Lipid nanoparticles: Composition, formulation, and application.

Lipid nanoparticles (LNPs) are lead non-viral vectors for delivering nucleic acids. LNPs can efficiently encapsulate nucleic acids, protect them from degradation, enhance cellular uptake and induce endosome escape, which show high transfection efficiency and low immunogenicity. In this review, we first introduce the LNP components, highlighting their critical roles in encapsulation, stability, delivery efficiency, and tissue tropism.

Box of Lessons: An Open Educational Resource for Exploring Biomolecular Structure and Function.

Structure-function relationships are a core concept in many STEM disciplines. Most biology curricula introduce students to macromolecules, their building blocks, and other small molecules that play key roles in biological processes. However, the shapes, interactions, and functions of these molecules are often discussed using schematic diagrams, ignoring the vast amounts of three-dimensional structural and bioinformatics data freely available from public data resources.

Enhanced ISGylation via USP18 Isopeptidase Inactivation Fails to Mitigate the Inflammatory or Functional Course of Coxsackievirus B3-Induced Myocarditis.

Background/aims: The ubiquitin-like protein ISG15 and its covalent conjugation to substrates (ISGylation) represent a critical interferon (IFN)-induced antiviral mechanism. USP18 is an ISG15-specific isopeptidase and a key negative regulator of type I IFN signaling. While inactivation of USP18's catalytic activity enhances ISGylation and promotes viral resistance, its role in modulating inflammation and cardiac function during CVB3-induced myocarditis remains unclear.

Purifying recombinant proteins from Nicotiana benthamiana for structural studies.

Structural biology is fundamental to understanding the molecular basis of biological processes. While machine learning-based protein structure prediction has advanced considerably, experimentally determined structures remain indispensable for guiding structure-function analyses and for improving predictive modeling. However, experimental studies of protein complexes continue to pose challenges, particularly due to the necessity of high protein concentrations and purity for downstream analyses such as cryogenic electron microscopy.

Characterization of the extrinsic and intrinsic signatures and therapeutic vulnerability of small cell lung cancers.

Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor strongly associated with exposure to tobacco carcinogens, is characterized by early dissemination and dismal prognosis with a five-year overall survival of less than 7%. High-frequency gain-of-function mutations in oncogenes are rarely reported, and intratumor heterogeneity (ITH) remains to be determined in SCLC. Here, via multiomics analyses of 314 SCLCs, we found that the ASCL1/MKI67 and ASCL1/CRIP2 clusters accounted for 74.

Centrosome dysfunction and autophagy dysregulation in renal cell carcinoma: Implications for tumor progression and therapy.

Renal cell carcinoma (RCC) is a heterogeneous kidney malignancy driven by complex genetic, molecular, and metabolic alterations. Emerging evidence implicates centrosome dysfunction and autophagy dysregulation in RCC initiation, progression, and resistance to therapy. The centrosome plays a critical role in mitotic fidelity, and its dysfunction often leads to chromosomal and genomic instability.

Engineering of a Complex of the DNase Domain of Colicin E9 with the Immunity Protein Im9 Activated by the Protease pS273R of African Swine Fever Virus.

African swine fever virus (ASFV) is a large DNA virus that causes a highly lethal disease in pigs and currently has no effective vaccines or antiviral treatments available. We designed a protein switch that combines the DNase domain of colicin E9 (DNase E9) and its inhibitor Im9 with the viral protease cleavage site. The complex is only destroyed in the presence of an ASFV pS273R protease, which releases DNase activity.

Design and Synthesis of Structurally Novel Acridospiroisoxazole Derivatives and Their Antifungal Activity Study.

The persistent threat posed by phytopathogenic fungi to agricultural systems underscores the critical need for novel fungicides. Here, we synthesized and characterized a series of novel acridospiroisoxazole derivatives (H1-H36) using H/C NMR and mass spectrometry. The absolute configuration of compound H23 was confirmed using single-crystal x-ray diffraction analysis.

Intrauterine hyperglycemia impairs mouse primordial germ cell development and fertility by sex-specific epigenetic reprogramming interference.

Adverse intrauterine environments, such as hyperglycemia, impair sexual reproduction and species continuity, yet the underlying mechanisms remain poorly understood. In this study, we demonstrated that intrauterine hyperglycemia significantly disrupted primordial germ cell (PGC) development, especially in female offspring, thus reducing fertility. Using Oct4-EGFP transgenic mice with intrauterine hyperglycemia exposure, we revealed that hyperglycemia compromised sexually specific chromatin accessibility and DNA methylation reprogramming during PGC development.

Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.

Liver cancer, particularly hepatocellular carcinoma (HCC), poses significant treatment challenges due to chemoresistance and cancer recurrence. Similar to customs at the border, the liver detoxifies incoming chemicals via efflux pumps and overexpresses ATP-binding cassette (ABC) drug exporters, leading to chemoresistance. ABC contains a multihomosubunit structure and a revolving transport mechanism, actively effluxing drugs from cancer cells, thereby reducing intracellular drug accumulation and therapeutic efficacy.

Wild bats hunt insects faster under lit conditions by integrating acoustic and visual information.

Animals can improve their decision-making abilities by integrating information from multiple senses, which is especially beneficial when living in fluctuating environments. However, understanding how wild predators may use multimodal sensing when hunting prey in split-second interactions remains largely unexplored. As nocturnal hunters, bats rely on echolocation to navigate and to locate evasive prey, yet they have retained functional vision, despite the associated costs.

Transcription reshapes RNA hairpin folding pathways revealed by all-atom molecular dynamics simulations.

The divergence in folding pathways between RNA co-transcriptional folding (CTF) and free folding (FF) is crucial for understanding dynamic functional regulation of RNAs. Here, we developed a simplified all-atom molecular dynamics framework to systematically compare the folding kinetics of an RNA hairpin (PDB:1ZIH) under CTF and FF conditions. By analyzing over 800 microseconds of simulated trajectory, we found that despite convergence to identical native conformations across CTF simulations (with varied transcription rates) and FF simulations, they exhibit distinct preferences for the folding pathways defined by the order of base-pair formation.

Deletion of ABIN1-LIR motifs impairs hepatic lipid homeostasis and mitophagy via AMPK-TFEB axis in mice.

The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.

A Quantitative Assessment of the Phagocytosis of Allogeneic and Xenogeneic Erythrocytes by Rat Macrophages In Vitro.

Xenogeneic cell transplantation often faces significant immune rejection, even in immunodeficient animal models. Among residual immune components, macrophages can actively phagocytose transplanted human cells, posing a challenge to long-term engraftment. To address this, we developed a standardized in vitro assay to quantify macrophage-mediated phagocytosis of human versus rat red blood cells (RBCs).

Influenza A virus circumvents the innate immune response through the sequestration of double-stranded RNA.

Double-stranded RNA (dsRNA), which induces an innate immune response against viral infections, is rarely detected in influenza A virus (IAV)-infected cells. Nevertheless, we previously reported that the influenza A viral ribonucleoprotein (vRNP) complex generates looped dsRNAs during RNA synthesis . This finding suggests that IAV possesses a specific mechanism for sequestering dsRNA within infected cells, thereby enabling viral evasion of the innate immune response.

Transcriptomic data sets for serovar Typhimurium 14028S that survived ingestion by , hydrogen peroxide treatment, or starvation.

is a pathogenic bacterium that can survive in hostile environments and inside heterotrophic protozoan cells. Here, we present transcriptomic data for grown in a rich medium, cultured under starvation conditions, treated with hydrogen peroxide, and extracted from cells after 8 and 15 h of infection.

Nasal Cytology and Clinical Rhinology Support a Translational Integrative Neuroscience Perspective.

Nasal cytology is evolving into a promising tool for diagnosing neurological and psychiatric disorders, especially those such as Alzheimer's and Parkinson's diseases. Moreover, recent research has indicated that biomarkers differ greatly between samples taken before and after death. Nasal cytology might help to identify the early stages of cognitive decline.

Evaluating endometrial response to human chorionic gonadotropin: alterations in epigenetic regulation and extracellular vesicle cargo of endometrial stromal cells.

Study Question: What is the effect of hCG on the epigenetic profile and the expression of other molecular factors in endometrial stromal cells (ESCs)?

Summary Answer: Our findings suggest that hCG treatment alters the molecular environment of decidualized ESCs, potentially influencing implantation and immune regulation through epigenetic modifications and changes in the levels of secreted proteins and micro-ribonucleic acids (miRNAs).

What Is Known Already: Embryo implantation depends not only on the quality of the embryo but also on the receptivity of the endometrium, the specialized lining of the uterus that undergoes dynamic changes to support pregnancy. Effective communication between the maternal and fetal compartments, facilitated by molecular signals and cellular interactions, is essential for successful implantation.

Benchmarking Ploidy Estimation Methods for Bulk and Single-Cell Whole Genome Sequencing.

Maintaining cellular ploidy is critical for normal physiological processes, although gains in ploidy are frequently observed during development, tissue regeneration, and metabolism, and potentially contribute to aneuploidy, thereby promoting tumor evolution. Although numerous computational tools have been developed to estimate cellular ploidy from whole-genome sequencing (WGS) data at bulk or single-cell resolution, to the knowledge, no systematic comparison of their performance has been conducted. Here, a benchmarking study is presented of 11 methods for bulk WGS and 8 methods for single-cell WGS data, utilizing both experimental and simulated datasets derived from diploid cells mixed with aneuploid or polyploid cells.

Mammalian motile cilia: Structure, formation, organization, and function.

Cilia are membrane-covered hair-like organelles built on specialized centrioles and conserved throughout eukaryotic evolution. They are either motile or immotile, serving respectively as versatile signaling antennae or elegant beating nanomachines. Accordingly, their dysfunctions cause a wide variety of developmental and degenerative disorders, which in human are syndromes termed ciliopathies.

Developing a collaborative network for cystic fibrosis in Africa: A call to action.

Background: Cystic fibrosis (CF) is a genetic disorder that remains underrecognized across Africa, where limited diagnostic capacity, low awareness, and competing health priorities contribute to delayed or missed diagnoses [1-4]. Although increasing data suggests CF is more prevalent than previously believed in Africa, survival remains poor [1]. These challenges do not only affect people with CF (pwCF) in Africa but also have implications for global understanding of the disease, particularly among populations historically excluded from CF research and treatment advances.

Optimization of 2,3-dihydrophthalazine-1,4-dione PARP inhibitor scaffold for nanomolar potency and specificity towards human PARP10.

PARP10 is a potential drug target due to its overexpression in several cancer types and its roles in DNA repair mechanisms and tumorigenesis. In this study, we performed an optimization campaign on our earlier compounds based on a 2,3-dihydrophthalazine-1,4-dione scaffold which emerged with dual PARP10 and PARP15 inhibitory activity. The specific aim was to improve the potency and selectivity towards PARP10.

Unveiling the role of biomolecular condensates in cellular function and cancer.

Biomolecular condensates (BMCs) are membrane-less organelles formed through liquid-liquid phase separation, primarily driven by multivalent interactions between scaffold and client molecules. These dynamic compartments enable cells to spatially and temporally organize biochemical reactions by locally concentrating specific biomolecules, thereby enhancing the frequency of productive molecular interactions and increasing reaction rates. BMCs are integral to normal cellular physiology, with well-characterized examples including the nucleolus and Cajal bodies.

Enriched Environment Alleviate AD Pathological Progression by Reducing Microglia Complement Signaling in Aged Male APP/PS1 Mice.

Alzheimer's disease (AD) is influenced by genetic and environmental factors. Previous studies showed that enriched environments improved memory and reduced amyloid plaques in AD mice, but the underlying mechanisms remain unclear. This study investigated the effects and mechanisms of enriched environments on AD pathology and cognitive function in aged APP/PS1 mice.

Constraint-based metabolic modeling reveals metabolic properties underpinning the unprecedented growth of Chlorella ohadii.

Comparative molecular and physiological analyses of organisms from one taxonomic group grown under similar conditions offer a strategy to identify gene targets for trait improvement. While this strategy can also be performed in silico using genome-scale metabolic models for the compared organisms, we continue to lack solutions for the de novo generation of such models, particularly for eukaryotes. To facilitate model-driven identification of gene targets for growth improvement in green algae, here we present a semiautomated platform for de novo generation of genome-scale algal metabolic models.