Revisiting the druggable genome using predicted structures and data mining.

Identification of novel drug targets is a key component of modern drug discovery. While antimalarial targets are often identified through the mechanism of action studies on phenotypically derived inhibitors, this method tends to be time- and resource-consuming. The discoverable target space is also constrained by existing compound libraries and phenotypic assay conditions.

Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control.

Kisspeptin (KP) signaling in the brain is defined by the anatomical distribution of KP-producing neurons, their fibers, receptors, and connectivity. Technological advances have prompted a re-evaluation of these chemoanatomical aspects, originally studied in the early years after the discovery of KP and its receptor Kiss1r. Previously, we characterized (Hernández et al.

Accelerating discovery of bioactive ligands with pharmacophore-informed generative models.

Deep generative models have advanced drug discovery but often generate compounds with limited structural novelty, providing constrained inspiration for medicinal chemists. To address this, we develop TransPharmer, a generative model that integrates ligand-based interpretable pharmacophore fingerprints with a generative pre-training transformer (GPT)-based framework for de novo molecule generation. TransPharmer excels in unconditioned distribution learning, de novo generation, and scaffold elaboration under pharmacophoric constraints.

The challenge of treating hepatitis C virus infection in children with comorbidities.

Unlabelled: Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment and enabled the treatment of those who could not be treated using interferon. The aim of this work was to assess the efficacy and safety of oral DAAs in HCV-infected children with associated comorbidities. This analytical retrospective study included children with HCV mono-infection versus those with associated comorbidities.

Vacancy Ordered Double Perovskites [N(CH3)4]2SnX6 (X = Cl, Br, I): Thermal Phase Transition and Wide Range Optical Absorption.

TMA)2SnX6 (TMA = tetramethylammonium; X = Cl, Br, I) compounds form vacancy-ordered halide double perovskites (VODPs) with TMA+ cation in the A-site, Sn4+ cation in the M-site and X- anion in the halide site. This study reports the synthesis and structural phase transition of (TMA)₂SnCl₆, (TMA)2SnCl0.7Br5.

Structural insights of mechanochemically amorphised MIL-125-NH.

In this work, we investigated the response of the metal-organic framework MIL-125-NH to ball-milling. Both localised and bulk analyses revealed prolongued ball-milling results in a complete loss of long-range structural order. Investigation of this disorder revealed partial retention of the local bonding of the secondary building unit, suggesting structure collapse progressed primarily through metal-linker bond breakage.

Poly(hydrazinophosphine diazide)s (PHPDs): Hybrid Organic-Inorganic Polymers via Polycondensation between PN Cages and Organic Diazides.

Organic polymers generally feature 1-dimensional chains or 2-dimensional rings in their backbones since synthetic challenges limit the availability of 3-dimensional monomers. Inorganic cages are less strained and more accessible, offering an alternative route to explore this parameter space. However, only two families─carboranes and polyhedral oligomeric silsesquioxanes (POSS)─have been well-studied, revealing materials with valuable mechanical and thermal properties.

Crystal Structures, Phase Transition, and Optical Properties of Two Rare Earth Borate Fluorides: α- and β-BaGdBOF.

Borate materials possess diverse crystal structures and exhibit outstanding physical properties, making them highly suitable for optical applications. In this work, two new compounds, α-BaGdBOF and β-BaGdBOF, were synthesized by the high-temperature solid solution method and a temperature-controlled phase transition from α-BaGdBOF to β-BaGdBOF was observed. In the crystal structures of α-BaGdBOF and β-BaGdBOF, the [BO] basic building unit and the [GdOF] polyhedra are interconnected to form a complex three-dimensional network.

Expression and Purification of SARS-related Spike Glycoproteins for Cryo-EM Analysis.

Coronaviridae spike glycoproteins mediate viral entry and fusion to host cells through binding to host receptors (i.e., ACE2, DPP4) and are key components in determining viral host range, making them targets for antiviral research.

Direct hydroxyproline radiocarbon dating of the Lapedo child (Abrigo do Lagar Velho, Leiria, Portugal).

The 1998 discovery of a nearly intact Gravettian human burial in the Lapedo Valley (Leiria, Portugal) propelled the Lagar Velho rockshelter to worldwide fame. The ochre-stained skeleton of the Lapedo child, a juvenile aged around four or five, exhibited a mosaic of Neanderthal and anatomically modern human features argued to reflect admixture between the two human populations. Here, we present direct compound-specific radiocarbon dates for the child's skeleton [27,780 to 28,550 calibrated years before present (cal B.

Characterization of a G. max × G. soja nested association mapping population and identification of loci controlling seed composition traits from wild soybean.

Wild soybean (Glycine soja Siebold & Zucc.) has valuable genetic diversity for improved disease resistance, stress tolerance, seed protein content and seed sulfur-containing amino acid concentrations. Many studies have reported loci controlling seed composition traits based on cultivated soybean populations, but wild soybean has been largely overlooked.

Intra-tumoral susceptibility signals in brain gliomas: where do we stand?

Nowadays, the genetic and biomolecular profile of neoplasms-related with their biological behaviour-have become a key issue in oncology, as they influence many aspects of both diagnosis and treatment. In the neuro-oncology field, neuroradiological research has recently explored the potential of non-invasively predicting the molecular phenotype of primary brain neoplasms, particularly gliomas, based on magnetic resonance imaging (MRI), using both conventional and advanced imaging techniques. Among these, diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), MR spectroscopy (MRS) and susceptibility-weighted imaging (SWI) and have been used to explore various aspects of glioma biology, including predicting treatment response and understanding treatment-related changes during follow-up imaging.

3D Printed Materials with Nanovoxelated Elastic Moduli.

Fabrication methods that synthesize materials with higher precision and complexity at ever smaller scales are rapidly developing. Despite such advances, generating complex 3D materials with controlled mechanical properties at the nanoscale remains challenging. Exerting precise control over mechanical properties at the nanoscale would enable material strengths near theoretical maxima, and the replication of natural structures with hitherto unattainable strength-to-weight ratios.

Surface-enhanced Raman spectroscopy in pharmaceutical analysis: from component determination to mechanism research.

Surface-enhanced Raman spectroscopy (SERS) technology, possessing extraordinary sensitivity and an outstanding ability to furnish molecular-level information, has emerged as a revolutionary technique within the domain of analytical chemistry. This review comprehensively and in-depthly investigates the application of SERS in the field of pharmaceutical analysis, encompassing detailed analyses in diverse aspects such as ingredient identification, quality control, mechanism of action, and efficacy evaluation. Firstly, we introduce the key aspects of SERS technology, including its working principle, substrate preparation methods, and crucial factors in the experimental design process.

Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.

Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B.

Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases.

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci.

Cancer Photodynamic Therapy Enabled by Water-Soluble Chlorophyll Protein.

Photodynamic therapy (PDT) has been utilized to treat various malignant cancers for more than a century. However, many photosensitizers (e.g.

Ultrafast on-demand exciton formation in a single-molecule junction by tailored terahertz pulses.

The ultrafast manipulation of molecular states by charge transfer is essential for characterizing and controlling molecular dynamics. In this study, we demonstrated exciton formation in a single molecule through ultrafast electron tunneling processes between a molecule and a metal tip of a scanning tunneling microscope (STM) using a phase-controlled terahertz (THz) pulse. The pronounced luminescence of the well-defined molecular system under the distinct carrier-envelope phase of the THz pulse revealed that sequential state-selective electron-tunneling processes to the frontier molecular orbitals promoted ultrafast exciton formation in the molecule at the STM junction.

Optimal control-based nuclear spin cross-polarization in the presence of complicating anisotropic interactions.

Cross-polarization is an indispensable part of solid state nuclear magnetic resonance spectroscopy to enhance sensitivity and extract structural information. However, the presence of certain anisotropic interactions, including chemical shift anisotropy and quadrupolar coupling, makes the inter-nuclear spin correlation experiments challenging. This impedes characterization of numerous materials and pharmaceutical compounds containing isotopes, such as F with large chemical shift anisotropy and Li, Na, Al, , with quadrupolar coupling.

Structure and supramolecular organization of silver nitrate modified epoxy or amino terminated liquid oligoethers.

The behavior of silver nitrate in non-aqueous liquid oligomeric media-aromatic and aliphatic diglycidyl ethers and aliphatic diamine-has been investigated. By employing UV-visible spectrophotometry and dynamic light scattering, it has been shown that in diglycidyl oligomers, regardless of the nature of the monomeric unit, the formation of silver nanoparticles occurs, and the kinetics of this process has been studied. At the same time, in the medium of aliphatic diamine, the reduction of silver ions is absent, indicating the formation of a complex compound.

Comprehensive review of chickpea (Cicer arietinum): Nutritional significance, health benefits, techno-functionalities, and food applications.

Chickpeas (Cicer arietinum L.) are globally valued legume known for their affordability, nutritional significance, and health benefits. They are rich in protein, fiber, vitamins, and minerals such as iron, zinc, folate, and magnesium.

Improved Orthogonality in Naphthalimide/Cyanine Dyad Boosts Superoxide Generation: a Tumor-Targeted Type-I Photosensitizer for Photodynamic Therapy of Tumor by Inducing Ferroptosis.

It is highly desired to achieve Type-I photosensitizer (PS) to overcome the hypoxic limitation found in most clinically used PSs. Herein, a new heavy-atom-free Type-I PS T-BNCy5 is presented by incorporating a biotin-modified naphthalimide (NI) unit into the meso-position of a N-benzyl-functionalized, strongly photon-capturing pentamethine cyanine (Cy5) dye. Such molecular engineering induces a rigid orthogonal geometry between NI and Cy5 units by introducing an intramolecular sandwich-like π-π stacking assembly, which effectively promotes intersystem crossing (ISC) and greatly extends the triplet-state lifetime (τ = 389 µs), thereby markedly improving the superoxide (O )-generating ability.

Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age.

Folate receptor alpha (FRα) has long been the focus of therapeutics development in oncology across several solid tumors, notably ovarian, lung, and subsets of breast cancers. Its multiple roles in cellular metabolism and carcinogenesis and tumor-specific overexpression relative to normal tissues render FRα an attractive target for biological therapies. Here we review the biological significance, expression distribution, and characteristics of FRα as a highly promising and now established therapy target.

Optical signature of retinal Tau fibrillation.

Fibrillated Tau proteins are believed to be a signature of Alzheimer's disease (AD) and may be potentially employed as a biosensor for AD early detection. Several studies revealed the presence of Tau accumulation and aggregation in the retina, similar to that observed in the brains of individuals with AD. These retinal changes can be non-invasively visualised through AD-related scores derived from reflectance measurements of the patient fundus.

Structural and antigenic characterization of Babesia Bovis HAP2 domains.

The tick-borne apicomplexan parasite Babesia bovis causes bovine babesiosis which leads to enormous food and economic losses around the world. The existing resources to manage this disease are limited and have pitfalls, therefore, introduction of new strategies is urgently needed. B.