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IntroductionImmune infiltration within the tumor microenvironment (TME) plays a significant role in the onset and progression of hepatocellular carcinoma (HCC). Machine learning applied to pathological images offers a practical means to explore the TME at the cellular level. Our former research employed a transfer learning procedure to adapt a convolutional neural network (CNN) model for cell recognition, which could recognize tumor cells, lymphocytes, and stromal cells autonomously and accurately within the images. This study introduces a novel immune classification system based on the modified CNN model.MethodPatients with HCC from both Beijing Hospital and The Cancer Genome Atlas (TCGA) database were included in this study. Additionally, least absolute shrinkage and selection operator (LASSO) analyses, along with logistic regression, were utilized to develop a prognostic model. We proposed an immune classification based on the percentage of lymphocytes, with a threshold set at the median lymphocyte percentage.ResultPatients were categorized into high or low infiltration subtypes based on whether their lymphocyte percentages were above or below the median, respectively. Patients with different immune infiltration subtypes exhibited varying clinical features and distinct TME characteristics. The low-infiltration subtype showed a higher incidence of hypertension and fatty liver, more advanced tumor stages, downregulated immune-related genes, and higher infiltration of immunosuppressive cells. A reliable prognostic model for predicting early recurrence of HCC based on clinical features and immune classification was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves was 0.918 and 0.814 for the training and test sets, respectively.DiscussionIn conclusion, we proposed a novel immune classification system based on cell information extracted from pathological slices, provides a novel tool for prognostic evaluation in HCC.

The challenge of distributing molten iron involves the optimal allocation of blast furnace output to various steelmaking furnaces, considering the blast furnace’s production capacity and the steelmaking converter’s consumption capacity. The primary objective is to prioritize the distribution from the blast furnace to achieve a balance between iron and steel production while ensuring that the volume of hot metal within the system remains within a safe range. To address this, a constrained multi-objective nonlinear programming model is abstracted. A linear weighting method combines multiple objectives into a single objective function, while the Lagrange multiplier method addresses constraints. The proposed hybrid Archimedes optimization algorithm effectively solves this problem, demonstrating significant improvements in time efficiency and precision compared to existing methods.

The rapid development of the Internet has facilitated expression, sharing, and interaction on social networks, but some speech may contain harmful discrimination. Therefore, it is crucial to classify such speech. In this paper, we collected discriminatory data from Sina Weibo and propose the improved Synthetic Minority Over-sampling Technique (SMOTE) algorithm based on Latent Dirichlet Allocation (LDA) to improve data quality and balance. And we propose a new integration method integrating Support Vector Machine (SVM) and Random Forest (RF). The experimental results demonstrate that the integrated model exhibits enhanced precision, recall, and F1 score by 6.0%, 5.4%, and 5.7%, respectively, in comparison with SVM alone. Moreover, it exhibits the best performance in comparison with other machine learning methods. Furthermore, the positive impact of improved SMOTE and this integrated method on model classification is also confirmed in ablation experiments.

Marine fishery resources are linked to global food security and the livelihoods of millions of people, but their sustainability is seriously affected by the overexpansion of fishing activities. The regulation of fishing activities of fishing vessels has been based on ineffective data sources. Fortunately, rapid developments in nighttime light remote sensing have provided effective data for the formulation of marine fisheries regulations. We conducted a series of experiments to explore the application of Luojia1-01 (LJ-01) nighttime light images for the extraction of information on fishing vessels to provide effective data support for the formulation of marine fisheries regulations. First, a series of preprocessing operations, including radiation correction and masking of the offshore oil and gas platforms were performed on the original image. The preprocessed single-band nighttime light image was combined with two stretching methods to form a triband image. Sample labelling of lit fishing boats was performed. Then, by comparing YOLOv5 metrics, YOLO-V5s was chosen as the base framework of the model, and a small-target detection layer was added to improve the detection of lit fishing vessels. The method developed in this study accurately and effectively detected lit fishing boats in LJ1-01 images with strong robustness and generalizability, and the accuracy of detection rate reached 96.6 %. The precision was improved by 10 % compared to the original YOLO-V5s model that used raw data. The recall rate was improved from 85.4 to 93 %, and the average accuracy(map@0.5) was improved from 85.4 to 93.1 %. The developed model can be successfully used for the extraction of lit fishing boats and for other applications based on medium- and high-resolution nighttime satellite data.

Summary: Primary somatosensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:peripheral nervous system (PNS) borderline where OPCs are absent. Most axons stop in contact with a dense network of OPC processes. Live imaging, immuno-electron microscopy (immuno-EM), and OPC-dorsal root ganglia (DRG) co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.

Braid-like coronary artery is very rare. It is featured by the division of the coronary artery into multiple tortuous small channels that later converge into a normal lumen at any segment of the coronary artery. We presented a case of a 27-year-old male patient with occasional chest pain. In coronary CT angiography (CCTA) and coronary angiography, a braid-like appearance was found in the right coronary artery. After multidisciplinary discussion, it was speculated to be a woven coronary artery (WCA). We conducted a literature review about woven coronary arteries.

Fisheries provide high-quality protein for many people, and their sustainable use is of global concern. Light trapping is a widely used fishing method that takes advantage of the phototropism of fish. Remote sensing technology allows for the monitoring of lit fishing vessels at sea from the air at night, which supports the sustainable management of fisheries. To investigate the potential of different nighttime light remote sensing data for lit fishing vessel identification and applications, we used the fuzzy evaluation method to quantitatively assess images in terms of their radiometric and geometric quality, and Otsu’s method to compare the effects of lit fishing vessel identification. Three kinds of nighttime lighting data from the Defense Meteorological Satellite Program/Operational Linescan System (DMSP/OLS), Visible infrared imaging radiometer suite day/night band (VIIRS/DNB), and Luojia1-01(LJ1-01) were analyzed, compared, and application pointers were constructed. The results are as follows. ①In the image radiation quality evaluation, the information entropy, clarity, and noise performance of the LJ1-01 image are higher than those of the DMSP/OLS and VIIRS/DNB images, where the information entropy value of the LJ1-01 image is nearly 10 times that of VIIRS/DNB and 23 times that of DMSP/OLS. The average gradient value is 14 times that of the image from VIIRS/DNB and 1,600 times that of DMSP/OLS, while its noise is only about 2/3 of the VIIRS/DNB image and 1/3 of the DMSP/OLS image. In the geometric quality assessment, the geometric positioning accuracy and ground sampling accuracy of the VIIRS/DNB image is the best among the three images, with a relative difference percentage of 100.1%, and the LJ1-01 and DMSP/OLS images are relatively lower, at 96.9% and 92.3%, respectively. ② The detection of squid fishing vessels in the Northwest Pacific is taken as an example to compare the identification effects of three types of data: DMSP/OLS, VIIRS/DNB, and LJ1-01. Among these data, DMSP/OLS can effectively identify the position of the lit fishing boat, and VIIRS/DNB images can accurately estimate the spatial position and number of lit fishing boats with large distances. However, in the case of fishing boats gathering or clustering, the number of fishing vessels could not be identified. This led to the detected number of lit fishing vessels being less than the real value. For the VIIRS/DNB and LJ1-01 images with a 5′×8′ span in the same spatiotemporal range using the same batch of pelagic squid fishing vessels, LJ1-01 extracted 18 fishing vessels. VIIRS/DNB extracted 15, indicating that LJ1-01 can distinguish multiple fishing vessels in the lighted overlapping area, thus accurately identifying the number of fishing vessels. The application pointing table generated based on the results of the three data analyses can provide a reference for sensor/image selection for nighttime light remote sensing fishery applications and a basis for more refined fishing vessel identification, extraction, and monitoring.

BackgroundGlioma, the most prevalent malignant intracranial tumor, poses a significant threat to patients due to its high morbidity and mortality rates, but its prognostic indicators remain inaccurate. Although TRAF-associated NF-kB activator (TANK) interacts and cross-regulates with cytokines and microenvironmental immune cells, it is unclear whether TANK plays a role in the immunologically heterogeneous gliomas.MethodsTANK mRNA expression patterns in public databases were analyzed, and qPCR and IHC were performed in an in-house cohort to confirm the clinical significance of TANK. Then, we systematically evaluated the relationship between TANK expression and immune characteristics in the glioma microenvironment. Additionally, we evaluated the ability of TANK to predict treatment response in glioma. TANK-associated risk scores were developed by LASSO-Cox regression and machine learning, and their prognostic ability was tested.ResultsTANK was specifically overexpressed in glioma and enriched in the malignant phenotype, and its overexpression was related to poor prognosis. The presence of a tumor microenvironment that is immunosuppressive was evident by the negative correlations between TANK expression and immunomodulators, steps in the cancer immunity cycle, and immune checkpoints. Notably, treatment for cancer may be more effective when immunotherapy is combined with anti-TANK therapy. Prognosis could be accurately predicted by the TANK-related risk score.ConclusionsHigh expression of TANK is associated with the malignant phenotype of glioma, as it shapes an immunosuppressive tumor microenvironment. Additionally, TANK can be used as a predictive biomarker for responses to various treatments and prognosis.

Primary cardiac intimal sarcoma, an extremely rare cardiac tumor subtype, is often mis-diagnosed owing to its rarity and non-specific clinical and radiological features. We report a case of cardiac intimal sarcoma mimicking atrial myxoma in which the clinical presentation and multimodality imaging are described in detail, and diagnostic challenges are highlighted.

This reports outlines a rare case of primary right atrial angiosarcoma with multiple metastases. Multimodality imaging and histopathology confirmed the diagnosis of primary cardiac angiosarcoma and multiple metastases. We present the details of the presentation, multimodality imaging findings, and clinical management. The patient was followed up by cardiac MRI (CMRI) 2 months after therapy, the cardiac tumor and pulmonary metastases decreased markedly. Up to now, the patient has undergone four cycles of chemotherapy and immunotherapy.

During the highly infectious pandemic of coronavirus disease 2019 (COVID-19), artificial intelligence (AI) has provided support in addressing challenges and accelerating achievements in controlling this public health crisis. It has been applied in fields varying from outbreak forecasting to patient management and drug/vaccine development. In this paper, we specifically review the current status of AI-based approaches for patient management. Limitations and challenges still exist, and further needs are highlighted.

The engineered “obligate” anaerobic Salmonella typhimurium strain YB1 shows a prominent ability to repress tumor growth and metastasis, which has great potential as a novel cancer immunotherapy. However, the antitumor mechanism of YB1 remains unelucidated. To resolve the proteome dynamics induced by the engineered bacteria, we applied tumor temporal proteome profiling on murine bladder tumors after intravenous injection of either YB1 or PBS as a negative control. Our data suggests that during the two weeks treatment of YB1 injections, the cured tumors experienced three distinct phases of the immune response. Two days after injection, the innate immune response was activated, particularly the complement and blood coagulation pathways. In the meantime, the phagocytosis was initiated. The professional phagocytes such as macrophages and neutrophils were recruited, especially the infiltration of iNOS+ and CD68+ cells was enhanced. Seven days after injection, substantial amount of T cells was observed at the invasion margin of the tumor. As a result, the tumor shrunk significantly. Overall, the temporal proteome profiling can systematically reveal the YB1 induced immune responses in tumor, showing great promise for elucidating the mechanism of bacteria-mediated cancer immunotherapy.

Abstract Nerve injury‐induced maladaptive changes of gene expression in dorsal root ganglion (DRG) neurons contribute to neuropathic pain. Long non‐coding RNAs (lncRNAs) are emerging as key regulators of gene expression. Here, a conserved lncRNA is reported, named DRG‐specifically enriched lncRNA (DS‐lncRNA) for its high expression in DRG neurons. Peripheral nerve injury downregulates DS‐lncRNA in injured DRG due, in part, to silencing of POU domain, class 4, transcription factor 3, a transcription factor that interacts with the DS‐lncRNA gene promoter. Rescuing DS‐lncRNA downregulation blocks nerve injury‐induced increases in the transcriptional cofactor RALY‐triggered DRG Ehmt2 mRNA and its encoding G9a protein, reverses the G9a‐controlled downregulation of opioid receptors and Kcna2 in injured DRG, and attenuates nerve injury‐induced pain hypersensitivities in male mice. Conversely, DS‐lncRNA downregulation increases RALY‐triggered Ehmt2/G9a expression and correspondingly decreases opioid receptor and Kcna2 expression in DRG, leading to neuropathic pain symptoms in male mice in the absence of nerve injury. Mechanistically, downregulated DS‐lncRNA promotes more binding of increased RALY to RNA polymerase II and the Ehmt2 gene promoter and enhances Ehmt2 transcription in injured DRG. Thus, downregulation of DS‐lncRNA likely contributes to neuropathic pain by negatively regulating the expression of RALY‐triggered Ehmt2/G9a, a key neuropathic pain player, in DRG neurons.

In this paper, a direct computational method is presented which combines optical flow and structure from motion (SfM) by putting the SfM problem in the framework of optical flow estimation. In other word, the optical flow is reparametrized in term of the camera's motion and scene's depth, resulting in a similar variation optimization as in optical flow estimation. Meanwhile, three techniques are proposed to improve the accuracy and robustness of the direct approach, including the fast guided interpolation (FGI), the left-right consistency constraint and the soft segment constraint. Experimental results on the Middlebury dataset and KITTI2012 dataset show that the proposed approach can achieve highly-accurate 3D reconstruction with the dense and smooth surface which results in a state-of-the-art performance in optical flow.

Background: Accumulating evidence has revealed that coronavirus disease 2019 (COVID-19) patients may be complicated with myocardial injury during hospitalization. However, data regarding persistent cardiac involvement in patients who recovered from COVID-19 are limited. Our goal is to further explore the sustained impact of COVID-19 during follow-up, focusing on the cardiac involvement in the recovered patients.Methods: In this prospective observational follow-up study, we enrolled a total of 40 COVID-19 patients (20 with and 20 without cardiac injury during hospitalization) who were discharged from Zhongnan Hospital of Wuhan University for more than 6 months, and 27 patients (13 with and 14 without cardiac injury during hospitalization) were finally included in the analysis. Clinical information including self-reported symptoms, medications, laboratory findings, Short Form 36-item scores, 6-min walk test, clinical events, electrocardiogram assessment, echocardiography measurement, and cardiac magnetic resonance imaging was collected and analyzed.Results: Among 27 patients finally included, none of patients reported any obvious cardiopulmonary symptoms at the 6-month follow-up. There were no statistically significant differences in terms of the quality of life and exercise capacity between the patients with and without cardiac injury. No significant abnormalities were detected in electrocardiogram manifestations in both groups, except for nonspecific ST-T changes, premature beats, sinus tachycardia/bradycardia, PR interval prolongation, and bundle-branch block. All patients showed normal cardiac structure and function, without any statistical differences between patients with and without cardiac injury by echocardiography. Compared with patients without cardiac injury, patients with cardiac injury exhibited a significantly higher positive proportion in late gadolinium enhancement sequences [7/13 (53.8%) vs. 1/14 (7.1%), p = 0.013], accompanied by the elevation of circulating ST2 level [median (interquartile range) = 16.6 (12.1, 22.5) vs. 12.5 (9.5, 16.7); p = 0.044]. Patients with cardiac injury presented higher levels of aspartate aminotransferase, creatinine, high-sensitivity troponin I, lactate dehydrogenase, and N-terminal pro–B-type natriuretic peptide than those without cardiac injury, although these indexes were within the normal range for all recovered patients at the 6-month follow-up. Among patients with cardiac injury, patients with positive late gadolinium enhancement presented higher cardiac biomarker (high-sensitivity troponin I) and inflammatory factor (high-sensitivity C-reactive protein) on admission than the late gadolinium enhancement–negative subgroup.Conclusions: Our preliminary 6-month follow-up study with a limited number of patients revealed persistent cardiac involvement in 29.6% (8/27) of recovered patients from COVID-19 after discharge. Patients with cardiac injury during hospitalization were more prone to develop cardiac fibrosis during their recovery. Among patients with cardiac injury, those with relatively higher cardiac biomarkers and inflammatory factors on admission appeared more likely to have cardiac involvement in the convalescence phase.

Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.

Abstract Background Previous studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin. Methods The collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund’s adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording. Results Oral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA. Conclusions Our results demonstrate that curcumin attenuates CIA through the “gut-brain axis” by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

Deep learning proves its promising results in various domains. The automatic identification of plant diseases with deep convolutional neural networks attracts a lot of attention at present. This article extends stochastic gradient descent momentum optimizer and presents a discount momentum (DM) deep learning optimizer for plant diseases identification. To examine the recognition and generalization capability of the DM optimizer, we discuss the hyper-parameter tuning and convolutional neural networks models across the plantvillage dataset. We further conduct comparison experiments on popular non-adaptive learning rate methods. The proposed approach achieves an average validation accuracy of no less than 97% for plant diseases prediction on several state-of-the-art deep learning models and holds a low sensitivity to hyper-parameter settings. Experimental results demonstrate that the DM method can bring a higher identification performance, while still maintaining a competitive performance over other non-adaptive learning rate methods in terms of both training speed and generalization.

ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R–induced pain remains un explored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079. A similar effect was observed with a P2X7R agonist, BzATP, and was attenuated by a NADPH oxidase inhibitor apocynin. Intrathecal administration of BzATP resulted in ROS production in the spinal cord and oxidative DNA damage in dorsal horn neurons. BzATP also induced robust biphasic spontaneous nociceptive behavior. Pre-treatment with A438079 abolished all BzATP-induced nociceptive behaviors, while ROS scavengers dose-dependently attenuated the secondary response. Here, we provide evidence that neuronal P2X7R activation leads to ROS production and subsequent nociceptive pain in mice. Together, the data indicate that P2X7R-induced ROS play a critical role in the P2X7R signaling pathway of the CNS.

Store-operated calcium channels (SOCs) are highly calcium-selective channels that mediate calcium entry in various cell types. We have previously reported that intraplantar injection of YM-58483 (a SOC inhibitor) attenuates chronic pain. A previous study has reported that the function of SOCs in dorsal root ganglia (DRG) is enhanced after nerve injury, suggesting that SOCs may play a peripheral role in chronic pain. However, the expression, functional distribution and significance of the SOC family in DRG neurons remain elusive and the key components that mediate SOC entry (SOCE) are still controversial. Here, we demonstrated that the SOC family (STIM1, STIM2, Orai1, Orai2, and Orai3) was expressed in DRGs and STIM1 was mainly present in small- and medium-sized DRG neurons. Using confocal live cell imaging, Ca2+ imaging and electrophysiology techniques, we demonstrated that depletion of the endoplasmic reticulum Ca2+ stores induced STIM1 and STIM2 translocation, and that inhibition of STIM1 or blockage of Orai channels with pharmacological tools attenuated SOCE and SOC currents. Using the small inhibitory RNA knockdown approach, we identified STIM1, STIM2, Orai1, and Orai3 as the key components of SOCs mediating SOCE in DRG neurons. Importantly, activation of SOCs by thapsigargin induced plasma membrane depolarization and increased neuronal excitability, which were completely abolished by inhibition of SOCs or double knockdown of Orai1 and Orai3. Our findings suggest that SOCs exert an excitatory action in DRG neurons and provide a potential peripheral mechanism for modulation of pain hypersensitivity by SOC inhibition.

Gender and sex differences in pain recognition and drug responses have been reported in clinical trials and experimental models of pain. Among antidepressants, contradictory results have been observed in patients treated with selective serotonin reuptake inhibitors (SSRIs). This study evaluated sex differences in response to the SSRI fluoxetine after chronic administration in the mouse formalin test. Adult male and female CD1 mice were intraperitoneally injected with fluoxetine (10 mg/kg) for 21 days and subjected to pain assessment. Fluoxetine treatment reduced the second phase of the formalin test only in female mice without producing behavioral changes in males. We also observed that fluoxetine was able to specifically increase the expression of metabotropic glutamate receptor type-2 (mGlu2) in females. Also a reduced expression of the epigenetic modifying enzyme, histone deacetylase 2 (HDAC2), in dorsal root ganglia (DRG) and dorsal horn (DH) together with an increase histone 3 acetylation (H3) level was observed in females but not in males. With this study we provide evidence that fluoxetine induces sex specific changes in HDAC2 and mGlu2 expression in the DH of the spinal cord and in DRGs and suggests a molecular explanation for the analgesic effects in female mice.

To provide a basis for controlling the quality of rhubarb under artificial cultivation, the present work was designed to evaluate the contents of 14 active pharmaceutical ingredients (API) of rhubarb in major rhubarb production areas in China and analyze the correlations between the contents of API and such factors as species, geographic distribution and soil. The levels of fourteen API in rhubarb were measured using HPLC. The geographic distributions were collected using GPS and the nutrients in the soil were measured using the methods in the literature. The results showed that the levels of major API vary significantly among plants of different locations according to variance analysis. The species factor has few obvious effect on the overall properties of the rhubarb by the cluster analysis because of the two source species occurring in all divided three groups. However, Rheum tanguticum Maxim.ex Balf. is less effective at synthesizing and accumulating 9 API out of 14 than Rheum palmatum L. The correlation analysis and regression analysis also indicated that a lower latitude should be considered in the accumulation of API and a lower longitude should be considered to produce more compound anthraquinones. Lower levels of total P, rapidly available P and available molybdenum (Mo) and higher available K and available Zn in the soil were significantly correlated to accumulation of API in rhubarb. These results provide a basis for the clinical application and controlling the levels of the major API of rhubarb during artificial cultivation.

The prevalence and levels of Listeria monocytogenes in retail raw foods covering most provincial capitals in China were studied with testing of 1036 samples of vegetables, edible mushrooms, raw meat, aquatic products and quick-frozen products from September 2012 to January 2014. The total prevalence of Listeria monocytogenes was 20.0% (207/1036), and the most probable number (MPN) values of 65.7% of the positive samples ranged from 0.3 to 110 MPN/g. Geographical differences were observed in this survey, and the results of both qualitative and quantitative methods indicated that the levels in the samples from North China were higher than those in the samples from South China. A total of 248 isolates were analyzed, of which approximately half belonged to molecular serogroup 1/2a-3a (45.2%), followed by 1/2b-3b-7 (30.6%), 1/2c-3c (16.1%), 4b-4d-4e (5.2%) and 4a-4c (2.8%). Most of the isolates carried hly (100%), inlB (98.8%), inlA (99.6%), inlC (98.0%) and inlJ (99.2%), and 44.8% of the isolates were llsX-positive. Seventeen epidemic clones (ECs) were detected, with 7 strains belonging to ECI (2.8%) and 10 belonging to ECIII (4.03%). Resistance to clindamycin (46.8%) was commonly observed, and 59 strains (23.8%) were susceptible to all 14 tested antibiotics, whereas 84 (33.9%) showed an intermediate level of resistance or were resistant to two or more antibiotics, including 7 multi-resistant strains that exhibited resistance to more than 10 antibiotics. The data obtained in the present study provides useful information for assessment of the possible risk posed to Chinese consumers, and this information will have a significant public health impact in China. Furthermore, the presence of virulence markers, epidemic clones, as well as the antibiotic resistance amongst the isolates strongly implies that many of these strains might be capable of causing listeriosis, and more accurate treatment of human listeriosis with effective antibiotics should be considered. This research represents a more full-scale and systematical investigation of the prevalence of L. monocytogenes in retail raw foods in China, and it provides baseline information for Chinese regulatory authorities that will aid in the formulation of a regulatory framework for controlling L. monocytogenes with the aim of improving the microbiological safety of raw foods.

Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 3'-UTR of voltage-gated sodium channel Scn11a, alpha 2/delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain.

Peripheral sensitization is one of the primary mechanisms underlying the pathogenesis of chronic pain. However, candidate molecules involved in peripheral sensitization remain incompletely understood. We have shown that store-operated calcium channels (SOCs) are expressed in the dorsal root ganglion (DRG) neurons. Whether SOCs contribute to peripheral sensitization associated with chronic inflammatory pain is elusive. Here we report that global or conditional deletion of Orai1 attenuates Complete Freund's adjuvant (CFA)-induced pain hypersensitivity in both male and female mice. To further establish the role of Orai1 in inflammatory pain, we performed calcium imaging and patch-clamp recordings in wild-type (WT) and Orai1 knockout (KO) DRG neurons. We found that SOC function was significantly enhanced in WT but not in Orai1 KO DRG neurons from CFA- and carrageenan-injected mice. Interestingly, the Orai1 protein level in L3/4 DRGs was not altered under inflammatory conditions. To understand how Orai1 is modulated under inflammatory pain conditions, prostaglandin E2 (PGE2) was used to sensitize DRG neurons. PGE2-induced increase in neuronal excitability and pain hypersensitivity was significantly reduced in Orai1 KO mice. PGE2-induced potentiation of SOC entry (SOCE) was observed in WT, but not in Orai1 KO DRG neurons. This effect was attenuated by a PGE2 receptor 1 (EP1) antagonist and mimicked by an EP1 agonist. Inhibition of Gq/11, PKC, or ERK abolished PGE2- induced SOCE increase, indicating PGE2-induced SOCE enhancement is mediated by EP1-mediated downstream cascade. These findings demonstrate that Orai1 plays an important role in peripheral sensitization. Our study also provides new insight into molecular mechanisms underlying PGE2-induced modulation of inflammatory pain. [ABSTRACT FROM AUTHOR]

Abstract Particulate matter 2.5 (PM2.5) pollution has emerged as a major global public health concern because of its adverse effects on human health. Our group has previously demonstrated that PM2.5 exposure can seriously impair ovarian function. However, the underlying mechanisms remain a mystery. This study verifies ovarian damage in mice, evidenced by inflammatory cell infiltration and follicular atresia, following 5 months of PM2.5 exposure via tracheal drip (35 µg/m³ for low dose and 150 µg/m³ for high dose). In addition, PM2.5 exposure inhibited the cell viability of human granulosa cells (KGN) and induced apoptosis at the concentrations of 50, 100, and 150 µg/mL for 24 h. The apoptosis of KGN cells induced by inflammation contributes to follicular atresia. Furthermore, we conducted RNA-sequencing analysis to identify the genes and pathways triggered by PM2.5 (100 µg/mL) exposure, which decreases the KGN cell viability. We found a significant increase in Activating Transcription Factor 3 (ATF3). Further mechanistic studies reveal a strong association between PM2.5-induced apoptosis, inflammation, and ATF3 with its downstream oxidative stress signals. In summary, the ATF3 pathway serves a vital role in the ovarian injury caused by PM2.5 exposures.

There is research evidence that creative agency has attracted worldwide attention in mainstream education as it could foster learners’ active roles in taking control of their creative processes. However, without appropriate supporting tools, students may struggle to convey their ideas in complex creative practices. Digital storytelling and mobile technology are regarded as proper supportive tools to cultivate creative agency in English as a Foreign Language (EFL) learning. In addition, concept mapping could improve students’ creative thinking and knowledge activation. However, to the best of our knowledge, the effect of integrating mobile storytelling and concept mapping on promoting creative agency in EFL learning contexts remains unclear. Accordingly, this quasi-experimental study explored how a concept mapping-based mobile storytelling approach contributed to learners’ creative agency by examining 102 sixth-grade primary school students’ EFL performance and creative agency products, creative self-efficacy, agentic engagement, self-regulation, and motivation to learn English. The results of this study revealed that the experimental group with the concept mapping-guided mobile storytelling for creative agency approach outperformed the control group with the storyboard scaffolding-guided mobile storytelling for creative agency approach in all of the above aspects. This study provides new insights for teachers to motivate students’ creative agency in EFL learning from the process-oriented creativity and product-oriented perspectives (i.e., setting goals, designing creative plans with concept maps, reflecting on issues, and evaluating creation).