AMARO: All Heavy-Atom Transferable Neural Network Potentials of Protein Thermodynamics.

All-atom molecular simulations offer detailed insights into macromolecular phenomena, but their substantial computational cost hinders the exploration of complex biological processes. We introduce Advanced Machine-learning Atomic Representation Omni-force-field (AMARO), a new neural network potential (NNP) that combines an O(3)-equivariant message-passing neural network architecture, TensorNet, with a coarse-graining map that excludes hydrogen atoms. AMARO demonstrates the feasibility of training coarser NNP, without prior energy terms, to run stable protein dynamics with scalability and generalization capabilities.

Deciphering Chemical Rules for Drug Penetration into Strongyloides.

Strongyloidiasis, a parasitic infection, presents a significant public health challenge in tropical regions due to the limited repertoire of effective treatments. The screening of chemical libraries against the therapeutically relevant third-stage larvae (L3) of the model parasite yielded meager success rates. This situation is reminiscent of Gram-negative bacteria, where drug entry is a limiting factor.

Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma.

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated.

16S rDNA Sequencing for Bacterial Identification in Preterm Infants with Suspected Early-Onset Neonatal Sepsis.

Background: The high prevalence of suspected early-onset neonatal sepsis among preterm infants leads to immediate antibiotic administration upon admission. Notably, most blood cultures for suspected early-onset neonatal sepsis do not yield a causative pathogen. This study aimed to assess polymerase chain reaction (PCR) targeting the variable region V4 of the 16S ribosomal gene (16S rDNA) and Sanger sequencing for bacterial identification in preterm infants with suspected early-onset neonatal sepsis.

Promising anti-proliferative indolic benzenesulfonamides alter mechanisms with sulfonamide nitrogen substituents.

Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use.

TorchMD-Net 2.0: Fast Neural Network Potentials for Molecular Simulations.

Achieving a balance between computational speed, prediction accuracy, and universal applicability in molecular simulations has been a persistent challenge. This paper presents substantial advancements in TorchMD-Net software, a pivotal step forward in the shift from conventional force fields to neural network-based potentials. The evolution of TorchMD-Net into a more comprehensive and versatile framework is highlighted, incorporating cutting-edge architectures such as TensorNet.

Current drug strategies for the treatment and control of schistosomiasis.

Introduction: Schistosomiasis, one of the current Neglected Tropical Diseases (NTDs) affects over 230 million people globally, with nearly 700 million at risk in more than 74 countries. Praziquantel (PZQ) has served as the primary treatment for the past four decades; however, its effectiveness is limited as it solely eliminates adult worms. In regions where infections are frequent, PZQ exhibits only temporary efficacy and has restricted potential to disrupt the prolonged transmission of the disease.

TorchMD-Net 2.0: Fast Neural Network Potentials for Molecular Simulations.

Achieving a balance between computational speed, prediction accuracy, and universal applicability in molecular simulations has been a persistent challenge. This paper presents substantial advancements in the TorchMD-Net software, a pivotal step forward in the shift from conventional force fields to neural network-based potentials. The evolution of TorchMD-Net into a more comprehensive and versatile framework is highlighted, incorporating cutting-edge architectures such as TensorNet.

MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.

Background And Purpose: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications.

OpenMM 8: Molecular Dynamics Simulation with Machine Learning Potentials.

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy.

Experimental structure based drug design (SBDD) applications for anti-leishmanial drugs: A paradigm shift?

Leishmaniasis is a group of neglected tropical diseases caused by at least 20 species of Leishmania protozoa, which are spread by the bite of infected sandflies. There are three main forms of the disease: cutaneous leishmaniasis (CL, the most common), visceral leishmaniasis (VL, also known as kala-azar, the most serious), and mucocutaneous leishmaniasis. One billion people live in areas endemic to leishmaniasis, with an annual estimation of 30,000 new cases of VL and more than 1 million of CL.

Frentizole, a Nontoxic Immunosuppressive Drug, and Its Analogs Display Antitumor Activity via Tubulin Inhibition.

Antimitotic agents are one of the more successful types of anticancer drugs, but they suffer from toxicity and resistance. The application of approved drugs to new indications (i.e.

Multifunctional materials for catalyst-specific heating and thermometry in tandem catalysis.

A multifunctional material design, integrating catalytic as well as auxiliary magnetic susception and contactless thermal sensing functionalities, unlocks catalyst-specific heating and thermometry for spatially proximate solid catalysts in a single reactor. The new concept alleviates temperature incompatibilities in tandem catalysis, as showcased for the direct production of propene from ethene, sequential olefin dimerization and metathesis reactions.

Targeting 7KCh-Induced Cell Death Response Mediated by p38, P2X7 and GSDME in Retinal Pigment Epithelium Cells with Sterculic Acid.

Age-related macular degeneration (AMD) is the main cause of blindness in developed countries. AMD is characterized by the formation of drusen, which are lipidic deposits, between retinal pigment epithelium (RPE) and the choroid. One of the main molecules accumulated in drusen is 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative.

OpenMM 8: Molecular Dynamics Simulation with Machine Learning Potentials.

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy.

GuaB3, an overlooked enzyme in cyanobacteria's toolbox that sheds light on IMP dehydrogenase evolution.

IMP dehydrogenase and GMP reductase are enzymes from the same protein family with analogous structures and catalytic mechanisms that have gained attention because of their essential roles in nucleotide metabolism and as potential drug targets. This study focusses on GuaB3, a less-explored enzyme within this family. Phylogenetic analysis uncovers GuaB3's independent evolution from other members of the family and it predominantly occurs in Cyanobacteria.

A hypothermia mimetic molecule (zr17-2) reduces ganglion cell death, gliosis, and electroretinogram distortion in male rats subjected to perinatal asphyxia.

Perinatal asphyxia (PA) represents a major problem in perinatology and may cause visual losses, including blindness. We, and others, have shown that hypothermia prevents retinal symptoms associated to PA. In the present work, we evaluate whether a hypothermia mimetic small molecule, zr17-2, has similar effects in the context of PA.

Predicting the size and morphology of nanoparticle clusters driven by biomolecular recognition.

Nanoparticle aggregation is a driving principle of innovative materials and biosensing methodologies, improving transduction capabilities displayed by optical, electrical or magnetic measurements. This aggregation can be driven by the biomolecular recognition between target biomolecules (analytes) and receptors bound onto nanoparticle surface. Despite theoretical advances on modelling the entropic interaction in similar systems, predictions of the fractal morphologies of the nanoclusters of bioconjugated nanoparticles are lacking.

Aqueous Extracts of Fermented Macrofungi Cultivated in Oilseed Cakes as a Carbon Source for Probiotic Bacteria and Potential Antibacterial Activity.

Plant biomass colonized by macrofungi can contain molecules with bioactive properties with applications to human/animal health. This work aimed to verify antibacterial activities from aqueous extracts from oil seed cakes of (JSC) and cottonseed (CSC), fermented by macrofungi for probiotic bacteria cultivation. sp.

Novel Tetrazole Derivatives Targeting Tubulin Endowed with Antiproliferative Activity against Glioblastoma Cells.

Increasing awareness of the structure of microtubules has made tubulin a relevant target for the research of novel chemotherapies. Furthermore, the particularly high sensitivity of glioblastoma multiforme (GBM) cells to microtubule disruption could open new doors in the search for new anti-GBM treatments. However, the difficulties in developing potent anti-tubulin drugs endowed with improved pharmacokinetic properties necessitates the expansion of medicinal chemistry campaigns.

Real-World Safety and Efficacy Clinical Data of an Improved Allergen-Specific Immunotherapy Product for the Treatment of Bee Venom Allergy.

The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test).

Identification of 7-Ketocholesterol-Modulated Pathways and Sterculic Acid Protective Effect in Retinal Pigmented Epithelium Cells by Using Genome-Wide Transcriptomic Analysis.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. AMD is characterized by the formation of lipidic deposits between the retinal pigment epithelium (RPE) and the choroid called drusen. 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative, is closely related to AMD as it is one of the main molecules accumulated in drusen.