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The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H2O2-treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury.

Small extracellular vesicles (sEVs) are a type of extracellular vesicle that carries many types of molecular information. The identification of sEVs is essential for the non-invasive detection and treatment of illnesses. Hence, there is a significant need for the development of simple, sensitive, and precise methods for sEV detection. Herein, a DNA tweezers-based assay utilizing a “turn-on” mechanism and proximity ligation was suggested for the efficient and rapid detection of sEVs through amplified fluorescence. The target facilitates the proximity combination of the C1 probe and C2 probe, resulting in the formation of a complete extended sequence. The elongated sequence can cyclically initiate the hairpin probe (HP), leading to the activation of DNA tweezers. An excellent linear correlation was achieved, with a limit of detection of 57 particles per μL. Furthermore, it has been effectively employed to analyze sEVs under intricate experimental conditions, demonstrating a promising and pragmatic prospect for future applications. Given that the identification of sEVs was successfully accomplished using a single-step method that exhibited exceptional sensitivity and strong resistance to interference, the proposed technique has the potential to provide a beneficial platform for accurate recognition of sEVs and early detection of diseases.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high vascularity and frequent metastasis. Tumor-associated abnormal vasculature was reported to accelerate TNBC metastasis. Scutellarin (SC) is a natural flavonoid with a cardiovascular protective function. In this study, SC reduced TNBC metastasis and alleviated tumor-associated vascular endothelial barrier injury in vivo. SC rescued the tumor necrosis factor-α (TNFα)-induced diminishment of endothelial junctional proteins and dysfunction of the endothelial barrier in vitro. SC reduced the increased transendothelial migration of TNBC cells through a monolayer composed of TNFα-stimulated human mammary microvascular endothelial cells (HMMECs) or human umbilical vein endothelial cells (HUVECs). TNFα induced the nuclear translocation of enhancer of zeste homolog-2 (EZH2), and its chemical inhibitor GSK126 blocked TNFα-induced endothelial barrier disruption and subsequent TNBC transendothelial migration. TNF receptor 2 (TNFR2) is the main receptor by which TNFα regulates endothelial barrier breakdown. Extracellular signal-regulated protein kinase (ERK)1/2 was found to be downstream of TNFα/TNFR2 and upstream of EZH2. Additionally, SC abrogated the TNFR2-ERK1/2-EZH2 signaling axis both in vivo and in vitro. Our results suggest that SC reduced TNBC metastasis by suppressing TNFα-initiated vascular endothelial barrier breakdown through rescuing the reduced expression of junctional proteins by regulating the TNFR2-ERK1/2-EZH2 signaling pathway.

Insects damaging and penetrating plastic packaged materials has been reported since the 1950s. Radical innovation breakthroughs of plastic biodegradation have been initiated since the discovery of biodegradation of plastics by Tenebrio molitorlarvae in 2015 followed by Galleria mellonellain 2017. Here we review updated studies on the insect-mediated biodegradation of plastics. Plastic biodegradation by insect larvae, mainly by some species of darkling beetles (Tenebrionidae) and pyralid moths (Pyralidae) is currently a highly active and potentially transformative area of research. Over the past eight years, publications have increased explosively, including discoveries of the ability of different insect species to biodegrade plastics, biodegradation performance, and the contribution of host and microbiomes, impacts of polymer types and their physic-chemical properties, and responsible enzymes secreted by the host and gut microbes. To date, almost all major plastics including polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PUR), and polystyrene (PS) can be biodegraded by T. molitorand ten other insect species representing the Tenebrionidae and Pyralidae families. The biodegradation processes are symbiotic reactions or performed by synergistic efforts of both host and gut-microbes to rapidly depolymerize and biodegrade plastics with hourly half-lives. The digestive ezymens and bioreagents screted by the insects play an essential role in plasatic biodegradation in certain species of Tenebrionidae and Pyralidae families. New research on the insect itself, gut microbiomes, transcriptomes, proteomes and metabolomes has evaluated the mechanisms of plastic biodegradation in insects. We conclude this review by discussing future research perspectives on insect-mediated biodegradation of plastics.

Our previous studies indicate that resistance induction using first-generation tyrosine kinase inhibitors (TKIs) in lung cancer is accompanied with p120-catenin (p120ctn) cytoplasmic translocation from the membrane. However, the molecular mechanism underlying p120ctn intracytoplasmic translocation has not yet been reported. We performed immunohistochemistry to detect the correlation of p120ctn distribution with protein tyrosine phosphatase non-receptor type 12 (PTP-PEST) and p120ctn Y335 phosphorylation levels in non–small cell lung cancer (NSCLC) patients. After resistance induction using first-generation TKIs in lung cancer cells, Western blotting and substrate trapping were used to assess PTP-PEST expression and its influence on p120ctn Y335 phosphorylation, as well as the role of p120ctn Y335 phosphorylation on the association of p120ctn with E-cadherin and p120ctn membrane/cytoplasm translocation. In 197 samples collected from NSCLC patients, cytoplasmic p120ctn and enhanced p120ctn Y335 phosphorylation were associated with decreased PTP-PEST. After resistance induction using gefitinib, decreased PTP-PEST expression was accompanied by enhanced phosphorylation of p120ctn Y335 and p120ctn translocated to the cytoplasm. In gefitinib-resistant cells, PTP-PEST overexpression restrained p120ctn Y335 phosphorylation and restored membrane p120ctn expression. PTP-PEST enhanced the interaction of p120ctn with E-cadherin and elevated p120ctn membrane expression. However, increased p120ctn-Y335F mutant had no effect on p120ctn interaction with E-cadherin and membrane/cytoplasm translocation compared with the control group. In conclusion, resistance to first-generation TKIs inhibited PTP-PEST expression, which promoted p120ctn-Y335 phosphorylation and reduced the interaction of p120ctn with E-cadherin, resulting in p120ctn cytoplasmic translocation.

As a new type of pollutants in the marine environment, microplastics have attracted increasing attention from scientific researchers and environmental protection workers in China and abroad. However, for the microplastic pollution in sea areas in China, there are a very limited number of studies on its current status and few reviews of research on the microplastics. This paper reviews the surveys and researches of microplastics in the Bohai Sea, the Yellow Sea, the East China Sea, the South China Sea, and main estuaries in China carried out in recent years and proposes an outlook for future work, aiming to provide research suggestions and solutions for ecological protection against microplastic pollution in sea areas in China. Previous studies have shown that microplastics are widely distributed in water bodies and sediments in sea areas and major estuaries in China. The Pearl River Estuary, in the South China Sea suffers the most serious microplastic pollution, followed by the Bohai Sea. In contrast, the microplastic pollution in the Yellow Sea and the East China Sea is comparatively slight. Microplastics in sea areas in China are mainly fibrous and are concentrated in offshore areas with developed industry and a dense population (especially around estuaries and bays). In addition, they are widely affected by human activities, such as shipping, aquaculture, industry, and sewage discharge. Here the authors suggest unifying measurement units and research methods and developing related standard systems to carry out researches related to microplastics. Furthermore, this paper also suggests further deepening researches on both the source-sink process of microplastics and nanoscale microplastics while enhancing the development and implementation of related policies, aiming to promote researches and control of microplastics in sea areas in China.

As a new type of pollutants in the marine environment, microplastics have attracted increasing attention from scientific researchers and environmental protection workers in China and abroad. However, for the microplastic pollution in sea areas in China, there are a very limited number of studies on its current status and few reviews of research on the microplastics. This paper reviews the surveys and researches of microplastics in the Bohai Sea, the Yellow Sea, the East China Sea, the South China Sea, and main estuaries in China carried out in recent years and proposes an outlook for future work, aiming to provide research suggestions and solutions for ecological protection against microplastic pollution in sea areas in China. Previous studies have shown that microplastics are widely distributed in water bodies and sediments in sea areas and major estuaries in China. The Pearl River Estuary, in the South China Sea suffers the most serious microplastic pollution, followed by the Bohai Sea. In contrast, the microplastic pollution in the Yellow Sea and the East China Sea is comparatively slight. Microplastics in sea areas in China are mainly fibrous and are concentrated in offshore areas with developed industry and a dense population (especially around estuaries and bays). In addition, they are widely affected by human activities, such as shipping, aquaculture, industry, and sewage discharge. Here the authors suggest unifying measurement units and research methods and developing related standard systems to carry out researches related to microplastics. Furthermore, this paper also suggests further deepening researches on both the source-sink process of microplastics and nanoscale microplastics while enhancing the development and implementation of related policies, aiming to promote researches and control of microplastics in sea areas in China.

The intersection of the Kyushu-Palau Ridge (KPR) and the Central Basin Rift (CBR) of the West Philippine Basin (WPB) is a relic of a trench-trench-rift (TTR) type triple-junction, which preserves some pivotal information on the cessation of the seafloor spreading of the WPB, the emplacement and disintegration of the proto-Izu-Bonin-Mariana (IBM) Arc, and the transition from initial rifting to steady-state spreading of the Parece Vela Basin (PVB). However, the structural characteristics of this triple-junction have not been thoroughly understood. In this paper, using the newly acquired multi-beam bathymetric, gravity, and magnetic data obtained by the Qingdao Institute of Marine Geology, China Geological Survey, the authors depict the topographic, gravity, and magnetic characteristics of the triple-junction and adjacent region. Calculations including the upward continuations and total horizontal derivatives of gravity anomaly are also performed to highlight the major structural features and discontinuities. Based on these works, the morphological and structural features and their formation mechanisms are analyzed. The results show that the last episode amagmatic extension along the CBR led to the formation of a deep rift valley, which extends eastward and incised the KPR. The morphological and structural fabrics of the KPR near and to the south of the triple-junction are consistent with those of the western PVB, manifesting as a series of NNE-SSW- and N-S-trending ridges and troughs, which were produced by the extensional faults associated with the initial rifting of the PVB. The superposition of the above two reasons induced the prominent discontinuity of the KPR in deep and shallow crustal structures between 15°N–15°30′N and 13°30′N–14°N. Combined with previous authors’ results, we propose that the stress produced by the early spreading of the PVB transmitted westward and promoted the final stage amagmatic extension of the CBR. The eastward propagation of the CBR destroyed the KPR, of which the magmatism had decayed or ceased at that time. The destruction mechanism of the KPR associated with the rifting of the PVB varies along strike the KPR. Adjacent to the triple-junction, the KPR was destroyed mainly due to the oblique intersection of the PVB rifting center. Whereas south of the triple-junction, the KPR was destroyed by the E-W-directional extensional faulting on its whole width.

The neonatal heart possesses the ability to proliferate and the capacity to regenerate after injury; however, the mechanisms underlying these processes are not fully understood. Melatonin has been shown to protect the heart against myocardial injury through mitigating oxidative stress, reducing apoptosis, inhibiting mitochondrial fission, etc. In this study, we investigated whether melatonin regulated cardiomyocyte proliferation and promoted cardiac repair in mice with myocardial infarction (MI), which was induced by ligation of the left anterior descending coronary artery. We showed that melatonin administration significantly improved the cardiac functions accompanied by markedly enhanced cardiomyocyte proliferation in MI mice. In neonatal mouse cardiomyocytes, treatment with melatonin (1 μM) greatly suppressed miR-143-3p levels. Silencing of miR-143-3p stimulated cardiomyocytes to re-enter the cell cycle. On the contrary, overexpression of miR-143-3p inhibited the mitosis of cardiomyocytes and abrogated cardiomyocyte mitosis induced by exposure to melatonin. Moreover, Yap and Ctnnd1 were identified as the target genes of miR-143-3p. In cardiomyocytes, inhibition of miR-143-3p increased the protein expression of Yap and Ctnnd1. Melatonin treatment also enhanced Yap and Ctnnd1 protein levels. Furthermore, Yap siRNA and Ctnnd1 siRNA attenuated melatonin-induced cell cycle re-entry of cardiomyocytes. We showed that the effect of melatonin on cardiomyocyte proliferation and cardiac regeneration was impeded by the melatonin receptor inhibitor luzindole. Silencing miR-143-3p abrogated the inhibition of luzindole on cardiomyocyte proliferation. In addition, both MT1 and MT2 siRNA could cancel the beneficial effects of melatonin on cardiomyocyte proliferation. Collectively, the results suggest that melatonin induces cardiomyocyte proliferation and heart regeneration after MI by regulating the miR-143-3p/Yap/Ctnnd1 signaling pathway, providing a new therapeutic strategy for cardiac regeneration.

Optoelectronic synapses integrating synaptic and optical-sensing functions exhibit large advantages in neuromorphic computing for visual information processing and complex learning, recognition, and memory in an energy-efficient way. However, electric stimulation is still essential for existing optoelectronic synapses to realize bidirectional weight-updating, restricting the processing speed, bandwidth, and integration density of the devices. Herein, a two-terminal optical synapse based on a wafer-scale pyrenyl graphdiyne/graphene/PbS quantum dot heterostructure is proposed that can emulate both the excitatory and inhibitory synaptic behaviors in an optical pathway. The simple device architecture and low-dimensional features of the heterostructure endow the optical synapse with robust flexibility for wearable electronics. This optical synapse features a linear and symmetric conductance-update trajectory with numerous conductance states and low noise, which facilitates the demonstration of accurate and effective pattern recognition with a strong fault-tolerant capability even at bending states. A series of logic functions and associative learning capabilities have been demonstrated by the optical synapses in optical pathways, significantly enhancing the information processing capability for neuromorphic computing. Moreover, an integrated visible information sensing memory processing system based on the optical synapse array is constructed to perform real-time detection, in situimage memorization, and distinction tasks. This work is an important step toward the development of optogenetics-inspired neuromorphic computing and adaptive parallel processing networks for wearable electronics.

Long-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) patients remains poor because of tumor recurrence. To improve the prognosis of HCC patients after LT, we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center.

Graphdiyne is a new two-dimensional carbon allotrope with many attractive properties and has been widely used in various applications. However, the synthesis of large-area, high-quality, and ultrathin (especially monolayer) graphdiyne and its analogues remains a challenge, hindering its application in optoelectronic devices. Here, a wafer-scale monolayer pyrenyl graphdiyne (Pyr-GDY) film is obtained on hexagonal boron nitride (hBN) via a van der Waals epitaxial strategy, and top-floating-gated multibit nonvolatile optoelectronic memory based on Pyr-GDY/hBN/graphene is constructed, using Pyr-GDY as a photoresponsive top-floating gate. Benefiting from the excellent charge trapping capability and strong absorption of the graphdiyne film, as well as the top-floating-gated structure and the ultrathin hBN film used in the device, the optoelectronic memory exhibits high storage performance and robust reliability. A huge difference in the current between the programmed and erased states (>26 μA μm–1at Vds= 0.1 V) and a prolonged retention time (>105s) enable the device to achieve multibit storage, for which eight and nine distinct storage levels (3-bit) are obtained by applying periodic gate voltages and optical pulses in the programming and erasing processes, respectively. This work provides an important step toward realizing versatile graphdiyne-based optoelectronic devices in the future.

•In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different.•In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day.•In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group.

With the continuous development of the oblique photography technique, it has been used more and more widely in the field of geological disasters. It can quickly obtain the three-dimensional (3D) real scene model of dangerous mountainous areas under the premise of ensuring the safety of personnel while restoring the real geographic information as much as possible. However, geological disaster areas are often accompanied by many adverse factors such as cliffs and dense vegetation. Based on this, the paper introduced the flight line design of oblique photogrammetry, analyzed the multi-platform data fusion processing, studied the multi-period data dynamic evaluation technology and proposed the application methods of data acquisition, early warning, disaster assessment and decision management suitable for geological disaster identification through the analysis of actual cases, which will help geologists to plan and control geological work more scientifically and rationally, improve work efficiency and reduce the potential personnel safety hazards in the process of geological survey, to offer technical support to the application of oblique photogrammetry in geological disaster identification and decision making and provide the scientific basis for personal and property safety protection and later-stage geological disaster management in disaster areas.

The sedimentary environment and ecological system in the South Yellow Sea (SYS) changed dramatically due to sea level change caused by glacial-interglacial cycles. The authors report the use of marine biomarkers (brassicasterol, dinosterol and C37alkenones) and terrigenous biomarkers (C28+C30+C32n-alkanols) in core DLC70-3 from the SYS to reconstruct the variation in the phytoplankton productivity and community structure and possible mechanisms during the middle Pleistocene. The results show that the primary productivity and that of single algae presented a consistent trend for the whole core during the middle Pleistocene, which was high during interglacial periods and low during glacial periods, with the highest being in marine isotope stage (MIS) 5–9 and MIS 19–21. The main reason is that the Yellow Sea Warm Current (YSWC) carried much of high temperature, high salinity water into the SYS, causing upwelling and vertical mixing and stirring, which increased the nutrient supply in the photosynthetic layer. The phytoplankton community structure mainly showed an increase in the relative content of haptophytes in MIS 5–9 and MIS 19–21, while the relative content of diatoms and dinoflagellates decreased; there was no evidence for a haptophyte content in other stages. The results reveal a shift from a coccolitho-phorid-dominated community during MIS 5 –9 and MIS 19 –21 to a diatom-dominated community during the other stages, mainly as a result of surface salinity variation, attributed to the invasion of the YSWC during high sea level periods.

A comparative comparative study on the detrital mineral composition of stream sediments of the Yangtze River (Changjiang) and Yellow River (Huanghe) shows that, light minerals of the Yangtze River basin were mainly quartz, feldspar, and detritus, the compositional characteristics of light minerals differed among tributaries, the main stream had a generally higher maturity index than tributaries; heavy mineral content tended to decrease progressively from the upper stream to lower stream of the Yangtze River, the primary assemblage was magnetite-hornblende-augite-garnet-epidote, and diagnostic minerals of different river basins were capable of indicating the nature and distribution of the source rock. Detrital mineral assemblages in sediments of tributaries and the main stream of the Yellow River were basically similar, Primary heavy mineral assemblage was opaque mineral-garnet-epidote-carbonate mineral and alteration mineral. Variations in the contents of garnet, opaque mineral, and hornblende mainly reflected the degree of sedimentary differentiation in suspended sediment and the hydrodynamic intensity of a drainage system. The heavy mineral differentiation index Frevealed sedimentary differentiation of diagnostic detrital mineral composition due to changes in regional hydrodynamic intensity and can serve as an indicator for studying the dynamic sedimentary environment of a single-provenance river and the degree of sedimentary differentiation of its detrital minerals. Changes in detrital mineral content of the Yellow River was not completely controlled by provenance but reflected gravity sorting of the detrital mineral due to variations in the ephemeral river hydrodynamic intensity and sedimentary environment, however the index changing of Yangtze River were mainly influenced by the complex sediment sources. Therefore caution must be exercised in using the detrital mineral composition of marginal sea to determine the contribution of the Yangtze River and Yellow River.

The Ningshao Plain experienced sea-level fluctuation and climate change in the Holocene and gave birth to a Neolithic Civilization, the Hemudu Culture (about 5000 BC). Using XRD method, this paper studied the clay mineralogy of sediments in core HMD-1301 from Hemudu Site area in Ningshao Plain. Results show that the clay mineral assemblages in all samples are quite consistent. They are dominated by illite (about 57%) and smectite (about 26%), and a small amount of kaolinite (about 6%) and chlorite (about 9%). In addition, illite, chlorite, and kaolinite are originated mainly from eolian loesses. Smectite is resulted mainly from chemical weathering of local volcanic rocks outcropped. Illite crystallinity indicates the climatic characteristics of the source region, and illite chemistry index reflects the climate nature of the sedimentary area. It is our understanding that water medium properties in a sedimentary environment affect clay mineral assemblage and the distribution, based on which were cognized the Holocene transgression-regression events in the Hemudu Site area. These mineral indices are well comparable with geochemical indicators in identifying the transgression-regression events. We believe that these events affected the ancient civilization of the ancient residential communities at the time.

Magnetic greigite may be a valuable indicator for methane emissions in the geological past, if its formation pathway and diagenetic environment can be unambiguously defined. Here, we investigate sulfur isotopic compositions of iron sulfides and ferrous iron concentrations of thick greigite‐bearing sediments (TGBSs) in the South Yellow Sea, a shallow marginal sea with strong methane emissions. For the first time, isotopically heavy iron sulfides (up to 28.7‰ in δ34S and 0.19‰ in Δ33S) and enrichments of ferrous iron in the TGBSs are observed. We interpret the data as indicating synchronic occurrences of anaerobic oxidation of methane coupled to sulfate and iron reductions, which occur in coastal methanic zones with limited sulfate availability and therefore probably imply leakages of methane. Consequently, we suggest that greigite is a promising geological indicator for tracing methane liberated from coastal sediments, accounting for ∼60% of the currently rising global marine methane budget. Greigite (Fe3S4) is an easily detected ferromagnetic mineral and extensively observed in shallow coastal sediments, where strong methane emissions to the atmosphere prevail. It probably forms in a relatively sulfur‐poor environment associated with the consumption of methane by sulfate reduction. Here, we found a unique sulfur isotope fingerprinting in iron sulfides and enrichment of ferrous iron in these greigite‐bearing sediments, likely defining a methanic condition associated with potential coastal methane leakages. Our study highlights the intrinsic linkage between methane and greigite formation, supports that greigite may be a potential indicator for quantifying the global natural methane budget, and therefore has paleoenvironmental implications for geological global warming events. Isotopically heavy sulfides (both δ34S and Δ33S) and enrichment of ferrous iron are synchronically observed in greigite‐bearing sedimentsPyrite with elevated Δ33S in thick greigite‐bearing sediments likely formed under a methanic conditionGreigite is a potentially useful tracer for methane leakages from coastal sediments Isotopically heavy sulfides (both δ34S and Δ33S) and enrichment of ferrous iron are synchronically observed in greigite‐bearing sediments Pyrite with elevated Δ33S in thick greigite‐bearing sediments likely formed under a methanic condition Greigite is a potentially useful tracer for methane leakages from coastal sediments