Understanding the unique mechanism of ferroptosis: a promising therapeutic target

Ferroptosis is an iron-dependent form of regulated cell death and is characterized by high concentrations of intracellular lipid peroxide and a redox imbalance in the cells. Ferroptosis shows distinct morphological and biological features compared with other prominent mechanisms of programmed cell death. The distinct characteristics of ferroptosis include the dysfunction of the lipid peroxide repair enzyme glutathione peroxidase 4, the presence of ferrous iron overload, and the lipid peroxidation of polyunsaturated fatty acids. Several other metabolic pathways (including iron, lipid, and amino acid metabolism) and ferritinophagy, as well as transcription factors, can modulate ferroptosis. However, to date, the molecular mechanism of ferroptosis has not been elucidated. This review outlines the discovery, characterization, regulatory mechanisms, and crosstalk of ferroptosis. Further, we have noted the controversial elements in the ferroptosis-related mechanisms. Our inferences may provide a partial reference for developing strategies to regulate ferroptosis

Microstructure and electrical properties of Nb‐doped SrTiO3‐BiFeO3 based lead‐free ceramics

In this work, Nb-doped 0.75SrTiO3-0.25BiFeO3 (ST-BF) lead-free ceramics are designed and synthesized using a conventional solid-state reaction method. The influence of Nb doping on the microstructure, dielectric, and electrical properties are systematically investigated. With the increase of Nb concentration, the crystal structure of ST-BF remains pseudo-cubic as exhibited in the X-ray diffraction patterns. The grain size is found to increase from 0.33 to 6.23 μm, and then decrease to 1.88 μm by Nb doping, along with a clear heterogeneous core–shell microstructure. A relatively low dielectric loss (∼0.1, at 1 kHz) and a stable dielectric constant (∼700, at 1 kHz) are obtained for the 0.03 Nb-doped ST-BF composition at room temperature. Impedance spectroscopy analysis shows that Nb doping in ST-BF increases the total resistivity, forming an electrically conductive core and a nonconductive shell, with enhanced activation energy. The results may provide a feasible approach to develop novel ST-based lead-free dielectric ceramics for capacitor application

Precursory characteristics and disaster prevention of rock burst in roadway excavation in steeply inclined extra-thick coal seam

With the gradual coal mining of deep rock burst mine, the impact accompanying roadway excavation becomes more and more intense. Aiming at the problem of effective prevention and control of rock burst in roadway excavation, taking the steep seam mine in the Wudong Coal Mine as an example, the temporal and spatial precursor characteristics of rock burst in roadway excavation were analyzed by microseismic monitoring. Combined with the numerical simulation analysis of stress and energy changes in roadway excavation, the mechanism of rock burst in roadway excavation was revealed, and the prevention and control strategy of rock burst in steeply inclined extra-thick coal seam roadway was put forward, which was verified by field engineering practice. The results show that the total energy of microseisms is extremely low for 2−5 days or there is an energy latency of at least 4 days before the rock burst occurs due to roadway excavation in steeply inclined extra-thick coal seam. Within 5 days before rock burst occurs, there is a high-frequency fluctuation period of maximum energy ratio for more than 3 days. There is an obvious lack of earthquake before the rock burst occurs, and the occurrence position is concentrated in the range of minimum value of microseismic energy near the heading face, or in the range of minimum value of microseismic frequency near the extreme value of microseismic energy, and the rock burst event is located in the area with high impact deformation energy index. The hard overburden structure of horizontal sublevel fully mechanized caving mining in steeply inclined extra-thick coal seam is not easy to break, which makes the stress concentration on both sides of upper horizontal goaf exist in roadway excavation. The stress between the front of the heading face and the bottom of the roadway squeezed by the roof and floor strata is concentrated and the energy accumulation is remarkable. With the increase of the heading depth of the roadway, the stress concentration and energy accumulation are further enhanced, which is easy to induce dynamic disasters such as rock burst. The prevention and control strategies of rock burst was established through comprehensive analysis, which consist of face blasting pressure relief, roadway drilling pressure relief and reinforcement support, and scaffolding in complex areas. Combined with the temporal and spatial precursory anomalies of rock burst, it provides an opportunity to strengthen the unloading pressure in time. Through the pressure relief of working face and roadway, the accumulated microseismic energy of more than 1×105 J per day did not occur during the excavation. After the support was optimized and the complex area was protected, the daily average microseismic energy of roadway excavation decreased to 2.2 kJ, and the proportion of microseismic events above 1 kJ decreased, and the overall section of roadway was flat

High-throughput sequencing reveals hub genes for human early embryonic development arrest in vitro fertilization: a pilot study

Many clinical studies have shown that embryos of in vitro fertilization (IVF) are often prone to developmental arrest, which leads to recurrent failure of IVF treatment. Early embryonic arrest has always been an urgent clinical problem in assisted reproduction centers. However, the molecular mechanisms underlying early embryonic development arrest remain largely unknown. The objective of this study is to investigate potential candidate hub genes and key signaling pathways involved in early stages of embryonic development. RNA-seq analysis was performed on normal and arrest embryos to study the changes of gene expression during early embryonic development. A total of 520 genes exhibiting differential expression were identified, with 174 genes being upregulated and 346 genes being downregulated. Upregulated genes show enrichment in biosynthesis, cellular proliferation and differentiation, and epigenetic regulation. While downregulated genes exhibit enrichment in transcriptional activity, epigenetic regulation, cell cycle progression, cellular proliferation and ubiquitination. The STRING (search tool for the retravel of interacting genes/proteins) database was utilized to analyze protein-protein interactions among these genes, aiming to enhance comprehension of the potential role of these differentially expressed genes (DEGs). A total of 22 hub genes (highly connected genes) were identified among the DEGs using Cytoscape software. Of these, ERBB2 and VEGFA were upregulated, while the remaining 20 genes (CCNB1, CCNA2, DICER1, NOTCH1, UBE2B, UBE2N, PRMT5, UBE2D1, MAPK3, SOX9, UBE2C, UB2D2, EGF, ACTB, UBA52, SHH, KRAS, UBE2E1, ADAM17 and BRCA2) were downregulated. These hub genes are associated with crucial biological processes such as ubiquitination, cellular senescence, cell proliferation and differentiation, and cell cycle. Among these hub genes, CCNA2 and CCNB1 may be involved in controlling cell cycle, which are critical process in early embryonic development

Cross-cultural adaptation and validation of the PedsQL™ stem cell transplant module in China: A methodological and cross-sectional study

BackgroundHematopoietic stem cell transplantation (HSCT), as a mature technology, has significantly improved the survival rate of children. However, there lack efficient scales to assess the quality of life (QoL) of children with HSCT in China, which has important implications in the care of this population. This study aimed to translate the original English Pediatric Quality of Life Inventory™ (PedsQL™) Stem Cell Transplant Module into a Chinese mandarin version, and evaluate its reliability.MethodsChildren of ages 2–18 years who had received HSCT at Children's Hospital of Nanjing Medical University and Children's Hospital of Fudan University were recruited. Children or their parents were asked to fill the PedsQL™ 4.0 Generic Core Scales, PedsQL™ Stem Cell Transplant Module, and PedsQL™ Family Information Form. Feasibility was evaluated by completion rate and the percentage of missing items, reliability by the internal consistency and test-retest reliability, and validity by factor analysis and correlation analysis between the scores of total scale and each dimension.ResultsA total of 120 children (mean age 6.37, SD = 3.674) and some parents were included. A low percentage of items were missed in returned reports. Cronbach's alpha coefficient reached 0.70 in the majority of dimensions of both child self-report and parent proxy-report. Test-retest reliability was 0.685 in parents' forms and 0.765 in child's forms. Eight factors were extracted, with a cumulative contribution rate of 74.54%. The correlation between PedsQL™ 4.0 and Transplant Module was 0.748 for children self-report and 0.808 for parent proxy-report.ConclusionsThis study provides evidence that the Chinese mandarin version of the PedsQL™ Stem Cell Transplant is feasible, reliable and valid in evaluating the QoL of Chinese children after HSCT

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates

The draft genomes of five agriculturally important African orphan crops

Background: Continuous growth of the world population is expected to double the worldwide demand for food by 2050. Eighty-eight percent of countries current face a serious burden of malnutrition, especially in Africa and South and South-East Asia. About 95% of the food energy needs of humans are fulfilled by just 30 species, of which wheat, maize and rice provide the majority of calories. Therefore, to diversify and stabilize global food supply, enhance agricultural productivity and tackle malnutrition, greater use of neglected or underutilized local plants (so-called 'orphan crops‘, but also including a few plants of special significance to agriculture, agroforestry and nutrition) could be a partial solution.Results: Here, we present draft genome information from five agriculturally, biologically, medicinally and economically important underutilized plants native to Africa; Vigna subterranea, Lablab purpureus, Faidherbia albida, Sclerocarya birrea, and Moringa oleifera. Assembled genomes range in size from 217 to 654 Mb. In V. subterranea, L. purpureus, F. albida, S. birrea and M. oleifera we have predicted 31707, 20946, 28979, 18937, 18451 protein-coding genes, respectively. By further analysing the expansion and contraction of selected gene families, we have characterized root nodule symbiosis genes, transcription factors and starch biosynthesis-related genes in these genomes.Conclusions: These genome data will be useful to identify and characterize agronomically important genes and understand their modes of action, enabling genomics-based, evolutionary studies, and breeding strategies to design faster, more focused and predictable crop improvement programs

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve