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Gene therapy has a wide range of applications for various types of pathologies. Viral methods of gene delivery provide high levels of gene expression but have various safety concerns. Non-viral methods are largely known to provide lower levels of expression. We aim to address this issue by using plasmid DNA with smaller backbones to increase gene expression levels when delivered using non-viral methods. In this study we compare gene expression levels between two vectors with firefly luciferase encoding gene insert using liposome complexes and gene electrotransfer as delivery methods. A 2-fold reduction in plasmid vector backbone size, disproportionately enhanced gene expression levels more than 10-fold in rat tenocytes in vitro, and rat myocardium in vivo, while improvements in delivery to the skin were more moderate.Tendon injuries are a common athletic injury that have been increasing in prevalence. While there are current clinical treatments for tendon injuries, they have relatively long recovery times and often do not restore native function of the tendon. In the current study, gene electrotransfer (GET) parameters for delivery to the skin were optimized with monophasic and biphasic pulses with reporter and effector genes towards optimizing underlying tendon healing. Tissue twitching and damage, as well as gene expression and distribution were evaluated. Bioprinted collagen scaffolds, mimicking healthy tendon structure were then implanted subcutaneously for biocompatibility and angiogenesis analyses when combined with GET to accelerate healing. GET of human fibroblast FGF2 significantly increased angiogenesis and biocompatibility of the bioprinted implants when compared to implant only sites. The combination of bioprinted collagen fibers and angiogenic GET therapy may lead to better graft biocompatibility in tendon repair.Studying the acceptance of exoskeletons in industry has gained increased attention. Exoskeletons (wearable support devices) are envisioned to alleviate heavy work. Examining what factors influence the use of exoskeletons is important, because influencing these factors could positively contribute to the adoption of industrial exoskeletons. The factors identified in this paper have been systematically derived from empirical research with (potential future) end users, most of whom have tried on an exoskeleton. Our framework with factors influencing the acceptance of industrial exoskeletons can be used during the (ideally iterative) design, (re)development and evaluation phase of new or existing exoskeletons. This could improve the quality of exoskeletons since this allows designers to already consider acceptance factors early in the design process instead of finding out what is important late in the design process during (field) testing. In turn, this might accelerate the adoption of exoskeletons. Also, our framework can be used to study the ongoing introduction of exoskeletons at work since it also addresses policy decisions companies interested in implementing exoskeletons should consider.Exoskeletons have shown significant impact at reducing the biomechanical demand on muscles during repetitive lifting and overhead tasks in non-healthcare industries. However, the benefits of exoskeletons are yet to be realized in the operating room, particularly as work-related musculoskeletal disorders continue to be a concern for surgeons. This study quantified the effect of using neck, arm, and trunk exoskeletons on muscle activity while assuming typical postures held in the operating room. Fourteen participants were recruited to participate in this study. In this two-part experiment participants were asked to 1) hold a series of neck flexion, arm abduction and trunk flexion postures seen in surgical procedures, and 2) perform a simulated surgical task requiring five different trunk flexion posture levels. Participants were required to complete these tasks with and without passive exoskeleton(s). This study showed that even for postures held short time periods, exoskeletons are beneficial at reducing the demand on muscles; however, the reduction in muscle demand depends on body segment and postural angle, as intended with these passive exoskeletons. Furthermore, for the simulated surgical task with awkward trunk flexion postures (10-65°), the trunk exoskeletons showed a significant reduction in the rate of rise in back muscle sEMG (+1.365%MVC/min vs. +0.769%MVC/min for non-dominant lumbar extensor muscles, p = 0.0108; +1.377%MVC/min vs. +0.770%MVC/min for the dominant lumbar extensor muscles, p = 0.0196) over 25 min, consequently resulting in improved trunk subjective discomfort scores (7.34 vs. 4.30, p less then 0.05), with no impact on the neck and shoulder biomechanical demand. The results from this study indicate that exoskeletons may be a potential intervention to reduce biomechanical loading during surgery.Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host-gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but it remains largely unknown how the highly variable genomes of gut bacteria interact with host BA metabolism. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete clusters showed correlations with BA metabolism. Metagenome-wide association analysis identified 809 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the largest microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and it highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.

Hepatocellular carcinoma (HCC) is a substantial health concern worldwide. Increasing studies have suggested that circle RNAs (circRNAs) function as new regulators in HCC progression. The present work explored the role of hsa_circ_0007059 (circ_0007059) in the developing process of hepatocarcinogenesis.

The circ_0007059 level in HCC was determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and northern blot. Its biological role in HCC cells was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, Transwell, sphere formation and western blotting analyses. selleck inhibitor Bioinformatics analysis, luciferase reporter, and RNA immunoprecipitation (RIP) assays were used to test the regulatory mechanisms of circ_0007059.

Our results revealed that circ_0007059 expression was downregulated in HCC samples and cells. Moreover, circ_0007059 overexpression inhibited HCC cell proliferation, migration, invasion, and stem cell-like property, and strengthened cell apoptosis. In mechanism, circ_0007059 suppressed AKT/mTOR pathway by positively regulating phosphatase and tensin homolog (PTEN) expression. Additionally, circ_0007059 acted as a positive regulator of PTEN through controlling the availability of miR-421. Rescue assays demonstrated that PTEN knockdown or SC79 (AKT agonist) eliminated the effect of circ_0007059 on HCC cell phenotypes.

Circ_0007059 sponges miR-421 to inhibit oncogenic cellular process in HCC by mediating the PTEN-AKT/mTOR pathway.

Circ_0007059 sponges miR-421 to inhibit oncogenic cellular process in HCC by mediating the PTEN-AKT/mTOR pathway.Efforts to prevent intimate partner violence (IPV) have been informed by emerging research on common triggers of IPV and the importance of engaging with couple dynamics. This paper reports on secondary data analysis from the qualitative evaluations of the SASA! intervention in Uganda, (conducted in 2012 involving 40 community members) and the Indashyikirwa intervention in Rwanda, (conducted between 2014 and 2018 involving 14 couples and 36 other stakeholders). It explores the under-researched linkages between romantic jealousy and IPV, and describes how these interventions mitigated it. A qualitative approach using interviews and focus groups with women and men was used. Overall, jealousy was common in both settings, and led to relationship challenges including breakdown of trust; quarrels about resources; conflict, controlling behaviours, and ultimately, physical and emotional IPV. Jealousy was seen to operate through different gendered pathways. Participants described women to question men about their whereendered pathways, and consequences of romantic jealousy to inform context-specific programming.Using data from organ transplant medicine in Germany, we propose a method for understanding the content of unwritten rules supportive of violations of written rules in light of the "German Organ Transplant Scandal". Grounded in the sociology of organizational crime, we reconstruct the cultural repertoires of medical professionals working with organ allocation when confronted with the applicable guidelines using collective mindset analysis. Four dimensions of cognitive and normative rules of interpretation were identified and discussed as a an occupational-professional form of deviance. Apart from not relying on data from the alleged perpetrators and still gazing at the latent structures of meaning behind misconduct, our approach offers a more general methodological framework for empirical studies of the unwritten rules at work in an organizational field where wrongdoing has been reported.Agricultural intensification is a key strategy to help meet increasing demand for food and bioenergy. It has the potential to reduce direct and indirect land use change (LUC) and associated environmental impacts while contributing to a favorable economic performance of the agriculture sector. We conduct an integral analysis of environmental and economic impacts of LUC from projected agricultural intensification and bioenergy production in the Orinoquia region in 2030. We compare three agricultural intensification scenarios (low, medium, high) and a reference scenario, which assumes a business-as-usual development of agricultural production. The results show that with current inefficient management or with only very little intensification between 26% and 93% of the existing natural vegetation areas will be converted to agricultural land to meet increasing food demand. This results in the loss of biodiversity by 53% and increased water consumption by 111%. In the medium and high scenarios, the intensification aduction intensification in the Orinoquia region is a mechanism that could reduce the pressure on natural land and its associated environmental and economic impacts.This study assessed variation in the supraorbital and orbital region of the Middle Pleistocene hominins (MPHs), sometimes called Homo heidelbergensis s.l., to test whether it matched the expectations of intraspecific variation. The morphological distinctiveness and relative variation of this region, which is relatively well represented in the hominin fossil record, was analyzed quantitatively in a comparative taxonomic framework. Coordinates of 230 3D landmarks (20) and sliding semilandmarks (210) were collected from 704 specimens from species of Homo, Australopithecus, Paranthropus, Gorilla, Pan, Papio, and Macaca. Results showed that the MPHs had expected levels of morphological distinctiveness and intragroup and intergroup variation in supraorbital and orbital morphology, relative to commonly recognized non-hominin catarrhine species. However, the Procrustes distances between this group and H. sapiens were significantly higher than expected for two closely related catarrhine species. Furthermore, this study showed that variation within the MPH could be similarly well contained within existing hypodigms of H.