Excited Charge Separation in a π-Interacting Phenothiazine-Zinc Porphyrin-Fullerene Donor-Acceptor Conjugate.

We have designed, synthesized, and characterized a donor-acceptor triad, SPS-PPY-C60, that consists of a π-interacting phenothiazine-linked porphyrin as a donor and sensitizer and fullerene as an acceptor to seek charge separation upon photoexcitation. The optical absorption spectrum revealed red-shifted Soret and Q-bands of porphyrin due to charge transfer-type interactions involving the two ethynyl bridges carrying electron-rich and electron-poor substituents. The redox properties suggested that the phenothiazine-porphyrin part of the molecule is easier to oxidize and the fullerene part is easier to reduce. DFT calculations supported the redox properties wherein the electron density of the highest molecular orbital (HOMO) was distributed over the donor phenothiazine-porphyrin entity while the lowest unoccupied molecular orbital (LUMO) was distributed over the fullerene acceptor. TD-DFT studies suggested the involvement of both the S2 and S1 states in the charge transfer process. The steady-state emission spectrum, when excited either at porphyrin Soret or visible band absorption maxima, revealed quenched emission both in nonpolar and polar solvents, suggesting the occurrence of excited state events. Finally, femtosecond transient absorption spectral studies were performed to witness the charge separation by utilizing solvents of different polarities. The transient data was further analyzed by GloTarAn by fitting the data with appropriate models to describe photochemical events. From this, the average lifetime of the charge-separated state calculated was found to be 169 ps in benzonitrile, 319 ps in dichlorobenzene, 1.7 ns in toluene for Soret band excitation, and ∼320 ps for Q-band excitation in benzonitrile.

Breaking the Barriers: Machine-Learning-Based c-RASAR Approach for Accurate Blood-Brain Barrier Permeability Prediction.

The intricate nature of the blood-brain barrier (BBB) poses a significant challenge in predicting drug permeability, which is crucial for assessing central nervous system (CNS) drug efficacy and safety. This research utilizes an innovative approach, the classification read-across structure-activity relationship (c-RASAR) framework, that leverages machine learning (ML) to enhance the accuracy of BBB permeability predictions. The c-RASAR framework seamlessly integrates principles from both read-across and QSAR methodologies, underscoring the need to consider similarity-related aspects during the development of the c-RASAR model. It is crucial to note that the primary goal of this research is not to introduce yet another model for predicting BBB permeability but rather to showcase the refinement in predicting the BBB permeability of organic compounds through the introduction of a c-RASAR approach. This groundbreaking methodology aims to elevate the accuracy of assessing neuropharmacological implications and streamline the process of drug development. In this study, an ML-based c-RASAR linear discriminant analysis (LDA) model was developed using a dataset of 7807 compounds, encompassing both BBB-permeable and -nonpermeable substances sourced from the B3DB database (freely accessible from https://github.com/theochem/B3DB), for predicting BBB permeability in lead discovery for CNS drugs. The model's predictive capability was then validated using three external sets: one containing 276,518 natural products (NPs) from the LOTUS database (accessible from https://lotus.naturalproducts.net/download) for data gap filling, another comprising 13,002 drug-like/drug compounds from the DrugBank database (available from https://go.drugbank.com/), and a third set of 56 FDA-approved drugs to assess the model's reliability. Further diversifying the predictive arsenal, various other ML-based c-RASAR models were also developed for comparison purposes. The proposed c-RASAR framework emerged as a powerful tool for predicting BBB permeability. This research not only advances the understanding of molecular determinants influencing CNS drug permeability but also provides a versatile computational platform for the rapid assessment of diverse compounds, facilitating informed decision-making in drug development and design.

An analysis of suicidal and self-injurious behavior reports with antiseizure medications in the FDA adverse event database.

BACKGROUND: Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior. METHODS: Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control. RESULTS: Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286). CONCLUSIONS: Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.

LIGNOCELLULOSIC BIOMASS FOR BIOCHAR PRODUCTION: A GREEN INITIATIVE ON BIOWASTE CONVERSION FOR PHARMACEUTICAL AND OTHER EMERGING POLLUTANT REMOVAL.

Lignocellulosic waste generation and their improper disposal has accelerated the problems associated with increased greenhouse gas emissions and associated environmental pollution. Constructive ways to manage and mitigate the pollution associated with lignocellulosic waste has propelled the research on biochar production using lignocellulose-based substrates. The sustainability of various biochar production technologies in employing lignocellulosic biomass as feedstock for biochar production not only aids in the lignocellulosic biomass valorization but also helps in carbon neutralization and carbon utilization. Functionalization of biochar through various physicochemical methods helps in improving their functional properties majorly by reducing the size of the biochar particles to nanoscale and modifying their surface properties. The usage of engineered biochar as nano adsorbents for environmental applications like dye absorption, removal of organic pollutants and endocrine disrupting compounds from wastewater has been the thrust areas of research in the past few decades. This review presents a comprehensive outlook on the up-to-date research findings related to the production and engineering of biochar from lignocellulosic biomass and their applications in environmental remediation especially with respect to wastewater treatment. Further a detailed discussion on various biochar activation methods and the future scope of biochar research is presented in this review work.

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.

Volar Lunate Dislocation: A Case Report.

Introduction: Perilunate dislocations are rare high-energy injuries which may often have the potential to cause lifelong disability of the wrist if not addressed optimally. Hence, early recognition, diagnosis, and intervention are of paramount importance in the restoring function and prevention of morbidity. Lunate dislocations are the fourth and last stage of perilunate dislocations being extremely rare, with volar dislocations representing <3% of perilunate dislocations. Case Report: A 24-year-old man suffered from an alleged history of fall from a bike on an outstretched hand following which he developed complaints of pain and swelling in the right wrist. On examination, the patient has relative sensory loss over the lateral half of the palm with no vascular deficit. An accurate range of motion could not be documented due to severe pain. Standard digital X-rays revealed lunate displaced and angulated volarly with a typical "spilled teacup" appearance along with radial and ulnar styloid fractures. Management: The patient was initially given an attempt of closed reduction which was not successful and was followed with open reduction and internal fixation with both volar and dorsal approach with Kirschner wires. The patient's wrist was immobilized for 6 weeks with below elbow cast with the removal of k wires at 8 weeks after which wrist ROM exercises were started. Results: The patient was followed up for 6 months and now has a functional range of motion of the wrist with no sensory deficit and is able to continue with his profession as a car mechanic. Conclusion: Mayfield progression Stage 4 perilunate dislocations are uncommon with a poor prognosis if not addressed timely. Hence, these injuries need to be identified early and optimally managed with surgical intervention for a favorable outcome.

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.

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.

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.

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.

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.

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.

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.

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.

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.