Utilization of abandoned oil well logs and seismic data for modeling and assessing deep geothermal energy resources: A case study.

Hammam Faraun (HF) geothermal site in Egypt shows potential for addressing energy demand and fossil fuel shortages. This study utilizes abandoned oil well logs, seismic data, and surface geology to assess HF geothermal energy resources. Seismic interpretation identified a significant clysmic fault parallel to Hammam Faraun fault (HFF), named CLB fault. The two faults together create a renewable geothermal cycle through circulation of mixed formation-sea waters. Petrophysics revealed two main geothermal reservoirs: the Nubian sandstone reservoir and the Eocene Thebes carbonate reservoir with water saturation values approaching 100 %. Corrected borehole temperatures indicated reservoir temperatures around 120 °C and 140 °C for the Thebes and Nubian reservoirs, respectively. Fracture analysis and stress state provided insights into subsurface fractures. A geomechanical model demonstrated the impact of different stresses and pore pressure on geothermal fluid flow. NE-SW oriented fractures showed a higher dilation tendency due to aquathermal expansion. The integrated conceptual geothermal model suggested a magma chamber beneath HF as the heat source, related to Oligo-Miocene volcanic activity. The breached relay ramp and fault-related open fracture system serve as pathways for geothermal fluids. Evaluation of the geothermal potential utilized volumetric calculations and Monte Carlo simulation. The estimated hot water volumes were 1.72 km3, 4.242 km3, and 5.332 km3 for the Nubian reservoir in the onshore part, Thebes reservoir in the offshore part, and Nubian reservoir in the offshore part, respectively. The results indicate a medium enthalpy resource suitable for electricity generation using a Kalina geothermal power plant. The predicted geothermal power output is promising, with an average power output of 9.64 MWe, 21.38 MWe, and 43.76 MWe for the Nubian reservoir in the onshore part, Thebes reservoir in the offshore part, and Nubian reservoir in the offshore part, respectively. These outputs can potentially supply electricity to approximately 12,000, 29,000 and 53,000 households, respectively.

Does Gender Affect the Outcomes of Myocardial Revascularization for Left-Main Coronary Artery Disease?

Currently, gender is not considered in the choice of the revascularization strategy for patients with unprotected left main coronary artery (ULMCA) disease. This study analyzed the effect of gender on the outcomes of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) in patients with ULMCA disease. Females who had PCI (n = 328) were compared with females who had CABG (n = 132) and PCI in males (n = 894) was compared with CABG (n = 784). Females with CABG had higher overall hospital mortality and major adverse cardiovascular events (MACE) than females with PCI. Male patients with CABG had higher MACE; however, mortality did not differ between males with CABG vs PCI. In female patients, follow-up mortality was significantly higher in CABG patients, and target lesion revascularization was higher in patients with PCI. Male patients had no difference in mortality and MACE between groups; however, MI was higher with CABG, and congestive heart failure was higher with PCI. In conclusion, women with ULMCA disease treated with PCI could have better survival with lower MACE compared with CABG. These differences were not evident in males treated with either CABG or PCI. PCI could be the preferred revascularization strategy in women with ULMCA disease.

End-capped engineering of Quinoxaline core-based non-fullerene acceptor materials with improved power conversion efficiency.

Improving the light-harvesting efficiency and boosting open circuit voltage are crucial challenges for enhancing the efficiency of organic solar cells. This work introduces seven new molecules (SA1-SA7) to upgrade the optoelectronic and photovoltaic properties of Q-C-F molecule-based solar cells. All recently designed molecules have the same alkyl-substituted Quinoxaline core and CPDT donor but vary in the end-capped acceptor subunits. All the investigated molecules have revealed superior properties than the model (R) by having absorbance ranging from 681 nm to 782 nm in the gaseous medium while 726 nm-861 nm in chloroform solvent, with the lowest band gap ranging from 1.91 to 2.19 eV SA1 molecule demonstrated the highest λmax (861 nm) in chloroform solvent and the lowest band gap (1.91 eV). SA2 molecule has manifested highest dipole moment (4.5089 D), lower exciton binding energy in gaseous (0.33 eV) and chloroform solvent (0.47 eV), and lower charge mobility of hole (0.0077693) and electron (0.0042470). At the same time, SA7 showed the highest open circuit voltage (1.56 eV) and fill factor (0.9166) due to solid electron-pulling acceptor moieties. From these supportive outcomes, it is inferred that our computationally investigated molecules may be promising candidates to be used in advanced versions of OSCs in the upcoming period.

Intralesional Pentoxifylline Injection Versus Triamcinolone Acetonide in Treating localized Alopecia Areata: A Comparative Study.

Objective: Alopecia areata (AA) is a common form of potentially reversible non-scarring hair disorder characterized by limited patchy hair loss (alopecia areata), loss of all scalp hair (alopecia totalis), or all body hair (alopecia universalis). Several lines of treatment have been used with variable outcomes. We aimed to compare the efficacy of intralesional pentoxifylline (PTX) and triamcinolone acetonide (TRA) injection in the treatment of alopecia areata. Methods: Our study included 60 patients with localized AA recruited from the Dermatology Outpatient Clinics of Al-Azhar University Hospitals. Patients were divided into two groups of alopecia areata patches; Group A who received intralesional TRA injections while Group B received intralesional PTX. Results: The study showed that both modalities are effective in treating AA and each modality has its own advantages. According to the response, patients were grouped into three categories: partial response (0-33% terminal hair regrowth), moderate response (33-66% terminal hair regrowth), and high response (66-100% terminal hair regrowth). The high response after use of the PTX was found in 50 percent of patients. The high response was observed in 46.6 percent of patients treated with TRA. Limitations: Small sample size and short follow-up period. Conclusion: This study showed that intralesional injection of PTX seems to be effective and safe treatment for localized AA and could be used as a good alternative to triamcinolone acetonide.

Pro-Apoptotic Activity of Epi-Obtusane against Cervical Cancer: Nano Formulation, In Silico Molecular Docking, and Pharmacological Network Analysis.

Cancer is a major disease that threatens human health all over the world. Intervention and prevention in premalignant processes are successful ways to prevent cancer from striking. On the other hand, the marine ecosystem is a treasure storehouse of promising bioactive metabolites. The use of such marine products can be optimized by selecting a suitable nanocarrier. Therefore, epi-obtusane, previously isolated from Aplysia oculifera, was investigated for its potential anticancer effects toward cervical cancer through a series of in vitro assays in HeLa cells using the MTT assay method. Additionally, the sesquiterpene was encapsulated within a liposomal formulation (size = 130.8 ± 50.3, PDI = 0.462, zeta potential -12.3 ± 2.3), and the antiproliferative potential of epi-obtusane was investigated against the human cervical cancer cell line HeLa before and after encapsulation with liposomes. Epi-obtusane exhibited a potent effect against the HeLa cell line, while the formulated molecule with liposomes increased the in vitro antiproliferative activity. Additionally, cell cycle arrest analysis, as well as the apoptosis assay, performed via FITC-Annexin-V/propidium iodide double staining (flow cytofluorimetry), were carried out. The pharmacological network enabled us to deliver further insights into the mechanism of epi-obtusane, suggesting that STAT3 might be targeted by the compound. Moreover, molecular docking showed a comparable binding score of the isolated compound towards the STAT3 SH2 domain. The targets possess an anticancer effect through the endometrial cancer pathway, regulation of DNA templated transcription, and nitric oxide synthase, as mentioned by the KEGG and ShinyGo 7.1 databases.

Inherent efficacies of pyrazole-based derivatives for cancer therapy: the interface between experiment and in silico.

There has been an increasing trend in the design of novel pyrazole derivatives for desired biological applications. For a cost-effective strategy, scientists have implemented various computational drug design tools to go hand in hand with experiments for the design and discovery of potentially effective pyrazole-based therapeutics. This review highlights the milestones of pyrazole-containing inhibitors and the use of molecular modeling techniques in conjunction with experimental studies to provide a view of the binding mechanism of these compounds. The review focuses on the established targets that play a key role in cancer therapy, including proteins involved in tubulin polymerization, carbonic anhydrase and tyrosine kinase. Overall, using both experimental and computational methods in drug design represents a promising approach to cancer therapy.

Discovery and optimization of 2,3-diaryl-1,3-thiazolidin-4-one-based derivatives as potent and selective cytotoxic agents with anti-inflammatory activity.

Several studies have indicated the potential therapeutic outcomes of combining selective COX-2 inhibitors with tubulin-targeting anticancer agents. In the current study, a novel series of thiazolidin-4-one-based derivatives (7a-q) was designed by merging the pharmacophoric features of some COXs inhibitors and tubulin polymerization inhibitors. Compounds 7a-q were synthesized and evaluated for their cytotoxic activity against MCF7, HT29, and A2780 cancer cell lines (IC50 = 0.02-17.02 µM). The cytotoxicity of 7a-q was also assessed against normal MRC5 cells (IC50 = 0.47-13.46 µM). Compounds 7c, 7i, and 7j, the most active in the MTT assay, significantly reduced the number of HT29 colonies compared to the control. Compounds 7c, 7i, and 7j also induced significant decreases in the tumor volumes and masses in Ehrlich solid carcinoma-bearing mice compared to the control. The three compounds also exhibited significant anti-HT29 migration activity in the wound-healing assay. They have also induced cell cycle arrest in HT29 cells at the S and G2/M phases. In addition, they induced significant increases in both early and late apoptotic events in HT29 cells compared to the control, where 7j showed the highest effect. On the other hand, compound 7j (1 µM) displayed weak inhibitory activity against tubulin polymerization compared to colchicine (3 µM). On the other hand, compounds 7a-q inhibited the activity of COX-2 (IC50 = 0.42-29.11 µM) compared to celecoxib (IC50 = 0.86 µM). In addition, 7c, 7i, and 7j showed moderate inhibition of inflammation in rats compared to indomethacin, with better GIT safety profiles. Molecular docking analysis revealed that 7c, 7i, and 7j have higher binding free energies towards COX-2 than COX-1. These above results suggested that 7j could serve as a potential anticancer drug candidate.

Exploration of charge transfer analysis and photovoltaics properties of A-D-A type non-fullerene phenazine based molecules to enhance the organic solar cell properties.

To intensify the photovoltaic properties of organic solar cells, density functional theory (DFT) based computational techniques were implemented on six non-fullerene A-D-A type small molecules (N1-N6) modified from reference molecule (R) which consists of phenazine fused with 1,4- Dimethyl-4H-3,7-dithia-4-aza- cyclopenta [α] pentalene on both sides with one of its phenyl rings acting as the central donor unit, further attached with 2-(5,6-Difluoro-2-methylene-3-oxo-indan-1-ylidene)-malononitrile acceptor groups at terminal sites. All proposed compounds have a phenazine base modified with a variety of substituents at the terminals. Transition density matrix, density of states, frontier molecular orbitals, intramolecular charge transfer abilities and optoelectronic properties of these compounds were investigated using B3LYP/6-31G (d, p) and B3LYP/6-31G++ (d,p) level of theory. All six designed compounds exhibited a bathochromic sift in their λmax as compared to the R molecule. All designed molecules also have reduced band gap and smaller excitation energy than R. Among all, N6 exhibited highest λmax and lowest bandgap as compared to reference molecule indicating its promising photovoltaic properties. Decreased hole and electron reorganization energy in several of the suggested compounds is indicative of greater charge mobility in them. PTB7-Th donor was employed to calculate open circuit voltage of all investigated molecules. N1-N5 molecules had improved optoelectronic properties, significant probable power conversion efficiency as evident from their absorption aspects, high values of Voc, and fill factor, compared to R molecule. Designed A-D-A type NF based molecules make OSCs ideal for use in wearable devices, building-integrated photovoltaics and smart fabrics.

Combination of an Oxindole Derivative with (-)-ß-Elemene Alters Cell Death Pathways in FLT3/ITD+ Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is one of the cancers that grow most aggressively. The challenges in AML management are huge, despite many treatment options. Mutations in FLT3 tyrosine kinase receptors make the currently available therapies less responsive. Therefore, there is a need to find new lead molecules that can specifically target mutated FLT3 to block growth factor signaling and inhibit AML cell proliferation. Our previous studies on FLT3-mutated AML cells demonstrated that ß-elemene and compound 5a showed strong inhibition of proliferation by blocking the mutated FLT3 receptor and altering the key apoptotic genes responsible for apoptosis. Furthermore, we hypothesized that both ß-elemene and compound 5a could be therapeutically effective. Therefore, combining these drugs against mutated FLT3 cells could be promising. In this context, dose-matrix combination-based cellular inhibition analyses, cell morphology studies and profiling of 43 different apoptotic protein targets via combinatorial treatment were performed. Our studies provide strong evidence for the hypothesis that ß-elemene and compound 5a combination considerably increased the therapeutic potential of both compounds by enhancing the activation of several key targets implicated in AML cell death.

Solvothermal-based synthesis of barium stannate nanosheets coupled with copper manganate nanoparticles for efficient photooxidation of tetracycline under visible light.

Photocatalytic oxidation of antibiotic waste over semiconducting heterojunction photocatalysts is considered eco-friendly because it is simple and operates under light irradiation. In this work, we apply a solvothermal-based process for obtaining high surface area barium stannate (BaSnO3) nanosheets followed by adding 3.0-12.0 wt% of spinel copper manganate (CuMn2O4) nanoparticles to form n-n CuMn2O4/BaSnO3 heterojunction photocatalyst after calcination process. The CuMn2O4-supported BaSnO3 nanosheets exhibit mesostructure surfaces with a high surface area range of 133-150 m2g-1. Moreover, introducing CuMn2O4 to BaSnO3 shows a significant broadening in visible light absorption range due to bandgap reduction down to 2.78 eV in 9.0% CuMn2O4/BaSnO3 compared to 3.0 eV for pure BaSnO3. The produced CuMn2O4/BaSnO3 is used for photooxidation of tetracycline (TC) in water as emerging antibiotic waste under visible light. The photooxidation of TC exhibits the first-order reaction model. The specific dose of 9.0 wt% CuMn2O4/BaSnO3 at 2.4 gL-1 displays the highest-performed and recyclable photocatalyst for total oxidation of TC after 90 min. This sustainable photoactivity is attributed to the improved light harvesting and charges migration upon coupling between CuMn2O4 and BaSnO3.

A DFT approach for finding therapeutic potential of graphyne as a nanocarrier in the doxorubicin drug delivery to treat cancer.

In the present work, the drug-loading efficacy of graphyne (GYN) for doxorubicin (DOX) drug is investigated for the first time by using density functional theory (DFT). Doxorubicin drug is effective in the cure of numerous types of cancer including bone cancer, gastric, thyroid, bladder, ovarian, breast, and soft tissue cancer. Doxorubicin drug prevents the cell division process by intercalating in the double-helix of DNA and stopping its replication. The optimized, geometrical, energetic, and excited-state characteristics of graphyne (GYN), doxorubicin drug (DOX), and doxorubicin-graphyne complex (DOX@GYN complex) are calculated to see how effective it is as a carrier. The DOX drug interacted with GYN with an adsorption-energy of -1.57 eV (gas-phase). The interaction of GYN with DOX drug is investigated using NCI (non-covalent interaction) analysis. The findings of this analysis showed that the DOX@GYN complex has weak forces of interaction. Charge transfer from doxorubicin drug to GYN during DOX@GYN complex formation is described by charge-decomposition analysis and HOMO-LUMO analysis. The increased dipole-moment (8.41 D) of the DOX@GYN in contrast with therapeutic agent DOX and GYN indicated that the drug will move easily in the biochemical system. Furthermore, the photo-induced electron-transfer process is explored for excited states, and it reveals that upon interaction, fluorescence-quenching will occur in the complex DOX@GYN. In addition, the influence of the positive and negative charge states on the GYN and DOX@GYN is also considered. Overall, the findings indicated that the GYN could be exploited as an effective drug-transporter for the delivery of doxorubicin drug. Investigators will be inspired to look at another 2D nanomaterials for drug transport applications as a result of this theoretical work.

Quantum Chemical Approach of Hexaammine (NH3)6 complexant with alkali and alkaline earth metals for their potential use as NLO materials.

In this study, nine new electron rich compounds are presented, and their electronic, geometrical, and nonlinear optical (NLO) characteristics have been investigated by using the Density functional theory. The basic design principle of these compounds is placing alkaline earth metal (AEM) inside and alkali metal (AM) outside the hexaammine complexant. The properties of nine newly designed compounds are contrasted with the reference molecule (Hexaammine). The effect of this doping on Hexaamine complexant is explored by different analyses such as electron density distribution map (EDDM), frontier molecular orbitals (FMOs), density of states (DOS) absorption maximum (λmax), hyperpolarizabilities, dipole moment, transition density matrix (TDM). Non-covalent interaction (NCI) study assisted with isosurfaces has been accomplished to explore the vibrational frequencies and types of synergy. The doping of hexaammine complexant with AM and AEM significantly improved its characteristics by reducing values of HOMO-LUMO energy gaps from 10.7eV to 3.15eV compared to 10.7 eV of hexaammine. The polarizability and hyperpolarizability (αo and ßo) values inquisitively increase from 72 to 919 au and 4.31 × 10-31 to 2.00 × 10-27esu respectively. The higher values of hyperpolarizability in comparison to hexaammine (taken as a reference molecule) are credited to the presence of additional electrons. The absorption profile of the newly designed molecules clearly illustrates that they are highly accompanied by higher λmax showing maximum absorbance in red and far-red regions ranging from 654.07 nm to 783.94 nm. These newly designed compounds have superior outcomes having effectiveness for using them as proficient NLO materials and have a gateway for advanced investigation of more stable and highly progressive NLO materials.

CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.

BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study. METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded. RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution. CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.

Intralesional methotrexate in the treatment of localized vitiligo: A pilot study.

BACKGROUND/OBJECTIVES: Vitiligo is an immune-mediated skin disorder that targets epidermal melanocytes leading to the appearance of depigmented skin patches. Different treatment modalities have been reported with varied efficacy. We tried to evaluate the safety and efficacy of intralesional methotrexate in treating localized areas of vitiligo. METHODS: Thirty participants with localized patches of vitiligo were recruited. They were treated with intralesional injections of methotrexate every 2 weeks for a maximum of six sessions. At the end of the study, the degree of repigmentation was categorized into: excellent improvement (>75% repigmentation), good improvement (50%-75% repigmentation), fair improvement (25%-50% repigmentation) and poor improvement (<25% repigmentation). RESULTS: We included 7 males (23.3%) and 23 females (76.7%). Their mean age was 33.6 ± 8.6 years. The duration of the disease ranged from 1 to 22 years. Four patients had a family history of vitiligo. At the end of the study, there was a highly statistically significant improvement (p < 0.001) after treatment regarding repigmentation. CONCLUSIONS: This study showed that intralesional methotrexate is a safe and effective treatment option for patients with localized vitiligo lesions. Further studies on a larger scale are needed to evaluate the long-term effects of treatment and detect the ideal dose to be injected.

A novel surgical technique for treatment of cervical vertebral stenotic myelopathy (wobbler syndrome) in a filly.

Cervical vertebral stenotic myelopathy (CVSM), also known as equine wobbler syndrome or cervical ataxia, is a devastating neurological syndrome resulting from compression of the spinal cord at the cervical region. This report describes a novel surgical technique for treatment of 16-month-old Arabian filly with CVSM. The filly showed grade 4 ataxia, hypermetria, weakness of the hind limbs, stumbling during walking, and abnormal gait. Case history, clinical signs and myelography revealed spinal cord compression between the C3 and C4 and C4-C5. The filly underwent a novel surgical interference for decompression and stabilization of the point of stenosis using specially designed titanium plate and intervertebral spacer. Evidence of arthrodesis with absence of complications was confirmed by periodic radiography over eight months of postoperative care. The new technique applied in this cervical surgery was efficient for the decompression and stabilization of the vertebrae, allowing arthrodesis development and remission of the clinical signs. The obtained results encourage further assessment of this novel procedure in horses clinically affected by CVSM.

Designing of Thiophene [3, 2-b] Pyrrole Ring-Based NFAs for High-Performance Electron Transport Materials: A DFT Study.

Among the blended components of a photoactive layer in organic photovoltaic (OPV) cells, the acceptor is of high importance. This importance is attributed to its increased ability to withdraw electrons toward itself for their effective transport toward the respective electrode. In this research work, seven new non-fullerene acceptors were designed for their possible utilization in the OPVs. These molecules were designed through side-chain engineering of the PTBTP-4F molecule, with its fused pyrrole ring-based donor core and different strongly electron-withdrawing acceptors. To elucidate their effectiveness, the band gaps, absorption characteristics, chemical reactivity indices, and photovoltaic parameters of all of the architecture molecules were compared with the reference. Through various computational software, transition density matrices, graphs of absorption, and density of states were also plotted for these molecules. From some chemical reactivity indices and electron mobility values, it was proposed that our newly designed molecules could be better electron-transporting materials than the reference. Among all, TP1, due to its most stabilized frontier molecular orbitals, lowest band gap and excitation energies, highest absorption maxima in both the solvent and gas medium, least hardness, highest ionization potential, superior electron affinity, lowest electron reorganization energy, as well as highest rate constant of charge hopping, seemed to be the best molecule in terms of its electron-withdrawing abilities in the photoactive layer blend. In addition, in terms of all of the photovoltaic parameters, TP4-TP7 was perceived to be better suited in comparison to TPR. Thus, all our suggested molecules could act as superior acceptors to TPR.

Potential drug candidates as P-glycoprotein inhibitors to reverse multidrug resistance in cancer: an in silico drug discovery study.

The failure of chemotherapy in the treatment of carcinoma is mainly due to the development of multidrug resistance (MDR), which is largely caused by the overexpression of P-glycoprotein (P-gp/ABCB1/MDR1). Until recently, the 3D structure of the P-gp transporter has not been experimentally resolved, which restricted the discovery of prospective P-gp inhibitors utilizing in silico techniques. In this study, the binding energies of 512 drug candidates in clinical or investigational stages were assessed as potential P-gp inhibitors employing in silico methods. On the basis of the available experimental data, the performance of the AutoDock4.2.6 software to predict the drug-P-gp binding mode was initially validated. Molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics-generalized Born surface area (MM-GBSA) binding energy computations were subsequently conducted to screen the investigated drug candidates. Based on the current results, five promising drug candidates, namely valspodar, dactinomycin, elbasvir, temsirolimus, and sirolimus, showed promising binding energies against P-gp transporter with ΔGbinding values of -126.7, -112.1, -111.9, -102.9, and -101.4 kcal/mol, respectively. The post-MD analyses revealed the energetical and structural stabilities of the identified drug candidates in complex with the P-gp transporter. Furthermore, in order to mimic the physiological conditions, the potent drugs complexed with the P-gp were subjected to 100 ns MD simulations in an explicit membrane-water environment. The pharmacokinetic properties of the identified drugs were predicted and demonstrated good ADMET characteristics. Overall, these results indicated that valspodar, dactinomycin, elbasvir, temsirolimus, and sirolimus hold promise as prospective P-gp inhibitors and warrant further invitro/invivo investigations.

Theoretical framework for achieving high V oc in non-fused non-fullerene terthiophene-based end-capped modified derivatives for potential applications in organic photovoltaics.

Non-fused ring-based OSCs are an excellent choice, which is attributed to their low cost and flexibility in applications. However, developing efficient and stable non-fused ring-based OSCs is still a big challenge. In this work, with the intent to increase V oc for enhanced performance, seven new molecules derived from a pre-existing A-D-A type A3T-5 molecule are proposed. Different important optical, electronic and efficiency-related attributes of molecules are studied using the DFT approach. It is discovered that newly devised molecules possess the optimum features required to construct proficient OSCs. They possess a small band gap ranging from 2.22-2.29 eV and planar geometries. Six of seven newly proposed molecules have less excitation energy, a higher absorption coefficient and higher dipole moment than A3T-5 in both gaseous and solvent phases. The A3T-7 molecule exhibited the maximum improvement in optoelectronic properties showing the highest λ max at 697 nm and the lowest E x of 1.77 eV. The proposed molecules have lower ionization potential values, reorganization energies of electrons and interaction coefficients than the A3T-5 molecule. The V oc of six newly developed molecules is higher (V oc ranging from 1.46-1.72 eV) than that of A3T-5 (V oc = 1.55 eV). Similarly, almost all the proposed molecules except W6 exhibited improvement in fill factor compared to the A3T-5 reference. This remarkable improvement in efficiency-associated parameters (V oc and FF) proves that these molecules can be successfully used as an advanced version of terthiophene-based OSCs in the future.

Exploring Probenecid Derived 1,3,4-Oxadiazole-Phthalimide Hybrid as α-Amylase Inhibitor: Synthesis, Structural Investigation, and Molecular Modeling.

1,3,4-Oxadiazole moiety is a crucial pharmacophore in many biologically active compounds. In a typical synthesis, probenecid was subjected to a sequence of reactions to obtain a 1,3,4-oxadiazole-phthalimide hybrid (PESMP) in high yields. The NMR (1H and 13C) spectroscopic analysis initially confirmed the structure of PESMP. Further spectral aspects were validated based on a single-crystal XRD analysis. Experimental findings were confirmed afterwards by executing a Hirshfeld surface (HS) analysis and quantum mechanical computations. The HS analysis showed the role of the π⋯π stacking interactions in PESMP. PESMP was found to have a high stability and lower reactivity in terms of global reactivity parameters. α-Amylase inhibition studies revealed that the PESMP was a good inhibitor of α-amylase with an s value of 10.60 ± 0.16 µg/mL compared with that of standard acarbose (IC50 = 8.80 ± 0.21 µg/mL). Molecular docking was also utilized to reveal the binding pose and features of PESMP against the α-amylase enzyme. Via docking computations, the high potency of PESMP and acarbose towards the α-amylase enzyme was unveiled and confirmed by docking scores of -7.4 and -9.4 kcal/mol, respectively. These findings shine a new light on the potential of PESMP compounds as α-amylase inhibitors.

Outcomes of Left Main Revascularization in Patients with Anemia: Gulf Left Main Registry.

INTRODUCTION: The aim of this study was to evaluate the effects of baseline anemia and anemia following revascularization on outcomes in patients with unprotected left main coronary artery (ULMCA) disease. METHODS: This was a retrospective, multicenter, observational study conducted between January 2015 and December 2019. The data on patients with ULMCA who underwent revascularization through percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were stratified by the hemoglobin level at baseline into anemic and non-anemic groups to compare in-hospital events. The pre-discharge hemoglobin following revascularization was categorized into very low (<80 g/L for men and women), low (≥80 and ≤119 g/L for women and ≤129 g/L for men), and normal (≥130 g/L for men and ≥120 g/L for women) to assess impact on follow-up outcomes. RESULTS: A total of 2,138 patients were included, 796 (37.2%) of whom had anemia at baseline. A total of 319 developed anemia after revascularization and moved from being non-anemic at baseline to anemic at discharge. There was no difference in hospital major adverse cardiac and cerebrovascular event (MACCE) and mortality between CABG and PCI in anemic patients. At a median follow-up time of 20 months (interquartile range [IQR]: 27), patients with pre-discharge anemia who underwent PCI had a higher incidence of congestive heart failure (CHF) (p < 0.0001), and those who underwent CABG had significantly higher follow-up mortality (HR: 9.85 (95% CI: 2.53-38.43), p = 0.001). CONCLUSION: In this Gulf LM study, baseline anemia had no impact upon in-hospital MACCE and total mortality following revascularization (PCI or CABG). However, pre-discharge anemia is associated with worse outcomes after ULMCA disease revascularization, with significantly higher all-cause mortality in patients who had CABG, and a higher incidence of CHF in PCI patients, at a median follow-up time of 20 months (IQR: 27).