Interleukin-18 enhances vascular calcification and osteogenic differentiation of vascular smooth muscle cells through TRPM7 channel activation

Objective—Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is a key mechanism of VC. Recent studies show that IL-18 (interleukin-18) favors VC while TRPM7 (transient receptor potential melastatin 7) channel upregulation inhibits VC. However, the relationship between IL-18 and TRPM7 is unclear. We questioned whether IL-18 enhances VC and osteogenic differentiation of VSMCs through TRPM7 channel activation. Approach and Results—Coronary artery calcification and serum IL-18 were measured in patients by computed tomographic scanning and enzyme-linked immunosorbent assay, respectively. Primary rat VSMCs calcification were induced by high inorganic phosphate and exposed to IL-18. VSMCs were also treated with TRPM7 antagonist 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA to block TRPM7 channel activity and expression. TRPM7 currents were recorded by patch-clamp. Human studies showed that serum IL-18 levels were positively associated with coronary artery calcium scores (r=0.91; P<0.001). In VSMCs, IL-18 significantly decreased expression of contractile markers α-smooth muscle actin, smooth muscle 22 α, and increased calcium deposition, alkaline phosphatase activity, and expression of osteogenic differentiation markers bone morphogenetic protein-2, Runx2, and osteocalcin (P<0.05). IL-18 increased TRPM7 expression through ERK1/2 signaling activation, and TRPM7 currents were augmented by IL-18 treatment. Inhibition of TRPM7 channel by 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA prevented IL-18–enhanced osteogenic differentiation and VSMCs calcification. Conclusions—These findings suggest that coronary artery calcification is associated with increased IL-18 levels. IL-18 enhances VSMCs osteogenic differentiation and subsequent VC induced by β-glycerophosphate via TRPM7 channel activation. Accordingly, IL-18 may contribute to VC in proinflammatory conditions

Photo-able Urban Green-Blue Spaces

Urban green–blue spaces (UGBSs) are increasingly integrated into the urban fabric transformation, playing a pivotal role in shaping everyday interactions and experiences with nature in the Anthropocene era. Crowdsourcing, facilitated by digital technologies, has emerged as a novel methodological advance for accessing subjective place-based information, allowing the public to produce and share photographs at an unprecedented scale. As people can now readily capture and disseminate images on social media from virtually any location, these photographs contribute to the digital representation of places. Many studies have leveraged social media imagery to explore mental maps of cities, place perceptions, and ecosystem services. This raises fundamental questions: What are the UGBSs that promote photography across cities? What are the similarities and differences among cities’ photogenic UGBSs? And how do cities’ photogenic UGBSs relate to the happiness of their inhabitants? This study investigates these questions through an analysis of 203,020 photographs, taken from social media, of sites across 186 cities over a five-year period (2014 to 2018). Employing Google Cloud Vision and topic modelling with a state-of-the-art neural network model, photographs are clustered and used to identify cross-city features. The correlation between prevalence of photogenic UGBSs and levels of happiness is investigated using linear regression analysis. The results show that UGBSs eliciting photography practice are predominantly characterised by water-related subjects, confirming a widespread aesthetic appreciation for urban blue spaces. Perceptions of UGBSs exhibit significant variability among cities, offering a metric to assess environmental policy efficacy. Lastly, a positive association is found in high-income contexts between number of social media photographs of UGBSs and subjective well-being, while this correlation is not significant in middle- and low-income contexts. This sheds light on human–nature relationships by providing global evidence of how aesthetic appreciation of urban nature influences human well-being

A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

BACKGROUND: The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV), however, possesses several mechanisms to evade complement-mediated lysis (CoML) and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH) through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. PRESENTATION OF THE HYPOTHESIS: Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively) linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d)-Fc), can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. TESTING THE HYPOTHESIS: Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d)-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of (anti-gp120 × anti-C3d)-Fc lysis of HIV compared to untreated virus. IMPLICATIONS OF THE HYPOTHESIS: The targeted complement activator, (anti-gp120 × anti-C3d)-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells

Mobility Justice in Rural California: Examining Transportation Barriers and Adaptations in Carless Households

This report describes the scope and scale of car access in rural areas, identifies barriers that rural zero-car and car-deficit households face in their mobility and access, and proposes personal and policy-level adaptations that would help these households achieve their mobility and access needs using descriptive analysis from US census microdata and interviews with 22 residents of California’s Central Valley. Results indicate that 5% of rural residents are fully carless and 18% live in a car-deficit household with less than one vehicle per adult. Both zero-car and car-deficit households tend to be in the Central Valley. Zero-car and car-deficit households in rural areas tend to be more socioeconomically disadvantaged than in nonrural areas. Both groups earn lower household incomes, are more likely to be Black, Latino, or Asian, have lower educational attainment, have more disabilities, have higher housing-cost burdens, and are more likely to be unemployed than their counterparts in nonrural areas. Almost half of workers in rural zero-car households drive alone to work compared to about a quarter in nonrural zero-car households, while mode shares are similar for car-deficit and car fully equipped households. Rural zero-car households are more likely to carpool and far less likely to take public transit. Three major themes emerged from the interviews. First, a commonality uniting the interview participants was the practice of relying on their social networks to get rides or obtain vehicle access. Second, the cost of car ownership and operation was high, placing vehicles out of reach for many. Third, alternatives to car access included public transit, medical transportation services, and car sharing, put poor availability often caused individuals to forgo trips. Interview participants shared a variety of options they saw as solutions to overcoming their barriers to lack of car access. While obtaining a vehicle was not absent from their preferred solutions, most preferred better personal access to transportation without the burden of private car ownership. The findings from demonstrate some of the complexities to consider when addressing transportation barriers in rural areas, where carlessness is less prevalent but solutions may be harder to implement than in urban areas.View the NCST Project Webpag

Exploring Better Black-Box Test Case Prioritization via Log Analysis

Test case prioritization (TCP) has been widely studied in regression testing, which aims to optimize the execution order of test cases so as to detect more faults earlier. TCP has been divided into white-box test case prioritization (WTCP) and black-box test case prioritization (BTCP). WTCP can achieve better prioritization effectiveness by utilizing source code information, but is not applicable in many practical scenarios (where source code is unavailable, e.g., outsourced testing). BTCP has the benefit of not relying on source code information, but tends to be less effective than WTCP. That is, both WTCP and BTCP suffer from limitations in the practical use. To improve the practicability of TCP, we aim to explore better BTCP, significantly bridging the effectiveness gap between BTCP and WTCP. In this work, instead of statically analyzing test cases themselves in existing BTCP techniques, we conduct the first study to explore whether this goal can be achieved via log analysis. Specifically, we propose to mine test logs produced during test execution to more sufficiently reflect test behaviors, and design a new BTCP framework (called LogTCP), including log pre-processing, log representation, and test case prioritization components. Based on the LogTCP framework, we instantiate seven log-based BTCP techniques by combining different log representation strategies with different prioritization strategies. We conduct an empirical study to explore the effectiveness of LogTCP. Based on 10 diverse open-source Java projects from GitHub, we compared LogTCP with three representative BTCP techniques and four representative WTCP techniques. Our results show that all of our LogTCP techniques largely perform better than all the BTCP techniques in average fault detection, to the extent that then become competitive to the WTCP techniques. That demonstrates the great potential of logs in practical TCP.</jats:p

Genome-wide DNA methylation analysis of pulmonary function in middle and old-aged Chinese monozygotic twins

Background Previous studies have determined the epigenetic association between DNA methylation and pulmonary function among various ethnics, whereas this association is largely unknown in Chinese adults. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and pulmonary function among middle-aged Chinese monozygotic twins. Methods The monozygotic twin sample was drawn from the Qingdao Twin Registry. Pulmonary function was measured by three parameters including forced expiratory volume the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear mixed effect model was used to regress the methylation level of CpG sites on pulmonary function. After that, we applied Genomic Regions Enrichment of Annotations Tool (GREAT) to predict the genomic regions enrichment, and used comb-p python library to detect differentially methylated regions (DMRs). Gene expression analysis was conducted to validate the results of differentially methylated analyses. Results We identified 112 CpG sites with the level of P < 1 x 10(-4) which were annotated to 40 genes. We identified 12 common enriched pathways of three pulmonary function parameters. We detected 39 DMRs located at 23 genes, of which PRDM1 was related to decreased pulmonary function, and MPL, LTB4R2, and EPHB3 were related to increased pulmonary function. The gene expression analyses validated DIP2C, ASB2, SLC6A5, and GAS6 related to decreased pulmonary function. Conclusion Our DNA methylation sequencing analysis on identical twins provides new references for the epigenetic regulation on pulmonary function. Several CpG sites, genes, biological pathways and DMRs are considered as possible crucial to pulmonary function.Peer reviewe

Identifying the critical factors of transmission efficiency loss in China’s natural gas network

China’s market-oriented reform supports the sustainable development of energy mix and the low-carbon target, and natural gas has bridged the transition from traditional fossil energy to clean and renewable energies. The third-party access policy, launched recently by China’s natural gas market, drives the decouple between gas trade and transport. The decouple might lead to the transmission resources of physical network not optimally used, which is caused by the contractual arrangement between entry and exit capacities in commercial network. Aiming at this issue, we established a mathematical programming with equilibrium constraints (MPEC) to integrate the allocations of commercial capacity and physical flows, based on a minimum cost maximum flow problem (MCMF) abstracted from China’s existing gas network. The MPEC model was then used to strategically evaluate the transmission efficiency, and identify the critical factors of its loss. Our results show that there is transmission efficiency loss of China’s gas network from the shortage of geospatial gas supply and the invisible segmentation of gas network due to interdicted cost of pipeline, bottleneck of pipeline capacity and economic radius of gas supply chains to transport gas. Therefore, the critical factor of the loss to be identified will be helpful for strategically reducing the cost of decoupling gas trade and transport.publishedVersio

Various steaming durations alter digestion, absorption, and fermentation by human gut microbiota outcomes of Polygonatum cyrtonema Hua polysaccharides

IntroductionDifferent steaming durations dramatically alter the structure of Polygonatum cyrtonema polysaccharides (PCPs). This study aimed to compare characteristics of digestion, absorption, and fermentation by gut microbiota across four representative PCPs from different steaming durations (0, 4, 8, and 12 h), each with unique molecular weights and monosaccharide profiles.MethodsChemical composition of the four PCPs was analyzed. Digestibility was evaluated using an in vitro saliva-gastrointestinal digestion model. Absorption characteristics were assessed with a Caco-2 monolayer model, and impacts on gut microbiota composition and short chain fatty acid (SCFA) levels were analyzed using in vitro fermentation with human gut microbiota.ResultsLonger steaming durations altered the chemical profiles of PCPs, reducing carbohydrate content (84.87–49.58%) and increasing levels of uronic acid (13.99–19.61%), protein (1.07–5.43%), and polyphenols (0.05–2.75%). Four PCPs were unaffected by saliva digestion but showed enhanced gastrointestinal digestibility, with reducing sugar content rising from 4.06% (P0) to 38.5% (P12). The four PCPs showed varying absorption characteristics, with P0 having the highest permeability coefficient value of 9.59 × 10−8 cm/s. However, all PCPs exhibited poor permeability, favoring gut microbiota fermentation. The four PCPs altered gut microbiota composition and elevated SCFA production, but levels declined progressively with longer steaming durations. All PCPs significantly increased the abundance of Bacteroidota, Firmicutes, and Actinobacteriota, making them the dominant bacterial phyla. Additionally, all PCPs significantly increased the abundance of Bifidobacterium, Prevotella, and Faecalibacterium compared to the control group, which, along with Bacteroides, became the dominant microbiota. Increasing the steaming duration led to a reduction in Prevotella levels, with PCPs from raw rhizomes showing the highest relative abundance at 24.90%. PCPs from moderately steamed rhizomes (4 h) led to a significant rise in Faecalibacterium (7.73%) among four PCPs. P8 and P12, derived from extensively steamed rhizomes (≥8 h), exhibited similar gut microbiota compositions, with significantly higher relative abundances of Bacteroides (20.23–20.30%) and Bifidobacterium (21.05–21.51%) compared to P0 and P4.DiscussionThis research highlights the importance of adjusting steaming durations to maximize the probiotic potential of P. cyrtonema polysaccharides, enhancing their effectiveness in modulating gut microbiota and SCFA levels

A missing link in the estuarine nitrogen cycle?: coupled nitrification-denitrification mediated by suspended particulate matter

In estuarine and coastal ecosystems, the majority of previous studies have considered coupled nitrification-denitrification (CND) processes to be exclusively sediment based, with little focus onsuspended particulate matter (SPM) in the water column. Here, we present evidence of CND processes in the water column of Hangzhou Bay, one of the largest macrotidal embayments in the world

Demographic change and housing markets in an aging society

"Population aging in the United States (U.S.) has reached an inflection point. The population who are aged 65 and above increased by 19.7 percent between 2010 and 2016, compared with a 4.8 percent increase among the total population. There is a lack of research about how population aging impacts local housing markets at the county level in the United States. My thesis aims to address this research gap. I use fixed effects models to study the causal relationship between the increasing size of the elderly population and housing prices from 1990 to 2010. The results suggest that population aging has no effect on housing prices in general nor any effect on the price of smaller homes (those with two bedrooms or less). However, there is modest evidence that the increase of the elderly population may contribute significant declines in the price of larger houses (with three bedrooms or more). The findings potentially have important implications for urban planning and housing policy. Identifying the need of housing units inhabited by the elderly population helps planners facilitate the appropriate allocation of permitted newly built housing units (for example, smaller homes for the elderly). It will benefit the well-being of the elderly as population aging becomes an imperative issue."--Page ii.Thesis (M.U.R.P.)--Michigan State University. Urban and Regional Planning, 2019Includes bibliographical references (pages 64-67