Synthesis and Electrocatalytic Applications of Layer-Structured Metal Chalcogenides Composites.

Featured with the attractive properties such as large surface area, unique atomic layer thickness, excellent electronic conductivity, and superior catalytic activity, layered metal chalcogenides (LMCs) have received considerable research attention in electrocatalytic applications. In this review, the approaches developed to synthesize LMCs-based electrocatalysts are summarized. Recent progress in LMCs-based composites for electrochemical energy conversion applications including oxygen reduction reaction, carbon dioxide reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, overall water splitting, and nitrogen reduction reaction is reviewed, and the potential opportunities and practical obstacles for the development of LMCs-based composites as high-performing active substances for electrocatalytic applications are also discussed. This review may provide an inspiring guidance for developing high-performance LMCs for electrochemical energy conversion applications.

One-Pot Synthesis of Ce-SSZ-39 Zeolite with Performance in the NH3-SCR Reaction.

Cu-SSZ-39 zeolite with 8-membered rings is regarded as a very promising catalyst in the NH3-SCR reaction, but its hydrothermal stability still remains to be improved. One of the solutions to promote hydrothermal stability is the insertion of rare earth elements in the product. Nevertheless, normal ion exchange of rare earth elements limits their contents in the zeolite product due to their large hydrated ionic radius and alkaline environment under hydrothermal conditions. Herein, we for the first time present a new method for the one-pot synthesis of Ce-SSZ-39 zeolite under solvent-free conditions. The key to success is the use of Ce-FAU zeolite as a precursor. The obtained product shows good crystallinity, sheet-like morphology, large BET surface area, and 4-coordinated Al species. Detailed investigations illustrate that Ce species in the Cu/Ce-SSZ-39 zeolite micropore can prevent the dealumination and thus formation of CuAlOx species during hydrothermal aging at 850 °C for 16 h, giving the excellent hydrothermal stability and thus showing the excellent catalytic performance in the NH3-SCR reaction. One-pot synthesis of Ce-SSZ-39 zeolite with excellent catalytic performance might open a new door for developing very efficient selective catalytic reduction (SCR) catalysts in near future.

Dynamic bidirectional relation between state mindfulness and suicidal ideation among female college students: The moderating effect of trait mindfulness.

Research has indicated that mindfulness is a protective factor against suicidal ideation. However, the dynamic reciprocal relation between them has been understudied. In this study, 110 female college students with suicidal ideation completed a measure of trait mindfulness and a 28-day diary of suicidal ideation and three-dimensional state mindfulness, including acting with awareness, present-moment attention, and nonjudgmental acceptance. Dynamic structural equation modeling was used to examine the dynamic and bidirectional effects between dimensions of state mindfulness and suicidal ideation and the moderating effect of trait mindfulness. Results showed that suicidal ideation predicted lower levels of present-moment attention the next day. More importantly, there was a dynamic and bidirectional relation between nonjudgmental acceptance and suicidal ideation for people with trait mindfulness higher than the average level (i.e., M + 0.15SD). Our findings suggested that studies and interventions on suicide should pay more attention to specific dimensions of state mindfulness and trait mindfulness.

Insights into the Synthesis of Spiral Beta Zeolite with Enhanced Catalytic Performance in VOC Abatement.

The rational synthesis of zeolites with designed morphology is a highly challenging task. In this study, we propose 1,5-bis(methylpiperidine)pentylammonium hydroxide (BMPPAOH) as an organic structure-directing agent (OSDA) based on theoretical calculations. The morphology of zeolite samples is characterized by XRD, SEM, TEM, N2 sorption isotherms, and UV Raman spectroscopy. This simple bis-quaternary ammonium salt favored the formation of spiral morphology in Beta zeolite spheres (S-Beta). The crystallization of zeolite in the presence of BMMPAOH is a two-stage process, where nanoparticles agglomerate into spheres in the early stages followed by the emergence of S-Beta crystals with spiral morphology. The synthesized Pt-S-Beta catalysts show higher catalytic activity in VOC abatement compared with other Pt-Beta samples.

From cross-lagged effects to feedback effects: Further insights into the estimation and interpretation of bidirectional relations.

Bidirectional relations have long been of interest in psychology and other social behavioral sciences. In recent years, the widespread use of intensive longitudinal data has provided new opportunities to examine dynamic bidirectional relations between variables. However, most previous studies have focused on the effect of one variable on the other (i.e., cross-lagged effects) rather than the overall effect representing the dynamic interplay between two variables (i.e., feedback effects), which we believe may be due to a lack of relevant methodological guidance. To quantify bidirectional relations as a whole, this study attempted to provide guidance for the estimation and interpretation of feedback effects based on dynamic structural equation models. First, we illustrated the estimation procedure for the average and person-specific feedback effects. Then, to facilitate the interpretation of feedback effects, we established an empirical benchmark by quantitatively synthesizing the results of relevant empirical studies. Finally, we used a set of empirical data to demonstrate how feedback effects can help (a) test theories based on bidirectional relations and (b) reveal correlates of individual differences in bidirectional relations. We also discussed the broad application prospects of feedback effects from a dynamic systems perspective. This study provides guidance for applied researchers interested in further examining feedback effects in bidirectional relations, and the shift from focusing on cross-lagged effects only to a comprehensive consideration of feedback effects may provide new insights into the study of bidirectional relations.

Phenotypic findings and pregnancy outcomes of fetal rare autosomal aneuploidies detected using chromosomal microarray analysis.

BACKGROUND: Aneuploidies are the most common chromosomal abnormality and the main genetic cause of adverse pregnancy outcomes. Since numerous studies have focused on common trisomies, relatively little is known about the association between phenotypic findings and rare autosomal aneuploidies (RAAs). We conducted a retrospective study of 48,904 cases for chromosomal microarray analysis in a large tertiary referral center and reported the overall frequencies, clinical manifestations, and outcomes of prenatal RAAs. RESULTS: A total of 90 RAAs were detected, of which 83 cases were mosaic trisomies and 7 were non-mosaic trisomies. Chromosomes 16, 22, and 9 were identified as the major chromosomes involving RAAs. The four predominant indications for prenatal diagnosis in our RAA cases were RAA-positive in noninvasive prenatal screening, advanced maternal age, ultrasound abnormalities, and high-risk for serum prenatal screening. Cardiovascular defects were the most frequently observed structural abnormalities, followed by musculoskeletal anomalies. Increased nuchal translucency and persistent left superior vena cava, the major soft marker abnormalities involved, were also observed in our RAA cases. Clinical outcomes were available for all RAAs, with 63 induced abortions and 27 live births recorded. CONCLUSIONS: Variable phenotypes and outcomes were observed, which were highly heterogeneous in cases of prenatal RAAs. Thus, a cautious and comprehensive strategy should be implemented during prenatal counseling for RAAs.

Hounsfield units on abdominal computed tomography: a new tool for predicting osteoporosis.

BACKGROUND: Osteoporosis can cause bone fractures and disability, but early diagnosis faces challenges. Our proposed diagnostic indicators offer a new approach for early detection, which benefits early identification. PURPOSE: To determine the most appropriate threshold for predicting osteoporosis in patients with each section of vertebral body. MATERIAL AND METHODS: A retrospective analysis of 210 patients, including 646 vertebrae, who had both abdominal computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) within six months. The correlation between DXA T-score and CT Hounsfield units (HU) values was tested by Pearson. The area under the curve (AUC) was calculated using the threshold obtained from the regression equation. RESULTS: The thresholds matching the T-score of -2.5 were 85, 95, 85, and 90 HU for the upper axial plane of the vertebral body (Lau), the middle axial plane of the vertebral body (Lam), the lower axial plane of the vertebral body (Lad), and the mid-sagittal plane of the vertebral body (Lsm), respectively. Defining osteoporosis using CT as Lau ≤ 85, Lam ≤ 95, Lad ≤ 85, or Lsm ≤ 90 HU had a specificity of 88.1% (116/134) and sensitivity of 90.8% (69/76) for distinguishing DXA osteoporosis of the lumbar spine in 210 patients. T-score ≤-2.5 defined as Lau ≤85 or Lam ≤95 or Lad ≤85 or Lsm ≤90 HU had a specificity of 85.9% (275/320) and sensitivity of 82.8% (270/326) for DXA T-score ≤-2.5 in 646 lumbar vertebrae. CONCLUSION: CT HU values obtained based on different sections of the vertebral body in abdominal CT can be used as a supplementary measure to assess osteoporosis.

Routine chest CT combined with the osteoporosis self-assessment tool for Asians (OSTA): a screening tool for patients with osteoporosis.

INTRODUCTION: The osteoporosis self-assessment tool for Asians (OSTA) is a common screening tool for osteoporosis. The seventh thoracic CT (CT-T7) Hounsfield unit (HU) measured by chest CT correlates with osteoporosis. This study aimed to investigate the diagnostic value of OSTA alone, CT-T7 alone, or the combination of OSTA and CT-T7 in osteoporosis. MATERIALS AND METHODS: In this study, 1268 participants were grouped into 586 men and 682 women. We established multiple linear regression models by combining CT-T7 and OSTA. Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose osteoporosis. RESULTS: In the male group, the mean age was 59.02 years, and 108 patients (18.4%) had osteoporosis. In the female group, the mean age was 63.23 years, and 308 patients (45.2%) had osteoporosis. By ROC curve comparison, the CT-T7 (male, AUC = 0.789, 95% CI 0.745-0.832; female, AUC = 0.835, 95% CI 0.805-0.864) in the diagnosis of osteoporosis was greater than the OSTA (male, AUC = 0.673, 95% CI 0.620-0.726; female, AUC = 0.775, 95% CI 0.741-0.810) in both the male and female groups (p < 0.001). When OSTA was combined with CT, the equation of multiple linear regression (MLR) was obtained as follows: female = 3.020-0.028*OSTA-0.004*CT-T7. In the female group, it was found that the AUC of MLR (AUC = 0.853, 95% CI 0.825-0.880) in the diagnosis of osteoporosis was larger than that of CT-T7 (p < 0.01). When the MLR was 2.65, the sensitivity and specificity were 53.9% and 90%, respectively. CONCLUSION: For a patient who has completed chest CT, CT-T7 (HU) combined with OSTA is recommended to identify the high-risk population of osteoporosis, and it has a higher diagnostic value than OSTA alone or CT-T7 alone, especially among females. For a female with MLR greater than 2.65, further DXA examination is needed.

TRIM32 inhibits the proliferation and migration of pulmonary artery smooth muscle cells through the inactivation of PI3K/Akt pathway in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fetal cardiovascular disease. Tripartite motif 32 (TRIM32) is a member of TRIM family that has been found to be involved in cardiovascular disease. However, the role of TRIM32 in PAH remains unclear. Here we investigated the effects of TRIM32 on hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) in vitro. Our results showed that TRIM32 protein level in the plasma samples from PAH patients was decreased as compared with healthy volunteers. Exposure to hypoxia condition caused a significant decrease in TRIM32 expression in PASMCs. Overexpression of TRIM32 inhibited hypoxia-induced proliferation and migration of PASMCs. TRIM32 overexpression elevated the increased apoptotic rate and caspase-3 activity in hypoxia-induced PASMCs. Moreover, overexpression of TRIM32 reversed hypoxia-induced down-regulation of myocardin, SM 22 and calponin, as well as up-regulation of osteopontin (OPN). Whereas, TRIM32 knockdown shwed the opposite effect. Furthermore, overexpression of TRIM32 inhibited hypoxia-induced activation of PI3K/Akt with decreased phosphorylated level of PI3K and Akt. Additionally, activation of PI3K/Akt by IGF-1 treatment reversed the effects of TRIM32 on hypoxia-induced PASMCs. In conclusion, these findings indicated that TRIM32 was involved in the development of PAH through regulating the proliferation, migration, apoptosis and dedifferentiation of PASMCs, which might be mediated by the PI3K/Akt signaling pathway. Thus, TRIM32 might be a potential target for PAH treatment.

Subconjunctival injection of tumor necrosis factor-α pre-stimulated bone marrow-derived mesenchymal stem cells enhances anti-inflammation and anti-fibrosis in ocular alkali burns.

PURPOSE: To investigate the therapeutic effect of subconjunctival injection of tumor necrosis factor-α (TNF-α) pre-stimulated bone marrow-derived mesenchymal stem cells (BMMSCs) on ocular alkali burns in a rat model. METHODS: After applying a 6 mm filter paper soaking in 1 N NaOH on the cornea of rats, the suspension of TNF-α pre-stimulated BMMSCs, BMMSCs and PBS were given subconjunctivally and respectively. Corneal epithelial defect, corneal opacity, inflammation as well as PTGS2 and TSG-6 expression on day 7 and fibrosis on day 14 were compared. RESULTS: TNF-α pre-stimulated BMMSCs group had a more predominate effect on promoting corneal epithelial repairing, decreasing corneal opacity, reducing inflammatory cells and CD68 + macrophages on day 7 and suppressing fibrosis on day 14 compared to BMMSCs group. Besides, it had significant increased expressions of PTGS2 and TSG-6 in vitro. Pre-treated with Indomethacin revealed a reverse effect on above-mentioned changes. CONCLUSION: Subconjunctival injection of TNF-α pre-stimulated BMMSCs enhanced anti-inflammatory and anti-fibrotic effect in ocular alkali burns, which was possibly though up regulation of PTGS2 and TSG-6 expression.

Advances in the Synthesis of Crystalline Metallosilicate Zeolites via Interlayer Expansion.

Given the numerous industrial applications of zeolites as adsorbents, catalysts, and ion-exchangers, the development of new zeolite structures is highly desired to expand their practical applications. Currently, a general route to develop new zeolite structures is to use interlayer expansion agents to connect layered silicates. In this review, we briefly summarize the novel zeolite structures constructed from the lamellar precursor zeolites MWW, RUB-36, PREFER, Nu-6(1), COK-5, and PLS-1 via interlayer expansion. The contents of the summary contain detailed experiments, physicochemical characterizations, possible expansion mechanisms, and catalytic properties. In addition, the insertion of metal heteroatoms (such as Ti, Fe, Sn) into the layered zeolite precursor through interlayer expansion, which could be helpful to modify the catalytic function, is discussed.

Factors affecting cell-free DNA fetal fraction: statistical analysis of 13,661 maternal plasmas for non-invasive prenatal screening.

BACKGROUND: The identification of cell-free fetal DNA (cffDNA) facilitated non-invasive prenatal screening (NIPS) through analysis of cffDNA in maternal plasma. However, challenges regarding its clinical implementation become apparent. Factors affecting fetal fraction should be clarified to guide its clinical application. RESULTS: A total of 13,661 pregnant subjects with singleton pregnancies who undertook NIPS were included in the study. Relationship of gestational age, maternal BMI, and maternal age with the cffDNA fetal fraction in maternal plasmas for NIPS was investigated. Compared with 13 weeks (12.74%) and 14-18 weeks group (12.73%), the fetal fraction in gestational ages of 19-23 weeks, 24-28 weeks, and more than 29 weeks groups significantly increased to 13.11%, 16.14%, and 21.17%, respectively (P < 0.01). Compared with fetal fraction of 14.54% in the maternal BMI group of < 18.5 kg/m2, the percentage of fetal fraction in the group of 18.5-24.9 kg/m2 (13.37%), 25-29.9 kg/m2 (12.20%), 30-34.9 kg/m2 (11.32%), and 35-39.9 kg/m2 (11.57%) decreased significantly (P < 0.01). Compared with the fetal fraction of 14.38% in the group of 18-24 years old, the fetal fraction in the maternal age group of 25-29 years old group (13.98%) (P < 0.05), 30-34 years old group (13.18%) (P < 0.01), 35-39 years old group (12.34%) (P < 0.01), and ≥ 40 years old (11.90%) group (P < 0.01) decreased significantly. CONCLUSIONS: The percentage of fetal fraction significantly increased with increase of gestational age. Decreased fetal fraction with increasing maternal BMI was found. Maternal age was also negatively related to the fetal fraction.

PAX3 silencing inhibits prostate cancer progression through the suppression of the TGF-ß/Smad signaling axis.

Multiple studies have confirmed the pro-oncogenic effects of PAX3 in an array of cancers, but its role in prostate cancer (PCa) remains largely undefined. The aim of this study is to investigate the role of PAX3 in PCa. PAX3 expression was compared between PCa tumor tissue and nontumor tissues and PCa cell lines and normal prostate epithelial cells (PNT2) by western blot analysis and immunohistochemistry staining. MTT and immunofluorescence assays were used to detect PCa cell proliferation. Flow cytometry was used to evaluate cell apoptosis in PCa. Transwell assays were used for the determination of cell migration and PCa cell invasion. PAX3 expression was higher in PCa tissues and human PCa cell lines. Moreover, PAX3 silencing inhibited the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of PCa cells, and increased the rates of apoptosis. PAX3 silencing inhibited transforming growth factor-ß (TGF-ß)/Smad signaling in PCa cells. The effects of si-PAX3 on the proliferation, apoptosis, metastasis, and EMT of PCa cells were alleviated by TGF-ß1 treatment. PAX3 silencing inhibits PCa progression through the inhibition of TGF-ß/Smad signaling. This reveals PAX3 as a novel biomarker and therapeutic target for future PCa treatments.

Cathodic electrodeposited Cu-BTC MOFs assembled from Cu(II) and trimesic acid for electrochemical determination of bisphenol A.

The authors describe a novel electrochemical determination method for bisphenol A (BPA) based on the electrosynthesised Cu-BTC (H3BTC: trimesic acid) films. Using H3BTC as the ligand, Cu(NO3)2 as the precursor of copper ions, and triethylamine hydrochloride (Et3NHCl) as the probase source, Cu-BTC films were directly deposited on glassy carbon electrode (GCE) surface via cathodic electrochemical reduction under -1.30 V. Considering the electrocatalytic activity of metal center Cu2+, Cu-BTC films were applied to construct the electrochemical determination platform for BPA. Chronocoulometry and electrochemical impedance spectroscopy were used to study the signal enhancement mechanism. The determination conditions were optimized. As a result, a sensitive electrochemical method was constructed for BPA. The peak currents, best measured at voltage of 0.496 V vs. SCE (KCl saturated calomel reference electrode), increase linearly in the range from 5.0 to 2000 nM. The value of determination limit is 0.72 nM. The proposed method was successfully applied to determine BPA in spiked urine, spiked waste water samples and plastic products. The results were in good agreement with those obtained for the same samples by high-performance liquid chromatography (HPLC). Graphical abstract Schematics for the construction of electrochemical determination for bisphenol A.

Overexpression of the lncRNA FER1L4 inhibits paclitaxel tolerance of ovarian cancer cells via the regulation of the MAPK signaling pathway.

To determine how the lncRNA FER1L4 in ovarian cancer cells influences paclitaxel (PTX) resistance, we examined the expression level of FER1L4 in human ovarian epithelial cell lines IOSE80 and HOSEpiC and human ovarian cancer cell lines OVCAR-3, Caov-3, and SKOV3 through RNA isolation and quantitative polymerase chain reaction (qRT-PCR). SKOV3 cell lines were treated with PTX. The cell survival rate and apoptosis rate of SKOV3 and SKOV3-PR at different PTX dose levels were evaluated. Next, qRT-PCR was performed to detect the expression of FER1L4 in SKOV3 and SKOV3-PR cell lines. SKOV3-PR cell lines were transfected with pcDNA3.1 as the control group (SKOV3-PR/pcDNA3.1) or pcDNA3.1-FER1L4 to upregulate the expression level of FER1L4 (SKOV3-PR/pcDNA3.1-FER1L4). The level of cell survival, apoptosis, and colony formation were compared between the two groups using MTT, flow cytometry analysis, and colony formation assay. To reveal the molecular mechanism, we measured the relative protein phosphorylation level of ERK and MAPK in SKOV3, SKOV3-PR, SKOV3-PR/pcDNA3.1, and SKOV3-PR/pcDNA3.1-FER1L4 groups using an enzyme-linked immunosorbent assay. The effects of SB203580 (a p38 MAPK inhibitor) on PTX were also investigated to reveal the function of the MAPK pathway on the PTX tolerance of SKOV3. In comparison with normal ovarian epithelial cells, FER1L4 was downregulated. The FER1L4 level was decreased in human ovarian cancer cells with drug resistance than in common ovarian cancer cells. The upregulation of FER1L4 could promote the PTX sensitivity of ovarian cancer cells. The increased level of FER1L4 could suppress the PTX resistance of ovarian cancer cells through the inhibition of the MAPK signaling pathway.

MicroRNA-501-3p restricts prostate cancer growth through regulating cell cycle-related and expression-elevated protein in tumor/cyclin D1 signaling.

MicroRNA-501-3p (miR-501-3p) has been reported as a novel cancer-related miRNA in many types of cancer. However, the precise biological function of miR-501-3p in prostate cancer remains unknown. In this study, we aimed to investigate the regulatory effect and mechanism of miR-501-3p on cell growth of prostate cancer cells. We found that miR-501-3p expression was significantly downregulated in prostate cancer tissues and cell lines. Gain-of-function experiments showed that upregulation of miR-501-3p expression significantly decreased cell proliferation and colony formation, and induced cell cycle arrest in the G0/G1 phase. Bioinformatics analysis predicted that cell cycle-related and expression-elevated protein in tumor (CREPT) was a potential target gene of miR-501-3p., and the results of our luciferase reporter assay confirmed that miR-501-3p bound to the 3'-untranslated region of CREPT at the predicted binding site. Moreover, miR-501-3p was shown to negatively regulate CREPT expression in prostate cancer cells. Correlation analysis showed that miR-501-3p was inversely correlated with CREPT expression in prostate cancer tissues. Knockdown studies revealed that miR-501-3p regulated the expression of cyclin D1 by targeting CREPT. Additionally, the inhibitory effect of miR-501-3p on prostate cancer cell growth was partially reversed by CREPT overexpression. Overall, these results suggest that miR-501-3p restricts prostate cancer cell growth by targeting CREPT to inhibit the expression of cyclin D1. These findings indicate that the miR-501-3p/CREPT/cyclin D1 axis plays a crucial role in the progression of prostate cancer and may serve as potential therapeutic target.

Association between fetal fraction at the second trimester and subsequent spontaneous preterm birth.

OBJECTIVE: To evaluate the association between the fetal fraction of cell-free DNA at the second trimester and subsequent spontaneous preterm birth. METHODS: In this retrospective cohort study, data were collected from women with singleton pregnancies who underwent noninvasive prenatal testing at 14 to 25 weeks of gestation. The eligible patients were classified into three groups according to pregnancy outcome: birth at ≥37 weeks of gestation (term group), delivery at <34 weeks of gestation (early spontaneous preterm), and delivery at 34+0 to 36+6  weeks of gestation (late spontaneous preterm). Stepwise linear regression was performed to determine the maternal characteristics associated with the fetal fraction of cell-free DNA. Logistic regression was used to determine the relationship between the fetal fraction of cell-free DNA and pregnancy outcomes by adjusting for history of preterm birth. RESULTS: A total of 8129 singleton pregnancies met the recruitment criteria. Among them, 7790 (95.83%) were in the term group, 284 (3.49%) were in the late spontaneous preterm group, and 55 (0.68%) were in the early spontaneous preterm group. The fetal fraction of cell-free DNA was negatively correlated with body mass index, maternal age, nulliparity, and history of spontaneous preterm birth; positively correlated with gestational age; and not correlated with assisted reproduction or surface antigen of hepatitis B virus (HBsAg) positivity. After adjusting for history of preterm birth, a logistic regression analysis demonstrated no statistically significant associations between the fetal fraction of cell-free DNA and spontaneous preterm birth in any of the preterm groups (<34 weeks, 34+0 to 36+6  weeks, and <37 weeks). CONCLUSION: Our preliminary study found no relationship between the fetal fraction on NIPT at the second trimester and subsequent spontaneous preterm birth.

[Prenatal diagnosis of a fetus with Mowat-Wilson syndrome].

OBJECTIVE: To explore the genetic basis for a fetus featuring increased nuchal thickness. METHODS: Routine G-banding karyotyping and single nucleotide polymrophism array were carried out to detect genomic copy number variations (CNVs) in the fetus. RESULTS: The fetus was found to harbor a heterozygous 3.8 Mb deletion in the 2q22.2-q22.3 region encompassing the ZEB2 gene, which is closely associated with Mowat-Wilson syndrome (MWS). CONCLUSION: Haploinsufficiency of the ZEB2 gene may predispose to MWS. Lack of knowledge regarding to the ultrasonographic features of MWS may lead to misdiagnosis of the syndrome.

Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. METHODS: We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America. Boys aged 7-16 years with nonsense mutation DMD and a baseline 6-minute walk distance (6MWD) of 150 m or more and 80% or less of the predicted normal value for age and height were randomly assigned (1:1), via permuted block randomisation (block size of four) using an interactive voice-response or web-response system, to receive ataluren orally three times daily (40 mg/kg per day) or matching placebo. Randomisation was stratified by age (<9 years vs ≥9 years), duration of previous corticosteroid use (6 months to <12 months vs ≥12 months), and baseline 6MWD (<350 m vs ≥350 m). Patients, parents and caregivers, investigational site personnel, PTC Therapeutics employees, and all other study personnel were masked to group allocation until after database lock. The primary endpoint was change in 6MWD from baseline to week 48. We additionally did a prespecified subgroup analysis of the primary endpoint, based on baseline 6MWD, which is reflective of anticipated rates of disease progression over 1 year. The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01826487. FINDINGS: Between March 26, 2013, and Aug 26, 2014, we randomly assigned 230 patients to receive ataluren (n=115) or placebo (n=115); 228 patients comprised the intention-to-treat population. The least-squares mean change in 6MWD from baseline to week 48 was -47·7 m (SE 9·3) for ataluren-treated patients and -60·7 m (9·3) for placebo-treated patients (difference 13·0 m [SE 10·4], 95% CI -7·4 to 33·4; p=0·213). The least-squares mean change for ataluren versus placebo in the prespecified subgroups was -7·7 m (SE 24·1, 95% CI -54·9 to 39·5; p=0·749) in the group with a 6MWD of less than 300 m, 42·9 m (15·9, 11·8-74·0; p=0·007) in the group with a 6MWD of 300 m or more to less than 400 m, and -9·5 m (17·2, -43·2 to 24·2; p=0·580) in the group with a 6MWD of 400 m or more. Ataluren was generally well tolerated and most treatment-emergent adverse events were mild to moderate in severity. Eight (3%) patients (n=4 per group) reported serious adverse events; all except one event in the placebo group (abnormal hepatic function deemed possibly related to treatment) were deemed unrelated to treatment. INTERPRETATION: Change in 6MWD did not differ significantly between patients in the ataluren group and those in the placebo group, neither in the intention-to-treat population nor in the prespecified subgroups with a baseline 6MWD of less than 300 m or 400 m or more. However, we recorded a significant effect of ataluren in the prespecified subgroup of patients with a baseline 6MWD of 300 m or more to less than 400 m. Baseline 6MWD values within this range were associated with a more predictable rate of decline over 1 year; this finding has implications for the design of future DMD trials with the 6-minute walk test as the endpoint. FUNDING: PTC Therapeutics.

The effects of cold atmospheric plasma on cell adhesion, differentiation, migration, apoptosis and drug sensitivity of multiple myeloma.

Cold atmospheric plasma was shown to induce cell apoptosis in numerous tumor cells. Recently, some other biological effects, such as induction of membrane permeation and suppression of migration, were discovered by plasma treatment in some types of tumor cells. In this study, we investigated the biological effects of plasma treatment on multiple myeloma cells. We detected the detachment of adherent myeloma cells by plasma, and the detachment area was correlated with higher density of hydroxyl radical in the gas phase of the plasma. Meanwhile, plasma could promote myeloma differentiation by up-regulating Blimp-1 and XBP-1 expression. The migration ability was suppressed by plasma treatment through decreasing of MMP-2 and MMP-9 secretion. In addition, plasma could increase bortezomib sensitivity and induce myeloma cell apoptosis. Taking together, combination with plasma treatment may enhance current chemotherapy and probably improve the outcomes.