In vivo and in vitro effects of Bletilla striata polysaccharide-loaded paclitaxel nanoparticles on human gastric cancer cells

Purpose: To investigate the in vivo and in vitro effects of paclitaxel nanoparticle (PTX)-loaded Bletilla striata polysaccharide (BSP) on human gastric cancer cells.Methods: Mice weighing 13 to 17 g and aged 4 to 6 weeks, were inoculated with human gastric gland cancer cell line (MKN45), and randomly assigned to five groups: control group, PTX-1 (10 mk/kg) group; PTX-2 (15 mg/kg) group, BSP-PTX-1 (10 mg/kg) group, and BSP-PTX-2 (15 mg/kg) group. The antiproliferative influence of BSP-PTX and its cellular target were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and fluorescence microscopy, respectively.Results: Inhibition of MKN45 cells was significantly higher in BSP-PTX group (88.24 %) than in PTX group (76.74 %, p < 0.05). More BSP-PTX entered the cells than PTX. Tumor inhibition was significantly low in PTX-1 group (37.58 %), relative to the BSP-PTX-I group (45.00 %, p < 0.5). In addition, tumor inhibition was significantly lower in PTX-2 group (52.35 %) than in BSP-PTX-2 group (69.80 %, p < 0.5). The weight gain of mice was lower in the PTX or BSP-PTX groups than in control mice, while the weight gain of mice in BSP-PTX-2 group (26.35 %) was significantly higher than that of PTX-2 group (19.43 %, p < 0.5).Conclusion: Bletilla striata polysaccharide-loaded paclitaxel nanoparticles enhance drug delivery, and effectively and safely exert anti-proliferative effect on MKN45 cells and in mice. Thus, these nanoparticles have good potential for development into anti-gastric cancer agents for clinical application.Keywords: Bletilla striata polysaccharide, Paclitaxel nanoparticles, Human gastric cancer cells, Tumor target, Liver cance

Comprehensive Analysis, Discussion and Suggestion on the Current Situation of Cardiopulmonary Resuscitation and Automatic External Defibrillator in General Public in China

The number of sudden cardiac death (SCD) has increased year by year, which has become one of the main causes of death in China. Timely cardiopulmonary resuscitation (CPR) and timely and accurate use of automatic external defibrillator (AED) can greatly improve the survival rate of patients with sudden cardiac death. Because the large probability of sudden cardiac death occurs outside the hospital, it is very important for the general public to master first aid skills. This paper will mine all kinds of data from multi-dimensional and multi-angle, analyze the mastery of public first aid skills in China, and provide practical suggestions and ideas for popularizing first aid skills in the future

Quantum exploration algorithms for multi-armed bandits

Identifying the best arm of a multi-armed bandit is a central problem in bandit optimization. We study a quantum computational version of this problem with coherent oracle access to states encoding the reward probabilities of each arm as quantum amplitudes. Specifically, we show that we can find the best arm with fixed confidence using $\tilde{O}\bigl(\sqrt{\sum_{i=2}^n\Delta^{\smash{-2}}_i}\bigr)$ quantum queries, where $\Delta_{i}$ represents the difference between the mean reward of the best arm and the $i^\text{th}$-best arm. This algorithm, based on variable-time amplitude amplification and estimation, gives a quadratic speedup compared to the best possible classical result. We also prove a matching quantum lower bound (up to poly-logarithmic factors).Comment: 18 pages, 1 figure. To appear in the Thirty-Fifth AAAI Conference on Artificial Intelligence (AAAI 2021

Endothelial toll-like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a.

We previously reported that the canonical innate immune receptor toll-like receptor 4 (TLR4) is critical in maintaining lung integrity. However, the molecular mechanisms via which TLR4 mediates its effect remained unclear. In the present study, we identified distinct contributions of lung endothelial cells (Ec) and epithelial cells TLR4 to pulmonary homeostasis using genetic-specific, lung- and cell-targeted in vivo methods. Emphysema was significantly prevented via the reconstituting of human TLR4 expression in the lung Ec of TLR4-/- mice. Lung Ec-silencing of TLR4 in wild-type mice induced emphysema, highlighting the specific and distinct role of Ec-expressed TLR4 in maintaining lung integrity. We also identified a previously unrecognized role of TLR4 in preventing expression of p16INK4a , a senescence-associated gene. Lung Ec-p16INK4a -silencing prevented TLR4-/- induced emphysema, revealing a new functional role for p16INK4a in lungs. TLR4 suppressed endogenous p16INK4a expression via HDAC2-mediated deacetylation of histone H4. These findings suggest a novel role for TLR4 in maintaining of lung homeostasis via epigenetic regulation of senescence-related gene expression

ARLTS1 polymorphisms and basal cell carcinoma of the skin

Polymorphisms in the ARLTS1 gene, a member of the Ras super-family, have been associated with susceptibility in different cancer types. The involvement of the gene in apoptotic signalling motivated us to study the role of ARLTS1 polymorphic variations in basal cell carcinoma of the skin (BCC). In a case-control study, 529 cases diagnosed with BCC and 533 controls from Hungary, Romania and Slovakia were genotyped for the S99S (297G>A), P131L (392C>T), L132L (396G>C), C148R (442T>C) and W149X (446G>A) polymorphisms in the ARLTS1 gene. No significant association between any of the single nucleotide polymorphisms (SNP) and risk of BCC (S99S, odds ratio (OR) 0.96, 95% confidence interval (CI) 0.60-1.53; P131L, OR 1.31 95%CI 0.74-2.31; L132L, OR 0.50, 95%CI 0.02-7.07; C148R, OR 0.50, 95%CI 0.69-1.18; and W149X, OR 1.01, 95%CI 0.37-2.79) was detected. Furthermore, no significant difference in the distribution of haplotypes due to five polymorphisms in the ARLTS1 gene was found between the BCC cases and controls. Our data rule out an association between variants in ARLTS1 and risk of BCC in the investigated population

FederatedScope-LLM: A Comprehensive Package for Fine-tuning Large Language Models in Federated Learning

LLMs have demonstrated great capabilities in various NLP tasks. Different entities can further improve the performance of those LLMs on their specific downstream tasks by fine-tuning LLMs. When several entities have similar interested tasks, but their data cannot be shared because of privacy concerns regulations, federated learning (FL) is a mainstream solution to leverage the data of different entities. However, fine-tuning LLMs in federated learning settings still lacks adequate support from existing FL frameworks because it has to deal with optimizing the consumption of significant communication and computational resources, data preparation for different tasks, and distinct information protection demands. This paper first discusses these challenges of federated fine-tuning LLMs, and introduces our package FS-LLM as a main contribution, which consists of the following components: (1) we build an end-to-end benchmarking pipeline, automizing the processes of dataset preprocessing, federated fine-tuning execution, and performance evaluation on federated LLM fine-tuning; (2) we provide comprehensive federated parameter-efficient fine-tuning algorithm implementations and versatile programming interfaces for future extension in FL scenarios with low communication and computation costs, even without accessing the full model; (3) we adopt several accelerating and resource-efficient operators for fine-tuning LLMs with limited resources and the flexible pluggable sub-routines for interdisciplinary study. We conduct extensive experiments to validate the effectiveness of FS-LLM and benchmark advanced LLMs with state-of-the-art parameter-efficient fine-tuning algorithms in FL settings, which also yields valuable insights into federated fine-tuning LLMs for the research community. To facilitate further research and adoption, we release FS-LLM at https://github.com/alibaba/FederatedScope/tree/llm.Comment: Source code: https://github.com/alibaba/FederatedScope/tree/ll

Targeting ferroptosis as a promising therapeutic strategy to treat cardiomyopathy

Cardiomyopathies are a clinically heterogeneous group of cardiac diseases characterized by heart muscle damage, resulting in myocardium disorders, diminished cardiac function, heart failure, and even sudden cardiac death. The molecular mechanisms underlying the damage to cardiomyocytes remain unclear. Emerging studies have demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by iron dyshomeostasis and lipid peroxidation, contributes to the development of ischemic cardiomyopathy, diabetic cardiomyopathy, doxorubicin-induced cardiomyopathy, and septic cardiomyopathy. Numerous compounds have exerted potential therapeutic effects on cardiomyopathies by inhibiting ferroptosis. In this review, we summarize the core mechanism by which ferroptosis leads to the development of these cardiomyopathies. We emphasize the emerging types of therapeutic compounds that can inhibit ferroptosis and delineate their beneficial effects in treating cardiomyopathies. This review suggests that inhibiting ferroptosis pharmacologically may be a potential therapeutic strategy for cardiomyopathy treatment