Elemental data for Gonghai Lake sediments show significant effects of human activities on weathering processes after 1550 CE

The international Anthropocene Working Group has recognized the mid-20th centrury (ca. 1950 CE) as the onset of the Anthropocene, but human activities in China altered the land cover and influenced weathering processes much earlier. Changes in the elemental composition of sediment since 1000 CE from Gonghai Lake were studied, using X-ray Fluorescence element scanning (average time-resolution 3 years), to investigate the human impacts on weathering over time. We found that aluminum (Al) and calcium (Ca) containing minerals vary in the resistance to chemical weathering, and the concentrations of Al and Ca provide insights into the intensities of mechanical and chemical weathering respectively. The correlations between Al and Ca concentrations in these two periods, 1000–1550 CE and 1550–1950 CE changed from negative to positive, owing to that agricultural activities evidently enhanced both mechanical and chemical weathering during the latter stage. In addition, the Al and Ca concentrations recorded a border reclamation project in the 16th century and two catastrophic population decreases from 1630s to 1640s and 1850s–1870s. After 1950 CE, the concentrations of Al and Ca became uncorrelated, because weathering processes around Gonghai Lake were impacted by the enhanced anthropogenic perturbations in the Anthropocene

PARP10 influences the proliferation of colorectal carcinoma cells, a preliminary study

PARP10 is an intracellular mono-ADP ribosyltransferase and recent reports suggest that it regulates proliferation of some cell types. However, its effect on the proliferation of colorectal carcinoma cells has not yet been systematically reported. We explored the influence of PARP10 on the proliferation of several colorectal carcinoma cell types and carried out initial studies on the underlying mechanisms. Inhibition of the enzymatic activity of PARP10 led to significantly decreases in proliferative ability in LoVo cells and CT26 cells in vitro and suppressed growth of CT26 tumours in the subaxilliary region in Balb/c mice in vivo. Cell-cycle arrest accompanied these observations. Expression of the nuclear transfer factor β-catenin and it translocation to the nucleus were also affected and the expression of its associated signal proteins Axin2 and c-Myb were increased and decreased, respectively. We demonstrate that PARP10 promotes proliferation of those colorectal carcinoma cells which express significant levels of PARP10. This promotion is suppressed when the enzymatic activity is inhibited. β-Catenin is likely to be the mediator of the antiproliferative effect

The survival of murine hepatitis virus (a surrogate of SARS-CoV-2) on conventional packaging materials under cold chain conditions

IntroductionThe cold chain conditions have been suggested to facilitate long-distance transmission of SARS-CoV-2, but it is unclear how viable the virus is on cold chain packaging materials.MethodsThis study used the MHV-JHM strain of murine hepatitis virus as a model organism to investigate the viability of SARS-CoV-2 on foam, plastic, cardboard, and wood sheets at different temperatures (−40°C, −20°C, and 4°C). In addition, the ability of peracetic acid and sodium hypochlorite to eliminate the MHV-JHM on plastic and cardboard sheets were also evaluated.ResultsThe results indicate that MHV-JHM can survive on foam, plastic, or cardboard sheets for up to 28 days at −40°C and −20°C, and up to 14 days on foam and plastic surfaces at 4°C. Although viral nucleic acids were still detectable after storing at 4°C for 28 days, the corresponding virus titer was below the limit of quantification (LOQ).DiscussionThe study highlights that a positive nucleic acid test result may not indicate that the virus is still viable, and confirms that peracetic acid and sodium hypochlorite can effectively eliminate MHV-JHM on packaging materials under cold chain conditions

Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation

IntroductionThe complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present in vitro and ex vivo data on the mechanism of action of zilucoplan for the inhibition of C5 activation, including two clinically relevant C5 polymorphisms at R885.MethodsThe interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers.ResultsZilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the in vitro activation of C5 clinical variants at R885 that have been previously reported to respond poorly to eculizumab treatment. Zilucoplan was further demonstrated to interfere with the formation of C5b6 and inhibit red blood cell (RBC) hemolysis induced by plasmin-mediated non-canonical C5 activation. Zilucoplan demonstrated greater permeability than a monoclonal C5 antibody in a reconstituted basement membrane model, providing a rationale for the rapid onset of action of zilucoplan observed in clinical studies.ConclusionOur findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan

Progress and hotspot of diet or exercise therapy in the treatment of non-alcoholic fatty liver disease

IntroductionThe primary treatment for non-alcoholic fatty liver disease (NAFLD) is modifying lifestyle through dietary or exercise interventions. In recent decades, it has received increasing attention. However, the lack of bibliometric analysis has posed a challenge for researchers seeking to understand the overall trends in this field.MethodsAs of February 3rd, 2024, 876 articles on treating NAFLD through diet or exercise therapy from 2013 to 2023 had been retrieved. Two software tools, VOSviewer and CiteSpace, were utilized to analyze the growth of publications, countries, institutions, authors, journals, citations, and keywords. Additionally, the keywords with strong citation burstiness were identified to determine the changes and future trends of research hotspots in this field.ResultsChina had the highest number of articles, followed by the United States and South Korea. Yonsei University and Nutrients were the institutions and journals with the most significant contributions. Professor Younossi Zobair M, from the United States, is the most prolific author in this field. Through analyzing the keywords, three research hotspots were identified: research on the pathogenesis of NAFLD, research on the treatment modalities of NAFLD, and research on the risk factors and diagnosis methods of NAFLD. In recent years, the research emphasis in this field has changed, suggesting that future research will focus on two frontier keywords: “oxidative stress” and “aerobic capacity.”ConclusionIn the past eleven years, the attention in this field was still rising, and the authors, journals, countries and so on had formed a considerable cooperative relationship. There were also many highly influential and productive researchers in this field. It is speculated that new research will continue around “aerobic exercise” and “oxidative stress” in the future

The Sihailongwan Maar Lake, northeastern China as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Sihailongwan Maar Lake, located in Northeast China, is a candidate Global boundary Stratotype Section and Point (GSSP) for demarcation of the Anthropocene. The lake’s varved sediments are formed by alternating allogenic atmospheric inputs and authigenic lake processes and store a record of environmental and human impacts at a continental-global scale. Varve counting and radiometric dating provided a precise annual-resolution sediment chronology for the site. Time series records of radioactive (239,240Pu, 129I and soot 14C), chemical (spheroidal carbonaceous particles, polycyclic aromatic hydrocarbons, soot, heavy metals, δ13C, etc), physical (magnetic susceptibility and grayscale) and biological (environmental DNA) indicators all show rapid changes in the mid-20th century, coincident with clear lithological changes of the sediments. Statistical analyses of these proxies show a tipping point in 1954 CE. 239,240Pu activities follow a typical unimodal globally-distributed profile, and are proposed as the primary marker for the Anthropocene. A rapid increase in 239,240Pu activities at 88 mm depth in core SHLW21-Fr-13 (1953 CE) is synchronous with rapid changes of other anthropogenic proxies and the Great Acceleration, marking the onset of the Anthropocene. The results indicate that Sihailongwan Maar Lake is an ideal site for the Anthropocene GSSP

Investigation of the Performance of Neat and Modified Asphalt Binders

The Superpave binder specifications are performance-based criteria for binder selection for use in hot-mix asphalt mixtures. However, these specifications may not be applicable to modified binders. This research investigates the a new method for determining hot-mix asphalt mixing and compaction temperatures as well as the performance of neat (unmodified) and modified binders of the same performance grade. The first phase of the research focuses on determining mixing and compaction temperatures for hot-mix asphalt mixtures. Modified binders are shear rate and temperature dependent and the conventional methods of determining mixing and compaction temperatures can yield extreme results. The Zero Shear Viscosity theory is used as an alternative method to determine hot-mix asphalt mixing and compaction temperatures. The results reveal that the method is applicable to determining mixing and compaction temperatures for hot-mix asphalt mixtures containing modified binders, but additional work is needed in order to make the method applicable to neat binders. The second phase of the study investigates the performance of hot-mix asphalt mixtures containing neat and modified binders. Laboratory tests were performed on similar mixtures that contained neat and modified binders. Simple performance tests, such as accelerated rutting, flexural beam fatigue, and indirect tensile indicate that modified binders may contribute to improved hot-mix asphalt resistance to various distresses. Overall, performance-graded binders of the same grade appear to offer similar performance regardless of the high temperature at which the binder meets the high temperature specification