Synthesis, biological evaluation, and molecular docking of novel 1,3,4-substituted-thiadiazole derivatives as potential anticancer agent.

In an attempt to develop potent anti-cancer agents, a new 1,3,4-substituted-thiadiazole derivatives (8b-g), starting from 4-substituted-thiazol-2-chloroacetamides (4b-g), were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the hepatocellular carcinoma (HEPG-2), human lung carcinoma (A549), human breast carcinoma (MCF-7) and pseudo-normal human embryonic liver (L02) cancer cell lines by an MTT assay. Among all synthesized compounds, compound 8d showed the potent anti-cancer activities with GI50 values of 2.98, 2.85 and 2.53 µM against MCF-7, A549 and HepG-2 cell lines respectively as compared to standard drug Doxorubicin. Furthermore, molecular modelling studies have spotlighted the anchoring role of 1,3,4-substituted-thiadiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. Therefore, these results can provide promising starting points for further development of best anti-cancer agents.

Synergistic Enhancement of Water-Splitting Performance Using MOF-Derived Ceria-Modified g-C3N4 Nanocomposites: Synthesis, Performance Evaluation, and Stability Prediction with Machine Learning.

Diminishing the charge recombination rate by improving the photoelectrochemical (PEC) performance of graphitic carbon nitride (g-C3N4) is essential for better water oxidation. In this concern, this research explores the competent approach to enhance the PEC performance of g-C3N4 nanosheets (NSs), creating their nanocomposites (NCs) with metal-organic framework (MOF)-derived porous CeO2 nanobars (NBs) along with ZnO nanorods (NRs) and TiO2 nanoparticles (NPs). The synthesis involved preparing CeO2 NBs and g-C3N4 NSs through the calcination of respective precursors, while the sol-gel method is employed for ZnO NRs and TiO2 NPs. Following the subsequent analysis of the physicochemical properties of the materials, the binder-free brush-coating method is deployed to fabricate NC-based photoanodes, followed by an evaluation of the PEC performance through various electrochemical techniques. Remarkably, the binary g-C3N4/CeO2 NCs with 20 wt % CeO2 NBs (gC20 NCs) exhibited a significantly enhanced current density of 0.460 mA/cm2 at 1.23 V vs reversible hydrogen electrode, which is 2.3 times greater than that of bare g-C3N4 NSs (0.195 mA/cm2). Further improvements are observed with ternary gC20/TiO2 (gCT50) and gC20/ZnO (gCZ50) NCs, achieving current densities of 1.810 and 1.440 mA/cm2, respectively. These enhanced current densities are attributed to increased donor densities, reduced charge transfer resistances, and efficient charge transport within the NCs. In addition, higher surface areas with beneficial instinctive defects are perceived for gCT50 and gCZ50 NCs, as revealed by Brunauer-Emmett-Teller and electron spin resonance analysis. Finally, the stability of gCZ50 and gCT50 NC-based photoanodes is predicted and forecasted with the help of the recurrent neural network-based long short-term memory technique. Overall, this study demonstrates the efficacy of organic-inorganic hybrids for efficient photoanodes, facilitating advancements in water-splitting studies.

Synthesis, Biological and Molecular Docking Studies of Thiazole-Thiadiazole derivatives as potential Anti-Tuberculosis Agents.

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 µg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme.

Multilevel resistive switching in hydrothermally synthesized FeWO4 thin film-based memristive device for non-volatile memory application.

The memristors offer significant advantages as a key element in non-volatile and brain-inspired neuromorphic systems because of their salient features such as remarkable endurance, ability to store multiple bits, fast operation speed, and extremely low energy usage. This work reports the resistive switching (RS) characteristics of the hydrothermally synthesized iron tungstate (FeWO4) based thin film memristive device. The detailed physicochemical analysis was investigated using Rietveld's refinement, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) techniques. The fabricated Ag/FWO/FTO memristive device exhibits bipolar resistive switching (BRS) behavior. In addition, the devices exhibit negative differential resistance (NDR) at both positive and negative bias. The charge-flux relation portrayed the non-ideal or memristive nature of the devices. The reliability in the RS process was analyzed in detail using Weibull distribution and time series analysis techniques. The device exhibits stable and multilevel endurance and retention characteristics which demonstrates the suitability of the device for the high-density non-volatile memory application. The current conduction of the device was dominated by Ohmic and trap controlled-space charge limited current (TC-SCLC) mechanisms and filamentary RS process responsible for the BRS in the device. In a nutshell, the present investigations reveal the potential use of the iron tungstate for the fabrication of memristive devices for the non-volatile memory application.

CogniFiber: Harnessing Biocompatible and Biodegradable 1D Collagen Nanofibers for Sustainable Nonvolatile Memory and Synaptic Learning Applications.

Here, resistive switching (RS) devices are fabricated using naturally abundant, nontoxic, biocompatible, and biodegradable biomaterials. For this purpose, 1D chitosan nanofibers (NFs), collagen NFs, and chitosan-collagen NFs are synthesized by using an electrospinning technique. Among different NFs, the collagen-NFs-based device shows promising RS characteristics. In particular, the optimized Ag/collagen NFs/fluorine-doped tin oxide RS device shows a voltage-tunable analog memory behavior and good nonvolatile memory properties. Moreover, it can also mimic various biological synaptic learning properties and can be used for pattern classification applications with the help of the spiking neural network. The time series analysis technique is employed to model and predict the switching variations of the RS device. Moreover, the collagen NFs have shown good cytotoxicity and anticancer properties, suggesting excellent biocompatibility as a switching layer. The biocompatibility of collagen NFs is explored with the help of NRK-52E (Normal Rat Kidney cell line) and MCF-7 (Michigan Cancer Foundation-7 cancer cell line). Additionally, the biodegradability of the device is evaluated through a physical transient test. This work provides a vital step toward developing a biocompatible and biodegradable switching material for sustainable nonvolatile memory and neuromorphic computing applications.

Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes.

BACKGROUND: Analysing genomes of animal model organisms is widely used for understanding the genetic basis of complex traits and diseases, such as obesity, for which only a few mouse models exist, however, without their lean counterparts. OBJECTIVE: To analyse genetic differences in the unique mouse models of polygenic obesity (Fat line) and leanness (Lean line) originating from the same base population and established by divergent selection over more than 60 generations. METHODS: Genetic variability was analysed using WGS. Variants were identified with GATK and annotated with Ensembl VEP. g.Profiler, WebGestalt, and KEGG were used for GO and pathway enrichment analysis. miRNA seed regions were obtained with miRPathDB 2.0, LncRRIsearch was used to predict targets of identified lncRNAs, and genes influencing adipose tissue amount were searched using the IMPC database. RESULTS: WGS analysis revealed 6.3 million SNPs, 1.3 million were new. Thousands of potentially impactful SNPs were identified, including within 24 genes related to adipose tissue amount. SNP density was highest in pseudogenes and regulatory RNAs. The Lean line carries SNP rs248726381 in the seed region of mmu-miR-3086-3p, which may affect fatty acid metabolism. KEGG analysis showed deleterious missense variants in immune response and diabetes genes, with food perception pathways being most enriched. Gene prioritisation considering SNP GERP scores, variant consequences, and allele comparison with other mouse lines identified seven novel obesity candidate genes: 4930441H08Rik, Aff3, Fam237b, Gm36633, Pced1a, Tecrl, and Zfp536. CONCLUSION: WGS revealed many genetic differences between the lines that accumulated over the selection period, including variants with potential negative impacts on gene function. Given the increasing availability of mouse strains and genetic polymorphism catalogues, the study is a valuable resource for researchers to study obesity.

Transforming native exosomes to engineered drug vehicles: A smart solution to modern cancer theranostics.

Exosomes have been the hidden treasure of the cell in terms of cellular interactions, transportation and therapy. The native exosomes (NEx) secreted by the parent cells hold promising aspects in cancer diagnosis and therapy. NEx has low immunogenicity, high biocompatibility, low toxicity and high stability which enables them to be an ideal prognostic biomarker in cancer diagnosis. However, due to heterogeneity, NEx lacks specificity and accuracy to be used as therapeutic drug delivery vehicle in cancer therapy. Transforming these NEx with their innate structure and multiple receptors to engineered exosomes (EEx) can provide better opportunities in the field of cancer theranostics. The surface of the NEx exhibits numeric receptors which can be modified to pave the direction of its therapeutic drug delivery in cancer therapy. Through surface membrane, EEx can be modified with increased drug loading potentiality and higher target specificity to act as a therapeutic nanocarrier for drug delivery. This review provides insights into promising aspects of NEx as a prognostic biomarker and drug delivery tool along with its need for the transformation to EEx in cancer theranostics. We have also highlighted different methods associated with NEx transformations, their nano-bio interaction with recipient cells and major challenges of EEx for clinical application in cancer theranostics.

Environment-Induced Degradation of Shape Memory Alloys: Role of Alloying and Nature of Environment.

Shape memory effects coupled with superelasticity are the distinctive characteristics of shape memory alloys (SMAs), a type of metal. When these alloys are subject to thermomechanical processing, they have the inherent ability to react to stimuli, such as heat. As a result, these alloys have established their usefulness in a variety of fields and have in recent years been chosen for use in stents, sensors, actuators, and several other forms of life-saving medical equipment. When it comes to the shape memory materials, nickel-titanium (Ni-Ti) alloys are in the forefront and have been chosen for use in a spectrum of demanding applications. As shape memory alloys (SMAs) are chosen for use in critical environments, such as blood streams (arteries and veins), orthodontic applications, orthopedic implants, and high temperature surroundings, such as actuators in aircraft engines, the phenomenon of environment-induced degradation is of both interest and concern. Hence, the environment-induced degradation behavior of the shape memory alloys (SMAs) needs to be studied to find viable ways to improve their resistance to an aggressive environment. The degradation that occurs upon exposure to an aggressive environment is often referred to as corrosion. Environment-induced degradation, or corrosion, being an unavoidable factor, certain techniques can be used for the purpose of enhancing the degradation resistance of shape memory alloys (SMAs). In this paper, we present and discuss the specific role of microstructure and contribution of environment to the degradation behavior of shape memory alloys (SMAs) while concurrently providing methods to resist both the development and growth of the degradation caused by the environment.

Management of Open Tibial Diaphyseal Fractures by Limb Reconstruction System As Primary and Definitive Treatment: A Prospective Cohort Study.

Background One of the most frequent long bone fractures that most orthopaedic surgeons see is a tibial diaphyseal fracture. The tibia has more open fractures than any other major long bone because it is covered by skin for the majority of its length. The best course of therapy is still up for debate due to the high occurrence of comorbidities linked to these fractures. Materials and methods In this prospective study, 30 patients who met the inclusion criteria were admitted to the Department of Orthopaedics of Shri B. M. Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India. The period of study was from January 2021 to May 2022. The patients were followed up for a period of six months. Longer follow-up was required for some patients. Results In our study, there were 26 (86.7%) male and four (13.3%) female patients. The mode of injury was road traffic accidents in all cases. The functional outcomes obtained using the modified Anderson and Hutchinson's criteria were good results in 22 (73.3%), moderate results in five (16.7%), and poor results in three (10%) of the study population. Pin tract infections (six cases; 20%) and shortening (eight cases; 26.7%) were the most frequent complications Conclusion Because of the ease of use, good fracture stability, adjustable geometry, light weight, reasonable price, and patient friendliness, the limb reconstruction system (LRS) provides an excellent alternative treatment option for treating compound fractures of the tibia.

Functional Outcomes of Tibia Fractures Treated With Intramedullary Interlocking Nails by Suprapatellar Approach: A Prospective Study.

Background Tibia fractures are the most common lower extremity fractures. The subcutaneous anatomy of this long bone predisposes it to high fracture frequency in a high-energy trauma. The tibia is a major weight-bearing, long tubular bone that is axially and rotationally unstable when fractured, which ideally necessitates its surgical fixation in adults. Tibia fractures can be treated with a variety of choice of implants and surgical approaches. This study aims to assess the clinical and functional outcomes of a tibia fracture treated with intramedullary interlocking nails by a suprapatellar approach. Methodology A total of 32 patients were selected from patients admitted at Shri B. M. Patil Medical College and Research Centre with tibia fractures between January 2021 and May 2022. All the patients were treated with closed reduction and internal fixation with intramedullary interlocking nails by suprapatellar approach with a semi-extended knee position. All patients were followed up clinically and radiologically at regular intervals of six weeks, three months, six months, and one year. All functional outcomes were assessed based on modified Lysholm knee scores. Results A total of 31 patients showed union at the fracture site. One patient had nonunion and implant failure at the distal locking site, and two patients had persistent anterior knee pain at the end of one year. Functional outcome assessment based on modified Lysholm scores had excellent results, with a mean score of 95. Patients were followed up for a mean of 11.5 months. The mean time of union was observed as 12.5 months. Conclusions Suprapatellar tibia nailing is an effective alternative approach with ease of reduction and decreased intraoperative fluoroscopy time. The entry is in line with the medullary cavity preventing malreduction of proximal and distal tibia fractures. The additional proximal locking option also increases the stability of implant fixation.

Self-Assembled Lanthanum Oxide Nanoflakes by Electrodeposition Technique for Resistive Switching Memory and Artificial Synaptic Devices.

In recent years, many metal oxides have been rigorously studied to be employed as solid electrolytes for resistive switching (RS) devices. Among these solid electrolytes, lanthanum oxide (La2 O3 ) is comparatively less explored for RS applications. Given this, the present work focuses on the electrodeposition of La2 O3 switching layers and the investigation of their RS properties for memory and neuromorphic computing applications. Initially, the electrodeposited La2 O3 switching layers are thoroughly characterized by various analytical techniques. The electrochemical impedance spectroscopy (EIS) and Mott-Schottky techniques are probed to understand the in situ electrodeposition, RS mechanism, and n-type semiconducting nature of the fabricated La2 O3 switching layers. All the fabricated devices exhibit bipolar RS characteristics with excellent endurance and stable retention. Moreover, the device mimics the various bio-synaptic properties such as potentiation-depression, excitatory post-synaptic currents, and paired-pulse facilitation. It is demonstrated that the fabricated devices are non-ideal memristors based on double-valued charge-flux characteristics. The switching variation of the device is studied using the Weibull distribution technique and modeled and predicted by the time series analysis technique. Based on electrical and EIS results, a possible filamentary-based RS mechanism is suggested. The present results assert that La2 O3 is a promising solid electrolyte for memory and brain-inspired applications.

Comparative Study of Clinical Severity and Biochemical Markers in Pre COVID-19 and COVID-19 Rhino-Orbito Cerebral Mucormycosis.

In view of high surge of sinonasal mucormycosis cases after the second wave of covid 19, present study was planned to know and compare the clinical severity of the disease and also to better understand the difference in the biochemical markers during precovid and post covid period. This retrospective observational study included all cases of sinonasal mucormycosis which were treated in our institute from August 2012 to August 2021. Details of these cases were collected from hospital database system. Biochemical parameters included FBS, HbA1C, urine ketone bodies, blood pH and creatinine. Clinical severity score was measured using self-structured severity scoring system. We found that out of 74 cases treated in our hospital 28 cases were in pre covid period while 46 cases belonged to covid 19 period. Higher male predominance was seen during post covid period (76% vs. 60%). Urine ketone bodies were positive in 7% patients in precovid period compared to 26% in post-covid period. FBS and HbA1C were high approximately 80 and 90% patients respectively in both groups. Clinical severity was significantly high in post covid patients. The present study showed that in spite of similar biochemical profile. The severity of mucormycosis was high in covid positive patients. This study shows that Covid-19 is an independent high risk factor in mucormycosis patients.

BiVO4 As a Sustainable and Emerging Photocatalyst: Synthesis Methodologies, Engineering Properties, and Its Volatile Organic Compounds Degradation Efficiency.

Bismuth vanadate (BiVO4) is one of the best bismuth-based semiconducting materials because of its narrow band gap energy, good visible light absorption, unique physical and chemical characteristics, and non-toxic nature. In addition, BiVO4 with different morphologies has been synthesized and exhibited excellent visible light photocatalytic efficiency in the degradation of various organic pollutants, including volatile organic compounds (VOCs). Nevertheless, the commercial scale utilization of BiVO4 is significantly limited because of the poor separation (faster recombination rate) and transport ability of photogenerated electron-hole pairs. So, engineering/modifications of BiVO4 materials are performed to enhance their structural, electronic, and morphological properties. Thus, this review article aims to provide a critical overview of advanced oxidation processes (AOPs), various semiconducting nanomaterials, BiVO4 synthesis methodologies, engineering of BiVO4 properties through making binary and ternary nanocomposites, and coupling with metals/non-metals and metal nanoparticles and the development of Z-scheme type nanocomposites, etc., and their visible light photocatalytic efficiency in VOCs degradation. In addition, future challenges and the way forward for improving the commercial-scale application of BiVO4-based semiconducting nanomaterials are also discussed. Thus, we hope that this review is a valuable resource for designing BiVO4-based nanocomposites with superior visible-light-driven photocatalytic efficiency in VOCs degradation.

Thermodynamics of Azo Dye Adsorption on a Newly Synthesized Titania-Doped Silica Aerogel by Cogelation: A Comparative Investigation with Silica Aerogels and Activated Charcoal.

The adsorption isotherms of azo dyes on a newly synthesized titania-doped silica (TdS) aerogel compared to silica aerogels and activated charcoal (AC) are systematically investigated. Monolithic TdS aerogels were synthesized by the cogelation process followed by supercritical drying of tetraethyl orthosilicate (TEOS) as a gel precursor and titanium(IV) isopropoxide (TTIP) as a metal complex precursor for co-polymerization in ethanol solvent. An acid-base catalyst was used for the hydrolysis and condensation of TEOS and TTIP. The effect of Ti4+ doping in a silica aerogel on the mesoporous structure and the adsorption capacity of methylene blue (MB) and crystal violet (CV) dyes were evaluated from the UV-vis absorption spectra. In order to compare the adsorption isotherms, the surface areas of silica and TdS aerogels were first normalized with respect to AC, as adsorption is a surface phenomenon. The azo dye equilibrium adsorption data were analyzed using different isotherm equations and found to follow the Langmuir adsorption isotherm. The maximum monolayer adsorption capacities for the adsorbent TdS aerogel normalized with the AC of the Langmuir isotherm are 131.58 and 159.89 mg/g for MB and CV dyes, respectively. From the Langmuir curve fitting, the Q max value of the TdS aerogel was found to increase by 1.22-fold compared to AC, while it increased 1.25-1.53-fold compared to the silica aerogel. After four cycles, regeneration efficiency values for MB and CV dyes are about 84 and 80%, respectively. The study demonstrates the excellent potential and recovery rate of silica and TdS aerogel adsorbents in removing dyes from wastewater. The pore volume and average pore size of the new aerogel, TdS, were found to be lower than those of the silica aerogel. Thus, a new TdS aerogel with a high capacity of adsorption of azo dyes is successfully achieved.

Sprayed FeWO4 thin film-based memristive device with negative differential resistance effect for non-volatile memory and synaptic learning applications.

Resistive switching (RS) memories have attracted great attention as promising solutions to next-generation non-volatile memories and computing technologies because of their simple device configuration, high on/off ratio, low power consumption, fast switching, long retention, and significant cyclic stability. In this work, uniform and adherent iron tungstate (FeWO4) thin films were synthesized by the spray pyrolysis method with various precursor solution volumes, and these were tested as a switching layer for the fabrication of Ag/FWO/FTO memristive devices. The detailed structural investigation was done through various analytical and physio-chemical characterizations viz. X-ray diffraction (XRD) and its Rietveld refinement, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) techniques. The results reveal the pure and single-phase FeWO4 compound thin film formation. Surface morphological study shows the spherical particle formation having a diameter in the range of 20 to 40 nm. The RS characteristics of the Ag/FWO/FTO memristive device demonstrate non-volatile memory characteristics with significant endurance and retention properties. Interestingly, the memory devices show stable and reproducible negative differential resistance (NDR) effects. The in-depth statistical analysis suggests the good operational uniformity of the device. Moreover, the switching voltages of the Ag/FWO/FTO memristive device were modeled using the time series analysis technique by utilizing Holt's Winter Exponential Smoothing (HWES) approach. Additionally, the device mimics bio-synaptic properties such as potentiation/depression, excitatory post-synaptic current (EPSC), and spike-timing-dependent plasticity (STDP) learning rules. For the present device, the space-charge-limited current (SCLC) and trap-controlled-SCLC effects dominated during positive and negative bias I-V characteristics, respectively. The RS mechanism dominated in the low resistance state (LRS), and the high resistance state (HRS) was explained based on the formation and rupture of conductive filament composed of Ag ions and oxygen vacancies. This work demonstrates the RS in the metal tungstate-based memristive devices and demonstrates a low-cost approach for fabricating memristive devices.

Multiple periodontal abscesses with atypical segmental teeth mobility in a nonperiodontitis case: A periodontal alarm of postcoronavirus disease-2019 mucormycosis.

The coronavirus pandemic, constantly mutating virus, and newer complications arising with each passing day have put health workers in jeopardy. One such serious complication being reported is mucormycosis. It is a deadly and rapidly spreading infection resulting in angioinvasion and tissue necrosis. In precoronavirus disease (COVID) era mucormycosis was observed mainly in patients having comorbidities such as diabetes, neutropenia, or previous history of organ transplant. In the present case report, a systemically healthy patient presented with mucormycosis postcoronavirus disease-2019 infection. The patient presented with atypical periodontal findings such as multiple periodontal abscesses, segmental teeth mobility, and deep periodontal pockets confined to the maxillary right quadrant. This form of presentation should be a wake-up call for all dental professionals to be in the constant lookout for any signs and symptoms of mucormycosis even in seemingly nonhigh-risk patients.

A Mini-review on Recent Advances in Synthesis of Dihydropyrano [3, 2-c] chromenes Using Magnetic Nanocatalysts.

The development of an active, selective, and long-term selective catalyst for the synthesis of biologically active heterocycles is still challenging. However, magnetic nanocatalysts have divergent applications like high efficiency, selectivity, consumption, and reusability. The current review explores a detailed survey of the latest information on synthetic methods of Pyrano [3, 2-c] chromene derivatives using different magnetic nanocatalysts. Numerous studies on the synthesis of these practical compounds have been stimulated by the special qualities and wide-ranging applications of pyrano coumarins and the nanoparticles were tested for their catalytic effectiveness in a one-pot, three-component reaction involving aldehydes, malononitrile, and 4-hydroxycoumarin for the manufacturing of dihydropyrano [3, 2-c] chromenes (coumarins).

Unraveling the importance of fabrication parameters of copper oxide-based resistive switching memory devices by machine learning techniques.

In the present study, various statistical and machine learning (ML) techniques were used to understand how device fabrication parameters affect the performance of copper oxide-based resistive switching (RS) devices. In the present case, the data was collected from copper oxide RS devices-based research articles, published between 2008 to 2022. Initially, different patterns present in the data were analyzed by statistical techniques. Then, the classification and regression tree algorithm (CART) and decision tree (DT) ML algorithms were implemented to get the device fabrication guidelines for the continuous and categorical features of copper oxide-based RS devices, respectively. In the next step, the random forest algorithm was found to be suitable for the prediction of continuous-type features as compared to a linear model and artificial neural network (ANN). Moreover, the DT algorithm predicts the performance of categorical-type features very well. The feature importance score was calculated for each continuous and categorical feature by the gradient boosting (GB) algorithm. Finally, the suggested ML guidelines were employed to fabricate the copper oxide-based RS device and demonstrated its non-volatile memory properties. The results of ML algorithms and experimental devices are in good agreement with each other, suggesting the importance of ML techniques for understanding and optimizing memory devices.

Pyrazolopyrimidinone Based Selective Inhibitors of PDE5 for the Treatment of Erectile Dysfunction.

Continuing research with our earlier finding of sildenafil based analogs in the search of new inhibitors of PDE5 for erectile dysfunction suggested that there is a scope of modifications at N-methylpiperazine ring with hydrophobic region followed by hydrogen bond donor or acceptor region. However, the leads identified earlier had some limitations like poor pharmacokinetic (PK) profile, low aqueous solubility and poor bioavailability. In this direction, a new series of sildenafil based analogs were designed, synthesized and screened for their PDE5 inhibitory activity. In this series compound 18 was found to have excellent in vitro activity with selectivity towards PDE5 isozyme, also the in vivo activity and pharmacokinetic profile was excellent. The cyp inhibition and CaCO2 permeability was also excellent for compound 18.

Regulatory de novo mutations underlying intellectual disability.

The genetic aetiology of a major fraction of patients with intellectual disability (ID) remains unknown. De novo mutations (DNMs) in protein-coding genes explain up to 40% of cases, but the potential role of regulatory DNMs is still poorly understood. We sequenced 63 whole genomes from 21 ID probands and their unaffected parents. In addition, we analysed 30 previously sequenced genomes from exome-negative ID probands. We found that regulatory DNMs were selectively enriched in fetal brain-specific enhancers as compared with adult brain enhancers. DNM-containing enhancers were associated with genes that show preferential expression in the prefrontal cortex. Furthermore, we identified recurrently mutated enhancer clusters that regulate genes involved in nervous system development (CSMD1, OLFM1, and POU3F3). Most of the DNMs from ID probands showed allele-specific enhancer activity when tested using luciferase assay. Using CRISPR-mediated mutation and editing of epigenomic marks, we show that DNMs at regulatory elements affect the expression of putative target genes. Our results, therefore, provide new evidence to indicate that DNMs in fetal brain-specific enhancers play an essential role in the aetiology of ID.