Combining Hard Shell with Soft Core to Enhance Enzyme Activity and Resist External Disturbances.

Immobilizing enzymes onto solid supports having enhanced catalytic activity and resistance to harsh external conditions is considered as a promising and critical method of broadening enzymatic applications in biosensing, biocatalysis, and biomedical devices; however, it is considerably hampered by limited strategies. Here, a core-shell strategy involving a soft-core hexahistidine metal assembly (HmA) is innovatively developed and characterized with encapsulated enzymes (catalase (CAT), horseradish peroxidase, glucose oxidase (GOx), and cascade enzymes (CAT+GOx)) and hard porous shells (zeolitic imidazolate framework (ZIF), ZIF-8, ZIF-67, ZIF-90, calcium carbonate, and hydroxyapatite). The enzyme-friendly environment provided by the embedded HmA proves beneficial for enhanced catalytic activity, which is particularly effective in preserving fragile enzymes that will have been deactivated without the HmA core during the mineralization of porous shells.

Artificial Intelligence in Detecting and Segmenting Vertical Misfit of Prosthesis in Radiographic Images of Dental Implants: A Cross-Sectional Analysis.

Objective: This study evaluated ResNet-50 and U-Net models for detecting and segmenting vertical misfit in dental implant crowns using periapical radiographic images.

Methods: Periapical radiographs of dental implant crowns were classified by two experts based on the presence of vertical misfit (reference group). The misfit area was manually annotated in images exhibiting vertical misfit.

Self-Immobilizing Fluorogenic Probe for In Situ Labeling of Granzyme B Activity in Host Immune Response to Bacterial Infections.

Bacterial infections, particularly those caused by drug-resistant bacteria, represent a pressing global health challenge. During the interaction between pathogen infection and host defense, bacterial infections initiate the host's immune response, which involves the activation of proteases that play a critical role in antibacterial defense. Granzyme B (GzmB), a key immune-related biomarker associated with cytotoxic T lymphocytes (CTLs), plays a pivotal role in this process.

A Homozygous Variant in HSD17B1 Identified in Women With Poor Ovarian Response.

An increasing number of patients utilizing in vitro fertilization (IVF) and assisted reproductive technology (ART) are characterized as impaired or poor ovarian responders (PORs). Owing to its unclear molecular etiology, the management of patients with age-related ovarian characteristics remains a controversial and complex clinical concern. Therefore, it is important to identify and understand the etiological causes behind POR to develop more effective and efficient management strategies for these patients.

Photobiomodulation Combined With Human Umbilical Cord Mesenchymal Stem Cells Modulates the Polarization of Microglia.

Neuroinflammation plays a key role in the development of neurodegenerative diseases, with microglia regulating this process through pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) modulate neuroinflammation by secreting anti-inflammatory cytokines. Photobiomodulation (PBM), a non-invasive therapy, has demonstrated significant potential in alleviating neuroinflammation.

3D-Printed Myocardium-Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction.

Despite advancements in engineered heart tissue (EHT), challenges persist in achieving accurate dimensional accuracy of scaffolds and maturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), a primary source of functional cardiac cells. Drawing inspiration from cardiac muscle fiber arrangement, a three-dimensional (3D)-printed multi-layered microporous polycaprolactone (PCL) scaffold is created with interlayer angles set at 45° to replicate the precise structure of native cardiac tissue. Compared with the control group and 90° PCL scaffolds, the 45° PCL scaffolds exhibited superior biocompatibility for cell culture and improved hiPSC-CM maturation in calcium handling.

Improved Efficacy of Triple-Negative Breast Cancer Immunotherapy via Hydrogel-Based Co-Delivery of CAR-T Cells and Mitophagy Agonist.

Leaky and structurally abnormal blood vessels and increased pressure in the tumor interstitium reduce the infiltration of CAR-T cells in solid tumors, including triple-negative breast cancer (TNBC). Furthermore, high burden of tumor cells may cause reduction of infiltrating CAR-T cells and their functional exhaustion. In this study, various effector-to-target (E:T) ratio experiments are established to model the treatment using CAR-T cells in leukemia (high E:T ratio) and solid tumor (low E:T ratio).

Nuclear Condensates of WW Domain-Containing Adaptor With Coiled-Coil Regulate Mitophagy via Alternative Splicing.

Biomolecular condensates segregate nuclei into discrete regions, facilitating the execution of distinct biological functions. Here, it is identified that the WW domain containing adaptor with coiled-coil (WAC) is localized to nuclear speckles via its WW domain and plays a pivotal role in regulating alternative splicing through the formation of biomolecular condensates via its C-terminal coiled-coil (CC) domain. WAC acts as a scaffold protein and facilitates the integration of RNA-binding motif 12 (RBM12) into nuclear speckles, where RBM12 potentially interacts with the spliceosomal U5 small nuclear ribonucleoprotein (snRNP).

Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth.

Colorectal cancer (CRC) usually creates an immunosuppressive microenvironment, thereby hindering immunotherapy response. Effective treatment options remain elusive. Using scRNA-seq analysis in a tumor-bearing murine model, it is found that lobeline, an alkaloid from the herbal medicine lobelia, promotes polarization of tumor-associated macrophages (TAMs) toward M1-like TAMs while inhibiting their polarization toward M2-like TAMs.

Position statement on longitudinal cracks and fractures of teeth.

This position statement is a consensus view of an expert committee convened by the European Society of Endodontology (ESE). The statement is based on current clinical and scientific evidence as well as the collective reflective practice of the committee. The aim is to provide clinicians with evidence-based, authoritative information on the aetiology, clinical presentation, and management of cracks and fractures that typically manifest along the long axis of the crown and/or root.

Trends, Characteristics and Outcomes in Breast Cancer Survivors With STEMI.

Breast cancer is the most common malignancy among women. While advances in detection and treatment have improved survival, breast cancer survivors face an increased risk of cardiovascular disease. However, limited data exist on cardiac outcomes after ST-elevation myocardial infarction (STEMI) in this population.

Temporal and Spatial Metabolic Shifts Revealing the Transition from Ulcerative Colitis to Colitis-Associated Colorectal Cancer.

Patients with ulcerative colitis (UC) have a higher risk of developing colorectal cancer (CRC), however, the metabolic shifts during the UC-to-CRC transition remain elusive. In this study, an AOM-DSS-induced three-stage colitis-associated colorectal cancer (CAC) model is constructed and targeted metabolomics analysis and pathway enrichment are performed, uncovering the metabolic changes in this transition. Spatial metabolic trajectories in the "normal-to-normal adjacent tissue (NAT)-to-tumor" transition, and temporal metabolic trajectories in the "colitis-to-dysplasia-to-carcinoma" transition are identified through K-means clustering of 74 spatially and 77 temporally differential metabolites, respectively.

Two-dimensional inverse double sandwich CoB: strain-induced non-magnetic to ferromagnetic transition.

A full-scale structural search was performed using density functional theory calculations and a universal structural prediction evolutionary algorithm. This produced a lowest energy two-dimensional (2D) CoB structure. The CoB-1 global minimum structure has unusual inverse double sandwich features.

Programmed Transformation of Osteogenesis Microenvironment by a Multifunctional Hydrogel to Enhance Repair of Infectious Bone Defects.

Repair of infectious bone defects remains a serious problem in clinical practice owing to the high risk of infection and excessive reactive oxygen species (ROS) during the early stage, and the residual bacteria and delayed Osseo integrated interface in the later stage, which jointly creates a complex and dynamic microenvironment and leads to bone non-union. The melatonin carbon dots (MCDs) possess antibacterial and osteogenesis abilities, greatly simplifying the composition of a multifunctional material. Therefore, a multifunctional hydrogel containing MCDs (GH-MCD) is developed to meet the multi-stage and complex repair needs of infectious bone injury in this study.

A Highly Bioactive Organic-Inorganic Nanoparticle for Activating Wnt10b Mediated Osteogenesis by Specifically Anchor CCN3 Protein.

The rapid and efficient bone regeneration is still in unsatisfactory outcomes, demonstrating alternative strategy and molecular mechanism is necessary. Nanoscale biomaterials have shown some promising results in enhancing bone regeneration, however, the detailed interaction mechanism between nanomaterial and cells/tissue formation is not clear. Herein, a molecular-based inorganic-organic nanomaterial poly(citrate-siloxane) (PCS) is reported which can rapidly enhance osteogenic differentiation and bone formation through a special interaction with the cellular surface communication network factor 3 (CCN3), further activating the Wnt10b/β-catenin signaling pathway.

Smart Mesoporous Silica Nanoparticles in Cancer: Diagnosis, Treatment, Immunogenicity, and Clinical Translation.

In cancer research and personalized medicine, mesoporous silica nanoparticles (MSNs) have emerged as a significant breakthrough in both cancer treatment and diagnosis. MSNs offer targeted drug delivery, enhancing therapeutic effectiveness while minimizing adverse effects on healthy cells. Due to their unique characteristics, MSNs provide targeted drug delivery, maximizing therapeutic effectiveness with minimal adverse effects on healthy cells.

Delivery of Islatravir via High Drug-Load, Long-acting Microarray Patches for the Prevention or Treatment of Human Immunodeficiency Virus.

This research focuses on developing and characterizing islatravir-loaded dissolving microarray patches (MAPs) to provide an effective, minimally invasive treatment option for human immunodeficiency virus (HIV-1) prevention and treatment. The research involves manufacturing these MAPs using a double-casting approach, and conducting in vitro and in vivo evaluations. Results show that the MAPs have excellent needle fidelity, structural integrity, and mechanical strength.

Universal Hydrogel Carrier Enhances Bone Graft Success: Preclinical and Clinical Evaluation.

Orthopedic, maxillofacial, and complex dentoalveolar bone grafting procedures that require donor-site bone harvesting can be associated with post-surgical complications. There has been widespread adoption of exogenously sourced particulate bone graft materials (BGM) for bone regenerative procedures; however, the particulate nature of these materials may lead to compromised healing outcomes, mainly attributed to structural collapse of the BGM, prolonged tissue healing. In this study, a fully synthetic thermoresponsive hydrogel-based universal carrier matrix (TX) that forms flowable and shapable putties with different BGMs while spatially preserving the particles in a 3D scaffold at the implantation site is introduced.

An on-Demand Oxygen Nano-vehicle Sensitizing Protein and Nucleic Acid Drug Augment Immunotherapy.

Hypoxia severely limits the antitumor immunotherapy for breast cancer. Although efforts to alleviate tumor hypoxia and drug delivery using diverse nanostructures achieve promising results, the creation of a versatile controllable oxygen-releasing nano-platform for co-delivery with immunostimulatory molecules remains a persistent challenge. To address this problem, a versatile oxygen controllable releasing vehicle PFOB@F127@PDA (PFPNPs) is developed, which effectively co-delivered either protein drug lactate oxidase (LOX) or nucleic acids drug unmethylated cytosine-phosphate-guanine oligonucleotide (CpG ODNs).

Therapeutic Black Phosphorus Nanosheets Elicit Neutrophil Response for Enhanced Tumor Suppression.

Black phosphorus (BP) has demonstrated potential as a drug carrier and photothermal agent in cancer therapy; however, its intrinsic functions in cancer treatment remain underexplored. This study investigates the immunomodulatory effects of polyethylene glycol-functionalized BP (BP-PEG) nanosheets in breast cancer models. Using immunocompetent mouse models-including 4T1 orthotopic BALB/c mice and MMTV-PyMT transgenic mice, it is found that BP-PEG significantly inhibits tumor growth and metastasis without directly inducing cytotoxicity in tumor cells.

WDR74-Mediated Ribosome Biogenesis and Proteome Dynamics During Mouse Preimplantation Development.

Preimplantation embryonic development is orchestrated by dynamic changes in the proteome and transcriptome, regulated by mechanisms such as maternal-to-zygotic transition. Here, we employed label-free quantitative proteomics to comprehensively analyze proteome dynamics from germinal vesicle oocytes to blastocysts in mouse embryos. We identified 3490 proteins, including 715 consistently detected across all stages, revealing stage-specific changes in proteins associated with translation, protein modification, and mitochondrial metabolism.

Intermittent Fasting Ameliorates β-Amyloid Deposition and Cognitive Impairment Accompanied by Decreased Lipid Droplet Aggregation Within Microglia in an Alzheimer's Disease Model.

Scope: Alzheimer's disease (AD) is the most prevalent form of dementia, lack of effective therapeutic interventions. In this study, we investigate the impact of intermittent fasting (IF), an alternative strategy of calorie restriction, on cognitive functions and AD-like pathology in a transgenic mouse model of AD.

Methods And Results: APP/PS1 mice at 6 months were randomly allocated to two dietary groups: one receiving ad libitum (AL) feeding and the other undergoing IF for 1 month.

Hypotensive Episodes Identified on 24-Hour Ambulatory Blood Pressure and Impaired Cognitive Function: Insights From the SPRINT Study.

Background: Hypotensive episodes detected by 24-hour ambulatory blood pressure (BP) monitoring capture daily cumulative hypotensive stress and could be clinically relevant to cognitive impairment, but this relationship remains unclear.

Methods: We included participants from the Systolic Blood Pressure Intervention Trial (receiving intensive or standard BP treatment) who had 24-hour ambulatory BP monitoring measured near the 27-month visit and subsequent biannual cognitive assessments. We evaluated the associations of hypotensive episodes (defined as systolic BP drops of ≥20 mm Hg between 2 consecutive measurements that reached <100 mm Hg) and hypotensive duration (cumulative time of systolic BP <100 mm Hg) with subsequent cognitive function using adjusted linear mixed models.

Women's health care committee, Japan Society of Obstetrics and Gynecology: Annual report-2024.

The Women's Health Care Committee was established in 2010 to improve the health of women. In the current academic year, this committee established seven subcommittees aimed at understanding diseases related to various age groups of women, including adolescence, sexual maturity, and menopause, and promoting research to improve the quality of life. Additionally, socially significant research has focused on infections, particularly resistant bacteria.