Identification of potential JNK3 inhibitors through virtual screening, molecular docking and molecular dynamics simulation as therapeutics for Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurological disorder and no effective drug is available for its treatment. Numerous pathological conditions are believed to be responsible for the initiation and development of AD including c-Jun N-terminal kinases (JNKs). The JNKs are one of the enzymes from the mitogen-activated protein kinase (MAPK) family that controls the phosphorylation of various transcription factors on serine and threonine residues, and hold significant responsibilities in tasks like gene expression, cell proliferation, differentiation, and apoptosis. Since, JNK3 is primarily expressed in the brain hence its increased levels in the brain are associated with the AD pathology promoting neurofibrillary tangles, senile plaques, neuroinflammation, and nerve cell apoptosis. The current research work is focused on the development of novel JNK inhibitors as therapeutics for AD employing a structure-based virtual screening (SBVS) approach. The ZINC database (14634052 compounds) was investigated after employing pan assay interference (PAINs), drug-likeness, and diversity picking filter to distinguish molecules interacting with JNK3 by following three docking precision criteria: High Throughput Virtual Screening (HTVS), Standard Precision (SP), and Extra Precision (XP) & MMGBSA. Five lead molecules showed a better docking score in the range of -13.091 to -14.051 kcal/mol better than the reference compound (- 11.828 kcal/mol). The lead compounds displayed acceptable pharmacokinetic properties and were subjected to molecular dynamic simulations of 100 ns and binding free energy calculations. All the lead molecules showed stable RMSD and hydrogen bond interactions throughout the trajectory. The ∆GMM/PBSA_total score for the lead compounds ZINC220382956, ZINC147071339, ZINC207081127, ZINC205151456, ZINC1228819126, and CC-930 was calculated and found to be - 31.39, - 42.8, - 37.04, - 39.01, - 36.5, - 34.16 kcal/mol, respectively. Thus, it was concluded that the lead molecules identified in these studies have the potential to be explored as potent JNK3 inhibitors.

Multi-modal medical image fusion using improved dual-channel PCNN.

This paper proposes a medical image fusion method in the non-subsampled shearlet transform (NSST) domain to combine a gray-scale image with the respective pseudo-color image obtained through different imaging modalities. The proposed method applies a novel improved dual-channel pulse-coupled neural network (IDPCNN) model to fuse the high-pass sub-images, whereas the Prewitt operator is combined with maximum regional energy (MRE) to construct the fused low-pass sub-image. First, the gray-scale image and luminance of the pseudo-color image are decomposed using NSST to find the respective sub-images. Second, the low-pass sub-images are fused by the Prewitt operator and MRE-based rule. Third, the proposed IDPCNN is utilized to get the fused high-pass sub-images from the respective high-pass sub-images. Fourth, the luminance of the fused image is obtained by applying inverse NSST on the fused sub-images, which is combined with the chrominance components of the pseudo-color image to construct the fused image. A total of 28 diverse medical image pairs, 11 existing methods, and nine objective metrics are used in the experiment. Qualitative and quantitative fusion results show that the proposed method is competitive with and even outpaces some of the existing medical fusion approaches. It is also shown that the proposed method efficiently combines two gray-scale images.

Natural resource-derived NiO nanoparticles via aloe vera for high-performance symmetric supercapacitor.

This investigation reported a one-step green synthesis of nickel oxide nanoparticles (NiO NPs) using aloe vera leaves extract solution for their application in a supercapacitor. This method used aloe vera leaves as a reducing agent, which is very simple and cost-effective. The synthesized NPs were thoroughly characterized using various techniques. The X-ray diffraction analysis unequivocally confirmed the crystalline nature; field emission scanning electron microscopy and transmission electron microscopy images showed different shapes and forms of an agglomerated cluster of synthesized NPs. The absorption spectra were recorded from UV visible spectroscopy, while Fourier transform infrared spectroscopy provided insights into the functional groups present. Electrochemical assessments were carried out via cyclic voltammetry, galvanostatic charging-discharging and electrochemical impedance spectroscopy. These experiments were performed using a 2 M KOH electrolyte within a 1.0 V potential window. Impressively, the single electrode displayed a remarkable specific capacitance of 462 F g-1 at a scan rate of 1 mV s-1 and 336 F g-1 at a current density of 0.76 A g-1. Further, a symmetric two-electrode device (NiO||NiO) has been successfully fabricated by employing a separator between the electrodes. The device exhibited an exceptional specific capacitance of approximately 239 F g-1, along with an energy density of 47.8 Wh kg-1 and a power density of 545 W kg-1 at 1 A g-1 current density within a 1.2 V potential window. The fabricated device also shows a retention capacity of 89% at 10 A g-1 after 2000 cycles with 114% of columbic efficiency. The present study underscores the effectiveness of the green synthesis approach in producing NiO NPs and establishes their potential as highly promising candidates for supercapacitor applications, showcasing both excellent electrochemical performance in a three-electrode system and remarkable stability in a practical two-electrode device. The results collectively highlight the efficacy of the green approach in producing NiO NPs, establishing its potential as a highly promising candidate for supercapacitor application.

Thermochromic Nanocellulose Films for Temperature-Adaptive Passive Cooling.

Energy efficiency in habitation spaces is a pivotal topic for maintaining energy sufficiency, cutting climate impact, and facilitating economic savings; thus, there is a critical need for solutions aimed at tackling this problem. One viable approach involves complementing active cooling methods with powerless or passive cooling ones. Moreover, considerable scope remains for the development of passive radiative cooling solutions based on sustainable materials. Cellulose, characterized by its abundance, renewability, and biodegradability, emerges as a promising material for this purpose due to its notable radiative cooling potential exploiting the mid-infrared (MIR) atmospheric transmission window (8-13 µm). In this work, we propose the utilization of thermochromic (TC) materials in conjunction with cellulose nanofibrils (CNF) to confer temperature-dependent adaptivity to hybrid CNF films. We employ a concept where high reflection, coupled with MIR emission in the heated state, facilitates cooling, while high visible light absorption in the cold state allows heating, thus enabling adaptive thermal regulation. CNF films were doped with black-to-leuco TC particles, and a thin silver layer was optionally applied to the films. The films exhibited a rapid transition (within 1 s) in their optical properties at ∼22 °C, becoming transparent above the transition temperature. Visible range transmittance of all samples ranged from 60 to 90%, with pronounced absorption in the 8-13 µm range. The cooling potential of the films was measured at 1-4 °C without any Ag layer and ∼10 °C with a Ag layer. In outdoor field testing, a peak cooling value of 12 °C was achieved during bright sunshine, which is comparable to a commercial solar film. A simulation model was also built based on the experimental results. The concept presented in this study extends beyond applications as standalone films but has applicability also in glass coatings. Overall, this work opens the door for a novel application opportunity for green cellulose-based materials.

Protein-protein interaction network analysis for the identification of novel multi-target inhibitors and target miRNAs against Alzheimer's disease.

This study presents a strategy for extracting significant gene complexes and then provides prospective therapeutics for AD. In this research, a total of 7905 reports published from 1981 to 2022 were retrieved. Following a review of all those articles, only the genetic association studies on AD were considered. Finally, there is a list of 453 Alzheimer-related genes in our dataset for network analysis. To this end, an experimentally derived protein-protein interaction (PPI) network from the String database was utilized to extract four meaningful gene complexes functionally interconnected using Cytoscape v3.9.1 software. The acquired gene complexes were subjected to an enrichment analysis using the ClueGO v2.5.9 tool to emphasize the most significant biological processes and pathways. Afterward, extracted gene complexes were used to extract the drugs related to AD from DGI v3.0 database and introduce some new drugs which may be helpful for this disease. Finally, a comprehensive network that included every gene connected to each gene complex group as well as the drug targets for each gene has been shown. Moreover, molecular docking studies have been performed with the selected compounds to identify the interaction pattern with the respective targets. Finally, we proposed a list of 62 compounds as multi-targeted directed drug-like compounds with a degree value between 2 and 5 and 30 compounds as target-specific drug-like compounds, which have not been proclaimed as AD-related drugs in prior scientific and medical investigations. Then, new drugs were suggested that can be experimentally examined for future work. In addition to this, four bipartite networks representing each group's genes and target miRNAs were established to introduce target miRNAs by using the miRWalk v3 server.

Reconsidering the discontinuation of M.Phil. programs in clinical psychology and psychiatric social work: An imperative for India's mental health future.

This viewpoint critically examines the New Education Policy (NEP) 2020's decision to discontinue M.Phil. programs in Clinical Psychology and Psychiatric Social Work in India. It explores the crucial roles these programs play in addressing the country's shortage of mental health professionals and evaluates the potential impact of this decision on mental healthcare. The article advocates for the necessity of these programs in maintaining the quality and accessibility of mental health services and calls for a reconsidered policy approach that balances educational reforms with the specialized needs of the mental health sector.

Creative pursuits for mental health and well-being.

This clinical practice guide traces the role of art and creativity in mental health and well-being. This is a difficult task since the evidence from research spans a wide variety of fine art forms and different aspects of creativity. Hence, we have tried to combine both evidence-based research as well as our clinical experience and practice in the field of arts in utilizing creative pursuits as a life skill and a well-being initiative. The focus of the guidelines is preventive and promotional with relevance to mental health. We also hope that this should be a beginning in encouraging psychiatrists in India to use art-based therapies in their clinical practice. This will further our knowledge of how arts can be a therapeutic intervention as well as a well-being tool. It will also build on the evidence base on how art impacts our mental health. Creativity is undeniably one of humanity's most valued traits; the capacity to produce new ideas, innovations, and art is perhaps the most striking characteristic of the human brain. "Art" has evolved, and what is art, has been redefined over human history. The domain of "art" refers to the diverse range of activities that often use imagination to express ideas and feelings. Whilst the boundaries of what constitutes art or creativity may sometimes appear esoteric, we still can identify a range of creative pursuits: visual, musical, verbal, literary, dance, or creative pursuits related to our body movements and a range of forms of newer integrated forms and those that use technology are recognized as art forms. As in most ancient traditions, in India, we have a plethora of fine art traditions many of which have a highly systematic practice around their learning. We believe this is an asset that we need to nurture and celebrate. We begin by tracing the footsteps of Indian fine arts being a mental health promotional tool in ancient India. We then proceed to describe the scope of creative pursuits for different populations and its relevance in school and child mental health. We offer suggestions as to how creative art forms can be utilized in a practical way in daily life, schools, and care of the elderly. It is to be noted that the entire focus here is the process of creativity and not the completed product or the achievement related to the same. Hence, it is relevant to each one of us and to anyone who wishes to be healthy.

Cryo-EM analyses of dimerized spliceosomes provide new insights into the functions of B complex proteins.

The B complex is a key intermediate stage of spliceosome assembly. To improve the structural resolution of monomeric, human spliceosomal B (hB) complexes and thereby generate a more comprehensive hB molecular model, we determined the cryo-EM structure of B complex dimers formed in the presence of ATP γ S. The enhanced resolution of these complexes allows a finer molecular dissection of how the 5' splice site (5'ss) is recognized in hB, and new insights into molecular interactions of FBP21, SNU23 and PRP38 with the U6/5'ss helix and with each other. It also reveals that SMU1 and RED are present as a heterotetrameric complex and are located at the interface of the B dimer protomers. We further show that MFAP1 and UBL5 form a 5' exon binding channel in hB, and elucidate the molecular contacts stabilizing the 5' exon at this stage. Our studies thus yield more accurate models of protein and RNA components of hB complexes. They further allow the localization of additional proteins and protein domains (such as SF3B6, BUD31 and TCERG1) whose position was not previously known, thereby uncovering new functions for B-specific and other hB proteins during pre-mRNA splicing.

Chronic aquatic toxicity assessment of diverse chemicals on Daphnia magna using QSAR and chemical read-across.

We have modeled here chronic Daphnia toxicity taking pNOEC (negative logarithm of no observed effect concentration in mM) and pEC50 (negative logarithm of half-maximal effective concentration in mM) as endpoints using QSAR and chemical read-across approaches. The QSAR models were developed by strictly obeying the OECD guidelines and were found to be reliable, predictive, accurate, and robust. From the selected features in the developed models, we have found that an increase in lipophilicity and saturation, the presence of electrophilic or electronegative or heavy atoms, the presence of sulphur, amine, and their related functionality, an increase in mean atomic polarizability, and higher number of (thio-) carbamates (aromatic) groups are responsible for chronic toxicity. Therefore, this information might be useful for the development of environmentally friendly and safer chemicals and data-gap filling as well as reducing the use of identified toxic chemicals which have chronic toxic effects on aquatic ecosystems. Approved classes of drugs from DrugBank databases and diverse groups of chemicals from the Chemical and Product Categories (CPDat) database were also assessed through the developed models.

Early Detection of Oral Potentially Malignant Disorders: A Review on Prospective Screening Methods with Regard to Global Challenges.

Oral cancer is a cancer type that is widely prevalent in low-and middle-income countries with a high mortality rate, and poor quality of life for patients after treatment. Early treatment of cancer increases patient survival, improves quality of life and results in less morbidity and a better prognosis. To reach this goal, early detection of malignancies using technologies that can be used in remote and low resource areas is desirable. Such technologies should be affordable, accurate, and easy to use and interpret. This review surveys different technologies that have the potentials of implementation in primary health and general dental practice, considering global perspectives and with a focus on the population in India, where oral cancer is highly prevalent. The technologies reviewed include both sample-based methods, such as saliva and blood analysis and brush biopsy, and more direct screening of the oral cavity including fluorescence, Raman techniques, and optical coherence tomography. Digitalisation, followed by automated artificial intelligence based analysis, are key elements in facilitating wide access to these technologies, to non-specialist personnel and in rural areas, increasing quality and objectivity of the analysis while simultaneously reducing the labour and need for highly trained specialists.

Role of vaginal microbiota in idiopathic infertility: a prospective study.

OBJECTIVE: The causes of idiopathic infertility are still not known; however, it may be associated with microbial etiologies. The present study examines the vaginal microbiota of infertile as well as fertile women longitudinally. METHODOLOGY: The study was presented and accepted by the Institutional Ethical Committee of Shri Mata Vaishno Devi University, Katra, Jammu and Kashmir (India). An observational, prospective, multicenteric investigation was conducted at the Department of Obstetrics and Gynecology, Government Medical College Jammu, and its affiliated hospitals in Jammu and Kashmir (India). In order to examine the microbial composition, a cohort of 80 female individuals were involved in the screening process. The investigation involved sequencing of the V3-V4 region of 16S rRNA gene, which was subsequently analyzed using the Mothur pipeline. RESULTS: The study revealed that the vaginal microbiota of infertile women differed from that of healthy women who had previously given birth without any complications. Both populations have variations in their alpha as well as beta diversity and taxonomical composition. The microbial profiles in the cases of infertility are characterized by elevated levels of Gardnerella, Prevotella, Atopobium, and Enterococcus whereas a higher level of Lactobacillus iners was observed in case of fertile women. CONCLUSION: In conclusion, it can be inferred that the composition of the vaginal microbiome potentially exerts a significant influence on females afflicted with idiopathic infertility.

3D-QSAR-based pharmacophore modelling of quinazoline derivatives for the identification of acetylcholinesterase inhibitors through virtual screening, molecular docking, molecular dynamics and DFT studies.

Alzheimer's disease (AD) is a progressive neurological disorder responsible for the cognitive dysfunction and cognitive impairment in the patients. Acetylcholinesterase inhibitors (AChEIs) are used to treat AD however, these only provided symptomatic relief and more efficient drug molecules are desired for the effective treatment of the disease. In this article, ligand-based drug-designing strategy was used to develop and validate a field-based 3D-QSAR pharmacophore model on quinazoline-based AChEIs reported in the literature. The validated pharmacophore model (AAAHR_1) was used as a prefilter to screen an ASINEX database via virtual screening workflow (VSW). The hits generated were subjected to MM-GBSA to identify potential AChEIs and top three scoring molecules (BAS 05264565, LEG 12727144 and SYN 22339886) were evaluated for thermodynamic stability at the target site using molecular dynamic simulations. Additionally, DFT study was performed to predict the reactivity of lead molecules towards acetylcholinesterase (AChE). Thus, by utilising various computational tools, three molecules were identified as potent AChEIs that can be developed as potential drug candidates for the treatment of AD.Communicated by Ramaswamy H. Sarma.

Commercialization potential of PET (polyethylene terephthalate) recycled nanomaterials: A review on validation parameters.

Polyethylene Terephthalate (PET) is a polymer which is considered as one of the major contaminants to the environment. The PET waste materials can be recycled to produce value-added products. PET can be converted to nanoparticles, nanofibers, nanocomposites, and nano coatings. To extend the applications of PET nanomaterials, understanding its commercialization potential is important. In addition, knowledge about the factors affecting recycling of PET based nanomaterials is essential. The presented review is focused on understanding the PET commercialization aspects, keeping in mind market analysis, growth drivers, regulatory affairs, safety considerations, issues associated with scale-up, manufacturing challenges, economic viability, and cost-effectiveness. In addition, the paper elaborates the challenges associated with the use of PET based nanomaterials. These challenges include PET contamination to water, soil, sediments, and human exposure to PET nanomaterials. Moreover, the paper discusses in detail about the factors affecting PET recycling, commercialization, and circular economy with specific emphasis on life cycle assessment (LCA) of PET recycled nanomaterials.

Iodine-PEG as a unique combination for the metal-free synthesis of flavonoids through iodonium-triiodide ion-pair complexation.

An efficient metal-free single-step protocol has been developed for the direct synthesis of flavones from 2-hydroxyacetophenone and substituted benzaldehydes. This chemical transformation is exclusively promoted by the iodonium-triiodide ion couple formed through iodine and PEG-400 complexation. The triiodide anion not only helps in the abstraction of a proton from the acetophenone but also promotes the cyclization of intermediate chalcone to the corresponding flavones. The flavones were obtained in very high yields without using any toxic metal catalysts or harsh reaction conditions. The reaction mechanism was established through a series of test reactions and entrapping of reaction intermediates. The developed protocol provides direct access to flavones in high yields under milder reaction conditions with great substrate compatibility, including hydroxylated derivatives.

Recent advances in nanotechnology-based modifications of micro/nano PET plastics for green energy applications.

Poly(ethylene terephthalate) (PET) plastic is an omnipresent synthetic polymer in our lives, which causes negative impacts on the ecosystem. It is crucial to take mandatory action to control the usage and sustainable disposal of PET plastics. Recycling plastics using nanotechnology offers potential solutions to the challenges associated with traditional plastic recycling methods. Nano-based degradation techniques improve the degradation process through the influence of catalysts. It also plays a crucial role in enhancing the efficiency and effectiveness of recycling processes and modifying them into value-added products. The modified PET waste plastics can be utilized to manufacture batteries, supercapacitors, sensors, and so on. The waste PET modification methods have massive potential for research, which can play major role in removing post-consumer plastic waste. The present review discusses the effects of micro/nano plastics in terrestrial and marine ecosystems and its impacts on plants and animals. Briefly, the degradation and bio-degradation methods in recent research were explored. The depolymerization methods used for the production of monomers from PET waste plastics were discussed in detail. Carbon nanotubes, fullerene, and graphene nanosheets synthesized from PET waste plastics were delineated. The reuse of nanotechnologically modified PET waste plastics for potential green energy storage products, such as batteries, supercapacitors, and sensors were presented in this review.

Cloning, expression, and characterization of a novel thermo-acidophilic l-asparaginase of Pseudomonas aeruginosa CSPS4.

In the present investigation, a soil isolate Pseudomonas aeruginosa CSPS4 was used for retrieving the l-asparaginase encoding gene (Asn_PA) of size 1089 bp. The gene was successfully cloned into the pET28a (+) vector and expressed into E. coli BL21(DE3) for characterization of the protein. The recombinant rAsn_PA enzyme was purified by affinity chromatography using Ni-NTA2+ resins. Molecular weight analysis using SDS-PAGE unveiled rAsn_PA as a monomeric protein of molecular weight ~ 35 kDa. On characterization, the recombinant rAsn_PA showed optimum pH and temperature of 6.0 and 60 °C, respectively, along with significant stability at 50-70 °C, along with 50% residual activity at 80 °C after 3 h of incubation. Similarly, the rAsn_PA exhibited asparaginase activity over a broad pH range between 4 and 8. The enzyme was not significantly inhibited in the presence of detergents. The rAsn_PA was grouped into the asparaginase-glutaminase family II due to the glutaminase activity. The purified rAsn_PA showed antitumor activity by exhibiting a cytotoxic effect on three different cell lines, where IC50 of purified rAsn_PA was 2.3 IU, 3.7 IU, and 20.5 IU for HL-60, MOLM-13, and K-562 cell lines, respectively. Thus, recombinant rAsn_PA of P. aeruginosa CSPS4 may also be explored as an antitumor agent after reducing or minimizing the glutaminase activity. Thermo-acidophilic properties of rAsn_PA make it a novel enzyme that needs to be further investigated.

Nonsense-mediated mRNA decay pathway in plants under stress: general gene regulatory mechanism and advances.

MAIN CONCLUSION: Nonsense-mediated mRNA decay in eukaryotes is vital to cellular homeostasis. Further knowledge of its putative role in plant RNA metabolism under stress is pivotal to developing fitness-optimizing strategies. Nonsense-mediated mRNA decay (NMD), part of the mRNA surveillance pathway, is an evolutionarily conserved form of gene regulation in all living organisms. Degradation of mRNA-bearing premature termination codons and regulation of physiological RNA levels highlight NMD's role in shaping the cellular transcriptome. Initially regarded as purely a tool for cellular RNA quality control, NMD is now considered to mediate various aspects of plant developmental processes and responses to environmental changes. Here we offer a basic understanding of NMD in eukaryotes by explaining the concept of premature termination codon recognition and NMD complex formation. We also provide a detailed overview of the NMD mechanism and its role in gene regulation. The potential role of effectors, including ABCE1, in ribosome recycling during the translation process is also explained. Recent reports of alternatively spliced variants of corresponding genes targeted by NMD in Arabidopsis thaliana are provided in tabular format. Detailed figures are also provided to clarify the NMD concept in plants. In particular, accumulating evidence shows that NMD can serve as a novel alternative strategy for genetic manipulation and can help design RNA-based therapies to combat stress in plants. A key point of emphasis is its function as a gene regulatory mechanism as well as its dynamic regulation by environmental and developmental factors. Overall, a detailed molecular understanding of the NMD mechanism can lead to further diverse applications, such as improving cellular homeostasis in living organisms.