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The sulfur and nitrogen moieties of methylphenyl sulfoximine (MPS)-enabled aryl thioamides are independently involved in annulation with unactivated alkynes to construct the unusual 6,6-fused thiopyranoisoquinoline skeletons. The MPS directing group plays a vital role in making this unprecedented Ru-catalyzed one-pot double annulation of aryl thioamides with alkynes chemo- and regioselective. Both the o,o'-C-H bonds of the aryl motif are sequentially functionalized to form four bonds [C-C, C-S and C-C, C-N] in a single operation by overcoming the undisputed challenges, viz. the "S" poisoning effect on the transition-metal catalyst and the susceptibility of S to oxidation. The novel isothiochromene-1-one skeletons are successfully constructed, as the annulation is initiated with S in preference over the N motif of thioamides with alkynes. The preliminary photophysical properties of the thiopyrano-isoquinoline derivatives are also discussed.Cryo-electron microscopy (cryo-EM) has emerged as a vital tool to reveal the native structure of beam-sensitive biomolecules and materials. p-Hydroxy-cinnamic Acid in vivo Yet high-resolution cryo-EM analysis is still limited by the poorly controlled specimen preparation and urgently demands a robust supporting film material to prepare desirable samples. Here, we developed a bilayer Janus graphene membrane with the top-layer graphene being functionalized to interact with target molecules on the surface, while the bottom layer being kept intact to reinforce its mechanical steadiness. The ultraclean and atomically thin bilayer Janus membrane prepared by our protocol on one hand generates almost no extra noise and on the other hand reduces the specimen motion during cryo-EM imaging, thus allowing the atomic-resolution characterization of surface functional groups. Using such Janus membranes in cryo-EM specimen preparation, we were able to directly image the lithium dendrite and reconstruct macromolecules at near-atomic resolution. Our results demonstrate the bilayer Janus design as a promising supporting material for high-resolution cryo-EM and EM imaging.Hikizimycin (1) is a potent anthelmintic and antibacterial natural product. The core 4-amino-4-deoxyundecose sugar (hikosamine) of 1 consists of an 11-carbon linear chain substituted with one amino group and 10 hydroxy groups. The C1 and C6O positions of the 10 contiguous stereocenters are further appended by a cytosine base and a 3-amino-3-deoxyglucose sugar (kanosamine), respectively. Since the structural determination in the early 1970s, synthetic chemists have been attracted by this exceedingly complex structure and have investigated the full chemical construction of 1. These synthetic efforts culminated in four syntheses of the protected hikosamines and two total syntheses of 1. In this Perspective, we summarize the strategies and tactics utilized in these syntheses to showcase the evolution of modern natural product synthesis.Generally, single organic or inorganic inhibitors could effectively inhibit corrosion for metallic materials; however, there are rarely reports about the hybrid corrosion inhibitors consisting of organic and inorganic inhibitors. Thus, in this work, we synthesize a hybrid environment-friendly water-soluble corrosion inhibitor (Sb quantum dots) containing Sb, Sb2O3, Sb2O4, and carbon using the electrochemical exfoliation method. The inhibition effectiveness in short- and long-term immersion tests is measured using electrochemical methods, weight loss, and surface analysis. The results exhibit that the corrosion inhibition efficiency sensitively relates to the concentration of Sb quantum dots (SQDs), which achieves the largest value as the concentration of SQDs increases to 200 mg/L. Atomic force microscopy, scanning electron microscopy, and contact angle analysis reveal that the SQDs well-disperse on and cover the Q235 steel surface at 200 mg/L. According to the Langmuir adsorption data, the physicochemical adsorption and effective antioxidation of SQDs on the passivated Q235 steel surface are in charge of the effective corrosion inhibition efficiency in 0.5 M H2SO4 solution.Current ambient ionization sources for mass spectrometry (MS) are typically connected to gas cylinders, high-voltage supply, injection pump, and other accessory equipment, which hinder the popularization of MS in the field of on-site detection. Here, we developed a wireless pocket-size "MasSpec Pointer" (weights 65 g) based on arc discharge powered by a 3.7 V polymer Li battery for ambient ionization MS. A high voltage of 5600 V and 20 kHz was generated from the boost coil to penetrate air and form a plasma. The relative standard deviation (RSD) of the high-voltage pulses is 3.8%, leading to a stable discharge and a good quantification performance. A mini diaphragm pump was used to cool the plasma from ∼600 to ∼40 °C and to blow the plasma into a jet, which facilitates sampling. MasSpec Pointer can work well at both positive- and negative-ion modes without any modification and can quickly test gaseous, liquid, or solid samples. The limit of detection of this device for atrazine (an agrochemical) is lower than 0.1 ng/mL. MasSpec Pointer has shown its ability to pinpoint the double-bond location of fatty acid isomers without derivatization reagents or light illumination. Agrochemicals from the surface of an apple and daily chemicals from the surface of a finger were detected successfully using MasSpec Pointer coupled with a miniature mass spectrometer. We believe the "point-and-shoot" device coupled with mini-MS brings the hope for an age of detecting chemicals on-site by nonprofessionals.Alzheimer's disease (AD) is a neurodegenerative disease associated with amyloid-β (Aβ) deposition, leading to neurotoxicity (oxidative stress and neuroinflammation) and gut microbiota imbalance. Resveratrol (Res) has neuroprotective properties, but its bioavailability in vivo is very low. Herein, we developed a small Res-selenium-peptide nanocomposite to enable the application of Res for eliminating Aβ aggregate-induced neurotoxicity and mitigating gut microbiota disorder in aluminum chloride (AlCl3) and d-galactose(d-gal)-induced AD model mice. Res functional selenium nanoparticles (Res@SeNPs) (8 ± 0.34 nm) were prepared first, after which the surface of Res@SeNPs was decorated with a blood-brain barrier transport peptide (TGN peptide) to generate Res-selenium-peptide nanocomposites (TGN-Res@SeNPs) (14 ± 0.12 nm). Oral administration of TGN-Res@SeNPs improves cognitive disorder through (1) interacting with Aβ and decreasing Aβ aggregation, effectively inhibiting Aβ deposition in the hippocampus; (2) decreasing Aβ-induced reactive oxygen species (ROS) and increasing activity of antioxidation enzymes in PC12 cells and in vivo; (3) down-regulating Aβ-induced neuroinflammation via the nuclear factor kappa B/mitogen-activated protein kinase/Akt signal pathway in BV-2 cells and in vivo; and (4) alleviating gut microbiota disorder, particularly with respect to oxidative stress and inflammatory-related bacteria such as Alistipes, Helicobacter, Rikenella, Desulfovibrio, and Faecalibaculum. Thus, we anticipate that Res-selenium-peptide nanocomposites will offer a new potential strategy for the treatment of AD.As a global health challenge, hepatocellular carcinoma (HCC) is strongly associated with chronic inflammation. Targeting inflammation, particularly inflammatory factors, is regarded as an important strategy for HCC diagnosis and treatment. Pyroglutamic aminopeptidase I (PGP-I), a common exopeptidase, was recently identified as a novel inflammatory cytokine in cells. However, whether PGP-I is involved in HCC development and can be regarded as a biomarker remains unclear. To address this issue, endogenous PGP-I was imaged in live cells and in vivo, and the related biochemical and pathological processes were analyzed accordingly with a newly developed fluorogenic PGP-I biosensor. Bioimaging with the specific biosensor demonstrated the aberrant expression of PGP-I in HCC cell lines and tumor-bearing nude mice. Moreover, overexpression of PGP-I in HCC cells promoted tumor progression, whereas knockdown of PGP-I significantly suppressed tumor cell growth and migration. The activity of PGP-I was further identified to be highly related to the phosphorylation of STAT3, which could be impeded by the natural product parthenolide. Collectively, these findings suggest that PGP-I, which can promote hepatocellular tumor progression through the classical inflammation-/tumor-related IL-6/STAT3 pathway, may serve as a potential HCC biomarker and therapeutic target.Kinase-focused inhibitors previously revealed compounds with differential activity against different stages of Plasmodium falciparum gametocytes. MMV666810, a 2-aminopyrazine, is more active on late-stage gametocytes, while a pyrazolopyridine, MMV674850, preferentially targets early-stage gametocytes. Here, we probe the biological mechanisms underpinning this differential stage-specific killing using in-depth transcriptome fingerprinting. Compound-specific chemogenomic profiles were observed with MMV674850 treatment associated with biological processes shared between asexual blood stage parasites and early-stage gametocytes but not late-stage gametocytes. MMV666810 has a distinct profile with clustered gene sets associated primarily with late-stage gametocyte development, including Ca2+-dependent protein kinases (CDPK1 and 5) and serine/threonine protein kinases (FIKK). Chemogenomic profiling therefore highlights essential processes in late-stage gametocytes, on a transcriptional level. This information is important to prioritize compounds that preferentially compromise late-stage gametocytes for further development as transmission-blocking antimalarials.
We present a patient with bifacial weakness and paraesthesia subtype of Guillain-Barré syndrome (GBS), which occurred 1 month after a SARS-CoV-2 infection. While GBS as complication of SARS-CoV-2 infection has been described many times, only a few cases of post-COVID-19 bifacial weakness and paraesthesia are known to date.
A 59-year-old man presented with thoracoradicular pain, paraesthesias of hands and feet, as well as progressive bilateral facial palsy. Neurological examination revealed a hyporeflexia of his lower limbs and hypoaesthesia of his hands and feet. Clinical and electrophysiological findings as well as CSF analysis were consistent with bifacial weakness and paraesthesia. The patient's condition improved promptly after 5 days of intravenous immunoglobulin therapy.
We suspect bifacial weakness and paraesthesia to be a possible post-infectious complication of COVID-19. Hence, it is a differential diagnosis of facial nerve palsy in association with SARS-CoV-2 infection. Considering the rarity of GBS and bifacial weakness and paraesthesia, it appears unlikely that bigger trials elucidating the causal relation between them and SARS-CoV-2 infection will be available in the future.
We suspect bifacial weakness and paraesthesia to be a possible post-infectious complication of COVID-19. Hence, it is a differential diagnosis of facial nerve palsy in association with SARS-CoV-2 infection. Considering the rarity of GBS and bifacial weakness and paraesthesia, it appears unlikely that bigger trials elucidating the causal relation between them and SARS-CoV-2 infection will be available in the future.
Website: https://www.selleckchem.com/products/hydroxy-cinnamic-acid.html
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