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Homogenous melting at superheating temperature is commonly described by classical nucleation theory (CNT), but the atomic mechanism of the formation and development of critical liquid nuclei is still unclear. Molecular dynamics simulations were conducted to analyze the melting process of Ta. It is found that the process of subcritical liquid clusters evolving into critical liquid nucleus occupies most of the melting time, and merging between neighboring liquid clusters is the main path for subcritical liquid clusters to grow in size. Total melting time is strongly affected by the distribution of formation sites of subcritical liquid clusters, which has been considered random in homogenous melting. This work depicts a clear picture of the formation and development of liquid phase during the homogeneous melting process at superheating temperature and suggests an internal factor of melting mechanism.
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The field of oncology has transformed in recent years, with treatments shifting from traditional surgical resection and radiation therapy to more diverse and customized approaches, one of which is immunotherapy. ICD (immunogenic cell death) belongs to a class of regulatory cell death modalities that reactivate the immune response by facilitating the interaction between apoptotic cells and immune cells and releasing specific signaling molecules, and DAMPs (damage-associated molecular patterns). The inducers of ICD can elevate the expression of specific proteins to optimize the TME (tumor microenvironment). The use of nanotechnology has shown its unique potential. Nanomaterials, due to their tunability, targeting, and biocompatibility, have become powerful tools for drug delivery, immunomodulators, etc., and have shown significant efficacy in clinical trials. In particular, these nanomaterials can effectively activate the ICD, trigger a potent anti-tumor immune response, and maintain long-term tumor suppression. Different types of nanomaterials, such as biological cell membrane-modified nanoparticles, self-assembled nanostructures, metallic nanoparticles, mesoporous materials, and hydrogels, play their respective roles in ICD induction due to their unique structures and mechanisms of action. Therefore, this review will explore the latest advances in the application of these common nanomaterials in tumor ICD induction and discuss how they can provide new strategies and tools for cancer therapy. By gaining a deeper understanding of the mechanism of action of these nanomaterials, researchers can develop more precise and effective therapeutic approaches to improve the prognosis and quality of life of cancer patients. Moreover, these strategies hold the promise to overcome resistance to conventional therapies, minimize side effects, and lead to more personalized treatment regimens, ultimately benefiting cancer treatment.
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Morte Celular Imunogênica , Imunoterapia , Nanoestruturas , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Morte Celular Imunogênica/efeitos dos fármacos , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Animais , Imunoterapia/métodos , Microambiente Tumoral/imunologiaRESUMO
Irreversible bone defects resulting from trauma, infection, and degenerative illnesses have emerged as a significant health concern. Structurally and functionally controllable hydrogels made by bone tissue engineering (BTE) have become promising biomaterials. Natural proteins are able to establish connections with autologous proteins through unique biologically active regions. Hydrogels based on proteins can simulate the bone microenvironment and regulate the biological behavior of stem cells in the tissue niche, making them candidates for research related to bone regeneration. This article reviews the biological functions of various natural macromolecular proteins (such as collagen, gelatin, fibrin, and silk fibroin) and highlights their special advantages as hydrogels. Then the latest research trends on cross-linking modified macromolecular protein hydrogels with improved mechanical properties and composite hydrogels loaded with exogenous micromolecular proteins have been discussed. Finally, the applications of protein hydrogels, such as 3D printed hydrogels, microspheres, and injectable hydrogels, were introduced, aiming to provide a reference for the repair of clinical bone defects.
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To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.
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Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Vacina Antipólio de Vírus Inativado , Vacinas Combinadas , Humanos , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/administração & dosagem , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Lactente , Vacinas Combinadas/efeitos adversos , Vacinas Combinadas/administração & dosagem , China/epidemiologia , Feminino , Masculino , Vacinação/efeitos adversos , Infecções por Haemophilus/prevenção & controle , Esquemas de Imunização , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagemRESUMO
Background: Earlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology. Methods: Genome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis. From the largest meta-analysis GWAS, encompassing 18,169 controls and 12,488 cases, summary statistics data on gliomas was extracted. Summarized statistics for NDs, including Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) were obtained from the GWAS of European ancestry. Inverse variance weighted (IVW) method was elected as the core MR approach with weighted median (WM) method and MR-Egger method as complementary methods. In addition, sensitivity analyses were performed. A Bonferroni correction was used to correct the results. Results: Genetically predicted glioma had been related to decreased risk of AD. Specifically, for all glioma (IVW: OR = 0.93, 95% CI = 0.90-0.96, p = 4.88 × 10-6) and glioblastoma (GBM) (IVW: OR = 0.93, 95% CI = 0.91-0.95, p = 5.11 × 10-9). We also found that genetically predicted all glioma has a suggestive causative association with MS (IVW: OR = 0.90, 95% CI = 0.81-1.00, p = 0.045). There was no evidence of causal association between glioma and ALS or PD. According to the results of reverse MR analysis, no discernible causal connection of NDs was found on glioma. Sensitivity analyses validated the robustness of the above associations. Conclusion: We report evidence in support of potential causal associations of different glioma subtypes with AD and MS. More studies are required to uncover the underlying mechanisms of these findings.
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The magnetoelectric material has attracted multidisciplinary interest in the past decade for its potential to accommodate various functions. Especially, the external electric field can drive the quantum behaviors of such materials via the spin-electric coupling effect, with the advantages of high spatial resolution and low energy cost. In this work, the spin-electric coupling effect of Mn2+-doped ferroelectric organic-inorganic hybrid perovskite [(CH3)3NCH2Cl]CdCl3 with a large piezoelectric effect was investigated. The electric field manipulation efficiency for the allowed transitions was determined by the pulsed electron paramagnetic resonance. The orientation-included Hamiltonian of the spin-electric coupling effect was obtained via simulating the angle-dependent electric field modulated continuous-wave electron paramagnetic resonance. The results demonstrate that the applied electric field affects not only the principal values of the zero-field splitting tensor but also its principal axis directions. This work proposes and exemplifies a route to understand the spin-electric coupling effect originating from the crystal field imposed on a spin ion being modified by the applied electric field, which may guide the rational screening and designing of hybrid perovskite ferroelectrics that satisfy the efficiency requirement of electric field manipulation of spins in quantum information applications.
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Background: Systemic lupus erythematosus (SLE) is a persistent inflammatory disease caused by an autoimmune response that predominantly affects multiple organs and systems. Growing evidence highlights the critical role of precision-targeted therapies in the management of SLE. Surprisingly, only a handful of bibliometric studies have thoroughly assessed this area. This study attempts to assess the global landscape of literature output and research trends related to precision-targeted therapy for SLE. Method: Publications related to precision-targeted therapy for SLE from 2003 to 2023 were searched in the Web of Science Core Collection (WoSCC) database. VOSviewers, CiteSpace and the R package "bibliometrix" were used to perform this bibliometric analysis. Results: A total of 3700 papers were retrieved, showing a steady annual increase in publications from 2003 to 2022. The United States led the field with the highest number of papers (36.1 %) and secured the top position in terms of citation frequency (59,889) and H-index (115). Anhui Medical University System claimed the top spot with an impressive output of 70 papers. Principal investigators Tsokos, George C. C., and Lu, Qianjin led the research effort. Among the journals, Frontiers in Immunology stood out, publishing the highest number of articles with 191. In particular, precision-targeted therapy for SLE has become a major research focus in recent years, covering aspects such as T cells, B cells, oxidative stress, remission, and PHASE-III. Conclusion: This bibliometric study of ours systematically analyses research trends in precision targeted therapy for systemic lupus erythematosus, and this information identifies the research frontiers and hot directions in recent years and will serve as a reference for scientists working on targeted therapies.
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Background: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action. Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKß were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models. Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKß acted as key regulatory factor in renal injury and the expression of IKKß was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKß expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKß overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKß and attenuating IKKß/NF-κB pathway. Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKß/NF-κB pathway, which indicates targeting IKKß has an enormous potential for treating CKD.
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Insuficiência Renal Crônica , Sesquiterpenos , Animais , Humanos , Masculino , Camundongos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fibrose/tratamento farmacológico , Quinase I-kappa B/metabolismo , Quinase I-kappa B/antagonistas & inibidores , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismoRESUMO
Zn anode protection in Zn-ion batteries (ZIBs) face great challenges of high Zn utilization rate (i.e., depth of discharge, DOD) and high current density due to the large difficulty in obtaining an extreme overall RTC (relative texture coefficient) of Zn (002) plane. Through the potent interaction of Mn(III)aq and H+ with distinct Zn crystal planes under an electric field, large-size Zn foils with a breakthrough (002) plane RTC of 99% (i.e., close to Zn single crystal) are electrodeposited on texture-less substrates, which is also applicable from recycled Zn. The ultra-high (002) plane RTC remarkably enhances cyclic performance of the Zn anode (70% DOD @ 45.5 mA cm-2), and the DOD is even up to 95% (@ 28.1 mA cm-2) with an electrolyte additive of polyaniline. Furthermore, MnO2, the by-product of electrodeposition, is directly used as cathode of both coin cell and pouch battery, surpassing the cyclic performance exhibited by the majority of Zn||MnO2 batteries in previous instances. These results demonstrate the great potential of our strategy for high-performance, low-cost and large-scale ZIBs.
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Objectives: To investigate the effects and the related signaling pathway of miR-362-3p on OS. Methods: The bioinformatics analysis approaches were employed to investigate the target pathway of miR-362-3p. After the 143B and U2OS cells and nu/nu male mice were randomly divided into blank control (BC) group, normal control (NC) group, and overexpression group (OG), the CCK-8, EdU staining, wound healing assay, Transwell assay, and TUNEL staining were adopted to respectively determine the effects of overexpressed miR-362-3p on the cell viability, proliferation, migration, invasion, and apoptosis of 143B and U2OS cells in vitro, tumor area assay and hematoxylin and eosin staining were employed to respectively determine the effects of overexpressed miR-362-3p on the growth and pathological injury of OS tissue in vivo. The qRT-PCR, Western blot, and immunohistochemical staining were applied to respectively investigate the effects of overexpressed miR-362-3p on the IL6ST/JAK2/STAT3 pathway in OS in vivo and in vitro. Results: The bioinformatics analysis approaches combined qRT-PCR indicated that the IL6ST/JAK2/STAT3 is one of the target pathways of miR-362-3p. Compared with NC, the cell viability, proliferation, migration, and invasion of 143B and U2OS cells were dramatically (P < 0.01) inhibited but the apoptosis was prominently (P <0 .0001) promoted in OG. Compared with NC, the growth of OS tissue was significantly (P < 0.05) suppressed and the pathological injury of OS tissue was substantially aggravated in OG. The gene expression levels of IL6ST, JAK2, and STAT3 and the protein expression levels of IL6ST, JAK2, p-JAK2, STAT3, and p-STAT3 in 143B and U2OS cells were memorably (P < 0.0001) lower in OG than those in NC. In addition, the positively stained areas of proteins of IL6ST, JAK2, p-JAK2, STAT3, and p-STAT3 of OS tissue in OG were markedly (P < 0.01) reduced compared with those in NC. Conclusion: The overexpression of miR362-3p alleviates OS by inhibiting the IL6ST/JAK2/STAT3 pathway in vivo and in vitro.
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Apoptose , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Janus Quinase 2 , MicroRNAs , Osteossarcoma , Fator de Transcrição STAT3 , Transdução de Sinais , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Apoptose/genética , Masculino , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor gp130 de Citocina/metabolismo , Receptor gp130 de Citocina/genética , Biologia Computacional/métodos , Modelos Animais de Doenças , Sobrevivência Celular/genéticaRESUMO
Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in Neuroligin-3 (NLG3) genes are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we find the conditional knockout of NLG3 (NLG3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. NLG3 knockout in MS causes hyperactivity of MS-GABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induces social memory deficits and sleep loss in C57BL/6 mice. In contrast, inactivation of these neurons ameliorates social memory deficits and sleep loss in NLG3-CKO mice. Sleep deprivation leads to social memory deficits, while social isolation causes sleep loss, both resulting in a reduction of NLG3 expression and an increase in activity of GABAergic neurons in MS from C57BL/6 mice. Furthermore, MS-GABA-innervated CA2 neurons specifically regulate social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively control sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MS-GABA neurons impair social memory and disrupt sleep resulting from NLG3 knockout in MS, and achieve the modality specificity through their divergent downstream targets.
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Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug-resistant bacteria, rendering ineffective immune responses and even life-threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid-catechol interaction, the multifunctional bismuth-based polypeptide nanonets (PLBA-Bi-Fe-TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid-functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement-enhanced high-contact network-driven multiple efficiency, PLBA-Bi-Fe-TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic-resistant bacterial biofilms, while Fe-TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro-inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial-associated infections at all stages through synergetic treatment.
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The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features of the TME include metabolic reprogramming, hypoxia, chronic inflammation, and tumor immunosuppression. Previous studies suggest that senescence-associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME. Specifically, hypoxic adaptation, metabolic dysregulation, and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation, thereby promoting the progression of tumor events. This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor-adapted TME, with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells. The available findings suggest that components of the TME collectively contribute to the progression of tumor events. The potential applications and challenges of targeted cellular senescence-based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence-related research.
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Coastal areas, situated at the critical juncture of sea-land interaction, are confronted with significant challenges from coastal erosion and flooding. It is imperative to evaluate these risks and offer scientific guidance to foster regional sustainable development. This article developed a coastal risk assessment model based on grid scale, integrating both coastal exposure and socio-ecological environment. Fourteen indicators were selected, aiming to offer a systematic approach for estimating and comparing disaster risks in coastal areas. This risk assessment model was applied to Shanghai, New York, Sydney, San Francisco, Randstad, and Tokyo metropolitan areas. The results indicate: (1) Accounting for the protective role of habitat types like mangroves and the distance attenuation effect offered a more precise representation of hazard situation; (2) The integration of the Game Theory weighting method with both subjective Analytic Hierarchy Process and objective CRITIC weighting enhanced the scientific validity and rationality of the results by minimizing deviations between subjective and objective weights; (3) Shanghai exhibited the highest average hazard and vulnerability, San Francisco had the lowest average hazard and Sydney had the lowest average vulnerability; In terms of comprehensive risk, Shanghai possessed the highest average risk, while Sydney presented the lowest. The proposed model framework is designed to swiftly identify high-risk zones, providing detailed information references for local governments to devise efficacious risk management and prevention strategies.
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Bone defect is one of the urgent problems to be solved in clinics, and it is very important to construct efficient scaffold materials to facilitate bone tissue regeneration. Hydrogels, characterized by their unique three-dimensional network structure, serve as excellent biological scaffold materials. Their internal pores are capable of loading osteogenic drugs to expedite bone formation. The rate and quality of new bone formation are intimately linked with immune regulation and vascular remodeling. The strategic sequential release of drugs to balance inflammation and regulate vascular remodeling is crucial for initiating the osteogenic process. Through the design of hydrogel microstructures, it is possible to achieve sequential drug release and the drug action time can be prolonged, thereby catering to the multi-systemic collaborative regulation needs of osteosynthesis. The drug release rate within the hydrogel is governed by swelling control systems, physical control systems, chemical control systems, and environmental control systems. Utilizing these control systems to design hydrogel materials capable of multi-drug delivery optimizes the construction of the bone microenvironment. Consequently, this facilitates the spatiotemporal controlled released of drugs, promoting bone tissue regeneration. This paper reviews the principles of the controlled release system of various sustained-release hydrogels and the advancements in research on hydrogel multi-drug delivery systems for bone tissue regeneration.
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Regeneração Óssea , Preparações de Ação Retardada , Hidrogéis , Hidrogéis/química , Regeneração Óssea/efeitos dos fármacos , Humanos , Animais , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Osteogênese/efeitos dos fármacos , Alicerces Teciduais/químicaRESUMO
Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.
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Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4+ T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.
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COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Células T Auxiliares Foliculares , Humanos , COVID-19/imunologia , Idoso , Masculino , Feminino , SARS-CoV-2/imunologia , Células T Auxiliares Foliculares/imunologia , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Linfócitos T Reguladores/imunologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Fatores Etários , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Imunidade Adaptativa/imunologiaRESUMO
The extensive utilization of pesticides results in their frequent detection in aquatic environments, often as complex mixtures, posing risks to aquatic organisms. The hook snout carp (Opsariichthys bidens) serves as a valuable bioindicator for evaluating the impacts of environmental pollutants in aquatic ecosystems. However, few studies examined the toxic effects of pesticides on O.bidens, let alone the characterization of the combined effects resulting from their mixtures. This study aims to elucidate the toxic effects of beta-cypermethrin and pyraclostrobin on O.bidens, individually and in combination, focusing on biochemical, transcriptional, and molecular responses. By organizing and analyzing the toxicogenomic databases, both pesticides were identified as a contributor to processes such as apoptosis, oxidative stress, and inflammatory responses. The acute toxicity test revealed comparable acute toxicity of beta-cypermethrin and pyraclostrobin on O.bidens, with LC50 being 0.019 and 0.027 mg/L, respectively, whereas the LC50 decreased to 0.0057 and 0.0079 mg/L under the combined exposure, indicating potential synergistic effects. The activities of enzymes involved in oxidative stress and detoxification were significantly altered after exposure, with superoxide dismutase (SOD) and catalase (CAT) increasing, while malondialdehyde (MDA) levels decreased. The activity of CYP450s was significantly changed. Likewise, the expression levels of genes (mn-sod, p53, esr, il-8) associated with oxidative stress, apoptosis, endocrine and immune systems were significantly increased. Combined exposure to the pesticides significantly exacerbated the aforementioned biological processes in O.bidens. Furthermore, both pesticides can modify protein activity by binding to the surface of SOD molecules and altering protein conformation, contributing to the elevated enzyme activity. Through the investigation of the synergistic toxic effects of pesticides and molecular mechanisms in O.bidens, our findings highlight the importance of assessing the combined effects of pesticide mixtures in aquatic environments.
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Carpas , Piretrinas , Estrobilurinas , Poluentes Químicos da Água , Piretrinas/toxicidade , Animais , Poluentes Químicos da Água/toxicidade , Carpas/genética , Carpas/metabolismo , Estrobilurinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Inseticidas/toxicidade , Carbamatos/toxicidade , Testes de Toxicidade AgudaRESUMO
Motor imagery (MI) based brain computer interface (BCI) has been extensively studied to improve motor recovery for stroke patients by inducing neuroplasticity. However, due to the lower spatial resolution and signal-to-noise ratio (SNR) of electroencephalograph (EEG), MI based BCI system that involves decoding hand movements within the same limb remains lower classification accuracy and poorer practicality. To overcome the limitations, an adaptive hybrid BCI system combining MI and steady-state visually evoked potential (SSVEP) is developed to improve decoding accuracy while enhancing neural engagement. On the one hand, the SSVEP evoked by visual stimuli based on action-state flickering coding approach significantly improves the recognition accuracy compared to the pure MI based BCI. On the other hand, to reduce the impact of SSVEP on MI due to the dual-task interference effect, the event-related desynchronization (ERD) based neural engagement is monitored and employed for feedback in real-time to ensure the effective execution of MI tasks. Eight healthy subjects and six post-stroke patients were recruited to verify the effectiveness of the system. The results showed that the four-class gesture recognition accuracies of healthy individuals and patients could be improved to 94.37 ± 4.77 % and 79.38 ± 6.26 %, respectively. Moreover, the designed hybrid BCI could maintain the same degree of neural engagement as observed when subjects solely performed MI tasks. These phenomena demonstrated the interactivity and clinical utility of the developed system for the rehabilitation of hand function in stroke patients.
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Interfaces Cérebro-Computador , Eletroencefalografia , Potenciais Evocados Visuais , Mãos , Reabilitação do Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Masculino , Eletroencefalografia/métodos , Feminino , Potenciais Evocados Visuais/fisiologia , Pessoa de Meia-Idade , Adulto , Algoritmos , Imaginação/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Gestos , Idoso , Voluntários Saudáveis , Adulto Jovem , Estimulação Luminosa , Razão Sinal-Ruído , Reprodutibilidade dos TestesRESUMO
Several (inter)national longitudinal dementia observational datasets encompassing demographic information, neuroimaging, biomarkers, neuropsychological evaluations, and muti-omics data, have ushered in a new era of potential for integrating machine learning (ML) into dementia research and clinical practice. ML, with its proficiency in handling multi-modal and high-dimensional data, has emerged as an innovative technique to facilitate early diagnosis, differential diagnosis, and to predict onset and progression of mild cognitive impairment and dementia. In this review, we evaluate current and potential applications of ML, including its history in dementia research, how it compares to traditional statistics, the types of datasets it uses and the general workflow. Moreover, we identify the technical barriers and challenges of ML implementations in clinical practice. Overall, this review provides a comprehensive understanding of ML with non-technical explanations for broader accessibility to biomedical scientists and clinicians.