Endovascular Treatment for Complex Vascular Pathologies in the Pediatric Population: Experience from a Center with Dual-Trained Neurosurgeons.

OBJECTIVE: Endovascular treatment of complex vascular pathologies in the pediatric population is often performed by non-pediatric subspecialists with adaptation of equipment and techniques developed for adult patients. We aimed to report our center's experience with safety and outcomes of endovascular treatments for pediatric vascular pathologies. METHODS: We performed a retrospective review of our endovascular database. All patients ≤18 years who underwent endovascular treatment between January 1, 2004 and December 1, 2022 were included. RESULTS: During the study time frame, 118 cerebral angiograms were performed for interventional purposes in 55 patients. Of these patients, 8(14.5%) had intracranial aneurysms, 21(38.2%) had intracranial arteriovenous malformations (AVMs), 6(10.9%) had tumors, 5(9.1%) had arterial occlusions (n=3) or dissections (n=2), 8(14.5%) had vein of Galen malformations, and 7(12.7%) had other cerebrovascular conditions. Of the total 118 procedures, access-site complications occurred in 2(1.7%), intraprocedural complications occurred in 3(2.5%), and transient neurological deficits were observed after 2(1.7%). Treatment-related mortality occurred in 1(1.8%) patient. CONCLUSIONS: Neurointervention in pediatric patients was safe and effective in our experience.

A Theoretical Investigation for Exploring the Potential Performance of Non-Fullerene Organic Solar Cells Through Side-Chain Engineering Having Diphenylamino Groups to Enhance Photovoltaic Properties.

The development of ecofriendly fabrication phenomenon is essential requirement for commercialization of non-fullerene acceptors. Recently, end-capped modeling is employed for computational design of five non-fullerene acceptors to elevate various photovoltaic properties. All new molecules are formulated by altering the peripheral acceptors of CH3-2F and DFT methodology is employed to explore the opto-electronic, morphological and charge transfer analysis. From the computational investigation, all reported molecules manifested red shifted absorption with remarkable reduced band gap. Among investigated molecules, FA1-FA3 evinced effectively decreased value of band gaps and designed molecules have low excitation energy justifying proficient charge transference. The lower values of binding energy of FA1 and FA2 suggest their facile exciton dissociation leading to improved charge mobility. By blending with J61 donor, FA4 have sufficiently enhanced value of VOC (1.72 eV) and fill factor (0.9228). Energy loss of the model (R) is 0.57 eV and statistical calculation demonstrate that all our modified molecules except FA3 has profoundly reduced energy loss compelling in its pivotal utilization. From accessible supportive outcomes of recent investigation, it is recommended that our modified chromophore exhibit remarkable noteworthy applications in solar cells for forthcoming innovations.

Juvenile Nasopharyngeal Angiofibroma: A Case Study on the Diagnostic and Surgical Challenges in an Adolescent Male.

A rare and locally aggressive vascular tumor, juvenile nasopharyngeal angiofibroma (JNA) mostly affects male teenagers. This paper describes a 14-year-old male patient who presented with lethargy and recurrent nasal bleeding, which are symptoms of JNA. CT and MRI scans confirmed a vascular mass with a significant local invasion originating from the sphenopalatine foramen. After a CT angiography, which revealed the tumor's large blood supply and helped with efficient excision, a focused surgical strategy was designed. Histopathology verified the benign nature of the tumor, and the operation was successful and the patient had a smooth recovery. This case adds to the little literature on JNA. It highlights the need for healthcare professionals to be aware of the requirement of early identification and careful presurgical preparation in managing the illness.

In silico design of peptide inhibitors for Dengue virus to treat Dengue virus-associated infections.

Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.

Sex disparity of DAPT noncompliance in patients with left main stem PCI with DES.

This retrospective study aims to explore the sex disparity in dual antiplatelet therapy (DAPT) noncompliance among left main stem percutaneous coronary intervention (PCI) patients with drug-eluting stent (DES) and identify predictors associated with non-adherence. Data were collected from the medical records of 1585 patients, including 1104 males and 481 females, who underwent left main stem PCI with DES. Baseline characteristics, angiographic features, and DAPT compliance rates at 1 month and 12 months were analyzed. Univariate logistic regression was used to identify predictors of DAPT noncompliance. The overall DAPT noncompliance rate at 1 month was 8.5%, increasing to 15.5% at 12 months. Females exhibited slightly higher noncompliance rates than males at both 1 month (15.6% vs 14.5%) and 12 months (28.1% vs 19.0%), although the difference was not statistically significant. Smoking status showed a modest impact on non-adherence, with current smokers exhibiting a lower noncompliance rate (14.9% at 1 month). Prior coronary artery disease history was associated with increased noncompliance at 12 months (18.9%). Angiographic characteristics, including lesion location and Syntax score, had no consistent association with DAPT noncompliance. This study highlights sex disparity in DAPT noncompliance among patients undergoing left main stem PCI with DES. Comorbidities, socioeconomic status, smoking status, and prior coronary artery disease history were identified as predictors of non-adherence.

Diagnostic Approach to Equine Testicular Disorders.

Management of breeding stallions is crucial to equine reproduction. The longevity of the breeding career is the ultimate objective, whether the stallion is used for natural cover or for semen collection and artificial insemination. Stud farm veterinarians should be aware of the techniques used to evaluate testicular function and the diagnostic approach to testicular disorders in cases of emergency. This paper presents the clinical methods used to evaluate testicular health, including palpation, ultrasonography, biopsy, and fine-needle aspiration. The discussion of testicular disorders is broken down into four categories: congenital disorders (cryptorchidism, monorchidism, and testicular hypoplasia), differential diagnosis of scrotal enlargement, differential diagnosis of causes of progressive testicular enlargement, and differential diagnosis of testicular asymmetry or reduction in size with an emphasis on testicular degeneration. The sudden increase in testicular size is often accompanied by severe clinical signs and is a major cause for referral of stallion for surgery. Testicular disorders are illustrated with clinical cases seen by the authors.

Influence of agro-wastes derived biochar and their composite on reducing the mobility of toxic heavy metals and their bioavailability in industrial contaminated soils.

The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.

The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.

Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein.

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.

Pesticide reduction: clustering organic croplands.

Organic and conventional farms often coexist, yet their proximity does not ensure compatibility. Larsen et al. reveal that being surrounded by organic fields reduces pesticide usage in organic fields but increases it in conventional fields. We discuss these findings, emphasizing the need to cluster organic croplands for reduced pesticide use.

Integrated Approach to Hydrogeochemical Assessment of Groundwater Quality in Major Industrial Zone of Punjab, Pakistan.

Groundwater contamination with arsenic (As) is a significant concern in Pakistan's Punjab Province. This study analyzed 69 groundwater samples from Faisalabad, Gujranwala, Lahore, and Multan to understand hydrogeochemistry, health impacts, contamination sources, and drinking suitability. Results revealed varying as concentrations across districts, with distinctive cation and anion orders. Faisalabad exhibited Na+ > Mg2+ > Ca2+ > K+ > Fe2+ for cations and SO42- > Cl- > HCO3- > NO3- > F- for anions. Gujranwala showed Na+ > Ca2+ > Mg2+ > K+ for cations and HCO3- > SO42- > Cl- > NO3- > F- for anions. In Lahore, demonstrated: Na+ > Ca2+ > Mg2+ > Fe > K+ for cations and HCO3- > SO42- > Cl- > NO3- > F- for anions. Multan indicated K+ > Ca2+ > Mg2+ > Na+ > Fe for cations and HCO3- > SO42- > Cl- > F- > NO3- ) for anions. Hydrochemical facies were identified as CaHCO3 and CaMgCl types. Principal Component Analysis (PCA), highlighted the influence of natural processes and human activities on groundwater pollution. Water Quality Index (WQI) result reveal that most samples met water quality standards. The carcinogenic risk values for children exceeded permissible limits in all districts, emphasizing a significant cancer risk. The study highlights the need for rigorous monitoring to mitigate (As) contamination and protect public health from associated hazards.

A novel approach for credit card fraud transaction detection using deep reinforcement learning scheme.

Online transactions are still the backbone of the financial industry worldwide today. Millions of consumers use credit cards for their daily transactions, which has led to an exponential rise in credit card fraud. Over time, many variations and schemes of fraudulent transactions have been reported. Nevertheless, it remains a difficult task to detect credit card fraud in real-time. It can be assumed that each person has a unique transaction pattern that may change over time. The work in this article aims to (1) understand how deep reinforcement learning can play an important role in detecting credit card fraud with changing human patterns, and (2) develop a solution architecture for real-time fraud detection. Our proposed model utilizes the Deep Q network for real-time detection. The Kaggle dataset available online was used to train and test the model. As a result, a validation performance of 97.10% was achieved with the proposed deep learning component. In addition, the reinforcement learning component has a learning rate of 80%. The proposed model was able to learn patterns autonomously based on previous events. It adapts to the pattern changes over time and can take them into account without further manual training.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

A theoretical investigation for improving the performance of non-fullerene organic solar cells through side-chain engineering of BTR non-fused-ring electron acceptors.

In the current quantum chemical study, indacenodithiophene donor core-based the end-capped alterations of the reference chromophore BTR drafted eight A2-A1-D-A1-A2 type small non-fullerene acceptors. All the computational simulations were executed under MPW1PW91/6-31G (d, p) level of DFT. The UV-Vis absorption, open circuit voltage, electron affinity, ionization potential, the density of states, reorganization energy, orbital analysis, and non-covalent interactions were studied and compared with BTR. Several molecules of our modeled series BT1-BT8 have shown distinctive features that are better than those of the BTR. The open circuit voltage (VOC) of BT5 has a favorable impact, allowing it to replace BTR in the field of organic solar cells. The charge carrier motilities for proposed molecules generated extraordinary findings when matched to the reference one (BTR). Further charge transmission was confirmed by creating the complex with a PM6 donor molecule. The remarkable dipole moment contributes to the formation of non-covalent bond interactions with chloroform, resulting in superior charge mobility. Based on these findings, it can be said that every tailored molecule has the potential to surpass chromophore molecule (BTR) in OSCs. So, all tailored molecules may enhance the efficiency of photovoltaic cells due to the involvement of potent terminal electron-capturing acceptor2 moieties. Considering these obtained results, these newly presented molecules can be regarded for developing efficient solar devices in the future.

Comparison between Woven EndoBridge and coiling with and without stent assistance for intracranial bifurcation and wide-neck aneurysms: a comprehensive systematic review and meta-analysis.

OBJECTIVE: The recent introduction of the Woven EndoBridge (WEB) has presented an alternative treatment modality for intracranial bifurcation and wide-neck aneurysms with a growing body of literature evaluating its efficacy. However, no previous systematic review has focused on comparing WEB with previously using endovascular approaches, specifically primary coiling (PC) and stent-assisted coiling (SAC). Herein, the authors present the first systematic review summarizing available literature to reach a consensus regarding the safety and effectiveness of WEB. METHODS: A systematic review of articles identified through a search of PubMed, Embase, Scopus, and Web of Science was conducted. Studies were included if they compared WEB with PC or SAC from any aspect for intracranial aneurysms. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions tool. Meta-analyses of the outcomes based on stent use and rupture status were performed. RESULTS: A total of 16 studies were included. The three endovascular approaches were comparable in terms of baseline characteristics except for older age and smaller aneurysm neck in the PC group (p < 0.05). Moreover, the follow-up duration was shorter in the WEB group (p < 0.05). Although the WEB group demonstrated lower complete and adequate immediate occlusion rates (p < 0.01), the rates at follow-up evaluations were comparable with SAC and PC (p = 0.61 and p = 0.27, respectively). The WEB group experienced significantly fewer unfavorable neurological outcomes than the SAC group (p = 0.04), while comparable to the PC group (p = 0.36). Retreatment rates were comparable between WEB and coiling (p = 0.92). The WEB group had fewer hemorrhagic and thromboembolic complications (p < 0.01 and p = 0.01, respectively), with similar neurological and procedure-related complications compared with combined PC and SAC groups. Lastly, mortality was comparable among the different endovascular approaches. CONCLUSIONS: This study provides evidence on the noninferiority of WEB compared with PC and SAC in terms of angiographic outcomes. Meanwhile, our findings on lower complication rates, cost, and improved operative aspects associated with WEB establish this novel endovascular treatment as a safe and effective alternative for the treatment of bifurcation and wide-neck aneurysms.

Identification of small molecular inhibitors of SIRT3 by computational and biochemical approaches a potential target of breast cancer.

Sirtuin 3 (SIRT3) belongs to the Sirtuin protein family, which consists of NAD+-dependent lysine deacylase, involved in the regulation of various cellular activities. Dysregulation of SIRT3 activity has been linked to several types of cancer, including breast cancer. Because of its ability to stimulate adaptive metabolic pathways, it can aid in the survival and proliferation of breast cancer cells. Finding new chemical compounds targeted towards SIRT3 was the primary goal of the current investigation. Virtual screening of ~ 800 compounds using molecular docking techniques yielded 8 active hits with favorable binding affinities and poses. Docking studies verified that the final eight compounds formed stable contacts with the catalytic domain of SIRT3. Those compounds have good pharmacokinetic/dynamic properties and gastrointestinal absorption. Based on excellent pharmacokinetic and pharmacodynamic properties, two compounds (MI-44 and MI-217) were subjected to MD simulation. Upon drug interaction, molecular dynamics simulations demonstrate mild alterations in the structure of proteins and stability. Binding free energy calculations revealed that compounds MI-44 (- 45.61 ± 0.064 kcal/mol) and MI-217 (- 41.65 ± 0.089 kcal/mol) showed the maximum energy, suggesting an intense preference for the SIRT3 catalytic site for attachment. The in-vitro MTT assay on breast cancer cell line (MDA-MB-231) and an apoptotic assay for these potential compounds (MI-44/MI-217) was also performed, with flow cytometry to determine the compound's ability to cause apoptosis in breast cancer cells. The percentage of apoptotic cells (including early and late apoptotic cells) increased from 1.94% in control to 79.37% for MI-44 and 85.37% for MI-217 at 15 µM. Apoptotic cell death was effectively induced by these two compounds in a flow cytometry assay indicating them as a good inhibitor of human SIRT3. Based on our findings, MI-44 and MI-217 merit additional investigation as possible breast cancer therapeutics.

Designing efficient materials for high-performance of non-fullerene organic solar cells through side-chain engineering on DBT-4F derivatives by non-fused-ring electron acceptors.

CONTEXT: For the advancement in fields of organic and perovskite solar cells, various techniques of structural alterations are being employed on previously reported chromophores. In this study, the end-capped engineering is carried out on DBT-4F (R) by modifying terminal acceptors to improve optoelectronic and photovoltaic attributes. Seven molecules (AD1-AD7) are modeled using different push-pull acceptors. DFT/B3LYP/6-31G along with its time-dependent approach (TD-DFT) are on a payroll to investigate ground state geometries, absorption maxima (λmax), energy gap (Eg), excitation energy (Ex), internal reorganization energy, light harvesting efficiency (LHE), dielectric constant, open circuit voltage (VOC), fill factor (FF), etc. of OSCs. AD1 displayed the lowest band gap (1.76 eV), highest λmax (876 nm), lowest Ex (1.41 eV), and lowest binding energy (0.21 eV). Among various calculated parameters, all of the sketched molecules demonstrated greater dielectric constant when compared to R. The highest dielectric constant was exhibited by AD3 (56.26). AD5 exhibited maximum LHE (0.9980). Lower reorganization energies demonstrated improved charge mobility. AD5 and AD7 (1.63 and 1.68 eV) have higher values of VOC than R (1.51 eV). All novel molecules having outperforming attributes will be better candidates to enhance the efficacy of OSCs for future use. METHODS: Precisely, a DFT and TD-DFT analysis on all of the proposed organic molecules were conducted, using the functional MPW1PW91 at 6-31G (d,p) basis set to examine their optoelectronic aspects, additionally the solvent-state computations were studied with a TD-SCF simulation. For all these simulations, Guassian 09 and GuassView 5.0 were employed. Moreover, the Origin 6.0, Multiwfn 3.8, and PyMOlyze 1.1 software were utilized for the visual depiction of the graphs of absorption, TDM, and DOS, respectively of the studied molecules. A number of crucial aspects such as FMOs, bandgaps, light-harvesting efficiency, electrostatic potential, dipole moment, ionization potential, open-circuit voltage, fill factor, binding energy, interaction coefficient, chemical hardness-softness, and electrophilicity index were also investigated for the studied molecules.

Improving Access to Anti-HDV Testing: Development and Validation of an Affordable In-House ELISA Assay.

In certain low-income nations, the hepatitis Delta virus and hepatitis B virus (HBV) pose a serious medical burden, where the prevalence of hepatitis B surface antigen (HBsAg) is greater than 8%. Especially in rural places, irregular diagnostic exams are the main restriction and reason for underestimation. Utilizing serum samples from a Pakistani isolate, an internal ELISA for the quick identification of anti-HDV was created, and the effectiveness of the test was compared to a commercial diagnostic kit. HDV-positive serum samples were collected, and a highly antigenic domain of HDAg antigen was derived from them. This antigenic HDAg was expressed in a bacterial expression system, purified by Ni-chromatography, and confirmed by SDS-PAGE and Western blot analysis. The purified antigen was utilized to develop an in-house ELISA assay for anti-HDV antibody detection of the patient's serum samples at very low cost. Purified antigens and positive and negative controls can detect anti-HDV (antibodies) in ELISA plates. The in-house developed kit's efficiency was compared with that of a commercial kit (Witech Inc., USA) by the mean optical density values of both kits. No significant difference was observed (a P value of 0.576) by applying statistical analysis. The newly developed in-house ELISA is equally efficient compared to commercial kits, and these may be useful in regular diagnostic laboratories, especially for analyzing local isolates.

Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics.

BACKGROUND/AIM: The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus's main protease (Mpro), crucial for viral replication, is a promising strategy. OBJECTIVE: The current study aims to discover novel inhibitors of Mpro. METHODS: The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity. The selected compound's toxicity was examined using the MTT assay on a human BJ cell line. RESULTS: Compound C1 exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro's active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein's active pocket, showing superior binding interactions. in vitro assays validated their inhibitory effects, with C1 having the most significant potency (IC50 = 2.85 µM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile. CONCLUSION: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.

Cangrelor for neurointerventional procedures: A systematic review.

Thromboembolism is a complication of neurointerventional procedures that requires patients to be placed under antiplatelet therapy. Current options for antiplatelet therapies have a delayed onset of action that prevents a rapid door to puncture transition for patents presenting in acute settings. Cangrelor (Kengreal, Chiesi, USA) is an intravenous P2Y12 platelet inhibitor approved in percutaneous coronary interventions that has an immediate onset of action and half-life between 2 and 6 min. Thus, the goal of this study is to report on the safety, effectiveness, and indications for using Cangrelor in neurointerventional procedures. A systematic review of studies describing the use of Cangrelor in neurointervention was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was conducted on PubMed, Ovid Medline, and Embase databases through June 2023. Seventeen studies with 314 patients met inclusion criteria. The most common indication for Cangrelor use was acute ischemic strokes: 70% followed by aneurysms 27.4%. The Infusion protocol varied from 5 to 30 µg/kg bolus and 1 to 4 µg/kg/min infusion with 30 µg/kg bolus and 4 µg/kg/min infusion being reported in 64.7% of studies. Intra-operative platelet reacting unit levels were below 200 in all the studies that reported it, and the percentage of hemorrhagic, thromboembolic, and deaths occurrence in this patient cohort was respectively 11.1%, 4.8%, and 8.6%. Cangrelor appears to be a promising P2Y12 platelet inhibitor for neurointerventional procedures. However, large, randomized trials are needed to determine the full range of its effects in neurointerventional procedures.

Evaluation Health Risks and Sorption of Hexavalent Chromium (Cr(VI) by Biochar and Iron Doped Zinc Oxide Modified Biochar (Fe-ZnO@BC) Using Trifolium: A Green Synthesis Technique.

Contamination of aquatic and terrestrial environment with hexavalent chromium Cr(VI) is one of the major hazards worldwide due its carcinogenicity, persistency and immobility. Different research techniques have been adopted for Cr(VI) remediation present in terrestrial and aquatic media, while adsorption being the most advance, low cost, environmentally friendly and common method. The present study discussed the mechanisms of Parthenium hysterophorus derived biochar, iron-doped zinc oxide nanoparticles (nFe-ZnO) and Fe-ZnO modified biochar (Fe-ZnO@BC) involved in Cr(VI) mobility and bioavailability. Pot experiments were conducted to study the effect of Parthenium hysterophorus derived biochar, nFe-ZnO and Fe-ZnO@BC application rates (2%, 2 mg/kg, 10 mg/kg, respectively). The results indicated that the addition of soil amendments reduced Cr(VI) mobility. The findings revealed that the reduction in chromium mobility was observed by P. hysterophorus BC, and Fe-ZnO@BC but nFe-ZnO application significantly (p = 0.05) reduced Cr(VI) and CrT uptake as compared to the control treatments. The results of SEM coupled with EDS showed a high micropores and channel, smooth surface which helped in adsorption, and may enhance soil conditions. The concentration index (CI) by different amendments in trifolium plant was followed the descending order as: nFe-ZnO > Fe-ZnO@BC > P. hysterophorus BC after 30, 60 and 90 days of harvesting, respectively. In addition, human health risk index was found less than one (H1 < 1.0) in amended soils as compared to control treatments.