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Fibroblast growth factor receptors 1 (FGFR1) is an emerging target for the development of anticancer drugs. Uncontrolled expression of FGFR1 is strongly associated with a number of different types of cancers. Apart from a few FGFR inhibitors, the FGFR family members have not been thoroughly studied to produce clinically effective anticancer drugs. The application of proper computational techniques may aid in understanding the mechanism of protein–ligand complex formation, which may provide a better notion for developing potent FGFR1 inhibitors. In this study, a variety of computational techniques, including 3D-QSAR, flexible docking and MD simulation followed by MMGB/PBSA, H-bonds and distance analysis, have been performed to systematically explore the binding mechanism of pyrrolo-pyrimidine derivatives against FGFR1. The 3D-QSAR model was generated to deduce the structural determinants of FGFR1 inhibition. The high q2 and r2 values for the CoMFA and CoMSIA models indicated that the created 3D-QSAR models could reliably predict the bioactivities of FGFR1 inhibitors. The computed binding free energies (MMGB/PBSA) for the selected compounds were consistent with the ranking of their experimental binding affinities against FGFR1. Furthermore, per-residue energy decomposition analysis revealed that the residues Lys514 in catalytic region, Asn568, Glu571 in solvent accessible portion and Asp641 in DFG motif exhibited a strong tendency to mediate ligand–protein interactions through the hydrogen bonding and Van Der Waals interactions. These findings may benefit researchers in gaining better knowledge of FGFR1 inhibition and may serve as a guideline for the development of novel and highly effective FGFR1 inhibitors. Communicated by Ramaswamy H. Sarma

The present study aimed to investigate chemical formulations of water samples collected from area extended between Ras Al–Halal and El Haniea, Libya. The geographic location of the Mediterranean governs the water temperature and salinity. The hot climate of the eastern basin raises the water temperature, causing increased evaporation and high salinities. The present study included visiting the study sites (8 stations on the eastern coast of Libya) during winter and summer seasons 2019. The concentration of different water quality parameters was analyzed and reported accordingly. The palnktonic composition was also evaluated.

This article mainly examines stem cells related patents. We first provided a general background on patents. Then, we investigated patents and how they influence innovation in general, and stem cells in particular. Challenges to patenting inventions and innovations associated with stem cells’ field of study in the US and Europe are provided.

This work presents an analytical study of the parametric instability of cylindrical panels containing functionally graded porous exposed to static and dynamic periodic axial loads under simply supported boundary conditions. Based on Hamilton’s principle, the governing equation of motion by using first-order shear deformation theory (FSDT) has been obtained. By applying the Galerkin technique, an excitation frequency expression is derived, which helps identify areas of instability of functionally graded porous cylindrical panels. Numerical simulations are used to validate the analytical results. Eventually, the impacts of the porosity coefficient, porosity distribution method, static and dynamic periodic axial loads, panel angle, circumferential wave number, and cylindrical panel characteristics on the region of instability are displayed in the section of results and discussions. The findings show that when the porosity is further from the surface, the more stable the structure is. Furthermore, a small angle of the cylindrical panels gives a better dynamic response than a large angle. In addition, increased static and dynamic loads lead to an expansion of areas of instability.

Solid-supported catalysts play efficient and crucial roles in organic synthesis. A solid-supported palladium(II) complex based on chitosan was synthesized and fully characterized using all possible tools (Fourier transform infrared spectroscopy, thermogravimetry analysis, differential scanning calorimetry, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, inductively coupled plasma atomic emission spectrometry, scanning electron microscopy, transmission electron microscopy, and Brunauer-Emmett-Teller analysis). The catalytic activity of the solid-phase catalyst in Suzuki cross-coupling reactions was evaluated in aqueous solvents under both conventional heating and microwave irradiation conditions. The recyclability and thermal stability of the prepared catalyst were also examined, and the catalyst was found to be active till five consecutive runs without a notable loss of activity under the microwave condition, with the turnover number and turnover frequency values reaching 19,019 and 114,114 h

Objectives This study aimed to explore the preparedness of pharmacy students to actively participate in public health services by examining their attitude towards and knowledge about the national public health programmes (NPHPs). Methods A cross-sectional study was conducted using an online questionnaire survey of the students in Unaizah College of Pharmacy (UCP) and College of Pharmacy Main Campus (CPMC), Qassim University, between October 2019 and February 2020. Key findings A total of 100 out of 125 students responded to the questionnaire at a response rate of 80%. While the majority (77%) of the participants agreed on the necessity for pharmacists to know about the NPHPs, 71% reported they did not learn about National Health Policy in their pharmacy curriculum. Also, a small number of pharmacy students, at 16%, believed that their current knowledge about the NPHPs was sufficient or very sufficient. Lastly, 81% of the participants felt that they had an important or very important role to play in the NPHPs. Conclusions The majority of the participants expressed interest in more education on public health during their pharmacy education. Their interest supports the advancement of public health education to facilitate greater involvement of pharmacists in public health services.

The purpose of the paper is to systematically review the literature of enablers and challenges for implementation and adoption e-health service. The review aims to identify the most critical success factors and barriers related with the development and growth of the e-health services under different circumstances. A total 68 relevant publications related to enablers and challenges of e-health services were selected from a total 694 research papers. These publications were thoroughly reviewed to find out the critical factors influencing the e-health services. The findings indicate that there are five broad factors viz. technological, environmental, organizational, social and economical along with four major stakeholders’ viz. citizens, patients, caregivers and service providers which influence the e-health services. These factors act as enablers as well as challenges for proper implementation and adoption of e-health services in different situations. On the basis of the findings of the review, a conceptual diamond model of e-health services adoption has been proposed.

A comparative study was conducted on serum blood samples collected from smoker and non smoker of some Libyan population. Different liver and Kidney functions were estimated included: GOT,GPT,Total bilirubin and ALK.PH of liver functions beside creatinine and urea of Kidney functions. The results recorded that the contents of: Total bilirubin in the smokers blood samples were ranged between (0.3 – 1.8), GOT (6 – 36), GPT (8 – 37) and ALK.PH contents were ranged between (76 – 226). On other hand the same parameters in the blood of non smokers samples were ranged as following: (0.3 – 1.1) , (15 – 27) , (12 – 22) and (122 – 226), respectively. Also effect of cigarette smoking on renal functions was indicated by serum creatinine and urea ,where the contents of serum creatinine and urea in smoker people showed high values of urea. The contents of urea of smoker samples were ( 29.8 ± 7.62) comparing with non smoker blood samples of (25 .05 ± 4.37 ).

During the winter and summer of 2019, eight study sites in eastern Libya were used to establish meiofauna diversity in the Southern Mediterranean Sea's near-shore sandy bottom surf region. The physicochemical characteristics of surface water at the study sites were mostly similar. Seventeen taxa of floatable meiofauna (extracted from sediment samples by floatation) were identified, sixteen during winter and ten during summer: By number of individuals per taxon, Nematoda and Foraminifera were the most abundant taxa. The other available taxa were Rhabdocoela, Xanacoelomorpha, Gastrotrichs, Polychaeta, Kinorhyncha, and Urodasys. Four non-floatable meiofauna taxa were encountered (Foraminifera, Mussel, Gastropod, and Ostracoda). This low diversity of floatable and non-floatable meiofauna was possibly due to the strong wave action prevailing in the region and the adjacent deleterious anthropogenic activities. Meiofaunal diversity was higher in winter than in summer, possibly due to the higher dissolved phosphorus concentration during this season. The causes of the between-site differences in meiofaunal diversity are unclear, but differences in adjacent coastal anthropogenic activities might had more impact than differences in the prevailing physicochemical traits of the interstitial habitat. New practical techniques for collecting and identifying the smaller meiofauna are needed.

Pyrazole-, isoxazole- and pyrrole-ring fused derivatives of C60.

Introduction: The area of “Green Synthesis of Nano-medicine,” as compared to its synthetic counterparts, is a relatively safer research technology for various biomedical applications, including identification, therapeutic application, and prevention of pathological conditions, pain control, safety, and development of human wellness. The present study explored the synthesis and characterization of AgNPs using the ethanolic extract of Piper cubeba fruit as a reducing and stabilizing agent and its potential as an enzyme inhibitory agent. Urease inhibitors are helpful against many severe diseases, including gastric ulcers induced by Helicobacter pylori.Method: The fruits of the Piper cubeba plant were taken and ground to a fine powder. Plant material was added to 500 ml ethanol, and the mixture was filtered. The solvent of the filtrate was evaporated, and a thick, gummy extract was obtained and stored at 4°C in the refrigerator. AgNPs were green synthesized from solutions of AgNO3 using the P. cubeba extract, which was indicated by a change in the color from light brown to deep brown. The synthesized AgNPs were characterized via Ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM).Results and Discussion: Analysis showed the reduction of Ag+ to Ag0 at room temperature (25°C), and the average particle size of AgNPs was in the range of 40–80 nm. Consequently, the synthesized AgNPs were evaluated for their anti-urease activity. The maximum urease inhibition of the Piper cubeba ethanolic extract was 88.5% at 5 mg conc., and of derived nanoparticles was 78.6% at 0.05 mg conc. The results were nearly similar to the control drug, i.e., thiourea (0.5 and 0.6 mM conc., respectively).Conclusion: The study concluded that the P. cubeba extract, as well as its green-derived AgNPs, might prove to be a better and safer substitute for their enzyme inhibitory potential in emerging medicine and novel drug delivery techniques to improve and maintain human health.

Obesity is a global epidemic that threatens to deplete health-care resources by increasing the prevalence of diabetes, heart disease, hypertension, and cancer. Obesity is the leading preventable cause of death worldwide, affecting both adults and children. Obesity has two effects: an increase in the bulk of adipose tissue and an increase in pathogenetic product release by larger fat cells. This view of obesity as a disease allows for a straightforward distinction between the negative effects of obesity caused by fat bulk and those caused by fat cell metabolic effects. Obesity stigma causes social difficulties, sleep apnea is caused in part by increased parapharyngeal fat deposits, and osteoarthritis is caused by the wear and tear on joints caused by carrying an enlarged quantity of fat fall under the first category. A wide range of policy issues could have an impact on food ecosystems. Fiscal food policies, obligatory nutrition panels on the formulation and reformulation of manufactured foods, food and nutrition labelling implementation, and limiting marketing and advertising prohibitions on unhealthy foods are among these topics. In this review, we overview current evidences on health consequences of obesity.

This study was carried out on archeological samples which collected from one of the most important ancient cities which located at eastern north side of Libya, these cities called (Cyrene and Abolonia Cyrene). Different samples were collected from the outside surface of the studied samples. The contents of lead (pb) and cadmium (Cd) were determined b using atomic absorption instrument. The results showed small variations for the studied metals between the studied samples. The concluded that the source of the detected metals are mainly due to the effects of air pollutions by the dust of machines and cars.

This study which carried out on some indicators including (Phenol red and Bromo phenol Blue). Different solvents were used including (Methanol, propanol, DMF and DMSO). The effect of solvents on the λ max and absorbance values were investigated. The results recorded that the λmax values were effected and changed according to the polarities of the applied solvents. Also, the obtained results showed changes in the absorbance values after applied solvents compared with the original absorbance values. Keywords: Bromophenol blue; Phenol red; Effect of solvents on electronic transitions

يعتبر ارتفاع ضغط الدم قاتلاً صامتاً يزيد من معدلات الإصابة بالأمراض والوفيات , وهو واحد من أكثر الأمراض شيوعاً التي تؤثر بشكل كبير على القلب والأوعية الدموية والدماغ والكلى وترتبط الإصابة به مع ارتفاع مرتسم الدهون وتعتبر من أكثر عوامل الخطورة شيوعاً لارتفاع ضغط الدم ، اشتملت الدراسة (89) عينة وبواقع 57)) عينة مصابة بمرض ارتفاع ضغط الدم مكونة من (27) أنثى و(30) ذكر و(32) عينة سيطرة مكونة من (13) أنثى و(19) ذكر تراوحت أعمارهم بين (85-30) سنة , أشارت نتائج قياس تركيز كل من (الكوليسترول Chol والكليسيريدات الثلاثية TG والبروتينات الدهنية عالية الكثافة HDL والبروتينات الدهنية واطئة الكثافة LDL والبروتينات الدهنية واطئة الكثافة جداً VLDL والابوليبوبروتين B والسكري ) لدى المرضى المصابين بارتفاع ضغط الدم مقارنة بالأصحاء , إلى ارتفاع معنوي في المتوسط الحسابي لمستوى تركيز الكوليسترول لدى مرضى ارتفاع ضغط الدم والذي بلغ 187.3 mg/dL مقارنة بالأصحاء والذي بلغ 158.8 mg/dL. اما الكليسيريدات الثلاثية فقد بلغ تركيزها لدى المرضى 177.3 mg/dL مقارنة بالأصحاء والذي بلغ 144.2 mg/dL. بينما أظهرت نتائج البروتينات الدهنية وجود انخفاض معنوي كبير في مستوى تركيز اﻟ HDL لدى مرضى ارتفاع ضغط الدم الذي بلغ 37.42 mg/dl ، مقارنة بالأصحاء والذي بلغ 46.10 mg/dL . وكان كل من مستويات LDL و VLDL ، ذوى ارتفاع معنوي كبير في مستوى تركيزهما لدى المرضى إذ بلغا 113.4 و 34.36 mg/dL على التوالي ، مقارنة بتركيزهما في الأصحاء إذ بلغا 81.2 و 29.33 mg/dL على التوالي. كما سجل ارتفاع معنوي في مستوى تركيز الابوليبوبروتين B لدى مرضى ارتفاع ضغط الدم إذ بلغ 2017 ng/ml ، مقارنة بمستوى تركيز لدى الأصحاء والذي بلغ 1830 mg/ml بينما بينت النتائج أن تركيز كلوكوز الدم لم يسجل فروق معنوية بين أمصال دم المرضى الذي بلغ 94.4 ± 23.5 mg/dl في حين كانت (88.7 ± 22.1) mg/dl في أمصال دم الأصحاء كمجموعة سيطرة.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski’s rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.

Transient osteoporosis of the hip, or acute bone marrow edema syndrome, is a rare condition characterized by a decrease in bone mineral density of the proximal femur, which resolves with conservative management over 6-24 months. At presentation, the patient complains of sudden onset of localized pain in the hip, which is aggravated by weight-bearing. However, the prevalence and risk factors for this condition are still unclear. ObjectiveThis is a retrospective investigation that involved collecting data from patients' records in a tertiary hospital in Saudi Arabia. Included candidates were patients who presented with hip pain, had an MRI done between 2016 and 2019 inclusive, and were older than 14 years. The collected data involved the age and gender of patients, the hip's affected side, and the diagnosis. Data analysis was executed through SPSS version 26 (IBM Corp., Armonk, NY).Three hundred and fourteen patients matched our inclusion criteria. The prevalence of transient osteoporosis of the hip was 2.5%. All of them were males and half were above 40 years, 50% had pain in the left side, and 75% had a small joint effusion. The femoral head was the most affected part of the joint in patients with transient osteoporosis of the hip. Among our patients, the most common cause of hip pain was gluteus medius tendonitis (12.9%), where 33.1% of patients with hip pain had normal examination and investigations, and 15.2% had more than one condition. Risk factors for transient osteoporosis of the hip are pain in the left hip joint (p-value=0.023) and an age between 41 and 50 years (p-value=0.012).The prevalence of transient osteoporosis of the hip is low, yet it requires confirmation by studies with a more robust design. Males older than 40 years and left-side hip pain are at higher risk.

As English has become the preferred language for recording current innovation and technological breakthroughs, text is the essential medium through which EFL learners enhance their writing abilities. Desirable though it may be, the researcher's experience has shown that most male students have just rudimentary L2 writing skills and are unable to write coherent passages in English. This implies a chasm between learners' lexical and cohesive connections and earlier research has focused on ways and means to bridge this gap. However, the current study is ground-breaking in this field as it explores the efficacy of task-oriented training in filling this chasm. Using linguistic learning methods, the current research examines the efficacy of lexical and cohesive links in enhancing undergraduates' writing. The study sample comprises 35 learners from an intermediate EFL reading class who are exposed to an intervention lasting 15 weeks. Data analysis shows that in the post-test, the learners' grammatical and vocabulary skills are enhanced dramatically, particularly in the discourse analysis sections. Furthermore, during group work activities, (i) students are more engaged and motivated, and they acquire more knowledge about the language system, identification, cause and effect, “if” clause and the purpose and function of using the passages given; (ii) half of the students' grammar proficiency and use of lexical items was correct in the writing output. Finally, the study shows that the biggest obstacle that the students faced in their writings and which they struggle to master is the use of the “if” clause which only 13 students could finally master. In addition, the study shows that (73%) of the students could master the discursive linkers in their writings better than the lexical or grammatical elements. Ultimately, the present study offers practical consequences that EFL teachers may want to contemplate including in their future classes.

In the present work, we reported the synthesis of Schiff bases from 4-phenoxy-5-sulfamoylbenzoic acid motif. The reaction was carried out by substitution of different aldehyde and ketones at sulfamoyl group of sulfamoylbenzoic acid. The generated substituted products (4a–4i) possessed potent structure activity relationship and exhibited drug like properties. The structures of synthesized compounds were characterized on the basis of FT-IR, 1H NMR, 13C NMR and mass spectroscopic data. The effects of synthesized products were investigated on urease enzyme through anti-urease enzyme inhibition assay (Weather burn method). These compounds were further evaluated for antibacterial potential. The Rationale behind the assessment of antibacterial activity was to investigate the synthesized compound's dual mode action against urease and virulent bacterial strains in order to develop a lead candidate for the treatment of GIT diseases such as gastric and peptic ulcers, as well as hepatic encephalopathy. The synthesized derivatives have outstanding anti-urease and antibacterial action, as is evident from in vitro and in silico studies. As a result, these compounds (3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid; 4a-4i) might be explored further as a potential lead for the development of potent inhibitors in the future.

Background: Covid-19 is one of the most serious pandemic outbreaks in history the world ever experienced. Its emergency and reemergence poses a substantial threat to nurses who often get close contact with patients, their knowledge and skills on managing the suspected and confirmed cases serve the foundation for positive response toward the outbreak; thus this study aimed at assessing the knowledge and skills of Zanzibar nurses on Covid-19Methods: A descriptive cross-section web-based survey was conducted in a set of 139 nurses from Zanzibar to assess their knowledge and skills for the covid-19 pandemic outbreak. Multistage sampling was employed to select the regions, hospitals and final the participants. Computer-generated questionnaires with a total of 50 items were used to collect information on the recruited respondents; data were analyzed using SPSS software. Results: The assessment of knowledge and skills on covid-19 among frontline nurses from Zanzibar indicate that; the overall mean score knowledge of all respondents was (20.7±3.06) ranged from 13-26 while the overall cognitive skills scores were (20.69±3.06) ranged from 8-18. Age, level of education and working experience were found to be a significant predictor for both knowledge and skills on covid-19 at the level of 5% while working at the referral was only significant to skill. Conclusion: The participants were knowledgeable and skilled regarding the topic of interest however this competence wasn’t directly associated with the study domain of covid-19 rather were significantly associated with other domains related to nursing activities such as IPC and general nursing care.

Objective To determine the preference for dacryocystorhinostomy (DCR), patient selection criteria for endoscopic DCR, endoscopic DCR technique, and barriers to adoption of endoscopic DCR. Method Cross-sectional study conducted from May-December 2021. A survey was sent to oculoplastic surgeons. Questions on demographic characteristics, type of clinical practice, technique preferences, barriers and facilitators to adoption of endoscopic DCR were included. Results 245 participants completed the survey. Most respondents were located at an urban site (84%), were in private practice (66%), and had been in practice for more than 10 years (58.9%). Sixty one percent perform external DCR as the first line procedure for treating primary nasolacrimal duct obstruction. The most common factor influencing the surgeon's decision to perform endoscopic DCR was the patient's request (37%) followed by endonasal exam (32%). The most common barrier for not performing endoscopic DCR was the lack of experience and lack of training during fellowship (42%). The most worrisome complication for most respondents was failure of the procedure (48%), followed by bleeding (30.3%). Eighty one percent believe surgical mentorship and supervision during initial cases would facilitate endoscopic DCR learning. Conclusions External Dacryocystorhinostomy is the preferred technique for treating primary acquired nasolacrimal duct obstruction. Learning endoscopic DCR early during fellowship training and high surgical volume to improve the learning curve dramatically impacts the adoption of the procedure.

Tea is the third most consumed beverage in Saudi Arabia (a country in the Middle East) after water and Arabian coffee. Hence, a large amount of consumed tea leaves is discarded as solid waste. Waste tea leaves (WTLs) have no commercial value and could be considered as an environmentally sustainable costless material. This work aimed to manufacture an adsorbent material from the discarded WTLs and charge-transfer (CT) interaction and use this adsorbent material effectively for the removal of different kinds of pollutants from water. The adsorbent material was manufactured in three steps. First, a CrFeO3 metal composite was synthesized from the CT interaction between FeCl3 and CrCl3 with urea. Second, activated carbons were prepared from consumed WTLs using facile and clean treatments of pre-carbonization, and a simple potassium hydroxide (KOH) activation treatment. Finally, the adsorbent material was fabricated by grounding CrFeO3 composite with the activated carbons in a 1:10 molar ratio (metal composite to activated carbons). The prepared materials were characterized spectroscopically and morphologically using FT-IR, XRD, SEM/EDX, and TEM analysis. The synthesized absorbent material was used to adsorb two organic dyes (Azocarmine G2; M1, and Methyl violet 2B; M2), and two commercial pesticides (Tiller 480SL; M3, and Acochem 25% WP; M4) from aqueous solution, and it showed promising adsorption efficacy. The minimum adsorbent material’s dosage to obtain a maximum removal efficiency (R%) for M1, M2, M3, and M4 removal from 100 mL solution (100 mg/L) was 0.11, 0.14, 0.13, and 0.12 g, respectively. The max R% for M1 (96.8%) was achieved in the first 45 min, the max R% for M2, 95.5%, was achieved during the first 55 min, and the max R% for M3 (96.4%) was achieved in the first 35 min, while the max R% for M4, 98.6%, was achieved during the first 35 min.

The decision-making process behind the selection of a gas turbine engine (GT) is crucial and must be made in accordance with economic, environmental, and technical requirements. This paper presents the relevant economic, exergoeconomic and exergoenvironmental analyses for four GT engines with different compressor configurations. The GT engine configurations are identified according to the type of compressor: axial, axial-centrifugal, two-stage centrifugal, and centrifugal-centrifugal. The performances of the four GT engines were validated against manufacturer supplied data using specialized software. The economic analysis, a detailed life cycle costing considering the cost to be paid per unit net power obtained from the GT, and subsequent shortest payback period showed that the GT with centrifugal-centrifugal compressor was most economically feasible. This was followed, in order, by the GT-axial, GT-axial-centrifugal, and finally the GT-two-stage centrifugal configuration, where the cost of ownership for a 20 year plan ranges between 8000 USD/kW to about 12,000 USD/kW at different operational scenarios during the life cycle costing. Exergoeconomic assessment provided useful information to enhance the cost-effectiveness of all four systems by evaluating each component separately. The axial-centrifugal configuration registered the lowest CO2 emissions (about 0.7 kg/kWh); all environmental indicators confirmed it is the most environmentally friendly option.

The presence of the p-aryl/cyclohexyl ring in the N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazine carbothioamide derivative (2C) is reported to enhance the antifungal properties when compared to those of itraconazole. Serum albumins present in plasma bind and transport ligands, including pharmaceuticals. This study explored 2C interactions with BSA using spectroscopic methods such as fluorescence and UV-visible spectroscopy. In order to acquire a deeper comprehension of how BSA interacts with binding pockets, a molecular docking study was carried out. The fluorescence of BSA was quenched by 2C via a static quenching mechanism since a decrease in quenching constants was observed from 1.27 × 105 to 1.14 × 105. Thermodynamic parameters indicated hydrogen and van der Waals forces responsible for the BSA–2C complex formation with binding constants ranging between 2.91 × 105 and 1.29 × 105, which suggest a strong binding interaction. Site marker studies displayed that 2C binds to BSA’s subdomains IIA and IIIA. Molecular docking studies were conducted to further comprehend the molecular mechanism of the BSA–2C interaction. The toxicity of 2C was predicted by Derek Nexus software. Human and mammalian carcinogenicity and skin sensitivity predictions were associated with a reasoning level of equivocal, inferring 2C to be a potential drug candidate.

In this work, nanosized zeolite X modified with glutamic acid was facilely synthesized as a novel composite. Also, the synthesized zeolite X/glutamic acid composite was identified using various instruments such as XRD, CHN, FT-IR, and FE-SEM. The FE-SEM image confirmed that the fabricated composite has a cotton-like structure. Also, the XRD pattern confirmed the presence of a wide XRD peak at 2Ɵ = 23°. Hence, this confirmed that the crystalline structure of zeolite X interfered or combined over amorphous surroundings. Besides, the synthesized zeolite X/glutamic acid composite was employed as an adsorbent for the efficient removal of Co(II) ions from aqueous media. Moreover, the highest removal efficiency is achieved at pH = 6, time = 100 min, and temperature = 298 K. The experimental results were matched well with the Langmuir equilibrium isotherm and pseudo-second-order kinetic model. The maximum adsorption capacity of the synthesized composite is 120.90 ± 3.94 mg/g. Additionally, the removal of Co(II) ions is chemical, exothermic, and spontaneous.

Synapse or dendritic spine loss is the strongest correlate of cognitive decline in Alzheimer’s disease (AD), and neurofibrillary tangles (NFTs), but not amyloid-β plaques, associate more closely with transition to mild cognitive impairment. Yet, how dendritic spine architecture is affected by hyperphosphorylated tau is still an ongoing question. To address this, we combined cell and biochemical analyses of the Tau P301S mouse line (PS19). Individual pyramidal neurons in the hippocampus and medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D morphometry analysis. In the hippocampus, PS19 mice and non-transgenic (NTG) littermates displayed equivalent spine density at 6 and 9 months, but both genotypes exhibited age-related thin spine loss. PS19 mice exhibited significant increases in synaptic tau protein levels and mean dendritic spine head diameter with age. This suggests that CA1 pyramidal neurons in PS19 mice may undergo spine remodeling in response to tau accumulation and age. In the mPFC, spine density was similar among PS19 mice and NTG littermates at 6 and 9 months, but age-related reductions in synaptic tau levels were observed among PS19 mice. Collectively, these studies reveal brain region-specific changes in dendritic spine density and morphology in response to age and the presence of hyperphosphorylated tau in the PS19 mouse line.

A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC50 ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out for all the tested candidates against VEGFR-2. Compound 17b was the most potent VEGFR-2 inhibitor (IC50 = 2.7 nM). Mechanistic investigation including cell cycle arrest and apoptosis was performed for compound 17b against HepG-2 cells, and the results revealed that 17b induced cell apoptosis and arrested cell cycle in the G2/M phase. Moreover, apoptosis analyses were conducted for compound 17b to evaluate its apoptotic potential. The results showed upregulation in caspase-3 and caspase-9 levels, and improving the Bax/Bcl-2 ratio by more than 10-fold. Docking studies were performed to determine the possible interaction with the VEGFR-2 active site. Further docking studies were carried out for compound 17b against cytochrome P450 to present such compounds as non-inhibitors. In silico ADMET, toxicity, and physico-chemical properties revealed that most of the synthesized members have acceptable values of drug-likeness. Finally, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties.

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2′-O-Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection via a cap formation process. In this study, we propose a new potential inhibitor for SARS COV-2 2′-O-methyltransferase (nsp16). A fragment library was screened against the co-crystal structure of the SARS COV-2 2′-O-methyltransferase complexed with Sinefungin (nsp16 – PDB ID: 6WKQ), and consequently the best proposed fragments were linked via a de novo approach to build molecule AP-20. Molecule AP-20 displayed a superior docking score to Sinefungin and reproduced the key interactions in the binding site of 2′-O-methyltransferase. Three molecular dynamic simulations of the 2′-O-methyltransferase apo structure and its complexed forms with AP-20 and Sinefungin were performed for 150 nano-seconds to provide insights on the dynamic nature of such setups and to assess the stability of the proposed AP-20/enzyme complex. AP-20/enzyme complex demonstrated better stability for the ligand–enzyme complex compared to Sinefungin in a respective setup. Furthermore, MM-PBSA binding free energy calculations showed a better profile for AP-20/enzyme complex compared to Sinefungin/enzyme complex emphasizing the potential inhibitory effect of AP-20 on SARS COV-2 2′-O-methyltransferase. We endorse our designed molecule AP-20 to be further explored via experimental evaluations to confront the spread of the emerging COVID-19. Also, in silico ADME profiling has ascribed to AP-20 an excellent safety and metabolic stability profile.

Recently, the focus has been shifting toward Quorum sensing inhibitors which reduce Pseudomonas aeruginosa virulence factors, alleviating infections. In this work, me-ta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor for the