Azine Based Oligoesteric Chemosensors for Cu2+ Ion Detection: Synthesis, Structural Characterization, and Theoretical Investigations.

Synthesized monomer and its three oligoesters were characterized by techniques such as 1H, 13C{1H}, IR, UV, GPC and applied to chemosensor applications. A series of metal ions was studied with fluorophores to evaluate the sensitivity towards Cu2+ ion. The fluorophores results exhibit the selective and sensitive "Turn off" fluorescence response with Cu2+ ion in DMF/H2O (1:1, pH: 7.4, fluorophore: 5 µM) solution. Binding stoichiometry and binding constant of fluorophores were calculated using Stern-Volmer equation and Benesi-Hildebrand plots, respectively. Structure of fluorophores were studied using DFT, B3LYP/6-311 + + G(d,p) level basis set. Quenching mechanisms and electrical properties of fluorophores were explained with theoretical outcomes. Iodine doped and undoped oligoesters electrical conductivity were studied in solid-state and the conductivity was gradually increased with increase the contact time of iodine with oligoesters. At different frequencies and temperatures, the dielectric measurement was calculated using the two-probe method. Among all oligoesters, DMDAP exhibited high electrical conductivity and DMDMP has a higher dielectric constant value than other oligoesters.

Loss of cytoplasmic FMR1-interacting protein 2 (CYFIP2) induces browning in 3T3-L1 adipocytes via repression of GABA-BR and activation of mTORC1.

Obesity and related metabolic disorders are epidemic diseases. Promoting thermogenesis and a functional increase in the browning of white adipocytes may counteract obesity. On the other hand, the molecular mechanism that regulates brown and beige fat-mediated thermogenesis is unclear. This article reports a molecular network led by cytoplasmic FMR1-interacting protein 2 (CYFIP2) that negatively regulates adipocyte browning in white adipocytes. Although the function of CYFIP2 in Fragile X Syndrome (FXS) and autism have been reported, its physiological roles in adipocytes remain elusive. Therefore, this study examined the physiological consequences of its deprivation in cultured 3T3-L1 white adipocytes using loss-of-function studies. Combined real-time quantitative reverse-transcription polymerase chain reaction and immunoblot analysis showed that the loss of CYFIP2 induces fat browning, as evidenced by the gene and protein expression levels of the brown fat-associated markers. A deficiency of CYFIP2 promoted mitochondrial biogenesis and significantly enhanced the expression of the core set beige fat-specific genes (Cd137, Cidea, Cited1, Tbx1, and Tmem26) and proteins (PGC-1α, PRDM16, and UCP1). In addition, a CYFIP2 deficiency promoted lipid catabolism and suppressed adipogenesis, lipogenesis, and autophagy. A mechanistic study showed that the loss of CYFIP2 induces browning in white adipocytes, independently via the activation of mTORC1 and suppression of the GABA-BR signaling pathway. The present data revealed a previously unidentified mechanism of CYFIP2 in the browning of white adipocytes and emphasized the potential of CYFIP2 as a pharmacotherapeutic target for treating obesity and other metabolic disorders.

Loss of family with sequence similarity 107, member A (FAM107A) induces browning in 3T3-L1 adipocytes.

Induction of white fat browning (beiging) and activation of brown fat has been considered a promising strategy to treat obesity and associated metabolic complications. However, the molecular mechanisms regulating brown and beige fat-mediated thermogenesis remains unclear. Our study aimed to identify genes with a hitherto unknown mechanism in the metabolic functions of adipocytes and identified family with sequence similarity 107, member A (FAM107A) as a factor that interferes with fat browning in white adipocytes. We explored physiological roles of FAM107A in cultured 3T3-L1 white adipocytes and HIB1B brown adipocytes by using FAM107A-deficient adipocytes. Significant loss in FAM107A gene functionality induced fat browning was evidenced by evaluating the gene and protein expression level of brown fat-associated markers through real-time qRT-PCR and immunoblot analysis, respectively. Deficiency of FAM107A promoted mitochondrial biogenesis and significantly upregulated core fat-browning marker proteins (PGC-1α, PRDM16, and UCP1) and beige-specific genes (Cd137, Cited1, Tbx1, and Tmem26). Furthermore, FAM107A increased adipogenesis and negatively regulated lipid metabolism in 3T3-L1 adipocytes. In addition, in-silico analysis revealed a strong interaction between FAM107A and ß3-AR based on their energy binding score. Next, mechanistic study revealed that specific knockdown of FAM107A induces browning in white adipocytes via activation of ß3-AR, AMPK and p38 MAPK-dependent signaling pathways. Our data unveiled a previously unknown mechanism of FAM107A in the regulation of lipid metabolism and identified its significant role in metabolic homeostasis. This highlighted the potential of FAM107A as a pharmacotherapeutic target in treating obesity and related metabolic disorders.

Environmental benignity of a pesticide in soft colloidal hydrodispersive nanometric form with improved toxic precision towards the target organisms than non-target organisms.

Mosquito-borne diseases are of major concern as they cause devastating health effects, morbidity, and mortality in the human population. Conventional pesticides have failed to curb the mosquito population due to the development of insensitivity in mosquitoes. Hence, higher dosages of pesticides along with their toxic solubilizers have been employed, which have led to raise in pesticide pollution load, environmental toxicity, and human health concerns. As a realisation for the requirement of alternative pesticides, the present study has involved in the formulation of a hydrodispersive nanometric colloidal form of deltamethrin (NDM), a type-II pyrethroid pesticide, from its hydroimmisicible parental form (PDM). The mean hydrodynamic diameter of the droplets was found to be 30.6±4.6nm by dynamic light scattering study (DLS). High-resolution transmission electron micrographs have revealed the spherical structure of the droplets with a size range of 35-40nm. The NDM was found to possess sedimentation resistance, intrinsic and hydrodispersive stability. The toxicity of NDM and PDM was comparatively investigated on target organisms (Culex tritaeniorhynchus and Culex quinquefasciatus mosquitoes) and non-target organisms (Allium cepa - Bioindicator of toxicants and Rhizobium sp. - Soil bacteria). As comparative to PDM, NDM has exerted higher efficacy on adult mosquito and larval population, even at low-level concentrations. However, in the case of non-target organisms, the NDM toxicity was lower than PDM. Comprehensively, the study has concluded the potential advantage of formulating conventional pesticides into nanometric soft colloidal form for the improved toxic precision on target organisms (mosquitoes). This ensures the ability of NDM to combat against the mosquito population even at lower concentrations, thereby reducing the pesticide exposure load towards the environment and human population.