Gliomas are the most common and recalcitrant intracranial tumors, approximately a quarter of which are classified as lower-grade gliomas (WHO II–III). Although the prognosis of lower-grade gliomas ...(LGGs) is significantly better than that of higher-grade gliomas, as a highly heterogeneous tumor type, the prognosis of LGGs varies greatly based on the molecular diagnosis. IDH wild-type used to be regarded as a dismal prognostic biomarker in LGGs; however, several studies revealed that IDH wild-type LGGs might not always be equivalent to glioblastoma (WHO IV). Hence, we hypothesize that underlying biological events in LGGs can result in different prognosis. In our study, transcriptome profiling was performed in 24 samples of LGG, and the results showed that the expression of phospholipase Cγ1 (PLCG1) was significantly correlated with IDH1/2 status and patients' clinical outcome. Furthermore, the cancer genome atlas (TCGA) and the Chinese glioma genome atlas (CGGA) databases verified that elevated PLCG1 expression was associated with tumor progression and poor survival in LGG patients. Moreover, PLCG1-targeted siRNA dramatically affected the growth, migration and invasiveness of IDH wild-type LGG cell lines. In in vitro and in vivo experiments, the PLC-targeted drug significantly suppressed the tumor growth of IDH wild-type LGG cell lines in vitro and tumors in mouse models. Taken together, our results demonstrated that higher PLCG1 expression was associated with tumor growth and worse prognosis in IDH wild-type LGGs and PLCG1 could serve as a potential therapeutic target for IDH wild-type LGG patients.
The mRNA expression levels of phospholipase Cγ1 (PLCG1) are much higher in IDH wild-type (IDHwt) lower-grade gliomas (LGGs) than in that of IDH mutant (IDHmut) LGGs. Higher PLCG1expression in IDHwt LGGs indicates poor clinical outcome. PLCG1 amplification may act as the key mechanism of PLCG1 upregulation. Depletion of PLCG1 expression can inhibits proliferation and invasion of IDHwt LGG cell lines in vitro and in vivo. The PLC inhibitor U73122 may therefore be a potential therapeutical agent for IDHwt LGGs.
Angiogenesis is a necessary process for solid tumor growth. Cellular markers for endothelial cell proliferation are potential targets for identifying the vasculature of tumors in homeostasis. Here we ...customize the behaviors of engineered cells to recognize Apj, a surface marker of the neovascular endothelium, using synthetic Notch (synNotch) receptors. We designed apelin-based synNotch receptors (AsNRs) that can specifically interact with Apj and then stimulate synNotch pathways. Cells engineered with AsNRs have the ability to sense the proliferation of endothelial cells (ECs). Designed for different synNotch pathways, engineered cells express different proteins to respond to angiogenic signals; therefore, angiogenesis can be detected by cells engineered with AsNRs. Furthermore, T cells customized with AsNRs can sense the proliferation of vascular endothelial cells. As solid tumors generally require vascular support, AsNRs are potential tools for the detection and therapy of a variety of solid tumors in adults.
Quantitative identification of long-term changes in the abundance of Japanese anchovy (
Engraulis japonicus
) in the Yellow Sea is particularly important for understanding evolutionary processes of ...the Yellow Sea ecosystem. Unfortunately, the driving mechanisms of climate variability on the anchovy are still unclear due to the lack of long-term observational data. In this study, we used the fish scale deposition rate in the central Yellow Sea to reconstruct the time series of the anchovy stock over the past 400 a. On this basis, we further explored the impacts of the Pacific Decadal Oscillation (PDO) on the anchovy. Our results show that the anchovy stock is positively correlated with the PDO on a decadal time scale. In addition, anchovy abundance was relatively high during 1620–1860 AD (the Little Ice Age, LIA), though in a state of constant fluctuation; anchovy abundance maintained at a relatively low level after ∼1860 AD. In particular, followed by overfishing since the 1980s, the anchovy stock has declined sharply. Based on these findings, we infer that fluctuations of the anchovy stock may be regulated by basin-scale “atmosphere-ocean” interactions. Nevertheless, the role of overfishing should not be ignored.
Surgery plays a critical role in the treatment of malignant glioma. However, due to the infiltrative growth and brain shift, it is difficult for neurosurgeons to distinguish malignant glioma margins ...with the naked eye and with preoperative examinations. Therefore, several technologies were developed to determine precise tumor margins intraoperatively. Here, we introduced four intraoperative technologies to delineate malignant glioma margin, namely, magnetic resonance imaging, fluorescence-guided surgery, Raman histology, and mass spectrometry. By tracing their detecting principles and developments, we reviewed their advantages and disadvantages respectively and imagined future trends.
The morphology and surroundings of cells have been routinely used by pathologists to diagnose the pathological subtypes of gliomas and to assess the malignancy of tumors. Thanks to the advent and ...development of digital pathology technology, it is possible to automatically analyze whole slides of tissue and focus on the nucleus in order to derive a quantitative assessment that can be used for grading, classification, and diagnosis. During the process of computer-assisted diagnosis, the accurate location and segmentation of nuclei from hematoxylin and eosin (H&E)-stained histopathological images is an important step. In this paper, we proposed a U-Net-based multi-task learning network in which the boundary and region information is utilized to improve the segmentation accuracy of glioma nuclei, especially overlapping ones. To refine the segmentation, a classification model is used to predict the boundary, a regression model is used to predict the distance map, and the final segmentation is obtained by using the fusion layers. The proposed approach was compared with other specially designed boundary-aware methods by using a pathological section dataset that consists of 320 glioma cases from the Huashan Hospital at Fudan University. Both the pixel-level and object-level evaluations showed that the structural modification is effective in segmentation with an F1-score of 0.82, a Hausdorff distance (HD) of 3.95, and an aggregated Jaccard index (AJI) of 0.66 (+0.46%, -3.75%, and +4.09% compared with the unimproved methods, respectively). In addition, comparative experiments on multi-organ nuclei segmentation (MoNuSeg) open dataset proved the advanced nature of the proposed method in the field of nuclei segmentation, especially separating touching objects. The proposed method obtains an AJI of 0.59 and an F1-score of 0.79.
This article explores the impact mechanism of different types of environmental regulations on corporate green technology innovation (GTI). The research focuses on analyzing three types of ...environmental regulations: command based environmental regulation (ER1), market-oriented environmental regulation (ER2), and voluntary environmental regulation (ER3), and how they affect corporate GTI. This study selected enterprise GTI as the dependent variable and measured it by the number of applications for green invention patents and green utility model patents. The independent variables are the three types of environmental regulations mentioned above. According to data from Chinese A-share listed companies. Using benchmark regression models to analyze the impact of different environmental regulations on GTI, and constructing a moderating effect model to study the role of corporate R&D investment and government support in the process of environmental regulations affecting GTI. The results indicate that (1) ER1, ER2, and ER3 can all promote enterprise GTI, and the three environmental regulatory methods have a better synergistic effect. (2) R&D investment has a positive correlation with the relationship between ER2 and GTI, and a negative correlation with ER 3 and ER 1. (3) There are differences in the GTI performance of enterprises in different regions, ownership nature, factor density, and industry types under the influence of environmental regulations. (4) The impact of environmental regulatory policies on corporate GTI is mainly short-term. This study provides a new perspective on how environmental regulations affect corporate GTI, especially in the context of developing countries like China. The research findings emphasize the role of different types of environmental regulations in incentivizing corporate GTI, while also pointing out factors that governments need to consider when formulating environmental policies, such as regional differences and corporate characteristics, which are of great significance for promoting green development of enterprises and achieving broader sustainable development goals.
With rapid economic expansion, China is faced with environmental challenges like air pollution and greenhouse gas emissions. Shifting from conventional fossil fuels to renewable energy (REN) sources ...is critical to facilitate sustainable development in China. Compared to coal and oil, REN such as solar and wind energy emit less carbon emissions. Fostering innovation of REN technologies is thus essential for China's green transition. This study aims to analyze the impact of REN technology innovation on China's economic growth using panel data models. The results demonstrate that advancing REN technologies significantly promotes GDP increase in China. Targeted policy incentives must be implemented to accelerate REN technology progression and adoption across the country. Transitioning towards REN systems will be instrumental for China to achieve environmental sustainability while maintaining economic growth.
China has dominated global aquaculture production for more than two decades. Aquaculture production in China increased from 24.6 million metric tons (mmt) in 2000 to 47.5 mmt in 2014, an increment of ...93.1%. Along with the fast‐growing aquaculture industry, aquafeed production in China increased from 5.1 mmt in 2000 to 19.0 mmt in 2014, an increment of 272.5%. However, despite the rapid increase in aquafeed production, the fishmeal usage in aquafeeds in China has remained stable over the years. Fishmeal imports into China remained relatively steady at 1.0–1.5 mmt per annum from 2000 to 2014. An often unacknowledged fact is that China contributes more than 60% to the world aquaculture production at a cost of only 25–30% of the world fishmeal output. This review attempts to explain why the fishmeal usage has not increased proportionately with the increasing aquafeed production in China from several angles: (i) the current status of fishmeal usage in Chinese aquaculture; (ii) the relationship between the decreasing dietary inclusions of fishmeal and improved feed techniques, especially the use of alternative protein sources for fishmeal; (iii) the dominance of Chinese aquaculture by low trophic level species of plants, filter feeders, herbivores and omnivores and consequent low demands for fishmeal; and (iv) the increasing price of fishmeal and the management of exploitation of wild fisheries in the main fishmeal exporting countries to China. The trends and prospects of fishmeal usage in the future in Chinese aquaculture and the associated consequences are also addressed. Like other countries, China is now actively developing both resource conservation‐based capture fisheries and environment‐friendly freshwater and marine aquaculture systems. Aquaculture will be the main source of aquatic food in the future and will also indirectly contribute to save the world wild fisheries, and China will be main player that will continue to contribute towards this end.
Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes ...of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated.
C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism.
Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH.
Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.
Elucidating the mechanisms of fluctuations in fish populations are key to sustainable fisheries management. However, limited data combined with climate variability and fishing further constrain our ...understanding of fish population dynamics. Fortunately, marine sedimentary archives of fish abundance and environmental changes in the past, may provide new insights into long-term fish population fluctuations. Here, we used 150-year sediment records of the abundance of Japanese anchovy (
Engraulis japonicus
) scales, phytoplankton, and zooplankton biomarkers, and δ
15
N data previously reported from the central Yellow Sea (YS). We discussed the linkages of the anchovy abundance to ecosystem structure and sea surface temperatures (SSTs). Principal component analysis (PCA) identified negative effects of strong stratification (higher δ
15
N) and high abundance of haptophytes (higher alkenone content) on the anchovy stock through our analytical period (~1860–2005 AD). In addition, we found positive relationships between the anchovy abundance and plankton productivity in proxies before the period of intense fishing (1860–1980 AD), indicating bottom-up processes affecting the anchovy stock. However, the bottom-up processes became unclear under excessive fishing. This was possibly due to overfishing becoming a major driver after 1980, thereby altering the cascading of the marine ecosystem towards a different structure. Climate variability seems to indirectly influence the anchovy stock through bottom-up control via a cascading effect from the changes in the North Pacific Gyre Oscillation (NPGO) or the Pacific North American pattern (PNAP). The impacts of these changes on the hydrodynamic features of YS in turn influence the productivity of plankton prey for the anchovy. Collectively, our findings suggest that synergistic effects of climate and fishing on the anchovy need to be paid greater attention. Our results also contribute to an improved understanding of fish population fluctuations in other seas.
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