Characteristics of patients with Wilson disease in the United States: An insurance claims database study.

BACKGROUND: Wilson disease (WD) is a progressive, potentially fatal degenerative disease affecting the liver and central nervous system. Given its low prevalence, collecting data on large cohorts of patients with WD is challenging. Comprehensive insurance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare diseases. AIM: To describe patients with WD in the United States, their treatment and clinical outcome, using a large insurance claims database. METHODS: This retrospective, longitudinal study was performed in the Clarivate Real-World Data Product database. All patients with ≥ 2 claims associated with an International Classification of Diseases 10 (ICD-10) diagnostic code for WD (E83.01) between 2016 and 2021 were included and followed until death or study end. Patients were divided into two groups by whether or not they were documented to have received a specific treatment for WD. Clinical manifestations, hospitalisations, liver transplantation and death were documented. RESULTS: Overall, 5376 patients with an ICD-10 diagnostic code for WD were identified. The mean age at inclusion was 41.2 years and 52.0% were men. A specific WD treatment was documented for 885 patients (15.1%), although the number of patients taking zinc salts may be underestimated due to over the counter purchase. At inclusion, the mean age of patients with a documented treatment was 36.6 ± 17.8 years vs 42.2 ± 19.6 years in those without a documented treatment. During follow-up, 273 patients (5.1%) died. Compared with the American general population, the standardised mortality ratio was 2.19. The proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0% and the mean age at death 52.7 years. CONCLUSION: Patients treated for WD in the United States had an excess early mortality compared with the American population. These findings indicate that there is a significant unmet need for effective treatment for WD in the United States.

Beyond A and B Compartments: how major nuclear locales define nuclear genome organization and function.

Models of nuclear genome organization often propose a binary division into active versus inactive compartments, yet they overlook nuclear bodies. Here we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Whereas gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent species of southeast Asia.

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian sub-continent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent, it extends from the Himalayas to Sikkim, Meghalaya, Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological, microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory, hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus.

Green Synthesis of Reduced Graphene Oxide Using the Tinospora cordifolia Plant Extract: Exploring Its Potential for Methylene Blue Dye Degradation and Antibacterial Activity.

Graphene has attracted significant attention recently due to its unique mechanical, electrical, thermal, and optical properties. The present study focuses on synthesizing green rGO using the Tinospora cordifolia plant extract by mixing it in a suspension of graphene oxide. The plant extract of T. cordifolia acts as a reducing agent and is cost-effective, renewable, and eco-friendly. Green-synthesized rGO (G-rGO) was characterized using FTIR, HR-SEM, EDX, and HR-XRD analyses. G-rGO consists of nanosheets with an average width of approximately 30 nm. G-rGO has a range of hydrodynamic radius (270-470) nm and an average ζ potential of -29.9 mV. Further, G-rGO was used as a nanoadsorbent for optimal exclusion of methylene blue (MB) dye using the response surface methodology (RSM). Adsorption results confirmed 94.85% MB dye removal with 58.81 mg g-1 adsorption capacity at optimum conditions. The G-rGO's antibacterial activity was also tested against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria, finding the exhibited zone of inhibition of 10, 11, and 15 mm and 10, 13, and 17 mm at 20, 40, and 80 µg mL-1 concentrations of G-rGO, respectively.

Lead optimization based design, synthesis, and pharmacological evaluation of quinazoline derivatives as multi-targeting agents for Alzheimer's disease treatment.

The complexity and multifaceted nature of Alzheimer's disease (AD) have driven us to further explore quinazoline scaffolds as multi-targeting agents for AD treatment. The lead optimization strategy was utilized in designing of new series of derivatives (AK-1 to AK-14) followed by synthesis, characterization, and pharmacological evaluation against human cholinesterase's (hChE) and ß-secretase (hBACE-1) enzymes. Amongst them, compounds AK-1, AK-2, and AK-3 showed good and significant inhibitory activity against both hAChE and hBACE-1 enzymes with favorable permeation across the blood-brain barrier. The most active compound AK-2 revealed significant propidium iodide (PI) displacement from the AChE-PAS region and was non-neurotoxic against SH-SY5Y cell lines. The lead molecule (AK-2) also showed Aß aggregation inhibition in a self- and AChE-induced Aß aggregation, Thioflavin-T assay. Further, compound AK-2 significantly ameliorated Aß-induced cognitive deficits in the Aß-induced Morris water maze rat model and demonstrated a significant rescue in eye phenotype in the Aꞵ-phenotypic drosophila model of AD. Ex-vivo immunohistochemistry (IHC) analysis on hippocampal rat brains showed reduced Aß and BACE-1 protein levels. Compound AK-2 suggested good oral absorption via pharmacokinetic studies and displayed a good and stable ligand-protein interaction in in-silico molecular modeling analysis. Thus, the compound AK-2 can be regarded as a lead molecule and should be investigated further for the treatment of AD.

Non-ketotic hyperglycinaemia masquerading as a hypotonic-hyporesponsive episode following vaccination in an infant.

Non-ketotic hyperglycinaemia (NKH) is an inborn error of glycine metabolism with autosomal recessive inheritance. A female infant presented to our emergency department with intractable seizures, lethargy and hypotonia, 2 weeks after her routine vaccination. Detailed infective and metabolic workup revealed normal blood sugar, ketone, lactate ammonia, and a high level of glycine in serum and cerebrospinal fluid suggesting NKH. Diagnosis of NKH was further confirmed on genetic analysis for AMT gene mutation. The child showed clinical improvement with oral sodium benzoate. Here, we report the inheritance, pathophysiology, diagnostic approach, genetic confirmation, management and prognosis of a child with NKH.

Pulmonary drug delivery devices and nanosystems as potential treatment strategies for acute respiratory distress syndrome (ARDS).

Despite advances in drug delivery technologies, treating acute respiratory distress syndrome (ARDS) is challenging due to pathophysiological barriers such as lung injury, oedema fluid build-up, and lung inflammation. Active pharmaceutical ingredients (API) can be delivered directly to the lung site of action with the use of aerosol-based drug delivery devices, and this circumvents the hepatic first-pass effect and improves the bioavailability of drugs. This review discusses the various challenges and barriers for pulmonary drug delivery, current interventions for delivery, considerations for effective drug delivery, and the use of nanoparticle drug delivery carriers as potential strategies for delivering therapeutics in ARDS. Nanosystems have the added benefit of entrapping drugs, increase pulmonary drug bioavailability, and using biocompatible and biodegradable excipients that can facilitate targeted and/or controlled delivery. These systems provide an alternative to existing conventional systems. An effective way to deliver drugs for the treatment of ARDS can be by using colloidal systems that are aerosolized or inhaled. Drug distribution to the deeper pulmonary tissues is necessary due to the significant endothelial cell destruction that is prevalent in ARDS. The particle size of nanoparticles (<0.5 µm) makes them ideal candidates for treating ARDS as they can reach the alveoli. A look into the various potential benefits and limitations of nanosystems used for other lung disorders is also considered to indicate how they may be useful for the potential treatment of ARDS.

Aerosol-PM2.5 Dynamics: In-situ and satellite observations under the influence of regional crop residue burning in post-monsoon over Delhi-NCR, India.

The increasing air pollution in the urban atmosphere is adversely impacts the environment, climate and human health. The alarming degradation of air quality, atmospheric conditions, economy and human life due to air pollution needs significant in-depth studies to ascertain causes, contributions and impacts for developing and implementing an effective policy to combat these issues. This work lies in its multifaceted approach towards comprehensive understanding and mitigating severe pollution episodes in Delhi and its surrounding areas. We investigated the aerosol dynamics in the post-monsoon season (PMS) from 2019 to 2022 under the influence of both crop residue burning and meteorological conditions. The study involves a broad spectrum of factors, including PM2.5 concentrations, active fire events, and meteorological parameters, shedding light on previously unexplored studies. The average AOD550 (0.79) and PM2.5 concentration (140.12 µg/m³) were the highest in 2019. PM2.5 was higher from mid-October to mid-November each year, exceeding the WHO guideline of 15 µg/m³ (24 h) by 27-34 times, signifying a public health emergency. A moderate to strong correlation between PM2.5 and AOD was found (r = 0.65) in 2021. The hotspot region accounts for almost 50% (2019), 47.51% (2020), 57.91% (2021) and 36.61% (2022) of the total fire events. A statistically significant negative non-linear correlation (r) was observed between wind speed (WS) and both AOD and PM2.5 concentration, influencing air quality over the region. HYSPLIT model and Windrose result show the movement of air masses predominated from the North and North-West direction during PMS. This study suggest to promotes strategies such as alternative waste management, encouraging modern agricultural practices in hot-spot regions, and enforcing strict emission norms for industries and vehicles to reducing air pollution and its detrimental effects on public health in the region and also highlights the need for future possibilities of research to attract the global attention.

Nonenzymatic dual glucose sensing on boronic acid modified zeolitic imidazolate framework-67 nanoparticles for diabetes management.

For early diabetes identification and management, the progression of an uncomplicated and exceedingly responsive glucose testing technology is crucial. In this study, we present a new sensor incorporating a composite of metal organic framework (MOF) based on cobalt, coated with boronic acid to facilitate selective glucose binding. Additionally, we successfully employed a highly sensitive electro-optical immunosensor for the detection of subtle changes in concentration of the diabetes biomarker glycated haemoglobin (HbA1c), using zeolitic imidazolate framework-67 (ZIF-67) coated with polydopamine which further modified with boronic acid. Utilizing the polymerization characteristics of dopamine and the NH2 groups, a bonding structure is formed between ZIF-67 and 4-carboxyphenylboronic acid. ZIF-67 composite served as an effective substrate for immobilising 4-carboxyphenylboronic acid binding agent, ensuring precise and highly selective glucose identification. The sensing response was evaluated through both electrochemical and optical methods, confirming its efficacy. Under optimized experimental condition, the ZIF-67 based sensor demonstrated a broad detection range of 50-500 mg dL-1, a low limit of detection (LOD) of 9.87 mg dL-1 and a high correlation coefficient of 0.98. Furthermore, the 4-carboxyphenylboronic acid-conjugated ZIF-67-based sensor platform exhibited remarkable sensitivity and selectivity in optical-based detection for glycated haemoglobin within the clinical range of 4.7-11.3%, achieving a LOD of 3.7%. These findings highlight the potential of the 4-carboxyphenylboronic acid-conjugated ZIF-67-based electro-optical sensor as a highly sensitive platform for diabetes detection.

A Novel Intrauterine Device for the Spatio-Temporal Release of Norethindrone Acetate as a Counter-Estrogenic Intervention in the Genitourinary Syndrome of Menopause.

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas-Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

Mucosal-Type Chronic Otitis Media: Clinical Predictors of Postoperative Success.

OBJECTIVES: Chronic otitis media (COM) remains a global disease, a burden, and a challenge. Predicting its treatment's postoperative success based on clinical presentation has not been reported, particularly for the mucosal (tubotympanic/safe) type. METHODS:  A prospective descriptive study of patients with mucosal-type COM was done to identify clinical predictors of improved postoperative hearing outcomes and successful graft uptakes. RESULTS: Among the 110 ears studied, tympanoplasty was performed in 76 and cortical mastoidectomy with tympanoplasty in 34, based on six weeks of discharge-free or persistent discharge, respectively; all were treated with postoperative intranasal steroid spray. Eustachian tube dysfunction was noted in 96.4%. All patients with a history of ear discharge over five years had ossicular discontinuity, and those with persistent discharge had nonpatent aditus. Normal postoperative hearing was attained in most patients with less than one year of ear discharge. Surgical intervention within a year achieved normal hearing and graft success of 100% with type I tympanoplasty using the fascia alone in discharge-free ears and cortical mastoidectomy with tympanoplasty using cartilage-fascia graft in discharging ears, despite Eustachian tube dysfunction. In the latter group, graft success in type II tympanoplasty was 76.9%. CONCLUSION:  Ear discharge is the prime predictor of postoperative success in mucosal-type COM, as its duration and persistence dictate the time and type of surgical intervention. Duration of more than five years is directly proportional to pre-operative hearing loss with ossicular involvement and inversely proportional to postoperative hearing improvement, necessitating early surgical intervention, despite it being the mucosal or "safe type." Ear discharge-free for six weeks is an indicator of tympanoplasty. Persistent ear discharge, despite nonotogenic confounders, suggests aditus nonpatency, indicates the need for cortical mastoidectomy, and necessitates achieving its patency along with tympanoplasty. A surgical decision-making algorithm for the best possible surgical outcome in the chronic mucosal type of OM is also suggested.

Dissociation of H2O2 on water surfaces (ice and water droplets).

OH radicals are an important constituent of the atmosphere. Therefore, all reactions that act as a source of OH radicals are important. It is known that photo-dissociation of H2O2 is an important source of OH radicals in the atmosphere. In the present study, using Born-Oppenheimer molecular dynamics simulations, we have shown that the H2O2 molecule can dissociate thermally on water droplets, as well as on the surface of ice, to form OH radicals. Furthermore, the dissociation of H2O2 was found to be very fast (less than 50 fs) on the ice surface compared with on the water droplets. We believe this route for the formation of OH radicals could be more critical than photo-dissociation, as it can take place both during the day and at night, but further studies with more sophisticated theoretical approaches or experiments are required to confirm this hypothesis.

Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery.

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of -17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

Expression profiling of stemness markers in testicular germline stem cells from neonatal and adult Swiss albino mice during their transdifferentiation in vitro.

BACKGROUND: Spermatogonial stem cells (SSCs) were considered to be stem cells with limited potencies due to their existence in adult organisms. However, the production of spermatogonial stem cell colonies with broader differentiation capabilities in primary germ cell cultures from mice of select genetic backgrounds (C57BL6/Tg14, ddY, FVB and 129/Ola) indicated that SSCs from these strains were pluripotent. METHODS: We established primary cultures of SSCs from neonatal and adult Swiss 3T3 Albino mice. Stemness of SSC colonies were evaluated by performing real-time PCR and immunofluorescence analysis for a panel of chosen stemness markers. Differentiation potentials of SSCs were examined by attempting the generation of embryoid bodies and evaluating the expression of ectodermal, mesodermal and endodermal markers using immunofluorescence and real-time PCR analysis. RESULTS: Spermatogonial stem cells from neonatal and mature mice testes colonised in vitro and formed compact spermatogonial stem cell colonies in culture. The presence of stem cell markers ALPL, ITGA6 and CD9 indicated stemness in these colonies. The differentiation potential of these SSC colonies was demonstrated by their transformation into embryoid bodies upon withdrawal of growth factors from the culture medium. SSC colonies and embryoid bodies formed were evaluated using immunofluorescence and real-time PCR analysis. Embryoid body like structures derived from both neonatal and adult mouse testis were quite similar in terms of the expression of germ layer markers. CONCLUSION: These results strongly suggest that SSC-derived EB-like structures could be used for further differentiation into cells of interest in cell-based therapeutics.

The role, relevance and management of immune exhaustion in bovine infectious diseases.

Immune exhaustion is a state of immune cell dysfunction that occurs most commonly following chronic exposure to an antigen which persists after the immune response fails to remove it. Exhaustion has been studied most thoroughly with several cancers, but has also been observed in several chronic infectious diseases. The topic has mainly been studied with CD8+ T cells, but it can also occur with CD4+ T cells and other immune cell types too. Exhaustion is characterized by a hierarchical loss of effector cell functions, up-regulation of immuno-inhibitory receptors, disruption of metabolic activities, and altered chromatin landscapes. Exhaustion has received minimal attention so far in diseases of veterinary significance and this review's purpose is to describe examples where immune exhaustion is occurring in several bovine disease situations. We also describe methodology to evaluate immune exhaustion as well as the prospects of controlling exhaustion and achieving a more suitable outcome of therapy in some chronic disease scenarios.

Elevated troponin levels as a predictor of mortality in patients with acute stroke: a systematic review and meta-analysis.

Background and Aim: The prognostic potential of cardiac troponin (cTn) in acute stroke patients has been a subject of ongoing debate. Our objective was to provide a comprehensive evidence for predicting mortality in acute stroke patients by using the elevated troponin levels. Methods: We conducted an extensive literature search, including PubMed, EMbase, and Trip Databases, covering studies published up to September 30, 2023. We computed risk ratios (RR) with 95% confidence intervals (CIs), performed sensitivity analysis, and conducted trial sequential analysis (TSA). Results: In total, 53 studies were analyzed, with 37 focusing on acute ischemic stroke (AIS), 11 on subarachnoid hemorrhage (SAH), and 7 on Intracerebral hemorrhage (ICH). Elevated cTn levels were significantly showed a higher predictive risk for In-hospital mortality in both AIS (RR=3.80, 95% CI; 2.82 to 5.12) as well as SAH (RR=2.23, 95% CI; 1.64 to 3.02). However, no significant predictive risk between elevated cTn levels and in-hospital mortality for ICH patients (RR=1.13, 95% CI: 0.46 to 2.79). A similar pattern was observed for elevated cTn levels, indicating an increased risk of last follow-up mortality for AIS (RR=2.41, 95% CI: 1.98 to 2.93) and SAH (RR=3.08, 95% CI: 2.25 to 4.21). Conclusion: Elevated troponin levels can serve as a promising predictive marker for both in-hospital and last follow-up mortality in AIS and SAH patients but not in ICH patients. Further prospective studies are needed to validate our findings along with exploring the preventive management of mortality in acute stroke settings.

In silico and network pharmacology analysis of fucosterol: a potent anticancer bioactive compound against HCC.

The Fucaceae family of marine brown algae includes Ascophyllum nodosum. Fucosterol (FSL) is a unique bioactive component that was identified through GC-MS analysis of the hydroalcoholic extract of A. nodosum. Fucosterol's mechanism of action towards hepatocellular cancer was clarified using network pharmacology and docking study techniques. The probable target gene of FSL has been predicted using the TargetNet and SwissTargetPred databases. GeneCards and the DisGNet database were used to check the targeted genes of FSL. By using the web programme Venny 2.1, the overlaps of FSL and HCC disease demonstrated that 18 genes (1.3%) were obtained as targeted genes Via the STRING database, a protein-protein interaction (PPI) network with 18 common target genes was constructed. With the aid of CytoNCA, hub genes were screened using the Cytoscape software, and the targets' hub genes were exported into the ShinyGo online tool for study of KEGG and gene ontology enrichment. Using the software AutoDock, a hub gene molecular docking study was performed. Ten genes, including AR, CYP19A1, ESR1, ESR2, TNF, PPARA, PPARG, HMGCR, SRC, and IGF1R, were obtained. The 10 targeted hubs docked with FSL successfully. The active components FSL of ASD, the FSL, are engaged in fatty liver disease, cancer pathways, and other signalling pathways, which could prove beneficial for the management of HCC.

Design, synthesis, and biological evaluation of some 2-(3-oxo-5,6-diphenyl-1,2,4-triazin-2(3H)-yl)-N-phenylacetamide hybrids as MTDLs for Alzheimer's disease therapy.

Inspite of established symptomatic relief drug targets, a multi targeting approach is highly in demand to cure Alzheimer's disease (AD). Simultaneous inhibition of cholinesterase (ChE), ß secretase-1 (BACE-1) and Dyrk1A could be promising in complete cure of AD. A series of 18 diaryl triazine based molecular hybrids were successfully designed, synthesized, and tested for their hChE, hBACE-1, Dyrk1A and Aß aggregation inhibitory potentials. Compounds S-11 and S-12 were the representative molecules amongst the series with multi-targeted inhibitory effects. Compound S-12 showed hAChE inhibition (IC50 value = 0.486 ± 0.047 µM), BACE-1 inhibition (IC50 value = 0.542 ± 0.099 µM) along with good anti-Aß aggregation effects in thioflavin-T assay. Only compound S-02 of the series has shown Dyrk1A inhibition (IC50 value = 2.000 ± 0.360 µM). Compound S-12 has also demonstrated no neurotoxic liabilities against SH-SY5Y as compared to donepezil. The in vivo behavioral studies of the compound S-12 in the scopolamine- and Aß-induced animal models also demonstrated attanuation of learning and memory functions in rats models having AD-like characteristics. The ex vivo studies, on the rat hippocampal brain demonstrated reduction in certain biochemical markers of the AD brain with a significant increase in ACh level. The Western blot and Immunohistochemistry further revealed lower tau, APP and BACE-1 molecular levels. The drosophilla AD model also revealed improved eyephenotype after treatment with compound S-12. The molecular docking studies of the compounds suggested that compound S-12 was interacting with the ChE-PAS & CAS residues and catalytic dyad residues of the BACE-1 enzymes. The 100 ns molecular dynamics simulation studies of the ligand-protein complexed with hAChE and hBACE-1 also suggested stable ligand-protein confirmation throughout the simulation run.

Catalytic synergy of WS2-anchored PdSe2 for highly sensitive hydrogen gas sensor.

Hydrogen (H2) is widely used in industrial processes and is one of the well-known choices for storage of renewable energy. H2 detection has become crucial for safety in manufacturing, storage, and transportation due to its strong explosivity. To overcome the issue of explosion, there is a need for highly selective and sensitive H2 sensors that can function at low temperatures. In this research, we have adequately fabricated an unreported van der Waals (vdWs) PdSe2/WS2 heterostructure, which exhibits exceptional properties as a H2 sensor. The formation of these heterostructure devices involves the direct selenization process using chemical vapor deposition (CVD) of Pd films that have been deposited on the substrate of SiO2/Si by DC sputtering, followed by drop casting of WS2 nanoparticles prepared by a hydrothermal method onto device substrates including pre-patterned electrodes. The confirmation of the heterostructure has been done through the utilization of powder X-ray diffraction (XRD), depth-dependent X-ray photoelectron spectroscopy (XPS) and field-emission scanning electron microscopy (FE-SEM) techniques. Also, the average roughness of thin films is decided by Atomic Force Microscopy (AFM). The comprehensive research shows that the PdSe2/WS2 heterostructure-based sensor produces a response that is equivalent to 67.4% towards 50 ppm H2 at 100 °C. The response could be a result of the heterostructure effect and the superior selectivity for H2 gas in contrast to other gases, including NO2, CH4, CO and CO2, suggesting tremendous potential for H2 detection. Significantly, the sensor exhibits fast response and a recovery time of 31.5 s and 136.6 s, respectively. Moreover, the explanation of the improvement in gas sensitivity was suggested by exploiting the energy band positioning of the PdSe2/WS2 heterostructure, along with a detailed study of variations in the surface potential. This study has the potential to provide a road map for the advancement of gas sensors utilizing two-dimensional (2D) vdWs heterostructures, which exhibit superior performance at low temperatures.