Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice.

Major depressive disorder (MDD) is a prevalent and devastating mental illness. To date, the diagnosis of MDD is largely dependent on clinical interviews and questionnaires and still lacks a reliable biomarker. DNA methylation has a stable and reversible nature and is likely associated with the course and therapeutic efficacy of complex diseases, which may play an important role in the etiology of a disease. Here, we identified and validated a DNA methylation biomarker for MDD from four independent cohorts of the Chinese Han population. First, we integrated the analysis of the DNA methylation microarray (n = 80) and RNA expression microarray data (n = 40) and identified BICD2 as the top-ranked gene. In the replication phase, we employed the Sequenom MassARRAY method to confirm the DNA hypermethylation change in a large sample size (n = 1,346) and used the methylation-sensitive restriction enzymes and a quantitative PCR approach (MSE-qPCR) and qPCR method to confirm the correlation between DNA hypermethylation and mRNA down-regulation of BICD2 (n = 60). The results were replicated in the peripheral blood of mice with depressive-like behaviors, while in the hippocampus of mice, Bicd2 showed DNA hypomethylation and mRNA/protein up-regulation. Hippocampal Bicd2 knockdown demonstrates antidepressant action in the chronic unpredictable mild stress (CUMS) mouse model of depression, which may be mediated by increased BDNF expression. Our study identified a potential DNA methylation biomarker and investigated its functional implications, which could be exploited to improve the diagnosis and treatment of MDD.

DTSyn: a dual-transformer-based neural network to predict synergistic drug combinations.

Drug combination therapies are superior to monotherapy for cancer treatment in many ways. Identifying novel drug combinations by screening is challenging for the wet-lab experiments due to the time-consuming process of the enormous search space of possible drug pairs. Thus, computational methods have been developed to predict drug pairs with potential synergistic functions. Notwithstanding the success of current models, understanding the mechanism of drug synergy from a chemical-gene-tissue interaction perspective lacks study, hindering current algorithms from drug mechanism study. Here, we proposed a deep neural network model termed DTSyn (Dual Transformer encoder model for drug pair Synergy prediction) based on a multi-head attention mechanism to identify novel drug combinations. We designed a fine-granularity transformer encoder to capture chemical substructure-gene and gene-gene associations and a coarse-granularity transformer encoder to extract chemical-chemical and chemical-cell line interactions. DTSyn achieved the highest receiver operating characteristic area under the curve of 0.73, 0.78. 0.82 and 0.81 on four different cross-validation tasks, outperforming all competing methods. Further, DTSyn achieved the best True Positive Rate (TPR) over five independent data sets. The ablation study showed that both transformer encoder blocks contributed to the performance of DTSyn. In addition, DTSyn can extract interactions among chemicals and cell lines, representing the potential mechanisms of drug action. By leveraging the attention mechanism and pretrained gene embeddings, DTSyn shows improved interpretability ability. Thus, we envision our model as a valuable tool to prioritize synergistic drug pairs with chemical and cell line gene expression profile.

Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs.

Cancer cells can survive chemotherapy-induced stress, but how they recover from it is not known. Using a temporal multiomics approach, we delineate the global mechanisms of proteotoxic stress resolution in multiple myeloma cells recovering from proteasome inhibition. Our observations define layered and protracted programs for stress resolution that encompass extensive changes across the transcriptome, proteome, and metabolome. Cellular recovery from proteasome inhibition involved protracted and dynamic changes of glucose and lipid metabolism and suppression of mitochondrial function. We demonstrate that recovering cells are more vulnerable to specific insults than acutely stressed cells and identify the general control nonderepressable 2 (GCN2)-driven cellular response to amino acid scarcity as a key recovery-associated vulnerability. Using a transcriptome analysis pipeline, we further show that GCN2 is also a stress-independent bona fide target in transcriptional signature-defined subsets of solid cancers that share molecular characteristics. Thus, identifying cellular trade-offs tied to the resolution of chemotherapy-induced stress in tumor cells may reveal new therapeutic targets and routes for cancer therapy optimization.

SARS-CoV-2 N Protein Antagonizes Stress Granule Assembly and IFN Production by Interacting with G3BPs to Facilitate Viral Replication.

SARS-CoV-2 is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19) and poses a significant threat to global health. N protein (NP), which is a major pathogenic protein among betacoronaviruses, binds to the viral RNA genome to allow viral genome packaging and viral particle release. Recent studies showed that NP antagonizes interferon (IFN) induction and mediates phase separation. Using live SARS-CoV-2 viruses, this study provides solid evidence showing that SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming G3BP1-mediated antiviral innate immunity. G3BP1 conditional knockout mice (g3bp1fl/fL, Sftpc-Cre) exhibit significantly higher lung viral loads after SARS-CoV-2 infection than wild-type mice. Our findings contribute to the growing body of knowledge regarding the pathogenicity of NPSARS-CoV-2 and provide insight into new therapeutics targeting NPSARS-CoV-2. IMPORTANCE In this study, by in vitro assay and live SARS-CoV-2 virus infection, we provide solid evidence that the SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming antiviral innate immunity mediated by G3BP1 in A549 cell lines and G3BP1 conditional knockout mice (g3bp1-cKO) mice, which provide in-depth evidence showing the mechanism underlying NP-related SARS-CoV-2 pathogenesis through G3BPs.

Effects of short-term and long-term exposure to ambient air pollution and temperature on long recovery duration in COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has spread rapidly around the world since December 8, 2019. However, the key factors affecting the duration of recovery from COVID-19 remain unclear. OBJECTIVE: To investigate the associations of long recovery duration of COVID-19 patients with ambient air pollution, temperature, and diurnal temperature range (DTR) exposure. METHODS: A total of 427 confirmed cases in Changsha during the first wave of the epidemic in January 2020 were selected. We used inverse distance weighting (IDW) method to estimate personal exposure to seven ambient air pollutants (PM2.5, PM2.5-10, PM10, SO2, NO2, CO, and O3) at each subject's home address. Meteorological conditions included temperature and DTR. Multiple logistic regression model was used to investigate the relationship of air pollution exposure during short-term (past week and past month) and long-term (past three months) with recovery duration among COVID-19 patients. RESULTS: We found that long recovery duration among COVID-19 patients was positively associated with short-term exposure to CO during past week with OR (95% CI) = 1.42 (1.01-2.00) and PM2.5, NO2, and CO during past month with ORs (95% CI) = 2.00 (1.30-3.07) and 1.95 (1.30-2.93), and was negatively related with short-term exposure to O3 during past week and past month with ORs (95% CI) = 0.68 (0.46-0.99) and 0.41 (0.27-0.62), respectively. No association was observed for long-term exposure to air pollution during past three months. Furthermore, increased temperature during past three months elevated risk of long recovery duration in VOCID-19 patients, while DTR exposure during past week and past month decreased the risk. Male and younger patients were more susceptible to the effect of air pollution on long recovery duration, while female and older patients were more affected by exposure to temperature and DTR. CONCLUSION: Our findings suggest that both TRAP exposure and temperature indicators play important roles in prolonged recovery among COVID-19 patients, especially for the sensitive populations, which provide potential strategies for effective reduction and early prevention of long recovery duration of COVID-19.

Combined effect of preconceptional and prenatal exposure to air pollution and temperature on childhood pneumonia: A case-control study.

Mounting evidence have linked ambient air pollution and temperature with childhood pneumonia, but it is unclear whether there is an interaction between air pollution and temperature on childhood pneumonia. We aim to assess the combined effect of ambient air pollution and temperature exposure during preconception and pregnancy on pneumonia by a case-control study of 1510 children aged 0-14 years in Changsha, China. We obtained the data of childhood pneumonia from XiangYa Hospital electrical records. We estimated personal exposure to outdoor air pollution (PM10, SO2 and NO2) by inverse distance weighted (IDW) method and temperature indicators. Multiple logistic regression models were used to evaluate associations of childhood pneumonia with air pollution, temperature (T), and diurnal temperature variation (DTV). We found that exposure to industry-related air pollution (PM10 and SO2) during preconception and pregnancy were associated with childhood pneumonia, with ORs (95% CI) of 1.72 (1.48-1.98) and 2.96 (2.50-3.51) during 1 year before pregnancy and 1.83 (1.59-2.11) and 3.43 (2.83-4.17) in pregnancy. Childhood pneumonia was negatively associated with T exposure during 1 year before pregnancy and pregnancy, with ORs (95% CI) of 0.57 (0.41-0.80) and 0.85 (0.74-0.98). DTV exposure during pregnancy especially during the 1st and 2nd trimesters significantly increased pneumonia risk, with ORS (95% CI) of 1.77 (1.19-2.64), 1.47 (1.18-1.83), and 1.37 (1.07-1.76) respectively. We further observed interactions of PM10 and SO2 exposure with low T and high DTV during conception and pregnancy in relation to childhood pneumonia. This study suggests that there were interactions air pollution with temperature and DTV on pneumonia development.

Early life exposure to outdoor air pollution and indoor environmental factors on the development of childhood allergy from early symptoms to diseases.

BACKGROUND: The prevalence of childhood allergies has increased during past decades leading to serious hospitalization and heavy burden worldwide, yet the key factors responsible for the onset of early symptoms and development of diagnosed diseases are unclear. OBJECTIVE: To explore the role of early life exposure to ambient air pollution and indoor environmental factors on early allergic symptoms and doctor diagnosed allergic diseases. METHODS: A retrospective cohort study of 2598 preschool children was conducted at 36 kindergartens in Changsha, China from September of 2011 to February of 2012. A questionnaire was developed to survey each child's early onset of allergic symptoms (wheeze and rhinitis-like symptoms) and doctor diagnosis of allergic diseases (asthma and rhinitis) as well as home environments. Each mother's and child's exposures to ambient air pollutants (PM10, SO2, and NO2) and temperature were estimated for in utero and postnatal periods. The associations of early symptoms and diagnosed diseases with outdoor air pollution and indoor environmental variables were examined by logistic regression models. RESULTS: Childhood early allergic symptoms (33.9%) including wheeze (14.7%) and rhinitis-like symptoms (25.4%) before 2 years old were not associated with outdoor air pollution exposure but was significantly associated with maternal exposure of window condensation at home in pregnancy with ORs (95% CI) of 1.33 (1.11-1.59), 1.30 (1.01-1.67) and 1.27 (1.04-1.55) respectively, and was associated with new furniture during first year after birth with OR (95% CI) of 1.43 (1.02-2.02) for early wheeze. Childhood diagnosed allergic diseases (28.4%) containing asthma (6.7%) and allergic rhinitis (AR) (7.2%) were significantly associated with both outdoor air pollutants (mainly for SO2 and NO2) during first 3 years and indoor new furniture, redecoration, and window condensation. We found that sex, age, parental atopy, maternal productive age, environmental tobacco smoke (ETS), antibiotics use, economic stress, early and late introduction of complementary foods, and outdoor air pollution modified the effects of home environmental exposure in early life on early allergic symptoms and diagnosed allergic diseases. CONCLUSION: Our study indicates that early life exposure to indoor environmental factors plays a key role in early onset of allergic symptoms in children, and further exposure to ambient air pollution and indoor environmental factors contribute to the later development of asthma and allergic rhinitis.

Assessment of radial artery atherosclerosis in acute coronary syndrome patients: an in vivo study using optical coherence tomography.

BACKGROUND: Radial artery (RA) atherosclerosis in acute coronary syndrome (ACS) patients has not been systematically observed in vivo. The study aims to characterize plaque morphology and intimal hyperplasia of the RA in patients with ACS, using optical coherence tomography (OCT). METHODS: In this retrospective study involving 239 ACS patients underwent RA OCT without guidewire shadow, 3 groups were divided according to the following criteria: radial artery plaque (RAP) group included patients with fibrous, lipid or calcified plaque; patients without RAP were further classified into radial intimal hyperplasia (RIH) group (intima media thickness ratio [IMR] ≥ 1) or normal group (IMR < 1). The presence and characteristics of RAP and its related risk factors were identified. RESULTS: The RAP, RIH and normal groups included 76 (31.8%), 69 (28.9%) and 94 (39.3%) patients, respectively. Patients in RAP group were the oldest, compared with those in the RIH and normal groups (p < 0.001), and more frequently had triple vessel disease (p = 0.004). The percentage of plaque rupture (72.4% vs. 56.4%, p = 0.018) and calcification (42.1% vs. 27.6%, p = 0.026) at culprit lesion were significantly higher in patients with RAP than those without RAP. A total of 148 RAP were revealed by OCT, including fibrous (72, 48.6%), lipid (50, 33.8%) and calcified plaques (26, 17.6%). The microvessels were also frequently observed in the RAP group than that in RIH and normal groups (59.2% vs. 8.7% vs. 9.6%, p < 0.001). Multivariate logistic regression analysis showed that age, diabetes, and smoking history (all p < 0.05) were independent risk factors for RAP. CONCLUSIONS: In terms of insights gained from OCT, RA atherosclerosis is not uncommon in ACS patients by OCT, sharing several morphological characters with early coronary atherosclerosis. Aging, diabetes, and smoking are risk factors for RAP.

Effect of preconceptional, prenatal and postnatal exposure to home environmental factors on childhood pneumonia: A key role in early life exposure.

BACKGROUND: Increasing evidence have associated pneumonia with early exposure to ambient air pollution. However, the role of indoor environmental factors exposure in early life on childhood pneumonia remains unclear. OBJECTIVE: To examine the association between indoor environmental factors exposure during different timing windows and childhood pneumonia, and to identify the key indoor factor(s) in different critical window(s). METHODS: A retrospective cohort study of 8689 pre-schoolers was performed in Changsha, China during 2019-2020. Our questionnaire survey was designed to collect information on pre-schooler's outcome and residential environmental exposure containing indoor pollution and allergens during 1 year before pregnancy, pregnancy, first year, and past year. The associations were further estimated stratified by personal exposure level of outdoor NO2, CO, temperature (T) and different covariates. Associations were assessed by multiple logistic regression model in terms of odds ratio (OR) of 95% confidence interval (CI). RESULTS: Pre-schooler's pneumonia was significantly related with exposure of new furniture, redecoration, mold/damp stains, and mold or damp clothing or bedding exposure during the four periods, with the strongest associations observed during 1 year before pregnancy based on multi-window model, with ORs (95% CI) of 1.27 (1.12-1.44), 1.26 (1.09-1.46), 1.34 (1.14-1.57), and 1.28 (1.05-1.56) respectively. Environmental tobacco smoke (ETS) including both parental and grandparental smoking were significantly related with increased risk of pre-schooler's pneumonia, and ETS played a more important role in early life, with ORs (95% CI) of 1.17 (1.01-1.36) and 1.19 (1.02-1.39) in pregnancy and first year. Indoor plants particularly nonflowering plants significantly elevated pneumonia risk but only in past year, with ORs (95% CI) of 1.17 (1.05-1.30) and 1.14 (1.03-1.26). Higher pneumonia risk was observed for renovation exposure in pre-birth compared to post-birth, while mold/dampness exerted an accumulative effect with the highest risk for exposure during both pre- and post-birth. Living near traffic road and exposure to high level of traffic-related air pollution and high temperature significantly increased pneumonia risk. Sensitivity analysis found that some sub-groups were more susceptible to pneumonia risk of home environment exposure. CONCLUSION: Early life exposure to indoor environmental factors plays an important role in pneumonia development, supporting the hypothesis of "Preconceptional and Fetal Origin of Childhood Pneumonia" and "Developmental Origins of Health and Pneumonia".

Effects of early life exposure to home environmental factors on childhood allergic rhinitis: Modifications by outdoor air pollution and temperature.

BACKGROUND: There is growing evidence that allergic rhinitis (AR) is associated with indoor environmental factors, but their role in childhood AR during early life remains unclear. OBJECTIVE: To investigate the association of preconceptional, prenatal, early postnatal, and current exposure to home environmental factors with childhood AR, and to further explore whether this association can be interacted by outdoor air pollution and temperature. METHODS: A retrospective cohort study of 8689 preschool children was conducted during 2019-2020 in Changsha, China. A standard questionnaire was used to collect data on each family's health outcomes and home environments. We considered home environmental exposures during one year before conception, pregnancy, first year of life, and past year. Associations of indoor air pollution and allergens with AR were assessed by multiple logistic regression models. RESULTS: Pre-birth exposure to indoor air pollution emitted by new furniture or redecoration and dampness related allergen derived from mold/damp stains and mold/damp clothes or bedding during 1 year before conception and pregnancy was significantly associated with increased AR, with adjusted ORs (95% CI) ranging from 1.35 (1.05-1.75) to 1.87 (1.55-2.27). Childhood AR was also significantly related with post-birth exposure to dampness related indoor allergen including mold/damp stains and mold/damp clothes or bedding in first year and past year and pollen allergen including total and nonflowing plants in past year, with a range of ORs (95% CI) from 1.20 (1.01-1.42) to 1.79 (1.42-2.27). We identified that pre-birth, particularly in utero exposure to both indoor air pollution from renovation and dampness related allergens, played a key role in AR development compared to post-birth exposures, and accumulative effect was observed with the highest risk of AR. High exposure to traffic-related air pollution (TRAP) including outdoor PM2.5, NO2, CO, and O3, as well as living near traffic road not only significantly increased adverse effect of home environmental factors but also decreased protective effect of household dogs on childhood AR. Early life exposure to low temperature in pregnancy and high temperature in first year significantly increased AR risk of home environmental exposure. Sensitivity analysis indicated that some sub-groups were more susceptible to AR risk of home environmental exposure. CONCLUSION: Our study suggests that pre-birth exposure to home environmental factors played an important role in AR development and this effect can be interacted by TRAP and temperature, which supports a hypothesis of "(pre)fetal origin of childhood AR".

Runx1 is sufficient for blood cell formation from non-hemogenic endothelial cells in vivo only during early embryogenesis.

Hematopoietic cells differentiate during embryogenesis from a population of endothelial cells called hemogenic endothelium (HE) in a process called the endothelial-to-hematopoietic transition (EHT). The transcription factor Runx1 is required for EHT, but for how long and which endothelial cells are competent to respond to Runx1 are not known. Here, we show that the ability of Runx1 to induce EHT in non-hemogenic endothelial cells depends on the anatomical location of the cell and the developmental age of the conceptus. Ectopic expression of Runx1 in non-hemogenic endothelial cells between embryonic day (E) 7.5 and E8.5 promoted the formation of erythro-myeloid progenitors (EMPs) specifically in the yolk sac, the dorsal aorta and the heart. The increase in EMPs was accompanied by a higher frequency of HE cells able to differentiate into EMPs in vitro Expression of Runx1 just 1 day later (E8.5-E9.5) failed to induce the ectopic formation of EMPs. Therefore, endothelial cells, located in specific sites in the conceptus, have a short developmental window of competency during which they can respond to Runx1 and differentiate into blood cells.

Efficacy and safety of systemic treatments for patients with recurrent/metastatic head and neck squamous cell carcinoma: A systematic review and network meta-analysis.

A variety of systemic chemotherapy regimens have been used for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most guidelines have been derived from a single clinical trial, and no studies have comprehensively compared their efficacy and safety. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases. Eligible studies reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and ≥ 3 adverse events rate (AEs). Eighteen eligible trials involving 4930 patients and 15 treatment regimens were included. The results suggest that patients with R/M HNSCC exhibit better tumor response with the cetuximab/platinum/5-FU, pembrolizumab/platinum/5-FU or pembrolizumab alone, accompanied by a low AE rate. Nivolumab also showed better efficacy than other single agents. Immunotherapy has achieved better efficacy.

Bivalirudin vs. Heparin on Radial Artery Thrombosis during Transradial Coronary Intervention: An Optical Coherence Tomography Study.

OBJECTIVES: This study aimed to evaluate the antithrombotic efficacy between bivalirudin and unfractionated heparin (UFH) on radial artery thrombosis (RAT) during transradial coronary intervention (TRI) by optical coherence tomography (OCT). METHODS AND RESULTS: We consecutively reviewed a total of 307 patients who underwent radial artery OCT inspection after TRI in our centre from October 2017 to January 2019; afterwards, 211 screened patients were divided into the UFH group (n = 144) and the bivalirudin group (n = 67) according to their anticoagulation strategy during TRI. The thrombosis in the radial artery was observed in 51 cases (24.17%) with a median thrombus volume of 0.054 mm3 (0.024, 0.334) and median thrombus score of 7 (4, 15). Thrombus occurred in 28 cases in the bivalirudin group with an incidence of 41.8%, which was significantly higher than that in the UFH group (n = 23, 16.0%, P < 0.001). This difference was even more remarkable after propensity score matching (bivalirudin group n = 22, 42.3% vs. UHF group n = 11, 13.9%, P < 0.001). Multivariate logistic analysis revealed that bivalirudin increased the RAT risk by 3.872 times (95% CI 2.006-8.354, P < 0.001) after adjustment for the other predictors. CONCLUSION: In this present study, the use of bivalirudin was associated with a higher risk of RAT than UFH. It highlighted UFH should be a more considerable choice to prevent radial artery access thrombosis in TRI.

Construction of a DNA vaccine and its protective effect on largemouth bass (Micropterus salmoides) challenged with largemouth bass virus (LMBV).

Largemouth bass virus (LMBV) is the causative agent of a disease causing high mortality rates in largemouth bass during summer. However, there is little information available about the development of vaccines for LMBV disease. Hence, a DNA vaccine, named pCDNA3.1(+)-MCP-Flag, was constructed by inserting the cloned LMBV major capsid protein (MCP) gene into the pCDNA3.1(+)-Flag plasmid. The expression of the recombinant plasmid was confirmed by Western blot (WB) and RT-PCR. The WB result revealed that the MCP protein produced a band of approximately 53 kDa, consistent with the expected result. The RT-PCR results also confirmed that MCP was transcribed in the EPC cells transfected with the recombinant plasmid. The largemouth bass in the DNA vaccine group were immunized with the pCDNA3.1(+)-MCP-Flag plasmid by pectoral fin base injection, and the relative percent survival (RPS) of fish challenged with LMBV was 63%. The relative immunological analyses were as follows. Compared with the PBS and pCDNA3.1(+) groups, the DNA vaccine group showed significantly upregulated expression of IL-1ß, IL-8, TNF-α and Mx in the spleen, head kidney and liver. All largemouth bass immunized with the DNA vaccine produced a high titre of LMBV-specific neutralizing antibody during the immunization period. The titre was 1:375 ± 40 and peaked at 14 days post-vaccination. The expression of the recombinant plasmid was analysed in the tissues of the DNA vaccine group by RT-PCR. The recombinant plasmid was expressed in the spleen, head kidney and liver, and MCP protein was successfully expressed after vaccination. In conclusion, the recombinant plasmid expressing LMBV MCP induced significant immune responses in largemouth bass, and might represent a potential LMBV vaccine candidate for largemouth bass.

Bioinformatics Analysis and High-Throughput Sequencing to Identify Differentially Expressed Genes in Nebulin Gene (NEB) Mutations Mice.

BACKGROUND High-throughput sequencing of the pathological tissue of 59 patients with thyroid cancer was compared with the normal population. It was found that the mutation frequency of the Nebulin gene (NEB) at amino acid 1133 locus of thyroid cancer patients was much higher than that of the normal population, suggesting that NEB mutation may be related to thyroid cancer. Therefore, we constructed the NEB mutant mice for further investigation. MATERIAL AND METHODS The RNA extracted from the thyroid of wild-type and NEB mutant mice was analyzed by high-throughput sequencing, and the differential expression was analyzed by edgeR software. Several differentially expressed genes were selected for quantitative real-time PCR (qRT-PCR) verification, and these genes were analyzed with Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS A total of 624 genes were significantly enriched. Analysis of GO function and pathway significant enrichment showed that differentially expressed genes were enriched in thyroid cancer, myocardial contraction, and autoimmune thyroid disease. The qRT-PCR results were consistent with the high-throughput sequencing results. CONCLUSIONS Our data indicate that the expression of some cancer-driving genes and cancer suppressor genes are significantly changed in NEB mutant mice compared to wild-type mice, which suggests that NEB function plays an important role in regulating the expression of cancer-related genes in the thyroid gland.

Preparation of Porous Activated Carbons for High Performance Supercapacitors from Taixi Anthracite by Multi-Stage Activation.

Coal-based porous materials for supercapacitors were successfully prepared using Taixi anthracite (TXA) by multi-stage activation. The characterization and electrochemical tests of activated carbons (ACs) prepared in different stages demonstrated that the AC from the third-stage activation (ACIII) shows good porous structures and excellent electrochemical performances. ACIII exhibited a fine specific capacitance of 199 F g-1 at a current density of 1 A g-1 in the three-electrode system, with 6 mol L-1 KOH as the electrolyte. The specific capacitance of ACIII remained 190 F g-1 even despite increasing the current density to 5 A g-1, indicating a good rate of electrochemical performance. Moreover, its specific capacitance remained at 98.1% of the initial value after 5000 galvanostatic charge-discharge (GCD) cycle tests at a current density of 1 A g-1, suggesting that the ACIII has excellent cycle performance as electrode materials for supercapacitors. This study provides a promising approach for fabricating high performance electrode materials from high-rank coals, which could facilitate efficient and clean utilization of high-rank coals.

Hierarchical Specification of Pruriceptors by Runt-Domain Transcription Factor Runx1.

The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch, and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. They express the natriuretic peptide type B (NPPB), as well as a cohort of receptors and neuropeptides that have been implicated in chronic itch manifestation, including the interleukin-31 receptor A (IL-31ra) and its coreceptor oncostatin M receptor (Osmr), the cysteinyl leukotriene receptor 2 (Cysltr2), somatostatin, and neurotensin. However, how these neurons are generated during development remains unclear. Here we report that Runx1 is required to establish all these molecular features of NPPB+ neurons. We further show that while early embryonic Runx1 activity is required for the formation of NPPB+ cells, at later stages Runx1 switches to a genetic repressor and thus its downregulation becomes a prerequisite for the proper development of these pruriceptors. This mode by Runx1 is analogous to that in controlling another group of pruriceptors that specifically express the chloroquine receptor MrgprA3. Finally, behavioral studies using both sexes of mice revealed marked deficits in processing acute and chronic itch in Runx1 conditional knock-out mice, possibly attributable to impaired development of various pruriceptors.SIGNIFICANCE STATEMENT Our studies reveal a generalized control mode by Runx1 for pruriceptor development and consolidate a hierarchical control mechanism for the formation of sensory neurons transmitting distinct modalities. Among dorsal root ganglion neurons that initially express the neurotrophin receptor TrkA, Runx1 is necessary for the proper development of those neurons that innervate tissues derived from the ectoderm such as skin epidermis and hair follicles. These Runx1-dependent cutaneous sensory neurons are then divided into two groups based on persistent or transient Runx1 expression. The Runx1-persistent group is involved in transmitting mechanical and thermal information, whereas the Runx1-transient group transmits pruriceptive information. Such hierarchical control mechanisms may provide a developmental solution for the formation of sensory circuits that transmit distinct modalities.

Safety and Efficacy of Using a Single Transradial MAC Guiding Catheter for Coronary Angiography and Intervention in Patients with ST Elevation Myocardial Infarction.

BACKGROUND: There are limited data on the impact of using a single dedicated radial guiding catheter in primary percutaneous coronary intervention (PCI) via radial access. OBJECTIVES: To investigate the effect of using a single guiding catheter (MAC 3.5) for left and right coronary angiography and intervention on catheterization laboratory door to balloon (C2B) time in patients with ST elevation myocardial infarction (STEMI). METHODS: Three hundred and sixty patients were randomized (1:1) to using a single MAC3.5 guiding catheter (MAC group) or diagnostic Tiger catheter first for coronary angiography followed by guiding catheter selection (control group) for intervention. The primary outcomes were C2B. The secondary outcomes were major adverse cardiac events (MACE) at 30 days and 6 months. RESULTS: Median C2B time (16.6 min, interquartile range [IQR] 14.3-20.2 min vs 19.0 min, IQR 14.3-23.1 min; P < 0.001), total procedure time (31.0 min, IQR 26.4-37.7 min vs 34.8 min, IQR 29.7-42.5 min, P < 0.001), and overall fluoroscopy time (8.0 min, IQR 6.4-10.4 min vs 8.8 min, IQR 6.5-12.2, P = 0.04) were significantly reduced in MAC Group. Contrast consumption were similar among both groups (103 ± 37 ml vs 110 ± 41 ml, P = 0.16). The MACE rate in MAC group and control group was 3.3 versus 4.4% (P = 0.586) at 30 days and 3.3 versus 5.0% (P = 0.429) at 6 months, respectively. CONCLUSIONS: A single MAC3.5 guiding catheter for coronary angiography and intervention can shorten C2B time, procedure time, and fluoroscopy time. (RAPID study; NCT01759043).

Diagnostic Value of Methylated Septin9 for Colorectal Cancer Screening: A Meta-Analysis.

BACKGROUND Septin9 is a member of GTP-binding protein family, and is used as a predictive diagnostic index. However, it has not been widely adopted due to inconsistent results reported in the literature. The present study was performed to determine the diagnostic accuracy of methylated Septin9 (mSEPT9) for colorectal cancer (CRC) and to evaluate its utility in CRC screening. MATERIAL AND METHODS After reviewing relevant studies, accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratio [PLR/NLR], and diagnostic odds ratio [DOR]) were calculated for mSEPT9 in the diagnosis of CRC. Overall test performance was summarized using summary receiver operating characteristic curve analysis. Potential between-study heterogeneity was explored by use of a meta-regression model. We divided included studies into Epi proColon test and non-Epi proColon test subgroups. We compared the effects of mSEPT9 and fecal occult blood test (FOBT) for CRC screening. RESULTS A total of 9870 subjects in 14 studies were recruited. Pooled sensitivity and specificity, PLR, NLR, DOR, and corresponding 95% confidence intervals (CI) of mSEPT9 for CRC diagnosis were 0.66 (95% CI: 0.64-0.69), 0.91 (95% CI: 0.90-0.91), 5.59 (95% CI: 4.03-7.74), 0.37 (95% CI: 0.29-0.48), and 16.79 (95% CI: 10.54-26.76), respectively. The area under the summary ROC curve (AUC) was 0.8563. The AUCs in the Epi proColon test and non-Epi proColon test for CRC diagnosis were 0.8709 and 0.7968, respectively. In head-to-head comparison, AUC of mSEPT9 and FOBT for CRC diagnosis were 0.7857 and 0.6571, respectively. CONCLUSIONS The present study demonstrates that mSEPT9 can be a good diagnostic biomarker complementary to FOBT as a screening tool for CRC.