Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.

PdRh-Sensitized Iron Oxide Ultrathin Film Sensors and Mechanistic Investigation by Operando TEM and DFT Calculation.

Metal oxide semiconductor (MOS) thin films are of critical importance to both fundamental research and practical applications of gas sensors. Herein, a high-performance H2 sensor based on palladium (Pd) and rhodium (Rh) co-functionalized Fe2 O3 films with an ultrathin thickness of 8.9 nm deposited by using atomic layer deposition is reported. The sensor delivers an exceptional response of 105.9 toward 10 ppm H2 at 230 °C, as well as high selectivity, immunity to humidity, and low detection limit (43 ppb), which are superior to the reported MOS sensors. Importantly, the Fe2 O3 film sensor under dynamic H2 detection is for the first time observed by operando transmission electron microscopy, which provides deterministic evidence for structure evolution of MOS during sensing reactions. To further reveal the sensing mechanism, density functional theory calculations are performed to elucidate the sensitization effect of PdRh catalysts. Mechanistic studies suggest that Pd promotes the adsorption and dissociation of H2 to generate PdHx , while Rh promotes the dissociation of oxygen adsorbed on the surface, thereby jointly promoting the redox reactions on the films. A wireless H2 detection system is also successfully demonstrated using the thin film sensors, certifying a great potential of the strategy to practical sensors.

CYD0281, a Bcl-2 BH4 domain antagonist, inhibits tumor angiogenesis and breast cancer tumor growth.

BACKGROUND: B-cell lymphoma 2 (Bcl-2) family proteins are key regulators of apoptosis, which possess four conserved Bcl-2 homologies (BH) domains. Among the BH domains, the BH3 domain is considered as a potent 'death domain' while the BH4 domain is required for anti-apoptotic activity. Bcl-2 can be converted to a pro-apoptotic molecule through the removal or mutation of the BH4 domain. Bcl-2 is considered as an inducer of angiogenesis, which can promote tumor vascular network formation and further afford nutrients and oxygen to promote tumor progression. However, whether disrupting the function of the BH4 domain to convert Bcl-2 into a pro-apoptotic molecule could make Bcl-2 possess the potential for anti-angiogenic therapy remains to be defined. METHODS: CYD0281 was designed and synthesized according to the lead structure of BDA-366, and its function on inducing a conformational change of Bcl-2 was further evaluated via immunoprecipitation (IP) and immunofluorescence (IF) assays. Moreover, the function of CYD0281 on apoptosis of endothelial cells was analyzed via cell viability, flow cytometry, and western blotting assays. Additionally, the role of CYD0281 on angiogenesis in vitro was determined via endothelial cell migration and tube formation assays and rat aortic ring assay. Chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models, breast cancer cell xenograft tumor on CAM and in mouse models as well as the Matrigel plug angiogenesis assay were used to explore the effects of CYD0281 on angiogenesis in vivo. RESULTS: We identified a novel potent small-molecule Bcl-2-BH4 domain antagonist, CYD0281, which exhibited significant anti-angiogenic effects both in vitro and in vivo, and further inhibited breast cancer tumor growth. CYD0281 was found to induce conformational changes in Bcl-2 through the exposure of the BH3 domain and convert Bcl-2 from an anti-apoptotic molecule into a cell death inducer, thereby resulting in the apoptosis of vascular endothelial cells. CONCLUSIONS: This study has revealed CYD0281 as a novel Bcl-2-BH4 antagonist that induces conformational changes of Bcl-2 to convert to a pro-apoptotic molecule. Our findings indicate that CYD0281 plays a crucial role in anti-angiogenesis and may be further developed as a potential anti-tumor drug candidate for breast cancer. This work also provides a potential anti-angiogenic strategy for breast cancer treatment.

Emerging single atom catalysts in gas sensors.

Single atom catalysts (SACs) offer unprecedented opportunities for high-efficiency reactions taking place in many important fields of catalytic processes, electrochemistry, and photoreactions. Due to their maximized atomic utilization and unique electronic and chemical properties, SACs can provide high activity and excellent selectivity for gas adsorption and electron transport, leveraging SACs that enhance the detection sensitivity and selectivity to target gases. In the past few years, SACs including both noble (Pt, Pd, Au, etc.) and non-noble (Mn, Ni, Zn etc.) metals have been demonstrated to be very useful in optimizing sensing performances. However, a comprehensive review on this topic is still missing. Herein, we summarize the synthesis technologies of SACs that are applicable to gas sensors. The electronic and chemical interactions between SACs and host sensing materials, which are crucial to sensor functions, are discussed. Then, we highlight the application progress of various SACs in gas sensors. Prospects in the creation of new sensing materials with emerging SACs and versatile supports are also present. Finally, the challenges and prospects of SACs in the future development of sensors are analyzed.

EPAC inhibitor suppresses angiogenesis and tumor growth of triple-negative breast cancer.

AIMS: Exchange protein directly activated by cAMP 1 (EPAC1), a major isoform of guanine nucleotide exchange factors, is highly expressed in vascular endothelia cells and regulates angiogenesis in the retina. High intratumor microvascular densities (MVD) resulting from angiogenesis is responsible for breast cancer development. Downregulation of EPAC1 in tumor cell reduces triple-negative breast cancer (TNBC)-induced angiogenesis. However, whether Epac1 expressed in vascular endothelial cells contributes to angiogenesis and tumor development of TNBC remains elusive. MAIN METHODS: We employed NY0123, a previously identified potent EPAC inhibitor, to explore the anti-angiogenic biological role of EPAC1 in vitro and in vivo through vascular endothelial cells, rat aortic ring, Matrigel plug, and chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) assays, as well as the in vivo xenograft tumor models of TNBC in both chick embryo and mice. KEY FINDINGS: Inhibiting EPAC1 in vascular endothelial cells by NY0123 significantly suppresses angiogenesis and tumor growth of TNBC. In addition, NY0123 possesses a better inhibitory efficacy than ESI-09, a reported specific EPAC inhibitor tool compound. Importantly, inhibiting EPAC1 in vascular endothelia cells regulates the typical angiogenic signaling network, which is associated with not only vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR2) signaling, but also PI3K/AKT, MEK/ERK and Notch pathway. CONCLUSIONS: Our findings support that EPAC1 may serve as an effective anti-angiogenic therapeutic target of TNBC, and EPAC inhibitor NY0123 has the therapeutic potential to be developed for the treatment of TNBC.

Smartphone-based interventions in the secondary prevention of cardiovascular disease: A meta-analysis.

BACKGROUND: A variety of reviews have indicated the effectiveness of smartphone-based interventions in preventing secondary cardiovascular disease (CVD). However, few studies have focused on clinical outcomes. OBJECTIVE: This meta-analysis aimed to evaluate the potential benefits of application interventions and short message service (SMS) interventions on CVD outcomes. METHODS: Electronic databases were searched to identify randomized controlled trials (RCT) investigating an application or SMS intervention for secondary CVD prevention. Primary outcomes included major adverse cardiovascular events (MACE), cardiovascular death, and cardiac hospitalization. Secondary outcomes were cardiovascular risk factors (BMI, blood pressure, and cholesterol). RESULTS: A total of 26 RCTs were included, with 16 investigating applications and 10 assessing SMS. Overall, there was no significant difference in MACE, cardiovascular death, and cardiac hospitalization when comparing application interventions with usual care, as well as comparing SMS with usual care. Subgroup analysis revealed that patients who received applications without a medical interface had a significantly lower incidence of MACE (OR = 0.56; 95% CI: 0.33, 0.98). Participants who received applications with a medical interface showed a tendency towards higher rates of cardiac hospitalization (OR = 2.03; 95% CI: 0.85, 4.87). Significant reduction in waist circumference (SMD =-0.80; 95% CI: -1.58, -0.03) was found in application interventions compared to usual care; while significant reductions in SBP (SMD =-0.08; 95% CI: -0.15, -0.01) and TC (SMD =-0.31; 95% CI: -0.57, -0.08) were found in SMS interventions compared to usual care. CONCLUSION: Smartphone-based interventions, including applications and SMS, have the potential to benefit the secondary prevention of CVD. Applications may reduce the incidence of cardiovascular-related adverse events, while SMS interventions may improve cardiovascular risk factors.

Social App to Improve Warfarin Therapy in Post-MHVR Chinese Patients: A Randomized Controlled Trial.

Background: Poor anticoagulation quality was a major problem among warfarin-treated patients, which called for innovative and effective methods to improve it. Objective: To investigate whether social app could be used to reduce warfarin-associated adverse events among post-MHVR Chinese patients. Method: 735 warfarin-treated patients (aged 50.8 ± 9.6 years, 59.9% female) were enrolled and randomized to a social app care group (warfarin therapy was guided by experienced clinicians via a social app) or a routine care group (warfarin therapy was managed through traditional in-office visits) at a 1 : 1 ratio. Ending points (bleeding and thrombotic events) were recorded during an 18-month follow-up period. Results: A total of 718 patients were included in analysis. 57 of them suffered warfarin-associated adverse events, including 30 major bleedings and 27 thrombotic events. The time in the therapeutic range (TTR, Rosendaal method) in the social app group was 71.5%, which was significantly better than 52.6% in the routine care group (difference: 18.8%, 95% CI: 16.8-20.8). Compared with the patients from the social app group, patients under routine care experienced more bleeding (hazard ratio (HR): 2.31, 95% CI: 1.13-4.72). The social app care group had lower variation (0.55 vs. 0.70) in the international normalized ratio (INR) values and fewer incidents of extremely high INR (e.g., INR > 5.0, 0.87% vs. 3.42%) than the routine care group. Conclusions: Social app management could significantly improve warfarin control and was associated with a reduction in bleeding risk. This trial was registered with NCT03264937.

Skipping Breakfast Is Associated with Hypertension in Adults: A Meta-Analysis.

Previous studies evaluating the association between skipping breakfast and hypertension in adult population showed inconsistent results. We performed a meta-analysis to systematically evaluate the association. Observational studies which evaluated the relationship between skipping breakfast and hypertension in adult population with multivariate analyses were identified by systematic search of PubMed, Embase, and Web of Science databases. A random-effect model which incorporated the potential intrastudy heterogeneity was used for the meta-analysis. A total of six observational studies with 14189 adults were included, and 3577 of them were breakfast skippers. Pooled results showed that skipping breakfast was independently associated with hypertension in these populations (adjusted odds ratio (OR): 1.20, 95% confidence interval: 1.08 to 1.33, P < 0.001) with no significant heterogeneity (I 2 = 0%). Sensitivity by excluding one study at a time showed consistent results (OR: 1.18 to 1.22, all P <0.01). Subgroup analyses showed that the association between skipping breakfast and hypertension in adults was consistent in the general population and in patients with type 2 diabetes, in studies from different countries, in cohort and cross-sectional studies, in breakfast skippers defined as taking breakfast ≤3 days/week and as self-reported habitual breakfast skipping, and in studies with and without adjustment of body mass index (Pfor subgroup difference, all P>0.10). In conclusion, skipping breakfast is associated with hypertension in the adult population.

Comparing the efficacy and safety of tenofovir and adefovir or combined drug treatment for the treatment of chronic hepatitis B infection: a systematic review and meta-analysis.

Background: Chronic hepatitis B (CHB) affects a vast population globally. A variety of drugs are available for the treatment of CHB, including tenofovir (TDF) and adefovir (ADV). However, the efficacy of monotherapy drug treatment is inconclusive, the safety and efficacy of TDF remain unclear, more data are needed to be included and combined drug treatment is considered to exhibit higher efficacy. To explore this issue, we performed a current literature review and meta-analysis to compare the efficacy and safety of ADV vs. TDF, TDF vs. ADV + lamivudine (LAM); TDF vs. ADV + entecavir (ETV). Methods: We systematically searched China National Knowledge Infrastructure, the Cochrane Library, Embase, PubMed, Chinese VIP, and Wanfang Data, for relevant clinical trials since July 2015, all included studies were based on PICOS principles and evaluated independently by the reviewers in accordance with the Cochrane Handbook (Rob2.0). A meta-analysis was performed by using Review Manager 5.4. Results: We included a total of 32 studies, including 31 randomized controlled trials and one retrospective study involving 2,473 patients. The results revealed a low risk of bias in included studies, that the virologic response of TDF was superior to ADV (P<0.05). And TDF was also superior to ADV in Serum creatinine levels, Immunologic function, and safety profile. However, when ADV was combined with other medications, it was superior to TDF in alanine aminotransferase (ALT) level and Tbil level and adverse reactions, but on other indicators, TDF was superior to drug combination therapy. Conclusions: Results showed that TDF was superior to ADV in the parameters of ALT, hepatitis B virus (HBV)-DNA reduction, HBeAg-negative conversion rate, safety, and total bilirubin levels in patients with CHB. However, when ADV was combined with LAM or ETV, they often showed the same therapeutic effect as TDF in parameters such as ALT level and Tbil level and combined therapy can effectively reduce the occurrence of adverse reactions. In this study, because the sample source countries were limited, a greater number of global studies are needed in the future to verify the current findings.

A Prognostics Method Based on Back Propagation Neural Network for Corroded Pipelines.

A method that employs the back propagation (BP) neural network is used to predict the growth of corrosion defect in pipelines. This method considers more diversified parameters that affect the pipeline's corrosion rate, including pipe parameters, service life, corrosion type, corrosion location, corrosion direction, and corrosion amount in a three-dimensional direction. The initial corrosion time is also considered, and, on this basis, the uncertainties of the initial corrosion time and the corrosion size are added to the BP neural network model. In this paper, three kinds of pipeline corrosion growth models are constructed: the traditional corrosion model, the corrosion model considering the uncertainties of initial corrosion time and corrosion depth, and corrosion model also considering the uncertainties of corrosion size (length, width, depth). The rationality and effectiveness of the proposed prediction models are verified by three case studies: the uniform model, the exponential model, and the gamma process model. The proposed models can be widely used in the prediction and management of pipeline corrosion.

Plasma-induced oxygen vacancies enabled ultrathin ZnO films for highly sensitive detection of triethylamine.

Metal oxide semiconductor (MOS) thin films hold great promise for electronic devices such as gas sensors. However, the low surface activity of pristine MOS often leads to inferior sensitivity and the sensitization mechanism of ultrathin MOS films has received rare attention. Herein, we report a high performance gas sensor based on plasma-etched ZnO thin films. The ultrathin ZnO films (20 nm) were deposited on SiO2 wafers by atomic layer deposition (ALD), which enables high-throughput production of sensor devices. The ZnO sensor shows typical n-type conductivity, which is highly variable to the exposure of triethylamine (TEA). Annealing temperature of the films is found to impact the sensor response, revealing calcination at a moderate temperature, i.e. 700 °C, leads to the best response. Further treatment by Ar plasma results in a remarkable decrease of sensor working temperature from 300 °C of untreated films to 250 °C and nearly 4-fold enhancement in the sensor response to 10 ppm TEA. Notably, the plasma-treated ZnO sensor also shows decent response even at room temperature (RT), which has been seldom reported for ZnO-based sensors. Structure and mechanism investigations reveal that the superior sensor properties are derived from the abundant oxygen vacancies generated by Ar plasma etching.