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Yiqi Yangyin Decoction (YYD) is a classic traditional Chinese medicine (TCM) formulation to treat lung cancer in clinic. Nevertheless, the active ingredients, key targets, and molecular mechanisms for YYD are still poorly understood. This study is focused on elucidating the pharmacological mechanism of YYD in non-small-cell lung cancer (NSCLC) by using a combined network pharmacology approach and biological experiment validation. Online bioinformatics tools showed that 40 bioactive compounds and 229 putative targets of YYD were associated with anti-NSCLC activity. Protein-Protein Interaction (PPI) network demonstrated AKT1, SRC, JUN, TP53, and EGFR as the top five key targets for YYD against NSCLC. Through enrichment analysis, YYD was found to affect cell proliferation and apoptosis in NSCLC possibly by PI3K-AKT signaling. Molecular docking confirmed a strong binding between the main compounds (quercetin or luteolin) and EGFR. As demonstrated by CCK-8, EdU, and colony formation assays, we found a significant inhibition of YYD on cell proliferation. Moreover, YYD treatment induced cell cycle arrest by affecting p53, p21, and cyclin D1 expression. YYD administration enhanced apoptosis by changing the expression of cleaved caspase-3, Bax, and Bcl-2. Mechanistically, YYD resulted in a significant inactivation of EGFR-PI3K-AKT signaling. Furthermore, EGFR activator significantly reversed YYD-mediated proliferation inhibition and apoptosis. YYD also showed an inhibitory effect on tumor growth in mice. Together, YYD might target the EGFR-PI3K-AKT pathway to repress NSCLC progression. [ABSTRACT FROM AUTHOR]

Numerous high‐elevation alpine plants of the Qinghai‐Tibet Plateau (QTP) also have disjunct distribution in adjacent low‐altitude mountains. The out‐of‐QTP versus into‐the‐QTP hypothesis of alpine plants provide strong evidence for the highly disputed assumption of the massive ice sheet developed in the central plateau during the Last Glacial Maximum (LGM). In this study, we sequenced the genomes of most known populations of Megadenia, a monospecific alpine genus of Brassicaceae distributed primarily in the QTP, though rarely found in adjacent low‐elevation mountains of north China and Russia (NC‐R). All sequenced samples clustered into four geographic genetic groups: one pair was in the QTP and another was in NC‐R. The latter pair is nested within the former, and these findings support the out‐of‐QTP hypothesis. Dating the four genetic groups and niche distribution suggested that Megadenia migrated out of the QTP to adjacent regions during the LGM. The NC‐R group showed a decrease in the effective population sizes. In addition, the genes with high genetic divergences in the QTP group were mainly involved in habitat adaptations during low‐altitude colonization. These findings reject the hypothesis of development massive ice sheets, and support glacial survival of alpine plants within, as well as further migration out of, the QTP. [ABSTRACT FROM AUTHOR]

To compare the micropore structure of marine-continental transitional shale with marine shale, organic geochemical, field emission scanning electron microscopy, and low-temperature nitrogen adsorption experiments were conducted on shale samples from the Shanxi Formation in the eastern Ordos Basin and the Longmaxi Formation in the southern Sichuan Basin. The results show that Shanxi Formation shale has a smaller specific surface area and pore volume than Longmaxi Formation shale; therefore, the transitional shales fail to provide sufficient pore spaces for the effective storage and preservation of natural gas. Both the transitional and marine shales are in an overmature stage with high total organic carbon content, but they differ considerably in pore types and development degrees. Inorganic pores and fractures are dominantly developed in transitional shales, such as intragranular pores and clay mineral interlayer fractures, while organic nanopores are rarely developed. In contrast, organic pores are the dominant pore type in the marine shales and inorganic pores are rarely observed. The fractal analysis also shows that pore structure complexity and heterogeneity are quite different. These differences were related to different organic types, i.e., type I of marine shale and type III of transitional shale. Marine Longmaxi shale has experienced liquid hydrocarbon cracking, gas generation, and pore-forming processes, providing good conditions for natural gas to be preserved. However, during the evolution of transitional Shanxi shale, gas cannot be effectively preserved due to the lack of the above evolution processes, leading to the poor gas-bearing property. The detailed comparison of the micropore structure between the transitional and marine shales is of great importance for the future exploitation of marine-continental transitional shale gas in China. [ABSTRACT FROM AUTHOR]

The effect of clay minerals on the methane adsorption capacity of shales is a basic issue that needs to be clarified and is of great significance for understanding the adsorption characteristics and mechanisms of shale gas. In this study, a variety of experimental methods, including XRD, LTNA, HPMA experiments, were conducted on 82 marine shale samples from the Wufeng–Longmaxi Formation of 10 evaluation wells in the southern Sichuan Basin of China. The controlling factors of adsorption capacities were determined through a correlation analysis with pore characteristics and mineral composition. In terms of mineral composition, organic matter (OM) is the most key methane adsorbent in marine shale, and clay minerals have little effect on methane adsorption. The ultra-low adsorption capacity of illite and chlorite and the hydrophilicity and water absorption ability of clay minerals are the main reasons for their limited effect on gas adsorption in marine shales. From the perspective of the pore structure, the micropore and mesopore specific surface areas (SSAs) control the methane adsorption capacity of marine shales, which are mainly provided by OM. Clay minerals have no relationship with SSAs, regardless of mesopores or micropores. In the competitive adsorption process of OM and clay minerals, OM has an absolute advantage. Clay minerals become carriers for water absorption, due to their interlayer polarity and water wettability. Based on the analysis of a large number of experimental datasets, this study clarified the key problem of whether clay minerals in marine shales control methane adsorption. [ABSTRACT FROM AUTHOR]

2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients' target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis. [ABSTRACT FROM AUTHOR]

High resolution multibeam bathymetry revealed the occurrence of numerous craterlike depressions, so-called pockmarks, in the sea floor of the North Yellow Sea Basin (NYSB). To investigate whether these pockmarks are related to any type of fluid flow or gas seepage from subsurface stratum, acoustic survey and box samplings were conducted in a selected area containing several typical pockmarks. This allowed for an integrated analysis of the morphology, distribution, and subsurface strata as well as a direct comparison of seafloor characteristics among different areas inside and outside of a pockmark. Additionally, surface sediments were analyzed for particle structure and grain size. Based on the combination of multibeam bathymetry and backscatter intensity data, 282 seafloor depressions were accurately identified. Moreover, the formation of pockmark can be attributed to existence of gas chimneys and other shallow gases revealed by shallow seismic profile records in the subsurface strata. Sediments inside and outside the pockmark showed remarkable discrepancies in terms of grain size, and benthic fauna. Additionally, strong internal reflection area was observed inside the depressions where benthic habitats are abundant and sediments contain strawberry pyrite and carbonate cementation. Side scan sonar also recorded sediment plumes in the water column, which indicates that the pockmarks are still active. Several "pearl-string-like" accumulations of pockmark were found in the study area, which well agree with the distribution of buried channels and lakes. These results thus provide new insights in interpreting shallow water fluid seepage, with implications for our current knowledge of overall sedimentation process in offshore continental shelves. • Active fluid seepage in shallow water continental shelf environment • Shallow-gas related acoustic features recorded on sub-bottom acoustic data • Benthic fauna anomalies, and strawberry pyrite associated with seafloor seeps • The large but shallow pockmarks can be ascribed to low fluid pressure. • String like distribution of pockmarks controlled by subsurface buried channels. [ABSTRACT FROM AUTHOR]

Quantitative understanding of human communication behavior, one of the fundamental human activities, is of great value in many practical problems, ranging from urban planning to emergency management. Most of the recent studies have focused on human communication under normal situations. Here, we study the temporal patterns of emergency calls, which is a special kind of human communication activity under emergency circumstances, by analyzing a dataset of emergency call records that collected from a metropolitan city in China during a five year period. We find that most individuals rarely make emergency calls. The distribution of inter-call durations decays as double power law along with an exponential tail. We also discover that, comparing with the normal communication activities, the activity of calling the emergency number shows more significant characteristics of burstiness and memory. We further demonstrate that the behavior of calling the emergency number when people encounter extreme events could be explained by an event-driven memory process. [ABSTRACT FROM AUTHOR]

Certain high-risk factors related to the death of COVID-19 have been reported, however, there were few studies on a death prediction model. This study was conducted to delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) of different degree and establish a death prediction model. In this multi-centered, retrospective, observational study, we enrolled 523 COVID-19 cases discharged before February 20, 2020 in Henan Province, China, compared clinical data, screened for high-risk fatal factors, built a death prediction model and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan. Out of the 523 cases, 429 were mild, 78 severe survivors, 16 non-survivors. The non-survivors with median age 71 were older and had more comorbidities than the mild and severe survivors. Non-survivors had a relatively delay in hospitalization, with higher white blood cell count, neutrophil percentage, D-dimer, LDH, BNP, and PCT levels and lower proportion of eosinophils, lymphocytes and albumin. Discriminative models were constructed by using random forest with 16 non-survivors and 78 severe survivors. Age was the leading risk factors for poor prognosis, with AUC of 0.907 (95% CI 0.831-0.983). Mixed model constructed with combination of age, demographics, symptoms, and laboratory findings at admission had better performance ( p = 0.021) with a generalized AUC of 0.9852 (95% CI 0.961-1). We chose 0.441 as death prediction threshold (with 0.85 sensitivity and 0.987 specificity) and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan successfully. Mixed model can accurately predict clinical outcomes of COVID-19 patients., (Copyright © 2020 Ma, Li, Jiao, Shi, An, Feng, Xing, Liang, Chen, Li, Li, Ren, Sun, Cui, Zhou, Cheng, Jiao, Wang, Xing, Shen, Zhang, Xu and Yu.)