25 results on '"Xin Shan"'
Search Results
2. Recognition of Aedes aegypti Mosquito Saliva Protein LTRIN by the Human Receptor LTβR for Controlling the Immune Response
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Su Ning Loh, Ian Russell Anthony, Edem Gavor, Xin Shan Lim, R. Manjunatha Kini, Yu Keung Mok, and J. Sivaraman
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mosquito ,saliva protein ,Zika virus ,human receptor ,EF-hand ,Biology (General) ,QH301-705.5 - Abstract
Salivary proteins from mosquitoes have received significant attention lately due to their potential to develop therapeutic treatments or vaccines for mosquito-borne diseases. Here, we report the characterization of LTRIN (lymphotoxin beta receptor inhibitor), a salivary protein known to enhance the pathogenicity of ZIKV by interrupting the LTβR-initiated NF-κB signaling pathway and, therefore, diminish the immune responses. We demonstrated that the truncated C-terminal LTRIN (ΔLTRIN) is a dimeric protein with a stable alpha helix-dominant secondary structure, which possibly aids in withstanding the temperature fluctuations during blood-feeding events. ΔLTRIN possesses two Ca2+ binding EF-hand domains, with the second EF-hand motif playing a more significant role in interacting with LTβR. Additionally, we mapped the primary binding regions of ΔLTRIN on LTβR using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and identified that 91QEKAHIAEHMDVPIDTSKMSEQELQFHY118 from the N-terminal of ΔLTRIN is the major interacting region. Together, our studies provide insight into the recognition of LTRIN by LTβR. This finding may aid in a future therapeutic and transmission-blocking vaccine development against ZIKV.
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- 2024
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3. Synthesis of branched arabinogalactans up to a 140-mer from Panax notoginseng and their anti-pancreatic-cancer activity
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Qin, Xianjin, Xu, Chenghao, Liu, Mingli, Zeng, Fansheng, Yao, Wenlong, Deng, Yi, Xu, Tianfu, Sun, Shengyuan, Sun, Dongyue, Mo, Juan, and Ye, Xin-Shan
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- 2024
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4. Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia
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Peng, Hao, Xin, Shan, Pfeiffer, Susanne, Müller, Constanze, Merl-Pham, Juliane, Hauck, Stefanie M., Harter, Patrick N., Spitzer, Daniel, Devraj, Kavi, Varynskyi, Borys, Arzberger, Thomas, Momma, Stefan, and Schick, Joel A.
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- 2024
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5. Publisher Correction: Synthesis of branched arabinogalactans up to a 140-mer from Panax notoginseng and their anti-pancreatic-cancer activity
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Qin, Xianjin, Xu, Chenghao, Liu, Mingli, Zeng, Fansheng, Yao, Wenlong, Deng, Yi, Xu, Tianfu, Sun, Shengyuan, Sun, Dongyue, Mo, Juan, and Ye, Xin-Shan
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- 2024
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6. A multiomics analysis-assisted deep learning model identifies a macrophage-oriented module as a potential therapeutic target in colorectal cancer
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Bao, Xuanwen, Li, Qiong, Chen, Dong, Dai, Xiaomeng, Liu, Chuan, Tian, Weihong, Zhang, Hangyu, Jin, Yuzhi, Wang, Yin, Cheng, Jinlin, Lai, Chunyu, Ye, Chanqi, Xin, Shan, Li, Xin, Su, Ge, Ding, Yongfeng, Xiong, Yangyang, Xie, Jindong, Tano, Vincent, Wang, Yanfang, Fu, Wenguang, Deng, Shuiguang, Fang, Weijia, Sheng, Jianpeng, Ruan, Jian, and Zhao, Peng
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- 2024
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7. Differential Nitrous oxide emission and microbiota succession in constructed wetlands induced by nitrogen forms
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Wang, Jun-Feng, Huang, Jia-Wei, Cai, Ze-Xiang, Li, Qu-Sheng, Sun, Yun-Yun, Zhou, Huan-Zhan, Zhu, Hui, Song, Xin-Shan, and Wu, Hai-Ming
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- 2024
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8. Donor Preactivation-Based Glycan Assembly: from Manual to Automated Synthesis
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Yao, Wenlong, primary and Ye, Xin-Shan, additional
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- 2024
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9. Pan‐Cancer Single‐Cell and Spatial‐Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy
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Liu, Chuan, primary, Xie, Jindong, additional, Lin, Bo, additional, Tian, Weihong, additional, Wu, Yifan, additional, Xin, Shan, additional, Hong, Libing, additional, Li, Xin, additional, Liu, Lulu, additional, Jin, Yuzhi, additional, Tang, Hailin, additional, Deng, Xinpei, additional, Zou, Yutian, additional, Zheng, Shaoquan, additional, Fang, Weijia, additional, Cheng, Jinlin, additional, Dai, Xiaomeng, additional, Bao, Xuanwen, additional, and Zhao, Peng, additional
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- 2024
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10. Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China.
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Ting Wang, Meng-yan Li, Xin-shan Cai, Qiu-sheng Cheng, Ze Li, Ting-ting Liu, Lin-fu Zhou, Hong-hao Wang, Guo-dong Feng, Marais, Ben J., and Gang Zhao
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TUBERCULOSIS ,TUBERCULOUS meningitis ,PROGNOSIS ,SYMPTOMS ,CENTRAL nervous system ,CEREBROSPINAL fluid - Abstract
Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome--assessed using the modified Barthel disability index--were recorded and compared. Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score = 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio = 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score = 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (=15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Deterministic Conversion of Hyperentangled States with Error‐Heralded Quantum Units.
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Du, Fang‐Fang, Ma, Ming, Ren, Xue‐Mei, Fan, Gang, Du, Xin‐Shan, Li, Ling‐Hui, Fan, Zhi‐Guo, and Guo, Jing
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QUANTUM states ,INFORMATION technology ,DEGREES of freedom ,HUMAN geography ,QUANTUM efficiency ,QUANTUM entanglement ,PHOTON pairs ,PHOTON scattering - Abstract
In the paper, the possibility of two complete conversions is investigated, one is from the two‐photon hyperentangled Knill–Laflamme–Milburn (KLM) state to hyperentangled Bell states, the other is from three‐photon KLM state to the hyperentangled Greenberger–Horne–Zeilinger states, for photonic systems hyper‐encoded in polarization and spatial degrees of freedom assisted by error‐heralded quantum units (EHQUs). The system inhomogeneity and/or the imperfect photon scattering often restrict the performance of effective conversions of two types of hyperentangled states, and result in the reductions of the fidelity and the efficiency in tangible quantum information technologies. The polarization EHQU and spatial EHQU are two critical tools for actualizing two hyperentangled conversions in a heralded way, as the errors stemming from the system inhomogeneity and practically imperfect scattering are converted into efficacious responses of the detectors in our protocols. Thus, the fidelities of these conversion cases keep unchanged and have close to unity fidelities, which deepen the understanding of the properties of hyperentanglement. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy
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Verma, Nipun, primary, Renauer, Paul A., additional, Dong, Chuanpeng, additional, Xin, Shan, additional, Lin, Qianqian, additional, Zhang, Feifei, additional, Glazer, Peter M., additional, and Chen, Sidi, additional
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- 2024
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13. Recognition of Aedes aegypti Mosquito Saliva Protein LTRIN by the Human Receptor LTβR for Controlling the Immune Response
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Loh, Su Ning, primary, Anthony, Ian Russell, additional, Gavor, Edem, additional, Lim, Xin Shan, additional, Kini, R. Manjunatha, additional, Mok, Yu Keung, additional, and Sivaraman, J., additional
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- 2024
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14. YOLOv5-Sewer: Lightweight Sewer Defect Detection Model.
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Zhao, Xingliang, Xiao, Ning, Cai, Zhaoyang, and Xin, Shan
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SEWERAGE ,NECK ,SPEED - Abstract
In the field of defect detection in sewers, some researches focus on high accuracy. However, it is challenging for portable on-site devices to provide high performance. This paper proposes a lightweight sewer defect detection model, You Only Look Once (YOLO) v5-Sewer. Firstly, the backbone network of YOLOv5s is replaced with a stacked MobileNetV3 block. Secondly, the C3 module of the neck of YOLOv5s is improved with a C3-Faster module. Thirdly, to compensate for the accuracy loss due to the lightweight network, a channel attention (CA) and convolutional block attention module (CBAM) are added to the proposed method. Finally, the Efficient Intersection over Union (EIOU) is adopted as the localization loss function. Experimental validation on the dataset shows that YOLOv5-Sewer achieves a 1.5% reduction in mean Average Precision (mAP) while reducing floating-point operations by 68%, the number of parameters by 55%, and the model size by 54%, compared to the YOLOv5s model. The detection speed reaches 112 frames per second (FPS) with the GPU (RTX 3070Ti). This model successfully implements a lightweight design while maintaining the detection accuracy, enhancing its functionality on low-performance devices. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Investigating the impact of elevated urinary trace elements on non-alcoholic fatty liver disease using vibration-controlled transient elastography
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Chenxiao Wang, Xin Shang, Yu Fu, Panpan Guo, Ping Wang, and Shuxun Yan
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trace elements ,urine ,non-alcoholic fatty liver disease ,VCTE ,dose-response relationship ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
IntroductionNon-alcoholic fatty liver disease (NAFLD) is a global public health concern. However, limited data are available on urinary trace elements and NAFLD caused by various exposure factors. This study aimed to investigate the relationship between the presence of 16 trace elements in urine and NAFLD using data from the National Health and Nutrition Examination Survey (NHANES).MethodsBy utilizing the NHANES data from 2017 to 2018, 1613 participants who fulfilled the research criteria were identified from the initial pool of 2979 participants with available urine trace element detection data. Among them, 706 individuals had been diagnosed with NAFLD based on a coefficient of attenuation parameter (CAP) value of at least 274 db/m, determined using vibration-controlled transient elastography (VCTE); whereas the remaining 907 participants were classified as non-NAFLD. The data obtained were used to construct univariate and multivariate logistic regression models and restricted cubic spline models (RCS) analyses.ResultsThe presence of arsenic, iodine, barium, cesium, molybdenum, lead, tin, and tungsten in the urine of individuals with NAFLD showed a positive correlation with the likelihood of developing NAFLD. The risk of NAFLD had a non-linear dose-dependent relationship with urinary iodine, molybdenum, barium, and cesium. NAFLD was also associated with elevated levels of barium and cesium in urine, which were identified as significant risk factors.ConclusionThese findings suggest a positive association between exposure to trace elements in the urine and the risk of NAFLD. Specifically, urinary barium and cesium appeared to have the greatest impact on the risk of NAFLD. These results provide novel insights into the diagnosis and treatment of NAFLD.
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- 2024
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16. Optimization of the gas flow system in a selective laser melting chamber using numerical methods
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Zirong Zhou, Yongxing Li, Xiaoxuan Chen, Xin Shang, Kunzheng Gou, and Lijuan Pang
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Mechanical engineering and machinery ,TJ1-1570 - Abstract
A well-designed flow field is a key factor to improve the surface quality of products by removing spatter, which is often generated during the selective laser melting (SLM) process. In the present study, three typical schemes are developed for the gas flow system of large-scale SLM equipment. In this regard, the flow deviation and velocity increase indices are implemented to characterize the flow uniformity in the chamber and gas flow velocity in the clearing area. The obtained results show that the inlet size significantly improves the flow uniformity and the segmented inlet increases the flow velocity above the machining surface. More specifically, when the velocity deviation index decreases from 0.3335 to 0.1538, the corresponding velocity index increases from 10.16% to 29.83%. To improve the flow uniformity on the machining surface, the effect of the inlet flow rate on the airflow over the machining surface is investigated. The obtained results show that when the inlet flow rate reduces to 0.2 m/s, the removal spatter improves while the airflow remains uniform. The results of this study can provide a reference for the design of SLM gas flow systems.
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- 2024
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17. Effect of Spatter Behavior on Mechanical Properties and Surface Roughness of Printed Parts during PBF-LM of 316L
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Xiaoxuan Chen, Jialei Song, Wei Zhang, Xin Shang, Yizhe Li, Shenggui Chen, Jiahao Lin, and Zirong Zhou
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additive manufacturing ,selective laser melting ,spatter behavior ,parts quality ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
The spatter generated by the interaction between laser and powder during Powder Bed Fusion-Laser Melting (PBF-LM) can significantly affect the quality of printed parts. A high-speed camera is used to observe the dynamic process of spatter’s behavior under different layer thickness and laser powers during the printing process, and to analyze the printed samples’ surface roughness, microstructure, and mechanical properties. In terms of spatter image processing, employing an optical flow approach to track and quantify the number of spatters efficiently eliminates statistical redundancy and improves statistical correctness. It is found that under the same laser power, the number of spatters produced by the laser scan direction with the gas flow (LSD-W) is more than that by the laser scan direction against the gas flow (LSD-A), and the number of spatters produced increases with the increase of laser power. Analyzing the mechanical properties and surface roughness of the printed samples under different process parameters quantitatively reveals that differences in the spatter amount generated under different process parameters in the PBF-LM process is not the determining factor affecting the difference in tensile strength of printed parts. During LSD-W, the number of spatters generated at laser power of 170 W and layer thickness of 0.03 mm is 87, and the tensile strength of the printed sample is 618 MPa. During LSD-W, the number of spatters generated at laser power of 320 W and layer thickness of 0.05 mm is 211, and the tensile strength of the printed sample is 680 MPa. Instead, spatter generation has a more direct impact on the surface roughness of printed parts. The layer thickness is 0.03 mm, the laser power is 170 W, and (Ra = 2.372 μm) is the surface roughness of the sample. The layer thickness is 0.05 mm, the laser power is 320 W, and (Ra = 8.163 μm) is the surface roughness of the sample.
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- 2024
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18. Investigation of the biocontrol mechanism of a novel Pseudomonas species against phytopathogenic Fusarium graminearum revealed by multi-omics integration analysis.
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Jiawei Dai, Zhaofeng Xu, Ning Yang, Hamiguli Tuerxunjiang, Xin Shan, Yuting Diao, Jiahui Zhao, Meiqi Ma, Xiang Li, Ming Xiao, and Junmin Pei
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MULTIOMICS , *FUSARIUM , *HYDROCYANIC acid , *TRICARBOXYLIC acids , *PSEUDOMONAS , *SOIL quality , *FUNGAL viruses - Abstract
Phytopathogenic Fusarium graminearum poses significant threats to crop health and soil quality. Although our laboratory-cultivated Pseudomonas sp. P13 exhibited potential biocontrol capacities, its effectiveness against F. graminearum and underlying antifungal mechanisms are still unclear. In light of this, our study investigated a significant inhibitory effect of P13 on F. graminearum T1, both in vitro and in a soil environment. Conducting genomic, metabolomic, and transcriptomic analyses of P13, we sought to identify evidence supporting its antagonistic effects on T1. The results revealed the potential of P13, a novel Pseudomonas species, to produce active antifungal components, including phenazine-1-carboxylate (PCA), hydrogen cyanide (HCN), and siderophores [pyoverdine (Pvd) and histicorrugatin (Hcs)], as well as the dynamic adaptive changes in the metabolic pathways of P13 related to these active ingredients. During the logarithmic growth stage, T1-exposed P13 strategically upregulated PCA and HCN biosynthesis, along with transient inhibition of the tricarboxylic acid (TCA) cycle. However, with growth stabilization, upregulation of PCA and HCN synthesis ceased, whereas the TCA cycle was enhanced, increasing siderophores secretion (Pvd and Hcs), suggesting that this mechanism might have caused continuous inhibition of T1. These findings improved our comprehension of the biocontrol mechanisms of P13 and provided the foundation for potential application of Pseudomonas strains in the biocontrol of phytopathogenic F. graminearum. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Photooxidation triggered ultralong afterglow in carbon nanodots
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Guang-Song Zheng, Cheng-Long Shen, Chun-Yao Niu, Qing Lou, Tian-Ci Jiang, Peng-Fei Li, Xiao-Jing Shi, Run-Wei Song, Yuan Deng, Chao-Fan Lv, Kai-Kai Liu, Jin-Hao Zang, Zhe Cheng, Lin Dong, and Chong-Xin Shan
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Science - Abstract
Abstract It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection.
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- 2024
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20. Silicon Vacancies Diamond/Silk/PVA Hierarchical Physical Unclonable Functions for Multi‐Level Encryption
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Fuhang Jiao, Chaonan Lin, Lin Dong, Xin Mao, Yi Wu, Fuying Dong, Zhenfeng Zhang, Junlu Sun, Shunfang Li, Xun Yang, Kaikai Liu, Lijun Wang, and Chong‐Xin Shan
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anticounterfeit ,diamond ,phase separation ,physical unclonable function ,silicon vacancy ,Science - Abstract
Abstract Physical unclonable functions (PUFs) have emerged as a promising encryption technology, utilizing intrinsic physical identifiers that offer enhanced security and tamper resistance. Multi‐level PUFs boost system complexity, thereby improving system reliability and fault tolerance. However, crosstalk‐free multi‐level PUFs remain a persistent challenge. In this study, a hierarchical PUF system that harnesses the spontaneous phase separation of silk fibroin /PVA blend and the random distribution of silicon‐vacancy diamonds within the blend is presented. The thermodynamic instability of phase separation and inherent unpredictability of diamond dispersion gives rise to intricate random patterns at two distinct scales, enabling time‐efficient hierarchical authentication for cryptographic keys. These patterns are complementary yet independent, inherently resistant to replication and damage thus affording robust security and reliability to the proposed system. Furthermore, customized authentication algorithms are constructed: visual PUFs authentication utilizes neural network combined structural similarity index measure, while spectral PUFs authentication employs Hamming distance and cross‐correlation bit operation. This hierarchical PUF system attains a high recognition rate without interscale crosstalk. Additionally, the coding capacity is exponentially enhanced using M‐ary encoding to reinforce multi‐level encryption. Hierarchical PUFs hold significant potential for immediate application, offering unprecedented data protection and cryptographic key authentication capabilities.
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- 2024
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21. Differential Nitrous oxide emission and microbiota succession in constructed wetlands induced by nitrogen forms
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Jun-Feng Wang, Jia-Wei Huang, Ze-Xiang Cai, Qu-Sheng Li, Yun-Yun Sun, Huan-Zhan Zhou, Hui Zhu, Xin-Shan Song, and Hai-Ming Wu
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Constructed wetlands ,Nitrogen form ,COD/N ratio ,Nitrous oxide ,Metabolomics and metagenomics ,Environmental sciences ,GE1-350 - Abstract
Nitrous oxide (N2O) emission during the sewage treatment process is a serious environmental issue that requires attention. However, the N2O emission in constructed wetlands (CWs) as affected by different nitrogen forms in influents remain largely unknown. This study investigated the N2O emission profiles driven by microorganisms in CWs when exposed to two typical nitrogen sources (NH4+-N or NO3–-N) along with different carbon source supply (COD/N ratios: 3, 6, and 9). The results showed that CWs receiving NO3–-N caused a slight increase in total nitrogen removal (by up to 11.8 %). This increase was accomplished by an enrichment of key bacteria groups, including denitrifiers, dissimilatory nitrate reducers, and assimilatory nitrate reducers, which enhanced the stability of microbial interaction. Additionally, it led to a greater abundance of denitrification genes (e.g., nirK, norB, norC, and nosZ) as inferred from the database. Consequently, this led to a gradual increase in N2O emission from 66.51 to 486.77 ug-N/(m2·h) as the COD/N ratio increased in CWs. Conversely, in CWs receiving NH4+-N, an increasing influent COD/N ratio had a negative impact on nitrogen biotransformation. This resulted in fluctuating trend of N2O emissions, which decreased initially, followed by an increase at later stage (with values of 122.87, 44.00, and 148.59 ug-N/(m2·h)). Furthermore, NH4+-N in the aquatic improved the nitrogen uptake by plants and promoted the production of more root exudates. As a result, it adjusted the nitrogen-transforming function, ultimately reducing N2O emissions in CWs. This study highlights the divergence in microbiota succession and nitrogen transformation in CWs induced by nitrogen form and COD/N ratio, contributing to a better understanding of the microbial mechanisms of N2O emission in CWs with NH4+-N or NO3–-N at different COD/N ratios.
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- 2024
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22. Sialic Acids Blockade-Based Chemo-Immunotherapy Featuring Cancer Cell Chemosensitivity and Antitumor Immune Response Synergies.
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Zhang X, Li ZY, Xiao JH, Hao PF, Mo J, Zheng XJ, Geng YQ, and Ye XS
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Immune checkpoint blockade (ICB) has significantly improved the prognosis of patients with cancer, although the majority of such patients achieve low response rates; consequently, new therapeutic approaches are urgently needed. The upregulation of sialic acid-containing glycans is a common characteristic of cancer-related glycosylation, which drives disease progression and immune escape via numerous pathways. Herein, the development of self-assembled core-shell nanoscale coordination polymer nanoparticles loaded with a sialyltransferase inhibitor, referred to as NCP-STI which effectively stripped diverse sialoglycans from cancer cells, providing an antibody-independent pattern to disrupt the emerging Siglec-sialic acid glyco-immune checkpoint is reported. Furthermore, NCP-STI inhibits sialylation of the concentrated nucleoside transporter 1 (CNT1), promotes the intracellular accumulation of anticancer agent gemcitabine (Gem), and enhances Gem-induced immunogenic cell death (ICD). As a result, the combination of NCP-STI and Gem (NCP-STI/Gem) evokes a robust antitumor immune response and exhibits superior efficacy in restraining the growth of multiple murine tumors and pulmonary metastasis. Collectively, the findings demonstrate a novel form of small molecule-based chemo-immunotherapy approach which features sialic acids blockade that enables cooperative effects of cancer cell chemosensitivity and antitumor immune responses for cancer treatment., (© 2024 Wiley‐VCH GmbH.)
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- 2024
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23. Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China.
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Wang T, Li MY, Cai XS, Cheng QS, Li Z, Liu TT, Zhou LF, Wang HH, Feng GD, Marais BJ, and Zhao G
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Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China., Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared., Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death., Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Cai, Cheng, Li, Liu, Zhou, Wang, Feng, Marais and Zhao.)
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- 2024
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24. Decoherence-free-subspace-based deterministic conversions for entangled states with heralded robust-fidelity quantum gates.
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Du FF, Ren XM, Fan ZG, Li LH, Du XS, Ma M, Fan G, and Guo J
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The decoherence-free subspace (DFS) serves as a protective shield against certain types of environmental noise, allowing the system to remain coherent for extended periods of time. In this paper, we propose two protocols, i.e., one converts two-logic-qubit Knill-Laflamme-Milburn (KLM) state to two-logic-qubit Bell states, and the other converts three-logic-qubit KLM state to three-logic-qubit Greenberger-Horne-Zeilinger states, through cavity-assisted interaction in DFS. Especially, our innovative protocols achieve their objectives in a heralded way, thus enhancing experimental accessibility. Moreover, single photon detectors are incorporated into the setup, which can predict potential failures and ensure seamless interaction between the nitrogen-vacancy center and photons. Rigorous analyses and evaluations of two schemes demonstrate their abilities to achieve near-unit fidelities in principle and exceptional efficiencies. Further, our protocols offer progressive solutions to the challenges posed by decoherence, providing a pathway towards practical quantum technologies.
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- 2024
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25. Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy.
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Verma N, Renauer PA, Dong C, Xin S, Lin Q, Zhang F, Glazer PM, and Chen S
- Abstract
Radiotherapy (RT), is a fundamental treatment for malignant tumors and is used in over half of cancer patients. As radiation can promote anti-tumor immune effects, a promising therapeutic strategy is to combine radiation with immune checkpoint inhibitors (ICIs). However, the genetic determinants that impact therapeutic response in the context of combination therapy with radiation and ICI have not been systematically investigated. To unbiasedly identify the tumor intrinsic genetic factors governing such responses, we perform a set of genome-scale CRISPR screens in melanoma cells for cancer survival in response to low-dose genotoxic radiation treatment, in the context of CD8 T cell co-culture and with anti-PD1 checkpoint blockade antibody. Two actin capping proteins, Capza3 and Capg , emerge as top hits that upon inactivation promote the survival of melanoma cells in such settings. Capza3 and Capg knockouts (KOs) in mouse and human cancer cells display persistent DNA damage due to impaired homology directed repair (HDR); along with increased radiation, chemotherapy, and DNA repair inhibitor sensitivity. However, when cancer cells with these genes inactivated were exposed to sublethal radiation, inactivation of such actin capping protein promotes activation of the STING pathway, induction of inhibitory CEACAM1 ligand expression and resistance to CD8 T cell killing. Patient cancer genomics analysis reveals an increased mutational burden in patients with inactivating mutations in CAPG and/or CAPZA3 , at levels comparable to other HDR associated genes. There is also a positive correlation between CAPG expression and activation of immune related pathways and CD8 T cell tumor infiltration. Our results unveil the critical roles of actin binding proteins for efficient HDR within cancer cells and demonstrate a previously unrecognized regulatory mechanism of therapeutic response to radiation and immunotherapy.
- Published
- 2024
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