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High Mountain Asia (HMA) has experienced a spatial imbalance in water resources in recent decades, partly because of a dipolar pattern of precipitation changes known as South Drying-North Wetting1. These changes can be influenced by both human activities and internal climate variability2,3. Although climate projections indicate a future widespread wetting trend over HMA1,4, the timing and mechanism of the transition from a dipolar to a monopolar pattern remain unknown. Here we demonstrate that the observed dipolar precipitation change in HMA during summer is primarily driven by westerly- and monsoon-associated precipitation patterns. The weakening of the Asian westerly jet, caused by the uneven emission of anthropogenic aerosols, favoured a dipolar precipitation trend from 1951 to 2020. Moreover, the phase transition of the Interdecadal Pacific Oscillation induces an out-of-phase precipitation change between the core region of the South Asian monsoon and southeastern HMA. Under medium- or high-emission scenarios, corresponding to a global warming of 0.6-1.1 °C compared with the present, the dipolar pattern is projected to shift to a monopolar wetting trend in the 2040s. This shift in precipitation patterns is mainly attributed to the intensified jet stream resulting from reduced emissions of anthropogenic aerosols. These findings underscore the importance of considering the impact of aerosol emission reduction in future social planning by policymakers.
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Ar , Altitude , Clima , Chuva , Aerossóis/análise , Ásia , Aquecimento Global , Estações do Ano , Ar/análise , Ar/normas , Atividades Humanas , Oceano PacíficoRESUMO
Phosphoglycerate mutase 1 (PGAM1) is a key node enzyme that diverts the metabolic reactions from glycolysis into its shunts to support macromolecule biosynthesis for rapid and sustainable cell proliferation. It is prevalent that PGAM1 activity is upregulated in various tumors; however, the underlying mechanism remains unclear. Here, we unveil that pyruvate kinase M2 (PKM2) moonlights as a histidine kinase in a phosphoenolpyruvate (PEP)-dependent manner to catalyze PGAM1 H11 phosphorylation, that is essential for PGAM1 activity. Moreover, monomeric and dimeric but not tetrameric PKM2 are efficient to phosphorylate and activate PGAM1. In response to epidermal growth factor signaling, Src-catalyzed PGAM1 Y119 phosphorylation is a prerequisite for PKM2 binding and the subsequent PGAM1 H11 phosphorylation, which constitutes a discrepancy between tumor and normal cells. A PGAM1-derived pY119-containing cell-permeable peptide or Y119 mutation disrupts the interaction of PGAM1 with PKM2 and PGAM1 H11 phosphorylation, dampening the glycolysis shunts and tumor growth. Together, these results identify a function of PKM2 as a histidine kinase, and illustrate the importance of enzyme crosstalk as a regulatory mode during metabolic reprogramming and tumorigenesis.
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Glicólise , Fosfoglicerato Mutase , Hormônios Tireóideos , Humanos , Fosfoglicerato Mutase/metabolismo , Fosfoglicerato Mutase/genética , Fosforilação , Animais , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/genética , Camundongos , Proteínas de Ligação a Hormônio da Tireoide , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Linhagem Celular Tumoral , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genéticaRESUMO
Elevated lipid synthesis is one of the best-characterized metabolic alterations in cancer and crucial for membrane expansion. As a key rate-limiting enzyme in de novo fatty acid synthesis, ATP-citrate lyase (ACLY) is frequently up-regulated in tumors and regulated by posttranslational modifications (PTMs). Despite emerging evidence showing O-GlcNAcylation on ACLY, its biological function still remains unknown. Here, we observed a significant upregulation of ACLY O-GlcNAcylation in various types of human tumor cells and tissues and identified S979 as a major O-GlcNAcylation site. Importantly, S979 O-GlcNAcylation is required for substrate CoA binding and crucial for ACLY enzymatic activity. Moreover, it is sensitive to glucose fluctuation and decisive for fatty acid synthesis as well as tumor cell proliferation. In response to EGF stimulation, both S979 O-GlcNAcylation and previously characterized S455 phosphorylation played indispensable role in the regulation of ACLY activity and cell proliferation; however, they functioned independently from each other. In vivo, streptozocin treatment- and EGFR overexpression-induced growth of xenograft tumors was mitigated once S979 was mutated. Collectively, this work helps comprehend how cells interrogate the nutrient enrichment for proliferation and suggests that although mammalian cell proliferation is controlled by mitogen signaling, the ancient nutrition-sensing mechanism is conserved and still efficacious in the cells of multicellular organisms.
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ATP Citrato (pro-S)-Liase , Proliferação de Células , Glucose , Lipogênese , Humanos , ATP Citrato (pro-S)-Liase/metabolismo , ATP Citrato (pro-S)-Liase/genética , Glucose/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Processamento de Proteína Pós-Traducional , Fosforilação , GlicosilaçãoRESUMO
BACKGROUND: Mesenchymal stem/stromal cells (MSCs) have been acknowledged as the most important stromal cells in the bone marrow (BM) microenvironment for physiologic hematopoiesis and the concomitant hematologic malignancies. However, the systematic and detailed dissection of the biological and transcriptomic signatures of BM-MSCs in multiple myeloma (MM) are largely unknown. METHODS: In this study, we isolated and identified BM-MSCs from 10 primary MM patients and 10 healthy donors (HD). On the one hand, we compared the multifaceted biological characteristics of the indicated two BM-MSCs, including biomarker expression pattern, multilineage differentiation potential, stemness and karyotyping, together with the cellular vitality and immunosuppressive property. On the other hand, we took advantage of RNA-SEQ and bioinformatics analysis to verify the similarities and differences at the transcriptomic level between MM-MSCs and HD-MSCs. RESULTS: As to biological phenotypes and biofunctions, MM-MSCs revealed conservation in immunophenotype, stemness and differentiation towards adipocytes and chondrocytes with HD-MSCs, whereas with impaired osteogenic differentiation potential, cellular vitality and immunosuppressive property. As to transcriptomic properties, MM-MSCs revealed multidimensional alterations in gene expression profiling and genetic variations. CONCLUSIONS: Overall, our date systematic and detailed reflected the multifaceted similarities and variations between MM-MSCs and HD-MSCs both at the cellular and molecular levels, and in particular, the alterations of immunomodulation and cellular viability of MM-MSCs, which wound benefit the further exploration of the pathogenesis and new drug application (NDA) of multiple myeloma from the view of BM-MSCs.
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Aconite is the processed product of the seed root of Aconitum carmichaelii Debx. Aconite is a commonly used traditional Chinese medicine, which is generally used after processing. Black aconite, light aconite, and salted aconite are three different processed aconite products. They have the effects of restoring yang and saving energy enemy, dispersing cold, and relieving pain. However, clinical aconite poisoning cases have frequently been reported. In our study, we investigated the effects of three different processed aconite products on the changes of metabolites in vivo. A total of 42 rats were randomly divided into seven groups with six rats in each group. After three consecutive days of intragastric administration of 2.7 g/kg of the aconite-processed product, rat serums were obtained. The rat metabolites were detected using liquid chromatography-tandem mass spectrometry. The altered metabolites related to aconite-processed products were discovered by statistical analysis using metaboanalyst software. Our study is the first time to comprehensively evaluate the effects of three different processed aconite products on rat metabolites based on pseudotargeted metabolomics.
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Aconitum , Medicamentos de Ervas Chinesas , Ratos , Animais , Aconitum/química , Medicamentos de Ervas Chinesas/análise , Raízes de Plantas/química , Medicina Tradicional Chinesa , Cromatografia Líquida , Metabolômica/métodosRESUMO
AIM: To investigate the knowledge level and clinical practice of neonatal intensive care unit nurses on the whole process of hypothermia prevention in preterm infants. DESIGN: A polycentric descriptive cross-sectional study was conducted in 23 hospitals in Shandong province involving 254 neonatal intensive care unit nurses. METHODS: An evidence-based knowledge and clinical practice questionnaire on hypothermia prevention in preterm infants and a general information questionnaire were used to collect data. SPSS and EXCEL 24.0 database were used for data statistics and analysis. RESULTS: Nearly one-third of nurses were unclear about the definition of mild hypothermia and heat preservation measures during labour management and resuscitation. Knowledge about the correct rate of amniotic fluid evaporation was low. The higher the hospital level and nurses' education level, professional title, work experience, and position, the higher the knowledge level. The clinical practice of nurses differed in terms of body temperature assessment tools, measurement sites, and measurement frequency for premature infants. CONCLUSIONS: Nurses in neonatal intensive care units need to apply evidence-based knowledge and carry out practice interventions to ensure preterm infants' safe transition from the delivery room to the neonatal intensive care unit. IMPACT: There have been few studies evaluating neonatal nurses' knowledge and practices with regards to the preventing hypothermia of premature infants from delivery room to neonatal intensive care unit. The study identifies the deficiencies and problems in temperature management that can be attributed to the knowledge level of nurses. The findings will help improve the current curriculum, teaching strategies, and the nurses' knowledge levels, preventing premature hypothermia in infants. REPORTING METHOD: This study adhered to the STROBE statement for observational studies and obtained approval (KYLL-2023LW045) from the ethics committee of The Second Hospital of Shandong University. The other 22 third- and second-level hospitals, as our alliance members, recognized our chairperson status within the alliance and were willing to join our academic activities. Mutual responsibility for ethical filing between alliance units. PUBLIC CONTRIBUTION: 254 nurses were recruited from 23 tertiary and secondary public hospitals in Shandong province. No public or patient involvement. Members of the research group used the Questionnaire Star platform to prepare the electronic questionnaire, including obtaining informed consent, taking precautions for questionnaire completion, and using the aforementioned measurement tools. The project research team contacted the head nurses of 23 neonatal intensive care units in Shandong Province. After obtaining consent from the head nurses, they were asked to send the requirements and link of the electronic questionnaire to their WeChat management group. The nurses go through each question and make a choice which has two options of 'agree' or 'disagree.' Based on their answers, nurses were evaluated as having 'mastered' or 'not mastered' each item. Each 'mastered' item (correct answer) was given a score of 4; an item 'not mastered' (incorrect answer) was given a score of 0. The total score ranged from 0 to 100.
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AIMS: This work aims to analyse the current state of the professional identity of Chinese nurses; examine the relationship amongst regulatory focus, organizational silence and professional identity and determine how regulatory focus affects the relationship between professional identity and organizational silence. DESIGN: This study conducted a cross-sectional survey. METHODS: From June to August 2023, 420 nurses from six hospitals in Hunan Province, China, were selected through convenience sampling and surveyed by using a general information questionnaire, the regulatory focus scale, the organizational silence scale and the professional identity scale. The relationship amongst the regulatory focus, organizational silence and professional identity of nurses was examined by utilizing SPSS 25.0 and the mediating role of regulatory focus between organizational silence and nurses' professional identity was examined by applying AMOS 24.0. RESULTS: Nurses had a moderate level of professional identity. Professional identity was positively correlated with regulatory focus and negatively correlated with organizational silence. Regulatory focus was negatively correlated with organizational silence. Mediation effect studies revealed that organizational silence and professional identity were partially mediated by regulatory focus. CONCLUSION: In accordance with research showing that nurses' organizational silence can indirectly affect professional identity via regulatory focus, clinical nursing managers should concentrate on the interaction amongst these three variables to strengthen professional identity. IMPACT: The results of this study serve as a reminder to nurses to select a preventive or promotive focus based on their career objectives and to effectively express their views to enhance their professional identity. This also reminds nursing managers assess nurse-led regulatory focus, identify their underlying qualities and understand their professional aspirations and career orientation, create a good atmosphere for advice and encourage nurses to express their views, so as to improve nurses 'professional identity. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Recursos Humanos de Enfermagem Hospitalar , Identificação Social , Humanos , Estudos Transversais , Adulto , Feminino , Masculino , China , Recursos Humanos de Enfermagem Hospitalar/psicologia , Inquéritos e Questionários , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Cultura Organizacional , Adulto JovemRESUMO
OBJECTIVE: Despite the benefits, the rate of genetic testing among first-degree relatives (FDRs; parents, children, and siblings) remains low, and the barriers to undergoing testing among FDRs in China are not clear. We explored the reasons why FDRs refused genetic testing. METHODS: Semi-structured face-to-face interviews were conducted with 22 patients and 27 FDRs. Participants were recruited at an urban tertiary hospital in Guangzhou, South China. We used qualitative content analysis to analyse the transcripts of audio recordings and identify major themes and subthemes. RESULTS: Three major themes emerged related to FDRs' low rate of participation in genetic testing. First, there is cognitive distance from genetic testing/cancer and a lack of knowledge of preventive medicine that deepens the 'fatalistic' attitude towards cancer among FDRs, which leads to an enormous gap between their knowledge and understanding of genetic testing. Second, medical consultation is not valued in Confucianism, and the view of cancer as 'bad news' and the risk of cancer as a curse makes cancer a metaphor, which leads to exhausting arguments when persuading FDRs to undergo genetic testing. Third, physical distance from the hospital, loss of privacy, possible discrimination in many social activities and genetic testing as a source of stress and anxiety lead FDRs to fear the disruption of their daily lives. CONCLUSIONS: There are many barriers to genetic testing among the FDRs of hereditary cancer patients originating from the national social and cultural context. Healthcare professionals should develop interventions rooted in culture and promote cancer risk communication between hereditary cancer patients and FDRs.
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Predisposição Genética para Doença , Neoplasias , Criança , Humanos , Confucionismo , Metáfora , Testes Genéticos , Neoplasias/genéticaRESUMO
AIMS AND OBJECTIVES: The aim of this study was to describe the prevalence of reproductive concerns among young female patients with colorectal cancer and explore the associated factors. BACKGROUND: With the trend of longer survival and younger age at diagnosis of colorectal cancer patients, reproductive concerns have become increasingly prevalent among young female colorectal cancer patients. DESIGN: Cross-sectional design. METHODS: The study included 150 young female patients with colorectal cancer who completed cancer treatment at 2 hospitals in Guangzhou, China, between November 2020 and December 2021 completed an investigation comprising A general questionnaire, The Reproductive Concerns After Cancer scale, The Family Adaptation and Cohesion Evaluation Scale II and unmet fertility information needs questionnaire. Multivariable linear regression analysis was performed in order to identify factors that influence reproductive concerns. This study was prepared and is reported according to the STROBE checklist. RESULTS: The mean (SD) score on the Reproductive Concerns After Cancer scale was 54.78 ± 8.97. The highest score was for the children's health subscale (3.84 ± .92) and the lowest was for acceptance (2.24 ± .70). Multiple regression analysis showed that patients with fewer children, female children, lower education level (less than undergraduate degree), earlier disease stage, lower family function and higher unmet need for fertility information had more reproductive concerns, which explained 26.9% of the total variation of the model. CONCLUSIONS: The patients with fewer children, female children, low cultural degree (less than bachelor), early clinical patients, poorer family function and higher unmet fertility information needs had higher reproductive concerns. RELEVANCE TO CLINICAL PRACTICE: These findings can guide the development of interventions to mitigate reproductive concerns, including understand and meet their fertility information needs, improve the level of family function. PATIENT OR PUBLIC CONTRIBUTION: Survey questionnaires were completed by participants among young female with colorectal cancer in this study.
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Neoplasias Colorretais , Reprodução , Criança , Humanos , Feminino , Estudos Transversais , Inquéritos e Questionários , PrevalênciaRESUMO
The sex-determining region Y-box 7 (Sox7) is an important member of the SOX F family, which is characterized by a high-mobility-group DNA-binding domain. Previous studies have demonstrated the role of SOX7 in cardiovascular development. SOX7 expression could be detected in normal adult tissues. Furthermore, the expression levels of SOX7 were different in different tumors. Most studies showed the downregulation of SOX7 in tumors, while some studies reported its upregulation in tumors. In this review, we first summarized the upstream regulators (including transcription factors, microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and some exogenous regulators) and downstream molecules (including factors in the Wnt/ß-catenin signaling pathway and some other signaling pathways) of SOX7. Then, the roles of SOX7 in multiple tumors were presented. Finally, the significance of divergent SOX7 expression during cardiovascular development was briefly discussed. The information compiled in this study characterized SOX7 during tumorigenesis and cardiovascular development, which should facilitate the design of future research and promote SOX7 as a therapeutic target.
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Carcinogênese , Doenças Cardiovasculares/patologia , Biologia do Desenvolvimento , Neoplasias/patologia , Fatores de Transcrição SOXF/metabolismo , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Fatores de Transcrição SOXF/genética , Transdução de SinaisRESUMO
The Ebbinghaus illusion (EI) is an optical illusion of relative size perception that reflects the contextual integration ability in the visual modality. The current study investigated the genetic basis of two subtypes of EI, EI overestimation, and EI underestimation in humans, using quantitative genomic analyses. A total of 2825 Chinese adults were tested on their magnitudes of EI overestimation and underestimation using the method of adjustment, a standard psychophysical protocol. Heritability estimation based on common single nucleotide polymorphisms (SNPs) revealed a moderate heritability (34.3%) of EI overestimation but a nonsignificant heritability of EI underestimation. A meta-analysis of two phases (phase 1: n = 1986, phase 2: n = 839) of genome-wide association study (GWAS) discovered 1969 and 58 SNPs reaching genome-wide significance for EI overestimation and EI underestimation, respectively. Among these SNPs, 55 linkage-disequilibrium-independent SNPs were associated with EI overestimation in phase 1 with genome-wide significance and their associations could be confirmed in phase 2 cohort. Gene-based analyses found seven genes to be associated with EI overestimation at the genome-wide level, two from meta-analysis, and five from classical two-stage analysis. Overall, this study provided consistent evidence for a substantial genetic basis of the Ebbinghaus illusion.
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Estudo de Associação Genômica Ampla , Ilusões Ópticas/fisiologia , Percepção de Tamanho/fisiologia , Adolescente , Adulto , Povo Asiático/genética , Etnicidade/genética , Feminino , Genótipo , Humanos , Individualidade , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Córtex Visual/anatomia & histologia , Adulto JovemRESUMO
Given the numerous industrial applications of zeolites as adsorbents, catalysts, and ion-exchangers, the development of new zeolite structures is highly desired to expand their practical applications. Currently, a general route to develop new zeolite structures is to use interlayer expansion agents to connect layered silicates. In this review, we briefly summarize the novel zeolite structures constructed from the lamellar precursor zeolites MWW, RUB-36, PREFER, Nu-6(1), COK-5, and PLS-1 via interlayer expansion. The contents of the summary contain detailed experiments, physicochemical characterizations, possible expansion mechanisms, and catalytic properties. In addition, the insertion of metal heteroatoms (such as Ti, Fe, Sn) into the layered zeolite precursor through interlayer expansion, which could be helpful to modify the catalytic function, is discussed.
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To explore the effect of light intensity in cultivating environment on the hepetoprotective activity of Sedum sarmentosum, S. sarmentosum were planted under five water treatments for 60 days, namely 100% full sunlight(G1), 77% full sunlight(G2), 60% full sunlight(G3), 38% full sunlight(G4), and 16% full sunlight(G5) and CCl_4 drug-induced liver injury model in vitro was used. Cell viability, cell cycle, and cell apoptosis were individually detected by MTT, PI single staining, and Annexin-V FITC/PI double staining assays. Additionally, ALT, AST and antioxidant index in supernatant were determined by colorimetry. And the relationship among the protective effects, chemical composition and antioxidant activity were also analyzed. The results showed that S. sarmentosum aqueous extract could significantly improve the HepG2 cell viability. Among the five S. sarmentosum groups, the cell viability of G1(100% full sunlight) treatment was the highest, and the cell apoptosis was the least. Meanwhile, the level of ALT, AST, and MDA in G1 was the lowest, but it achieved the highest level of SOD and GSH. Moderate light shading(60% full light) also improved the effect of protecting liver and reducing the enzyme. It was found that cell viability was positively correlated with ferricion reducing capacity. ALT activity was positively correlated with isorhamnetin content. Taken together, different light intensity had great influence on hepatoprotective effect of S. sarmentosum, which may be related to its antioxidant capacity. From the perspective of hepetoprotective activity, S. sarmentosum should be planted under full light.
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Doença Hepática Induzida por Substâncias e Drogas , Sedum , Antioxidantes , Células Hep G2 , Humanos , Fígado , Extratos Vegetais/farmacologia , ÁguaRESUMO
Based on ~1H-NMR metabonomics technique and Western blot assay, the anti-inflammatory mechanism of Crepis crocea was discussed. In this study, male SD rats were treated with water extract(2.5 g·kg~(-1)) and dexamethasone acetate(6.25×10~(-4) g·kg~(-1)) for one week, and the inflammation model was induced by lipopolysaccharide(LPS). Then the counts of inflammatory cells white blood ceel(WBC), eosinophil(EO), lymphocyte(LY), basophils(BA) and neutrophils(NE) in whole blood of rats were observed. The levels of serum inflammatory factors tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), IL-6 and the expression of nuclear factor-κB(NF-κB) signaling pathway p65 and p-IκBα proteins in lung tissues were detected, and the change rules of serum endogenous metabolites were analyzed by ~1H-NMR metabonomics technique. The levels of TNF-α, IL-1ß, IL-6 and NF-κB signaling pathway p65 and p-IκBα proteins were combined with ~1H-NMR metabonomics to study the anti-inflammatory mechanism of C. crocea. The results showed that the water extract of C. crocea significantly decreased the number of WBC, NE, EO, increased the number of BA and LY, decreased the levels of TNF-α, IL-1ß, IL-6 and the expression of p65 and p-IκBα protein in NF-κB signaling pathway, and effectively alleviated the inflammatory symptoms. In the correlation analysis of differential metabolites regulated of C. crocea, four significant metabolites were obtained, including glycine, creatine, methionine and succinic acid. The anti-inflammatory mechanism of C. crocea may be related to the decrease of TNF-α, IL-1ß, IL-6 levels and the protein expression of NF-κB signaling pathway, as well as the regulation of glycine, creatine, methionine and succinic acid metabolism.
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Anti-Inflamatórios/farmacologia , Crepis/química , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Citocinas/sangue , Lipopolissacarídeos , Masculino , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Sprague-DawleyRESUMO
Non-fullerene all-small-molecule organic solar cells (NFSM-OSCs) have shown potential as OSCs, owing to their high purity, easy synthesis and good reproducibility. However, challenges in the modulation of phase separation morphology have limited their development. Herein, two novel small molecular donors, BTEC-1F and BTEC-2F, derived from the small molecule DCAO3TBDTT, are synthesized. Using Y6 as the acceptor, devices based on non-fluorinated DCAO3TBDTT showed an open circuit voltage (Voc ) of 0.804â V and a power conversion efficiency (PCE) of 10.64 %. Mono-fluorinated BTEC-1F showed an increased Voc of 0.870â V and a PCE of 11.33 %. The fill factor (FF) of di-fluorinated BTEC-2F-based NFSM-OSC was improved to 72.35 % resulting in a PCE of 13.34 %, which is higher than that of BTEC-1F (61.35 %) and DCAO3TBDTT (60.95 %). To our knowledge, this is the highest PCE for NFSM-OSCs. BTEC-2F had a more compact molecular stacking and a lower crystallinity which enhanced phase separation and carrier transport.
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Visual cognition in humans has traditionally been studied with cognitive behavioral methods and brain imaging, but much less with genetic methods. Perceptual rivalry, an important phenomenon in visual cognition, is the spontaneous perceptual alternation that occurs between two distinct interpretations of a physically constant visual stimulus (e.g., binocular rivalry stimuli) or a perceptually ambiguous stimulus (e.g., the Necker cube). The switching rate varies dramatically across individuals and can be voluntarily modulated by observers. Here, we adopted a genomic approach to systematically investigate the genetics underlying binocular rivalry, Necker cube rivalry and voluntary modulation of Necker cube rivalry in young Chinese adults (Homo sapiens, 81% female, 20 ± 1 years old) at multiple levels, including common single nucleotide polymorphism (SNP)-based heritability estimation, SNP-based genome-wide association study (GWAS), gene-based analysis, and pathway analysis. We performed a pilot GWAS in 2441 individuals and replicated it in an independent cohort of 943 individuals. Common SNP-based heritability was estimated to be 25% for spontaneous perceptual rivalry. SNPs rs184765639 and rs75595941 were associated with voluntary modulation, and imaging data suggested genotypic difference of rs184765639 in the surface area of the left caudal-middle frontal cortex. Additionally, converging evidence from multilevel analyses associated genes such as PRMT1 with perceptual switching rate, and MIR1178 with voluntary modulation strength. In summary, this study discovered specific genetic contributions to perceptual rivalry and its voluntary modulation in human beings. These findings may promote our understanding of psychiatric disorders, as perceptual rivalry is a potential psychiatric biomarker.SIGNIFICANCE STATEMENT Perceptual rivalry is an important visual phenomenon in which our perception of a physically constant visual input spontaneously switches between two different states. There are individual variations in perceptual switching rate and voluntary modulation strength. Our genomic analyses reveal several loci associated with these two kinds of variation. Because perceptual rivalry is thought to be relevant to and potentially an endophenotype for psychiatric disorders, these results may help understand not only visual cognition, but also psychiatric disorders.
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Cognição/fisiologia , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Estimulação Luminosa/métodos , Percepção Visual/fisiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto JovemRESUMO
Sea bass (Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological mechanisms of inflammation of sea bass remain scarce. Hence, this study aims to investigate the molecular mechanisms of the anti-inflammatory activity of sea bass. Anti-inflammatory activities of sea bass were assessed using dextran sulfate sodium (DSS)-induced colitis in a mice model and lipopolysaccharide (LPS)-activated macrophages model. Low body weight and short colon length were observed in DSS-fed mice that were significantly recovered upon sea bass treatments. Moreover, the colon histopathology score showed that sea bass-treated mice had decreased crypt damage, focal inflammation infiltration and the extent of inflammation, suggesting that treatment with sea bass could attenuate intestinal inflammation. In addition, the in-vitro study conjointly indicated that sea bass could suppress the inflammatory mediators in LPS-activated macrophage by inhibiting the TLR4-linked pathway. The present findings demonstrated that sea bass has an inhibitory effect on TLR4 signaling; thus, it could be a promising candidate for treating inflammation-associated conditions. A further justification for the clinical application of sea bass in treating inflammation-associated conditions is necessary.
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Anti-Inflamatórios/uso terapêutico , Bass , Colite Ulcerativa/dietoterapia , Macrófagos/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Suplementos Nutricionais , Produtos Pesqueiros , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Extratos de Tecidos/administração & dosagem , Extratos de Tecidos/farmacologia , Extratos de Tecidos/uso terapêuticoRESUMO
To characterize the chemical constituents of Huanbei Zhike Prescription by ultra-high performance liquid chromatography-time of flight mass spectrometry( UPLC-Q-TOF-MS/MS). A Thermo Syncronls C18 column( 2. 1 mm×100 mm,1. 7 µm) was used with methanol( A)-0. 1% formic acid solution( B) as the mobile phase for gradient elution. The injection volume was 2 µL; the column temperature was 40 â; the flow rate was 0. 3 m L·min-1; and electrospray ionization( ESI) source was used to collect data in positive and negative ion modes. The ion scanning range was m/z 50-1 200,with capillary voltage of 3 000 V,ion source temperature of100 â,atomization gas flow rate of 50 L·h-1,desolvent gas flow rate of 800 L·h-1,desolvent temperature of 400 â,cone hole voltage of 40 V,with argon as the collision gas and the collision energy was 20-35 V. The excimer ion peak information was analyzed by Waters UNIFI data processing software. The molecular formula with error within 1×10-5 was compared with the data in database to identify the compounds. The secondary fragment ion information of the target compound was selected,and then compared with the retention time and fragmentation patterns provided by the database and the existing literature to further confirm the compositions and structures of the compounds. A total of 68 main compounds in Huanbei Zhike Prescription were identified,including 38 flavonoids,10 organic acids,6 terpenoids and 10 nitrogen-containing compounds,of which 12 compounds were verified by the control substances. This method is rapid and accurate,which provides a new strategy for the qualitative analysis of the chemical constituents of Huanbei Zhike Prescription,and lays a foundation for the further study and quality control of the compound pharmacodynamic substance.
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Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Espectrometria de Massas em Tandem , Terpenos/análiseRESUMO
Prolonged isolated thrombocytopenia (PT) is a severe complication in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether the megakaryoctic potential of hematopoietic stem cells (HSCs) in bone marrow is intact and what factors drive the pathological process of PT remain elusive. A retrospective study in patients (n = 285) receiving HSCT revealed that the occurrence of PT was approximately 8% and the number of platelets and megakaryocytes in PT patients is much lower compared with control subjects. To test whether the deficiency of thrombopoiesis was caused by the activities of HSCs, the megakaryocytic differentiation potential of HSCs before or after transplantation was assessed. Interestingly, a substantial decrease of megakaryocytic differentiation was observed 2 weeks after transplantation of HSCs in all of the allo-HSCT recipients. However, 4 weeks after transplantation, the ability of HSCs to generate CD41+CD42b+ megakaryocytes in successful platelet engraftment patients recovered to the same level as those of HSCs before implantation. In contrast, HSCs derived from PT patients throughout the postimplantation period exhibited poor survival and failed to differentiate properly. A protein array analysis demonstrated that multiple inflammation-associated cytokines were elevated in allo-HSCT recipients with PT. Among them, insulin-like growth factor-binding protein 1 and regulated on activation, normal T cell expressed and secreted were found to significantly suppress the proliferation and megakaryocytic differentiation of HSCs in vitro. Our results suggested that the occurrence of PT may be attributed, at least partially, to the damage to HSC function caused by inflammation-associated cytokines after HSCT. These findings shed light on the mechanism underlying HSC megakaryocytic differentiation in PT patients and may provide potential new strategies for treating PT patients after HSCT.
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Quimiocina CCL5/farmacologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/farmacologia , Megacariócitos/citologia , Trombocitopenia/etiologia , Adulto , Diferenciação Celular , Citocinas , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombocitopenia/patologia , Transplante Homólogo/efeitos adversosRESUMO
Cognitive impairment and personality disorders are severe comorbidities commonly observed in patients with epilepsy, and together they decrease the quality of patients' life. This study aimed to evaluate cognitive function and personality traits in patients with epilepsy with the Wechsler Adult Intelligence Scale-Chinese revised and Eysenck Personality Questionnaire and investigate the underlying influencing factors. Compared with the control group, our results showed that patients with epilepsy were presented with significant cognitive impairment and particular personality traits. Epileptic seizure-related factors including earlier age of onset, longer duration of epileptic history, and higher seizure frequency were significantly associated with the observed defects in cognition and personality traits. In addition, the temporal lobe was more likely to affect cognition and personality, and the left hemisphere was closely related to verbal intelligence quotient, which needs to be the focus of future research. These results will be instrumental for guiding the treatment of epilepsy.