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Core to understanding emotion are subjective experiences and their expression in facial behavior. Past studies have largely focused on six emotions and prototypical facial poses, reflecting limitations in scale and narrow assumptions about the variety of emotions and their patterns of expression. We examine 45,231 facial reactions to 2,185 evocative videos, largely in North America, Europe, and Japan, collecting participants' self-reported experiences in English or Japanese and manual and automated annotations of facial movement. Guided by Semantic Space Theory, we uncover 21 dimensions of emotion in the self-reported experiences of participants in Japan, the United States, and Western Europe, and considerable cross-cultural similarities in experience. Facial expressions predict at least 12 dimensions of experience, despite massive individual differences in experience. We find considerable cross-cultural convergence in the facial actions involved in the expression of emotion, and culture-specific display tendencies-many facial movements differ in intensity in Japan compared to the U.S./Canada and Europe but represent similar experiences. These results quantitatively detail that people in dramatically different cultures experience and express emotion in a high-dimensional, categorical, and similar but complex fashion.
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BACKGROUND: Buyang Huanwu Decoction (BHD) is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. This study was designed to investigate the effects of BHD on ischemic stroke (IS) and its underlying mechanism. METHODS: The middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) rat brain microvascular endothelial cell (RBMVEC) models were established. Brain infarction size and neurological score were calculated following MCAO surgery. Evans blue was used to measure blood brain barrier (BBB) permeability. Cell counting kit-8 (CCK-8) and TUNEL assays were performed to evaluate the cell viability and apoptosis of RBMVECs. Dual-luciferase reporter assay was used to analyze the transcriptional activities of apoptosis-related genes. RESULTS: Results showed that higher infarction volume, neurological scores, and BBB permeability in the MCAO group rats were reduced after BHD treatment. Drug serum (DS) treatment had no impact on the normal RBMVECs' cell viability and cell apoptosis. Besides, DS treatment decreased the lactate production, glucose uptake, and extracellular acidification rate in normal and OGD/R-induced RBMVECs. DS treatment downregulated the protein levels of pan-lysine lactylation (kla), histone H3 lysine 18 lactylation (H3K18la), and the transcriptional of apoptotic protease activating factor-1 (Apaf-1) in OGD/R-treated RBMVECs. In addition, Apaf-1 overexpression decreased cell viability and increased apoptosis and glycolysis activity of OGD/R-treated RBMVECs. CONCLUSION: In summary, BHD inhibited glycolysis and apoptosis via suppressing the pan-kla and H3K18la protein levels and the Apaf-1 transcriptional activity, thus restraining the progression of IS.
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Apoptose , Medicamentos de Ervas Chinesas , Células Endoteliais , Glicólise , AVC Isquêmico , Ratos Sprague-Dawley , Animais , Medicamentos de Ervas Chinesas/farmacologia , Apoptose/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glicólise/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , Ratos , Masculino , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Glucose/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Modelos Animais de DoençasRESUMO
Previous research has demonstrated that individuals from Western cultures exhibit categorical perception (CP) in their judgments of emotional faces. However, the extent to which this phenomenon characterises the judgments of facial expressions among East Asians remains relatively unexplored. Building upon recent findings showing that East Asians are more likely than Westerners to see a mixture of emotions in facial expressions of anger and disgust, the present research aimed to investigate whether East Asians also display CP for angry and disgusted faces. To address this question, participants from Canada and China were recruited to discriminate pairs of faces along the anger-disgust continuum. The results revealed the presence of CP in both cultural groups, as participants consistently exhibited higher accuracy and faster response latencies when discriminating between-category pairs of expressions compared to within-category pairs. Moreover, the magnitude of CP did not vary significantly across cultures. These findings provide novel evidence supporting the existence of CP for facial expressions in both East Asian and Western cultures, suggesting that CP is a perceptual phenomenon that transcends cultural boundaries. This research contributes to the growing literature on cross-cultural perceptions of facial expressions by deepening our understanding of how facial expressions are perceived categorically across cultures.
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Introduction: Research indicates that individuals experiencing hemorrhagic stroke face a greater likelihood of developing lower extremity deep vein thrombosis (DVT) compared to those with ischemic stroke. This study aimed to assess the predictive capacity of the Caprini risk assessment model (RAM), D-dimer (D-D) levels, and fibrinogen (FIB) levels for lower extremity DVT in patients with spontaneous intracerebral hemorrhage (sICH). Methodology: This study involved a retrospective analysis of medical records from all sICH patients admitted to Shanghai General Hospital between June 2020 and June 2023. Within 48 h of admission, patients underwent routine screening via color Doppler ultrasonography (CDUS). Patients were categorized into the DVT and control groups based on the occurrence of lower extremity DVT during hospitalization. Differences in Caprini RAM, D-dimer, and FIB levels between the two groups were compared. The sensitivity and specificity of combined Caprini RAM, peripheral blood D-dimer, and FIB levels in predicting lower extremity DVT in sICH patients were analyzed. Receiver operating characteristic (ROC) curves assessed the overall predictive accuracy of Caprini RAM, D-D, and FIB levels. Results: The study involving 842 sICH patients revealed 225 patients with DVT and 617 patients without DVT. Caprini RAM, D-D, and FIB levels were significantly higher in the DVT group compared to the control group (P < 0.05). Sensitivity values for Caprini RAM, D-D, and FIB levels in predicting lower extremity DVT in sICH patients were 0.920, 0.893, and 0.680, respectively, while specificities were 0.840, 0.680, and 0.747, respectively. The ROC curve analysis demonstrated an area under the curve (AUC) of 0.947 for combined DVT prediction, with 97.33% sensitivity and 92.00% specificity, indicating superior predictive value compared to individual applications of Caprini RAM, D-D, and FIB levels. Conclusion: The combined utilization of Caprini RAM, D-D, and FIB levels holds significant clinical relevance in predicting lower extremity DVT in sICH patients.
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The model of M2-like tumor-associated macrophages (TAMs) is an increasingly attractive model for the study of TAMs. However, the detailed process of M2-like TAMs polarization induced by lactic acid or conditioned medium from Lewis cells (LCM) and the identification of M2-like TAMs is not yet available. In this protocol, we present the detailed methods to induce M2-like TAMs polarization and verify its functionality in order to better carry out related research. For complete details on the use and execution of this protocol, please refer to Fang et al.1.
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Ácido Láctico , Macrófagos Associados a Tumor , Meios de Cultivo Condicionados/farmacologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Animais , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos BiológicosRESUMO
Introduction: Nail stem cell (NSC) differentiation plays a vital role in maintaining nail homeostasis and facilitating digit regeneration. Recently, onychofibroblasts (OFs), specialized mesenchymal cells beneath the nail matrix, have emerged as potential regulators of NSC differentiation. However, limited understanding of OFs' cellular properties and transcriptomic profiles hinders our comprehension of their role. This study aims to characterize human OFs and investigate their involvement in NSC differentiation. Methods: Human OFs were isolated and characterized for their mesenchymal stem cell (MSC)-like phenotype through flow cytometry and multilineage differentiation assays. Bulk RNA-seq analysis was conducted on three samples of OFs and control fibroblasts from human nail units to delineate their molecular features. Integrated analysis with scRNA-seq data was performed to identify key signaling pathways involved in OF-induced NSC differentiation. Co-culture experiments, siRNA transfection, RT-qPCR, and immunocytochemistry were employed to investigate the effect of OF-derived soluble proteins on NSC differentiation. Drug treatments, RT-qPCR, western blotting, and immunocytochemistry were used to verify the regulation of candidate signaling pathways on NSC differentiation in vitro. Results: Human OFs exhibited slow cell cycle kinetics, expressed typical MSC markers, and demonstrated multilineage differentiation potential. Bulk RNA-seq analysis revealed differential gene expression in OFs compared to control fibroblasts, highlighting their role in coordinating nail development. Integrated analysis identified BMP4 as a pivotal signal for OFs to participate in NSC differentiation through mesenchymal-epithelial interactions, with the TGF-beta pathway possibly mediating this signal. OFs synthesized and secreted more BMP4 than control fibroblasts, and BMP4 derived from OFs induced NSC differentiation in a co-culture model. Recombinant human BMP4 activated the TGF-beta pathway in NSCs, leading to cell differentiation, while the BMP type I receptor inhibitor LDN193189 attenuated this effect. Discussion: This study characterizes the cellular and molecular features of human OFs, demonstrating their ability to regulate NSC differentiation via the TGF-beta signaling pathway. These findings establish a connection between the dermal microenvironment and NSC differentiation, suggesting the potential of OFs, in conjunction with NSCs, for developing novel therapies targeting nail and digit defects, even severe limb amputation.
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BACKGROUND: The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. METHODS: Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund's adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and ß-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. ß-galactosidase (ß-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. RESULTS: Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P < 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P < 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/ß-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P < 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P < 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca2+ responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P < 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P < 0.05 vs. Panx1 KO group; P < 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/ß-catenin signaling (P < 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P < 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P < 0.01 vs. WT group). Analysis of ß-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG. CONCLUSIONS: The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain, where similar studies revealed a prominent role for glial Panx1. The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.
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Conexinas , Proteínas do Tecido Nervoso , Animais , Conexinas/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Modelos Animais de Doenças , Dor/fisiopatologia , Dor/etiologia , Neurônios/metabolismo , Inflamação/fisiopatologia , Camundongos Knockout , MasculinoRESUMO
Allergic asthma (AA) is a common breathing disorder clinically characterized by the high occurrence of acute and continuous inflammation. However, the current treatment options for AA are lacking in effectiveness and diversity. In this study, we determined that the cell membrane receptor of gamma-glutamyl transferase (GGT) was highly overexpressed on the inflammatory cells that infiltrate the pulmonary tissues in AA cases. Therefore, we developed a GGT-specific dendrimer-dexamethasone conjugate (GSHDDC) that could be administered via aerosol inhalation to treat AA in a rapid and sustained manner. The GSHDDC was fabricated by the covalent attachment of 6-hydroxyhexyl acrylate-modified dexamethasone to polyamidoamine dendrimers via a carbonic ester linkage and the amino Michael addition, followed by the surface modification of the dendrimers with the GGT substrate of glutathione. After aerosol inhalation by the AA mice, the small particle-sized GSHDDC could easily diffuse into pulmonary alveoli and touch with the inflammatory cells via the glutathione ligand/GGT receptor-mediated recognition. The overexpressed GGT on the surface of inflammatory cells then triggers the gamma-glutamyl transfer reactions of glutathione to generate positively charged primary amines, thereby inducing rapid cationization-mediated cellular endocytosis into the inflammatory cells. The dexamethasone was gradually released by the intracellular enzyme hydrolysis, enabling sustained anti-inflammatory effects (e.g., reducing eosinophil infiltration, decreasing the levels of inflammatory factors) in the ovalbumin-induced AA mice. This study demonstrates the effectiveness of an inhalational and active inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient AA therapy.
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Asma , Dendrímeros , Animais , Camundongos , Aerossóis e Gotículas Respiratórios , Asma/tratamento farmacológico , Glutationa , Dexametasona/farmacologiaRESUMO
When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.
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Asco , Humanos , Julgamento , Princípios Morais , Ira , EmoçõesRESUMO
Cross-cultural studies of the meaning of facial expressions have largely focused on judgments of small sets of stereotypical images by small numbers of people. Here, we used large-scale data collection and machine learning to map what facial expressions convey in six countries. Using a mimicry paradigm, 5,833 participants formed facial expressions found in 4,659 naturalistic images, resulting in 423,193 participant-generated facial expressions. In their own language, participants also rated each expression in terms of 48 emotions and mental states. A deep neural network tasked with predicting the culture-specific meanings people attributed to facial movements while ignoring physical appearance and context discovered 28 distinct dimensions of facial expression, with 21 dimensions showing strong evidence of universality and the remainder showing varying degrees of cultural specificity. These results capture the underlying dimensions of the meanings of facial expressions within and across cultures in unprecedented detail.
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OBJECTIVE: To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). METHODS: This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1-3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded. RESULTS: A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = -0.413, p = 0.026) and NT-proBNP (r = -0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = -0.408, p = 0.028) and NT-proBNP (r = -0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95-52.36), MFI (OR 7.85, 95% CI 1.73-35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP. CONCLUSION: SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.
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Lúpus Eritematoso Sistêmico , Hipertensão Arterial Pulmonar , Humanos , Lúpus Eritematoso Sistêmico/complicações , Prognóstico , Hipertensão Arterial Pulmonar/etiologia , Curva ROC , Sensibilidade e Especificidade , Estudos ProspectivosRESUMO
Although androgen deprivation therapy (ADT) by the anti-androgen drug enzalutamide (Enz) may improve the survival level of patients with castration-resistant prostate cancer (CRPC), most patients may eventually fail due to the acquired resistance. The reprogramming of glucose metabolism is one type of the paramount hallmarks of cancers. PKM2 (Pyruvate kinase isozyme typeM2) is a speed-limiting enzyme in the glycolytic mechanism, and has high expression in a variety of cancers. Emerging evidence has unveiled that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have impact on tumor development and therapeutic efficacy by regulating PKM2 expression. Herein, we found that lncRNA SNHG3, a highly expressed lncRNA in CRPC via bioinformatics analysis, promoted the invasive ability and the Enz resistance of the PCa cells. KEGG pathway enrichment analysis indicated that glucose metabolic process was tightly correlated with lncRNA SNHG3 level, suggesting lncRNA SNHG3 may affect glucose metabolism. Indeed, glucose uptake and lactate content determinations confirmed that lncRNA SNHG3 promoted the process of glycolysis. Mechanistic dissection demonstrated that lncRNA SNHG3 facilitated the advance of CRPC by adjusting the expression of PKM2. Further explorations unraveled the role of lncRNA SNHG3 as a 'sponge' of miR-139-5p and released its binding with PKM2 mRNA, leading to PKM2 up-regulation. Together, Our studies suggest that lncRNA SNHG3 / miR-139-5p / PKM2 pathway promotes the development of CRPC via regulating glycolysis process and provides valuable insight into a novel therapeutic approach for the disordered disease.
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Benzamidas , MicroRNAs , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Androgênios , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Glicólise/genética , Glucose , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition-induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet-induced insulin-resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF-κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes.
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Fatores de Transcrição de Zíper de Leucina Básica , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Humanos , Camundongos , Tecido Adiposo/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Resistência à Insulina/genética , Macrófagos/metabolismo , Obesidade/metabolismoRESUMO
Facial expressions in daily life typically change from one emotional state to another. To understand how people process emotions, it is important to know not only how current facial expressions are interpreted but also recent past expressions. While researchers have recently focused on perceptions of current expressions, little is known about how past expressions are gauged and about cultural differences in this process. The present research investigated whether and how evaluations of past facial expressions are influenced by subsequent expressions, and whether this process varies across East Asian and Western cultures. Specifically, Chinese and Canadian participants judged the degree of positivity/negativity of past expressions after viewing expressions that changed from past emotions-low-intensity smiles (Experiment 1), high-intensity smiles (Experiment 2), and anger (Experiment 3)-to current positive or negative emotions (collected between 2019 and 2020). All three experiments consistently found an assimilation effect, whereby past expressions were rated more positively when the current expression was positive than when the current expression was negative. Moreover, this assimilation effect was consistently greater in Chinese than in Canadian participants. Together, these findings suggest that the interpretation of past facial expressions assimilates toward the valence of subsequent expressions and that the impact of this temporal emotional context is more pronounced in Eastern relative to Western cultures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Comparação Transcultural , Emoções , Expressão Facial , Humanos , Ira , CanadáRESUMO
Clinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164_165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases.
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Miopia , Humanos , Mutação , Miopia/genética , Sequenciamento do Exoma , OlhoRESUMO
Security and privacy have always been key concerns for individuals in various edge-assisted services. In this paper, we present a feasible quantum solution to an important primitive of secure multiparty computations, i.e., Secure Multiparty Logical AND (SMLA), in which n participants can securely compute logical AND of n private bits. In order to ensure perfect security and achieve good feasibility, we introduce a semi-honest edge server and two non-collusive fog nodes, and design a secure and feasible edge-assisted quantum protocol for SMLA, which cleverly utilizes Secure Multiparty XOR to implement SMLA group by group. Furthermore, we focus on applications of this quantum primitive protocol and design two quantum protocols for Multiple Private Set Intersection and Anonymous One-vote Veto. Compared with classical related protocols, our proposed quantum protocols obtain higher security, which can be guaranteed by the basic principles of quantum mechanics.
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Prolyl hydroxylase domain (PHD) enzymes change HIF activity according to oxygen signal; whether it is regulated by other physiological conditions remains largely unknown. Here, we report that PHD3 is induced by fasting and regulates hepatic gluconeogenesis through interaction and hydroxylation of CRTC2. Pro129 and Pro615 hydroxylation of CRTC2 following PHD3 activation is necessary for its association with cAMP-response element binding protein (CREB) and nuclear translocation, and enhanced binding to promoters of gluconeogenic genes by fasting or forskolin. CRTC2 hydroxylation-stimulated gluconeogenic gene expression is independent of SIK-mediated phosphorylation of CRTC2. Liver-specific knockout of PHD3 (PHD3 LKO) or prolyl hydroxylase-deficient knockin mice (PHD3 KI) show attenuated fasting gluconeogenic genes, glycemia, and hepatic capacity to produce glucose during fasting or fed with high-fat, high-sucrose diet. Importantly, Pro615 hydroxylation of CRTC2 by PHD3 is increased in livers of fasted mice, diet-induced insulin resistance or genetically obese ob/ob mice, and humans with diabetes. These findings increase our understanding of molecular mechanisms linking protein hydroxylation to gluconeogenesis and may offer therapeutic potential for treating excessive gluconeogenesis, hyperglycemia, and type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Glucose , Humanos , Camundongos , Animais , Glucose/metabolismo , Prolina/metabolismo , Hidroxilação , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Gluconeogênese/fisiologia , Prolil Hidroxilases/metabolismo , Hepatócitos/metabolismo , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The aim of this study was to determine the clinical outcomes of vascularized hemi-metatarsal composite tissue transfer for the reconstruction of type IIIB hypoplastic thumbs. METHODS: Twenty-eight patients with type IIIB hypoplastic thumbs treated with vascularized hemi-metatarsal composite tissue transfer were included in this retrospective study with a mean follow-up of 2.4 years. Preoperative digital subtraction angiography was performed to examine the vessel variance. Clinical measures included grip and pinch strength, scar status, and Kapandji thumb opposition score. Subjective Pediatric Outcomes Data Collection Instrument scores and parent satisfaction were also evaluated. RESULTS: Radial arteries were hypoplastic in 82.1% of the cases, and the common palmar digital artery was chosen as the recipient vessel for the tissue transfer. There was no neurovascular complication. The only donor-site complication was a metatarsal fracture that healed with casting. Key pinch and tripod pinch were 29.5% and 45.8% of the normal side, respectively. The mean grip strength was 51.7% of the unaffected side. The mean Kapandji score was 6. The Pediatric Outcomes Data Collection Instrument scores were high for global function; upper extremity function; transfer; and basic mobility, happiness, and comfort. The Vancouver Scar Scale showed an average score of 2.1. All parents were satisfied with the clinical outcomes. CONCLUSION: Vascularized hemi-metatarsal composite tissue transfer for type IIIB thumb hypoplasia can provide improved subjective outcomes and is a feasible method for the attainment of a five-digit hand. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
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Ossos do Metatarso , Polegar , Criança , Humanos , Polegar/anormalidades , Estudos Retrospectivos , CicatrizRESUMO
In this study, we aim to investigate retinal thickness (RT) and superficial vascular density (SVD) differences between patients with systemic sclerosis (SSc) and healthy controls (HCs) by optical coherence tomography angiography (OCTA). Sixteen patients with a definitive SSc diagnosis without clinical signs of retinopathy and 16 normal control subjects were recruited. All individuals underwent OCTA scanning to assess macular RT and SVD. We divided each image into nine subregions as the early treatment diabetic retinopathy study (ETDRS). Visual acuity (VA) was considerably different between patients with SSc (32 eyes) and control subjects (32 eyes) (p < 0.001). Compared to the control group, individuals with SSc had decreased inner RT in inner superior, outer superior, outer temporal, inner temporal, center, and inner nasal regions (p < 0.05). Outer RT was decreased in the outer and inner temporal regions, and full RT was decreased in the regions of outer superior, inner superior, inner temporal, and outer temporal, in comparison to the control group (p < 0.05). Patients with SSc had significant reduction of SVD in the inner and outer of both superior and temporal, besides outer nasal regions than controls. (p < 0.05). Moreover, SVD was significantly associated with the outer temporal region of patients suffering from SSc (p < 0.05). Diagnostic Sensitivity of RT and SVD of Inner Superior Regions in SSc, as indicated by areas under curves of the Receiver Operating Characteristic (ROC), were 0.874 (95% CI: 0.786-0.962) and 0.827 (95% CI: 0.704-0.950), respectively. In conclusion, VA may be affected by RT variations inside the macula in patients with SSc. Measuring RT with OCTA could be a useful predictor of early diagnosis.
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Retinopatia Diabética , Macula Lutea , Doenças Retinianas , Escleroderma Sistêmico , Humanos , RetinaRESUMO
Tumor cell-derived lactate has been recognized as the key driver of polarization in tumor-associated macrophages (TAMs). Intratumoral lactate can be transported into macrophages to fuel the TCA cycle, which is mediated by mitochondrial pyruvate carrier (MPC). At the heart of intracellular metabolism, MPC-mediated transport has been investigated in studies which suggested its role and importance in the process of TAMs polarization. However, previous studies relied on pharmacological inhibition instead of genetic approaches to evaluate the role of MPC in TAMs polarization. Here, we demonstrated that genetic depletion of MPC blocks the entry of lactate into mitochondria in macrophages. However, MPC-mediated metabolism was dispensable for IL-4/lactate-induced macrophages polarization as well as tumor growth. In addition, MPC depletion had no impact on hypoxia-inducible factor 1α (HIF-1α) stabilization and histone lactylation, both of which are required for TAMs polarization. Our study suggests that lactate itself, rather than its downstream metabolites, is responsible for TAMs polarization.