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Phase change materials could store and release heat energy through phase change. However, the shortcomings of low thermal conductivity in the photothermal conversion process and easy leakage in the solid-liquid conversion seriously hinder the application of heat energy utilization. Graphene had high thermal conductivity, and it was an ideal material for improving the solar absorption, solar energy conversion and thermal conductivity of phase change materials. In this paper, a graphene aerogel composed of copper nanowires (CuNWs)/2-acrylamide-2-methylpropanesulfonic acid (AMPS) was designed. The thermal conductivity and shape stability of phase change materials for solar-thermal-electrical conversion applications were enhanced by composite CuNWs. Furthermore, PAMPS was coated on the surface of copper nanowires to avoid the oxidation of copper nanowires, and the sulfonic acid group of PAMPS was used to induce CuNWs to disperse uniformLy on the graphene sheets, which further constructed a good conductive network. After vacuum impregnation of PW, the best thermal conductivity phase change composite (PW-CuNWs@PAMPS-GA (1:1)) was obtained. The PCC loaded with CuNWs with the same graphene content achieved a thermal conductivity of 1.46 W/(m·K) and a high latent heat of 206.8 J/g. The latent heat retention rate was as high as 99.57 %. The photothermal conversion efficiency of PW-CuNWs@PAMPS-GA (1:1) was remarkable at 96.4 %. Due to its excellent solar-thermal-electrical conversion efficiency, the output voltage and output current were 800.8 mV and 85.8 mA, respectively, at a solar analog intensity of 5 kW/m2. Even after the sunlight was stopped, the voltage output could be maintained for a while by releasing the heat energy stored in the phase change composite. [Display omitted] [ABSTRACT FROM AUTHOR]

Borehole heat exchangers (BHEs) are often used to harvest geothermal energy at shallower depths. The standard increase in temperature with depth is generally ignored. Without high quality electricity generation as with enhanced geothermal systems (EGS) there is a lack of financial incentive for drilling deeper for higher temperatures. This temperature increase, or geothermal gradient, is rarely captured by analytical BHE models for building heating and cooling. In this paper we present a new analytical model for a coaxial borehole heat exchanger (CBHE) that specifically considers geothermal gradient. We first verify our model output by comparing results with existing numerical and experimental results under the same configuration of CBHE. To further investigate our model's sensitivity towards fluid flow direction, geothermal gradient, and borehole thermal resistance, we also compare the temperature distributions and rate of heat gain/loss along the flow direction within the entire proposed CBHE. We identify the best flow direction with annulus as inlet in heat extraction mode, confirm positive influence of increasing geothermal gradients towards the heat extraction, and confirm a nonlinear correlation between the borehole thermal resistance with the output fluid temperature and amount of heat extracted. This study can provide a useful analytical simulation tool and important guide to design of CBHE. • A new segmented-line source model includes influences of geothermal gradient. • The new model allows calculation of fluid, borehole, soil temperatures. • A preliminary parametric investigation is conducted for coaxial borehole heat exchanger. • Potential to be used in future optimizations of coaxial borehole heat exchanger designs. [ABSTRACT FROM AUTHOR]

We can use the concept of exergy to analyze a human body as a heat emitter: while generating heat continuously, the body remains at roughly the same temperature through physiological responses such as shivering, sweating, breathing thus raising/decreasing the core and/or skin temperature to maintain effective heat dissipation. Existing literature provides an estimated exergy consumption rate of the human body ranging from 2 to 5 W / m 2 , while nearly unanimously agreeing on a local exergy consumption minima points to potential individual thermal comfort. To clarify the underlying assumptions used in the existing human body exergy models, we analytically and numerically reviewed the terms used for assessing metabolism, radiation, evaporation, and convection exergy changes of the human body in this paper. We observed overestimations of exergy from metabolism, underestimations of exergy change through radiation, and some caveats in the signage of convective exergy losses in the results we obtained. We were also able to propose an improved expression to estimate human body radiation exergy exchanges as well as selecting reference temperatures that are more process-specific. Future studies that provide experimental verification of these models were also deemed necessary. • Term-by-term comparison of existing human body exergy model expressions; • Showed T op/E cons minima combination for male/female occupants across age span; • Compared linear radiant heat transfer coefficient against actual radiation heat transfer; • Showed how reference temperature affects the sign of evaporation exergy loss. [ABSTRACT FROM AUTHOR]

Common coatings have unsatisfactory long-term anticorrosion performance due to poor barrier property. In this work, LDH-MoO 4 2− nano-filler (KGO@LM) modified by KH-570 and GO was prepared to improve the long-term corrosion resistance of epoxy resin (EP) coating. The filler integrates the three functions of barrier, chloride ion trapping and self-repair, and has good dispersion and compatibility in EP. After soaking in 3.5 wt% NaCl solution for 28 days, the low-frequency impedance of KGO@LM coating was still as high as 1.02 × 108 Ω·cm2, while the remaining value of EP coating was only 2.63 × 106 Ω cm2,so the addition of KGO@LM filler significantly improved the anticorrosive effect of EP coating. After soaking in 3.5 wt% NaCl solution for 18 h, the low-frequency impedance of the scratched KGO@LM/EP coating was 1.5 orders of magnitude higher than that of the EP coating, which proved that the designed filler had a significant corrosion inhibiting effect. Therefore, it is believed that this work can provide some inspirations for other researchers to develop long-term anticorrosion coatings. [Display omitted] • The prepared filler effectively improves the dispersion and compatibility in epoxy resin. • The packing set barrier, chloride ion capture and self-repair three functions in one. • The coating with the filler has long-term anticorrosion effect. [ABSTRACT FROM AUTHOR]

Abstract The globe thermometer has been considered a reliable instrument to quantify mean radiant temperature (MRT) since Bedford & Warner isolated its readings from air movement in their 1934 paper so that radiation could be quantified. Recent expanded use of radiant heating and cooling systems has presented new challenges for the usage of globe thermometers in the built environment by causing additional radiant asymmetries and performance expectations. Therefore, we replicate the original Bedford & Warner work to reconsider and develop a more holistic understanding of black globe performance and the determination of MRT in buildings. We recreate the MRT and air temperature separation to investigate the accuracy of globe thermometers on measuring MRTs. A radiantly heated open-plan laboratory and a radiantly cooled conference room were selected and measured with multiple globe thermometers and non-contacting infrared sensors. The globe temperature results were then corrected with air movement to produce MRTs and compared against MRTs simulated from measured surface temperatures. We demonstrate a significant impact of air speed on the MRTs obtained from globe thermometers. We also illustrate a less-investigated non-graybody emissivity variation and spatial variation of MRTs of up to 5 °C at the same height. We believe the increasing temporal and spatial resolution of digital sensors may create new challenges for using globe thermometers to measure MRTs, since fluctuating readings may camouflage potential MRT changes. Through a validation of our spatial MRT distribution with experimental results, we believe there is a need for better sensors that could spatially resolve MRTs, and recognize issues with both air speed and emissivity. [ABSTRACT FROM AUTHOR]

Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16 -related interferon-inducible genes implicated in innate immunity. The re-expression of CD1 or IFI16 murine orthologs in immuno-competent mice abrogates tumorigenesis, accompanied by the activation of anti-tumor immunity. Thus, early epigenetic changes may shape tumorigenesis, targeting co-located genes within defined chromosomal loci. Hypomethylation domains are detectable in blood specimens enriched for CTCs. [Display omitted] • 40 core hypomethylated domains, shared across prostate CTCs, arise early in tumorigenesis • Hypomethylation silences immune-related genes, sparing adjacent proliferation genes • The CD1A-IFI16 immune locus is consistently silenced by hypomethylation in cancer • Hypomethylated domains are detected in CTC-enriched blood in localized prostate cancer Analysis of primary prostate cancer and circulating tumor cells reveals how DNA hypomethylation during early prostate tumorigenesis silences immune surveillance genes while sparing proliferation-associated genes. [ABSTRACT FROM AUTHOR]

The Thermoheliodome is an experimental pavilion that explores cooling without air conditioning. The two research aims were to explore the use of indirect evaporative cooling and the geometric reflection of radiant cooling. For evaporative cooling we utilize a cooling tower outside of the pavilion to indirectly supply water chilled near the wet-bulb temperature. The radiant cooling system is made up of 55 coaxial chilled pipes each located in the central axis of cones with reflective surfaces that spectrally reflect the surface of the pipes and expand their radiant view factor to the occupants inside the pavilion. The specific geometry was digitally fabricated using an industrial robot and hot-wire foam cutter. The mean radiant temperature (MRT) was shown to be significantly decreased using thermal imaging cameras and with a novel scanning MRT sensor. The radiant cooling delivered from the fluid is maximized by reflection and concentration of heat emitted by occupants on the pipes, while the convective cooling of the air is minimized because only the small pipes are cooled and the reflecting surfaces are not, so the convective heat transfer surface area is small. Under typical indoor office conditions the ratio of radiant to convective cooling is slightly greater than one. For the Thermoheliodome the radiant ratio was greater than 10. Occupant surveys found that although the air temperature was not modified, they felt that inside the space there is a cooling sensation ( p ≤ 0.01). The day of the survey they felt on average 3 °C cooler. [ABSTRACT FROM AUTHOR]

DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development. However, its dynamic patterns have not been analysed at the genome scale in human pre-implantation embryos due to technical difficulties and the scarcity of required materials. Here we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by reduced representation bisulphite sequencing and whole-genome bisulphite sequencing. We show that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome is much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei is already lower than that in female pronuclei. The inverse correlation between promoter methylation and gene expression gradually strengthens during early embryonic development, reaching its peak at the post-implantation stage. Furthermore, we show that active genes, with the trimethylation of histone H3 at lysine 4 (H3K4me3) mark at the promoter regions in pluripotent human embryonic stem cells, are essentially devoid of DNA methylation in both mature gametes and throughout pre-implantation development. Finally, we also show that long interspersed nuclear elements or short interspersed nuclear elements that are evolutionarily young are demethylated to a milder extent compared to older elements in the same family and have higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Our work provides insights into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements. [ABSTRACT FROM AUTHOR]

Deregulation of oncogenic signals in cancer triggers replication stress. Immediate early genes (IEGs) are rapidly and transiently expressed following stressful signals, contributing to an integrated response. Here, we find that the orphan nuclear receptor NR4A1 localizes across the gene body and 3′ UTR of IEGs, where it inhibits transcriptional elongation by RNA Pol II, generating R-loops and accessible chromatin domains. Acute replication stress causes immediate dissociation of NR4A1 and a burst of transcriptionally poised IEG expression. Ectopic expression of NR4A1 enhances tumorigenesis by breast cancer cells, while its deletion leads to massive chromosomal instability and proliferative failure, driven by deregulated expression of its IEG target, FOS. Approximately half of breast and other primary cancers exhibit accessible chromatin domains at IEG gene bodies, consistent with this stress-regulatory pathway. Cancers that have retained this mechanism in adapting to oncogenic replication stress may be dependent on NR4A1 for their proliferation. [Display omitted] • NR4A1 specifically localizes to IEG gene bodies suppressing transcriptional elongation • Acute replication stress triggers NR4A1 release, triggering burst of IEG expression • NR4A1 deletion deregulates expression of the IEG FOS , triggering mitotic catastrophe • The NR4A1-IEG pathway denotes differentiated cancers with a favorable prognosis Studying tumorigenesis by patient-derived breast cancer cells, Guo et al. identify NR4A1 as a master regulator of replication stress-induced immediate early gene expression through a transcriptional processing checkpoint. Suppression of NR4A1 in cancer cells dependent on this pathway triggers mitotic catastrophe through unregulated expression of the IEG family member FOS. [ABSTRACT FROM AUTHOR]

Determining variations in air temperature and mean radiant temperature (MRT), two primary environmental parameters directly linked to thermal comfort, can be challenging. The ease and effectiveness of both measurement and simulation are quite different for determining air temperature and MRT. We review these challenges and present an experiment demonstrating how these differences in complexity and resolution can lead to challenges coupling these variables, whose effect on thermal comfort is interdependent. Bearing these challenges in mind, we measured and simulated the air temperatures and MRTs inside a radiantly heated high bay laboratory space. We found the spatial variation of the MRTs to vary by 5 ° C at the elevation of 1.3 m, which is much larger than the variations observed in air temperature. The variations in measured air temperature were up to 2 ° C. This calls for improvement to current tools and methodologies for measuring and simulating the radiant environment, particularly at locations closer to the exterior envelope where hot and cold surfaces affect both air temperature and MRT. It is important to improve the evaluation techniques for MRT, as we observe its spatial variation to be much greater than that of air temperature, while its measurement is limited and usually ignored in practice. • Simulated and modeled air and mean radiant temperatures distributions. • Used angle-factor-based MRT characterization when modeling 3D MRT. • Demonstrated rarely-captured spatial MRT variation in an indoor environment. • Discussed existing limitations in using Ta to evaluate indoor thermal environment. • Showed importance of integral indoor environment sensing and monitoring. [ABSTRACT FROM AUTHOR]

Mean radiant temperature is central to our understanding of the radiant heat exchange between the human body and surrounding environment. This paper will present a review of the concept's evolution including its qualitative definition, methods of quantitative evaluation and corresponding challenges. In the process, this review suggests that more effort needs to be invested in addressing the geometric complexities of radiant heat transfer in research into MRT; the ASHRAE definition is broad and is liable to simplification, and research which uses the definition relies on a variety of simplifications, often without acknowledging the degree of geometric complexity which exists in reality. Existing means of obtaining an estimate of mean radiant temperature range from direct measurements using globe thermometers or net radiometers, to computational simulations, and are widely used for studies within indoor and outdoor environments. Previous literature studying the correlation between air temperature and MRT has found equivalence ratios, the relative importance of convection to radiation, ranging from 0.71 to 1.4, however, it is often assumed to be 1.0 in current research practices. We also identified a rapid increase in the usage of MRT in biometeorological studies during the last ten years on top of the increased usage in indoor environment sensing and modeling in light of recent developments in heating and cooling systems. Recent efforts to include the short-wave component in indoor MRT characterization have shown an increase in cooling capacity of radiant floors from 32 to 110 W/m2; significantly decreasing peak energy demand. • We have expanded the conclusion section with both numerical conclusions and expanded discussions on the limitations of existing MRT usages. • Included new citations that covers the latest development of MRT research and standardization effort (ASHRAE Standard 55-2017, for example). • Adding new illustration of the MRT as a concept in relation to the human body geometry. • Expanded review on how indoor MRT variations due to shortwave radiation are characterized [ABSTRACT FROM AUTHOR]

The optimization of the sintering process for ceramic stereolithography-based additive manufacturing is attracting high interest important due to its correlation with the final properties of the fabricated parts. In this work, a photosensitive zirconia suspension with low viscosity and high solid loading (48 vol%) was prepared using surface-modified zirconia ceramic powders, resulting in an improvement in long-term stability. The correlations between the sintering temperature (1400–1520 °C) and mechanical properties were investigated. The results showed that and the as-sintered zirconia parts exhibited a relatively high density of 99.5 ± 0.1 % and three-point flexural strength of 821 ± 65 MPa as well as excellent fracture toughness (4.37 ± 0.22 MPa m1/2) sintering at 1480 °C, which was attributed to the highly homogeneous microstructure without obvious pores or crack. The obtained insights regarding the correlation between sintering temperature, relative density, and flexural strength can provide practical guidance for the future applications of zirconia ceramics. [ABSTRACT FROM AUTHOR]

Study Question: Is it possible to evaluate the methylome of individual oocytes to investigate the DNA methylome alterations in metaphase II (MII) oocytes with reduced embryo developmental potential?Summary Answer: The DNA methylome of each human first polar body (PB1) closely mirrored that of its sibling MII oocyte; hypermethylated long interspersed nuclear element (LINE) and long terminal repeats (LTRs) and methylation aberrations in PB1 promoter regions may indicate poor embryo development.What Is Known Already: The developmental potential of an embryo is determined by the oocyte's developmental competence, and the PB1 is a good substitute to examine the chromosomal status of the corresponding oocyte. However, DNA methylation, a key epigenetic modification, also regulates gene expression and embryo development.Study Design, Size, Duration: Twelve pairs of PB1s and sibling MII oocytes were biopsied and sequenced to compare their methylomes. To further investigate the methylome of PB1s and the potential epigenetic factors that may affect oocyte quality, MII oocytes (n = 74) were fertilized through ICSI, while PB1s were biopsied and profiled to measure DNA methylation. The corresponding embryos were further cultured to track their development potential. The oocytes and sperm samples used in this study were donated by healthy volunteers with signed informed consent.Participants/materials, Setting, Methods: Single-cell methylome sequencing was applied to obtain the DNA methylation profiles of PB1s and oocytes. The DNA methylome of PB1s was compared between the respective group of oocytes that progressed to blastocysts and the group of oocytes that failed to develop. DNA methylation levels of corresponding regions and differentially methylated regions were calculated using customized Perl and R scripts. RNA-seq data were downloaded from a previously published paper and reanalysed.Main Results and the Role Of Chance: The results from PB1-MII oocyte pair validated that PB1 contains nearly the same methylome (average Pearson correlation is 0.92) with sibling MII oocyte. LINE and LTR expression increased markedly after fertilization. Moreover, the DNA methylation levels in LINE (including LINE1 and LINE2) and LTR were significantly higher in the PB1s of embryos that could not reach the blastocyst stage (Wilcoxon-Matt-Whitney test, P < 0.05). DNA methylation in PB1 promoters correlated negatively with gene expression of MII oocyte. Regarding the methylation status of the promoter regions, 66 genes were hypermethylated in the developmental arrested group, with their related functions (significantly enriched in several Gene Ontology terms) including transcription, positive regulation of adenylate cyclase activity, mitogen-activated protein kinase (MAPK) cascade and intracellular oestrogen receptor signalling pathway.Large Scale Data: N/A.Limitations, Reasons For Caution: Data analysis performed in this study focused on the competence of human oocytes and compared them with maternal genetic and epigenetic profiles. Therefore, data regarding the potential regulatory roles of paternal genomes in embryo development are lacking.Wider Implications Of the Findings: The results from PB1-oocyte pairs demonstrated that PB1s shared similar methylomes with their sibling oocytes. The selection of the good embryos for transfer should not only rely on morphology but also consider the DNA methylation of the corresponding PB1 and therefore MII oocyte. The application of early-stage analysis of PB1 offers an option for high-quality oocyte and embryo selection, which provides an additional tool for elective single embryo transfer in assisted reproduction.Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2018YFC1004003, 2017YFA0103801), the National Natural Science Foundation of China (81730038, 3187144, 81521002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020703). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Identifying expressed somatic mutations from single-cell RNA sequencing data de novo is challenging but highly valuable. We propose RESA – Recurrently Expressed SNV Analysis, a computational framework to identify expressed somatic mutations from scRNA-seq data. RESA achieves an average precision of 0.77 on three in silico spike-in datasets. In extensive benchmarking against existing methods using 19 datasets, RESA consistently outperforms them. Furthermore, we applied RESA to analyze intratumor mutational heterogeneity in a melanoma drug resistance dataset. By enabling high precision detection of expressed somatic mutations, RESA substantially enhances the reliability of mutational analysis in scRNA-seq. RESA is available at https://github.com/ShenLab-Genomics/RESA. [ABSTRACT FROM AUTHOR]

Summary Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental-stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation, with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes. [ABSTRACT FROM AUTHOR]

Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. Here we apply single-cell RNA sequencing (RNA-Seq) analysis to 124 individual cells from human preimplantation embryos and human embryonic stem cells (hESCs) at different passages. The number of maternally expressed genes detected in our data set is 22,687, including 8,701 long noncoding RNAs (lncRNAs), which represents a significant increase from 9,735 maternal genes detected previously by cDNA microarray. We discovered 2,733 novel lncRNAs, many of which are expressed in specific developmental stages. To address the long-standing question whether gene expression signatures of human epiblast (EPI) and in vitro hESCs are the same, we found that EPI cells and primary hESC outgrowth have dramatically different transcriptomes, with 1,498 genes showing differential expression between them. This work provides a comprehensive framework of the transcriptome landscapes of human early embryos and hESCs. [ABSTRACT FROM AUTHOR]

The indoor environment directly affects health and comfort as humans spend most of the day indoors. However, improperly controlled ventilation systems can expend unnecessary energy and increase health risks, while improved thermal and air quality can often result in higher energy consumption. One way to approach this dilemma is by understanding the effectiveness of the variables influencing indoor air quality (IAQ) related health and comfort. The objective of this paper is to highlight evidence and variables from empirical and deterministic models, which are combined in analytical models that current machine learning techniques often overlook. This paper reviews the analytical models and identifies the corresponding input variables, discussing their application in models based on artificial neural networks (ANNs) and reinforcement learning (RL). ANN and RL models have accurately described non-linear systems with uncertain dynamics and provided predictive and adaptive control strategies. The first part of this study focuses on the most common thermal comfort models and their variables, mainly related to steady-state and adaptive models. The second part reviews typical models of determining indoor air pollutants and their relationship with ventilation requirements and health effects. Forty-five works closely related to the field are summarized in multiple tables. The last part identifies the factors needed to predict thermal comfort and IAQ. • Analytical models and its variables of IAQ related thermal comfort are discussed. • Analytical models and its variables of IAQ related health are investigated. • ANNs have emerged as the most used technique to define building sensing systems. • RL is an efficient one for improving human-building interaction. • Improving thermal comfort and health while lessening energy use is feasible. [ABSTRACT FROM AUTHOR]

Abstract Although passive building envelope systems dominate contemporary building design, active building envelope (ABE) research, development, and deployment are rapidly growing and present many new ways to address building energy efficiency at the façade level. This paper presents a comprehensive review on the state-of-art-research on ABEs for improving building energy efficiency. First, a clarified concept of ABE is put forward based on two conditions: The ability of lowering cooling/heating loads in buildings, and performing energy transformation as the key judging factors. Second, four major categories of ABEs, namely air-based, water-based, solid-based and kinetic façades, are discussed in terms of their system structural and functional features as well as system performance. In addition, a statistical analysis is performed for a better understanding of current research focus, general trends, as well as research methods. It is found that technical research on ABEs has dramatically increased but the ratio of ABE to general façade studies remains stable. In terms of research methods and approaches, numerical simulations are dominant. Some specific comments on limitations of current ABE studies and general suggestions for the future studies are discussed. Future work suggests the need for contributions from a wide range of scientists, engineers, and architects in the building industry and beyond to push forward building energy efficiency. Highlights • A new and effective definition of active building envelope is proposed. • Research tendency, distributions and study methods offer a clear map of active building envelopes. • A state-of-the-art review and discussion is presented for active building envelopes. • Outlooks and recommendations for active envelopes can facilitate its further development. [ABSTRACT FROM AUTHOR]

Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced. The cancer cells’ DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue and those of repetitive element long interspersed nuclear element 1. Our work demonstrates the feasibility of reconstructing genetic lineages and tracing their epigenomic and transcriptomic dynamics with single-cell multiomics sequencing. [ABSTRACT FROM AUTHOR]