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Methylation of histone H3 lysine-79 (H3K79) is an epigenetic mark for gene regulation in development, cellular differentiation, and disease progression. However, how this histone mark is translated into downstream effects remains poorly understood owing to a lack of knowledge about its readers. We developed a nucleosome-based photoaffinity probe to capture proteins that recognize H3K79 dimethylation (H3K79me2) in a nucleosomal context. In combination with a quantitative proteomics approach, this probe identified menin as a H3K79me2 reader. A cryo-electron microscopy structure of menin bound to an H3K79me2 nucleosome revealed that menin engages with the nucleosome using its fingers and palm domains and recognizes the methylation mark through a p-cation interaction. In cells, menin is selectively associated with H3K79me2 on chromatin, particularly in gene bodies. © 2023 American Association for the Advancement of Science. All rights reserved.

Honghao Yu,* Yiping Wu,* Boyu Zhang, Mingchen Xiong, Yi Yi, Qi Zhang, Min Wu Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi Zhang; Min Wu, Tel +86 15951072198 ; +86 13554254796, Email zhangqi06172@163.com; wumin@hust.edu.cnBackground: Skin wound is a widespread health problem and brings extraordinary burdens to patients. Exosomes derived from adipose-derived stem cells (ADSC-Exos) are considered promising strategies for repairing skin wounds. E2F1 is a member of the E2F family of transcription factors involved in cell growth and apoptosis. E2F1 deficiency in mice enhances wound healing by improving collagen deposition and angiogenesis. Additionally, E2F1 can regulate the transcription and paracrine activity of multiple miRNAs, which will inevitably reshape the paracrine expression profile of ADSC-Exos. This study aimed to investigate the impact of transcription factor E2F1 deficiency on the functions of ADSC-Exos in promoting wound healing.Methods: First, we obtained ADSCs from subcutaneous adipose tissues of WT and E2F1–/– C57BL/6 mice and separated their exosomes, denoted as ADSCWT-Exos and ADSCE2F1-/--Exos. The wound healing effects of ADSCWT-Exos and ADSCE2F1-/--Exos in full-thickness skin wound models were investigated by wound images, H&E staining, and immunohistochemical staining. For the in vitro study, the abilities of ADSCWT-Exos and ADSCE2F1-/--Exos to promote cell activities, collagen formation, and angiogenesis were evaluated. The potential mechanism by which ADSCE2F1-/--Exos promote wound healing was determined by miRNA sequencing, ChIP‒qPCR, and dual-luciferase assays.Results: ADSCE2F1-/--Exos accelerated wound healing by promoting collagen formation and angiogenesis. As a result, compared with the lower wound healing rate of 3

Xiaoxue Liang,1,* Ping Chen,2,* Baoguo Deng,2,* Feng-Hui Sun,1,* Yongqiang Yang,3– 5 Yanxian Yang,3,4 Ruowen He,3,4 Mingyang Qin,2 Yiping Wu,3,4 Fan Yang,2 Guo-Bao Tian,3,4 Min Dai1 1School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan Province, People’s Republic of China; 2School of Basic Medical Science, Xinxiang Medical University, Xinxiang, Henan Province, People’s Republic of China; 3Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong Province, People’s Republic of China; 5School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Dai, School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 28-62739128, Email daimin1015@163.comPurpose: To compare antimicrobial resistance, virulence, clinical characteristics, and risk factors between carbapenem-resistant K. pneumoniae (CRKP) and carbapenem-susceptible K. pneumoniae (CSKP) isolates from patients with bloodstream infections (BSIs) in China.Patients and Methods: The clinical data of 103 patients with K. pneumoniae BSI from 10 hospitals were retrospectively analyzed. The minimum inhibitory concentrations of 15 antibiotics against the bacteria were determined. A Galleria mellonella infection model was used to evaluate virulence of the isolates. Kaplan–Meier curves were calculated to evaluate the 28-day and in-hospital survival rates of the isolates. The risk factors for CRKP and CSKP infection and respective mortality rate were evaluated by univariate analysis, and independent risk factors were evaluated using the multivariate logistic regression m

Minmin Lin,1,* Yongqiang Yang,2– 4,* Yanxian Yang,2,3,* Guanping Chen,5 Ruowen He,2,3 Yiping Wu,2,3 Lan-Lan Zhong,2,3 Mohamed Abd El-Gawad El-Sayed Ahmed,2,3,6 Siyuan Feng,2,3 Cong Shen,2,3 Xin Wen,2,3 Jin Huang,1 Hongyu Li,7 Xiaobin Zheng,1 Guo-Bao Tian2,3 1Department of Respiratory Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, People’s Republic of China; 2Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, People’s Republic of China; 3Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, People’s Republic of China; 4School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510006, People’s Republic of China; 5Sun Yat-sen University School of Medicine, Guangzhou 510006, People’s Republic of China; 6Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST), Cairo, 6th of October City, Egypt; 7Department of Laboratory, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Bao Tian; Xiaobin Zheng Email tiangb@mail.sysu.edu.cn; zhxbin@mail.sysu.edu.cnBackground: Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae are potentially life-threatening related to poorer outcomes. Colistin is considered one of the last-resort treatments against human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Therefore, emergence of strains from the blood that co-harboring mcr and carbapenem resistance genes were considered as a serious problem.Purpose: In this study, two mcr-9-harboring MDR Enterobacter cloacae isolates BSI034 and BSI072 recovered from BSI patients were identified, one of which co-harbored mc

Despite the widely recognized importance of aquatic processes for bridging gaps in the global carbon cycle, there is still a lack of understanding of the role of riverbed processes for carbon flows and stocks in aquatic environments. Here, we added a sediment diagenesis and sediment carbon (C) resuspension module into the SWAT-C model and tested it for simulating both particulate organic C (POC) and dissolved organic C (DOC) fluxes using 4 years of monthly observations (2014–2017) in the Tuckahoe watershed (TW) in the U.S. Mid-Atlantic region. Sensitivity analyses show that parameters that regulate POC deposition in river networks are more sensitive than those that determine C resuspension from sediments. Further analyses indicate that allochthonous contributions to POC and DOC are about 36.6 and 46 kgC ha−1 year−1, respectively, while autochthonous contributions are less than 0.72 kgC ha−1 year−1 for both POC and DOC (less than 2% of allochthonous sources). The net deposition of POC on the riverbed (i.e., 11.4 kgC ha−1 year−1) retained ca. 31% of terrestrial inputs of POC. In addition, average annual buried C was 0.34 kgC ha−1 year−1, accounting for only 1% of terrestrial POC inputs or 3% of net POC deposition. The results indicate that about 79% of deposited organic C was converted to inorganic C (CH4 and CO2) in the sediment and eventually released into the overlying water column. This study serves as an exploratory study on estimation of C fluxes from terrestrial to aquatic environments at the watershed scale. We demonstrated capabilities of the SWAT-C model to simulate C cycling from uplands to riverine ecosystems and estimated C sinks and sources in aquatic environments. Overall, the results highlight the importance of including carbon cycle dynamics within the riverbed in order to accurately estimate aquatic carbon fluxes and stocks. The new capabilities of SWAT-C are expected to serve as a useful tool to account for those processes in watershed C balance ass

Taking advantage of decentralization reform that enlarges the authority of county government in China, we construct a quasi-experiment. Using a large sample of Chinese firms, we show that after the implementation of decentralization reform, firms located in decentralized counties experienced a significant increase in investment expenditure compared with other firms. We also find that after the decentralization reform, state owned enterprises (SOEs) experienced greater increase in investment expenditure on average compared with non-SOEs, and that, within non-SOEs, collective firms have an even larger increase in investments, followed by foreign firms and private firms. Further analysis shows that the influence of decentralization reform was more significant in more developed markets, and that the increased investment was associated with improved productivity, which was more pronounced in SOEs. These results are robust to an alternative sample and endogeneity issues. Overall, these findings support the view that decentralization reform improves government efficiency and creates positive externalities, thereby encouraging firms to invest.

The large deposit, in Xinjiang, is hosted in carbonaceous turbidite and is similar to the Mulongtau gold deposit in Uzbekistan. It is controlled by a series of shear zones with early ductile and later brittle characteristics. The ore-forming fluid was complex, with Au, Sb and Ag contents more than 12 times higher than those of early quartz-carbonate veins. The Pb and C isotope ratios of the ore indicate that it is of deep crustal origin. The ore-forming waters were probably mixtures of water from depth and meteoric water. It is thought that a deep magmatic chamber could have existed in the area, with metallogeny related to the motion of the heat source and the ore-forming fluid characterised by the mixture between deep and shallow crustal material., The large deposit, in Xinjiang, is hosted in carbonaceous turbidite and is similar to the Mulongtau gold deposit in Uzbekistan. It is controlled by a series of shear zones with early ductile and later brittle characteristics. The ore-forming fluid was complex, with Au, Sb and Ag contents more than 12 times higher than those of early quartz-carbonate veins. The Pb and C isotope ratios of the ore indicate that it is of deep crustal origin. The ore-forming waters were probably mixtures of water from depth and meteoric water. It is thought that a deep magmatic chamber could have existed in the area, with metallogeny related to the motion of the heat source and the ore-forming fluid characterised by the mixture between deep and shallow crustal material.

The properties of aggregates used in asphalt concretes are very important to the performance of the pavements in which the asphalt concretes are used. Often pavement distress, such as stripping and rutting, can be traced directly to the aggregates used. Clearly, proper aggregate selection is necessary for attaining desired performance. Numerous tests have been developed to empirically characterize aggregate without, necessarily, a strong relationship with the performance of the final products incorporating these aggregates. This seems to be particularly true for aggregate "toughness and abrasion resistance" and "durability and soundness". The purpose of this research was to identify and evaluate toughness/abrasion resistance and durability/soundness tests for characterizing aggregate used in asphalt concrete and to determine those test methods that best correlate with field performance. Based on a review of literature and specifications, laboratory tests for characterizing aggregate toughness/abrasion resistance and durability/soundness were selected. Sixteen aggregate sources with poor to good performance histories were identified for evaluation with the selected suite of tests. Performance histories of pavements containing these aggregates in asphalt concrete layers were established through personal contacts with state transportation agencies and performance evaluation questionnaires. Aggregate properties from laboratory tests were correlated with field performance. The Micro-Deval and magnesium sulfate soundness tests provide the best correlations with field performance of asphalt concrete, and are recommended for characterizing aggregate toughness/abrasion resistance and durability/soundness. Tables, figures, references. 26p.