Bimin Kang ameliorates the minimal persistent inflammation in allergic rhinitis by reducing BCL11B expression and regulating ILC2 plasticity.

ETHNOPHARMACOLOGICAL RELEVANCE: Minimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. AIM OF THE STUDY: This study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. MATERIAL AND METHODS: The effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rß2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. RESULTS: BMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rß2 and IL-18/IL-18Rα signaling pathways in MPI mice. CONCLUSION: By downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.

Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

m6Aexpress-enet: Predicting the regulatory expression m6A sites by an enet-regularization negative binomial regression model.

As the most abundant mRNA modification, m6A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6Aexpress-enet) to predict which m6A site could potentially regulate its gene expression. Comprehensive evaluations on simulated datasets demonstrate that m6Aexpress-enet could achieve the top prediction performance. Applying m6Aexpress-enet on real MeRIP-seq data from human lymphoblastoid cell lines, we have uncovered the complex regulatory pattern of predicted m6A sites and their unique enrichment pathway of the constructed co-methylation modules. m6Aexpress-enet proves itself as a powerful tool to enable biologists to discover the mechanism of m6A regulatory gene expression. Furthermore, the source code and the step-by-step implementation of m6Aexpress-enet is freely accessed at https://github.com/tengzhangs/m6Aexpress-enet.

Visible-light-driven water-soluble zinc oxide quantum dots for efficient control of citrus canker.

BACKGROUND: Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a devastating bacterial disease that reduces citrus yield and quality, posing a serious threat to the citrus industry. Several conventional chemicals have been used to control citrus canker. However, this approach often leads to the excessive use of chemical agents, can exacerbate environmental pollution and promotes the development of resistant Xcc. Therefore, there is significant interest in the development of efficient and environmentally friendly technologies to control citrus canker. RESULTS: In this study, water-soluble ZnO quantum dots (ZnO QDs) were synthesised as an efficient nanopesticide against Xcc. The results showed that the antibacterial activity of ZnO QDs irradiated with visible light [half-maximal effective concentration (EC50) = 33.18 µg mL-1] was ~3.5 times higher than that of the dark-treated group (EC50 = 114.80 µg mL-1). ZnO QDs induced the generation of reactive oxygen species (•OH, •O- 2 and 1O2) under light irradiation, resulting in DNA damage, cytoplasmic destruction, and decreased catalase and superoxide dismutase activities. Transcription analysis showed downregulation of Xcc genes related to 'biofilms, virulence, adhesion' and 'DNA transfer' exposure to ZnO QDs. More importantly, ZnO QDs also promoted the growth of citrus. CONCLUSION: This research provides new insights into the photocatalytic antibacterial mechanisms of ZnO QDs and supports the development of more efficient and safer ZnO QDs-based nanopesticides to control citrus canker. © 2024 Society of Chemical Industry.

Path-BigBird: An AI-Driven Transformer Approach to Classification of Cancer Pathology Reports.

PURPOSE: Surgical pathology reports are critical for cancer diagnosis and management. To accurately extract information about tumor characteristics from pathology reports in near real time, we explore the impact of using domain-specific transformer models that understand cancer pathology reports. METHODS: We built a pathology transformer model, Path-BigBird, by using 2.7 million pathology reports from six SEER cancer registries. We then compare different variations of Path-BigBird with two less computationally intensive methods: Hierarchical Self-Attention Network (HiSAN) classification model and an off-the-shelf clinical transformer model (Clinical BigBird). We use five pathology information extraction tasks for evaluation: site, subsite, laterality, histology, and behavior. Model performance is evaluated by using macro and micro F1 scores. RESULTS: We found that Path-BigBird and Clinical BigBird outperformed the HiSAN in all tasks. Clinical BigBird performed better on the site and laterality tasks. Versions of the Path-BigBird model performed best on the two most difficult tasks: subsite (micro F1 score of 72.53, macro F1 score of 35.76) and histology (micro F1 score of 80.96, macro F1 score of 37.94). The largest performance gains over the HiSAN model were for histology, for which a Path-BigBird model increased the micro F1 score by 1.44 points and the macro F1 score by 3.55 points. Overall, the results suggest that a Path-BigBird model with a vocabulary derived from well-curated and deidentified data is the best-performing model. CONCLUSION: The Path-BigBird pathology transformer model improves automated information extraction from pathology reports. Although Path-BigBird outperforms Clinical BigBird and HiSAN, these less computationally expensive models still have utility when resources are constrained.

Synthesis and anti-tumor activity evaluation of 1H-pyrrolo[2,3-b]pyridine-2-carboxamide derivatives with phenyl sulfonamide groups as potent RSK2 inhibitors.

Ribosome S6 Protein Kinase 2 (RSK2) is involved in many signal pathways such as cell growth, proliferation, survival and migration in tumors. Also, RSK2 can phosphorylate YB-1, which induces the expression of tumor initiating cells, leading to poor prognosis of triple negative breast cancer. Herein, phenyl sulfonamide was introduced to a series of 1H-pyrrolo[2,3-b]pyridine-2-carboxamide derivatives to obtain novel RSK2 inhibitors which were evaluated RSK2 inhibitory activity and proliferation inhibitory activity against MDA-MB-468. The newly introduced sulfonamide group was observed to form a hydrogen bond with target residue LEU-74 which played crucial role in activity. The results showed that most of compounds exhibited RSK2 enzyme inhibitory with IC50 up to 1.7 nM. Compound B1 exhibited the strongest MDA-MB-468 cell anti-proliferation activity (IC50 = 0.13 µM). The in vivo tumor growth inhibitory activities were evaluated with compounds B1-B3 in MDA-MB-468 xenograft model which gave up to 54.6% of TGI.

The NLR immune receptor ADR1 and lipase-like proteins EDS1 and PAD4 mediate stomatal immunity in Nicotiana benthamiana and Arabidopsis.

In the presence of pathogenic bacteria, plants close their stomata to prevent pathogen entry. Intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogenic effectors and activate effector-triggered immune responses. However, the regulatory and molecular mechanisms of stomatal immunity involving NLR immune receptors are unknown. Here, we show that the Nicotiana benthamiana RPW8-NLR central immune receptor ACTIVATED DISEASE RESISTANCE 1 (NbADR1), together with the key immune proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (NbEDS1) and PHYTOALEXIN DEFICIENT 4 (NbPAD4), plays an essential role in bacterial pathogen- and flg22-induced stomatal immunity by regulating the expression of salicylic acid (SA) and abscisic acid (ABA) biosynthesis or response-related genes. NbADR1 recruits NbEDS1 and NbPAD4 in stomata to form a stomatal immune response complex. The transcription factor NbWRKY40e, in association with NbEDS1 and NbPAD4, modulates the expression of SA and ABA biosynthesis or response-related genes to influence stomatal immunity. NbADR1, NbEDS1, and NbPAD4 are required for the pathogen infection-enhanced binding of NbWRKY40e to the ISOCHORISMATE SYNTHASE 1 promoter. Moreover, the ADR1-EDS1-PAD4 module regulates stomatal immunity in Arabidopsis (Arabidopsis thaliana). Collectively, our findings show the pivotal role of the core intracellular immune receptor module ADR1-EDS1-PAD4 in stomatal immunity, which enables plants to limit pathogen entry.

Deep learning uncertainty quantification for clinical text classification.

INTRODUCTION: Machine learning algorithms are expected to work side-by-side with humans in decision-making pipelines. Thus, the ability of classifiers to make reliable decisions is of paramount importance. Deep neural networks (DNNs) represent the state-of-the-art models to address real-world classification. Although the strength of activation in DNNs is often correlated with the network's confidence, in-depth analyses are needed to establish whether they are well calibrated. METHOD: In this paper, we demonstrate the use of DNN-based classification tools to benefit cancer registries by automating information extraction of disease at diagnosis and at surgery from electronic text pathology reports from the US National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) population-based cancer registries. In particular, we introduce multiple methods for selective classification to achieve a target level of accuracy on multiple classification tasks while minimizing the rejection amount-that is, the number of electronic pathology reports for which the model's predictions are unreliable. We evaluate the proposed methods by comparing our approach with the current in-house deep learning-based abstaining classifier. RESULTS: Overall, all the proposed selective classification methods effectively allow for achieving the targeted level of accuracy or higher in a trade-off analysis aimed to minimize the rejection rate. On in-distribution validation and holdout test data, with all the proposed methods, we achieve on all tasks the required target level of accuracy with a lower rejection rate than the deep abstaining classifier (DAC). Interpreting the results for the out-of-distribution test data is more complex; nevertheless, in this case as well, the rejection rate from the best among the proposed methods achieving 97% accuracy or higher is lower than the rejection rate based on the DAC. CONCLUSIONS: We show that although both approaches can flag those samples that should be manually reviewed and labeled by human annotators, the newly proposed methods retain a larger fraction and do so without retraining-thus offering a reduced computational cost compared with the in-house deep learning-based abstaining classifier.

Phase Transition Liquid Metal Enabled Emerging Biomedical Technologies and Applications.

Phase change materials that can absorb or release large amounts of heat during phase transition, play a critical role in many important processes, including heat dissipation, thermal energy storage, and solar energy utilization. In general, phase change materials are usually encapsulated in passive modules to provide assurance for energy management. The shape and mechanical changes of these materials are greatly ignored. An emerging class of phase change materials, liquid metals (LMs) have attracted significant interest beyond thermal management, including in transformable robots, flexible electronics, soft actuators, and biomedicine. Interestingly, the melting point of LM is highly tunable around body temperature, allowing it to experience considerable stiffness change when interacting with human organisms during solid-liquid change, which brings about novel phenomena, applied technologies, and therapeutic methods, such as mechanical destruction of tumors, neural electrode implantation technique, and embolization therapy. This review focuses on the technology, regulation, and application of the phase change process along with diverse changes of LM to facilitate emerging biomedical applications based on the influences of mechanical stiffness change and versatile regulation strategies. Typical applications will also be categorized and summarized. Lastly, the advantages and challenges of using the unique and reversible process for biomedicine will be discussed.

Comparison of efficacy between unilateral biportal endoscopic lumbar fusion versus minimally invasive transforaminal lumbar fusion in the treatment of lumbar degenerative diseases: A systematic review and meta-analysis.

BACKGROUND: To evaluate the clinical efficacy and prognosis of unilateral biportal endoscopic lumbar fusion (ULIF) and minimally invasive transforaminal lumbar fusion (MIS-TLIF) for lumbar degenerative diseases. METHODS: Chinese and English databases were retrieved for the period from database creation to December 31, 2022. Case-control studies on unilateral biportal endoscopic lumbar fusion were collected. The observation indexes consisted of operation times, intraoperative blood loss, postoperative drainage volume, length of hospital stay, postoperative pain score, postoperative oswestry disability index score, postoperative MacNab excellent and good rate, imaging fusion rate at the last follow-up, and complications. The NO rating table was employed to assess the quality of the included literature, and a meta-analysis was conducted using Revman5.4.1 and Stata17. RESULTS: Ten studies with 738 surgical patients were considered, including 347 patients in the ULIF group and 391 in the MIS-TLIF group. This Meta-analysis demonstrated statistically significant differences in mean operation duration, intraoperative blood loss, postoperative drainage volume, length of hospital stay, and early postoperative (1-2W) visual analogue scale/score (VAS) scores for back pain. No significant differences were observed in the final follow-up postoperative VAS scores for back pain, postoperative leg VAS score, postoperative oswestry disability index score, excellent and good rate of postoperative modified MacNab, imaging fusion rate, and complications. CONCLUSION: Compared with the MIS-TLIF group, the ULIF group had longer operation time, lower intraoperative blood loss and postoperative drainage volume, lower lumbar VAS score in the early postoperative period, and shorter hospital stay. ULIF is less invasive than traditional MIS-TLIF, making it a trustworthy surgical option for lumbar degenerative diseases with comparable fusion efficiency, superior MacNab rate, and complication rate.

Laparoscopic Photoacoustic Imaging System Based on Side-Illumination Diffusing Fibers.

OBJECTIVE: To develop a flexible miniaturized photoacoustic (PA) imaging probe for detecting anatomical structures during laparoscopic surgery. The proposed probe aimed to facilitate intraoperative detection of blood vessels and nerve bundles embedded in tissue not directly visible to the operating physician to preserve these delicate and vital structures. METHODS: We modified a commercially available ultrasound laparoscopic probe by incorporating custom-fabricated side-illumination diffusing fibers that illuminate the probe's field of view. The probe geometry, including the position and orientation of the fibers and the emission angle, was determined using computational models of light propagation in the simulation and subsequently validated through experimental studies. RESULTS: In wire phantom studies within an optical scattering medium, the probe achieved an imaging resolution of 0.43 ±0.09 mm and a signal-to-noise ratio of 31.2±1.84 dB. We also conducted an ex vivo study using a rat model, demonstrating the successful detection of blood vessels and nerves. CONCLUSION: Our results indicate the viability of a side-illumination diffusing fiber PA imaging system for guidance during laparoscopic surgery. SIGNIFICANCE: The potential clinical translation of this technology could enhance the preservation of critical vascular structures and nerves, thereby minimizing post-operative complications.

Endovascular treatment strategies and a new classification for multiple aneurysms of the ipsilateral ophthalmic segment of the internal carotid artery.

OBJECTIVE: Aneurysms occurring in the ophthalmic segment (C6) of the internal carotid artery (ICA) have complex anatomy. This poses a challenge for the use of traditional open surgery, which is gradually being replaced by endovascular treatment (EVT). However, multiple aneurysm (MA) EVT, especially in MAs occurring ipsilaterally, has not been specifically described or discussed. The present study aimed to propose a more concise clinical classification standard for ipsilateral C6 ICA MAs and report on the clinical experience with EVT. METHODS: The cases of 18 patients with ipsilateral C6 ICA MAs treated with EVT were retrospectively reviewed. The treatment results and procedure-related complications were recorded, and clinical and angiographic follow-ups were performed at least six months after surgery. RESULTS: A total of 38 ipsilateral C6 ICA aneurysms were treated during the study period and classified into four main types and six total subtypes based on anatomical features. There was a failure to coil through the stent in one aneurysm, while the remaining 37 were successfully treated using various EVT methods. Of these, 36 were completely concluded. One aneurysm had a size reduction, and one had no changes during the angiographic follow-up. All Tubridge flow diverter stents were patent. All patients achieved satisfactory clinical outcomes and were independent at the final follow-up. CONCLUSION: EVT may be safe and feasible for the treatment of C6 ICA MAs. Traditional stent-assisted coiling methods, the Willis covered stent, and the double-layered low-profile visualized intraluminal support stent all achieved favorable results. The flow diverter stent is also considered a safe and efficient option for selected aneurysms, but the visual deficit risk should be considered. The present study introduces a new EVT classification option based on the anatomical features of an aneurysm.

Design and Protocol for Beijing Hospital Takayasu Arteritis (BeTA) Biobank.

BACKGROUND: Although hundreds of studies have been conducted, our understanding of the pathogenesis, indications for surgical intervention, and disease markers of Takayasu arteritis (TAK) are still limited. Collection of biological specimens, clinical data and imaging data will facilitate translational research and clinical studies. In this study, we aim to introduce the design and protocol for the Beijing Hospital Takayasu Arteritis (BeTA) Biobank. METHODS: Based in the Department of Vascular Surgery of Beijing Hospital and Beijing Hospital Clinical Biological Sample Management Center, the BeTA Biobank is composed of clinical data and sample data from patients with TAK requiring surgical treatment. All clinical data of participants are collected, including demographic characteristics, laboratory tests, imaging results, operation information, perioperative complications, follow-up data, etc. Both blood samples including plasma, serum and cells, and vascular tissues or perivascular adipose tissue are collected and stored. These samples will promote the establishment of a multiomic database for TAK and help to identify disease markers and to explore potential targets for specific future drugs for TAK.

Comparison of cortical versus cancellous bone fixation in tendon-to-bone healing with a rat trans-calcaneal suture model for Achilles tendon sleeve avulsion.

BACKGROUND: Trans-calcaneal suture technique is an economical and effective method for repairing Achilles tendon sleeve avulsion. Whether cancellous bone fixation upon this technique could accelerate tendon-to-bone healing is unknown. The purpose of this study is to compare the effect of cortical versus cancellous bone fixation on tendon-bone healing with a novel rat trans-calcaneal suture model. METHODS: Trans-calcaneal suture treatment was carried out on the right hindlimb in male Sprague-Dawley rats (N = 80). They were randomly divided into the cortical group (Achilles fixed to the calcaneal cortical bone, n = 40) and the cancellous group (Achilles fixed to the calcaneal cancellous bone, n = 40). Gait analysis and immunohistochemistry were performed 1, 4, 7, and 14 days after the operation. Gross observation, biomechanical analysis, micro-CT, and histological analysis were performed 4 and 8 weeks after surgery. Independent-samples t tests were used for comparison between groups. RESULTS: At 1, 4, and 7 days, the swing time of the affected limb in the cancellous group decreased, while the duty cycle, the maximum contact area, the print area, and the mean intensity increased significantly. The cross-sectional area of the tendon-bone junction in the cancellous group was smaller, and the failure load and stiffness were higher 4 weeks after the operation. The cancellous group showed more proportion of new bone and a relatively well-organized and dense connective tissue interface with better fibrocartilage-like tissue at 4 weeks after the operation. The ratio of ED2 + macrophages in the cancellous group was significantly higher than in the cortical group on 1, 4, 7, and 14 days. There were no significant differences in gait at 2 weeks, in appearance, biomechanics, new bone formation, and histology at 8 weeks after surgery between the two groups. CONCLUSION: In the new rat trans-calcaneal suture model, cancellous fixation can accelerate tendon-to-bone healing in the early stage, which perhaps is related to the abundant bone marrow tissue in the cancellous bone that modulates the inflammatory processes.

SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/ß-catenin signaling pathway.

PURPOSE: SMEK1, also known as PP4R3α, the regulatory subunit 3α of serine and threonine phosphatase PP4, participates in diversely critical biological processes such as the integration of centromere, deacetylation of histones, asymmetric divisions of neuroblast, and other crucial cellular activities. SMEK1 was formerly reported to play a part in carcinogenesis. This study aims to reveal the role of SMEK1 in lung adenocarcinoma and the underlying molecular mechanism. METHODS: Using immunohistochemical (IHC) staining, the protein level of SMEK1 in lung adenocarcinoma and adjacent non-tumor tissue was detected. The functional role of SMEK1 in cell proliferation and invasion was explored using cell counting kit-8 and Transwell assay, respectively. Xenograft tumor experiment was used to investigate the effect of SMEK1 on tumor growth in vivo. The alteration of Wnt/ß-catenin signaling pathway was detected by Western blotting, quantitative PCR, and dual-luciferase reporter assays. RESULTS: SMEK1 was highly expressed at the protein level in lung adenocarcinoma compared to the adjacent non-tumor tissue. In vitro, suppression of SMEK1 significantly decreased the proliferation, migration, and invasion of lung adenocarcinoma cell lines, while overexpression of SMEK1 enhanced above abilities. The xenograft model demonstrated that down-regulation of SMEK1 significantly inhibited tumor growth in vivo. In addition, we found that SMEK1 could positively regulate Wnt/ß-catenin signaling in lung adenocarcinoma cell lines. CONCLUSIONS: SMEK1 exerts a cancer-promoting effect in lung adenocarcinoma by activating Wnt/ß-catenin signaling.

Polyphenol-Enriched Protein Oleogels as Potential Delivery Systems of Omega-3 Fatty Acids.

Omega-3 polyunsaturated fatty acids (n-3 FAs) are essential nutrients and are considered effective in improving human health. Recent studies highlight the importance of the combination of n-3 FAs and polyphenols for limiting the oxidation of n-3 FAs and exhibiting synergistic beneficial effects. Herein, we developed a novel formulation technology to prepare oleogels that could be used for the codelivery of n-3 FAs and polyphenols with high loading efficacy and oxidative stability. These oleogels are made from algal oil with polyphenol-enriched whey protein microgel (WPM) particles as gelling agents via simple and scalable ball milling technology. The oxidative status, fatty acid composition, and volatiles of protein oleogels during accelerated storage were systematically assessed by stoichiometry and gas chromatography-mass spectrometry. These results showed that protein oleogels could overcome several challenges associated with the formulation of n-3 oils, including long-term oxidative stability and improved sensory and textural properties. The protein oleogel system could provide an excellent convenience for formulating multiple nutrients and nutraceuticals with integrating health effects, which are expected to be used in the care of highly vulnerable populations, including children, the elderly, and patients.

Using ensembles and distillation to optimize the deployment of deep learning models for the classification of electronic cancer pathology reports.

Objective: We aim to reduce overfitting and model overconfidence by distilling the knowledge of an ensemble of deep learning models into a single model for the classification of cancer pathology reports. Materials and Methods: We consider the text classification problem that involves 5 individual tasks. The baseline model consists of a multitask convolutional neural network (MtCNN), and the implemented ensemble (teacher) consists of 1000 MtCNNs. We performed knowledge transfer by training a single model (student) with soft labels derived through the aggregation of ensemble predictions. We evaluate performance based on accuracy and abstention rates by using softmax thresholding. Results: The student model outperforms the baseline MtCNN in terms of abstention rates and accuracy, thereby allowing the model to be used with a larger volume of documents when deployed. The highest boost was observed for subsite and histology, for which the student model classified an additional 1.81% reports for subsite and 3.33% reports for histology. Discussion: Ensemble predictions provide a useful strategy for quantifying the uncertainty inherent in labeled data and thereby enable the construction of soft labels with estimated probabilities for multiple classes for a given document. Training models with the derived soft labels reduce model confidence in difficult-to-classify documents, thereby leading to a reduction in the number of highly confident wrong predictions. Conclusions: Ensemble model distillation is a simple tool to reduce model overconfidence in problems with extreme class imbalance and noisy datasets. These methods can facilitate the deployment of deep learning models in high-risk domains with low computational resources where minimizing inference time is required.

Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization.

Depression is a mood disorder which causes a huge economic burden to both families and societies. However, those monoamine-based antidepressants used in clinical practice have been found to have various limitations. Therefore, currently it is very necessary to explore novel antidepressant targets and medications. As a main active component extracted from Scutellariae radix, oroxylin A possesses many pharmacological functions such as anti-cancer, anti-inflammation and neuroprotection. Here, the present study aims to investigate whether oroxylin A possess antidepressant-like actions using the chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) models of depression, forced swim test, tail suspension test, open field test, sucrose preference test, western blotting, immunofluorescence and viral-mediated gene interference. Our results revealed that treatment of oroxylin A fully prevented both the CUMS-induced and CRS-induced depressive-like behaviors in mice. Moreover, the protecting effects of oroxylin A against CUMS and CRS on mice behaviors were accompanied with a significant enhancement on the levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase B (pTrkB), phosphorylated cAMP-response element binding protein (pCREB) and neurogenesis in the hippocampus. Furthermore, genetic knockdown of BDNF and TrkB in the hippocampus remarkably abolished the antidepressant-like efficacy of oroxylin A in both the CUMS and CRS models of depression, proving that the hippocampal BDNF-TrkB system participates in the antidepressant mechanism of oroxylin A. In summary, our findings are the first evidence showing that oroxylin A possesses potential of being an antidepressant candidate.