A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the ...impact of circulating exosomes on HCC development and recurrence. One‐shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha‐fetoprotein (AFP), but exosome‐free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR‐92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR‐92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR‐92b. The hepatoma‐derived exosomal miR‐92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell‐mediated cytotoxicity. Furthermore, higher expression of miR‐92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma‐derived exosomal miR‐92b. The value of circulating exosomal miR‐92b may predict the risk of posttransplant HCC recurrence.
This study demonstrates the impact of circulating exosomes on liver cancer development in rats, explores functional roles of exosomal miR‐92b in the tumor microenvironment, and verifies its clinical value for early prediction of posttransplant hepatocellular carcinoma recurrence.
In a smart home linked to a smart grid (SG), demand-side management (DSM) has the potential to reduce electricity costs and carbon/chlorofluorocarbon emissions, which are associated with electricity ...used in today's modern society. To meet continuously increasing electrical energy demands requested from downstream sectors in an SG, energy management systems (EMS), developed with paradigms of artificial intelligence (AI) across Internet of things (IoT) and conducted in fields of interest, monitor, manage, and analyze industrial, commercial, and residential electrical appliances efficiently in response to demand response (DR) signals as DSM. Usually, a DSM service provided by utilities for consumers in an SG is based on cloud-centered data science analytics. However, such cloud-centered data science analytics service involved for DSM is mostly far away from on-site IoT end devices, such as DR switches/power meters/smart meters, which is usually unacceptable for latency-sensitive user-centric IoT applications in DSM. This implies that, for instance, IoT end devices deployed on-site for latency-sensitive user-centric IoT applications in DSM should be aware of immediately analytical, interpretable, and real-time actionable data insights processed on and identified by IoT end devices at IoT sources. Therefore, this work designs and implements a smart edge analytics-empowered power meter prototype considering advanced AI in DSM for smart homes. The prototype in this work works in a cloud analytics-assisted electrical EMS architecture, which is designed and implemented as edge analytics in the architecture described and developed toward a next-generation smart sensing infrastructure for smart homes. Two different types of AI deployed on-site on the prototype are conducted for DSM and compared in this work. The experimentation reported in this work shows the architecture described with the prototype in this work is feasible and workable.
DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated ...5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology.
Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing. At the same time, we carried out total RNA sequencing (RNA-seq) to analyze the transcriptomes of brain regions and liver tissues.
Our results reveal preferential 5hmC enrichment in the gene bodies of expressed genes, and 5hmC levels of many protein-coding genes are positively correlated with RNA expression intensity. However, more than 75% of genes with low or no 5hmC enrichment are genes encode for mitochondrial proteins and ribosomal proteins despite being actively transcribed, implying different transcriptional regulation mechanisms of these housekeeping genes. Brain regions developed from the same embryonic structures have more similar 5hmC profiles. Also, the genic 5hmC enrichment pattern is highly tissue-specific, and 5hmC marks genes involving in tissue-specific biological processes. Sex chromosomes are mostly depleted of 5hmC, and the X inactive specific transcript (Xist) gene located on the X chromosome is the only gene to show sex-specific 5hmC enrichment.
This is the first report of the whole-genome 5hmC methylome of five major brain structures and liver tissues in mice of both sexes. This study offers a comprehensive resource for future work of mammalian cytosine methylation dynamics. Our findings offer additional evidence that suggests 5hmC is an active epigenetic mark stably maintained after the global reprogramming event during early embryonic development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intestinal homeostasis depends on interactions between the intestinal epithelium, the immune system and the microbiota. Because of these complicated connections, there are many problems that need to ...be solved. Current research has indicated that genes targeted by Wnt signaling are responsible for controlling intestinal stem cell fate and for modulating intestinal homeostasis. Our data show that loss of frizzled 7 (Fzd7), an important element in Wnt signaling, interrupts the differentiation of mouse intestinal stem cells into absorptive progenitors instead of secretory progenitors (precursors of goblet and Paneth cells). The alteration in canonical Wnt and Notch signaling pathways interrupts epithelial homeostasis, resulting in a decrease in physical protection in the intestine. Several phenotypes in our Fzd7-deleted model were similar to the features of enterocolitis, such as shortened intestines, decreased numbers of goblet cells and Paneth cells, and severe inflammation. Additionally, loss of Fzd7 exacerbated the defects in a chemical-induced colitis model and could initiate tumorigenesis. These findings may provide important information for the discovery of efficient therapeutic methods to treat enterocolitis and related cancers in the intestines.
Background
Dyspepsia is a prevalent condition in the general population. Besides organic causes, the differential diagnosis of dyspepsia includes functional dyspepsia (FD) and gastroparesis (GP) ...which share similar pathophysiological mechanisms and clinical presentation. So far, no study investigated the prevalence of FD and GP in a primary care in Belgium.
Methods
Data were obtained from Intego, a Flemish‐Belgian general practice‐based morbidity registration network. From 586,164 patients between 2000 and 2021, we selected patients with ICD‐10 code for FD and GP. Patients with organic gastrointestinal diseases were excluded. We determined demographics and comorbidities of FD/GP. For prevalence and incidence calculation, we included those who consulted their general practitioners at least once in the given year. Pair‐wise comparison was conducted to access the impact of comorbidities on risk of FD/GP.
Key Results
Between 2011 and 2021, the prevalence of FD/GP ranged from 1.03% to 1.21%. The incidence of FD/GP ranged from 109 to 142 per 100,000 adults. In total 5242 cases of FD/GP were identified. These cases shared commonly coexisting diagnoses of gastroesophageal reflux disease (18.8%), irritable bowel syndrome (17.1%), and chronic constipation (18.7%). Patients with somatization/anxiety/depression had significantly higher risk of FD/GP, compared to the control (OR 1.38, 95% CI 1.19–1.61, p < 0.01).
Conclusions and Inferences
The prevalence (1.03%–1.21%) and incidence (109–142/100,000) of FD/GP in primary care over last decade appear to conflict with epidemiological research in the general population. The discrepancies suggest a potential lack of awareness of FD and GP among physicians and/or patients in Flemish‐Belgium.
The prevalence (1.03%–1.21%) and incidence (109–142/100,000) of functional dyspepsia/gastroparesis in primary care remained stable over the past decade in primary care and were less prevalent than in the general population. The discrepancies suggest a potential lack of awareness of two entities among physicians and/or patients in Flemish‐Belgium.
Epithelial ovarian cancer (OC) is a heterogenous disease consisting of five major histologically distinct subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), endometrioid (ENOC), clear ...cell (CCOC) and mucinous (MOC). Although HGSOC is the most prevalent subtype, representing 70-80% of cases, a 2013 landmark study by Domcke et al. found that the most frequently used OC cell lines are not molecularly representative of this subtype. This raises the question, if not HGSOC, from which subtype do these cell lines derive? Indeed, non-HGSOC subtypes often respond poorly to chemotherapy; therefore, representative models are imperative for developing new targeted therapeutics.
Non-negative matrix factorisation (NMF) was applied to transcriptomic data from 44 OC cell lines in the Cancer Cell Line Encyclopedia, assessing the quality of clustering into 2-10 groups. Epithelial OC subtypes were assigned to cell lines optimally clustered into five transcriptionally distinct classes, confirmed by integration with subtype-specific mutations. A transcriptional subtype classifier was then developed by trialling three machine learning algorithms using subtype-specific metagenes defined by NMF. The ability of classifiers to predict subtype was tested using RNA sequencing of a living biobank of patient-derived OC models.
Application of NMF optimally clustered the 44 cell lines into five transcriptionally distinct groups. Close inspection of orthogonal datasets revealed this five-cluster delineation corresponds to the five major OC subtypes. This NMF-based classification validates the Domcke et al. analysis, in identifying lines most representative of HGSOC, and additionally identifies models representing the four other subtypes. However, NMF of the cell lines into two clusters did not align with the dualistic model of OC and suggests this classification is an oversimplification. Subtype designation of patient-derived models by a random forest transcriptional classifier aligned with prior diagnosis in 76% of unambiguous cases. In cases where there was disagreement, this often indicated potential alternative diagnosis, supported by a review of histological, molecular and clinical features.
This robust classification informs the selection of the most appropriate models for all five histotypes. Following further refinement on larger training cohorts, the transcriptional classification may represent a useful tool to support the classification of new model systems of OC subtypes.
Capreomycidine (Cap) is a nonproteinogenic amino acid and building block of nonribosomal peptide (NRP) natural products. We report the formation and activation of Cap in capreomycin biosynthesis. ...CmnC and CmnD catalyzed hydroxylation and cyclization, respectively, of l‐Arg to form l‐Cap. l‐Cap is then adenylated by CmnG‐A before being incorporated into the nonribosomal peptide. The co‐crystal structures of CmnG‐A with l‐Cap and adenosine nucleotides provide insights into the specificity and engineering opportunities of this unique adenylation domain.
The crystal structures of CmnG‐A, which activates a nonproteinogenic amino acid l‐Cap, provide insights into the specificity and engineering opportunities of adenylation domains.
: Walking while performing cognitive and motor tasks simultaneously interferes with gait performance and may lead to falls in older adults with mild cognitive impairment (MCI). Executive function, ...which seems to play a key role in dual-task gait performance, can be improved by combined physical and cognitive training. Virtual reality (VR) has the potential to assist rehabilitation, and its effect on physical and cognitive function requires further investigation. The purpose of this study was to assess the effects of VR-based physical and cognitive training on executive function and dual-task gait performance in older adults with MCI, as well as to compare VR-based physical and cognitive training with traditional combined physical and cognitive training.
: Thirty-four community-dwelling older adults with MCI were randomly assigned into either a VR-based physical and cognitive training (VR) group or a combined traditional physical and cognitive training (CPC) group for 36 sessions over 12 weeks. Outcome measures included executive function Stroop Color and Word Test (SCWT) and trail making test (TMT) A and B, gait performance (gait speed, stride length, and cadence) and dual-task costs (DTCs). Walking tasks were performed during single-task walking, walking while performing serial subtraction (cognitive dual task), and walking while carrying a tray (motor dual task). The GAIT Up system was used to evaluate gait parameters including speed, stride length, cadence and DTCs. DTC were defined as 100 * (single-task gait parameters - dual-task gait parameters)/single-task gait parameters.
: Both groups showed significant improvements in the SCWT and single-task and motor dual-task gait performance measures. However, only the VR group showed improvements in cognitive dual-task gait performance and the DTC of cadence. Moreover, the VR group showed more improvements than the CPC group in the TMT-B and DTC of cadence with borderline significances.
: A 12-week VR-based physical and cognitive training program led to significant improvements in dual-task gait performance in older adults with MCI, which may be attributed to improvements in executive function.
To achieve the goal of carbon emission reduction, a number of countries have implemented carbon tax policies, and carbon pricing has become an important tool. This paper discusses the interactions ...between a government and an enterprise for implementing carbon taxes over time or by level of tax, considering greenhouse gas emission. We examine the impacts of various carbon tax policies on enterprises' investments in new technology, their reductions in production quantity, and governments' tax remittances. A case study of the strategic responses of three firms in Taiwan's electronics, cement, and steel industries to two carbon emission policies promulgated by government shows that appropriate levels of tax can induce an enterprise to alter its production processes to achieve emission reduction as part of a long-term business strategy.
The
Polysaccharide (BSP), a natural polysaccharide derived from the east Asian terrestrial orchid
, is an anti-inflammatory, antiviral, and antioxidant polysaccharide. Traditionally, it has been used ...to treat hemostasis and for wound healing. In this study, BSP was blended with methylcellulose (MC) and methylparaben (MP) to create a hydrogel through a self-assembly route as a wound dressing. The developed hydrogels were designed as M2B
, M5B
, and M8B
. M stands for MC, and the number represents a percentage. Whereas the second letter of B stands for BSP, and
refers to the percentage variation of BSP:
= 0.5%, 1%, and 2%. All the developed MB hydrogels contained β-glucopyranosyl and α-mannopyranosyl, and rheology test had a tan δ value ≥ 0.5. The pore sizes of the hydrogels decreased by increasing the MC and BSP content, and they had better properties with respect to water loss and their swelling ratio. Evaluations in vitro and in vivo showed that all of the developed MB hydrogels have good cell viability and wound-healing properties. The M8B2 hydrogel group was found to be superior to the others from within the developed MB hydrogels. Therefore, we believe that the M8B2 hydrogel formulation has a high potential for development as a wound dressing.
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