Fei Ma

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.

MicroRNAs (miRNAs) are a class of non-coding RNA that post-transcriptionally regulates the expression of target genes by binding to mRNAs. As one form of alternative splicing, intron retention has influence upon mRNA modification and protein encoding. The effect of miRNA on mRNA containing retained intron within 3' UTR, however, has not been systematically elucidated. Here, we examined a total of 2864 human genes which contain at least one retained intron from the MAASE and ASD databases and found 387 genes having contained retained introns within 3' UTR. The effect of retained introns upon miRNA targets was explored with three web-based programs for miRNA prediction including miRanda, TargetScanS and PicTar. The results showed that retained introns can increase putative miRNA targets in human mRNA. Retained introns have higher chances than other regions of 3' UTR in involving the site of miRNAs targets of most genes which contain putative miRNA targets within it. Furthermore, some transcripts contain miRNA targets solely because of the retained introns in 3' UTR. In addition, we examined those 'Ignored' retained introns by miRanda software and the results indicated that miRNAs may contain many more putative targets.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition. Despite the availability of current therapies that offer partial symptom relief, they fall short of adequately protecting the intestinal barrier. In this study, an advanced nanodrug formulation (OLA@MΦ NPs) is developed by coating macrophage membranes onto polymeric organic nanoparticles encapsulating olaparib. When loaded into pH-responsive capsules, an intestine-decipher engineered capsule (cp-OLA@MΦ NPs) is successfully formulated. Upon oral administration in septic mice, these capsules withstand gastric acid and release their contents in the intestine, specifically targeting injured tissues. The released OLA@MΦ NPs effectively neutralize pro-inflammatory cytokines via macrophage membrane receptors, while olaparib inhibits intestinal epithelial parthanatos (a form of programmed cell death) by suppressing poly(ADP-ribose) polymerase 1 (PARP1) activation. This strategy significantly reduces bacterial translocation, slows the progression of sepsis, and enhances survival in septic mice, thus presenting a promising therapeutic approach for sepsis in clinical applications.

The popularity of microservices in industry has sparked much attention in the research community. Despite significant progress in microservice deployment for resource-intensive services and applications at the network edge, the intricate dependencies among microservices are often overlooked, and some studies underestimate the importance of system context extraction in deployment strategies. This paper addresses these issues by formulating the microservice deployment problem as a max-min problem, considering system cost and quality of service (QoS) jointly. We first study the attention-based microservice representation (AMR) method to achieve effective system context extraction. In this way, the contributions of different computing power providers (users, edge servers, or cloud servers) in the networks can be effectively paid attention to. Subsequently, we propose the attention-modified soft actor-critic (ASAC) algorithm to tackle the microservice deployment problem. ASAC leverages attention mechanisms to enhance decision-making and adapt to changing system dynamics. Our simulation results demonstrate ASAC's effectiveness, prioritizing average system cost and reward compared to the other state-of-the-art algorithms.