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Aim: Obesity has been associated with changes in autophagy and its increasing prevalence among pregnant women is implicated in higher rates of placental-mediated complications of pregnancy such as pre-eclampsia and intrauterine growth restriction. Autophagy is involved in normal placentation, thus changes in autophagy may lead to impaired placental function and development. The aim of this study was to investigate the connection between obesity and autophagy in the placenta in otherwise uncomplicated pregnancies., Methods: Immunohistochemistry and western blot analysis were done on placental and omental samples from obese (body mass index [BMI] ≥30 kg/m 2 ) and normal weight (BMI <25 kg/m 2 ) pregnant women with singleton pregnancies undergoing planned Caesarean delivery without labor at term. Samples were analyzed for autophagic markers LC3B and p62 in the peripheral, middle and central regions of the placenta and in omental adipocytes, milky spots and vasculature., Results: As pre-pregnancy BMI increased, there was an increase in both placental and fetal weight as well as decreased levels of LC3B in the central region of the placenta (P = 0.0046). Within the obese patient group, LC3B levels were significantly decreased in the placentas of male fetuses compared to females (P < 0.0001). Adipocytes, compared to milky spots and vasculature, had lower levels of p62 (P = 0.0127) and LC3B (P = 0.003) in obese omenta and lower levels of LC3B in control omenta (P = 0.0071)., Conclusion: Obesity leads to reduced placental autophagy in uncomplicated pregnancies; thus, changes in autophagy may be involved in the underlying mechanisms of obesity-related placental diseases of pregnancy., (© 2020 Japan Society of Obstetrics and Gynecology.)

Doublecortin-like kinase 1 (DCLK1) is involved in tumorigenesis, tumor growth and metastasis, and epithelial-to-mesenchymal transition in many digestive tract tumors. It is reportedly highly expressed in Barrett's esophagus and esophageal adenocarcinoma, but its effects on the occurrence and progression of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, real-time PCR and western blot analysis confirmed significant upregulation of DCLK1 expression in human ESCC tissues and cell lines. CCK-8 assay showed that transfection with siRNA against DCLK1 (si-DCLK1) markedly inhibited cell proliferation and colony formation in the ESCC cell lines Eca109 and TE1. Transwell assay revealed that si-DCLK1 transfection inhibited the migratory and invasive capacities of Eca109 and TE1 cells. Moreover, si-DCLK1 increased the chemosensitivity of these cells to cisplatin, as indicated by inhibited cell viability and colony formation, and increased ROS and apoptosis in cisplatin-treated cells. Western blot assay revealed that expression of nuclear β-catenin and c-Myc was significantly increased in ESCC tissues and that si-DCLK1 markedly downregulated nuclear β-catenin and c-Myc in Eca109 cells. Treatment with lithium chloride, an activator of β-catenin signaling, partially abolished the si-DCLK1-induced inhibition of proliferation, migration, invasion, and chemoresistance of ESCC cells. These findings suggest that knockdown of DCLK1 may inhibit the progression of ESCC by regulating proliferation, migration, invasion, and chemosensitivity via suppressing the β-catenin/c-Myc pathway, supporting a promising therapeutic target against ESCC.

Saccharomyces cerevisiae is a widely used eukaryotic model and microbial cell factory. RNA interference (RNAi) is a conserved regulatory mechanism among eukaryotes but absent from S. cerevisiae . Recent reconstitution of RNAi machinery in S. cerevisiae enables the use of this powerful tool for strain engineering. Here we first discuss the introduction of heterologous RNAi pathways in S. cerevisiae , and the design of various expression cassettes of RNAi precursor reagents for tunable, dynamic, and genome-wide regulation. We then summarize notable examples of RNAi-assisted functional genomics and metabolic engineering studies in S. cerevisiae . We conclude with the future challenges and opportunities of RNAi-based approaches, as well as the potential of other regulatory RNAs in advancing yeast engineering., (Copyright © 2020 Chen, Guo, Zhang and Si.)

Background: Foxtail millet [Setaria italica (L.) P. Beauv.] is an excellent crop known for its superior level of drought tolerance across the world. Especially, less water is needed during its germination period than the other cereal crops. However, the knowledge of the mechanisms underlying the abiotic stress effects on seed germination of foxtail millet is largely unknown., Results: The water uptake pattern of foxtail millet seeds was ploted during germination period, according to which the germination time course of millet was separated into three phases. We sequenced the transcriptome of foxtail millet seeds, which were treated by PEG during different germination phases after sowing. The transcriptional studies revealed that more DEGs were identified during the further increase in water uptake period (phase III) than during the rapid initial uptake period (phase I) and the plateau period (phase II) under PEG stress. The pathway analysis of DEGs showed that the highly enriched categories were related to phenylpropanoid biosynthesis, plant hormone signal transduction and phenylalanine metabolism during phase III. The 20 phenylpropanoids-related genes of germinating foxtail millet were found to be down-regulated during the further increase in water uptake period under PEG stress. Further expression analysis identified 4 genes of phenylalanine ammonia-lyase, 4-coumarate-CoA ligase 3, cinnamoyl-CoA reductase 1, cationic peroxidase SPC4 in phenylpropanoids-related pathway, which played important roles in foxtail millet in response to PEG stress during different germination periods. The studies of metabolites in phenylpropanoid biosynthesis pathway revealed that higher amount of cinnamic acid was accumulated in germinating seeds under PEG stress, while the contents of p-coumaric acid, caffeic acid, ferulic acid and sinapic acid were decreased. And the effects of five phenolic compounds on germination and growth of foxtail millet showed that 1 mM concentration of cinnamic acid inhibited shoot and root growth, especially root development. Ferulic acid, caffeic acid, sinapic acid and p-coumaric acid could increase the root length and root/sprout in lower concentration., Conclusions: These findings suggest that key genes and metabolites of foxtail millet related with phenylpropanoids pathway may play prominent roles in the regulation of resistance to drought during germination. Foxtail millet can probably avoid drought by regulating the levels of endogenous allelochemicals.

Background: Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown., Methods: Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients., Results: Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367-0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342-0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways., Conclusions: In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.

Background: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19., Methods: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias., Results: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76-5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients., Conclusions: We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.

Background and Objective: There are technical challenges to complete occlusion of small (<5 mm) ruptured intracranial aneurysms (SRAs) using endovascular treatment (EVT). This study analyzed factors influencing immediate angiographic results in SRAs after EVT., Material and Methods: Intraoperative angiograms and medical records of 290 patients, who underwent EVT for SRAs at 2 stroke centers in China between January 2009 and October 2016, were retrospectively reviewed and evaluated., Results: Immediate complete occlusion was achieved in 213 (73.4%) aneurysms. Aneurysms with a smaller aspect ratio, those less than 3 mm in size, irregular shape, small basal outpouching, multiple aneurysms, poorer Hunt and Hess grade, and location of communication arteries demonstrated higher rates of incomplete occlusion, although the differences were not statistically significant. Multivariate logistic regression analysis revealed that SRAs with parent artery stenosis greater than or equal to 50% and lobulation demonstrated a higher incidence of incomplete occlusion. Intra-procedural rupture occurred in 13 (6.1%) patients in the complete occlusion group, and 3 (3.9%) in the incomplete occlusion group (P = .467). Thromboembolic complications occurred in 3 (1.0%) patients, and 4 (1.9%) underwent decompressive craniotomy after EVT, all of whom were in the complete occlusion group. Nine (4.2%) patients in the complete occlusion group and 2 (2.6%) in the incomplete occlusion group (P = .733) experienced intraprocedural vasospasm, with corresponding morbidity and mortality rates of 15.0% and 2.1%, respectively., Conclusions: Proximal parent artery stenosis greater than or equal to 50% and lobulation were independent predictors of incomplete occlusion in patients with SRAs. Higher rates of intraprocedural rupture, thromboembolic complications, intraprocedural vasospasm, and mortality were found in the complete occlusion group; however, these differences were not statistically significant. Complete occlusion of SRAs may be achieved without additional mortality and perioperative complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Simultaneous identification of multiple single genes and multi-gene prognostic signatures with higher efficacy in liver cancer has rarely been reported. Here, 1,173 genes potentially related to the liver cancer prognosis were mined with Coremine, and the gene expression and survival data in 370 samples for overall survival (OS) and 319 samples for disease-free survival (DFS) were retrieved from The Cancer Genome Atlas. Numerous survival analyses results revealed that 39 genes and 28 genes significantly associated with DFS and OS in liver cancer, including 18 and 12 novel genes that have not been systematically reported in relation to the liver cancer prognosis, respectively. Next, totally 9,139 three-gene combinations (including 816 constructed by 18 novel genes) for predicting DFS and 3,276 three-gene combinations (including 220 constructed by 12 novel genes) for predicting OS were constructed based on the above genes, and the top 15 of these four parts three-gene combinations were selected and shown. Moreover, a huge difference between high and low expression group of these three-gene combination was detected, with median survival difference of DFS up to 65.01 months, and of OS up to 83.57 months. The high or low expression group of these three-gene combinations can predict the longest prognosis of DFS and OS is 71.91 months and 102.66 months, and the shortest is 6.24 months and 13.96 months. Quantitative real-time polymerase chain reaction and immunohistochemistry reconfirmed that three genes F2, GOT2 , and TRPV1 contained in one of the above combinations, are significantly dysregulated in liver cancer tissues, low expression of F2, GOT2 , and TRPV1 is associated with poor prognosis in liver cancer. Overall, we discovered a few novel single genes and multi-gene combinations biomarkers that are closely related to the long-term prognosis of liver cancer, and they can be potential therapeutic targets for liver cancer., (Copyright © 2020 Liu, Liu, Liu, Xiao, Guo, Qin, Wu, Liang, Liang, Li, Zhang, Yang, Luo, Lei, Tan, Yin and Zeng.)

Radiotherapy with or without concurrent chemotherapy is the standard treatment for nasopharyngeal carcinoma (NPC) patients, whose efficacy is limited partly by intrinsic and acquired radioresistance. DNA methyltransferase 3B (DNMT3B) has been reported to participate in tumorigenesis via DNA methylation, but its role in mediating progression and radioresistance of NPC remains unclear. Therefore, we conducted the following studies to explore the relationship between DNMT3B and NPC. Here, we found that DNMT3B was elevated in NPC tissues and predicted the poor prognosis of NPC patients. We demonstrated for the first time that ionizing radiation could induce DNMT3B, which might be one of the reasons for radioresistance. Silencing of DNMT3B inhibited migration and invasion via suppressing epithelial-mesenchymal transition (EMT) in NPC cells. Furthermore, silencing DNMT3B restored and activated p53 and p21 via DNA demethylation, which led to cell cycle arrest and apoptosis, resulting in increased radiosensitivity of NPC both in vitro and in vivo . DNMT3B functions as a novel oncogene in the radioresistance of NPC through regulating EMT, cell cycle, and apoptosis. Therefore, DNMT3B could be a potential target for NPC treatment., (© 2020 The Author(s).)

The purpose of this study was to investigate whether aerobic exercise training inhibits atherosclerosis via the reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) expression in balloon-induced common carotid arteries of a high-fat-diet rats. Male SD (Sprague Dawley) rats fed an eight-weeks high-fat diet were randomly divided into three groups; these were the sham-operated control (SC), the balloon-induced control (BIC) and the balloon-induced exercise (BIE). The aerobic exercise training groups were performed on a treadmill. The major findings were as follows: first, body weight gain was significantly decreased by aerobic exercise training compared to the BIC without change of energy intake. Second, neointimal formation was significantly inhibited by aerobic exercise training in the balloon-induced common carotid arteries of high-fat-diet rats compared to the BIC. Third, low-density lipoprotein (LDL) receptor (LDLr) expression was significantly increased by aerobic exercise training in the livers of the high-fat diet group compared to the BIC, but not the proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. Fourth, aerobic exercise training significantly decreased the expression of PCSK9, the lectin-like oxidized LDL receptor-1 (LOX-1), and vascular cell adhesion molecule-1 (VCAM-1) in balloon-induced common carotid arteries of high-fat-diet rats compared to the BIC. In conclusion, our results suggest that aerobic exercise training increases LDLr in the liver and inhibits neointimal formation via the reduction of PCSK9 and LOX-1 in balloon-induced common carotid arteries of high-fat-diet-induced rats., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Red and near-infrared light detection is vital for numerous applications, including full-color imaging, optical communication, and machine vision. However, this development is hindered by a limited choice of small band gap and narrow-bandwidth materials. Here, we report a device principle with a simple organic planar heterojunction architecture that enables a selective activation of excitons for tuning the photoresponse spectra to fabricate thin-film, filterless, red-light organic photodiodes. A sequential solution-processed active layer is formed by depositing the top layer of PC 71 BM onto the predeposited bottom layer of doped P3HT. By adjusting the ratio of PTB7 in P3HT, an improved responsivity and a red-shift of the photoresponse peak from 645 to 745 nm are demonstrated simultaneously. Furthermore, the responsivity of 745 nm is enhanced over 5 times with a narrow full width at half-maximum of ∼50 nm at optimized doping ratio compared to the pristine PTB7 device. As a result, a high specific detectivity in excess of 10 12 Jones and broad linear dynamic range of 103 dB are achieved. This design concept shows the possibility of realizing tunable red-light selectivity even at relatively thin-film thickness, which is intriguing for the implementation of high-resolution image sensors in the near future.

Following publication of the original article [1], the authors reported an error in Fig. 1f.

Riluzole is approved by the FDA as an amyotrophic lateral sclerosis (ALS) drug. Previous studies showed that treatment with riluzole suppressed the proliferation of many cancer cells. However, little is known about its effects on nasopharyngeal carcinoma (NPC) and its molecular mode of action. In this study, we determined the effect of riluzole on apoptosis, cell cycle, migration, and invasion in NPC cell lines and investigated its mechanism at the molecular level. By using the human NPC cell lines CNE1, CNE2, and HNE1, we revealed that riluzole effectively inhibited viability of the NPC cell lines in dose- and time-dependent manners. Furthermore, riluzole dose-dependently induced apoptosis and G2/M cell cycle arrest in the NPC cell lines. After combination with radiotherapy (RT), greater cytotoxicity was achieved than with riluzole or RT alone in vitro and vivo . This was associated with the activation of ataxia telangiectasia mutated (ATM) and phosphoinositide p53 pathways. P53 silencing reduced cell reactiveness to riluzole therapy. These observations demonstrate that the riluzole-activated ATM/P53 pathway is directly involved in radiation-induced apoptosis of NPC cells. Given the acceptable side effect, combining of riluzole and radiotherapy is promising in NPC treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Epithelial ovarian cancer is characterized by universal TP53 mutations, which result in G1/S checkpoint deficiencies. Therefore, it is hypothesized that the abrogation of the G2/M checkpoint with Wee1 inhibitor might preferentially sensitize TP53-defective ovarian cancer cells. Given the extremely high molecular diversity in ovarian cancer, one approach to improving the clinical efficacy is to identify drug combinations that either broaden the applicable spectrum or circumvent resistance. Here, through a high-throughput unbiased proteomic profiling (RPPA), we found the complementary activated mTOR pathway contributes greatly to Wee1 inhibitor resistance. A combination of Wee1 and mTOR inhibits synergistically inhibiting tumor growth in ovarian cancer cell lines and patient-derived xenograft that closely mimic the heterogeneity of patient tumors. Mechanistically, dual Wee1/mTOR inhibition induced massive DNA replication stress, leading to fork stalling and DNA damage. Moreover, we found that the addition of nucleotide metabolic substrate dNTPs alleviated replication stress, restored the cell cycle and reduced apoptosis to some extent, supporting dNTPs depletion is necessary for the synergy between Wee1 and mTOR inhibits. These results suggest that our study opening up a wider therapeutic window of Wee1 inhibitor for the treatment in epithelial ovarian cancers., Competing Interests: None., (AJCR Copyright © 2020.)

Purpose: To perform a systematic review to answer the following: (1) What are the floor and ceiling (F/C) effects of the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive test (CAT) domains of physical function (PF), upper extremity physical function (UE), pain interference (PI), and depression (D) in adult orthopaedic patients? (2) Do the PROMIS-PF and PROMIS-PI domains have differing F/C effects depending on use in upper extremity, lower extremity, spine, neck, and back, or trauma patients?., Methods: (Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed, the review was registered on PROSPERO, and the methodological index for non-randomized studies was used for this systematic review. Studies reporting the F/C effects of at least 1 of 4 PROMIS CAT domains in orthopaedic patient cohorts accessed through PubMed and Embase on October 30, 2018, were included. F/C effects for each study were reported within forest plots., Results: Forty-three studies were included. Generally, varying cohorts demonstrated no F/C effects for PROMIS-PF (0%-9.0%), variable ceiling effects for PROMIS-UE (lower in v2.0; 0%-28.2%), variable floor effects for PROMIS-PI (0%-19.0%), and significant floor effects for PROMIS-D (0.4%-23.4%)., Conclusions: The orthopaedic literature demonstrated generally favorable floor and ceiling effects for PROMIS CAT domains, with the exception of variable ceiling effects for PROMIS-UE (the newer version exhibits only minor effects), variable floor effects for PROMIS-PI, and significant floor effects for PROMIS-D. In addition, the F/C effects of PROMIS-PF did not vary based on patient population. Although the floor effects of PROMIS-PI did vary based on patient population, the variability does not appear to be based solely on anatomic location. The PROMIS-PF and PROMIS-UE v2.0 demonstrate consistently low floor and ceiling effects. However, the PROMIS-PI and PROMIS-D may need modification before widespread adoption for clinical and research purposes., Level of Evidence: III; systematic review of Level I-III studies., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

High-grade serous ovarian cancer (HGSOC), with its high recurrence rates, urges for reasonable therapeutic strategies that can prolong overall survival. A tumor microenvironment (TME) discloses prognostic and prospective information on cancer, such as the expression level of PD-1 or PD-L1. However, in HGSOC, the impact of the therapies aiming at these targets remains unsatisfying. Tumor-associated macrophages (TAMs) in HGSOC make up a large part of the TMEs and transform between diverse phenotypes under different treatments. AZD5153 inhibiting BRD4, as a potential therapeutic strategy for HGSOC, was demonstrated to confer controversial plasticity on TAMs, which shows the need to uncover its impact on TAMs in HGSOC. Therefore, we established models for TAMs and TAMs co-culturing with T lymphocytes in vitro . Via RT-PCR and flow cytometry, we find that AZD5153 resets TAMs from M2-type macrophages to M1-like macrophages, consequently promoting pro-inflammatory cytokine secretion and thus activating CD8 + cytotoxic T lymphocytes (CTLs) in vitro . This modification occurs on MAF transcripts in TAMs and modified by BRD4, which is the target of AZD5153. Importantly, the 3-D microfluid model demonstrates that AZD5153 sensitizes ovarian cancer to anti-PD-L1 therapy. Our results clarify that besides eliminating tumor cells directly, AZD5153 works as a regulator of the TAM phenotype, providing a novel strategy combining AZD5153 and PD-1/PD-L1 antibody that could benefit HGSOC patients., (Copyright © 2020 Li, Fu, Yang, Guo, Wu, Huang, Zhang, Xiao, Li, Wang, Hu, Sun and Chen.)

Ovarian cancer selective metastasizes to the omentum contributing to the poor prognosis associated with ovarian cancer. However, the mechanism underlining this propensity and therapeutic approaches to counter this process has not been fully elucidated. Here, we show that MCP-1 produced by omental adipocytes binding to its cognate receptor CCR-2 on ovarian cancer cells facilitates migration and omental metastasis by activating the PI3K/AKT/mTOR pathway and its downstream effectors HIF-1α and VEGF-A in cell lines, xenografts, and transgenic murine models. MCP-1 antibody significantly decreased tumor burden and increased survival of mice in vivo. Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells. Together this suggests a novel target of MCP-1/CCR-2 axis that could benefit ovarian cancer patients.

Lead-free halide double perovskites (HDPs) are promising candidates for high-performance solar cells because of their environmentally-friendly property and chemical stability in air. The power conversion efficiency of HDPs-based solar cells needs to be further improved before their commercialization in the market. It requires a thoughtful understanding of the correlation between their specific structure and property. Here, the structural and optical properties of an important HDP-based (NH 4 ) 2 SeBr 6 are investigated under high pressure. A dramatic piezochromism is found with the increase in pressure. Optical absorption spectra reveal the pressure-induced red-shift in bandgap with two distinct anomalies at 6.57 and 11.18 GPa, and the energy tunability reaches 360 meV within 20.02 GPa. Combined with structural characterizations, Raman and infrared spectra, and theoretical calculations using density functional theory, results reveal that, the first anomaly is caused by the formation of a Br-Br bond among the [SeBr 6 ] 2- octahedra, and the latter is attributed to a cubic-to-tetragonal phase transition. These results provide a clear correlation between the chemical bonding and optical properties of (NH 4 ) 2 SeBr 6 . It is believed that the proposed strategy paves the way to optimize the optoelectronic properties of HDPs and further stimulate the development of next-generation clear energy based on HDPs solar cells., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Although Sb doping is regarded as the most effective method to regulate the carrier concentration within the optimum range for ZrNiSn-based half-Heusler (HH) alloys, the resulting thermal conductivity remains high. Hence, the aim of this study was to investigate the effect of "diagonal-rule" doping; that is, the Zr site was displaced by Ta, which can simultaneously enhance the electrical conductivity and reduce the lattice thermal conductivity. The solid-solubility limit of Ta in the ZrNiSn matrix was determined to be x = 0.04. The highest ZT , 0.72, was achieved at 923 K for Zr 0.98 Ta 0.02 NiSn. In addition, ZT avg increased by 10.2% for Zr 0.98 Ta 0.02 NiSn compared with that for ZrNiSn 0.99 Sb 0.01 at 873 K, which was mainly attributed to the reduced lattice thermal conductivity of Zr 0.98 Ta 0.02 NiSn. These results suggest that Ta doping is more effective than Sb doping in ZrNiSn-based HH alloys. In addition, the microhardness of Zr 1-x Ta x NiSn was substantially improved with increasing Ta content and was also much higher than that of other traditional thermoelectric materials.

Strong scattering medium brings great difficulties to image objects. Optical memory effect makes it possible to image through strong random scattering medium in a limited angle field-of-view (FOV). The limitation of FOV results in a limited optical memory effect range, which prevents the optical memory effect to be applied to real imaging applications. In this paper, a kind of practical convolutional neural network called PDSNet (Pragmatic De-scatter ConvNet) is constructed to image objects hidden behind different scattering media. The proposed method can expand at least 40 times of the optical memory effect range with a average PSNR above 24dB, and enable to image complex objects in real time, even for objects with untrained scales. The provided experiments can verify its accurateness and efficiency.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

Background: Cisplatin-based chemotherapy is the first-line treatment for ovarian cancer. However, acquired resistance to cisplatin treatment often occurs in epithelial ovarian cancer, and effective and practical methods for overcoming this obstacle are urgently needed. The study aimed to demonstrate the synergistic effect of clarithromycin (CAM) with cisplatin to inhibit ovarian carcinoma cells growth in vitro and in vivo., Results: We performed CCK-8 assay to detect apoptosis rates in response to CAM alone or in combination with cisplatin, which were further confirmed by Annexin V and PI staining methods and western blotting. Mechanistically, CAM could reduce endogenous antioxidant enzyme expression and increase the levels of reactive oxygen species (ROS) to augment the cytotoxic effect of cisplatin. Meanwhile, a tumor xenograft model in athymic BALB/c-nude mice demonstrated that CAM combined with cisplatin resulted in reduced tumor growth and weight compared with cisplatin alone., Conclusion: Collectively, our results indicate that CAM works synergistically with cisplatin to inhibit ovarian cancer cell growth, which may be manipulated by a ROS-mediated mechanism that enhances cisplatin therapy, and offers a novel strategy for overcoming cisplatin therapy resistance.

In this paper, the microstructures and corrosion behaviors of as-cast Mg-5Sn- x Ga alloys with varying Ga content ( x = 0, 0.5, 1, 2, 3 wt %) were investigated. The results indicated that Ga could not only adequately refine the grain structure of the alloys, but could also improve the corrosion resistance. The microstructures of all alloys exhibited typical dendritic morphology. No Ga-rich secondary phases were detected when 0.5 wt % Ga was added, while only the morphology of Mg 2 Sn phase was changed. However, when the addition rate of Ga exceeded 0.5 wt %, an Mg 5 Ga 2 intermetallic compound started to form from the interdendritic region. The volume fraction of Mg 5 Ga 2 monotonically increased with the increasing Ga addition level. Although Mg 5 Ga 2 phase was cathode phase, its pitting sensitivity was weaker than Mg 2 Sn. In addition, the standard potential of Ga (-0.55 V) was lower than that of Sn (-0.14 V), which relieved the driving force of the secondary phases for the micro-galvanic corrosion. An optimized composition of 3 wt % Ga was concluded based on the immersion tests and polarization measurements, which recorded the best corrosion resistance.

Background: To reveal roles of reactive oxygen species (ROS) status in chemotherapy resistance and to develop a ROS scoring system for prognosis prediction in ovarian cancer., Methods: We tested the sensitizing effects of ROS elevating drugs to cisplatin (cDDP) in ovarian cancer both in vitro and in vivo. A ROS scoring system was developed using The Cancer Genome Atlas (TCGA) database of ovarian cancer. The associations between ROS scores and overall survival (OS) were analyzed in TCGA, Tothill dataset, and our in-house dataset (TJ dataset)., Results: ROS-inducing drugs increased cisplatin-induced ovarian cancer cell injury in vitro and in vivo. ROS scoring system was established using 25 ROS-related genes. Patients were divided into low (scores 0-12) and high (scores 13-25) score groups. Improved patient survival was associated with higher scores (TCGA dataset hazard ratio (HR) = 0.43, P < 0.001; Tothill dataset HR = 0.65, P = 0.022; TJ dataset HR = 0.40, P = 0.003). The score was also significantly associated with OS in multiple datasets (TCGA dataset r 2  = 0.574, P = 0.032; Thothill dataset r 2  = 0.266, P = 0.049; TJ dataset r 2  = 0.632, P = 0.001) and with cisplatin sensitivity in ovarian cancer cell lines (r 2  = 0.799, P = 0.016) when used as a continuous variable. The scoring system showed better prognostic performance than other clinical factors by receiver operating characteristic (ROC) curves (TCGA dataset area under the curve (AUC) = 0.71 v.s. 0.65, Tothill dataset AUC = 0.73 v.s. 0.67, TJ dataset AUC = 0.74 v.s. 0.66)., Conclusions: ROS status is associated with chemotherapy resistance. ROS score system might be a prognostic biomarker in predicting the survival benefit from ovarian cancer patients.

Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Aβ 25-35 -stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-β peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Aβ 1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six β-carboline alkaloids (1-6), seven canthin-6-one alkaloids (7-13), and five quassinoids (14-18). Among them, four β-carbolines (1-3, and 6) and six canthin-6-ones (7-11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ni-Mn-Sn ferromagnetic shape memory alloys (FSMAs) have promise for application in efficient solid-state refrigeration. However, the simultaneous achievement of giant magnetocaloric effect (MCE) and excellent mechanical properties and high working temperature in these materials is always the challenge. Computation-guided materials design techniques provide an efficient way to design and identify new magnetocaloric materials. Herein, a new strategy of multidoping is presented. First, we conduct a detailed and comprehensive first-principles study and predict that Ni-Mn-Sn FSMAs with co-doping 6.25 atom % Cu and 6.25-12.5 atom % Co can realize the multiobjective optimization of magnetocaloric material. Then, it is confirmed by experiment and we report on Ni 40 Co 8 Mn 37 Sn 9 Cu 6 FSMA exhibiting a large magnetic entropy change (34.8 J/(kg K)) of a large value in the prevalent MCE materials at high temperature (∼344 K) and whose compression stress and strain (∼1072.0 MPa and ∼11.9%) are both the largest among Ni-Mn-based MCE materials. Notably, the effect of Co and Cu doping is not simply stacked because they play opposite roles in Curie temperature ( T C ) and martensitic transformation temperature ( T M ). So, achieving the balance of their effect to combine their merits in a very narrow window is the key step. This approach of multielement doping holds promise to be extended to other magnetocaloric materials to enhance their multiple properties simultaneously.

In the present paper, mesoporous InVO 4 /TiO 2 nanobelts with diameter about 400 nm have been synthesized by elaborately designed electrospinning process. The microstructures of InVO 4 /TiO 2 nanobelts are characterized in detail, and their photoelectrocatalytic properties are comprehensively investigated by the photocatalytic degradation tests with tetracycline (TTC) and rhodamine B (RhB) waste water. Furthermore, the energy bandgap and density of states of orthorhombic InVO 4 and anatase TiO 2 are modeled and analyzed by density functional theory. Compared with single InVO 4 nanobelts and TiO 2 nanofibers, mesoporous InVO 4 /TiO 2 nanobelts possess the extraordinary photocatalytic efficiencies and exceptional cycle performances, which may be ascribed to the successful construction of heterostructures between InVO 4 and TiO 2 and unique one-dimensional belt structures., (© 2019 American Society for Photobiology.)

Mutations in the forkhead box O 3a (FOXO3a) gene are closely related to the progression of several types of cancers. However, few studies explore the relationship between FOXO3a and nasopharyngeal carcinoma (NPC). Our findings demonstrate that silencing FOXO3a promotes tumor radioresistance of NPC in vitro and in vivo through inducing EMT and activating Wnt/β-catenin signal pathway. These data establish that FOXO3a can be a novel and reliable NPC marker and a potential therapeutic target against NPC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Remote sensing (RS)-based models play an important role in estimating and monitoring terrestrial ecosystem gross primary productivity (GPP). Several RS-based GPP models have been developed using different criteria, yet the sensitivities to environmental factors vary among models; thus, a comparison of model sensitivity is necessary for analyzing and interpreting results and for choosing suitable models. In this study, we globally evaluated and compared the sensitivities of 14 RS-based models (2 process-, 4 vegetation-index-, 5 light-use-efficiency, and 3 machine-learning-based models) and benchmarked them against GPP responses to climatic factors measured at flux sites and to elevated CO 2 concentrations measured at free-air CO 2 enrichment experiment sites. The results demonstrated that the models with relatively high sensitivity to increasing atmospheric CO 2 concentrations showed a higher increasing GPP trend. The fundamental difference in the CO 2 effect in the models' algorithm either considers the effect of CO 2 through changes in greenness indices (nine models) or introduces the influences on photosynthesis (three models). The overall effects of temperature and radiation, in terms of both magnitude and sign, vary among the models, while the models respond relatively consistently to variations in precipitation. Spatially, larger differences among model sensitivity to climatic factors occur in the tropics; at high latitudes, models have a consistent and obvious positive response to variations in temperature and radiation, and precipitation significantly enhances the GPP in mid-latitudes. Compared with the results calculated by flux-site measurements, the model performance differed substantially among different sites. However, the sensitivities of most models are basically within the confidence interval of the flux-site results. In general, the comparison revealed that models differed substantially in the effect of environmental regulations, particularly CO 2 fertilization and water stress, on GPP, and none of the models performed consistently better across the different ecosystems and under the various external conditions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: The ideal stroke classification system needs to have validity, high reliability and applicability among different stroke research settings. The Chinese Ischemic Stroke Subclassification (CISS) and the Subtypes of Ischemic Stroke Classification System (SPARKLE) have emerged recently but have not been tested using agreement analysis. As a result, the objective of this study is to investigate the level of agreement among stroke subtype classifications using CISS, SPARKLE and Trial of Org 10172 in Acute Stroke Treatment (TOAST). We also analyse the inter-rater reliability of CISS., Methods: The data include 623 inpatients who have had an ischaemic stroke, accrued from Beijing Tiantan Hospital between 1 October 2015 and 19 April 2016. According to the diagnostic standards of the three subtype classification systems, 299 inpatients who satisfied the requirements of our study were independently classified with etiological subtypes, and we compared the three subclassifications., Results: There was substantial overall agreement among the three classification systems: CISS versus SPARKLE (kappa value=0.684, p<0.001), CISS versus TOAST (kappa value=0.615, p<0.001) and SPARKLE versus TOAST (kappa value=0.675, p<0.001). The inter-rater reliability of CISS was excellent (kappa value=0.857, p<0.001). Furthermore, among the three subtype classification systems, the variance analysis results of the etiological subtypes were not uniform., Conclusion: There were generally substantial agreements among three ischaemic stroke etiological classification systems. CISS is a valid and reliable classification system, with which different stroke research centres can apply and compare data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The organic permeable base transistor (OPBT) is currently the fastest organic transistor with a transition frequency of 40 MHz. It relies on a thin aluminum base electrode to control the transistor current. This electrode is surrounded by a native oxide layer for passivation, currently created by oxidation in air. However, this process is not reliable and leads to large performance variations between samples, slow production, and relatively high leakage currents. Here, for the first time it is demonstrated that electrochemical anodization can be conveniently employed for the fabrication of high-performance OPBTs with vastly reduced leakage currents and more controlled process parameters. Very large transmission factors of 99.9996% are achieved, while excellent on/off ratios of 5 × 10 5 and high on-currents greater than 300 mA cm -2 show that the C 60 semiconductor layer can withstand the electrochemical anodization. These results make anodization an intriguing option for innovative organic transistor design., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma (NPC), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC. SALL4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL4 expression with radioresistance of NPC. It was revealed that SALL4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL4 silencing increased radiation-induced DNA damage, apoptosis, and G2/M arrest in CNE2 and CNE2R cells. Moreover, knockdown of SALL4 impaired the expression of p-ATM, p-Chk2, p-p53, and anti-apoptosis protein Bcl-2, while pro-apoptosis protein was upregulated. These findings indicate that SALL4 could induce radioresistance via ATM/Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article “… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article., (Copyright © 2019. Published by Elsevier Inc.)

Background: Vibrio parahaemolyticus causes not only various diseases in aquaculture animals but also seafood-borne illness in humans. Outer membrane proteins (OMPs) are species-specific proteins found in bilayer membranes of gram-negative bacteria. Egg yolk immunoglobulin (IgY) has been reported to serve as oral administration of antibodies against bacteria and virus., Results: The present research extracted and identified OMPs from V. parahaemolyticus, and then the extracted OMPs were used to immunize hens to obtain specific IgY. The efficacy of IgY against V. parahaemolyticus were investigated in vitro and in vivo. The specific IgY effectively inhibited the growth of V. parahaemolyticus in liquid medium rather than Escherichia coli and Staphylococcus aureus. Specific IgY antibodies were incorporated into extruded food pellets and fed to bacteria-challenged white pacific shrimp to observe the anti-bacterial effect in vivo. The bacterial loads in muscles of V. parahaemolyticus infected shrimp fed with specific IgY-included diets were significantly fewer than those fed with non-specific IgY-included diets. The superoxide dismutase activities in muscles of infected shrimp fed with specific IgY-included diets were significantly higher than the control group., Conclusion: The results suggested that the specific IgY effectively inhibited the growth of V. parahaemolyticus and introduced passive immunity to shrimp. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Objective: To observe and evaluate the therapeutic efficacy of LVIS stent and Enterprise stent assisted coil in embolization of vertebral artery dissection aneurysm (VDA). Methods: Clinical data of 96 patients with VDAs treated by LVIS stent and Enterprise stent assisted coil were analyzed retrospectively between January, 2013 and June, 2017.Of all, the LVIS stent assisted coil was performed in 28 patients (LVIS-stent group) and Enterprise in 68 patients (Enterprise-stent group). The clinical and imaging follow-up were performed. The instant embolization rate, complications, and recurrence rate were analyzed and compared between the two groups. Results: Instant angiographic results:in the LVIS stent group, complete occlusion was achieved in 17 VDAs (60.7%), near-complete occlusion in 10VDAs (35.7%), and partial occlusion in 1 VDA (3.6%). In the Enterprise stent group, complete occlusion was achieved in 27 VDAs (39.7%), near-complete occlusion in 34VDAs(50.0%), partial occlusion in 7VDAs (10.3%). Procedure-related complications occurred in 3 patients (10.7%) in LVIS stent group and 3 patients (4.4%) in Enterprise stent group. DSA follow-up was performed during 6 to 12 months after surgery, and 10 patients with vertebral artery dissection aneurysm recurred, 2 in the LVIS group and 8 in the Enterprise stent group. The latest modified Rankin Scale score was 0 in 55 patients,1 in 13, 2 in 1, 3 in 1, and 6 in 1. Among them, all follow-up patients in the LVIS stent group had good prognosis, while in the Enterprise stent group, 50 patients (94.4%) had a good prognosis. Conclusions: The stent-assisted coils have a higher degree of embolization in the vertebral artery dissection aneurysms, a higher rate of near-total embolization, a lower incidence of neurological complications, and a good prognosis. The complete andnear-complete occlusion rates and the incidence of neurological complicationsin the LVIS group was higher than that in the Enterprise groupand the recurrence ratesin the LVIS group was lower than that in the Enterprise group,both with no statistically significant difference.

With intensification of climate change and human activities, warming and drying trend has brought severe challenges to pastoral areas in arid and semi-arid regions. Consequently, it becomes imperative to explore non-stationarity features of drought in such regions. In this research, the SPEIbase v2.4 datasets with a 0.5 degree spatial resolution was employed to extract Standardized Precipitation Evapotranspiration Index (SPEI) in Inner Mongolia, China. We explored non-stationarity characteristics of drought using Breaks For Additive Seasonal and Trend (BFAST) method, investigated the variation characteristics of drought intensity in each time interval using intensity analysis method, and finally assessed the spatial and temporal gathering characteristics of drought with Empirical Orthogonal Function (EOF). The results showed that trend of regional drought had a tendency towards drought conditions, which is particularly significant from the year 1945 onwards in the overall Inner Mongolia. We have explored a long behavior of drought in semiarid and central regions of cold semihumid climate zone throughout the whole study period, and detected a drying trend in northeastern regions of Inner Mongolia at the latter decades. The overall drought intensity displayed an increasing trend first, which was followed by a decreasing trend, among which the extreme drought was dominant in period of 1960-1970. EOF mode1 showed that variation intensity of drought showed a not significantly increasing trend in the entire region, and the drought with high amplitude was likely to occur in the central region. EOF mode2 showed that variation intensity of drought displayed the opposite phases between the eastern and the western regions. The northeastern regions were prone to display a high amplitude of drought., (Copyright © 2018. Published by Elsevier B.V.)

Background: The incidence of concussions is increasing in Major League Baseball (MLB), and the cost of these injuries in 2008 was reportedly as high as US$423 million. Team officials are more aware of concussion injuries, and one measure to address this issue was the creation of a concussion-specific 7-day disabled list (DL) in 2011., Purpose: To evaluate concussion trends among MLB players and the impact of concussion-specific 7-day DL status on postinjury player performance and team financials., Study Design: Descriptive epidemiology study., Methods: From 2005 to 2016, a total of 112 players placed on the DL because of a concussion were identified using the MLB website and were verified using established news databases. Salary information for players was collected using MLB published data, and cost was calculated with a previously published formula utilizing the injured player's salary per game and adding the cost of his replacement. Performance metrics were compared before and after the rule change., Results: The mean number of days on the DL decreased from 38.8 before 2011 to 29.2 after 2011. The mean annual cost per player before 2011 was $1.1 million and decreased to $565,000 after the rule change. Regression analyses demonstrated a downward trend in the mean cost ( R = -0.61, P < .001). A comparison of postinjury performance metrics showed no significant differences with decreased time on the DL., Conclusion: The minimum 7-day DL change has not had a negative impact on reporting; instead, it has demonstrated decreased time on the DL and lower associated team costs. Performance metrics demonstrated no differences compared with before the rule change, suggesting that players are not negatively affected by decreased time on the DL., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: V.J.S. is a consultant for Arthrex, CDC Medical, Pacira Pharmaceuticals, Encore Medical, and Zimmer Biomet; receives research support from Exactech, Pacira Pharmaceuticals, Arthrex, and Tornier; and has received hospitality payments from Stryker and DePuy. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Ovarian carcinoma is caused by multiple factors, but its etiology associated with microbes and infection is unknown. Using 16S rRNA high-throughput sequencing methods, the diversity and composition of the microbiota from ovarian cancer tissues (25 samples) and normal distal fallopian tube tissues (25 samples) were analyzed. High-throughput sequencing showed that the diversity and richness indexes were significantly decreased in ovarian cancer tissues compared to tissues from normal distal fallopian tubes. The ratio of the two phyla for Proteobacteria/Firmicutes was notably increased in ovarian cancer, which revealed that microbial composition change might be associated with the process of ovarian cancer development. In addition, transcriptome-sequencing (RNA-seq) analyses suggested that the transcriptional profiles were statistically different between ovarian carcinoma and normal distal fallopian tubes. Moreover, a set of genes including 84 different inflammation-associated or immune-associated genes, which had been named as the human antibacterial-response genes were also modulated expression. Therefore, we hypothesize that the microbial composition change, as a novel risk factor, may be involving the initiation and progression of ovarian cancer via influencing and regulating the local immune microenvironment of fallopian tubes except for regular pathways.

Medulloblastoma is a primitive neuroectodermal-derived brain tumor and the most common malignant brain tumor in children. Triptolide (TPL) is the major active component extracted from Tripterygium wilfordii Hook F. This study aimed to explore the effects of TPL on medulloblastoma cell proliferation, migration, and apoptosis, as well as the underlying possible molecular mechanism. Viability, proliferation, and apoptosis of Daoy cells were measured using cell counting kit-8 assay, 5-bromo-2'-deoxyuridine incorporation assay, and Guava Nexin assay, respectively. Cell migration was detected using two-chamber transwell assay and wound healing assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of microRNA-138 (miR-138) in Daoy cells. Cell transfection was used to change the expression of miR-138 in cells. Western blot analysis was used to analyze the expression of key factors involved in cell apoptosis, cell migration, the phosphatidylinositol 3-kinase (PI3K)/protein kinase 3 (AKT) pathway, and the Notch pathway in Daoy cells. We found that TPL significantly inhibited the viability, proliferation, and migration of Daoy cells but promoted Daoy cell apoptosis. The expression levels of matrix metalloproteinases (MMP)-2 and MMP-9 after TPL treatment were decreased. The expression of miR-138 in Daoy cells after TPL treatment was increased. Suppression of miR-138 obviously reversed the TPL-induced Daoy cell proliferation, migration inhibition, and cell apoptosis enhancement, as well as the inactivation of the PI3K/AKT and Notch pathways. Cyclin-dependent kinase 6 (CDK6) was a direct target gene of miR-138, which might be involved in the antitumor effects of TPL on Daoy cells. In conclusion, our study verified that TPL exerted anticancer effects on medulloblastoma cells possibly via upregulating miR-138 and inactivating the PI3K/AKT and Notch pathways., (© 2018 Wiley Periodicals, Inc.)

Ice cream is a complex multi-phase colloidal soft-solid and its three-dimensional microstructure plays a critical role in determining the oral sensory experience or mouthfeel. Using in-line phase contrast synchrotron X-ray tomography, we capture the rapid evolution of the ice cream microstructure during heat shock conditions in situ and operando , on a time scale of minutes. The further evolution of the ice cream microstructure during storage and abuse was captured using ex situ tomography on a time scale of days. The morphology of the ice crystals and unfrozen matrix during these thermal cycles was quantified as an indicator for the texture and oral sensory perception. Our results reveal that the coarsening is due to both Ostwald ripening and physical agglomeration, enhancing our understanding of the microstructural evolution of ice cream during both manufacturing and storage. The microstructural evolution of this complex material was quantified, providing new insights into the behavior of soft-solids and semi-solids, including many foodstuffs, and invaluable data to both inform and validate models of their processing.

Riboflavin (vitamin B2), a cis-diol-containing compound, is an essential vitamin for maintaining human health mainly in energy metabolism and is a critical component of enzyme cofactors and flavoproteins. Thus, the determination of riboflavin in food products is essential in riboflavin-fortified foods. However, analysis of riboflavin at natural levels in foods or biological samples is difficult because of its very low concentration level and the presence of undesirable matrix effects which could interfere with the measuring system. Thus, it is essential to develop efficient and selective enrichment approaches for riboflavin. Molecularly imprinted polymers can be well used for riboflavin extraction and pre-concentration from food samples. In this study, we present riboflavin-imprinted magnetic nanoparticles as an ideal sorbent for the selective enrichment of riboflavin followed by direct fluorometric determination. The riboflavin-imprinted magnetic nanoparticles were prepared according to a newly reported strategy, called boronate affinity-based surface initiated imprinting. Magnetic nanoparticles and vinylphenylboronic acid were used as supporting materials and a functional monomer, respectively. The prepared riboflavin-imprinted magnetic nanoparticles exhibited several significant advantages, such as excellent selectivity, high binding affinity and low binding pH toward riboflavin, which made the molecularly imprinted material become an ideal sorbent for the selective enrichment of riboflavin. The prepared riboflavin-imprinted magnetic nanoparticles were successfully applied to the analysis of riboflavin in milk.

Objectives: We analyzed the relationship between plasma miR-143/145 and serum MMP-9 in patients with unruptured or ruptured intracranial aneurysms (IAs) to identify new biomarkers for predicting rupture in IAs., Patients and Methods: We prospectively enrolled 24 consecutive patients, including seven patients without IAs as a control group, nine patients with unruptured IAs, and eight patients with ruptured IAs (enrolled within 3 days after rupture). Plasma miR-143/145 and MMP-9 were measured in blood samples collected from the femoral artery. Spearman ρ values were used for correlation analyses., Results: The level of plasma miR-143/145 in patients with ruptured IAs was significantly lower than that of the control group. Moreover, patients with ruptured IAs had a significantly higher level of serum MMP-9 compared with that in patients with unruptured IAs and in control patients. A lower level of plasma miR-143 was significantly correlated with a lower level of plasma miR-145 (Spearman ρ = 0.771; P <  0.0001)., Conclusion: These findings showed that a lower of plasma miR-143/145 is potentially associated with IA formation, while higher serum MMP-9 levels may be associated with IA rupture and could serve as a useful biomarker for the evaluation of IA rupture., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives/hypothesis: To characterize health burden and determine the associated level of equality of laryngeal carcinoma (LC) burden at a global level., Methods: One hundred eighty-four countries were organized by socioeconomic status using Human Development Index (HDI) categorizations provided by the United Nations Development Program. Disability-adjusted life years (DALYs), obtained from The Global Health Data Exchange, were calculated and compared between each HDI category for the period from 1990 to 2015. Equality of LC burden was then evaluated with concentration indices., Results: Global LC burden, as measured by age-standardized DALYs, has improved significantly over the 25-year period studied. This burden has declined for very high, high, and medium HDI countries, whereas it has remained unchanged for low HDI countries. The majority of LC global burden was found in high socioeconomic countries before 2010 and has shifted toward low socioeconomic countries, as indicated by concentration indices. Over the last 25 years, Central and Eastern Europe continue to have the largest disease burden in the world., Conclusion: This is the first analysis that we are aware of investigating health disparities of LC at a global level. The global burden of the disease has declined, which is a trend corresponding with significantly reduced smoking behaviors in developed countries. Although the global inequality gap decreased between 2010 and 2015, there remain reasons for concern. Smoking continues to trend upward in low socioeconomic countries, which could increase LC burden in low socioeconomic countries in the near future. A new global initiative directed toward low socioeconomic countries may yield dividends in preventing subsequent disparities in the LC burden., Level of Evidence: 4. Laryngoscope, 128:2039-2053, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Measuring time-resolved spectra is crucial in inertial confinement fusion and radiation source development experiments. An elliptically bent crystal spectrometer is designed to measure X-rays in the range of 2.5-11.0 keV, which was achieved using four different lattice spacings of 0.8512, 0.6687, 0.4246, and 0.2749 nm with spectral resolution E / δE of ∼500. The X-rays emitted from a source at one focus of the ellipse undergo Bragg reflection off a crystal and pass through the second focus of the ellipse to a streak camera slit with 18-mm length and 80- μ m width to generate a time-resolved spectrum. An alignment method for the time-resolved spectrometer was developed with the straight line connecting the centers of the two small holes on the fabricated substrate being the axis of the ellipse, thus allowing the spacing between the source and the elliptical crystal to be tuned to couple with the streak camera. The time-resolved spectrometer's performance was experimentally tested at the Shenguang II laser facility. The results indicate that its performance is close to that predicted theoretically.

Due to the contradiction between mechanical properties and electrical conductivity, it is not easy to fabricate materials with both high strength and good wear resistance with favourable electrical conductivity for the application of electrical materials. In addition, strength and wear resistance do not always present a uniform growth trend at the same time. Herein, a novel copper matrix composite reinforced by in situ synthesized ZrB 2 microparticles and nano Cu 5 Zr precipitates is successfully prepared by a casting method and sequential heat treatments. The Cu/dual-scale particulate composite possesses a desired trade-off of strength, electrical conductivity and wear resistance. ZrB 2 microparticles form from Zr and B elements in copper melts, and nanoscale Cu 5 Zr precipitates form in the matrix after solid solution and aging treatments. The ZrB 2 microparticles, nano Cu 5 Zr precipitates, and well-bonded interfaces contribute to a high tensile strength of 591 MPa and superior wear resistance, with a relative electrical conductivity of 83.7% International Annealed Copper Standard., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)