In vitro and in vivo models define a molecular signature reference for human embryonic notochordal cells.

Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-ß inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.

Research on the purification efficiency and mechanism for road runoff pollutants in pervious concrete with recycled aggregates.

The use of recycled aggregate (RA) in pervious concrete (PC) is a green approach that can effectively mitigate urban waterlogging, excessive RA, and runoff pollution, thereby enhancing the urban ecological environment. This article focuses on the long-term purification efficiency of runoff pollutants by PC at different porosities and RA dosages. Moreover, the purification mechanism of pollutants by recycled aggregate pervious concrete (RAPC) was revealed utilizing particle size analysis, microstructure, and elemental analysis. Finally, the recovery effects of different maintenance approaches on the purification capacity of RAPC were explored. The results indicate that an increase in the RA dosage reduced the effective porosity of PC, thereby decreasing the permeability of RAPC. In addition, PC with a lower porosity demonstrated a slightly greater purification effectiveness for pollutants. However, the utilization of RA significantly enhanced the purification capacity of PC for various pollutants, primarily by leveraging advantages in terms of pore structure, micromorphology, and surface chemical composition. Additionally, RAPC exhibited nearly 100 % retention effectiveness for particles larger than 68.95 µm but relatively lower purification efficiency for particles ranging from 1.541 to 17.11 µm. In particular, it displayed the poorest purification performance for particles with a diameter of 6.396 µm. The surface of RAPC's pore channels exhibited a loose state with high porosity and appeared rough and uneven with numerous pits and grooves. RAPC had a larger surface area and contained more components, such as SiO2, CaCO3, and Al2O3, than regular PC. Therefore, RAPC possessed a higher purification capacity. High-pressure flushing (HPF) and sodium citrate flushing (SCF) under different maintenance frequencies significantly contributed to the recovery of the purification efficiency of RAPC. However, overall, a lower maintenance frequency led to a less favorable recovery effect. Furthermore, SCF had a better recovery effect than HPF.

Digital inspection techniques of modular integrated construction.

As a new construction form, modular integrated construction (MiC) can effectively improve the construction quality and productivity, especially for the construction of high-density and high-rise buildings. However, the current MiC quality inspection relies on manual inspection, which is inefficient and unreliable. Systematic research on digital inspection techniques (DITs) is fragmented and unable to fully realize the potential of the MiC industry. This study aims to explore the current state of DIT applications in MiC and to summarize the knowledge in the field through an analysis of 248 relevant literatures. Accordingly, this study combines bibliometric analysis, and a system engineering evaluation approach based on 3D structures (time, knowledge, and logic) to provide an overview of the current state of DIT development. The overview includes the application of DITs from a whole life cycle perspective, the DIT knowledge structure, specific DIT applications, as well as current challenges and future prospects.

Recommendations for intervertebral disc notochordal cell investigation: From isolation to characterization.

Background: Lineage-tracing experiments have established that the central region of the mature intervertebral disc, the nucleus pulposus (NP), develops from the embryonic structure called "the notochord". However, changes in the cells derived from the notochord which form the NP (i.e., notochordal cells [NCs]), in terms of their phenotype and functional identity from early developmental stages to skeletal maturation are less understood. These key issues require further investigation to better comprehend the role of NCs in homeostasis and degeneration as well as their potential for regeneration. Progress in utilizing NCs is currently hampered due to poor consistency and lack of consensus methodology for in vitro NC extraction, manipulation, and characterization. Methods: Here, an international group has come together to provide key recommendations and methodologies for NC isolation within key species, numeration, in vitro manipulation and culture, and characterization. Results: Recommeded protocols are provided for isolation and culture of NCs. Experimental testing provided recommended methodology for numeration of NCs. The issues of cryopreservation are demonstrated, and a pannel of immunohistochemical markers are provided to inform NC characterization. Conclusions: Together we hope this article provides a road map for in vitro studies of NCs to support advances in research into NC physiology and their potential in regenerative therapies.

Extensible carbon emission factor database: empirical study for the Chinese construction industry.

A carbon emission factor (CEF) database is required for the basis of carbon emission calculation in construction projects. However, the default values for existing CEF databases cannot cover the complex resources involved in a construction project. Therefore, this paper proposes a three-step method to guide the establishment of an extensible CEF database for the construction industry, including (1) data collection and parser, (2) data extension, and (3) data encoding and storage. The data extension mechanisms provide the supply chain perspective considering temporal issues and the accounting perspective to streamline the process. Aiming to address the lack of a comprehensive CEF database for the construction industry in China, this paper uses this method to establish a carbon emission factor database for the Chinese construction industry (CEFD for CCI). This database is open and free with 646 CEFs, including five parts: energy, human, material, machinery, and greenspace. This paper provides a way for developing and less developed countries to establish an expandable CEF database, which benefits the parser, extension, encoding, and storage of new resources, as well as computer access.

What is the "DNA" of healthy buildings? A critical review and future directions.

Since the outbreak of COVID-19, buildings that provide improved performance have aroused extensive discussion. Nowadays, the connotation of healthy building is becoming complex, performance metrics for healthy buildings vary significantly from different regions in the world and there may be information asymmetry among stakeholders. Consequently, building health performance cannot be effectively achieved. However, previous studies have launched extensive reviews on green building, and there remains a lack of comprehensive and systematic reviews on healthy buildings. To address the above issues, therefore, this research aims to (1) conduct a thorough review of healthy building research and reveal its nature; and (2) identify the current research gaps and propose possible future research directions. Content analysis using NVivo were applied to review 238 relevant publications. A DNA framework of healthy buildings, which clarifies the characteristics, triggers, guides and actions, was then constructed for better understanding of the nature of them. Subsequently, the application of DNA framework and the directions of future research were discussed. Six future research directions were finally recommended, including life-cycle thinking, standard systems improvement, policies & regulations, awareness increase, healthy building examination, and multidisciplinary integration. This research differs from previous ones because it painted a panorama of previous healthy building research. Findings of this research contribute to reveal knowledge map of healthy buildings, guide researchers to fill existing knowledge gaps, provide a standardized platform for healthy building stakeholders, and promote high-quality development of healthy buildings.

Evaluating Toronto Hospitals' COVID-19 Visitor Policy Using Accountability for Reasonableness.

In March 2020, the Toronto Region COVID-19 Hospital Operations Table developed a policy to guide visitor restrictions at six hospitals (Toronto Region COVID-19 Hospital Operations Table 2021). We conducted nine interviews with the developers and implementers of the policy based on the accountability for reasonableness (A4R) framework. Participants agreed that the A4R principles were met suggesting fair development and implementation of the policy. However, recurrent themes suggested that the policy disadvantaged those unable to advocate for themselves and that there were unaccounted costs to patients, such as lost time and function. We suggest that visitor policies incorporate equity considerations upfront and predetermine metrics to measure harms to patients.

Peptide location fingerprinting identifies species- and tissue-conserved structural remodelling of proteins as a consequence of ageing and disease.

Extracellular matrices (ECMs) in the intervertebral disc (IVD), lung and artery are thought to undergo age-dependant accumulation of damage by chronic exposure to mechanisms such as reactive oxygen species, proteases and glycation. It is unknown whether this damage accumulation is species-dependant (via differing lifespans and hence cumulative exposures) or whether it can influence the progression of age-related diseases such as atherosclerosis. Peptide location fingerprinting (PLF) is a new proteomic analysis method, capable of the non-targeted identification of structure-associated changes within proteins. Here we applied PLF to publicly available ageing human IVD (outer annulus fibrosus), ageing mouse lung and human arterial atherosclerosis datasets and bioinformatically identified novel target proteins alongside common age-associated differences within protein structures which were conserved between three ECM-rich organs, two species, three IVD tissue regions, sexes and in an age-related disease. We identify peptide yield differences across protein structures which coincide with biological regions, potentially reflecting the functional consequences of ageing or atherosclerosis for macromolecular assemblies (collagen VI), enzyme/inhibitor activity (alpha-2 macroglobulin), activation states (complement C3) and interaction states (laminins, perlecan, fibronectin, filamin-A, collagen XIV and apolipoprotein-B). Furthermore, we show that alpha-2 macroglobulin and collagen XIV exhibit possible shared structural consequences in IVD ageing and arterial atherosclerosis, providing novel links between an age-related disease and intrinsic ageing. Crucially, we also demonstrate that fibronectin, laminin beta chains and filamin-A all exhibit conserved age-associated structural differences between mouse lung and human IVD, providing evidence that ECM, and their associating proteins, may be subjected to potentially similar mechanisms or consequences of ageing across both species, irrespective of differences in lifespan and tissue function.

The effect of vitamin D supplementation on serum levels of fibroblast growth factor- 23: A systematic review and meta-analysis of randomized controlled trials.

Previous studies of the effect of vtamin D on serum levels of fibroblast growth factor- 23 (FGF-23) have yeilded an inconsistent findings. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to investigate the effect of vitamin D supplementation on serum levels of FGF-23. PubMed, Scopus, ISI Web of Science, and the Cochrane Library were searched, from database inception to November 2020, for RCTs that evaluated the effects of native or active vitamin D supplementation on serum levels of FGF-23 in adults. Weighted mean difference (WMD) were calculated and random effects meta-analysis was used to estimate the overall effects. Twenty-seven trials were included in the meta-analysis. Supplementation with native vitamin D (23 studies, n = 2247 participants; weighted mean difference [WMD] = 0.5 pg/mL, 95 % CI: -0.52 to 1.51, P = 0.33; I2 = 29.9 %), and active vitamin D (5 studies, n = 342 participants, WMD = 29.45 pg/mL, 95 % CI: -3.9 to 62.81, P = 0.08; I2 = 99.3%) had no significant effects on serum FGF-23 concentration. In subgroup analyses, supplementation with ergocalciferol (3 studies, n = 205 participants; WMD = 18.27 pg/mL, 95 % CI: 5.36-31.17, P = 0.006), and daily dosing regimens (9 studies, n = 1374 participants; WMD = 0.41 pg/mL, 95 % CI: 0.22 to 0.59, P < 0.001) increased serum FGF-23 levels compared to control. Overall, our findings revealed no significan effect of vitamin D supplementation on serum FGF-23 concentration. However, further high quality, large-scale studies are needed to better elucidate this relationship.

Peptide Location Fingerprinting Reveals Tissue Region-Specific Differences in Protein Structures in an Ageing Human Organ.

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus) identified 268 proteins with age-associated structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and -resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I α2, collagen II α1 and collagen V α1, were located within their triple-helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance. Several proteins (collagen V α1, collagen II α1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young samples, suggesting that some ageing mechanisms may act locally within tissues. This study not only reveals possible age-associated differences in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF as a proteomic tool to aid in biomarker discovery.

Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model-An ORS spine section initiative.

Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and scored; hence, the weight for quantifying the disc histopathology is equally distributed and not driven by only a few features. We tested the new histopathological scoring criteria using images of lumbar and coccygeal discs from different IDD models of both sexes, including genetic, needle-punctured, static compressive models, and natural aging mice spanning neonatal to old age stages. Moreover, disc sections from common histological preparation techniques and stains including H&E, SafraninO/Fast green, and FAST were analyzed to enable better cross-study comparisons. Fleiss's multi-rater agreement test shows significant agreement by both experienced and novice multiple raters for all 14 features on several mouse models and sections prepared using various histological techniques. The sensitivity and specificity of the new scoring system was validated using artificial intelligence and supervised and unsupervised machine learning algorithms, including artificial neural networks, k-means clustering, and principal component analysis. Finally, we applied the new scoring system on established disc degeneration models and demonstrated high sensitivity and specificity of histopathological scoring changes. Overall, the new histopathological scoring system offers the ability to quantify histological changes in mouse models of disc degeneration and regeneration with high sensitivity and specificity.

PRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling.

Mice are commonly used to study intervertebral disc (IVD) biology and related diseases such as IVD degeneration. Discs from both the lumbar and tail regions are used. However, little is known about compartmental characteristics in the different regions, nor their relevance to the human setting, where a functional IVD unit depends on a homeostatic proteome. Here, we address these major gaps through comprehensive proteomic profiling and in-depth analyses of 8-week-old healthy murine discs, followed by comparisons with human. Leveraging on a dataset of over 2,700 proteins from 31 proteomic profiles, we identified key molecular and cellular differences between disc compartments and spine levels, but not gender. The nucleus pulposus (NP) and annulus fibrosus (AF) compartments differ the most, both in matrisome and cellularity contents. Differences in the matrisome are consistent with the fibrous nature required for tensile strength in the AF and hydration property in the NP. Novel findings for the NP cells included an enrichment in cell junction proteins for cell-cell communication (Cdh2, Dsp and Gja1) and osmoregulation (Slc12a2 and Wnk1). In NP cells, we detected heterogeneity of vacuolar organelles; where about half have potential lysosomal function (Vamp3, Copb2, Lamp1/2, Lamtor1), some contain lipid droplets and others with undefined contents. The AF is enriched in proteins for the oxidative stress responses (Sod3 and Clu). Interestingly, mitochondrial proteins are elevated in the lumbar than tail IVDs that may reflect differences in metabolic requirement. Relative to the human, cellular and structural information are conserved for the AF. Even though the NP is more divergent between mouse and human, there are similarities at the level of cell biology. Further, common cross-species markers were identified for both NP (KRT8/19, CD109) and AF (COL12A1). Overall, mouse is a relevant model to study IVD biology, and an understanding of the limitation will facilitate research planning and data interpretation, maximizing the translation of research findings to human IVDs.

Physical Activity and the Home Environment of Pre-School-Aged Children in Urban Bangladesh.

Physical activity (PA) is a key determinant of health and development, yet few studies have examined PA levels and risk factors for low PA among young children in low- and middle-income countries. This study aimed to describe the PA and sedentary (SED) behavior levels of preschool-aged children in Dhaka, Bangladesh, and to estimate the associations between potential risk factors in the home built environment and moderate to vigorous PA (MVPA). In a sample of preschool-aged children (n = 65) in Dhaka, PA and SED behavior were measured for 7 days using ActiGraph GT3X-BT accelerometers. Characteristics of the home built environment, socioeconomic factors, and anthropometry were also measured. Linear mixed-effects models were used to estimate multivariable-adjusted associations between characteristics of the home environment and MVPA. Preschool-aged children spent a mean (±standard deviation) 421 ± 48 and 82 ± 23 min per day sedentary and in MVPA, respectively. There were no statistically significant associations between factors in the home built environment (indoor area, presence of an open stairwell, and presence of gross motor activity facilitating items) and MVPA. These findings suggest that the studied characteristics of the home built environment may not significantly influence the MVPA observed among preschool-aged children in Dhaka. Future research should focus on other structural and behavioral factors that facilitate PA among young children in dense urban settings.

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics.

The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics.

The backbone of vertebrate animals consists of a series of bones called vertebrae that are joined together by disc-like structures that allow the back to move and distribute forces to protect it during daily activities. It is common for these intervertebral discs to degenerate with age, resulting in back pain and severely reducing quality of life. The mechanical features of intervertebral discs are the result of their proteins. These include extracellular matrix proteins, which form the external scaffolding that binds cells together in a tissue, and signaling proteins, which allow cells to communicate. However, how the levels of different proteins in each region of the disc vary with time has not been fully examined. To establish how protein composition changes with age, Tam, Chen et al. quantified the protein levels and gene activity (which leads to protein production) of intervertebral discs from young and old deceased individuals. They found that the position of different mixtures of proteins in the intervertebral disc changes with age, and that young people have high levels of extracellular matrix proteins and signaling proteins. Levels of these proteins decreased as people got older, as did the amount of proteins produced. To determine which region of the intervertebral disc different proteins were in, Tam, Chen et al. also performed magnetic resonance imaging (MRI) of the samples to correlate image intensity (which represents water content) with the corresponding protein signature. The data obtained provides a high-quality map of how the location of different proteins changes with age, and is available online under the name DIPPER. This database is an informative resource for research into skeletal biology, and it will likely advance the understanding of intervertebral disc degeneration in humans and animals, potentially leading to the development of new treatment strategies for this condition.

Challenges in current construction and demolition waste recycling: A China study.

China produced a large amount of construction and demolition (C&D) waste, owing to the rapid development of construction industry. Although a set of policies and regulations are being drafted in China for promoting C&D waste recycling, execution of these policies in practice seems to be far from effective. Currently, approximately 75% of Chinese cities are still surrounded by large volumes of C&D waste. Therefore, identification of challenges in the development of C&D waste management, specially recycling, is essential. This paper employs site visits to 10 recycling plants in 10 Chinese cities (Shanghai, Hangzhou, Suzhou, Chongqing, Chengdu, Xi'an, Changsha, Shenzhen, Nanjing, and Zhoukou) and interviews with 25 industry practitioners for examining the challenges. Eight challenges are identified: (1) unstable source of C&D waste for recycling, (2) absence of subsidies for recycling activities and high cost for land use, (3) insufficient attention paid to design for waste minimisation, (4) absence of regulations on on-site sorting, (5) unregulated landfill activities, (6) a lack of coordination among different government administration departments, (7) a lack of accurate estimation of waste quantity and distribution, and (8) a lack of an effective waste tracing system. Recommendations to address these challenges are presented. The results of this study are expected to aid policy makers in formulation of proper C&D waste management in China and provide a useful reference for researchers who are interested in C&D waste recycling industry.

Directed Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells.

Intervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-ß pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration.

A load-carrier perspective examination on the change of ecological environment carrying capacity during urbanization process in China.

Urbanization has prompted a dramatic social and economic development during the past decades in China. As a long-term national strategy, urbanization can only be implemented effectively with sufficient and sustainable ecological environment resources. By appreciating that the ecological environment carrying capacity (EECC) is a yardstick for guiding the practice of sustainable urban development, it is therefore pressing to examine the change of EECC adequately, so that the sustainable urbanization can be addressed appropriately. This paper develops a new method from load-carrier perspective to explore the change of EECC performance in the rapid urbanizing China. The EECC performance on water, land, atmosphere and overall perspectives were measured for 30 provinces in China based on the established method. The results show that most provinces in China are experiencing an improving EECC performance during the urbanization process, particularly with an obvious progress in land dimension. In referring to the spatial difference of overall EECC performance, the gap between 30 provinces has been narrowing during surveyed years. However, few provinces including Chongqing, Shandong and Jiangxi have undergone a degradation in overall EECC performance. The EECC performance in atmosphere dimension is still considered as a challenge faced by most provinces, evidenced by high level of PM2.5 concentration. These research findings provide valuable references not only for Chinese governments to formulate effective policy instruments and strategy measures for improving ecological environmental carrying status, but also for researchers to further study in the ecological environment carrying capacity in the context of other countries.

Zinc Supplementation and Body Weight: A Systematic Review and Dose-Response Meta-analysis of Randomized Controlled Trials.

The aim of this study was to determine the effect of zinc supplementation on anthropometric measures. In this systematic review and dose-response meta-analysis, we searched PubMed, Scopus, ISI Web of Science, and the Cochrane Library from database inception to August 2018 for relevant randomized controlled trials. Mean differences and SDs for each outcome were pooled using a random-effects model. Furthermore, a dose-response analysis for zinc dosage was performed using a fractional polynomial model. Quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Twenty-seven trials (n = 1438 participants) were included in the meta-analysis. There were no significant changes in anthropometric measures after zinc supplementation in the overall analysis. However, subgroup analyses revealed that zinc supplementation increased body weight in individuals undergoing hemodialysis (HD) [3 trials, n = 154 participants; weighted mean difference (WMD) = 1.02 kg; 95% CI: 0.38, 1.65 kg; P = 0.002; I2 = 11.4%] and decreased body weight in subjects who are overweight/obese but otherwise healthy (5 trials, n = 245 participants; WMD = -0.55 kg; 95% CI: -1.06, -0.04 kg; P = 0.03; I2 = 31.5%). Dose-response analyses revealed a significant nonlinear effect of supplementation dosage on BMI (P = 0.001). Our data suggest that zinc supplementation increases body weight in patients undergoing HD and decreases body weight in individuals who are overweight/obese but otherwise healthy, although after normalization for study duration, the association observed in subjects who are overweight/obese disappeared. Although more high-quality studies are needed to reach a definitive conclusion, our study supports the view that zinc may be associated with body weight.