This paper presents an experimental study on rolling shear (RS) strength properties of non-edge-glued cross-laminated timber (CLT) made out of New Zealand Radiata pine (
Pinus radiata
) structural ...timber. CLT specimens with 35 and 20 mm thick laminations were studied to evaluate the influence of lamination thickness on the RS strength of CLT. Short-span three-point bending tests were used to introduce high RS stresses in cross layers of CLT specimens and facilitate the RS failure mechanism. Modified planar shear tests from the conventional two-plate planar shear tests were also used to evaluate the RS strength properties. It was found that two test methods yielded comparable RS strength properties and the lamination thickness significantly affected RS strength of the CLT specimens. The test results also indicated that the recommended characteristic RS strength values of CLT products in Europe and Canada might be over conservative. Also, it might be more efficient to specify different RS strength values for CLT with different lamination thickness given the minimum width-to-depth ratio of laminations is satisfied.
Cyclic GMP-AMP (cGAMP) synthase (cGAS) detects infections or tissue damage by binding to microbial or self DNA in the cytoplasm
. Upon binding DNA, cGAS produces cGAMP that binds to and activates the ...adaptor protein STING, which then activates the kinases IKK and TBK1 to induce interferons and other cytokines
. Here we report that STING also activates autophagy through a mechanism that is independent of TBK1 activation and interferon induction. Upon binding cGAMP, STING translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and the Golgi in a process that is dependent on the COP-II complex and ARF GTPases. STING-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis. cGAMP induced LC3 lipidation through a pathway that is dependent on WIPI2 and ATG5 but independent of the ULK and VPS34-beclin kinase complexes. Furthermore, we show that cGAMP-induced autophagy is important for the clearance of DNA and viruses in the cytosol. Interestingly, STING from the sea anemone Nematostella vectensis induces autophagy but not interferons in response to stimulation by cGAMP, which suggests that induction of autophagy is a primordial function of the cGAS-STING pathway.
The discovery of cancer immune surveillance and immunotherapy has opened up a new era of cancer treatment. Immunotherapies modulate a patient's immune system to specifically eliminate cancer cells; ...thus, it is considered a very different approach from classic cancer therapies that usually induce DNA damage to cause cell death in a cell-intrinsic manner. However, recent studies have revealed that classic cancer therapies such as radiotherapy and chemotherapy also elicit antitumor immunity, which plays an essential role in their therapeutic efficacy. The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the downstream effector Stimulator of Interferon Genes (STING) have been determined to be critical for this interplay. Here, we review the antitumor roles of the cGAS-STING pathway during tumorigenesis, cancer immune surveillance, and cancer therapies. We also highlight classic cancer therapies that elicit antitumor immune responses through cGAS activation.
Organophosphate flame retardants (OPFRs) have been detected in various environmental matrices and have been identified as emerging contaminants (EC). Given the adverse influence of OPFRs, many ...researchers have focused on the absorption, bioaccumulation, metabolism, and internal exposure processes of OPFRs in animals and humans. This paper first reviews the evolution of various types of flame retardants (FRs) and the environmental pollution of OPFRs, the different absorption pathways of OPFRs by animals and humans (such as inhalation, ingestion, skin absorption and absorption), and then summarizes the environmental impacts of OPFRs, including their biological toxicity, bioaccumulation, persistence, migration, endocrine disruption and carcinogenicity. Based on limited available data and results, this study also summarizes the bioaccumulation and biomagnification potential of OPFRs in different types of biological and food nets. In addition, a new governance idea for the replacement of existing OPFRs from the source is proposed, seeking environmentally friendly alternatives to OPFRs in order to provide new ideas and theoretical guidance for the removal of OPFRs.
Xinnaotongluo liquid has been used to improve the clinical symptoms of patients with myocardial infarction. However, the molecular mechanism of Xinnaotongluo liquid is not completely understood. H9c2 ...cells exposed to hypoxia/reoxygenation (H/R) was used to simulate damage to cardiomyocytes in myocardial infarction in vitro. The biological indicators of H9c2 cells were measured by cell counting kit-8, enzyme linked immunoabsorbent assay, and western blot assay. In H/R-induced H9c2 cells, a markedly reduced murine double minute 2 (MDM2) was observed. However, the addition of Xinnaotongluo liquid increased MDM2 expression in H/R-induced H9c2 cells. And MDM2 overexpression strengthened the beneficial effects of Xinnaotongluo liquid on H9c2 cells from the perspective of alleviating oxidative damage, cellular inflammation, apoptosis and ferroptosis of H/R-induced H9c2 cells. Moreover, MDM2 overexpression reduced the protein expression of p53 and Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3). Whereas, STEAP3 overexpression hindered the function of MDM2-overexpression in H/R-induced H9c2 cells. Our results insinuated that Xinnaotongluo liquid could protect H9c2 cells from H/R-induced damage by regulating MDM2/STEAP3, which provide a potential theoretical basis for further explaining the working mechanism of Xinnaotongluo liquid.
•A numerical model of propane condensation in a minichannel was proposed and verified.•The effect of inclined angle on heat transfer and frictional pressure drop was analyzed.•The refrigerant charge ...of R290 in different inclined minichannels was analyzed.•Flow pattern is less effected by inclined angle and more effected by mass flux.•Refrigerant charge of R290 in vertical pipe is 8% lower than that in horizontal one.
As an ideal pollution-free refrigerant, R290 has been acceleratingly widely used. It is important to enhance the heat transfer performance and decrease the refrigerant charge of R290 in heat exchangers for its flammable and explosive properties. For this purpose, the research on condensation flow and refrigerant charge of R290 in a minichannel with different inclined angles is numerically carried out to obtain the optimal inclined angle. In the simulation, the VOF multiphase flow model and SST k−ω turbulence model are used for transient calculation, and the effect of surface tension is analyzed. The results show that as the inclined angle increases, heat transfer coefficient and frictional pressure drop increase. For heat transfer coefficient and refrigerant charge, the optimal inclined angle is 90° (downward flow), which is different from the existing results of R134a in a large channel. When G = 100, 200 kg/(m2s), at high vapor quality (x>0.8), heat transfer coefficient and frictional pressure drop almost do not increase with the increase of vapor quality. With the increase of inclined angle and mass flux, the refrigerant charge of R290 in a minichannel shows a downward trend. The maximum reduction is about 8% under the same heat transfer rate and heat transfer temperature difference. Therefore, changing the inclined angle is an effective approach to reduce the refrigerant charge of R290 in minichannel heat exchangers.
Esophageal squamous cell cancer (ESCC) is the major pathologic type of esophageal cancer in Asian population. To systematically evaluate the mutational features underlying clinical characteristics, ...we establish the integrated dataset of ESCC-META that consists of 1930 ESCC genomes from 33 datasets. The data process pipelines lead to well homogeneity of this integrated cohort for further analysis. We identified 11 mutational signatures in ESCC, some of which are related to clinical features, and firstly detect the significant mutated hotspots in TGFBR2 and IRF2BPL. We screen the survival related mutational features and found some genes had different prognostic impacts between early and late stage, such as PIK3CA and NFE2L2. Based on the results, an applicable approach of mutational score is proposed and validated to predict prognosis in ESCC. As an open-sourced, quality-controlled and updating mutational landscape, the ESCC-META dataset could facilitate further genomic and translational study in this field.
Shape morphing of stimuli‐responsive composite hydrogels has received considerable attention in different research fields. Although various multilayer structures with dissimilar materials are studied ...to achieve shape morphing, combining swellable hydrogel layers with non‐swellable layers results in issues with interface adhesion and structural integrity. In this study, single‐hydrogel‐based bilayer actuators comprising poly(N‐isopropylacrylamide) (PNIPAM) matrices and graphene oxide (GO)–PNIPAM hinges are presented. Upon temperature rising, the PNIPAM hydrogel acts as the passive layer due to the formation of dense microstructures near the surface (i.e., the skin layer effect), whereas the GO‐PNIPAM hydrogel functions as the active layer, maintaining porous due to structural modification by the presence of GO. Under light exposure, the GO‐PNIPAM hinges experience selective heating due to the photothermal effect of GO. Consequently, the resulting bilayer structures exhibit programmable dual‐responsive 3D shape morphing. Additionally, the folding kinetics of these actuators can be adjusted based on the applied stimulus (temperature changes or light), as they are driven by different mechanisms, the skin layer, or photothermal effects, respectively. Furthermore, the hinge‐based bilayer structures demonstrate walking and steering locomotion by light exposure. This approach can lead to advances in soft robotics, biomimetic systems, and autonomous soft actuators in hydrogel‐based systems.
The hinge‐based bilayer structures consisting of multi‐stimuli‐responsive hydrogel‐based hinges and a temperature‐responsive hydrogel matrix can undergo self‐folding upon heating and light exposure. The folding angles and kinetics of the bilayer structure are controlled by the geometry of the hinge and different external stimuli, respectively. Furthermore, this single‐hydrogel‐based bilayer structure demonstrates walking and steering locomotion as autonomous actuators and soft robots.
The current trade war between the United States and China is unprecedented in modern history. This study introduces a database of tariff increases resulting from the trade war and quantifies the ...impacts using the canonical GTAPinGAMS model calibrated to the recently released GTAP version 10 accounts. We find that the remaining tariff increases as of March 2020 after the phase one trade deal decrease welfare in China by 1.7% and welfare in the United States by 0.2%. Impacts on sectoral revenue are reported for both countries. China's exports to and imports from the United States are reduced by 52.3% and 49.3%. The trade flow between the United States and China will be diverted to their major trade partners resulting in higher welfare in those countries, including many Asian countries. The estimated impacts are robust to using alternative trade elasticities and are amplified in the absence of the phase one tariff reductions.
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