| 1. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Jin, Ying-Hui, et al.
(author)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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In: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Journal article (peer-reviewed)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 3. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 4. |
- Yang, Wen-Jing, et al.
(author)
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Heparanase from triple-negative breast cancer and platelets acts as an enhancer of metastasis
- 2020
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In: International Journal of Oncology. - : SPANDIDOS PUBL LTD. - 1019-6439 .- 1791-2423. ; 57:4, s. 890-904
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Journal article (peer-reviewed)abstract
- Triple-negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia-inducible factor-1a (HIF-1a)/vascular endothelial growth factor-a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti-Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.
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| 5. |
- Zeng, Jiangyuan, et al.
(author)
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Innovations in science, technology, engineering, and policy (iSTEP) for addressing environmental issues towards sustainable development
- 2024
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In: The Innovation Geoscience. - : Innovation Press. - 2959-8753. ; 2:3
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Journal article (peer-reviewed)abstract
- Sustainable development depends on the integration of the economy, society, and environment. Yet, escalating environmental challenges pose threats to both society and the economy. Despite progress in addressing environmental issues to promote sustainability, knowledge gaps in scientific research, technological advancement, engineering practice, and policy development persist. In this review, we aim to narrow these gaps by proposing innovation-based solutions and refining existing paradigms. Reviewing past research and actions, we first elucidate the evolution of sustainability science and the essence of sustainable development and its assessment. Secondly, we summarize current major environmental issues, including global warming and climate change, biodiversity loss, land degradation and desertification, and environmental pollution, as well as their relationships with sustainability and the achievement of Sustainable Development Goals (SDGs). Subsequently, this review critically evaluates the role of innovations in science, technology, engineering, and policy (iSTEP) and their synergies in advancing sustainability and SDGs. While their sequential relationships may vary based on specific contexts or sustainability scenarios within the iSTEP framework, each component reinforces the others, fostering continuous improvement. Finally, this review offers recommendations and future perspectives for formulating sustainability roadmaps. Recommendations include fostering a vision of sustainability, promoting interdisciplinary collaboration, and encouraging transboundary cooperation among stakeholders for future sustainability endeavors.
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| 6. |
- Byun, Jinyoung, et al.
(author)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
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In: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
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Journal article (peer-reviewed)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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| 7. |
- Chen, Zhishan, et al.
(author)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 8. |
- Fan, Qunping, 1989, et al.
(author)
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Over 14% efficiency all-polymer solar cells enabled by a low bandgap polymer acceptor with low energy loss and efficient charge separation
- 2020
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In: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 13:12, s. 5017-5027
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Journal article (peer-reviewed)abstract
- Obtaining both high open-circuit voltage (V-oc) and short-circuit current density (J(sc)) has been a major challenge for efficient all-polymer solar cells (all-PSCs). Herein, we developed a polymer acceptor PF5-Y5 with excellent optical absorption capability (onset extending to similar to 880 nm and maximum absorption coefficient exceeding 105 cm(-1) in a film), high electron mobility (3.18 x 10(3) cm(2) V-1 s(-1)) and high LUMO level (-3.84 eV) to address such a challenge. As a result, the PBDB-T:PF5-Y5-based all-PSCs achieved a high power conversion efficiency of up to 14.45% with both a high Voc (0.946 V) and a high Jsc (20.65 mA cm(-2)), due to the high and broad absorption coverage, small energy loss (0.57 eV) and efficient charge separation and transport in the device, which are among the best values in the all-PSC field. In addition, the all-PSC shows a similar to 15% improvement in PCE compared to its counterpart small molecule acceptor (Y5)-based device. Our results suggest that PF5-Y5 is a very promising polymer acceptor candidate for applications in efficient all-PSCs.
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| 9. |
- Fernandez-Rozadilla, Ceres, et al.
(author)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 10. |
- Jiang, Kui, et al.
(author)
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Suppressed recombination loss in organic photovoltaics adopting a planar-mixed heterojunction architecture
- 2022
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In: Nature Energy. - : NATURE PORTFOLIO. - 2058-7546. ; 7:11, s. 1076-1086
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Journal article (peer-reviewed)abstract
- At present, high-performance organic photovoltaics mostly adopt a bulk-heterojunction architecture, in which exciton dissociation is facilitated by charge-transfer states formed at numerous donor-acceptor (D-A) heterojunctions. However, the spin character of charge-transfer states originated from recombination of photocarriers allows relaxation to the lowest-energy triplet exciton (T-1) at these heterojunctions, causing photocurrent loss. Here we find that this loss pathway can be alleviated in sequentially processed planar-mixed heterojunction (PMHJ) devices, employing donor and acceptor with intrinsically weaker exciton binding strengths. The reduced D-A intermixing in PMHJ alleviates non-geminate recombination at D-A contacts, limiting the chance of relaxation, thus suppressing T-1 formation without sacrificing exciton dissociation efficiency. This resulted in devices with high power conversion efficiencies of >19%. We elucidate the working mechanisms for PMHJs and discuss the implications for material design, device engineering and photophysics, thus providing a comprehensive grounding for future organic photovoltaics to reach their full promise. Organic solar cells with a bulk-heterojunction architecture suffer from photocurrent loss driven by triplet states. Now, Jiang et al. show that sequentially deposited donor-acceptor planar-mixed heterojunctions suppress triplet formation, enabling efficiencies over 19%.
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| 11. |
- Xia, Xinxin, et al.
(author)
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Revealing the crystalline packing structure of Y6 in the active layer of organic solar cells: the critical role of solvent additives
- 2023
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In: Journal of Materials Chemistry A. - : ROYAL SOC CHEMISTRY. - 2050-7488 .- 2050-7496. ; 11:40, s. 21895-21907
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Journal article (peer-reviewed)abstract
- The bulk heterojunction (BHJ) morphology of photovoltaic materials is crucial to the fundamental optoelectronic properties of organic solar cells (OSCs). However, in the photoactive layer, the intrinsic crystalline packing structure of Y6, currently the hallmark molecule among Y-series non-fullerene acceptors (NFAs), has not been unambiguously determined. Here, employing grazing-incidence wide-angle X-ray scattering (GIWAXS), we managed to uncover the intrinsic crystalline packing structure of Y6 in the BHJ active layer of OSCs, which is found to be different from its single-crystal structure reported previously. Moreover, we find that solvent additive 1-chloronaphthalene (CN) can induce highly ordered packing of Y6 in BHJ thin films. With the help of atomistic molecular dynamics simulations, it is revealed that pi-pi interactions generally exist between naphthalene derivatives and IC terminals of Y6 analogues, which would essentially improve their long-range ordering. Our work reveals the intrinsic crystalline packing structure of Y6 in the BHJ active layer as well as its crystallization mechanism in thin films, thus providing direct correlations between this crystalline packing and the device characteristics and photophysical properties.
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| 12. |
- Xiao, Yiming, et al.
(author)
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Multiscale dilated convolutional subdomain adaptation network with attention for unsupervised fault diagnosis of rotating machinery cross operating conditions
- 2022
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In: Measurement. - : Elsevier. - 0263-2241 .- 1873-412X. ; 204
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Journal article (peer-reviewed)abstract
- Unsupervised cross-domain fault diagnosis research of rotating machinery has significant implications. However, some issues remain to be solved. For example, convolutional neural network cannot capture discriminative information in vibration signals from different scales. In addition, the extracted features should be selected to enhance informative features and suppress redundant features. Finally, global domain adaptation methods may cause different subdomains of source and target domains to be too close. To address these challenges, this paper proposes a multiscale dilated convolutional subdomain adaptation network with attention. Firstly, a multiscale dilated convolutional module is developed to extract fault features at different scales. Secondly, a squeeze-and-excitation attention mechanism is built to assign channel-level weights to these features. Finally, local maximum mean discrepancy is constructed to adapt corresponding subdomains of the two domains. The proposed method is applied to perform various unsupervised cross-domain fault diagnosis tasks, and the experimental results demonstrate its superior diagnostic performance.
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| 13. |
- Zhang, Gan-Lin, et al.
(author)
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Significance of host heparanase in promoting tumor growth and metastasis
- 2020
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In: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 93, s. 25-42
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Journal article (peer-reviewed)abstract
- Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Much of the impact of heparanase on tumor progression is related to its function in mediating tumor-host crosstalk, priming the tumor microenvironment to better support tumor growth and metastasis. We have utilized mice over-expressing (Hpa-tg) heparanase to reveal the role of host heparanase in tumor initiation, growth and metastasis. While in wild type mice tumor development in response to DMBA carcinogenesis was restricted to the mammary gland, Hpa-tg mice developed tumors also in their lungs and liver, associating with reduced survival of the tumor-bearing mice. Consistently, xenograft tumors (lymphoma, melanoma, lung carcinoma, pancreatic carcinoma) transplanted in Hpa-tg mice exhibited accelerated tumor growth and shorter survival of the tumor-bearing mice compared with wild type mice. Hpa-tg mice were also more prone to the development of metastases following intravenous or subcutaneous injection of tumor cells. In some models, the growth advantage was associated with infiltration of heparanase-high host cells into the tumors. However, in other models, heparanase-high host cells were not detected in the primary tumor, implying that the growth advantage in Hpa-tg mice is due to systemic factors. Indeed, we found that plasma from Hpa-tg mice enhanced tumor cell migration and invasion attributed to increased levels of pro-tumorigenic factors (i.e., RANKL, SPARC, MIP-2) in the plasma of Hpa-Tg vs. wild type mice. Furthermore, tumor aggressiveness and short survival time were demonstrated in wild type mice transplanted with bone marrow derived from Hpa-tg but not wild type mice. These results were attributed, among other factors, to upregulation of pro-tumorigenic (i.e., IL35+) and downregulation of anti-tumorigenic (i.e., IFN-γ+) T-cell subpopulations in the spleen, lymph nodes and blood of Hpa-tg vs. wild type mice and their increased infiltration into the primary tumor. Collectively, our results emphasize the significance of host heparanase in mediating the pro-tumorigenic and pro-metastatic interactions between the tumor cells and the host tumor microenvironment, immune cells and systemic factors.
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