A disrupted FOXP3 transcriptional signature underpins systemic regulatory T cell insufficiency in early pregnancy failure.

Regulatory T (Treg) cell defects are implicated in disorders of embryo implantation and placental development, but the origins of Treg cell dysfunction are unknown. Here, we comprehensively analyzed the phenotypes and transcriptional profile of peripheral blood Treg cells in individuals with early pregnancy failure (EPF). Compared to fertile subjects, EPF subjects had 32% fewer total Treg cells and 54% fewer CD45RA+CCR7+ naive Treg cells among CD4+ T cells, an altered Treg cell phenotype with reduced transcription factor FOXP3 and suppressive marker CTLA4 expression, and lower Treg:Th1 and Treg:Th17 ratios. RNA sequencing demonstrated an aberrant gene expression profile, with upregulation of pro-inflammatory genes including CSF2, IL4, IL17A, IL21, and IFNG in EPF Treg cells. In silico analysis revealed 25% of the Treg cell dysregulated genes are targets of FOXP3. We conclude that EPF is associated with systemic Treg cell defects arising due to disrupted FOXP3 transcriptional control and loss of lineage fidelity.

[Introduction of a tool to assess Risk of Bias in Non-randomized Studies-of Exposure (2022)].

This article introduces the contents of the latest edition Risk of Bias in Non-randomized Studies-of Exposure (ROBINS-E) published in June 2022 [ROBINS-E (2022)], and gives some examples about its usage. ROBINS-E is a tool for assessing the risk of bias in non-randomized studies-of exposure. Compared with ROBINS-E (2019), ROBINS-E (2022) adds more bias for observational studies, covers a more comprehensive range of bias, and adds the assessment of the external authenticity of the study. ROBINS-E (2022) adds a preliminary evaluation process to improve the efficiency of evaluation. In addition, ROBINS-E (2022) visualizes and instrumentalizes the use of signal problems in the form of path graph, making it more convenient to use. ROBINS-E (2022), although more consideration has been given to the issue of co-exposure, still does not address the problem of effect modification in co-exposure, and there is still room to expand the applicable research.

Reticulons 1 and 3 are essential for axonal growth and synaptic maintenance associated with intellectual development.

Reticulon (RTN) proteins are a family of proteins biochemically identified for shaping tubular endoplasmic reticulum, a subcellular structure important for vesicular transport and cell-to-cell communication. In our recent study of mice with knockout of both reticulon 1 (Rtn1) and Rtn3, we discovered that Rtn1-/-;Rtn3-/- (brief as R1R3dKO) mice exhibited neonatal lethality, despite the fact that mice deficient in either RTN1 or RTN3 alone exhibit no discernible phenotypes. This has been the first case to find early lethality in animals with deletion of partial members of RTN proteins. The complete penetrance for neonatal lethality can be attributed to multiple defects including the impaired neuromuscular junction found in the diaphragm. We also observed significantly impaired axonal growth in a regional-specific manner, detected by immunohistochemical staining with antibodies to neurofilament light chain and neurofilament medium chain. Ultrastructural examination by electron microscopy revealed a significant reduction in synaptic active zone length in the hippocampus. Mechanistic exploration by unbiased proteomic assays revealed reduction of proteins such as FMR1, Staufen2, Cyfip1, Cullin-4B and PDE2a, which are known components in the fragile X mental retardation pathway. Together, our results reveal that RTN1 and RTN3 are required to orchestrate neurofilament organization and intact synaptic structure of the central nervous system.

[Effect of health management service for hypertension patients under framework of Basic Public Health Service Project: a regression discontinuity design].

Objective: To evaluate the effect of health management service on hypertension patients (HMSFHP) under the framework of the Basic Public Health Service Project by using regression discontinuity design. Methods: The participants were enrolled from an observational cohort survey in 2015 and followed up was conducted in 2019. The participants with SBP 130-150 mmHg and/or DBP 80-100 mmHg in the baseline survey of the cohort in 2015 were included in the present study. Additionally, we obtained the dates of participants receiving HMSFHP and their blood pressure data from follow-up records, physical examination records and telephone interview. The participants were divided into intervention group and control group based on the cutoff points, i.e. SBP ≥140 mmHg and/or DBP ≥90 mmHg. The local linear regression model were used to estimate the effect of HMSFHP on reducing blood pressure of the participants. Results: After adjusting for age, sex and time length of receiving HMSFHP, the results of the model including participants with 80-100 mmHg for DBP in 2015 indicated that, for the participants who received HMSFHP, the DBP decreased by 6.66 mmHg from 2015 to 2019. For the participants with SBP 130-150 mmHg in 2015, the reduction estimate of the model was -6.17 mmHg, the difference was not significant (P=0.178), suggesting that receiving HMSFHP did not cause change in SBP for the participants who received HMSFHP. Conclusion: Receiving HMSFHP had effect to reduce DBP, and HMSFHP had a positive effect on the control of blood pressure in patients with hypertension.

Progesterone receptor mediates ovulatory transcription through RUNX transcription factor interactions and chromatin remodelling.

Progesterone receptor (PGR) plays diverse roles in reproductive tissues and thus coordinates mammalian fertility. In the ovary, rapid acute induction of PGR is the key determinant of ovulation through transcriptional control of a unique set of genes that culminates in follicle rupture. However, the molecular mechanisms for this specialized PGR function in ovulation is poorly understood. We have assembled a detailed genomic profile of PGR action through combined ATAC-seq, RNA-seq and ChIP-seq analysis in wildtype and isoform-specific PGR null mice. We demonstrate that stimulating ovulation rapidly reprograms chromatin accessibility in two-thirds of sites, correlating with altered gene expression. An ovary-specific PGR action involving interaction with RUNX transcription factors was observed with 70% of PGR-bound regions also bound by RUNX1. These transcriptional complexes direct PGR binding to proximal promoter regions. Additionally, direct PGR binding to the canonical NR3C motif enable chromatin accessibility. Together these PGR actions mediate induction of essential ovulatory genes. Our findings highlight a novel PGR transcriptional mechanism specific to ovulation, providing new targets for infertility treatments or new contraceptives that block ovulation.

Parallel recovery of chromatin accessibility and gene expression dynamics from frozen human regulatory T cells.

Epigenetic features such as DNA accessibility dictate transcriptional regulation in a cell type- and cell state- specific manner, and mapping this in health vs. disease in clinically relevant material is opening the door to new mechanistic insights and new targets for therapy. Assay for Transposase Accessible Chromatin Sequencing (ATAC-seq) allows chromatin accessibility profiling from low cell input, making it tractable on rare cell populations, such as regulatory T (Treg) cells. However, little is known about the compatibility of the assay with cryopreserved rare cell populations. Here we demonstrate the robustness of an ATAC-seq protocol comparing primary Treg cells recovered from fresh or cryopreserved PBMC samples, in the steady state and in response to stimulation. We extend this method to explore the feasibility of conducting simultaneous quantitation of chromatin accessibility and transcriptome from a single aliquot of 50,000 cryopreserved Treg cells. Profiling of chromatin accessibility and gene expression in parallel within the same pool of cells controls for cellular heterogeneity and is particularly beneficial when constrained by limited input material. Overall, we observed a high correlation of accessibility patterns and transcription factor dynamics between fresh and cryopreserved samples. Furthermore, highly similar transcriptomic profiles were obtained from whole cells and from the supernatants recovered from ATAC-seq reactions. We highlight the feasibility of applying these techniques to profile the epigenomic landscape of cells recovered from cryopreservation biorepositories.

Cymbopogom Citratus Essential Oils: A Promising Source of Antifungals Against Panax Notoginseng-Associated Pathogenic Fungi.

Due to the great threat of chemical pesticides to the ecosystem environment, it is a long-term goal to find environmentally friendly green pesticides. Essential oils (EOs) are considered weapons in plant chemical defense and are important sources of green pesticides. Therefore, the antifungal effects and action mechanisms of Cymbopogom citratus (C. citratus) EOs against seven kinds of Panax notoginseng (P. notoginseng) pathogenic fungi were investigated. Oxford Cup results showed that C. citratus EOs had an excellent detraction effects against seven fungi of P. notoginseng. Gas chromatography-mass spectrometry (GC-MS) was used to construct the chemical profiles of C. citratus EOs, disclosed that the main categories are terpenes and oxygenated terpenes. In addition, compared with the hymexazol, the minimum inhibitory concentration (MIC) showed that EOs and their main components had strong antifungal activities. Besides, EOs had a synergistic effect with hymexazol (a chemical pesticide). The antifungal mechanism of C. citratus EOs was studied by using Fusarium oxysporum (F. oxysporum) as the dominant pathogen. C. citratus EOs may affect the metabolism of fungi and induce mycotoxins to destroy the cell wall to achieve antifungal effects. Finally, EOs were found to significantly retard P. notoginseng infection by F. oxysporum. According to our research, C. citratus EOs are potential green antifungal agent that can be used in the cultivation of P. notoginseng.

Sex difference in the expression of PD-1 of non-small cell lung cancer.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

[Clinical features of immune checkpoint inhibitor-related myositis in patients with urological cancer].

OBJECTIVE: Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients. METHODS: The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes. RESULTS: The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (P=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3+, CD4+, CD8+, CD20+ lymphocytes and CD68+ macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin. CONCLUSION: Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.

Quantification of Immunostained Caspase-9 in Retinal Tissue.

The family of caspases is known to mediate many cellular pathways beyond cell death, including cell differentiation, axonal pathfinding, and proliferation. Since the identification of the family of cell death proteases, there has been a search for tools to identify and expand the function of specific family members in development, health, and disease states. However, many of the currently commercially available caspase tools that are widely used are not specific for the targeted caspase. In this report, we delineate the approach we have used to identify, validate, and target caspase-9 in the nervous system using a novel inhibitor and genetic approaches with immunohistochemical read-outs. Specifically, we used the retinal neuronal tissue as a model to identify and validate the presence and function of caspases. This approach enables the interrogation of cell-type specific apoptotic and non-apoptotic caspase-9 functions and can be applied to other complex tissues and caspases of interest. Understanding the functions of caspases can help to expand current knowledge in cell biology, and can also be advantageous to identify potential therapeutic targets due to their involvement in disease.

3DFAACTS-SNP: using regulatory T cell-specific epigenomics data to uncover candidate mechanisms of type 1 diabetes (T1D) risk.

BACKGROUND: Genome-wide association studies (GWAS) have enabled the discovery of single nucleotide polymorphisms (SNPs) that are significantly associated with many autoimmune diseases including type 1 diabetes (T1D). However, many of the identified variants lie in non-coding regions, limiting the identification of mechanisms that contribute to autoimmune disease progression. To address this problem, we developed a variant filtering workflow called 3DFAACTS-SNP to link genetic variants to target genes in a cell-specific manner. Here, we use 3DFAACTS-SNP to identify candidate SNPs and target genes associated with the loss of immune tolerance in regulatory T cells (Treg) in T1D. RESULTS: Using 3DFAACTS-SNP, we identified from a list of 1228 previously fine-mapped variants, 36 SNPs with plausible Treg-specific mechanisms of action. The integration of cell type-specific chromosome conformation capture data in 3DFAACTS-SNP identified 266 regulatory regions and 47 candidate target genes that interact with these variant-containing regions in Treg cells. We further demonstrated the utility of the workflow by applying it to three other SNP autoimmune datasets, identifying 16 Treg-centric candidate variants and 60 interacting genes. Finally, we demonstrate the broad utility of 3DFAACTS-SNP for functional annotation of all known common (> 10% allele frequency) variants from the Genome Aggregation Database (gnomAD). We identified 9376 candidate variants and 4968 candidate target genes, generating a list of potential sites for future T1D or other autoimmune disease research. CONCLUSIONS: We demonstrate that it is possible to further prioritise variants that contribute to T1D based on regulatory function, and illustrate the power of using cell type-specific multi-omics datasets to determine disease mechanisms. Our workflow can be customised to any cell type for which the individual datasets for functional annotation have been generated, giving broad applicability and utility.

Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial.

STUDY OBJECTIVES: The long-term effect of continuous positive airway pressure (CPAP) on 24-hour blood pressure (BP) in patients at high risk with obstructive sleep apnea (OSA) is uncertain. We aimed to determine the effect of CPAP treatment on ambulatory BP in individuals with moderate or severe OSA and cardiovascular disease or multiple cardiovascular disease risk factors without severe sleepiness. METHODS: In this randomized, controlled, parallel group study, 169 participants were randomly assigned to CPAP treatment or the control group. The primary outcome was the change in mean 24-hour systolic BP between groups from baseline to the average of 6- and 12-month measurements using mixed-effect linear regression models. RESULTS: The 24-hour systolic BP did not significantly differ by group, although there was a trend of decrease in the CPAP group (treatment effect -2.7 mm Hg [95% confidence interval -5.9 to 0.6]; P = .105) compared with control. CPAP had the greatest effect on nighttime systolic BP (treatment effect -5.9 mm Hg [95% confidence interval -9.9 to -1.9]; P = .004). Similar improvements in other nocturnal BP indices were observed. CONCLUSIONS: In patients at high risk with moderate-severe OSA without severe sleepiness, CPAP resulted in modest BP improvements over 6 to 12 months of follow-up, with possibly larger effects for nocturnal BP. Use of office blood pressure may underestimate the effect of CPAP on BP profile in patients with OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Sleep Apnea Intervention for Cardiovascular Disease Reduction; Identifier: NCT01261390; URL: https://clinicaltrials.gov/ct2/show/NCT01261390. CITATION: Zhao YY, Wang R, Gleason KJ, et al. Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial. J Clin Sleep Med. 2022;18(8):1899-1907.

Activities-specific performance frequency can accurately detect fallers in elderly populations: an alternative method for quantifying activity restrictions.

BACKGROUND: The high prevalence of falling among older adults constitutes a major public and clinical health concern. Many elderly persons may develop activities-specific restriction due to the risk of falling. This highlights the need for relevant evaluative tools. METHODS: This cross-sectional study used activities-specific performance frequency indicators to quantify activity restrictions in elderly participants, with all measures based on items from the Activities-Specific Balance Confidence (ABC) scale. Specifically, we tested for correlations between activities-specific performance frequency and balance confidence, functional balance/mobility, and fall history. There were 88 elderly participants, including 28 with stroke, 30 with Parkinson's disease, and 30 with no neurological diseases. In addition to their activities-specific performance frequency measures, we collected a series of demographic and health-related characteristics from each participant. We analyzed between-group differences in activities-specific performance frequency and other demographic and health-related characteristics via the one-way analysis of variance and Kruskal-Wallis test. Next, we used the Spearman's rank correlation test and binary logistic regression to investigate the correlations between activities-specific performance frequency and demographic/other health-related characteristics. RESULTS: There were significant group differences in performance frequency for all ABC activity items except for walking around the house, average ABC scores, and functional balance/mobility among normal older adults, participants with strokes and those with Parkinson's disease. Activities-specific performance frequency showed stronger correlations with activities-relevant functional mobility (r=0.250-0.713 for 15 items with significant correlations, 13 activity items with r≧0.4) than with balance confidence (r=0.279-0.668 for 13 items with significant correlations, 10 activity items with r≧0.4). The performance frequency of walking in crowds/bumped was the most sensitive measure for predicting fallers (odd ratio=3.310, p<0.05). CONCLUSIONS: This study proposed and validated the usage of activities-specific performance frequency as an alternative method for quantifying activity restrictions among older adults.

Landward zones of mangroves are sinks for both land and water borne anthropogenic debris.

The hotspots for mangrove diversity and plastic emissions from rivers overlap in Asia, however very few studies have investigated anthropogenic marine debris (AMD) pollution in these threatened coastal ecosystems. Despite Hong Kong's position at the mouth of the Pearl River, a major source of mismanaged waste in Asia, the mangroves in Hong Kong have never been extensively surveyed for AMD. Here we assessed the patterns of AMD abundance within 18 mangrove forests across Hong Kong surveying both their landward and seaward zones. We recorded and categorised, according to their material and potential uses, both the amount of debris items and area they covered, to better quantify its potential impact on the mangroves. Across Hong Kong mangroves, the average abundance of debris was 1.45 ± 0.38 (SE) items m-2, with an average coverage of 6.05 ± 1.59%. Plastic formed a high proportion of AMD accounting for 70.31% by number of items and 49.71% by area covered, followed by glass/ceramics and wood/bamboo. Disposable food packaging, fishing gear and industrial and construction related waste were the major sources of AMD we documented. On average, we recorded about six times more debris items m-2 at the landward sites than at the seaward one, but these abundances varied between the East and the West coastlines of Hong Kong. Our data confirms the hypothesis that landward areas of mangrove forests act as traps and retain marine borne debris, but they also suggest that direct dumping of waste from the land could represent a serious impact for these forests placed in between the land and the sea. More research is needed to ascertain the impact of land disposed debris on mangrove degradation, and this study strongly advocates for a cultural shift about the perception of these forests by the public.

[Association between physical activity and risk of stroke among adults aged 40 years and above: a prospective cohort study].

Objective: To examine the effect of physical activity (PA) on the incident risk of stroke among adults aged 40 years and above. Methods: The baseline data including PA and demographic characteristics were obtained from the Adult Chronic Disease Surveillance with population representativeness in Ningbo in 2015. The follow-up data of interested health outcomes from 2015 to 2019 were retrieved from a population-based Integrated Noncommunicable Disease Collaborative Management System in Ningbo. The two databases were matched to form a queue. PA was divided into three levels of low-intensity, moderate-intensity, and vigorous-intensity according to the metabolic equivalents (METs) spent per week. Cox regression model was used to calculate the hazard ratio (HR) and 95% confidence interval. Results: A total of 3 353 subjects were included at baseline survey in 2015. Until Dec 31, 2019, there had been 31 stroke events had occurred since then, with accumulative incidence rate of 242/100 000, and an average follow-up time of (50.28±2.54) months. When adjusted for gender, age, education level, smoking status, alcohol consumption, BMI and hypertension, multivariate Cox regression analysis showed that greater PA was associated with a 37.9% reduction of incidence of stroke (HR=0.621,95%CI:0.393-0.983). Compared with those who had low-intensity PA, those who were with vigorous-intensity. PA appeared associated with a 63.1% decrease in the incidence of stroke (HR=0.369, 95%CI: 0.139-0.976). However, there was no statistical significance with moderate-intensity PA (HR=0.712,95%CI:0.323-1.569), noticed. Conclusions: Greater PA is likely to reduce the incidence of stroke. Our findings indicated that people should be encouraged to increase the PA level and developing a healthy supportive environment in the community.

Skin Lesion Segmentation Using Deep Learning with Auxiliary Task.

Skin lesion segmentation is a primary step for skin lesion analysis, which can benefit the subsequent classification task. It is a challenging task since the boundaries of pigment regions may be fuzzy and the entire lesion may share a similar color. Prevalent deep learning methods for skin lesion segmentation make predictions by ensembling different convolutional neural networks (CNN), aggregating multi-scale information, or by multi-task learning framework. The main purpose of doing so is trying to make use of as much information as possible so as to make robust predictions. A multi-task learning framework has been proved to be beneficial for the skin lesion segmentation task, which is usually incorporated with the skin lesion classification task. However, multi-task learning requires extra labeling information which may not be available for the skin lesion images. In this paper, a novel CNN architecture using auxiliary information is proposed. Edge prediction, as an auxiliary task, is performed simultaneously with the segmentation task. A cross-connection layer module is proposed, where the intermediate feature maps of each task are fed into the subblocks of the other task which can implicitly guide the neural network to focus on the boundary region of the segmentation task. In addition, a multi-scale feature aggregation module is proposed, which makes use of features of different scales and enhances the performance of the proposed method. Experimental results show that the proposed method obtains a better performance compared with the state-of-the-art methods with a Jaccard Index (JA) of 79.46, Accuracy (ACC) of 94.32, SEN of 88.76 with only one integrated model, which can be learned in an end-to-end manner.

Effects of Central Obesity on Esophageal Epithelial Barrier Function.

INTRODUCTION: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER). METHODS: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured. RESULTS: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients. DISCUSSION: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.

Crystal structures and mechanical properties of osmium diboride at high pressure.

We have investigated the crystal structures and mechanical properties of osmium diboride (OsB2) based on the density functional theory. The structures of OsB2 from 0 to 400 GPa were predicted using the particle swarm optimization algorithm structure prediction technique. The orthorhombic Pmmn structure of OsB2 (oP6-OsB2) was found to be the most stable phase under zero pressure and it will transfer to the hexagonal P63/mmc structure (hP6-OsB2) around 12.4 GPa. Meanwhile, we have discovered a new stable orthorhombic Immm structure (oI12-OsB2) above 379.6 GPa. After that, a thorough and comprehensive investigation on mechanical properties of different OsB2 phases is performed in this work. Further studies showed that the hardness of oP6-OsB2 and hP6-OsB2 at zero pressure is 15.6 and 20.1 GPa, while that for oI12-OsB2 under 400 GPa is 15.4 GPa, indicating that these three phases should be potentially hard materials rather than superhard materials. Finally, the pressure-temperature phase diagram of OsB2 is constructed for the first time by using the quasi-harmonic approximation method. Our results showed that the transition pressures of oP6-OsB2 → hP6-OsB2 and hP6-OsB2 → oI12-OsB2 all decreases appreciably with the increase of temperature.

New biomarker for lung cancer - focus on circSETD3.

In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinib-resistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.

A real-time light-scattering technique for tailings solids measurement.

This study presents the concept of an economic in situ light-scattering sensor for real-time measurement of the solid content in tailings facilities. An experimental setup using a blue (405 nm wavelength) laser diode and silicon photodiodes was constructed to measure the angular distribution of the intensity of scattered light. It was found that the angular intensity of scattered light for tailing samples follows a cosn (θ) relation with n ≈ 1.5, where θ is the angle between the laser beam and the photodiode. An angular value of θ = 20° was chosen for the sensor design based on a high signal-to-noise ratio. The setup was used to determine the relation between scattered light intensity and solids content using a thickened tailings underflow from an oil sands facility and Kaolin as a model material. It was observed that the intensity of scattered light tends to increase with an increase in solids content, with qualitatively similar settling behavior for the two materials but at largely different time scales. An insertion-based prototype was built and tested in a large (2.7 m height) settling column with treated mature fine tailings, and the light-scattering data were verified by standard gravimetric method and gamma-ray measurements. In general, good agreement was established between these measurements in the absence of optical fouling, which demonstrates the potential of the sensor as an effective tool for tailings management.