Chemodiversity of dissolved organic matter exports from subtropical humid catchment driven by hydrological connectivity.

The quantity and quality of dissolved organic matter (DOM) exported from source areas are closely related to hydrological linkage between source areas and streams, that is hydrological connectivity. However, understanding of how hydrological connectivity regulates the export of catchment DOM components remains inadequate. In this study, high-frequency monitoring of groundwater and runoff from subtropical humid catchment was conducted for 20 months, and hydrological connectivity was quantitatively characterized by considering both surface and subsurface hydrological processes. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was utilized to investigate the DOM molecular composition. Results showed that over half of the areas in the catchment could not persistently establish hydrological connectivity with the stream during the rainfall. The average proportion of lignin was the highest in DOM components, followed by tannin and proteins. Additionally, both modified aromaticity index and double bond equivalence reached maximums at peak discharge, reflecting terrestrial materials could increase DOM aromaticity and unsaturated degree. Partial least square-structural equation modeling revealed significantly direct effects of rainfall, antecedent conditions, and hydrological connectivity on dissolved organic carbon (DOC) export. Furthermore, nonlinear relationships were observed between hydrological connectivity and DOC, tannin, and condensed aromatics. Specifically, the instantaneous DOC flux increased dramatically when the hydrological connectivity strength exceeded 0.14; tannin and condensed aromatics exhibited a rapid increase with rising connectivity strength, but remained stable at connectivity strength above 0.25. However, hydrological connectivity showed no significant correlation with unstable components (such as lipids, protein, amino sugars, and carbohydrates). These results provide new insights into hydrological controls on the quantity and quality of DOM export and contribute to developing appropriate catchment management strategies for carbon storage.

Comparing and contrasting barriers in augmentative alternative communication use in nonspeaking autism and complex communication needs: multi-stakeholder perspectives.

Augmentative alternative communication (AAC) devices or systems are often prescribed to minimally verbal or nonspeaking autistic individuals and other individuals with complex communication needs to facilitate communication or as an alternative to spoken language. AAC use can result in communication gains and improved quality of life for minimally verbal or nonspeaking individuals. Despite this, AAC abandonment is high, limiting societal participation of the individual on the autism spectrum with complex communication needs. Our study is a novel exploration of the barriers of AAC use from a multi-stakeholder perspective, and a qualitative analysis of similarities and differences between stakeholders. We conducted semi-structured interviews and focus groups with 30 parent-carers, educators and clinicians currently supporting AAC users in Western Australia and analysed the data using reflexive thematic analysis. Barriers from each stakeholder group were coded, resulting in 17 subthemes forming five main themes common to all stakeholders: Stakeholder Knowledge, Stakeholder Attitudes and Stigma, Resources, AAC User Engagement, and Device Fit. Contrasting perspectives included actual and perceived stigma associated with AAC use (parent-carers vs clinicians); different struggles with resources and knowledge (parent-carers vs clinicians and educators); and a lack of clinician communication in the processes that determined AAC-fit for school environments (educators only). Findings are discussed in the context of improving inter-stakeholder collaboration and capacity building in Australian health service and practice to better support minimally verbal or nonspeaking autistic individuals and individuals with complex communication needs. Suggestions are also offered for communication partner training.

TSUnet-CC: Temporal Spectrogram Unet embedding Cross Channel-wise attention mechanism for MDD identification.

Automatic detection of major depressive disorder (MDD) with multiple-channel electroencephalography (EEG) signals is of great significance for treatment of the mental diseases. In a U-net network, clear EEG signals are fed to obtain temporal feature tensor through encoder and decoder networks with several convolution operations. Moreover, the clear EEG signals can be converted into multi-scale spectrogram to obtain the rich saliency information and then the spectrogram feature tensor can be extracted by another symmetrical U-net. The temporal and spectrogram feature tensors can provide more comprehensive information, but may also contain redundant information, which may affect the detection of MDD. To deal with such issue, this paper proposed a novel Temporal Spectrogram Unet (TSUnet-CC), which embeds the cross channel-wise attention mechanism for multiple-channel EEGbased MDD identification. We make three novel contributions: 1) multi-scale saliency-encoded spectrogram using Fourierbased approach to capture rich saliency information under different scales, 2) TSUnet network using a symmetrical twostream U-net architecture that learns multiple temporal and spectrogram feature tensors in time and frequency domains, and 3) cross channel-wise block enabling the larger weights of key feature channels that contain MDD information. The leaveone-subject-out experiments show that our proposed TSUnetCC gains high performance with a classification accuracy up to 98.55% and 99.22% in eyes closed and eyes open datasets, which outperformed some state-of-the-art methods and revealed its clinical potential.

The efficacy of mindfulness-based therapy for anxiety, social skills, and aggressive behaviors in children and young people with Autism Spectrum Disorder: A systematic review.

Introduction: The purpose of this systematic review was to examine the efficacy of mindfulness-based interventions for improving anxiety, social skills, and aggressive behaviors in children and young people (CYP) with Autism Spectrum Disorder (ASD); summarize the results across clinic, home, and school contexts; and evaluate the quality of these interventions for clinical practice. Methods: A search of the PsycINFO, Medline (Ovid), Web of Science, and Scopus databases was conducted in June 2021, and no date restrictions were applied. Inclusion criteria were quantitative or qualitative research implementing a mindfulness-based intervention for CYP aged 6-25 years with a diagnosis of ASD, Pervasive Development Disorder, or Asperger's Syndrome. Results: We identified 23 articles for inclusion including within subject pre- and post-testing, multiple baselines, and randomized control trials, among other research designs. Of these, a quality analysis conducted using an ASD research-specific risk of bias tool found over half (14) were of weak methodological quality, whereas only four and five were found to be of strong and adequate quality, respectively. Discussion: While the results of this systematic review suggest promising evidence for the use of mindfulness-based interventions to improve anxiety, social skills, and aggressive behaviors in CYP with ASD, results should be interpreted with caution due to the limitations resulting from the overall weak quality of the studies.The review protocol was pre-registered on PROSPERO (CRD42021259125) and can be viewed at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=259125.

Convolutional neural network assistance significantly improves dermatologists' diagnosis of cutaneous tumours using clinical images.

BACKGROUND: Convolutional neural networks (CNNs) have demonstrated expert-level performance in cutaneous tumour classification using clinical images, but most previous studies have focused on dermatologist-versus-CNN comparisons rather than their combination. The objective of our study was to evaluate the potential impact of CNN assistance on dermatologists for clinical image interpretation. METHODS: A multi-class CNN was trained and validated using a dataset of 25,773 clinical images comprising 10 categories of cutaneous tumours. The CNN's performance was tested on an independent dataset of 2107 images. A total of 400 images (40 per category) were randomly selected from the test dataset. A fully crossed, self-control, multi-reader multi-case (MRMC) study was conducted to compare the performance of 18 board-certified dermatologists (experience: 13/18 ≤ 10 years; 5/18＞10 years) in interpreting the 400 clinical images with or without CNN assistance. RESULTS: The CNN achieved an overall accuracy of 78.45% and kappa of 0.73 in the classification of 10 types of cutaneous tumours on 2107 images. CNN-assisted dermatologists achieved a higher accuracy (76.60% vs. 62.78%, P < 0.001) and kappa (0.74 vs. 0.59, P < 0.001) than unassisted dermatologists in interpreting the 400 clinical images. Dermatologists with less experience benefited more from CNN assistance. At the binary classification level (malignant or benign), the sensitivity (89.56% vs. 83.21%, P < 0.001) and specificity (87.90% vs. 80.92%, P < 0.001) of dermatologists with CNN assistance were also significantly improved than those without. CONCLUSIONS: CNN assistance improved dermatologist accuracy in interpreting cutaneous tumours and could further boost the acceptance of this new technique.

[Progress in prevention and control of Nipah virus disease].

Nipah virus disease (NVD) is a newly emerged zoonosis with a case fatality rate of 40%-75%. NVD is a severe threat to human health and the development of livestock farming. NVD has become one of the emerging infectious diseases with great concern globally during more than 20 years. Nipah virus (NiV) is a pathogen for NVD, the natural host of which is Fruit bats of the Pteropodidae family. The clinical spectrum of NiV infection is broad, including asymptomatic infection, acute respiratory infection, fatal encephalitis, and even death. Since NiV was first identified in Malaysia in 1999, it has been prevalent mainly in Southeast Asia and South Asia. NiV is primarily transmitted to humans through bat-pig-human, contaminated food. Currently, there are no specific therapeutic drugs and vaccines for NVD. Although there are no cases of NVD reported in China, which has close personnel and trade exchanges with major NVD-endemic countries, and NiV antibody has also been detected in relevant bats. There is a potential risk of importing NVD and domestic outbreaks in the future in this country. This paper provides a systematic review of the research progress in the prevention and control of NVD etiology, epidemiology, clinical manifestations and laboratory diagnosis to help relevant staff to understand NVD more comprehensively and systematically.

Glutamine Imaging: A New Avenue for Glioma Management.

The glutamine pathway is emerging as an important marker of cancer prognosis and a target for new treatments. In gliomas, the most common type of brain tumors, metabolic reprogramming leads to abnormal consumption of glutamine as an energy source, and increased glutamine concentrations are associated with treatment resistance and proliferation. A key challenge in the development of glutamine-based biomarkers and therapies is the limited number of in vivo tools to noninvasively assess local glutamine metabolism and monitor its changes. In this review, we describe the importance of glutamine metabolism in gliomas and review the current landscape of translational and emerging imaging techniques to measure glutamine in the brain. These techniques include MRS, PET, SPECT, and preclinical methods such as fluorescence and mass spectrometry imaging. Finally, we discuss the roadblocks that must be overcome before incorporating glutamine into a personalized approach for glioma management.

[Analysis of screening results and risk factors of high-risk populations of lung cancer in Nanchang city from 2018 to 2019].

Objective: To collate and analyze the screening results of high-risk lung cancer populations in communities in Nanchang from 2018 to 2019, and to explore the lung-positive nodules and risk factors for lung cancer. Methods: Data of the screening subjects in 8 administrative districts and 15 street health service centers in Nanchang city, Jiangxi province from November 2018 to October 2019 were collected, people at high risk of lung cancer was assessed, clinical screening of high-risk groups of lung cancer was conducted by low-dose helical computed tomography (LDCT), and risk factors for suspected lung cancer and lung-positive nodules were analyzed. Results: Of the 25 871 people participated in screening, 5 220 were at high risk for lung cancer and 15 374 without other malignant tumors were at high risk. There were 2 417 cases participated in clinical LDCT screening, including 193 cases of lung-positive nodules, 67 cases of suspected lung cancer, 912 cases of other lung diseases, the positive rate of lung cancer or lung-positive nodules was 10.76% (260/2 417). Univariate analysis showed that age, coarse grain intake, oil intake, housing heating, passive smoking, alcohol consumption and mental trauma were associated with positive pulmonary nodules or lung cancer (all P<0.05). Multivariate analysis showed that gender, age, housing heating, smoking and drinking were related to the occurrence of lung nodules or lung cancer (all P<0.05). Conclusions: Men are more likely to develop lung cancer or lung-positive nodules than women. The age is an independent risk factor for lung-positive nodules or lung cancer. In a certain range, age will increase the incidence of lung cancer, housing heating may be the protective factor for lung cancer, while smoking and drinking are risk factors.

LncRNA DGCR5 promotes non-small cell lung cancer progression via sponging miR-218-5p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA DGCR5 promotes non-small cell lung cancer progression via sponging miR-218-5p, by J. Wang, H.-Z. Shu, C.-Y. Xu, S.-G. Guo, published in Eur Rev Med Pharmacol Sci 2019; 23 (22): 9947-9954-DOI: 10.26355/eurrev_201911_19561-PMID: 31799664" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19561.

MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway, by D.-W. Wang, Y.-Q. Wang, H.-S. Shu, published in Eur Rev Med Pharmacol Sci 2018; 22 (5): 1241-1248-DOI: 10.26355/eurrev_201803_14464-PMID: 29565480" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14464.

RNA interference of tyrosine hydroxylase caused rapid mortality by impairing cuticle formation in Nilaparvata lugens (Hemiptera: Delphacidae).

BACKGROUND: The application of RNA interference (RNAi) technique in controlling agricultural insect pests has been receiving much attention since the discovery of RNAi. The brown planthopper (BPH) Nilaparvata lugens, a notorious pest of rice, has evolved a high level of resistance to many kinds of insecticides. Tyrosine hydroxylase (Th) is an indispensable survival gene in holometabolous insects, playing key roles in cuticle tanning and immunity. In this study, we investigated whether Th could be used as a potential target in controlling N. lugens. RESULTS: Here, we demonstrated that NlTh had a periodical expression pattern during molting with the highest level observed in epidermis. Dysfunction of NlTH by dsNlTh microinjection or 3-IT feeding similarly caused rapid death of N. lugens. Compared with dsGFP control BPHs, dsNlTh injected BPHs (i) had cuticle pigmentation and sclerotizaton defects; (ii) had less endocuticle lamella in tergum integument; (iii) showed higher mortality during the molting process as a result of defective cuticle shedding; (iv) showed feeding disorders indicated by a low number of probe wound dots on rice; (v) had more vulnerable cuticle. CONCLUSION: This study demonstrated that TH orthologues play a conservative and crucial role for exocuticle tanning in both holometabolous and hemimetabolous insects, and NlTh could be targeted for RNAi-mediated BPH control. The rapid lethal phenotype of NlTH dysfunction BPHs partly induced by cuticle formation defects. © 2020 Society of Chemical Industry.

Investigation of empathy amongst dietetic interns at selected primary and tertiary health-care facilities.

AIM: Empathy is an essential aspect in the delivery of quality nutrition care and promoting better outcomes in patients. With an increased emphasis of patient-centred care in dietetic practice, empathy should underpin the construct of the curriculum in dietetic education. The present study investigated the empathy level of dietetic interns through self-reporting measures and patients' perception. METHODS: This cross-sectional study was conducted on a total of 57 dietetic interns and 99 patients from primary and tertiary health care settings. The dietetic interns completed the Toronto Empathy Questionnaire (TEQ) while the Consultation and Relational Empathy (CARE) measure was self-administered by patients. Socio-demographic information of participants was collected. RESULTS: The dietetic interns' mean (standard deviation [SD]) TEQ scores were 46.90 ± 5.28 and 47.78 ± 5.34 in primary and tertiary care, respectively. CARE measure scores rated by patients in the primary care were 38.61 ± 8.38 and for tertiary setting, the scores were slightly higher (39.47 ± 7.65). The settings, gender, ethnicity and period of internship did not affect dietetic interns' empathy level. In primary care, CARE scores were significantly different between patients' age grouping (P = 0.007). CONCLUSIONS: Findings from the present study showed that patients' age significantly affected their perception of dietetic interns' empathy in primary health care. These preliminary findings could facilitate an understanding of the level of empathy amongst interns for consideration in the future design of dietetic training.

LncRNA DGCR5 promotes non-small cell lung cancer progression via sponging miR-218-5p.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is one of the most ordinary malignant tumors worldwide. Recent researches have proved that long noncoding RNAs (lncRNAs) play vital roles in many diseases. The aim of this study was to investigate the exact function of lncRNA DiGeorge syndrome critical region gene 5 (DGCR5) in the development of NSCLC. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect DGCR5 expression in paired NSCLC patients' tissue samples and cell lines. The function of DGCR5 in NSCLC was detected through wound healing assay and transwell assay in vitro. Besides, mechanism assays were conducted to observe the interaction between DGCR5 and microRNA-218-5p (miR-218-5p). RESULTS: DGCR5 was remarkably highly expressed in NSCLC tissues compared to that of adjacent normal tissues. The migration and invasion of NSCLC cells were significantly promoted via overexpression of DGCR5. However, the silence of DGCR5 significantly inhibited NSCLC cell migration and invasion. Moreover, RT-qPCR results revealed that miR-218-5p was down-regulated via overexpression of DGCR5, while miR-218-5p was up-regulated after the knockdown of DGCR5. Further experiments showed that miR-218-5p was a direct target of DGCR5 in NSCLC. CONCLUSIONS: DGCR5 enhances NSCLC cell migration and invasion via targeting miR-218-5p, indicating that DGCR5 may be a potential therapeutic target in NSCLC.

Identity and virulence properties of Aeromonas isolates from healthy Northern snakehead (Channa argus) in China.

Members of the genus Aeromonas are opportunistic pathogen of a variety of aquatic animals that exhibits multidrug resistance, phenotypes, virulence genes and virulence. The present study described the species distribution and the potential pathogenicity of Aeromonas isolated from healthy Northern snakehead (Channa argus) in China. Molecular identification revealed that A. veronii biovar veronii (69/167; 41·3%) and A. hydrophila (41/167; 24·6%) were the most common species found in Northern snakehead intestine based on sequencing of the 16S rRNA gene and DNA gyrase subunit B protein. The distribution of seven virulence factors including aer (84·4%), act (80·8%), ser (40·1%), Aha (27·5%), lip (23·4%), exu (15·0%) and LuxS (12·6%) were determined exclusively in Aeromonas isolates. All the seven virulence genes were present in 9·6% (16/167), among which 11 strains were identified as A. veronii biovar veronii. For the strains harbouring seven virulence genes, the 50% lethal doses (LD50 ) of isolates were lower compared to the isolates carrying two virulence genes. The challenge tests revealed that isolate W31 had the lowest lethal dose, causing 50% mortality at 4·5 × 103 colony-forming units (CFU) per ml. Furthermore, histopathology of Northern snakehead infected with Aeromonas strains showed necrosis and congestion in liver, spleen and kidney and also damage to the intestine. This study confirms that the Aeromonas strains isolated from healthy Northern snakehead may be a cause of concern for public health. SIGNIFICANCE AND IMPACT OF THE STUDY: Aeromonas species are widely distributed in aquatic environments and have considerable virulence potential. The aim of this study was to identify Aeromonas strains isolated from healthy Northern snakehead, and to investigate if Aeromonas species isolated from healthy fish potential pathogenicity with special reference to virulence and epidemiology studies.

Serum immunoinflammation-related protein complexes discriminate between inflammatory bowel disease and colorectal cancer.

PURPOSE: Inflammatory bowel disease (IBD) is an important risk factor for colon cancer. Novel serum immunoinflammation-related protein complexes (IIRPCs) have shown associations with early cancer detection. Herein, we investigated the potential of serum IIRPCs for discriminating between IBD and colorectal cancer (CRC) patients. METHODS: Serum protein complexes of 65 healthy controls, 57 CRC, 69 (ulcerative colitis) UC, and 67 (Crohn's disease) CD patients were isolated by native-PAGE. The gray values of serum IIRPCs bands in the gel were quantified using Quantity One software. The receiver-operating characteristic (ROC) curves were constructed to assess the discriminating ability by calculating the area under the ROC curve. RESULTS: The serum IIRPCs levels in IBD and CRC patients were significantly elevated compared to healthy controls. ROC analysis indicated certain diagnostic ability of serum IIRPCs in differentiating IBD from CRC. Specifically, "a3" complex discriminated UC from CRC, with an AUC value of 0.722, sensitivity of 69.4% and specificity of 63.8%. Similarly, "b4" complex discriminated UC from CRC, with an AUC value of 0.709, sensitivity of 70.4%, and specificity of 60.0%. In addition, the "a3" complex also discriminated CD from CRC, with an AUC value of 0.785, sensitivity of 73.1%, and specificity of 74.1%, while the "b4" complex showed a tendency to discriminate CD from CRC, with an AUC value of 0.663, sensitivity of 67.9% and specificity of 50.0%. Thus, an equation based on multiple IIRPCs was built to further improve the discriminating power. CONCLUSIONS: Serum IIRPCs can be used to discriminate IBD from CRC and may also be associated with early screening of colitis-associated cancer.

Pseudo CT Estimation using Patch-based Joint Dictionary Learning.

Magnetic resonance (MR) simulators have recently gained popularity; it avoids the unnecessary radiation exposure associated with Computed Tomography (CT) when used for radiation therapy planning. We propose a method for pseudo CT estimation from MR images based on joint dictionary learning. Patient-specific anatomical features were extracted from the aligned training images and adopted as signatures for each voxel. The most relevant and informative features were identified to train the joint dictionary learning-based model. The well-trained dictionary was used to predict the pseudo CT of a new patient. This prediction technique was validated with a clinical study of 12 patients with MR and CT images of the brain. The mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross correlation (NCC) indexes were used to quantify the prediction accuracy. We compared our proposed method with a state-of-the-art dictionary learning method. Overall our proposed method significantly improves the prediction accuracy over the state-of-the-art dictionary learning method. We have investigated a novel joint dictionary Iearning- based approach to predict CT images from routine MRIs and demonstrated its reliability. This CT prediction technique could be a useful tool for MRI-based radiation treatment planning or attenuation correction for quantifying PET images for PET/MR imaging.

Role of spinal cyclooxygenase-2 and prostaglandin E2 in fentanyl-induced hyperalgesia in rats.

BACKGROUND: Accumulated evidence suggests that spinal cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) may be implicated in the development of opioid-induced hyperalgesia. METHODS: Rats received subcutaneous fentanyl injections at different doses (20-80 µg kg-1), four separate times at 15-min intervals. Some rats only received fentanyl (60 µg kg-1 × 4 doses) with or without surgical incision. Fentanyl-induced hyperalgesia was evaluated via a tail-pressure or paw-withdrawal test. The concentrations of spinal COX-2, EP-1 receptor (EP-1R) mRNA, and PGE2 were measured. The effects of the COX-2 inhibitor, parecoxib (intraperitoneal 10 mg kg-1), or the EP-1R antagonist, SC51089 (intraperitoneal 100 µg kg-1), on hyperalgesia and spinal PGE2 were examined. RESULTS: Acute repeated injections of fentanyl dose-dependently induced mechanical hyperalgesia, which reached a peak at the 1st day and persisted for 1-4 days postinjection. This hyperalgesia could be partly or totally prevented by the pretreatment of either parecoxib or SC51089. Consistently, the levels of spinal COX-2 mRNA and PGE2 were also dose-dependently increased, reaching a peak at the first day and persisting for 2 days postinjection. Pretreatment with parecoxib could block the increase in spinal PGE2 and had no effects on spinal COX-2 and EP-1R mRNA. Fentanyl injection enhanced incision-induced mechanical and thermal hyperalgesia. CONCLUSIONS: Acute repeated fentanyl administration dose-dependently produced mechanical hyperalgesia and augmented surgery induced postoperative hyperalgesia. This behavioural change was paralleled with an increase in spinal COX-2 mRNA and PGE2 after fentanyl administration. Inhibition of COX-2 or blockade of EP-1R can partly or totally prevent hyperalgesia.

MiR-16 inhibits pituitary adenoma cell proliferation via the suppression of ERK/MAPK signal pathway.

OBJECTIVE: Extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signal pathway participates in cell proliferation, cycle, and apoptosis. MiR-16 is down-regulated in the pituitary tumor. This study investigated the role and related mechanism of miR-16 on pituitary tumor proliferation, cycle, and apoptosis. PATIENTS AND METHODS: Dual-luciferase reporter assay was conducted to demonstrate the targeted regulation between miR-16 and MEK1. MiiR-16, MEK1, p-ERK1/2, Survivin and Cyclin D1 expression were compared between normal embryonic pituitary cells, HP75 tumor cells. Flow cytometry detection measured cell proliferation and cycle. Cultured HP75 cells were divided into four groups: miR-NC, miR-16 mimic, si-NC, and si-MEK1. Expressions of miR-16, MEK1, p-ERK1/2, Survivin, and Cyclin D1 were compared, and cell proliferation, cycle, and apoptosis were tested by flow cytometry. RESULTS: Bioinformatics analysis showed complementary binding sites between miR-16 and MEK1. Dual luciferase reporter assay validated the direct regulation between miR-16 and MEK1. Compared to that of normal pituitary tissues, significantly lower miR-16 expression, but higher MEK1 level were found in adenoma tissues. Compared to normal embryonic pituitary cells, the level of miR-16 was decreased, while the expressions of p-ERK1/2, Survivin, and Cyclin D1, along with cell proliferation or S or G2/M phase ratio were up-regulated in the group of HP75 cells. Transfection of miR-16 mimic or si-MEK1 remarkably suppressed the expressions of MEK1, p-ERK1/2, Survivin or Cyclin D1 in HP75 cells, inhibited cell proliferation and induced apoptosis and cycle arrest. CONCLUSIONS: MiR-16 inhibited ERK/MAPK pathway activity via the suppression of MEK1 expression, and further suppressed proliferation of pituitary tumor cells.

Stereoselective Differences between the Reinforcing and Motivational Effects of Cathinone-Derived 4-Methylmethcathinone (Mephedrone) In Self-Administering Rats.

Mephedrone (4-methylmethcathinone (4-MMC)) (MEPH) is a new psychoactive substance (NPS) of the synthetic cathinone class. MEPH has a chiral center and exists as two enantiomers (R-,S-MEPH), yet stereospecific effects of MEPH have not been extensively investigated in preclinical assays. Because significant behavioral and neurochemical differences can exist between enantiomers, probing effects of stereochemistry on biological activity enables separation of adverse and therapeutic effects. Our prior work showed that R-MEPH, relative to S-MEPH, produced greater locomotor activation, place preference, and facilitation of brain reward thresholds in rodents. The present study sought to determine if MEPH enantiomers display stereospecific reward and reinforcement in rat self-administration assays. In Experiment 1, rats were trained to self-administer racemic MEPH (0.50 mg/kg/inf), and dose substitution effects of R-MEPH (0.50 mg/kg/inf) and S-MEPH (0.25, 0.50, 2.00 mg/kg/inf) were examined. In Experiment 2, separate rats were trained to self-administer R-MEPH (0.25, 0.50, 2.00 mg/kg/inf) or S-MEPH (0.25, 0.50, 2.00 mg/kg/inf) and were thereafter evaluated under progressive-ratio access conditions. Within this cohort, 50 kHz ultrasonic vocalizations (USVs) were recorded to measure potential differences in subjective positive affect associated with MEPH enantiomer self-administration. We identified enantiomer- and dose-dependent effects on infusions earned during self-administration following acquisition of racemic MEPH, with greatest infusions under low-effort, fixed-ratio 1 access conditions from low-dose S-MEPH self-administration. When taxed with progressive-ratio access conditions, rats trained to self-administer R-MEPH showed higher break points than those of rats trained to self-administer S-MEPH. Additionally, R-MEPH elicited greatest rates of 50 kHz USVs compared to S-MEPH. Taken together, these data suggest that the R-enantiomer of MEPH is primarily responsible for the rewarding, reinforcing, and motivational properties of racemic MEPH, which increases our understanding of stereospecific preferences pertaining to MEPH abuse.