Klotho-derived peptide KP1 ameliorates SARS-CoV-2-associated acute kidney injury

Introduction: The severe cases of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often present with acute kidney injury (AKI). Although old age and preexisting medical conditions have been identified as principal risk factors for COVID-19-associated AKI, the molecular basis behind such a connection remains unknown. In this study, we investigated the pathogenic role of Klotho deficiency in COVID-19-associated AKI and explored the therapeutic potential of Klotho-derived peptide 1 (KP1).Methods: We assessed the susceptibility of Klotho deficient Kl/Kl mice to developing AKI after expression of SARS-CoV-2 N protein. The role of KP1 in ameliorating tubular injury was investigated by using cultured proximal tubular cells (HK-2) in vitro and mouse model of ischemia-reperfusion injury (IRI) in vivo.Results: Renal Klotho expression was markedly downregulated in various chronic kidney disease (CKD) models and in aged mice. Compared to wild-type counterparts, mutant KL/KL mice were susceptible to overexpression of SARS-CoV-2 N protein and developed kidney lesions resembling AKI. In vitro, expression of N protein alone induced HK-2 cells to express markers of tubular injury, cellular senescence, apoptosis and epithelial-mesenchymal transition, whereas both KP1 and Klotho abolished these lesions. Furthermore, KP1 mitigated kidney dysfunction, alleviated tubular injury and inhibited apoptosis in AKI model induced by IRI and N protein.Conclusion: These findings suggest that Klotho deficiency is a key determinant of developing COVID-19-associated AKI. As such, KP1, a small peptide recapitulating Klotho function, could be an effective therapeutic for alleviating AKI in COVID-19 patients

Maternal Prepregnancy Body Mass Index and Gestational Weight Gain on Pregnancy Outcomes

Objective: The aim of the present study was to evaluate the single and joint associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) with pregnancy outcomes in Tianjin, China. Methods: Between June 2009 and May 2011, health care records of 33,973 pregnant women were collected and their children were measured for birth weight and birth length. The independent and joint associations of prepregnancy BMI and GWG based on the Institute of Medicine (IOM) guidelines with the risks of pregnancy and neonatal outcomes were examined by using Logistic Regression. Results: After adjustment for all confounding factors, maternal prepregnancy BMI was positively associated with risks of gestational diabetes mellitus (GDM), pregnancy-induced hypertension, caesarean delivery, preterm delivery, large-for-gestational age infant (LGA), and macrosomia, and inversely associated with risks of small-for-gestational age infant (SGA) and low birth weight. Maternal excessive GWG was associated with increased risks of pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia, and decreased risks of preterm delivery, SGA, and low birth weight. Maternal inadequate GWG was associated with increased risks of preterm delivery and SGA, and decreased risks of LGA and macrosomia, compared with maternal adequate GWG. Women with both prepregnancy obesity and excessive GWG had 2.2–5.9 folds higher risks of GDM, pregnancy-induced hypertension, caesarean delivery, LGA, and macrosomia compared with women with normal prepregnancy BMI and adequate GWG. Conclusions: Maternal prepregnancy obesity and excessive GWG were associated with greater risks of pregnancy-induced hypertension, caesarean delivery, and greater infant size at birth. Health care providers should inform women to start the pregnancy with a BMI in the normal weight category and limit their GWG to the range specified for their prepregnancy BMI

The potential mechanism of Aidi injection against neuroblastoma—an investigation based on network pharmacology analysis

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP).Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein–protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells.Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug–compound–hub target gene–pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells.Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research

South China Sea Rifted Margin Testing hypotheses for lithosphere thinning during continental breakup: Drilling at the South China Sea rifted margin

International Ocean Discovery Program Expedition 368 is the second of two consecutive cruises that form the South China Sea Rifted Margin program. Expeditions 367 and 368 share the common key objectives of testing scientific hypotheses of breakup of the northern South China Sea (SCS) margin and comparing its rifting style and history to other nonvolcanic or magma-poor rifted margins. Four primary sites were selected for the overall program: one in the outer margin high (OMH) and three seaward of the OMH on distinct, margin-parallel basement ridges. These three ridges are informally labeled A, B, and C. They are located within the continent-ocean transition (COT) zone ranging from the OMH to the interpreted steady-state oceanic crust (Ridge C) of the SCS. The main scientific objectives include 1. Determining the nature of the basement within crustal units across the COT of the SCS that are critical to constrain style of rifting, 2. Constraining the time interval from initial crustal extension and plate rupture to the initial generation of igneous ocean crust, 3. Constraining vertical crustal movements during breakup, and 4. Examining the nature of igneous activity from rifting to seafloor spreading. In addition, the sediment cores from the drill sites targeting primarily tectonic and basement objectives will provide information on the Cenozoic regional environmental development of the Southeast Asia margin. Expedition 368 was planned to drill at two primary sites (U1501 and U1503) at the OMH and Ridge C, respectively. However, based on drilling results from Expedition 367, Expedition 368 chose to insert an alternate site on Ridge A (Site U1502). In total, the expedition completed operations at four sites (U1501, U1502, U1504, and U1505). Site U1503, however, was not completed beyond casing to 990 m because of mechanical problems with the drilling equipment that limited the expedition from 25 May 2017 to the end of the expedition to operate with a drill string not longer than 3400 m. New alternate Site U1504 proposed during Expedition 367 met this condition. Site U1505 also met the operational constraints of the 3400 m drill string (total) and was an alternate site for the already drilled Site U1501. At Site U1501, we cored to 697.1 m in 9.4 days, with 78.5% recovery. We also drilled ahead for 433.5 m in Hole U1501D and then logged downhole data from 78.3 to 399.3 m. In 19.3 days at Site U1502, we penetrated 1679.0 m, set 723.7 m of casing and cored a total of 576.3 m with 53.5% recovery, and collected downhole log data from 785.3 to 875.3 m and seismic data through the 10¾ inch casing. At Site U1503, we penetrated 995.1 m, setting 991.5 m of 10¾ inch casing, but no cores were taken. At Site U1504, we took 40 rotary core barrel (RCB) cores over two holes. The cored interval between both holes was 277.3 m with 26.8% recovery. An 88.2 m interval was drilled in Hole U1504B. At Site U1505, we cored 668.0 m with 101.1% recovery. Logging data was collected from 80.1 to 341.2 m. Operations at this site covered 6.1 days. Except for Site U1505, we drilled to acoustic basement, which prior to the expedition, except for Site U1501, had been interpreted to be crystalline basement. A total of 6.65 days were lost due to mechanical breakdown or waiting on spare supplies for repair of drilling equipment. At Site U1501 on the OMH, coring ~45 m into the acoustic basement sampled highly lithified sandstone to conglomerate of presumed Mesozoic age overlain by siliciclastic Eocene pre- to synrift sediments of Oligocene age and topped by primarily carbonaceous postrift sediments of early Miocene to Pleistocene age. Site U1502 on Ridge A was cased to 723.7 m. At this site, we recovered 180 m of hydrothermally altered brecciated basalts comprising sheet and pillow lavas below deep-marine sediments of Oligocene to late Miocene age. Coring was not performed within the upper 380 m (~Pliocene-Pleistocene) at Site U1502. At Site U1503 on Ridge C, 991.5 m of casing was installed in preparation for the planned deep drilling to ~1800 m, but no coring was performed due to mechanical failures, and the site was abandoned without further activity. Coring at Site U1504 on the OMH ~45 km east of Site U1501 recovered metamorphic schist to gneiss (greenschist facies) below late Eocene (?) carbonate rocks (partly reef debris) and early Miocene to Pleistocene sediments. At Site U1505, we cored to 480.15 m through Pleistocene to late Oligocene mainly carbonaceous ooze followed at depth by early Oligocene to late Eocene siliciclastic sediments. Efforts were made at every drill site to correlate the core with the seismic data and seismic stratigraphic unconformities interpreted within the Eocene to Plio-Pleistocene sedimentary sequence prior to drilling. The predrilling interpretation of ages of these unconformities was in general confirmed by drilling results. As a result of the constraints on the length of drill string that could be deployed during the later part of Expedition 368, the secondary expedition objectives addressing the environmental history of the SCS and Southeast Asia received more focus than planned because these sites are located in shallower water depths and required less penetration depth. This forced change in emphasis, however, was without fatal consequences for the primary tectonic objectives. The two expeditions together provided solid evidence for a process of breakup that included vigorous synrift magmatism as opposed to the often-favored interpretation of the SCS margin as a magma-starved margin

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Heat-Labile Enterotoxin-Induced PERK-CHOP Pathway Activation Causes Intestinal Epithelial Cell Apoptosis

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea among children and travelers in developing countries, and heat-labile enterotoxin (LT) is one of the most important virulence factors. The pathogenesis of and virulence factors associated with ETEC have been well-characterized; however, the extent to which ETEC damages host cells remains unclear. In this study, we found that LT could induce decreases in intestinal epithelial cell viability and induce apoptosis in a dose- and time- dependent manner in both HCT-8 and Caco-2 cells. We analyzed the expression profiles of apoptosis-related proteins via protein array technology and found that Bax, p-p53(S46), cleaved caspase-3, and TNFRI/TNFRSF1A expression levels were significantly up-regulated in wild-type ETEC- but not in ΔLT ETEC-infected HCT-8 cells. Bax is essential for endoplasmic reticulum (ER) stress-triggered apoptosis, and our RNAi experiments showed that the PERK-eIF2-CHOP pathway and reactive oxygen species (ROS) are also main participants in this process. LT-induced ROS generation was decreased in CHOP-knockdown HCT-8 cells compared to that in control cells. Moreover, pretreatment with the ROS inhibitor NAC down-regulated GRP78, CHOP, Bim, and cleaved caspase-3 expression, resulting in a reduction in the apoptosis rate from 36.2 to 20.3% in LT-treated HCT-8 cells. Furthermore, ROS inhibition also attenuated LT-induced apoptosis in the small intestinal mucosa in the ETEC-inoculation mouse model

Influence of Deposition Temperature on Microstructures and Mechanical Properties of Magnetron Sputtered V-Al-Si-N Coatings

The V-Al-Si-N coatings were deposited by RF reactive magnetron sputtering on substrates of Si(100) and WC-Co Alloy. The influence of the deposition temperature on the microstructures and mechanical properties of the coatings were investigated with X-ray diffraction, scanning electron microscopy and nano-indentation, and tribometer. The results show that the deposition temperature strongly affects the crystallinity and mechanical behavior. For example, grown at room temperature, high defect density and large residual stress were observed in the coatings; at 300℃, fairly long columnar grains stand vertically in the porous coating; at 500℃,(200)preferentially oriented, smaller grains formed in the compact coatings with a hardness of 29.7 GPa and a wear-rate of 6.1*10~(-17) m~3 order of magnitude lower than that of the coatings grown at RT. Besides, the temperature increase resulted in a significant improvement of tribological property and a slight decrease of hardness

偏压对Cr-Si-N涂层的结构与性能的影响

The Cr-Si-N coatings were synthesized by magnetron co-sputtering of Cr and Si targets on substrates of Si (100), Corning Eagle glass and 304 stainless-steel. The influence of the bias voltage on the microstructures and mechanical properties was investigated with X-ray diffraction,scanning electron microscopy,nano-indenter,residual stress analyzer and tribometer. The results show that the bias voltage has a major impact on the growth of Cr-Si-N coatings. To be specific, as the bias voltage varied from 0.0 to -50 V,the XRD peaks slowly shifted to smaller angle, possibly because of the lattice distortion induced by residual stress; the Cr-Si-N coatings became more compact and thinner, accompanied by a size reduction of columnar grains; the hardness rapidly increased from 12.4 GPa at 0.0 V to 35.5 GPa at -50 V;and the wear-rate changed in a weak decrease-increase mode, being the lowest at -10 V