Supramolecular polyrotaxane-based nano-theranostics enable cancer-cell stiffening for enhanced T-cell-mediated anticancer immunotherapy.

Despite the tremendous therapeutic promise of activating stimulators of interferon genes (STING) enable to prime robust de novo T-cell responses, biomechanics-mediated immune inhibitory pathways hinder the cytotoxicity of T cells against tumor cells. Blocking cancer cell biomechanics-mediated evasion provides a feasible strategy for augmenting STING activation-mediated anti-tumor therapeutic efficacy. Here, we fabricate a redox-responsive Methyl-β-cyclodextrin (MeβCD)-based supramolecular polyrotaxanes (MSPs), where the amphiphilic diselenide-bridged axle polymer loads MeβCD by the host-guest interaction and end-caping with two near-infrared (NIR) fluorescence probes IR783.

Managing interactional breakdowns with children with ASD: Therapists' practices when directives face challenges in therapeutic interactions.

Effective interventions to promote language competence, cognitive abilities and integrate these skills into daily activities for children with autism spectrum disorder (ASD) often involve providing guidance and training through specific tasks, typically delivered by speech and language therapists through directive interactions. However, engaging children with ASD in such activities is not straightforward and often fraught with challenges. Yet we know very little about how practitioners cope when the interaction breaks down, for example, due to misunderstandings or failures to engage.

Semiconducting Open-Shell Radicals for Precise Tumor Activatable Phototheranostics.

Semiconducting open-shell radicals (SORs) have promising potential for the development of phototheranostic agents, enabling tumor bioimaging and boosting tumorous reactive oxygen species (ROS). Herein, a new class of semiconducting perylene diimide (PDI), designated as PDI(Br) with various numbers of bromine (Br) atoms modified on PDI's bay/ortho positions is reported. PDI(Br) is demonstrated to transform into a radical anion, [PDI(Br)], in a reducing solution, with a typical g-value of 2.

Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies.

In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases.

Alkoxylation and Phosphorylation of Pyrimidine Disulfides: Green Synthesis of Alkoxypyrimidine Thioethers and Pyrimidine Phosphorothioates.

This paper addresses a novel, green, and sustainable method to construct new C-S and P-S bonds by cleaving the S-S bond in pyrimidine disulfide under various conditions. The first alkoxylation and phosphorylation of pyrimidine disulfide are effectively accomplished by this approach. Compared to the methods reported, this approach provides more benefits, including the utilization of eco-friendly solvents, straightforward procedure, mild reaction conditions, high atomic efficiency, and a broad range of applicable substrates.

Optimized design for using of double-barrel vascularized fibular flap in various types of mandibular defects.

Background/purpose: The functional and aesthetic reconstruction of the mandible can be achieved by using the double-barrel vascularized free fibula flap. The purpose of this study was to use multiple integrated techniques to more effectively reconstruct the mandible, some contains of our unique ideas.

Materials And Methods: 21 patients were included in this study.

IdenHerb: A strategy for identifying constitutive herbs of herbal products by screening exclusive ions of each herb from large-scale multi-group LC-MS data.

Identification of constitutive herbs in an herbal product is critical for ensuring its quality and efficacy. However, current identification methods often lack universality, entail long durations, and involve complex procedures. Therefore, there is an urgent need to develop innovative methods for identifying constitutive herbs.

PET-Assessed Metabolic Tumor Volume Across the Spectrum of Solid-Organ Malignancies: A Review of the Literature.

Solid-organ malignancies represent a significant disease burden and remain one of the leading causes of death globally. In the past few decades, the rapid evolution of imaging modalities has shifted the paradigm towards image-based precision medicine, especially in the care of patients with solid-organ malignancies. Metabolic tumor volume (MTV) is one such semi-quantitative parameter obtained from positron emission tomography (PET) imaging with F-fluorodeoxyglucose (FDG) that has been shown to have significant implications in the clinical oncology setting.

Single-cell chromatin accessibility landscape profiling reveals the diversity of epigenetic regulation in the rat nervous system.

The mammalian nervous system controls complex functions through highly specialized and interacting structures. Single-cell sequencing can provide information on cell-type-specific chromatin structure and regulatory elements, revealing differences in chromatin organization between different cell types and their potential roles of these differences in brain function. Here, we generated a chromatin accessibility dataset through single-cell ATAC-seq of 174,593 high-quality nuclei from 16 adult rat brain regions.

LILRB4 as a novel immunotherapeutic target for multiple diseases.

Immune checkpoints are critical for maintaining autoimmune homeostasis and are implicated in various autoimmune diseases, with their significance increasingly recognized. Investigating the functions and mechanisms of these checkpoints is essential for the development of more effective treatments. Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4) stands out as a unique immune checkpoint, with limited expression in most normal tissues but prominent presence in various hematological and solid tumors.

Polysaccharide lyase PL3.3 possibly potentiating Clostridioides difficile clinical symptoms based on complete genome analysis of RT046/ST35 and RT012/ST54.

Clostridioides difficile has rapidly become a major cause of nosocomial infectious diarrhea worldwide due to the misuse of antibiotics. Our previous study confirmed that RT046/ST35 strain is associated with more severe clinical symptoms compared to RT012/ST54 strain. We conducted genome comparison of the RT046/ST35 and RT012/ST54 strains using whole-genome sequencing technology.

A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors.

Background: Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine was synergistic, ribociclib was evaluated in combination with gemcitabine to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).

Methods: In this single arm multicohort phase I trial, we evaluated the safety and efficacy of ribociclib plus gemcitabine in patients with advanced solid tumors. Patients received gemcitabine intravenously on days 1 and 8 followed by ribociclib days 8-14, with treatment repeated every 3 weeks.

Single-Cell Multi-omics Assessment of Spinal Cord Injury Blocking via Cerium-doped Upconversion Antioxidant Nanoenzymes.

Spinal cord injury (SCI) impairs the central nervous system and induces the myelin-sheath-deterioration because of reactive oxygen species (ROS), further hindering the recovery of function. Herein, the simultaneously emergency treatment and dynamic luminescence severity assessment (SETLSA) strategy is designed for SCI based on cerium (Ce)-doped upconversion antioxidant nanoenzymes (Ce@UCNP-BCH). Ce@UCNP-BCH can not only efficiently eliminate the SCI localized ROS, but dynamically monitor the oxidative state in the SCI repair process using a ratiometric luminescence signal.

Effects of BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats.

Background: Simulated microgravity environment can lead to gastrointestinal motility disturbance. The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor (SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells. Moreover, intestinal flora can also affect the regulation of SCF/c-kit signaling pathway, thus affecting the expression of Cajal stromal cells.

Inflammatory disease in people with multiple sclerosis treated with immune checkpoint inhibitors.

This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms.

Multi-omics analysis reveals interactions between host and microbes in Bama miniature pigs during weaning.

Introduction: There are complex interactions between host and gut microbes during weaning, many of the mechanisms are not yet fully understood. Previous research mainly focuses on commercial pigs, whereas limited information has been known about the host and gut microbe interactions in miniature pigs.

Methods: To address the issue in Bama miniature piglets that were weaned 30 days after birth, we collected samples on days 25 and 36 for metabolomics, transcriptomics, and microgenomics analysis.

Placental and Fetal Microbiota in Rhesus Macaque: A Case Study Using Metagenomic Sequencing.

Recent evidence challenging the notion of a sterile intrauterine environment has sparked research into the origins and effects of fetal microbiota on immunity development during gestation. Rhesus macaques (RMs) serve as valuable nonhuman primate models due to their similarities to humans in development, placental structure, and immune response. In this study, metagenomic analysis was applied to the placenta, umbilical cord, spleen, gastrointestinal tissues of an unborn RM fetus, and the maternal intestine, revealing the diversity and functionality of microbes in these tissues.

Activatable Molecular Probes With Clinical Promise for NIR-II Fluorescent Imaging.

The second near-infrared window (NIR-II) fluorescence imaging has been widely adopted in basic scientific research and preclinical applications due to its exceptional spatiotemporal resolution and deep tissue penetration. Among the various fluorescent agents, organic small-molecule fluorophores are considered the most promising candidates for clinical translation, owing to their well-defined chemical structures, tunable optical properties, and excellent biocompatibility. However, many currently available NIR-II fluorophores exhibit an "always-on" fluorescence signal, which leads to background noise and compromises diagnostic accuracy during disease detection.

Recommending surgical or non-surgical treatments in medical consultations: The case in Chinese contexts.

Objectives: This study examines the design and delivery of surgical and non-surgical treatment recommendations in China.

Methods: We examined 936-minute recordings of medical consultations using conversation analysis. Data were collected from two tertiary hospitals in China.

Morphological modulation of starch chains from nanorod to nanospindle via temperature-controlling rearrangement.

Polymorphic nanoparticles, including starch nanoparticles (SNPs), have increasingly attracted attention, particularly rod-shaped variants, which are used for constructing anisotropic systems. Compared to symmetrically spherical particles, they show superior properties such as gastrointestinal retention for functional nutrients/drugs delivery and mechanical enhancement of filled materials, but their controlled fabrication remains a challenge. In this study, we yielded polymorphic SNPs with nearly axisymmetric geometries through a combined alkaline hydrolysis and nanoprecipitation method, followed by temperature-controlling rearrangement.

A supramolecular assembly strategy for the treatment of rheumatoid arthritis with ultrasound-augmented inflammatory microenvironment reprograming.

As regulators and promotors of joint erosion, pro-inflammatory M1-like macrophages play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). Here, we develop a supramolecular self-assembly (PCSN@MTX) of molybdenum (Mo) based polyoxometalate (POM), β-cyclodextrin (β-CD), and methotrexate (MTX), in which the MTX is loaded by host-guest interaction. PCSN@MTX shows inhibition of synovial M1-like macrophages polarization to alleviate RA.

Exercise: a non-drug strategy of NK cell activation.

Natural killer (NK) cells are a critical component of the innate immune system and one of the immune cells most sensitive to exercise. So far, it is widely believed that moderate exercise can significantly enhance the proliferation and activity of NK cells, strengthening immune function. However, the impact of exercise on NK cells is a dynamic and complex process.

Tumor organoids for primary liver cancers: A systematic review of current applications in diagnostics, disease modeling, and drug screening.

Background & Aims: Liver cancer-related deaths are projected to exceed one million annually by 2030. Existing therapies have significant limitations, including severe side effects and inconsistent efficacy. Innovative therapeutic approaches to address primary liver cancer (PLC) have led to the ongoing development of tumor-derived organoids.