1,3-Dibenz­yloxy-5-(bromo­meth­yl)benzene

In the title compound, C21H19BrO2, the dihedral angles between the central benzene ring and the two peripheral rings are 50.28 (5) and 69.75 (2)°. The O—CH2 bonds lie in the plane of the central ring and adopt a syn–anti conformation

Hydrogels enable negative pressure in water for efficient heat utilization and transfer

Metastable water in negative pressure can provide giant passive driving pressure up to several megapascals for efficient evaporation-driven flow, however, the practical applications with negative pressure are rare due to the challenges of generating and maintaining large negative pressure. In this work, we report a novel structure with thin hydrogel films as evaporation surfaces and robust porous substrates as the supports, and obtain a high negative pressure of -1.61 MPa through water evaporation. Molecular dynamics simulations elucidate the essential role of strong interaction between water molecules and polymer chains in generating the negative pressure. With such a large negative pressure, we demonstrate a streaming potential generator that spontaneously converts environmental energy into electricity and outputs a voltage of 1.06 V. Moreover, we propose a "negative pressure heat pipe" for the first time, which achieves a high heat transfer density of 11.2 kW cm-2 with a flow length of 1 m, showing the potential of negative pressure in efficient heat utilization and transfer.Comment: 43 pages, 18 figure

An Oseen Two-Level Stabilized Mixed Finite-Element Method for the 2D/3D Stationary Navier-Stokes Equations

We investigate an Oseen two-level stabilized finite-element method based on the local pressure projection for the 2D/3D steady Navier-Stokes equations by the lowest order conforming finite-element pairs (i.e., Q1−P0 and P1−P0). Firstly, in contrast to other stabilized methods, they are parameter free, no calculation of higher-order derivatives and edge-based data structures, implemented at the element level with minimal cost. In addition, the Oseen two-level stabilized method involves solving one small nonlinear Navier-Stokes problem on the coarse mesh with mesh size H, a large general Stokes equation on the fine mesh with mesh size h=O(H)2. The Oseen two-level stabilized finite-element method provides an approximate solution (uh,ph) with the convergence rate of the same order as the usual stabilized finite-element solutions, which involves solving a large Navier-Stokes problem on a fine mesh with mesh size h. Therefore, the method presented in this paper can save a large amount of computational time. Finally, numerical tests confirm the theoretical results. Conclusion can be drawn that the Oseen two-level stabilized finite-element method is simple and efficient for solving the 2D/3D steady Navier-Stokes equations

The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, lacking effective therapy. Many TNBCs show remarkable response to carboplatin-based chemotherapy, but often develop resistance over time. With increasing use of carboplatin in the clinic, there is a pressing need to identify vulnerabilities of carboplatin-resistant tumors. In this study, we generated carboplatin-resistant TNBC MDA-MB-468 cell line and patient derived TNBC xenograft models. Mass spectrometry-based proteome profiling demonstrated that carboplatin resistance in TNBC is linked to drastic metabolism rewiring and upregulation of anti-oxidative response that supports cell replication by maintaining low levels of DNA damage in the presence of carboplatin. Carboplatin-resistant cells also exhibited dysregulation of the mitotic checkpoint. A kinome shRNA screen revealed that carboplatin-resistant cells are vulnerable to the depletion of the mitotic checkpoint regulators, whereas the checkpoint kinases CHEK1 and WEE1 are indispensable for the survival of carboplatin-resistant cells in the presence of carboplatin. We confirmed that pharmacological inhibition of CHEK1 by prexasertib in the presence of carboplatin is well tolerated by mice and suppresses the growth of carboplatin-resistant TNBC xenografts. Thus, abrogation of the mitotic checkpoint by CHEK1 inhibition re-sensitizes carboplatin-resistant TNBCs to carboplatin and represents a potential strategy for the treatment of carboplatin-resistant TNBCs

Stress-induced lncRNA LASTR fosters cancer cell fitness by regulating the activity of the U4/U6 recycling factor SART3

Dysregulated splicing is a common event in cancer even in the absence of mutations in the core splicing machinery. The aberrant long non-coding transcriptome constitutes an uncharacterized level of regulation of post-transcriptional events in cancer. Here, we found that the stress-induced long non-coding RNA (lncRNA), LINCO2657 or LASTR (lncRNA associated with SART3 regulation of splicing), is upregulated in hypoxic breast cancer and is essential for the growth of LASTR-positive triple-negative breast tumors. LASTR is upregulated in several types of epithelial cancers due to the activation of the stress-induced JNK/c-JUN pathway. Using a mass-spectrometry based approach, we identified the RNA-splicing factor SART3 as a LASTR-interacting partner. We found that LASTR promotes splicing efficiency by controlling SART3 association with the U4 and U6 small nuclear ribonucleoproteins (snRNP) during spliceosome recycling. Intron retention induced by LASTR depletion downregulates expression of essential genes, ultimately decreasing the fitness of cancer cells

Effect of night shift work on metabolic syndrome in adults who suffered from earthquake stress in early life

ObjectiveTo examine the role of night shift work on the risk of metabolic syndrome (MetS) in adults suffered from earthquakes prenatally or as infants and to analyse the effect of stress on factors that influence MetS in this population.MethodsWe included 870 subjects from 2014 to 2015. All subjects work as miners for the Kailuan Mining Group and were born were living in Tangshan. Participants were classified into two groups on basis of their work schedules: day shift and night shift. They were further classified into the prenatal exposure group, the infancy exposure group, and the control group based on their age during the Tangshan earthquake. This study was conducted 38 years after the earthquake. Participants’ general demographic data, smoking and drinking habits, as well as work schedules were collected. All participants’ sleep status was assessed with the Pittsburgh Sleep Quality Index. The measurement of all subjects’ waist circumference and blood pressure was made, and triglycerides, fasting blood glucose, high-density lipoproteins, and low-density lipoproteins were measured by collecting blood samples. The definition of MetS was made after the guidelines for preventing and controlling type 2 diabetes in China (2017 Edition).ResultsA total of 187 (21.5%) workers were determined to have MetS. The incidence of MetS was greatly higher in night shift workers who were exposed to an earthquake during infancy than in day shift workers (χ2 = 8.053, p = 0.005). A multivariate logistic regression analysis displayed male participants had a higher risk develop MetS than female participants (p = 0.042, OR = 0.368, 95% CI = 0.140, 0.965). Current smokers (p = 0.030, OR = 1.520, 95%CI = 1.042, 2.218) and participants who sleep fewer than 7 h per night (p = 0.015, OR = 1.638, 95%CI = 1.101, 2.437) had a higher risk of MetS. Prenatal earthquake stress was also a risk element for MetS (p = 0.012, OR = 1.644, 95%CI = 1.115, 2.423).ConclusionThe risk of MetS is significantly higher in night shift workers exposed to earthquake stress during infancy than day shift workers. Earthquake exposure during pregnancy is an independent risk factor for MetS. Smoking and sleeping less than 7 h have a higher risk of MetS than the control group

Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States

Objectives: To evaluate excess deaths of gastrointestinal, liver, and pancreatic diseases in the United States during the COVID-19 pandemic.Methods: We retrieved weekly death counts from National Vital Statistics System and fitted them with a quasi-Poisson regression model. Cause-specific excess deaths were calculated by the difference between observed and expected deaths with adjustment for temporal trend and seasonality. Demographic disparities and temporal-spatial patterns were evaluated for different diseases.Results: From March 2020 to September 2022, the increased mortality (measured by excess risks) for Clostridium difficile colitis, gastrointestinal hemorrhage, and acute pancreatitis were 35.9%; 24.8%; and 20.6% higher than the expected. For alcoholic liver disease, fibrosis/cirrhosis, and hepatic failure, the excess risks were 1.4–2.8 times higher among younger inhabitants than older inhabitants. The excess deaths of selected diseases were persistently observed across multiple epidemic waves with fluctuating trends for gastrointestinal hemorrhage and fibrosis/cirrhosis and an increasing trend for C. difficile colitis.Conclusion: The persistently observed excess deaths of digestive diseases highlights the importance for healthcare authorities to develop sustainable strategies in response to the long-term circulating of SARS-CoV-2 in the community

Is Asthma Related to Choroidal Neovascularization?

BACKGROUND: Age-related degeneration (AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. PRINCIPAL FINDINGS: The epidemiological study showed that asthma was related to choroidal neovascularization (CNV) subtype (OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α'-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. SIGNIFICANCE: This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice