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[Illuminating the nanoscopic whole world of trojans simply by fluorescence super-resolution microscopy].
Herein, we report the synthesis and evaluation of pyrvinium-based antimalarial and antitubercular compounds. Pyrvinium is an FDA approved drug for the treatment of pinworm infection, and it has been reported to have antiparasitic and antimicrobial activities. Pyrvinium contains quinoline core coupled with pyrrole. We replaced the pyrrole with various aryl or heteroaryl substituents to generate pyrvinium analogs. The profiling of these compounds against malaria parasite P. falciparum 3D7 revealed analogs with better antimalarial activity than pyrvinium pamoate. Compound 14 and 16 showed IC50 of 23 nM and 60 nM against P. falciparum 3D7, respectively. These compounds were also effective against drug-resistant malaria parasite P. falciparum Dd2 with IC50 of 53 nM and 97 nM, respectively. Nintedanib The cytotoxicity against CHO-K1, HEK and NRK-49F cells revealed better selectivity index for these new analogs compared to pyrvinium. Additionally, this series of compounds showed activity against M. tuberculosis H37Rv; particularly compounds 10, 13, 14 and 16 showed equipotent antitubercular activity to that of pyrvinium pamoate. The compounds 14 and 16 should be taken forward as leads for further optimization. Robust transport of therapeutic peptides and other medicinal molecules across tight epithelial barriers would overcome the major obstacle to oral delivery. We have already demonstrated that peptides conjugated to gangliosides (GM1 and GM3) having non-native short N-acyl groups hijack the endogenous process of intracellular lipid sorting resulting in transcytosis and delivery across epithelial barriers in vitro and in vivo. Here, we report synthetic methodologies to covalently conjugate peptides directly to short-acyl-chain C6-ceramides. We found that the short-acyl-chain ceramide domain is solely responsible for transcytosis in vitro. This clarifies and expands the platform of short-acyl-chain sphingolipids for conjugated peptide delivery across tight mucosal cell barriers from gangliosides to just the ceramide itself. Most mammalian species have a vomeronasal organ that detects specific chemical substances, such as pheromones. Mucous fluid covering the vomeronasal sensory epithelium is secreted by vomeronasal glands, and the properties of these fluids have been suggested to be involved in chemical detection. Histological studies using periodic acid-Schiff (PAS) and Alcian blue pH 2.5 (AB) stains, which respectively detect natural and acidic polysaccharides, have suggested variations in the nature of the vomeronasal glands among species. Here, we investigated the responsivity of the vomeronasal glands to PAS and AB stains in eight Laurasiatheria species. All species studied herein possessed vomeronasal glands that stained positive for PAS, like other many reported species. The vomeronasal glands of dogs and minks - like rodents, were AB-negative, whereas those of cows, goats, sika deer, musk shrews and two bat species were positive. Considering the present findings and previous reports, the vomeronasal glands in most of Laurasiatheria species appear to be fundamentally abundant in acidic polysaccharides, whereas those in carnivores essentially contains neutral polysaccharides. Lignocellulosic biomass is the most plentiful renewable biomolecule and an alternative bioresource for the production of biofuels and biochemicals in biorefineries. But biomass recalcitrance is a bottleneck in their usage, thus necessitating their pretreatment for hydrolysis. Most pretreatment technologies, result in toxic by-products or have lower yield. Ionic liquids (ILs) have successfully advanced as 'greener and recyclable' alternatives to volatile organic solvents for lignocellulosic biomass dissolution. This review covers recent developments made in usage of IL-based techniques with focus on biomass breakdown mechanism, process parameter design, impact of cation and anion groups, and the advantageous impact of ILs on the subsequent processing of the fractionated biomass. Progress and barriers for large-scale commercial usage of ILs in emerging biorefineries were critically evaluated using the principles of economies of scale and green chemistry in an environmentally sustainable way. The Ebolavirus vaccine (rVSVΔG-ZEBOV-GP) is stored at -80 to -60 °C and should be kept frozen for transport. Due to significant logistical challenges, frozen transport is not feasible for some remote locations. To determine if local distribution at 2-8 °C is a potential option for these locations, a study was conducted to evaluate the impact of agitation on the thawed vaccine. After up to 7 days of constant agitation, no impact on vaccine potency was evident for the agitated vaccine versus the corresponding vaccine kept stationary at 2-8 °C. In conclusion, in-country transport of the Ebolavirus vaccine, rVSVΔG-ZEBOV-GP, at 2-8 °C appears to be a feasible option for those remote locations where significant logistical challenges prohibit transporting the vaccine at -80 to -60 °C. OBJECTIVE To describe symptoms and fertility and quality of life outcomes after isthmocele surgery. STUDY DESIGN We conducted a retrospective study on from January 2012 to December 2017 in two tertiary referral centers in Rennes (France). All the patients diagnosed with isthmocele and operated were included. They all underwent isthmocele surgery by hysteroscopy, vaginal way or laparotomy. RESULTS The following data were collected surgical procedure, symptoms and fertility before and after surgery, patient satisfaction about the surgery, and quality of life after surgery. Eighteen patients were included. The mean duration of follow-up was 15 months. Surgical procedures consisted of hysteroscopy (n = 5/18, 27.8%), vaginal surgery (n = 8/18, 44.4%) and laparotomy (n = 5/18, 27.8%). Surgical indications were secondary infertility (n = 10/18, 55 %), pelvic pain (n = 5/18, 28%) and abnormal uterine bleeding (n = 3/18, 17%). Among patients with abnormal uterine bleeding, improvement was obtained after hysteroscopy, INTRODUCTION The SEPAR Spanish Bronchiectasis Registry (RIBRON) began as a platform for the collection of longitudinal data on patients with this disease. The objective of this study is to describe its operation and to analyze the characteristics of bronchiectasis patients according to sex. METHODS A total of 1912 adult patients diagnosed with bronchiectasis in 43 centers were included between February 2015 and 2019. All patients had complete data consisting of at least 79 basic required variables, controlled by an external audit. RESULTS Mean age was 67.6 (15.2) years; 63.9% were women. The most common symptom was productive cough (78.3%) which was mucopurulent-purulent in 45.9% of cases. The most common etiology was post-infectious (40.4%), while 18.5% were idiopathic. Pseudomonas aeruginosa was the most frequently isolated microorganism (40.4%), of which 25.6% were associated with chronic infection. The annual number of mild-to-moderate/severe exacerbations was 1.62 (1.9)/0.59 (1.3). Half of the patients (50%) presented with airflow obstruction (17% severe). The most frequent radiological localization was lower lobes. The average FACED/E-FACED/BSI values were 2.06 (1.7)/2.67 (2.2)/7.8 (4.5), respectively. Overall, 66.7% of patients were taking inhaled corticosteroids, 19.2% macrolides, and 19.5% inhaled antibiotics. Women presented a less severe profile than men in clinical and functional terms, and a similar infectious, radiological and therapeutic profile. CONCLUSIONS RIBRON represents an excellent map of the characteristics of bronchiectasis in our country. Two thirds of patients are women who presented lower disease severity as a specific characteristic. L.U.BACKGROUND Adolescents and young adults with a sexual interest in young children represent an underserved population. The needs of this group, and their implications for child sexual abuse prevention program development, are not well understood. OBJECTIVE The objective of this research is to advance knowledge about adolescents and young adults with a sexual interest in children to better inform the development of effective prevention and mental health efforts. PARTICIPANTS AND SETTING The sample consisted of 30 young adults, ages 18-30, from North America, South America, Europe, and Australia. METHODS Researchers conducted telephone interviews with participants, and asked about when their interest in children emerged, how they responded to this sexual interest, and what resources could have been helpful during this process. Participants also completed a brief, online survey. Interviews were transcribed and analyzed using Dedoose software. RESULTS Participants reported that their sexual interest in children emerged during adolescence, and as part of that process, they experienced a variety of emotions, including fear, shame, and feelings of isolation. Participants also noted the need for role models who are sexually interested in children and successfully navigating life, positive messaging, and support from families and the community. CONCLUSIONS Young people with a sexual interest in children are largely hidden, vulnerable, and looking for help. Findings from this research can be used to direct the development of the prevention and mental health programs that are responsive to the needs of this community. CLP1 plays an essential role in the protein complex involved in mRNA 3'-end formation and polyadenylation as well as in the tRNA splicing endonuclease (TSEN) complex involved in the splicing of precursor tRNAs. NOL9 localizes in the nucleolus of cells and plays an essential role in ribosomal RNA maturation. Both CLP1 and NOL9 are RNA kinases that phosphorylate the 5' end of RNAs. From the evidence that phosphorylation of the 5' end of a siRNA is essential for its efficient RNA cleavage, it was expected that CLP1 and NOL9 would be corresponding molecules. However, there had been no direct evidence that this is the case. In this study, murine NOL9 showed no apparent RNA kinase activity in cells or even in an RNA kinase assay using recombinant murine NOL9 protein. Although siRNA efficiency was decreased in CLP1 kinase-dead (Clp1K/K) cells, it was not influenced by NOL9 overexpression. These findings indicate that in mouse cells it is CLP1 that mainly acts to phosphorylate the 5' end of RNAs in the siRNA pathway, with no apparent involvement of NOL9. Skin aging cannot be escaped, being due to both intrinsic and extrinsic stimuli. They lead to a reduced extracellular collagen matrix in the dermis, along with a higher degradation by metalloproteases (MMPs) activity, as well as a lower differentiation and function of epidermis keratinocytes, characterized by wrinkling and loss of skin elasticity. One of the recent technology to overcome this skin aging process is the use of radiofrequency (RF) and ultrasound (US) technologies which use thermal stimulation to induce neocollagenesis in the skin. But no explanations exist on the involved pathways. Our hypothesis is that RF-US generated heat increases the collagen formation via the heat shock protein 47 (HSP47) induction, a heat sensitive protein related to the collagen expression. To confirm this hypothesis, normal human skin substitutes were subjected to RF-US treatment and results were monitored after 24 and 44 h. RNA sequencing showed a significant induction for the genes related to the epidermis differentiation processes.
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