LncRNA RASAL2-AS1 promotes METTL14-mediated m6A methylation in the proliferation and progression of head and neck squamous cell carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of the 6-methyladenosine (m6A) epigenetic modification, playing a role in the initiation and progression of tumors. However, the regulatory mechanisms in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we investigated the molecular regulatory mechanisms of the lncRNA RASAL2-AS1 in the occurrence and development of HNSCC tumors. METHODS: A bioinformatics analysis was conducted to analyze the expression level of RASAL2-AS1 in HNSCC and normal tissues. RASAL2-AS1 mRNA and protein levels were detected using RT-PCR and Western blotting. Wound healing, transwell assays, flow cytometry, M6A dot blot, and RNA immunoprecipitation experiments were conducted to explore the regulatory role of the RASAL2-AS1 and downstream targets METTL14/LIS1 signaling pathway in HNSCC. Immunohistochemical examination was conducted to evaluate the expression of METTL14 and LIS1 in HNSCC and normal tissues. A tumor xenograft model of BALB/c nude mice was established to assess the impact of RASAL2-AS1 on cell proliferation and growth. RESULTS: RASAL2-AS1 high expression in HNSCC and cells deteriorated with survival rates of HNSCC. RASAL2-AS1 overexpression in HNSCC accelerated cell migration, colony formation, cell proliferation, cell cycle in S stage, while RASAL2-AS1 knockdown in HNSC cells inhibited cell cycle in G1 stage. After silencing METTL14, the above effects induced by overexpression of the RASAL2-AS1 were reversed. RASAL2-AS1 overexpression prompted LIS1 expression, whereas RASAL2-AS1 silencing reduced LIS1 levels in HNSCC cells, which was confirmed by immunohistological staining. Results demonstrated elevated expression of METTL14 or LIS1 in tongue cancer tissues. Overexpression of RASAL2-AS1 promoted tumor weight and tumor volume, which was counteracted by pcDNA3.1 RASAL2-AS1 plus silencing METTL14 and METTL14 and LIS1 were significantly decreased. CONCLUSION: Our study highlights the functional importance of the LncRNA RASAL2-AS1 in HNSCC and might assist in the development of a prognostic stratification and therapeutic approach. Which regulates HNSCC with the dependence of m6a manner.

A patient information mining network for drug recommendation.

As an important task of natural language processing, medication recommendation aims to recommend medication combinations according to the electronic health record, which can also be regarded as a multi-label classification task. But patients often have multiple diseases simultaneously, and the model must consider drug-drug interactions (DDI) of medication combinations when recommending medications, making medication recommendation more difficult. There is little existing work to explore the changes in patient conditions. However, these changes may point to future trends in patient conditions that are critical for reducing DDI rates in recommended drug combinations. In this paper, we proposed the Patient Information Mining Network (PIMNet), which models the current core medications of patient by mining the temporal and spatial changes of patient medication order and patient condition vector, and allocates some auxiliary medications as the currently recommended medication combination. The experimental results show that the proposed model greatly reduces the recommended DDI of medications while achieving results no lower than the state-of-the-art results.

Progress of the COVID-19: Persistence, Effectiveness, and Immune Escape of the Neutralizing Antibody in Convalescent Serum.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in "SAlpha", "SBeta", "SDelta", and "SOmicron", respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.

Conditional Probability Joint Extraction of Nested Biomedical Events: Design of a Unified Extraction Framework Based on Neural Networks.

BACKGROUND: Event extraction is essential for natural language processing. In the biomedical field, the nested event phenomenon (event A as a participating role of event B) makes extracting this event more difficult than extracting a single event. Therefore, the performance of nested biomedical events is always underwhelming. In addition, previous works relied on a pipeline to build an event extraction model, which ignored the dependence between trigger recognition and event argument detection tasks and produced significant cascading errors. OBJECTIVE: This study aims to design a unified framework to jointly train biomedical event triggers and arguments and improve the performance of extracting nested biomedical events. METHODS: We proposed an end-to-end joint extraction model that considers the probability distribution of triggers to alleviate cascading errors. Moreover, we integrated the syntactic structure into an attention-based gate graph convolutional network to capture potential interrelations between triggers and related entities, which improved the performance of extracting nested biomedical events. RESULTS: The experimental results demonstrated that our proposed method achieved the best F1 score on the multilevel event extraction biomedical event extraction corpus and achieved a favorable performance on the biomedical natural language processing shared task 2011 Genia event corpus. CONCLUSIONS: Our conditional probability joint extraction model is good at extracting nested biomedical events because of the joint extraction mechanism and the syntax graph structure. Moreover, as our model did not rely on external knowledge and specific feature engineering, it had a particular generalization performance.

Parrondo paradoxical walk using four-sided quantum coins.

Two losing games can be played in a certain manner to produce a winning outcome-a phenomenon known as Parrondo's paradox. Of particular interest is the emergence of quantum game theory and the attempt to model known Parrondo's games through quantum computation notation. In this article, we investigate whether flipping four-sided quantum coins will result in the emergence of Parrondo's paradox. We discover that by playing two losing games A and B in a sequential order, a winning scenario can be derived. Furthermore, four-sided quantum coin is the first instance where the ratcheting effect from the classical Parrondo's game is necessary. Crucially, our study is designed with quantum protocols as its basis and does not have a direct classical counterpart.

A microfluidic platform culturing two cell lines paralleled under in-vivo like fluidic microenvironment for testing the tumor targeting of nanoparticles.

Nanoparticles are attractive in medicine because their surfaces can be chemically modified for targeting specific disease cells, especially for cancer. Providing an in-vivo like platform is crucial to evaluate the biological behaviours of nanoparticles. This paper presents a microfluidic device that could culture two cell lines in parallel in in-vivo like fluidic microenvironments and be used for testing the tumor targeting of folic acid - cholesterol - chitosan (FACC) nanoparticles. The uniformity and uniformity of flow fields inside the cell culture units are investigated using the finite element method and particle tracking technology. HeLa and A549 cells are cultured in the microfluidic chip under continuous media supplementation, mimicking the fluid microenvironment in vivo. Cell introducing processes are presented by the flow behaviours of inks with different colours. The two cell lines are identified by detecting folate receptors on the cellular membranes. The growth curves of the two cell lines are measured. The two cell lines cultured paralleled inside the microfluidic device are treated with FITC-FACC to investigate the targeting of FACC. The tumor targeting of FACC are also detected by in vivo imaging of HeLa cells growth in nude mice models. The results indicate that the microfluidic device could provide a dynamic, uniform and stable fluidic microenvironment to test the tumor targeting of FACC nanoparticles.

Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery.

In order to decrease the toxicity of paclitaxel (PTX) and increase the efficiency, we developed an amphiphilic PTX injection system using a biodegradable and biocompatible polymer synthesized by folic acid, cholesterol, and chitosan (FACC). This FACC-based polymer had a low critical concentration (64.13µg/ml) and could self-assemble in aqueous condition to form nanoscale micelles. The particle sizes of FACC-PTX micelles were 253.2±0.56 nm, the encapsulation efficiency and loading capacity of these FACC-PTX micelles were 65.1±0.23% and 9.1±0.16%, respectively. The cumulative release rate was about 85% at pH 5.0 which was higher than that at pH 7.4 (76%). This pH-dependent release behavior was highly suggesting that PTX release from FACC-PTX micelles might be higher in a weak acidic tumor microenvironment and lower toxic for normal cells. The anti-cancer effectiveness of FACC-PTX micelles was investigated by in vitro cytotoxicity and targeting study. The results revealed that FACC micelles have non-toxic on cells as evidenced by high cell viability found (86% to 100%) in the cells cultured with various concentrations of FACC micelles (1 to 500 µg/ml). Targeting study indicated that the cytotoxic efficacy of FACC-PTX micelles was significantly higher than that with Taxol® in the Hela cells (folate receptor-positive cells). These findings indicated that the anticancer efficiency of PTX can be enhanced by adding some cancer cell positive receptor into drug carrier and the FACC micelle was a potential tumor targeting carrier for PXT delivery.