Microglia, circadian rhythm and lifestyle factors.

Microglia, a vital homeostasis-keeper of the central nervous system, perform critical functions such as synaptic pruning, clearance of cellular debris, and participation in neuroinflammatory processes. Recent research has shown that microglia exhibit strong circadian rhythms that not only actively regulate their own immune activity, but also affect neuronal function. Disruptions of the circadian clock have been linked to a higher risk of developing a variety of diseases. In this article we will provide an overview of how lifestyle factors impact microglial function, with a focus on disruptions caused by irregular sleep-wake patterns, reduced physical activity, and eating at the wrong time-of-day. We will also discuss the potential connection between these lifestyle factors, disrupted circadian rhythms, and the role of microglia in keeping brain health.

Microglial phagolysosome dysfunction and altered neural communication amplify phenotypic severity in Prader-Willi Syndrome with larger deletion.

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype.

Highly dispersed Cu-Cu2O-CeOx interfaces on reduced graphene oxide for CO2 electroreduction to C2+ products.

The Cu0-Cu+ interfaces play a key role in the electrochemical CO2 reduction reaction (CO2RR) to produce multi-carbon products (C2+), however, it is difficult for Cu+ to exist stably under reducing conditions. Herein, we construct highly dispersed and stable Cu-Cu2O-CeOx interface on reduced graphene oxide (rGO) for CO2 electroreduction to C2+ products. During the synthesis process, utilizing strong electrostatic interactions, the complex ions of Cu2+ and Ce3+ are uniformly adsorbed on the surface of graphene oxide. Then, under the solvothermal reaction of ethylene glycol and thiourea, the two metal complex ions are converted into highly dispersed and ultrafine Cu2S-CeOx nanocomposites on rGO. Interestingly, CeOx and thiourea synergistically regulate the generation of only Cu+. Under the CO2RR process, the reconstruction of Cu2S promotes the formation of Cu0 and Cu2O species. CeOx stabilizes partial Cu+ species and promotes the formation of Cu-Cu2O-CeOx composite interface. With the help of synergistic effect of Cu0, Cu+ and CeOx, the optimized reaction interface achieves the Faradaic efficiency (FE) of 74.5 % for C2+ products with the current density of 230 mA cm-2 at -0.9 V versus the reversible hydrogen electrode. In situ attenuate total reflectance-infrared absorption spectroscopy (ATR-IRAS) spectra show that the composite interfaces promote the adsorption and activation of H2O and CO2, improve the surface coverage of CO intermediates (*CO), and thus accelerate the CC coupling process.

An orexin-receptor-2-mediated heart-brain axis in cardiac pain.

Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR. We further showed that OX2R agonism could partially rescue acute myocardial infarction by reducing sympathetic overactivation. Our data indicate that epicardial application of OX2R agonist exerts a cardioprotective effect by attenuating CSAR. This OX2R-mediated heart-brain axis may provide therapeutic targets for acute cardiovascular diseases.

Preparation and characterization of egg white protein film incorporated with epigallocatechin gallate and its application on pork preservation.

The aim of this study was to develop the composite films with antioxidant and biodegradable activity based on egg white protein (EWP) and epigallocatechin gallate (EGCG). Water susceptibility, light transmittance, microstructure and antioxidant properties of the composite films without and with EGCG were fully characterized. It was noted that the addition of EGCG might decrease the moisture content, water solubility and swelling capacity. SEM micrographs revealed that discontinuous blocks and rough surfaces were caused by increasing concentration of EGCG, whereas compact and homogeneous particles appeared when the concentration of EGCG reached to 80 µmol/L. Moreover, the biodegradability of the composite films was demonstrated by the soil degradation properties that they can be almost completely degraded within ten days. Experimental results on the application in chilled fresh pork showed that the EWP-based films could play an antioxidant role when incorporated with EGCG, indicating their great potential for food packaging.

Ultrafine NiFe-Based (Oxy)Hydroxide Nanosheet Arrays with Rich Edge Planes and Superhydrophilic-Superaerophobic Characteristics for Oxygen Evolution Reaction.

NiFe-based (oxy)hydroxides are the benchmark catalysts for the oxygen evolution reaction (OER) in alkaline medium, however, it is still challenging to control their structures and compositions. Herein, molybdates (NiFe(MoO4 )x ) are applied as unique precursors to synthesize ultrafine Mo modified NiFeOx Hy (oxy)hydroxide nanosheet arrays. The electrochemical activation process enables the molybdate ions (MoO4 2- ) in the precursors gradually dissolve, and at the same time, hydroxide ions (OH- ) in the electrolyte diffuse into the precursor and react with Ni2+ and Fe3+ ions in confined space to produce ultrafine NiFeOx Hy (oxy)hydroxides nanosheets (<10 nm), which are densely arranged into microporous arrays and maintain the rod-like morphology of the precursor. Such dense ultrafine nanosheet arrays produce rich edge planes on the surface of NiFeOx Hy (oxy)hydroxides to expose more active sites. More importantly, the capillary phenomenon of microporous structures and hydrophilic hydroxyl groups induce the superhydrophilicity and the rough surface produces the superaerophobic characteristic for bubbles. With these advantages, the optimized catalyst exhibits excellent performance for OER, with a small overpotential of 182 mV at 10 mA cm-2 and long-term stability (200 h) at 200 mA cm-2 . Theoretical calculations show that the modification of Mo enhances the electron delocalization and optimizes the adsorption of intermediates.

Decreased Expression of Urethral Caveolin-1, -2, and -3 in the Rat Model of Overactive Bladder: Potential Mediator of Functional Interaction of Urethra and Urinary Bladder.

PURPOSE: To investigate the effect of detrusor overactivity (DO) on the urethral expression of caveolin (CAV)-1, -2, and -3 of urethra in an animal model of cyclophosphamide (CYP)-induced cystitis rat. METHODS: Female Sprague-Dawley rats were divided into the control group (n=20) and the cystitis group (n=20). Cystitis was induced by intraperitoneal injection of CYP (200 mg/kg). An urodynamic study was done 3 days after the CYP injection to measure functional change of the urinary bladder and urethra. Cellular localization and expression of CAV-1, -2, and -3 in the rat urethra were determined by immunohistochemistry (IHC) and Western blot. RESULTS: Urodynamic experiments demonstrated a decreased contraction interval in the cystitis group compared to the control (3.9±1.0 minutes vs. 6.6±1.2 minutes, P<0.05). Conversely, contraction pressure increased significantly in the cystitis group compared to the control (22.4±0.7 mmHg vs. 11.5±0.4 mmHg, P<0.05). The urethral pressure was decreased in the cystitis group compared to the control (4.05 ±2.5 mmHg vs. 5.8 ±2.8 mmHg, P <0.05). The IHC and Western blot data showed that CAV-1, -2, and -3 expression decreased significantly in the cystitis group compared control group (P<0.05). CONCLUSION: The decreased urethral CAV-1, -2, and -3 in the DO rats suggests that CAVs might be related with the functional change of urethra in association with DO of urinay bladder.

Monolayer NaW2O2Br6: a gate tunable near-infrared hyperbolic plasmonic surface.

Electrically tunable hyperbolic polaritons in two dimensional (2D) materials can offer unexplored opportunities in integrating photonics and nano-optoelectronics into a single chip. Here, we suggest that monolayer NaW2O2Br6 can host electrically tunable hyperbolic plasmon polaritons for infrared light via first-principles calculations. 2D monolayer NaW2O2Br6 exhibits an extremely anisotropic metallic property: conducting for one direction but almost insulating for the other direction, which could be considered as a 2D analogue of metal/dielectric multilayers, a typical structure for hyperbolic metamaterials. More interestingly, we also demonstrate that the hyperbolic properties in the near-infrared range, including the hyperbolic windows, figure of merit, and propagation directions of plasmon beams, can be effectively modulated by carrier doping at the order of 1013 cm-2, which even can be accessed by solid-gated field effect transistors. Thus, it is anticipated that monolayer NaW2O2Br6 has a great potential in constructing field programmable polariton nanodevices for emerging and diverse photonic applications.

Orexin receptor type 2 agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation.

Orexin signaling has been associated with energy expenditure and brown adipose tissue (BAT) function. However, conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis. In this study, we show that a specific orexin receptor type 2 (OX2R) agonist [Ala11, D-Leu15]-OxB (OB-Ala) inhibited intrascapular brown adipose tissue (iBAT) thermogenesis by reducing sympathetic output to iBAT. This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself. Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus. Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop. Our study uncovers a novel primary action site of orexin in the regulation of energy balance.

Specific Silencing of Microglial Gene Expression in the Rat Brain by Nanoparticle-Based Small Interfering RNA Delivery.

Microglia are the major innate immune cells in the brain and are essential for maintaining homeostasis in a neuronal microenvironment. Currently, a genetic tool to modify microglial gene expression in specific brain regions is not available. In this report, we introduce a tailor-designed method that uses lipid and polymer hybridized nanoparticles (LPNPs) for the local delivery of small interfering RNAs (siRNAs), allowing the silencing of specific microglial genes in the hypothalamus. Our physical characterization proved that this LPNP-siRNA was uniform and stable. We demonstrated that, due to their natural phagocytic behavior, microglial cells are the dominant cell type taking up these LPNPs in the hypothalamus of rats. We then tested the silencing efficiency of LPNPs carrying a cluster of differentiation molecule 11b (CD11b) or Toll-like receptor 4 (TLR4) siRNA using different in vivo and in vitro approaches. In cultured microglial cells treated with LPNP-CD11b siRNA or LPNP-TLR4 siRNA, we found a silencing efficiency at protein expression levels of 65 or 77%, respectively. In line with this finding, immunohistochemistry and western blotting results from in vivo experiments showed that LPNP-CD11b siRNA significantly inhibited microglial CD11b protein expression in the hypothalamus. Furthermore, following lipopolysaccharide (LPS) stimulation of cultured microglial cells, gene expression of the TLR4 downstream signaling component myeloid differentiation factor 88 and its associated cytokines was significantly inhibited in LPNP-TLR4 siRNA-treated microglial cells compared with cells treated with LPNP-scrambled siRNA. Finally, after LPNP-TLR4 siRNA injection into the rat hypothalamus, we observed a significant reduction in microglial activation in response to LPS compared with the control rats injected with LPNP-scrambled siRNA. Our results indicate that LPNP-siRNA is a promising tool to manipulate microglial activity locally in the brain and may serve as a prophylactic approach to prevent microglial dysfunction-associated diseases.

Intestinal expression of ACE2 in mice with high-fat diet-induced obesity and neonates exposed to maternal high-fat diet.

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) is threatening global health and is especially pronounced in patients with chronic metabolic syndromes. Meanwhile, a significant proportion of patients present with digestive symptoms since angiotensin-converting enzyme 2 (ACE2), which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the intestine. The aim of this study was to evaluate the effects of a high-fat diet (HFD) and a maternal HFD on the intestinal ACE2 levels in adults and neonates. METHODS: We examined intestinal ACE2 protein levels in mice with diet-induced obesity (DIO) and neonatal mice exposed to a maternal HFD. We also investigated Ace2 mRNA expression in intestinal macrophages. RESULTS: Intestinal ACE2 protein levels were increased in DIO mice but decreased in offspring exposed to a maternal HFD compared with chow-fed controls. Ace2 mRNA expression in intestinal macrophages was detected and downregulated in DIO mice. Additionally, higher intestinal ACE2 protein levels were observed in neonates than in adult mice. CONCLUSIONS: The influence of an HFD on intestinal ACE2 protein levels is opposite in adults and neonates. Macrophages might also be involved in SARS-CoV-2 intestinal infection. These findings provide some clues for the outcomes of patients with COVID-19 with metabolic syndromes.

Lung Cancer and Granuloma Identification Using a Deep Learning Model to Extract 3-Dimensional Radiomics Features in CT Imaging.

BACKGROUND: We aimed to evaluate a deep learning (DL) model combining perinodular and intranodular radiomics features and clinical features for preoperative differentiation of solitary granuloma nodules (GNs) from solid lung cancer nodules in patients with spiculation, lobulation, or pleural indentation on CT. PATIENTS AND METHODS: We retrospectively recruited 915 patients with solitary solid pulmonary nodules and suspicious signs of malignancy. Data including clinical characteristics and subjective CT findings were obtained. A 3-dimensional U-Net-based DL model was used for tumor segmentation and extraction of 3-dimensional radiomics features. We used the Maximum Relevance and Minimum Redundancy (mRMR) algorithm and the eXtreme Gradient Boosting (XGBoost) algorithm to select the intranodular, perinodular, and gross nodular radiomics features. We propose a medical image DL (IDL) model, a clinical image DL (CIDL) model, a radiomics DL (RDL) model, and a clinical image radiomics DL (CIRDL) model to preoperatively differentiate GNs from solid lung cancer. Five-fold cross-validation was used to select and evaluate the models. The prediction performance of the models was evaluated using receiver operating characteristic and calibration curves. RESULTS: The CIRDL model achieved the best performance in differentiating between GNs and solid lung cancer (area under the curve [AUC] = 0.9069), which was significantly higher compared with the IDL (AUC = 0.8322), CIDL (AUC = 0.8652), intra-RDL (AUC = 0.8583), peri-RDL (AUC = 0.8259), and gross-RDL (AUC = 0.8705) models. CONCLUSION: The proposed CIRDL model is a noninvasive diagnostic tool to differentiate between granuloma nodules and solid lung cancer nodules and reduce the need for invasive diagnostic and surgical procedures.

Changes in stability and in vitro digestion of egg-protein stabilized emulsions and ß-carotene gels in the presence of sodium tripolyphosphate.

BACKGROUND: Egg proteins are effective emulsifiers and gelators in food systems. However, the physicochemical stability and control release properties of egg-protein stabilized emulsions and gels need to be further improved. The potential of sodium tripolyphosphate (St) to improve the functionality of egg proteins was evaluated. RESULTS: The emulsions with St had smaller particle sizes and higher zeta potential, leading to better physical stability. Furthermore, the oxidation stability increased with increasing St contents, possibly due to its metal chelating capacity and the improved emulsifying activity of whole-egg dispersions. Phosphate had a positive impact on the chemical stability of ß-carotene in whole-egg liquids and gels, decreasing the degradation during thermal treatment. The gel made with St was firm and broke down slowly, leading to a low rate of digestion and ß-carotene release in simulated gastric fluid. CONCLUSION: This study shows that St is useful to improve the egg proteins stabilized emulsions and gels, which is applicable in the development of emulsion-based food grade gel products. © 2021 Society of Chemical Industry.

Effect of manipulative reduction combined with air enema on intestinal mucosal immune function in children with intussusception.

OBJECTIVE: To explore the effect of manipulative reduction combined with air enema on intestinal mucosal immune function in children with intussusception. METHODS: This is a prospective randomized controlled study in which 60 children with primary intussusception admitted to Hebei Children's Hospital from October 2018 to October 2019 were selected for this study. They were randomly divided into two groups. The 30 patients in the experimental group underwent manipulative reduction and air enema reduction, and 30 patients in the control group underwent only air enema reduction. Pain scores and pressure during enema were recorded and analyzed. Fasting blood of children in the experimental group were drawn to test the serum T lymphocyte subsets CD3+, CD4+, CD8+ levels, B lymphocyte subsets CD19+ level, and NK cell subsets CD56+ levels before reduction. Among them, fasting blood of 28 children with successful reduction were drawn again in the morning after reduction, and the indicators of each immune cell subgroup before and after reduction were analyzed. Two children with unsuccessful reduction were no longer tested for these indicators. RESULTS: Twenty-Eight children in the experimental group had successful reduction, and two children with unsuccessful reduction were changed to open surgery (28/30). Twenty five Children in the control group had successful reduction, and five were changed to open surgery (25/30). There was no significant difference in the success rate of reduction between two groups (p>0.05). Close observation for 12~24h after reduction found that none of the children had signs of peritonitis. The pain score and reduction pressure of the observation group were lower than those of the control group, and the difference was statistically significant (p<0.05). The levels of serum CD3+, CD4+, and CD8+ after reduction in the experimental group were significantly higher than before reduction, and the difference was statistically significant (p<0.05). CD19+ level was significantly lower than before reduction, and the difference was statistically significant (p<0.05). There was no significant difference in changes of other indicators. CONCLUSIONS: Manipulative reduction combined with air enema reduction can relieve pain and air injection pressure during enema, reduce reperfusion injury caused by intestinal ischemia, and protect intestinal mucosal immune function, which is a favored treatment.

The Effect of Rev-erbα Agonist SR9011 on the Immune Response and Cell Metabolism of Microglia.

Microglia are the immune cells of the brain. Hyperactivation of microglia contributes to the pathology of metabolic and neuroinflammatory diseases. Evidence has emerged that links the circadian clock, cellular metabolism, and immune activity in microglia. Rev-erb nuclear receptors are known for their regulatory role in both the molecular clock and cell metabolism, and have recently been found to play an important role in neuroinflammation. The Rev-erbα agonist SR9011 disrupts circadian rhythm by altering intracellular clock machinery. However, the exact role of Rev-erbα in microglial immunometabolism remains to be elucidated. In the current study, we explored whether SR9011 also had such a detrimental impact on microglial immunometabolic functions. Primary microglia were isolated from 1-3 days old Sprague-Dawley rat pups. The expression of clock genes, cytokines and metabolic genes was evaluated using RT-PCR and rhythmic expression was analyzed. Phagocytic activity was determined by the uptake capacity of fluorescent microspheres. Mitochondria function was evaluated by measuring oxygen consumption rate and extracellular acidification rate. We found that key cytokines and metabolic genes are rhythmically expressed in microglia. SR9011 disturbed rhythmic expression of clock genes in microglia. Pro-inflammatory cytokine expression was attenuated by SR9011 during an immune challenge by TNFα, while expression of the anti-inflammatory cytokine Il10 was stimulated. Moreover, SR9011 decreased phagocytic activity, mitochondrial respiration, ATP production, and metabolic gene expression. Our study highlights the link between the intrinsic clock and immunometabolism of microglia. We show that Rev-erbα is implicated in both metabolic homeostasis and the inflammatory responses in microglia, which has important implications for the treatment of metabolic and neuroinflammatory diseases.

Using the modified Delphi method to research the influencing factors of long-term health-related quality of life in patients with unruptured intracranial aneurysms after endovascular treatment.

BACKGROUND: The purpose of this study was to use the modified Delphi method to identify the influencing factors of health-related quality of life (HRQoL) in patients with unruptured intracranial aneurysms (UIAs) after endovascular treatment. METHODS: A modified Delphi method to obtain expert consensus on the content of potential influencing factors of HRQoL in patients with UIAs treated by endovascular intervention was employed. The research team consists of three neuroradiologists and one epidemiologist from Xuanwu Hospital of Capital Medical University. They randomly selected 21 well-known experts in cerebrovascular disease diagnosis and treatment as participating experts. The importance of the indicator is based on the 5-Likert scale. The standard deviation (SD), coefficient of variation (CV), mean ( x ¯ ), and minimum and maximum scores of each indicator were calculated. The consistency was described by Kendall coefficient of concordance with a p value < 0.05 indicating that the expert consistency was high. RESULT: Twenty-one and 18 questionnaires were responded in 2 rounds, with effective response rates of 85.7% and 100.0%, respectively. The average authoritative coefficient (Cr) of all 21 experts was 0.88, familiarity with the indicators (Cs) was 0.82, and the judgment basis of the indicators (Ca) was 0.94. Eventually, the x ¯ values of arterial puncture hematoma, hyperlipidemia, gender, marital status, and hospitalization for other diseases were lower than 3.5; CV for marital status and gender was higher than 0.35. The Kendall coefficient of concordance in the first round was 0.19 (p < 0.001), and the second round was 0.15 (p < 0.001). CONCLUSION: In this study, the factors affecting the recovery of HRQoL after endovascular treatment in patients with UIAs were analyzed by the modified Delphi method, which provided a valuable evidence for the clinical management and daily life guidance for UIAs patients.

Oxygenated polycyclic aromatic hydrocarbons from ambient particulate matter induce electrophysiological instability in cardiomyocytes.

BACKGROUND: Epidemiologic studies have suggested that elevated concentrations of particulate matter (PM) are strongly associated with an increased risk of developing cardiovascular diseases, including arrhythmia. However, the cellular and molecular mechanisms by which PM exposure causes arrhythmia and the component that is mainly responsible for this adverse effect remains to be established. In this study, the arrhythmogenicity of mobilized organic matter from two different types of PM collected during summer (SPM) and winter (WPM) seasons in the Seoul metropolitan area was evaluated. In addition, differential effects between polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (oxy-PAHs) on the induction of electrophysiological instability were examined. RESULTS: We extracted the bioavailable organic contents of ambient PM, measuring 10 µm or less in diameter, collected from the Seoul metropolitan area using a high-volume air sampler. Significant alterations in all factors tested for association with electrophysiological instability, such as intracellular Ca2+ levels, reactive oxygen species (ROS) generation, and mRNA levels of the Ca2+-regulating proteins, sarcoplasmic reticulum Ca2+ATPase (SERCA2a), Ca2+/calmodulin-dependent protein kinase II (CaMK II), and ryanodine receptor 2 (RyR2) were observed in cardiomyocytes treated with PM. Moreover, the alterations were higher in WPM-treated cardiomyocytes than in SPM-treated cardiomyocytes. Three-fold more oxy-PAH concentrations were observed in WPM than SPM. As expected, electrophysiological instability was induced higher in oxy-PAHs (9,10-anthraquinone, AQ or 7,12-benz(a) anthraquinone, BAQ)-treated cardiomyocytes than in PAHs (anthracene, ANT or benz(a) anthracene, BaA)-treated cardiomyocytes; oxy-PAHs infusion of cells mediated by aryl hydrocarbon receptor (AhR) was faster than PAHs infusion. In addition, ROS formation and expression of calcium-related genes were markedly more altered in cells treated with oxy-PAHs compared to those treated with PAHs. CONCLUSIONS: The concentrations of oxy-PAHs in PM were found to be higher in winter than in summer, which might lead to greater electrophysiological instability through the ROS generation and disruption of calcium regulation.

Deep Convolutional Neural Networks-Based Automatic Breast Segmentation and Mass Detection in DCE-MRI.

Breast segmentation and mass detection in medical images are important for diagnosis and treatment follow-up. Automation of these challenging tasks can assist radiologists by reducing the high manual workload of breast cancer analysis. In this paper, deep convolutional neural networks (DCNN) were employed for breast segmentation and mass detection in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). First, the region of the breasts was segmented from the remaining body parts by building a fully convolutional neural network based on U-Net++. Using the method of deep learning to extract the target area can help to reduce the interference external to the breast. Second, a faster region with convolutional neural network (Faster RCNN) was used for mass detection on segmented breast images. The dataset of DCE-MRI used in this study was obtained from 75 patients, and a 5-fold cross validation method was adopted. The statistical analysis of breast region segmentation was carried out by computing the Dice similarity coefficient (DSC), Jaccard coefficient, and segmentation sensitivity. For validation of breast mass detection, the sensitivity with the number of false positives per case was computed and analyzed. The Dice and Jaccard coefficients and the segmentation sensitivity value for breast region segmentation were 0.951, 0.908, and 0.948, respectively, which were better than those of the original U-Net algorithm, and the average sensitivity for mass detection achieved 0.874 with 3.4 false positives per case.

Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN).

Translation is spatiotemporally regulated and endoplasmic reticulum (ER)-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, which suggests that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, which suggests that PARN might play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. The ER-anchored PARN modulated DNA damage response and thereby cell viability by promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy. These findings revealed that highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and PARN might contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

Induced reflection in Tamm plasmon systems.

We present an induced reflection response analogue to electromagnetically induced transparency (EIT) in a novel Tamm plasmon system, consisting of a thin metal film and a Bragg grating with a defect layer. The results show that an induced narrow peak can be generated in the original broad reflection dip, which is attributed to the coupling and interference between the Tamm plasmon and defect modes in the grating structure. It is found that the EIT-like induced reflection is strongly dependent on the thickness of defect layer, grating period number between the metal and defect layers, thickness of Bragg grating layer, refractive index of defect layer, and thickness of metal film. Additionally, the induced reflection can be dynamically tuned by adjusting the angle of incident light. The numerical simulations agree extremely well with theoretical calculations. The coupling strength between the Tamm plasmon and defect modes is determined by the above parameters. These results will provide a new avenue for light field control and devices in multilayer photonic systems.