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Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis, angiosteosis, and vascular aging. Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell. Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering, regenerative medicine, and medical devices. Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells (VECs) and smooth muscle cells (VSMCs). Interestingly, our findings demonstrate that, with the increase of substrate stiffness, the autophagy level of VECs and VSMCs showed differential changes: endothelial autophagy levels reduced, leading to the reductions in a range of gene expression associated with endothelial function; while, autophagy levels of VSMCs increased, showing a transition from contractile to the synthetic phenotype. We further demonstrate that, by inhibiting cell autophagy, the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased, suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing. Although the underlying mechanism requires further study, this work highlights the relationship of substrate stiffness, autophagy, and vascular cell behaviors, and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications.

C14H16N6O8Ni, monoclinic, P21/n (no. 14), a = 6.3975(3) Å, b = 11.6712(5) Å, c = 11.7199(5) Å, β = 96.677(4)°, V = 869.15(7) Å3, Z = 2, R gt(F) = 0.0340, wR ref(F 2) = 0.0789, T = 291 K.

Abstract Background Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis. Main text We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020. Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries. Conclusions It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.

Several studies have been undertaken to develop instruments to measure English teachers' TPACK, but few studies have measured English teachers' TPACK to develop meaningful relationships among technology, content, and pedagogy in the context whereby literacy should be associated with a range of semiotic modes beyond the written language. The interactions with a wider range of texts across modes, media and contexts point to the need for an instrument that can measure English teachers' TPACK in the context of teaching multimodal literacies. In this study, we investigated what factors and items were necessary for examining pre-service teachers' TPACK in multimodal literacy teaching. The proposed TPACK instrument was validated with 220 pre-service teachers across three institutions in Indonesia, China, and Australia. The study shows that the proposed eight-factor instrument generally expressed acceptable validity and reliability and was appropriate for assessing pre-service teachers' TPACK for multimodal literacies. Implications and further research are discussed with the aim of equipping pre-service teachers with the capabilities to integrate content, pedagogy, technology and understand the complex interdependence of contextually bound factors that influence their classroom readiness in teaching multimodal literacies.

A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. Part of the fraction 2 was taken out, followed by adjusting its pH to 4.2. After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. This study provides a reference to promote the high-value utilization of flaxseed meals.

Solvent effects in catalytic reactions have received widespread attention as they can promote reaction rates and product selectivities by orders of magnitude. It is well accepted that the stable five‐membered cyclic intermediates formed between the solvent molecules and Ti species are crucial to the alkene epoxidation in a heterogeneous Ti(IV)−H2O2 system. However, the direct spectroscopic evidence of these intermediates is still missing and the corresponding reaction pathway for the alkene epoxidation remains unclear. By combining in situ 13C MAS NMR, two‐dimensional (2D) 1H−13C heteronuclear correlation (HETCOR) NMR spectroscopy and theoretical calculations, the five‐membered ring structures, where the protic solvents (ROH), and aprotic solvent (acetone), coordinate and stabilize the active Ti species, are identified for the first time over Ti‐Beta/H2O2 system. Moreover, the role of these cyclic intermediates in the alkene epoxidation/hydration conversion is clarified. These results provide new insights into the solvent effect in liquid‐phase epoxidation/hydration reactions over Ti(IV)−H2O2 system. [ABSTRACT FROM AUTHOR]

In previous research simulating steelmaking ladles using cold water models, the dosage/volume of the salt tracer solution is one of the factors that has been overlooked by researchers to a certain extent. Previous studies have demonstrated that salt tracers may influence the flow and measured mixing time of fluids in water models. Based on a water model scaled down from an industrial 130-ton ladle by a ratio of 1:3, this study investigates the impact of salt tracer dosage on the transport and mixing of tracers in the water model of gas-stirred ladle with a moderate gas flow rate. A preliminary uncertainty analysis of the experimental mixing time is performed, and the standard deviations were found to be less than 15%. It was observed in the experiments that the transport paths of tracers in the ladle can be classified into two trends. A common trend is that the injected salt solution tracer is asymmetrically transported towards the left sidewall of the ladle by the main circulation. In another trend, the injected salt solution tracer is transported both by the main circulation to the left side wall and by downward flow towards the gas column. The downward flow may be accelerated and become a major flow pattern when the tracer volume increases. For the dimensionless concentration curve, the sinusoidal type, which represents a rapid mixing, is observed at the top surface monitoring points, while the parabolic type is observed at the bottom monitoring points. An exception is the monitoring point at the right-side bottom (close to the asymmetric gas nozzle area), where both sinusoidal-type and parabolic-type curves are observed. Regarding the effect of tracer volume on the curve and mixing time, the curves at the top surface monitoring points are less influenced but curves at the bottom monitoring points are noticeably influenced by the tracer volume. A trend of decreasing and then increasing as the tracer volume increases was found at the top surface monitoring points, while the mixing times at the bottom monitoring points decrease with the increase in the tracer volume. [ABSTRACT FROM AUTHOR]

The digital application gap and relative poverty caused by the development of digital technology are both important factors affecting sustainable economic dynamics. This paper explores the impact of digital technology development on the relative poverty of urban households in China, using the China Household Tracking Survey CFPS2010–2018 and the word frequency crawling technology of Python software. The results indicate that failure to adapt to the demands of digital technology may result in a multidimensional digital technology application gap, leading to increased income inequality among urban households and a higher likelihood of relative poverty. In economically developed areas, households headed by individuals with low levels of education and high levels of family support should be particularly mindful of the phenomenon of digital poverty. This paper expands the research scope of relative poverty and deepens the understanding of the relationship between digital technology and economic development, which is beneficial for the government to accelerate the construction of internal and external support mechanisms and to effectively address the challenges posed by sustainable economic development. [ABSTRACT FROM AUTHOR]

Abstract Background The genus Ligusticum consists of approximately 60 species distributed in the Northern Hemisphere. It is one of the most taxonomically difficult taxa within Apiaceae, largely due to the varied morphological characteristics. To investigate the plastome evolution and phylogenetic relationships of Ligusticum, we determined the complete plastome sequences of eight Ligusticum species using a de novo assembly approach. Results Through a comprehensive comparative analysis, we found that the eight plastomes were similar in terms of repeat sequence, SSR, codon usage, and RNA editing site. However, compared with the other seven species, L. delavayi exhibited striking differences in genome size, gene number, IR/SC borders, and sequence identity. Most of the genes remained under the purifying selection, whereas four genes showed relaxed selection, namely ccsA, rpoA, ycf1, and ycf2. Non-monophyly of Ligusticum species was inferred from the plastomes and internal transcribed spacer (ITS) sequences phylogenetic analyses. Conclusion The plastome tree and ITS tree produced incongruent tree topologies, which may be attributed to the hybridization and incomplete lineage sorting. Our study highlighted the advantage of plastome with mass informative sites in resolving phylogenetic relationships. Moreover, combined with the previous studies, we considered that the current taxonomy system of Ligusticum needs to be improved and revised. In summary, our study provides new insights into the plastome evolution, phylogeny, and taxonomy of Ligusticum species.

Tribe Lilieae, encompassing Lilium, Notholirion, Cardiocrinum, and Fritillaria, includes economically important crops with a horticultural and medicinal value. It is considered to be a core lineage of Liliaceae, but phylogenetic relationships within it, and the timing of the origin of individual clades, remain incompletely resolved. To address these issues, we reconstructed the evolutionary history of the tribe. We sequenced 45 Liliaceae plastomes and combined them with publicly available data (for a total of 139 plastomes) to explore the systematics, origin, divergence, and evolution of Lilieae. Our taxon sampling covers all ten sections of Lilium, all Cardiocrinum species, three Notholirion species, and major phylogenetic clades of Fritillaria. Our phylogenetic analysis confirms the monophyly of major sections/subgenera of Lilium and Fritillaria with strong support. We dated the origin of Lilieae to the Eocene, with genera and species radiations inferred to have occurred in the Miocene. The reconstruction of the ancestral area implies that Lilieae may have originated from the Qinghai-Tibet Plateau (QTP): the Himalayas and Hengduan Mountains and uplifting of the QTP likely promoted divergence within the tribe. Ancestral-state reconstructions of the bulb component number (including bulblets and scales) show a strong correlation with the genus-level phylogenetic diversity in Lilieae. They also predict that the most recent common ancestor of Lilieae had bulbs with numerous bulblets. Based on these observations, we predicted that climatic oscillations associated with the QTP uplift played an important role in the evolution of the Lilieae bulb. Our findings provide a well-supported picture of evolutionary relationships and a useful framework for understanding the pathway of bulb evolution within Lilieae, contributing to a better understanding of the evolutionary history of lilies.

A high Mandard score may indicate the tumor is insensitive to chemotherapy. We analyzed tumor regression and lymph node response under different Mandard scores to assess the impact of Mandard score on prognosis. Methods. Mandard scores and ypN stage of postoperative pathological reports were recorded. The results were reviewed by a professional pathologist. The radiologist compared the tumor regression before and after chemotherapy by computed tomography (CT). The survival of all patients was obtained by telephone follow-up. Multivariate Cox regression was used to assess the relationship between overall risk of death and Mandard score, imaging evaluation, and ypN stage. Results. In the Mandard score (4-5) group, the median survival time for PR and ypN0 patients was 68.5 and 76.7 months. While in the Mandard score (1-2) group, the median survival time for PD and ypN3a patients was 15.6 and 14.5 months. Imaging evaluation of tumor regression (PR 68.5 months, SD 27.8 months, and PD 10.2 months) and lymph node remission (ypN0 76.7 months, ypN1 61.6 months, ypN2 18.0 months, ypN3a 18.7 months, and ypN3b 18.3 months) showed improved survival. Mandard score, imaging evaluation, and ypN stage are important prognostic factors affecting prognosis. Conclusion. A high Mandard score does not mean neoadjuvant chemotherapy is ineffective in gastric cancer. Patients with imaging evaluation of tumor regression and ypN stage reduction may benefit from neoadjuvant chemotherapy.

The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.