Zero carbon building has been regarded as an important approach in reducing the carbon emissions associated with buildings. However, despite significant policy drivers, the uptake of this approach ...has been low. This paper examines the concepts and develops a theoretical model of the system boundaries of zero carbon buildings. Previous research is largely grounded in the net (nearly) zero carbon/energy parameter and focuses on buildings operations. However, there is increasing awareness of the need for lifecycle approaches to address carbon emissions and for boundaries to be defined to help elaborate the concept and guide research. The developed model covers eight types of boundaries, the policy timeframe, building lifecycle, geographic, climatic, stakeholder, sector, density and institutional boundaries. These boundaries are dynamic and interactive. It is concluded that zero carbon buildings should be regarded as complex socio-technical systems, but should not be exaggerated as surrogates for sustainable buildings. The findings are confirmed with case studies of five pioneering zero carbon buildings worldwide. The case studies demonstrate the great diversity and complexity of zero carbon building boundaries and assert that without the explicit specification of the boundaries, the comparison of cases in different contexts is like “comparing apples to pears.”
The purpose of this research was to improve the sorption ability of Pb and Cd by promoting the ion exchange and precipitation capacity of biochar. The adsorption performance and mechanisms of Pb and ...Cd in wastewater using coconut shell biochar modified with magnesium were investigated. After modification, the total adsorption capacity (Qt) of Pb and Cd on Mg-coated biochar (MgBC400) increased by 20 and 30 times compared with the unmodified biochar (BC400), respectively. The removal of Pb and Cd to biochar was attributed to ion exchange (Qe), mineral precipitation (Qp), interaction with oxygen functional groups (OFGs) (Qf), and metal-π electron coordination (Qπ). Compared with the BC400, the adsorption capacity of the four fractions of MgBC400 increased especially the ion exchange and precipitation. The Qe values of MgBC400 were almost 49 and 59 times that of BC400 in the adsorption of Pb and Cd, respectively. The Qp values of MgBC400 increased by 214.4 and 81.7 mg/g, respectively. Ion exchange and mineral precipitation dominated the adsorption of Pb and Cd by MgBC400.
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•The Qt of Pb2+/Cd2+ on MgB400 increased by 20/30 times, compared with B400.•The Qe of MgB400 was 49/59 times that of B400 in the adsorption of Pb2+/Cd2+.•MgB400 had a higher affinity for lead than cadmium.•Ion exchange and precipitation dominate the sorption of Pb2+/Cd2+ by MgB400.•MgO participated in ion exchange and precipitation processes.
The heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC ...tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8
T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8
T and immune-suppressive TNFRSF4
Treg cells in tumours might derive from peripheral CX3CR1
CD8
T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3
DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3
DCs, Treg, exhausted CD8
T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.
Long non-coding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte ...malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression.
In this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP) was performed to explore the mechanism of miRNA-lncRNA sponging.
We firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H
O
and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs) by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4.
Our study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and may serve as novel targets for the development of new countermeasures of CCA.
As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human ...organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing.
We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH
fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues.
The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.
Measurement-device-independent quantum key distribution (MDI QKD) removes all detector side channels and enables secure QKD with an untrusted relay. It is suitable for building a star-type quantum ...access network, where the complicated and expensive measurement devices are placed in the central untrusted relay and each user requires only a low-cost transmitter, such as an integrated photonic chip. Here, we experimentally demonstrate a 1.25-GHz silicon photonic chip-based MDI QKD system using polarization encoding. The photonic chip transmitters integrate the necessary encoding components for a standard QKD source. We implement random modulations of polarization states and decoy intensities, and demonstrate a finite-key secret rate of31bit/sover 36-dB channel loss (or 180-km standard fiber). This key rate is higher than state-of-the-art MDI QKD experiments. The results show that silicon photonic chip-based MDI QKD, benefiting from miniaturization, low-cost manufacture, and compatibility with CMOS microelectronics, is a promising solution for future quantum secure networks.
Cold atoms with laser-induced spin-orbit (SO) interactions provide a platform to explore quantum physics beyond natural conditions of solids. Here we propose and experimentally realize ...two-dimensional (2D) SO coupling and topological bands for a rubidium-87 degenerate gas through an optical Raman lattice, without phase-locking or fine-tuning of optical potentials. A controllable crossover between 2D and 1D SO couplings is studied, and the SO effects and nontrivial band topology are observed by measuring the atomic cloud distribution and spin texture in momentum space. Our realization of 2D SO coupling with advantages of small heating and topological stability opens a broad avenue in cold atoms to study exotic quantum phases, including topological superfluids.
Bioactive species, including reactive oxygen species (ROS, including O
2
&z.rad;
−
, H
2
O
2
, HOCl,
1
O
2
, &z.rad;OH, HOBr,
etc.
), reactive nitrogen species (RNS, including ONOO
−
, NO, NO
2
, ...HNO,
etc.
), reactive sulfur species (RSS, including GSH, Hcy, Cys, H
2
S, H
2
S
n
, SO
2
derivatives,
etc.
), ATP, HCHO, CO and so on, are a highly important category of molecules in living cells. The dynamic fluctuations of these molecules in subcellular microenvironments determine cellular homeostasis, signal conduction, immunity and metabolism. However, their abnormal expressions can cause disorders which are associated with diverse major diseases. Monitoring bioactive molecules in subcellular structures is therefore critical for bioanalysis and related drug discovery. With the emergence of organelle-targeted fluorescent probes, significant progress has been made in subcellular imaging. Among the developed subcellular localization fluorescent tools, ROS, RNS and RSS (RONSS) probes are highly attractive, owing to their potential for revealing the physiological and pathological functions of these highly reactive, interactive and interconvertible molecules during diverse biological events, which are rather significant for advancing our understanding of different life phenomena and exploring new technologies for life regulation. This review mainly illustrates the design principles, detection mechanisms, current challenges, and potential future directions of organelle-targeted fluorescent probes toward RONSS.
The dynamic fluctuations of bioactive species in living cells are associated with numerous physiological and pathological phenomena. The emergence of organelle-targeted fluorescent probes has significantly facilitated our understanding on the biological functions of these species. This review describes the design, applications, challenges and potential directions of organelle-targeted bioactive species probes.
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, ...we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy. Mechanistically, LATS1/2-null tumor cells secrete nucleic-acid-rich extracellular vesicles, which induce a type I interferon response via the Toll-like receptors-MYD88/TRIF pathway. LATS1/2 deletion in tumors thus improves tumor immunogenicity, leading to tumor destruction by enhancing anti-tumor immune responses. Our observations uncover a key role of the Hippo pathway in modulating tumor immunogenicity and demonstrate a proof of concept for targeting LATS1/2 in cancer immunotherapy.
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•LATS1/2 deletion in tumor cells inhibits tumor growth in vivo•Loss of LATS1/2 induces anti-tumor immune responses•Extracellular vesicles from LATS1/2-null tumors stimulate the host TLRs-IFN pathway•LATS1/2 deletion enhances tumor vaccine efficacy
The Hippo pathway, known to be tumor suppressive, is surprisingly found to have a role in suppressing anti-tumor immune responses. Loss of the LATS1/2 kinases results in the induction of innate and adaptive immune responses that reduce tumor growth and improves vaccine efficacy.
With the increasing availability of large-scale GWAS summary data on various traits, Mendelian randomization (MR) has become commonly used to infer causality between a pair of traits, an exposure and ...an outcome. It depends on using genetic variants, typically SNPs, as instrumental variables (IVs). The inverse-variance weighted (IVW) method (with a fixed-effect meta-analysis model) is most powerful when all IVs are valid; however, when horizontal pleiotropy is present, it may lead to biased inference. On the other hand, Egger regression is one of the most widely used methods robust to (uncorrelated) pleiotropy, but it suffers from loss of power. We propose a two-component mixture of regressions to combine and thus take advantage of both IVW and Egger regression; it is often both more efficient (i.e. higher powered) and more robust to pleiotropy (i.e. controlling type I error) than either IVW or Egger regression alone by accounting for both valid and invalid IVs respectively. We propose a model averaging approach and a novel data perturbation scheme to account for uncertainties in model/IV selection, leading to more robust statistical inference for finite samples. Through extensive simulations and applications to the GWAS summary data of 48 risk factor-disease pairs and 63 genetically uncorrelated trait pairs, we showcase that our proposed methods could often control type I error better while achieving much higher power than IVW and Egger regression (and sometimes than several other new/popular MR methods). We expect that our proposed methods will be a useful addition to the toolbox of Mendelian randomization for causal inference.
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