Anthropogenic influence on 2018 summer persistent heavy and daily extreme rainfall in central western China

Anthropogenic forcing has reduced the probability of summer persistent heavy rainfall in central western China similar to 2018 by ~47%, but increased that of daily extremes by ~1.5 times, based on HadGEM3-GA6 ensembles

Observation of Dirac hierarchy in three-dimensional acoustic topological insulators

Dirac cones (DCs) play a pivotal role in various unique phenomena ranging from massless electrons in graphene to robust surface states in topological insulators (TIs). Recent studies have theoretically revealed a full Dirac hierarchy comprising an eightfold bulk DC, a fourfold surface DC, and a twofold hinge DC, associated with a hierarchy of topological phases including first-order to third-order three-dimensional (3D) topological insulators, using the same 3D base lattice. Here, we report the first experimental observation of the Dirac hierarchy in 3D acoustic TIs. Using acoustic measurements, we unambiguously reveal that lifting of multifold DCs in each hierarchy can induce two-dimensional (2D) topological surface states with a fourfold DC in a first-order 3D TI, one-dimensional (1D) topological hinge states with a twofold DC in a second-order 3D TI, and zero-dimensional (0D) topological corner states in a third-order 3D TI. Our work not only expands the fundamental research scope of Dirac physics, but also opens up a new route for multidimensional robust wave manipulation

High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99 = 207 µM). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99 = 70.7 µM), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic

Collective Human Behavior in Cascading System: Discovery, Modeling and Applications

The collective behavior, describing spontaneously emerging social processes and events, is ubiquitous in both physical society and online social media. The knowledge of collective behavior is critical in understanding and predicting social movements, fads, riots and so on. However, detecting, quantifying and modeling the collective behavior in online social media at large scale are seldom unexplored. In this paper, we examine a real-world online social media with more than 1.7 million information spreading records, which explicitly document the detailed human behavior in this online information cascading system. We observe evident collective behavior in information cascading, and then propose metrics to quantify the collectivity. We find that previous information cascading models cannot capture the collective behavior in the real-world and thus never utilize it. Furthermore, we propose a generative framework with a latent user interest layer to capture the collective behavior in cascading system. Our framework achieves high accuracy in modeling the information cascades with respect to popularity, structure and collectivity. By leveraging the knowledge of collective behavior, our model shows the capability of making predictions without temporal features or early-stage information. Our framework can serve as a more generalized one in modeling cascading system, and, together with empirical discovery and applications, advance our understanding of human behavior

Curcumin Inhibits Growth of Human NCI-H292 Lung Squamous Cell Carcinoma Cells by Increasing FOXA2 Expression

Lung squamous cell carcinoma (LSCC) is a common histological lung cancer subtype, but unlike lung adenocarcinoma, limited therapeutic options are available for treatment. Curcumin, a natural compound, may have anticancer effects in various cancer cells, but how it may be used to treat LSCC has not been well studied. Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer effects and explored underlying potential mechanisms of action. Curcumin treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time-dependent manner. FOXA2 expression was decreased in LSCC tissues compared with adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells proliferation. Inhibition of cell proliferation by curcumin was attenuated by FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6) significantly inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative regulators of STAT3 activity, were upregulated by curcumin treatment. Thus, curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via regulation of STAT3 signaling pathways

Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt Pathway During Allergic Asthma

Background/Aims: A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms. Methods: The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level. Results: We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells. Conclusion: Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma