Search

Liquid biopsy has the advantage of diagnosing diseases in a non-invasive manner. Seminal plasma contains secretions from the bilateral testes, epididymides, seminal vesicles, bulbourethral glands, and the prostate. These organs are relatively small and contain delicate tubes that are prone to damage by invasive diagnosis. Cell-free seminal nucleic acids are a newly emerged item in liquid biopsy. Here, we present a comprehensive overview of all known cell-free DNA and cell-free RNAs (mRNA, miRNA, lncRNA, circRNA, piRNA, YRNA, tsRNA, etc.) and discuss their roles as biomarker candidates in liquid biopsy. With great advantages, including high stability, sensitivity, representability, and non-invasiveness, cell-free DNA/RNAs may be developed as promising biomarkers for the screening, diagnosis, prognosis, and follow-up of diseases in semen-secreting organs. Moreover, RNAs in semen may participate in important processes, including sperm maturation, early embryo development, and transgenerational disease inheritance, which may be developed as potential treatment targets for future clinical use.

Massive open online courses (MOOCs) , which offer open access and widespread interactive participation through the internet, are quickly becoming the preferred method for online and remote learning. Several MOOC platforms offer the service of course recommendation to users, to improve the learning experience of users. Despite the usefulness of this service, we consider that recommending courses to users directly may neglect their varying degrees of expertise. To mitigate this gap, we examine an interesting problem of concept recommendation in this paper, which can be viewed as recommending knowledge to users in a fine-grained way. We put forward a novel approach, termed HinCRec-RL, for C oncept Rec ommendation in MOOCs, which is based on H eterogeneous I nformation N etworks and R einforcement L earning . In particular, we propose to shape the problem of concept recommendation within a reinforcement learning framework to characterize the dynamic interaction between users and knowledge concepts in MOOCs. Furthermore, we propose to form the interactions among users, courses, videos, and concepts into a heterogeneous information network (HIN) to learn the semantic user representations better. We then employ an attentional graph neural network to represent the users in the HIN, based on meta-paths. Extensive experiments are conducted on a real-world dataset collected from a Chinese MOOC platform, XuetangX , to validate the efficacy of our proposed HinCRec-RL. Experimental results and analysis demonstrate that our proposed HinCRec-RL performs well when compared with several state-of-the-art models.

Background: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. Methods: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (K Ca 2.3 and K Ca 3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. Results: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial K Ca 2.3 or K Ca 3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of K Ca 2.3/K Ca 3.1 with elevated cytosolic Ca 2+ . Further, chronic S1P stimulation enhanced expression of K Ca 2.3 and K Ca 3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca 2+ signaling or downstream Ca 2+ -activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of K Ca 2.3 and K Ca 3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of K Ca 2.3 and K Ca 3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. Conclusions: This study provides evidence for the mechanistic role of K Ca 2.3/K Ca 3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.

Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalization in the paediatric population. Low airway surface pH impairs antimicrobial host defence and worsens airway inflammation. Inhaled Optate safely raises airway surface pH in humans and raises intracellular pH in primary human airway epithelial cells (HAECs)in vitro. We aimed to determine if raising intracellular pH with Optate would decrease infection and replication of RSV in primary HAECs.We cultured HAECs from healthy subjects in both air-liquid interface (ALI) and submerged conditions. We infected HAECs with green fluorescent protein-labelled RSV (GFP-RSV; MOI 1) and treated them with Optate or phosphate buffered saline control. We collected supernatant after a four-hour incubation and then every 24 h. We used fluorescence intensity, fluorescent particle counts, plaque assays, western blots, and enzyme-linked immunosorbent assays (ELISA) to quantitate infection.In submerged culture, fluorescence intensity decreased in Optate-treated cells (48H p=0.0174, 72H p=viawestern blot and ELISA (pviaELISA (p=0.001). Additionally, RSV infection decreased as Optate concentration increased in a dose-dependent manner (pIn conclusion, Optate inhibits RSV infection in primary HAECs in a dose-dependent manner. These findings suggest Optate may have potential as an inhaled therapeutic for patients with RSV.

A star-shaped polymer (Star-PEG-PCL2) was synthesized to with PCL and PEG, and used as a stationary phase for gas chromatography. The statically coated Star-PEG-PCL2 column exhibited an efficiency of 2260 plates/m determined by naphthalene at 120 °C and moderate polarity. The Star-PEG-PCL2 column showed high resolution performance for isomers of a wide ranging polarity, including methylnaphthalenes, halogenated benzenes, nitrobenzene, phenols, and anilines, and displayed dual-nature selectivity for a mixture of 17 analytes. Also, the Star-PEG-PCL2 column exhibited good separation performance and column inertness for Grob test mixture and a series of cis-/trans-isomers. In addition, it exhibited advantageous separation performance over the commercial HP-35 and PEG-20M columns for chloroaniline and bromoaniline isomers through its unique three-dimensional framework. In conclusion, it has good potential as a new stationary phase for separating a variety of analytes because of its special structure and excellent separation performance.

Enzymatically catalyzed cross-linking is a hydrogel fabrication method that generally is considered to have lower cytotoxicity than traditional chemical cross-linking methods. In order to optimize the properties of injectable hydrogels and expand their applications, an enzyme-catalyzed cross-linked injectable hydrogel was designed. The tyramine-modified gelatin (G-T) was formed into a stable injectable hydrogel by the combination of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) catalysis. 1H NMR spectroscopy was used to demonstrate the successful modification of gelatin by tyramine. The surface morphology of the prepared hydrogels was characterized jointly by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Rheological tests demonstrated the tunable mechanical strength, formation kinetics, shear thinning and good self-recovery properties of the hydrogels. In addition, the hydrogels can be formed into various shapes by injection. The hydrogel network structure is complex and interlaced, as such it is suitable to encapsulate drugs for controlled release. The drug release from the prepared hydrogels followed the Peppas–Sahlin model and belonged to Fickian diffusion. This study constructed injectable hydrogels through the enzyme-catalyzed cross-linking of modified gelatin and applied the hydrogels for drug release, which is expected to expand the application in biomedical fields.

BACKGROUND: High-speed health trains are important tools and guarantees in major accidents, epidemic pandemics, disasters, and warfare health care, and the health trains currently developed for common train platforms have more functional defects. OBJECTIVE: The purpose of this study is to analyze the relationship between the medical transfer system and the medical system, and to obtain a better medical transfer train formation through the established model. METHODS: Based on the case study of medical transport tools, this paper analyzes the components and interrelationships of the medical transport system and the medical system, and then analyzes the medical transport task process of the health train by using the hierarchical task analysis (HTA) method. Combined with the Chinese standard EMU, a medical transport task model of the high-speed health train is established. Through this model, the functional compartment unit of the high-speed health train and the marshaling scheme of the high-speed health train are obtained. RESULTS: The expert system is used to evaluate the scheme. The results show that the train formation scheme formulated by the model in this paper is superior to other train formation schemes in three indicators, meeting the requirements of large medical transfer tasks. CONCLUSION: The results of this study can improve the ability of on-site treatment of patients, and can provide a basis for the research and development of a high-speed health train, which has a certain practical application value.

Broadband all-optical wavelength conversion (AOWC) for hybrid wavelength- and mode-division multiplexing (WDM-MDM) signals is experimentally demonstrated based on degenerate four-wave mixing in a silicon chip with a parallel dispersion-optimized multimode nonlinear waveguide and mode (de)multiplexers. By simultaneously coupling two modes into the waveguide using an optical fiber array, the intermodal crosstalk is measured to be as low as -25.9 dB for the fundamental mode of the transverse electric mode (TE0) (or -23.6 dB for the first-order mode TE1), and the conversion efficiency is -25.4 dB for TE0 (or -26.3 dB for TE1) mode. A wide conversion bandwidth of ∼68 nm is measured except for the influence of the crosstalk, which is the first time to experimentally demonstrate the broadband wavelength conversion for MDM signal. Using a 4 × 10 Gbit/s on-off keying (OOK) hybrid WDM-MDM signal, four AOWC channels are obtained on the idlers and the power penalty of each channel is less than 2.7 dB at the bit-error-ratio of 1 × 10-9.

COVID-19 results in increased incidence of cardiac arrhythmias, including atrial fibrillation (AF). However, little is known about the combined effect of AF and COVID-19 on patient outcomes. This study aimed to determine if AF, specifically new-onset AF (NOAF), is associated with increased risk of mortality and major adverse cardiovascular events (MACEs) in hospitalized patients with COVID-19. This multicenter retrospective analysis identified 2,732 patients with COVID-19 admitted between March and December 2020. Data points were manually reviewed in the patients' electronic health records. Multivariate logistic regression was used to assess if AF was associated with death or MACE. Patients with AF (6.4%) had an increased risk of mortality (risk ratio 2.249, 95% confidence interval [CI] 1.766 to 2.864, p0.001) and MACE (risk ratio 1.753, 95% CI 1.473 to 2.085, p0.001) compared with those with sinus rhythm. Patients with NOAF had an increased risk of mortality compared with those with existing AF (odds ratio 19.30, 95% CI 5.39 to 69.30, p0.001); the risk of MACE was comparable between NOAF and patients with existing AF (p = 1). AF during hospitalization with COVID-19 is associated with a higher risk of mortality and MACE. NOAF in patients with COVID-19 is associated with a higher risk of mortality but a similar risk of MACE compared with patients with existing AF.

Background: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. Methods: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. Results: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01–1.06], skin cancer (HR, 1.11; 95% CI, 1.07–1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01–1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79–0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction Conclusions: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. Impact: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Most of the previous TMDC-photon coupling devices were mainly based on A exciton due to its high oscillator strength and large exciton binding energy. Less effort has been focused on the modulation of the emission of B exciton and Rydberg states in TMDCs, especially in monolayer WS2. Here, we demonstrate that the photoluminescence (PL) emission of WS2-microcavity coupling devices can be tailored in a broad visible wavelength range (490 nm–720 nm). In contrast to the intrinsic PL emission of monolayer WS2, 25-fold enhanced B exciton emission and significant PL emission from the 2s Rydberg state can be observed. From the transient absorption (TA) measurements, the strongly coupled hybrid states based on B exciton can be remarkably fingerprinted. Furthermore, the strongly enhanced PL emission from the coupled B exciton has been demonstrated due to the strongly increased lower polariton (LP) state population and the internal conversion pathway being blocked in the strong coupling regime. Besides, the remarkable PL emission from the 2s Rydberg state is also revealed and confirmed by the additional ground state bleaching signal in TA spectra. These physical mechanisms about tailoring the PL emission in low dimensional TMDCs can provide significant references for constructing highly efficient optoelectronic devices.