Establishing a General Atomistic Model for the Stratum Corneum Lipid Matrix Based on Experimental Data for Skin Permeation Studies.

Understanding the permeation of drugs through the intercellular lipid matrix of the stratum corneum layer of skin is crucial for effective transdermal delivery. Molecular dynamics simulations can provide molecular insights into the permeation process. In this study, we developed a new atomistic model representing the multilamellar arrangement of lipids in the stratum corneum intercellular space for permeation studies.

Estimating protein-ligand interactions with geometric deep learning and mixture density models.

Understanding the interactions between a ligand and its molecular target is crucial in guiding the optimization of molecules for any drug design workflow. Multiple experimental and computational methods have been developed to better understand these intermolecular interactions. With the availability of a large number of structural datasets, there is a need for developing statistical frameworks that improve upon existing physicsbased solutions.

Investigating the interaction pattern of FDA approved compounds with GidB to understand their potential as antibiotics.

() drug resistance is a major challenge in eradicating its infection globally. is continuously evolving to overcome the anti-TB drug stress and retain its survival inside the host cells. This continuous evolution of can only be tackled by the continuous search for novel drug targets as well as developing new therapeutics.

Enhanced depletion of MLL-fusion proteins in acute leukemia: potential for improved therapeutic outcomes.

Rearrangements of the MLL (KMT2A) locus are associated with aggressive leukaemia of both myeloid and lymphoid lineages, that present profound therapeutic challenges in pediatric and adult patient populations. MLL-fusion genes resulting from these rearrangements function as driving oncogenes and have been the focus of research aimed at understanding mechanisms underlying their leukemogenic activity and revealing novel therapeutic opportunities. Inspired by the paradigm of depleting the PML-RARA fusion protein in acute promyelocytic leukemia using all-trans retinoic acid and arsenic trioxide, we conducted a screen to identify FDA-approved drugs capable of depleting MLL-fusion protein expression in leukemia cells.

Identifying High-Quality Leads among Screened Anticancerous Compounds Using SMILES Representations.

Cancer is a lethal disease that affects numerous people worldwide. Chemotherapy stands as one of the most effective treatment regimens to combat cancer. Nevertheless, anticancer drugs face a high failure rate due to safety and efficacy issues.

Follow-up report of fundus findings of tuberous sclerosis-associated retinal astrocytoma of two siblings.

A late adolescent with tuberous sclerosis (TS) presented with reduced vision in one eye to our tertiary care university hospital 4 years ago. Fundus examination revealed multiple retinal astrocytic hamartomas (RAHs) in both eyes. His younger sibling, who also had TS, was found to have RAH on retinal screening.

DNA shape features improve prediction of CRISPR/Cas9 activity.

The CRISPR/Cas9 genome editing technology has transformed basic and translational research in biology and medicine. However, the advances are hindered by off-target effects and a paucity in the knowledge of the mechanism of the Cas9 protein. Machine learning models have been proposed for the prediction of Cas9 activity at unintended sites, yet feature engineering plays a major role in the outcome of the predictors.

Molecular insights into the binding interactions and energetics of the omicron spike variant with hACE2 and a neutralizing antibody.

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since 2019 has led to a continuous evolution of viral variants, with the latest concern being the Omicron (B.1.1.

Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester.

Background: The recent COVID-19 (coronavirus disease 2019) pandemic triggered research on the development of new vaccines/drugs, repurposing of clinically approved drugs, and assessment of natural anti-COVID-19 compounds. Based on the gender difference in the severity of the disease, such as a higher number of men hospitalized and in intense care units, variations in sex hormones have been predicted to play a role in disease susceptibility. Cell surface receptors (Angiotensin-Converting Enzyme 2; ACE2 and a connected transmembrane protease serine 2- TMPSS2) are upregulated by androgens.

M-Ionic: prediction of metal-ion-binding sites from sequence using residue embeddings.

Motivation: Understanding metal-protein interaction can provide structural and functional insights into cellular processes. As the number of protein sequences increases, developing fast yet precise computational approaches to predict and annotate metal-binding sites becomes imperative. Quick and resource-efficient pre-trained protein language model (pLM) embeddings have successfully predicted binding sites from protein sequences despite not using structural or evolutionary features (multiple sequence alignments).

TCR-ESM: Employing protein language embeddings to predict TCR-peptide-MHC binding.

Cognate target identification for T-cell receptors (TCRs) is a significant barrier in T-cell therapy development, which may be overcome by accurately predicting TCR interaction with peptide-bound major histocompatibility complex (pMHC). In this study, we have employed peptide embeddings learned from a large protein language model- Evolutionary Scale Modeling (ESM), to predict TCR-pMHC binding. The TCR-ESM model presented outperforms existing predictors.

Molecular insights to the anti-COVID-19 potential of α-, β- and γ-cyclodextrins.

SARS-CoV-2 viral infection is regulated by the host cell receptors ACE2 and TMPRSS2, and therefore the effect of various natural and synthetic compounds on these receptors has recently been the subject of investigations. Cyclodextrins, naturally occurring polysaccharides derived from starch, are soluble in water and have a hydrophobic cavity at their center enabling them to accommodate small molecules and utilize them as carriers in the food, supplements, and pharmaceutical industries to improve the solubility, stability, and bioavailability of target compounds. In the current study, computational molecular simulations were used to investigate the ability of α-, β- and γ-Cyclodextrins on human cell surface receptors.

Improved Machine Learning-Based Model for the Classification of Off-Targets in the CRISPR/Cpf1 System.

Targeted nucleases are widely used for altering the specific location of the genome with precision. The endonucleases facilitate efficient genome editing via designing a guide RNA (gRNA) consisting of a 20-nucleotide target sequence. gRNA preferably binds to the target location, but the on- and off-target activities of gRNAs vary widely.

Construction and characterization of a temperature-sensitive pRC4 replicon for Rhodococcus and Gordonia.

Temperature-sensitive plasmids are useful for genome engineering and several synthetic biology applications. There are only limited reports on temperature-sensitive plasmids for Rhodococcus and none for Gordonia. Here, we report the construction of a temperature-sensitive pRC4 replicon that is functional in Rhodococcus and Gordonia.

Generated heat at implant site during gradual and single-drill protocols among Indian patients.

Excessive heat generation during bone drilling for dental implant placement is a known risk factor for bone necrosis and delayed healing. Therefore, it is of interest to evaluate the maximum change in temperature during and after preparation of the implant site for an implant diameter of 4.2 using gradual drilling and single drilling protocols.

A systematic comparison of human mitochondrial genome assembly tools.

Background: Mitochondria are the cell organelles that produce most of the chemical energy required to power the cell's biochemical reactions. Despite being a part of a eukaryotic host cell, the mitochondria contain a separate genome whose origin is linked with the endosymbiosis of a prokaryotic cell by the host cell and encode independent genomic information throughout their genomes. Mitochondrial genomes accommodate essential genes and are regularly utilized in biotechnology and phylogenetics.

A Cross-Sectional Study to Analyze the Correlation Between Alexithymia and Dental Neglect in Persons Pursuing Dental Care.

Background Alexithymia is a personality trait involving difficulties in emotional regulation (difficulties in identifying feelings, difficulties in describing feelings, and externally oriented thinking). It has a negative impact on health as it evokes poor personal hygiene, poor nutrition, and unhealthy behaviors in affected subjects. Identifying alexithymia in the dental setup is vital as it can compromise the patient-dentist relationship, especially in subjects neglecting oral hygiene.

Photocatalytic CO Conversion into Solar Fuels Using Carbon-Based Materials-A Review.

Carbon materials with elusive 0D, 1D, 2D, and 3D nanostructures and high surface area provide certain emerging applications in electrocatalytic and photocatalytic CO utilization. Since carbon possesses high electrical conductivity, it expels the photogenerated electrons from the catalytic surface and can tune the photocatalytic activity in the visible-light region. However, the photocatalytic efficiency of pristine carbon is comparatively low due to the high recombination of photogenerated carriers.

Effect of Withaferin-A, Withanone, and Caffeic Acid Phenethyl Ester on DNA Methyltransferases: Potential in Epigenetic Cancer Therapy.

Background: DNA methyltransferases (DNMTs) have been reported to be potential drug targets in various cancers. The major hurdle in inhibiting DNMTs is the lack of knowledge about different DNMTs and their role in the hypermethylation of gene promoters in cancer cells. Lack of information on specificity, stability, and higher toxicity of previously reported DNMT inhibitors is the major reason for inadequate epigenetic cancer therapy.

Polypharmacological repurposing approach identifies approved drugs as potential inhibitors of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing.

Hybrid Multitask Learning Reveals Sequence Features Driving Specificity in the CRISPR/Cas9 System.

CRISPR/Cas9 technology is capable of precisely editing genomes and is at the heart of various scientific and medical advances in recent times. The advances in biomedical research are hindered because of the inadvertent burden on the genome when genome editors are employed-the off-target effects. Although experimental screens to detect off-targets have allowed understanding the activity of Cas9, that knowledge remains incomplete as the rules do not extrapolate well to new target sequences.

Association of Risk Factors among Nasal and Orbital Mucormycosis in Coronavirus Disease 2019 Infection: A Cross-Sectional Study.

Purpose: To study the risk factors of mucormycosis and analyze their association among nasal and orbital mucormycosis in Coronavirus disease 2019 (COVID-19) infection.

Methods: All patients diagnosed of rhino-orbito-cerebral mucormycosis (ROCM) with previous COVID-19 infection were included in the study. The details such as age, sex, presence of co-morbidities, and serum ferritin levels were collected.