HCC in vivo. Polypyrimidine tract-binding protein 3 (PTBP3) was identified as a direct target gene of miR-297 in HCC cell lines, and mediated the function of miR-297 in HCC cells. In clinical samples, miR-297 levels have a tendency to decrease, but there are no statistically significant differences. Furthermore, in vitro cell experiments confirmed that overexpression of miR-297 could inhibit the PI3K/AKT signaling pathway by down-regulating PTBP3 expression, thereby inhibiting the proliferation, migration and invasion of HCC cells. In conclusion, our results revealed that miR-297 could down-regulate the expression of PTBP3 and inhibit the activation of PI3K/AKT signaling pathway, thereby preventing HCC growth, migration and invasion.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , MicroRNAs/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genéticaRESUMO
Manganese (Mn) is an essential trace element that maintains many normal physiological functions. However, multi-system disorders would occur once overexposure to Mn, especially neurotoxicity. Despite evidence demonstrating the critical role of ROS-activated JNK/FOXO3a signaling pathway in neuronal survival, the specific mechanisms by which it contributes to Mn-induced neurotoxicity are still unclear. The objectives of this study was to examine the modulation of the JNK/FOXO3a signaling pathway, which is activated by ROS, in Mn-induced apoptosis, using a rat brain astrocyte cell line (CTX cells). This study found that a dose-dependent decrease in cell viability of CTX cells was observed with 150, 200, 250, 300 µmol/L Mn. The results of apoptosis-related protein assay showed that Mn decreased the expression of anti-apoptotic protein Bcl-2 and enhanced the expression of apoptosis-related proteins like Bax and Cleaved-Caspase3. In addition, treatment with Mn resulted in elevated ROS levels and increased phosphorylation levels of JNK. Conversely, phosphorylation of nuclear transcription factors FOXO3a, which regulates expression of transcription factors including Bim and PUMA, was decreased. Depletion of ROS by N-acetyl-L-cysteine (NAC) and inhibition of the JNK pathway by SP600125 prevented Mn-induced JNK/FOXO3a pathway activation and, more importantly, the level of apoptosis was also significantly reduced. Confirmation of Mn-induced apoptosis in CTX cells through ROS generation and activation of the JNK/FOXO3a signaling pathway was the outcome of this study. These findings offer fresh insights into the neurotoxic mechanisms of Mn and therapeutic targets following Mn exposure.
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Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.
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Mercúrio , Feminino , Gravidez , Humanos , Estudos Transversais , China , Mercúrio/análise , Fatores de Risco , Comportamento AlimentarRESUMO
Environmental methylmercury (MeHg) exposure has gained global attention owing to its serious health hazards, especially neurotoxicity. Ferroptosis is a novel form of programmed cell death characterized by lipid peroxidation and iron overload. However, the occurrence of ferroptosis and its underlying mechanisms have not been fully elucidated in the methylmercury-induced neurotoxicity and the role of Nrf2 in MeHg-induced ferroptosis remains unexplored. In this study, we verified that MeHg decreased cell viability in a dose- and time-dependent manner in the Rat Brain Astrocytes cells (CTX cells). MeHg (3.5 µmol/L) exposure induced CTX cells to undergo ferroptosis, as evidenced by glutathione (GSH) depletion, lipid peroxidation, and iron overload, which was significantly rescued by the ferroptosis-specific inhibitors Ferrostatin-1 and Deferoxamine. MeHg directly disrupted the process of GSH metabolism by downregulating of SLC7A11 and GPX4 and interfered with intracellular iron homeostasis through inhibition of iron storage and export. Simultaneously, the expression of Nrf2 was upregulated by MeHg in CTX cells. Hence, the inhibition of Nrf2 activity further downregulated the levels of GPX4, SLC7A11, FTH1, and SLC40A1, which aggravated MeHg-induced ferroptosis to a greater extent. Overall, our findings provided evidence that ferroptosis played a critical role in MeHg-induced neurotoxicity, and suppressing Nrf2 activity further exacerbated MeHg-induced ferroptosis in CTX cells.
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Ferroptose , Sobrecarga de Ferro , Compostos de Metilmercúrio , Ratos , Animais , Compostos de Metilmercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Ferro , Homeostase , Glutationa/metabolismoRESUMO
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by immune dysregulation. Restoration of the balance between regulatory T (Tregs) and T helper 17 (Th17) cells improves UC symptoms. Human amniotic epithelial cells (hAECs) have emerged as a promising therapeutic option for UC because of their immunomodulatory properties. In this study, we aimed to optimize and maximize the therapeutic potential of hAECs by pre-treating them with tumor necrosis factor (TNF)-α and interferon (IFN)-γ (pre-hAECs) for UC treatment. We evaluated the efficacy of hAECs and pre-hAECs in treating dextran sulfate sodium (DSS)-induced colitis mice. Compared to hAECs, pre-hAECs were found to be more effective in alleviating colitis in acute DSS mouse models than in the controls. Additionally, pre-hAEC treatment significantly reduced weight loss, shortened the colon length, decreased the disease activity index, and effectively maintained the recovery of colon epithelial cells. Furthermore, pre-hAEC treatment significantly inhibited the production of pro-inflammatory cytokines, such as interleukin (IL)-1ß and TNF-α, and promoted the expression of anti-inflammatory cytokines, such as IL-10. Both in vivo and in vitro studies revealed that pre-treatment with hAECs significantly increased the number of Treg cells, decreased the numbers of Th1, Th2, and Th17 cells, and regulated the balance of Th17/Treg cells. In conclusion, our results revealed that hAECs pre-treated with TNF-α and IFN-γ were highly effective in treating UC, suggesting their potential as therapeutic candidates for UC immunotherapy.
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Colite Ulcerativa , Colite , Humanos , Animais , Camundongos , Citocinas/metabolismo , Linfócitos T Reguladores , Fator de Necrose Tumoral alfa/metabolismo , Colite/terapia , Colite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Anti-Inflamatórios/uso terapêutico , Sulfato de Dextrana/farmacologia , Células Th17 , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Toll-like receptor 7 (TLR7) is highly expressed in dendritic cells (DCs) and B cells, and its aberrant activation can promote disease progression in systemic lupus erythematosus (SLE). We utilized structure-based virtual screening and experimental validation to screen natural products from TargetMol for potential TLR7 antagonists. Our results of molecular docking and molecular dynamics simulation showed that Mogroside V (MV) strongly interacted with TLR7, with stable open-TLR7-MV and close-TLR7-MV complexes. Furthermore, in vitro experiments demonstrated that MV significantly inhibited B cell differentiation in a concentration-dependent manner. In addition to TLR7, we also revealed a strong interaction of MV with all TLRs, including TLR4. The above results suggested that MV might be a potential TLR7 antagonist deserving of further study.
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Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.
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Fator Neurotrófico Derivado do Encéfalo , Chumbo , Feminino , Ratos , Animais , Masculino , Ratos Sprague-Dawley , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Chumbo/metabolismo , Transdução de Sinais , Hipocampo/metabolismo , Suplementos Nutricionais , Aprendizagem em LabirintoRESUMO
Wound repair is challenging for traditional wound dressings. New bioactive dressings need to be developed urgently. Herein, we reported a highly bioactive silk protein wound dressing (SPD) with natural silk fiber-sericin hydrogel interpenetrating double network structure, which combines the dual characteristics of natural silk and sericin hydrogel. Silk fiber scaffolds were secreted directly from silkworms bred by regulating their spinning behaviors. Sericin in SPD is obtained by dissolving silkworm cocoons at high temperature and high pressure, while it remains intact activities to self-assemble a hydrogel. To explore the effect of SPD, we first systematically evaluated its physicochemical properties and biological activitiesin vitro. The SPD exhibits high porosity, prominent mechanical strength, pH-responsive degradability, and excellent anti-oxidation and cell compatibility. Besides, SPD can load and maintain long-term drug release. Based on the satisfactory performance of SPDin vitro, effectivein vivotreatment was achieved in a mouse full-thickness wound model, as demonstrated by a significantly accelerated wound healing process, promote the regeneration of hair follicles and sebaceous glands, increased expression of vascular endothelial growth factor, and reduced inflammation. Further, resveratrol was loaded into SPD to enhance the effects of anti-oxidation and anti-inflammation for wound healing. Our investigation shows that SPD with excellent physicochemical and biological properties applied in a murine full-thickness skin wound model resulted in remarkable and efficient acceleration of healing process, which may inspire the design of new, effective, and safer medical materials for tissue regeneration.
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Bombyx , Sericinas , Camundongos , Animais , Sericinas/química , Sericinas/farmacologia , Resveratrol , Hidrogéis/química , Fator A de Crescimento do Endotélio Vascular/farmacologia , Seda/química , Cicatrização , BandagensRESUMO
Retinoid X receptor alpha (RXRα) is an important therapeutic target of cancer. Recently, small molecules (e.g.,XS-060 and its derivatives), which can significantly induce RXRα-dependent mitotic arrest by inhibiting pRXRα-PLK1 interaction, have been demonstrated as excellent anticancer agents. To further obtain novel RXR-targeted antimitotic agents with excellent bioactivity and drug-like properties, we herein synthesized two new series of bipyridine amide derivatives with XS-060 as the lead compound. In the reporter gene assay, most synthesized compounds showed antagonistic activity against RXRα. The most active compound, bipyridine amide B9 (BPA-B9), showed better activity than XS-060, with excellent RXRα-binding affinity (KD = 39.29 ± 1.12 nM) and anti-proliferative activity against MDA-MB-231 (IC50 = 16 nM, SI > 3). Besides, a docking study revealed a proper fitting of BPA-B9 into the coactivator binding site of RXRα, rationalizing its potent antagonistic effect on RXRα transactivation. Further, the mechanism studies revealed that the anticancer activity of BPA-B9 was dependent on its cellular RXRα-targeted mechanism, such as inhibiting pRXRα-PLK1 interaction and inducing RXRα-dependent mitotic arrest. Besides, BPA-B9 displayed better pharmacokinetics than the lead XS-060. Further, animal assays indicated BPA-B9 had significant anticancer efficacy in vivo with no considerable side effects. Together, our study reveals a novel RXRα ligand BPA-B9 targeting the pRXRα-PLK1 interaction, with great potential as a promising anticancer drug candidate for further development.
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Amidas , Antineoplásicos , Animais , Antineoplásicos/farmacologia , Sítios de Ligação , Receptor X Retinoide alfa/química , Receptor X Retinoide alfa/metabolismoRESUMO
It is attractive and challenging to develop a bioactive dressing based on native nondestructive sericin. Here, a native sericin wound dressing was secreted directly by silkworms bred through regulating their spinning behaviors. To be excited, our first reported wound dressing possesses original unique features of natural sericin, including natural structures and bioactivities. Besides, it has a porous fibrous network structure with a porosity of 75 %, thus achieving excellent air permeability. Moreover, the wound dressing exhibits pH-responsive degradability, softness, and super absorbency properties whose equilibrium water contents are no less than 75 % in various pH conditions. Furthermore, the sericin wound dressing demonstrates high mechanical strength, reaching 2.5 MPa tensile strength. Importantly, we confirmed good cell compatibility of sericin wound dressing that can support cell viability, proliferation, and migration for a long time. When tested in a mouse full-thickness skin wound model, the wound dressing efficiently accelerated the healing process. Our findings suggest that the sericin wound dressing has promising application and commercial value in wound repair.
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Bombyx , Sericinas , Camundongos , Animais , Sericinas/farmacologia , Sericinas/química , Cicatrização , Bandagens , PorosidadeRESUMO
"Green development" has become the way for countries around the world to strengthen industries, and it is an important part of China's high-quality economic development. The key for China to strike a balance between economic growth and environmental management is to optimize green total factor productivity (GTFP). This paper measures the GTFP of industry in 30 provinces of China from 2003 to 2019, based on the perspective of energy and carbon emission constraints. It empirically examines the spatial disequilibrium and dynamic evolution of industrial GTFP in China using Dagum Gini coefficients, Kernel density estimation, and Markov chain analysis. The study finds that, (1) although China's industrial GTFP is not high, it shows an increasing trend. The industrial GTFP in the southern region is higher than that in the northern region. (2) Technical efficiency is the shortcoming of China's industrial GTFP improvement. Technological progress is the main driving force of China's industrial GTFP improvement. (3) The relative and absolute differences in China'' industrial GTFP, technical efficiency, and technological progress have all shown a widening trend. Regional differences between the southern and northern regions are the main source of relative differences in industrial GTFP, technical efficiency, and technological progress. (4) China's industrial GTFP shows a clear "club convergence" phenomenon and the "Matthew effect." However, after the introduction of the spatial factor, the "club convergence" phenomenon and the "Matthew effect" have weakened. The driving effect of industrial GTFP on neighboring provinces is stronger in the south than in the north. This paper enriches the analysis of industrial GTFP and provides an important basis for the coordinated regional development of Chinese industry.
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Carbono , China , Desenvolvimento Econômico , Eficiência , IndústriasRESUMO
The extent to which neurodevelopment is affected by prenatal lead exposure has not been conclusive. In addition, studies on the effects of sex on these relationships are inconsistent. The aim of this study was to investigate the impact of cord blood lead on neurodevelopment in children within sex subgroups. A total of 275 mother-child pairs from the Shanghai mother-child cohort were included. Umbilical cord blood lead was measured using graphite furnace atomic absorption spectrophotometry. The Bayley Scales for Infant Development-III (BSID-III) was used to measure the neurodevelopment of infants at the age of 18 ± 1.5 months. The median and interquartile range of cord blood lead levels in the total participants, male, and female children were 44.0 (24.5) µg/L, 44.0 (24.3) µg/L, and 46.0 (24.0) µg/L, respectively. According to multiple linear regression, cord blood lead concentrations showed a negative association with fine motor scores in all models associated with female children (ß = -1.5; 95%confidence interval: -2.6, -0.4). However, prenatal lead levels were not associated with any of the BSID-III scores in male children. In addition, cord serum DHA was found positively related to fine motor scores in male children. Our findings suggest that prenatal lead exposure could lead to decreased motor function, although this phenomenon was only observed in female children. And DHA may be a protective factor against lead exposure in boys. Thus, further studies are needed to investigate the associations between prenatal lead exposure and neurobehavioral development, as well as the mechanism of sex differences.