Background: COVID-19 is still present in the world, though the extent varies by region and country. According to the World Health Organization, there have been over 617 million confirmed cases of COVID-19 and over 13 million deaths worldwide since the pandemic began on March 10, 2023. Aims and Objectives: This is a study conducted with the aim of providing biomarkers to predict COVID-19 disease progression and mortality based on red cell indices and platelet indices which are commonly measured as part of a complete blood count (CBC). Materials and Methods: A prospective study was conducted during the peak of the second wave of COVID-19 from March 2021 to June 2021. The study included 540 patients who were admitted to the Government General Hospital, Nizamabad, and had tested positive for COVID-19 by RT-PCR. Red Blood Cell (RBC), Hematocrit (HCT), Red cell indices like Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Haemoglobin Concentration (MCHC), Red Cell Distribution width (RDW) and Platelet indices like Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Plateletcrit (PCT), Platelet–Large Cell Ratio were taken from CBC analyzer Sysmex XN-1000 and analyzed statistically. The patients were then followed up for a period of 14 days to track their outcomes. Results: In the data, majority were male n=334 (62%) and n=280 (38%) were female. 70.37% (n=380) were survivors and 29.63% (n=160) were non-survivors. Red blood cell, red cell indices such as RDW-CV and RDW-SD, and platelet indices such as PCT and PDW were significantly higher in non-survivors compared to survivors with P<0.05. Conclusion: Non-survivors had significantly higher levels of RDW-CV, RDW-SD, PCT, and PDW compared to survivors. These parameters in combination can be useful for predicting COVID-19 mortality at early stage in forthcoming waves.
Alzheimer's disease (AD) is a neurological disease that disturbs the memory, thinking skills, and behavior of the affected person. AD is a complex disease caused by the breakdown of acetylcholine via acetylcholinesterase (AChE). The present study aimed to assess the synthetic inhibitors of AChE that could be used to treat AD. For this purpose, synthetic compounds of oxadiazole derivatives (15-35) were evaluated and identified as promising inhibitors of AChE, exhibiting IC50 varying between 41.87 ± 0.67 and 1580.25 ± 0.7 μM. The kinetic parameters indicated that all the studied compounds bind to the allosteric site and decrease the efficiency of the AChE enzyme. In silico docking analysis showed that the majority of the compounds interact with the anionic subsite and Per-Arnt-Sim domain of AChE and are stabilized by various bonds including π-π and hydrogen bonding. The stability of the most potent compounds 16 and 17 with AChE interaction was confirmed by molecular dynamics simulations. Moreover, all compounds exhibited concentration-dependent calcium (Ca2+) antagonistic and spasmolytic activities. Among the whole series of oxadiazole derivatives, compounds 16 and 17 displayed the highest activities on spontaneous and potassium (K+)-induced contraction. Therefore, the AChE inhibitory potential, cytotoxicity safe profile, and Ca2+ antagonistic ability of these compounds make them potential therapeutic agents against AD and its associated problems in the future.
Background: Tyrosinase enzyme is one of the important targets to reduce melanoma and other skin disorders. Standard inhibitors of tyrosinase enzyme including arbutin and kojic acid are less effective. Some NSAIDs such as acetylsalicylic acid, mefanamic acid, and diclofenac are known to possess inhibitory potential against melanogenesis. The current study deals with the screening of tyrosinase inhibitory potential of S-naproxen derivatives. Methods: Synthetic S-naproxen derivatives 1-33 were evaluated for tyrosinase inhibitory activity in vitro. Results: Six compounds 2, 8, 9, 20, 21, and 29 showed good to moderate activity in the range of (IC50 = 21.05 ± 0.9-53.22 ± 0.7 µM) as compared to the standard kojic acid (IC50 = 16.9 ± 1.3 µM). Compound 9 (IC50 = 21.05 ± 0.9 µM) was found to be significantly active and showed activity close to the standard. Compounds 2 (IC50 = 33.23 ± 1.1 µM), 8 (IC50 = 42.10 ± 1.0 µM), 20 (IC50 = 35.40 ± 0.4 µM), 21 (IC50 = 41.01 ± 0.6 ±M), and 29 (IC50 = 53.22 ± 0.7 µM) were found to be moderately active. Structure-activity relationship (SAR) was rationalized on the basis of different substituents and functionalities present on the main scaffold. Conclusion: This study has identified a number of compounds derived from S-naproxen with comparable tyrosinase inhibitory activity.
Some promising antagonists viz. Trichoderma harzianum, Trichoderma viride, Aspergillus niger, Aspergillus flavus and Penicillium sp. were selected and evaluated for their comparative efficacy against the red rot pathogen Colletotrichum falcatum under laboratory conditions following the dual culture technique. All the tested antagonists except Penicillium sp. prominently inhibited the mycelial growth of C. falcatum. After 12 days of incubation, the antagonists showed full radial growth by which they encircled, slowed down the growth and sometimes overran the mycelia of C. falcatum on PDA. Penicillium sp. had no effect in restricting the growth of the pathogenic fungi under similar conditions. Keywords: Biocontrol, Colletotrichum falcatum, sugarcane, antagonists
Abstract Proximity labelling provides a powerful in vivo tool to characterize the proteome of sub-cellular structures and the interactome of specific proteins. Using the highly active biotin ligase TurboID, we optimize a proximity labelling protocol for C. elegans . We use this protocol to characterise the proteomes of the worm’s gut, muscle, skin, and nervous system. We express TurboID exclusively in the pair of AFD neurons and show we can identify known and previously unknown proteins expressed selectively in AFD. We knock TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identify many known ELKS-1 interacting proteins as well as previously uncharacterised synaptic proteins. Versatile vectors, and the inherent advantage of C. elegans for biochemistry, make proximity labelling a valuable addition to the nematode’s armory. Teaser We optimize a TurboID proximity labeling protocol for C. elegans and use it to characterize tissue and synaptic proteomes
Abstract Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17–MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.
The preparation of side-chain-to-side-chain-cyclised peptides through lactam bridge formation requires orthogonal protecting groups for side-chain amino and carboxylate functionalities. Use of the 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl ester (Dmab) group for this role in the protection of the glutamyl side-chain resulted in the formation of unexpected side-products. During synthesis of fully protected peptide targets, Nα-pyroglutamyl chain-terminated peptides were observed. Pyroglutamyl peptides were not observed in analogous peptides synthesised using the traditional tert-butyl ester protecting group. Selective removal of the Dmab group proceeds through a two-stage procedure, hydrazinolytic cleavage of the dimedone moiety followed by 1,6-elimination of the resulting peptide-glutamyl 4-aminobenzyl ester. The latter reaction is sufficiently slow to allow isolation of the transiently stable glutamyl derived 4-aminobenzyl ester peptide. Attempted side-chain-to-side-chain cyclisation (through orthogonally protected Glu and Lys residues) of peptides prepared via Glu(ODmab) failed and led to modification of the Lys Nε-amino group when 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) was used as carboxy-activating reagent. Analogous peptides prepared utilising allyl side-chain protection for glutamyl residues were successfully cyclised using HBTU.
During the typesetting of the article above an error was introduced that resulted in 9 missing nucleotides on page 10. Please see the corrections, which are set in red in Figure below. Production apologizes for the error.
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