Exploring 0D lead-free metal halide with highly efficient blue light emission and high-sensitivity photodetection.

Environmentally friendly and highly efficient blue luminescent materials are an unremitting pursuit in the optoelectronic field. Herein, we assembled a new 0D lead-free metal halide of (F-PPA)ZnBr4, which exhibits narrow blue light emission with a remarkable PLQY of 50.15%, high stability and high detection sensitivity toward UV light. These results indicate the potential for the application of low-dimensional zinc-based halides in multiple optoelectronic devices.

Inundative practice for screening siRNA management candidates against a notorious predatory beetle using olfactory silencing.

Calosoma maximoviczi, a predatory pest beetle, poses a significant threat to wild silk farm production due to its predation on wild silkworms. Given the coexistence of this species with beneficial silkworms in the farm orchards, chemical pesticides are not an ideal solution for controlling its population. In this study, we employed a comprehensive multi-target RNA interference (RNAi) approach to disrupt the olfactory perception of C. maximoviczi through independently silencing 16 odorant receptors (ORs) in the respective genders. Specifically, gene-specific siRNAs were designed to target a panel of ORs, allowing us to investigate the specific interactions between odorant receptors and ligands within this species. Our investigation led to identifying four candidate siOR groups that effectively disrupted the beetle's olfactory tracking of various odorant ligands associated with different trophic levels. Furthermore, we observed sex-specific differences in innate RNAi responses reflected by subsequent gene expression, physiological and behavioral consequences, underscoring the complexity of olfactory signaling and emphasizing the significance of considering species/sex-specific traits when implementing pest control measures. These findings advance our understanding of olfactory coding patterns in C. maximoviczi beetles and establish a foundation for future research in the field of pest management strategies.

Prognostic value of neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte ratios and Glasgow prognostic score in osteosarcoma: A meta-analysis.

BACKGROUND: Some studies investigated the prognostic role of several blood biomarkers, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR) and Glasgow prognostic score (GPS), in osteosarcoma, but their results were inconsistent with each other. AIM: To identify the prognostic value of NLR, PLR, LMR and GPS in osteosarcoma patients through reviewing relevant studies. METHODS: The PubMed, EMBASE, Web of Science and CNKI databases were searched up to October 2, 2021. The primary and second outcomes were overall survival (OS) and disease-free survival (DFS), respectively. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association between these indicators and prognosis of osteosarcoma patients. RESULTS: A total of 13 studies involving 2087 patients were eventually included. The pooled results demonstrated that higher NLR and GPS were significantly associated with poorer OS (HR = 1.88, 95%CI: 1.38-2.55, P < 0.001; HR = 2.19, 95%CI: 1.64-2.94, P < 0.001) and DFS (HR = 1.67, 95%CI: 1.37-2.04, P < 0.001; HR = 2.50, 95%CI: 1.39-4.48, P < 0.001). However, no significant relationship of PLR and LMR and OS (P = 0.085; P = 0.338) and DFS (P = 0.396; P = 0.124) was observed. CONCLUSION: Higher NLR and GPS were related with worse prognosis and might serve as novel prognostic indicators for osteosarcoma patients.

Differential diagnosis between hepatic alveolar echinococcosis and intrahepatic cholangiocarcinoma with conventional ultrasound and contrast-enhanced ultrasound.

BACKGROUND: Misclassifications of hepatic alveolar echinococcosis (HAE) as intrahepatic cholangiocarcinoma (ICC) may lead to inappropriate treatment strategies. The aim of this study was to explore the differential diagnosis with conventional ultrasound and contrast-enhanced ultrasound (CEUS). METHODS: Sixty HAE lesions with 60 propensity score-matched ICC lesions were retrospectively collected. The 120 lesions were randomly divided into a training set (n = 80) and a testing set (n = 40). In the training set, the most useful independent conventional ultrasound and CEUS features was selected for differentiating between HAE and ICC. Then, a simplified US scoring system for diagnosing HAE was constructed based on selected features with weighted coefficients. The constructed US score for HAE was validated in both the training set and the testing set, and diagnostic performance was evaluated. RESULTS: Compared with ICC lesions, HAE lesions were mostly located in the right lobe and had mixed echogenicity, a pseudocystic appearance and foci calcifications on conventional ultrasound. On CEUS, HAE lesions showed more regular rim-like enhancement than ICC lesions and had late washout with a long enhancement duration. The simplified US score consisted of echogenicity, pseudocystic/calcification, bile duct dilatation, enhancement pattern, enhancement duration, and marked washout. In the testing set, the sensitivity, specificity, LR+, LR- and the area under the ROC curve for the score to differentiate HAE from ICC were 80.0, 81.3%, 4.27, 0.25 and 0.905, respectively. CONCLUSIONS: The US score based on typical features from both conventional ultrasound and CEUS could accurately differentiate HAE from ICC.

Association between promoter DNA methylation and gene expression in the pathogenesis of ischemic stroke.

To assess DNA methylation sites as well as gene expression related to ischemic stroke (IS) and comprehensively reveal their correlation and possible pathological mechanisms, we implemented (1) genome-wide DNA methylation profiling from the GEO repository related to IS with and without symptoms; (2) identification of differentially methylation positions (DMPs) and genes (DMGs), functional enrichment analysis along with DMG regulatory network construction; (3) validation tests of 2 differential methylation positions of interest as well as analogous gene expression in other datasets and in IS patients and controls; and (4) correlation analysis of DNA methylation and mRNA expression data. In total, 870 DMPs were physically located within 693 DMGs. After disease ontology (DO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), protein-protein interaction (PPI) network construction as well as module analysis, HLA-DRB1 and HLA-DQB1 were identified. Their expression was validated in 4 other datasets but was significant in only 1, and the expression was lower in the IS group (P < 0.05). After validation in IS patients and controls, we found that these two genes showed more hypermethylation and lower expression levels in the IS group (P < 0.001). The methylation of genes was negatively associated with their expression (P < 0.05). The current study recognized a connection among DNA methylation and gene expression and emphasized the prominence of HLA-DRB1 and HLA-DQB1 in IS pathogenesis.

Effects of soil warming on soil microbial extracellular enzyme activities with different depths in a young Chinese fir (Cunninghamia lanceolata)plantation of subtropics.

Extracellular enzyme activitie (EEAs) are a sensitive indicator of microbial function and soil organic matter decomposition in response to climate warming. Up to now, most studies of climate warming and their effects on EEAs have been restricted on the relatively carbon rich topsoil (the upper 20 cm of the soil), whereas little is known about EEAs in subsoil (below 30 cm depth). This study focused on the responses of EEAs to soil warming in a subtropical forest at depths of 0-10 cm, 10-20 cm, 20-40 cm and 40-60 cm. The examined extracellular enzymes included ß-glucosidase (BG), cellobiohydrolase (CBH), phenoloxidase (PHO) and peroxidase (PEO), all being involved in the C-cycle. The results showed that, 1) warming significantly increased all EEAs (18%-69%) at the depth of 0-10 cm and 10-20 cm. Below the depth of 20 cm, warming did no affect or suppressed EEAs (13%-31%), except increasing PHO (10%) at 20-40 cm. 2) Results from the redundancy analysis showed that the EEAs were mainly driven by ammonium nitrogen (NH4+-N) and soil moisture (M) in organic carbon rich topsoil. Warming enhanced nutrient competition between soil microorganisms and plants. Thus, it increased EEAs to meet NH4+-N demands of microorganisms. In subsoil with relatively low substrate availability, the EEAs were dominated by dissolved organic matter and microbial biomass (MBC). Warming increased dissolved organic matter and thus provided more substrates for microorganisms, which relieved the dependence of microbes on EEAs. Consequently, warming diminished EEAs in subsoils. Our results suggested that EEAs at the four depths showed different responses to warming. In addition, environmental factors accounting for the variances in EEAs under soil warming condition were different at topsoil and subsoil. Paying more attention to microbes at different soil depths has important implications to precisely predict ecosystem C cycling in response to global warming.

c­Jun N­terminal kinase inhibition attenuates early brain injury induced neuronal apoptosis via decreasing p53 phosphorylation and mitochondrial apoptotic pathway activation in subarachnoid hemorrhage rats.

Early brain injury (EBI)­induced neuronal apoptosis is primarily responsible for the subsequent complications of aneurysmal subarachnoid hemorrhage (aSAH), which may increase the risk of mortality in patients with aSAH. c­Jun N­terminal kinase (JNK) has been demonstrated to be a promoter of EBI­induced cell apoptosis, although the mechanism has yet to be fully elucidated. The present study aimed to explore whether the role of JNK1 is associated with tumor protein p53 (p53), which is one of the most important factor that triggers cell apoptosis. JNK1 expression was downregulated via in vivo small interfering RNA transfection in an aSAH rat model in order to assess differences in the behavior, survival times, morphology and genetics of the experimental animals. The results revealed that JNK1 inhibition improved the neurological scores and survival times of SAH rats by interrupting cascaded neuronal apoptosis. The interruption of EBI­induced neuronal apoptosis may originate from a decrease in the level of p53 phosphorylation and deactivation of the downstream mitochondrial apoptotic pathway. Taken together, these results suggest that JNK1 may be a promising target for improving the prognosis of patients with aSAH.

miR-204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.

Gliomas are the most common type of malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. Despite advances in treatments during past decades, prognosis of the disease remains poor, with a median survival time of 12-14 months. Future studies on the molecular mechanism of the disease may provide the theoretical basis to identify new targets for effective therapies. The present study revealed that in glioblastoma cells, the overexpression of cytochrome P450, family 27, subfamily A, polypeptide 1 (CYP27A1) promoted proliferation, while silencing of CYP27A1 inhibited proliferation, without affecting migration and invasion. CYP27A1 protein was upregulated in glioblastoma tissues, indicating that CYP27A1 is an oncogene. The downregulation of specific microRNAs (miRNA) may contribute to the upregulation of oncogenes in glioblastoma. A common strategy was used to predict target miRNAs of CPY27A1 using the miRanda algorithm. miR-211 and miR-204 could target the 3'untranslated region of CPY27A1 mRNA. Additional studies confirmed that the overexpression of miR-204 inhibited CPY27A1 expression in glioblastoma cells. Finally, it was identified that miR-204 was downregulated in glioblastoma and that its overexpression inhibited proliferation, migration and invasion in glioblastoma cells. Thus, it was concluded that miR-204 functions as a tumor suppressor gene, at least partly by suppressing CYP27A1 in glioblastoma.

Selective Electrochemical Reduction of Carbon Dioxide Using Cu Based Metal Organic Framework for CO2 Capture.

The conversion efficiency and product selectivity of the electroreduction of carbon dioxide have been largely limited by the low CO2 solubility in aqueous solution. To relieve this problem, Cu3(BTC)2 (Cu-MOF) as CO2 capture agent was introduced into a carbon paper based gas diffusion electrode (GDE) in this study. The faradaic efficiencies (FEs) of CH4 on GDE with Cu-MOF weight ratio in the range of 7.5-10% are 2-3-fold higher than that of GDE without Cu-MOF addition under negative potentials (-2.3 to -2.5 V vs SCE), and the FE of the competitive hydrogen evolution reaction (HER) is reduced to 30%. This work paves the way to develop GDE with high catalytic activity for ERC.

Prevalence and composition of CHD at different altitudes in Tibet: a cross-sectional study.

BACKGROUND: The prevalence of CHD has been well described worldwide except in Tibet. This study aimed to illustrate the prevalence and composition of CHD in Tibetan children according to altitude. Methods and results In the first part, we prospectively recruited 7088 unselected Tibetan children (4-17 years) from south-west Tibet. The total prevalence of CHD increased from 4.6/1000 below 4200 m to 13.4/1000 above 4700 m, with a female-to-male ratio of 1.3:3.1. The total prevalence and female prevalence of patent ductus arteriosus increased more than 10-fold. Females living above 4700 m had exceptionally high prevalence of patent ductus arteriosus (14.9/1000). The prevalence of atrial septal defect was comparable among different altitudes (3.3-3.8/1000). The prevalence of ventricular septal defect was 1.3/1000 below 4700 m, and no cases were found above this altitude. In the second part, we retrospectively reviewed the clinical data of 383 CHD children in Tibet and 73 children at lower altitudes. The percentage of isolated ventricular septal defect decreased from 54.8 to 3.1%, and the percentage of isolated patent ductus arteriosus increased from 8.2 to 68.4% with elevation. Children living below 4200 m (10.4-13.7%) had a larger proportion of complex CHD than those above this altitude (2.0-3.1%). Of the 20 Tibetan children with complex CHD, 14 (70.0%) lived below 4200 m. CONCLUSIONS: A wide variation in CHD prevalence and composition existed in Tibetan children among different altitudes.

Transthoracic contrast echocardiography using vitamin B6 and sodium bicarbonate as contrast agents for the diagnosis of patent foramen ovale.

To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ2=5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=-2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.

Enhanced upconversion luminescence from ZnO/Zn hybrid nanostructures induced on a Zn foil by femtosecond laser ablation.

ZnO/Zn hybrid nanostructures including nanowires and nanonets were induced on a Zn foil by using 400-nm femtosecond (fs) laser pulses with a low repetition rate of 1 kHz and duration of 100 fs. The laser fluence was chosen to be slightly above the ablation threshold of Zn. The luminescence of the formed ZnO/Zn hybrid nanostructures was examined by using fs laser pulses with a high repetition rate of 76 MHz and duration of ~130 fs through both single-photon and multiphoton excitation. While the luminescence spectrum under the single-photon excitation exhibited a single peak at ~480 nm, a broadband upconversion luminescence with many ripples was observed under the multiphoton excitation. More interestingly, the upconversion luminescence of the ZnO/Zn hybrid nanostructures was significantly enhanced by the underlying Zn nanostructures which induced strongly localized electric field. The enhancement of the upconversion luminescence was verified by the short lifetime of only ~79 ps observed for the ZnO/Zn hybrid nanostructures, which is nearly one order of magnitude smaller as compared with the luminescence lifetime of the ZnO nanorods synthesized by using the chemical coprecipitation method. The localization of electric field in the ZnO/Zn hybrid nanostructures was confirmed by the numerical simulations based the finite-difference time-domain technique.

FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma.

Glioblastoma is the most common primary malignancy of the adult central nervous system (CNS) and is associated with an exceptionally poor prognosis. Elucidation of the pathogenesis and molecular changes will help us to further understand the pathogenesis and progression of the disease and offer new therapeutic targets. FUS1 (TUSC2, tumor suppressor candidate 2) is a tumor-suppressor gene located on human chromosome 3p21. Restoration of FUS1 function in human non-small cell lung cancer (NSCLC) cells was found to significantly inhibit tumor cell growth and modulate the chemosensitivity of lung cancer cells. Yet, its role in human glioblastoma has rarely been addressed. In the present study, we demonstrated that low expression of FUS1 was detected in high-grade human glioma, implying that FUS1 expression is negatively associated with progression of the disease. Subsequent studies confirmed that FUS1 overexpression inhibited the proliferation, migration and invasion of human glioblastoma cells. In addition, we found that FUS1 overexpression significantly upregulated miR-197 expression in the glioblastoma cells. We also revealed that miR-197 suppressed the proliferation, migration and invasion of the cells as well as the silencing of miR-197 attenuated the biological functions of FUS1. Using human glioblastoma tissue samples, we demonstrated that miR-197 is negatively associated with metastasis. All the results demonstrated that FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma and implied that restoration of FUS1 and miR-197 could be new therapeutic strategies for glioblastoma.

Formation of 100-nm periodic structures on a titanium surface by exploiting the oxidation and third harmonic generation induced by femtosecond laser pulses.

Periodic surface structures with periods as small as about one-tenth of the irradiating femtosecond (fs) laser light wavelength were created on the surface of a titanium (Ti) foil by exploiting laser-induced oxidation and third harmonic generation (THG). They were achieved by using 100-fs laser pulses with a repetition rate of 1 kHz and a wavelength ranging from 1.4 to 2.2 µm. It was revealed that an extremely thin TixOy layer was formed on the surface of the Ti foil after irradiating fs laser light with a fluence smaller than the ablation threshold of Ti, leading to a significant enhancement in THG which may exceed the ablation threshold of TixOy. As compared with Ti, the maximum efficacy factor for TixOy appears at a larger normalized wavevector in the direction perpendicular to the polarization of the fs laser light. As a result, the THG-dominated laser ablation of TixOy induces 100-nm periodic structures parallel to the polarization of the fs laser light. The depth of the periodic structures was found to be ~10 nm by atomic force microscopy and the formation of the thin TixOy layer was verified by energy dispersive X-ray spectroscopy.

Prevalence and predictors of decreased glomerular filtration rate in tibetan children with congenital heart disease.

OBJECTIVES: To assess the prevalence of decreased glomerular filtration rate (GFR) in Tibetan children with congenital heart disease (CHD) and its associated risk factors. METHODS: A total of 207 Tibetan children attending authors' center for treatment of CHD from May 2012 through November 2012, were included in the study. GFR was estimated with the Schwartz formula (eGFR). RESULTS: The mean eGFR was 104.3±16.6 mL/min/1.73 m2, and decreased in 21 children (10.1%). In the cyanotic category, eGFR was decreased only in severely cyanotic individuals. In the acyanotic category with left ventricular overload, children with decreased eGFR were younger, more commonly lived in areas above 4,700 m, and had higher left ventricular internal dimensions indexed by body surface areas (LVID/BSA) (53.8±6.9 vs. 40.1±6.8 mm/m2, P<0.001) compared with those with normal eGFR. Multivariate analysis identified LVID/BSA as the only independent predictor for decreased eGFR (OR: 1.329, 95% CI: 1.177~1.501, P<0.001). Receiver operating characteristic analysis showed the area under curve for LVID/BSA was 0.921 (95% CI: 0.863 ~ 0.980, P<0.001), with the optimal cutoff value of 49.8 mm/m2 (sensitivity: 75.0%, specificity: 93.9%). In the remaining category, decreased eGFR was only observed in those living above 4,700 m. CONCLUSIONS: One tenth of Tibetan children with CHD had decreased eGFR. The risk factors included severe cyanosis, younger age, living above 4,700 m and higher LVID/BSA.

Sequence analysis of mitochondrial ND1 gene can reveal the genetic structure and origin of Bactrocera dorsalis s.s.

BACKGROUND: The oriental fruit fly, Bactrocera dorsalis s.s., is one of the most important quarantine pests in many countries, including China. Although the oriental fruit fly has been investigated extensively, its origins and genetic structure remain disputed. In this study, the NADH dehydrogenase subunit 1 (ND1) gene was used as a genetic marker to examine the genetic diversity, population structure, and gene flow of B. dorsalis s.s. throughout its range in China and southeast Asia. RESULTS: Haplotype networks and phylogenetic analysis indicated two distinguishable lineages of the fly population but provided no strong support for geographical subdivision in B. philippinensis. Demographic analysis revealed rapid expansion of B. dorsalis s.s. populations in China and Southeast Asia in the recent years. The greatest amount of genetic diversity was observed in Manila, Pattaya, and Bangkok, and asymmetric migration patterns were observed in different parts of China. The data collected here further show that B. dorsalis s.s. in Yunnan, Guangdong, and Fujian Provinces, and in Taiwan might have different origins within southeast Asia. CONCLUSIONS: Using the mitochondrial ND1 gene, the results of the present study showed B. dorsalis s.s. from different parts of China to have different genetic structures and origins. B. dorsalis s.s. in China and southeast Asia was found to have experienced rapid expansion in recent years. Data further support the existence of two distinguishable lineages of B. dorsalis s.s. in China and indicate genetic diversity and gene flow from multiple origins.The sequences in this paper have been deposited in GenBank/NCBI under accession numbers KC413034-KC413367.

Referral by outreach specialist reduces hospitalisation costs of rural patients with digestive tract cancer: a report from medical consortium in China.

INTRODUCTION: The authors examined the effect of referrals from outreach specialists on total hospitalisation costs of rural Chinese patients receiving surgical treatment for digestive tract cancer at a tertiary hospital within a vertically integrated medical consortium. METHODS: A retrospective cohort study was conducted within the Taiyuan Central Hospital medical consortium between January 2008 and December 2010. This consortium consists of Taiyuan Central Hospital (a tertiary hospital) and three county hospitals in Taiyuan city, the capital of Shanxi province in China. Patients admitted for surgery to treat digestive tract cancer (N=359) were assigned to control (direct admission without referral), referral by local doctor (RL), or referral by outreach specialist (RO) groups according to referral type. Length of stay (LOS) and hospitalisation costs were examined. Regression-adjusted costs were estimated by a multivariate model that controlled for gender, age, type of cancer, Charlson Comorbidity Index (CCI) score, and referral type. RESULTS: Significant differences were found between the three groups (p<0.001) for LOS and total hospitalisation costs. Both were highest for the control group, followed by RL and then the RO groups (LOS: 28.3 ± 4.9, 24.2 ± 5.9, and 19.2 ± 3.7 days; hospitalisation cost: Chinese yuan (CNY)35,087.87 ± 6208.30, 32,853.38 ± 5195.40, and 29,794.56 ± 5250.20). CONCLUSION: A strong association was found between RO and substantially reduced hospitalisation costs in patients receiving digestive tract cancer surgery within the medical consortium as compared to RL. This finding suggests that the strengthened collaboration between outreach specialists and local doctors, herein referred to as the green referral channel, is the key factor leading to reduced hospitalisation costs.

Curcumin suppresses malignant glioma cells growth and induces apoptosis by inhibition of SHH/GLI1 signaling pathway in vitro and vivo.

AIMS: To study the role of curcumin on glioma cells via the SHH/GLI1 pathway in vitro and vivo. METHODS: The effects of curcumin on proliferation, migration, apoptosis, SHH/GLI1 signaling, and GLI1 target genes expression were evaluated in multiple glioma cell lines in vitro. A U87-implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI1. RESULTS: Curcumin showed cytotoxic effects on glioma cell lines in vitro. Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose- and time-dependent manner. Several GLI1-dependent target genes (CyclinD1, Bcl-2, Foxm1) were also downregulated. Curcumin treatment prevented GLI1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group. CONCLUSION: This study shows that curcumin holds a great promise for SHH/GLI1 targeted therapy against gliomas.

MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma.

AIMS: Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro-RNAs that acted as endogenous sequence-specific suppressors of gene expression. METHODS AND RESULTS: Using computational and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl-1 mRNA. Overexpression of miR-139 led to a clear decrease in Mcl-1 expression in gliomas. Reporter assays revealed direct post-transcriptional regulation involving miR-139 and the 3'-untranslated region of Mcl-1. Human glioma tissues with low expression of miR-139 displayed higher expression of Mcl-1 protein than those with high expression, suggesting that low miR-139 contributes to Mcl-1 overexpression. In addition, upregulation of miR-139 suppressed the proliferation and enhanced temozolomide (TMZ)-induced apoptosis. Finally, we observed that Mcl-1 knockdown resulted in similar effects compared with miR-139 transfection. CONCLUSION: Our results suggested that miR-139 negatively regulated Mcl-1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma.