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Dynamically controlling the post-translational modification of the ε-amino groups of lysine residues is critical for regulating many cellular events. Increasing studies have revealed that many important diseases, including cancer and neurological disorders, are associated with the malfunction of lysine deacylases and demethylases. Developing fluorescent probes that are capable of detecting lysine deacylase and demethylase activity is highly useful for interrogating their roles in epigenetic regulation and diseases. Due to the distinct substrate recognition of these epigenetic eraser enzymes, designing a universal strategy for detecting their activity poses substantial difficulty. Moreover, designing activity-based probes for differentiating their demethylation states is even more challenging and still remains largely unexplored. Herein, we report a universal strategy to construct probes that can detect the enzymatic activity of epigenetic "erasers" through NBD-based long-distance intramolecular reactions. The probes can be easily prepared by installing the O-NBD group at the C-terminal residue of specific peptide substrates by click chemistry. Based on this strategy, detecting the activity of lysine deacetylase, desuccinylase, or demethylase with superior sensitivity and selectivity has been successfully achieved through single-step probe development. Furthermore, the demethylase probe based on this strategy is capable of distinguishing different demethylation states by both absorption and fluorescence lifetime readout. We envision that these newly developed probes will provide powerful tools to facilitate drug discovery in epigenetics in the future.

Protein-templated biomineralization provides a robust strategy for the synthesis of protein–rare earth fluoride hybrid nanoflowers, which display high enzymatic stability and finely tunable luminescence.

The development of high-performance biocompatible batteries is pivotal in personalized health-care devices such as pacemakers and neuro-stimulators. We have for the first time developed a one-pot collagen-assisted biomineralization strategy to create hierarchical CuO nanostructures. Recombinant collagen has been demonstrated as an excellent biotemplate to delicately tune the morphologies of copper oxide mesocrystals. The initial formation of Cu(OH)2 nanoneedles gradually turned into leaf-like CuO nanostructures with branched edges and a compact middle during the biomineralization process. The as-prepared leaf-like CuO mesocrystals exhibited an attractive electrochemical performance, and may have great potential as a promising anode material for lithium-ion batteries. Notably, collagen also acts as an excellent functional agent to endow the CuO nanomaterials with high biocompatibility and bioactivity. The environmentally friendly method assisted by collagen provides novel opportunities for the construction of advanced CuO nanomaterials that have a well-controlled morphology, function and electrochemical performance, and which may have promising applications in implantable health-care electronics.

The ecological evolution and relevant factors in semi-arid and arid regions is a research focus on climate changes. One such region, the mountain-oasis-desert coupling system in Xinjiang, China, is...

The construction of potent peptide probes for selectively detecting denatured collagen is crucial for a variety of widespread diseases. However, all of the denatured collagen-targeting peptide probes found till date primarily utilized the repetitive (Gly-X-Y) n sequences with exclusively imino acids Pro and Hyp in the X and Y positions, which stabilized the triple helical conformation of the peptide probes, resulting in severe obstacles for their clinical applications. A novel series of peptide probes have been constructed by incorporating nonimino acids at the X position of the (GPO)3GXO(GPO)4 sequence, while the X-site residue is varied as Tyr, Phe, Asp, and Ala, respectively. Peptide probes FAM-GYO and FAM-GFO containing aromatic residues Tyr and Phe at the X position showed similarly high binding affinity and tissue-staining efficacy as the well-established peptide probe FAM-GPO, while peptide probes FAM-GDO and FAM-GAO with the corresponding charged residue Asp and the hydrophobic residue Ala indicated much weaker binding affinity and tissue-staining capability. Furthermore, FAM-GYO and FAM-GFO could specifically detect denatured collagen in different types of mouse connective tissues and efficiently stain various human pathological tissues. We have revealed for the first time that the incorporation of nonimino acids, particularly aromatic residues at the X and Y positions of the repetitive (Gly-X-Y) n sequences, may provide a convenient strategy to create novel robust collagen-targeting peptide probes, which have promising diagnostic applications in collagen-involved diseases.

Transcontinental exchange emerged and intensified in northern China since the late fifth millennium BP (Before present), especially in the arc, which was the core area of the eastern part of the trans-Eurasian exchange during the Late Neolithic and the Bronze Age. In the arc, the exchange profoundly affected the human subsistence strategy and human-environment relationship. Relative to the crop patterns and human diets during the Bronze Age in northern China, systematic investigations of zooarcheological data based on broad spatial and temporal framework to understand the influence of introduced livestock and indigenous livestock on human subsistence are lacking. To show the spatial-temporal variation in animal utilization patterns and its relation to prehistoric trans-Eurasian exchange, the zooarcheological data from 40 sites in northern China dated between 5000 and 2500 BP were analyzed. The strategy of animal utilization in northern China changed substantially from 5000 to 2500 BP, with notable spatial features in different chronological phases. From 5000 to 4300 BP, wild mammals and indigenous livestock (pig, dog) use dominated in the arc and the North China Plain (NCP). During 4300–3500 BP, the importance of introduced livestock (cattle, sheep/goat, horse) exceeded that of indigenous livestock in the arc, whereas indigenous livestock continued to dominate in the NCP. Indigenous livestock acted as the most important animal subsistence in northern China, although the exploitation of introduced livestock increased during 3500–2000 BP. These spatio-temporal differences in animal utilization appear to be closely associated with the prehistoric trans-Eurasian exchange, but were also affected by local environment, agriculture development, and climate change.

The development of robust collagen assays is crucial in the diagnosis and treatment of various pathological conditions. Peptide probes composed of the (Gly-Pro-Hyp)n sequences have received extensi...

Cancer treatment currently still faces crucial challenges in therapeutic effectiveness, precision, and complexity. Photodynamic therapy (PDT) as a non-invasive tactic has earned widespread popularity for its excellent therapeutic output, flexibility, and restrained toxicity. Nonetheless, drawbacks, including low efficiency, poor cancer specificity, and limited therapeutic depth, remain considerable during the cancer treatment. Although great effort has been made to improve the performance, the overall efficiency and biosafety are still ambiguous and unable to meet urgent clinical needs. Herein, this study integrates merits from previous PDT strategies and develops a cancer-targeting, activatable, biosafe photosensitizer. Owing to excellent self-assembly ability, this photosensitizer can be conveniently prepared as multifunctional nano-photosensitizers, namely MBNPs, and applied to in vivo cancer phototheranostics in "all-in-one" mode. This study successfully verifies the mechanism of MBNPs, then deploys them to cell-based and in vivo cancer PDT. Based on the unique cancer microenvironment, MBNPs achieve precise distribution, accumulation, and activation towards the tumor, releasing methylene blue as a potent photosensitizer for phototherapy. The PDT outcome demonstrates MBNPs' superior cancer specificity, remarkable PDT efficacy, and negligible toxicity. Meanwhile, in vivo NIR fluorescence and photoacoustic imaging have been utilized to guide the PDT treatment synergistically. Additionally, the biosafety of the MBNPs-based PDT treatment is ensured, thus providing potential for future clinical studies.

The study of human dietary structures is an effective means of elucidating the subsistence patterns of our prehistoric ancestors and can highlight the processes through which humans interacted with the environment. We conducted stable isotope and archeobotanical analyses of human, animal, and plant remains at the Jiangxifen site, dated to ~900–400 BC, to explore human paleodiets and determine the environmental adaptation strategies adopted by humans in the middle valley of the Jinshajiang River in Yunnan Province. Humans predominantly consumed C4 foods (e.g., millet) and C4 food-fed animal protein sources, with smaller contributions from C3 food plants (e.g., rice) and C3 food-fed animal protein sources. We argued that the local dry-hot environment was the reason for the accessibility of C4 plants in the studied area. A comparison of our results with previously published archeobotanical data and isotopic evidence from human bones in other Bronze Age sites in Yunnan Province revealed high spatial variability in diets of human and subsistence strategies during this period. These differences were caused by the highly varying living environment of each region, which was related to fragmentation resulting from the geomorphological features of Yunnan Province.

With the rise of deep learning in the field of compute vision, more and more researchers began to use CNNs for automatic recognition of micro-expressions, and achieved better performance than traditional methods. However, there is a overfitting problem with these methods. CNN focuses on local information and loses the global semantic information in the image. In this paper, we propose a novel micro-expression recognition method based on Apex frame and multi-head self-attention enhanced convolutional network. It consists of three parts: (1) The pre-processing part performs face detection, face alignment, cutting into uniform size and positioning Apex frames on micro-expressions; (2) Optical flow calculation of Apex frames, calculates TVL1 optical flow from Onset frames to Apex frames, and obtains horizontal and vertical optical flow component images; (3) A shallow network (AACNet) is designed to extract and classify the optical flow image components obtained in (2). The results has greatly improved over the benchmark method (LBP-TOP). The state-of-the-art results were achieved on the MEGC2019 database (UF1: 0.7572, UAR: 0.7564).

Stable isotopic analyses of the remains of plants that have been unearthed from archaeological sites are often featured as key indicators of crop cultivation and the living environment. However, systematic archaeobotanical studies have not been applied widely in Chinese historical sites, especially in those from the Tang dynasty. This paper aims to use carbon and nitrogen isotopic analyses to reveal the potential influence of water and fertilizer conditions on the size of millet chaffs that were excavated from the Chashancun cemetery. To achieve this, >3600 uncharred broomcorn and foxtail millet chaff remains were measured. Furthermore, 30 broomcorn millet samples and 30 foxtail millet samples were selected to analyze the carbon and nitrogen isotopes, respectively. The widths and thicknesses of the broomcorn millet chaffs ranged from 1.11 to 2.38 mm and from 0.95 to 2.24 mm, respectively, while those of the foxtail millet chaffs ranged from 0.95 to 1.94 mm and from 0.69 to 1.90 mm, respectively. The δ13C and δ15N values of the broomcorn millet chaffs ranged from −13.0‰ to −12.0‰ and from 15.7‰ to 17.8‰, respectively, while those of the foxtail millet chaffs ranged from −14.0‰ to −12.9‰ and from 15.7‰ to 18.8‰, respectively. The results show correlations between the millet chaff size and the carbon/nitrogen isotopic values, suggesting that water and fertilizer conditions might have significantly affected millet grain yield during the late seventh century in northwestern China.

Denatured collagen is a key biomarker for various critical diseases such as cancer. Peptide probes with the repetitive (Gly-Pro-Hyp)n sequences have recently been found to selectively target denatured collagen; however, thermal or UV pretreatment is required to drive the peptides into the monomer conformation, which poses a substantial challenge for clinical applications. We herein construct two peptide probes, FAM-GOO and FAM-GPP, consisting of the repetitive (Gly-Hyp-Hyp)8 and (Gly-Pro-Pro)8 sequences, respectively. The CD, fluorescence and colorimetric studies have consistently revealed that FAM-GOO showed strong capability of forming the triple helical structure, while FAM-GPP pronouncedly displayed the single stranded conformation at temperatures as low as 4 °C. The binding experiments have indicated that both peptide probes could recognize denatured collagen with high specificity, and FAM-GPP remarkably did not need the preheating treatment. The tissue staining results have shown that preheated FAM-GOO and unheated FAM-GPP could target denatured collagen in a wide variety of rat frozen and human FFPE tissue sections. Compared with antibodies specific for a certain type of collagen, both FAM-GOO and FAM-GPP act as broad-spectrum probes for the selective detection of denatured collagen of different types and from different species. Importantly, FAM-GPP possessed the unique capability of maintaining the monomer conformation by itself, thus avoiding the potential risks of the thermal or UV pretreatment. This novel peptide probe provides a handy and versatile biosensor for specifically targeting denatured collagen, which has attractive potential in the diagnosis and therapeutics of collagen-involved diseases.

Coastal harmful algal blooms (HABs) in China’s seas have attracted researchers’ attention for decades. Among the four seas of China, the HAB frequency is the highest in the East China Sea (ECS). The impact of climate change and anthropogenic dominant factors on HABs is not well quantified and the response of HABs to the changing climate is also not clear. Here, we compiled a time series of observation-based HAB events since the 1980s and performed a regional assessment to elucidate the dominant drivers of HAB events in the ECS. The results showed that the increase in the frequency of HAB events in the ECS between 2000 and 2003 was associated with increases in dissolved inorganic phosphorus and sea surface temperature anomalies as well as decreasing summer precipitation. The declining annual frequency in HAB events in the ECS after 2003 was associated with the two climatological factors, most notably, precipitation. Under the “business-as-usual” scenario, climate change will increase the annual HAB events in the ECS from the historical frequency (1985–2013) by more than five-fold by the end of 21st century. These findings demonstrated that management strategies based on reducing nutrient loading also need to consider the effects of climate change in the future.

Supplemental material, Table_S1_HOL-20-0032-Review for The impact of early trans-Eurasian exchange on animal utilization in northern China during 5000–2500 BP by Guanghui Dong, Linyao Du and Wenyu Wei in The Holocene

Controlled fabrication of CaCO3 nanoparticles with an exquisite polymorph and morphology has received intensive attention due to their broad industrial and biomedical applications. Herein we have created trypsin–CaCO3 hybrid nanoparticles with a well-controlled morphology and a crystal phase via a very mild biomineralization process. The incubation of a mixture of sodium carbonate and calcium chloride at room temperature using trypsin as the biotemplate leads to predominantly calcite mesocrystals with porous sphere-like nanostructures. The trypsin–CaCO3 hybrid nanospheres behave as superior nano-biocatalysts, which display high stability against thermal and chemical denaturation as well as excellent reusability. We have demonstrated that trypsin not only acts as a novel robust biotemplate to mediate the growth of CaCO3 crystals, but also enhances their biological properties as an excellent enzyme. This indicates that biomineralization may provide a facile and environmentally amiable approach to immobilize enzymes on calcium carbonate nanoparticles. Our studies could greatly enhance the understanding of the mechanism of the protein-mediated biomineralization of CaCO3, and extend the applications of CaCO3-based composite nanostructured biomaterials.

Surface ozone (O3) pollution events are becoming more frequent and have recently emerged as a severe air pollution problem in China. However, the spatial–temporal distribution of surface O3, as well as its primary synoptic and meteorological drivers, remains poorly understood. The purpose of this study was to identify the key synoptic and meteorological drivers of O3 pollution in different regions of China. To achieve this goal, this study established meteorology overlaps of regional O3 pollution events in space and time and applied a comprehensive statistical model selection method for optimal synoptic and meteorological models, based on a newly released O3 dataset for 2015–2018. It was observed that extreme regional O3 pollution events (duration >7 d) occurred more frequently and exhibited a high co-occurrence frequency (>50%) with air stagnation (AS). Moreover, the beginning and end of 69% of the regional O3 pollution events coincided with regional daily maximum temperature changes. The intensity of AS is the dominant driver of O3 pollution event intensity across most of the six selected megacity regions. Although other meteorological drivers, such as the intensity of hot days (HD) and meridional wind of 10 m were also important, their impacts varied according to the region. Overall, increase in extreme AS and HD led to the worsening of regional O3 pollution events. These findings imply that mitigating regional O3 pollution should consider changing synoptic and meteorological conditions.