Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration.

Angiotensin II (Ang II) plays a central role in vascular smooth muscle cell (VSMC) proliferation and migration, being key to regulate vascular function and promote vascular remodeling in cardiovascular diseases. We recently showed that miR-31-5p promoted oxidative stress in spontaneously hypertensive rats. In this study, we aim to investigate whether miR-31-5p and fibronectin type III domain-containing 5 (FNDC5) contribute to Ang II-induced VSMC proliferation and migration. Experiments were performed in primary VSMCs of wide-type (WT) and FNDC5-/- mice as well as the rat A7r5 cell line. We found that Ang II increased miR-31-5p level, reduced FNDC5 expression and stimulated VSMC proliferation and migration, which were aggravated by miR-31-5p mimic, and prevented by miR-31-5p inhibitor in VSMCs. The Ang II-induced VSMC proliferation were prevented by exogenous FNDC5 in both WT and FNDC5-/- mice, while the effects were more significant in FNDC5-/- mice. Furthermore, exogenous FNDC5 reversed the effects of miR-31-5p mimic on VSMC proliferation and migration in Ang II-treated VSMCs. Meanwhile, FNDC5 deficiency prevented the effects of miR-31-5p inhibitor on VSMC proliferation and migration in Ang II-treated VSMCs. In conclusion, our findings demonstrate that the miR-31-5p upregulation and the following FNDC5 downregulation contribute to Ang II-induced VSMC proliferation and migration.

[Therapeutic effect of Shengjiang Powder on experimental autoimmune encephalomyelitis mice through IL-6/JAK2/STAT3 signaling pathway:based on HPLC].

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.

Impact of Selective Renal Afferent Denervation on Oxidative Stress and Vascular Remodeling in Spontaneously Hypertensive Rats.

Oxidative stress and sustained sympathetic over-activity contribute to the pathogenesis of hypertension. Catheter-based renal denervation has been used as a strategy for treatment of resistant hypertension, which interrupts both afferent and efferent renal fibers. However, it is unknown whether selective renal afferent denervation (RAD) may play beneficial roles in attenuating oxidative stress and sympathetic activity in hypertension. This study investigated the impact of selective RAD on hypertension and vascular remodeling. Nine-week-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were subjected to selective renal afferent denervation (RAD) with 33 mM of capsaicin for 15 min. Treatment with the vehicle of capsaicin was used as a control. The selective denervation was confirmed by the reduced calcitonin gene-related peptide expression and the undamaged renal sympathetic nerve activity response to the stimulation of adipose white tissue. Selective RAD reduced plasma norepinephrine levels, improved heart rate variability (HRV) and attenuated hypertension in SHR.It reduced NADPH oxidase (NOX) expression and activity, and superoxide production in the hypothalamic paraventricular nucleus (PVN), aorta and mesenteric artery of SHR. Moreover, the selective RAD attenuated the vascular remodeling of the aorta and mesenteric artery of SHR. These results indicate that selective removal of renal afferents attenuates sympathetic activity, oxidative stress, vascular remodeling and hypertension in SHR. The attenuated superoxide signaling in the PVN is involved in the attenuation of sympathetic activity in SHR, and the reduced sympathetic activity at least partially contributes to the attenuation of vascular oxidative stress and remodeling in the arteries of hypertensive rats.

Salusin-ß in Intermediate Dorsal Motor Nucleus of the Vagus Regulates Sympathetic-Parasympathetic Balance and Blood Pressure.

The dorsal motor nucleus of the vagus (DMV) is known to control vagal activity. It is unknown whether the DMV regulates sympathetic activity and whether salusin-ß in the DMV contributes to autonomic nervous activity. We investigated the roles of salusin-ß in DMV in regulating sympathetic-parasympathetic balance and its underline mechanisms. Microinjections were carried out in the DMV and hypothalamic paraventricular nucleus (PVN) in male adult anesthetized rats. Renal sympathetic nerve activity (RSNA), blood pressure and heart rate were recorded. Immunohistochemistry for salusin-ß and reactive oxidative species (ROS) production in the DMV were examined. Salusin-ß was expressed in the intermediate DMV (iDMV). Salusin-ß in the iDMV not only inhibited RSNA but also enhanced vagal activity and thereby reduced blood pressure and heart rate. The roles of salusin-ß in causing vagal activation were mediated by NAD(P)H oxidase-dependent superoxide anion production in the iDMV. The roles of salusin-ß in inhibiting RSNA were mediated by not only the NAD(P)H oxidase-originated superoxide anion production in the iDMV but also the γ-aminobutyric acid (GABA)A receptor activation in PVN. Moreover, endogenous salusin-ß and ROS production in the iDMV play a tonic role in inhibiting RSNA. These results indicate that salusin-ß in the iDMV inhibits sympathetic activity and enhances vagal activity, and thereby reduces blood pressure and heart rate, which are mediated by NAD(P)H oxidase-dependent ROS production in the iDMV. Moreover, GABAA receptor in the PVN mediates the effect of salusin-ß on sympathetic inhibition. Endogenous salusin-ß and ROS production in the iDMV play a tonic role in inhibiting sympathetic activity.

miR-31-5p Promotes Oxidative Stress and Vascular Smooth Muscle Cell Migration in Spontaneously Hypertensive Rats via Inhibiting FNDC5 Expression.

Oxidative stress and the migration of vascular smooth muscle cells (VSMCs) are important for vascular remodeling in a variety of vascular diseases. miR-31-5p promotes cell migration in colorectal cancer cells but inhibits cell migration in renal cell carcinoma. However, whether miR-31-5p is involved in oxidative stress and VSMC migration remains unknown. This study shows the crucial roles of miR-31-5p in oxidative stress and VSMC migration, as well as underlying mechanisms. Experiments were carried out in primary VSMCs from aortic media of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), as well as the A7r5 cell line. Oxidative stress was assessed by NADPH oxidase (NOX) expression, NOX activity, and reactive oxygen species (ROS) production. Cell migration was evaluated with a Boyden chamber assay and a wound healing assay. The miR-31-5p mimic and inhibitor promoted and attenuated oxidative stress and cell migration in the VSMCs of SHR, respectively. A dual-luciferase reporter assay indicated that miR-31-5p targeted the 3'UTR domain of FNDC5. The miR-31-5p level was raised and FNDC5 expression was reduced in the VSMCs of SHR compared with those of WKY. The miR-31-5p mimic reduced FNDC5 expression in the A7r5 cells and the VSMCs of both WKY and SHR, while the miR-31-5p inhibitor only increased FNDC5 expression in the VSMCs of SHR. Exogenous FNDC5 attenuated not only the oxidative stress and VSMC migration in SHR but also the roles of the miR-31-5p mimic in inducing oxidative stress and VSMC migration. These results indicate that miR-31-5p promotes oxidative stress and VSMC migration in SHR via inhibiting FNDC5 expression. The increased miR-31-5p and reduced FNDC5 in the VSMCs of SHR contribute to enhanced oxidative stress and cell migration.

A review of psychological interventions for internet addiction.

Internet addiction (IA) may constitute a widespread and serious mental problem. Previous reviews have not fully considered potential factors that may contribute to therapeutic outcomes or predict behavioral changes. Such information is relevant to understand the active ingredients of interventions and to develop more efficacious treatments that target features of IA. This systematic review was designed to relate theories of IA to treatments, describe studies of psychotherapies for IA, and propose a model of addiction and interventions based on extant studies. A computer database search of PubMed, PsychINFO, ScienceDirect, China National Knowledge Infrastructure, and Google Scholar was conducted to identify all available research evidence on psychological treatments for IA (N = 31 studies). Among these psychological interventions, the targeted reduction of addiction-related impulsivity and craving, improvement of cognitive maladjustment, and alleviation of family problems have been investigated in IA interventions. The targeted domains and intervention methods are not mutually exclusive, and further research is needed to demonstrate the effective components and mechanisms of action for treatments of IA. Such research will help generate more efficacious evidence-based interventions.

Extracellular vesicle-mediated miR135a-5p transfer in hypertensive rat contributes to vascular smooth muscle cell proliferation via targeting FNDC5.

Background Extracellular vesicles (EVs) from vascular adventitial fibroblasts (AFs) contribute to the proliferation of vascular smooth muscle cells (VSMCs) and vascular remodeling in spontaneously hypertensive rat (SHR). This study shows the crucial roles of EVs-mediated miR135a-5p transfer in VSMC proliferation and the underlying mechanisms in hypertension. Methods AFs and VSMCs were obtained from the aorta of Wistar-Kyoto rat (WKY) and SHR. EVs were isolated from the culture of AFs with ultracentrifugation method. Results MiR135a-5p level in SHR-EVs was significantly increased. MiR135a-5p inhibitor prevented the SHR-EVs-induced VSMC proliferation. Fibronectin type III domain containing 5 (FNDC5) was a target gene of miR135a-5p. FNDC5 level was lower in VSMCs of SHR. MiR135a-5p inhibitor not only increased FNDC5 expression, but reversed the SHR-EVs-induced FNDC5 downregulation in VSMCs of SHR. MiR135a-5p mimic inhibited FNDC5 expression, but failed to promote the SHR-EVs-induced FNDC5 downregulation in VSMCs of SHR. Exogenous FNDC5 prevented the SHR-EVs-induced VSMC proliferation of both WKY and SHR. Knockdown of miR135a-5p in fibroblasts completely prevented the upregulation of miR135a-5p in the EVs. The SHR-EVs from the miR135a-5p knockdown-treated fibroblasts lost their roles in inhibiting FNDC5 expression and promoting proliferation in VSMCs of both WKY and SHR. Conclusions Increased miR135a-5p in the SHR-EVs promoted VSMC proliferation of WKY and SHR via inhibiting FNDC5 expression. MiR135a-5p and FNDC5 are crucial targets for intervention of VSMC proliferation in hypertension.

Resting-state connectome-based support-vector-machine predictive modeling of internet gaming disorder.

Internet gaming disorder (IGD), a worldwide mental health issue, has been widely studied using neuroimaging techniques during the last decade. Although dysfunctions in resting-state functional connectivity have been reported in IGD, mapping relationships from abnormal connectivity patterns to behavioral measures have not been fully investigated. Connectome-based predictive modeling (CPM)-a recently developed machine-learning approach-has been used to examine potential neural mechanisms in addictions and other psychiatric disorders. To identify the resting-state connections associated with IGD, we modified the CPM approach by replacing its core learning algorithm with a support vector machine. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 72 individuals with IGD and 41 healthy comparison participants. The modified CPM was conducted with respect to classification and regression. A comparison of whole-brain and network-based analyses showed that the default-mode network (DMN) is the most informative network in predicting IGD both in classification (individual identification accuracy = 78.76%) and regression (correspondence between predicted and actual psychometric scale score: r = 0.44, P < 0.001). To facilitate the characterization of the aberrant resting-state activity in the DMN, the identified networks have been mapped into a three-subsystem division of the DMN. Results suggest that individual differences in DMN function at rest could advance our understanding of IGD and variability in disorder etiology and intervention outcomes.

Efficacy of single-session transcranial direct current stimulation on addiction-related inhibitory control and craving: a randomized trial in males with Internet gaming disorder.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.

A role for the right dorsolateral prefrontal cortex in enhancing regulation of both craving and negative emotions in internet gaming disorder: A randomized trial.

Reward-seeking and relief from negative emotions are two central motivational drives underlying addictions. Impaired executive control over craving and negative emotions contributes to compulsive addictive behaviors. Neuroimaging evidence has implicated the prefrontal cortex (PFC) in regulating craving or emotions. This study aims at examining whether anodal transcranial direct current stimulation (tDCS) over a specific region of the PFC would enhance both regulation processes. Thirty-three men with internet gaming disorder received active (1.5 mA for 20 minutes) and sham tDCS over the right dorsolateral PFC (dlPFC) one week apart in a randomized order. During each stimulation session, participants regulated craving for gaming during a regulation of craving (ROC) task and negative emotions during an emotion regulation (ER) task using cognitive reappraisal. Subjective ratings of craving and negative emotions and skin conductance responses (SCRs) were recorded. For both craving and negative emotions, tDCS of the right dlPFC facilitated downregulation and upregulation: active relative to sham tDCS decreased ratings (ROC: 95% CI of difference -1.38 to -0.56, p < 0.001; ER: -1.65 to -0.70, p < 0.001) and/or SCRs (ROC: -1.99 to -0.41 µs, p = 0.004) for downregulation, and increased ratings (ROC: 0.24 to 0.82, p = 0.001; ER: 0.26 to 0.72, p < 0.001) for upregulation. These findings provide the first experimental evidence confirming that tDCS of the right dlPFC enhances both craving- and negative-emotion-regulation. This suggests a promising approach for concurrently enhancing executive control over two central motivational drives underlying addictions.

MiR155-5p Inhibits Cell Migration and Oxidative Stress in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats.

Migration of vascular smooth muscle cells (VSMCs) is essential for vascular reconstruction in hypertension and several vascular diseases. Our recent study showed that extracellular vesicles derived from vascular adventitial fibroblasts of normal rats inhibited VSMC proliferation by delivering miR155-5p to VSMCs. It is unknown whether miR155-5p inhibits cell migration and oxidative stress in VSMCs of spontaneously hypertensive rats (SHR) and in angiotensin II (Ang II)-treated VSMCs. The purpose of this study was to determine the role of miR155-5p in VSMC migration and its underlying mechanisms. Primary VSMCs were isolated from the aortic media of Wistar-Kyoto rats (WKY) and SHR. Wound healing assay and Boyden chamber assay were used to evaluate VSMC migration. A miR155-5p mimic inhibited, and a miR155-5p inhibitor promoted the migration of VSMC of SHR but had no significant effect on the migration of VSMC of WKY. The miR155-5p mimic inhibited angiotensin-converting enzyme (ACE) mRNA and protein expression in VSMCs. It also reduced superoxide anion production, NAD(P)H oxidase (NOX) activity, as well as NOX2, interleukin-1ß (IL-1ß), and tumor necrosis factor α (TNF-α) expression levels in VSMCs of SHR but not in VSMCs of WKY rats. Overexpression of miR155-5p inhibited VSMC migration and superoxide anion and IL-1ß production in VSMCs of SHR but had no impact on exogenous Ang II-induced VSMC migration and on superoxide anion and IL-1ß production in WKY rats and SHR. These results indicate that miR155-5p inhibits VSMC migration in SHR by suppressing ACE expression and its downstream production of Ang II, superoxide anion, and inflammatory factors. However, miR155-5p had no effects on exogenous Ang II-induced VSMC migration.

Impaired regulation of both addiction-related and primary rewards in individuals with internet gaming disorder.

Poor executive function (EF) has been implicated in addictions. Among "hot" EFs (i.e., those involving motivations and emotions), poor regulation of craving has been proposed to underlie addiction development in substance-use disorders (SUDs), making such regulation a potential treatment target. However, regulation of craving remains poorly understood in internet gaming disorder (IGD). Additionally, prior studies of cold EFs (e.g., inhibition and cognitive flexibility under neutral conditions) in IGD have provided mixed results and mostly included only male subjects. We addressed these issues by instructing 54 participants (26 with IGD including males and females, and 28 control subjects) to perform a regulation-of-craving (ROC) task and a Stroop color-word-interference task. Compared to control subjects, individuals with IGD revealed deficits in regulation for both gaming- and food-related craving, but no differences in Stroop performance. The current study provides initial empirical support suggesting regulation impairments for both addiction-related and primary rewards among individuals with IGD. The findings are consistent with studies in SUDs, suggesting that impaired regulation of craving may be a relevant transdiagnostic construct across SUDs and behavioral addictions. The findings suggest targeting regulation of "hot" processes should be considered in IGD treatment development.

The Role of Follow-up Evaluation in the Diagnostic Algorithm of Idiopathic Interstitial Pneumonia: A Retrospective Study.

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.

Aggregation-induced emission of luminol: a novel strategy for fluorescence ratiometric detection of ALP and As(v) with high sensitivity and selectivity.

A novel dual-emission fluorescence ratiometric probe of luminol-Tb-GMP CPNPs for highly sensitive and selective detection of ALP and As(v) has been constructed based on the stimulus responsivity of luminol. The introduction of luminol as a ligand for Tb3+, combined with GMP, leads to a sensor which is more robust, sensitive, and efficient.

Separation of chiral compounds using magnetic molecularly imprinted polymer nanoparticles as stationary phase by microchip capillary electrochromatography.

In this work, a simple and rapid approach was developed for separation and detection of chiral compounds based on a magnetic molecularly imprinted polymer modified poly(dimethylsiloxane) (PDMS) microchip coupled with electrochemical detection. Molecularly imprinted polymers were prepared employing Fe3 O4 nanoparticles (NPs) as the supporting substrate and norepinephrine as the functional monomer in the presence of template molecule in a weak alkaline solution. After extracting the embedded template molecules, Fe3 O4 @polynorepinephrine NPs (MIP-Fe3 O4 @PNE NPs) showed specific molecular recognition selectivity and high affinity towards the template molecule, which were then used as stationary phase of microchip capillary electrochromatography for chiral compounds separation. Mandelic acid and histidine enantiomers were used as model compounds to test the chiral stationary phase. By using R-mandelic acid as the template molecule, mandelic acid enantiomer was effectively separated and detected on the MIP-Fe3 O4 @PNE NPs modified PDMS microchip. Moreover, the successful separation of histidine enantiomers on the MIP-Fe3 O4 @PNE NPs modified microchip using L-histidine as template molecule was also achieved.

[Protective effect of Ginkgo biloba extract on paracetamol-induced acute hepatic injury in mice].

OBJECTIVE: To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism. METHODS: Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg-1)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1. RESULTS: Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(P<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(P<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(P<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(P<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). The high-dose of GBE possessed the most obvious treatment effect among them. CONCLUSIONS: GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.

One-step preparation and application of mussel-inspired poly(norepinephrine)-coated polydimethylsiloxane microchip for separation of chiral compounds.

In this paper, using the self-polymerization of norepinephrine (NE) and its favorable film-forming property, a simple and green preparation approach was developed to modify a PDMS channel for enantioseparation of chiral compounds. After the PDMS microchip was filled with NE solution, poly(norepinephrine) (PNE) film was gradually formed and deposited on the inner wall of microchannel as permanent coating via the oxidation of NE by the oxygen dissolved in the solution. Due to possessing plentiful catechol and amine functional groups, the PNE-coated PDMS microchip exhibited much better wettability, more stable and suppressed EOF, and less nonspecific adsorption. The water contact angle and EOF of PNE-coated PDMS substrate were measured to be 13° and 1.68 × 10(-4) cm(2) V(-1) s(-1) , compared to those of 108° and 2.24 × 10(-4) cm(2) V(-1) s(-1) from the untreated one, respectively. Different kinds of chiral compounds, such as amino acid enantiomer, drug enantiomer, and peptide enantiomer were efficiently separated utilizing a separation length of 37 mm coupled with in-column amperometric detection on the PNE-coated PDMS microchips. This facile mussel-inspired PNE-based microchip system exhibited strong recognition ability, high-performance, admirable reproducibility, and stability, which may have potential use in the complex biological analysis.

Diagnostic yield and postoperative mortality associated with surgical lung biopsy for evaluation of interstitial lung diseases: A systematic review and meta-analysis.

OBJECTIVES: Surgical lung biopsy plays an important role in providing pathologic results, thus complementing the diagnostic rationale for suspected interstitial lung diseases. We performed a systematic review and meta-analysis regarding the diagnostic yield and postoperative mortality rate of surgical lung biopsy in patients with suspected interstitial lung diseases because of the wide variation in previously reported effectiveness and safety concerns. METHODS: We systematically searched for published studies between 2000 and 2014 evaluating surgical lung biopsy in the diagnosis of interstitial lung diseases. Subgroup analysis was performed to identify the possible source of study heterogeneity. RESULTS: Twenty-three studies contributed 2148 patients for the analysis. The median diagnostic yield was 95% (range, 42%-100%), with idiopathic pulmonary fibrosis as the most frequent diagnosis (618, 33.5%). Surgical lung biopsy was mainly guided by high-resolution computed tomography manifestations. Biopsy site, biopsy number, and the surgical lung biopsy method may not be associated with the diagnostic accuracy. The pooled postoperative mortality rate for included studies was 3.6% (95% confidence interval, 2.1-5.5), with significant heterogeneity observed. Subgroup analysis revealed that exclusion criteria based on immunocompromised status, mechanical ventilation, and severe respiratory dysfunction (diffusing capacity of lung for carbon monoxide <35% or forced vital capacity <55% predicted), but not surgical lung biopsy technique or underlying interstitial lung disease subtype, may be possible sources of heterogeneity. CONCLUSIONS: We demonstrated a satisfactory diagnostic performance with a favorable safety profile of surgical lung biopsy in the diagnosis of suspected interstitial lung diseases. Surgical lung biopsy is especially recommended in patients with clinical information indicative but atypical of idiopathic pulmonary fibrosis, whereas the benefit of surgical lung biopsy should be carefully balanced against the risk for patients with immunocompromised status, mechanical ventilation dependence, or severe respiratory dysfunction.

Witness of unsatisfiability for a random 3-satisfiability formula.

The random 3-satisfiability (3-SAT) problem is in the unsatisfiable (UNSAT) phase when the clause density α exceeds a critical value α(s)≈4.267. Rigorously proving the unsatisfiability of a given large 3-SAT instance is, however, extremely difficult. In this paper we apply the mean-field theory of statistical physics to the unsatisfiability problem, and show that a reduction to 3-XORSAT, which permits the construction of a specific type of UNSAT witnesses (Feige-Kim-Ofek witnesses), is possible when the clause density α>19. We then construct Feige-Kim-Ofek witnesses for single 3-SAT instances through a simple random sampling algorithm and a focused local search algorithm. The random sampling algorithm works only when α scales at least linearly with the variable number N, but the focused local search algorithm works for clause density α>cN(b) with b≈0.59 and prefactor c≈8. The exponent b can be further decreased by enlarging the single parameter S of the focused local search algorithm.