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الملخص: أهداف البحث: يشكل مرض السكري عبئا اقتصاديا كبيرا على البلدان في جميع أنحاء العالم. إن التكاليف المرتبطة بإدارة مرض السكري، بما في ذلك خدمات الرعاية الصحية والأدوية ومعدات المراقبة وخسائر الإنتاجية، كبيرة. ويقدر الاتحاد الدولي للسكري أن نفقات الرعاية الصحية العالمية المتعلقة بمرض السكري ومضاعفاته تتجاوز مئات المليارات من الدولارات سنويا. ولذلك، هناك حاجة ماسة لتطوير أدوية فعالة للغاية، وبأسعار معقولة، ويمكن للمجتمع الوصول إليها بسهولة. طريقة البحث: تستكشف الدراسة الحالية التعديلات الهيكلية لمشتقات 1،4-ديهيدروبيريدين لتحديد مثبطات محددة للألفا أميليز بهدف تطوير أدوية أكثر فعالية ويمكن الوصول إليها لمرض السكري، وتم تقييم القدرة التنبؤية والملزمة للمركبات المصممة. كما تم إجراء دراسات التشابه الدوائي والحركية الدوائية للمركبات المعدلة. النتائج: أشارت نتائج الدراسة إلى أن المعادلة الأولى أظهرت أعلى مستوى من الدقة بسبب توافقها مع معايير التقييم الداخلية والخارجية. علاوة على ذلك، أظهر تصميم نظائرها الخمسة القوية باستخدام تصميم الدواء القائم على الهيكل تفاعلًا إيجابيا عند مقارنته بالقالب والأكاربوز. بالإضافة إلى ذلك، أشارت الدراسات الشاملة حول الخصائص الشبيهة بالأدوية والحركية الدوائية لمركبات التصميم إلى سلامتها عن طريق الفم وملامحها الدوائية الإيجابية. الاستنتاجات: تظهر نظائرها التصميمية وعدا بتطوير عوامل جديدة لخفض السكر في الدم، مع سماتها الإيجابية وأدائها في الدراسة مما يجعلها مرشحة محتملة لمزيد من البحث في تحسين علاجات الحالات المرتبطة بارتفاع نسبة السكر في الدم. Abstract: Objectives: Diabetes places a substantial economic burden on countries worldwide. The costs associated with diabetes management, including healthcare services, medications, monitoring equipment, and productivity losses, are substantial. The International Diabetes Federation has estimated that global healthcare expenditures associated with diabetes and its complications exceed hundreds of billions of dollars annually. Therefore, a critical need exists to develop drugs that are highly effective, affordable, and easily accessible to society. Methods: This study explored the structural modification of 1,4-DHP derivatives to identify specific α-amylase inhibitors, with the aim of developing more effective and accessible drugs for diabetes. We evaluated the activity and binding ability of the designed compounds. In addition, we performed drug-likeness and pharmacokinetic studies on the modified compounds. Results: Equation (1) had the highest accuracy, on the basis of internal and external assessment parameters, including R2int = 0.852, R2adj = 0.803, Q2cv = 0.731, and R2ext = 0.884. Moreover, the five potent analogs identified through structure-based drug design demonstrated a more favorable interaction than observed for the template or acarbose. Additionally, comprehensive studies on the drug-like properties and pharmacokinetics of the designed compounds supported their oral safety and favorable pharmacokinetic profiles. Conclusions: The designed analogs show promise for developing new hypoglycemic agents. Their positive attributes and performance suggest that they may potentially serve as candidates for further research in improving treatments for high blood sugar-associated conditions.

الملخص: أهداف البحث: يعتبر بروتين كيناز ''ب.ر.أ.ف.في-600إي'' هدفا علاجيا جذابا وأساسيا في علاج سرطان الجلد وأنواع أخرى من الأورام. ومع ذلك، فإن مقاومته للمثبطات والآثار الجانبية المعروفة لبعض المثبطات المحددة تستلزم التحقيق في مثبطات جديدة وفعالة. طريقة البحث: في العمل الحالي، تم استخدام استراتيجيات المحاكاة بالكمبيوتر مثل محاكاة الالتحام الجزيئي وحسابات نظرية الكثافة الوظيفية وتقييم الحرائك الدوائية، لتحديد مثبطات ''ب.ر.أ.ف.في-600إي'' المحتملة من مجموعة من 31 أريلاميدا جديدا مركبا قائما على الفلافون. النتائج: أظهرت نتيجة الالتحام أن أربعة مركبات (10 ، 11 ، 28 ، 31) لديها درجات مقبولة. ظهرت النتيجة (-124.365 و -129.365 و -135.878 و -117.081 على التوالي) كأكثر مثبطات ''ب.ر.أ.ف.في-600إي'' نشاطا وفعالية والتي تصدرت فيميورافينيب. أثبت ظهور روابط الهيدروجين والتفاعلات الكارهة للماء مع المخلفات الأساسية لـ ''ب.ر.أ.ف.في-600إي'' الاستقرار العالي لهذه المجمعات. تم حساب الطاقة للمدارات الجزيئية الحدودية مثل أعلى مدار جزيئي مشغول وأدنى مدار جزيئي غير مشغول وفجوة الطاقة ومعلمات التفاعل الأخرى باستخدام نظرية الكثافة الوظيفية. تم فحص الأسطح المدارية الجزيئية الحدودية والإمكانات الكهروستاتيكية لإثبات توزيعات كثافة الشحنة التي قد تكون مرتبطة بالنشاط المضاد للسرطان. وبالمثل، كشفت المركبات المختارة عن خصائص دوائية فائقة وفقا لقواعد التشابه الدوائي (التوافر البيولوجي) وخصائص الحرائك الدوائية. الاستنتاجات: وبالتالي، تم التعرف على المركبات المختارة كمرشحات قوية لـ ''ب.ر.أ.ف.في-600إي'' بخصائص حركية دوائية فائقة، ويمكن اقتراحها كعقاقير مرشحة واعدة للسرطان. Abstract: Objectives: The V600E-BRAF protein kinase is an attractive and essential therapeutic target in melanoma and other tumors. However, because of its resistance to the known inhibitors and side effects of some identified inhibitors, new potent inhibitors need to be identified. Methods: In the present work, in silico strategies such as the molecular docking simulation, DFT (Density-Functional-Theory) computations, and pharmacokinetic evaluation were used to determine potential V600E-BRAF inhibitors from a set of 31 synthesized novel flavone-based arylamides. Results: The docking result demonstrated that four compounds (10, 11, 28, and 31) had acceptable docking scores (MolDock score of −167.523 kcal mol−1, −158.168 kcal mol−1, −160.581 kcal mol−1,−162.302 kcal mol−1, and a Rerank score of −124.365, −129.365, −135.878 and −117.081, respectively) appeared as most active and potent V600E-BRAF inhibitors that topped vemurafenib (−158.139 and −118.607 kcal mol−1). The appearance of H-bonds and hydrophobic interactions with essential residues for V600E-BRAF proved the high stability of these complexes. The energy for the frontier molecular orbitals such as HOMO, LUMO, energy gap, and other reactivity parameters was computed using DFT. The frontier molecular-orbital surfaces and electrostatic potentials (EPs) were investigated to demonstrate the charge-density distributions that might be linked to anticancer activity. Similarly, the chosen compounds revealed superior pharmacological properties according to the drug-likeness rules (bioavailability) and pharmacokinetic properties. Conclusion: The chosen compounds were recognized as potent V600E-BRAF inhibitors with superior pharmacokinetic properties and could be promising cancer drug candidates.

المخلص: أهداف البحث: كيناز ''ب.ر.أ. ف-في. 600.إي''. هو هدف علاجي أساسي في سرطان الجلد وأنواع أخرى من الأورام. تستلزم مقاومته للمثبطات والآثار الجانبية المعروفة لبعض المثبطات المحددة الاستقصاء عن مثبطات جديدة وفعالة. طرق البحث: في العمل الحالي، تم استخدام استراتيجيات في السيليكون مثل محاكاة الالتحام الجزيئي وتقييم الحرائك الدوائية وحسابات نظرية الكثافة الوظيفية لتحديد مثبطات ''ب.ر.أ. ف-في. 600.إي'' المحتملة من مجموعة من 72 مركبا مضادا للسرطان من قاعدة بيانات ''بوبكيم''. النتائج: ما مجموعه خمسة جزيئات من الدرجة الأولى (12 ، 15 ، 30 ، 31 ، 35) مع درجات رائعة في الالتحام (درجة مولدوك:> 90 كيلو كالوري مول -1 ، ونقاط إعادة التصنيف:> 60 كيلو كالوري مول -1) تم اختيارها. تم اكتشاف العديد من تفاعلات الارتباط المحتملة بين الجزيئات المقترحة و ''ب.ر.أ. ف-في. 600.إي''. أثبت ظهور الروابط الهيدروجينية والتفاعلات الكارهة للماء مع المخلفات الأساسية لـ ''ب.ر.أ. ف-في. 600.إي'' الثبات العالي لهذه المجمعات. أظهرت المركبات المختارة خصائص دوائية فائقة وفقا لقواعد التشابه الدوائي (التوافر البيولوجي) وخصائص الحرائك الدوائية. وبالمثل، تم حساب الطاقة الخاصة بالمدارات الجزيئية الحدودية مثل المدار الجزيئي الأعلى المشغول، وأدنى المدار الجزيئي غير المشغول، وفجوة الطاقة، ومعلمات التفاعل الأخرى باستخدام نظرية الكثافة الوظيفية. تم فحص الأسطح المدارية الجزيئية الحدودية والإمكانات الكهروستاتيكية لإثبات توزيعات كثافة الشحنة التي قد تكون مرتبطة بالنشاط المضاد للسرطان. الاستنتاجات: وبالتالي، تم التعرف على المركبات المختارة كضربات قوية لـ ''ب.ر.أ. ف-في. 600.إي''. بخصائص حركية دوائية فائقة، ويمكن اقتراحها كعقاقير مرشحة واعدة للسرطان. Abstract: Objectives: V600E-BRAF kinase is an essential therapeutic target in melanoma and other types of tumors. Because of its resistance to known inhibitors and the adverse effects of some identified inhibitors, investigation of new potent inhibitors is necessary. Methods: In the present work, in silico strategies such as molecular docking simulation, pharmacokinetic evaluation, and density functional theory (DFT) computations were used to identify potential V600E-BRAF inhibitors from a set of 72 anticancer compounds in the PubChem database. Results: Five top-ranked molecules (12, 15, 30, 31, and 35) with excellent docking scores (MolDock score ≥90 kcal mol−1, Rerank score ≥60 kcal mol−1) were selected. Several potential binding interactions were discovered between the molecules and V600E-BRAF. The formation of H-bonds and hydrophobic interactions with essential residues of V600E-BRAF suggested the high stability of these complexes. The selected compounds had excellent pharmacological properties according to the drug likeness rules (bioavailability) and pharmacokinetic properties. Similarly, the energy for the frontier molecular orbitals, such as the HOMO, LUMO, energy gap, and other reactivity parameters, was computed with DFT. The frontier molecular orbital surfaces and electrostatic potentials were investigated to demonstrate the charge-density distributions potentially associated with anticancer activity. Conclusion: The identified compounds were found to be potent hit compounds for V600E-BRAF inhibition with superior pharmacokinetic properties; therefore, they may be promising cancer drug candidates.

Identification of estrogen receptor (ER) agonists among environmental toxicants is essential for assessing the potential impact of toxicants on human health. Using 2D autocorrelation descriptors as predictor variables, two binary logistic regression models were developed to identify active ER agonists among hydroxylated polychlorinated biphenyls (OH-PCBs). The classifications made by the two models on the training set compounds resulted in accuracy, sensitivity and specificity of 95.9 %, 93.9 % and 97.6 % for ERα dataset and 91.9 %, 90.9 % and 92.7 % for ERβ dataset. The areas under the ROC curves, constructed with the training set data, were found to be 0.985 and 0.987 for the two models. Predictions made by models I and II correctly classified 84.0 % and 88.0 % of the test set compounds and 89.8 % and 85.8% of the cross-validation set compounds respectively. The two classification-based QSAR models proposed in this paper are considered robust and reliable for rapid identification of ERα and ERβ agonists among OH-PCB congeners.

ABSTRACTBackground : Erythroid cells play important roles in hemostasis and disease. However, there is still significant knowledge gap regarding stress erythropoiesis.Methods : Two single-cell RNAseq datasets of erythroid cells on GEO with accession numbers GSE149938 and GSE184916 were obtained. The datasets from two sources, bone marrow and peripheral blood were analyzed using Seurat v4.1.1, and other tools in R. QC metrics were performed, data were normalized and scaled. Principal components that capture the variation of the data were determined. In clustering the cells, KNN graph was constructed and Louvain algorithm was applied to optimize the standard modularity function. Clusters were defined via differential expression of features.Results We identified 9 different cell types, with a particular cluster representing the stress erythroids. The clusters showed differentially expressed genes as observed from the gene signature plot. The stress erythroid cluster differentially expressed some genes including ALAS2, HEMGN, and GUK1.Conclusion The erythroid population was found to be heterogeneous, with a distinct sub-cell type constituting the stress erythroids; this may have important implications for our knowledge of steady-state and stress erythropoiesis, and the markers found in this cluster may prove useful for future research into the dynamics of stress erythroid progenitor cell differentiation.

الملخص: أهداف البحث: يسعى هذا البحث إلى تطوير نموذج رياضي يربط بين ميزات نوسكابين الهيكلية ونشاطه المضاد للأورام، ويشرح طريقة الارتباط بين مركبات نوسكابين والمستقبل المستهدف (توبولين) من خلال عملية الإرساء، وتصميم مركبات نوسكابين جديدة بناء على المعرفة والمعلومات التي تم الحصول عليها من النموذج وعملية الإرساء، والتنبؤ بخصائص الحرائك الدوائية/التشابه الدوائي لهذه المركبات الجديدة كعامل مضاد للورم ضد ورم البنكرياس. طرق البحث: تم استخدام نهج علاقة البنية-الفعالية الكمية، وعملية الإرساء الجزيئي، وأدوات قائمة على الإنترنت للتنبؤ بالحرائك الدوائية وتشابه الأدوية للمركبات الجديدة. النتائج: تم بناء نموذج ''علاقة البنية-الفعالية الكمية'' مع معلمات تحقق جيدة وجودة ملاءمة باستخدام ٧٠٪ من البيانات كمجموعة تدريب واستخدمت النسبة المتبقية ٣٠٪ في التحقق من صحة النموذج خارجيًا للتأكد من قدرته التنبؤية كمجموعة اختبار. أظهرت ثلاثة مركبات جديدة (مصممة) دي٣ و دي٤ و دي٦ بدرجة ربط أفضل تبلغ −١١.٢ و −١٠.٢ و ١٠.٦ كيلوكالوري/مول على التوالي تقاربا أعلى تجاه مستقبلات توبولين مقارنة بالقالب (المركب الأصلي) و اللجين المتبلور المشترك بدرجة ربط ٩.٢. الاستنتاجات: يعتبر نهج علاقة البنية-الفعالية الكمية وعملية الإرساء الجزيئي نهجا مهما في البحث عن الأدوية الحديثة، والذي تم استخدامه في هذا العمل. أظهرت دراسات الحرائك الدوائية للمركبات الجديدة المختارة خصائص دوائية أفضل ويمكن استخدامها كمركب ناجح في البحث عن الأدوية المضادة للأورام وتحديدا ورم البنكرياس. Abstract: Objective: This research aims to develop a mathematical model that relates the structural features of noscapine with anti-tumor activity, to explains the mode of binding between noscapine compounds and the target receptor tubulin by docking analysis. By considering the results of docking analysis and predictions of pharmacokinetic properties/drug likeness, we designed novel noscapine compounds as anti-tumor agents against pancreatic cancer. Methods: We used an in silico quantitative structure–activity relationship (QSAR) approach, molecular docking analysis and online tools for pharmacokinetics and drug likeness prediction to develop novel compounds. Results: A QSAR model with good validations parameters and quality of fit (R2 = 0.9731, Q2CV = 0.9434, R2adj = 0.9647 and R2test set = 0.8343) was built utilizing 70% of the dataset as a training set and the remaining 30% as an external validation to ascertain its predictive capability. Three novel compounds were designed: D3, D4 and D6 with binding scores of −11.2, −10.2 and 10.6 kcal/mol, respectively, exhibiting high affinity towards the tubulin receptor than the template (parent compound) and the co-crystallized ligand (E∗) with a binding score of 9.2 kcal/mol. Conclusion: The QSAR approach and molecular docking analysis is an important approach for modern drug discovery. Pharmacokinetics studies of the selected novel compounds revealed good drug properties and can be used as candidate compounds for the development of anti-tumor agents for pancreatic cancer.

Abstract Background Preparation of Ipomoea asarifolia (Desr) (Convolvulaceae) is widely used in traditional African medicine for the treatments of different kinds of ailments such as syphilis, malaria, convulsions and rheumatism. Aim The anticonvulsant properties of fractions of leaf of Ipomoea asarifolia (Desr); n-butanol (BF), chloroform, n-hexane and residual aqueous fractions (RAF) were evaluated on animals. Results The RAF at dose of 75 mg/kg (P

Fluorine-Doped Tin Oxide (FTO) thin films were deposited on a glass substrate using the spin coating technique and then annealed in both open air and nitrogen environments at temperatures between 500°C and 600°C. This study examined how annealing temperature affects the structural and electrical properties of the films. X-ray diffraction (XRD) analysis showed that the films had a polycrystalline structure, predominantly with the (110) plane. As the annealing temperature is increased, the crystal size also increased, leading to lower dislocation density and higher electron mobility. The resistivity of the films decreased with higher annealing temperatures, reaching its lowest value at 600°C. These findings indicate that annealing temperature is crucial for optimizing the structural and electrical properties of FTO thin films made via spin coating. The optimal annealing conditions were found to be 600°C in open air, resulting in a resistivity of 2.47x10-3 Ω-cm, sheet resistance of 1.08x10-2 Ω/square, the largest grain size of 18.41 nm, and the lowest values for dislocation density (2.95x1015 lines/cm²) and micro-strain (1.97x10-3). [ABSTRACT FROM AUTHOR]

Microalgal biomass provides a renewable source of biofuels and other green products. However, in order to realize economically viable microalgal biorefinery, strategic identification and utilization of suitable microalgal feedstock is fundamental. Here, a multi-step suboptimal screening strategy was used to target promising microalgae strains from selected freshwaters of the study area. The resulting strains were found to be affiliated to seven closely-related genera of the family Scenedesmaceae, as revealed by both morphologic and molecular characterization. Following initial screening under upper psychrophilic to optimum mesophilic (irregular temperature of 14.1 to 35.9°C) cultivation conditions, superior strains were chosen for further studies. Further cultivation of the selected strains under moderate to extreme mesophilic cultivation conditions (irregular temperature of 25.7 to 42.2°C), yielded up to 74.12 mgL-1day-1, 19.96 mgL-1day-1, 48.56%, 3.34 μg/mL and 1.20 μg/mL, for biomass productivity, lipid productivity, carbohydrate content, pigments content and carotenoids content respectively. These performances were deemed promising compared with some previous, optimum conditions-based reports. Interestingly, the fatty acids profile and the high carotenoids content of the studied strains revealed possible tolerance to the stress caused by the changing suboptimal cultivation conditions. Overall, strains AY1, CM6, LY2 and KL10 were exceptional and may present sustainable, promising feedstock for utilization in large-scale generation of green products, including biodiesel, bioethanol, pigments and dietary supplements. The findings of this study, which exposed promising, eurythermal strains, would expand the current knowledge on the search for promising microalgae strains capable of performing under the largely uncontrolled large-scale cultivation settings.

Microalgae-based wastewater treatment systems (AWWTS) have recently shown promise in the mitigation of antibiotic resistance genes (ARGs) from municipal wastewater (MWW). However, due to the large number of ARGs that exist in MWW, the use of indirect conventional water quality parameters to monitor ARGs reduction in wastewater would make the process less burdensome and economically affordable. In order to establish a robust relationship between the ARGs and water quality parameters, the current study employed different microalgae strains in monoculture (CM2, KL10) and multi-species combinations (CK and WW) for the MWW treatment under outdoor environmental conditions. The studied genes were quantified in the MWW influents and effluents using real-time PCR. All the cultures substantially improved the physicochemical qualities of the MWW. Out of the 14 genes analyzed in this study, tetO, tetW, tetX and ermB were decreased beyond detection within the first 4 days of treatment in all the cultures. Other genes, including blaCTX, sul1, cmlA, aadA, int1 and uidA were also decreased beyond a 2 log reduction value (LRV). The mobile genetic element, int1, correlated positively with most of the ARGs, especially sul1 (r ≤ 0.99, p < 0.01) and aadA (r ≤ 0.97, p < 0.01). Similarly, the Escherichia coli indicator gene, uidA, correlated positively with the studied genes, especially with aadA, blaCTX, blaTEM and cmlA (r ≤ 0.99 for each, p < 0.01). Some of the studied genes also correlated positively with total dissolved solids (TDS) (r ≤ 0.98, p < 0.01), and/or negatively with total suspended solids (TSS) (r ≤ −0.98, p < 0.01) and pH (r ≤ −0.98, p < 0.01). Among the tested cultures, both monocultures, i.e., KL10 and CM2 were found to be more consistent in gene suppression than their multi-species counterparts. The findings revealed water quality parameters such as TDS, TSS and E. coli as reliable proxies for ARGs mitigation in AWWTS and further highlight the superiority of monocultures over multi-species cultures in terms of gene suppression from the MWW stream.

Lagoons along the Red Sea are socio-economically important but most vulnerable ecosystems. Strong evaporation, strengthened due to global warming, leads to high salinity and high temperature in surface water, which exacerbate physiological stress in mangroves. Rabigh Lagoon is characterized by unusually large spatial differences in nutrient dynamics and physicochemical parameters. We conducted a multi-approach study to demonstrate how environmental factors cause growth retardation and stress in mangroves. There were significant variations (P < 0.05) in water salinities and temperatures, nitrogen and phosphorus abundance in sediments, and antioxidants in mangroves among 8 sites across the lagoon. Salinity and water temperature rapidly increased from the northern where Red Sea seawater enters to the southern end, but dissolved oxygen declined. High salinity (44.9), high surface water temperature (28.8°C) and relatively high nutrients at the southern end of the lagoon (S8) corresponded to high concentrations of antioxidants. High δ13C (−12.4‰) and δ15N (4.9‰) in the sediments at S8 also reveal relatively high nutrient level due to stagnant water, camel grazing, and runoff bringing in fertilizer from agriculture activities in the catchments during seasonal flooding events. Principal component analyses showed that N and P limitation at the lagoon entrance is the leading cause for mangrove stress, while high salinity, temperature, and low dissolved oxygen are the predominant factors for high antioxidants concentrations at the southern end of the lagoon.

The need for light intensity has made dye degradation very costly for industry. In this work, Fenton reagent was used for the efficient degradation of an aqueous solution of dye without the need for a light source. The influences of the pH of the media, the initial concentrations of Fe2+, H2O2, and methylene blue (MB) dye; in addition to temperature on the oxidation of MB dye were studied. The optimum amounts of the Fenton reagent were 4mM of Fe2+ and 70mM of H2O2 at 20 mg/L of dye. The optimum ratio of 0.05 of Fe2+/H2O2 was found to give the best result for the decolorization of dye. The Fenton process was effective at pH 3 with a maximum dye decolorization efficiency of 98.8% within 30 min of reaction, corresponding to a COD removal of 85%. The decolorization process was thermodynamically feasible, spontaneous, and endothermic. The activation energy (Ea) was 33.6 kJ/mol suggesting that the degradation reaction proceeded with a low energy barrier.

The tubers of Chlorophytum alismifolium (Liliaceae) are widely used in Nigerian Herbal Medicine to treat diabetes mellitus and their efficacy is widely acclaimed among the rural communities of Northern Nigeria. This study was aimed at investigating the antihyperglycaemic potential of the tuber extract of Chlorophytum alismifolium (CAE) in streptozotocin-induced hyperglycaemic rats. Phytochemical screening and oral median lethal dose (LD50) estimation of CAE in rats were carried out. Antihyperglycaemic screening of the extract (at oral doses of 150, 300 and 600 mg/kg) was performed using normal and streptozotocin-induced hyperglycaemic rats for 28 days. Fasting blood glucose levels were measured and serum lipids were analyzed. Liver, kidney, heart and pancreatic tissues were examined for histopathological damages using standard histological processing. Phytochemical screening revealed the presence alkaloids, saponins, flavonoids, triterpenes and glycosides. Oral LD50 was estimated to be >5000 mg/kg body weight in rats. C. alismifolium extract at all the doses tested showed blood glucose lowering effect. Statistical significant (p