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Thermal barrier coatings, which are widely used in aero-engines and gas turbines, can reduce the surface temperature and improve the effective service time of superalloy due to low thermal conductivity and good temperature resistance. The performance and lifetime of the thermal barrier coating are directly affected by the material and structure of the ceramic top coating. The method of adjusting the microstructure of ceramic coating with controlled raw material powder can reduce the strain-stress mismatch in the coating, and has the advantages of flexible operation, remarkable effect and wide control range. In order to solve problems of low strain tolerance and insufficient thermal shock resistance in traditional coatings, our team successfully has prepared ceramic microspheres with hierarchy pore structure by using electrostatic spraying combined with phase inversion theory（ESP）. Compared with traditional hollow microspheres, the ESP microstructure of nano-pores and finger-like pores lead to high sintering resistance, low thermal conductivity, high specific strength and >95% thermal reflectivity. With the retention of the hierarchy structure, the coating has good fracture toughness and strain tolerance, where the thermal cycle life of the coating is increased by more than ~2 times. ESP technology provides a fast feedback control method for new thermal barrier coating materials from material design to engineering application, such as rare earth zirconate, rare earth tantalate and rare earth doped YSZ high entropy system. With the in-depth study of material mechanics, optics, thermodynamics and the precise control of internal topological structure, the hierarchy pore structure will be more widely used in aerospace, military defense, fluorescence temperature measurement and other fields in the future.

Abstract The landscape of current cancer immunotherapy is dominated by antibodies targeting PD-1/PD-L1 and CTLA-4 that have transformed cancer therapy, yet their efficacy is limited by primary and acquired resistance. The blockade of additional immune checkpoints, especially TIGIT and LAG-3, has been extensively explored, but so far only a LAG-3 antibody has been approved for combination with nivolumab to treat unresectable or metastatic melanoma. Here we report the development of a PDL1 × TIGIT bi-specific antibody (bsAb) GB265, a PDL1 × LAG3 bsAb GB266, and a PDL1 × TIGIT × LAG3 tri-specific antibody (tsAb) GB266T, all with intact Fc function. In in vitro cell-based assays, these antibodies promote greater T cell expansion and tumor cell killing than benchmark antibodies and antibody combinations in an Fc-dependent manner, likely by facilitating T cell interactions (bridging) with cancer cells and monocytes, in addition to blocking immune checkpoints. In animal models, GB265 and GB266T antibodies outperformed benchmarks in tumor suppression. This study demonstrates the potential of a new generation of multispecific checkpoint inhibitors to overcome resistance to current monospecific checkpoint antibodies or their combinations for the treatment of human cancers.

Collagen type I, commonly derived from xenogenic sources, is extensively used as a biomaterial for tissue engineering applications. However, the use of xenogenic collagen is typically associated with species specific variation in mechanical, structural, and biological properties that are known to influence cellular response and remodeling. In addition, immunological complications and risks of disease transmission are also major concerns. The goal of this study is to characterize a new xeno-free human skin-derived collagen and assess its applicability as a bioink for cell-laden 3 D bioprinting. Four different concentrations of human collagen (i.e., 0.5 mg/mL, 1 mg/mL, 3 mg/mL and 6 mg/mL) were employed for the synthesis of collagen hydrogels. In addition, bovine collagen was used as a xenogenic control. Results from SDS-PAGE analysis showed the presence of α1, α2, and β chains, confirming that the integrity of type I human collagen is maintained post isolation. Polymerization rate and compressive modulus increased significantly with increase in the concentration of human collagen. When comparing two different sources of collagen, the polymerization rate of xenogenic collagen was significantly faster (p < 0.05) than human collagen while the compressive modulus was comparable. Raman spectroscopy showed a large peak in the Amide I band around 1600 cm−1, indicating a dense and supraorganized fibrillar structure in human collagen hydrogels. Conversely, Amide I band intensity for xenogenic collagen was comparable to that of Amide II and Amide III bands. Further, the use of 6 mg/mL human collagen as a bioink yielded 3 D printed constructs with high shape fidelity and cell viability. On the other hand, xenogenic collagen failed to yield stable 3 D printed constructs. Together, the results from this study provides an impetus for using human-derived collagen as a viable alternative to xenogenic sources for 3 D bioprinting of clinically relevant scaffolds for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Pervious concrete is a three-phase structure, including the pore phase, aggregate phase and paste phase. Currently, the pore phase of pervious concrete can easily be identified with CT and image processing technology. However, there are still technical limitations to identifying the aggregate and paste phases. This paper aims to establish a three-phase structure analysis method for pervious concrete based on deep learning. 30 images of the cross section of nine groups of color-pervious concrete specimens with different coarse aggregate sizes were obtained to form the initial dataset. The initial dataset was preprocessed, labeled and extended, and four deep learning frameworks were selected to train the three-phase structure identification models. By comparing and analyzing the identification effects of different models, the model suitable for three-phase structure identification was determined. The segmentation accuracy of each phase was evaluated. The results show that the method for preparing the dataset required for three-phase structure identification model training could improve identification accuracy. The model can accurately identify the three-phase structure with fewer false and missed identifications. The descending order of three-phase structure identification accuracy was pore phase＞aggregate phase＞paste phase. This was related to the quality of the dataset and annotation accuracy. • A method for preparing the data set required for three-phase structure identification model training was proposed. • Models for identifying the three-phase structure of pervious concrete were trained. • The Mask R-CNN model was evaluated and compared with other models. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) of tissues is susceptible to modification by inflammation-associated oxidants. Considerable data support a role for hypochlorous acid (HOCl), generated by the leukocyte-derived heme-protein myeloperoxidase (MPO) in these changes. HOCl can modify isolated ECM proteins and cell-derived matrix, with this resulting in decreased cell adhesion, modulated proliferation and gene expression, and phenotypic changes. Whether this arises from free HOCl, or via site-specific reactions is unresolved. Here we examine the mechanisms of MPO-mediated changes to human coronary smooth muscle cell ECM. MPO is shown to co-localize with matrix fibronectin as detected by confocal microscopy, and bound active MPO can initiate ECM modification, as detected by decreased antibody recognition of fibronectin, versican and type IV collagen, and formation of protein carbonyls and HOCl-mediated damage. These changes are recapitulated by a glucose/glucose oxidase/MPO system where low continuous fluxes of H2O2 are generated. HOCl-induced modifications enhance MPO binding to ECM proteins as detected by ELISA and MPO activity measurements. These data demonstrate that MPO-generated HOCl induces ECM modification by interacting with ECM proteins in a site-specific manner, and generates alterations that increase MPO adhesion. This is proposed to give rise to an increasing cycle of alterations that contribute to tissue damage. [ABSTRACT FROM AUTHOR]

Background and purpose: Although observational studies have reported a positive association between depression and ischemic stroke, causality remains inconclusive. We aimed to assess the causal relationship of major depressive disorder (MDD) with ischemic stroke, especially with the small vessel stroke (SVS) subtype. Methods: We used 72 independent single-nucleotide polymorphisms associated with MDD in a genome-wide association study (GWAS) from the Psychiatric Genetics Consortium as instrumental variables. The corresponding data for ischemic stroke and its subtypes of European ancestry were available from the MEGASTROKE consortium of 34,217 ischemic stroke cases and 406,111 controls. Primary Mendelian randomization estimates were calculated with inverse-variance weighted method, and several alternate methods and multiple sensitivity analyses were also performed. Results: We found that genetic predisposition to higher risk of MDD was associated with higher risk of SVS, with an odds ratio of 1.33 (95% confidence interval, 1.08–1.65; p = 0.009) per log-odds increment in MDD risk, but not with large artery stroke (OR, 1.08; 95% CI 0.83–1.41; p = 0.559), cardioembolic stroke (OR, 0.98; 95% CI 0.80–1.20; p = 0.833), or all ischemic stroke (OR, 1.03; 95% CI 0.92–1.15; p = 0.633). The association of MDD with SVS was overall robust to sensitivity analyses. Conclusions: We provided evidence for a possible causal effect of MDD on increased risk of SVS. Future researches are required to investigate whether rational intervention on depression may help to reduce societal burden of SVS. [ABSTRACT FROM AUTHOR]

The development of early warning systems for landslide hazards has long been a challenge because the accuracy of such systems is limited by both the complicated underlying mechanisms of landslides and the lack of in situ data. In this study, we implemented a multivariate threshold criterion that integrates in situ monitoring data and data from unsaturated hydro-mechanical analyses as an early warning system for rainfall-induced landslides in the Wenchuan earthquake region of China. The results indicate that rainfall intensity is closely correlated with the probability of landslide occurrence. Variations in matric suction and suction stress were obtained from in situ measurements and used to quantify the soil water retention curve, which presented clear hysteresis characteristics. The impacts of rainfall infiltration on slope failure in post-earthquake landslide areas under transient rainfall conditions were quantified by hydro-mechanical modelling theories. Variations in the suction stress of unsaturated soil were used to calculate the safety factor. The influence of hydrological hysteresis processes on the slope failure mechanism was analysed. Multivariate threshold criteria that include the intensity–probability (I-P) threshold, soil moisture and matric suction based on in situ big data and unsaturated slope stability analysis benchmarks are proposed for use in an early warning system for rainfall-induced landslides. [ABSTRACT FROM AUTHOR]

Toppling failure is a common instability mode for counter-inclined slopes, but the failure mechanisms involved present an ongoing engineering challenge in the geotechnical field. This study analyzes the instability failure mode of large-scale toppling failure at a counter-inclined slope on the southwestern stope of the Changshanhao open-pit gold mine. An instability failure is found here that mainly comes through two forms; one is the flexural-toppling and vertical fractures that form due to induced toppling failure at front-edge faults, the other one is bending-toppling failure and vertical fractures that form in trailing-edge steeply dipping faults. A simple mechanical mechanism for toppling failure is then established based on superimposed cantilever beam theory. By applying the maximum tensile stress strength criterion of brittle failure, a computational formula is derived for the depth to which vertical fractures extend in counter-inclined toppling failure, taking the effect of blasting vibration load into account. The relationship between the structural parameters of a cantilever beamslice and slope stability under blasting vibration are investigated. Geophysical evidence for the depth of fracturing and the related failure mechanism is then obtained using the transient surface wave method. The results of this geophysical prospecting indicate that it is feasible to simplify the rock formation as a cantilever beam slice and investigate the toppling failure of a counter-inclined rock slope under blasting vibration load using a quasi-static method. The applicability of the present research to this region is thus validated, indicating that this approach can also provide useful input for other similar engineering applications. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) influences the structure and function of the arterial wall and modulates the behavior of vascular cells through ECM-cell interactions. Alterations to the ECM have been implicated in multiple pathological processes, including atherosclerosis which is characterized by low-grade chronic inflammation and the infiltration and proliferation of smooth muscle cells during disease development. Considerable evidence has been presented for a role for inflammation-derived oxidation in atherogenesis, with enzymatically-active myeloperoxidase (MPO), elevated levels of 3-chlorotyrosine (a biomarker of MPO-catalyzed damage) and oxidized ECM materials detected in advanced human atherosclerotic lesions. Whether oxidant-modified ECM contributes to the altered behavior of smooth muscle cells is however unclear. This study therefore investigated the effects of hypochlorous acid (HOCl), a major MPO-derived oxidant, on the structure of the native ECM synthesized by human coronary artery smooth muscle cells (HCAMSCs) and whether modified ECM proteins affected HCASMC adhesion, proliferation and gene expression. Exposure of native HCASMC-derived ECM to reagent HOCl or a MPO-Cl--H 2 O 2 system resulted in extensive ECM modifications as evidenced by the loss of antibody recognition of epitopes on type IV collagen, laminin, versican and fibronectin. Oxidation of HCASMC ECM markedly reduced HCASMC adhesion to matrix components, but facilitated subsequent proliferation in vitro. Multiple genes were upregulated in HCASMCs in response to HOCl-modified HCASMC-ECM including interleukin-6 (IL-6), fibronectin (FN1) and matrix-metalloproteinases (MMPs). These data reveal a mechanism through which inflammation-induced ECM-modification may contribute to the behavioral switching of HCASMCs, a key process in plaque formation during the development of atherosclerosis. Image 1 • Atherosclerosis is characterized by chronic low grade inflammation and matrix modification. • Inflammation can drive oxidative modifications to matrix components. • Oxidation modulates smooth muscle cell-derived matrix composition and structure. • Oxidized matrix modulates smooth muscle cell adhesion, proliferation and gene expression. • Matrix oxidation can induce behavioral switching of smooth muscle cells. [ABSTRACT FROM AUTHOR]

【Objective】 Variation in crop yield is the consequence of many natural and anthropogenic factors, and disentangling their impacts is important for improving agricultural management but difficult. The purpose of this paper is to propose and compared different methods to isolate the impacts of meteorological change on crop yield based on long time series of maize yield in Yellow River-water irrigated region in Ninxia province of China. 【Method】 The analysis is based on maize yield measured from1988 to 2019 in 6 counties located in the Yellow River-watered irrigation areas. We compared three methods for the separation: five -year moving average method, quadratic exponential smoothing method, and five-point quadratic smoothing method. The consistent correlation coefficient, trend coincidence conformity analysis method, consistency of climate change characteristics, which lead to the same rise-fall in meteorological yield, were used as the evaluation criteria. Their applicability and rationality were compared and analyzed. All methods were calibrated based on the relationship between meteorological factors and maize yield. 【Result】 All methods can fit the yield trend well. Compared with the average yield trend, the consistency correlation coefficients of all three methods were >0.5, suggesting that there was no significant difference between these methods for fitting the yield trend. The advantage of the quadratic exponential smoothing method and the five-point quadratic smoothing method is that they accurately describe the change in the yield as affected by national productivity and national policy. The change in the yield due to meteorological factors estimated by the five-point quadratic smoothing method described the effect of inter-annual meteorological factors better, and its associated meteorological yield model is able to describe the relationship between the meteorological factors and the maize yield. 【Conclusion】 Comprehensive analysis showed that the five-point quadratic smoothing method modeled the yield change due to meteorological factors better than the other two methods.

Backgrounds: The incidence of melanosis coli (MC) has gradually increased annually, attracting significant attention and efforts into this field. A potential risk for MC is the long-term use of anthraquinone laxatives in patients with constipation. Most traditional cathartic drugs are made from herbs containing anthraquinone compounds. This review aims to provide guidance for the application of traditional Chinese herbs containing anthraquinones for physicians and researchers.Materials and methods: We reviewed risk factors and pathogenesis of MC, and natural anthraquinones isolated from TCM herbs. We searched Pubmed and CNKI databases for literature related to MC with keywords such as“traditional Chinese medicine”, “Chinese herbs”, “anthraquinones”, and “melanosis coli”. The literature is current to January 2023 when the searches were last completed. After the literature retrieval, the TCM herbs containing anthraquinones (including component identification and anthraquinone content determination) applied in clinical were selected. According to the collected evidence, we provide a list of herbs containing anthraquinones that could cause MC.Results: We identified 20 herbs belonging to 7 families represented by Polygonaceae, Fabaceae, Rhamnaceae, and Rubiaceae, which may play a role in the pathogenesis of MC. Among these, the herbs most commonly used include Dahuang (Rhei Radix et Rhizome), Heshouwu (Radix Polygoni Multiflori), Huzhang (Rhizoma Polygoni Cuspidati), Juemingzi (Semen Cassiae), Luhui (Aloe) and Qiancao (Rubiae Radix et Rhizoma).Conclusion: Due to a lack of awareness of the chemical composition of TCM herbs, many patients with constipation and even some TCM physicians take cathartic herbal remedies containing abundant anthraquinones to relieve defecation disturbances, resulting in long-term dependence on these herbs, which is potentially associated with most cases of MC. When such treatments are prescribed, TCM physicians should avoid long-term use in large doses to reduce their harm on colonic health. Individuals who take healthcare products containing these herbs should also be under the supervision of a doctor.