Long-Term Natural Hydroxyapatite and Synthetic Collagen Hydroxyapatite Enhance Bone Regeneration and Implant Fixation Similar to Allograft in a Sheep Model of Implant Integration.

There is an increasing demand for a suitable bone substitute to replace current clinical gold standard autografts or allografts. Majority of previous studies have focused on the early effects of substitutes on bone formation, while information on their long-term efficacies remains limited. This study investigated the efficacies of natural hydroxyapatite (nHA) derived from oyster shells and synthetic hydroxyapatite mixed with collagen (COL/HA) or chitosan (CS/HA) on bone regeneration and implant fixation in sheep.

Structure-Based Design of "Head-to-Tail" Macrocyclic PROTACs.

Macrocyclization is a compelling strategy for conventional drug design for improving biological activity, target specificity, and metabolic stability, but it was rarely applied to the design of PROTACs possibly due to the mechanism and structural complexity. Herein, we report the rational design of the first series of "Head-to-Tail" macrocyclic PROTACs. The resulting molecule exhibited pronounced Brd4 protein degradation with low nM DC values while almost totally dismissing the "hook effect", which is a general character and common concern of a PROTAC, in multiple cancer cell lines.

Superolateral capsule pathway: a new arthroscopic viewing approach for spotting femoral fixation device in anterior cruciate ligament reconstruction.

Background: This study aimed to describe the arthroscopic superlateral capsule pathway technique for spotting femoral fixation device deployment, and to compare the results with normal procedure.

Methods: A total of 69 patients underwent ACLR (Anterior Cruciate Ligament Reconstruction) with or without the SCP (superolateral capsule pathway) during procedure were retrospectively selected and evaluated. A total of 36 patients underwent SCP and 33 patients underwent ACLR without SCP.

Multimodal Trajectory Prediction for Diverse Vehicle Types in Autonomous Driving with Heterogeneous Data and Physical Constraints.

The accurate prediction of vehicle behavior is crucial for autonomous driving systems, impacting their safety and efficiency in complex urban environments. To address the challenge of multi-agent trajectory prediction, we propose a novel model integrating multiple input modalities, including historical trajectories, map data, vehicle features, and interaction information. Our approach employs a Conditional Variational Autoencoder (CVAE) framework with a decoder that predicts control actions using the Gaussian Mixture Model (GMM) and then converts these actions into dynamically feasible trajectories through a bicycle model.

Pesticide avermectin B1a exerts cytotoxicity by blocking the interaction between mini-chromosome maintenance 6 protein (MCM6) and chromatin licensing and DNA replication factor 1 (CDT1).

Avermectin B1a, a widely used pesticide, has recently raised safety concerns since it possesses potential cytotoxicity toward mammalian cells. Nevertheless, the exact mechanisms that underlie the cytotoxicity induced by avermectin B1a remain elusive. The loading of the mini-chromosome maintenance 6 protein (MCM6) onto chromatin at replication origins by chromatin licensing and DNA replication factor 1 (CDT1) is an essential step for licensing DNA for replication.

YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway.

Background: Although imatinib (IM) and subsequent tyrosine kinase inhibitors (TKIs) significantly improve the prognosis of GIST patients by delaying metastasis and recurrence, most patients experience limited efficacy due to toxicity and secondary resistance. We evaluated Yes-associated protein (YAP), a coactivator of the Hippo pathway accounting for IM resistance and aggressive GIST phenotypes, in GISTs. The degradation of YAP is mediated by FBXW7, and FBXW7 predicts recurrence and IM efficacy for GIST patients.

The regulation of ovarian degeneration in Pampus argenteus by heat shock protein genes under low-temperature stress.

Temperature is a crucial environmental factor that significantly impacts the growth, development, metabolism, and physiological functions of fish. To study the effects of low-temperature on the gonadal development of silver pomfret (Pampus argenteus), a cold period by gradually lowering the water temperature from 18°C to 9°C was simulated. The results showed that hsp70, hsp90a, and hsp90b were widely expressed in the tissues of P.

Biomechanical comparison of Gofried positive support reduction of Pauwels type III femoral neck fractures: A finite elements analysis.

Objective: This study aims to investigate the biomechanical characteristics of non-anatomical reduction and different screw positions on the stability of Pauwels type III femoral neck fractures.

Methods: Three-dimensional finite element models of femoral neck fractures were constructed using CT images. Four types of internal fixation methods were simulated, including biplane double-supported screw fixation (BDSF), three inverted triangular parallel cannulated screws (3CS), new parallel cannulated screws with posterior screws moving down (New 3CS), and two parallel cannulated screws (2CS).

Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader.

Neuronal LAMP2A-mediated reduction of adenylyl cyclases induces acute neurodegenerative responses and neuroinflammation after ischemic stroke.

Lysosomes regulate cellular metabolism to maintain cell survival, but the mechanisms whereby they determine neuronal cell fate after acute metabolic stress are unknown. Neuron-enriched lysosomal membrane protein LAMP2A is involved in selective chaperone-mediated autophagy and exosome loading. This study demonstrates that abnormalities in the neuronal LAMP2A-lysosomal pathway cause neurological deficits following ischemic stroke and that this is an early inducer of the PANoptosis-like molecular pathway and neuroinflammation, simultaneously inducing upregulation of FADD, RIPK3, and MLKL after ischemia.

Emergency department discharges directly to hospice: Longitudinal assessment of a streamlined referral program.

Introduction: 80 % of Americans wish to die somewhere other than a hospital, and hospice is an essential resource for providing such care. The emergency department (ED) is an important location for identifying patients with end-of-life care needs and providing access to hospice. The objective of this study was to analyze a quality improvement (QI) program designed to increase the number of patients referred directly to hospice from the ED, without the need for an observation stay and without access to in-hospital hospice.

Folylpolyglutamate synthetase inactivation in relapsed ALL induces a druggable folate metabolic vulnerability.

Aims: The antifolate methotrexate (MTX) is an anchor drug used in acute lymphoblastic leukemia (ALL) with poorly understood chemoresistance mechanisms in relapse. Herein we find decreased folate polyglutamylation network activities and inactivating FPGS mutations, both of which could induce MTX resistance and folate metabolic vulnerability in relapsed ALL.

Methods: We utilized integrated systems biology analysis of transcriptomic and genomic data from relapse ALL cohorts to infer hidden ALL relapse drivers and related genetic alternations during clonal evolution.

Molecular Dynamics Investigation of Metastable Structure and Hybridization Bond Evolution in High-Entropy CoCrFeNi Heterostructured Amorphous Carbon Films.

Heterogeneous element doping in amorphous carbon films can reduce residual stresses and improve plastic deformation. Nevertheless, the effects of dopant content and size on the metastable transition mechanism between sp-C and sp-C atoms during the deformation process are unclear and difficult to be in situ observed and researched, experimentally. In this work, the mechanical properties and the structural evolution during the nanoindentation of amorphous CoCrFeNi sphere-doped carbon heterostructured films with different radii were simulated.

An Energy Efficient and Temperature Stable Digital FLL-based Wakeup Timer with Time-Domain Temperature Compensation.

This brief presents an on-chip digital intensive frequency-locked loop (DFLL)-based wakeup timer with a time-domain temperature compensation featuring a embedded temperature sensor. The proposed compensation exploits the deterministic temperature characteristics of two complementary resistors to stabilize the timer's operating frequency across the temperature by modulating the activation time window of the two resistors. As a result, it achieves a fine trimming step (± 1 ppm), allowing a small frequency error after trimming (<± 20 ppm).

Dietary effects of vitamin C on antioxidant capacity, intestinal microbiota and the resistance of pathogenic bacteria in cultured Silver pomfret (Pampus argenteus).

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively.

Recombinant Art v4.01 protein produces immunological tolerance by subcutaneous immunotherapy in a wormwood pollen-driven allergic asthma female mouse model.

Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and cross-sensitization. It is also referred to as Wormwood due to its origin.

Effectiveness and Safety of Superimposed High-Frequency Jet Ventilation in Rigid Bronchoscopy: A Single-Center, Retrospective Study.

Superimposed high-frequency jet ventilation (SHFJV) is a new type of jet ventilation, but its safety and effectiveness in rigid bronchoscopy have not been fully verified, especially in patients with airway stenosis and preoperative cardiovascular disease. This study is intended to retrospectively analyze the effectiveness and safety of SHFJV in the endobronchial treatment under rigid bronchoscopy. A total of 363 patients were included in this study.

Electrical impedance detects early stages of bone healing: An in vivo explanatory study of tibial fractures in rabbits.

Purpose: Healing after bone fracture is assessed by clinical examination and frequent radiographs, which expose patients to radiation and lack standardisation. This study aimed to explore electrical impedance patterns during bone healing using electrical impedance spectroscopy in 18 rabbits subjected to tibial fracture stabilised with an external fixator.

Methods: Impedance was measured daily across the fracture site at a frequency range of 5 Hz to 1 MHz.

Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling.

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear.