A rare homozygous variant in TERT gene causing variable bone marrow failure, fragility fractures, rib anomalies and extremely short telomere lengths with high serum IgE.

By whole exome sequencing, we identified a homozygous c.2086 C→T (p.R696C) TERT mutation in patients who present with a spectrum of variable bone marrow failure (BMF), raccoon eyes, dystrophic nails, rib anomalies, fragility fractures (FFs), high IgE level, extremely short telomere lengths (TLs), and skewed numbers of cytotoxic T cells with B and NK cytopenia. Haploinsufficiency in the other family members resulted in short TL and osteopenia. These patients also had the lowest bone mineral density Z-score compared to other BMF-patients. Danazol/zoledronic acid improved the outcomes of BMF and FFs. This causative TERT variant has been observed in one family afflicted with dyskeratosis congenita (DC), and thus, we also define a second report and new phenotype related to the variant which should be suspected in severe cases of DC with co-existent BMF, FFs, high IgE level and rib anomalies.

Mechanistic aspects of reactive metabolite formation in clomethiazole catalyzed biotransformation by cytochrome P450 enzymes.

Clomethiazole (CLM), a sedative and anticonvulsant drug, is commonly employed for the treatment of alcohol withdrawal syndrome because it suppresses cytochrome P450 (P450) activity associated with the generation of free radicals and liver damage. The catalyzed biotransformation of thiazole-containing drugs by P450 is known to afford reactive metabolites. These metabolites can alter the biological functions of macromolecules and result in toxicity and adverse drug interactions. Multitargeted molecular modeling and quantum chemical DFT calculations were performed to explore the binding modes and molecular mechanisms underlying the mechanism-based inactivation (MBI) of P450 by CLM. The mechanistic details associated with reactive metabolite formation from further metabolic processes were extensively assessed. Seven possible routes were proposed for CLM-P450 biotransformation including CLM hydroxylation, sulfoxidation, N-oxidation, CN epoxidation (oxaziridine formation), and CC epoxidation. The results revealed a degree of preference for the C-N epoxidation pathway because of the low energy requirements of its rate-determining step (8.74 and 10.07 kcal mol-1 for LS and HS states, respectively). A kinetic competition for the CLM-methyl hydroxylation pathway was detected because the H-abstraction energy barrier was relatively comparable to the thermodynamically prevailing oxaziridine formation rate-determining step (12.58 and 14.52 kcal mol-1 for quartet and doublet states, respectively). Our studies assessed the mechanisms of covalent nucleophilic epoxide adduct formation through nucleophilic addition, hydrolysis of epoxidation products, and nonenzymatic degradation. CLM was shown to display P450-inhibitory activity by forming covalent adducts rather than further metabolization to reactive metabolites. The outcomes of molecular docking allowed assessing the binding profile of CLM with three human P450 isozymes, namely, CYP2E1, CYP3A4, and CYP2D6.

Effect of copper doping on plasmonic nanofilms for high performance photovoltaic energy applications.

In the current era, alternative but environment-friendly sources of energy have gained attention to meet the growing energy demands. In particular, the focus of research has been solar energy and using it to fulfill energy demands. Solar energy is either directly converted into electrical energy or stored for later use. Solar cells are a practical way to turn solar energy into electrical energy. Various materials are being investigated to manufacture solar cell devices that can absorb a maximum number of photons present in sunlight. The present study reports thermally evaporated in situ Cu-doped SnS photon absorber thin films with tunable physical properties. This study mainly explored the effects of changing Cu concentrations on the physical features of light absorption of SnS thin films. The thin films were formed by simultaneous resistive heating of Cu and SnS powders on glass substrates at 150 °C. The X-ray diffraction patterns revealed pure SnS thin films having orthorhombic polycrystalline crystal structures oriented preferentially along the (111) plane. Raman spectroscopy confirmed this phase purity. Photoconductivity studies showed phase dependence on Cu content that improved with increasing concentrations of Cu. The optical bandgap energy was also found to be dependent on Cu content and was observed at 1.10-1.47 eV for SnS thin films with variation in the Cu content, i.e., 0-18%. According to the hot probe method, all films displayed p-type conductivity for the substitution of Cu metal atoms. These findings demonstrated that the prepared thin films are substantial candidates as low-cost, suitably efficient, thin-film solar cells featuring environmentally-friendly active layers that absorb sunlight.

Unusual pattern of thrombotic events in young adult non-critically ill patients with COVID-19 may result from an undiagnosed inherited and acquired form of thrombophilia.

In 145 previously healthy non-critically ill young adults, coronavirus disease 2019 (COVID-19)-related symptoms, risk factors for thrombosis, coagulation and inflammatory parameters were compared, with 29 patients reporting unusual thrombotic events (UTEs) and 116 not having thrombotic events. The inflammatory indices, coagulation and prothrombotic platelet phenotype (PTPP) were significantly higher in patients with UTEs versus those without. Patients with UTEs were categorised according to detection of thrombophilic genes (TGs), coagulation and inflammatory markers to the non-TG and TG subcohort. A total of 38 UTEs were identified, which included splanchnic vein thrombosis (SVT; 11), stroke (six), cerebral vein thrombosis (five), thrombotic microangiopathy (four), limb ischaemia and inferior vena cava thrombosis (three each), ST-segment elevation myocardial infarction (two), superior vena cava thrombosis (two), upper limb deep venous thrombosis and retinal vein thrombosis, one each. We found a 55% prevalence of TGs mainly heterozygous coagulation factor II, thrombin (FII)-G20210A, Janus kinase 2 (JAK2)-V617F, protein-S, and antithrombin III deficiency with a high (76·9%) prevalence of venous UTEs, multiple vessels thrombosis, and recurrence rate among the TG versus non-TG subcohort. The presence of JAK2-V617F, and FII-G20210A mutations was linked with SVT. Thrombosis in the non-TG subcohort was associated with more haemorrhagic problems, thrombosis progression and a significantly higher level of inflammatory markers, PTPP, mean platelet volume, von Willebrand factor, and factor VIII, which remained high for up to 6 months, as well as elevated D-dimer. Acquired and inherited thrombophilia with endotheliopathy appeared to be a relevant mechanism to explain the occurrence of UTEs that are not correlated to COVID-19 severity.

Immobilization of lanthanide doped aluminate phosphor onto recycled polyester toward the development of long-persistent photoluminescence smart window.

Smart window can be defined as switchable material whose light transmission is altered upon exposure to light, voltage, or heat. However, smart windows are usually produced from expensive and breakable glass materials. Herein, transparent smart window with long-persistent phosphorescence, high optical transmittance, ultraviolet (UV) protection, rigid, high photostability and durability, an d superhydrophobicity was developed from recycled polyester (PET). Recycled polyester waste (RBW) was simply immobilized with different ratios of lanthanide-doped aluminate nanoparticles (LdAN) to provide a long-persistent phosphorescent polyester smart window (LdAN@PET) with an abili ty to persist emitting light for extended time periods. The solid-state high temperature technique was used to prepare lanthanide-doped aluminate (LdA) micro-scale powder. Then, the top-down technique was applied to afford the corresponding LdAN. Recycled shredded recycled polyester bottles were charged into a hot bath to provide a clear plastic shred bulk, which was then well-mixed with LdAN and drop-casted to provide long-persistent luminescent smart window. In order to improve the phosphor dispersion in the PET bulk, LdAN was synthesized in the nanoparticle form which was characterized utilizing transmission electron microscopy (TEM). For better preparation of translucent smart window of long-persistent phosphorescent polyester, LdAN must be homogeneously dispersed in the PET matrix without agglomeration. The morphology and chemical composition were studied by Fourier-transform infrared (FTIR) spectra), X-ray fluorescence (XRF) analysis, scanning electron microscopy (SEM), and energy-dispersion X-ray spectroscopy (EDX). In addition, spectral profiles of excitation and emission, and decay and lifetime were used to better understand the photoluminescence properties. The hardness properties were also investigated. The developed phosphorescent transparent polyester smart window demonstrated a color switch to intense green underneath UV irradiation and greenish-yellow under darkness as verified by CIELab color parameters. The afterglow polyester smart window showed an absorption wavelength at 365 nm and two phosphorescence intensities at 442 and 512 nm. An enhanced UV protection, photostability and hydrophobic activity were detected. The luminescent polyester substrates with lower LdAN ratios demonstrated rapid and reversible fluorescent photochromic activity beneath the UV light. The luminescent polyester substrates with higher LdAN contents displayed long-persistent phosphorescence afterglow. The current strategy can be simply applied for the production of smart windows, low thickness anti-counterfeiting films and warning signs.

Synthesis of New Hybrid Structured Magnetite Crosslinked Poly Ionic Liquid for Efficient Removal of Coomassie Brilliant Blue R-250 Dye in Aqueous Medium.

In this work, new crosslinked pyridinium poly ionic liquid and its magnetite hybrid structured composite were prepared and applied to remove the toxic dye Coomassie Brilliant Blue (CBB-R250) from aqueous solutions. In this respect, vinyl pyridine, maleic anhydride, and dibromo nonane were used to prepare crosslinked quaternized vinyl pyridinium/maleic anhydride ionic liquid (CQVP-MA). Furthermore, a linear copolymer was prepared by the reaction of vinyl pyridine with bromo nonane followed by its copolymerization with maleic anhydride in order to use it as a capping agent for magnetite nanoparticles. The monodisperse MNPs were incorporated into the crosslinked PIL (CQVP-MA) by ultrasonication to prepare CQVP-MA/Fe3O4 composite to facilitate its recovery using an external magnetic field and enhance its adsorption capacity. The chemical structures, thermal stabilities, zeta potential, particle size, EDS, and SEM of the prepared CQVP-MA and CQVP-MA/Fe3O4 were investigated. Adsorption kinetics, isotherms, and mechanisms of CB-R250 elimination from aqueous solutions using CQVP-MA and CQVP-MA/Fe3O4 were also studied, and the results revealed that the pseudo second-order kinetic model and the Langmuir isotherm model were the most suitable to describe the CBB adsorption from an aqueous solution. The adsorption capacities of CQVP-MA and CQVP-MA/Fe3O4 were found to be 1040 and 1198, respectively, which are more than those for previously reported material in the literature with reasonable stability for five cycles.

Acute human parvovirus B19 infection triggers immune-mediated transient bone marrow failure syndrome, extreme direct hyperbilirubinaemia and acute hepatitis in patients with hereditary haemolytic anaemias: multicentre prospective pathophysiological study.

A total of 244 patients with hereditary haemolytic anaemias (HHA) were screened for acute symptomatic human parvovirus B19 infection (HPV-B19) in a prospective study. To assess the risks associated with HPV-B19 infection, patients were classified into Group I and Group II according to presence or absence (symptoms, signs and specific serology) of acute HPV-B19 infection respectively. In all, 131 (53·7%) patients had ß-thalassaemia, 75 (30·7%) hereditary spherocytosis (HS), 27 (11·1%) sickle cell anaemia (SCA) and 11 (4·5%) glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 33 (13·5%) patients who presented with symptomatic HPV-B19 infection, 19 (57·5%) had HS, nine (27·3%) had ß-thalassaemia and five (15·2%) had SCA. In Group I, there were significant differences in the mean white blood cell, red blood cell and platelet counts, haemoglobin concentration, total bilirubin (TB), alanine aminotransferase, aspartate aminotransferase and serum creatinine (all P < 0·001) compared to Group II. In all, 27 (81·8%) patients had arthropathy and bone marrow failure (BMF); 13 (39·4%) had acute kidney injury (AKI), more in SCA (80%); and 12 (36·4%) patients had hepatitis, more in HS (66·8%). Five (15·2%) patients with HS had BMF, AKI, nervous system involvement and extreme hyperbilirubinaemia (TB range 26·3-84·7 mg/dl). Five (15·2%) patients had haemophagocytic syndrome. Two patients with HS combined with Type-I autoimmune hepatitis presented with transient BMF. Complete recovery or stabilisation was noted at 12 months in every patient except for one patient with SCA who died during the infection. HPV-B19 must be suspected and screened in patients with HHA with typical and atypical presentations with careful follow-up.

Holmium laser enucleation of the prostate versus bipolar transurethral enucleation of the prostate in management of benign prostatic hyperplasia: A randomized controlled trial.

OBJECTIVE: To evaluate the safety, efficacy and cost-effectiveness of holmium enucleation of the prostate and bipolar transurethral enucleation of the prostate. METHODS: In our randomized controlled trial, 120 patients were allocated into two equal groups representing holmium enucleation of the prostate and bipolar enucleation of the prostate. Operative parameters were recorded according to operative, enucleation and resection time in addition to the intraoperative complications. Patients were followed up at 1, 3 and 12 months postoperative to assess the prostate size, post-voiding residual urine, International Prostate Symptom Score, peak urine flow rate and quality of life, and compared with the preoperative parameters. Cost analysis was evaluated for both procedures. RESULTS: We evaluated 107 patients who finished our follow up and their data were analyzed. The prostate size was 135.2 ± 34.8 mL and 125 ± 26.9 mL for holmium enucleation of the prostate and bipolar enucleation of the prostate, respectively. Holmium enucleation of the prostate was associated with a shorter operative time of 83.43 ± 6.92 min compared with 94.7 ± 12.2 min in bipolar enucleation of the prostate groups. Holmium enucleation of the prostate was associated with an earlier catheter removal time and shorter hospital stay compared with bipolar enucleation of the prostate. Postoperative International Prostate Symptom Score, quality of life, post-voiding residual urine, peak urine flow rate, prostate-specific antigen and prostate volume reduction were comparable between both groups, and they both showed statistically significant improvement compared with their preoperative parameters. In the cost analysis, holmium enucleation of the prostate was more cost-effective than bipolar enucleation of the prostate. CONCLUSION: Both holmium enucleation of the prostate and bipolar enucleation of the prostate are safe and effective in the surgical management of large prostatic adenomas. Holmium enucleation of the prostate has a shorter operative time and hospital stay with earlier catheter removal time, and is more cost-effective than bipolar enucleation of the prostate.

Hybrid Ionic Silver and Magnetite Microgels Nanocomposites for Efficient Removal of Methylene Blue.

The ionic crosslinked 2-acrylamido-2-methylpropane sulfonic acid-co-acrylic acid hydrogel, AMPS/AA and its Ag and Fe3O4 composites were synthesized using an in situ technique. The surface charge, particle sizes, morphology, and thermal stability of the prepared AMPS/AA-Ag and AMPS/AA-Fe3O4 composites were evaluated using different analytical techniques and their adsorption characteristics were evaluated to remove the methylene blue cationic dye, MB, from their aqueous solutions at optimum conditions. Also, the same monomers were used to synthesize AMPS/AA microgel and its Ag and Fe3O4 nanocomposites, which were synthesized using the same technique. The AMPS/AA-Fe3O4 nanocomposite was selected as conventional iron-supported catalyst due to the presence of both Fe(II) and Fe(III) species besides its magnetic properties that allow their easy, fast, and inexpensive separation from the aqueous solution. It was then evaluated as a heterogeneous catalyst for complete MB degradation from aqueous solution by heterogeneous Fenton oxidation. It achieved a high rate of degradation, degrading 100 mg L-1 of MB during a short time of 35 min as compared with the reported literature.

Is supine a preferred position for percutaneous nephrolithotomy in the pediatric age group? A randomized controlled study.

BACKGROUND: The aim is to evaluate supine versus prone position in mini-percutaneous nephrolithotomy in pediatric renal urolithiasis management. METHODS: A randomized controlled trial was constructed to evaluate supine versus prone position in pediatric PCNL. Seventy pediatric patients with a stone burden ≥1.5 cm were randomized into two groups. RESULTS: Sixty-three patients were available for evaluation in our study with no significant difference in the perioperative demographic data. The supine group showed a shorter operation time of 43.9 min compared to 73.5 min in the prone group. The stone-free rate was higher in the supine group, with a 93.9% SFR compared to 83.3% in the prone group. The supine group showed a shorter hospital stay of 2.0±1.0 days, compared to 3.20±1.56 days in the prone group. No significant difference was seen in the perioperative complication rate and fluoroscopy time between both groups. CONCLUSIONS: Supine mini-percutaneous nephrolithotomy is safe and effective in managing pediatric renal stones, with a higher stone-free rate, less operative time, and less hospital stay compared to the prone position.

Stereoselective synthesis and X-ray structure determination of novel 1,2-dihydroquinolinehydrazonopropanoate derivatives.

A novel series of 1,2-dihydroquinolinhydrazonopropanoate have been synthesized via a convenient aza-Michael addition reaction between hydrazinylquinolinones and ethyl propiolate in ethanol under refluxing temperature. The structures for all obtained products were confirmed with FTIR, NMR spectrums, as well as mass spectrometry. In addition, the monoclinic structure for compounds 8a, 8c, and 8d was also confirmed via X-ray crystallography analyses. The E-configuration for the obtained products was confirmed form the X-ray analysis. On the other hand, the crystal packing shows that the intermolecular and hydrogen bonds between atoms are parallel to the bc plan.

Risk factors of stone residual after retrograde intrarenal surgery: A prospective cohort study.

BACKGROUND: Complete removal of renal stones is crucial for optimal patient outcomes, but recent studies have reported residual stones after retrograde intrarenal surgery (RIRS). This study aimed to identify the associated risk factors to improve patient management and treatment selection. METHODS: This cohort study was conducted over 18 months at two hospitals and recruited adult patients with renal stones less than 3 cm. Preoperative assessment included medical history, physical examination, laboratory tests, and radiological imaging. Intraoperative and postoperative data collection and follow-up were conducted to evaluate surgical success and potential complications. RESULTS: A total of 100 patients were included, with a mean age of 45.3 ± 10.7 years and a mean BMI of 26.2 ± 1.4 kg/m2. Approximately 19% of the patients had residual stones after the RIRS procedure. The RUSS score showed good diagnostic performance with an AUC of 0.843, and the optimal cut point was ⩾2.0 with a sensitivity of 52.6% and specificity of 95.1%. Independent predictors of residual stones were multiple sites (OR = 24.98; p = 0.002), multiple stones (OR = 13.62, p = 0.002), stone size of 21-30 mm (OR = 4.91, p = 0.038), lower calyx site (OR = 4.85, p = 0.033), and surgeon experience of fewer than 50 cases (OR = 6.82, p = 0.020). CONCLUSIONS: This study identifies several factors associated with residual stones after RIRS for renal stones, including stone size, location, number, and surgeon experience. The study suggests that the RUSS score can be used as a reliable tool for predicting the likelihood of residual stones, which can help clinicians in patient selection and treatment planning.

One-Step Synthesis of New Amphiphilic Nonionic Surfactants Based on Alkylamine and Poly(ethylene glycol) Dimethacrylate for Demulsification of Arabian Heavy Crude Oil Emulsions.

New non-ionic surfactants based on alkylamine and poly(ethylene glycol) dimethacrylate were synthesized by one-step Aza-Michael addition reaction. The surfactants' chemical compositions, surface and interfacial activities, micellization, and zeta potential were characterized. Their surface and interfacial activities recommended the application as demulsifiers for water in Arabian heavy oil emulsions (w/o). The demulsification of this type of emulsion has attracted researchers' attention because of its high stability with water droplets in the microscale. The outcome of using the prepared surfactants showed high performance as emulsion breakers, as the demulsification efficiency reached 100% for w/o emulsions with different water to oil ratios (50:50, 30:70, and 10:90).

Redox active pyridine-3,5-di-carboxylate- and 1,2,3,4-cyclopentane tetra-carboxylate-based cobalt metal-organic frameworks for hybrid supercapacitors.

In the pursuit of developing superior energy storage devices, an integrated approach has been advocated to harness the desirable features of both batteries and supercapacitors, particularly their high energy density, and high-power density. Consequently, the emergence of hybrid supercapacitors has become a subject of increasing interest, as they offer the potential to merge the complementary attributes of these two technologies into a single device, thereby surpassing the limitations of conventional energy storage systems. In this context the Metal-Organic Frameworks (MOFs), consisting of metal centers and organic linkers, have emerged as highly trending materials for energy storage by virtue of their high porosity. Here, we investigate the electrochemical performance of cobalt-pyridine-3,5-di-carboxylate-MOF (Co-PDC-MOF) and cobalt-1,2,3,4-cyclopentane tetra-carboxylate-MOF (Co-CPTC-MOF). In the setup involving the analysis of Co-PDC-MOF and Co-CPTC-MOF materials, a configuration comprising three electrodes was utilized. Drawing upon the promising initial properties of CPTC, a battery device was fabricated, comprising Co-CPTC-MOF, and activated carbon (AC) electrodes. Retaining a reversible capacity of 97% the device showcased impressive energy and power density of 20.7 W h g-1 and 2608.5 W kg-1, respectively. Dunn's model was employed, to gain deeper insights into the capacitive and diffusive contributions of the device.

A bimetallic Fe-Mg MOF with a dual role as an electrode in asymmetric supercapacitors and an efficient electrocatalyst for hydrogen evolution reaction (HER).

In this work, a novel bimetallic Fe-Mg/MOF was synthesized through a cost-effective and rapid hydrothermal process. The structure, morphology, and composition were examined using X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy. Further, the Brunauer-Emmett-Teller (BET) measurement showed a 324 m2 g-1 surface area for Fe-Mg/MOF. The Fe-Mg/MOF achieved 1825 C g-1 capacity at 1.2 A g-1 current density, which is higher than simple Fe-MOF (1144 C g-1) and Mg-MOF (1401 C g-1). To assess the long-term stability of the asymmetric device, the bimetallic MOF supercapattery underwent 1000 charge/discharge cycles and retained 85% of its initial capacity. The energy and power densities were calculated to be 57 W h kg-1 and 2393 W kg-1, respectively. Additionally, Fe-Mg/MOF showed superior electrocatalytic performance in hydrogen evolution reaction (HER) by demonstrating a smaller Tafel slope of 51.43 mV dec-1. Our research lays the foundation for enhancing the efficiency of energy storage technologies, paving the way for more sustainable and robust energy solutions.

Development of ZnO-GO-NiO membrane for removal of lead and cadmium heavy metal ions from wastewater.

The presence of heavy metal (HM) ions, such as lead, cadmium, and chromium in industrial wastewater discharge are major contaminants that pose a risk to human health. These HMs should separate from the wastewater to ensure the reuse of the discharged water in the process and mitigate their environmental impacts. The distinctive mechanical properties of 2D graphene oxide (GO), and the antifouling characteristics of metal oxides (ZnO/NiO) nanoparticles combined to produce composites supporting special features for wastewater treatment. This study employed solution casting and phase inversion methods to synthesize PSF-based GO, ZnO-GO, and ZnO-GO-NiO mixed matrix membranes and the effects of variation in composition on the removal of lead (Pb2+) and cadmium (Cd2+) ion was examined. Several characterization techniques including X-ray diffraction analysis, scanning electron microscopy, energy dispersive X-ray, and Fourier transform infrared spectroscopy were applied to analyze the synthesized NPs and MMMs. The composite membranes were also analyzed in terms of their porosity, permeability, hydrophilicity, surface roughness, zeta potential, thermal stability, mechanical strength, and flux regeneration at various transmembrane pressures (2-3 kgcm-2), and pH value (5.5). The highest adsorption capacities were measured to be 308.16 mg g-1 and 354.80 mg g-1 for Pb (II) and Cd (II), respectively, for membrane (M4_A) having 0.3 wt% of ZnO-GO-NiO nanocomposite, at 200 mg L-1 of feed concentration and 1.60 mL min-1 of permeate flux. The Pb (II) and Cd (II) adsorption breakthrough curves were created, and the results of the experiment were compared with the data of the Thomas model.

Comparison Between Mini-Percutaneous Nephrolithotomy and Standard Percutaneous Nephrolithotomy in Management of Large Renal Stones: A Randomized, Controlled Clinical Trial.

Objectives: The aim of this study was to compare mini-percutaneous nephrolithotomy (PNL) and standard PNL in management of renal stones (20-40 mm) with regard to the operative time, fluoroscopy time, blood loss, stone-free rate, and postoperative complications. Subjects and Methods: This prospective, randomized comparative study was carried out on 93 patients divided into two groups: Group A included 44 patients who underwent standard PNL, whereas Group B included 49 patients who underwent mini-PNL. Results: Standard PNL showed shorter operative time, yet longer hospitalization and nephrostomy and catheterization time. The mean drop in hemoglobin level was significantly lower in the mini-PNL group. In the 1st postoperative week, the stone-free rate was higher in the standard PNL group, but this was statistically insignificant. However, 4 weeks postoperatively, the stone-free rate was significantly higher in Group A. Postoperative pain and the need for postoperative analgesia were significantly higher in standard PNL patients. Conclusions: Standard PNL achieved a higher stone-free rate and shorter operative time, while mini-PNL had the advantage of shorter hospitalization time and lower incidence of pain and postoperative complications.

Wood as a green and sustainable alternative for environmentally friendly & flexible electronic devices.

Electronic are usually constructed from non-renewable, non-biodegradable, and hazardous materials. Due to the frequent upgrading or discarding of electronic devices, which contributes significantly to environmental pollution, there is a high demand for electronics made from renewable and biodegradable materials with less harmful components. To this end, due to their flexibility, strong mechanical, and optical properties, wood-based electronics have become very appealing as substrates especially for flexible electronics and optoelectronics. However, incorporating numerous features including high conductivity and transparency, flexibility, and mechanical robustness into an environmentally friendly electronic device remains very challenging. Herein, authors have provided the techniques used to fabricate sustainable wood based flexible electronics coupled with their chemical, mechanical, optical, thermal, thermomechanical, and surface properties for various applications. Additionally, the synthesis of a conductive ink based on lignin and the development of translucent wood as a substrate are covered. Future developments and broader applications of wood-based flexible materials are discussed in the final section of the study, with an emphasis on their potential in fields including wearable electronics, renewable energy, and biomedical devices. This research improves upon prior efforts by demonstrating new ways to simultaneously attain better mechanical and optical qualities and environmental sustainability.

Therapeutic Path to Triple Knockout: Investigating the Pan-inhibitory Mechanisms of AKT, CDK9, and TNKS2 by a novel 2-Phenylquinazolinone derivative in Cancer Therapy- An In-Silico Investigation.

BACKGROUND: Blocking the oncogenic Wnt//ß-catenin pathway has of late been investigated as a viable therapeutic approach in the treatment of cancer. This involves the multi-targeting of certain members of the tankyrase-kinase family; tankyrase 2 (TNKS2), protein kinase B (AKT), and cyclin-dependent kinase 9 (CDK9), which propagate the oncogenic Wnt/ß-catenin signalling pathway. METHODS: During a recent investigation, the pharmacological activity of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one was repurposed to serve as a 'triple-target' inhibitor of TNKS2, AKT and CDK9. Yet, the molecular mechanism that surrounds its multi-targeting activity remains unanswered. As such, this study aims to explore the pan-inhibitory mechanism of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one towards AKT, CDK9, and TNKS2, using in silico techniques. RESULTS: Results revealed favourable binding affinities of -34.17 kcal/mol, -28.74 kcal/mol, and -27.30 kcal/mol for 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one towards TNKS2, CDK9, and AKT, respectively. Pan-inhibitory binding of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one is illustrated by close interaction with specific residues on tankyrase-kinase. Structurally, 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one had an impact on the flexibility, solvent-accessible surface area, and stability of all three proteins, which was illustrated by numerous modifications observed in the unbound as well as the bound states of the structures, which evidenced the disruption of their biological function. Prediction of the pharmacokinetics and physicochemical properties of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one further established its inhibitory potential, evidenced by the favourable absorption, metabolism, excretion, and minimal toxicity properties. CONCLUSION: The following structural insights provide a starting point for understanding the pan-inhibitory activity of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one. Determining the criticality of the interactions that exist between the pyrimidine ring and catalytic residues could offer insight into the structure-based design of innovative tankyrase-kinase inhibitors with enhanced therapeutic effects.

Multi-dimensional structural footprint identification for the design of potential scaffolds targeting METTL3 in cancer treatment from natural compounds.

CONTEXT: [Formula: see text]-adenosine-methyltransferase (METTL3) is the catalytic domain of the 'writer' proteins which is involved in the post modifications of [Formula: see text]-methyladinosine ([Formula: see text]). Though its activities are essential in many biological processes, it has been implicated in several types of cancer. Thus, drug developers and researchers are relentlessly in search of small molecule inhibitors that can ameliorate the oncogenic activities of METTL3. Currently, STM2457 is a potent, highly selective inhibitor of METTL3 but is yet to be approved. METHODS: In this study, we employed structure-based virtual screening through consensus docking by using AutoDock Vina in PyRx interface and Glide virtual screening workflow of Schrodinger Glide. Thermodynamics via MM-PBSA calculations was further used to rank the compounds based on their total free binding energies. All atom molecular dynamics simulations were performed using AMBER 18 package. FF14SB force fields and Antechamber were used to parameterize the protein and compounds respectively. Post analysis of generated trajectories was analyzed with CPPTRAJ and PTRAJ modules incorporated in the AMBER package while Discovery studio and UCSF Chimera were used for visualization, and origin data tool used to plot all graphs. RESULTS: Three compounds with total free binding energies higher than STM2457 were selected for extended molecular dynamics simulations. The compounds, SANCDB0370, SANCDB0867, and SANCDB1033, exhibited stability and deeper penetration into the hydrophobic core of the protein. They engaged in relatively stronger intermolecular interactions involving hydrogen bonds with resultant increase in stability, reduced flexibility, and decrease in the surface area of the protein available for solvent interactions suggesting an induced folding of the catalytic domain. Furthermore, in silico pharmacokinetics and physicochemical analysis of the compounds revealed good properties suggesting these compounds could serve as promising MEETL3 entry inhibitors upon modifications and optimizations as presented by natural compounds. Further biochemical testing and experimentations would aid in the discovery of effective inhibitors against the berserk activities of METTL3.