Short-term learning of the vestibulo-ocular reflex induced by a custom interactive computer game.

Retinal image slip during head rotation drives motor learning in the rotational vestibulo-ocular reflex (VOR) and forms the basis of gaze-stability exercises that treat vestibular dysfunction. Clinical exercises, however, are unengaging, cannot easily be titrated to the level of impairment, and provide neither direct feedback nor tracking of the patient's adherence, performance, and progress. To address this, we have developed a custom application for VOR training based on an interactive computer game. In this study, we tested the ability of this game to induce VOR learning in individuals with normal vestibular function, and we compared the efficacy of single-step and incremental learning protocols. Eighteen participants played the game twice on different days. All participants tolerated the game and were able to complete both sessions. The game scenario incorporated a series of brief head rotations, similar to active head impulses, that were paired with a dynamic acuity task and with a visual-vestibular mismatch (VVM) intended to increase VOR gain (single-step: 300 successful trials at ×1.5 viewing; incremental: 100 trials each of ×1.13, ×1.33, and ×1.5 viewing). Overall, VOR gain increased by 15 ± 4.7% (mean ± 95% CI, P < 0.001). Gains increased similarly for active and passive head rotations, and, contrary to our hypothesis, there was little effect of the learning strategy. This study shows that an interactive computer game provides robust VOR training and has the potential to deliver effective, engaging, and trackable gaze-stability exercises to patients with a range of vestibular dysfunctions.NEW & NOTEWORTHY This study demonstrates the feasibility and efficacy of a customized computer game to induce motor learning in the high-frequency rotational vestibulo-ocular reflex. It provides a physiological basis for the deployment of this technology to clinical vestibular rehabilitation.

Overcoming Periodic Stripe Noise in Infrared Linear Array Images: The Fourier-Assisted Correlative Denoising Method.

Infrared linear array detectors frequently experience vertical, low-frequency, and periodic stripe noise during imaging, stemming from electro-mechanical interference. Unlike conventional periodic disturbances, this interference showcases long periodicities and is uniquely columnar in orientation. Its presence, especially within the low-frequency domain, renders conventional filtering techniques ineffective and, at times, detrimental to image quality. Addressing this challenge, we introduce Fourier-Assisted Correlative Denoising (FACD), a correlation-centric denoising approach tailored for such unique interference patterns. This mechanism begins with the capture of a pure background image, inclusive of periodic noise, during the non-uniform correction phase of the infrared detector. Leveraging the noise's frequency domain attributes, we extract a one-dimensional single-cycle noise signal. The infrared image is subsequently segmented into parts, and using the detected noise periodicity, the one-dimensional signals for each segment are computed. By leveraging the correlation between these signals and the benchmark one-dimensional noise pattern, we ascertain the noise profile within each segment. This profile is then employed for spatial domain denoising across the entire image frame. Empirical assessments confirm that the FACD outperforms contemporary denoising techniques by augmenting the peak signal-to-noise ratio by approximately 2.5 dB, underscoring its superior robustness. Furthermore, in light of its specificity to this noise model, FACD rapidly denoises high-resolution real infrared linear array scans, thus meeting the stringent real-time and resolution imperatives of advanced infrared linear array scanning apparatuses.

Factors affecting colonoscopy screening among first-degree relatives of colorectal cancer patients: A mixed-method systematic review.

BACKGROUND: First-degree relatives (FDRs) of colorectal cancer (CRC) patients have a higher risk of developing CRC than the general population. Ensuring that these at-risk populations receive colonoscopy screening is an effective strategy for reducing the increased risk, but the rates remain low. Colonoscopy screening behavior is influenced by factors at multiple levels. However, most previous reviews failed to review them and their interactions systematically. AIMS: To explore factors influencing FDRs' colonoscopy screening behavior according to the ecological model. METHOD: A mixed-method systematic review was performed in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. A comprehensive literature search was conducted using eight bibliographic databases (Medline, EMBASE, PubMed, the Cochrane Library, Scopus, China National Knowledge Infrastructure, Wan Fang Data, and China Biology Medicine) for the period from January 1995 to February 2023. The Joanna Briggs Institute critical appraisal checklists were applied to assess studies qualities. A convergent integrated approach was used for data synthesis and integration. RESULTS: In total, 24 articles reporting on 23 studies were included. Only one study was rated low quality, and the other 22 studies were rated moderate to high quality. The findings revealed that certain factors and their interactions affected FDRs' colonoscopy screening behaviors according to the ecological model, including misconceptions about CRC and colonoscopy, concerns about the procedure, perceived susceptibility to developing CRC, health motivation, fear of CRC, fatalism, the recommendation from CRC patients, and recommendations from physicians, colonoscopy schedules, cancer taboo, health insurance and cost of colonoscopy. LINK EVIDENCE TO ACTION: Family communication-centered multilevel interventions are recommended to promote colonoscopy screening behavior among FDRs of CRC patients.

Coptidis Rhizoma processed with Evodia Rutaecarpa improves the effect on ulcerative colitis by increasing intestinal energy metabolites alpha-ketoglutarate and Lactobacillus reuteri.

BACKGROUND: Evodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated. PURPOSE: Coptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology. STUDY DESIGN: A preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays. METHODS: Mice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and ß-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice. RESULTS: ECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/ß-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity. CONCLUSION: ECR processing improves the therapeutic effects of UC via the α-KG-L. reuteri-epithelial regeneration axis.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

Geniposide ameliorates atherosclerosis by regulating macrophage polarization via perivascular adipocyte-derived CXCL14.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis. AIM OF THE STUDY: To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage polarization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT). MATERIALS AND METHODS: ApoE-/- mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays. RESULTS: The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE-/- mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geniposide increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells. CONCLUSION: In summary, our findings suggest that geniposide protects ApoE-/- mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment.

Baicalin inhibits hepatocellular carcinoma cell growth and metastasis by suppressing ROCK1 signaling.

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3ß, and ß-catenin, whereas it up-regulated the expressions of GSK-3ß and p-ß-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3ß/ß-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK-3ß/ß-catenin signaling.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Translation and validation: standard Chinese version of the skin tear knowledge assessment instrument (OASES).

Objective: Skin tears (STs) are acute cutaneous trauma and have become an increasingly common global health problem. International studies have shown barriers to the prevention and management of ST and the relevance of the role of nurses in implementation. The purpose of this study was to adapt an existing tool to measure nurses' knowledge of the prevention, assessment, and management of STs. Methods: Skin tear knowledge assessment instrument (OASES) is a knowledge survey tool for skin lacerations developed by Van Tiggelen et al. in 2020. The standard Chinese version of OASES was formed by translating and cross-cultural adaption of source tools following Brislin's translation model, and content validity and translation quality were determined by Delphi method. A psychometric assessment of 341 nurses was then performed to assess item difficulty, discrimination, and quality of response selection in the standard Chinese version of OASES. In addition, construct validity was established by test-retest procedures and known-group techniques. Results: The standard Chinese version had good content validity and moderate difficulty. It was found that the discrimination was very good: all groups with higher professional level (theoretically expected) scored significantly higher than those with lower professional level (theoretically expected). The stability of the tool was sufficient. Conclusions: The standard Chinese version of OASES exhibits good psychometric properties and can be used and disseminated to nurses in a Chinese cultural context to assess knowledge about STs. However, it should be noted that the tool was only validated with nurses in cancer hospitals.

Bayesian group testing with dilution effects.

A Bayesian framework for group testing under dilution effects has been developed, using lattice-based models. This work has particular relevance given the pressing public health need to enhance testing capacity for coronavirus disease 2019 and future pandemics, and the need for wide-scale and repeated testing for surveillance under constantly varying conditions. The proposed Bayesian approach allows for dilution effects in group testing and for general test response distributions beyond just binary outcomes. It is shown that even under strong dilution effects, an intuitive group testing selection rule that relies on the model order structure, referred to as the Bayesian halving algorithm, has attractive optimal convergence properties. Analogous look-ahead rules that can reduce the number of stages in classification by selecting several pooled tests at a time are proposed and evaluated as well. Group testing is demonstrated to provide great savings over individual testing in the number of tests needed, even for moderately high prevalence levels. However, there is a trade-off with higher number of testing stages, and increased variability. A web-based calculator is introduced to assist in weighing these factors and to guide decisions on when and how to pool under various conditions. High-performance distributed computing methods have also been implemented for considering larger pool sizes, when savings from group testing can be even more dramatic.

Biejiajian pill inhibits progression of hepatocellular carcinoma by downregulating PDGFRß signaling in cancer-associated fibroblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Biejiajian pill (BJJP) is a canonical formula that is clinically used to treat chronic liver disease, especially to decrease the incidence of hepatocellular carcinoma (HCC). However, the mechanisms underlying the prevention of HCC progression by BJJP remain unclear. AIM OF THE STUDY: This study aimed to determine whether BJJP inhibits HCC progression by downregulating platelet-derived growth factor receptor beta (PDGFRß) signaling in cancer-associated fibroblasts (CAFs) in a mouse model of diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced HCC. MATERIALS AND METHODS: C57BL/6 male mice were intraperitoneally injected with DEN 2 weeks after birth, followed by repeated injections of CCl4 weekly from 6 weeks of age onwards, to recapitulate features of HCC. At week 14, BJJP was orally administered to mice. The effects of BJJP on HCC progression were evaluated using histology, immunohistochemistry, and serum biochemical marker levels. Transcriptome analysis, molecular docking, quantitative real-time PCR, and Western blot were used to study the genes targeted by BJJP and the associated signaling pathway. The effects of BJJP on PDGFRß signaling in CAFs and the underlying mechanism were demonstrated. RESULTS: BJJP treatment significantly suppressed carcinogenesis and cancer progression, and it ameliorated liver inflammation in mice with HCC. A total of 176 genes, including PDGFRß, were significantly downregulated after BJJP treatment and five components of BJJP with high binding affinity to PDGFRß were identified. BJJP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK3ß) by suppressing PDGFRß expression in CAFs, and it also downregulated the expression of the downstream proteins hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A). Furthermore, BJJP-containing serum consistently reduced PDGFRß, HGF, and VEGF-A expression levels in HSC-derived CAFs in vitro. Importantly, PDGF-BB induced PDGFRß activation in CAFs and both BJJP and sunitinib (a kinase inhibitor) inhibited PDGF-BB/PDGFRß signaling. CONCLUSION: BJJP inhibits the progression of HCC through suppressing VEGF-A and HGF expression in CAFs by downregulating PDGFRß signaling.

Erratum: MicroRNA-30a-3p acts as a tumor suppressor in MHCC-97H hepatocellular carcinoma cells by targeting COX-2: Erratum.

[This corrects the article DOI: 10.7150/jca.52298.].

Consequences of anthropogenic activities and beach dynamics on vertical distribution of microplastics in the mid-intertidal sediments of Donghai Island, China.

Microplastic accumulation and resulting degradation are significant threats to the coastal ecosystems around the world. Baseline information on microplastics and their sources is of great importance for a permanent waste management system. The present study focused on the vertical distribution and characteristics of microplastics in the mid-intertidal zone of Donghai Island, China. At eight locations, sediment samples were collected from surface to a depth of 30 cm at intervals of 5 cm. Overall, we found five different polymer types, and vertical distributions of microplastics varied ranging from 0 to 200 particles/kg, with the mean value of 32.92±41.35 particles/kg. Sediment samples collected from all stations contained microplastics with high contribution of fibres. Intruded microplastic materials recorded in sediment samples at a depth of 30 cm demonstrate that microplastics may be present at depths greater than 30 cm. Scanning electron microscopy-energy dispersive X-ray (SEM-EDAX) analysis revealed presence of common elements in the microplastics surface (silicon, aluminium, magnesium, copper, and calcium). Based on the observations and results from this study, we suggest implementing a robust microplastic removal management program in Donghai Island to avoid serious microplastic intrusion effects on benthos and environmental contamination.

Biejiajian Pill Promotes the Infiltration of CD8+ T Cells in Hepatocellular Carcinoma by Regulating the Expression of CCL5.

Tumor-infiltrating CD8+T lymphocytes are mostly associated with a favorable prognosis in numerous cancers, including hepatocellular carcinoma (HCC). Biejiajian Pill (BJJP) is a common type of traditional Chinese medicine that is widely used in the treatment of HCC in China. Previous studies showed that BJJP suppressed the growth of HCC cells both in vivo and in vitro, by exerting direct cytotoxic effects on tumor cells. The present study demonstrated that in addition to direct cytotoxicity, BJJP inhibits the growth of tumor cells by promoting the infiltration of CD8+T cells into the tumor in H22-bearing mice. Mechanistically, chemokine ligand 5 (CCL5) was identified as one of the most highly expressed chemokines by tumor cells in vivo after treatment with BJJP. Additionally, CCL5 was knocked down in H22 cells and the results showed that knockdown of the gene significantly impaired the infiltration of CD8+T cells in vivo. Furthermore, the effects of BJJP on human HCC cell lines were assessed in vitro. Similarly, cells treated with BJJP had higher expression of CCL5 mRNA, which was consistent with increased levels of CCL5 protein in human tumor cells. These findings provide new insights into the anticancer effects of BJJP, which regulated the expression of CCL5 and the infiltration of CD8+T cells. The results, therefore, suggest that BJJP has great potential application in clinical practice.

Early Stopping in Experimentation With Real-Time Functional Magnetic Resonance Imaging Using a Modified Sequential Probability Ratio Test.

Introduction: Functional magnetic resonance imaging (fMRI) often involves long scanning durations to ensure the associated brain activity can be detected. However, excessive experimentation can lead to many undesirable effects, such as from learning and/or fatigue effects, discomfort for the subject, excessive motion artifacts and loss of sustained attention on task. Overly long experimentation can thus have a detrimental effect on signal quality and accurate voxel activation detection. Here, we propose dynamic experimentation with real-time fMRI using a novel statistically driven approach that invokes early stopping when sufficient statistical evidence for assessing the task-related activation is observed. Methods: Voxel-level sequential probability ratio test (SPRT) statistics based on general linear models (GLMs) were implemented on fMRI scans of a mathematical 1-back task from 12 healthy teenage subjects and 11 teenage subjects born extremely preterm (EPT). This approach is based on likelihood ratios and allows for systematic early stopping based on target statistical error thresholds. We adopt a two-stage estimation approach that allows for accurate estimates of GLM parameters before stopping is considered. Early stopping performance is reported for different first stage lengths, and activation results are compared with full durations. Finally, group comparisons are conducted with both early stopped and full duration scan data. Numerical parallelization was employed to facilitate completion of computations involving a new scan within every repetition time (TR). Results: Use of SPRT demonstrates the feasibility and efficiency gains of automated early stopping, with comparable activation detection as with full protocols. Dynamic stopping of stimulus administration was achieved in around half of subjects, with typical time savings of up to 33% (4 min on a 12 min scan). A group analysis produced similar patterns of activity for control subjects between early stopping and full duration scans. The EPT group, individually, demonstrated more variability in location and extent of the activations compared to the normal term control group. This was apparent in the EPT group results, reflected by fewer and smaller clusters. Conclusion: A systematic statistical approach for early stopping with real-time fMRI experimentation has been implemented. This dynamic approach has promise for reducing subject burden and fatigue effects.

Sinisan Protects Primary Hippocampal Neurons Against Corticosterone by Inhibiting Autophagy via the PI3K/Akt/mTOR Pathway.

Objective: Corticosterone causes significant neurotoxicity in primary hippocampal neurons which is associated with depression. Dysfunctional autophagy is implicated in cognitive impairment and depressive-like behavior. The traditional Chinese medicine Sinisan (SNS) is highly effective in clinical treatment of depression. However, the molecular mechanisms underlying therapeutic effects of SNS are unknown. Purpose: The aim of this study was to elucidate the protective effect of SNS and the underlying mechanisms against corticosterone-induced neuronal damage. Study Design: The effects of serum derived from rats containing SNS (or untreated controls) on the expression of autophagy-related molecules in primary rat hippocampal neurons exposed to different concentrations of corticosterone for different intervals were explored. Methods: CCK-8 assay, LDH assay were used to analyze cell viability and LDH activity. Western blot, qRT-PCR, and immunofluorescence assays were used to determine protein and mRNA expression levels of molecules such as LC3, p62, Beclin1, ULK1, PI3K, p-PI3K, Akt p-Akt, mTOR, p-mTOR, p70S6, p-p70S6, 4ebp1 and p-4ebp1. Results: Corticosterone induced a dose- and time-dependent reduction in cellular viability. Moreover, corticosterone (100-400 µM) treatment for 24 h increased LC3-II/LC3-I protein ratio, increased Beclin1 and ULK1 protein expression levels, and decreased p62, PI3K, p-PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein expression levels. Notably, SNS-containing serum reversed corticosterone-induced reduction of neuronal viability, and increased p62, PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein and mRNA expression levels. In addition, SNS-containing serum decreased LC3-II/LC3-I protein ratio, and downregulated Beclin1, and ULK1 protein and mRNA expression in primary hippocampal neurons. Conclusion: SNS protects primary hippocampal neurons against corticosterone-induced neurotoxicity by preventing excessive autophagy through activation of PI3K/AKT/mTOR pathway.

MicroRNA-30a-3p acts as a tumor suppressor in MHCC-97H hepatocellular carcinoma cells by targeting COX-2.

MicroRNAs (miRNAs) are small, noncoding RNAs which can bind to target mRNAs and regulate gene expression. Increasing evidences suggest that miRNAs play an important role in driving hepatocellular carcinoma (HCC) progression by regulating tumor cell proliferation, apoptosis, invasion, and migration. In this study, we demonstrated that the expression of microRNA-30a-3p (miR-30a-3p) was reduced in HCC cell lines in comparison to immortalized liver cell line, LO2. Augmented miR-30a-3p level markedly inhibited MHCC-97H cell growth, migration and invasion in vitro. MiR-30a-3p was also found to inhibit tumor growth in vivo using tumor-bearing mice. Mechanismly, COX-2 was discovered to be a direct and functional target of miR-30a-3p in MHCC-97H cells. Raised miR-30a-3p expression reduced the transcriptional level of COX-2 in MHCC-97H cells, while genetically upregulated COX-2 expression was able to reverse the function of miR-30a-3p-mediated suppression of MHCC-97H cells growth, migration and invasion. In addition, we found that using a COX-2 inhibitor, celecoxib, could enhance the anti-metastatic role of miR-30a-3p in MHCC-97H cells. Lastly, we found that decreased COX-2 protein level affected PGE2 production, leading to lower Bcl-2, Caspase-3, MMP2 and MMP9 expression but higher Bax and E-cadherin expression, which in turn culminated in higher rates of cell death and lower rates of cell migration. Taken together, our findings demonstrate that miR-30a-3p could be a target for the treatment of hepatocellular carcinoma cells progression.

Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3ß/Snail Signaling Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the most usual cancers globally. In China, Biejiajian pill (BJJP), Traditional Chinese Medicine clinical prescription, is broadly utilized for the prevention and therapy of HCC. However, the mechanisms by which BJJP exerts its effects on the prevention of tumor invasion and metastasis are still largely unknown. In this study, in vitro multiple hepatic cancer cell lines and an in vivo xenograft mice model were used to validate the preventive effects and molecular mechanisms of BJJP in HCC. We established that BJJP significantly repressed the proliferation, metastasis and infiltration of HCC cells. Furthermore, BJJP remarkably suppressed HCC cell migration, as well as invasion via epithelial-mesenchymal transition (EMT) by modulating Snail expression, which was associated with the repression of Akt/GSK-3ß/Snail signaling axis activation. In vivo HCC xenograft results indicated that BJJP delayed HCC development and efficiently inhibited lung metastasis. Taken together, BJJP was shown to be an effective therapeutic agent against HCC through repression of the Akt/GSK-3ß/Snail signaling cascade and EMT.