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There is no definitive approach for assessing mesenteric ischemia and determining the optimal timing for endovascular intervention in the management of spontaneous isolated dissection of the superior mesenteric artery (SISMAD). A 56-year-old male with acute abdominal pain was diagnosed with SISMAD. After evaluating mesenteric ischemia through mesenteric fractional flow reserve (FFR), FFR was 0.72, and the patient was recommended conservative treatment for SISMAD, which involves fasting, total parenteral nutrition, and anticoagulation. The patient's syndrome was relieved after conservative treatment for 14 days without stent implantation. Over the next 5 years, no recurrence of abdominal pain or worsening of SISMAD was observed in the patient. Assessing the severity of mesenteric ischemia can be done through mesenteric FFR. Upon confirmation of the exclusion of risks related to dilatation or rupture of SISMAD aneurysm, an approach in favor of conservative management for SISMAD may indeed be considered pragmatic when the FFR exceeds 0.72.
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This study aimed to examine the relationship between blood pressure (BP) and blood pressure variability (BPV) during the first 24 hours from admission with 90-day functional outcomes in acute ischemic stroke (AIS) patients whose onset within 24 hours and receiving early argatroban treatment. The study recruited 214 AIS patients. BP was monitored using a cuff at 1-hour fixed intervals, and BP/BPV parameters [standard deviation (SD), coefficient of variation (CV), successive variation (SV), and average real variability (ARV)] were collected. Age, the National Institutes of Health Stroke Scale (NIHSS) score at admission, previous history of diabetes mellitus (DM), and infarction site (located in anterior circulation) were identified as independent factors affecting 90-day outcomes in multiple logistic regression. After adjusting for confounding variables, association between BP/BPV and 90-day modified Rankin Scale (mRS) was assessed using logistic regression models. In model 1 (adjusted for age and NIHSS score at admission), mean-systolic blood pressure (SBP) showed association with 90-day outcomes [1.068 (1.008, 1.131), Pâ =â .025]. In model 2 (adjusted for age, NIHSS score at admission, previous history of DM), mean-SBP [1.061 (1.001, 1.123), Pâ =â .045] and max-SBP [0.951 (0.906, 0.998), Pâ =â .040] showed relatively weak association with outcomes. In model 3 [adjusted for age, NIHSS score at admission, previous history of DM, infarct site (located in anterior circulation)], all BP values were not related with outcomes, meanwhile, none of the BPV parameters calculated from SBP, diastolic blood pressure and mean arterial pressure showed association with 90-day outcomes. Future prospective studies are required to assess the relationship between early BP/BPV parameters with 90-day outcomes and further clarify the reference values for BP parameters. This is important for effective BP/BPV management and improved patient prognosis.
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Presión Sanguínea , Accidente Cerebrovascular Isquémico , Humanos , Femenino , Masculino , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Anciano , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Resultado del Tratamiento , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Arginina/análogos & derivados , Ácidos PipecólicosRESUMEN
Sorghum northern anthracnose is a leaf disease affecting sorghum, which results in plant death and substantial yield loss. This study aimed to effectively understand the disease, clarify its biological characteristics, and evaluate the resistance of germplasm resources. A field sample was collected to isolate and purify the pathogen. The pathogen, identified as Kabatiella zeae Narita et Hiratsuka using both morphological and molecular techniques, was further confirmed as the causative agent of northern anthracnose of sorghum following Robert Koch's principles. The results revealed the optimal culture temperature to be 25 °C, preferred dark culture conditions, and the best growth on potato glucose agar medium with sucrose and L-leucine as the optimal carbon and nitrogen sources, respectively. A total of 138 sorghum germplasm resources were inoculated and evaluated using the isolated pathogen, with 20 lines (14.49%) exhibiting high resistance, 18 lines (13.04%) showing disease resistance, 27 lines (19.57%) demonstrating medium resistance, 37 lines (26.81%) being susceptible, and 36 lines (26.09%) classified as highly susceptible. The indoor fungicide screening was conducted through pathogen medium application, and enilconazole, pyraclostrobin, methylthiophanate, and flusilazole were screened for the best fungicide inhibition with a 100% inhibition rate compared with the control. This study provides reference for field pharmaceutical control in sorghum production.
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The silkworm is an incredibly valuable insect that produces silk through its silk gland. Within this organ, Fibroinase has been identified and named due to its ability to fibroin degradation. The expression of Fibroinase in the silk gland significantly increases during the larval-pupal stage, which might be associated with the degeneration of the silk gland. In this study, Fibroinase was overexpressed and knocked down specifically both in the middle and posterior silk glands, respectively, using transgenic technology. The investigation of silk gland development in these transgenic silkworms showed that Fibroinase plays a direct role in accelerating silk gland degeneration. The staining analyses performed in the silk glands of transgenic silkworms suggest that Fibroinase is involved in the processes of autophagy and apoptosis during silk gland degeneration. Further experiments demonstrated that Fibroinase, acting as a lysosomal regulator, negatively regulates autophagy via the mTOR (mechanistic target of rapamycin) pathway. Moreover, during apoptosis, Fibroinase could activate Caspase3 by increasing the activity of BmCaspase1, ultimately accelerating the apoptosis process. These findings enhance our understanding of the physiological role of Fibroinase in promoting silk gland degeneration, which plays a role in breaking down proteins in the silk gland and coordinating the regulation of autophagy and apoptosis.
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Objectives: Cardiogenic cerebral embolism (CCE) poses a significant health risk; however, there is a dearth of published prognostic prediction models addressing this issue. Our objective is to establish prognostic prediction models (PM) for predicting poor functional outcomes at 3 months in patients with acute CCE associated with non-valvular atrial fibrillation (NVAF) and perform both internal and external validations. Methods: We included a total of 730 CCE patients in the development cohort. The external regional validation cohort comprised 118 patients, while the external time-sequential validation cohort included 63 patients. Multiple imputation by chained equations (MICE) was utilized to address missing values and the least absolute shrink and selection operator (LASSO) regression was implemented through the glmnet package, to screen variables. Results: The 3-month prediction model for poor functional outcomes, denoted as N-ABCD2, was established using the following variables: NIHSS score at admission (N), Age (A), Brain natriuretic peptide (BNP), C-reactive protein (CRP), D-dimer polymers (D), and discharge with antithrombotic medication (D). The model's Akaike information criterion (AIC) was 637.98, and the area under Curve (AUC) for the development cohort, external regional, and time-sequential cohorts were 0.878 (95% CI, 0.854-0.902), 0.918 (95% CI, 0.857-0.979), and 0.839 (95% CI, 0.744-0.934), respectively. Conclusion: The N-ABCD2 model can accurately predict poor outcomes at 3 months for CCE patients with NVAF, demonstrating strong prediction abilities. Moreover, the model relies on objective variables that are readily obtainable in clinical practice, enhancing its convenience and applicability in clinical settings.
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BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.
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Shewanella oneidensis MR-1 has found widespread applications in pollutant transformation and bioenergy production, closely tied to its outstanding heme synthesis capabilities. However, this significant biosynthetic potential is still unexploited so far. Here, we turned this bacterium into a highly-efficient bio-factory for green synthesis of 5-Aminolevulinic Acid (5-ALA), an important chemical for broad applications in agriculture, medicine, and the food industries. The native C5 pathway genes of S. oneidensis was employed, together with the introduction of foreign anti-oxidation module, to establish the 5-ALA production module, resulting 87-fold higher 5-ALA yield and drastically enhanced tolerance than the wild type. Furthermore, the metabolic flux was regulated by using CRISPR interference and base editing techniques to suppress the competitive pathways to further improve the 5-ALA titer. The engineered strain exhibited 123-fold higher 5-ALA production capability than the wild type. This study not only provides an appealing new route for 5-ALA biosynthesis, but also presents a multi-dimensional modularized engineering strategy to broaden the application scope of S. oneidensis.
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Ácido Aminolevulínico , Ingeniería Metabólica , Shewanella , Shewanella/genética , Shewanella/metabolismo , Ácido Aminolevulínico/metabolismoRESUMEN
Alternative polyadenylation (APA), an important post-transcriptional regulatory mechanism, is aberrantly activated in cancerï¼but how APA functions in tumorigenesis remains elusive. We analyzed APA events in RNA-seq data in TCGA and reported 3'UTR alterations associated with esophageal squamous cell carcinoma (ESCC) patient prognosis and gene expression changes involving loss of tumor-suppressive miRNA binding sites. Moreover, we investigated the expression and function of cleavage and polyadenylation specific factor 3 (CPSF3), a key APA regulator in ESCC. By immunohistochemistry and qRT-PCR, we found that CPSF3 was highly expressed in ESCC tissues and associated with poor patient prognosis. Overexpression of CPSF3 enhanced, while knockdown of CPSF3 inhibited ESCC cell proliferation and migration in vitro and in vivo, as determined by colony formation, transwell assays and animal experiments. Iso-Seq and RNA-seq data analysis indicated that knockdown of CPSF3 favored use of the distal poly (A) site in the 3'UTR of Cornichon family AMPA receptor auxiliary protein 2 (CNIH2), resulting in a long-3'UTR CNIH2 isoform that produced less CNIH2 protein due to miR-125a-5p targeting and downregulating CNIH2 mRNA through a miR-125a-5p binding site in the long CNIH2 mRNA 3'UTR. Moreover, CPSF3-induced ESCC tumorigenicity was mediated by CNIH2. Taken together, CPSF3 promotes ESCC progression by upregulating CNIH2 expression through loss of miR-125a-5p-mediated CNIH2 repression through alternative splicing and polyadenylation of the CNIH2 mRNA 3'UTR.
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Proliferación Celular , Factor de Especificidad de Desdoblamiento y Poliadenilación , Progresión de la Enfermedad , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Poliadenilación , Animales , Femenino , Humanos , Masculino , Ratones , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular , Factor de Especificidad de Desdoblamiento y Poliadenilación/genética , Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico , Receptores AMPA/genética , Receptores AMPA/metabolismoRESUMEN
Silkworm is a highly valuable insect that produces silk through secretion by a silk gland. Within this gland, a type of cathepsin L protease called Fibroinase was identified as an enzyme for hydrolyzing the primary components of silk, including fibroin and sericin. Here, we determined the crystal structure of Fibroinase fromBombyx mori at a resolution of 1.56 Å. Comparative structural analysis revealed that Fibroinase adopted a similar structural pattern with papain-type cathepsin, consisting of an N-terminal domain and a C-terminal domain. The interface between the domains forms a substrate-binding cleft, where the E64 inhibitor noncovalently binds in a novel manner. Additionally, computational simulations combined with biochemical analysis allowed us to define the binding mode and inhibition mechanism of physiological inhibitor Bombyx cysteine protease inhibitor (BCPI) with Fibroinase. Moreover, the expression profiles and RNA interference of Fibroinase indicated its critical role in removing silk proteins in the silk gland lumen and the destruction of silk gland tissue during the larval-pupal metamorphosis. These findings enhance our understanding of the structural and biochemical features of Fibroinase and its inhibitors, while also providing evidence for the physiological role of Fibroinase in silk gland development.
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Two new nervogenic acid derivatives liparisnervosides Q (1) and R (5), as well as five known nervogenic acid derivatives (2-4, 6, 7) and four phenanthrenes (8-11) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray) Lindl.. Their structures were detremined using extensive spectroscopic techniques, including 1D, 2D NMR, and HR-ESI-MS, and acid hydrolysis. Furthermore, their antimicrobial and immunosuppressive activities were evaluated. Nervosine VII (3) exhibited antimicrobial activity against Staphylococcus aureus with an MIC of 62.5â µg/mL and inhibited the proliferation of human T cells with an IC50 value of 9.67±0.96â µM. These findings contribute to our understanding of the potential pharmacological properties of these compounds.
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Proliferación Celular , Inmunosupresores , Pruebas de Sensibilidad Microbiana , Fenantrenos , Staphylococcus aureus , Humanos , Inmunosupresores/farmacología , Inmunosupresores/química , Inmunosupresores/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fenantrenos/farmacología , Fenantrenos/química , Fenantrenos/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Linfocitos T/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Relación Dosis-Respuesta a DrogaRESUMEN
Background: Minor ischemic stroke (MIS) is associated with early neurological deterioration (END) and poor prognosis. Here, we investigated whether argatroban administration can mitigate MIS-associated END and improve functional outcomes by monitoring activated partial thrombin time (APTT). Methods: Data were collected for patients with MIS admitted to our hospital from January 2019 to December 2022. Patients were divided into a dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) and an argatroban group (aspirin + argatroban). Those in the latter group who achieved a target APTT of 1.5-3-fold that of baseline and <100 s at 2 h after argatroban infusion were included in the argatroban subgroup. The primary outcome was the END rate of the DAPT group versus that of the argatroban group or the argatroban subgroup. Secondary outcomes included the proportion of patients with modified Rankin Scale (mRS) 0-2 at 7 and 90 days. In addition, baseline date were compared between patients with and without END in the argatroban group. Results: 363 patients were included in the DAPT group and 270 in the argatroban group. There were no significant differences in any above outcome between them. 207 pairs were included in the DAPT group and the argatroban subgroup after 1:1 propensity score matching (PSM). Significant differences were observed in the proportion of END (OR, 2.337; 95% CI, 1.200-4.550, p = 0.011) and mRS 0-2 at 7 days (OR, 0.624; 95% CI, 0.415-0.939, p = 0.023), but not in mRS 0-2 at 90 days or the hemorrhagic events between the two groups. In the argatroban group, univariate analysis showed that the rate of diabetes (OR, 2.316; 95% CI, 1.107-4.482, p = 0.023), initial random blood glucose (OR, 1.235; 95% CI, 1.070-1.425, p = 0.004), drinking history (OR, 0.445; 95% CI, 0.210-0.940, p = 0.031) or those reaching the target APTT (OR, 0.418; 95% CI, 0.184-0.949, p = 0.033) was significantly different among patients with and without END. However, there were no statistical differences in these parameters between them following multivariate analysis. Conclusion: In patients with MIS, argatroban administration and reaching the target APTT can reduce the incidence of END and improve short-term functional prognosis.
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It is increasingly recognized that an important step towards improving overall health is to accurately measure biomarkers of health from the molecular activities prevalent in the oral cavity. We present a general methodology for computationally quantifying the activity of microbial functional pathways using metatranscriptomic data. We describe their implementation as a collection of eight oral pathway scores using a large salivary sample dataset (n = 9350), and we evaluate score associations with oropharyngeal disease phenotypes within an unseen independent cohort (n = 14,129). Through this validation, we show that the relevant oral pathway scores are significantly worse in individuals with periodontal disease, acid reflux, and nicotine addiction, compared with controls. Given these associations, we make the case to use these oral pathway scores to provide molecular health insights from simple, non-invasive saliva samples, and as molecular endpoints for actionable interventions to address the associated conditions.
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The subgingival microbiome has been implicated in oral and systemic diseases such as periodontitis and Alzheimer's disease. However, subgingival sampling is challenging. We developed a novel method of sampling the subgingival microbiome by rotationally swabbing the supragingival area, named subgingival-P (for proxy) samples. We sampled and metatranscriptomically analyzed subgingival and subgingival-P samples of three different teeth in 20 individuals. The subgingival-P samples were comparable to the subgingival samples in the relative abundances of microorganisms and microbial gene expression levels. Our data demonstrate that the novel method of collecting and analyzing the subgingival-P samples can act as a proxy for the subgingiva, paving the way for large and diverse studies investigating the role of the subgingival microbiome in health and disease.
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Microbiota , Periodontitis , Humanos , Encía , Microbiota/genéticaRESUMEN
BACKGROUND: To investigate the association of 10 genetic variations and 10 environmental factors with myopia of different severities in different age groups of children and adolescents in northeast China. METHODS: Parental history and genetic testing for myopia-related susceptibility genes were carried out in a cohort of children and adolescents aged 2-17 years. In addition, 10 single nucleotide polymorphism (SNP) sites for genotyping and 10 environmental risk factors were selected, and the differences between site variation and environmental factors in different age groups with different degrees of myopia were explored. RESULTS: A total of 2497 volunteers were recruited, including 2023 myopes and 474 non-myopes in the control group. From the cohort, 1160 subjects were sequenced for myopia SNP sites. Compared with the non-myopic group, the myopia of parents, outdoor activity less than 60 min per day, and a high-sugar diet were risk factors for developing myopia. Two syntrophin beta 1 (SNTB1) sites, rs4455882 and rs6469937 were found to be significantly associated with moderate myopia; fibroblast growth factor 10 (FGF10) rs339501 was significantly correlated with high myopia; and insulin-like growth factor 1 (IGF1) rs5742714 was significantly correlated with different degrees of myopia in the age group of <6 years. Finally, the FGF10 gene rs339501 SNP was significantly associated with moderate myopia and mild myopia in the 6- to 12-year-old age group. CONCLUSIONS: Our results indicate that myopia is affected by both environmental and genetic factors. To prevent and control myopia, attention should be paid to the parental history of myopia, a high-sugar diet should be avoided, and outdoor time should be adjusted according to the average daily sunshine. In addition, it is necessary to pay attention to the increased risk of myopia in school-age children caused by SNTB1 rs4455882, FGF10 rs339501, and IGF1 rs5742714.
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Miopía , Enfermedad Pulmonar Obstructiva Crónica , Adolescente , Niño , Humanos , Pueblo Asiatico , China/epidemiología , Miopía/etiología , Miopía/genética , Polimorfismo de Nucleótido Simple , Azúcares , Preescolar , Enfermedad Pulmonar Obstructiva Crónica/genéticaRESUMEN
INTRODUCTION: Assessment of near work-induced transient myopia (NITM) is important for permanent myopia development and progression. Atropine eye drop has been reported to be beneficial in reducing initial NITM and slowing down myopic progression. This study aimed to investigate the efficacy of 0.01% atropine in treating NITM and its possible association with the progression of refractive change in Chinese myopic children. METHODS AND ANALYSIS: The study is designed as a parallel assignment prospective, randomised, double-blinded, placebo-controlled trial conducted at He Eye Specialist Hospital in Shenyang, China. One hundred fifty participants will be randomly assigned in a 1:1 ratio to receive 0.01% atropine or placebo eye drop once nightly bilaterally for 1 year. Initial NITM, cycloplegic refraction, axial length, best-corrected visual acuity, intraocular pressure and pupil diameter will be measured at baseline, 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Visual Function Questionnaire will be administered at baseline and each follow-up visit. Adverse events also will be monitored and documented at each subsequent follow-up visit. ETHICS AND DISSEMINATION: A parallel assignment prospective, randomised, double-blinded, placebo-controlled trial to evaluate the efficacy of 0.01% atropine for near work-induced transient myopia and myopic progression registered on 10 September 2023. Ethics approval number: IRB (2023) K025.01. The study's findings will be shared regardless of the effect's direction. TRIAL REGISTRATION NUMBER: NCT06034366.
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Atropina , Miopía , Masculino , Niño , Humanos , Atropina/uso terapéutico , Estudios Prospectivos , Miopía/tratamiento farmacológico , Método Doble Ciego , Soluciones Oftálmicas/uso terapéutico , China , Progresión de la Enfermedad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Interoception plays a crucial role in maintaining bodily homeostasis and promoting survival, and is considered the basis of human emotion, cognition, and self-formation. A malfunction of interoception is increasingly suggested to be a fundamental component of different mental health conditions, and depressive disorders have been especially closely associated. Interoceptive signaling and processing depends on a system called the "interoceptive pathway," with the insula, located in the deep part of the lateral fissure, being the most important brain structure in this pathway. Neuroimaging studies have revealed alterations in the structure and function of the insula in a large number of individuals with depression, yet the precise relationship between these alterations and interoceptive dysfunction remains unclear. The goal of this review is to examine the evidence that exists for dysfunction of interoception in people with Major Depressive Disorder (MDD), and to determine the associated specific alterations in the structure and function of the insula revealed by neuroimaging. Overall, three aspects of the potential relationship between interoceptive dysfunction and alterations in insular function in people with depression have been assessed, namely clinical symptoms, quantitative measures of interoceptive function and ability, and interoceptive modulation. To conclude, several specific limitations of the published studies and important lines of enquiry for future research are offered.
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Peptide loading of MHC class II (MHCII) molecules is facilitated by HLA-DM (DM), which catalyzes CLIP release, stabilizes empty MHCII, and edits the MHCII-bound peptide repertoire. HLA-DO (DO) binds to DM and modulates its activity, resulting in an altered set of peptides presented at the cell surface. MHCII-peptide presentation in individuals with type 1 diabetes (T1D) is abnormal, leading to a breakdown in tolerance; however, no direct measurement of the MHCII pathway activity in T1D patients has been performed. In this study, we measured MHCII Ag-processing pathway activity in humans by determining MHCII, MHCII-CLIP, DM, and DO levels by flow cytometry for peripheral blood B cells, dendritic cells, and monocytes from 99 T1D patients and 97 controls. Results showed that MHCII levels were similar for all three APC subsets. In contrast, MHCII-CLIP levels, independent of sex, age at blood draw, disease duration, and diagnosis age, were significantly increased for all three APCs, with B cells showing the largest increase (3.4-fold). DM and DO levels, which usually directly correlate with MHCII-CLIP levels, were unexpectedly identical in T1D patients and controls. Gene expression profiling on PBMC RNA showed that DMB mRNA was significantly elevated in T1D patients with residual C-peptide. This resulted in higher levels of DM protein in B cells and dendritic cells. DO levels were also increased, suggesting that the MHCII pathway maybe differentially regulated in individuals with residual C-peptide. Collectively, these studies show a dysregulation of the MHCII Ag-processing pathway in patients with T1D.
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Diabetes Mellitus Tipo 1 , Antígenos HLA-D , Humanos , Antígenos HLA-D/genética , Péptido C , Leucocitos Mononucleares/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Péptidos/metabolismo , Presentación de AntígenoRESUMEN
Interfacial layers with brittle intermetallic compounds (IMC) greatly influence the performance of steel-aluminum friction stir lap welding (FSLW) joints. Thus, the formation and evolution of IMC between 7075-T6 aluminum alloy and galvanized DP590 steel in steel-aluminum FSLW joints were investigated. An FSLW numerical model was developed using the computational fluid dynamics method to analyze the interface temperature between the aluminum alloy and steel. Scanning electron microscopy (SEM) was conducted to observe the microstructure characterization and measure the IMC thickness. Phases among different joint zones were analyzed by X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS). IMC layer formation was predicted by the effective Gibbs free energy model presented in this paper according to thermodynamic principles. The Monte Carlo method was utilized to predict the thickness of IMC layers. It was found that the IMC layer at the interface of the welded joint is composed of Fe2Al5, FeAl3, and Al-Zn eutectic. The IMC thickness decreased from 4.3 µm to 0.8 µm with the increasing welding speed, which was consistent with the Monte Carlo simulation results.
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Objective: In developed countries, midday napping and nighttime sleep duration have been linked to long-term survival; however, little is known about such effects in less developed regions. Therefore, this study aimed to assess the associations of midday napping and nocturnal sleep with mortality in middle-aged and older Chinese adults. Methods: A nationwide cohort of 15,524 adults aged ≥ 45 years was enrolled from 28 provincial regions across mainland China and followed up from 2011 to 2018, using data from the Chinese Health and Retirement Longitudinal Study. Midday napping and nighttime sleep duration were assessed using standardized questionnaires. Cox proportional hazards models with random intercepts for the surveyed provinces were used to estimate hazard ratios ( HRs) of all-cause mortality, adjusting for sociodemographic characteristics, behavioral factors, and health status. Results: A total of 1,745 deaths occurred during a median follow-up of 7.1 years, and the mean (standard deviation) age was 59 (10.1) years at baseline. Compared with non-nappers, over 60 min nappers had a higher risk of all-cause mortality [ HR: 1.35, 95% confidence interval ( CI): 1.17-1.56], while no significant associations were observed among < 30 min nappers. Compared with sleep duration of 6-8 h/night, both short (< 6 h) and long (≥ 8 h) sleep duration were significantly associated with increased mortality, with corresponding HR (95% CI) estimates of 1.21 (1.05-1.38) and 1.26 (1.10-1.44), respectively. We observed significant patterns for greater risks associated with longer nap duration, with a P trend value < 0.001 for all-cause mortality. No significant evidence of an additive interaction was identified between midday napping and nighttime sleep. Conclusion: Long midday napping and inappropriate nighttime sleep were independently associated with an increased risk of all-cause mortality in middle-aged and older Chinese populations. Biological studies are needed to validate our findings and clarify the mechanisms underlying this association.
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Duración del Sueño , Sueño , Adulto , Persona de Mediana Edad , Humanos , Anciano , Estudios Longitudinales , Estudios Prospectivos , China/epidemiologíaRESUMEN
Pain is considered an unpleasant perceptual experience associated with actual or potential somatic and visceral harm. Human subjects have different sensitivity to painful stimulation, which may be related to different painful response pattern. Excellent studies using functional magnetic resonance imaging (fMRI) have found the effect of the functional organization of white matter (WM) on the descending pain modulatory system, which suggests that WM function is feasible during pain modulation. In this study, 26 pain sensitive (PS) subjects and 27 pain insensitive (PIS) subjects were recruited based on cold pressor test. Then, all subjects underwent the cold bottle test (CBT) in normal (26 degrees temperature stimulating) and cold (8 degrees temperature stimulating) conditions during fMRI scan, respectively. WM functional networks were obtained using K-means clustering, and the functional connectivity (FC) was assessed among WM networks, as well as gray matter (GM)-WM networks. Through repeated measures ANOVA, decreased FC was observed between the GM-cerebellum network and the WM-superior temporal network, as well as the WM-sensorimotor network in the PS group under the cold condition, while this difference was not found in PIS group. Importantly, the changed FC was positively correlated with the state and trait anxiety scores, respectively. This study highlighted that the WM functional network might play an integral part in pain processing, and an altered FC may be related to the descending pain modulatory system.