LncRNA DCRT Protects Against Dilated Cardiomyopathy by Preventing NDUFS2 Alternative Splicing by Binding to PTBP1.

BACKGROUND: Dilated cardiomyopathy is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in dilated cardiomyopathy; however, the underlying mechanisms remain unclear. Here, we explored the cardioprotective role of a heart-enriched long noncoding RNA, the dilated cardiomyopathy repressive transcript (DCRT), in maintaining mitochondrial function. METHODS: The DCRT knockout (DCRT-/-) mice and DCRT knockout cells were developed using CRISPR-Cas9 technology. Cardiac-specific DCRT transgenic mice were generated using α-myosin heavy chain promoter. Chromatin coimmunoprecipitation, RNA immunoprecipitation, Western blot, and isoform sequencing were performed to investigate the underlying mechanisms. RESULTS: We found that the long noncoding RNA DCRT was highly enriched in the normal heart tissues and that its expression was significantly downregulated in the myocardium of patients with dilated cardiomyopathy. DCRT-/- mice spontaneously developed cardiac dysfunction and enlargement with mitochondrial impairment. DCRT transgene or overexpression with the recombinant adeno-associated virus system in mice attenuated cardiac dysfunction induced by transverse aortic constriction treatment. Mechanistically, DCRT inhibited the third exon skipping of NDUFS2 (NADH dehydrogenase ubiquinone iron-sulfur protein 2) by directly binding to PTBP1 (polypyrimidine tract binding protein 1) in the nucleus of cardiomyocytes. Skipping of the third exon of NDUFS2 induced mitochondrial dysfunction by competitively inhibiting mitochondrial complex I activity and binding to PRDX5 (peroxiredoxin 5) and suppressing its antioxidant activity. Furthermore, coenzyme Q10 partially alleviated mitochondrial dysfunction in cardiomyocytes caused by DCRT reduction. CONCLUSIONS: Our study revealed that the loss of DCRT contributed to PTBP1-mediated exon skipping of NDUFS2, thereby inducing cardiac mitochondrial dysfunction during dilated cardiomyopathy development, which could be partially treated with coenzyme Q10 supplementation.

Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies.

The study aimed to identify the biomarkers for predicting coronary atherosclerotic lesions progression in patients with inflammatory bowel disease (IBD). Related transcriptome datasets were seized from Gene Expression Omnibus database. IBD-related modules were identified via Weighted Gene Co-expression Network Analysis. The 'Limma' was applied to screen differentially expressed genes between stable coronary artery disease (CAD) and acute myocardial infarction (AMI). Subsequently, we employed protein-protein interaction (PPI) network and three machine-learning strategies to further screen for candidate hub genes. Application of the receiver operating characteristics curve to quantitatively evaluate candidates to determine key diagnostic biomarkers, followed by a nomogram construction. Ultimately, we performed immune landscape analysis, single-gene GSEA and prediction of target-drugs. 3227 IBD-related module genes and 570 DEGs accounting for AMI were recognized. Intersection yielded 85 shared genes and mostly enriched in immune and inflammatory pathways. After filtering through PPI network and multi-machine learning algorithms, five candidate genes generated. Upon validation, CTSD, CEBPD, CYP27A1 were identified as key diagnostic biomarkers with a superior sensitivity and specificity (AUC > 0.8). Furthermore, all three genes were negatively correlated with CD4+ T cells and positively correlated with neutrophils. Single-gene GSEA highlighted the importance of pathogen invasion, metabolism, immune and inflammation responses during the pathogenesis of AMI. Ten target-drugs were predicted. The discovery of three peripheral blood biomarkers capable of predicting the risk of CAD proceeding into AMI in IBD patients. These identified biomarkers were negatively correlated with CD4+ T cells and positively correlated with neutrophils, indicating a latent therapeutic target.

Adaptive Fuzzy Integral Sliding Mode Cooperative Control Based on Time-Delay Estimation for Free-Floating Close-Chain Manipulators.

Space manipulators are expected to perform more challenging missions in on-orbit service (OOS) systems, but there are some unique characteristics that are not found on ground-based robots, such as dynamic coupling between space bases and manipulators, limited fuel supply, and working with unfixed bases. This paper focuses on trajectory-tracking control and internal force control for free-floating close-chain manipulators. First, the kinematics and dynamics of free-floating close-chain manipulators are given using the momentum conservation and spatial operator algebra (SOA) methodologies, respectively. Furthermore, an adaptive fuzzy integral sliding mode controller (AFISMC) based on time delay estimation (TDE) was designed for trajectory-tracking control, and a proportional-integral (PI) control strategy was adopted for internal force control. The global asymptotic stability of the proposed controller was proven by using the Lyapunov methodology. Three cases were conducted to verify the efficiency of the controller by using numerical simulations on two six-link manipulators with a free-floating base. The controller presents the desired tracking capability.

Association of serum five heavy metals level with all-cause and cause-specific mortality: a large population-based cohort study.

The study aimed to explore the association between five heavy metals exposure (Cadmium, Lead, Mercury, Manganese, and Selenium) and mortality [all-cause, cardiovascular disease (CVD), and cancer-related]. We integrated the data into the National Health and Nutrition Examination Survey from 2011 to 2018 years. A total of 16,092 participants were recruited. The link between heavy metals exposure and mortality was analyzed by constructing a restricted cubic spline (RCS) curve, Cox proportional hazard regression model, and subgroup analysis. The RCS curve was used to show a positive linear relationship between Cadmium, Lead, and all-cause mortality. In contrast, there was a negative linear correlation between Mercury and all-cause mortality. Additionally, Manganese and Selenium also had a J-shaped and L-shaped link with all-cause mortality. The positive linear, positive linear, negative liner, J-shaped, and L-shaped relationships were observed for Cadmium, Lead, Mercury, Manganese, and Selenium and CVD mortality, respectively. Cadmium, Lead, Mercury, and Selenium were observed to exhibit positive linear, U-shaped, negative linear, and L-shaped relationships with cancer-related mortality, respectively. There was an increase and then a decrease in the link between Manganese and cancer-related morality. This study revealed the correlation between the content of different elements and different types of mortality in the U.S. general population.

Novel Green Fluorescent Probe Stem From Carbon Quantum Dots for Specific Recognition of Tyrosinase in Serum and Living Cells.

Tyrosinase (TYR), an important biomarker for melanoma, offered significant information early detection of melanoma and may decrease the likelihood of mortality. Therefore, this article constructed a highly sensitive and selective green fluorescent functionalized carbon quantum dots (TYR-CQDs) for tyrosinase (TYR) activity detection by one-step hydrothermal protocol utilizing catechol, citric acid and urea as precursors. The prepared TYR-CQDs illustrated excellent linear relationship and broad linear range with a low detection limit, which exhibited high accuracy and recovery in quantitative determination of TYR in human serum samples. Furthermore, the TYR-CQDs had successfully realized intracellular TYR detection owing to excellent biocompatibility, high anti-interference ability and good cellular imaging capability, suggesting the potential biomedical applications in early diagnosis of melanoma and other tyrosinase-related diseases.

Downregulation of annexin A3 promotes ionizing radiation-induced EGFR activation and nuclear translocation and confers radioresistance in nasopharyngeal carcinoma.

Radioresistance currently poses a significant challenge to successful disease control of nasopharyngeal carcinoma (NPC). We previously uncovered that annexin A3 (ANXA3), a calcium-dependent phospholipid binding protein, is underexpressed in radioresistant NPC cells and mouse xenografts. This study aims to further unravel the mechanistic basis underlying ANXA3-mediated radioresistance in NPC. We show that either innate ANXA3 downregulation or short hairpin RNA(shRNA)-based knockdown of ANXA3 confers resistance to ionizing radiation (IR) in NPC both in vitro and in mouse xenograft models in vivo, whereas radiosensitization was observed when ANXA3 was ectopically expressed. Mechanistically, ANXA3 knockdown dramatically enhances IR-induced epidermal growth factor receptor (EGFR) phosphorylation and nuclear translocation, leading to increased post-IR phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) concomitant with markedly accelerated DNA DSB repair. In addition, pretreatment with cetuximab efficiently abrogated the radioresistant phenotype of ANXA3-low cells as well as the ANXA3 knockdown-induced post-IR EGFR nuclear accumulation, suggesting that EGFR is an essential mediator for ANXA3 depletion-mediated radioprotection in NPC. Collectively, this work reveals for the first time a critical role of ANXA3 in radiation survival and DNA repair mechanism of NPC and provides mechanistic evidence to support ANXA3 as a potential therapeutic target to improve radiocurability for NPC.

Association of Systemic Immune Inflammation Index with Estimated Pulse Wave Velocity, Atherogenic Index of Plasma, Triglyceride-Glucose Index, and Cardiovascular Disease: A Large Cross-Sectional Study.

In the U.S. general population, there is a lack of understanding regarding the association between the systemic immune inflammation (SII) index and estimated pulse wave velocity (ePWV), atherogenic index of plasma (AIP), and triglyceride-glucose (TyG) index and cardiovascular disease (CVD). As a result, the objective of our research was to investigate the association between the SII index and ePWV, AIP, and TyG index and incident CVD. We used the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 to conduct this study. The correlation between the SII index and ePWV, AIP, and TyG index was examined using generalized additive models with smooth functions. In addition, the association between SII index and triglyceride (TC), high-density lipoprotein cholesterol (HDL-C), and fast glucose (FBG) also were explored. Finally, we further performed multivariable logistic regression analysis, restricted cubic spline (RCS) plots, and subgroup analysis to study the connection between the SII index and CVD. Our analysis included 17389 subjects from the NHANES database. A substantial positive association existed between SII, WV, and the TyG index. In addition, with the increase of the SII index, AIP showed a trend of decreasing first, then rising, and then decreasing. The SII index was inversely and linearly associated with triglyceride (TG), while positively and linearly associated with fast glucose (FBG). However, high-density lipoprotein cholesterol (HDL-C) had a tendency of first declining, then climbing, and finally falling with the rise in the SII index. After adjusting for potential confounders, compared with the lowest quartiles, the odds ratios with 95% confidence intervals for CVD across the quartiles were 0.914 (0.777, 1.074), 0.935 (0.779, 1.096), and 1.112 (0.956, 1.293) for SII index. The RCS plot showed an inverse U-shaped curve relationship between the SII index and CVD. Overall, this study found a strong correlation between a higher SII index and ePWV and the TyG index. Additionally, these cross-sectional data also revealed a U-shaped connection between the SII index and CVD.

Exogenous brassinosteroids increases tolerance to shading by altering stress responses in mung bean (Vigna radiata L.).

Plant steroidal hormones, brassinosteroids, play a key role in various developmental processes of plants and the adaptation to various environmental stresses. The purpose of this research was to evaluate the effect of exogenous 24-epibrassinolide (EBR) application on the morphology, photosynthetic characteristics, chlorophyll fluorescence parameters, photosynthetic enzymes activities, and endogenous hormone content of mung bean (Vigna radiata L.) leaves under shading stress environment. Two mung bean cultivars, Xilv 1 and Yulv 1, were tested. The results showed that all of the investigated data were significantly affected by shading stress; however, foliar application of EBR increased the net photosynthetic rate, transpiration rate, stomatal conductance, and decreased intercellular CO2 concentration of mung bean leaves under shading condition. Increased photosynthetic capacity in EBR-treated leaves was accompanied by improvement in higher photosynthetic enzymes activities. EBR-treated leaves exhibited more quantum yield of PSII electron transport and efficiency of energy capture than the control, which was mainly due to clearer leaf anatomical structure such as palisade tissues and spongy tissues, further resulting in altered plant morphological characteristics. Moreover, the treatment with EBL regulated the endogenous hormone content, including the decreased gibberellins and increased brassinolide, although to different levels. Combined with the morphological and physiological responses, we concluded that exogenous EBR treatment is beneficial to enhancing plant tolerance to shading stress and mitigating injure from weak light. The modifications of the physiological metabolism through EBR application may be a potential strategy to weaken shading stress in the future sustainable agricultural production.

Downregulation of miR-34c-5p alleviates chronic intermittent hypoxia-induced myocardial damage by targeting sirtuin 1.

Numerous microRNAs (miRs) are abnormally expressed in response to hypoxia-induced myocardial damage. Herein, miR-34c-5p as a potential pharmaco-target was investigated in a mouse model of chronic intermittent hypoxia (CIH)-induced myocardial damage. A mouse model of myocardial damage was established using CIH with 7% or 21% O2 alternating 60 s for 12 h/day, 21% O2 for 12 h/day. AntagomiR-34c-5p (20 nM/0.1 ml; once a week for 12 weeks) was used as a miR-34c-5p inhibitor in a mouse model with tail-vein injection. In another experiment, mice were administrated with Sirt1 activator SRT1720 (50 mg/kg/day) by intraperitoneal injection. Gene Expression Omnibus database showed a significant upregulation of miR-34c-5p expression in the ischemic myocardium of male mice. In CIH-stimulated mice, miR-34c-5p expression was also significantly increased compared with normal mice. Treatment of antagomiR-34c-5p significantly restrained CIH-triggered myocardial apoptosis. After administration of antagomiR-34c-5p or Sirt1 activator SRT1720, cardiac hypertrophy and oxidative stress were attenuated in CIH-stimulated mice. We also found sirtuin 1 (Sirt1) as a direct target of miR-34c-5p, which was able to mediate Sirt1 protein expression in cardiomyocytes. AntagomiR-34c-5p injection markedly elevated Sirt1 protein expression in CIH-stimulated mice. AntagomiR-34c-5p or Sirt1 activator SRT1720 administration exhibited the antioxidative activity and cardioprotective roles in CIH-stimulated mice.

Prevalence of cardiovascular diseases in relation to total bone mineral density and prevalent fractures: A population-based cross-sectional study.

BACKGROUND AND AIM: We aimed to explore the relationship between total BMD and prevalent fractures and the risk of CVD in a female population in the United States (US). METHODS AND RESULTS: We undertook cross-sectional analyses of a female population participating in the US National Health and Nutrition Examination Survey (NHANES). Generalized linear models and restricted cubic spline curves were used to examine the association between total BMD and CVD. Subgroup analyses were also undertaken. A total of 13,707 women were enrolled. The restricted cubic spline curve revealed a linear and negative association between total BMD and CVD. The inflection point for the curve was identified at total BMD = 1.085 g/cm2. A negative relationship between total BMD and the prevalence of individual CVDs (angina and stroke) was noted (P < 0.05). In subgroup analyses stratified by race/ethnicity, hypertension, diabetes mellitus, and physical activity, a negative association existed in women who were non-Hispanic White, without hypertension, without diabetes mellitus, and who never participated in physical activity, respectively. In subgroup analyses stratified by age, this association also differed based on age. In addition, participants without history of fracture had significant lower probability of experiencing individual CVDs (angina pectoris, heart attack, and stroke) compared with those with history of fracture. CONCLUSIONS: We revealed a reduced prevalence of CVD associated with increased total BMD in a female population in the US. CVD risk decreased significantly if total BMD >1.085 g/cm2. Additionally, fracture-free individuals had much reduced odds of developing CVD.

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression.

Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodelling and heart failure after MI, as well as the molecular mechanisms involved. Male C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilised to determine the fibrotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analysed by qRT-PCR, and protein expression changes were assessed by Western blotting. Our findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro. CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

[Safety Analysis of Perioperative Period in Non-Small Cell Lung Cancer Patients with Comorbid Pneumoconiosis].

Objective: To explore the surgical safety of patients with comorbid non-small cell lung cancer (NSCLC) and pneumoconiosis. Methods: In this study, the clinical data of 165 NSCLC patients treated at West China Fourth Hospital, Sichuan University from August 2019 to May 2021 were collected. Among them, 21 patients with comorbid pneumoconiosis were included in the pneumoconiosis group, and the remaining 144 patients were included in the general group. Radical resection for lung cancer was performed in both groups. The perioperative clinical data, including preoperative, intraoperative and postoperative indicators, of the two groups were compared and analyzed. Results: There was no perioperative death in either group. The proportions of male patients and patients with smoking history in the pneumoconiosis group were significantly higher than those in the general group ( P<0.05). The body mass index (BMI), pulmonary ventilation function and diffusion function in the pneumoconiosis group were significantly lower than those in the general group ( P<0.05). There was no significant difference in the median operative time and the median volume of intraoperative blood loss between the pneumoconiosis group and the general group. In the pneumoconiosis group, the proportion of advanced tumors (stage Ⅱ/Ⅲ), incidence of postoperative complications, median duration of postoperative intubation, and postoperative length of hospital stay were higher/longer than those of the normal group ( P<0.05). Compared with the general group, the incidences of lymph node calcification, dense pleural adhesion and surgical method alteration (switching from thoracoscopic surgery to open surgery or video-assisted thoracoscopy) were also significantly higher in the pneumoconiosis group ( P<0.05). Univariate analysis showed that age, smoking history, pneumoconiosis, pulmonary ventilation dysfunction, lymph node calcification, dense pleural adhesion and the volume of intraoperative blood loss were the risk factors for postoperative complications. Further multivariate regression analysis demonstrated that smoking history ( OR=1.37, P<0.05), lymph node calcification ( OR=2.36, P<0.05) and pulmonary ventilation dysfunction ( OR=5.21, P<0.05) were independent risk factors for postoperative complications. Conclusion: NSCLC patients with comorbid pneumoconiosis face relatively greater risks during the perioperative period when they undergo radical resection for lung cancer. Therefore, the close attention of surgeons and the nursing staff should be raised accordingly.

Lateral monolayer MoS2 homojunction devices prepared by nitrogen plasma doping.

Monolayer MoS2 possesses good electron mobility, structural flexibility and a direct band gap, enabling it to be a promising candidate for flexible and wearable optoelectronic devices. In this article, the lateral monolayer MoS2 homojunctions were prepared by a nitrogen plasma selective doping technique. The monolayer MoS2 thin films were synthesized by chemical vapor deposition and characterized by photoluminescence, atom force microscope and Raman spectroscopy. The electronic and photoelectric properties of the lateral pn and npn homojunctions were discussed. The results showed that the rectifying ratio of the pn homojunction diode is ∼103. As a photodetector of pn homojunction, the optical responsivity is up to 48.5 A W-1, the external quantum efficiency is 11 301%, the detectivity is ∼109 Jones and the response time is 20 ms with the laser of 532 nm and the reverse bias voltage of 10 V. As a bipolar junction transistor of npn homojunction, the amplification coefficient reached ∼102. A controllable plasma doping technique, compatible with traditional CMOS process, is utilized to realize the monolayer MoS2 based pn and npn homojunctions, and it propels the potential applications of 2D materials in the electronic, optoelectronic devices and circuits.

The association between manganese exposure with cardiovascular disease in older adults: NHANES 2011-2018.

The aim of the current study was to explore possible connections between manganese exposure and the prevalence of cardiovascular disease (CVD) in older US adults. The relationship between serum manganese levels and CVD was explored in 2427 people aged 60 years and over using data from the National Health and Nutrition Examination Survey (NHANES) (2011-2018). Multivariate linear regression analysis was performed to investigate associations between CVD risk factors and serum manganese concentration. The relationship between manganese levels and the prevalence of CVD was probed using generalized linear models and restricted cubic spline curves. Stratified subgroup analysis was subsequently constructed to rule out spurious interactions between variables and manganese. Compared with the lowest quartile, the modified odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the manganese quartiles were 0.71 (OR: 0.51; CI: 1.00), 0.70 (0.50, 0.99), and 0.49 (0.34, 0.72). In the full adjusted model, a prominent negative relationship was observed between serum manganese concentration and CVD. A restricted cubic spline curve was used to show a nonlinear negative relationship between manganese concentration and CVD. In summary, manganese levels are negatively correlated with the risk of CVD in a nation-wide study of older US adults.

A three-dimensional self-standing Mo2C/nitrogen-doped graphene aerogel: Enhancement hydrogen production from landfill leachate wastewater in MFCs-AEC coupled system.

A hydrothermal-annealing method was adopted to form nitrogen-doped graphene aerogel-supported molybdenum carbide (Mo2C/NGA) materials by using graphene oxide (GO), poly (propylene glycol) bis(2-aminopropyl ether) (D400 for short) and ammonium molybdate as precursors. The annealing temperature and GO/D400 wt ratio played an important role on the materials structure and electrocatalytic activity. When the annealing temperature reached to 800 °C, the Mo2C was formed as an active component and improved obviously the hydrogen evolution reaction (HER) activity. After introducing the appropriate amount of D400, the Mo2C/NGA material not only had a firm porous monolithic framework, but also presented an increasing HER activity. Further, the Mo2C/NGA-based microbial fuel cells-ammonia electrolysis cell (MFCs-AEC) coupled system was constructed and operated for higher hydrogen production. The coupled system produced hydrogen of 198 mL g-1Mo2C/NGA in simulated ammonia-rich wastewater. As using the actual landfill leachate wastewater as substrate, there was 79.2 mL g-1Mo2C/NGA of hydrogen production. All of these were attributed to the porous structure with an interconnected network and the nitrogen-doped structure of the NGA.

Effect of microRNA-135a on Cell Proliferation, Migration, Invasion, Apoptosis and Tumor Angiogenesis Through the IGF-1/PI3K/Akt Signaling Pathway in Non-Small Cell Lung Cancer.

OBJECTIVE: This study explored the ability of microRNA-135a (miR-135a) to influence cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer (NSCLC). METHODS: NSCLC tissues and adjacent normal tissues were collected from 138 NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-135a and IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 mRNA; western blotting was used to determine the expression levels of IGF-1, PI3K and Akt protein; and enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of VEGF, bFGF and IL-8 protein. Human NSCLC cell lines (A549, H460, and H1299) and the human bronchial epithelial cell line (HBE) were selected. A549 cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, IGF-1 siRNA and miR-135a inhibitors + IGF-1 siRNA groups. The following were performed: an MTT assay to assess cell proliferation, a scratch test to detect cell migration, a Transwell assay to measure cell invasion, and a flow cytometry to analyze cell apoptosis. RESULTS: The expression level of miR-135a was lower while those of IGF-1, PI3K and Akt mRNA were higher in NSCLC tissues than in the adjacent normal tissues. Dual-luciferase reporter assay indicated IGF-1 as a target of miR-135a. The in vitro results showed that compared with the blank group, cell proliferation, migration and invasion were suppressed, mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 were reduced, and cell apoptosis was enhanced in the miR-135a mimics and IGF-1 siRNA groups. Compared with the IGF-1 siRNA group, cells in the miR-135a inhibitors + IGF-1 siRNA group demonstrated increased cell proliferation, migration and invasion, elevated mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 and reduced cell apoptosis. CONCLUSION: These findings indicated that miR-135a promotes cell apoptosis and inhibits cell proliferation, migration, invasion and tumor angiogenesis by targeting IGF-1 gene through the IGF-1/PI3K/Akt signaling pathway in NSCLC.

The Discrepant and Similar Responses of Genome-Wide Transcriptional Profiles between Drought and Cold Stresses in Cassava.

Background: Cassava, an important tropical crop, has remarkable drought tolerance, but is very sensitive to cold. The growth, development, and root productivity of cassava are all adversely affected under cold and drought. Methods: To profile the transcriptional response to cold and drought stresses, cassava seedlings were respectively subjected to 0, 6, 24, and 48 h of cold stress and 0, 4, 6, and 10 days of drought stress. Their folded leaves, fully extended leaves, and roots were respectively investigated using RNA-seq. Results: Many genes specifically and commonly responsive to cold and drought were revealed: genes related to basic cellular metabolism, tetrapyrrole synthesis, and brassinosteroid metabolism exclusively responded to cold; genes related to abiotic stress and ethylene metabolism exclusively responded to drought; and genes related to cell wall, photosynthesis, and carbohydrate metabolism, DNA synthesis/chromatic structure, abscisic acid and salicylic acid metabolism, and calcium signaling commonly responded to both cold and drought. Discussion: Combined with cold- and/or drought-responsive transcription factors, the regulatory networks responding to cold and drought in cassava were constructed. All these findings will improve our understanding of the specific and common responses to cold and drought in cassava, and shed light on genetic improvement of cold and drought tolerance in cassava.

Endogenous small-noncoding RNAs and their roles in chilling response and stress acclimation in Cassava.

BACKGROUND: Small noncoding RNA (sncRNA), including microRNAs (miRNAs) and endogenous small-interfering RNAs (endo-siRNAs) are key gene regulators in eukaryotes, playing critical roles in plant development and stress tolerance. Trans-acting siRNAs (ta-siRNAs), which are secondary siRNAs triggered by miRNAs, and siRNAs from natural antisense transcripts (nat-siRNAs) are two well-studied classes of endo-siRNAs. RESULTS: In order to understand sncRNAs' roles in plant chilling response and stress acclimation, we performed a comprehensive study of miRNAs and endo-siRNAs in Cassava (Manihot esculenta), a major source of food for the world populations in tropical regions. Combining Next-Generation sequencing and computational and experimental analyses, we profiled and characterized sncRNA species and mRNA genes from the plants that experienced severe and moderate chilling stresses, that underwent further severe chilling stress after chilling acclimation at moderate stress, and that grew under the normal condition. We also included castor bean (Ricinus communis) in our study to understand conservation of sncRNAs. In addition to known miRNAs, we identified 32 (22 and 10) novel miRNAs as well as 47 (26 and 21) putative secondary siRNA-yielding and 8 (7 and 1) nat-siRNA-yielding candidate loci in Cassava and castor bean, respectively. Among the expressed sncRNAs, 114 miRNAs, 12 ta-siRNAs and 2 nat-siRNAs showed significant expression changes under chilling stresses. CONCLUSION: Systematic and computational analysis of microRNAome and experimental validation collectively showed that miRNAs, ta-siRNAs, and possibly nat-siRNAs play important roles in chilling response and chilling acclimation in Cassava by regulating stress-related pathways, e.g. Auxin signal transduction. The conservation of these sncRNA might shed lights on the role of sncRNA-mediated pathways affected by chilling stress and stress acclimation in Euphorbiaceous plants.

Chilling acclimation provides immunity to stress by altering regulatory networks and inducing genes with protective functions in cassava.

BACKGROUND: Stress acclimation is an effective mechanism that plants acquired for adaption to dynamic environment. Even though generally considered to be sensitive to low temperature, Cassava, a major tropical crop, can be tolerant to much lower temperature after chilling acclimation. Improvement to chilling resistance could be beneficial to breeding. However, the underlying mechanism and the effects of chilling acclimation on chilling tolerance remain largely unexplored. RESULTS: In order to understand the mechanism of chilling acclimation, we profiled and analyzed the transcriptome and microRNAome of Cassava, using high-throughput deep sequencing, across the normal condition, a moderate chilling stress (14°C), a harsh stress (4°C) after chilling acclimation (14°C), and a chilling shock from 24°C to 4°C. The results revealed that moderate stress and chilling shock triggered comparable degrees of transcriptional perturbation, and more importantly, about two thirds of differentially expressed genes reversed their expression from up-regulation to down-regulation or vice versa in response to hash stress after experiencing moderate stress. In addition, microRNAs played important roles in the process of this massive genetic circuitry rewiring. Furthermore, function analysis revealed that chilling acclimation helped the plant develop immunity to further harsh stress by exclusively inducing genes with function for nutrient reservation therefore providing protection, whereas chilling shock induced genes with function for viral reproduction therefore causing damage. CONCLUSIONS: Our study revealed, for the first time, the molecular basis of chilling acclimation, and showed potential regulation role of microRNA in chilling response and acclimation in Euphorbia.

[Relationship between intermedin and atrial fibrosis in patients of hypertension combined with atrial fibrillation].

This study was aimed to evaluate the relationship between the changes of plasma intermedin (IMD) and atrial fibrosis in hypertensive patients with atrial fibrillation. During the period from 2010 to 2011, appropriate 150 subjects of out-patients (female 50%, male 50%) were selected in West China Hospital, Sichuan University, and were divided into three groups: the hypertension-only group, the hypertension combined with paroxysmal atrial fibrillation group and the hypertension combined with persistent atrial fibrillation group. Firstly, we collected the Physical examination results and medical history records of the patients. We then performed ultrasound cardiogram and blood biochemical tests on the patients. We also detected the plasma IMD and transforming growth factor ß1 (TGF-ß1) using ELISA. The results showed that compared with the hypertensive group, the plasma level of IMD, TGF-ß1 and left atrium director (LAD) in the hypertensive combined with atrial fibrillation group were higher significantly. Compared with the paroxymal atrial fibrillation group, the levels of IMD, TGF-ß1 and LAD were higher significantly in persistent atrial fibrillation group. Analysis of correlation and partial correlation showed that IMD was positively correlated with TGF-p1 (r=0.51, P<0. 001), IMD was positively correlated with LAD(r=0.59, P< 0.001), and TGF-ß1 was positively correlated with LAD (r = 0.57, P < 0.001). The results suggest that IMD might suppress the pathophysiological process of atrial fibrillation.