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Depressive-like phenotype induced through AAV-mediated overexpression regarding human being α-synuclein in midbrain dopaminergic nerves.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. Selleckchem CL-82198 After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC50 values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 (HEK293) at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.Botulinum toxins are neurotoxic modular proteins composed of a heavy chain and a light chain connected by a disulfide bond and are produced by Clostridium botulinum. Although lethally toxic, botulinum toxin in low doses is clinically effective in numerous medical conditions, including muscle spasticity, strabismus, hyperactive urinary bladder, excessive sweating, and migraine. Globally, several companies are now producing products containing botulinum toxin for medical and cosmetic purposes, including the reduction of facial wrinkles. To test the efficacy and toxicity of botulinum toxin, animal tests have been solely and widely used, resulting in the inevitable sacrifice of hundreds of animals. Hence, alternative methods are urgently required to replace animals in botulinum toxin testing. Here, the various alternative methods developed to test the toxicity and efficacy of botulinum toxins have been briefly reviewed and future perspectives have been detailed.Diabetes mellitus affects the colonic motility developing gastrointestinal symptoms, such as constipation. The aim of the study was to examine the role of intracellular signaling pathways contributing to colonic dysmotility in diabetes mellitus. To generate diabetes mellitus, the rats were injected by a single high dose of streptozotocin (65 mg/kg) intraperitoneally. The proximal colons from both normal and diabetic rats were contracted by applying an electrical field stimulation with pulse voltage of 40 V in amplitude and pulse duration of 1 ms at frequencies of 1, 2, 4, and 6 Hz. The muscle strips from both normal rats and rats with diabetes mellitus were pretreated with different antagonists and inhibitors. Rats with diabetes mellitus had lower motility than the control group. There were significant differences in the percentage of inhibition of contraction between normal rats and rats with diabetes mellitus after the incubation of tetrodotoxin (neuronal blocker), atropine (muscarinic receptor antagonist), prazosin (α1 adrenergic receptor antagonist), DPCPX (adenosine A1 receptor antagonist), verapamil (L-type Ca2+ channel blocker), U73122 (PLC inhibitor), ML-9 (MLCK inhibitor), udenafil (PDE5 inhibitor), and methylene blue (guanylate cyclase inhibitor). The protein expression of p-MLC and PDE5 were decreased in the diabetic group compared to the normal group. These results showed that the reduced colonic contractility resulted from the impaired neuronal conduction and decreased muscarinic receptor sensitivity, which resulted in decreased phosphorylation of MLC via MLCK, and cGMP activity through PDE5.Nanoarchitectonics of neutral Au6 cluster upon addition and removal of one electron have been studied using density functional based reactivity descriptors. We studied the response of various sites of cationic, neutral and anionic Au6 clusters towards impending electrophilic and nucleophilic attacks using DFT based local reactivity descriptors, viz, Fukui function for nucleophilic attack f+. Fukui function for electrophilic attack f-, relative nucleophilicity f+/f- and relative electrophilicity f+/f-. Based on these parameters different types of unique atoms have been identified for each cluster. Reactivity predictions for the unique atoms of the minimum energy planar triangular Au6 structure have been verified by using CO as a probe molecule. It has been found adsorption of CO molecules on gold cluster brings about structural changes in the cluster and that the CO molecule prefers the apex site for adsorption onto the triangular Au6 cluster as compared to the mid site.Novel composites with improved mechanical strength, thermally stability and better biodegradability were fabricated using polyester resin (PR) and euphorbia coagulum (EC) with natural bamboo fiber (BF) by a compression molding technique. The addition of EC makes the composite more pronounced for alkali-treated BF. The composites were characterized in terms of water absorption, mechanical, thermal and biodegradability. Composites showed considerable improvement in thermal stability, mechanical properties (flexural strength and impact strength) and biodegradability. EC modified composite shows maximum improvement in physico-mechanical properties compared to other composites. The inoculation of EC modified and unmodified composite with fungi resulted in higher growth on modified composite compared to unmodified composite. These novel composites could be labeled as sustainable material because they were prepared from low-cost BF and EC through a green approach. The composite material developed can be used in building constructions as wood substitution, automotive parts, sports goods, etc.Mesoporous TiO₂ films are synthesized through evaporation-induced self-assembly using poly(ethylene oxide-b-ε-caprolactone) diblock copolymers as a soft-template. Using small-angle X-ray scattering and scanning electron microscopy, we investigate the effect of the TiO₂/PEO-b-PCL ratio on the resulting nanoarchitectonic structure. After sputter-coating Au and Pt layers, these Au/TiO₂ and Pt/TiO₂ nanocomposite films display drastically enhanced photodegradation of rhodamine 6G under ultraviolet irradiation, due to the metal films inhibiting the rapid recombination of photogenerated charge carriers.
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