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Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.
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Ansiedade/metabolismo , Comportamento Animal/fisiologia , Encefalopatias Metabólicas/metabolismo , Estresse Psicológico/metabolismo , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Animais , Ansiedade/genética , Ansiedade/imunologia , Ansiedade/fisiopatologia , Encefalopatias Metabólicas/genética , Encefalopatias Metabólicas/fisiopatologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Dinâmica Mitocondrial/genética , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Análise de Célula Única , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Transcriptoma/genética , Xantina/metabolismoRESUMO
Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.
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Antioxidantes/farmacologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Selênio/farmacologia , Selenoproteína W/metabolismo , Células Th1/citologia , Diferenciação Celular/imunologia , Polaridade Celular , Colo/imunologia , Colo/patologia , Glicina Hidroximetiltransferase/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Ribonucleoproteínas/metabolismo , Células Th1/imunologia , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.
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Interferon Tipo I , Viroses , Camundongos , Animais , Viroses/genética , Antivirais , Imunidade Inata , Ubiquitinação , Fator Regulador 7 de Interferon/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de ApoptoseRESUMO
Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a high-resolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the D1 subunit is flexible, some waters near the active site are partially occupied, and differences in the PsbV subunit block the Large (O1) water channel. These features strongly influence the structural picture of PSII, especially as it pertains to the mechanism of water oxidation.
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Microscopia Crioeletrônica/métodos , Complexo de Proteína do Fotossistema II/ultraestrutura , Synechocystis/química , Proteínas de Bactérias/metabolismo , Conformação ProteicaRESUMO
Recent phylogenetic profiling of pneumococcal serotype 3 (Pn3) isolates revealed a dynamic interplay among major lineages with the emergence and global spread of a variant termed clade II. The cause of Pn3 clade II dissemination along with epidemiological and clinical ramifications are currently unknown. Here, we sought to explore biological characteristics of dominant Pn3 clades in a mouse model of pneumococcal invasive disease and carriage. Carriage and virulence potential were strain dependent with marked differences among clades. We found that clinical isolates from Pn3 clade II are less virulent and less invasive in mice compared to clade I isolates. We also observed that clade II isolates are carried for longer and at higher bacterial densities in mice compared to clade I isolates. Taken together, our data suggest that the epidemiological success of Pn3 clade II could be related to alterations in the pathogen's ability to cause invasive disease and to establish a robust carriage episode.
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Portador Sadio , Infecções Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Animais , Streptococcus pneumoniae/patogenicidade , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Infecções Pneumocócicas/microbiologia , Virulência , Camundongos , Portador Sadio/microbiologia , Modelos Animais de Doenças , Feminino , Humanos , FilogeniaRESUMO
The advancement of molecular electronics endeavors to build miniaturized electronic devices using molecules as the key building blocks by harnessing their internal structures and electronic orbitals. To date, linear planar conjugated or cross-conjugated molecules have been extensively employed in the fabrication of single-molecule devices, benefiting from their good conductivity and compatibility with electrode architectures. However, the development of multifunctional single-molecule devices, particularly those with unique charge transport properties, necessitates a more rigorous selection of molecular materials. Among different assortments of molecules suited for the construction of molecular circuits, Spiro-conjugated structures, specifically spirobifluorene derivatives, stand out as promising candidates due to their distinctive electronic properties. In this work, we focus on the charge transport characteristics of Spiro-conjugated molecules sandwiched between graphene nanogaps. Experiments reveal significant Coulomb blockade and distinct negative differential conductance effects. Beyond two-terminal device measurements, solid-state gate electrodes are utilized to create single-molecule transistors, successfully modulating the molecular energy levels to achieve an on/off ratio exceeding 1000. This endeavor not only offers valuable insights into the design and fabrication of future practical molecular devices, blessed with enhanced performance and functionality, but also presents a new paradigm for the investigation of fundamental physical phenomena.
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Doping polycyclic aromatic hydrocarbons with heteroatoms enables manipulation of their electronic structures. Herein, the structures and properties of phosphorus (P) doped heterosumanenes (HSEs) are regulated by varying the valence states of P-dopant. The phosphine sulfide (PV) and chalcogens (S, Se, Te) co-doped HSEs (1-3) are reduced to trivalent phosphorus (PIII) doped analogues 4-6. Then, the PIII-dopants on 4-6 are converted to phosphonium salts (R4P+), giving 7-9. The valence states of P-dopant show great influence on molecular geometries and electronic structures. Taking P and S co-doped HSEs as example, bowl-depths increase in the order of 1 (PV)<7 (R4P+)<4 (PIII), and the HOMO energy levels and HOMO-LUMO gaps increase to be 7<1<4. Consistent with the theoretical calculation, the first oxidation potentials decrease and the absorption/emission bands show blue shift from 7 to 1 to 4. The transformation of PV to PIII leads to large variations on the coordination with Ag+, owing to the alteration of coordination site from P=S to PIII. The phosphonium salts show ring-opening of phosphole rings under electrochemical reduction. It is found that chalcogen atoms play pivotal roles on coordination patterns of coordination complexes and the conversion rates of ring-opening reactions.
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BACKGROUND: The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. METHODS: In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRß, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. RESULTS: Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. CONCLUSION: Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.
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Aneurisma Intracraniano , Miócitos de Músculo Liso , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Animais , Feminino , Humanos , Masculino , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/metabolismo , Mutação , Miócitos de Músculo Liso/metabolismo , Fenótipo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Peixe-Zebra/genéticaRESUMO
BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.
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Falência Renal Crônica , Diálise Peritoneal , Peritonite , Humanos , Feminino , Estudos Prospectivos , Diálise Peritoneal/efeitos adversos , Diálise Renal/efeitos adversos , Hemoglobinas , Falência Renal Crônica/epidemiologia , Peritonite/etiologia , Estudos RetrospectivosRESUMO
Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses to benefit virus replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26), a TRIM family protein, has been shown to be involved in a broad range of biological processes involved in innate immunity, especially in regulating viral infection. Herein, we found that the expression of TRIM26 was significantly induced after PRV infection. Surprisingly, the overexpression of TRIM26 promoted PRV production, while the depletion of this protein inhibited virus replication, suggesting that TRIM26 could positively regulate PRV infection. Further analysis revealed that TRIM26 negatively regulates the innate immune response by targeting the RIG-I-triggered type I interferon signalling pathway. TRIM26 was physically associated with MAVS independent of viral infection and reduced MAVS expression. Mechanistically, we found that NDP52 interacted with both TRIM26 and MAVS and that TRIM26-induced MAVS degradation was almost entirely blocked in NDP52-knockdown cells, demonstrating that TRIM26 degrades MAVS through NDP52-mediated selective autophagy. Our results reveal a novel mechanism by which PRV escapes host antiviral innate immunity and provide insights into the crosstalk among virus infection, autophagy, and the innate immune response.
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Proteínas Adaptadoras de Transdução de Sinal , Autofagia , Imunidade Inata , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Suínos , Replicação Viral , Humanos , Transdução de Sinais , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: There are few studies on the safety of sub-maximal exercise testing of aerobic exercise in apparently healthy Chinese populations. The purpose of this study was to explore the frequency of exercise electrocardiography (ECG) abnormalities and the corresponding exercise intensities, as well as the associated influencing factors, during a symptom-limited stepwise incremental cardiopulmonary exercise test (CPET) in an apparently healthy Chinese population. METHODS: A cross-sectional study was done in four communities, one urban and one rural in the North (Beijing) and in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, respectively. Total of 1642 participants was recruited, 918 were eligible and completed demographic indicators, routine blood indicators, physical activity status, symptom-limited CPET and exercise ECG were included in the analysis. RESULTS: Of the exercise ECG outcomes, 10 (1.1%) were positive and occurred at exercise intensities ≥ 62.50% heart rate reserve (HRR); 44 (4.8%) were equivocal and 864 (94.1%) were normal. Individuals with Cardiovascular Disease Risk Factor (CVDRF) = 3-4 were 2.6 times more likely to have a equivocal and abnormal exercise ECG than those with CVDRF = 0-2. Exercise ECGs of individuals with CVDRF = 5-7 were 5.4 times more likely to be positive and abnormal than exercise ECGs of individuals with CVDRF = 0-2. CONCLUSIONS: The exercise intensity of 62.5% HRR can be used as a safe upper limit for safe participation in exercise in apparently healthy Chinese population; the greater the number of CVDRFs, the greater the likelihood of cardiovascular risk during exercise.
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Doenças Cardiovasculares , Eletrocardiografia , Teste de Esforço , Exercício Físico , Fatores de Risco de Doenças Cardíacas , Humanos , Estudos Transversais , Masculino , Feminino , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Doenças Cardiovasculares/epidemiologia , População do Leste AsiáticoRESUMO
Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation (LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application. Three groups of rats were exposed to either intermittent, continuous, or sham tFUS. We analyzed the neuromodulatory effects on motor cortical excitability by examining changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We also investigated the effects of different stimulation patterns on excitatory and inhibitory neural biomarkers, examining c-Fos and glutamic acid decarboxylase (GAD-65) expression using immunohistochemistry staining. Additionally, we evaluated the safety of tFUS by analyzing glial fibrillary acidic protein (GFAP) expression. The current results indicated that intermittent tFUS produced a facilitation effect on motor excitability, while continuous tFUS significantly inhibited motor excitability. Furthermore, neither tFUS approach caused injury to the stimulation sites in rats. Immunohistochemistry staining revealed increased c-Fos and decreased GAD-65 expression following intermittent tFUS. Conversely, continuous tFUS downregulated c-Fos and upregulated GAD-65 expression. In conclusion, our findings demonstrate that both intermittent and continuous tFUS effectively modulate cortical excitability. The neuromodulatory effects may result from the activation or deactivation of cortical neurons following tFUS intervention. These effects are considered safe and well-tolerated, highlighting the potential for using different patterns of tFUS in future clinical neuromodulatory applications.
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Potencial Evocado Motor , Córtex Motor , Plasticidade Neuronal , Estimulação Magnética Transcraniana , Animais , Córtex Motor/fisiologia , Ratos , Masculino , Potencial Evocado Motor/fisiologia , Estimulação Magnética Transcraniana/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ondas Ultrassônicas , Ratos Sprague-Dawley , Proteína Glial Fibrilar Ácida/metabolismo , Glutamato Descarboxilase/metabolismoRESUMO
There are three main classes of actin nucleation factors: Arp2/3 complexes, Spire and Formin. Spire assembles microfilaments by nucleating stable longitudinal tetramers and binding actin to the growing end of the microfilament. As early as 1999, Wellington et al. identified Spire as an actin nucleating agent, however, over the years, most studies have focused on Arp2/3 and Formin proteins; there has been relatively less research on Spire as a member of the actin nucleating factors. Recent studies have shown that Spire is involved in the vesicular transport through the synthesis of actin and plays an important role in neural development. In this paper, we reviewed the structure, expression and function of Spire, and its association with disease in order to identify meaningful potential directions for studies on Spire.
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Actinas , Proteínas dos Microfilamentos , Proteínas Nucleares , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/fisiologia , Humanos , Animais , Actinas/metabolismo , Actinas/fisiologia , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/fisiologiaRESUMO
Alzheimer's disease (AD) is a common neurodegenerative disease with the main manifestations of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an important role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory storage,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major pathological factor in the occurrence and development of AD.This article reviews the role and research progress in intracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloid ß,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling pathways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflammation.
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Doença de Alzheimer , Cálcio , Homeostase , Doença de Alzheimer/metabolismo , Humanos , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Sinalização do Cálcio/fisiologia , Mitocôndrias/metabolismo , Proteínas tau/metabolismo , Autofagia/fisiologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Neurônios/metabolismo , FosforilaçãoRESUMO
OBJECTIVE: To determine the percentile reference values and reference curves of total body fat percentage in children and adolescents by sex and age, and to evaluate the reliability of different anthropometric indicators in screening for obesity in children and adolescents in order to explore the validity and practicality of a large-scale screening tool for childhood obesity and its desirable thresholds. METHODS: A total of 5983 children and adolescents aged 6-18 years from six primary and secondary schools were selected by stratified randomised cluster sampling in Hangzhou City in 2023, and their weight, height, waist and hip circumferences were measured, and the children's total body fat content was measured using the bioelectrical resistance-antibody composition analyser. A generalised additive model(GAMLSS) was used to construct a percentile reference curve for children's body fat percentage, and the performance of each anthropometric measure in correctly classifying children and adolescents as obese was assessed using receiver operating characteristic(ROC) curves. RESULTS: Over the period 6-18 years, body fat percentage in girls tended to increase with age from year to year, whereas in boys it tended to increase and then decrease. Fat mass index was the main factor contributing to the difference in BMI at the same age and sex(the optimal cutoff values were 26.82 and 24.52, with AUC values of 0.988 and 0.992, respectively), and the contribution of fat mass index was greater in those with a higher BMI. BMI, which had the largest area under the curve for both boys and girls, was the best indicator for assessing obesity in children and adolescents; the waist-to-height ratio(WHtR), with small variability and equally large area under curve values(0.980 for boys and 0.970 for girls), could simultaneously meet the requirements of accuracy and practicality for obesity assessment in mass screening of children and adolescents. CONCLUSION: This study establish the percentile reference value and reference curve of body fat percentage of children and adolescents aged 6-18 years in Hangzhou based on bioelectrical impedance method, and found that WHtR is a simple, effective and practical screening tool for childhood obesity with low variability, which can provide a reference basis for evaluating growth and development and identifying obesity in children aged 6-18 years in this region.
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Índice de Massa Corporal , Humanos , Adolescente , Criança , Masculino , Feminino , China , Valores de Referência , Obesidade Infantil/diagnóstico , Programas de Rastreamento/métodos , Antropometria/métodos , Peso Corporal , Tecido AdiposoRESUMO
Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.
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Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Animais , Ratos , Masculino , Humanos , Fígado/efeitos dos fármacos , Fígado/química , Fígado/metabolismo , Espectrometria de Massas/métodos , Rim/efeitos dos fármacos , Rim/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus/tratamento farmacológicoRESUMO
Radical cation salts of π-conjugated polycycles are rich in physical properties. Herein, two kinds of hetera-buckybowls, ethoxy-substituted trithiasumanene (3SEt) and triselenasumanene (3SeEt), are synthesized as electron donors. Galvanostatic oxidation of them affords radical cation salts (3SEt)5 (TTFMPB)3 , (3SeEt)5 (TTFMPB)3 , (3SEt)4 PMA, and (3SeEt)4 PMA, where PMA is Keggin-type phosphomolybdate and TTFMPB is tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate. In these salts, 3SEt/3SeEt are partially charged and show distinct conformation change with the site charge and counter anions. In TTFMPB salts, (TTFMPB)- forms hexagonal channels that accommodate the packing columns of 3SEt/3SeEt. In particular, (3SEt)5 (TTFMPB)3 adopts the R3c space group and is a polar crystal with the columns of 3SEt all in the up-bowl direction. The PMA salts of 3SEt/3SeEt are polar crystals (C2 space group) with 3SEt/3SeEt being planar and forming columnar stacks. (3SeEt)4 PMA shows a structural modulation below 200â K, namely, negative thermal expansion (NTE) of the unit cell volume and enlargement of the intermolecular distances between neighboring 3SeEt molecules. The four salts are semiconductors with an activation energy of 0.18-0.38â eV. The conductivity of (3SeEt)4 PMA shows a reversible transition upon cooling and heating, in accordance to the NTE structural modulation. This work paves the way toward conducting materials based on hetera-buckybowls.
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Integration of spirocycles with buckybowls is a promising strategy to construct three-dimensional (3D) curved π-systems and to endow distinctive physicochemical features arising from buckybowls. Herein, a series of carbon-bridged spiro-type heterosumanenes (spiro-HSEs) were synthesized by combining 9,9'-spirobifluorene and dichalcogenasumanenes (DCSs). It is found that spiro-conjugation plays an important role in the geometric and electronic structures of spiro-HSEs. The bowl depth of DCSs moiety becomes larger in the spiro-HSEs. Owing to the Jahn-Teller (J-T) effect, two DCSs segments of spiro-HSEs have different bowl depths accompanied with the unequal distribution of charge in radical cation state. Taking advantage of the typical reactions of DCSs, selective transformations of spiro-HSEs have been adopted in accordance to the nature of chalcogen atoms (S, Se, Te) to bestow the value-added functionalities. The emissive property is enhanced by converting the thiophene rings of S-doped spiro-HSE into thiophene S,S-dioxides. A chiroptical polycycle could be produced by ring-opening of the edge benzene of Se-doped spiro-HSE. The covalent adduct of Te-doped spiro-HSE with Br2 forms non-centrosymmetric halogen-bonded networks, resulting in the high performance second-order nonlinear optics (NLO).
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Solid additives have drawn great attention due to their numerous appealing benefits in enhancing the power conversion efficiencies (PCEs) of organic solar cells (OSCs). To date, various strategies have been reported for the selection or design of non-volatile solid additives. However, the lack of a general design/evaluation principles for developing non-volatile solid additives often results in individual solid additives offering only one or two efficiency-boosting attributes. In this work, we propose an integrated omnidirectional strategy for designing non-volatile solid additives. By validating the method on the 4,5,9,10-pyrene diimide (PyDI) system, a novel non-volatile solid additive named PyMC5 was designed. PyMC5 is capable of enhancing device performance by establishing synergistic dual charge transfer channels, forming appropriate interactions with active layer materials, reducing non-radiative voltage loss and optimizing film morphology. Notably, the binary device (PM6:L8-BO) treated by PyMC5 achieved a PCE over 19.5%, ranking among the highest reported to date. In addition, the integration of PyMC5 mitigated the degradation process of the devices under photo- and thermal-stress conditions. This work demonstrates an efficient integrated omnidirectional approach for designing non-volatile solid additives, offering a promising avenue for further advancements in OSC development.
RESUMO
Generating circularly polarized luminescence (CPL) with simultaneous high photoluminescence quantum yield (PLQY) and dissymmetry factor (glum) is difficult due to usually unmatched electric transition dipole moment (µ) and magnetic transition dipole moment (m) of materials. Herein we tackle this issue by playing a "cascade cationic insertion" trick to achieve strong CPL (with PLQY of ~100 %) in lead-free metal halides with high glum values reaching -2.3×10-2 without using any chiral inducers. Achiral solvents of hydrochloric acid (HCl) and N, N-dimethylformamide (DMF) infiltrate the crystal lattice via asymmetric hydrogen bonding, distorting the perovskite structure to induce the "intrinsic" chirality. Surprisingly, additional insertion of Cs+ cation to substitute partial (CH3)2NH2 + transforms the chiral space group to achiral but the crystal maintains chiroptical activity. Further doping of Sb3+ stimulates strong photoluminescence as a result of self-trapped excitons (STEs) formation without disturbing the crystal framework. The chiral perovskites of indium-antimony chlorides embedded on LEDs chips demonstrate promising potential as CPL emitters. Our work presents rare cases of chiroptical activity of highly luminescent perovskites from only achiral building blocks via spontaneous resolution as a result of symmetry breaking.