Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects

High-resolution carbon isotope stratigraphy of the Lower and Middle Ordovician succession of the Yangtze Platform, China

Variation in the relative abundance of the stable carbon isotopes has been widely used to correlate Ordovician marine successions over the past two decades. To date, only a few of studies of Ordovician carbon chemostratigraphy have been conducted in South China. Most of the previous studies in this field have focused on specific time intervals and/or events in the Middle and Upper Ordovician. The Lower and Middle Ordovician of the Yangtze Platform is typically represented by a sedimentary succession dominated by carbonate rocks, which is ideal for studying the carbon chemostratigraphy. Three sections spanning the Nantsinkuan/Lunshan, Fenhsiang, Hunghuayuan, and Dawan/Zitai formations, corresponding to the TremadocianâDapingian in age, have been sampled for high-resolution δ13C chemostratigraphy. Our new δ13C data reveal five tie-points with the potential for global correlation: (1) a positive δ13C excursion in the lower Nantsinkuan Formation within the Tremadocian Rossodus manitouensis Zone; (2) an excursion with two peaks roughly within the late Tremadocian Paltodus âdeltiferâ Zone; (3) a positive δ13C shift in the lower Hunghuayuan Formation, within the early Floian Serratognathus diversus Zone; (4) a gradual positive δ13C shift in the late Floian, ranging from the uppermost S. diversus Zone to the basal Oepikodus evae Zone; (5) a minor negative shift in the lower Dawan/Zitai Formation, within the early Dapingian Baltoniodus triangularis Zone. These excursions are herein used for correlation of the Yangtze Platform strata with successions from South China, North China, the Argentine Precordillera, North America and Baltica. From a palaeogeographical perspective, the Gudongkou, Xiangshuidong and Daling sections represent depositional environments along an inner to outer ramp profile. The δ13C data from these sections show successively heavier (higher) δ13C values with increasing depositional depth, which can be interpreted as due to remineralization of organic carbon within the carbonate rocks formed in the shallow-water environment

Ordovician geology and stratigraphy of China: A synthesis

China presently comprises several tectonic blocks and regions assembled over geological time and having independent histories. During the Ordovician, these blocks included South China, North China, Tarim, Qaidam, Junggar, Qiangtang-Qamdo, Lhasa and partially Himalaya, Sibumasu and Indochina, as well as the Altay-Xingâan and Songpan-Garze fold belts, which were discrete but adjacent. Twelve stratigraphic megaregions bounded by tectonic sutures or major fault zones are recognised for the Ordovician System. Some of them are further subdivided into regions according to specific lithological and biotic facies or distinct stratigraphic successions. The palaeontological features and biostratigraphic framework of these stratigraphic megaregions and regions are summarised. The unified biostratigraphic framework presented herein includes 33 graptolite and 27 conodont biozones through the Ordovician, together with supplementary biozones, communities or associations of brachiopods, trilobites, cephalopods, chitinozoans, acritarchs and radiolarians. With the constraints of integrative chronostratigraphy, biostratigraphy, chemostratigraphy, cyclostratigraphy and magnetostratigraphy, along with some geochronological data, our understanding of the temporal and spatial distribution of the Ordovician lithostratigraphic units on these major blocks has been significantly advanced. The refined integrative stratigraphic framework of the Ordovician provides a precise constraint on the major tectonic orogenies and biotic events evident in China

Factors influencing householder self-evacuation in two Australian bushfires

The thesis investigated householder self-evacuation decision-making during bushfires in the Perth and Adelaide Hills in 2014 and 2015. It explored the factors that influenced householders’ decisions to evacuate, identified factors that predict self-evacuation and established the characteristics of self-evacuators. The Protective Action Decision Model (PADM) provided a conceptual framework for the research. Its theoretical and analytical usefulness in an Australian context, was assessed. A mixed methods research strategy was used involving quantitative telephone surveys of 457 bushfire-affected participants and face-to-face interviews of 109 participants in 59 households. The study concluded that environmental and social cues and warnings and householders’ perceptions of the threat, of hazard adjustments and of other stakeholders, influenced self-evacuation decision-making. Protective action perceptions, particularly the effectiveness of evacuating or not evacuating in protecting personal safety or property, were most important in predicting self-evacuation. Receipt of official warnings and the perception of likely impact of the bushfire on property were also important predictors. Undertaking long-run hazard adjustments, although not predictive of self-evacuation, was pivotal in shaping perceptions of the effectiveness of evacuating and remaining in protecting personal safety and property and indirectly influenced evacuation decisions. Seven archetypes that characterised householders’ self-evacuation attitudes and behaviour were identified. These included Threat, and Responsibility Deniers, Dependent, and Considered Evacuators, Community Guided and Experienced Independents all who took different decisional ‘rules of thumb’ and routes toward evacuating or remaining . The PADM needs to be split into two separate models to incorporate the influence of long-run hazard adjustments on protective action decision-making in an Australian bushfire. The findings suggest that future research on those who wait and see during a bushfire should take account of their decisional rules of thumb and that design and targeting of Australian bushfire safety policy should better account for self-evacuator characteristics

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Integrated conodont biostratigraphy and carbon isotope chemostratigraphy in the Lower–Middle Ordovician of southern Sweden reveals a complete record of the MDICE

One of the few and most complete records of the MDICE (Middle Darriwilian Isotope Carbon Excursion) is herein documented from Baltoscandia. Based on a core section penetrating the condensed Lower–Middle Ordovician succession (~46 m) on the island of Öland, southeastern Sweden, we provide an integrated scheme for carbon isotope chemostratigraphy (313 samples) and conodont biostratigraphy (29 samples) for this period. The carbonate succession in the Tingskullen core records 12 conodont zones and 6 subzones, including the Oepikodus evae, Trapezognathus diprion, Baltoniodus triangularis, B. navis, B. norrlandicus, Lenodus antivariabilis, L. variabilis, Yangtzeplacognathus crassus, Eoplacognathus pseudoplanus (Microzarkodina hagetiana and Microzarkodina ozarkodella subzones), E. suecicus, Pygodus serra (E. foliaceus, E. reclinatus, E. robustus and E. lindstroemi subzones) and Pygodus anserinus zones in ascending order. The δ13Ccarb record reveals an apparently complete record of the MDICE, including a rising limb, a well-defined peak and a falling limb. The anomaly covers a thickness of c. 27 m in the core and spans the Eoplacognathus pseudoplanus, E. suecicus, Pygodus serra and P. anserinus conodont zones. Combined with the new, detailed conodont biostratigraphy, the MDICE in the Tingskullen core can be used for detailed correlation with successions from Baltica, North America, the Argentine Precordillera, South China and North China