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Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.
Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose–response effects. This meta-analysis aimed to find the dose–response relationship between alcohol, coffee or tea consumption and cognitive deficits.
Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose–response relationship graphs.
The search identified 29 prospective studies from America, Japan, China and some European countries. The dose–response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92–0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits.
Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
Chinese men who have sex with men (MSM) are at high risk for depression, anxiety and suicide. The estimated prevalence of these problems is essential to guide public health policy, but published results vary. This meta-analysis aimed to estimate the prevalence of depressive symptoms, anxiety symptoms and suicide among Chinese MSM.
Systematic searches of EMBASE, MEDLINE, PsycINFO, PubMed, CNKI and Wanfang databases with languages restricted to Chinese and English for studies published before 10 September 2019 on the prevalence of depressive symptoms, anxiety symptoms, suicidal ideation, suicide plans and suicide attempts among Chinese MSM. Studies that were published in the peer-reviewed journals and used validated instruments to assess depression and anxiety were included. The characteristics of studies and the prevalence of depression and anxiety symptoms, suicidal ideation, suicide plans and suicide attempts were independently extracted by authors. Random-effects modelling was used to estimate the pooled rates. Subgroup analysis and univariate meta-regression were conducted to explore potential sources of heterogeneity. This study followed the PRISMA and MOOSE.
Sixty-seven studies were included. Fifty-two studies reported the prevalence of depressive symptoms, with a combined sample of 37 376 people, of whom 12 887 [43.2%; 95% confidence interval (CI), 38.9–47.5] reported depressive symptoms. Twenty-seven studies reported the prevalence of anxiety symptoms, with a combined sample of 10 531 people, of whom 3187 (32.2%; 95% CI, 28.3–36.6) reported anxiety symptoms. Twenty-three studies reported the prevalence of suicidal ideation, with a combined sample of 15 034 people, of whom 3416 (21.2%; 95% CI, 18.3–24.5) had suicidal ideation. Nine studies reported the prevalence of suicide plans, with a combined sample of 5271 people, of whom 401 (6.2%; 95% CI, 3.9–8.6) had suicide plans. Finally, 19 studies reported the prevalence of suicide attempts, with a combined sample of 27 936 people, of whom 1829 (7.3%; 95% CI, 5.6–9.0) had attempted suicide.
The mental health of Chinese MSM is poor compared with the general population. Efforts are warranted to develop interventions to prevent and alleviate mental health problems among this vulnerable population.
Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial activities, and has shown highly protective effects against enteropathogenic bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal pathogenic mycotoxins. The possible effect of curcumin on the alleviation of enterotoxicity induced by OTA is unknown. The effects of dietary curcumin supplementation on OTA-induced oxidative stress, intestinal barrier and mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex 1-day-old White Pekin ducklings with initial BW (43.4±0.1 g) were randomly assigned into controls (fed only the basal diet), a group fed an OTA-contaminated diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400 mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30 ducklings and treatment lasted for 21 days. There was a significant decrease in average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05); curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA group (P<0.05). Histopathological and ultrastructural examination showed clear signs of enterotoxicity caused by OTA, but these changes were largely prevented by curcumin supplementation. Curcumin decreased the concentrations of interleukin-1β, tumor necrosis factor-α and malondialdehyde, and increased the activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight junction protein 1 mRNA and protein levels, and decreased those of ρ-associated protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression of apoptosis-related genes, and downregulated mitochondrial transcription factors A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial (P<0.05). These results indicated that curcumin could protect ducks from OTA-induced impairment of intestinal barrier function and mitochondrial integrity.
MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate gene expression of target messenger RNAs (mRNAs) and miRNAs have been proven to play vital roles in skeletal muscle development. The miRNA-499-5p has been reported to be negatively related with the expression of Sox6, a critical transcription factor for the maintenance of fast-twitch skeletal muscle. In this study, we amplified a length of 2012-bp mRNA that contains a 1512-bp porcine Sox6 (pSox6) 3'UTR from skeletal muscle of a Duroc×Landrace×Yorkshire pig. By luciferase reporter assay we verified that pSox6 is a target of miR-499-5p. In extensor digitorum longus and Soleus muscles of pigs, the expression levels of miR-499-5p and pSox6 mRNA were also inversely correlated. Besides, overexpression of miR-499-5p in porcine satellite cells promoted the expression of MyHC I and MyHC IIa mRNA, along with a reduction of pSox6 mRNA. Taken together, these results indicate that miR-499-5p may facilitate the oxidative myofibers formation by downregulating pSox6 expression.
The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.
Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.
Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.
This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.
We derive zphot for sources in the entire (~0.4 deg2) H-HDF-N field with the EAzY code, based on PSF-matched broad-band (U band to IRAC 4.5 μm) photometry. Our catalog consists of a total of 131,678 sources. We find σNMAD = 0.029 for non-X-ray sources. We also classify each object as a star or galaxy through SED fitting. Furthermore, we match our catalog with the 2 Ms CDF-N main X-ray catalog. For the 462 matched non-stellar X-ray sources, we improve their zphot quality (σNMAD = 0.035) by adding three additional AGN templates. We make our photometry and zphot catalog publicly available.
The aim of this study was to investigate the variations in meat quality, lipid metabolism-related genes, myosin heavy chain (MyHC) isoform genes and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) gene mRNA expressions in longissimus dorsi muscle (LM) of two different pig breeds. Six Rongchang and six Landrace barrows were slaughtered at 161 days of age. Subsequently, meat quality traits and gene expression levels in LM were observed. Results showed that Rongchang pigs not only exhibited greater pH, CIE a*24 h and intramuscular fat content but also exhibited lower body weight, carcass weight, dressing percentage, LM area and CIE b*24 h compared with Landrace pigs (P<0.05). Meanwhile, the mRNA expression levels of the lipogenesis (peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and fatty acid synthase) and fatty acid uptake (lipoprotein lipase)-related genes were greater in the Rongchang (P<0.05), whereas the lipolysis (adipose triglyceride lipase and hormone sensitive lipase) and fatty acid oxidation (carnitine palmitoyltransferase-1B)-related genes were better expressed in the Landrace. Moreover, compared with the Landrace, the mRNA expression levels of MyHCI, MyHCIIa and MyHCIIx were greater, whereas the mRNA expression levels of MyHCIIb were lower in the Rongchang pigs (P<0.05). In addition, the mRNA expression levels of PGC-1α were greater in Rongchang pigs than in the Landrace (P<0.05), which can partly explain the differences in MyHC isoform gene expressions between Rongchang and Landrace pigs. Although the small number of samples does not allow to obtain a definitive conclusion, we can suggest that Rongchang pigs possess better meat quality, and the underlying molecular mechanisms responsible for the better meat quality in fatty pigs may be partly due to the higher mRNA expression levels of lipogenesis and fatty acid uptake-related genes, as well as the oxidative and intermediate muscle fibers, and due to the lower mRNA expression levels of lipolysis and fatty acid oxidation-related genes, as well as the glycolytic muscle fibers.
In New Zealand, agriculture is predominantly based on pastoral grazing systems and animal excreta deposited on soil during grazing have been identified as a major source of nitrous oxide (N2O) emissions. Forage brassicas (Brassica spp.) have been increasingly used to improve lamb performance. Compared with conventional forage perennial ryegrass (Lolium perenne L.), a common forage in New Zealand, forage brassicas have faster growth rates, higher dry matter production and higher nutritive value. The aim of this study was to determine the partitioning of dietary nitrogen (N) between urine and dung in the excreta from sheep fed forage brassica rape (B. napus subsp. oleifera L.) or ryegrass, and then to measure N2O emissions when the excreta from the two different feed sources were applied to a pasture soil. A sheep metabolism study was conducted to determine urine and dung-N outputs from sheep fed forage rape or ryegrass, and N partitioning between urine and dung. Urine and dung were collected and then used in a field plot experiment for measuring N2O emissions. The experimental site contained a perennial ryegrass/white clover pasture on a poorly drained silt-loam soil. The treatments included urine from sheep fed forage rape or ryegrass, dung from sheep fed forage rape or ryegrass, and a control without dung or urine applied. N2O emission measurements were carried out using a static chamber technique. For each excreta type, the total N2O emissions and emission factor (EF3; N2O–N emitted during the 3- or 8-month measurement period as a per cent of animal urine or dung-N applied, respectively) were calculated. Our results indicate that, in terms of per unit of N intake, a similar amount of N was excreted in urine from sheep fed either forage rape or ryegrass, but less dung N was excreted from sheep fed forage rape than ryegrass. The EF3 for urine from sheep fed forage rape was lower compared with urine from sheep fed ryegrass. This may have been because of plant secondary metabolites, such as glucosinolates in forage rape and their degradation products, are transferred to urine and affect soil N transformation processes. However, the difference in the EF3 for dung from sheep fed ryegrass and forage rape was not significant.
MicroRNAs are endogenous ~22nt RNAs that negatively regulate gene expression at the posttranscriptional level via binding to the 3′-untranslated region (3′UTR) of target mRNAs. The microRNA miR-27a was reported to depress the expression of myostatin, a critical inhibitor of skeletal myogenesis, by binding to its 3′UTR in mouse. In this study, we cloned the full-length 3′UTR of porcine myostatin by rapid amplification of 3′-cDNA ends (3′-RACE) and demonstrated that the 3′UTR of porcine myostatin is targeted by miR-27a. The phenomenon that the level of myostatin inversely correlated with miR-27a was observed in fat and heart of pigs and also in proliferating porcine myoblasts. Besides, overexpression of miR-27a in porcine myoblasts promoted cell proliferation by reducing the expression of myostatin. Our data suggest that miR-27a positive regulates porcine myoblast proliferation via targeting myostatin.
We investigated the seasonality of tuberculosis (TB) in Wuhan, China, to evaluate the increased risk of disease transmission during each season and to develop an effective TB control strategy. We applied spectral analysis to the weekly prevalence data of sputum smear positive (SSP) and sputum smear negative (SSN) pulmonary TB reported from 2006 to 2010. Cases of both SSP and SSN feature 1·0- and 0·5-year periodic modes. The least squares method was used to fit curves to the two periodic modes for SSP and SSN data. The curves demonstrated dominant peaks in spring similar to cases reported previously for other locations. Notably for SSP, dominant peaks were also observed in summer. The spring peaks of SSP and SSN were explained in terms of poorly ventilated and humid rooms and vitamin D deficiency. For the summer peaks of SSP, summer influenza epidemics in Wuhan may contribute to the increase in TB prevalence.
The self-referential memory (SRM) effect refers to the phenomenon that stimuli processed with reference to the self are better remembered than those referenced to others. Studies have shown that schizophrenia patients do not have this memorial advantage for self-referenced information. The current study investigated the electrophysiological mechanism of the abolished SRM effect in schizophrenia.
Twenty schizophrenia patients and 22 controls were recruited to complete an SRM task. We used a high-time resolution event-related potential (ERP) technique to analyze the electrophysiological differences between patients and controls during self- and other-reflection processing.
Behavior data indicated that healthy controls had a typical SRM bias that was absent in the schizophrenia patients. ERP comparison between groups showed that the schizophrenia patients presented smaller voltages in both self- and other-reflection conditions in the 160–260 ms (P2 component) and 800–1200 ms (positive slow wave) time windows over the pre/frontal cortex. Furthermore, the N2 amplitudes (270–380 ms) differed between self- and other-reflection conditions in patients but not in normal controls. More importantly, we found that the P3 amplitudes in the parietal cortex correlated significantly with the SRM bias score in the patients (r = –0.688).
These results provide comprehensive and direct electrophysiological evidence for self- and other-reflective dysfunction in schizophrenia patients and contribute to our understanding of the underlying neural substrates of the abolished SRM effect in schizophrenia.
The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms.
We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD.
Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9–6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt.
This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.