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Natural gas hydrate (NGH) has been widely considered as an alternative to conventional oil and gas resources in the future energy resource supply since Trofimuk’s first resource assessment in 1973. At least 29 global estimates have been published from various studies so far, among which 24 estimates are greater than the total conventional gas resources. If drawn in chronological order, the 29 historical resource estimates show a clear downward trend, reflecting the changes in our perception with respect to its resource potential with increasing our knowledge on the NGH with time. A time series of the 29 estimates was used to establish a statistical model for predict the future trend. The model produces an expected resource value of 41.46 × 10 12 m 3 at the year of 2050. The statistical trend projected future gas hydrate resource is only about 10% of total natural gas resource in conventional reservoir, consistent with estimates of global technically recoverable resources (TRR) in gas hydrate from Monte Carlo technique based on volumetric and material balance approaches. Considering the technical challenges and high cost in commercial production and the lack of competitive advantages compared with rapid growing unconventional and renewable resources, only those on the very top of the gas hydrate resource pyramid will be added to future energy supply. It is unlikely that the NGH will be the major energy source in the future.

Background： The emergency department （ED） has a pivotal influence on the management of acute heart failure （AHF）, but dataconcerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics. ED management, and short- and long-term clinical outcomes of AHF. Methods： This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median （interquartile range） for the continuous variables, or as number （percentage） for the categorical variables. Results： The median age of the enrolled patients was 71 （58 79） years, and 46.84% wvere women. In patients with AHH coronary heart disease （43.27%） was the most common etiology, andmyocardium ischemia （30.22%） was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics （79.28%） and vasodilators （74.90%）. Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively. Conclusions： Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.

Autophagy is activated to maintain cellular energy homeostasis in response to nutrient starvation. However, au- tophagy is not persistently activated, which is poorly understood at a mechanistic level. Here, we report that turn- over of FoxO1 is involved in the dynamic autophagic process caused by glutamine starvation. X-box-binding protein- lu （XBP-lu） has a critical role in FoxO1 degradation by recruiting FoxO1 to the 20S proteasome. In addition, the phosphorylation of XBP-lu by extracellular regulated protein kinasesl/2 （ERK1/2） on Ser61 and Ser176 was found to be critical for the increased interaction between XBP-lu and FoxO1 upon glutamine starvation. Furthermore, knockdown of XBP-lu caused the sustained level of FoxO1 and the persistent activation of autophagy, leading to a significant decrease in cell viability. Finally, the inverse correlation between XBP-lu and FoxO1 expression agrees well with the expression profiles observed in many human cancer tissues. Thus, our findings link the dynamic process of autophagy to XBP-lu-induced FoxO1 degradation.

Electroencephalography is a sensitive indicator for measuring brain condition, and can reflect early changes in brain function and severity of cerebral ischemia. However, it is not yet known whether electroencephalography can predict development of post-cerebral infarc- tion depression. A total of 321 patients with ischemic stroke underwent electroencephalography and Hamilton Depression Rating Scale assessment to analyze the relationship between electroencephalography and post-cerebral infarction depression. Our results show that electroencephalograms of ischemic stroke patients with depression exhibit low-amplitude alpha activity and slow theta activity. In con- trast, electroencephalograms of ischemic stroke patients without depression show fast beta activity and slow delta activity. ＂Ihese findings confirm that low-amplitude alpha activity and slow theta activity can be considered as independent predictors for post-cerebral infarction depression.

Recently, radiation pressure acceleration （RPA） has been proposed and extensively studied, which shows that circularly polarized （CP） laser pulses can accelerate mono-energetic ion bunches in a phase-stable-acceleration （PSA） way from ultrathin foils. It is found that self-orgizing proton beam can be stably accelerated to GeV in the interaction of a CP laser with a planar target at 1022 W/cm2. A project called Compact LAser Plasma proton Accelerator （CLAPA） is approved by MOST in China recently. A prototype of laser driven proton accelerator （1 to 15 MeV/1 Hz） based on the PSA mechanism and plasma lens is going to be built at Peking University in the next five years. It will be upgraded to 200 MeV later for applications such as cancer therapy, plasma imaging and fast ignitiou for inertial confine fusion.

To explore a practical and sustainable development path for Funiu Mountain World Geopark, the authors classified geo-heritage landscapes into 4 main categories, 12 categories and 20 sub-categories, according to Technical Specifications for Compiling Planning of National Geopark and other research results. Comparative significance of its typical geological heritages in domestic and international geoscience research was analyzed; scientific value of the geological remains was evaluated together with aesthetic value, science popularization and education value, and tourism development value.

LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells. FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion. Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.

How future multiple tropical cyclone events (MTCEs) could change is crucial for effective risk management and ensuring human safety, however, it remains unclear. This study projects changes in MTCEs by 2050 in the major basins of the Northern Hemisphere using high‐resolution climate models. Results show a significant increase in the frequency and duration of MTCEs over the North Atlantic (NA), a notable decrease over the western North Pacific (WNP), and little change over the eastern North Pacific (ENP). The increase in MTCEs over the NA is concentrated in August–September, while the decrease over the WNP occurs in most months. In contrast, the ENP exhibits large yet insignificant seasonal variation, suggesting considerable uncertainty in this basin. Further analysis shows that mid‐level vertical motion dominates the MTCE changes over the WNP, while vertical wind shear contributes the most to the NA, which may be linked to future changes in tropical convection. Plain Language Summary Multiple tropical cyclone (TC) events (MTCEs), that is two or more TCs simultaneously occurring in the same basin, pose great risks to human society. This study projects future changes in the MTCEs by 2050, showing a significant increase over the North Atlantic (NA) while a robust reduction over the western North Pacific (WNP). The future MTCEs over the eastern North Pacific (ENP) show little change relative to the present climate. The increase of MTCEs over the NA is concentrated in August–September, while the decrease over the WNP occurs nearly from April to November. In contrast, there is large yet insignificant seasonal variation over the ENP, which could lead to little change in annual MTCEs. Furthermore, these changes are primarily attributed to the changes in local large‐scale dynamic conditions associated with tropical convection in future decades. Key Points The projection of future multiple tropical cyclone events (MTCEs) shows a decline in the western North Pacific (WNP) but a significant increase in the North Atlantic (NA) The mid‐level vertical motion dominates the MTCE changes over the WNP, while vertical wind shear is important for the NA Future monthly MTCEs show large yet insignificant seasonal variation over the eastern North Pacific, causing little trend in annual MTCEs

The spatio-temporal distribution of phytoplankton is influenced by physical and chemical factors such as water temperature, salinity, dissolved oxygen, Ph and nutrients. Nitrogen （N） and phosphorus （P） are essential for the growth of phytoplankton, which play a key role in determining the abundance of phyto- plankton. The species composition, community similarity and diversity of phytoplankton affect the structure and function of ocean ecosystems. Marine phytoplankton can be used as a rapid and sensitive indicator reflecting environmental changes. The offshore area of Qinhuangdao is a spawning and feeding ground for fish, shrimp and crabs. However, this region has experienced an increase in frequency of red tides as a result of pollution and marine development. In 2010, red tides began in late May and ended in August. We evaluated the species composition, spatio-temporal distribution, community structure of phytoplankton and the relationship be- tween phytoplankton abundance and environmental factors based on data collected from May to September in 2010. The phytuplankton , belonging to 96 species, 46 genera, were identified. The phytoplankton community was primarily composed of Bacillariophyta and Pyrrophyta. The majority were neritic species or eurythermal and euryhaline cosmopolitan species, while the remainders were oceanic warm species or polagic species. The dominant species included Noctiluca scintiUans, Rhizosolenia stolterfothii, Ghaetoceros spp. , Goscinodiscus spp. , and Bacteriastrum spp.. A total of 48 red tide causative species were observed, accounting for 50% of total phytoplankton species. The average phytoplankton abundance ranged from 6.20 × 10^4 cells/m^3 to 4 129.53 × 10^4 cells/ms. Abundance peaked in September 2010 and reached the lowest value in July 2010. The diversity index values were all greater than 1.0, suggested that biodiversity and community structure was healthy. The highest indices of community structure and biodiversity were observed in September, and biediversity was the lowest in June. The community similarity of phytuplankton was relatively high and the similarity range was 40% -70% from May to September. The community similarity of phytoplankton successively were September 〉 July 〉 August 〉 May 〉 June. The average abundance of phytoplankton had significant negative correlation with salinity（ r = - 0. 734, P 〈 0. 01, N = 37 ） and significant positive correlation with inorganic nitrogen nutrients （ r = 0. 753, P 〈 0. 01, N = 37 ）. We concluded that inorganic nitrogen was the primary factor explaining the increase in phytoplankton abundance during the survey period. A canonical correspondence analysis of the relationship between phytoplankton species and environmental factors indicated that N/P, salinity, nitrate, silicate, nitrite and water temperature were the main environmental factors influencing community structure of phytoplankton in Qinhuangdac waters.

Introduction Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapies. Human platelet lysate represents an efficient alternative to fetal bovine serum for clinical-scale expansion of MSCs. Different media used in culture processes should maintain the biological characteristics of MSCs during multiple passages. However, bone marrow-derived MSCs and adipose tissue-derived MSCs have not yet been directly compared with each other under human platelet lysate conditions. This study aims to conduct a direct head-to-head comparison of the biological characteristics of the two types of MSCs under human platelet lysate-supplemented culture conditions for their ability to be used in regenerative medicine applications. Methods The bone marrow- and adipose tissue-derived MSCs were cultured under human platelet lysate conditions and their biological characteristics evaluated for cell therapy (morphology, immunophenotype, colony-forming unit-fibroblast efficiency, proliferation capacity, potential for mesodermal differentiation, secreted proteins, and immunomodulatory effects). Results Under human platelet lysate-supplemented culture conditions, bone marrow- and adipose tissue-derived MSCs exhibited similar fibroblast-like morphology and expression patterns of surface markers. Adipose tissue-derived MSCs had greater proliferative potential than bone marrow-derived MSCs, while no significantly difference in colony efficiency were observed between the two types of cells. However, bone marrow-derived MSCs possessed higher capacity toward osteogenic and chondrogenic differentiation compared with adipose tissue-derived MSCs, while similar adipogenic differentiation potential wase observed between the two types of cells. There were some differences between bone marrow- and adipose tissue-derived MSCs for several secreted proteins, such as cytokine (interferon-γ), growth factors (basic fibroblast growth factor, hepatocyte growth factor, and insulin-like growth factor-1), and chemokine (stem cell-derived factor-1). Adipose tissue-derived MSCs had more potent immunomodulatory effects than bone marrow-derived MSCs. Conclusions Adipose tissue-derived MSCs have biological advantages in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory effects, but bone marrow-derived MSCs have advantages in osteogenic and chondrogenic differentiation potential and secreted proteins (stem cell-derived factor-1 and hepatocyte growth factor); these biological advantages should be considered systematically when choosing the MSC source for specific clinical application.