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Holistic understanding of physio-pathological processes requires noninvasive 3D imaging in deep tissue across multiple spatial and temporal scales to link diverse transient subcellular behaviors with long-term physiogenesis. Despite broad applications of two-photon microscopy (TPM), there remains an inevitable tradeoff among spatiotemporal resolution, imaging volumes, and durations due to the point-scanning scheme, accumulated phototoxicity, and optical aberrations. Here, we harnessed the concept of synthetic aperture radar in TPM to achieve aberration-corrected 3D imaging of subcellular dynamics at a millisecond scale for over 100,000 large volumes in deep tissue, with three orders of magnitude reduction in photobleaching. With its advantages, we identified direct intercellular communications through migrasome generation following traumatic brain injury, visualized the formation process of germinal center in the mouse lymph node, and characterized heterogeneous cellular states in the mouse visual cortex, opening up a horizon for intravital imaging to understand the organizations and functions of biological systems at a holistic level.
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Imageamento Tridimensional , Animais , Camundongos , Imageamento Tridimensional/métodos , Microscopia Confocal/métodosRESUMO
Parkinson's disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes.
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Citrobacter rodentium , Dopamina , Infecções por Enterobacteriaceae , Camundongos Endogâmicos C57BL , Animais , Camundongos , Dopamina/metabolismo , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/patologia , Masculino , Feminino , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/microbiologia , Microbioma Gastrointestinal/fisiologiaRESUMO
Neuroinflammation is one of the core pathological features of Parkinson's disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD.
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Microglia , Doença de Parkinson , Animais , Camundongos , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Hipóxia/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Doenças Neuroinflamatórias , Doença de Parkinson/patologia , Imunidade TreinadaRESUMO
The removal of uranyl ions (UO2 2+) from water is challenging due to their chemical stability, low concentrations, complex water matrix, and technical limitations in extraction and separation. Herein, a novel molybdenum disulfide/graphene oxide heterojunction (MoS2/GO-H) is developed, serving as an effective electrode for capacitive deionization (CDI). By combining the inherent advantages of electroadsorption and electrocatalysis, an innovative electroadsorption-electrocatalysis system (EES) strategy is introduced. This system utilizes interface polarization at the MoS2 and GO interface, creating an additional electric field that significantly influences carrier behavior. The MoS2/GO-H electrode, with its extraordinary adsorption capacity of 805.57 mg g-1 under optimal conditions, effectively treated uranium-laden wastewater from a mine, achieving over 90% removal efficiency despite the presence of numerous competing ions at concentrations significantly higher than UO2 2+. Employing density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations, it is found that the MoS2/GO-H total charge density at the Fermi level, enhanced by interfacial polarization, surpasses that of separate MoS2 and GO, markedly boosting conductivity and electrocatalytic effectiveness.
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GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.
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Dissulfiram , Neurônios Dopaminérgicos , Microglia , Doença de Parkinson , Proteínas de Ligação a Fosfato , Piroptose , Piroptose/efeitos dos fármacos , Piroptose/fisiologia , Doença de Parkinson/metabolismo , Animais , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Microglia/metabolismo , Microglia/efeitos dos fármacos , Camundongos , Masculino , Humanos , Proteínas de Ligação a Fosfato/metabolismo , Dissulfiram/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Morte Celular/efeitos dos fármacos , Camundongos Knockout , GasderminasRESUMO
BACKGROUND: Deep learning (DL) is one of the latest approaches to artificial intelligence. As an unsupervised DL method, a generative adversarial network (GAN) can be used to synthesize new data. PURPOSE: To explore GAN applications in medicine and point out the significance of its existence for clinical medical research, as well as to provide a visual bibliometric analysis of GAN applications in the medical field in combination with the scientometric software Citespace and statistical analysis methods. MATERIAL AND METHODS: PubMed, MEDLINE, Web of Science, and Google Scholar were searched to identify studies of GAN in medical applications between 2017 and 2022. This study was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Citespace was used to analyze the number of publications, authors, institutions, and keywords of articles related to GAN in medical applications. RESULTS: The applications of GAN in medicine are not limited to medical image processing, but will also penetrate wider and more complex fields, or may be applied to clinical medicine. Eligibility criteria were the full texts of peer-reviewed journals reporting the application of GANs in medicine. Research selections included material published in English between 1 January 2017 and 1 December 2022. CONCLUSION: GAN has been fully applied to the medical field and will be more deeply and widely used in clinical medicine, especially in the field of privacy protection and medical diagnosis. However, clinical applications of GAN require consideration of ethical and legal issues. GAN-based applications should be well validated by expert radiologists.
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Inteligência Artificial , Pesquisa Biomédica , Humanos , Bibliometria , Processamento de Imagem Assistida por Computador , Revisão por ParesRESUMO
Histone deacetylase 6 (HDAC6) is involved in the regulation of protein aggregation and neuroinflammation, but its role in Parkinson's disease (PD) remains controversial. In this study, Hdac6-/- mice were generated by CRISPR-Cas9 technology for exploring the effect of HDAC6 on the pathological progression of PD. We found that male Hdac6-/- mice exhibit hyperactivity and certain anxiety. In the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, though motor injury was slightly alleviated by HDAC6 deficiency, dopamine (DA) depletion in the striatum, the decrease in the number of DA neurons in the substantia nigra (SN) and the reduction in DA neuronal terminals were not affected. In addition, activation of glial cells and the expression of α-synuclein, as well as the levels of apoptosis-related proteins in the nigrostriatal pathway, were not changed in MPTP-injected wild-type and Hdac6-/- mice. Therefore, HDAC6 deficiency leads to moderate alterations of behaviors and Parkinson's disease pathology in mice.
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Doença de Parkinson , Animais , Masculino , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Desacetilase 6 de Histona/genética , Desacetilase 6 de Histona/metabolismo , Camundongos Endogâmicos C57BL , Doença de Parkinson/metabolismo , Substância Negra/metabolismoRESUMO
The construction of novel fluorescent nanozymes is highly desirable for providing new strategies for nanozyme-based sensing systems. Herein, a novel ratiometric fluorescence sensing platform was constructed based on carbon dots (CDs) as both luminophores and nanozymes, which could realize the sensitive detection of hydrogen peroxide (H2O2). CDs with peroxidase-mimicking activity were prepared with a one-step hydrothermal method using L-histidine as an inexpensive precursor. CDs had bright blue fluorescence. Due to the pseudo-peroxidase activity, CDs catalyzed the oxidation of o-phenylenediamine (OPD) with H2O2 to generate 2,3-diaminophenolazine (DAP). The fluorescence resonance energy transfer (FRET) between CDs and DAP resulted in a decrease in the fluorescence of CDs and an increase in the fluorescence of DAP, leading to a ratiometric fluorescence system. The free radical trapping experiment was used to investigate the reactive oxygen radicals (ROS) in the catalytic process of CD nanozymes. The enzymatic parameters of CD nanozymes, including the Michaelis constant (Km) and the maximum initial reaction velocities (Vmax), were investigated. A good affinity for both OPD and H2O2 substrates was proven. Based on the FRET between CDs and OPD, a ratiometric fluorescence analysis of H2O2 was achieved and results ranged from 1 to 20 µM and 20 to 200 µM with a low limit of detection (LOD, 0.42 µM). The detection of H2O2 in milk was also achieved.
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Carbono , Pontos Quânticos , Peróxido de Hidrogênio/análise , Fenilenodiaminas , Peroxidases , Corantes Fluorescentes , Limite de DetecçãoRESUMO
Understanding the interaction between nanoparticles (NPs) and cell membranes is crucial for the design of NP-based drug delivery systems and for the assessment of the risks exerted by the NPs. Recent experimental and theoretical studies have shown that cell membranes can mediate attraction between NPs and form tubular structures to wrap multiple NPs. However, the cooperative wrapping process is still not well understood, and the shape effect of NPs is not considered. In this article, we use large-scale coarse-grained molecular dynamics (CGMD) simulations to study the cooperative wrapping of NPs when a varying number of NPs adhered to the membrane. Spherical, prolate and oblate NPs of different sizes are considered in this study. We find that, in addition to tubular structures, the membrane can form a pocket-like and a handle-like structure to wrap multiple NPs depending on the size and shape of the NPs. Furthermore, we find that NPs can mediate membrane hemifusion or fusion during this process. Our findings provide new insights into the interaction of NPs with the cell membrane.
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Membrana Celular/química , Lipídeos de Membrana/química , Tamanho da Partícula , Conformação Molecular , Simulação de Dinâmica Molecular , NanopartículasRESUMO
BACKGROUND: This study delves into the relationship between childhood trauma and adolescent depression symptoms, specifically examining the distinct roles of ruminative thinking and deliberate rumination in mediating this connection. The focus is on exploring whether these cognitive processes, namely ruminative thinking and deliberate rumination, operate differently and sequentially in mediating the impact of childhood emotional abuse (CEA) on the development of depression symptoms among Chinese adolescents. METHODS: The study involved gathering data from 489 adolescents, with a relatively balanced gender distribution (44.79 % males and 55.21 % females). The average age of the participants was 16.92 years, with a standard deviation of 0.67. Data collection took place in two Chinese high schools, and participants were tasked with completing assessments related to CEA, ruminative thinking, deliberate rumination, and depression symptoms. The interplay among these variables was then examined using a serial mediation model. RESULTS: The findings of the study indicate that CEA not only exhibited a direct association with adolescent depression symptoms but also exerted indirect effects through distinct mediating mechanisms involving ruminative thinking and deliberate rumination. Specifically, ruminative thinking was identified as a mediator, whereas deliberate rumination emerged as a buffer in the relationship between CEA and depression. Additionally, ruminative thinking and deliberate rumination partially masked the effect of CEA on adolescent depression symptoms in a sequential pattern. CONCLUSIONS: Regarding the link from CEA to adolescent depression symptoms, ruminative thinking is an adverse mediator while deliberate rumination appears to play a benign role. Consequently, the promotion of a shift from ruminative thinking to deliberate rumination is proposed as a promising strategy for alleviating the detrimental effects of CEA on adolescent depression.
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Depressão , Ruminação Cognitiva , Humanos , Adolescente , Feminino , Masculino , Depressão/psicologia , China/epidemiologia , Maus-Tratos Infantis/psicologia , Abuso Emocional/psicologia , Pensamento , População do Leste AsiáticoRESUMO
Light field disparity estimation is an essential task in computer vision. Currently, supervised learning-based methods have achieved better performance than both unsupervised and optimization-based methods. However, the generalization capacity of supervised methods on real-world data, where no ground truth is available for training, remains limited. In this paper, we argue that unsupervised methods can achieve not only much stronger generalization capacity on real-world data but also more accurate disparity estimation results on synthetic datasets. To fulfill this goal, we present the Occlusion Pattern Aware Loss, named OPAL, which successfully extracts and encodes general occlusion patterns inherent in the light field for calculating the disparity loss. OPAL enables: i) accurate and robust disparity estimation by teaching the network how to handle occlusions effectively and ii) significantly reduced network parameters required for accurate and efficient estimation. We further propose an EPI transformer and a gradient-based refinement module for achieving more accurate and pixel-aligned disparity estimation results. Extensive experiments demonstrate our method not only significantly improves the accuracy compared with SOTA unsupervised methods, but also possesses stronger generalization capacity on real-world data compared with SOTA supervised methods. Last but not least, the network training and inference efficiency are much higher than existing learning-based methods. Our code will be made publicly available.
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Sulfur (S) is an essential element for the growth of rice plants (Oryza sativa L.), crucial for enhancing crop yield and grain quality. However, its potential in mitigating thallium (Tl) toxicity in rice remains unclear. In this study, a hydroponic experiment was performed to investigate the effects of low, medium and high S application levels (LS, MS, HS) on Tl accumulation in rice at three Tl exposure levels (0, 0.5 and 1 mg·L-1). Our findings reveal that the exogenous S application could alleviate Tl toxicity, enhancing fresh weight and shoot length of rice plant. Additionally, HS (HS, SO42- content was 387.84 mg·L-1) group significantly increased chlorophyll and glutathione (GSH) content by 6.46 to 21.38 % and 2.15 to 7.31 % respectively, while reducing malondialdehyde (MDA) levels by 17.43 to 28.48 %, compared to MS (MS, SO42- content was 193.41 mg·L-1) group. Fe content in rice roots and iron plaque consistently increased with S provision under Tl-free and Tl-contaminated conditions. In Tl exposure environment, HS and LS (LS, SO42- content was 1.02 mg·L-1) groups exhibited significant differences in Fe contents and iron plaque in rice root. Moreover, in Tl exposure environment, S application reduced Tl concentration in iron plaque, root, and shoot, HS treatment showed Tl content reduction from 16.29 % to 25.89 %, compared to LS treatment. Our findings underscore the potential of S application in hydroponic environment to promote rice growth and mitigate Tl accumulation, offering insights for developing effective Tl remediation strategies by using S-contained fertilizers.
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Organic farming is a sustainable agricultural practice emphasizing natural inputs and ecological balance, and has garnered significant attention for its potential health and environmental benefits. However, a comprehensive evaluation of the emergent contaminants, particularly resistance and virulence genes within organic farming system, remains elusive. Here, a total of 36 soil samples from paired conventional and organic vegetable farms were collected from Jiangsu province, China. A systematic metagenomic approach was employed to investigate the prevalence, dispersal capability, pathogenic potential, and drivers of resistance and virulence genes across both organic and conventional systems. Our findings revealed a higher abundance of antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), and virulence factor genes (VFGs) in organic farming system, with ARGs exhibiting a particularly notable increase of 10.76% compared to the conventional one. Pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Mycobacterium tuberculosis were hosts carrying all four gene categories, highlighting their potential health implications. The neutral community model captured 77.1% and 71.9% of the variance in community dynamics within the conventional and organic farming systems, respectively, indicating that stochastic process was the predominant factor shaping gene communities. The relative smaller m value calculated in organic farming system (0.021 vs 0.023) indicated diminished gene exchange with external sources. Moreover, farming practices were observed to influence the resistance and virulence gene landscape by modifying soil properties, managing heavy metal stress, and steering mobile genetic elements (MGEs) dynamics. The study offers insights that can guide agricultural strategies to address potential health and ecological concerns.
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Agricultura Orgânica , Solo , Virulência/genética , Agricultura , Resistência Microbiana a Medicamentos/genética , Antibacterianos/farmacologia , Genes Bacterianos , Microbiologia do SoloRESUMO
The quartz sand-enhanced coagulation (QSEC) is an improved coagulation method for treating water, which uses quartz sand as a heavy medium to accelerate the sedimentation rate of flocs and reduce the sedimentation time. The factors that influence the QSEC effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc., and their reasonable setting is critical to the result of water treatment. This paper aimed to study the optimal conditions of QSEC; first, single-factor tests were conducted to explore the optimal range of influencing factors, followed by response surface methodology (RSM) tests to accurately determine the optimum values of significant factors. The results show that the addition of quartz sand did not improve the water quality of the coagulation treatment, it took only 140 s for the floc to sink to the bottom, and the sediment volume only accounted for 12.2% of the total sewage. The quartz sand dosage, the coagulant dosage, and sewage pH all had a significant impact on the coagulation effect, and resulted in inflection points. A QSEC-guiding model was derived through RSM tests, and subsequent model optimization and experimental validation revealed the optimal conditions for treating domestic sewage as follows: the polyaluminum chloride (PAC) dosage, cationic polyacrylamide (CPAM) dosage, the sewage pH, quartz sand dosage, stirring time, and settling time were 0.97 g/L, 2.25 mg/L, 7.22, 2 g/L, 5 min, and 30 min, respectively, and the turbidity of the treated sewage was reduced to 1.15 NTU.
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BACKGROUNDS: Cancer is a highly fatal disease which is close relative of miRNA aberrant expression and apoptosis disorders. Elucidation of the therapeutic efficacy through investigating the changes in miRNA and apoptosis holds immense importance in advancing the development of miRNA-based precision therapy. However, it remains a challenge as how to visually evaluate the efficacy during protocol optimization of miRNA-based anticancer drugs at the cellular level. Therefore, exploring effective and noninvasive methods for real-time monitoring of therapeutic efficacy in living cells is of great significance. RESULTS: Herein, we reported a novel fluorescent nanoprobe COF-H1/H2-Peptide for visually evaluating drug efficacy in living cells through amplified imaging of low-abundant miRNA-221 with catalytic hairpin assembly (CHA) circle amplification, as well as simultaneous caspase-3 imaging. With strong stability and good biocompatibility, this newly fabricated amplified nanoprobe showed high sensitivity and specificity for the detection of miRNA-221 and caspase-3, and the limit of detection (LOD) of miRNA-221 was as low as 2.79 pM. The fluorescent imaging results showed that this amplified nanoprobe could not only detect caspase-3 in living cells, but also effectively detect low levels of miRNA-221 with increasing anticancer drug concentration and treatment time. The smart nanoprobe had effective performance for optimizing miRNA-based drug treatment schedules by dual-color fluorescence imaging. SIGNIFICANCE: This nanoprobe combined CHA amplified detection of intracellular miRNA-221 and synchronous apoptosis imaging, with excellent sensitivity for the detection of cellular low-level miRNA, enabling the realization of real-time assessment of the efficacy of miRNA-based therapy in living cells. This work presents a promising approach for revealing the regulatory mechanisms between miRNAs and apoptosis in cancer occurrence, development, and treatment.
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Técnicas Biossensoriais , MicroRNAs , Humanos , MicroRNAs/genética , Caspase 3 , Apoptose , Células HeLa , Corantes Fluorescentes , Técnicas Biossensoriais/métodosRESUMO
The formation of peer attachment is vitally important for the mental health of adolescents. Additionally, converging evidences show that childhood emotional trauma leads to poor peer attachment during adolescence. However, little is known about the underlying mechanism accounting for the link between early emotional trauma and adolescent peer attachment. Therefore, the present study is intended to examine the relationship between childhood psychological maltreatment (CPM) and peer attachment among Chinese adolescents and reveal its underlying mechanism. In total, we collected data from 670 adolescents (36.5% males and 63.5% females, Mage = 16.44 years, SD = 0.78) attending two Chinese high schools. These participants completed measurement scales for CPM (emotional abuse and neglect), peer attachment, and emotion regulation strategies, including cognitive reappraisal (CR) and expressive suppression (ES). The multiple mediation models showed that emotional neglect negatively predicted adolescent peer attachment but that emotional abuse did not. Furthermore, the two emotion regulation strategies, CR and ES, completely mediated the relationship between emotional abuse and peer attachment and partially mediated the relationship between emotional neglect and peer attachment. These findings extend the existing studies on adolescent peer attachment and elucidate how childhood emotional trauma negatively influences adolescent peer attachment. In addition, the present results provide implications for improving the peer attachment of adolescents. On one hand, appropriate family intervention should be implemented to reduce CPM. On the other hand, schools can focus on improving the peer attachment of adolescents by enhancing their emotion regulation. Specifically, adolescents should be taught how to use adaptive strategies, such as CR, to regulate negative emotions.
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Maus-Tratos Infantis , Regulação Emocional , Apego ao Objeto , Grupo Associado , Adolescente , Criança , Feminino , Humanos , Masculino , Maus-Tratos Infantis/psicologia , População do Leste Asiático , Emoções , Instituições AcadêmicasRESUMO
Morchella sp. is a kind of precious medicinal and edible fungus with a unique flavor and is rich in various amino acids and organic germanium needed by the human body. Most notably, Morchella sp. polysaccharides have attracted widespread attention due to their significant bioactivity in recent years. At present, extensive studies have been carried out on the extraction methods, structural characterization and activity evaluation of Morchella sp. polysaccharides, which provides a good theoretical basis for its further development and application. However, the systematic summary of the related research of Morchella sp. polysaccharides has not been reported yet. Therefore, this review mainly focused on the isolation and purification methods, structural characterization, biological activities and structure-activity relationship of Morchella sp. polysaccharides. This work will help to have a better in-depth understanding of Morchella sp. polysaccharides and provide a scientific basis and direct reference for more scientific and rational applications.
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Ascomicetos , Polissacarídeos , Humanos , Polissacarídeos/química , Ascomicetos/química , Relação Estrutura-Atividade , Antioxidantes/farmacologiaRESUMO
AIMS: Parkinson's disease (PD) is a progressive neurodegenerative disorder. The etiology of PD is still elusive but neuroinflammation is proved to be an important contributor. Toll-like receptor 2 (TLR2) involves in the release of several inflammatory cytokines. Whether TLR2 serves as a mediator contributing to the damage of DA system in PD remain unclear. MAIN METHODS: Tlr2 knockout (Tlr2-/-) and wild-type (WT) mice were treated with a subacute regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). At 3, 7 and 14 days after MPTP injection, the behavioral performance, including the Pole test, the Rotarod test, the Rearing test and the Wire hang test was evaluated. Moreover, the PD-like phenotypes, including dopaminergic degeneration, the activation of glial cells and the α-Syn expression were systematically analyzed in the nigrostriatal pathway. Finally, the composition of gut microbiota in the MPTP-treated groups were assessed. KEY FINDINGS: TLR2 deficiency had no obvious impact on the dopaminergic injury at 3 and 7 days following MPTP administration. On the contrary, at 14 days post injection, TLR2 deficiency not only significantly attenuated motor deficits in the Pole test and the Rotarod test, and the nigrostriatal dopaminergic degeneration, but also mitigated α-Syn abnormality, astrocyte activation and neuroinflammation through the suppressed TLR2/MyD88/TRAF6/NF-κB signaling pathways. Additionally, the alteration of gut microbiota was also detected in the mutant mice. SIGNIFICANCE: These findings highlight the neuroprotective effect of TLR2-pathways at the late phase in the MPTP-induced PD mouse model.
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Fármacos Neuroprotetores , Doença de Parkinson , Animais , Camundongos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismoRESUMO
BACKGROUND: Adolescents are at risk of depression, and recent studies also found a high prevalence of depression among Chinese adolescents. Therefore, it is necessary to explore the risk and protective factors of depression among Chinese adolescents. OBJECTIVE: This study examined the direct effect of psychological maltreatment on depression symptoms in adolescents and the mediating roles of emotion regulation and social support in their relationship. METHOD: Data were collected from Chinese senior high school students (N = 687, 36.5 % males and 63.5 % females, Mage = 16.44 years, SD = 0.78) who completed the measures of psychological maltreatment, depression symptoms, perceived social support, and emotion regulation strategies, including cognitive reappraisal and expressive suppression. RESULTS: The results indicated that: (a) psychological maltreatment was positively correlated with depression symptoms; (b) the two emotion regulation strategies and perceived social support partially mediated the link between psychological maltreatment and depression symptoms separately; (c) the two emotion regulation strategies and perceived social support partially mediated the link between psychological maltreatment and depression symptoms in a sequential pattern. CONCLUSION: Psychological maltreatment was positively associated with depression symptoms in adolescents. Emotion regulation and perceived social support both significantly mediated the relationship between psychological maltreatment and depression symptoms.
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Depressão , Regulação Emocional , Masculino , Feminino , Adolescente , Humanos , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Apoio Social , Estudantes/psicologia , China/epidemiologiaRESUMO
Composting is an efficient way of disposing agricultural solid wastes as well as passivating heavy metals (HMs). Herein, equivalent (3%) biochar (BC) or lime (LM) were applied in rice straw and swine manure composting, with no additives applied as control group (CK). The results indicated that both the additives increased NO3--N content, organic matter degradation, humus formation, and HM immobilization in composting, and the overall improvement of lime was more significant. In addition, the additives optimized the bacterial community of compost, especially for thermophilic and mature phase. Lime stimulated the growth of Bacillus, Peptostreptococcus, Clostridium, Turicibacter, Clostridiaceae and Pseudomonas, which functioned well in HM passivation via biosorption, bioleaching, or promoting HM-humus formation by secreting hydrolases. Lime (3%) as additive is recommended in swine manure composting to promote composting maturity and reduce HM risk. The study present theoretical guidance in improving composting products quality for civil and industrial composting.