A vaccine platform targeting lung-resident memory CD4 T-cells provides protection against heterosubtypic influenza infections in mice and ferrets.

Lung tissue-resident memory T (T) cells induced by influenza vaccination are crucial for heterosubtypic immunity upon re-exposure to the influenza virus, enabling rapid and robust responses upon reactivation. To enhance the efficacy of influenza vaccines, we induce the generation of lung T cells following intranasal vaccination with a commercial influenza vaccine adjuvanted with NexaVant (NVT), a TLR3 agonist-based adjuvant. We demonstrate that intranasal immunization with the NVT-adjuvanted vaccine provides improved protection against influenza virus infections by inducing the generation of CD4 T cells in the lungs in a type I interferon-dependent manner.

Mapping inorganic crystal chemical space.

The combination of elements from the Periodic Table defines a vast chemical space. Only a small fraction of these combinations yields materials that occur naturally or are accessible synthetically. Here, we enumerate binary, ternary, and quaternary element and species combinations to produce an extensive library of over 10 stoichiometric inorganic compositions.

Multimodal Transformer for Property Prediction in Polymers.

In this work, we designed a multimodal transformer that combines both the Simplified Molecular Input Line Entry System (SMILES) and molecular graph representations to enhance the prediction of polymer properties. Three models with different embeddings (SMILES, SMILES + monomer, and SMILES + dimer) were employed to assess the performance of incorporating multimodal features into transformer architectures. Fine-tuning results across five properties (i.

Enhancing Structure-Property Relationships in Porous Materials through Transfer Learning and Cross-Material Few-Shot Learning.

Porous materials have emerged as promising solutions for a wide range of energy and environmental applications. However, the asymmetric development in the field of metal-organic frameworks (MOFs) has led to a data imbalance when it comes to MOFs versus other porous materials such as covalent organic frameworks (COFs), porous polymer networks (PPNs), and zeolites. To address this issue, we introduce PMTransformer (Porous Material Transformer), a multimodal Transformer model pretrained on a vast data set of 1.

Esr1 hypothalamic-habenula neurons shape aversive states.

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles and projection patterns.

Histone variant HTB4 delays leaf senescence by epigenetic control of Ib bHLH transcription factor-mediated iron homeostasis.

Leaf senescence is an orderly process regulated by multiple internal factors and diverse environmental stresses including nutrient deficiency. Histone variants are involved in regulating plant growth and development. However, their functions and underlying regulatory mechanisms in leaf senescence remain largely unclear.

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass.

The Discovery of GSK3640254, a Next-Generation Inhibitor of HIV-1 Maturation.

GSK3640254 is an HIV-1 maturation inhibitor (MI) that exhibits significantly improved antiviral activity toward a range of clinically relevant polymorphic variants with reduced sensitivity toward the second-generation MI GSK3532795 (BMS-955176). The key structural difference between GSK3640254 and its predecessor is the replacement of the -substituted benzoic acid moiety attached at the C-3 position of the triterpenoid core with a cyclohex-3-ene-1-carboxylic acid substituted with a CHF moiety at the carbon atom α- to the pharmacophoric carboxylic acid. This structural element provided a new vector with which to explore structure-activity relationships (SARs) and led to compounds with improved polymorphic coverage while preserving pharmacokinetic (PK) properties.

Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with Zr Radioisotope in Mice and Rats.

For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (Zr) after systemic intravenous administration in mice and rats.

Discovery of Heteroaryl Urea Isosteres for Formyl Peptide Receptor 2 Agonists.

Formyl peptide receptor 2 (FPR2) agonists have shown efficacy in inflammatory-driven animal disease models and have the potential to treat a range of diseases. Many reported synthetic agonists contain a phenylurea, which appears to be necessary for activity in the reported chemotypes. We set out to find isosteres for the phenylurea and focused our efforts on heteroaryl rings.

Ethylene responsive factor34 mediates stress-induced leaf senescence by regulating salt stress-responsive genes.

Leaf senescence proceeds with age but is modulated by various environmental stresses and hormones. Salt stress is one of the most well-known environmental stresses that accelerate leaf senescence. However, the molecular mechanisms that integrate salt stress signalling with leaf senescence programmes remain elusive.

Mining Insights on Metal-Organic Framework Synthesis from Scientific Literature Texts.

Identifying optimal synthesis conditions for metal-organic frameworks (MOFs) is a major challenge that can serve as a bottleneck for new materials discovery and development. A trial-and-error approach that relies on a chemist's intuition and knowledge has limitations in efficiency due to the large MOF synthesis space. To this end, 46,701 MOFs were data mined using our in-house developed code to extract their synthesis information from 28,565 MOF papers.

ORESARA 15, a PLATZ transcription factor, controls root meristem size through auxin and cytokinin signalling-related pathways.

An optimal size of post-embryonic root apical meristem (RAM) is achieved by a balance between cell division and differentiation. Despite extensive research, molecular mechanisms underlying the coordination of cell division and differentiation are still fragmentary. Here, we report that ORESARA 15 (ORE15), an Arabidopsis PLANT A/T-RICH SEQUENCE-AND ZINC-BINDING PROTEIN (PLATZ) transcription factor preferentially expressed in the RAM, determines RAM size.

Machine Learning Models That Integrate Tumor Texture and Perfusion Characteristics Using Low-Dose Breast Computed Tomography Are Promising for Predicting Histological Biomarkers and Treatment Failure in Breast Cancer Patients.

This prospective study enrolled 147 women with invasive breast cancer who underwent low-dose breast CT (80 kVp, 25 mAs, 1.01-1.38 mSv) before treatment.

Measurements of the Electrical Conductivity of Monolayer Graphene Flakes Using Conductive Atomic Force Microscopy.

The intrinsic electrical conductivity of graphene is one of the key factors affecting the electrical conductance of its assemblies, such as papers, films, powders, and composites. Here, the local electrical conductivity of the individual graphene flakes was investigated using conductive atomic force microscopy (C-AFM). An isolated graphene flake connected to a pre-fabricated electrode was scanned using an electrically biased tip, which generated a current map over the flake area.

P(III) vs P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to an Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist.

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than 16-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications.

Rosuvastatin Inhibits the Apoptosis of Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells by Inhibiting p38 via Autophagy.

The secretion of platelet-derived growth factors (PDGFs) into vascular smooth muscle cells (VSMCs) induced by specific stimuli, such as oxidized low-density lipoprotein (LDL) cholesterol, initially increases the proliferation and migration of VSMCs, and continuous stimulation leads to VSMC apoptosis, resulting in the formation of atheroma. Autophagy suppresses VSMC apoptosis, and statins can activate autophagy. Thus, this study aimed to investigate the mechanism of the autophagy-mediated vasoprotective activity of rosuvastatin, one of the most potent statins, in VSMCs continuously stimulated with PDGF-BB, a PDGF isoform, at a high concentration (100 ng/ml) to induce phenotypic switching of VSMC.

Polyelemental Nanoparticles as Catalysts for a Li-O Battery.

The development of highly efficient catalysts in the cathodes of rechargeable Li-O batteries is a considerable challenge. Polyelemental catalysts consisting of two or more kinds of hybridized catalysts are particularly interesting because the combination of the electrochemical properties of each catalyst component can significantly facilitate oxygen evolution and oxygen reduction reactions. Despite the recent advances that have been made in this field, the number of elements in the catalysts has been largely limited to two metals.

Regulation of autophagy by controlling Erk1/2 and mTOR for platelet-derived growth factor-BB-mediated vascular smooth muscle cell phenotype shift.

Aims: Vascular smooth muscle cell (VSMC) phenotype shift is involved in the pathophysiology of vascular injury or platelet-derived growth factor (PDGF)-induced abnormal proliferation and migration of VSMCs. We aimed to investigate the underlying mechanism involved in PDGF-mediated signaling pathways and autophagy regulation followed by VSMC phenotype shift.

Main Methods: The proliferation, migration and apoptosis of cultured rat aortic VSMCs were measured, and cells undergoing phenotype shift and autophagy were examined.

Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies.

Sustained-release formulations are important tools to convert efficacious molecules into therapeutic products. Hydrogels enable the rapid assessment of sustained-release strategies, which are important during preclinical development where drug quantities are limited and fast turnaround times are the norm. Most research in hydrogel-based drug delivery has focused around synthesizing new materials and polymers, with limited focus on structural characterization, technology developability and implementation.

Sodium propionate exerts anticancer effect in mice bearing breast cancer cell xenograft by regulating JAK2/STAT3/ROS/p38 MAPK signaling.

Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells.

Annulation reaction enables the identification of an exocyclic amide tricyclic chemotype as retinoic acid Receptor-Related orphan receptor gamma (RORγ/RORc) inverse agonists.

RORγt is the master regulator of the IL-23/IL-17 axis, a pathway that is clinically validated for the treatment of various immunological disorders. Over the last few years, our group has reported different chemotypes that potently act as inverse agonists of RORγt. One of them, the tricyclic pyrrolidine chemotype, has demonstrated biologic-like preclinical efficacy and has led to our clinical candidate BMS-986251.