Spatially Targeted PD-L1 Blockade for Restoring Exhausted Cytotoxic T Lymphocyte Rejuvenation to Potentiate Multimodal-Immune Synergistic Therapies for Breast Cancer Treatment.

The spatial dynamics and heterogeneity of programmed death-ligand 1 (PD-L1) expression within tumors pose significant challenges to the efficacy of PD-L1/programmed death receptor-1 (PD-1) immune checkpoint therapies. This study addresses these challenges by proposing a dual-mechanism strategy to modulate the spatial distribution and functional activity of PD-L1, thereby rejuvenating exhausted cytotoxic T lymphocytes and enhancing multimodal-immune synergistic cancer therapies. Specifically, a PD-L1 nanomodulator is engineered using a polydopamine nanoplatform, integrating a specific inhibitor D-peptide antagonist of PD-L1 for tumor membrane PD-L1 and metformin that can degrade intracellular PD-L1.

-Butoxycarbonyl-Modification Driven Disturbance of Molecular Ordering Enables High-Efficiency Dual Drugs Co-Assembly for Synergistic Tumor Inhibition.

The development of carrier-free drug delivery systems (CDDS) for tailored drug combinations posed a significant challenge, particularly in achieving efficient co-assembly while maintaining therapeutic efficacy. Herein, we proposed a co-assembly strategy based on molecular engineering. Paclitaxel (PTX) and 7-ethyl-10-hydroxycamptothecin (SN38) were chemically modified with -butoxycarbonyl (BOC) groups.

Triethylamine-mediated protonation-deprotonation unlocks dual-drug self assembly to suppress breast cancer progression and metastasis.

Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism.

Supramolecular artificial Nano-AUTACs enable tumor-specific metabolism protein degradation for synergistic immunotherapy.

Autophagy-targeting chimera (AUTAC) has emerged as a powerful modality that can selectively degrade tumor-related pathogenic proteins, but its low bioavailability and nonspecific distribution significantly restrict their therapeutic efficacy. Inspired by the guanine structure of AUTAC molecules, we here report supramolecular artificial Nano-AUTACs (GM NPs) engineered by AUTAC molecule GN [an indoleamine 2,3-dioxygenase (IDO) degrader] and nucleoside analog methotrexate (MTX) through supramolecular interactions for tumor-specific protein degradation. Their nanostructures allow for precise localization and delivery into cancer cells, where the intracellular acidic environment can disrupt the supramolecular interactions to release MTX for eradicating tumor cells, modulating tumor-associated macrophages, activating dendritic cells, and inducing autophagy.

Metal coordination nanotheranostics mediated by nucleoside metabolic inhibitors potentiate STING pathway activation for cancer metalloimmunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an effective way to initiate an immune response against tumors, and the research on agonists targeting STING has become a new hotspot in the development of antitumor drugs. However, as a novel STING agonist, the limited bioavailability and activation routes of manganese ions (Mn) significantly hinder its antitumor effects. To address these challenges, we have designed a metal-coordinated nucleoside metabolic inhibitor (gemcitabine, Gem)-induced metal nanotheranostic (MGP) with PEGylation.

Oral health-related quality of life and associated factors among a sample from East China with severe early childhood caries: a cross-sectional study.

Background: To investigate the oral health-related quality of life (OHRQoL) and associated factors among a sample from East China with severe early childhood caries (S-ECC).

Methods: A total of 316 children with S-ECC and their parents were recruited to participate in a cross-sectional study. Children were examined for caries status using criteria proposed by World Health Organization (WHO).

Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD-L1 in Cancer Therapy.

Cancer immunotherapy using anti-programmed death-ligand 1 (PD-L1) antibodies has been used in various clinical applications and achieved certain results. However, such limitations as autoimmunity, tumor hyperprogression, and overall low patient response rate impede its further clinical application. Mounting evidence has revealed that PD-L1 is not only present in tumor cell membrane but also in cytoplasm, exosome, or even nucleus.

Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection.

The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu&FK@RNPs), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain.

Clinical outcomes of dental treatment under general anesthesia and its effects on the caries activity and body growth of children: a 2-year retrospective study.

Objectives: To analyze clinical outcomes of dental treatment under general anesthesia (DGA) and its effects on children's caries activity status and body growth within 2 years after the treatment.

Materials And Methods: The case data and 2-year follow-up records of children who underwent DGA from February 2017 to February 2018 were collected and analyzed. The general characteristics of the sample, the success rates of treatment procedures, the caries recurrence rate, the caries activity test scores, and the BMI of all the children were described.

Dental maturation in a Chinese sample using Demirjian method.

Background: Dental calcification information is relevant for clinical, archaeological, and forensic applications. However, dental maturity measurements in current cohorts of Chinese children are insufficient.

Aim: This study aimed to establish the mandibular dental maturity table and determine the accuracy of dental age estimation using the Demirjian method in a Chinese sample.

[Radiographic study of the age for crown and root length completion stages of permanent teeth in male and female children].

Purpose: To determine the age medians for crown and root length completion stages of permanent teeth (except for the third molars) and to study gender differences in crown and root length completion stages by radiographic examinations.

Methods: The development of permanent teeth (except for the third molars) was evaluated from 3304 panoramic radiographs of children aged between 3 and 18 years by Haavikko's method. Statistical analysis was performed using SPSS 25.