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In most of developing countries, open dumpsites are frequently opted as the best choice to get rid of waste, but this type of practice has severe threats to the environment. This may be considered as one of the factors in contamination of soil and groundwater. The study examined the arsenic and physicochemical properties of soil around a municipal waste dumpsite in Rohtak city, Haryana. For Rohtak city, leachate secretion and generation of various gases at landfill site may be a factor in contamination of soil around the dumpsite. 13 samples of soil were collected from the surrounding area of dumpsite within 2 km area. Soil samples were tested for various parameters like pH, EC, moisture content, bulk density, water holding capacity, organic matter, chloride and arsenic. The pH values of the various samples of different locations ranged from 7.14 to 8.34, EC ranged from 1034-9536 add μS/cm with a mean value of 3484 μS/cm, organic matter of the soil samples of present study ranged from 1.26 to 3.16%. Water holding capacity of soil samples ranged from 51.02% to 59.14%, moisture content was found from 3.12 to 13.86%, bulk density was found from 1.28-1.89 g/cm³. Range of chloride content was 358-4165 mg/ kg with mean value 1679 mg/kg. Higher level of arsenic contamination is found in the surrounding soil samples, ranged from 410 ppb to 840 ppb with mean value of 618 ppb which may be due to leachate secretion at dumpsite area that make soil unsuitable for agricultural purposes. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal receptors. This lack of receptors renders TNBC unsuitable for targeted-based treatment, making it the most fatal and aggressive subtype of breast cancer. TNBC has a greater relapse rate, worse prognosis, and increased metastasis rate compared to non-TNBC because of its tendency to resist apoptosis, a programmed cell death triggered by most chemotherapeutic drugs, producing anticancer efficacy. This work describes two new drugs, TPH104c, and TPH104m, that induce a non-apoptotic form of cell death in TNBC. The incubation of TNBC cells with TPH104c or TPH104m causes cellular expansion and rupture without producing apoptotic characteristics, such as nuclear fragmentation, apoptotic blebbing, or caspase activation. TPH104c and TPH104m decreased the mitochondrial protein, division regulator, and dynamin-related protein 1 (DRP1). The level of DRP1 in TNBC cells affects the magnitude of cytotoxicity produced by TPH104c and TPH104m. Apoptosis induction with taxanes or anthracyclines is the primary therapy for TNBC. Cancer cells can develop resistance to anticancer drugs, causing them to recur and metastasize. Therefore, non-apoptotic cell death inducers could be a potential treatment to circumvent apoptotic drug resistance. In this study, we discovered two novel compounds, TPH104c and TPH104m, which induced non-apoptotic cell death in TNBC cells. These lead compounds were 15- to 30-fold more selective in TNBC cell lines and significantly decreased the proliferation of TNBC cells compared to that of normal mammary epithelial cell lines. TPH104c and TPH104m induced a unique type of non-apoptotic cell death, characterized by the absence of cellular shrinkage and the absence of nuclear fragmentation and apoptotic blebs. Although TPH104c and TPH104m induced the loss of the mitochondrial membrane potential, TPH104c- and TPH104m-induced cell death did not increase the levels of cytochrome c and intracellular reactive oxygen species (ROS) and caspase activation, and cell death was not rescued by incubating cells with the pan-caspase inhibitor, carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). Furthermore, TPH104c and TPH104m significantly downregulated the expression of the mitochondrial fission protein, DRP1, and their levels determined their cytotoxic efficacy. Overall, TPH104c and TPH104m induced non-apoptotic cell death, and further determination of their cell death mechanisms will aid in the development of new potent and efficacious anticancer drugs to treat TNBC. [ABSTRACT FROM AUTHOR]

β-secretase 1, one of the most important proteins, is an aspartate protease. This membrane-associated protein is used for treating Alzheimer's disease (AD). Several inhibitors have been pursued against β-secretase 1, but they still have not resulted effectively. Virtual screening based on pharmacophores has been shown to be useful for lead optimization and hit identification in the preliminary phase of developing a new drug. Here, we screen the commercially available databases to find the hits against β-secretase 1 for drug discovery against AD. Virtual screening for 200,000 compounds was done using the database from the Vitas-M Laboratory. The phase screen score was utilized to assess the screened hits. Molecular docking was performed on compounds with phase scores >1.9. According to the study, the 66H ligand of the crystal structure has the maximum performance against β-secretase 1. The redocking of the co-crystal ligand showed that the docked ligand was seamlessly united with the crystal structure. The reference complex had three hydrogen bonds with Asp93, Asp289, and Gly291; one van der Waals interaction with Gly74; and three hydrophobic interactions. After equilibration, the RMSD of the reference compound sustained a value of ~1.5 A until 30 ns and then boosted to 2.5 A. On comparison, the RMSD of the S1 complex steadily increased to ~2.5 A at 15 ns, displayed slight aberrations at approximately ~2.5-3 A until 80 ns, and then achieved steadiness toward the end of the simulation. The arrangements of proteins stayed condensed during the mockup when bonded to these complexes as stable Rg values showed. Furthermore, the MM/GBSA technique was employed to analyze both compounds' total binding free energies ^Gtotal). Our research study provides a new understanding of using 66H as anti-βsecretase 1 for drug development against AD. [ABSTRACT FROM AUTHOR]

Dendrites are tree-like structures with tiny spines specialized to receive excitatory synaptic transmission. Spino-dendritic plasticity, driven by neural activity, underlies the maintenance of neuronal connections crucial for proper circuit function. Abnormalities in dendritic morphology are frequently seen in epilepsy. However, the exact etiology or functional implications are not yet known. Therefore, to better comprehend the structure-function significance of this dendritic pathology in epilepsy, it is necessary to identify the common spino-dendritic disturbances present in both human and experimental models. Here, we describe the dendritic and spine structural profiles found across human refractory epilepsy as well as in animal models of developmental, acquired, and genetic epilepsies. [ABSTRACT FROM AUTHOR]

HLA‐C*17:78 differs from HLA‐C*17:03:01:03 by one nucleotide change C>T in exon 3 (GCG>GTG). [ABSTRACT FROM AUTHOR]

HLA‐A*33:33:02 differs from HLA‐A*33:33:01 by one synonymous nucleotide change C>T in exon 3 (TCC>TCT). [ABSTRACT FROM AUTHOR]