| 1. |
- Braun, Emelie, et al.
(författare)
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Comprehensive cell atlas of the first-trimester developing human brain
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 382:6667, s. 172-
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Tidskriftsartikel (refereegranskat)abstract
- The adult human brain comprises more than a thousand distinct neuronal and glial cell types, a diversity that emerges during early brain development. To reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics and uncovered cell states and trajectories in human brains at 5 to 14 postconceptional weeks (pcw). We identified 12 major classes that are organized as ~600 distinct cell states, which map to precise spatial anatomical domains at 5 pcw. We described detailed differentiation trajectories of the human forebrain and midbrain and found a large number of region-specific glioblasts that mature into distinct pre-astrocytes and pre–oligodendrocyte precursor cells. Our findings reveal the establishment of cell types during the first trimester of human brain development.
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| 2. |
- Chen, Zhen, et al.
(författare)
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Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a "Tail Switching" Strategy on a Piperazinyl Azetidine Skeleton
- 2019
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 62:7, s. 3336-3353
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Tidskriftsartikel (refereegranskat)abstract
- Monoacylglycerol lipase (MAGL) is a senile hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with C-11 or F-18. [C-11]8 ([C-11]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [C-11]17 ([C-11]PAD) and [F-18]37 ([F-18]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.
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| 3. |
- Cui, Manying, et al.
(författare)
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Regulation of Lithium-Ion Flux by Nanotopology Lithiophilic Boron-Oxygen Dipole in Solid Polymer Electrolytes for Lithium-Metal Batteries
- 2023
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Ingår i: Energy & Environmental Materials. - 2575-0356.
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Tidskriftsartikel (refereegranskat)abstract
- Inhomogeneous lithium-ion (Li+) deposition is one of the most crucial problems, which severely deteriorates the performance of solid-state lithium metal batteries (LMBs). Herein, we discovered that covalent organic framework (COF-1) with periodically arranged boron-oxygen dipole lithiophilic sites could directionally guide Li+ even deposition in asymmetric solid polymer electrolytes. This in situ prepared 3D cross-linked network Poly(ACMO-MBA) hybrid electrolyte simultaneously delivers outstanding ionic conductivity (1.02 × 10−3 S cm−1 at 30 °C) and excellent mechanical property (3.5 MPa). The defined nanosized channel in COF-1 selectively conducts Li+ increasing Li+ transference number to 0.67. Besides, The COF-1 layer and Poly(ACMO-MBA) also participate in forming a boron-rich and nitrogen-rich solid electrolyte interface to further improve the interfacial stability. The Li‖Li symmetric cell exhibits remarkable cyclic stability over 1000 h. The Li‖NCM523 full cell also delivers an outstanding lifespan over 400 cycles. Moreover, the Li‖LiFePO4 full cell stably cycles with a capacity retention of 85% after 500 cycles. the Li‖LiFePO4 pouch full exhibits excellent safety performance under pierced and cut conditions. This work thereby further broadens and complements the application of COF materials in polymer electrolyte for dendrite-free and high-energy-density solid-state LMBs.
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| 4. |
- Li, Xiaofei, et al.
(författare)
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Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin
- 2023
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Ingår i: Nature Neuroscience. - : Springer Nature. - 1097-6256 .- 1546-1726. ; 26:5, s. 891-901
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Tidskriftsartikel (refereegranskat)abstract
- The authors created a comprehensive developmental cell atlas for spatiotemporal gene expression of the human spinal cord, revealed species-specific regulation during development and used the atlas to infer novel markers for pediatric ependymomas. The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5-12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.
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| 5. |
- Nie, Junsheng, et al.
(författare)
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Loess Plateau storage of Northeastern Tibetan Plateau-derived Yellow River sediment
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Marine accumulations of terrigenous sediment are widely assumed to accurately record climatic- and tectonic-controlled mountain denudation and play an important role in understanding late Cenozoic mountain uplift and global cooling. Underpinning this is the assumption that the majority of sediment eroded from hinterland orogenic belts is transported to and ultimately stored in marine basins with little lag between erosion and deposition. Here we use a detailed and multi-technique sedimentary provenance dataset from the Yellow River to show that substantial amounts of sediment eroded from Northeast Tibet and carried by the river/'s upper reach are stored in the Chinese Loess Plateau and the western Mu Us desert. This finding revises our understanding of the origin of the Chinese Loess Plateau and provides a potential solution for mismatches between late Cenozoic terrestrial sedimentation and marine geochemistry records, as well as between global CO2 and erosion records.
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| 6. |
- Nie, Junsheng, et al.
(författare)
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Rapid incision of the Mekong River in the middle Miocene linked to monsoonal precipitation
- 2018
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 11, s. 944-948
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Tidskriftsartikel (refereegranskat)abstract
- The uplift of orogenic plateaus has been assumed to be coincident with the fluvial incision of the gorges that commonly cut plateau margins. The Mekong River, which drains the eastern Qiangtang Terrane and southeastern Tibetan Plateau, is one of the ten largest rivers in the world by water and sediment discharge. When the Mekong River was established remains highly debated-with estimates that range from more than 55 to less than 5 million years ago-despite being a key constraint on the elevation history of the Tibetan Plateau. Here we report low-temperature thermochronology data from river bedrock samples that reveal a phase of rapid downward incision (>700 m) of the Mekong River during the middle Miocene about 17 million years ago, long after the uplift of the central and southeastern Tibetan Plateau. However, this coincides with a period of enhanced East Asian summer monsoon precipitation over the region compared with the early Miocene. Using stream profile modelling, we demonstrate that such an increase in precipitation could have produced the observed incision in the Mekong River. In the absence of an obvious tectonic contribution, we suggest that the rapid incision of the Tibetan Plateau and the establishment of the Mekong River in the middle Miocene may be attributed to increased erosion during a period of high monsoon precipitation.
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| 7. |
- Sountoulidis, Alexandros, et al.
(författare)
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A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung
- 2023
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Ingår i: Nature Cell Biology. - : Springer Nature. - 1465-7392 .- 1476-4679.
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Tidskriftsartikel (refereegranskat)abstract
- Sountoulidis et al. provide a spatial gene expression atlas of human embryonic lung during the first trimester of gestation and identify 83 cell identities corresponding to stable cell types or transitional states. The lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a comprehensive topographic atlas of early human lung development. Here we report 83 cell states and several spatially resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated single-cell RNA sequencing and spatially resolved transcriptomics into a web-based, open platform for interactive exploration. We show distinct gene expression programmes, accompanying sequential events of cell differentiation and maturation of the secretory and neuroendocrine cell types in proximal epithelium. We define the origin of airway fibroblasts associated with airway smooth muscle in bronchovascular bundles and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.
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| 8. |
- Wang, Zhang, et al.
(författare)
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Testing contrasting models of the formation of the upper Yellow River usingheavy-mineral data from the Yinchuan Basin drill cores
- 2019
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Ingår i: Geophysical Research Letters. - : John Wiley & Sons. - 0094-8276 .- 1944-8007. ; 46:17-18, s. 10338-10345
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Tidskriftsartikel (refereegranskat)abstract
- The upper Yellow River drains the central and northeastern Tibetan Plateau. Understanding the origin of this river is essential for unraveling the interplay between fluvial incision, basement uplift, and climate change. However, the formation age of the upper Yellow River is highly debated, with estimates ranging from Eocene to late Pleistocene. In order to clarify the history of the upper Yellow River, we present a heavy-mineral dataset from drill core in the Yinchuan Basin, a depositional sink at the end of the upper Yellow River course. Our results reveal that the drainage area of the upper Yellow River (i.e., northeastern Tibetan Plateau) has been serving as a major sediment source region for the Yinchuan Basin since at least 3.3 Ma. A late Pleistocene formation of the upper Yellow River, and erosion of neighboring deserts or bounding mountains as an explanation for thick sediment accumulations in this area, is thus ruled out.
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| 9. |
- Yang, Jin, et al.
(författare)
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Climatic Forcing of Plio-Pleistocene Formation of the Modern Limpopo River, South Africa
- 2021
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 48:14
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the evolution of river systems in southern Africa is fundamental to constrain the evolution of landscape and sediment dispersal patterns. It is widely considered that the upper Zambezi River was connected with the Limpopo River during the Cretaceous, forming what was then the largest river in Africa. Crustal flexure during the Paleogene severed the upper Zambezi drainage from the Limpopo, setting the framework of the modern Zambezi and Limpopo River systems. We present first evidence-based on heavy-mineral assemblages from cores drilled offshore of the Limpopo River mouth and samples collected in different reaches of the modern Limpopo River, integrated with magnetic susceptibility, detrital-zircon geochronology, and geomorphological analysis-suggesting that the current Limpopo River formed recently in the Plio-Quaternary. Plio-Quaternary climate change is envisaged to have controlled the recent dynamics of river drainage and consequent distribution of sediment loads, as observed in many other transcontinental rivers worldwide.
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| 10. |
- Zhai, Yinghong, et al.
(författare)
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Atrial fibrillation increases the risk of all-cause dementia, Alzheimer's disease, and vascular dementia : A cohort study of 373, 415 participants in the UK Biobank
- 2024
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 351, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia.METHODS: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis.RESULTS: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis.LIMITATIONS: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed.CONCLUSIONS: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia.
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