A pH-Sensitive Delivery System for the Prevention of Dental Caries Using Salivary Protein

Dental caries remains one of the most common chronic diseases worldwide. In previous studies, salivary proteins (e.g. histatin 3, statherin) have demonstrated biological functions including the inhibition of crystal growth, antibacterial activities, which are directly related to tooth homeostasis and prevention of dental caries. However, proteins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to protect proteins against enzymatic degradation at physiological salivary pH, in addition to swell selectively at lower pH conditions to facilitate the release of the encapsulated proteins, as major oral complications occur under acidic conditions (e.g. dental caries and dental erosion). Four different types of chitosan polymers were investigated and the optimal CNs formulation was selected, the chosen formulation had a good batch to batch reproducibility with an average hydrodynamic diameter of 144 ± 6 nm, a polydispersity index of 0.15 ± 0.04, and a zeta potential of 18 ± 4 mV at the final pH of 6.2. Histatin 3 encapsulation and release profiles were characterized by cationic polyacrylamide gel electrophoresis. The CNs successfully encapsulated histatin 3 at 2%, 5% and 10% w/w loading ratios, they also selectively released histatin 3 under acidic conditions. Through protein degradation study in whole saliva supernatant, histatin 3 encapsulated inside the delivery system demonstrated a prolonged survival time compared to the free histatin 3. The results of this study have demonstrated the pH-responsive property and the protection offered by CNs

MODELLING AND SIMULATION OF NONLINEAR DYNAMIC FLOW FIELD AND TEMPERATURE FIELD OF DEPYROGENATION TUNNEL

Nonlinear dynamics plays a crucial role particularly in equipment validation of preparation production, validation results of which will significantly influence the results and period of drug registration in drug production processes. In this research, the flow field and temperature field simulation, calculation and analysis are creatively carried out in terms of depyrogenation tunnel, a very popular preparation drying-sterilization equipment in pharmaceutical processes with strong dynamic characteristics. After construction of 3D model of this equipment using Catia and mesh generation applying ANSYS, the computational fluid dynamic (CFD) method and verification of irrelevance method are carried out regarding 6.05 million of meshes to identify the flow velocity model and heat transfer model inside the equipment, to further provide methodology for pharmaceutical process validation and to further optimize the design of control methods. After calculation and simulation, the low-velocity vortices of different sizes inside the hood and the drying chamber are identified, which could cause vials to fall down; meanwhile, vials that are farther away from the outlet receives less heat exchange effect, which would shrink the effective sterilization area, indicating an inadequate validation methodology in pharmaceutical processes

Ph-sensitive chitosan nanoparticles for salivary protein delivery

Salivary proteins such as histatins (HTNs) have demonstrated critical biological functions directly related to tooth homeostasis and prevention of dental caries. However, HTNs are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparti-cles (CNs) have been proposed as potential carriers to protect proteins from enzymatic degradation at physiological salivary pH. Four different types of chitosan polymers were investigated and the optimal formulation had good batch to batch reproducibility, with an average hydrodynamic diame-ter of 144 ± 6 nm, a polydispersity index of 0.15 ± 0.04, and a zeta potential of 18 ± 4 mV at a final pH of 6.3. HTN3 encapsulation and release profiles were characterized by cationic polyacrylamide gel electrophoresis. The CNs successfully encapsulated HTN3 and selectively swelled at acidic pH to facilitate HTN3 release. Protection of HTN3 against enzymatic degradation was investigated in diluted whole saliva. HTN3 encapsulated in the CNs had a prolonged survival time compared to the free HTN3. CNs with and without HTN3 also successfully reduced biofilm weight and bacterial viability. The results of this study have demonstrated the suitability of CNs as potential protein carriers for oral applications, especially for complications occurring at acidic conditions

PathAsst: Redefining Pathology through Generative Foundation AI Assistant for Pathology

As advances in large language models (LLMs) and multimodal techniques continue to mature, the development of general-purpose multimodal large language models (MLLMs) has surged, with significant applications in natural image interpretation. However, the field of pathology has largely remained untapped in this regard, despite the growing need for accurate, timely, and personalized diagnostics. To bridge the gap in pathology MLLMs, we present the PathAsst in this study, which is a generative foundation AI assistant to revolutionize diagnostic and predictive analytics in pathology. To develop PathAsst, we collect over 142K high-quality pathology image-text pairs from a variety of reliable sources, including PubMed, comprehensive pathology textbooks, reputable pathology websites, and private data annotated by pathologists. Leveraging the advanced capabilities of ChatGPT/GPT-4, we generate over 180K instruction-following samples. Furthermore, we devise additional instruction-following data, specifically tailored for the invocation of the pathology-specific models, allowing the PathAsst to effectively interact with these models based on the input image and user intent, consequently enhancing the model's diagnostic capabilities. Subsequently, our PathAsst is trained based on Vicuna-13B language model in coordination with the CLIP vision encoder. The results of PathAsst show the potential of harnessing the AI-powered generative foundation model to improve pathology diagnosis and treatment processes. We are committed to open-sourcing our meticulously curated dataset, as well as a comprehensive toolkit designed to aid researchers in the extensive collection and preprocessing of their own datasets. Resources can be obtained at https://github.com/superjamessyx/Generative-Foundation-AI-Assistant-for-Pathology.Comment: 13 pages, 5 figures, conferenc

The Role of FGFR1 Gene Amplification as a Poor Prognostic Factor in Squamous Cell Lung Cancer: A Meta-Analysis of Published Data

Objectives. The prognostic factors of the fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) remain controversial. Methods. We conducted a meta-analysis of published studies from 1974 to February 2015. In absence of quality difference between studies of reporting significant and nonsignificant results, the relationship between FGFR1 amplification and clinicopathological parameters in NSCLC was analyzed. And also the combined hazard ratio (HR) and their corresponding 95% confidence interval (CI) were calculated in terms of overall survival. Results. 3178 patients (12 studies) were included in the analysis. It was shown that FGFR1 amplification was significantly more prevalent among male patients (RR 2.03, 95% CI 1.57-2.63) with squamous cell lung cancer (SQCC) (RR 3.49, 95% CI 2.62-4.64) and current smokers (RR 2.63, 95% CI 1.92-3.60). The pooled data also showed that the FGFR1 amplification was a poor prognostic factor in SQCC (HR 1.38, 95% CI 1.07-1.78), Asian patients (HR 1.78, 95% CI 1.22-2.60), and fluorescence in situ hybridization (FISH) method (HR 1.30, 95% CI 1.06-1.58). Conclusions. This meta-analysis strongly suggests that FGFR1 amplification occurs more frequently in male, SQCC and smokers, and it is a risk factor for poor prognosis among Asian patients with SQCC

Establishing chromosomal design-build-test-learn through a synthetic chromosome and its combinatorial reconfiguration

Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL with a redesigned synthetic Saccharomyces cerevisiae chromosome XV, synXV. We designed and built synXV to harbor strategically inserted features, modified elements, and synonymously recoded genes throughout the chromosome. Based on the recoded chromosome, we developed a method to enable chrDBTL: CRISPR-Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). CRIMiRE allowed the creation of customized wild-type/synthetic combinations, accelerating genotype-phenotype mapping and synthetic chromosome redesign. We also leveraged synXV as a "build-to-learn" model organism for translation studies by ribosome profiling. We conducted a locus-to-locus comparison of ribosome occupancy between synXV and the wild-type chromosome, providing insight into the effects of codon changes and redesigned features on translation dynamics in vivo. Overall, we established synXV as a versatile reconfigurable system that advances chrDBTL for understanding biological mechanisms and engineering strains. </p

Kinetic Theory Approach to Modeling of Cellular Repair Mechanisms under Genome Stress

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances