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Abstract Due to long-term exposure to outdoor environments, stone artifacts exhibit complex and varying degrees of disease that need to be conserved urgently in order to perpetuate their historical, artistic and scientific values. Owing to the varying degrees of damage inflicted upon cultural relics, discrepancies exist in intervention strategies and conservation materials employed. Hence, it is considerably crucial to conduct a scientific and precise assessment of the preservation status of cultural relics at an early stage for the advancement of cultural relic conservation efforts. In this research, three masonry components of the Hailongtun Fortress site were selected as study objects. A secondary fuzzy comprehensive evaluation system was established through selecting a total of 12 indicators from four aspects, namely, surface change, rock mass structure, physical properties and matrix weathering. The weight of each indicator was determined by using an improved AHP-EWM weight coupling model. The membership degree was calculated by selecting a modified ridge function. The asymmetric nearness method was employed in the final decision-making process so as to correct the error caused by the principle of maximum membership degree. The research shows that the results of the improved evaluation method are in line with the real damage degree of each masonry component, which provides a scientific and quantitative basis for determining the priority of the conservation of masonry components in the Hailongtun Fortress Site. This method is also a reference for carrying out the disease assessment and conservation of other types of cultural relics.

Purpose To quantify changes in colour vision immediately after exposure to different altitudes of low-pressure hypoxia.Methods The study involved 35 healthy participants (ages 20–26). Colour vision was assessed using the Farnsworth-Munsell 100-Hue test at eight different altitudes (condition 1: ground, condition 2: 3500 m, condition 3: 3500 m after 40 min, condition 4: 4000 m, condition 5: 4000 m after 40 min, condition 6: 4500 m, condition 7: 4500 m after 40 min, condition 8: back to the ground). Data were analysed using Analysis of Variance (ANOVA), paired t-test, and χ2 test .Results Total Error Score (TES) increased with altitude and hypoxia duration, with higher TES in condition 8 than in condition 1. There were significant TES differences between conditions 3 and 7, as well as 4 and 7. Friedman and repeated ANOVA tests revealed significant sector differences, with Blue-Yellow Partial Error Score (PES) greater than Red-Green PES, particularly on conditions 4, 5 and 8. Significant Red-Green PES differences were found between conditions 4 and 7, and Blue-Yellow PES between conditions 3 and 5, 7, 8. Tritan (Blue-Yellow) shift was most pronounced at high altitudes.Conclusions This experiment investigated acute low-pressure hypoxia’s effects on colour vision, supplementing chronic hypoxia research. Increased altitudes and exposure duration worsen colour vision, with effects persisting post-recovery. Tritan axis loss is most significant under hypoxia.

Purpose: Liver-expressed antimicrobial peptide-2 (LEAP2) is identified as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor type 1a (GHSR1a), its effect on the GHSR1a is contrary to the role of GHRELIN. Growth hormone (GH) is a crucial hormone for early development. Previous studies report that LEAP2 dose-dependently attenuates ghrelin-induced GH secretion, and Leap2-knockout mice exhibit increased plasma GH levels after GHRELIN administration. Clinical data revealed a possible correlation between LEAP2 and height development. However, the role of LEAP2 in early development remains unclear. This study aimed to investigate the role of LEAP2 in early development using leap2 mutant zebrafish larvae as a model. Method: We analyzed the conservation of LEAP2 peptide across multiple species and generated leap2 mutants in zebrafish by CRISPR-Cas9, dynamically observed and measured the growth and development of zebrafish larvae from fertilization to 5 day post fertilization (dpf). In situ hybridization, transcriptome sequencing, quantitative real-time PCR and Western blot were used to detect the expression levels of GH and its signaling in early stage of embryonic development. Result: Our data demonstrate that zebrafish with a knockout of the leap2 gene display a significant increase in hatching rate, body length, and the distance between their eyes, all without visible developmental defects in the early stages of development. In addition, both RNA and protein analyses revealed a significant increase in GH expression in leap2 mutant. Conclusion: In general, this study demonstrates that LEAP2 regulates the expression of GH during early development, particularly influencing body length.

The influence of 82B steel with Mo （mass fraction） of 0. 02%，0. 04%，0. 07% and 0. 11% on microstructures and properties after high temperature stretching at different temperatures and the toughness mechanism of Mo element on 82B high carbon steel were studied. The results showed that：（1） During 200-300 ℃ high temperatures tensile， four groups of experimental steels had good mechanical properties ， at 300 ℃ to reach the peak， it was optimal experiment group with Mo content 0. 11% ， tensile strength increased from 1 139 MPa to 1 192 MPa， yield strength slightly reduced to 736 MPa， elongation and section shrinkage significantly increased to 22% and 72. 9%. Compared to the experimental steels with 0. 02% Mo content， the yield strength reduced by about 5%， but the tensile strength increased by 5%， the elongation and section shrinkage increased significantly， and the plasticity increased simultaneously with the Mo content， with the temperature continued to rise， the mechanical properties tended to decrease as the materials start to soften.（2） When the Mo content was 0. 02% and 0. 04%， the microstructures except carburite gradually increased with the increasing of tensile temperature， sorbite and pearlite did not appear obvious changes， and the same as room temperature， when the Mo content increased to 0. 07% and 0. 11%， sorbite and pearlite clusters are progressively finer and more evenly distributed. At the same time， four groups of experimental steels showed blue brittleness during high temperature tensile at 300 ℃，through the fractures observation found that there was Al， Si and other elements of inclusions， and failure mode was ductile fracture， the fracture can mainly be divided into the shear lip areas and fiber areas，the shear lip areas with the increase in temperature gradually reduced.

BackgroundTo quantify the changes in dynamic visual acuity (DVA) and explain the hidden reasons after acute exposure to hypobaric hypoxia status.MethodsThe study group comprised 18 healthy male and 15 healthy female participants aged 20–24 years old. DVA was measured with the self-developed software of Meidixin (Tianjin) Co., Ltd. Measurements were taken at eight altitudes. Data analysis was performed using the Kolmogorov–Smirnov test, paired sample T-test, and two-way repeated measures analysis of variance (ANOVA) for repeated measurements.ResultsAt constant altitude, DVA showed an overall decreasing trend with increasing angular velocity and a fluctuating decrease at the vast majority of altitudes. At constant angular velocities, DVA gradually increased with altitude, with the most pronounced increase in DVA at altitude 5, and thereafter a gradual decrease in DVA as altitude increased. Finally, as altitude decreased, DVA increased again and reached a higher level at the end of the experiment, which was superior to the DVA in the initial state.ConclusionUnder a hypobaric hypoxic environment at high altitude, DVA was affected by the angular velocity and the degree of hypoxia, manifesting as an increase or decrease in DVA, which affects the pilot's observation of the display and control interfaces during the driving process, acquisition of information, and decision-making ability, which in turn may potentially jeopardize the safety of the flight.

IntroductionGhrelin is originally identified as the endogenous ligand for the growth hormone secretagogue receptor (GHSR) and partially acts by stimulating growth hormone (GH) release. Our previous studies have identified GHRELIN as a novel susceptibility gene for human attention-deficit hyperactivity disorder (ADHD), and ghrelin-depleted zebrafish (Danio rerio) display ADHD-like behaviors. However, the underlying molecular mechanism how ghrelin regulates hyperactivity-like behaviors is not yet known.ResultsHere, we performed RNA-sequencing analysis using adult ghrelinΔ/Δ zebrafish brains to investigate the underlying molecular mechanisms. We found that gh1 mRNA and genes related to the gh signaling pathway were significantly reduced at transcriptional expression levels. Quantitative polymerase chain reaction (qPCR) was performed and confirmed the downregulation of gh signaling pathway-related genes in ghrelinΔ/Δ zebrafish larvae and the brain of adult ghrelinΔ/Δ zebrafish. In addition, ghrelinΔ/Δ zebrafish displayed hyperactive and hyperreactive phenotypes, such as an increase in motor activity in swimming test and a hyperreactive phenotype under light/dark cycle stimulation, mimicking human ADHD symptoms. Intraperitoneal injection of recombinant human growth hormone (rhGH) partially rescued the hyperactivity and hyperreactive-like behaviors in ghrelin mutant zebrafish. ConclusionOur results indicated that ghrelin may regulate hyperactivity-like behaviors by mediating gh signaling pathway in zebrafish. And the protective effect of rhGH on ghrelinΔ/Δ zebrafish hyperactivity behavior provides new therapeutic clues for ADHD patients.

Six phenolic acids (PAs) with related structures, i.e., gallic acid (GA), syringic acid (SA), coumaric acid (CMA), caffeic acid (CFA), ferulic acid (FA), and chlorogenic acid (CA), were compared for their effects on the gelling properties of myofibrillar protein (MP) under oxidative conditions. Of the six PAs, only the smallest GA caused significant reductions of free amine and sulfhydryl content (by 26% and 7%, respectively, P < 0.05) and SA decreased protein carbonyl formation, while CA, the largest PA with an esterified quinic group, prevented oxidative loss of amines. All PAs quenched MP fluorescence with CA showing the highest efficacy (38% suppression). During thermal gelation, the GA-modified MP displayed the strongest myosin cross-linking. The elasticity (G′) and breaking strength of MP gels were markedly enhanced by the addition of PAs, and the final G′ value ranked in the order GA > CA > FA > CMA > SA > CFA, indicating complex roles of phenolic side groups.

Abstract The poor stability of CsPbX3 (X = Cl, Br, I) perovskite nanocrystals is the most impediment to its application in the field of photoelectrics. In this work, monodisperse CsPbBr3/TiO2 nanocrystals are successfully prepared by coating titanium precursor on the surface of colloidal CsPbBr3 nanocrystals at room temperature. The CsPbBr3/TiO2 nanocomposites exhibit excellent stability, remaining the identical particle size (9.2 nm), crystal structures and optical properties. Time-resolved photoluminescence decay shows that the lifetime of CsPbBr3/TiO2 nanocrystals is about 4.04 ns and keeps great stability after lasting two months in the air. Results show that the coating of TiO2 on CsPbBr3 NCs greatly suppressed the anion exchange and photodegradation, which are the main reasons for dramatically improving their chemical stability and photostability. The results provide an effective method to solve the stability problem of perovskite nanostructures and are expected to have a promising application in optoelectronic fields Article highlights 1. Prepared the all-inorganic CsPbBr3/TiO2 core/shell perovskite nanocrystals by an easy method. 2. Explored its essences of PL and lifetime of the synthesized CsPbBr3/TiO2 perovskite nanocrystals. 3. CsPbBr3/TiO2 nanocrystals show the great thermal stability after the post-annealing. 4. The CsPbBr3/TiO2 nanocrystals have a high PLQY and have a promising application in solar cells.

Abstract Background Apparent Young’s modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established. Results Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types. Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics. On substrates that were too rigid or too soft, fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity. On a substrate with ‘optimal’ stiffness (i.e., 3.5 kPa), the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity. The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP. Conclusions In summary, this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.

Business model innovation is critical to firm survival and success. Digital revolution has reshaped value-creation methods in recent years, spawning various novel business models. However, we still have limited understanding of how a start-up's business model innovation efforts translate into superior performance in the digital economy. Drawing on insights from the demand-side perspective, this study disassembles the business model innovation architecture into three elements—value proposition, value creation, and value capture innovation—and investigates how business model innovation contributes to digital start-up performance. Based on a survey of Chinese digital start-ups, we find that value proposition innovation is positively related to digital start-up performance. Moreover, this relationship is mediated by value creation and value capture innovation. This study contributes to business model research by examining the impact mechanism of business model innovation on firm performance and providing new insights into the demand-side perspective of business model innovation.

Summary: It is still a challenge for synthesizing ‘cellular niche-mimics’ in vitro with satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosis in vivo, here we optimized the in vitro liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogenesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.

Protein oxidation, a phenomenon that was not well recognized previously but now better understood, is a complex chemical process occurring ubiquitously in food systems and can be induced by processing treatments as well. While early research concentrated on muscle protein oxidation, later investigations included plant, milk, and egg proteins. The process of protein oxidation involves both radicals and nonradicals, and amino acid side chain groups are usually the site of initial oxidant attack which generates protein carbonyls, disulfide, dityrosine, and protein radicals. The ensuing alteration of protein conformational structures and formation of protein polymers and aggregates can result in significant changes in solubility and functionality, such as gelation, emulsification, foaming, and water-holding. Oxidant dose-dependent effects have been widely reported, i.e., mild-to-moderate oxidation may enhance the functionality while strong oxidation leads to insolubilization and functionality losses. Therefore, controlling the extent of protein oxidation in both animal and plant protein foods through oxidative and antioxidative strategies has been of wide interest in model system as well in in situ studies. This review presents a historical perspective of food protein oxidation research and provides an inclusive discussion of the impact of chemical and enzymatic oxidation on functional properties of meat, legume, cereal, dairy, and egg proteins based on the literature reports published in recent decades.

In this paper, we propose a reconfigurable electro-optic logic circuit, which can perform any combinatorial logic operations using a microring resonator (MRR)-based optical switching array. The operands are represented by electrical signals, which are applied to the corresponding MRRs to control their switching status. The operation results are directed to the output port in the form of light. For proof of concept, the circuit consisting of four thermooptic MRR-based optical switches is fabricated on the silicon-on-insulator (SOI) substrate using the commercial complementary metal-oxide-semiconductor (CMOS) fabrication process. Finally, several logic operations of four operands with the operation speed of 10 kb/s are demonstrated successfully.