Aristolochic acid induces acute kidney injury through ferroptosis

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism

Fine mapping of a QTL for ear size on porcine chromosome 5 and identification of high mobility group AT-hook 2 (HMGA2) as a positional candidate gene

<p>Abstract</p> <p>Background</p> <p>Ear size and shape are distinct conformation characteristics of pig breeds. Previously, we identified a significant quantitative trait locus (QTL) influencing ear surface on pig chromosome 5 in a White Duroc × Erhualian F₂resource population. This QTL explained more than 17% of the phenotypic variance.</p> <p>Methods</p> <p>Four new markers on pig chromosome 5 were genotyped across this F₂population. RT-PCR was performed to obtain expression profiles of different candidate genes in ear tissue. Standard association test, marker-assisted association test and F-drop test were applied to determine the effects of single nucleotide polymorphisms (SNP) on ear size. Three synthetic commercial lines were also used for the association test.</p> <p>Results</p> <p>We refined the QTL to an 8.7-cM interval and identified three positional candidate genes i.e. <it>HMGA2</it>, <it>SOX5 </it>and <it>PTHLH </it>that are expressed in ear tissue. Seven SNP within these three candidate genes were selected and genotyped in the F₂population. Of the seven SNP, <it>HMGA2 </it>SNP (JF748727: g.2836 A > G) showed the strongest association with ear size in the standard association test and marker-assisted association test. With the F-drop test, F value decreased by more than 97% only when the genotypes of <it>HMGA2 </it>g.2836 A > G were included as a fixed effect. Furthermore, the significant association between g.2836 A > G and ear size was also demonstrated in the synthetic commercial Sutai pig line. The haplotype-based association test showed that the phenotypic variance explained by <it>HMGA2 </it>was similar to that explained by the QTL and at a much higher level than by <it>SOX5</it>. More interestingly, <it>HMGA2 </it>is also located within the dog orthologous chromosome region, which has been shown to be associated with ear type and size.</p> <p>Conclusions</p> <p><it>HMGA2 </it>was the closest gene with a potential functional effect to the QTL or marker for ear size on chromosome 5. This study will contribute to identify the causative gene and mutation underlying this QTL.</p

Visualization analysis of research literature on early warning of geo-hazards based on meteorological factors in the past 20 years

Early warning of geo-hazards based on meteorological factors in China began in 2003, and early warning informations are issued to the public every year during the flood season to alert the public to guard against geo-hazards such as landslides, debris flows, and mudslides caused by rainfall. To better understand the current situation and future trends of research for early warning of geo-hazards based on meteorological factors, the visualization tool CiteSpace was utilized to review the domestic and foreign literature on geo-hazards meteorological risk warning published from 2003 to 2023 and construct the scientific knowledge map. The CNKI database and SCI-Expanded databases were used as data sources. The result show that: (1) The study of critical rainfall thresholds based on the relationship between historical rainfall and disaster is in the leading position in research on early warning of geo-hazards based on meteorological factors, and the study of rainfall-related thresholds will continue to be a research hotspot in the future. (2) Keyword cluster analysis shows that a large number of studies have conducted research on early warning and prediction models and critical thresholds of geo-hazards under different formation conditions, meteorological conditions, different types, and genetic models, indicating that refinement is an important direction for the development of early warning of geo-hazards based on meteorological factors. (3) In the international research, Chinese scholars account for 39% of the total number of publications, showing an absolute advantage in research on geo-hazards meteorological risk early warning. The research results objectively demonstrate the development context, domestic and foreign research hotspots, and trends of research on geo-hazards meteorological risk warning in China, aiming to contribute to the progress of geo-hazards research and early warning forcast business in China

Mechanism of rainfall-induced shallow landslide and stability prediction model

The rainfall-induced shallow landslides are primarily debris landslides, which features simultaneity with significant hazard, and the hydrological response mechanism of water table and soil moisture content to precipitation of this type of landslide is sophisticated, which makes it difficult to predict the slope stability accurately. To further study the influence of the rainfall-triggered internal hydrological responses on slope-stability, on-site precipitation infiltration monitoring, correlation analysis and mechanical analysis were carried out on the Houshanli landslide in Qingchuan County, Sichuan Province. The relationship between precipitation and water table was proposed based on climate and hydrological monitoring data obtained within three year interval. The response of rainfall infiltration, soil volumetric water content and water table were analyzed. The results indicate that: (1) groundwater exhibits periodic fluctuations throughout the year, characterized by three phases of slow decline, rapid decline, and rapid ascent; a linear negative correlation between precipitation and water table was found, and no significant correlation was observed with the water table increment; (2) through the infinite slope model and the relationship between precipitation and water table, a prediction model for shallow landslide stability was constructed. The precipitation threshold (81.8 mm/d) and water table threshold (0.73 m) were determined which has good agreement with the actual situations. This provides an early warning method for rainfall-induced shallow landslides by monitoring these two factors

Comprehensive evolutionary analysis of growth-regulating factor gene family revealing the potential molecular basis under multiple hormonal stress in Gramineae crops

Growth-regulating factors (GRFs) are plant-specific transcription factors that contain two highly conserved QLQ and WRC domains, which control a range of biological functions, including leaf growth, floral organ development, and phytohormone signaling. However, knowledge of the evolutionary patterns and driving forces of GRFs in Gramineae crops is limited and poorly characterized. In this study, a total of 96 GRFs were identified from eight crops of Brachypodium distachyon, Hordeum vulgare, Oryza sativa L. ssp. indica, Oryza rufipogon, Oryza sativa L. ssp. japonica, Setaria italic, Sorghum bicolor and Zea mays. Based on their protein sequences, the GRFs were classified into three groups. Evolutionary analysis indicated that the whole-genome or segmental duplication plays an essential role in the GRFs expansion, and the GRFs were negatively selected during the evolution of Gramineae crops. The GRFs protein function as transcriptional activators with distinctive structural motifs in different groups. In addition, the expression of GRFs was induced under multiple hormonal stress, including IAA, BR, GA3, 6BA, ABA, and MeJ treatments. Specifically, OjGRF11 was significantly induced by IAA at 6 h after phytohormone treatment. Transgenic experiments showed that roots overexpressing OjGRF11 were more sensitive to IAA and affect root elongation. This study will broaden our insights into the origin and evolution of the GRF family in Gramineae crops and will facilitate further research on GRF function

20-year early warning for regional geo-hazards risk in China: 2003-2022

Early warning of geo-hazards based on meteorological factors has played an important supportive role in disaster prevention and mitigation in China since its inception in 2003. This paper summarizes the the 20-year development process, technical methods, and disaster reduction effects of the early warning works. (1) The development process of early warning work process is divided into three stages: initiation and promotion (2003-2009), deepening cooperation (2010-2017), and reform and enhancement (2018-2022). (2) With 24-hour early warning work as the main content, a progressive warning model and a relatively complete warning service system have been gradually formed. (3) Three sets of early warning model technology and method systems have been gradually developed, including critical precipitation threshold model, the threshold model based on geo-hazards risk, and the dynamic early warning models, with the publication of industry standards for warning. (4) The spatial and temporal accuracy of warning products continues to improve, with the national and 26 provincial warning spatial accuracies exceeding 5 km × 5 km. The focus is on 24-hour warnings, with development towards 72-hour and medium- to long-term forecasts. Over 8 provincial-level and some municipal and county-level authorities have implemented 3-hour short-term warnings, gradually forming a work system to support service short impending warning response, medium-term prevention and long term deployment. (5) Where there is warning, there is response. The Ministry of Natural Resources has taken the national early warning as one of the bases for initiating defense responses, and 18 provinces have clarified the working mechanisms of the early warning response linkage. (6) The awareness of multi-party disaster prevention has been continuously enhanced. With strengthened inspections,evacuations, and successful risk aversion after receiving early warning information, the effectiveness of disaster prevention and mitigation is evident. The experience of early warning works in the past 20-year can provide reference for the next step in promoting the early warning of geo-hazards based on meteorological factors, supporting the enhancement of China’s capability and level of geo-hazards prevention and control work

Comprehensive Analysis of Peripheral Exosomal circRNAs in Large Artery Atherosclerotic Stroke

Exosomes are crucial vehicles in intercellular communication. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed (DE) exosomal circRNAs in five paired LAA and normal controls. Further, quantitative real-time PCR (qRT-PCR) was used to verify the RNA-Seq results in a cohort of stroke patients (32 versus 32). RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 DE circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs. Here, we show for the first time the comprehensive expression of exosomal circRNAs, which displayed the potential diagnostic and biological function in LAA stroke

Tunable spin-state bistability in a spin crossover molecular complex

The spin crossover (SCO) transitions at both the surface and over the entire volume of the [Fe{H2B(pz)2}2(bipy)] polycrystalline films on Al2O3 substrates have been studied, where pz  =  pyrazol-1-yl and bipy  =  2,2'-bipyridine. For [Fe{H2B(pz)2}2(bipy)] films of hundreds of nm thick, magnetometry and x-ray absorption spectroscopy measurements show thermal hysteresis in the SCO transition with temperature, although the transition in bulk [Fe{H2B(pz)2}2(bipy)] occurs in a non-hysteretic fashion at 157 K. While the size of the crystallites in those films are similar, the hysteresis becomes more prominent in thinner films, indicating a significant effect of the [Fe{H2B(pz)2}2(bipy)]/Al2O3 interface. Bistability of spin states, which can be inferred from the thermal hysteresis, was directly observed using temperature-dependent x-ray diffraction; the crystallites behave as spin-state domains that coexist during the transition. The difference between the spin state of molecules at the surface of the [Fe{H2B(pz)2}2(bipy)] films and that of the molecules within the films, during the thermal cycle, indicates that both cooperative (intermolecular) effects and coordination are implicated in perturbations to the SCO transition