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Background and Objectives: Rivaroxaban is a direct-acting anticoagulant used to prevent stroke in patients with atrial fibrillation. Rivaroxaban is a substrate for P-glycoprotein, which is encoded by the ABCB1 gene. Rivaroxaban is also metabolized by the CYP3A5 gene. Therefore, the current study is carried out to study the effects of polymorphisms in the ABCB1 and CYP3A5 genes, which may affect the plasma levels of rivaroxaban, with subsequent clinical outcomes (bleeding events) associated with the therapy. Materials and Methods: The study was conducted on 66 naive patients with atrial fibrillation treated with rivaroxaban. Blood samples of rivaroxaban were taken at 3 h and after 1 month following the administration of the drug to measure plasma levels. The blood level of rivaroxaban was measured with an HPLC-UV detector. Sanger sequencing was used to find polymorphisms in the targeted genes. Coagulation parameters were measured at 3 h and after 1 month of administration of rivaroxaban. Frequencies of bleeding events were recorded throughout the one-month course of drug therapy. Results: The heterozygous and homozygous mutant genotypes of ABCB1 (rs2032582, rs1045642, rs1128503, and rs4148738) and CYP3A5 (rs776746) showed lower plasma concentrations as compared to the wild-type genotype. ABCB1 (rs2032582, rs1045642, rs1128503, and rs4148738) and CYP3A5 (rs776746) gene polymorphisms had a statistically significant impact on the plasma concentration of rivaroxaban among the heterozygous and homozygous mutant genotypes compared to the wild-type genotype. The heterozygous variant of ABCB1 and homozygous variant of CYP3A5 suffered more events of bleeding. Conclusions: It was concluded that ABCB1 (rs2032582, rs1045642, rs1128503, and rs4148738) and CYP3A5 (rs776746) gene polymorphisms had a significant impact on the plasma levels of rivaroxaban in patients treated for atrial fibrillation on day three as well as after one month of the therapy. The lowest plasma levels were observed in patients with a homozygous variant of ABCB1 (rs2032582, rs1045642, or rs4148738) along with the CYP3A5*1/*3 allele. The heterozygous variant of ABCB1 SNPs and homozygous variant of CYP3A5 SNPs suffered more events of bleeding. [ABSTRACT FROM AUTHOR]

The Ziziphus genus, belonging to the Rhamnaceae family, holds significant economic, nutritional, and medicinal value. However, much remains to be discovered about its diversity and physical characteristics. Factors such as growth, resilience to changes, disease resistance, and unique features contribute to the quality of Ziziphus species. This study aims to investigate the genomes of 200 genotypes from five Ziziphus species: Ziziphus jujuba (Zj), Ziziphus nummularia (Zm), Ziziphus oxyphylla (Zx), Ziziphus mauritiana (Zm), and the cultivated variety Ziziphus jujube var. jujube, collected from Pakistan and China. Our goal is to identify single nucleotide polymorphisms (SNPs) associated with eight different traits and understand the genetic diversity within the selected Ziziphus species and their genotypes. Using high‐quality SNPs obtained through genotype‐by‐sequencing (GBS), we conducted population structure, phylogenetic, and principal coordinates analyses, identifying a total of 10,945 clean SNPs. These genotypes were categorized into two groups, A and B. Natural Ziziphus variants in Pakistan, specifically Z. jujuba and Z. nummularia, exhibited high levels of genetic diversity and polymorphic information content (PIC) of 0.46 and 0.41, respectively, compared to other species. Furthermore, we identified 15 influential candidate genes that play crucial roles in regulating agronomic traits, such as fruit width and diameter, leaf width, plant height, and stem diameter within this group. This study provides valuable insights that can be utilized in Ziziphus breeding efforts. [ABSTRACT FROM AUTHOR]

Shortage of water and the depletion of groundwater reserves are serious challenges in Pakistan. As a result, solutions including groundwater recharge and other forms of sustainable groundwater management are being considered. Water quality, aquifer characteristics, and the feasibility of refilling were just a few of the hydrogeological factors that were carefully examined in this study. Well-construction methods were also dissected for this study. All aspects of the well's construction were considered. The study's findings highlight the importance of selecting a proper location for replenishing groundwater wells. In addition, different recharge strategies, including basins for infiltration and injection wells, were evaluated to find the most appropriate method for the site. It also investigated how the replenishment of groundwater wells could affect the ecosystem. Mitigation measures, such as proper sealing of the well casing and monitoring of water quality parameters, were recommended to minimize potential risks and ensure the sustainability of the recharge operation. Taxila, a Hilly area of Pakistan, poses unique challenges for groundwater management and sustainability. The water table is lower as compared to other areas. In response to diminishing groundwater resources and increasing water stress, this research project aimed to design and install two groundwater recharging wells in the Taxila area. The study's primary objectives were to assess the effectiveness of these wells in recharging groundwater, evaluate their environmental impact, and provide insights into their potential for sustainable water resource management in hilly regions. The research involved comprehensive site selection, hydrogeological investigations, and the design and construction of two recharge wells. Detailed monitoring and data collection were carried out before, during, and after the installation of these wells to evaluate their impact on groundwater levels and quality. [ABSTRACT FROM AUTHOR]

Extract of Rosa moschata (RM) fruits was evaluated for the anti-schizophrenic and antidepressant activities. We first determined the neurotoxic effect of hydro-methanolic extract of RM using inverted-screen test. Further, the extract was tested in the ketamine-induced schizophrenia model and its antidepressant effect was assessed by tail suspension and forced swim test in mice. Different doses of extract were administered once/day to the animals for 14 consecutive days. Behavioral parameters were investigated 24h after last administration of drug/extract by performing Ymaze test, forced swim test and open field test. Results showed that TD50 of the extract was ~1000mg/Kg. Moreover, extract significantly increased % alternations in YMT, reduced immobility time in FST and enhanced locomotion in OFT compared to saline group. Similarly, RM extract decreased time of immobility in FST and TST significantly showed antidepressant effect. Thus, it was concluded that extract of RM has antipsychotic and antidepressant properties. [ABSTRACT FROM AUTHOR]