50 results on '"Yin W"'
Search Results
2. Tbps wide-field parallel optical wireless communications based on a metasurface beam splitter
- Author
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Yue Wu, Ji Chen, Yin Wang, Zhongyi Yuan, Chunyu Huang, Jiacheng Sun, Chengyi Feng, Muyang Li, Kai Qiu, Shining Zhu, Zaichen Zhang, and Tao Li
- Subjects
Science - Abstract
Abstract Optical wireless communication (OWC) stands out as one of the most promising technologies in the sixth-generation (6G) mobile networks. The establishment of high-quality optical links between transmitters and receivers plays a crucial role in OWC performances. Here, by a compact beam splitter composed of a metasurface and a fiber array, we proposed a wide-angle (~120°) OWC optical link scheme that can parallelly support up to 144 communication users. Utilizing high-speed optical module sources and wavelength division multiplexing technique, we demonstrated each user can achieve a communication speed of 200 Gbps which enables the entire system to support ultra-high communication capacity exceeding 28 Tbps. Furthermore, utilizing the metasurface polarization multiplexing, we implemented a full range wide-angle OWC without blind area nor crosstalk among users. Our OWC scheme simultaneously possesses the advantages of high-speed, wide communication area and multi-user parallel communications, paving the way for revolutionary high-performance OWC in the future.
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- 2024
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3. Adenine base editing-mediated exon skipping restores dystrophin in humanized Duchenne mouse model
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Jiajia Lin, Ming Jin, Dong Yang, Zhifang Li, Yu Zhang, Qingquan Xiao, Yin Wang, Yuyang Yu, Xiumei Zhang, Zhurui Shao, Linyu Shi, Shu Zhang, Wan-jin Chen, Ning Wang, Shiwen Wu, Hui Yang, Chunlong Xu, and Guoling Li
- Subjects
Science - Abstract
Abstract Duchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient’s DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.
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- 2024
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4. Elevated concentrations cause upright alpha-synuclein conformation at lipid interfaces
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Steven J. Roeters, Kris Strunge, Kasper B. Pedersen, Thaddeus W. Golbek, Mikkel Bregnhøj, Yuge Zhang, Yin Wang, Mingdong Dong, Janni Nielsen, Daniel E. Otzen, Birgit Schiøtt, and Tobias Weidner
- Subjects
Science - Abstract
Abstract The amyloid aggregation of α-synuclein (αS), related to Parkinson’s disease, can be catalyzed by lipid membranes. Despite the importance of lipid surfaces, the 3D-structure and orientation of lipid-bound αS is still not known in detail. Here, we report interface-specific vibrational sum-frequency generation (VSFG) experiments that reveal how monomeric αS binds to an anionic lipid interface over a large range of αS-lipid ratios. To interpret the experimental data, we present a frame-selection method ("ViscaSelect”) in which out-of-equilibrium molecular dynamics simulations are used to generate structural hypotheses that are compared to experimental amide-I spectra via excitonic spectral calculations. At low and physiological αS concentrations, we derive flat-lying helical structures as previously reported. However, at elevated and potentially disease-related concentrations, a transition to interface-protruding αS structures occurs. Such an upright conformation promotes lateral interactions between αS monomers and may explain how lipid membranes catalyze the formation of αS amyloids at elevated protein concentrations.
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- 2023
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5. Identification of a non-axisymmetric mode in laboratory experiments searching for standard magnetorotational instability
- Author
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Yin Wang, Erik P. Gilson, Fatima Ebrahimi, Jeremy Goodman, Kyle J. Caspary, Himawan W. Winarto, and Hantao Ji
- Subjects
Science - Abstract
Magnetohydrodynamic instabilities are related to different characteristics and behavior of fluids. Here the authors report an experiment and simulation combined study of a global non-axisymmetric MHD instability that exists at sufficiently large rotation rates and intermediate magnetic field strengths.
- Published
- 2022
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6. A highly conserved core bacterial microbiota with nitrogen-fixation capacity inhabits the xylem sap in maize plants
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Liyu Zhang, Meiling Zhang, Shuyu Huang, Lujun Li, Qiang Gao, Yin Wang, Shuiqing Zhang, Shaomin Huang, Liang Yuan, Yanchen Wen, Kailou Liu, Xichu Yu, Dongchu Li, Lu Zhang, Xinpeng Xu, Hailei Wei, Ping He, Wei Zhou, Laurent Philippot, and Chao Ai
- Subjects
Science - Abstract
The plant xylem microbiota remains understudied. Here, the authors characterise the xylem microbiota in maize plants finding that some bacteria carried N fixing genes. By using synthetic communities the authors confirm that xylem inhabiting and N fixing bacteria provide the host plant with N.
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- 2022
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7. Wafer-scale functional circuits based on two dimensional semiconductors with fabrication optimized by machine learning
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Xinyu Chen, Yufeng Xie, Yaochen Sheng, Hongwei Tang, Zeming Wang, Yu Wang, Yin Wang, Fuyou Liao, Jingyi Ma, Xiaojiao Guo, Ling Tong, Hanqi Liu, Hao Liu, Tianxiang Wu, Jiaxin Cao, Sitong Bu, Hui Shen, Fuyu Bai, Daming Huang, Jianan Deng, Antoine Riaud, Zihan Xu, Chenjian Wu, Shiwei Xing, Ye Lu, Shunli Ma, Zhengzong Sun, Zhongyin Xue, Zengfeng Di, Xiao Gong, David Wei Zhang, Peng Zhou, Jing Wan, and Wenzhong Bao
- Subjects
Science - Abstract
Here, the authors demonstrate the application of machine learning to optimize the device fabrication process for wafer-scale 2D semiconductors, and eventually fabricate digital, analog, and optoelectrical circuits.
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- 2021
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8. An in-memory computing architecture based on two-dimensional semiconductors for multiply-accumulate operations
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Yin Wang, Hongwei Tang, Yufeng Xie, Xinyu Chen, Shunli Ma, Zhengzong Sun, Qingqing Sun, Lin Chen, Hao Zhu, Jing Wan, Zihan Xu, David Wei Zhang, Peng Zhou, and Wenzhong Bao
- Subjects
Science - Abstract
In standard computing architectures, memory and logic circuits are separated, a feature that slows matrix operations vital to deep learning algorithms. Here, the authors present an alternate in-memory architecture and demonstrate a feasible approach for analog matrix multiplication.
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- 2021
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9. Plasma membrane H+-ATPase overexpression increases rice yield via simultaneous enhancement of nutrient uptake and photosynthesis
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Maoxing Zhang, Yin Wang, Xi Chen, Feiyun Xu, Ming Ding, Wenxiu Ye, Yuya Kawai, Yosuke Toda, Yuki Hayashi, Takamasa Suzuki, Houqing Zeng, Liang Xiao, Xin Xiao, Jin Xu, Shiwei Guo, Feng Yan, Qirong Shen, Guohua Xu, Toshinori Kinoshita, and Yiyong Zhu
- Subjects
Science - Abstract
Improved utilisation of nitrogen and carbon could boost agricultural productivity. Here Zhang et al. show that overexpression of a single gene, encoding the plasma membrane H+ -ATPase 1 OSA1, is able to increase both carbon fixation via photosynthesis and nitrogen assimilation via ammonium uptake in rice.
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- 2021
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10. Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation
- Author
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Yin Wang, Fang Yao, Lipeng Wang, Zheng Li, Zongna Ren, Dandan Li, Mingzhi Zhang, Leng Han, Shi-qiang Wang, Bingying Zhou, and Li Wang
- Subjects
Science - Abstract
How cardiomyocytes mature and what regulates this is unclear. Here, the authors use single-cell analysis to examine how the population of murine cardiac fibroblasts changes during development and affects maturation of cardiomyocytes.
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- 2020
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11. miR-93 regulates Msk2-mediated chromatin remodelling in diabetic nephropathy
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Shawn S. Badal, Yin Wang, Jianyin Long, David L. Corcoran, Benny H. Chang, Luan D. Truong, Yashpal S. Kanwar, Paul A. Overbeek, and Farhad R. Danesh
- Subjects
Science - Abstract
Podocyte injury is central to kidney dysfunction in diabetic nephropathy. Here the authors show that Msk2 is a target of miR-93 and this interaction mediates pathogenic chromatin remodelling in diabetic nephropathy.
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- 2016
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12. Machine learning enables the discovery of 2D Invar and anti-Invar monolayers.
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Tian S, Zhou K, Yin W, and Liu Y
- Abstract
Materials demonstrating positive thermal expansion (PTE) or negative thermal expansion (NTE) are quite common, whereas those exhibiting zero thermal expansion (ZTE) are notably scarce. In this work, we identify the mechanical descriptors, namely in-plane tensile stiffness and out-of-plane bending stiffness, that can effectively classify PTE and NTE 2D crystals. By utilizing high throughput calculations and the state-of-the-art symbolic regression method, these descriptors aid in the discovery of ZTE or 2D Invar monolayers with the linear thermal expansion coefficient (LTEC) within ±2 × 10
-6 K-1 in the middle range of temperatures. Additionally, the descriptors assist the discovery of large PTE and NTE 2D monolayers with the LTEC larger than ±15 × 10-6 K-1 , which are so-called 2D anti-Invar monolayers. Advancing our understanding of materials with exceptionally low or high thermal expansion is of substantial scientific and technological interest, particularly in the development of next-generation electronics at the nanometer or even Ångstrom scale., (© 2024. The Author(s).)- Published
- 2024
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13. Graphene-skinned alumina fiber fabricated through metalloid-catalytic graphene CVD growth on nonmetallic substrate and its mass production.
- Author
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Li W, Liang F, Sun X, Zheng K, Liu R, Yuan H, Cheng S, Wang J, Cheng Y, Huang K, Wang K, Yang Y, Yang F, Tu C, Mao X, Yin W, Cai A, Wang X, Qi Y, and Liu Z
- Abstract
Graphene growth on widely used dielectrics/insulators via chemical vapor deposition (CVD) is a strategy toward transfer-free applications of CVD graphene for the realization of advanced composite materials. Here, we develop graphene-skinned alumina fibers/fabrics (GAFs/GAFFs) through graphene CVD growth on commercial alumina fibers/fabrics (AFs/AFFs). We reveal a vapor-surface-solid growth model on a non-metallic substrate, which is distinct from the well-established vapor-solid model on conventional non-catalytic non-metallic substrates, but bears a closer resemblance to that observed on catalytic metallic substrates. The metalloid-catalytic growth of graphene on AFs/AFFs resulted in reduced growth temperature (~200 °C lower) and accelerated growth rate (~3.4 times faster) compared to that obtained on a representative non-metallic counterpart, quartz fiber. The fabricated GAFF features a wide-range tunable electrical conductivity (1-15000 Ω sq
-1 ), high tensile strength (>1.5 GPa), lightweight, flexibility, and a hierarchical macrostructure. These attributes are inherited from both graphene and AFF, making GAFF promising for various applications including electrical heating and electromagnetic interference shielding. Beyond laboratory level preparation, the stable mass production of large-scale GAFF has been achieved through a home-made roll-to-roll system with capacity of 468-93600 m2 /year depending on product specifications, providing foundations for the subsequent industrialization of this material, enabling its widespread adoption in various industries., (© 2024. The Author(s).)- Published
- 2024
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14. Multispecies-coadsorption-induced rapid preparation of graphene glass fiber fabric and applications in flexible pressure sensor.
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Wang K, Sun X, Cheng S, Cheng Y, Huang K, Liu R, Yuan H, Li W, Liang F, Yang Y, Yang F, Zheng K, Liang Z, Tu C, Liu M, Ma M, Ge Y, Jian M, Yin W, Qi Y, and Liu Z
- Abstract
Direct chemical vapor deposition (CVD) growth of graphene on dielectric/insulating materials is a promising strategy for subsequent transfer-free applications of graphene. However, graphene growth on noncatalytic substrates is faced with thorny issues, especially the limited growth rate, which severely hinders mass production and practical applications. Herein, graphene glass fiber fabric (GGFF) is developed by graphene CVD growth on glass fiber fabric. Dichloromethane is applied as a carbon precursor to accelerate graphene growth, which has a low decomposition energy barrier, and more importantly, the produced high-electronegativity Cl radical can enhance adsorption of active carbon species by Cl-CH
2 coadsorption and facilitate H detachment from graphene edges. Consequently, the growth rate is increased by ~3 orders of magnitude and carbon utilization by ~960-fold, compared with conventional methane precursor. The advantageous hierarchical conductive configuration of lightweight, flexible GGFF makes it an ultrasensitive pressure sensor for human motion and physiological monitoring, such as pulse and vocal signals., (© 2024. The Author(s).)- Published
- 2024
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15. Reduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice.
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Liang Y, Luo C, Sun L, Feng T, Yin W, Zhang Y, Mulholland MW, Zhang W, and Yin Y
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- Animals, Mice, Mice, Knockout, Male, Intestinal Absorption, Mice, Inbred C57BL, Wnt Signaling Pathway, Fatty Liver metabolism, Fatty Liver genetics, Fatty Acids metabolism, Receptors, Notch metabolism, Glucose metabolism, Receptors, G-Protein-Coupled metabolism, Receptors, G-Protein-Coupled genetics, Enterocytes metabolism, Lipid Metabolism, Diet, High-Fat, Intestinal Mucosa metabolism, Obesity metabolism, Obesity genetics
- Abstract
Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4
iKO ) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis., (© 2024. The Author(s).)- Published
- 2024
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16. Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer.
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Fu J, Ling J, Li CF, Tsai CL, Yin W, Hou J, Chen P, Cao Y, Kang Y, Sun Y, Xia X, Jiang Z, Furukawa K, Lu Y, Wu M, Huang Q, Yao J, Hawke DH, Pan BF, Zhao J, Huang J, Wang H, Bahassi EIM, Stambrook PJ, Huang P, Fleming JB, Maitra A, Tainer JA, Hung MC, Lin C, and Chiao PJ
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- Humans, Mice, Animals, Proto-Oncogene Proteins p21(ras) genetics, Proto-Oncogene Proteins p21(ras) metabolism, Metalloendopeptidases genetics, Metalloendopeptidases metabolism, Pancreatic Neoplasms pathology, Carcinoma, Pancreatic Ductal pathology
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of Kras
G12D -driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism., (© 2024. The Author(s).)- Published
- 2024
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17. Promoting high-voltage stability through local lattice distortion of halide solid electrolytes.
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Song Z, Wang T, Yang H, Kan WH, Chen Y, Yu Q, Wang L, Zhang Y, Dai Y, Chen H, Yin W, Honda T, Avdeev M, Xu H, Ma J, Huang Y, and Luo W
- Abstract
Stable solid electrolytes are essential to high-safety and high-energy-density lithium batteries, especially for applications with high-voltage cathodes. In such conditions, solid electrolytes may experience severe oxidation, decomposition, and deactivation during charging at high voltages, leading to inadequate cycling performance and even cell failure. Here, we address the high-voltage limitation of halide solid electrolytes by introducing local lattice distortion to confine the distribution of Cl
- , which effectively curbs kinetics of their oxidation. The confinement is realized by substituting In with multiple elements in Li3 InCl6 to give a high-entropy Li2.75 Y0.16 Er0.16 Yb0.16 In0.25 Zr0.25 Cl6 . Meanwhile, the lattice distortion promotes longer Li-Cl bonds, facilitating favorable activation of Li+ . Our results show that this high-entropy halide electrolyte boosts the cycle stability of all-solid-state battery by 250% improvement over 500 cycles. In particular, the cell provides a higher discharge capacity of 185 mAh g-1 by increasing the charge cut-off voltage to 4.6 V at a small current rate of 0.2 C, which is more challenging to electrolytes|cathode stability. These findings deepen our understanding of high-entropy materials, advancing their use in energy-related applications., (© 2024. The Author(s).)- Published
- 2024
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18. Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells.
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Zhang Y, Fang H, Wang G, Yuan G, Dong R, Luo J, Lyu Y, Wang Y, Li P, Zhou C, Yin W, Xiao H, Sun J, and Zeng X
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- Humans, Animals, Mice, Cyclosporine pharmacology, Allogeneic Cells, Immunosuppressive Agents pharmacology, T-Lymphocytes, Neoplasms
- Abstract
Chimeric antigen receptor (CAR)-T therapy requires autologous T lymphocytes from cancer patients, a process that is both costly and complex. Universal CAR-T cell treatment from allogeneic sources can overcome this limitation but is impeded by graft-versus-host disease (GvHD) and host versus-graft rejection (HvGR). Here, we introduce a mutated calcineurin subunit A (CNA) and a CD19-specific CAR into the T cell receptor α constant (TRAC) locus to generate cells that are resistant to the widely used immunosuppressant, cyclosporine A (CsA). These immunosuppressant-resistant universal (IRU) CAR-T cells display improved effector function in vitro and anti-tumour efficacy in a leukemia xenograft mouse model in the presence of CsA, compared with CAR-T cells carrying wild-type CNA. Moreover, IRU CAR-T cells retain effector function in vitro and in vivo in the presence of both allogeneic T cells and CsA. Lastly, CsA withdrawal restores HvGR, acting as a safety switch that can eliminate IRU CAR-T cells. These findings demonstrate the efficacy of CsA-resistant CAR-T cells as a universal, 'off-the-shelf' treatment option., (© 2023. The Author(s).)
- Published
- 2023
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19. Regulation of the physiology and virulence of Ralstonia solanacearum by the second messenger 2',3'-cyclic guanosine monophosphate.
- Author
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Li X, Yin W, Lin JD, Zhang Y, Guo Q, Wang G, Chen X, Cui B, Wang M, Chen M, Li P, He YW, Qian W, Luo H, Zhang LH, Liu XW, Song S, and Deng Y
- Subjects
- Humans, Virulence, Bacterial Proteins genetics, Bacterial Proteins metabolism, Cyclic GMP metabolism, Second Messenger Systems, Gene Expression Regulation, Bacterial, Biofilms, Guanosine Monophosphate, Ralstonia solanacearum metabolism
- Abstract
Previous studies have demonstrated that bis-(3',5')-cyclic diguanosine monophosphate (bis-3',5'-c-di-GMP) is a ubiquitous second messenger employed by bacteria. Here, we report that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions, quorum sensing (QS) signaling systems and virulence in Ralstonia solanacearum through the transcriptional regulator RSp0980. This signal specifically binds to RSp0980 with high affinity and thus abolishes the interaction between RSp0980 and the promoters of target genes. In-frame deletion of RSp0334, which contains an evolved GGDEF domain with a LLARLGGDQF motif required to catalyze 2',3'-cGMP to (2',5')(3',5')-cyclic diguanosine monophosphate (2',3'-c-di-GMP), altered the abovementioned important phenotypes through increasing the intracellular 2',3'-cGMP levels. Furthermore, we found that 2',3'-cGMP, its receptor and the evolved GGDEF domain with a LLARLGGDEF motif also exist in the human pathogen Salmonella typhimurium. Together, our work provides insights into the unusual function of the GGDEF domain of RSp0334 and the special regulatory mechanism of 2',3'-cGMP signal in bacteria., (© 2023. The Author(s).)
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- 2023
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20. CREB1-driven CXCR4 hi neutrophils promote skin inflammation in mouse models and human patients.
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Chen J, Bai Y, Xue K, Li Z, Zhu Z, Li Q, Yu C, Li B, Shen S, Qiao P, Li C, Luo Y, Qiao H, Dang E, Yin W, Gudjonsson JE, Wang G, and Shao S
- Subjects
- Animals, Humans, Mice, Disease Models, Animal, Inflammation, Neutrophils, Receptors, CXCR4 genetics, Skin, Cyclic AMP Response Element-Binding Protein genetics, Dermatitis, Psoriasis genetics
- Abstract
Neutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4
hi neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity. Compared to CXCR4lo neutrophils, CXCR4hi neutrophils have enhanced NETs formation, phagocytic function, neutrophil degranulation, and overexpression of pro-inflammatory cytokines and chemokines in vitro. This is accompanied by a metabolic shift in CXCR4hi neutrophils toward glycolysis and lactate release, thereby promoting vascular permeability and remodeling. CXCR4 expression in neutrophils is dependent on CREB1, a transcription factor activated by TNF and CXCL12, and regulated by de novo synthesis. In vivo, CXCR4hi neutrophil infiltration amplifies skin inflammation, whereas blockade of CXCR4hi neutrophils through CXCR4 or CXCL12 inhibition leads to suppression of immune responses. In this work, our study identifies CREB1 as a critical regulator of CXCR4hi neutrophil development and characterizes the contribution of CXCR4hi neutrophils to vascular remodeling and inflammatory responses in skin., (© 2023. Springer Nature Limited.)- Published
- 2023
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21. Author Correction: Structural insights into ligand recognition and activation of the medium-chain fatty acid-sensing receptor GPR84.
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Liu H, Zhang Q, He X, Jiang M, Wang S, Yan X, Cheng X, Liu Y, Nan FJ, Xu HE, Xie X, and Yin W
- Published
- 2023
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22. Structural insights into ligand recognition and activation of the medium-chain fatty acid-sensing receptor GPR84.
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Liu H, Zhang Q, He X, Jiang M, Wang S, Yan X, Cheng X, Liu Y, Nan FJ, Xu HE, Xie X, and Yin W
- Subjects
- Humans, Ligands, Cryoelectron Microscopy, Inflammation, Receptors, G-Protein-Coupled metabolism, Fatty Acids metabolism
- Abstract
GPR84 is an orphan class A G protein-coupled receptor (GPCR) that is predominantly expressed in immune cells and plays important roles in inflammation, fibrosis, and metabolism. Here, we present cryo-electron microscopy (cryo-EM) structures of Gα
i protein-coupled human GPR84 bound to a synthetic lipid-mimetic ligand, LY237, or a putative endogenous ligand, a medium-chain fatty acid (MCFA) 3-hydroxy lauric acid (3-OH-C12). Analysis of these two ligand-bound structures reveals a unique hydrophobic nonane tail -contacting patch, which forms a blocking wall to select MCFA-like agonists with the correct length. We also identify the structural features in GPR84 that coordinate the polar ends of LY237 and 3-OH-C12, including the interactions with the positively charged side chain of R172 and the downward movement of the extracellular loop 2 (ECL2). Together with molecular dynamics simulations and functional data, our structures reveal that ECL2 not only contributes to direct ligand binding, but also plays a pivotal role in ligand entry from the extracellular milieu. These insights into the structure and function of GPR84 could improve our understanding of ligand recognition, receptor activation, and Gαi -coupling of GPR84. Our structures could also facilitate rational drug discovery against inflammation and metabolic disorders targeting GPR84., (© 2023. The Author(s).)- Published
- 2023
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23. Fast synthesis of large-area bilayer graphene film on Cu.
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Zhang J, Liu X, Zhang M, Zhang R, Ta HQ, Sun J, Wang W, Zhu W, Fang T, Jia K, Sun X, Zhang X, Zhu Y, Shao J, Liu Y, Gao X, Yang Q, Sun L, Li Q, Liang F, Chen H, Zheng L, Wang F, Yin W, Wei X, Yin J, Gemming T, Rummeli MH, Liu H, Peng H, Lin L, and Liu Z
- Abstract
Bilayer graphene (BLG) is intriguing for its unique properties and potential applications in electronics, photonics, and mechanics. However, the chemical vapor deposition synthesis of large-area high-quality bilayer graphene on Cu is suffering from a low growth rate and limited bilayer coverage. Herein, we demonstrate the fast synthesis of meter-sized bilayer graphene film on commercial polycrystalline Cu foils by introducing trace CO
2 during high-temperature growth. Continuous bilayer graphene with a high ratio of AB-stacking structure can be obtained within 20 min, which exhibits enhanced mechanical strength, uniform transmittance, and low sheet resistance in large area. Moreover, 96 and 100% AB-stacking structures were achieved in bilayer graphene grown on single-crystal Cu(111) foil and ultraflat single-crystal Cu(111)/sapphire substrates, respectively. The AB-stacking bilayer graphene exhibits tunable bandgap and performs well in photodetection. This work provides important insights into the growth mechanism and the mass production of large-area high-quality BLG on Cu., (© 2023. The Author(s).)- Published
- 2023
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24. 3-sulfonyloxyaryl(mesityl)iodonium triflates as 1,2-benzdiyne precursors with activation via ortho-deprotonative elimination strategy.
- Author
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Yuan H, Yin W, Hu J, and Li Y
- Abstract
Benzyne has long captivated the attention of chemists and has gained numerous synthetic achievements. Among typical benzyne generation methods, removal of two vicinal substituents from 1,2-difunctionalized benzenes, i.e., Kobayashi's protocol, are prevailing, while ortho-deprotonative elimination from mono-substituted benzene lags far behind. Despite the advantages of atom economy and ready achievability of precursors, a bottle neck for ortho-deprotonative elimination strategy resides in the weak acidity of the ortho-hydrogen, which normally demands strong bases as the activating reagents. Here, an efficient aryne generation protocol is developed, where ortho-deprotonative elimination on 3-sulfonyloxyaryl(mesityl)iodonium triflates occurs under mild conditions and the generated 3-sulfonyloxyarynes can serve as efficient 1,2-benzdiyne synthons. This array of 1,2-benzdiyne precursors can be conveniently prepared with high functional group tolerance, and densely substituted scaffolds can be accessed as well. Carbonate and fluoride salts are found to serve as efficient activating reagents, which are the weakest bases used in ortho-deprotonative elimination strategies. Particularly, this scaffold has predictable chemoselective generation of the designated aryne intermediates. The success of this ortho-deprotonative elimination protocol sets up a unique platform with a broad spectrum of synthetic applications., (© 2023. The Author(s).)
- Published
- 2023
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25. Bacterial origins of thymidylate metabolism in Asgard archaea and Eukarya.
- Author
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Filée J, Becker HF, Mellottee L, Eddine RZ, Li Z, Yin W, Lambry JC, Liebl U, and Myllykallio H
- Subjects
- Phylogeny, Thymidylate Synthase genetics, Thymidylate Synthase metabolism, Bacteria genetics, Bacteria metabolism, Amino Acids metabolism, Folic Acid metabolism, DNA metabolism, Archaea metabolism, Eukaryota genetics, Eukaryota metabolism
- Abstract
Asgard archaea include the closest known archaeal relatives of eukaryotes. Here, we investigate the evolution and function of Asgard thymidylate synthases and other folate-dependent enzymes required for the biosynthesis of DNA, RNA, amino acids and vitamins, as well as syntrophic amino acid utilization. Phylogenies of Asgard folate-dependent enzymes are consistent with their horizontal transmission from various bacterial groups. We experimentally validate the functionality of thymidylate synthase ThyX of the cultured 'Candidatus Prometheoarchaeum syntrophicum'. The enzyme efficiently uses bacterial-like folates and is inhibited by mycobacterial ThyX inhibitors, even though the majority of experimentally tested archaea are known to use carbon carriers distinct from bacterial folates. Our phylogenetic analyses suggest that the eukaryotic thymidylate synthase, required for de novo DNA synthesis, is not closely related to archaeal enzymes and might have been transferred from bacteria to protoeukaryotes during eukaryogenesis. Altogether, our study suggests that the capacity of eukaryotic cells to duplicate their genetic material is a sum of archaeal (replisome) and bacterial (thymidylate synthase) characteristics. We also propose that recent prevalent lateral gene transfer from bacteria has markedly shaped the metabolism of Asgard archaea., (© 2023. The Author(s).)
- Published
- 2023
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26. Slight compositional variation-induced structural disorder-to-order transition enables fast Na + storage in layered transition metal oxides.
- Author
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Shi Y, Jiang P, Wang S, Chen W, Wei B, Lu X, Qian G, Kan WH, Chen H, Yin W, Sun Y, and Lu X
- Abstract
The omnipresent Na
+ /vacancy orderings change substantially with the composition that inevitably actuate the ionic diffusion in rechargeable batteries. Therefore, it may hold the key to the electrode design with high rate capability. Herein, the influence of Na+ /vacancy ordering on Na+ mobility is demonstrated firstly through a comparative investigation in P2-Na2/3 Ni1/3 Mn2/3 O2 and P2-Na2/3 Ni0.3 Mn0.7 O2 . The large zigzag Na+ /vacancy intralayer ordering is found to accelerate Na+ migration in P2-type Na2/3 Ni1/3 Mn2/3 O2 . By theoretical simulations, it is revealed that the Na+ ordering enables the P2-type Na2/3 Ni1/3 Mn2/3 O2 with higher diffusivities and lower activation energies of 200 meV with respect to the P3 one. The quantifying diffusional analysis further prove that the higher probability of the concerted Na+ ionic diffusion occurs in P2-type Na2/3 Ni1/3 Mn2/3 O2 due to the appropriate ratio of high energy ordered Na ions (Naf ) occupation. As a result, the interplay between the Na+ /vacancy ordering and Na+ kinetic is well understood in P2-type layered cathodes., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
27. Lithiated Prussian blue analogues as positive electrode active materials for stable non-aqueous lithium-ion batteries.
- Author
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Zhang Z, Avdeev M, Chen H, Yin W, Kan WH, and He G
- Abstract
Prussian blue analogues (PBAs) are appealing active materials for post-lithium electrochemical energy storage. However, PBAs are not generally suitable for non-aqueous Li-ion storage due to their instability upon prolonged cycling. Herein, we assess the feasibility of PBAs with various lithium content for non-aqueous Li-ion storage. We determine the crystal structure of the lithiated PBAs via neutron powder diffraction measurements and investigate the influence of water on structural stability and Li-ion migration through operando X-ray diffraction measurements and bond valence simulations. Furthermore, we demonstrate that a positive electrode containing Li
2-x FeFe(CN)6 ⋅nH2 O (0 ≤ x ≤ 2) active material coupled with a Li metal electrode and a LiPF6 -containing organic-based electrolyte in coin cell configuration delivers an initial discharge capacity of 142 mAh g-1 at 19 mA g-1 and a discharge capacity retention of 80.7% after 1000 cycles at 1.9 A g-1 . By replacing the lithium metal with a graphite-based negative electrode, we also report a coin cell capable of cycling for more than 370 cycles at 190 mA g-1 with a stable discharge capacity of about 105 mAh g-1 and a discharge capacity retention of 98% at 25 °C., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
28. Long-term whole blood DNA preservation by cost-efficient cryosilicification.
- Author
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Zhou L, Lei Q, Guo J, Gao Y, Shi J, Yu H, Yin W, Cao J, Xiao B, Andreo J, Ettlinger R, Jeffrey Brinker C, Wuttke S, and Zhu W
- Subjects
- Humans, Blood Preservation methods, Preservation, Biological methods, Oxygen, Ultraviolet Rays, DNA genetics
- Abstract
Deoxyribonucleic acid (DNA) is the blueprint of life, and cost-effective methods for its long-term storage could have many potential benefits to society. Here we present the method of in situ cryosilicification of whole blood cells, which allows long-term preservation of DNA. Importantly, our straightforward approach is inexpensive, reliable, and yields cryosilicified samples that fulfill the essential criteria for safe, long-term DNA preservation, namely robustness against external stressors, such as radical oxygen species or ultraviolet radiation, and long-term stability in humid conditions at elevated temperatures. Our approach could enable the room temperature storage of genomic information in book-size format for more than one thousand years (thermally equivalent), costing only 0.5 $/person. Additionally, our demonstration of 3D-printed DNA banking artefacts, could potentially allow 'artificial fossilization'., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
29. A medium-entropy transition metal oxide cathode for high-capacity lithium metal batteries.
- Author
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Pei Y, Chen Q, Wang M, Zhang P, Ren Q, Qin J, Xiao P, Song L, Chen Y, Yin W, Tong X, Zhen L, Wang P, and Xu CY
- Abstract
The limited capacity of the positive electrode active material in non-aqueous rechargeable lithium-based batteries acts as a stumbling block for developing high-energy storage devices. Although lithium transition metal oxides are high-capacity electrochemical active materials, the structural instability at high cell voltages (e.g., >4.3 V) detrimentally affects the battery performance. Here, to circumvent this issue, we propose a Li
1.46 Ni0.32 Mn1.2 O4-x (0 < x < 4) material capable of forming a medium-entropy state spinel phase with partial cation disordering after initial delithiation. Via physicochemical measurements and theoretical calculations, we demonstrate the structural disorder in delithiated Li1.46 Ni0.32 Mn1.2 O4-x , the direct shuttling of Li ions from octahedral sites to the spinel structure and the charge-compensation Mn3+ /Mn4+ cationic redox mechanism after the initial delithiation. When tested in a coin cell configuration in combination with a Li metal anode and a LiPF6 -based non-aqueous electrolyte, the Li1.46 Ni0.32 Mn1.2 O4-x -based positive electrode enables a discharge capacity of 314.1 mA h g-1 at 100 mA g-1 with an average cell discharge voltage of about 3.2 V at 25 ± 5 °C, which results in a calculated initial specific energy of 999.3 Wh kg-1 (based on mass of positive electrode's active material)., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
30. Structural insights into the peptide selectivity and activation of human neuromedin U receptors.
- Author
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You C, Zhang Y, Xu P, Huang S, Yin W, Eric Xu H, and Jiang Y
- Subjects
- Central Nervous System metabolism, Cryoelectron Microscopy, Humans, Obesity drug therapy, Receptors, Neurotransmitter metabolism
- Abstract
Neuromedin U receptors (NMURs), including NMUR1 and NMUR2, are a group of G
q/11 -coupled G protein-coupled receptors (GPCRs). NMUR1 and NMUR2 play distinct, pleiotropic physiological functions in peripheral tissues and in the central nervous system (CNS), respectively, according to their distinct tissue distributions. These receptors are stimulated by two endogenous neuropeptides, neuromedin U and S (NMU and NMS) with similar binding affinities. NMURs have gathered attention as potential drug targets for obesity and inflammatory disorders. Specifically, selective agonists for NMUR2 in peripheral tissue show promising long-term anti-obesity effects with fewer CNS-related side effects. However, the mechanisms of peptide binding specificity and receptor activation remain elusive. Here, we report four cryo-electron microscopy structures of Gq chimera-coupled NMUR1 and NMUR2 in complexes with NMU and NMS. These structures reveal the conserved overall peptide-binding mode and the mechanism of peptide selectivity for specific NMURs, as well as the common activation mechanism of the NMUR subfamily. Together, these findings provide insights into the molecular basis of the peptide recognition and offer an opportunity for the design of the selective drugs targeting NMURs., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
31. Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors.
- Author
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Duan J, Shen DD, Zhao T, Guo S, He X, Yin W, Xu P, Ji Y, Chen LN, Liu J, Zhang H, Liu Q, Shi Y, Cheng X, Jiang H, Eric Xu H, Zhang Y, Xie X, and Jiang Y
- Subjects
- Protein Binding, Receptors, G-Protein-Coupled metabolism, Receptors, Galanin metabolism, Signal Transduction, GTP-Binding Proteins metabolism, Galanin metabolism
- Abstract
Peptide hormones and neuropeptides are complex signaling molecules that predominately function through G protein-coupled receptors (GPCRs). Two unanswered questions remaining in the field of peptide-GPCR signaling systems pertain to the basis for the diverse binding modes of peptide ligands and the specificity of G protein coupling. Here, we report the structures of a neuropeptide, galanin, bound to its receptors, GAL1R and GAL2R, in complex with their primary G protein subtypes G
i and Gq , respectively. The structures reveal a unique binding pose of galanin, which almost 'lays flat' on the top of the receptor transmembrane domain pocket in an α-helical conformation, and acts as an 'allosteric-like' agonist via a distinct signal transduction cascade. The structures also uncover the important features of intracellular loop 2 (ICL2) that mediate specific interactions with Gq , thus determining the selective coupling of Gq to GAL2R. ICL2 replacement in Gi -coupled GAL1R, μOR, 5-HT1A R, and Gs -coupled β2 AR and D1R with that of GAL2R promotes Gq coupling of these receptors, highlighting the dominant roles of ICL2 in Gq selectivity. Together our results provide insights into peptide ligand recognition and allosteric activation of galanin receptors and uncover a general structural element for Gq coupling selectivity., (© 2022. The Author(s).)- Published
- 2022
- Full Text
- View/download PDF
32. In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy.
- Author
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Lei S, Zhang J, Blum NT, Li M, Zhang DY, Yin W, Zhao F, Lin J, and Huang P
- Subjects
- Catalysis, Glucose Oxidase, Humans, Molecular Imaging methods, Neoplasms diagnostic imaging, Neoplasms pathology, Neoplasms therapy, Photoacoustic Techniques methods
- Abstract
Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy., (© 2022. The Author(s).)
- Published
- 2022
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- View/download PDF
33. Glucocorticoid receptor regulates PD-L1 and MHC-I in pancreatic cancer cells to promote immune evasion and immunotherapy resistance.
- Author
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Deng Y, Xia X, Zhao Y, Zhao Z, Martinez C, Yin W, Yao J, Hang Q, Wu W, Zhang J, Yu Y, Xia W, Yao F, Zhao D, Sun Y, Ying H, Hung MC, and Ma L
- Subjects
- Animals, B7-H1 Antigen genetics, B7-H1 Antigen metabolism, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal therapy, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I metabolism, Humans, Immunoblotting, Immunotherapy methods, Kaplan-Meier Estimate, Mice, Inbred C57BL, Pancreatic Neoplasms genetics, Pancreatic Neoplasms therapy, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism, Reverse Transcriptase Polymerase Chain Reaction, Tumor Escape genetics, Mice, B7-H1 Antigen immunology, Carcinoma, Pancreatic Ductal immunology, Histocompatibility Antigens Class I immunology, Pancreatic Neoplasms immunology, Receptors, Glucocorticoid immunology, Tumor Escape immunology
- Abstract
Despite unprecedented responses of some cancers to immune checkpoint blockade (ICB) therapies, the application of checkpoint inhibitors in pancreatic cancer has been unsuccessful. Glucocorticoids and glucocorticoid receptor (GR) signaling are long thought to suppress immunity by acting on immune cells. Here we demonstrate a previously undescribed tumor cell-intrinsic role for GR in activating PD-L1 expression and repressing the major histocompatibility complex class I (MHC-I) expression in pancreatic ductal adenocarcinoma (PDAC) cells through transcriptional regulation. In mouse models of PDAC, either tumor cell-specific depletion or pharmacologic inhibition of GR leads to PD-L1 downregulation and MHC-I upregulation in tumor cells, which in turn promotes the infiltration and activity of cytotoxic T cells, enhances anti-tumor immunity, and overcomes resistance to ICB therapy. In patients with PDAC, GR expression correlates with high PD-L1 expression, low MHC-I expression, and poor survival. Our results reveal GR signaling in cancer cells as a tumor-intrinsic mechanism of immunosuppression and suggest that therapeutic targeting of GR is a promising way to sensitize pancreatic cancer to immunotherapy., (© 2021. The Author(s).)
- Published
- 2021
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- View/download PDF
34. Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor.
- Author
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Wang Y, Guo S, Zhuang Y, Yun Y, Xu P, He X, Guo J, Yin W, Xu HE, Xie X, and Jiang Y
- Subjects
- Amino Acid Sequence, Animals, Binding Sites, Cell Line, Cryoelectron Microscopy, GTP-Binding Protein alpha Subunits, Gq-G11 chemistry, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, Ghrelin metabolism, HEK293 Cells, Humans, Models, Molecular, Oligopeptides metabolism, Protein Binding, Receptors, Ghrelin metabolism, Receptors, Ghrelin ultrastructure, Oligopeptides chemistry, Receptors, Ghrelin chemistry
- Abstract
Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of G
q -coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor., (© 2021. The Author(s).)- Published
- 2021
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- View/download PDF
35. Author Correction: A chalcogenide-cluster-based semiconducting nanotube array with oriented photoconductive behavior.
- Author
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Tang J, Wang X, Zhang J, Wang J, Yin W, Li DS, and Wu T
- Published
- 2021
- Full Text
- View/download PDF
36. A chalcogenide-cluster-based semiconducting nanotube array with oriented photoconductive behavior.
- Author
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Tang J, Wang X, Zhang J, Wang J, Yin W, Li DS, and Wu T
- Abstract
The interesting physical and chemical properties of carbon nanotubes (CNTs) have prompted the search for diverse inorganic nanotubes with different compositions to expand the number of available nanotechnology applications. Among these materials, crystalline inorganic nanotubes with well-defined structures and uniform sizes are suitable for understanding structure-activity relationships. However, their preparation comes with large synthetic challenges owing to their inherent complexity. Herein, we report the example of a crystalline nanotube array based on a supertetrahedral chalcogenide cluster, K
3 [K(Cu2 Ge3 Se9 )(H2 O)] (1). To the best of our knowledge, this nanotube array possesses the largest diameter of crystalline inorganic nanotubes reported to date and exhibits an excellent structure-dependent electric conductivity and an oriented photoconductive behavior. This work represents a significant breakthrough both in terms of the structure of cluster-based metal chalcogenides and in the conductivity of crystalline nanotube arrays (i.e., an enhancement of ~4 orders of magnitude)., (© 2021. The Author(s).)- Published
- 2021
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- View/download PDF
37. A petascale automated imaging pipeline for mapping neuronal circuits with high-throughput transmission electron microscopy.
- Author
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Yin W, Brittain D, Borseth J, Scott ME, Williams D, Perkins J, Own CS, Murfitt M, Torres RM, Kapner D, Mahalingam G, Bleckert A, Castelli D, Reid D, Lee WA, Graham BJ, Takeno M, Bumbarger DJ, Farrell C, Reid RC, and da Costa NM
- Subjects
- Animals, Automation, Mice, Neocortex diagnostic imaging, Software, Image Processing, Computer-Assisted, Microscopy, Electron, Transmission, Nerve Net ultrastructure, Neurons ultrastructure
- Abstract
Electron microscopy (EM) is widely used for studying cellular structure and network connectivity in the brain. We have built a parallel imaging pipeline using transmission electron microscopes that scales this technology, implements 24/7 continuous autonomous imaging, and enables the acquisition of petascale datasets. The suitability of this architecture for large-scale imaging was demonstrated by acquiring a volume of more than 1 mm
3 of mouse neocortex, spanning four different visual areas at synaptic resolution, in less than 6 months. Over 26,500 ultrathin tissue sections from the same block were imaged, yielding a dataset of more than 2 petabytes. The combined burst acquisition rate of the pipeline is 3 Gpixel per sec and the net rate is 600 Mpixel per sec with six microscopes running in parallel. This work demonstrates the feasibility of acquiring EM datasets at the scale of cortical microcircuits in multiple brain regions and species.- Published
- 2020
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- View/download PDF
38. Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo.
- Author
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Yang J, Yin W, Van R, Yin K, Wang P, Zheng C, Zhu B, Ran K, Zhang C, Kumar M, Shao Y, and Ran C
- Subjects
- Animals, Luminescent Measurements methods, Mice, Molecular Imaging methods, Optical Imaging methods, Protein Aggregates, Amyloid beta-Peptides chemistry, Luminescence
- Abstract
Turn-on fluorescence imaging is routinely studied; however, turn-on chemiluminescence has been rarely explored for in vivo imaging. Herein, we report the design and validation of chemiluminescence probe ADLumin-1 as a turn-on probe for amyloid beta (Aβ) species. Two-photon imaging indicates that ADLumin-1 can efficiently cross the blood-brain barrier and provides excellent contrast for Aβ plaques and cerebral amyloid angiopathy. In vivo brain imaging shows that the chemiluminescence signal of ADLumin-1 from 5-month-old transgenic 5xFAD mice is 1.80-fold higher than that from the age-matched wild-type mice. Moreover, we demonstrate that it is feasible to further dually-amplify signal via chemiluminescence resonance energy transfer (DAS-CRET) using two non-conjugated smart probes (ADLumin-1 and CRANAD-3) in solutions, brain homogenates, and in vivo whole brain imaging. Our results show that DAS-CRET can provide a 2.25-fold margin between 5-month-old 5xFAD mice and wild type mice. We believe that our strategy could be extended to other aggregating-prone proteins.
- Published
- 2020
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- View/download PDF
39. Structural evolution at the oxidative and reductive limits in the first electrochemical cycle of Li 1.2 Ni 0.13 Mn 0.54 Co 0.13 O 2 .
- Author
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Yin W, Grimaud A, Rousse G, Abakumov AM, Senyshyn A, Zhang L, Trabesinger S, Iadecola A, Foix D, Giaume D, and Tarascon JM
- Abstract
High-energy-density lithium-rich materials are of significant interest for advanced lithium-ion batteries, provided that several roadblocks, such as voltage fade and poor energy efficiency are removed. However, this remains challenging as their functioning mechanisms during first cycle are not fully understood. Here we enlarge the cycling potential window for Li
1.2 Ni0.13 Mn0.54 Co0.13 O2 electrode, identifying novel structural evolution mechanism involving a structurally-densified single-phase A' formed under harsh oxidizing conditions throughout the crystallites and not only at the surface, in contrast to previous beliefs. We also recover a majority of first-cycle capacity loss by applying a constant-voltage step on discharge. Using highly reducing conditions we obtain additional capacity via a new low-potential P" phase, which is involved into triggering oxygen redox on charge. Altogether, these results provide deeper insights into the structural-composition evolution of Li1.2 Ni0.13 Mn0.54 Co0.13 O2 and will help to find measures to cure voltage fade and improve energy efficiency in this class of material.- Published
- 2020
- Full Text
- View/download PDF
40. Coordination assembly of 2D ordered organic metal chalcogenides with widely tunable electronic band gaps.
- Author
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Li Y, Jiang X, Fu Z, Huang Q, Wang GE, Deng WH, Wang C, Li Z, Yin W, Chen B, and Xu G
- Abstract
Engineering the band gap chemically by organic molecules is a powerful tool with which to optimize the properties of inorganic 2D materials. The obtained materials are however still limited by inhomogeneous compositions and properties at nanoscale and small adjustable band gap ranges. To overcome these problems in the traditional exfoliation and then organic modification strategy, an organic modification and then exfoliation strategy was explored in this work for preparing 2D organic metal chalcogenides (OMCs). Unlike the reported organically modified 2D materials, the inorganic layers of OMCs are fully covered by long-range ordered organic functional groups. By changing the electron-donating ability of the organic functional groups and the electronegativity of the metals, the band gaps of OMCs were varied by 0.83 eV and their conductivities were modulated by 9 orders of magnitude, which are 2 and 10
7 times higher than the highest values observed in the reported chemical methods, respectively.- Published
- 2020
- Full Text
- View/download PDF
41. Arf1-mediated lipid metabolism sustains cancer cells and its ablation induces anti-tumor immune responses in mice.
- Author
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Wang G, Xu J, Zhao J, Yin W, Liu D, Chen W, and Hou SX
- Subjects
- ADP-Ribosylation Factor 1 genetics, ADP-Ribosylation Factor 1 pharmacology, Alarmins, Animals, Antineoplastic Agents pharmacology, Cell Line, Tumor, Dendritic Cells immunology, Endoplasmic Reticulum Stress drug effects, Female, Gastrointestinal Neoplasms metabolism, Gastrointestinal Neoplasms pathology, Gastrointestinal Neoplasms therapy, Gene Knockdown Techniques, Humans, Lipolysis drug effects, Liver Neoplasms metabolism, Liver Neoplasms pathology, Liver Neoplasms therapy, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mitochondria drug effects, Neoplastic Stem Cells cytology, T-Lymphocytes immunology, Tamoxifen pharmacology, Vaccination, ADP-Ribosylation Factor 1 metabolism, Antineoplastic Agents immunology, Lipid Metabolism physiology, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells metabolism
- Abstract
Cancer stem cells (CSCs) may be responsible for treatment resistance, tumor metastasis, and disease recurrence. Here we demonstrate that the Arf1-mediated lipid metabolism sustains cells enriched with CSCs and its ablation induces anti-tumor immune responses in mice. Notably, Arf1 ablation in cancer cells induces mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells (DCs) at tumor sites. The activated immune system finally elicits antitumor immune surveillance by stimulating T-cell infiltration and activation. Furthermore, TCGA data analysis shows an inverse correlation between Arf1 expression and T-cell infiltration and activation along with patient survival in various human cancers. Our results reveal that Arf1-pathway knockdown not only kills CSCs but also elicits a tumor-specific immune response that converts dying CSCs into a therapeutic vaccine, leading to durable benefits.
- Published
- 2020
- Full Text
- View/download PDF
42. Octahedral gold-silver nanoframes with rich crystalline defects for efficient methanol oxidation manifesting a CO-promoting effect.
- Author
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Xiong L, Sun Z, Zhang X, Zhao L, Huang P, Chen X, Jin H, Sun H, Lian Y, Deng Z, Rümmerli MH, Yin W, Zhang D, Wang S, and Peng Y
- Abstract
Three-dimensional bimetallic nanoframes with high spatial diffusivity and surface heterogeneity possess remarkable catalytic activities owing to their highly exposed active surfaces and tunable electronic structure. Here we report a general one-pot strategy to prepare ultrathin octahedral Au
3 Ag nanoframes, with the formation mechanism explicitly elucidated through well-monitored temporal nanostructure evolution. Rich crystalline defects lead to lowered atomic coordination and varied electronic states of the metal atoms as evidenced by extensive structural characterizations. When used for electrocatalytic methanol oxidation, the Au3 Ag nanoframes demonstrate superior performance with a high specific activity of 3.38 mA cm-2 , 3.9 times that of the commercial Pt/C. More intriguingly, the kinetics of methanol oxidation on the Au3 Ag nanoframes is counter-intuitively promoted by carbon monoxide. The enhancement is ascribed to the altered reaction pathway and enhanced OH- co-adsorption on the defect-rich surfaces, which can be well understood from the d-band model and comprehensive density functional theory simulations.- Published
- 2019
- Full Text
- View/download PDF
43. Myh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease.
- Author
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Kim HT, Yin W, Jin YJ, Panza P, Gunawan F, Grohmann B, Buettner C, Sokol AM, Preussner J, Guenther S, Kostin S, Ruppert C, Bhagwat AM, Ma X, Graumann J, Looso M, Guenther A, Adelstein RS, Offermanns S, and Stainier DYR
- Subjects
- Amino Acid Sequence, Animals, Down-Regulation genetics, Emphysema pathology, Ethylnitrosourea, Female, Lung Diseases pathology, Male, Matrix Metalloproteinase 2 metabolism, Mesoderm metabolism, Mice, Inbred C57BL, Mutagenesis genetics, Mutation, Missense genetics, Myosin Heavy Chains chemistry, Myosin Heavy Chains genetics, Myosin Heavy Chains metabolism, Nonmuscle Myosin Type IIB chemistry, Nonmuscle Myosin Type IIB genetics, Nonmuscle Myosin Type IIB metabolism, Organogenesis, Phenotype, Pulmonary Alveoli embryology, Pulmonary Alveoli metabolism, Up-Regulation genetics, Extracellular Matrix metabolism, Lung Diseases metabolism, Myosin Heavy Chains deficiency, Nonmuscle Myosin Type IIB deficiency
- Abstract
Impaired alveolar formation and maintenance are features of many pulmonary diseases that are associated with significant morbidity and mortality. In a forward genetic screen for modulators of mouse lung development, we identified the non-muscle myosin II heavy chain gene, Myh10. Myh10 mutant pups exhibit cyanosis and respiratory distress, and die shortly after birth from differentiation defects in alveolar epithelium and mesenchyme. From omics analyses and follow up studies, we find decreased Thrombospondin expression accompanied with increased matrix metalloproteinase activity in both mutant lungs and cultured mutant fibroblasts, as well as disrupted extracellular matrix (ECM) remodeling. Loss of Myh10 specifically in mesenchymal cells results in ECM deposition defects and alveolar simplification. Notably, MYH10 expression is downregulated in the lung of emphysema patients. Altogether, our findings reveal critical roles for Myh10 in alveologenesis at least in part via the regulation of ECM remodeling, which may contribute to the pathogenesis of emphysema.
- Published
- 2018
- Full Text
- View/download PDF
44. Prevention of pancreatic acinar cell carcinoma by Roux-en-Y Gastric Bypass Surgery.
- Author
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He R, Yin Y, Yin W, Li Y, Zhao J, and Zhang W
- Subjects
- Animals, Apoptosis, Basic Helix-Loop-Helix Transcription Factors metabolism, Body Weight, Carcinoma, Acinar Cell pathology, Diet, High-Fat, Energy Intake, Glucose metabolism, Humans, Mechanistic Target of Rapamycin Complex 1 metabolism, Mice, Knockout, Neoplasm Metastasis, Nerve Tissue Proteins metabolism, Pancreatic Neoplasms pathology, Signal Transduction, Tuberous Sclerosis Complex 1 Protein metabolism, Carcinoma, Acinar Cell prevention & control, Gastric Bypass, Pancreatic Neoplasms prevention & control
- Abstract
Roux-en-Y Gastric Bypass Surgery (RYGB) prevents the occurrence of pancreatic cell acinar carcinoma (ACC) in male and female Ngn3-Tsc1-/- mice. Ngn3 directed Cre deletion of Tsc1 gene induced the development of pancreatic ACC. The transgenic mice with sham surgery demonstrated a cancer incidence of 96.7 ± 3.35% and survival rate of 67.0 ± 1.4% at the age of 300 days. Metastasis to liver and kidney was observed in 69.7 ± 9.7% and 44.3 ± 8.01% of these animals, respectively. All animals with RYGB performed at the age of 16 weeks survived free of pancreatic ACC up to the age of 300 days. RYGB significantly attenuated the activation of mTORC1 signaling and inhibition of tumor suppressor genes: p21, p27, and p53 in pancreatic ACC. Our studies demonstrate that bariatric surgery may limit the occurrence and growth of pancreatic ACC through the suppression of mTORC1 signaling in pancreas. RYGB shows promise for intervention of both metabolic dysfunction and organ cancer.
- Published
- 2018
- Full Text
- View/download PDF
45. The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tubulogenesis.
- Author
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Yin W, Kim HT, Wang S, Gunawan F, Wang L, Kishimoto K, Zhong H, Roman D, Preussner J, Guenther S, Graef V, Buettner C, Grohmann B, Looso M, Morimoto M, Mardon G, Offermanns S, and Stainier DYR
- Subjects
- Actin Cytoskeleton metabolism, Actin Cytoskeleton ultrastructure, Animals, Cell Polarity, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Ion Transport, Mice, Knockout, Muscle, Smooth cytology, Myocytes, Smooth Muscle cytology, Phosphorylation, Polymerization, Potassium Channels, Inwardly Rectifying deficiency, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, Trachea cytology, Trachea growth & development, Morphogenesis genetics, Muscle, Smooth metabolism, Myocytes, Smooth Muscle metabolism, Potassium Channels, Inwardly Rectifying genetics, Proto-Oncogene Proteins c-akt genetics, Trachea metabolism
- Abstract
Tubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13-mutant trachea phenotypes. These results provide insight into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.
- Published
- 2018
- Full Text
- View/download PDF
46. Molecular characterization of breast cancer CTCs associated with brain metastasis.
- Author
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Boral D, Vishnoi M, Liu HN, Yin W, Sprouse ML, Scamardo A, Hong DS, Tan TZ, Thiery JP, Chang JC, and Marchetti D
- Subjects
- Base Sequence, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Brain Neoplasms diagnosis, Brain Neoplasms secondary, Breast Neoplasms blood, Breast Neoplasms pathology, Early Detection of Cancer, Epithelial Cell Adhesion Molecule genetics, Female, Humans, Sequence Analysis, DNA methods, Brain Neoplasms genetics, Breast Neoplasms genetics, Gene Expression Regulation, Neoplastic, Neoplastic Cells, Circulating metabolism, Transcriptome genetics
- Abstract
The enumeration of EpCAM-positive circulating tumor cells (CTCs) has allowed estimation of overall metastatic burden in breast cancer patients. However, a thorough understanding of CTCs associated with breast cancer brain metastasis (BCBM) is necessary for early identification and evaluation of treatment response to BCBM. Here we report that BCBM CTCs is enriched in a distinct sub-population of cells identifiable by their biomarker expression and mutational content. Deriving from a comprehensive analysis of CTC transcriptomes, we discovered a unique "circulating tumor cell gene signature" that is distinct from primary breast cancer tissues. Further dissection of the circulating tumor cell gene signature identified signaling pathways associated with BCBM CTCs that may have roles in potentiating BCBM. This study proposes CTC biomarkers and signaling pathways implicated in BCBM that may be used either as a screening tool for brain micro-metastasis detection or for making rational treatment decisions and monitoring therapeutic response in patients with BCBM.Characterization of CTCs derived from breast cancer patients with brain metastasis (BCBM) may allow for early diagnosis of brain metastasis and/or help for treatment choice and its efficacy. In this study, the authors identify a unique signature, based on patient-derived CTCs transcriptomes, for BCBM- CTCs that is different from primary tumors.
- Published
- 2017
- Full Text
- View/download PDF
47. Beat frequency quartz-enhanced photoacoustic spectroscopy for fast and calibration-free continuous trace-gas monitoring.
- Author
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Wu H, Dong L, Zheng H, Yu Y, Ma W, Zhang L, Yin W, Xiao L, Jia S, and Tittel FK
- Abstract
Quartz-enhanced photoacoustic spectroscopy (QEPAS) is a sensitive gas detection technique which requires frequent calibration and has a long response time. Here we report beat frequency (BF) QEPAS that can be used for ultra-sensitive calibration-free trace-gas detection and fast spectral scan applications. The resonance frequency and Q-factor of the quartz tuning fork (QTF) as well as the trace-gas concentration can be obtained simultaneously by detecting the beat frequency signal generated when the transient response signal of the QTF is demodulated at its non-resonance frequency. Hence, BF-QEPAS avoids a calibration process and permits continuous monitoring of a targeted trace gas. Three semiconductor lasers were selected as the excitation source to verify the performance of the BF-QEPAS technique. The BF-QEPAS method is capable of measuring lower trace-gas concentration levels with shorter averaging times as compared to conventional PAS and QEPAS techniques and determines the electrical QTF parameters precisely.
- Published
- 2017
- Full Text
- View/download PDF
48. Evolutionary trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper.
- Author
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Yin W, Wang ZJ, Li QY, Lian JM, Zhou Y, Lu BZ, Jin LJ, Qiu PX, Zhang P, Zhu WB, Wen B, Huang YJ, Lin ZL, Qiu BT, Su XW, Yang HM, Zhang GJ, Yan GM, and Zhou Q
- Subjects
- Animals, Cell Lineage, Evolution, Molecular, Female, Forelimb, Gene Expression Profiling, Gene Expression Regulation, Genome, Hindlimb, Lizards genetics, Male, Phylogeny, Recombination, Genetic, Sex Chromosomes, Transcriptome, Biological Evolution, DNA Transposable Elements, Snakes anatomy & histology, Snakes genetics
- Abstract
Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes' history of molecular evolution.
- Published
- 2016
- Full Text
- View/download PDF
49. Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia.
- Author
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Lin J, Yin W, Smith MC, Song K, Leigh MW, Zariwala MA, Knowles MR, Ostrowski LE, and Nicastro D
- Subjects
- Cilia genetics, Cilia metabolism, DNA-Binding Proteins chemistry, DNA-Binding Proteins genetics, Humans, Kartagener Syndrome diagnosis, Kartagener Syndrome genetics, Cilia ultrastructure, Cryoelectron Microscopy methods, DNA-Binding Proteins metabolism, Electron Microscope Tomography methods, Kartagener Syndrome metabolism
- Abstract
Cilia play essential roles in normal human development and health; cilia dysfunction results in diseases such as primary ciliary dyskinesia (PCD). Despite their importance, the native structure of human cilia is unknown, and structural defects in the cilia of patients are often undetectable or remain elusive because of heterogeneity. Here we develop an approach that enables visualization of human (patient) cilia at high-resolution using cryo-electron tomography of samples obtained noninvasively by nasal scrape biopsy. We present the native 3D structures of normal and PCD-causing RSPH1-mutant human respiratory cilia in unprecedented detail; this allows comparisons of cilia structure across evolutionarily distant species and reveals the previously unknown primary defect and the heterogeneous secondary defects in RSPH1-mutant cilia. Our data provide evidence for structural and functional heterogeneity in radial spokes, suggest a mechanism for the milder RSPH1 PCD phenotype and demonstrate that cryo-electron tomography can be applied to human disease by directly imaging patient samples.
- Published
- 2014
- Full Text
- View/download PDF
50. Picornavirus uncoating intermediate captured in atomic detail.
- Author
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Ren J, Wang X, Hu Z, Gao Q, Sun Y, Li X, Porta C, Walter TS, Gilbert RJ, Zhao Y, Axford D, Williams M, McAuley K, Rowlands DJ, Yin W, Wang J, Stuart DI, Rao Z, and Fry EE
- Subjects
- Animals, Chlorocebus aethiops, Crystallography, X-Ray, Enterovirus, Humans, Models, Molecular, Molecular Conformation, Vero Cells, Viral Structural Proteins chemistry, Virion metabolism, Virus Internalization, Picornaviridae chemistry, Picornaviridae physiology, Virus Uncoating physiology
- Abstract
It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release.
- Published
- 2013
- Full Text
- View/download PDF
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