Hereditary human coagulation factor VII (FVII) deficiency is an inherited autosomal recessive hemorrhagic disease involving mutations in the F7 gene. The sites and types of F7 mutations may influence the coagulation activities of plasma FVII (FVII C) and severity of hemorrhage symptoms. However, the specific mutations that impact FVII activity are not completely known.

We tested the coagulation functions and plasma activities of FVII in seven patients recruited from six families with hereditary FVII deficiency and sequenced the F7 gene of the patients and their families. Then, we analyzed the genetic information from the six families and predicted the structures of the mutated proteins.

In this study, we detected 11 F7 mutations, including four novel mutations, in which the mutations p.Phe84Ser and p.Gly156Cys encoded the Gla and EGF domains of FVII, respectively, while the mutation p.Ser339Leu encoded the recognition site of the enzymatic protein and maintained the conformation of the catalytic domain structure. Meanwhile, the mutation in the 5' untranslated region (UTR) was closely associated with the mRNA regulatory sequence.

We have identified novel genetic mutations and performed pedigree analysis that shed light on the pathogenesis of hereditary human coagulation FVII deficiency and may contribute to the development of treatments for this disease.
We have identified novel genetic mutations and performed pedigree analysis that shed light on the pathogenesis of hereditary human coagulation FVII deficiency and may contribute to the development of treatments for this disease.A 55-year-old obese, diabetic and hypertensive female patient with history of cerebrovascular stroke 2 years ago was referred for echocardiography. Transthoracic echocardiography revealed a well-defined rounded mass located at the posterior mitral annulus. The mass had a sharp hyperechoic outer border and a central echolucency. Transesophageal and three-dimensional echocardiography confirmed these findings consistent with caseous calcification of the mitral annulus. This case presents a rare variant of mitral annular calcification considered in the differential diagnosis of cardiac masses that can be recognized by its characteristic appearance on echocardiography. As with mitral annular calcification, multiple cardiovascular risk factors are commonly associated.Conductive metal-organic frameworks (cMOFs) are emerging materials for various applications due to their high surface area, high porosity, and electrical conductivity. However, it is still challenging to develop cMOFs having high surface reactivity and durability. Here, highly active and stable cMOF are presented via the confinement of bimetallic nanoparticles (BNPs) in the pores of a 2D cMOF, where the confinement is guided by dipolar-interaction-induced site-specific nucleation. Heterogeneous metal precursors are bound to the pores of 2D cMOFs by dipolar interactions, and the subsequent reduction produces ultrasmall (≈1.54 nm) and well-dispersed PtRu NPs confined in the pores of the cMOF. PtRu-NP-decorated cMOFs exhibit significantly enhanced chemiresistive NO2 sensing performances, owing to the bimetallic synergies of PtRu NPs and the high surface area and porosity of cMOF. The approach paves the way for the synthesis of highly active and conductive porous materials via bimetallic and/or multimetallic NP loading.Extracellular vesicles (EVs) have emerged as key regulators of immune function across multiple diseases. Severe burn injury is a devastating trauma with significant immune dysfunction that results in an ∼12% mortality rate due to sepsis-induced organ failure, pneumonia, and other infections. Severe burn causes a biphasic immune response an early (0-72 h) hyper-inflammatory state, with release of damage-associated molecular pattern molecules, such as high-mobility group protein 1 (HMGB1), and proinflammatory cytokines (e.g., IL-1β), followed by an immunosuppressive state (1-2+ wk post injury), associated with increased susceptibility to life-threatening infections. We have reported that early after severe burn injury HMGB1 and IL-1β are enriched in plasma EVs. Here we tested the impact of EVs isolated after burn injury on phenotypic and functional consequences in vivo and in vitro using adoptive transfers of EV. EVs isolated early from mice that underwent a 20% total body surface area burn injury (burn EVs) caused similar hallmark cytokine responses in naïve mice to those seen in burned mice. Burn EVs transferred to RAW264.7 macrophages caused similar functional (i.e., cytokine secretion) and immune gene expression changes seen with their associated phase of post-burn immune dysfunction. Burn EVs isolated early (24 h) induced MCP-1, IL-12p70, and IFNγ, whereas EVs isolated later blunted RAW proinflammatory responses to bacterial endotoxin (LPS). We also describe significantly increased HMGB1 cargo in burn EVs purified days 1 to 7 after injury. Thus, burn EVs cause immune outcomes in naïve mice and macrophages similar to findings after severe burn injury, suggesting EVs promote post-burn immune dysfunction.
The therapeutic effect of acupuncture treatments (AT) on functional gastrointestinal disorders (FGIDs) is contentious. A meta-analysis was conducted to assess the efficacy and safety of acupuncture for FGIDs.

The Cochrane Library, EMBASE, PUBMED, Web of Science, Wanfang Database, China National Knowledge Infrastructure, and VIP Database were searched through December 31, 2019 with no language restrictions. Risk ratio (RR) with 95% confidence interval (CI) was calculated to determine the improvement in symptom severity after treatment.

A total of 61 randomized controlled trials (RCTs) on FGIDs were included. The pooled results illustrated the following compared to pharmacotherapy (RR 1.13, 95% CI 1.09-1.17), placebo acupuncture (RR 1.69, 95% CI 1.37-2.08), no specific treatment (RR 1.86, 95% CI 1.31-2.62), and AT as an adjuvant intervention to other active treatments (RR 1.25, 95% CI 1.21-1.30), AT had more favorable improvements in symptom severity; sub-group analysis results classified according to functional dyspepsia, irritable bowel syndrome, and functional constipation also supported this finding; and the incidence of adverse events was lower in AT than in other treatments (RR 0.75, 95% CI 0.56-0.99).

This meta-analysis found that AT was significantly associated with relief of FGIDs symptoms; however, the evidence level was moderate or low. Further data from rigorously designed and well powered RCTs are needed to verify the effectiveness and safety of AT as a FGIDs treatment.

CRD42020169508.
CRD42020169508.Anthropogenic transformation of land globally is threatening water resources in terms of quality and availability. Managing water resources to ensure sustainable utilization is important for a semiarid country such as South Africa. Bayesian networks (BNs) are probabilistic graphical models that have been applied globally to a range of water resources management studies; however, there has been very limited application of BNs to similar studies in South Africa. This article explores the benefits and challenges of BN application in the context of water resources management, specifically in relation to South Africa. A brief overview describes BNs, followed by details of some of the possible opportunities for BNs to benefit water resources management. These include the ability to use quantitative and qualitative information, data, and expert knowledge. BN models can be integrated into geographic information systems and predict impact of ecosystem services and sustainability indicators. With additional data and information, BNs can be updated, allowing for integration into an adaptive management process. Challenges in the application of BNs include oversimplification of complex systems, constraints of BNs with categorical nodes for continuous variables, unclear use of expert knowledge, and treatment of uncertainty. BNs have tremendous potential to guide decision making by providing a holistic approach to water resources management.Given limited resources for conservation, we adapted and scaled up a decision-support tool that is spatially explicit and links land and sea management decisions. We used open-access global geospatial datasets and software to inform the prioritization of future forest management interventions that can have the greatest benefit on marine conservation in Vanuatu (Oceania). We compared outputs from 2 global marine habitat maps to maximize sediment retention, water quality, and functioning coastal and marine ecosystems. By combining the outputs obtained from both marine habitat maps, we incorporated elements unique to each and provided higher confidence in prioritization results; priority sites for restoration were more sensitive to the source of data for habitat mapping. Regardless of marine habitat data source, prioritized areas were mostly located in watersheds on the windward side of the large high islands, which are exposed to higher tropical rainfall, upstream from large sections of coral reef and seagrass habitats. Thus, these areas are vulnerable to anthropogenic effects (e.g., land-use change). Forest protection and restoration in these areas can maintain clean water and functioning, productive ecosystems through sediment retention, which supports the well-being of neighboring communities. The nationwide application of this linked land-sea tool can help managers prioritize watershed-based management actions based on quantitative synergies and trade-offs across terrestrial and marine ecosystems in data-poor regions. Our framework can be used to guide implementation of land-to-sea management across the Pacific region and beyond. This article is protected by copyright. All rights reserved.Periodontitis is one of the most common oral diseases worldwide, and it is associated with various systemic diseases, including cognitive diseases. STAT3 regulates the inflammatory cascade and influences adaptive immunity by modulating Th17/Treg cell differentiation. In this study, we aimed to explore the effect of adaptive immunity inside and outside the brain on the association between periodontitis and cognitive impairment and understand the role of the STAT3 signaling pathway. We established Porphyromonas gingivalis LPS-induced periodontitis mice models by injecting P. https://www.selleckchem.com/products/noradrenaline-bitartrate-monohydrate-levophed.html gingivalis LPS into the gingival sulcus of mice. Behavioral tests showed that learning and memory abilities were impaired. The flow cytometry data showed an imbalance in the Th17/Treg ratio in the blood and brain samples of the mice. The expression of Th17-related cytokines (IL-1β, IL-17A, IL-21, and IL-22) increased, whereas that of Treg-related cytokines (IL-2 and IL-10) decreased in both the blood and the brain. The level of LPS increased and the STAT3 signaling pathway was activated during this process. These effects were reversed by C188-9, a STAT3 inhibitor. In conclusion, P. gingivalis LPS-induced periodontitis may promote the occurrence and progression of cognitive impairment by modulating the Th17/Treg balance inside and outside the brain. The STAT3 signaling pathway may have immunoregulatory effects on the mouth-to-brain axis.