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Soil physicochemical properties can not only reflect ecosystem integrity, land quality and biogeochemical processes, but also are impacted by diverse land use types formed by intensive human activities. Exploring the comprehensive function of land use types and environmental factors on soil properties are of great significance for the relative land management, nutrition cycling and agricultural sustainable development. And little previous studies considered the inherent relations between soil properties under the dual effects of the above two, especially in an area with high land use intensity. This study tried to achieve the comprehensive research of human activities and environmental factors on soil properties through the study of the functions on soil properties from the environment factors under different land use types in the Beijing-Tianjin-Hebei region, which is a typical area with the most intense human activities in China. In this study, soil samples were collected in an area typified by intensive human activities in the Baiyangdian Watershed in the Beijing-Tianjin-Hebei region. The relationships between soil properties and environmental factors as well as the relationships between soil properties and land use intensity were explored by principal component analysis and geographically weighted regression (GWR) respectively. Additionally, impacts on soil properties from environmental factors were explored by structural equation modeling (SEM). GWR results suggested that pH was positively related to land use intensity (LUI); comparatively, all other soil properties were negatively related to LUI. SEM results showed that precipitation, temperature, and elevation all had direct and indirect influences on soil properties. Moreover, soil organic carbon was not only directly affected by environmental factors, but also indirectly through total phosphorus content in residential areas and plain farmland, pH in mountainous farmland areas, and bulk density in residential areas and mountainous farmland. Our work focus on the combined function of environmental factors and land uses on soil properties under various land use types with different human activities intensities. Our main conclusion from the above findings was that precipitation and temperature are both important factors that impact soil properties. High temperature and improper agricultural activities also reduced soil carbon accumulation. These findings underscore that scientific fertilizer addition during farming and soil quality management such as planning a proper reclamation range should be advocated in areas with intensive human activities. Taken together, our research will allow for a better understanding of the variations in soil properties and other influential factors in the context of human activities. [Display omitted] • Comprehensive effects of land use and environmental factors were analyzed. • Direct, indirect, and total influences on soil properties were explored. • The interaction of land use and environment was important to soil properties. • Precipitation and temperature had significant impacts on soil organic carbon. [ABSTRACT FROM AUTHOR]

p53 was discovered 30 years ago. Extensive studies have been done on p53 since then, which makes p53 one of the most extensively studied genes. p53 has long been recognized as a key tumor suppressor. Cell cycle arrest, apoptosis and senescence have been traditionally recognized as the main functions of p53 in tumor suppression. Recently, some novel functions of p53 have been identified, including the regulation of energy metabolism, antioxidant defense, and microRNA expression and maturation, which all contribute to the role of p53 in tumor suppression. Furthermore, the contribution of p53 to normal biologic processes (e.g. reproduction and aging) and some other aspects of diseases (e.g. neurodegenerative diseases) is only now being appreciated. Here we will review recent advances in the study of some new functions of p53. [ABSTRACT FROM AUTHOR]

In response to stress, p53 initiates the transcriptional regulation of selected target genes and various cellular responses, including cell cycle arrest, apoptosis and senescence. Recent studies revealed two additional functions of p53 in the regulation of IGF-1/AKT/mTOR pathways and energy metabolism, contributing to p53''s role as a tumor suppressor. Oncogenic processes give rise to metabolic pathways focused upon the use of aerobic glycolysis (the Warburg effect) and the pentose shunt, providing higher levels of reducing activities. p53 shuts down these pathways and refocuses cells to utilize mitochondrial oxidative phosphorylation, thereby maximizing efficient ATP production and minimizing the synthesis of substrates for cell division. The use of these alternative metabolic pathways is an integral part of both normal and oncogenic phenotypes. [Copyright &y& Elsevier]

The Engineering Education Accreditation (EEA) has been adopted in colleges and universities worldwide. As a foundational component of practical teaching, cognitive internship is a focus of EEA, with the offline mode as the common teaching method, while the online mode has been increasingly used in recent years. To meet the requirements of EEA, the effects of the online and offline cognitive internships need to be analyzed and compared. Focusing on the demand, this paper proposes a comprehensive method combining the Goal Achievement Degree (GAD) and CIPP model. The majors of the School of Automotive Transport and Engineering at Wuhan University of Science and Technology (WUST), which include the fields of vehicle engineering, traffic engineering, traffic transport, and logistics engineering, are taken as the example to conduct this research. The main findings of this paper are as follows: (1) Compared with online cognitive internship, offline internship students have a stronger ability to enhance theoretical knowledge and perceive the environment. (2) Utilizing such an online teaching method could be helpful for cultivating students' analytical skills. (3) From the students' perspective, the lack of funding for teaching cognitive internships, both online and offline, is the most serious problem. (4) Students perceive that the online cognitive internship helps them to understand knowledge in class and determine career planning, but it does not provide the same effect on those as the offline cognitive internship. [ABSTRACT FROM AUTHOR]

Driven by energy shortages and climate concerns, the electric vehicles are popular around the world with their energy-saving and environmentally friendly advantages. As electric vehicle batteries (EVBs) mainly use lithium batteries, and the batteries' performance decreases with the increase of charging times, a large number of batteries are entering the end-of-life (EoL) stage. Recycling and reuse of EVBs are effective ways to reduce environmental pollution and promote resources utilization and is now a top priority. Building a recycling network is the foundation of battery recycling. However, there are few studies on battery recycling networks and the construction of recycling networks is expensive, which impedes the sustainable development of electric vehicles. Based on this, recycling network design is critical for EVB recycling. This paper first analyzes three strategies to deal with used batteries: remanufacturing, reuse, and recycling materials. Secondly, an EVB recycling network model is developed with the objective of minimizing the total cost and carbon emissions. The model solves the problem of siting the centers in the network and the vehicle routing in the recycling process. Finally, the model was applied to GEM (a Chinese company dedicated to circular economy) and validated using a greedy algorithm. In addition, the results show that logistics costs and operating costs account for the majority of the recycling network total expense, at 48.45% and 31%, respectively. Therefore, if companies want to further reduce the cost of EVB recycling, they should reduce logistics costs and operating costs. In summary, this paper provides a decision-making approach for EVB recycling enterprises to carry out recycling and reuse, and offers advice on how to promote the sustainable economic and environmental development of the electric vehicle battery industry. [ABSTRACT FROM AUTHOR]

Remanufacturing has gained great recognition in recent years due to its economic and environmental benefits and effectiveness in the value retention of waste products. Many studies on reverse logistics have considered remanufacturing as a key node for network optimization, but few literature reviews have explicitly mentioned remanufacturing as a main feature in their analysis. The aim of this review is to bridge this gap. In total, 125 papers on remanufacturing reverse logistics network design have been reviewed and conclusions have been drawn from four aspects: (1) in terms of network structure, the functional nodes of new hybrid facilities and the network structure combined with the remanufacturing technologies of products are the key points in the research. (2) In the mathematical model, the multi-objective function considered from different aspects, the uncertainty of recovery time and recovery channel in addition to quantity and quality, and the selection of appropriate algorithms are worth studying. (3) While considering product types, the research of a reverse logistics network of some products is urgently needed but inadequate, such as medical and furniture products. (4) As for cutting-edge technologies, the application of new technologies, such as intelligent remanufacturing technology and big data, will have a huge impact on the remanufacturing of a reverse logistics network and needs to be considered in our research. [ABSTRACT FROM AUTHOR]

Summary: We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with Mll-AF4-associated gene expression profiles in murine ALLs and in human MLL-rearranged leukemias. Human MLL-rearranged ALLs could be distinguished from other ALLs by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression. [Copyright &y& Elsevier]

Abstract: Objective: To investigate the role the lens dimensions played on the pathogenesis of primary angle-closure glaucoma. Methods: 38 eyes of 20 patients with primary angle-closure glaucoma(PACG) and 35 eyes of 22 normal individuals without ocular abnormalities were examined. The anatomical parameters of the lens and other structures of the anterior segment were calculated using B ultrasound, computer image processing and ultrasound biomicroscopy(UBM). The parameters were compared between the patients and normal subjects. Correlation analysis was used to determine the relationship between the radii of curvature of the anterior lens surface(RCALS) and the other parameters of the anterior segment. Results: Compared with the normal eyes, the eyes of PACG had thicker lens, steeper curvature of anterior lens surface, decreased depth of the anterior chamber, narrower chamber angle, and more anterior position of the ciliary bodies and lens. All these differences were significant(P <0.05 or P < 0.01). In the PACG group, the RCALS had significantly negative correlation with the central and peripheral lens thickness(P <0.01andP < 0.05 respectively), and had positive correlation with relative lens position, anterior chamber depth(ACD), angle-open distance at 500 um(AOD500), trabecular iris angle(TIA) and trabecular ciliary processes distance(TCPD,P <0.05orP <0.01). Conclusion: The occurrence of PACG is relevant to the abnormal anatomical structures of the anterior segment. Among all factors, the lens parameters play an important role in the pathogenesis. Increased lens thickness, relative more anterior position of lens, especially steepened curvature of anterior lens surface are predisposing factors of the pathologic phenomenon in PACG including pupillary blockage, shallow anterior chamber, secondary closure of chamber angle and elevation of intraocular pressure. [Copyright &y& Elsevier]

Chromium(VI) [Cr(VI)], a ubiquitous environmental contaminant, is a well-known carcinogen to both humans and experimental animals, although it is a weak mutagen by itself. Occupational exposure to Cr(VI) is strongly associated with a high incidence of lung cancer, but the underlying mechanisms remain unclear. Tobacco smoking is the major cause of lung cancer, and polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke are the major etiological agents. Since humans are frequently exposed to both Cr(VI) and PAHs, it is possible that Cr(VI) and PAHs have a synergistic effect on mutagenecity and cytotoxicity that contributes to the high incidence of lung cancer associated with exposure to both agents. In this study, we tested this possibility by determining the effect of Cr(VI) exposure on (±)-anti-7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE, an active metabolite of PAHs) induced cytotoxicity, mutagenicity, and DNA adduct formation in Chinese hamster ovary (CHO) cells. Using the adenine phosphoribosyltransferase (APRT+) → APRT- forward mutation assay, we found that while Cr(VI) alone induced low mutation frequency, it greatly enhanced BPDE-induced mutations in nucleotide excision repair (NER)-proficient CHO cells. Cr(VI) exposure also greatly enhanced BPDE-induced killing in NER-proficient cells. It is known that the cytotoxicity and mutagenicity of BPDE are mainly caused by the formation of DNA adduct, which are removed by NER. To test the possibility that the enhancement of cytotoxicity and mutagenicity by Cr(VI) is caused by the inhibition of NER, NER-deficient cells were used, and the enhancement effects of Cr(VI) were not observed in those cells. We further found that while Cr(VI) exposure does not change the total BPDE-DNA adduct formation, it significantly inhibited the repair of BPDE-DNA adducts from genomic DNA in NER-proficient cells. Using a host cell reactivation assay, we found that the repair of BPDE-DNA adduct in a luciferase reporter gene is greatly inhibited after Cr(VI) exposure in NER-proficient cells while not in NER-deficient cells. Together these results clearly demonstrate that Cr(VI) exposure can greatly enhance the mutagenicity and cytotoxicity of PAHs by inhibiting the cellular NER pathway, and this may constitute an important mechanism for Cr(VI)-induced human carcinogenesis. [ABSTRACT FROM AUTHOR]

Net primary production (NPP) serves as a critical proxy for monitoring changes in the global capacity for vegetation carbon sequestration. The assessment of the factors (i.e., human activities and climate changes) influencing NPP is of great value for the study of terrestrial systems. To investigate the influence of factors on grassland NPP, the ecologically vulnerable Qinghai–Tibet Plateau region was considered an appropriate study area for the period from 2000 to 2020. We innovated the use of the RICI index to quantitatively represent human activities and analyzed the effects of RICI and climatic factors on grassland NPP using the geographical detector. In addition, the future NPP was predicted through the integration of two modeling approaches: The Patch-Generating Land Use Simulation (PLUS) model and the Carnegie–Ames–Stanford Approach (CASA) model. The assessment revealed that the expanded grassland contributed 7.55 × 104 Gg C (Gg = 109 g) to the total NPP, whereas the deterioration of grassland resulted in a decline of 1.06 × 105 Gg C. The climatic factor was identified as the dominant factor in grassland restoration, representing 70.85% of the total NPP, as well as the dominant factor in grassland degradation, representing 92.54% of the total NPP. By subdividing the climate change and human activity factors into sub-factors and detecting them with a geographical detector, the results show that climate change and anthropogenic factors have significant ability to explain geographic variation in NPP to a considerable extent, and the effect on NPP is greater when the factors interact. The q-values of the Relative Impact Contribution Index (RICI) and the RICI of the land use change NPP are consistently greater than 0.6, with the RICI of the human management practices NPP and the evapotranspiration remaining at approximately 0.5. The analysis of the interaction between climate and human activity factors reveals an average impact of greater than 0.8. By 2030, the NPP of the natural development scenario, economic development scenario (ED), and ecological protection scenario (EP) show a decreasing trend due to climate change, the dominant factor, causing them to decrease. Human activities play a role in the improvement. The EP indicates a positive expansion in the growth rate of forests, water, and wetlands, while the ED reveals rapid urbanization. It is notable that this is accompanied by a temporary suspension of urban greening. [ABSTRACT FROM AUTHOR]

Ozone (O3) pollution has a profound impact on human health, vegetation development, and the ecological environment, making it a critical focus of global academic research. In recent years, O3 pollution in China has been on a steady rise, with ozone emerging as the sole conventional pollutant to consistently increase in concentration without any decline. This study conducted a quantitative analysis of O3 concentrations across 367 Chinese cities in 2019, examining spatial autocorrelation and local clustering of O3 levels, and investigated the diverse relationships between human activity factors and O3 concentration. The seasonal fluctuation of O3 exhibited the "M-type" pattern, with peak concentrations in winter and the lowest levels in summer. The center of O3 pollution migrated southeastward, with the area of highest concentration progressively shifting south along the eastern coast. Moreover, O3 concentration showed a strong positive correlation with population density, road freight volume, and industrial emissions, suggesting that human activities, vehicle emissions, and industrial operations are significant contributors to O3 production. The results provide comprehensive information on the characteristics, causes, and occurrence mechanism of O3 in Chinese cities that can be utilized by global government departments to formulate strategies to prevent and control O3 pollution. [ABSTRACT FROM AUTHOR]

Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied LSCs in mouse models of acute myelogenous leukemia (AML) induced either by coexpression of the Hoxa9 and Meis1a oncogenes or by the fusion oncoprotein MLL-AF9. We show that the Wnt/β-catenin signaling pathway is required for self-renewal of LSCs that are derived from either hematopoietic stem cells (HSC) or more differentiated granulocyte-macrophage progenitors (GMP). Because the Wnt/β-catenin pathway is normally active in HSCs but not in GMP, these results suggest that reactivation of β-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. β-catenin is not absolutely required for self-renewal of adult HSCs; thus, targeting the Wnt/β-catenin pathway may represent a new therapeutic opportunity in AML., Stem Cell and Regenerative Biology

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects. [ABSTRACT FROM AUTHOR]

The lack of high-spectral and high-resolution remote sensing data is impeding the differentiation of various fruit tree species that share comparable spectral and spatial features, especially for evergreen broadleaf trees in tropical and subtropical areas. Here, we propose a novel decision tree approach to map the spatial distribution of fruit trees at a 10 m spatial resolution based on the growth stage features extracted from Sentinel-1A (S-1A) time-series synthetic aperture radar (SAR) data. This novel method was applied to map the spatial distribution of fruit trees in Maoming City, which is known for its vast cultivation of fruit trees, such as litchi, citrus, and longan. The results showed that the key to extracting information on the distribution of fruit trees lies in the fact that the fruit ripening and expansion period attenuates the information on the vegetation of fruit trees, a characteristic of the reproductive period. Under VH polarization, different fruit tree growth stage traits were more separable and easier to distinguish. The optimal features, such as H v (high valley value of the 14 May, 26 May, and 7 June SAR data), T b (difference between the 7 June and 14 January SAR data), Cr (high valley value of the 13 July, 25 July, and 6 August SAR data), and L o (high valley value of the 23 September, 17 October, and 11 November SAR data), were constructed based on the optimal window. The thresholds for these features were set to 1, 1, 1.5, and 1, respectively. The classification model can effectively distinguish different fruit trees and extract distribution information with overall accuracy (OA) of 90.34% and a Kappa coefficient of 0.84. The proposed method extracts the spatial distribution information of different fruit trees more accurately and provides a reference for the extraction of more tropical and subtropical species. [ABSTRACT FROM AUTHOR]

High glucose (HG)-induced apoptosis of retinal ganglion cells (RGCs) contributes to the pathogenesis of diabetic retinopathy, which is one of the most common and severe complications of diabetes mellitus. Accumulating evidence has documented that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic retinopathy. However, the role of miRNAs in regulating HG-induced apoptosis of RGCs remains largely unknown. Various studies have suggested that miR-495 is an important regulator of cell apoptosis and survival. In this study, we aimed to investigate whether miR-495 is involved in regulating HG-induced apoptosis of RGCs and reveal its possible relevance in diabetic retinopathy. We found that miR-495 was significantly upregulated in HG-treated RGCs. Downregulation of miR-495 protected RGCs against HG-induced apoptosis, whereas overexpression of miR-495 had the opposite effect. Notably, Notch1 was identified as a target gene of miR-495, as miR-495 negatively regulated Notch1 expression and the Notch signaling pathway. Moreover, downregulation of miR-495 inhibited PTEN expression while promoting Akt activation. However, knockdown of Notch1 significantly abolished the protective effect of miR-495 inhibition against HG-induced apoptosis. Overall, our study suggests that downregulation of miR-495 alleviates HG-induced apoptosis of RGCs by targeting Notch1 to regulate PTEN/Akt signaling, which provides novel insights into understanding the pathogenesis of HG-induced apoptosis of RGCs. [ABSTRACT FROM AUTHOR]

Gymnocypris przewalskii (Naked carp), a native teleost, plays an important role in maintaining the ecological balance of Lake Qinghai (altitude, 3.2 km), the largest saline lake in China. In this study, a new gill cell line from G. przewalskii was developed using the explant technique and named as GPG. This cell line was maintained in Dulbecco's Modified Eagle Medium (DMEM) (high glucose), supplemented with 15% fetal bovine serum (FBS), and was successfully subcultured up to 32 passages. Meanwhile, this cell line was also authenticated by sequencing the mitochondrial cytochrome C oxidase subunit I (COI) and 16S rRNA genes and by chromosome analysis. With the Cytomegalovirus (CMV) promoter, the GPG cell line could express green fluorescent protein (GFP) at about 5% transfection efficiency. MTT test showed that Clostridium botulinum toxin (BTX) was toxic to the cell line. After cryopreservation with 10% dimethyl sulfoxide (DMSO), this cell line could be successfully revived at an efficiency over 70%. This study revealed that the GPG cell line could be used as materials for physio‐chemical investigation of G. przewalskii and also provided a tool for gene function study and toxicological reaction in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Nano-sized ceramic particle reinforced aluminum matrix composites fabricated using conventional stir casting technique usually present poor distribution of nanoparticles within the matrix and high porosity. In this study, nano-Al2O3/2024 composites were prepared by solid–liquid mixed casting combined with ultrasonic treatment. The obtained composite exhibited fine grain microstructure, reasonable Al2O3 nanoparticles distribution in the matrix, and low porosity. Solid–liquid mixed casting technique was effective in inhibiting the agglomeration of nanoparticles in the matrix. The application of ultrasonic vibration on the composite melt during the solidification not only refined the grain microstructure of the matrix, but also improved the distribution of nano-sized reinforcement. Compared with the matrix, the ultimate tensile strength and yield strength of 1wt.% nano-Al2O3/2024 composite were enhanced by 37% and 81%, respectively. The better tensile properties were attributed to the uniform distribution of reinforcement and grain refinement of aluminum matrix. [Copyright &y& Elsevier]

Naked carp (Gymnocypris przewalskii) is a migratory fish endemic to the Qinghai Lake, the largest inland saline-alkaline lake in China. Based on our previous results of comparative transcriptome sequencing, we found that pathways related to regulation of actin cytoskeleton, plasma membrane damage, and inflammation-related signaling were significantly enriched during saline-alkaline stress, suggesting involvement of annexin (ANN) family proteins in stress adaption in naked carp. Herein, to explore the role of annexin family in naked carp under saline-alkaline stress, twenty GpANNs family members were identified at the genome-wide scale, and bioinformatics and expression analysis under saline-alkaline stress were performed. The predicted subcellular localization showed that most members of GpANNs were distributed in the cytoplasm, and the rest were localized in the cytoskeleton, nucleus, or mitochondria, respectively. GpANNs family proteins contained specific type II Ca2+-binding motifs, actin-binding motifs, GTP-binding motifs, etc. Phylogenetic tree analysis showed that the annexin homologues from naked carp, carp (Cyprinus carpio), zebrafish (Danio rerio), and chinese cavefish (Sinocyclocheilus rhinocerous) were divided into eight groups, i.e. ANN1 ∼ 6, ANN11 and ANN13. But homologues of ANN7 ∼ 10 groups were not found in these three fish species. Twenty-eight, nineteen and twenty-nine orthologous gene pairs were identified between naked carp and carp, zebrafish and chinese cavefish, respectively. Six paralogous gene pairs were identified in naked carp, all of which had a Ka/Ks ratio less than one, suggesting that the GpANNs family may have undergone purifying selection pressure during evolution. Expression of GpANN3 was significantly up-regulated in the kidney tissue under saline-alkaline stress, while GpANN2 was significantly down-regulated. Similar trends of protein expression were also observed by Western blot, suggesting involvement of GpANN3 and GpANN2 in stress response. Confocal microscopy revealed that GpANN2 was localized in both cytoplasm and nucleus, but GpANN3 was preferentially localized in the cytoplasm. Our study demonstrated the role of annexins in stress adaption, and provided the basic information required for further function analyses in naked carp. • The annexin family were comprehensively analyzed in G. przewalskii for the first time, but ANN7 ∼ 10 memebers were lacked. • GpANNs contain a variety of motifs which may be important sites for protein function under saline-alkaline conditions. • GpANNs exhibited differential expression patterns in 12 different tissues under saline-alkaline stress. • In kidney, GpANN2 and GpANN3 significantly responded to saline-alkaline stress at both mRNA and protein levels. [ABSTRACT FROM AUTHOR]

• A multi-leveled ESP was constructed to help with large-scale ecological conservation. • This ESP can enhance synergistic conservation across scales (regions, basins, and nations). • Five key ecosystem services focused by Sustainable Development Goal 15 were used to identify ecological sources. Serious ecological crises have emerged in the Asian Water Tower region (17 countries centered on the Qinghai-Tibetan Plateau), making it a major priority and challenge for Asian and even global ecological conservation efforts. Constructing a multi-leveled ecological security pattern (ESP) based on the synergies among multiple ecosystem services (ESs) for this region can enhance the structural integrity, functional stability, and spatial connectivity of ecosystems. Therefore, based on a series of GIS spatial analysis methods, the minimum cumulative resistance model, and the analytic hierarchy process, this study measured the importance of five key ESs focused by Sustainable Development Goal 15 (including water conservation, carbon sequestration, sand fixation, soil conservation, and biodiversity conservation); and took fishnet scale as data calculation unit to construct a hierarchical ESP (including three levels of ecological sources and corridors) to provide evidence-based support for identifying and prioritizing synergistic conservation actions across scales (regions, nations, and basins). Overall, the ESP included a total of 534 sources and 656 corridors. Some key conservation obstacles in the region (e.g., edge effects and several human activities) and corresponding priority actions are provided, such as integrating the ESPs into long-term planning, enhancing the conservation and the restoration of both the extent and the quality of forests (e.g., increasing tree species richness), and increasing collaboration across scales for resource mobilization and synergistic land use. [ABSTRACT FROM AUTHOR]

Tumor suppressor p53 plays a central role in tumor suppression. p53 is the most frequently mutated gene in human cancer, and over half of human cancers contain p53 mutations. Majority of p53 mutations in cancer are missense mutations, leading to the expression of full-length mutant p53 (mutp53) protein. While the critical role of wild-type p53 in tumor suppression has been firmly established, mounting evidence has demonstrated that many tumor-associated mutp53 proteins not only lose the tumor-suppressive function of wild-type p53 but also gain new activities to promote tumorigenesis independently of wild-type p53, termed gain-of-function. Mutant p53 protein often accumulates to very high levels in tumors, contributing to malignant progression. Recently, mutp53 has become an attractive target for cancer therapy. Further understanding of the mechanisms underlying mutp53 protein accumulation and gain-of-function will accelerate the development of targeted therapies for human cancer harboring mutp53. In this review, we summarize the recent advances in the studies on mutp53 protein accumulation and gain-of-function and targeted therapies for mutp53 in human cancer. [ABSTRACT FROM AUTHOR]

Mercury species distribution in the flue gas from three typical coal-fired power plants have been investigated using a C-5000 sampler for Ontario Hydro Method (OHM) to evaluate specified Hg emission inventories in the largest coal-production province of China, Inner Mongolia. The feed coal, bottom ash, fly ash and gypsum have also been sampled in the field. Mercury emissions are in the dominant form of Hg 0 (>85%). The Hg 2+ (<15%) and the Hg p (<2%) emissions are minor fractions of Hg t in the flue gas. The wet limestone flue gas desulfurization device (WLFGD) showed much higher removal efficiency for Hg 2+ (87–95%) than for the other two Hg species. The input Hg/output Hg varied from 92% to 115% for the tested 3 coal-fried utility boilers during sampling time. We obtained comprehensive Hg discharge factors, including direct atmospheric Hg emission factors and indirect discharge factors of Hg associated with bottom ash, fly ash and gypsum, to the environment, designating the fates of Hg in coal. We estimated the Hg discharges from coal-fired power plants in Inner Mongolia in 2008–2014 and expanded to China. The maximum of direct Hg emissions from coal-fired power plants of Inner Mongolia was 24 Mg in 2012. The Chinese coal-fired power plants emitted directly 100 Mg Hg to the atmosphere every year at the nationwide air control actions. The maximum discharges of Hg associated with fly ash and gypsum of Inner Mongolia was 81 Mg and 11 Mg in 2012, respectively. The national Hg discharges with fly ash and gypsum every year are respectively about 300 Mg and 82 Mg, majority of which may be reemitted to the atmosphere by the utilization industry. Therefore, mercury emissions from coal-fired power plants are not the largest single source of Hg to the atmosphere in normal operation of the current efficient denitrification, particles control and desulfurization devices. Instead, the utilization industry of fly ash and gypsum would be emitting more Hg to the atmosphere. [ABSTRACT FROM AUTHOR]

Tumor-suppressor p53 plays a key role in tumor prevention. As a transcription factor, p53 transcriptionally regulates its target genes to initiate different biological processes in response to stress, including apoptosis, cell cycle arrest or senescence, to exert its function in tumor suppression. Recent studies have revealed that metabolic regulation is a novel function of p53. Metabolic changes have been regarded as a hallmark of tumors and a key contributor to tumor development. p53 regulates many different aspects of metabolism, including glycolysis, mitochondrial oxidative phosphorylation, pentose phosphate pathway, fatty acid synthesis and oxidation, to maintain the homeostasis of cellular metabolism, which contributes to the role of p53 in tumor suppression. p53 is frequently mutated in human tumors. In addition to loss of tumor suppressive function, tumor-associated mutant p53 proteins often gain new tumorigenic activities, termed gain-of-function of mutant p53. Recent studies have shown that mutant p53 mediates metabolic changes in tumors as a novel gain-of-function to promote tumor development. Here we review the functions and mechanisms of wild-type and mutant p53 in metabolic regulation, and discuss their potential roles in tumorigenesis. [ABSTRACT FROM AUTHOR]

Abstract: p63 and p73, two p53 family members, play crucial roles in development and tumor suppression. p63 and p73 have multiple isoforms, which have similar or distinct biological functions. Transactivation (TA) isoforms of p63 and p73 have high similarity with p53 and often have biological functions similar to p53. p53 plays an important role in nucleotide excision repair (NER) through transcriptional regulation of target genes involved in NER, including DDB2, XPC and GADD45. To investigate whether TAp63 and TAp73 play a similar role in NER, Saos2 cells with inducible expression of specific isoforms of TAp63 and TAp73, including TAp63α/β/γ and TAp73α/β/γ isoforms, were employed. Overexpression of TAp63γ significantly enhances NER of ultraviolet (UV)-induced DNA damage, including cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts, and enhances cell survival after UV irradiation in Soas2 cells. The enhancement of NER of UV-induced DNA damage by TAp63γ was also confirmed in H1299 cells with overexpression of TAp63γ. Consistently, knockdown of endogenous TAp63 decreases NER of UV-induced DNA damage in H1299 cells. TAp63α/β and TAp73α/β/γ isoforms do not have a clear effect on NER in Saos2 or H1299 cells. TAp63γ overexpression clearly induces the expression of DDB2, XPC and GADD45 at both RNA and protein levels. Furthermore, luciferase reporter assays show that TAp63γ transcriptionally activates DDB2, XPC and GADD45 genes through the regulation of the p53 binding elements in these genes. These results demonstrate that TAp63γ enhances NER to remove UV-induced DNA damage and maintain genomic stability through transcriptional induction of a set of NER proteins, which provides an additional important mechanism that contributes to the function of TAp63 in tumor suppression. [Copyright &y& Elsevier]

Summary: The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation-associated gene expression signature, whereas global gene expression remained largely unaffected. Suppression of MLL translocation-associated gene expression corresponded with dependence of MLL-AF9 leukemia on Dot1l in vivo. These data point to DOT1L as a potential therapeutic target in MLL-rearranged leukemia. [Copyright &y& Elsevier]

Summary: Tumor suppressor p53 plays a central role in tumor prevention. p53 protein levels and activity are under a tight and complex regulation in cells to maintain the proper function of p53. MicroRNAs play a key role in the regulation of gene expression. Here we report the regulation of p53 through miR-504. miR-504 acts as a negative regulator of human p53 through its direct binding to two sites in the p53 3′ untranslated region. Overexpression of miR-504 decreases p53 protein levels and functions in cells, including p53 transcriptional activity, p53-mediated apoptosis, and cell-cycle arrest in response to stress, and furthermore promotes tumorigenecity of cells in vivo. These results demonstrate the direct negative regulation of p53 by miR-504 as a mechanism for p53 regulation in cells, which highlights the importance of microRNAs in tumorigenesis. [Copyright &y& Elsevier]

Leukemia inhibitory factor (LIF) is a multi-functional cytokine of the interleukin-6 (IL-6) superfamily. Initially identified as a factor that inhibits the proliferation of murine myeloid leukemia cells, LIF displays a wide variety of important functions in a cell-, tissue- and context-dependent manner in many physiological and pathological processes, including regulating cell proliferation, pluripotent stem cell self-renewal, tissue/organ development and regeneration, neurogenesis and neural regeneration, maternal reproduction, inflammation, infection, immune response, and metabolism. Emerging evidence has shown that LIF plays an important but complex role in human cancers; while LIF displays a tumor suppressive function in some types of cancers, including leukemia, LIF is overexpressed and exerts an oncogenic function in many more types of cancers. Further, targeting LIF has been actively investigated as a novel strategy for cancer therapy. This review summarizes the recent advances in the studies on LIF in human cancers and its potential application in cancer therapy. A better understanding of the role of LIF in different types of cancers and its underlying mechanisms will help to develop more effective strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Competing Interests: Disclosure Statement None declared.

Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia., (© 2024. The Author(s).)

Radiation-induced gastrointestinal syndrome is a major complication and limiting factor for radiotherapy. Tumor suppressor p53 has a protective role in radiation-induced gastrointestinal toxicity. However, its underlying mechanism remains unclear. Here we report that regulating the IL12-p40/MHC class II signaling pathway is a critical mechanism by which p53 protects against radiation-induced gastrointestinal syndrome. p53 inhibits the expression of inflammatory cytokine IL12-p40, which in turn suppresses the expression of MHC class II on intestinal epithelial cells to suppress T cell activation and inflammation post-irradiation that causes intestinal stem cell damage. Anti-IL12-p40 neutralizing antibody inhibits inflammation and rescues the defects in intestinal epithelial regeneration post-irradiation in p53-deficient mice and prolongs mouse survival. These results uncover that the IL12-p40/MHC class II signaling mediates the essential role of p53 in ensuring intestinal stem cell function and proper immune reaction in response to radiation to protect mucosal epithelium, and suggest a potential therapeutic strategy to protect against radiation-induced gastrointestinal syndrome., (© 2024. The Author(s).)

Phosphorus and nitrogen pollution from agricultural nonpoint sources heavily burden the water environment, and a scientific calculating system is needed to calculate the pollutant loads under the water pollution treatment. This study established a system to calculate the coefficients of agricultural nonpoint source pollutants into water bodies in the subregion in Poyang Lake basin in the middle reach of the Yangtze River combining with multiple driving factors. Validation results showed that the errors of the typical unit were 30.58% for total phosphorus (TP), 13.43% for total nitrogen (TN) and 33.93% for ammonia nitrogen (NH 3 -N), respectively. The errors of the subregion were 26.92% for TP, 31.83% for TN and 29.15% for NH 3 -N, respectively. Besides, there were higher TP and TN loads in the east area of subregion in both units and county scales, which indicated the heavy phosphorus and nitrogen burden on water environment. In contrast, higher NH 3 -N loads occurred in the north area of subregion. The establishment of coefficient system for agricultural pollutants into water bodies and the pollutant loads calculation would provide enlightenment for water pollution treatment and agricultural nonpoint source pollution controlling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

RAB11 small GTPases and associated recycling endosome have been localized to mitotic spindles and implicated in regulating mitosis. However, the physiological significance of such regulation has not been observed in mammalian tissues. We have used newly engineered mouse models to investigate intestinal epithelial renewal in the absence of single or double isoforms of RAB11 family members: Rab11a and Rab11b. Comparing with single knockouts, mice with compound ablation demonstrate a defective cell cycle entry and robust mitotic arrest followed by apoptosis, leading to a total penetrance of lethality within 3 days of gene ablation. Upon Rab11 deletion ex vivo, enteroids show abnormal mitotic spindle formation and cell death. Untargeted proteomic profiling of Rab11a and Rab11b immunoprecipitates has uncovered a shared interactome containing mitotic spindle microtubule regulators. Disrupting Rab11 alters kinesin motor KIF11 function and impairs bipolar spindle formation and cell division. These data demonstrate that RAB11A and RAB11B redundantly control mitotic spindle function and intestinal progenitor cell division, a mechanism that may be utilized to govern the homeostasis and renewal of other mammalian tissues., (© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

The tumor suppressor TP53 is the most frequently mutated gene in human cancers. Mutant p53 (mutp53) proteins often accumulate to very high levels in human cancers to promote cancer progression through the gain-of-function (GOF) mechanism. Currently, the mechanism underlying mutp53 accumulation and GOF is incompletely understood. Here, we identified TRIM21 as a critical E3 ubiquitin ligase of mutp53 by screening for specific mutp53-interacting proteins. TRIM21 directly interacted with mutp53 but not WT p53, resulting in ubiquitination and degradation of mutp53 to suppress mutp53 GOF in tumorigenesis. TRIM21 deficiency in cancer cells promoted mutp53 accumulation and GOF in tumorigenesis. Compared with p53R172H knockin mice, which displayed mutp53 accumulation specifically in tumors but not normal tissues, TRIM21 deletion in p53R172H knockin mice resulted in mutp53 accumulation in normal tissues, an earlier tumor onset, and a shortened life span of mice. Furthermore, TRIM21 was frequently downregulated in some human cancers, including colorectal and breast cancers, and low TRIM21 expression was associated with poor prognosis in patients with cancers carrying mutp53. Our results revealed a critical mechanism underlying mutp53 accumulation in cancers and also uncovered an important tumor-suppressive function of TRIM21 and its mechanism in cancers carrying mutp53.

Natural vegetation has been proved to promote water purification in previous studies, while the relevant laws has not been excavated systematically. This research explored the relationships between vegetation cover and water quality indexes in Liaohe River Basin in China combined with self-organizing map (SOM) and geographically and temporally weighted regression (GTWR) innovatively and systematically based on the distributing heterogeneity of water quality conditions. Results showed that the central and northeast regions of the study area had serious organic and nutrient pollution, which needed targeted treatment. And SOM verified that high vegetation coverage with retention potential of organic and inorganic pollutants as well as nutrients improved water quality to some degree, while the excessive discharges of pollutants still had serious threats to nearby water environment despite the purification function of vegetation. GTWR indicated that the waterside vegetation was beneficial for dissolved oxygen increasing and contributed to the decreasing of organic pollutants and inorganic pollutants with reducibility. Natural vegetation also obsorbed nutrients like TN and TP to some degree. However, the retential potential of nitrogen and organic pollutants became not obvious when there were heavy pollution, which demonstrated that pollution sources should be controlled despite the purification function of vegetation. This study implied that natural vegetation purified water quality to some degree, while this function could not be revealed when there was too heavy pollution. These findings underscore that the pollutant discharge should be controlled though the natural vegetation in ecosystem promoted the purification of water bodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The glycolytic enzyme lactate dehydrogenase A (LDHA) is frequently overexpressed in cancer, which promotes glycolysis and cancer. The oncogenic effect of LDHA has been attributed to its glycolytic enzyme activity. Here we report an unexpected noncanonical oncogenic mechanism of LDHA; LDHA activates small GTPase Rac1 to promote cancer independently of its glycolytic enzyme activity. Mechanistically, LDHA interacts with the active form of Rac1, Rac1-GTP, to inhibit Rac1-GTP interaction with its negative regulator, GTPase-activating proteins, leading to Rac1 activation in cancer cells and mouse tissues. In clinical breast cancer specimens, LDHA overexpression is associated with higher Rac1 activity. Rac1 inhibition suppresses the oncogenic effect of LDHA. Combination inhibition of LDHA enzyme activity and Rac1 activity by small-molecule inhibitors displays a synergistic inhibitory effect on breast cancers with LDHA overexpression. These results reveal a critical oncogenic mechanism of LDHA and suggest a promising therapeutic strategy for breast cancers with LDHA overexpression., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Gymnocypris przewalskii (naked carp), a native teleost, plays an important role in the ecosystem of Qinghai Lake (altitude, 3.2 km) on the Qinghai-Tibet Plateau in China. We developed a new cell line from the muscle of G. przewalskii using the explant technique and named the cell line GPM. This cell line was maintained in DMEM medium (high glucose) supplemented with 15% fetal bovine serum (FBS). The cell line was successfully subcultured up to 32 passages and was authenticated by immunofluorescence assay, sequencing the mitochondrial cytochrome C oxidase subunit I (COI) and 16S rRNA genes, and by chromosome analysis. In the medium containing 15% FBS, the cell line could be passaged stably at 25 °C. The GPM cell line could express green fluorescent protein (GFP) with a CMV promoter with about 5% transfection efficiency. MTT tests showed that Clostridium botulinum toxin (BTX) was toxic to the cell line. The cell line could be successfully cryopreserved in liquid nitrogen with a revival efficiency of over 70%. This study demonstrated that the GPM cell line can be used as an important tool for understanding the physiological characteristics of G. przewalskii, and it can provide a resource for studying gene function and toxicological reactions in vitro., (© 2022. The Society for In Vitro Biology.)

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation, a widely used therapy for hematologic malignancies and blood disorders. Here, we report an unexpected role of cytokine leukemia inhibitory factor (LIF) in protecting against GVHD development. Administrating recombinant LIF protein (rLIF) protects mice from GVHD-induced tissue damage and lethality without compromising the graft-versus-leukemia activity, which is crucial to prevent tumor relapse. We found that rLIF decreases the infiltration and activation of donor immune cells and protects intestinal stem cells to ameliorate GVHD. Mechanistically, rLIF downregulates IL-12-p40 expression in recipient dendritic cells after irradiation through activating STAT1 signaling, which results in decreased major histocompatibility complex II levels on intestinal epithelial cells and decreased donor T-cell activation and infiltration. This study reveals a previously unidentified protective role of LIF for GVHD-induced tissue pathology and provides a potential effective therapeutic strategy to limit tissue pathology without compromising antileukemic efficacy., (© 2022 by The American Society of Hematology.)

Exploring the responses of greenhouse gas (GHG) emissions to land use conversion or reversion is significant for taking effective land use measures to alleviate global warming. A global meta-analysis was conducted to analyze the responses of carbon dioxide (CO 2 ), methane (CH 4 ), and nitrous oxide (N 2 O) emissions to land use conversion or reversion, and determine their temporal evolution, driving factors, and potential mechanisms. Our results showed that CH 4 and N 2 O responded positively to land use conversion while CO 2 responded negatively to the changes from natural herb and secondary forest to plantation. By comparison, CH 4 responded negatively to land use reversion and N 2 O also showed negative response to the reversion from agricultural land to forest. The conversion of land use weakened the function of natural forest and grassland as CH 4 sink and the artificial nitrogen (N) addition for plantation increased N source for N 2 O release from soil, while the reversion of land use could alleviate them to some degree. Besides, soil carbon would impact CO 2 emission for a long time after land use conversion, and secondary forest reached the CH 4 uptake level similar to that of primary forest after over 40 years. N 2 O responses had negative relationships with time interval under the conversions from forest to plantation, secondary forest, and pasture. In addition, meta-regression indicated that CH 4 had correlations with several environmental variables, and carbon-nitrogen ratio had contrary relationships with N 2 O emission responses to land use conversion and reversion. And the importance of driving factors displayed that CO 2 , CH 4 , and N 2 O response to land use conversion and reversion was easily affected by NH 4 + and soil moisture, mean annual temperature and NO 3 - , total nitrogen and mean annual temperature, respectively. This study would provide enlightenments for scientific land management and reduction of GHG emissions., (© 2022 John Wiley & Sons Ltd.)

Comprehensive efficiency analysis of wastewater treatment plants (WWPTs) in the alpine region with harsh environment and poor techniques as well as managing experience could provide targeted and effective improvement evidences for local wastewater treatment industry and help to improve the water quality of downstream reaches. In this paper, slack-based data envelopment analysis (SBM-DEA) was adopted to assess the operating efficiencies of WWPTs in northeast Qinghai-Tibet Plateau (QTP). Results showed that the average efficiency score for all WWPTs was 0.608, and 32.5% of WWPTs were efficient. Some WWPTs had large improvement potentials in operating costs and pollutant removal rates. Lowering expenditures and promoting facility construction for WWPTs to overcome the climate difficulties and improve management level was necessary according to their improvement potentials. In addition, the relative importance of the quantitative influential factors to efficiencies scores calculated by random forest regression (RFR) indicated that design capacity and temperature were important quantitative factors affecting the performance of WWPTs. Furthermore, geographical location and design capacity also had significant influence on the comprehensive efficiency of WWPTs verified by Kruskal-Wallis test. Our results highlight the importance of facilities upgrading, scientific management for WWPTs. And the relative improvement suggestions on overcoming the high and cold environment should also be considered for the efficient operations of WWTPs as well as the protection the aquatic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Gymnocypris przewalskii is the only high-land endemic teleost living in Qinghai Lake, the largest saline-alkaline lake in China. Its osmoregulatory physiology remains elusive due to a lack of precise identification of the response proteins. In the present study, DIA/SWATH was used to identify differentially expressed proteins (DEPs) under alkaline (pH = 10.1, carbonate buffer), saline (12‰, sodium chloride), and saline-alkaline [carbonate buffer (pH = 10.1) plus 11‰ sodium chloride] stresses. A total of 66,056 unique peptides representing 7,150 proteins and 230 DEPs [the false discovery rate (FDR) ≤ 0.05, fold change (FC) ≥ 1.5] were identified under different stresses. Comparative analyses of the proteome and transcriptome indicated that over 86% of DEPs did not show consistent trends with mRNA. In addition to consistent enrichment results under different stresses, the specific DEPs involved in saline-alkaline adaptation were primarily enriched in functions of homeostasis, hormone synthesis and reactions of defense response, complement activation and reproductive development. Meanwhile, a protein-protein interaction (PPI) network analysis of these specific DEPs indicated that the hub genes were ITGAX, MMP9, C3, F2, CD74, BTK, ANXA1, NCKAP1L, and CASP8. This study accurately isolated the genes that respond to stress, and the results could be helpful for understanding the physiological regulation mechanisms regarding salinity, alkalinity, and salinity-alkalinity interactions., (© 2022. The Author(s).)