With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.Retaining glycosidase mutants lacking its general acid/base catalytic residue are originally termed thioglycoligases which synthesize thio-linked disaccharides using sugar acceptor bearing a nucleophilic thiol group. A few thioglycoligases derived from retaining α-glycosidases have been classified into a new class of catalysts, O-glycoligases which transfer sugar moiety to a hydroxy group of sugar acceptors, resulting in the formation of O-linked glycosides or oligosaccharides. In this study, an efficient O-α-glucosylation of flavonoids was developed using an O-α-glycoligase derived from a thermostable α-glucosidase from Sulfolobus solfataricus (MalA-D416A). The O-glycoligase exhibited efficient transglycosylation activity with a broad substrate spectrum for all kinds of tested flavonoids including flavone, flavonol, flavanone, flavanonol, flavanol and isoflavone classes in yields of higher than 90%. The glucosylation by MalA-D416A preferred alkaline conditions, suggesting that pH-promoted deprotonation of hydroxyl groups of the flavonoids would accelerate turnover of covalent enzyme intermediate via transglucosylation. More importantly, the glucosylation of flavonoids by MalA-D416A was exclusively regioselective, resulting in the synthesis of flavonoid 7-O-α-glucosides as the sole product. Kinetic analysis and molecular dynamics simulations provided insights into the acceptor specificity and the regiospecificity of O-α-glucosylation by MalA-D416A. This pH promoted transglycosylation using O-α-glycoligases may prove to be a general synthesis route to flavonoid O-α-glycosides.The increasing amount of marine litter is a global issue that is also being experienced within the Manila Bay Philippines.  https://www.selleckchem.com/products/tiragolumab-anti-tigit.html  To better understand the behavior of litter within the bay, particle tracking simulations of floating litter released from several sources were conducted. Forward-in-time (PTM-FIT) simulation of particle movements showed that during the southwest monsoon season, litter particles released by river sources tend to accumulate toward five hotspots located along the northeastern coastline of the bay. Backward-in-time (PTM-BIT) simulation of particles released from the identified hotspots showed coastal and foreign sources contributing to the litter collected within these areas. PTM-FIT simulations during the southwest monsoon season showed that particles tend to circulate locally within the bay before being transported toward the hotspots. By contrast, PTM-FIT simulations during the northwest monsoon season showed that litter particles tend to travel toward the mouth of the bay, an implication for global marine litter pollution.We report seasonal and temporal variation of total organic carbon (TOC) in the eastern Arabian Sea (AS). In comparison to the deep, TOC in the top 100 m showed spatial variation with higher concentrations towards northern AS during North east monsoon (NEM) and South west monsoon (SWM). A comparison with the US-JGOFS data (1995) shows warmer temperatures, enhanced TOC and low chlorophyll in the recent years. High TOC is associated with Arabian Sea high saline waters (ASHSW), advected from the Arabian Gulf, might have resulted in an enhancement of TOC in the eastern AS. This excess TOC supports a high abundance of bacteria despite the low primary productivity. TOC oxidation accounted for 14.3% and 22.5% of oxygen consumption for waters with potential density between 24.5 and 27.3 kg/m3. This study attains great significance considering the missing links with respect to the role of transport processes in ocean deoxygenation under ongoing warming scenarios.So far, research on plant-associated macroinvertebrates, even if conducted on a large number of water bodies, has mostly focused on a relatively small area, permitting limited conclusions to be drawn regarding potentially broader geographic effects, including climate. Some recent studies have shown that the composition of epiphytic communities may differ considerably among climatic zones. To assess this phenomenon, we studied macroinvertebrates associated with the common reed Phragmites australis (Cav.) Trin. ex Steud in 46 shallow lakes using a common protocol. The lakes, located in nine countries, covered almost the entire European latitudinal range (from less then 48°N to 61°N) and captured much of the variability in lake size and nutrient content in the region. A Poisson Generalized Linear Mixed Model (GLMM) showed the number of macroinvertebrate epiphytic taxa to be negatively associated with water conductivity and positively associated with medium ice cover duration (approximately 1 month). A Gamma GLMM showed a positive effect of chlorophyll a on the density of macroinvertebrates, and a significantly greater density in lakes located at the lowest and highest latitudes.