Design of Multi-Target drugs of HDACs and other Anti-Alzheimer related Targets: Current strategies and future prospects in Alzheimer's diseases therapy.

Alzheimer disease (AD) is the most prevalent form of dementia that develops spontaneously in the elderly. It's worth mentioning that as people age, the epigenetic profile of the central nervous system cells changes, which may speed up the development of various neurodegenerative disorders including AD. Histone deacetylases (HDACs) are a class of epigenetic enzymes that can control gene expression without altering the gene sequence. Moreover, a promising strategy for multi-target hybrid design was proposed to potentially improve drug efficacy and reduce side effects. These hybrids are monocular drugs that contain various pharmacophore components and have the ability to bind to different targets at the same time. The HDACs ability to synergistically boost the performance of other anti-AD drugs, as well as the ease with which HDACs inhibitor cap group, can be modified. This has prompted numerous medicinal chemists to design a novel generation of HDACs multi-target inhibitors. Different HDACs inhibitors and other ones such as acetylcholinesterase, butyryl-cholinesterase, phosphodiesterase 9, phosphodiesterase 5 or glycogen synthase kinase 3ß inhibitors were merged into hybrids for treatment of AD. This review goes over the scientific rationale for targeting HDACs along with several other crucial targets in AD therapy. This review presents the latest hybrids of HDACs and other AD target pharmacophores.

Machine learning and interactive GUI for concrete compressive strength prediction.

Concrete compressive strength (CS) is a crucial performance parameter in concrete structure design. Reliable strength prediction reduces costs and time in design and prevents material waste from extensive mixture trials. Machine learning techniques solve structural engineering challenges such as CS prediction. This study used Machine Learning (ML) models to enhance the prediction of CS, analyzing 1030 experimental CS data ranging from 2.33 to 82.60 MPa from previous research databases. The ML models included both non-ensemble and ensemble types. The non-ensemble models were regression-based, evolutionary, neural network, and fuzzy-inference-system. Meanwhile, the ensemble models consisted of adaptive boosting, random forest, and gradient boosting. There were eight input parameters: cement, blast-furnace-slag, aggregates (coarse and fine), fly ash, water, superplasticizer, and curing days, with the CS as the output. Comprehensive performance evaluations include visual and quantitative methods and k-fold cross-validation to assess the study's reliability and accuracy. A sensitivity analysis using Shapley-Additive-exPlanations (SHAP) was conducted to understand better how each input variable affects CS. The findings showed that the Categorical-Gradient-Boosting (CatBoost) model was the most accurate prediction during the testing stage. It had the highest determination-coefficient (R2) of 0.966 and the lowest Root-Mean-Square-Error (RMSE) of 3.06 MPa. The SHAP analysis showed that the age of the concrete was the most critical factor in the predictive accuracy. Finally, a Graphical User Interface (GUI) was offered for designers to predict concrete CS quickly and economically instead of costly computational or experimental tests.

Petrographic and geochemical study of Precambrian and Paleozoic rocks in the western Anti-Atlas belt, Morocco: Facies, weathering, provenance and economic exploitation.

Detrital and volcanic-detrital rocks from the Ifni Buttonhole and Lakhssas Plateau were analyzed to determine their provenance, compositional maturity, and alteration source. Geochemically, the sediments were classified as arkoses, lithic arenites, grauwackes, sandstones, lithic arenites, and Fe-rich sands, indicating low compositional and mineralogical maturity. A high average SiO2 concentration and low Al2O3 were consistent with a low abundance of shale and clay components. The geochemical signatures of the detrital and volcano-detrital (RDVD) rocks indicate that they have undergone a moderate to low degree of chemical alteration. The CIA study also suggests that the granitic, granodioritic rocks represent the source provenance which, during weathering and transport, supplied the detritus to the supra-crustal units. The major trace element data suggest that these rocks are largely derived from felsic igneous rocks, namely granitoids, with a minor contribution from intermediate sources. The carbonate rocks do not represent a wide variety of facies: dolomitic limestone, calcareous limestone, and calcaro-dolomitic chert. Calcitic and dolomitic samples show a linear increase in SiO2, regardless of their CaO/LOI ratio values, which remain relatively constant. The highest SiO2 contents are observed in the calc-dolomitic chert. Geochemical analysis of RDVD from the Ifni buttonhole determined their origin, maturity, and alteration. Major oxides decreased with higher silica content, indicating quartz control. Samples, formed under semi-arid conditions, show maturity under stable deposition. They suggest a felsic, recycled source, with moderate alteration and zircon enrichment during recycling. In the study area, limestones and dolomites serve as materials applicable in the building sector, suitable for all types of concrete. The Taliwine Formation harbors Lower Cambrian dolomites and limestones, ideal for mosaic aggregates. Described as variable in color, compact, homogeneous, very hard, and resistant to alteration, the plutonic rocks form prominent peaks. They exhibit both subalkaline characteristics in granitoids and an alkaline trend in dolerite dykes. Most samples display minimal alteration, indicating the reliability of their major element compositions for geochemical analyses. These granitoids constitute valuable deposits for ornamental and building rock purposes.

Monitoring deforestation, forest health, and environmental criticality in a protected area periphery using Geospatial Techniques.

Protected areas in South Asia face significant challenges due to human disturbance and deforestation. The ongoing debate surrounds the recent surge in illegal encroachment of forest buffer zones in the Musali divisional secretariat division (DSD), which has led to a significant loss of forest cover over the past three decades. In this context, detecting changes in forest cover, assessing forest health, and evaluating environmental quality are crucial for sustainable forest management. As such, our efforts focused on assessing forest cover dynamics, forest health, and environmental conditions in the DSD from 1988 to 2022. We employed standardized image processing techniques, utilizing Landsat-5 (TM) and Landsat-8 (OLI) images. However, the forest area in the DSD has shown minimal changes, and environmental conditions and forest health have illustrated considerable spatial-temporal variations over the 34 years. The results indicated that 8.5 km2 (1.9%) of forest cover in the DSD has been converted to other land use classes. Overall, the Normalized Difference Vegetation Index (NDVI) has declined over time, while Land Surface Temperature (LST) exhibits an increasing trend. The regression results demonstrated a robust inverse relationship between LST and NDVI. The declining vegetation conditions and the increasing LST contribute to an increase in environmental criticality. The derived maps and indices will be beneficial for forest authorities in identifying highly sensitive locations. Additionally, they could enable land use planners to develop sustainable land management strategies.

An ecotourism suitability index for a world heritage city using GIS-multi criteria decision analysis techniques.

The concept of ecotourism has experienced a significant surge in popularity over the past two decades, primarily driven by the multitude of adverse impacts associated with mass tourism. The objective of the study was to develop a comprehensive ecotourism suitability index to guide policymakers in implementing tourism development policies. Given the considerable appeal of the study area to both local and international tourists, it is essential to conduct a systematic evaluation to pinpoint suitable areas for ecotourism development. This necessity arises from the study area's placement within a fragile ecosystem and its proximity to a UNESCO World Heritage site. We employed a Geographic Information Systems (GIS) integrated environment coupled with a fuzzy Multi-Criteria Decision Analysis (MCDA) methodology. The GIS-MCDA integrated framework leverages the Analytic Hierarchy Process (AHP) and a weighted linear combination that seeks to amalgamate many features and criteria to assess ecotourism potential by integrating 20 criteria into six separate categories: landscape, topography, accessibility, climate, forest and wildlife, and negative factors. Weights were allocated to each criterion and factor based on the expert's opinions of their impact on the development of ecotourism. The final ecotourism suitability index comprised five unique classes: very high, high, moderate, less, and not suitable. Results reveal that out of the total areas, 45.4 % (259 km2) are within the high and very high suitable classes. The sensitivity analysis suggested that ecotourism potentials are more favorable to forest and accessibility variables. The generated index can be utilized as a road map since validation verified a 64 % accuracy. Given the dearth of earlier research, this study provides vital support for the development of sustainable ecotourism projects in the study area.

Spatial analysis of leachate penetration at Lemna dumpsite, Calabar: Implications for sustainable waste management in Cross River State.

This study rigorously investigated the spatial analysis of leachate penetration at Lemna dumpsite, located in Calabar, Cross River State, Nigeria. Purposeful soil sampling, performed at specific intervals (5 m, 25 m, and 50 m) along the Electrical Resistivity profile line within the dumpsite, was augmented by water sample collection from five boreholes near Lemna dumpsite. Utilizing Electrical Resistivity Tomography (ERT) and Vertical Electric Sounding (VES) survey techniques, resistivity data were systematically gathered to comprehensively analyze the Leachate Penetration in the Lemna dumpsite. Laboratory analysis of soil and borehole water quality focused on Benzene, Toluene, Ethylbenzene, and Xylene (BTEX), with paired sample t-tests applied for statistical scrutiny. Analyzing the ERT and VES data employed sophisticated techniques embedded in Resistivity Two Dimension Invasion software and Advanced Geosciences Incorporation Earth Imager software. Substantial disparities (p < 0.05) emerged in the paired sample t-tests for BTEX in soil compared to National Environmental Standard Regulation and Enforcement Agency (NESREA) limits. Similarly, BTEX in borehole water displayed significant differences (p < 0.05) when compared to World Health Organization (WHO) standards, raising alarming concerns about the safety and portability of groundwater in the area. The examination of dumpsite leachate penetration revealed a resistivity anomaly of 8.01 Ωm and an inverse depth of 12.4 m, underscoring profound environmental implications and necessitating immediate remediation efforts. Additionally, Vulnerability and Aquifer Protective Capacity Index (VES) results, with a rating of <0.1, indicated severely compromised aquifer protective capacity, emphasizing the vulnerability of groundwater resources to further contamination. Our study advocates for strategic management, remediation, and monitoring measures to prevent contamination and safeguard water quality in the region.

Geochemical Evaluation of Paleocene Source Rocks in the Kohat Sub-Basin, Pakistan.

The Kohat sub-basin is one of the main hydrocarbon-producing sedimentary basins located in the northwest extension of the Indus Basin in Pakistan. It contains numerous proven and potential petroleum from the Cambrian to the Miocene. Conventional petroleum resources have been depleting rapidly over the last couple of years. Therefore, unconventional resources should be explored using a variety of geochemical and geophysical techniques to address the energy demands. Geochemical techniques, including total organic carbon (TOC) assessment, Rock-Eval pyrolysis, organic petrography, and biomarker studies, are essential for evaluating the potential of shale gas reservoirs to delineate future prospects in a basin. The source rock potential of the Paleocene rocks, including the Patala, Lockhart, and Hangu formations of the sub-basin, is evaluated using geochemical analyses on well cuttings from the Tolanj-01 well. The analyses include estimation of total organic carbon (TOC), Rock-Eval pyrolysis, and organic petrography (vitrinite reflectance) to evaluate the organic richness, thermal maturity, kerogen type, hydrocarbon type, and environment of deposition. Other techniques for extractable organic matter (EOM) include solid-liquid chromatographic separation of fractions, gas chromatography (GC-FID)/whole oil chromatography, and gas chromatography-mass spectrometry (GC-MS). The organic matter (TOC, wt %) analysis reveals that 18 (18) samples of the Hangu formation (0.08-1.8 wt %) show poor values, 12 (12) samples of the Lockhart formation (0.05-0.5 wt %) have poor to fair content, and 26 (26) samples of the Patala formation have poor to fair (0.08-0.19 wt %) TOC content. Rock-Eval pyrolysis studies including hydrogen index, oxygen index, Tmax, quantities of free hydrocarbons (S1, mg/g), and hydrocarbons produced from pyrolysis (S2, mg/g) are determined for the well-cut samples (56) of the Paleocene rocks. The hydrogen index values for the Hangu formation are lower than 200, and those for the Lockhart and Patala formations range between 100 and 250. A maceral analysis is also conducted on these samples, which reveal that the majority of the samples of the Paleocene units present in the basin belong to kerogen types II/III. The thermal maturity of the Hangu and Lockhart formations falls in the late-stage oil window, while that of the Patala formation falls in the peak to late oil window. The genetic potential (GP) for these rock units is also determined based on S1 and S2 values, which reveals that it is generally poor except for a few samples of the Hangu and Lockhart formations, which show fair GP values. For the organic petrography (vitrinite reflectance, R0), one sample from each unit is selected, which shows that the Hangu, Lockhart, and Patala formations fall in the category of the mature oil window with their R0 (%) values being 0.95, 0.89, and 0.82, respectively. The extracts (EOM) from these rock units are also analyzed to assess the depositional settings, biological source input, biodegradation, thermal maturity, etc. The greater values of pristine to phytane (Pr/Ph > 1) ratios for Hangu (1.33), Lockhart (1.23), and Patala (1.8) indicate an intermediate condition (suboxic), while a cross-plot of Pr/n-C17-Ph/n-C18 shows that the organic matter is deposited in a transitional setting. The ratios between C19TCT/C19 TCT + C23 TCT and C24 TeCT/C24TeCT + C23TCT biological source inputs are mainly of marine origin. Similarly, the ternary diagram of regular steranes (C27-C28-C29) shows a greater marine input. Lower values of the carbon preference index (CPI1) for Hangu (0.95), Lockhart (0.91), and Patala (1.04) indicate higher thermal maturity of the Paleocene rocks. Similarly, the methylphenanthrene index (MPI-1) values, Moretane index, and Pr/n-C17 vs Ph/n-C18 plots also show higher thermal maturity for these rock extracts.

Unconventional Reservoir Characterization of Patala Formation, Upper Indus Basin, Pakistan.

Unconventional hydrocarbon exploration is needed in the current oil and gas crisis scenario. Therefore, the development of conditions for unconventional hydrocarbon exploration is needed. In the Upper Indus Basin (UIB), Pakistan, the Patala Formation is one of the potential candidates for this unconventional exploration. It is a proven source rock at the regional level in the Kohat-Potwar sub-basin of UIB. This study aims to evaluate the shale gas potential of the rock in the Minwal-Joyamair area of the sub-basin. Developing a shale rock physics model is important for exploring and developing shale reservoirs due to the difference between unconventional shale and conventional sand reservoirs. These differences include mineral types, mineral characteristics, matrix pores, and fluid properties. To achieve the study's objectives, an integrated strategy provides for evaluating rock physics parameters, petrophysics, and geochemical analyses. This integrated approach indicates that the Patala Formation is a good potential reservoir for shale gas exploration. The Formation has a significant thickness (around 40-50 m), higher total organic carbon content (02-10%), higher brittleness index (0.44-0.56), and relatively shallow depth (2136-3223 m). These research findings suggested that the presence of organic and quartz-rich lithofacies can be considered as highly favorable "sweet spots" for shale-gas exploration in the UIB, Pakistan. Through proper understanding of the spatial and temporal distribution of these "sweet spots", shale-gas exploration can be developed as an effective strategy to exploit shale gas.

Reliable Tilt-depth estimates based on the stable computation of the tilt angle using robust vertical derivatives.

The Tilt-depth is a popular approach for determining depths of magnetic sources. As this method is based on the distance between contour levels of the tilt angle, it can lead to inaccurate depth estimates when the contour lines are distorted by the presence of noise. In this paper, we stabilize the Tilt-depth method based on the computation of stable vertical derivative obtained by the ß-VDR method. The presented method is demonstrated on synthetic magnetic anomalies and real magnetic data from the Arabian Shield. The results obtained from the synthetic examples coincide well with the actual depths. These results proved the utility of the presented method in cases where the field is corrupted by noise. The real example shows that the presented method can provide valuable information on subsurface structures of the area where the Tilt-depth estimates are consistent with the result of the horizontal tilt angle. The findings show that the presented method is less sensitive to noise and can provide source edges and depths more clearly and with higher accuracy.

Integration of a facile sustainable resonance Rayleigh scattering switchable-based system for feasible determination of centrophenoxine, a nootropic and antioxidant agent; application to crude materials and dosage forms.

The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15-47 ng mL-1, whereas the linearity was assessed to be in the range of 50-2000 ng mL-1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.

Mapping soil suitability using phenological information derived from MODIS time series data in a semi-arid region: A case study of Khouribga, Morocco.

To address the increasing global demand for food, it is crucial to implement sustainable agricultural practices, which include effective soil management techniques for enhancing productivity and environmental conditions. In this regard, a study was conducted to assess the efficacy of utilizing phenological metrics derived from satellite data in order to map and identify suitable agricultural soil within a semi-arid region. Two distinct methodologies were compared: one based on physicochemical soil parameters and the other utilizing the phenological response of vegetation through the application of the Normalized Difference Vegetation Index (NDVI) Modis-time series. The study findings indicated that the NDVI-based approach successfully identified a specific class of soil suitability for agriculture (referred to as S1) that could not be effectively mapped using the multi-criteria analysis (MCAD) method relying on soil physicochemical parameters. This S1 class of soil suitability accounted for approximately 5 % of the total study area. These outcomes suggest that phenological-based approaches offer greater potential for spatio-temporal monitoring of soil suitability status compared to MCAD, which heavily relies on discrete observations and necessitates frequent updates of soil parameters. The approach developed to map the soil-suitability is a valuable tool for sustainable agricultural development, and it can play an effective role in ensuring food security and conducting a land agriculture assessment.

Application of a white and green spectrofluorimetric approach for facile quantification of amlodipine, a hypotensive drug, in batch materials, dosage forms, and biological fluids; content homogeneity testing.

The suggested study adheres to a particular protocol to ensure that the process is environmentally friendly and sustainable. It is worth mentioning that several tools have been adopted as prospective measures of the method greenness. Fortunately, the established analytical method is identified as white by the white analytical chemistry (WAC) concept, which uses the red/ green/blue color scheme (RGB 12 tool) to combine ecological and functional factors for the first time in studying of the cited drug. Amlodipine (AMD), a cardiovascular treating agent, belongs to the dihydropyridine class of oral calcium channel-blocking agents. This article presents a novel, simple, green, one-pot-processed, fast, and ultrasensitive fluorimetric approach for monitoring and assessment of AMD using molecular-size-dependent fluorescence augmentation of the light scattering-driven signal of eosin, a biological stain at a wavelength of 415 nm. This enhancement was directly proportional to the size of the produced complex. The linearity range was from 30 to 900 ng mL-1 , with corresponding sensitivity limits (detection and quantitation levels) of 9.2 and 28 ng mL-1 , respectively. The planned approach was also successfully used to track AMD content in bulk, dosage forms, and bio-fluids (human plasma and urine). The developed method's eco-friendliness was established by different eco-rating metric tools.

Utility of Cilefa Pink B, a foodstuff dye as a fluoro-substrate in the devising of the first facile green Molecular-mass-Related Fluorescence Sensor for quantifying amlodipine in batched material and dosage forms; content uniformity evaluation.

This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea ofthe applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol-1. The medication's range of 0.050-1.00 µg mL-1 is directly correlated with this molecular massenlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL-1 (for the detection limit, LOD) and 0.042 µg mL-1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools.

Development and Assessment of 1,5-Diarylpyrazole/Oxime Hybrids Targeting EGFR and JNK-2 as Antiproliferative Agents: A Comprehensive Study through Synthesis, Molecular Docking, and Evaluation.

New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a-j, 8a-j, 9a-c, and 10a-c. The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d, 8g, 8i, and 10c inhibited EGFR with IC50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d, 8g, 8i, and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site.

Predicting sediment yield on different landuse surfaces in Calabar River Catchment, Nigeria.

This study predicts sediment yield on various landuse surfaces within the Calabar River Catchment, Nigeria. Five experimental plots of 31 by 23 cm (representing urban, farm, grass, bare, and forest surfaces) were established on a convex slope series with a 20% gradient, oriented along the slope strike. Rainfall, morphological, and hydraulic stations were derived for each plot. Multiple regressions and Factor analysis were employed to analyse the collected data. The research identifies critical factors influencing sediment yield, such as rainfall amount, rainfall intensity, slope gradient, slope length, sand, silt, clay, vegetation cover, and infiltration capacity. The results (p < 0.05) indicate that slope length, sand, silt, clay, infiltration capacity, and vegetation cover significantly influence sediment yield for urban, farmland, grassland, and bare surfaces, respectively. Factor analysis revealed strong correlations between sediment yield, silt, rainfall amount, rainfall intensity, and slope gradient. Case-wise diagnostics predictions indicate sediment yields for urban, bare, farm, grass, and vegetation-covered surfaces as 14.95 kg, 33.91 kg, 28.78 kg, 33.50 kg, and 5.66 kg, respectively. The regression model, with case-wise diagnostic residual statistics and standard prediction coefficients, provides valuable insights. For example, the forest surface exhibited a minimum sediment yield of -1.413 kg/m2 with each unit decrease in forest area, emphasising the significance of vegetation cover in sediment retention. Conversely, bare surfaces showed a maximum sediment yield of 0.843 kg/m2 with each unit increase in bare surface area, highlighting their heightened vulnerability to sediment erosion. Considering the implications of these findings, the development of urban master plans that incorporate well-designed landscaping and drainage systems is crucial, particularly in high rainfall catchments like the study area. Such measures can effectively mitigate sediment yield and address the adverse effects of land use changes on different surfaces.

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights.

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.

Lithospheric structural dynamics and geothermal modeling of the Western Arabian Shield.

Understanding the dynamics of suturing and cratonisation and their implications are vital in estimating the link between the lithospheric mantle architecture and geothermal resources. We propose new interpretations of the Western Arabian Shield's geodynamic styles and geothermal anomalies. In this work, features of the crust and mantle were interpreted from geophysical modeling to unravel the structural dynamics between the Arabian Shield and the Red Sea rift, as well as the influence of these mechanisms on the uplift of the Cenozoic basalts. Estimates of the lower crust thermal properties were also achieved. Spectral properties of the potential field were used to define the Curie isotherm, heat fluxes, geothermal gradients, radiogenic heat production, Moho configuration, and lithosphere-asthenosphere boundary. Results show new structural styles, micro-sutures, and significant thermal anomalies. The defined geothermal patterns were inferred to be due to localized initiation of tectonic and asthenospheric disequilibrium during the rifting episodes within the Red Sea. Also, magma mixing is initiated by the northward migration of magma from the Afar plume towards the Western Arabian Shield which drives local mantle melts beneath the western Arabia, thereby providing the pressure field required for magma ascent. The ascendant magma flow provides the heating source of geothermal reservoirs within the Western Arabian Shield. However, there are indications that during the episodes of rifting within the Red Sea and/or ancient Pan-African activities, the mixing process may have been altered resulting in crustal thinning and creating pathways of ascendant magma flow along the MMN volcanic line. Integrating geophysical and geothermal models indicated new zones of suturing and extensional tectonics between the amalgamated terranes. The geodynamic interpretation shows a new redistribution of terranes and continuous compressional and transtentional movements within the Arabian Shield.

Contamination and health risk assessment of groundwater along the Red Sea coast, Northwest Saudi Arabia.

Coastal groundwater is the major source of freshwater in coastal areas, due to shortage of the water resource in coastal zones. Groundwater samples were collected from 48 sites along the Saudi Red Sea coast between Rabigh and Yanbu to document the hydrogeochemical characteristics, water quality, and the health risks of nitrate, fluoride, nickel, copper, and zinc on adults and children. Groundwater chemistry indicated neutral to slightly alkaline nature, and the total dissolved salts (TDS) concentrations mainly increase towards the coastal plain. Major cations, major anions, and heavy metals (HMs) were in the order of Cl- > Na+ > SO42- > Ca2+ > HCO3- > NO3- > Mg2+ > K+, F- > Zn > Cu > Ni. Na-Cl, mixed Ca-Mg-Cl and Na-K-HCO3, CaCl, and Mg-HCO3 were the principal hydrochemical water types. Results of heavy metal pollution index (HPI), and water quality index (WQI) showed moderate to heavy pollution and unsuitable groundwater for human consumption mostly in the western side along the coastal plain, which might be influenced by the groundwater salinization. Principal component analysis (PCA) generated four components, which indicated the various sources of contamination. Hazard index (HI) of nitrate and fluoride were above the safety limit of 1, suggesting increase non-cancer health risk issues in both children and adults.

A new application of isoindole fluorophore derivative in sitagliptin antidiabetic medication assay: Application to dosage forms and biological fluid evaluation.

Dipeptidyl peptidase-4 enzyme suppressant is a unique category of oral antidiabetic medication. Sitagliptin (STG) is a perfect member of this category and is pharmaceutically marketed alone or in combination with metformin. Here, the ideal application of an isoindole derivative for STG assay was developed using a feasible, easy-to-use, economic, and affordable method. STG as an amino group donor can form a luminescent derivative: isoindole on interaction with o-phthalaldehyde and the existence of (2-mercaptoethanol) 0.02% (v/v) as a thiol group donor. Excitation (339.7 nm) and emission (434.6 nm) wavelengths were used to monitor the isoindole fluorophore yield; moreover, each experimental variable was carefully investigated and adjusted. The calibration graph was constructed by plotting fluorescence intensities against STG concentrations, and controlled linearity was observed at concentrations ranging from 50 to 1000 ng/ml. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were analyzed in depth to prove the technique validation. The implementation of the present technique was extended successfully to the evaluation of various types of STG dose forms and spiking samples of human plasma and urine. The developed technique was shown to be an effective, simple, and quick replacement for quality control and clinical study evaluation of STG.

Pollution Vulnerability of the Ghiss Nekkor Alluvial Aquifer in Al-Hoceima (Morocco), Using GIS-Based DRASTIC Model.

Groundwater resources of the alluvial aquifer Ghiss Nekkor, which covers an area of 100 km2, are the main source of domestic and agricultural freshwater supply in the region of Al Hoceima in Morocco. Due to human activities (overexploitation, increase in agricultural activity), this alluvial aquifer has become very sensitive to chemical pollution. The principal objective of this current study is to develop and implement a calibration method to assess, map, and estimate the vulnerability of the Ghiss Nekkor alluvial aquifer to pollution risk. In this work, the GIS-based DRASTIC model was used to estimate the inherent vulnerability to contamination of the Ghiss Nekkor alluvial aquifer with seven standard hydrogeological parameters. Nitrate (NO3) and electrical conductivity (EC) data were used to validate the DRASTIC map. The results of the vulnerability map analysis show that the vulnerability to contaminants varies from non-existent in the southwestern part of the plain (7.3% of the total area), to very high (14.5%). The vulnerability is moderate in the central and northeastern areas (26.9%), while it is high in the other areas (17.5%). Furthermore, the most sensitive areas are mainly concentrated near the coastal strip and the central plain on both sides of the Nekkor River. In these areas, the NO3 and EC values are above the maximum allowable limit of the World Health Organization. The results suggest that the DRASTIC model can be an effective tool for decision-makers concerned about managing groundwater sustainability.