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Abstract Background Human cytomegalovirus (HCMV) is a herpesvirus that can infect various cell types and modulate host gene expression and immune response. It has been associated with the pathogenesis of various cancers, but its molecular mechanisms remain elusive. Methods We comprehensively analyzed the expression of HCMV pathway genes across 26 cancer types using the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases. We also used bioinformatics tools to study immune invasion and tumor microenvironment in pan-cancer. Cox regression and machine learning were used to analyze prognostic genes and their relationship with drug sensitivity. Results We found that HCMV pathway genes are widely expressed in various cancers. Immune infiltration and the tumor microenvironment revealed that HCMV is involved in complex immune processes. We obtained prognostic genes for 25 cancers and significantly found 23 key genes in the HCMV pathway, which are significantly enriched in cellular chemotaxis and synaptic function and may be involved in disease progression. Notably, CaM family genes were up-regulated and AC family genes were down-regulated in most tumors. These hub genes correlate with sensitivity or resistance to various drugs, suggesting their potential as therapeutic targets. Conclusions Our study has revealed the role of the HCMV pathway in various cancers and provided insights into its molecular mechanism and therapeutic significance. It is worth noting that the key genes of the HCMV pathway may open up new doors for cancer prevention and treatment.

Abstract Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host–guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed. Graphical Abstract

Marine Spatial Planning (MSP) is essential for optimizing marine resources allocation and resolving conflicts in sea use, but it is challenged by the complex and multi-functional nature of maritime resources. This study utilizes participatory methods, inductive reasoning, and overlay analysis to explore both theoretical and practical aspects of compatible marine utilization models. The paper begins by clarifying the logic of compatible sea use through marine functional zoning and identifying its core characteristics: quantity, spatial conflict, and impacts on natural attributes. Building on China’s national territorial spatial planning reforms and practical experiences, the paper introduces three major categories of compatible marine use models: development sequencing compatibility, spatial coexistence compatibility, and functional synergy compatibility. A compatibility discrimination matrix is developed to assess these models across different marine functional areas. Combined with the compatibility discrimination results, taking the marine and coastal spatial planning of Yantai City in China as a case study, the paper analyzes the compatibility demands and planning strategies within various marine functional areas. Finally, it evaluates the risks associated with each compatibility model and proposes targeted control strategies tailored to the specific features of each model and characteristics of sea use activities. The research findings highlight the positive role of compatible sea use models in promoting marine economic development, enhancing spatial efficiency, and mitigating sea use conflicts. However, these models also present varying potential risks, necessitating differentiated control strategies aligned with legal frameworks and specific sea use activities. The study offers valuable insights for MSP and contributes to the efficient utilization of marine resources and the advancement of marine spatial governance.

4-1BB agonists for cancer immunotherapy have shown good preliminary efficacy in clinical trials, but several of the first-generation 4-1BB agonistic antibodies entering the clinic have failed due to safety issues. Selenium nanoparticles (SeNPs) exhibit anti-inflammatory, anti-tumor, antioxidant, and immune-modulating properties. In addition, they have been shown to have detoxifying effects and prevent oxidative liver damage. In this study, we used an anti-4-1BB antibody in combination with SeNPs to evaluate the anti-lung cancer effects in in vitro and in vivo experiments and explore the underlying mechanisms by pathological analyses, quantitative PCR, and enzyme-linked immunoassay. We found that 5 μmol·L–1 anti-4-1BB antibody combined with 1 μmol·L–1 SeNPs increased the expression of IFN-γ and promoted the killing effects of peripheral blood mononuclear cells on Lewis lung carcinoma cells, with a lethality rate up to 56.88 %. Experiments in tumor-bearing mice showed that the tumor inhibition rate was 58.61 % after treatment with 3.5 mg/kg anti-4-1BB antibody combined with 0.25 mg/kg SeNPs, and the liver function index returned to normal. When the combined treatment was compared with the antibody treatment alone, detection of immune relevant factors demonstrated that the expression of FOXP3, IL-2, IL-12, and TNF-α in the spleen was downregulated, whereas the expression of IFN-γ in the spleen, serum, and tumor was upregulated, accompanied by increased Fas ligand expression in the tumor tissues. Based on these findings, we get the conclusion that anti-4-1BB antibody combined with SeNPs may alleviate the immunosuppression of regulatory T cells, promote the immune cell proliferation and metastasis to synergistically kill tumor cells. This combination also reduces the inflammatory damage to normal tissues and slows overstimulation of the splenic immune response.

Abstract Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age‐related osteoarthritis (OA). In the present study, highly lubricated and drug‐loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)‐modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti‐chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA‐seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO‐/P53 pathway. Notably, the intra‐articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age‐related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

ABSTRACTAs the melting of Arctic ice accelerates, the Arctic Passage continues to grow. Geopolitical influence has increased the strategic value of the Passage, attracting the attention of countries around the world. The geopolitical environment of the Arctic Passage is not affected by single factors but is instead determined by the combined effects of multiple factors. This paper analyses the multi-dimensional geopolitical environment factors of the Arctic Passage, and extracts features to construct a multi-dimensional geopolitical environment index system, which takes the Northern Sea Route as an example to construct the Arctic Passage Geo-potential Model, and quantitatively analyse the geo-potential for different states in Eurasia with the development and utilization of the Arctic Passage. This paper combines clustering and similarity analysis to explore the geo-spatial pattern of the Northern Sea Route, and identifies two interest groups that are represented by Russia and the United States. We further analyse the preference of stakeholders in the jurisdiction of the Northern Sea Route. This exploration addresses a gap in the current discussion on the Arctic Passage’s geopolitical environment, which only considers a single factor, and it helps to explore new methods and ideas that will assist the quantitative evaluation and pattern analysis of the Arctic Passage’s geopolitical environment, especially in Eurasia. Meanwhile, it will provide a comprehensive reference for the development and utilization of the Arctic Passage about the geopolitical environment patterns.

As two spatial geographic units that are both independent of each other and closely linked, the land and sea have complex spatial interactions. Therefore, China implements the land-sea coordination policy (LSC) needs to be approached from a more macroscopic, systematic and comprehensive perspective. Based on the interregional externality theory, this study takes the land-sea coordination policy of China as an example, and focuses on the interaction process and manifestation between land and sea, and then explores the connotation and realization path of LSC. Firstly, we delineated the spatial unit and analyzed the land-sea interactions (LSI) using Vensim software. Secondly, the characteristics and manifestations of LSI are summarized from the perspective of interregional externalities. Finally, this study elucidates the foundational concept of implementing LSC and further propose actionable pathways for promoting land and sea development in a coordinated way, aimed at offering supportive decision-making insights for achieving LSC within the broader framework of China’s territorial spatial planning. Initiating LSC implementation involves strategies such as source control, process management, and interaction interface optimization. Deepening LSC effectiveness entails strengthening positive interregional externalities while mitigating negative interregional externalities.

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear.Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches.Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound–target–pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models.Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis.Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

Based on the panel data of 11 coastal Provinces (Autonomous Region, Municipalities) of China from 2006 to 2016, this paper estimated the green total factor productivity of China's marine economy, and used the mediation effect model to investigate the influence mechanism of aquatic product trade and environmental regulation on green total factor productivity of marine economy. The results showed that at the overall level, the aquatic products trade had a significant direct promoting effect on the green total factor productivity of China's marine economy, and the mediation effect of environmental regulation on the green total factor productivity of marine economy was significant. In terms of trade mode, the mediation effect of environmental regulation had a positive impact on the green total factor productivity of marine economy, but it did not offset the inhibitory effect of aquatic product export trade, while aquatic product import trade could significantly promote the improvement of the green total factor productivity of marine economy. At the regional level, the promoting effect of aquatic product trade on the green total factor productivity of marine economy in northern coastal areas was higher than that in southern. The trade of aquatic products in northern coastal areas played a promoting role in environmental regulation, while the opposite was true in southern.

Bone protein is a significant secondary product of the meat industry, comprising a substantial quantity of protein. These proteins could be broken down through enzymatic hydrolysis to generate antioxidant peptides. This study aimed to produce antioxidant peptides from bovine bone extract by enzymatic hydrolysis utilizing Flavourzyme and Protamex by optimizing enzyme amounts and time using the Box–Behnken design. The final optimized conditions obtained through the model were as follows: The amount of Flavourzyme was 1,100 U, the amount of Protamex was 2,814 U, and the time was 3.77 (h). Bovine bone extract hydrolysate (BBEH) was purified stepwise using ultrafiltration membranes with molecular cutoffs of 5, 3, and 1 kDa. To assess the antioxidant capacity of the fractions, several methods were used, including radical scavenging activity “1,1-diphenyl-2-picrylhydrazyl (DPPH),” “2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS),” metal chelating activity (MCA), reducing power (RP), and thiobarbituric acid assay (TBA). The results indicated that the ultrafiltration fraction with a molecular weight of less than 1 kDa showed significant antioxidant activity, with 48, 42, and 50% inhibition rates for DPPH, ABTS, and metal chelating, respectively. Using size exclusion chromatography, the fraction with a molecular weight less than 1 kDa was further separated into five sub-fractions: Frac-I, Frac-II, Frac-III, Frac-IV, and Frac-V. Sub-Frac-III, which exhibits significant DPPH radical scavenging activity (55%) and a reducing power of 0.8 at 700 nm, was separated into six sub-sub-fractions using reversed-phase HPLC (RP-HPLC) based on molecular weight and hydrophobicity. The sub-sub-fraction with the highest value for DPPH radical scavenging activity was sub-Fra-III-6, which exhibited approximately 69.45% activity. The sub-Fra-III-6 was analyzed using LC–MS/MS, which identified two specific peptides: Ala-Pro-Phe with a mass of 333.12 Da and Asp-His-Val with a mass of 369.14 Da. These two peptides are likely the primary peptides that might have a crucial role in antioxidant capacity. It can be concluded that BBEH is a valuable source of natural antioxidants and has the potential to serve as a viable resource in the cultured meat industry.

Abstract Coastal soil carbon stock is critical owing to the coexistence of terrestrial and marine carbon sinks and undergoes drastic changes under complex factors. Here we conduct surface soil organic carbon (SOC) stock mapping in northern China’s coastal areas in 2020 and 2010 based on large-scale field survey, remote sensing, and land cover data. Our results indicate that a 100 m resolution is the optimum mapping resolution for its good simulation accuracy and precise spatial details. The surface SOC stock and density in 2020 increased by 39.19% and 37.82%, respectively, compared with those in 2010 under extensive ecological restoration. The SOC densities of forests, grasslands, croplands, wetlands, and built-up areas increased by 72.58%, 74.25%, 41.39%, 4.58%, and 26.30% from 2010 to 2020, respectively. The study determines the optimum mapping resolution and denotes the positive effects of ecological restoration on coastal soil carbon.

Chlorine ions in the air are a key factor in the corrosion of offshore buildings. Mastering the distribution law of the chloride ion settlement rate (RCl−) in three-dimensional (3D) spatiality is helpful in protecting offshore buildings. The self-designed “kite-hanging wet candle method” was used to collect chloride ions in the air, using ion chromatography to analyze the chloride ion concentration of the sample solution, and obtained the annual RCl− in the offshore atmosphere at different vertical heights, using the Pearson correlation coefficient method to analyze the influence of environmental factors on the RCl−. The results show that the RCl− has a significant linear relationship with temperature, relative humidity and wind speed. Among them, the RCl− is positively correlated with temperature and negatively correlated with wind speed and relative humidity. In the vertical height range of 10–100 m, the RCl− presents a “⊂”-shaped distribution. In the range of 10–30 m, the RCl− is mainly controlled by the impact of ocean spray; in the range of 30–80 m, the RCl− is mainly controlled by marine aerosols; and in the range of 80 m–100 m, the RCl− is mainly controlled by marine aerosols and wind speed. Under the influence of wind direction and wind speed, the RCl− of the windward side is higher than that of the leeward side at different monitoring points, which are close to the coastline and at a low vertical height. Studying the distribution of the RCl− in 3D spatiality can effectively prevent and reduce its impact on offshore buildings.

Influenced by climate change, significant alterations in vegetation phenology have been observed globally. Grassland phenology is highly sensitive to climate change. However, research on the variations in grassland phenology and its responses to seasonal climatic changes in arid and semi-arid regions remains scarce. This study, utilizing Solar-Induced Chlorophyll Fluorescence (SIF) data, meteorological station data, and grassland type data, employs trend analysis and time series analysis to explore the trends of seasonal climatic variability and the sensitivity response of grassland phenology in Xinjiang to seasonal climates. The findings reveal the following: (1) The region experiences more pronounced warming in winter and spring than in summer and autumn, with ground temperature increments outpacing those of air temperatures. The summer season registers the peak in precipitation volume and rate of increase, where mountainous zones accrue more rainfall compared to basins and plains. The distribution of sunshine duration is characterized by higher values in eastern areas than in the west and more in the plains than in mountainous regions, potentially due to escalating cloudiness, which has contributed to a diminishing trend in sunshine hours across Xinjiang over the past 20 years. (2) Over the past two decades, the perennial greening phase of Xinjiang grasslands has predominantly occurred in early May, showing an overall trend of occurring earlier by approximately 5.47 days per decade, while the yellowing phase mainly occurs at the end of September and the beginning of October, demonstrating a delaying trend (6.61 days/decade). The average length of the growing season is 145 days, generally showing a slightly increasing trend (11.97 days/decade). (3) In spring, the rise in air and ground temperatures, along with increased sunshine duration, all promote grassland growth, leading to an earlier greening phase. Conversely, in autumn, increases in air temperature, ground temperature, and sunshine duration can inhibit grassland growth, resulting in an earlier yellowing phase. Increased precipitation in summer and autumn can delay the yellowing phase and extend the length of the grassland growing season. This research provides new insights into the factors influencing large-scale grassland phenology and offers references for grassland adaptation to future climate changes.

Climate change is a key issue receiving increasing global attention. Coastal areas play an important role in mitigating climate change because of enormous potentials for carbon sequestration. Simulating and evaluating the carbon storage, increment, and value of coastal areas is of considerable importance in achieving carbon neutrality. In this study, the South Coast of Hangzhou Bay in China was selected as the study area. A three-class carbon pool system was established based on vegetation and soil and considering the coastline as the boundary for comprehensively revealing the carbon sink in coastal areas and accurately distinguishing the roles of different carbon pools. Then, the maps of carbon storage and increment were generated by integrating the field and remote sensing data through “from point to area” spatial simulations. An accounting list was developed for systematically summarizing, precisely quantifying, and visually displaying the carbon storage, increment, and value following the three-class carbon pools. Results indicated that the carbon sink showed a gradient change from sea to land. Salt marshes had low storage but high increment, whereas areas above the coastline had the opposite characteristics. The total carbon storage of vegetation and soil were 1417.94 Gg and 3359.07 Gg, respectively, and their carbon increments during 2011–2022 were 309.17 Gg/yr and 29.46 Gg/yr, respectively. The carbon storage per area of vegetation and soil were 27.66 Mg/ha and 53.09 Mg/ha, respectively, and their carbon increments during 2011–2022 were 6.03 Mg/(ha yr) and 0.47 Mg/(ha yr), respectively. As the main body of blue carbon, salt marshes have achieved distinctly higher increment than the adjacent areas above the coastline. The carbon increment per area of soil was lower than 1/5 of vegetation in salt marshes. Mudflats had low carbon increment but large storage because of the extensive area. Alien species had higher increment in terms of vegetation but similar one from the perspective of soil compared with native species, denoting the low decrease of soil carbon sink when eliminating alien species. Considering the hazard of alien species to the health of coastal wetlands, this indicates the feasibility and necessity to develop the high-quality carbon sink in the study area. The carbon sink value based on the carbon stored in the soil summed to 1.68 million yuan, and were increased by 33%, 7%, 48%, and 45% in scenarios of baseline scenario, economic development, ecological protection, and comprehensive optimization, respectively. The present study validated the high carbon increment and immense increase potential and provided an applicable system to normalize carbon mapping and accounting in coastal areas.

Promoting the inclusion of blue carbon in market trading is crucial for recognizing its value and protecting the marine ecological environment. However, China currently does not have an internationally influential blue carbon market trading platform, which hampers the transmission of supply and demand in the blue carbon market and prevents the realization of blue carbon value. In this study, we analyze the feasibility and necessity of establishing a trading mode for the blue carbon market in China. The introduction of futures trading in the blue carbon market’s trading mode allows for the use of futures pricing methods and multiple financial instruments to address the challenges of income cost mismatch in blue carbon project development. The paper also discusses key strategies for the development of China’s blue carbon market, including the creation of a blue carbon trading methodology, the improvement of preservation and appreciation mechanisms, and the establishment of a unified trading platform. These strategies aim to provide intellectual support and decision-making reference for the construction of the market.

This paper put forward the concept of the polar coastal zone and expounded the definition and scope of the polar coastal zone and coastline from the connotation of the coastal zone, and analyzed the particularity and importance of the polar coastal zone. Then, the survey and monitoring practices related to the polar coastal zone were summarized from the perspectives of survey and monitoring technology development and related disciplines. At the same time, the frontier issues of polar coastal zone investigation and research were analyzed, also the development direction of the survey and monitoring of the ecological elements of polar coastal zone resources were proposed, that was, to make full use of remote sensing and on-site detection methods to explore regional resources, environmental and ecological elements, temporal and spatial variation characteristics of large-scale and long-term polar coastlines at a low cost. Finally, the knowledge and technology system of "dual-source-data mining-spatial coupling simulation-regional comprehensive assessment-impact simulation and prediction" was constructed, which provided a scientific and technological support for China to build a policy system of the management and protection of regional resource and ecology in the polar coastal zone.

Urban zones across the world have experienced a massive expansion in recent decades, affecting food production, carbon storage, and biodiversity, and further threatening the realization of the UN’s Sustainable Development Goals (SDGs), particularly SDG 2 (zero hunger), 13 (climate action), and 15 (life on land). These enormous impacts are even more worrying in coastal areas where urbanization has been continuously accelerated. However, we have a poor understanding about the magnitude of the reduction in natural habitat and crucial ecosystem services over time caused by urban expansion in coastal areas. Here we chose the coastal zone of eastern China using a high-resolution dataset of land-use/land-cover (LULC) to investigate the influences of urban growth on natural habitat and crucial ecosystem services from 1990 to 2018. The results showed that: (1) urban growth in China's coastal region resulted in an estimated reduction of 2061.14 km2 in natural habitat, 154.13 Tg C in carbon storage, 1.67 Tg C in cropland net primary production, and 148.02 × 103 in habitat quality; (2) cropland net primary production loss resulted in a 1.34 × 106 tons loss of crop production, which is comparable to meeting the basic food demands of 3.35 million hungry people for a year; (3) the overall degradation of habitat caused by urban expansion reached 1838.28 km2, with grade 1 degradation area accounting for the largest portion (801.18 km2), representing 43.58% of the total degradation; (4) the primary contributor to carbon storage loss (63.83%) was the large-scale conversion of cropland to urban areas, while habitat quality loss and degradation were primarily due to the occupation of forests by urban expansion (42.62%). Our results suggest that effective land-use planning must be implemented to coordinate urban growth, natural habitat protection, and cropland displacement in rapidly urbanizing coastal areas.

Chickpea (Cicer arietinum L.), an annual plant of the family Fabaceae is mainly grown in semiarid and temperate regions. Among pulses, cultivated worldwide chickpeas are considered an inexpensive and rich source of protein. Chickpea is a good source of protein and carbohydrate, fiber, and important source of essential minerals and vitamins. The quality of protein is better among other pulses. Consumption of chickpeas is related to beneficial health outcomes. Dietary peptides from the protein of chickpeas gaining more attention. Peptides can be obtained through acid, alkali, and enzymatic hydrolysis. Among all these, enzymatic hydrolysis is considered safe. Various enzymes are used for the production of peptides, i.e., flavorzyme, chymotrypsin, pepsin, alcalase, papain, and trypsin either alone or in combinations. Chickpea hydrolysate and peptides have various bioactivity including angiotensin 1-converting enzyme inhibition, digestive diseases, hypocholesterolemic, CVD, antioxidant activity, type 2 diabetes, anti-inflammatory, antimicrobial, and anticarcinogenic activity. This review summarizes the nutritional composition and bioactivity of hydrolysate and peptides obtained from chickpea protein. The literature shows that chickpea peptides and hydrolysate have various functional activities. But due to the limited research and technology, the sequences of peptides are unknown, due to which it is difficult to conduct the mechanism studies that how these peptides interact. Therefore, emphasis must be given to the optimization of the production of chickpea bioactive peptides, in vivo studies of chickpea bioactivity, and conducting human study trials to check the bioactivity of these peptides and hydrolysate.

In recent years, the Norwegian government has been vigorously promoting deep-sea mining. Norway's geological research and exploration, technical equipment development, environmental policy making and other aspects have been in the forefront of the world, taking the lead in providing the possibility for the commercialization of deep-sea mining. Based on its strong engineering equipment foundation and profound legal and policy accumulation, Norwegian government has actively changed the path of deep-sea mining according to the current situation, and has found a balance between commercial development and environmental protection. Based on the comparative analysis between China and Norway, this paper put forward suggestions in four aspects: 1) Accelerate cooperation between deep sea industry, university and research, drive the development of emerging industries; 2) Construct industrial policies for deep-sea mining based on deep-sea law; 3) Strengthen the research on deep-sea environmental protection and create an environmentally friendly deep-sea development route; 4) Grasp the international mechanism and strive for the initiative of international rules; so as to realize "deep sea development" as soon as possible.

Realizing the optimization of land development is an important goal of domestic economic and social development in the 13th five year plan and even in the longer future, the land-sea space development is one of the strategic points to achieve high-quality development. Currently, with the continuous expansion of the depth and breadth of China′s marine development and utilization, the contradiction between the increasing demand for sea utilization and the scarcity of sea resources and space has become increasingly prominent, which has put forward new requirements for coordinating the relationship between marine resources development and environmental protection as well as improving the modernization level of marine utilization. It has become an inevitable requirement for the construction of a marine powerful country in the new era to strengthen the construction of marine ecological civilization, coordinate the development of land and sea, maintain the health of coastal ecosystem and realize the benign interaction between marine development and protection. In specific practice, the following five points should be paid attention to: Plan coastal zone development scientifically and optimize the pattern of coastal zone development and utilization; Strengthen the control of coastal space use, refine and deepen the control tasks and enrich the control toolbox; Improve the level of frugal and intensive utilization of marine resources to achieve scientific and efficient utilization; Improve the carbon sink capacity of marine ecosystem and promote the development of blue carbon sink in coastal zone; Strengthen the market-oriented allocation of marine production factors and promote the transformation of the marine economy into a quality-oriented economy.

Changes in land surface properties during urbanization have a significant impact on variations in precipitation. Little research has been carried out on spatial heterogeneity and influence strength of the driving factors of precipitation changes at different urbanization scales. Using a trend analysis and multi-scale geographically weighted regression, this study analysed the spatial heterogeneity and impact scale of driving factors of precipitation changes in 156 urban units in the Beijing-Tianjin-Hebei urban agglomeration region (Jing-Jin-Ji). In summer, RAD (radiation), RHU (relative humidity), WIN (wind speed), and POP (urban population density) were found to act on a small regional scale, AOD (aerosol optical depth) on a medium regional scale, and NDVI (normalized difference vegetation index), NLI (night time light intensity), UHI (urban heat island intensity), and AREA (urban area size) on a global scale. In winter, AREA and WIN acted on a medium regional scale, UHI on a large regional scale, and AOD, NDVI and NLI on a global scale. Across the whole year, NDVI and AREA had a medium regional impact and NLI a large regional one. Variations in natural factors, such as RAD and RHU, had a great influence on the spatial heterogeneity of precipitation changes, whereas human factors, such as NLI and UHI, had a small influence. In summer, AOD mainly affected Tangshan and Qinhuangdao in the northeast and Cangzhou in the southeast of the Jing-Jin-Ji. RHU and AREA primarily affected the cities of Handan and Xingtai. In winter, NLI, AREA, WIN, and UHI had significant effects in the cities of Handan and Xingtai, with AREA being the most important factor. In the Shijiazhuang-Hengshui area, RAD and NLI played a significant role; in the Beijing-Zhangjiakou-Chengde area, the most important factor affecting precipitation changes was the variation in POP. These results provide a scientific basis for flood disaster risk management in the Jing-Jin-Ji and the establishment of differentiated climate policies in different cities.

Identifying and quantifying the impacts of human activity on island plant diversity can help inform their management. Here, we examined the spatial pattern of plant diversity across 11 inhabited islands near to, but outside, the Yangtze River Estuary in the Shengsi Archipelago, China, that represent a diverse range of environmental conditions and human activity levels. We quantified six factors (island morphology, landscape, proximity, ecology, terrain, and soil) and 30 environmental indicators, with different levels of human influence. Regression and canonical correction analyses were used to determine the effects of various factors on the spatial distribution of trees, shrubs, and herbs at four regional scales: sample, island, sub-archipelago, and archipelago. We recorded 287 vascular species belonging to 201 genera at 93 sampling sites in Shengsi, of which 10 invasive alien species at 60 sampling sites were recorded. The plants showed a diverse spatial distribution pattern at the sampling site scale because of the synergistic influence of multiple environmental factors. From the sub-archipelago and island scales, area and isolation are the most critical factors affecting the richness and diversity of shrubs and herbs. The diversity and distribution of trees is highly dependent on human residents, and herbs show strong adaptability on barren landscapes. At the site scale, when collinearity among environmental factors was eliminated, we found that soil bulk density and salinity were critical factors driving the distribution of shrubs and herbs, respectively.

Rapid global changes are altering regional hydrothermal conditions, especially in ecologically vulnerable areas such as coastal regions, subsequently influencing the dynamics of vegetation growth. However, there is limited research investigating the response of vegetation in these regions to extreme climates and the associated time lag-accumulation relationships. This study utilized a combined approach of gradual and abrupt analysis to examine the spatiotemporal patterns of vegetation dynamics in the coastal provinces of China from 2000 to 2019. Additionally, we evaluated the time lag-accumulation response of vegetation to extreme climate events. The results showed that (1) extreme high temperatures and extreme precipitation had increased over the past two decades, with greater warming observed in high latitudes and concentrated precipitation increases in water-rich southern regions; (2) both gradual and abrupt analyses indicate significant vegetation improvement in coastal provinces; (3) significant lag-accumulation relationships were observed between vegetation and extreme climate in the coastal regions of China, and the time-accumulation effects were stronger than the time lag effects. The accumulation time of extreme temperatures was typically less than one month, and the accumulation time of extreme precipitation was 2–3 months. These findings are important for predicting the growth trend of coastal vegetation, understanding environmental changes, and anticipating ecosystem evolution.

The annual plan for marine space utilization is one of the stipulation duties of Ministry of Natural Resources, and it is an effective measure to deal with the shortage of marine space resources, the inefficiency of space utilization and the damage to the marine resource environment. Since the reform of the ecological civilization system, China has further strengthened the control of the total amount and scale of natural resources, strengthened the binding role of the natural shore line retention rate, and attached importance to the restoration of land space and the disposal of historical problems left over from reclamation. Based on the reform spirit of natural resource management above this, the study proposed the concept of the annual plan for ocean marine space utilization, made a judgment and analysis of the control type of the annual plan for marine space utilization in the light of the classification of sea use, and constructed the index system of the annual plan for the use of marine space.

To promote the balanced and sustainable development of resources exploitation and environmental protection in international seabed area, improve the discourse power and execution of China in relevant field, this paper systematic analyzed the development characteristics of international seabed area environmental protection system and its existing problems. The paper also summarized China′s practice and expectation of environment protection in international seabed area, and put forward countermeasures and suggestions. The research results showed that the environmental protection system of international seabed area had experienced 4 stages: germination, formation, development and enrichment, and development features of which mainly included the renewal of the concept, the perfection of principles, and the definition of obligations and responsibilities. However, there were still some problems in the current environmental protection clauses in Exploitation of Mineral Resources in the Area, the environmental protection rights and responsibilities of non-contracting states to the United Nations Convention on the Law of the Sea, and the balance of interests. China actively practiced environmental protection of international seabed area by participating in the formulation of relevant systems and exploring domestic laws. In the future, formulating environmental protection standards, exploring policy environment and balancing the interest of all parties can improve the environmental protection system of international seabed area. China should continue to participate in the formulation of relevant international legislation system and improve domestic marine environmental protection system.

Pancreatic cancer (PC) is a malignant tumor with high malignancy that is difficult to diagnose and treat. PC is a major medical problem because of its low early diagnosis rate, high surgical mortality rate, low cure rate, and expensive related testing cost. Therefore, the significance of finding new markers for PC is self-evident. Semaphorins (Semas) have been shown to affect angiogenesis and lymphangiogenesis and can also directly affect the behavior of tumor cells. The expression and related action targets of its family members on PC are summarized in this review.

Abstract Background To develop and validate a risk prediction nomogram based on a deep learning convolutional neural networks (CNN) model and epidemiological characteristics for lung cancer screening in patients with small pulmonary nodules (SPN). Methods This study included three data sets. First, a CNN model was developed and tested on data set 1. Then, a hybrid prediction model was developed on data set 2 by multivariable binary logistic regression analysis. We combined the CNN model score and the selected epidemiological risk factors, and a risk prediction nomogram was presented. An independent multicenter cohort was used for model external validation. The performance of the nomogram was assessed with respect to its calibration and discrimination. Results The final hybrid model included the CNN model score and the screened risk factors included age, gender, smoking status and family history of cancer. The nomogram showed good discrimination and calibration with an area under the curve (AUC) of 91.6% (95% CI: 89.4%–93.5%), compare with the CNN model, the improvement was significance. The performance of the nomogram still showed good discrimination and good calibration in the multicenter validation cohort, with an AUC of 88.3% (95% CI: 83.1%–92.3%). Conclusions Our study showed that epidemiological characteristics should be considered in lung cancer screening, which can significantly improve the efficiency of the artificial intelligence (AI) model alone. We combined the CNN model score with Asian lung cancer epidemiological characteristics to develop a new nomogram to facilitate and accurately perform individualized lung cancer screening, especially for Asians.

Cobalt-based superalloys have good service performance in environments where nickel-based superalloys cannot work. A number of the studies focused on mechanical properties, microstructure evolution and hot deformation characteristics, but studies of meta-dynamic recrystallization (MDRX) behavior remain lacking. The MDRX behavior of GH5188 superalloy was investigated using two-stage hot compression tests. The kinetic model and grain size model were built to better describe the MDRX process. The good agreement between the predicted values and experimental values was verified. The effects of holding time, temperature, strain rate and intervals time on MDRX microstructure evolution were analyzed and discussed. The results show that by descending order of correlation was: intervals time, holding time, temperature and strain rate. The MDRX fraction and grain size increase with the increase of holding time, temperature, strain rate and intervals time. At low temperatures, MDRX grains grew up in the form of bowed grain boundaries. At high temperatures, the growth of MDRX grains was often accompanied by the generation of twinning bands. Twins were formed in the process of grain growth.

The evaluation of island carrying capacity is the premise for conducting the island spatial planning and can contributes to guiding island ecological conservation and socioeconomic developments. In this study, the island carrying capacities were evaluated for the three major development types, namely, ecological resource, agricultural production, and urban construction, based on the quantity and quality. The occupancy and vacancy rates of island carrying capacity were measured in different scenarios. Miaodao Archipelago and Dongtou Archipelago in China were selected as the study area to demonstrate the evaluation. The former is constituted all by spatially isolated rocky islands, while the latter is featured by the coexistence of the sandy and rocky islands and the connection with the mainland by bridges. The results indicated the high variances of occupancy and vacancy rates of island carrying capacity at multiple spatial scales. Across the two archipelagos, climate conditions, island composition, and spatial connections with the mainland controlled the spatial variance at this scale. For different types of islands, the sandy island presented distinctly higher occupancy and vacancy rates for agricultural production than the rocky islands. At the single island scale within the same archipelago, the developments of agricultural production and urban construction distinctly increased with the increase in the island area. The dependency of island constructions on the external world in Dongtou Archipelago was higher than that in Miaodao Archipelago. Meanwhile, the difference in traffic conditions between the two archipelagos did not distinctly influence the food dependency on the external world. Then, practical suggestions in terms of quantity control and quality promotion were proposed to improve the island carrying capacity.

Abstract High‐volume evacuations, disruptions to the supply chain, and fuel hoarding from non‐evacuees have led to localized fuel shortages lasting several days during recent hurricanes. While news reports mention fuel shortages in past hurricanes, the crowdsource platform Gasbuddy has quantified the fuel shortages in the recent hurricanes. The analysis of this fuel shortage data suggested fuel shortages exhibited characteristics of an epidemic. Here, a Susceptible‐ Infected‐Recovered (SIR) epidemic model is developed to study the evolution of fuel shortage during a hurricane evacuation. Additionally, we apply optimal control theory to identify an effective intervention strategy. The study found a linear correlation between traffic demand during the evacuation of Hurricane Irma and the resulting fuel shortage data. This correlation is used in conjunction with the Statewide Regional Evacuation Study Program (SRESP) surveys to estimate the evacuation traffic and fuel shortages for potential hurricanes affecting south Florida. Results indicate that evacuation of Miami‐Dade County in the event of a Category‐3 hurricane landfall in the region, could lead to fuel shortages in up to 90% of the local refuelling stations. The model indicates that this reduces to 28% by providing relief to 75% of the gas stations during the first two days of the evacuation.

Abstract Background Transposable elements (TE) account for more than 50% of human genome. It has been reported that some types of TEs are dynamically regulated in the reprogramming of human cell lines. However, it is largely unknown whether some TEs in Macaca mulatta are also regulated during the reprogramming of cell lines of monkey. Results Here, we systematically examined the transcriptional activities of TEs during the conversion of Macaca mulatta fibroblast cells to neuroepithelial stem cells (NESCs). Hundreds of TEs were dynamically regulated during the reprogramming of Macaca mulatta fibroblast cells. Furthermore, 48 Long Terminal Repeats (LTRs), as well as some integrase elements, of Macaca endogenous retrovirus 3 (MacERV3) were transiently activated during the early stages of the conversion process, some of which were further confirmed with PCR experiments. These LTRs were potentially bound by critical transcription factors for reprogramming, such as KLF4 and ETV5. Conclusion These results suggest that the transcription of TEs are delicately regulated during the reprogramming of Macaca mulatta fibroblast cells. Although the family of ERVs activated during the reprogramming of fibroblast cells in Macaca mulatta is different from those in the reprogramming of human fibroblast cells, our results suggest that the activation of some ERVs is a conserved mechanism in primates for converting fibroblast cells to stem cells.

Abstract An efficient and safe evacuation of passengers is important during emergencies. Overcapacity on a route can cause an increased evacuation time. Decision making is essential to optimally guide and distribute pedestrians to multiple routes while ensuring safety. Developing an optimal pedestrian path planning route while considering learning dynamics and uncertainties in the environment generated from pedestrian behaviour is challenging. While previous evacuation planning studies have focused on either simulation of realistic behaviours or simple route planning, the best route decisions with several intermediate decision‐points, especially under real‐time changing environments, have not been considered. This paper develops an optimal navigation model providing more navigation guidance for evacuation emergencies to minimize the total evacuation time while considering the influence of other passengers based on the social‐force model. The integration of the optimal navigation model was ultimately able to reduce the overall evacuation time of multiple scenarios presented with two different overall pedestrian totals. The overall maximum evacuation time savings presented was 10.6%.

Nanomedicines play an important role in cancer therapy; however, some drawbacks including unsatisfactory efficacy and side effects arising from indiscriminate drug release retard their clinical applications. Although functionalization of nanomedicines through covalent interactions can improve the pharmacokinetics and efficacy of the loaded drugs, complicated and tedious synthesis greatly limits the exploration of multifunctional nanoparticles. Herein, we utilize a supramolecular strategy to design a nanomedicine for targeted drug delivery through cucurbit[8]uril-based host–guest ternary complexation and successfully prepare prostate-specific membrane antigen (PSMA)-targeted supramolecular nanoparticles encapsulating doxorubicin (DOX). In vitro studies exhibit targeted modification via noncovalent enhance anticancer efficiency of DOX due to the increased cell uptake on account of receptor-mediated endocytosis. This design provides a new strategy for the development of sophisticated drug delivery systems and holds perspective potentials in precise cancer treatments.

Mutations that affect Treg cell function can cause lethal autoimmunity, but whether correcting these mutations can reverse established disease is unclear. Here, the authors correct Treg cell-specific Brg1 mutation in a minor fraction of Treg cells, which supercharges these cells to rescue mice from otherwise fatal IPEX-like autoimmunity.

Abstract Background Ophiorrhiza pumila, belonging to the genus Ophiorrhiza (Rubiaceae), is distributed throughout tropical and subtropical Asia. In this study, we evaluated for the first time the anti-proliferation and anti-migration effects of ethanol extract of O. pumila (OPE) on HepG2 and SMMC-7721 cells, and explored the related mechanism. Methods OPE was prepared by percolation with 95% ethanol and its main compounds were analyzed by HPLC-MS2. The anti-proliferation effect of OPE was evaluated by the CCK-8 assay and colony formation assay. Cell cycle distribution, apoptosis, and reactive oxygen species (ROS) level were detected by flow cytometry. Migration and invasion abilities were detected by Transwell migration/invasion assays. The expression of correlated proteins was determined using western blotting. Results A total of 5 tentative compounds were identified from OPE, including pumiloside, deoxypumiloside, camptothecin, aknadinine, and β-stigmasterol. OPE displayed strong cytostatic effects on HepG2 and SMMC-7721 cells. OPE induced G2/M phase cell cycle arrest, increased apoptosis, and augmented ROS production in these cell lines. In addition, OPE possessed a significant inhibition on cell migration and invasion by reduction of MMP-9 and MMP-2 expression. Moreover, OPE significantly suppressed the phosphorylation of p65. Conclusions Our data showed that OPE suppresses liver cancer cell proliferation and migration, which is possibly involved with the inhibition of the NF-κB pathway.

This study seeks to provide a basic approach to fulfill the spatial visualization of geopolitical environmental factors required for the navigation of vessels in the Arctic. Multi-dimensional geopolitical environmental factors of the Arctic Passage are analyzed and classified into geopolitics, geoeconomics, geo-military, geoculture, and laws and regulations related to geography. Their characteristics are extracted to form an attribute information table matching spatial layers. Based on the information category and basic characteristics, the spatial match method is applied and connected with the spatial layers to examine the spatial point, polyline, and polygon. According to the qualitative description, the study extracted the quantitative indicators for the following spatial-temporal pattern analysis. The standard deviational ellipse is used to analyze the spatial-temporal patterns and trends of the geopolitical environmental indicators of the Arctic Passage in the Arctic and Northeast Asia. The expansion and contraction of geoinformation coexist in the countries surrounding the Arctic Passage. The spatial-temporal changes indicate that the Arctic channel has a great economic impact on the Nordic countries and Northeast Asia, especially the coastal areas of China and Japan. The characteristic extraction and spatial match of the geopolitical environment provide integrated Arctic geoinformation inquiry and services for the diplomatic, administrative, and legal preparations required for Arctic navigation. Therefore, the geospatial analysis conducted provides scientific support and a basis for the geographical distribution and developing trends of visualization and spatial-temporal pattern in Arctic navigation. The results of this research will help decision-makers to make a comprehensive judgment on governance related to the sustainable development of the Arctic Passage.

Purpose – After the 19th CPC national congress, Chinese Communist Party and the government put forward higher requirements for the development of coastal zones, and it is urgent to establish an integrated coastal zone management system, so as to better guarantee the construction of maritime powers and regional coordinated development. The purpose of this paper is to aim at re-examining and positioning China’s integrated coastal zone management. Design/methodology/approach – This paper sorts out the current situation of coastal zone resources and environment, summarizes prominent problems and clarifies the path of comprehensive management of coastal zone based on the typicality and comprehensiveness of coastal ecosystem. Findings – Coastal zone is a typical area of “life community shared among mountains, rivers, forests, fields, lakes and grass.” However, there are three prominent problems at present, namely, separation between land and sea, separation among industry sectors and separation among administrative jurisdictions. Coastal zone planning and legislation are important measures to realize the comprehensive management of coastal zone. Originality/value – This paper puts forward some suggestions on the reform of coastal zone management from the perspective of planning and legislation.

Digital soil mapping (DSM) has been developed for decades and aims to accurately simulate the soil factors with low cost. However, it still cost considerably in coastal wetlands because of the high difficulty in field survey. A zonal simulation approach was proposed for decreasing the cost of field survey in the premise of high accuracy for soil organic carbon stock mapping in coastal wetlands, and Chongming Island, an important estuarine wetland in China, was used to demonstrate the study. A subzone with an area proportion lower than 20% was identified based on the typicalness of land surface characteristics and soil influencing factors for the whole study area. Entire and zonal simulations were conducted using abundant predictors sourced from remote sensing, partial least square regression, and 10-fold cross validation. The results revealed that root mean squared errors of entire and zonal simulations were 1.70 g/kg and 1.95 g/kg, respectively, which were in a low level compared with those in previous studies and indicated the high simulation accuracy. The zonal simulation exhibited a slightly lower accuracy than the entire simulation, while considerably decreased the cost by more than 50%. The decrease in the cost showed a much more practical significance than the increase in the accuracy in areas with high difficulty in field survey, and the geographical integrity and continuity of the whole study area, the typicalness of the selected subzone, and the spatial extent were the three key points when promoting the zonal simulation in DSM. The soil organic carbon stock in the study area was generally high in areas with good vegetation condition, low soil salinity, complex landscape configuration, and long distances from the sea. Human activities and the resulting landscape fragmentation have been the dominant factor that drives the spatial pattern of soil organic carbon stock.

Arsenic (III) is a toxic contaminant in water bodies, especially in drinking water reservoirs, and it is a great challenge to remove it from wastewater. For the successful extraction of arsenic (III), a nanocomposite material (ZnO–CuO/g–C3N4) has been synthesized by using the solution method. The large surface area and plenty of hydroxyl groups on the nanocomposite surface offer an ideal platform for the adsorption of arsenic (III) from water. Specifically, the reduction process involves a transformation from arsenic (III) to arsenic (V), which is favorable for the attachment to the –OH group. The modified surface and purity of the nanocomposite were characterized by SEM, EDX, XRD, FT–IR, HRTEM, and BET models. Furthermore, the impact of various aspects (temperatures, pH of the medium, the concentration of adsorbing materials) on adsorption capacity has been studied. The prepared sample displays the maximum adsorption capacity of arsenic (III) to be 98% at pH ~ 3 of the medium. Notably, the adsorption mechanism of arsenic species on the surface of ZnO–CuO/g–C3N4 nanocomposite at different pH values was explained by surface complexation and structural variations. Moreover, the recycling experiment and reusability of the adsorbent indicate that a synthesized nanocomposite has much better adsorption efficiency than other adsorbents. It is concluded that the ZnO–CuO/g–C3N4 nanocomposite can be a potential candidate for the enhanced removal of arsenic from water reservoirs.

Sandy islands suffer multiple external disturbances and thus experience drastic temporal ecological changes, and the two parts, that is, the states of essential components (Part 1) and the resilience under multiple disturbances (Part 2), are both indispensable to the sandy island ecosystem health. In this study, a model for the sandy island ecosystem health was established by integrating the two parts. In Part 1, the states were measured following the framework of vegetation, soil, and landscape, and a total of 12 factors in the three components were adopted. In Part 2, three typical disturbances, namely, geomorphological change, soil salinization, and human influence, were identified, and the resilience across different time intervals was measured by clarifying the intrinsic correlations between the components and disturbances. A sandy island ecosystem health index (SIEHI) was proposed based on the two parts, and Chongming Island was selected as the study area to demonstrate the model. The results indicated that the SIEHI continuously increased from 1988 to 2017, denoting the good effects of “Eco-Island construction” on Chongming Island. In different components and factors, the vegetation and soil components contributed more than the landscape component to the sandy island ecosystem health, and vegetation quality and soil carbon/nitrogen were the factors that made the most contributions. In different disturbances, the human influence played a major role in driving the spatiotemporal variations of the sandy island ecosystem health. Farming and building construction contributed the most and accounted for 37.12% and 35.59% of the total human influence, respectively, while traffic development exerted the highest influence per area. Then, influence coefficients of different human activities on the sandy island were determined, and measures for different functional zones were proposed for balancing the protection and development and achieving the sandy island ecosystem-based management.

Urbanization has a significant influence on precipitation, but existing studies lack the spatial and temporal heterogeneity analysis of its impact on precipitation in urban areas at different levels. This study investigates the spatial heterogeneity of precipitation and the influencing factors on six dimensions in 156 urban areas in the Beijing–Tianjin–Hebei urban agglomeration from 2000 to 2018, utilizing a mixed-methods analytical approach. The results show that the change in the natural factor layer caused by urbanization was the most important factor, affecting urban precipitation variation in summer and over the whole year, accounting for 34.5% and 10.7%, respectively. However, the contribution of the urban thermal environment in summer cannot be ignored, and the change in the urban thermal environment caused by human activities in winter is an important influencing factor. When considering the optimal combination of factors, relative humidity was shown to be significant in the spatial variations in precipitation during summer, which contributed 26.2%, followed by human activity as indicated by night-time light intensity. Over the whole year, aerosol optical depth makes the substantial contribution of 21.8% to urban precipitation change. These results provide benchmarks for improving the adaptability of urban-environment change and urban planning in the context of urbanization.

Abstract Background Hepatocellular carcinoma (HCC) is a malignant tumor that threatens global human health. High PKM2 expression is widely reported in multiple cancers, especially in HCC. This study aimed to explore the effects of PKM2 on global gene expression, metabolic damages, patient prognosis, and multiple transcriptional regulation relationships, as well as to identify several key metabolic genes and screen some small-molecule drugs. Methods Transcriptome and clinical HCC data were downloaded from the NIH-GDC repository. Information regarding the metabolic genes and subsystems was collected from the Recon 2 human metabolic model. Drug-protein interaction data were obtained from the DrugBank and UniProt databases. We defined patients with PKM2 expression levels ≥11.25 as the high-PKM2 group, and those with low PKM2 expression (

On December 17, 2020, the Chang’e-5 reentry spacecraft landed safely and brought back the lunar sample without damage. This paper describes the recovery system that has critically contributed to the scientific success of the Chang’e-5 missions and presents the technical requirements and constraints of the recovery system for the Chang’e-5 reentry spacecraft and discusses the design process of the recovery system, including the system composition, working procedure, and some other key aspects. Finally, the ground cover rejection tests and air drop and flight tests were carried out to confirm the design configuration. The results showed that the Chang’e-5 reentry spacecraft recovery system was designed correctly, and its functions and performances met the design requirements. A breakthrough in the recovery technology of the reentry spacecraft was achieved for Chinese first lunar sample-return mission.

Soil total organic carbon (TOC) and total nitrogen (TN) in estuarine areas show distinct heterogeneities in horizontal and vertical distributions due to complex influencing factors, and clarifying the horizontal and vertical distributions and their influencing factors is of great significance. In this study, the eastern Chongming Island in the Yangtze River estuary in China was selected as the study area, and the horizontal and vertical distributions of soil TOC and TN in different layers of 0–20 cm, 20–40 cm, and 40–60 cm were exhibited in maps and analyzed in different community types. Then, a total of 17 potential factors in aspects of soil, vegetation, atmosphere, landscape, and position were adopted and their single and synergistic effects on the spatial patterns of TOC and TN were identified from different perspectives. Results indicated that the mean values of TOC and TN in the entire study area decreased from surface to bottom layers. TOC and TN showed distinct spatial heterogeneities in different sampling sites and community types; they were generally high in the inner part and low in the alongshore areas in surface soils and showed opposite spatial characteristics in bottom soils; and woodland showed the highest TOC and TN in surface soils and the lowest values in bottom soils of different community types. TOC and TN in different layers, as well as the variations of TOC and TN across layers, exhibited specific and different spatial patterns under the complex factors. In soil factors, pH and available phosphorus showed the closest correlations with TOC and TN in different layers; in land surface factors, plant diversity and growth condition contributed the most to the horizontal distribution while plant growth condition and bare soil index exerted the highest influences on the vertical distribution.

Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.

Hurricanes are powerful agents of destruction with significant socioeconomic impacts. A persistent problem due to the large-scale evacuations during hurricanes in the southeastern United States is the fuel shortages during the evacuation. Computational models can aid in emergency preparedness and help mitigate the impacts of hurricanes. In this paper, we model the hurricane fuel shortages using the SIR epidemic model. We utilize the crowd-sourced data corresponding to Hurricane Irma and Florence to parametrize the model. An estimation technique based on Unscented Kalman filter (UKF) is employed to evaluate the SIR dynamic parameters. Finally, an optimal control approach for refueling based on a vaccination analogue is presented to effectively reduce the fuel shortages under a resource constraint. We find the basic reproduction number corresponding to fuel shortages in Miami during Hurricane Irma to be 3.98. Using the control model we estimated the level of intervention needed to mitigate the fuel-shortage epidemic. For example, our results indicate that for Naples- Fort Myers affected by Hurricane Irma, a per capita refueling rate of 0.1 for 2.2 days would have reduced the peak fuel shortage from 55% to 48% and a refueling rate of 0.75 for half a day before landfall would have reduced to 37%.

There is direct evidence for the spread of infectious diseases such as influenza, SARS, measles, and norovirus in locations where large groups of people gather at high densities e.g. theme parks, airports, etc. The mixing of susceptible and infectious individuals in these high people density man-made environments involves pedestrian movement which is generally not taken into account in modeling studies of disease dynamics. We address this problem through a multiscale model that combines pedestrian dynamics with stochastic infection spread models. The pedestrian dynamics model is utilized to generate the trajectories of motion and contacts between infected and susceptible individuals. We incorporate this information into a stochastic infection dynamics model with infection probability and contact radius as primary inputs. This generic model is applicable for several directly transmitted diseases by varying the input parameters related to infectivity and transmission mechanisms. Through this multiscale framework, we estimate the aggregate numbers and probabilities of newly infected people for different winding queue configurations. We find that the queue configuration has a significant impact on disease spread for a range of infection radii and transmission probabilities. We quantify the effectiveness of wall separators in suppressing the disease spread compared to rope separators. Further, we find that configurations with short aisles lower the infection spread when rope separators are used.

Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1) expression in mouse ESCs. Knockdown or knockout of Lef1 partially mimics the self-renewal-promoting effect of MEK inhibitors. Moreover, depletion of both Tcf3 and Lef1 enables maintenance of undifferentiated mouse ESCs without exogenous factors, cytokines or inhibitors. Transcriptome resequencing analysis reveals that LEF1 is closely associated with endoderm specification in ESCs. Thus, our study adds support to the notion that the key to maintaining the ESC ground state is to shield ESCs from differentiative cues.