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Research on individuals with a younger onset age of schizophrenia is important for identifying neurobiological processes derived from the interaction of genes and the environment that lead to the manifestation of schizophrenia. Schizophrenia has long been recognized as a disorder of dysconnectivity, but it is largely unknown how brain connectivity changes are associated with psychotic symptoms. Twenty-one adolescent-onset schizophrenia (AOS) patients and 21 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) was used to investigate local brain connectivity alterations in AOS. Regions with significant ReHo changes in patients were selected as "seeds" for further functional connectivity (FC) analysis and Granger causality analysis (GCA), and associations of the obtained functional brain measures with psychotic symptoms in patients with AOS were examined. Compared with HCs, AOS patients showed significantly increased ReHo in the right middle temporal gyrus (MTG), which was positively correlated with PANSS-positive scores, PSYRATS-delusion scores and auditory hallucination scores. With the MTG as the seed, lower connectivity with the bilateral postcentral gyrus (PCG) and higher connectivity with the right precuneus were observed in patients. The reduced FC between the right MTG and bilateral PCG was significantly and positively correlated with hallucination scores. GCA indicated decreased Granger causality from the right MTG to the left middle frontal gyrus (MFG) and from the right MFG to the right MTG in AOS patients, but such effects did not significantly associate with psychotic symptoms. Abnormalities in the connectivity within the MTG and its connectivity with other networks were identified and were significantly correlated with hallucination and delusion ratings. This region may be a key neural substrate of psychotic symptoms in AOS.
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The amygdala, known for its functional heterogeneity, plays a critical role in the neural mechanism of adolescent major depressive disorder (aMDD). However, changes in its subregional functional networks in relation to stressful factors remain unclear. We recruited 78 comorbidity-free, medication-naive aMDD patients and 40 matched healthy controls (HC) to explore changes in resting-state functional connectivity (FC) across four amygdala subregions: the centromedial nucleus (CM), the basolateral nucleus (LB), the superficial nucleus (SF), and the amygdalostriatal transition area (Astr). Then, we performed partial correlation analysis to investigate the relationship between amygdala subregional FC and stressful factors as measured by the Chinese Version of Family Environment Scale (FES-CV) and the Adolescent Self-Rated Life Events Scale (ASLEC). Compared to HC, aMDD patients demonstrated significantly decreased functional connectivity between the left CM and left precentral gyrus, as well as between left SF and left precentral gyrus, and between left LB and posterior cingulate gyrus (PCC)/precuneus. In aMDD group, left CM-precentral gyrus FC exhibited negative correlation with interpersonal relationship and punishment, and positive correlation with family cohesion and expressiveness. This study reveals distinct patterns of abnormal functional connectivity among amygdala subregions in aMDD. Our findings suggest that the CM network, in particular, may be involved in stress-related factors in aMDD, which provide a potential target for the prevention and treatment of adolescent depression.
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BACKGROUND: Adolescent depression shows high clinical heterogeneity. Brain functional networks serve as a powerful tool for investigating neural mechanisms underlying depression profiles. A key challenge is to characterize how variation in brain functional organization links to behavioral features and psychosocial environmental influences. METHODS: We recruited 80 adolescents with major depressive disorder (MDD) and 42 healthy controls (HCs). First, we estimated the differences in functional connectivity of resting-state networks (RSN) between the two groups. Then, we used sparse canonical correlation analysis to characterize patterns of associations between RSN connectivity and symptoms, cognition, and psychosocial environmental factors in MDD adolescents. Clustering analysis was applied to stratify patients into homogenous subtypes according to these brain-behavior-environment associations. RESULTS: MDD adolescents showed significantly hyperconnectivity between the ventral attention and cingulo-opercular networks compared with HCs. We identified one reliable pattern of covariation between RSN connectivity and clinical/environmental features in MDD adolescents. In this pattern, psychosocial factors, especially the interpersonal and family relationships, were major contributors to variation in connectivity of salience, cingulo-opercular, ventral attention, subcortical and somatosensory-motor networks. Based on this association, we categorized patients into two subgroups which showed different environment and symptoms characteristics, and distinct connectivity alterations. These differences were covered up when the patients were taken as a whole group. CONCLUSION: This study identified the environmental exposures associated with specific functional networks in MDD youths. Our findings emphasize the importance of the psychosocial context in assessing brain function alterations in adolescent depression and have the potential to promote targeted treatment and precise prevention.
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Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Adolescente , Transtorno Depressivo Maior/fisiopatologia , Feminino , Masculino , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Meio Social , Conectoma , Comportamento do Adolescente/fisiologiaRESUMO
The rapid advancement of human stem cell research and its expansion into emerging areas has resulted in an escalation of ethical challenges associated with these studies. As a result, there has been a corresponding increase in both the volume and complexity of institutional ethics reviews, coupled with higher expectations for the quality of the review process. In response to these challenges, this standard provides a comprehensive outline of the fundamental principles, content, types, and procedures of ethics review, specifically focusing on non-clinical human stem cell research. Its purpose is to provide clear operational and procedural guidelines, as well as recommendations, for the ethics review of such studies. The document was originally published by the Chinese Society for Cell Biology on August 30, 2022. It is our hope that the publication of these guidelines will facilitate the integration of ethical considerations and evaluations in a structured manner throughout the entire process of stem cell research, ultimately fostering a healthy and orderly development of the field.
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Pesquisa com Células-Tronco , HumanosRESUMO
Iron is an extraordinary promoter to impose nickel/cobalt (hydr)oxides as the most active oxygen evolution reaction catalysts, whereas the synergistic effect is actively debated. Here, we unveil that active oxygen species mediate a strong electrochemical interaction between iron oxides (FeOxHy) and the supporting metal oxyhydroxides. Our survey on the electrochemical behavior of nine supporting metal oxyhydroxides (M(O)OH) uncovers that FeOxHy synergistically promotes substrates that can produce active oxygen species exclusively. Tafel slopes correlate with the presence and kind of oxygen species. Moreover, the oxygen evolution reaction onset potentials of FeOxHy@M(O)OH coincide with the emerging potentials of active oxygen species, whereas large potential gaps are present for intact M(O)OH. Chemical probe experiments suggest that active oxygen species could act as proton acceptors and/or mediators for proton transfer and/or diffusion in cooperative catalysis. This discovery offers a new insight to understand the synergistic catalysis of Fe-based oxygen evolution reaction electrocatalysts.
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As China's stem cell industry continues to develop, increasing disputes concerning stem cell-based interventions have been brought before the courts. Nonetheless, there is variability in the courts' understanding and attitude toward the regulatory attributes of these interventions, which to some extent has multifaceted impacts on the stem cell field.
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Pesquisa com Células-Tronco , China , Pesquisa com Células-Tronco/legislação & jurisprudênciaRESUMO
Background: Insomnia is a commonly seen symptom in adolescents with major depressive disorder (MDD). The suprachiasmatic nucleus (SCN), which is the circadian rhythm regulation center, plays a crucial role in the regulation of sleep-wake circulation. Nevertheless, how SCN function contributes to the exact neural mechanisms underlying the associations between insomnia and depressive symptoms has not been explored in adolescents. In the current study, we aimed to explore the relationship between SCN functional connectivity (FC) and insomnia symptoms in adolescents with MDD using a seed-based FC method. Methods: In the current study, we recruited sixty-eight first-episode drug-naïve adolescents with MDD and classified them into high insomnia (MDD-HI) and low insomnia (MDD-LI) groups according to the sleep disturbance subscale of the Hamilton Depression Rating Scale (HAMD-S). Forty-three age/gender-matched healthy controls (HCs) were also recruited. SCN FC maps were generally for all subjects and compared among three groups using one-way ANOVA with age, gender and adjusted HAMD score as covariates. We used partial correlations to explore associations between altered FC and clinical symptoms, including sleep quality scores. Results: Adolescents with MDD showed worse sleep quality, which positively correlated with the severity of depression. Compared to MDD-LI and HCs, MDD-HI adolescents demonstrated significantly decreased FC between the right SCN and bilateral precuneus, and there was no significant difference between the MDD-LI and HC groups. The HAMD-S scores were negatively correlated with bilateral SCN-precuneus connectivity, and the retardation factor score of HAMD was negatively correlated with right SCN-precuneus connectivity. Conclusion: The altered FC between the SCN and precuneus may underline the neural mechanism of sleep-related symptoms in depressive adolescents and provide potential targets for personalized treatment strategies.
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Cost-effective electrochemical water splitting technology hinges on the development of efficient and durable catalysts for oxygen evolution reaction (OER). Spinel oxides (formula: AxB3-xO4) are structurally stable for real applications. Much effort has been devoted to improving the catalytic activity. Here, we report a eutectic dealloying strategy to activate the porous spinel NiFe2O4 nanowires with up to four metal cation substitutions. As-obtained spinel NiFeXO4 (X = Fe, Ni, Al, Mo, Co, Cr) delivers a benchmark current density of 10 mA·cm-2 at an overpotential of only 195 mV, outperforming most spinel phase OER electrocatalysts and comparable to the state-of-the-art NiFe hydroxides. It is stable for over 115 h of electrolysis. Aberration-corrected transmission electron microscopy, high-resolution electron energy loss spectroscopy, and atomic-scale strain mappings reveal that the multivalent cation substitutions result in substantial lattice distortion and significant electronic coupling of metal 3d and O 2p orbitals for increased covalency. Further theoretical calculations suggest that the NiFeXO4 are stabilized by the high configurational entropy, and their synergy favors the absorption of H2O molecules and lowers the adsorption energy barrier of the OOH* intermediate. The improved intrinsic activity together with the highly nanoporous structures contribute to the appealing apparent catalytic performances. The work demonstrates an effective approach for the synthesis of stable multicomponent spinel oxides and highlights the effectiveness of the multication substitution strategy for producing highly durable and active spinel catalysts, which meet multiplexed structure and superior property requirements in practical applications.
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Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.
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The aim of the present study was to compare the diagnostic performance of the main parameters derived from diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) regarding the detection and grading of hepatocellular carcinoma (HCC). A total of 78 patients diagnosed with HCC by biopsy were prospectively enrolled in the present study, and underwent routine magnetic resonance imaging (MRI), DWI, IVIM, DKI and contrast-enhanced MRI prior to surgery. Measurements, including mean diffusivity (MD), mean diffusional kurtosis (MK), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC), were compared with grading HCC using one-way ANOVA followed by the Student-Neuman-Keuls-q post-hoc test. Spearman's correlation coefficient was used to analyze the correlation between each parameter and pathological grade, while the diagnostic efficiency was evaluated using a receiver operating characteristic (ROC) curve. The 78 patients enrolled in the present study were grouped into highly (n=22), moderately (n=41) or poorly (n=15) differentiated HCC groups according to the criteria of Pathology and Genetics Tumors of the Digestive System. MK values differed significantly between different grades and decreased gradually with the degree of tumor differentiation. The MD, D and ADC values in the highly differentiated HCC group were significantly higher than those in the moderately or poorly differentiated HCC groups (all P<0.001), whereas no significant differences were observed in D* or f (P=0.502 and P=0.853, respectively). A significant correlation was observed between MK, MD, D and ADC, and HCC grades (r=0.705, r=0.570, r=0.423 and r=0.687, respectively). The comparison of the ROC curves of MK, MD, D, ADC, D* and f values for predicting highly differentiated HCC suggested that MK and D were the best indicators for predicting highly differentiated HCC, as the area under the ROC curve (AUC) of MK and D was significantly higher than that of ADC (Z=2.247 and 2.428, P=0.025 and 0.016, respectively), whereas non-statistically significant differences were observed in the AUC values between MK and D (Z=0.072; P=0.942). The DKI-derived MK and IVIM-derived D values had a similar diagnostic performance and were superior to ADC in discriminating the histological grade of HCC. In addition, the combination of MK and D values exhibited an improved diagnostic performance.
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Pt single-atom materials possess an ideal atom economy but suffer from limited intrinsic activity and side reaction of producing H2O2 in catalyzing the oxygen reduction reaction (ORR); platinum alloys have higher intrinsic activity but weak stability. Here, we demonstrate that anchoring platinum alloys on single-atom Pt-decorated carbon (Pt-SAC) surmounts their inherent deficiencies, thereby enabling a complete four-electron ORR pathway catalysis with high efficiency and durability. Pt3Co@Pt-SAC demonstrates an exceptional mass and specific activities 1 order of magnitude higher than those of commercial Pt/C. They are durable throughout 50000 cycles, showing only a 10 mV decay in half-wave potential. An in situ Raman analysis and theoretical calculations reveal that Pt3Co core nanocrystals modulate electron structures of the adjacent Pt single atoms to facilitate the intermediate absorption for fast kinetics. The superior durability is attributed to the shielding effect of the Pt-SAC coating, which significantly mitigates the dissolution of Pt3Co cores. The hybridizing strategy might promote the development of highly active and durable ORR catalysts.
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Electrocatalysts for the oxygen reduction reaction (ORR) play a central role in fuel cells and zinc-air batteries. Bimetal single atoms and nanoparticle hybrids are emerging ORR electrocatalysts, superior to the most exploited unary metal single-atom catalysts (SACs). Here, we report bimetal SAC-based nanofiber networks of Co3Fe7@Co/Fe-SAC for efficient ORR electrocatalysis and zinc-air batteries. A facile and easy-to-scale-up process is developed, and the versatility is validated in three hybrids. Strong electronic interaction is revealed between bimetal single atoms and alloy nanoparticles, leading to improved catalytic performances for ORR. Specifically, the Co3Fe7@Co/Fe-SAC hybrids exhibit a half-wave potential of 0.841 V in a basic electrolyte, comparable to the Pt/C electrocatalyst. Assembled in a zinc-air battery, a Co3Fe7@Co/Fe-SAC hybrid-based cell demonstrates a power density 1.8 times higher than the benchmark Pt/C-IrO2-based one, and it is stable for 150 cycles galvanostatic charge/discharge. The superior device performance is attributed to the appealing intrinsic activity, the carbon shielding effect for anti-leaching, and the hierarchical porous networks for large accessibility of active sites and favorable mass transport. Theoretical calculations suggest that alloy nanoparticles significantly improved the intrinsic catalytic activity of Fe single-atom sites at the expense of slightly lowering the activity of Co single-atom sites. This work presents a versatile process for the mass production of efficient composite electrocatalysts and highlights the power of bimetal single-atom-based hybrids and hierarchically porous structures for ORR device performances.
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Schizophrenia is a disorder resulting from aberrant brain networks and circuits. In the current study, we aimed to investigate specific network alterations in adolescent-onset schizophrenia (AOS) and to help identify the neurophysiological mechanisms of this adolescent disorder. We recruited forty-one subjects, including 20 AOS patients and 21 matched healthy controls (HCs), and we acquired brain images to examine the specific changes in functional network patterns using degree centrality (DC), which quantifies the strength of the local functional connectivity hubs. Whole-brain correlation analysis was applied to assess the relationships between clinical characteristics and DC measurements. The AOS group exhibited increased DC in the right inferior frontal lobe, right fusiform gyrus and right thalamus (p < 0.05, AlphaSim correction). Whole-brain correlation analysis found that the DC value in the right parahippocampus was positively correlated with PANSS-positive symptom scores (r = 0.80); DC in the right superior parietal lobe (SPL) was positively correlated with PANSS-negative symptom scores (r = 0.79); DC in the left precuneus was positively correlated with self-certainty (SC) scores (r = 0.70); and DC in the left medial frontal gyrus (MFG) was negatively correlated with self-reflectiveness (SR) scores (r = 0.69). We conclude that frontoparietal network and cortico-thalamo-cortical pathway disruptions could play key roles in the neurophysiological mechanisms underlying AOS. In AOS patients, the right parahippocampus and SPL are important structures associated with positive and negative symptoms, respectively, and the left precuneus and MFG contribute to deficits in cognitive insights.
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Preparações Farmacêuticas , Esquizofrenia , Adolescente , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico por imagemRESUMO
BACKGROUND: Family environment and life events have long been suggested to be associated with adolescent depression. The hippocampus plays a crucial role in the neural mechanism of major depressive disorder (MDD) through memory during stressful events. However, few studies have explored the exact neural mechanisms underlying these associations. Thus, the current study aimed to explore alterations in hippocampal functional connectivity (FC) in adolescent MDD based on resting-state functional magnetic resonance imaging and further investigate the relationship between hippocampal FC, environmental factors, and clinical symptom severity. METHODS: Hippocampal FC was calculated using the seed-based approach with the bilateral hippocampus as the seed for 111 adolescents with and without MDD; comparisons were made between participants with MDD and controls. We applied the Chinese version of the Family Environment Scale (FES-CV) and Adolescents Self-Rating Life Events Checklist (ASLEC) to evaluate family environment and life stress. Their relationship with hippocampal FC alterations was also investigated. RESULTS: We found that compared to controls, adolescents with MDD showed decreased connectivity between the left hippocampus and bilateral orbital frontal cortex (OFC) and right inferior temporal gyrus. In addition, the hippocampal-OFC connectivity was negatively correlated with conflict scores of the FES-CV in the MDD group and mediated the association between family conflict and depressive and anxiety symptoms. CONCLUSION: Our findings are novel in the field and demonstrate how family conflict contributes to MDD symptomatology through hippocampal-OFC connectivity; these findings may provide potential targets for personalized treatment strategies.