Notes

Flavonoids focusing on NRF2 within neurodegenerative disorders.
cases.

GeneDive is a comprehensive, broad-use biological interactions browser. The GeneDive application and information about its underlying system architecture are available at http//www.genedive.net. GeneDive Docker image is also available for download at this URL, allowing users to (1) import their own interaction data securely and privately; and (2) generate and test hypotheses across their own and other datasets.
GeneDive is a comprehensive, broad-use biological interactions browser. The GeneDive application and information about its underlying system architecture are available at http//www.genedive.net. GeneDive Docker image is also available for download at this URL, allowing users to (1) import their own interaction data securely and privately; and (2) generate and test hypotheses across their own and other datasets.Named entity recognition (NER) is a fundamental task in Chinese natural language processing (NLP) tasks. Recently, Chinese clinical NER has also attracted continuous research attention because it is an essential preparation for clinical data mining. The prevailing deep learning method for Chinese clinical NER is based on long short-term memory (LSTM) network. However, the recurrent structure of LSTM makes it difficult to utilize GPU parallelism which to some extent lowers the efficiency of models. Besides, when the sentence is long, LSTM can hardly capture global context information. To address these issues, we propose a novel and efficient model completely based on convolutional neural network (CNN) which can fully utilize GPU parallelism to improve model efficiency. Moreover, we construct multi-level CNN to capture short-term and long-term context information. We also design a simple attention mechanism to obtain global context information which is conductive to improving model performance in sequence labeling tasks. Besides, a data augmentation method is proposed to expand the data volume and try to explore more semantic information. Extensive experiments show that our model achieves competitive performance with higher efficiency compared with other remarkable clinical NER models.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing patients to quickly lose motor neurons. The disease is characterized by a fast functional impairment and ventilatory decline, leading most patients to die from respiratory failure. To estimate when patients should get ventilatory support, it is helpful to adequately profile the disease progression. For this purpose, we use dynamic Bayesian networks (DBNs), a machine learning model, that graphically represents the conditional dependencies among variables. However, the standard DBN framework only includes dynamic (time-dependent) variables, while most ALS datasets have dynamic and static (time-independent) observations. Therefore, we propose the sdtDBN framework, which learns optimal DBNs with static and dynamic variables. Besides learning DBNs from data, with polynomial-time complexity in the number of variables, the proposed framework enables the user to insert prior knowledge and to make inference in the learned DBNs. We use sdtDBNs to study the progression of 1214 patients from a Portuguese ALS dataset. First, we predict the values of every functional indicator in the patients' consultations, achieving results competitive with state-of-the-art studies. Then, we determine the influence of each variable in patients' decline before and after getting ventilatory support. This insightful information can lead clinicians to pay particular attention to specific variables when evaluating the patients, thus improving prognosis. The case study with ALS shows that sdtDBNs are a promising predictive and descriptive tool, which can also be applied to assess the progression of other diseases, given time-dependent and time-independent clinical observations.The context of medical conditions is an important feature to consider when processing clinical narratives. NegEx and its extension ConText became the most well-known rule-based systems that allow determining whether a medical condition is negated, historical or experienced by someone other than the patient in English clinical text. In this paper, we present a French adaptation and enrichment of FastContext which is the most recent, n-trie engine-based implementation of the ConText algorithm. We compiled an extensive list of French lexical cues by automatic and manual translation and enrichment. To evaluate French FastContext, we manually annotated the context of medical conditions present in two types of clinical narratives (i)death certificates and (ii)electronic health records. Results show good performance across different context values on both types of clinical notes (on average 0.93 and 0.86 F1, respectively). Furthermore, French FastContext outperforms previously reported French systems for negation detection when compared on the same datasets and it is the first implementation of contextual temporality and experiencer identification reported for French. Finally, French FastContext has been implemented within the SIFR Annotator a publicly accessible Web service to annotate French biomedical text data (http//bioportal.lirmm.fr/annotator). To our knowledge, this is the first implementation of a Web-based ConText-like system in a publicly accessible platform allowing non-natural-language-processing experts to both annotate and contextualize medical conditions in clinical notes.Draft genome sequence of the glucose tolerant beta glucosidase (GT-BGL) producing rare fungus Aspergillus unguis NII 08,123 was generated through Next Generation Sequencing (NGS). The genome size of the fungus was estimated to be 37.1 Mb. A total of 3116 contigs were assembled using SPades, and 15,161 proteins were predicted using AUGUSTUS 3.1. Among them, 13,850 proteins were annotated using UniProt. Distribution of CAZyme genes specifically those encoding lignocellulose degrading enzymes were analyzed and compared with those from the industrial cellulase producer Trichoderma reesei in view of the huge differences in detectable enzyme activities between the fungi, despite the ability of A. unguis to grow on lignocellulose as sole carbon source. Full length gene sequence of the inducible GT-BGL could be identified through tracing back from peptide mass fingerprint. A total of 403 CAZymes were predicted from the genome, which includes 232 glycoside hydrolases (GHs), 12 carbohydrate esterases (CEs), 109 glycosyl transferases (GTs), 15 polysaccharide lyases (PLs), and 35 genes with auxiliary activities (AAs). The high level of zinc finger motif containing transcription factors could possibly hint a tight regulation of the cellulolytic machinery, which may also explain the low cellulase activities even when a complete repertoire of cellulase degrading enzyme genes are present in the fungus.Liver fibrosis affects millions of people worldwide and is rising vastly over the past decades. With no viable therapies available, liver transplantation is the only curative treatment for advanced diseased patients. Excessive accumulation of aberrant extracellular matrix (ECM) proteins, mostly collagens, produced by activated hepatic stellate cells (HSCs), is a hallmark of liver fibrosis. Several studies have suggested an inverse correlation between collagen-I degrading matrix metalloproteinase-1 (MMP-1) serum levels and liver fibrosis progression highlighting reduced MMP-1 levels are associated with poor disease prognosis in patients with liver fibrosis. We hypothesized that delivery of MMP-1 might potentiate collagen degradation and attenuate fibrosis development. In this study, we report a novel approach for the delivery of MMP-1 using MMP-1 decorated polymersomes (MMPsomes), as a surface-active vesicle-based ECM therapeutic, for the treatment of liver fibrosis. The storage-stable and enzymatically activeclusion, our results demonstrate an innovative approach of MMP-1 delivery, using surface-decorated MMPsomes, for alleviating liver fibrosis.Most infectious agents use mucosal tissues as entry portals, thus, mucosae are frequently defined as a first line of defense against pathogens. Mucosal protection generally operates through antibody-mediated and cytotoxic T-cell responses which can be triggered by mucosal vaccines. Sublingual vaccination provides many advantages such as systemic and mucosal responses (both locally and at remote mucosal sites), besides being a needle-free administration route with high patient compliance and limited adverse effects. Buccal mucosa complexity nonetheless represents a challenge for vaccine administration, hence, many efforts were recently deployed to improve vaccine components, mucoadhesion and/or penetration. Several innovative approaches indeed confirmed that a robust and protective immunity can be achieved by sublingual vaccines. This review will then specify the most recent delivery systems and improvements developed to increase sublingual vaccines efficiency. We will focus our description on the immune mechanisms involved and the requirements for optimal sublingual immunization and mucosal protection.In the last decade, cellular forces in three-dimensional hydrogels that mimic the extracellular matrix have been calculated by means of Traction Force Microscopy (TFM). However, characterizing the accuracy limits of a traction recovery method is critical to avoid obscuring physiological information due to traction recovery errors. So far, 3D TFM algorithms have only been validated using simplified cell geometries, bypassing image processing steps or arbitrarily simulating focal adhesions. Moreover, it is still uncertain which of the two common traction recovery methods, i.e., forward and inverse, is more robust against the inherent challenges of 3D TFM. In this work, we established an advanced in silico validation framework that is applicable to any 3D TFM experimental setup and that can be used to correctly couple the experimental and computational aspects of 3D TFM. Advancements relate to the simultaneous incorporation of complex cell geometries, simulation of microscopy images of varying bead densities andn framework that mimics real TFM experimental conditions and that characterizes the expected errors of a 3D TFM workflow. We apply this framework to demonstrate the enhanced accuracy of a novel inverse traction recovery method that is illustrated in the context of an in vitro model of sprouting angiogenesis. Together, our study shows the importance of a proper traction recovery method to minimise errors and the need for an advanced framework to assess those errors.
Because medication adherence is linked to better diabetes outcomes, numerous interventions have aimed to improve adherence. However, suboptimal adherence persists and necessitate continued research into intervention strategies. This study evaluated the effectiveness of an intervention that combined storytelling and peer support to improve medication adherence and health outcomes in adults with diabetes.

Living Well with Diabetes was a cluster randomized controlled trial. Intervention participants received a six-month, 11-session peer-delivered behavioral diabetes self-care program over the phone. Control participants received a self-paced general health program. Outcomes were changes in medication adherence and physiologic measures (hemoglobin A1c, systolic blood pressure, low-density lipoprotein cholesterol, body mass index).

Of the 403 participants with follow-up data, mean age was 57 (±SD 11), 78% were female, 91% were African American, 56.4% had high school education or less, and 70% had an annual income of < $20,000. At follow-up, compared to controls, intervention participants had greater improvement in medication adherence (β=-0.25 [95% CI -0.35, -0.15]). Physiologic measures did not change significantly in either group. Intervention participants had significant improvements in beliefs about the necessity of medications (β=0.87 [95% CI 0.27, 1.47]) concerns about the negative effects of medication (β=-0.91 [95% CI -1.35, -0.47]), and beliefs that medications are harmful (β=-0.50 [95% CI -0.89, -0.10]). In addition, medication use self-efficacy significantly improved in intervention participants (β=1.0 [95% CI 0.23, 1.76]). 473 individuals were enrolled in the study and randomized.

Living Well intervention resulted in improved medication adherence, medication beliefs, and medication use self-efficacy but not improved risk factor levels.
Living Well intervention resulted in improved medication adherence, medication beliefs, and medication use self-efficacy but not improved risk factor levels.ED-INNOVATION (Emergency Department-INitiated bupreNOrphine VAlidaTION) is a Hybrid Type-1 Implementation-Effectiveness multisite emergency department (ED) study funded through The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM efforts to increase access to medications for opioid use disorder (OUD). We use components of Implementation Facilitation to enhance adoption of ED-initiated buprenorphine (BUP) at approximately 30 sites. Subsequently we compare the effectiveness of two BUP formulations, sublingual (SL-BUP) and 7-day extended-release injectable (CAM2038, XR-BUP) in a randomized clinical trial (RCT) of approximately 2000 patients with OUD on the primary outcome of engagement in formal addiction treatment at 7 days. Secondary outcomes assessed at 7 and 30 days include self-reported opioid use, craving and satisfaction, health service utilization, overdose events, and engagement in formal addiction treatment (30 days) and receipt of medications for OUD (at 7 and 30 days). A sample size of 1000 per group provides 90% power at the 2-sided significance level to detect a difference in the primary outcome of 8% and accommodates a 15% dropout rate. We will compare the cost effectiveness of the two treatments on the primary outcome using the incremental cost-effectiveness ratio. We will also conduct an ancillary study in approximately 75 patients experiencing minimal to no opioid withdrawal who will undergo XR-BUP initiation. If the ancillary study demonstrates safety, we will expand the eligibility criteria for the RCT to include individuals with minimal to no opioid withdrawal. The results of these studies will inform implementation of ED-initiated BUP in diverse EDs which has the potential to improve treatment access.Recruitment planning is needed to establish a foundation for obesity prevention research with high risk, disadvantaged perinatal adolescent populations. In the context of developing clinical trial protocols, investigators partnered with Mississippi's Nutrition Program for Women, Infants and Children (WIC) and adopted the Clinical Trials Transformative Initiative (CTTI) framework for recruitment planning to identify and mitigate challenges to recruitment early in the clinical trial development process. The recruitment protocol consisted of 20 passive strategies grounded in principles of partner and community engagement and was flexible, accommodating, altruistic, community-focused, and minimally burdensome to partners and participants. The recruitment goal included 150 adolescent-coparticipant dyads and 145 dyads (96.7%) were successfully recruited. Investigators demonstrated the feasibility of recruiting a disadvantaged and vulnerable perinatal adolescent population that is underrepresented in health research, in one of the most persistently impoverished and poor health regions in the U.S. Four important aspects of recruitment planning using the CTTI framework are discussed including (1) establishing partnerships with trusted community resources is a paramount investment; (2) dedicating time and resources to know and go to your community is invaluable; (3) fostering trust by offering convenient, continuous and clear communication; and (4) encouraging collaboration and participation through limiting partner and participant burden. Establishing organizational and community partnership requires a substantial amount of invaluable time and fosters recruitment success. Following the CTTI recommendations for recruitment planning led to a robust recruitment protocol that will be used in future intervention trials with an understudied perinatal adolescent population with high risk for poor maternal and fetal health outcomes.
Pragmatic and comparative effectiveness randomized controlled trials (RCTs) aim to be highly generalizable studies, with broad applicability and flexibility in methods. These trials also address recruitment issues by minimizing exclusions. The trials may also appeal to potential subjects because of lower risk and lower burdens of participation. We sought to examine rates of refusal and uses of waivers of informed consent in pragmatic and comparative effectiveness RCTs.

A systematic review of pragmatic and comparative effectiveness RCTs performed wholely or in part in the United States and first published in 2014 and 2017.

103 studies involving 105 discrete populations were included for review. Refusal data was collected for 71 RCTs. Overall, studies reported an average rate of 31.9% of potential subjects refused participation; on an individual basis, 38.4% of people asked to take part refused at some point during recruitment. 23 trials (22%) were performed, at least in part, with a waiver of informed consent, 7 (30%) of which provided any form of notice to subjects.

Overall refusal rates for pragmatic and comparative effectiveness RCTs appear roughly the same as other types of research, with studies reporting about a third of people solicited for participation refuse. Moreover, informed consent was waived in 22% (95% Binomial exact Confidence Interval 13.9-30.5%) of the trials, and further study is needed to understand when waivers are justified and when notice should be provided.
Overall refusal rates for pragmatic and comparative effectiveness RCTs appear roughly the same as other types of research, with studies reporting about a third of people solicited for participation refuse. Moreover, informed consent was waived in 22% (95% Binomial exact Confidence Interval 13.9-30.5%) of the trials, and further study is needed to understand when waivers are justified and when notice should be provided.Regular participation in physical activity benefits older adults physically and mentally. However, the availability and assessment of physical activity programs that are safe and appropriate for homebound older adults at risk for nursing home admission are limited. Here we describe the protocol for a randomized controlled trial that examines the effectiveness of a gentle physical activity program. Delivered by home care aides who regularly help hard-to-reach older home care clients with housekeeping and routine personal care services in the home, this program is implemented in a real-world context of caregiver-client dyads in a Medicaid-funded home care program. The trial uses a two-group repeated measures design (baseline, Month 4, and Month 8) with 300 pairs of eligible home care clients and their home care aides. The results from this trial could provide evidence and guidelines for a new model of home care, which would facilitate the working together of older home care clients and their home care aides to maintain or improve the functional status of nursing home-eligible older adults.The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an evolutionarily conserved histone acetyltransferase complex that has a critical role in histone acetylation, gene expression, and various developmental processes in eukaryotes. However, little is known about the composition and function of the SAGA complex in plants. In this study, we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits but also four plant-specific subunits three functionally redundant paralogs, SCS1, SCS2A, and SCS2B (SCS1/2A/2B), and a TAF-like subunit, TAFL. Mutations in SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the genes encoding conserved SAGA subunits HAG1 and ADA2B, including delayed juvenile-to-adult phase transition, late flowering, and increased trichome density. Furthermore, we demonstrated that SCS1/2A/2B are required for the function of the SAGA complex in histone acetylation, thereby promoting the transcription of development-related genes. These results together suggest that SCS1/2A/2B are core subunits of the SAGA complex in Arabidopsis. Compared with SAGA complexes in other eukaryotes, the SAGA complexes in plants have evolved unique features that are necessary for normal growth and development.
To investigate the monthly and seasonal variation in adult osteoporotic fragility fractures and the association with weather.

12-year observational study of a UK Fracture Liaison Service (outpatient secondary care setting). Database analyses of the records of adult outpatients aged 50years and older with fragility fractures. Weather data were obtained from the UK's national Meteorological Office. In the seasonality analyses, we tested for the association between months and seasons (determinants), respectively, and outpatient attendances, by analysis of variance (ANOVA) and Tukey's test. In the meteorological analyses, the determinants were mean temperature, mean daily maximum and minimum temperature, number of days of rain, total rainfall and number of days of frost, per month, respectively. We explored the association of each meteorological variable with outpatient attendances, by regression models.

The Fracture Liaison Service recorded 25,454 fragility fractures. We found significant monthly and seasonal variation in attendances for fractures of the radius or ulna; humerus; ankle, foot, tibia or fibula (ANOVA, all p-values <0.05). Fractures of the radius or ulna and humerus peaked in December and winter. Fractures of the ankle, foot, tibia or fibula peaked in July, August and summer. U-shaped associations were showed between each temperature parameter and fractures. Days of frost were directly associated with fractures of the radius or ulna (p-value <0.001) and humerus (p-value 0.002).

Different types of fragility fractures present different seasonal patterns. Weather may modulate their seasonality and consequent healthcare utilisation.
Different types of fragility fractures present different seasonal patterns. Weather may modulate their seasonality and consequent healthcare utilisation.Irradiation therapy causes bone deterioration and increased risk for skeletal-related events. Irradiation interferes with trabecular architecture through increased osteoclastic activity, decreased osteoblastic activity, and increased adipocyte expansion in the bone marrow (BM), which further compounds bone-related disease. Neutralizing antibodies to sclerostin (Scl-Ab) increase bone mass and strength by increasing bone formation and reducing bone resorption. We hypothesized that treatment with Scl-Ab would attenuate the adverse effects of irradiation by increasing bone volume and decreasing BM adipose tissue (BMAT), resulting in better quality bone. In this study, 12-week-old female C57BL/6J mice were exposed to 6 Gy whole-body irradiation or were non-irradiated, then administered Scl-Ab (25 mg/kg) or vehicle weekly for 5 weeks. Femoral μCT analysis confirmed that the overall effect of IR significantly decreased trabecular bone volume/total volume (Tb.BV/TV) (2-way ANOVA, p less then 0.0001) with a -43.8% lypothesis that Scl-Ab ameliorates the deleterious effects of whole-body irradiation on bone and adipose tissue in a mouse model. Our findings suggest that future research into localized and systemic therapies after irradiation exposure is warranted.
Cystic fibrosis (CF) bone disease (CFBD) has attracted considerable recent interest from researchers, although several aspects of CFBD pathophysiology remain poorly understood. The objective of this research was to investigate CFBD in children with CF and its relation to clinical and bone metabolism markers.

In a prospective observational study of 68 patients with CF and 63 healthy controls, we studied bone turnover biomarkers and bone mineral density (BMD). The biomarkers included osteocalcin, total-alkaline phosphatase, bone-alkaline phosphatase, N-terminal propeptide of type-1-procollagen, osteoprotegerin (OPG), interleukine-6, tumor necrosis factor alpha (TNF-α), type-1-collagen cross-linked C-telopeptide (CTX), parathormone (PTH), 25-vitamin D, 1,25-vitamin D, calcium and phosphorus. BMD was examined in lumbar spine, comparing two healthy Spanish populations. Two regression analyses were applied to any significant associations to evaluate predictors of BMD and of CF, expressed as odds ratios (OR) with 95% confidence intervals.

After adjusting for age, sex, and height Z-score, gains in BMD LS in children and adolescents (6-16years) with CF were not less than in healthy reference population. Patients with CF showed significant associations with different bone turnover biomarkers. Age, gender, body mass index, PTH, CTX and OPG were significant predictors of BMD (R
=0.866, p<0,001). Moreover, we found that PTH (OR=1.070; 95% CI 1.019-1.123), and TNFα (OR=2.173; 95% CI 1.514-3.118) were significantly linked to CF, and calcium (OR=0.115; 95% CI 0.025-0.524), 1,25-vitamin D (OR=0.979; 95% CI 0.962 0.996) and OPG (OR=0.189; 95% CI 0.073-0.489) were significant reduced.

A normal bone mineral density along with altered remodeling was found in CF patients with a normal nutritional status and without acute lung disease.
A normal bone mineral density along with altered remodeling was found in CF patients with a normal nutritional status and without acute lung disease.Biopolymers, as chitosan and alginate, have gained prominence in the biomedical area, mainly for application in wound dressings, as partial replacements for synthetic polymers. The present work aimed to compare the influence of the antimicrobial agent incorporation form on the properties of films prepared by casting. The chitosan/alginate-based films were manufactured containing oregano essential oil (OEO) or ground oregano leaves (OR). The OEO was chosen due to its excellent pharmacological properties, and the substitution by OR can represent an advantageous alternative for minimizing the final cost of the product, by removing the oil extraction step. The films, with different amounts of OEO and OR, were characterized in terms of their morphological, physicochemical, mechanical and antimicrobial properties. The films had properties according to desirable for wound dressing application water vapor flux less than 35 g m-2 h-1, moderate liquid absorption capacity, and similar mechanical properties to human skin. All developed films showed antimicrobial activity against the bacteria Escherichia coli and Staphylococcus aureus. Formulations containing OEO presented the largest inhibition zones, although OR showed high potential for the proposed use. These results suggest that films developed, with both OEO and ground oregano leaves, are promising for use as dressings.There is an urgent need for wound dressings to treat partial-thickness burns. Hydrogels are a promising material that can maintain hydration to promote necrotic tissue removal. Tilapia peptides (TP) and hydroxyapatite (HA) were incorporated into chitosan system to prepare new types of hydrogels. The hydrogels were cross-linking by tannin (TA), which were developed to promote rapid wound healing in a New Zealand rabbit partial-thickness burn model. Nanohydroxyapatite (NHA) was synthesized by coprecipitation method, which made hydrogels have a highly porous structure comprised of interconnected pores, excellent water absorption and low hemolysis. Besides, the hydrogels showed excellent antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as the cytocompatibility on endothelial cells. Moreover, the hydrogels promoted epithelial and dermal regeneration, reduce the expression of TNF-α and IL-6 and promote the skin regeneration by enhancing expression of collagen, STAT3, and VEGF.Lignins are phenolic macromolecules that have several applications. In this work, we examine some biological activities of a lignin-like macromolecule isolated from the Crataeva tapia leaves, not yet studied to evaluate its potential applications in medicinal and cosmetic formulations. Lignin was obtained by alkaline delignification and its physical-chemical characterization was made by means of FT-IR, UV-Vis, NMR spectroscopy, elementary analysis, molecular mass determination and thermal analysis. Lignin is of the GSH type, with levels of hydrogen (5.10%), oxygen (27.18%), carbon (67.60%), nitrogen (0.12%) and phenolic content of 189.6 ± 9.6 mg GAE/g. In addition, it is a thermally stable macromolecule with low antioxidant activity. Cytotoxicity and cytokine production were assessed by flow cytometry. The photoprotective activity was evaluated by adding different concentrations of lignin to a commercial cream. Lignin was not cytotoxic, it stimulated the production of TNF-α, IL-6 and IL-10 and did not promote a significant change in nitric oxide levels. In addition, this macromolecule was able to promote increased absorption of ultraviolet light from a commercial cream. These results reinforce the ethnopharmacological use of C. tapia leaves and suggest the need for further studies to determine the potential medicinal and cosmetic applications (sunscreen) of lignin from C. tapia leaves.In the past two decades, significant progress has been made in the past two decades towards the understanding of the basic mechanisms underlying cancer growth and angiogenesis. In this context, receptor tyrosine kinases (RTKs) play a pivotal role in cell proliferation, differentiation, growth, motility, invasion, and angiogenesis, all of which contribute to tumor growth and progression. Mutations in RTKs lead to abnormal signal transductions in several pathways such as Ras-Raf, MEK-MAPK, PI3K-AKT and mTOR pathways, affecting a wide range of biological functions including cell proliferation, survival, migration and vascular permeability. Increasing evidence demonstrates that multiple kinases are involved in angiogenesis including RTKs such as vascular endothelial growth factor, platelet derived growth factor, epidermal growth factor, insulin-like growth factor-1, macrophage colony-stimulating factor, nerve growth factor, fibroblast growth factor, Hepatocyte Growth factor, Tie 1 & 2, Tek, Flt-3, Flt-4 and Eph receptors. Overactivation of RTKs and its downstream regulation is implicated in tumor initiation and angiogenesis, representing one of the hallmarks of cancer. This review discusses the role of RTKs, PI3K, and mTOR, their involvement, and their implication in pro-oncogenic cellular processes and angiogenesis with effective approaches and newly approved drugs to inhibit their unrestrained action.Hydrogel-based wound dressings have been intensively studied as promising materials for wound healing and care. The mixed-mode thiol-acrylate photopolymerization is used in this paper for alginate/poloxamer hydrogels formation. First, the alginate was modified with thiol groups using the esterification reaction with cysteamine, and second, the terminal hydroxyl groups of poloxamer were esterified with acryloyl chloride to introduce polymerizable acrylate groups. Finally, the cross-linking reaction between the two macromers was performed to produce degradable alginate/poloxamer hydrogels. The optimum conditions for the photo-initiated reaction were studied in order to obtain high gel fractions. The resulting hydrogels have high swelling capacity in simulated physiological conditions, good elasticity and strength, and appropriate porosity, some of the physico-chemical properties required for their applications as wound dressings/patches. The biological assays show that the alginate/poloxamer hydrogels induce proliferation of human keratinocyte and have an anti-inflammatory effect on lipopolysaccharides (LPS)-activated keratinocytes by inhibiting the extracellular signal-regulated kinases (ERK)/ nuclear factor (NF)-kB/ tumor necrosis factor (TNF)-α signalling pathway. Taken together, the results showed that the chemical cross-linked alginate/poloxamer hydrogels may function as a dressing/patch applied directly on the skin lesion to heal the wound by reducing the exacerbated inflammation, the main cause of wound healing delay and local infection.The study aims to develop a novel nanohybrid shear-thinning hydrogel with fast gelation, and variable mechanical and biological properties. This nanohybrid hydrogel was developed via self-assembly guest-host interaction between β-cyclodextrin modified alginate (host macromere, Alg-CD) and adamantine modified graphene oxide (guest macromere, Ad-GO) and subsequent ionic crosslinking process. We found that the rheological and mechanical properties of hydrogels were controlled via macromere concentration and the host guest macromere ratio, due to the modulation of crosslinking density and network structure. Noticeably, 12%(12) dual-crosslinked hydrogel (2DC12) significantly improved the strength (1.3-folds) and toughness compared to 10%(14) dual-crosslinked hydrogel (4DC10). Furthermore, the hydrogel erosion and cytocompatibility relied on the designed parameters. Remarkably, 2DC12 showed less than 20% weight loss after 20 days of incubation in physiological solution and more than 200% cell survival after five days. In conclusion, the nanohybrid Alg-GO hydrogel could be used as an injectable hydrogel for soft tissue engineering applications.The present work focuses on the development of cellulose nanofibrils (CNF) film that derived from sustainable biomass resources, which potentially to work as bio-based conductive membranes that assembled into supercapacitors. The chemically purified cellulose was isolated from different parts of coconut (coconut shell and its husk) and further subjected to 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation for CNF preparation. Physicochemical properties of prepared CNFs were studied in terms of chemical characteristics & crystallinity, surface functionalities, surface morphology, and thermal properties. Both coconut shell-derived CNF and coconut husk-derived CNF fulfilled with nanocellulose's characteristics with fibres width ranged of 70-120 nm and 150-330 nm, respectively. CNF films were further prepared by solvent casting method to measure the modulus elasticity, piezoelectric and dielectric properties of the films. Mechanical study indicated that coconut shell-derived CNF film showed a higher value of elastic modulus than the coconut husk-derived CNF film, which was 8.39 GPa and 5.36 GPa, respectively. The effectiveness of electrical aspects for CNF films are well correlated with the crystallinity and thermal properties, associated with it's composition of different coconut's part.The present work aims to examine the structural properties of polyurethanes bio-composites with mole ratios of alginate and chitosan. For this concern, a two-step reaction mechanism was carried out; in the first step isocyanate (-NCO) terminated pre-polymer was synthesized by the reaction of hexamethylene diisocyanate (HMDI) and hydroxyl-terminated polybutadiene (HTPB). The pre-polymer was further extended with 1,4-butanediol (BDO), chitosan (CS) and alginate (ALG) in the second step. Structural and functional group elucidation was done by using Fourier Transform Infra-red (FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy. The crystallinity of the prepared samples was investigated by using X-ray diffraction (XRD) method, the maximum observed intensity was 7704 a.u. The thermal properties of polyurethane composites were carried out using thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC). The TGA results showed that thermal stability of RPU-5 was 20 °C more than RPU-1 at each corresponding degradation temperature. It is observed all physical parameters like crystallinity, glass transition temperature, melting point are much dependent on ratio of chain extenders. Overall, CS based samples along with small amount of ALG showed better thermal properties.Effects of Elm tree sawdust pretreatments using alkali and alkaline earth metals (NaCl, KCl, CaCl2, MgCl2 and Elm tree ash) and deashing solutions (water, HCl, HNO3 and aqua regia) before the carbonization process on the porosity of produced activated carbons and Pb (II) and Cr (VI) adsorption were studied. The activated carbons were characterized by pore size distribution, surface area, FTIR, and SEM-EDX analysies. Based on the results, HCl leaching pretreatment of the biomass increased the activated carbon adsorption capacity of Cr (VI) from 114 to 190 mg g-1. The treatment of biomass with alkali and alkali earth metal salts, especially MgCl2, remarkably increased the activated carbon adsorption capacity of Pb (II) from 233 to 1430 mg g-1. The results indicated that Pb (II) adsorption was attributed to both the mesoporous structure of activated carbon and the abundance of Mg on the activated carbon's surface. On the other hand, the micropores played a major role in Cr (VI) adsorption capacity. The development of the micro- or mesoporous structure of activated carbons through pretreatment of lignocellulosic precursor could be an approach for providing high performance activated carbons for Pb (II) and Cr (VI) removal from aqueous solutions.The present study aimed to produce thermoplastic starch films with different concentrations of thermoplastic pectin and the addition of 4% lignin microparticles as a reinforcing and active agent. The pectin improved the modulus of elasticity, and decreased the elongation at break. In addition, it improved the UV light protection to 100% at 320 nm and 95.9% at 400 nm. The incorporation of lignin microparticles improved the thermal stability of the blends made with 25% and 50% thermoplastic pectin when compared to the pectin-free blends. The blend with 25% thermoplastic pectin led to an increase of 75.8% and 34% in elongation at break and deformation of the films, respectively. This blend also improved the UV light protection to 100% due to its dark brown color. Regarding the permeability properties, the films with 25% and 50% thermoplastic pectin showed lower oxygen permeability (48% and 65%) and an increase in the antioxidant activities from 2.7% to 71.08% and 4.1% to 79.28%, respectively. Thus, the polymer blend with 25% thermoplastic pectin with the incorporation of lignin microparticles proved to be a good alternative for use in foods sensitive to the effects of oxygen and UV light.Fatty acid desaturase catalyzes the desaturation reactions by insertion of double bonds into the fatty acyl chain, producing unsaturated fatty acids. Though soluble fatty acid desaturases have been studied widely in advanced organisms, there are very limited studies of membrane fatty acid desaturases due to the difficulty of generating recombinant desaturase. Brassica napus is a rapeseed, which possesses a range of different membrane-bound desaturases capable of producing fatty acids including Δ3, Δ4, Δ8, Δ9, Δ12, and Δ15 fatty acids. The 1155 bp open reading frame of Δ12 fatty acid desaturase (FAD12) from Brassica napus codes for 383 amino acid residues with a molecular weight of 44 kDa. It was expressed in Escherichia coli at 37 °C in soluble and insoluble forms when induced with 0.5 mM IPTG. Soluble FAD12 has been purified using Ni2+-Sepharose affinity chromatography with a total protein yield of 0.728 mg/mL. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that desaturase activity of FAD12 could produce linoleic acid from oleic acid at a retention time of 17.6 with a conversion rate of 47%. Characterization of purified FAD12 revealed the optimal temperature of FAD12 was 50 °C with 2 mM preferred substrate concentration of oleic acid. Analysis of circular dichroism (CD) showed FAD12 was made up of 47.3% and 0.9% of alpha-helix and β-sheet secondary structures. The predicted Tm value was 50.2 °C.Cell fate and morphologies are influenced by the mechanical property of matrix. However, the relevant works about the dynamic adjustable of matrix mechanical property is rare and most of them need extra stimulation, such as the controllable of the degradation. In this study, double crosslinking (DC) hydrogels are fabricated by sequential covalent crosslinking and electrostatic interactions between hyaluronic acid and poly-lysine. Without any extra stimulation or treatment, the compressive stress of DC-hydrogels increases from 22.4 ± 9.4 kPa to 320.1 ± 6.6 kPa with the elongation of incubation time in DMEM solution. The change of compressive stress of matrix induced the morphology of L929 fibroblast cells adjusted from the distributed round shape to spheroid cell clusters and finally to spread shape. RNA sequence analysis also demonstrated that the differentially gene expression and GO enrichment between the cells seeded on the DC-hydrogel with different incubation time. In addition, by increasing the electrostatic interactions ratio of the hydrogel, the biodegradation, compressive stress and energy dissipation of the DC-hydrogels were also significantly improved. Therefore, our study provides new and critical insights into the design strategy to achieve DC-hydrogels which can in situ alter cells morphology and open up a new avenue for the application of disease therapy.Catalases catalyze the decomposition of hydrogen peroxide into water and oxygen. Limited reports are available on characterization of manganese-catalases. We describe here molecular cloning and expression in Escherichia coli of a putative manganese-catalase gene from mesophilic bacterium, Bacillus subtilis R5. The gene product, CatBsu, produced as a soluble protein, was purified to apparent homogeneity and biochemically characterized. The absorption spectra and nonsignificant inhibition by sodium azide indicated that it is a manganese-catalase. The protein was in homohexameric form in solution, with a subunit molecular weight of 30 kDa, containing ~2 Mn2+ and ~1 Ca2+ per subunit. CatBsu showed highest activity at pH 8.0 and 55 °C. It was found to be highly active with a specific activity of 25,290 μmol min-1 mg-1 and apparent Km and kcat values of 98 mM and 1.27 × 104 s-1 subunit-1, respectively. Although from a mesophilic source, it exhibited a half-life of 2 h at 80 °C. Furthermore, the active site and metal binding residues in CatBsu were predicted by homology modelling and molecular docking. To the best of our knowledge, this is the first characterization of a manganese-catalase from genus Bacillus.This work explores the electrospinnability of low-sulfonate Kraft lignin (LSL)/polyvinylpyrrolidone (PVP) solutions in N,N-dimethylformamide (DMF) and the ability of the different micro- and nano-architectures generated to structure castor oil. LSL/PVP solutions were prepared at different concentrations (8-15 wt%) and LSLPVP ratios (9010-0100) and physico-chemically and rheologically characterized. The morphology of electrospun nanostructures mainly depends on the rheological properties of the solution. Electrosprayed nanoparticles or micro-sized particles connected by thin filaments were obtained from solutions with low LSL/PVP concentrations and/or high LSLPVP ratios, whereas beaded or bead-free nanofibers were produced by increasing concentration and/or decreasing LSLPVP ratio, due to enhanced extensional viscoelastic properties and non-Newtonian characteristics. Electrospun LSL/PVP nanofibers are able to form oleogels by simply dispersing them into castor oil at concentrations between 10 and 30 wt%. The rheological properties of the oleogels may be tailored by modifying the LSLPVP ratio and nanofibers content. The potential application of these oleogels as bio-based lubricants was also explored in a tribological cell. Satisfactory friction and wear results are achieved when using oleogels structured by nanofibers mats with enhanced gel-like properties as lubricants. Overall, electrospinning of lignin/PVP solutions can be proposed as a simple and effective method to produce nanofibers for oil structuring.African swine fever virus (ASFV), a re-emerging DNA virus, causes a highly contagious disease for domestic pigs. It is running rife worldwide and threatening the global swine industry. Protein p54 is an attractive candidate for ASFV diagnostic and vaccine design. In this work, we designed a peptide to mimic the N-terminal domain (NTD) of ASFV p54 and pretested it with sera from ASFV-infected pigs. The peptide could be well recognized by the sera, implying that the NTD of p54 contained some potential linear B cell epitopes. Then, the conjugates of the peptide with bovine serum albumin were used as the immunogen to generate monoclonal antibodies (mAbs). A total of six mAbs specific to the NTD of ASFV p54 protein were developed. Five of them well reacted with ASFV HLJ/18 strain and recognized a same linear B cell epitope 5FFQPV9. Furthermore, epitope 5FFQPV9 could be well recognized by ASFV-positive sera from natural infected pigs, suggesting that it was a natural linear B-cell epitope. Conservation analysis indicated that epitope 5FFQPV9 were highly conserved among ASFV epidemic isolates belonging to genotype I and II. Alanine-scanning mutagenesis further revealed that the residues (6F to 9V) of epitope 5FFQPV9 were the core binding sites for antibody recognition. This is the first research to characterize specific mAbs against NTD of p54 protein. These findings may help further understand the function of p54 protein and the improvement of ASFV diagnosis.In the frame of developing sustainable, eco-friendly and high performance materials, microcrystalline cellulose modified through silane coupling agent (MCC Si) is used as a reinforcing agent of benzoxazine resin to manufacture composites at different loadings of 5, 10, 15, 20 wt%. The structural, morphological and crystallinity characterizations of the modified MCC were initially performed to scrutinize the changes and confirm the modification. Then, an investigation on the crosslinking process of the prepared composites was held through curing kinetic study employing isoconversional methods. The kinetic data revealed a decrease in the average values of activation energy and the pre-exponential factor, particularly for composite supplemented with 10% MCC Si, whereas all samples disclosed a tendency of an autocatalytic curing mechanism. Furthermore, the study of the dynamic mechanical properties and degradation features of the cured specimens, respectively, indicated a superior stiffness attributable to the good interaction between BA-a and MCC Si, and enhanced thermal stability for the composites compared to pristine resin.A variety of factors can cause vaginal loss. The patients are suffering from great psychological and physical pain, and there is an urgent need for vagina reconstruction. 3D-bioprinting is expected to achieve vaginal morphological restoration and true functional reconstruction. The current study aimed to explore the biomimetic 3D vagina tissue printing with acellular vagina matrix (AVM) bioink. The AVM from pig was converted to bioink by 15% gelatin and 3% sodium alginate mixed with the AVM solution. Rheology, scanning electron microscopy and HE staining were performed to characterize the bioink's viscosity, morphologies and biocompatibility. After printing, the viability of bone marrow mesenchymal stem cells (BMSCs) in the printed 3D scaffolds in vitro was investigated by a live/dead assay kit. Then, subcutaneous transplantation in rats were divided randomly into 3D scaffold group and 3D scaffold encapsulating CM-Dil-labeled BMSCs group. The results of HE, immunohistochemistry and immunofluorescence staining revealed that 3D scaffold encapsulating BMSCs expressed significant effects on the vascularization and epithelization of the printed vagina tissue, and the BMSCs could acquire the phenotype of vaginal epithelial cells and endothelial-like cells. The work showed that the biomimetic 3D vagina tissue with AVM bioink encapsulating BMSCs is a promising approach for vagina reconstruction.In recent years, our understanding of neural circuits associated with depression has increased. Although inherited factors are known to influence individual differences in the risk for this disorder, it has been difficult to identify specific genes that moderate circuit functions affecting depression. Genome-wide association studies have identified genetic variants of Cntn1 that are linked to major depressive disorders. Cntn1, a subset of the neural cell adhesion protein and immunoglobulin supergene family, participates in cell contact formation and axonal growth control and plays a role in degenerative and inflammatory disorders. However, neuronal substrates that mediate Cntn1 action on depression-like phenotypes and involved mechanisms are unclear. Here, we exploited chronic unpredictable stress (CUS) exposure and found that CUS treatment significantly increased hippocampal Cntn1 messenger RNA and protein expression in both mice and rats, but not in the medial prefrontal cortex, which presented a region-speal mechanisms underlying the risk of depression-related disorders.
Treatment of pain associated with osteoarthritis (OA) is unsatisfactory and innovative approaches are needed. The secretome from human adipose-derived mesenchymal stem cells (hASC-Conditioned Medium, CM) has been successfully used to relieve painful symptoms in models of chronic pain. The aim of this study was to explore the efficacy of the hASC-CM to control pain and neuroinflammation in an animal model of OA.

OA was induced in mice by intra-articular monosodium-iodoacetate (MIA) injection. Thermal hyperalgesia and mechanical allodynia were assessed. Once hypersensitivity was established (7days after MIA), hASC-CM was injected by IA, IPL and IV route and its effect monitored over time. Neuroinflammation in nerve, dorsal root ganglia and spinal cord was evaluated measuring proinflammatory markers and mediators by RT-qPCR. Protein content analysis of secretome by Mass Spectrometry was performed.

A single injection with hASC-CM induced a fast and long lasting antihyperalgesic and antiallodynic effect. Thesensitization.Impaired amyloid-β (Aβ) clearance is believed to be a primary cause of Alzheimer's disease (AD), and peripheral abnormalities in Aβ clearance have recently been linked to AD pathogenesis and progression. Data from recent genome-wide association studies have linked genetic risk factors associated with altered functions of more immune cells to AD pathology. Here, we first identified correlations of Smad3 signaling activation in peripheral macrophages with AD progression and phagocytosis of Aβ. Then, manipulating the Smad3 signaling regulated macrophage phagocytosis of Aβ and induced switch of macrophage inflammatory phenotypes in our cell cultures. In our mouse models, flag-tagged or fluorescent-dye conjugated Aβ was injected into the lateral ventricles or tail veins, and traced. Interestingly, blocking Smad3 signaling efficiently increased Aβ clearance by macrophages, reduced Aβ in the periphery and thereby enhanced Aβ efflux from the brain. Moreover, in our APP/PS1 transgenic AD model mice, Smad3 inhibition significantly attenuated Aβ deposition and neuroinflammation, and ameliorated cognitive deficits, probably by enhancing the peripheral clearance of Aβ.
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