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Endoplasmic reticulum (ER) stress has been demonstrated to prompt various cardiovascular risks although the underlying mechanism remains elusive. Protein tyrosine phosphatase-1B (PTP1B) serves as an essential negative regulator for insulin signaling. This study examined the role of PTP1B in ER stress-induced myocardial anomalies and underlying mechanism involved with a focus on autophagy. WT and PTP1B knockout mice were subjected to the ER stress inducer tunicamycin (1 mg/kg). Cardiac function was evaluated with echocardiography and an Ion-Optix MyoCam system. Western blot analysis was used to monitor the levels of ER stress, autophagy and insulin signaling including insulin receptor substrate (IRS), tribbles homolog 3 (TRIB3), Atg5/7, p62 and LC3-II. Our results showed that ER stress resulted in compromised echocardiographic and cardiomyocyte contractile function, intracellular Ca 2 + mishandling, ER stress, O 2 − production, apoptosis, the effects of which (with the exception of ER stress) were significantly attenuated or negated by PTP1B ablation. Levels of serine phosphorylation of IRS-1, TRIB3, Atg5/7, LC3B and the autophagy adaptor p62 were significantly upregulated while IRS-1 tyrosine phosphorylation was reduced by tunicamycin, the effect of which were obliterated by PTP1B ablation. In vitro study revealed that the autophagy inducer rapamycin and TRIB3 overexpression cancelled PTP1B ablation-offered beneficial effects on cardiomyocyte function or O 2 − production in murine cardiomyocytes or H9C2 myoblasts. Antioxidant or gene silencing of TRIB3 mimicked PTP1B ablation-induced protective effects. These findings collectively suggested that PTP1B ablation protects against ER stress-induced cardiac anomalies through regulation of autophagy. [ABSTRACT FROM AUTHOR]

Activation of κ-opioid receptor (KOR) ameliorates myocardial ischemia/reperfusion (I/R) injury; however, cardioprotective effects of KOR stimulation disappear in type 1 diabetic subjects with hyperglycemia. The molecular mechanisms underlying this phenomenon remain unknown. Here we found that KOR expression was obviously downregulated and KOR agonism-induced contractile-regulatory and cardioprotective effects were significantly impaired in hearts isolated from streptozotocin (STZ) injection-induced diabetic mice. These in vivo data identified cardiac KOR desensitization as a novel characteristic of the diabetic heart. In cultured cardiomyocytes, high glucose (HG) caused obvious KOR downregulation, accompanied by an upregulation of G protein coupled receptor kinase-2 (GRK2). We found that HG exposure increased the interaction between GRK2 and KOR. More importantly, HG-induced KOR downregulation was reversed by small interfering RNA (siRNA)-mediated GRK2 inhibition. GRK2 knockdown also restored KOR agonism-mediated protection against simulated I/R injury in cardiomyocytes. These in vitro data revealed an essential role of GRK2 in HG-induced KOR desensitization. Finally, cardiac-specific GRK2 knockdown by intramyocardial siRNA injection blocked KOR downregulation and restored contractile-regulatory and cardioprotective effects of KOR agonism in hearts of diabetic mice. In conclusion, these data for the first time demonstrate that GRK2 upregulation is largely responsible for cardiac KOR desensitization in diabetic individuals, which provides novel insights into the management of myocardial I/R injury in patients with diabetes. [ABSTRACT FROM AUTHOR]

In HVAC control problems, model-based optimal control methods have been extensively studied and verified by many researchers, but they highly depend on the accuracy of the model, a large amount of historical data, and the deployment of different sensors. With respect to the above problems, this paper proposed a Multi-Agent deep reinforcement learning method for the building Cooling Water System Control (MA-CWSC) to optimize the load distribution, cooling tower fan frequency, and cooling water pump frequency of different types of chillers, which provide a model-free and online learning mechanism. In the learning process, unlike the traditional reinforcement learning methods, the proposed control method uses five agents to control different controllable parts by parallel learning, which can greatly reduce the action space and speed up the convergence rate. In order to verify the effectiveness of the propose-d control method, based on the actual building cooling water system parameters and related historical data, we construct an experimental building cooling water system model, and moreover, we test the MA-CWSC method, model-based control method (optimal control method), baseline method, and single-agent deep reinforcement learning (deep Q-network). The experimental results show that the energy saving performance of the proposed MA-CWSC method is significantly better than the rule-based control method (11.1% improvement), and is very close to that of the model-based control method (only 0.5% difference). In addition, the MA-CWSC method has a faster learning rate compared to the deep Q-network (DQN) control method. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cell (MSC) implantation is a promising option for liver repair, but their poor retention in the injured liver milieu critically blunts therapeutic effects. The aim is to clarify the mechanisms underlying massive MSC loss post‐implantation and establish corresponding improvement strategies. MSC loss primarily occurs within the initial hours after implantation into the injured liver milieu or under reactive oxygen species (ROS) stress. Surprisingly, ferroptosis is identified as the culprit for rapid depletion. In ferroptosis‐ or ROS‐provoking MSCs, branched‐chain amino acid transaminase‐1 (BCAT1) is dramatically decreased, and its downregulation renders MSC susceptible to ferroptosis via suppressing the transcription of glutathione peroxidase‐4 (GPX4), a vital ferroptosis defensing enzyme. BCAT1 downregulation impedes GPX4 transcription via a rapid‐responsive metabolism‐epigenetics coordinating mechanism, involving α‐ketoglutarate accumulation, histone 3 lysine 9 trimethylation loss, and early growth response protein‐1 upregulation. Approaches to suppress ferroptosis (e.g., incorporating ferroptosis inhibitors in injection solvent and overexpressing BCAT1) significantly improve MSC retention and liver‐protective effects post‐implantation. This study provides the first evidence indicating that excessive MSC ferroptosis is the nonnegligible culprit for their rapid depletion and insufficient therapeutic efficacy after implantation into the injured liver milieu. Strategies suppressing MSC ferroptosis are conducive to optimizing MSC‐based therapy. [ABSTRACT FROM AUTHOR]

A 1 × 4 optical splitter (OS) is proposed for TE modes based on a self-collimation (SC) effect ring resonator (SCRR) in an air-hole type silicon photonic crystal. A 1 × 4 OS consists of four beam splitters formed by varying the radii of the air holes. Utilizing multiple-beam interference theory, the theoretical transmission spectra at each port in the OS were analyzed. By forming four splitters in a SCRR properly, self-collimation light can come out from four ports with the light-intensity ratio we set. OSs were investigated using the two-dimensional finite-difference time-domain (FDTD) simulation technique. The simulation results have good agreement with the theoretical prediction. Because of its small dimensions, whole silicon material, and air-hole type, this structure may have an important role in photonic integrated circuits. [ABSTRACT FROM PUBLISHER]

Abstract: We report here 1×3 and 1×2 photonic drop splitters (PDSs) with different splitting ratios based on self-collimation ring resonators (SCRRs) in an air-hole silicon photonic crystal. An 1×3 PDS consists of four beam splitters and an 1×2 PDS consists of three beam splitters and one mirror. Light propagates in the PDSs employing self-collimation effect. The theoretical transmission spectra at different drop ports in PDSs were analyzed with the multiple-beam interference theory. Then they were investigated with the finite-difference time-domain (FDTD) simulation technique. The simulation results agree well with the theoretical prediction. For the drop wavelength 1550nm, the free spectral range of the PDSs is about 29nm, which almost covers the whole optical communication C-band window. Because of small dimensions, air-hole structure and whole-silicon material, the proposed PDSs hold great potentials for applications in photonic integrated circuits. [Copyright &y& Elsevier]

Abstract: A polarization beam splitter based on a self-collimation Mach–Zehnder interferometer (SMZI) in a hole-type silicon photonic crystal was proposed and numerically demonstrated. Utilizing polarization dependence of the transmission spectra of the SMZI and polarization peak matching (PPM) method, the SMZI can work as a polarization beam splitter (PBS) by selecting appropriate path length difference in the structure. Because of its intrinsic operating principle, the PBS possesses high polarization extinction ratios (PERs). As its dimensions are only several operating wavelengths, the PBS may have practical applications in photonic integrated circuits. [ABSTRACT FROM AUTHOR]

Abstract: We show theoretically that the upper and lower cutoff frequencies of the guided band in a 2D photonic crystal coupled-cavity waveguide can be controlled independently or synchronously by changing two configuration parameters of the waveguide simultaneously. The independent control range for the lower and upper cutoff frequencies can be as large as 68.6% and 67.9% of photonic band gap, respectively. The two cutoff frequencies can also be tuned in the same direction over equal distances up to 25.7% of photonic band gap. These results offer an efficient way for designing the various dispersion relations for photonic crystal waveguides. [Copyright &y& Elsevier]

Urban industrial areas were being built globally, which decreased key geographical separation between agriculture and industrial areas, especially in developing countries. Now, limited studies concerned coordinated the vegetables and soil management for toxic elements (TEs) in this mixed land system. To fill this gap, an integrated environmental multi-media risk management method was explored based on laboratory analysis, health risk assessment, uncertainty control, and source apportionment. The Chinese Beihu area of Wuhan City was selected as a typical case and the measurements of Zn, Cr, Cu, Pb, As, and Cd in soil revealed that TEs pollution was slight and concentrations met the Chinese standards. Meanwhile, some vegetables exceeded corresponding standard limits. To further quantify negative health effects posed by the studied TEs both in soils and vegetables, an established fuzzy health risk assessment for farmers was employed and the results indicated that the soil exposure of As and the vegetable consumption needed the priority control. The carcinogenic risk (CR) of As in soil was [4.60E-6, 1.45E-5] and the cumulative CR (sum of CR As , CR Pb and CR Cd) in leafy vegetables was [1.08E-4, 1.38E-4], which was higher than that of the other vegetables. Preventing soil oral exposure and reducing self-grown vegetable consumption (30%–50%) were proven as effective risk interventions via uncertainty control methods. Spatially, the risk grades under maximum membership principle decreased from south to north in the Beihu area, and the south area was identified as the priority control area. Source apportionment identified four source patterns (Zn-Cr-Cu, Pb, As, and Cd) for soil, and the probable bioaccumulation mechanisms for leafy vegetables by multivariate statistical analyses. Finally, the integrated management strategies were formulated from perspectives of the risk sources, exposure pathways and the scenario. Unlabelled Image • Integrated health risk in a typical farmland near industrial complex was explored. • Priority control element and pathway were gotten via fuzzy health risk model. • Soil As exposure and vegetable consumption were important contributors of CR. • Bajifu Avenue-Green Road was priority control area by multi-spatial analysis. • Cd, Pb and As were correlated in migration patterns of soil-vegetable media. [ABSTRACT FROM AUTHOR]

Background: Although many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI.Methods: Consecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values.Results: Of 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively).Conclusion: Serum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI. [ABSTRACT FROM AUTHOR]

Facing the challengeable PM2.5 pollution management across China, it is of significance to identify key pollution driving factors with a nation-region-city perspective and establish targeted joint management strategies on the trans-provincial scale. To identity hot study regions, the spatiotemporal pollution variation of PM2.5 in 2016 was explored using multi-scale spatial autocorrelation analysis based on the ground monitoring data for Chinese 366 cities. In the identified study regions, the relationship of natural factors and PM2.5 was analyzed on annual and daily scales via the correlation analyses, and the multiple socioeconomic driving forces of PM2.5 were identified utilizing geographic weighted regression (GWR) and principal component analysis. Consequently, 111 cities were identified as the hot regions, where their annual means of PM2.5 (AM) were 60.40 ± 14.23 μg·m−3 exceeding the Chinese level II standard and WHO Air Quality Guideline IT-1 (35 μg·m−3). The elevation and annual accumulative rainfall were found to be negatively correlated with the AM (p < 0.01). The increase of temperature and wind speed mainly helped daily PM2.5 reduce. Furthermore, the sensitive socioeconomic factors, mainly including the added value of the industry, the per capita gross domestic product and the per capital annual disposable income, were identified due to GWR. Then, based on the found spatial heterogeneity of sensitive factors, the selected 111 cities were identified into four types (Q 1 , Q 2 , Q 3 , Q 4) and two sub-regions, Q 1 +Q 2 (13+49 cities) and Q 3 +Q 4 (27+22 cities). Finally, for multi-scale environmental sustainability and equity, the joint management strategies were formulated for each cities pattern based on their feature of sensitive pollution driving forces and city role positioning. Image 1 • Spatiotemporal patterns of PM2.5 in 366 Chinese cities were explored on multi-scale. • Increase of elevation, rainfall/wind, temperature help annual/daily PM2.5 reduce. • PM2.5 was sensitive to social factors like Added value of industry, Per Capita GDP. • 111 hot cities were identified into four types on spatially heterogeneous features. • Joint management strategies were formulated for each kind based on driving factors. [ABSTRACT FROM AUTHOR]

Low‐dimensional organic–inorganic metal halides (OIMHs) have emerged as promising light emitters due to their broadband emission originating from self‐trapped excitons (STE), especially for Cu‐based OIMHs. Herein, Cu(I)‐based OIMH with a structure of (TPP)2Cu4I6·2DMSO (TPP stays for tetraphenylphosphonium, and DMSO – for dimethyl sulfoxide) has been synthesized, both in form of single crystals and as a microcrystalline powder. This compound exhibits a broadband green emission with a peak at 515 nm and a full width at half‐maximum of 78 nm, and a near‐unity photoluminescence quantum yield of 99.5%. Experimental data supported by theoretical calculations indicate that the STE emission is responsible for the green emission with a long lifetime of 2.53 µs. Down‐conversion light‐emitting device with a high luminous efficiency of 50 lm W−1 based on this compound have been fabricated, and white light has also been achieved with a high color rendering index of 96.7. Moreover, green emissive (TPP)2Cu4I6·2DMSO is utilized in scintillators for X‐ray detection and imaging, and as a luminescent ink for encryption applications. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate spirituality and attitudes toward death among rural and urban elderly. We asked 134 older adults from rural areas and 128 from urban areas to complete a self-administrated questionnaire including the Spiritual Self-assessment Scale and Death Attitude Scale. The fear and anxiety of death, escape acceptance, natural acceptance, approach acceptance, and death avoidance scores of older adults living in rural areas were higher than those living in urban areas. The construction of social infrastructure and medical care should be strengthened in rural areas so as to improve older adults' attitudes toward death. [ABSTRACT FROM AUTHOR]

Obesity has become a worldwide pandemic and is associated with various metabolic diseases such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. Fas-activated serine/threonine kinase (Fastk) is a multifunctional protein localized in the mitochondrion; however, the role of Fastk in obesity-related metabolic disorders remains unexplored. Here we found that Fastk expression was specifically induced in livers of high fat (HF) diet-fed mice and in saturated fatty acid (such as palmitate)-loaded hepatocytes. Genetic ablation of Fastk ameliorated HF diet-induced insulin resistance, glucose intolerance, and hepatic steatosis. Further studies confirmed that Fastk knockout suppressed hepatic gluconeogenesis and lipogenesis in HF diet-stressed livers and in palmitate-loaded hepatocytes. Mechanistically, Fastk ablation significantly preserved sirtuin-1 (SIRT1) expression and activity in livers of HF diet-fed mice and in palmitate-loaded hepatocytes. Inhibition of SIRT1 activity by EX-527 (a specific inhibitor of SIRT1) totally abolished the suppressive effects of Fastk knockout on gluconeogenesis and lipogenesis in cultured hepatocytes. In conclusion, these data for the first time demonstrate that Fastk critically controls hepatic gluconeogenesis and lipogenesis mainly through modulating SIRT1 signaling. Intervening Fastk expression or activity might be a promising therapeutic strategy for the treatment of obesity-associated metabolic diseases. Image 1 • Fastk is specifically induced in livers of obese individuals and in saturated fatty acid-loaded hepatocytes. • Fastk is a key modulator of hepatic gluconeogenesis and lipogenesis. • Genetic knockout of Fastk ameliorates obesity-associated metabolic disorders. • Fastk is a novel therapeutic target for prevention of obesity-associated metabolic diseases. [ABSTRACT FROM AUTHOR]

Abstract Insulin resistance leads to myocardial contractile dysfunction and deranged autophagy although the underlying mechanism or targeted therapeutic strategy is still lacking. This study was designed to examine the impact of inhibition of the cytochrome P450 2E1 (CYP2E1) enzyme on myocardial function and mitochondrial autophagy (mitophagy) in an Akt2 knockout model of insulin resistance. Adult wild-type (WT) and Akt2−/− mice were treated with the CYP2E1 inhibitor diallyl sulfide (100 mg/kg/d, i.p.) for 4 weeks. Cardiac geometry and function were assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate autophagy, mitophagy, inducible NOS (iNOS), and the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex. Akt2 deletion triggered insulin resistance, compromised cardiac contractile and intracellular Ca2+ property, mitochondrial ultrastructural damage, elevated O2– production, as well as suppressed autophagy and mitophagy, accompanied with elevated levels of NLRP3 and iNOS, the effects of which were significantly attenuated or ablated by diallyl sulfide. In vitro studies revealed that the NLRP3 activator nigericin nullified diallyl sulfide-offered benefit against Akt2 knockout on cardiomyocyte mechanical function and mitophagy (using Western blot and colocalization of GFP-LC3 and MitoTracker Red). Moreover, inhibition of iNOS but not mitochondrial ROS production attenuated Akt2 deletion-induced activation of NLRP3, substantiating a role for iNOS-mediated NLRP3 in insulin resistance-induced changes in mitophagy and cardiac dysfunction. In conclusion, these data depict that insulin resistance through CYP2E1 may contribute to the pathogenesis of myopathic changes including myocardial contractile dysfunction, oxidative stress and mitochondrial injury, possibly through activation of iNOS and NLRP3 signaling. Highlights • We examined the effect of CYP2E1 inhibition on cardiac anomalies in Akt2 knockout-induced insulin resistance model. • CYP2E1 inhibition protects insulin resistance-induced cardiac contractile anomalies; • The beneficial effect of CYP2E1 inhibition in insulin resistance was related to improved autophagy and mitophagy. [ABSTRACT FROM AUTHOR]

B Mesenchymal Stromal Cell (MSC) Ferroptosis b As reported in article number 2206439 by Ling Tao, Fuyang Zhang, and co-workers, MSCs are seriously damaged by the reactive oxygen species (ROS) after injection into the injured liver milieu and rapidly deplete due to ferroptosis driven by ROS-induced lipid peroxidation, like the devouring fire in the forest threatening the entered firefighters. Strategies reducing ferroptosis, such as incorporating ferroptosis inhibitors or overexpressing BCAT1, protect the implanted MSCs from ROS-irritated ferroptosis, hence improving MSC retention and therapeutic effectiveness, similar to the firefighters are shielded by the firefighting clothing and equipment. Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism-Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu (Adv. Sci. 13/2023). [Extracted from the article]

Background/Aims: Neuronostatin, derived from the somatostatin preprohormone, was recently identified to be produced by several tissues exerting a role in cardiovascular regulation and metabolism. Nonetheless, the precise mechanism behind neuronostatin-elicited myocardial responses remains elusive. Methods: This study was designed to elucidate the impact of neuronostatin on cardiac contractile function and the underlying mechanism of action involved. Adult male C57 BL/6 mice were subjected to a bolus injection of neuronostatin (50 μg/kg, i.p.). Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ handling properties were monitored to evaluate the effect of neuronostatin on cardiac function. Western blot analysis was used to examine potential signaling mechanisms involved. Results: Neuronostatin administration suppressed myocardial and cardiomyocyte contractile function and disturbed intracellular Ca2+ homeostasis. We observed enlarged LVESD (with unchanged LVEDD), reduced fractional shortening, depressed peak shortening, maximal velocity of shortening/relengthening, resting and electrically-stimulated rise in intracellular Ca2+, and prolonged relengthening duration in hearts from neuronostatin-treated mice. These effects were accompanied by downregulation of phosphorylation of sarcoplasmic reticulum Ca2+-ATPase (SERCA) and phospholamban (PLB) and activation of AMPK. Conclusion: Our data suggest that the cardiac depressant properties of neuronostatin possibly associated with loss of SERCA phosphorylation and AMPK activation. These findings revealed a potent inhibitory capacity for neuronostatin on cardiac function, the physiological relevance of which deserves further study. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic alcoholism often causes liver injuries characterized by hepatic steatosis, inflammation as well as oxidative stress and finally leads to advanced cirrhosis and liver cancer. Fas-activated serine/threonine kinase (FASTK) and its homologs are gradually known as multifunctional proteins involved in various biological processes; however, the role of FASTK and its family members in alcoholic liver disease (ALD) is still unexplored. Here we found that, among FASTK family members, the expression of FASTK was specifically induced both in livers of mice received chronic ethanol ingestion and in ethanol-stimulated hepatocytes. Animal studies showed that genetic deletion of FASTK attenuated chronic ethanol ingestion-induced liver damage, steatosis, and inflammation. Moreover, FASTK deficiency was associated with improved oxidative/anti-oxidative system homeostasis and reduced reactive oxygen species (ROS) generation in livers upon chronic ethanol stimulation. Importantly, FASTK ablation preserved hepatic sirtuin-1 (SIRT1) expression/activity upon chronic ethanol ingestion and SIRT1 silencing via adenovirus-mediated small interfering RNA transfer diminished FASTK deletion-elicited beneficial effects on alcohol-associated hepatic steatosis, inflammation, and oxidative stress. Mechanistically, ethanol increased the phosphorylation of human antigen R (HuR, a RNA binding protein that stabilizes SIRT1 mRNA) and triggered the dissociation of HuR-SIRT1 mRNA complex, in turn promoting SIRT1 mRNA decay. Genetic deletion of FASTK diminished ethanol-induced HuR phosphorylation and HuR-SIRT1 mRNA complex dissociation, thereby enhancing SIRT1 mRNA stability. Collectively, these findings for the first time highlight a critical role of FASTK in the pathogenesis of ALD and implicate HuR-SIRT1 mRNA complex involves in this process. • Hepatic FASTK expression is specifically induced in an alcoholic liver disease (ALD) model. • Genetic FASTK ablation ameliorates ALD progression through modulating liver steatosis, inflammation, and oxidative stress. • SIRT1 is an indispensable molecule for FASTK deletion-mediated beneficial effects on ALD progression. • FASTK modulates SIRT1 mRNA stability through influencing HuR-SIRT1 mRNA complex formation. [ABSTRACT FROM AUTHOR]

Abstract The aim of Image super-resolution (SR) is to recover high-resolution images from low-resolution ones. By virtue of the great success in numerous computer vision tasks achieved by the convolutional neural networks (CNNs), it is a nice direction to tackle the SR problem using CNNs. Despite progress in accuracy of SR using deeper CNNs, those models are almost trained base upon supervised way. In this paper, we propose a deep unsupervised learning approach for SR with a Generative Adversarial Network (GAN) framework, which is composed of a deep convolutional generator network with dense connections and a discriminator. A sub-pixel convolutional layer is operated on the top of the generator to upscale the inputs, and the standard convolutions are all implemented in the LR space, which leads to a fast restoration. The generator is trained to directly recover the high-resolution image from the low-resolution image. Strided convolution and ReLU activations are employed in the discriminator to distinguish the HR images from the produced HR images. The generator model is optimized with a combination of a data error, a regular term and an adversarial loss, which ensures local–global contents consistency and pixel faithfulness. Note that no labeled training data is employed during the training. Comparisons with several state-of-the-art supervised learn-based methods, experimental results demonstrate that the proposed model achieves a comparable result in terms of both quantitative and qualitative measurements, and it also implies the feasibility and effectiveness of the proposed unsupervised learning-based single-image super-resolution algorithm. Highlights • A new Super-Resolution model to solve ill-posed problem with unsupervised learning. • A regularizer for smoothing continual section of image and preserving sharp edge. • A loss function for training the proposed SR model with end-to-end learning manner. • Detailed study for regular items and downsampling strategies. • Comparable SR performance with faster inference speed. [ABSTRACT FROM AUTHOR]

The property of surface wave at the interface between a dielectric half-space and a photonic hypercrystals (PHC) containing graphene-based hyperbolic metamaterial (GHMM) is investigated. It is observed that the propagation length, figure-of-merit (FOM), absorption resonance, nanoscale mode confinement and penetration depth of surface wave can be tuned by varying the Fermi energy of graphene sheets via electrostatic biasing. It is also found that the surface states in the hypercrystal containing GHMM allow for both high wave numbers and long propagation lengths at the same time. It is shown that the surface wave in the PHC has extremely low group velocity and the magnitude of group velocity can be well regulated. Here we also analyse the optical forces from the surface wave in the case of Rayleigh particles, and large and tunable radiation force component has been observed. [ABSTRACT FROM AUTHOR]

Aims The farnesoid X receptor (FXR) is a member of the metabolic nuclear receptor superfamily that plays a critical regulatory role in cardiovascular physiology/pathology. However, the role of systemic FXR activation in the chronic phase in myocardial infarction (MI)-induced cardiac remodelling and dysfunction remains unclear. In this study, we aimed to elucidate the role of long-term FXR activation on post-MI cardiac remodelling and dysfunction. Methods and results Mice underwent either MI surgery or sham operation. At 1 week after MI, both sham and MI mice were gavaged with 25 mg/kg/d of a synthetic FXR agonist (GW4064) or a vehicle control for 7 weeks, and cardiac performance was assessed by consecutive echocardiography studies. Administration of GW4064 significantly increased left ventricular ejection fraction at 4 weeks and 8 weeks after MI (both P  < 0.01). Moreover, GW4064 treatment increased angiogenesis and mitochondrial biogenesis, reduced cardiomyocyte loss and inflammation, and ameliorated cardiac remodelling as evidenced by heart weight, lung weight, atrial natriuretic peptide/brain natriuretic peptide levels, and myocardial fibrosis at 8 weeks post-MI. At the molecular level, GW4064 significantly increased FXR mRNA expression and transcriptional activity in heart tissue. Moreover, over-expression of myocardial FXR failed to exert significant cardioprotection in vivo , indicating that GW4064 improved post-MI heart remodelling and function independent of myocardial FXR expression/activity. Among the four down-stream soluble molecules of FXR, plasma adiponectin was most significantly increased by GW4064. In cultured adipocytes, GW4064 increased mRNA levels and protein expression of adiponectin. Conditioned medium of GW4064-treated adipocytes activated AMPK-PGC-1α signalling and reduced hypoxia-induced cardiomyocyte apoptosis, all of which were attenuated by an adiponectin neutralizing anti-body. More importantly, when knocking-out adiponectin in mice, the cardioprotective effects of GW4064 were attenuated. Conclusions We are the first to show that FXR agonism ameliorated post-MI cardiac dysfunction and remodelling by stimulating adiponectin secretion. Thus, we demonstrated that FXR agonism is a potential therapeutic strategy in post-MI heart failure. [ABSTRACT FROM AUTHOR]

Diabetes is a major health problem worldwide. As well-known, diabetes greatly increases cardiac vulnerability to ischemia/reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Nucleostemin (NS) is a nucleolar protein that controls ribosomal biogenesis and exerts cardioprotective effects against I/R injury. However, whether NS-mediated ribosomal biogenesis regulates ischemic vulnerability of diabetic hearts remains unanswered. Utilizing myocardial I/R mouse models, we found that cardiac NS expression significantly increased in response to I/R in normal diet (ND)-fed mice. Surprisingly, cardiac NS failed to be upregulated in high fat diet (HFD)-induced diabetic mice, accompanied by obvious ribosomal dysfunction. Compared with ND group, cardiac specific overexpression of NS by adenovirus (AV) injection significantly restored I/R-induced ribosomal function enhancement, reduced cardiomyocyte apoptosis, improved cardiac function, and decreased infarct sizes in diabetic mice. Notably, co-treatment of homoharringtonine (HHT), a selective inhibitor of ribosomal function, totally blocked NS-mediated cardioprotective effects against I/R injury. Furthermore, in cultured cardiomyocytes, saturated fatty acids treatment, but not high glucose exposure, significantly inhibited simulated I/R-induced NS upregulation and ribosomal function improvement. In conclusion, these data for the first time demonstrate that NS dysregulation induced by saturated fatty acids exposure might be an important cause of increased ischemic vulnerability to I/R injury in diabetic hearts. Targeting NS dysregulation and subsequent ribosomal dysfunction could be a promising therapeutic strategy for diabetic I/R injury management. [ABSTRACT FROM AUTHOR]

Background: Microglia can not only detrimentally augment secondary injury but also potentially promote recovery. However, the mechanism underlying the regulation of microglial phenotypes after stroke remains unclear.Methods: Mice were subjected to middle cerebral artery occlusion for 60 min. At 3 days after reperfusion, the effects of activation and suppression of triggering receptor expressed on myeloid cells 2 on immunocyte phenotypes (n = 5), neurobehavioral scores (n = 7), infarct volumes (n = 8), and neuronal apoptosis (n = 7) were analyzed. In vitro, cultured microglia were exposed to oxygen-glucose deprivation for 4 h. Inflammatory cytokines, cellular viability (n = 8), neuronal apoptosis (n = 7), and triggering receptor expressed on myeloid cells 2 expression (n = 5) were evaluated in the presence or absence of triggering receptor expressed on myeloid cell-specific small interfering RNA or triggering receptor expressed on myeloid cells 2 overexpression lentivirus.Results: Triggering receptor expressed on myeloid cells 2 expression in the ischemic penumbra peaked at 3 days after ischemia-reperfusion injury (4.4 ± 0.1-fold, P = 0.0004) and was enhanced in interleukin-4/interleukin-13-treated microglia in vitro (1.7 ± 0.2-fold, P = 0.0119). After oxygen-glucose deprivation, triggering receptor expressed on myeloid cells 2 conferred neuroprotection by regulating the phenotypic conversion of microglia and inflammatory cytokine release. Intraperitoneal administration of triggering receptor expressed on myeloid cells 2 agonist heat shock protein 60 or unilateral delivery of a recombinant triggering receptor expressed on myeloid cells 2 lentivirus into the cerebral ventricle induced a significant neuroprotective effect in mice (apoptotic neurons decreased to 31.3 ± 7.6%; infarct volume decreased to 44.9 ± 5.3%). All values are presented as the mean ± SD.Conclusions: Activation or up-regulation of triggering receptor expressed on myeloid cells 2 promoted the phenotypic conversion of microglia and decreased the number of apoptotic neurons. Our study suggests that triggering receptor expressed on myeloid cells 2 is a novel regulator of microglial phenotypes and may be a potential therapeutic target for stroke. [ABSTRACT FROM AUTHOR]

Although the production process of liquid crystal display model has been automated, the quality detection still depends on manual work. Mura defect is one of the common defects appearing in TFT-LCD modules. Since mura defect is not significantly different from the common background, it is difficult to detect. This paper presents a deep channel attention-based classification network (DCANet), which acts as a powerful feature extractor for object detectors, and proposes an antagonistic training algorithm based on convolution neural network. By the proposed training approach, the deep learning-based object detectors can achieve high accuracy even with a small number of training samples of mura defect. The experimental results show that compared to vanilla training method, the deep learning-based detectors trained by our proposed method could significantly improve their performance on mura defect detection with a few training samples. Even trained on only 600 samples, the mistake rate and miss rate are only 8.08% and 0.267% respectively, which can completely fulfill the enterprise's requirements of 10% and 0.3%. • A lightweight backbone network based upon dense blocks with channel attention (DCANet) is proposed and analyzed. • A data augment method of generate antagonistic sample is presented. • An antagonistic training framework is proposed to train deep learning-based object detectors. • Detailed study for the proposed backbone network and training algorithm. [ABSTRACT FROM AUTHOR]

Menopause increases the risk of cardiometabolic diseases in women. This circumstance is usually attributed to a deficiency in circulating estrogen levels although the underlying mechanism remains elusive. Given the pivotal role of AMP-activated protein kinase (AMPK) in the regulation of energy metabolism and cardiac function, this study was designed to examine the role of AMPK in estrogen deficiency and replacement-exerted cardiomyocyte responses. Adult female WT and AMPK kinase dead (KD) mice were subjected to bilateral ovariectomy (OVX) or sham operation. A cohort of ovariectomized mice received 17β-estradiol (E2) (40 μg/kg/day, i.p.) for 6 weeks. Mechanical and intracellular Ca 2+ properties were evaluated including peak shortening (PS), time-to-PS (TPS), time-to-90%-relengthening (TR 90 ), and maximal velocity of shortening/relengthening (±dL/dt). Levels of AMPK, Akt JNK, ACC, SERCA, membrane Glut4, AS160 and PGC-1α were assessed using Western blot. OVX significantly decreased PS, ±dL/dt and intracellular Ca 2+ rise in responsible to electric stimulus, prolonged TR 90 and intracellular Ca 2+ decay without affecting TPS and resting intracellular Ca 2+ , the effects of which were reconciled by E2 replacement. Western blot analysis depicted that OVX suppressed phosphorylation of Akt AMPK and ACC although it promoted JNK phosphorylation, the effects of which were mitigated or significantly attenuated by E2 treatment in WT but not KD mice. Moreover, OVX procedure downregulated SERCA2a and membrane Glut4 while inhibiting AS160 phosphorylation without affecting PGC-1α levels. In vitro study revealed that E2 corrected cardiomyocyte contractile dysfunction elicited by OVX in cardiomyocytes from WT but not the AMPK kinase dead mice. Taken together, these data suggest that E2 treatment ameliorates estrogen deficiency-induced changes in cardiac contractile function possibly through an AMPK-dependent mechanism. [ABSTRACT FROM AUTHOR]

A 1 × 4 optical demultiplexer (OD) based on the self-collimation (SC) effect in hole-type silicon photonic crystal (PC) was proposed, and its performance was numerically demonstrated. The 1 × 4 OD consists of two cascaded Mach–Zehnder interferometers and an independent mirror. It has a total of four splitters and five mirrors. The simulation results indicate that by selecting the correct optical path length, the input SC beam with four evenly spaced frequencies can be demultiplexed into four output ports in the 1 × 4 OD. If the center working wavelength is 1550 nm, the free spectral range of the 1 × 4 OD is about 23 nm, which almost covers the whole optical communication C-band window. The size of the structure is on the order of 50 μm. Because of its simple structure, small size, and single material, it has potential application value in future photonic integrated circuits. [ABSTRACT FROM AUTHOR]

A new channel drop filter (CDF) is proposed based on a race-track photonic crystal ring resonator composed of square-lattice cylindrical silicon rods in air. By using a two-dimensional finite-difference, time-domain numerical technique, the modal behavior of two representative CDFs, parallel and perpendicular, has been analyzed. The analyses include the impact of additional scatterer size, scatterer amount and their position on the performance of proposed CDFs, such as drop efficiency and quality factor (Q). For the parallel CDF, about 130 spectral Q and 99% drop efficiency can be optimally achieved at 1363 nm channel with 0.145 periodicity scatterer size, whereas for the perpendicular one, about 180 spectral Q and 99% drop efficiency can be optimally obtained at 1366 nm channel with 0.165 periodicity scatterer size. By increasing the number of scatterers, the efficiency of both configurations can be enhanced. No obvious variation is obtained by changing the scatterer position. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that the lip products are polluted by heavy metals, which would inevitably cause safety problems with long-term exposure, but few studies have focused on their deeper health risk assessments. This study sets out to identify the lip cosmetics in good sale from Chinese e-commerce market utilizing Python crawler and then explore the probabilistic health risks caused by 6 trace elements in 34 most popular lip cosmetics with Monte Carlo simulation. The results found that there was no obvious non-carcinogenic risk to humans. As for high users, the carcinogenic risk levels of Cr exceeded the acceptable risk recommended by USEPA, approximately 10% and 25% for lipsticks and lip glosses, respectively. Cr was regarded as the priority metal for risk control in the present study. Finally, it was recommended that the minimum use period limit for using up one lip product ranged from 0.54 months to 5.74 months. Overall, this study appears to be the first to conduct a probabilistic health risk assessment of trace elements in lip products, which would be of significance for policy makers to take effective strategies to minimize exposure health risk and contamination. ga1 • It is the first study to conduct probabilistic health risk assessments of trace elements in lip cosmetics based on Python. • Lip balms accumulated relatively lower metal levels compared with others except for Pb. • Over 10% of the integrated cancer risks of Cr for high users exceeded the acceptable limit. • It was recommended the use period for using up one lipstick was no less than 5.74 months. [ABSTRACT FROM AUTHOR]

In facing the challenge of PM2.5 pollution across China, an overall macro-evaluation of the spatiotemporal pollution distribution and health risk of PM2.5-bound heavy metals at a national level is urgently needed. This study involved a bibliometric analysis of 8 PM2.5-bound heavy metals (Cd, Cr, Hg, As, Pb, Cu, Zn, Ni) in the 27 major cities across China from 2013 to 2019 that was combined with valid data from the published scientific literature. Based on time weight vector, the spatiotemporal metal distributions and their integrated enrichment factors were analyzed, and then a fuzzy health risk assessment model was established to synthetically screen regional priority control regions/pollutants, and explore the pollution trend. The integrated concentrations of As (19.44 ng/m3) and Cd (4.12 ng/m3) in most cities exceeded the limits of the Chinese Ambient Air Quality Standards, while Hg (0.81 ng/m3) and Pb (137.10 ng/m3) did not. Spatially, PM2.5-bound heavy metal pollution generally increased from southern to northern China, with North and Northwest of China being relatively hot regions. For integrated health risks, children (3.31) faced higher non-carcinogenic risks than adults (1.69), with As, Cd, and Cr as the main contributors. The total carcinogenic risk varied from 4.86 × 10−6 to 1.3 × 10−3. The total carcinogenic risk of 77.78% of major cities has reached Grade V (moderate-high risk) or above, and the risk contributions of Cr and As accounted for the largest proportion. The temporal variations showed that the pollution had a recent declining trend in most cities. Finally, 10 major cities and their corresponding metals were determined as the priority control cities/metals. The targeted risk management policies were developed for the identified hierarchical hot cities and their priority pollutants to control were based on the regional pollution trend and source characteristics. Image 1 • Spatiotemporal heavy metals in PM2.5 was investigated in the Chinese major cities. • Fuzzy exposure assessment model was established to identify hot pollutants/areas. • Integrated heavy metals in PM2.5 increased gradually from south to north China. • Priority control metals were As, Cr, Cd, especially in north and northwest China. • Targeted policies for priority control regions were formulated on source analysis. [ABSTRACT FROM AUTHOR]

Determination of the pulmonary bioaccessible fraction and its induced health risk with respect to the toxic metals present in tobacco smoke is a significant issue, in terms of scientific and proactive management of clean tobacco production and smoker health. China, the world's largest producer and consumer of tobacco, has about 350 million smokers. The four typical toxic metals in the 20 top selling cigarette brands in China were investigated. The mean levels of As, Cd, Ni, and Pb in tobacco were 0.3891 μg/g, 3.8431 μg/g, 2.4356 μg/g, and 2.7718 μg/g, respectively. Pulmonary bioaccessibility was analyzed by extraction using simulated lung fluid (SLF), where the average rates of As, Cd, Ni, and Pb transferring from tobacco to SLF by mainstream smoke (RSLF) were 7.85%, 2.85%, 0.86%, and 3.45%, respectively. Considering the inhalation pathway of mainstream smoke, an improved health risk assessment (HRA) was conducted using local exposure parameters and fuzzification of sensitive variables. With consideration of the exposure differences of smokers, Cd and As were identified as the priority control metals, and B05, B11, B12, and B19 among the 20 brands (named B01–B20) were found to be the priority control brands. Furthermore, it is worth noting that the membership degrees of a small portion of brands which approached 50% could warn decision-makers of potentially misleading uncertainties. The daily consumption limit (DCL) for each studied brand was calculated, under the risk standard value of Level II (1.00E-05), generally ranging from 1 to 4 cigarette(s) per day. Spatially, DCLs in Southern, Southwestern, and Eastern China were relatively lower than those in other regions. At present, it is of significance to establish a national life-cycle supervisory system for Cd and As. Findings about the health risks posed by toxic metals through the tobacco–smoke–lung exposure pathway can provide scientific risk management reference for smokers, related managers, and producers. Image 1 • Toxic metals in the selected 20 Chinese best-selling cigarettes were investigated. • Pulmonary bioaccessibility of toxic metals was analyzed using simulated lung fluid. • Transfer rates from mainstream smoke to simulated lung fluids (RSLF) were detected. • Health risk posed by tobacco metals was assessed with fuzzy theory and RSLF. • Cd and As need priority control and cigarette consumption limits of brands are 1–4/d. [ABSTRACT FROM AUTHOR]

A photonic crystal Gires–Tournois interferometer (PCGTI) based on the self-collimation effect in two-dimensional photonic crystal (PC) is proposed and numerically investigated using finite-difference time-domain (FDTD) simulations. The PCGTI is composed of two 100% reflecting mirrors, a partially reflecting mirror and a beam splitter. Both of hole-type and rod-type PCGTIs have rectangular-shaped transmission spectra. So, they can work as bandpass/bandstop filters with appropriate structure parameters. If the central normalized frequency corresponds to 1550 nm , the TE bandpass and bandstop bandwidths for the hole-type PCGTI are 15 nm and 18 nm respectively, while the TM bandpass and bandstop bandwidths for the rod-type PCGTI are both 20 nm. As its size is on the order of 10 micrometers, the PCGTI may have potential applications in the future photonic integrated circuits. • We are the first to propose the design of Gires–Tournois interferometer (GTI) based on the self-collimation (SC) phenomenon in two-dimensional photonic crystals. • Both of hole-type and rod-type PCGTIs have rectangularshaped transmission spectra. So they can work as bandpass/bandstop filters with appropriate structure parameters. • As its size is on the order of 10 micrometers, the PCGTI may have potential applications in the future photonic integrated circuits. [ABSTRACT FROM AUTHOR]

China is home to the world's largest cigarette maker, and with more than 320 million smokers, accounts for a fifth of world annual deaths from smoking-related diseases. Basic tobacco characteristics and its lead (Pb) and cadmium (Cd) contents of the 20 best-selling Chinese cigarette brands were detected using wet digestion-inductively coupled plasma mass spectrometry. Pb and Cd contents of the selected brands of cigarettes ranged from 1.3861 μg/g to 7.7124 μg/g and 2.9137 μg/g to 5.4841 μg/g, respectively, showing a significant correlation with tobacco weight per cigarette. Fuzzy health risk assessment via inhaling pathway of mainstream smoke was carried out for Pb and Cd based on the regional exposure parameters and fuzzification of the key variables. Results indicated the indexes of (non-)carcinogenic risk of tobacco Pb in all studied brands were below the corresponding general acceptable risk criteria, while that of tobacco Cd exceeded. Cd was identified as the priority control metal in the studied cigarettes. Moreover, the maximum membership probabilities of E08, E09, S11, S18 and S19 were in marginal range of 50%–60%, showing existed uncertainties and possibly misleading decision-makers. Spatially, the carcinogenic risks posed by regional cigarette Cd showed a relatively high level in the Southern, Southwestern and Northern China. Based on Level II for carcinogenic risk (1.00E-05), the limit daily consumption and limit concentration of Cd were obtained for each brand, and the result ranges were generally 2–4 cigarettes per day and 0.5–1.7 μg/g. Presently, it is of significance for the related international/local decision-makers to establish a comprehensive supervisory framework and system for Cd (and other typical toxic metals) in cigarettes from its life cycle perspective. Image 1 • 20 best-selling cigarette brands across the Chinese six regions were investigated. • Smoking health risk posed by tobacco Pb and Cd was assessed with fuzzy theory. • Cd in the selected cigarettes was found to pose certain health threats to smokers. • Regional limit concentrations for Cd were established on health risk guidelines. • Daily consumption limits were recommended according to the different brands. [ABSTRACT FROM AUTHOR]

The authors design a photonic crystal Mach-Zehnder interferometer by utilizing the self-collimated beams and the bending and splitting mechanisms of line defects. Using this interferometer, they investigate the phase shift of the reflected and transmitted self-collimated beams over the line defects. In addition, on the basis of the intensity-asymmetric unidirectional-output design, they demonstrate that such interferometers can function as an intensity detector or an ultrafast optical switch when the material of photonic crystal is nonlinear. [ABSTRACT FROM AUTHOR]

We investigated whether glutamate receptor subunit 2 (GluR2) is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice. Two hours after electric acupuncture (EA) pretreatment, global cerebral ischemia (GCI) was induced by bilateral common carotid artery occlusion (BCCAO) for 20 min. The GluR2 expression was examined in the hippocampus after reperfusion. Cell survival, neuronal apoptosis, the Bax/Bcl-2 ratio and neurological scores were evaluated at 24 h after BCCAO in the presence or absence of the GluR2 inhibitor. Furthermore, the GluR2 was determined in the presence and absence of CB1R inhibitor. Our results showed EA pretreatment enhanced expression of GluR2 in the hippocampus 2 h after reperfusion. Moreover, EA pretreatment improved neurological outcome, promoted cell survival, inhibited neuronal apoptosis, and decreased the Bax/Bcl-2 ratio after reperfusion. GluR2 knockdown by GluR2 siRNA effectively reversed the beneficial effects of EA pretreatment. Furthermore, CB1R siRNA and two CB1R antagonists blocked the elevation of GluR2 expression by EA pretreatment, whereas the two CB1R agonists up-regulated GluR2 expression as EA pretreatment. In conclusion, GluR2 up-regulation is involved in neuroprotection of EA pretreatment against GCI through CB1R, suggesting that GluR2 may be a novel target for stroke intervention. [ABSTRACT FROM AUTHOR]