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

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Research progress and prospects of ecosystem carbon sequestration under climate change (1992–2022)

Climate change is extensively affecting the global ecosystem, especially the ecosystem carbon sequestration and sequestration potential, which are issues of global concern. The proposed concept of “carbon neutrality” in 2020 has brought ecological carbon sequestration to the forefront. Therefore, the research on climate change and ecosystem carbon sequestration need to be systematically reviewed, summarized, and examined. Based on the Web of Science database, this paper analyzed 4005 articles (1992–2022 year) after rigorous screening via a bibliometrics analysis and then presented the research trends and future research focus of ecological carbon sequestration. The following conclusions are drawn: (1) the research over the last 30 years has steadily improved, and the annual number of publications has increased in a cubic polynomial fashion (R2 = 0.9937), with 87.57 % of the total publications appearing after 2009. Global Change Biology and Science of the Total Environment are the most influential journals in the field; (2) participation in such research is becoming increasingly common with expanding research areas covering Eurasia, America, Oceania, and Africa. The United States and China are the most productive and influential countries; (3) the diversity of this research is increasing, and the research content is becoming more explicit and systematic. Most research focuses on climate change, carbon sequestration, management, land-use changes, and nitrogen and soil organic carbon; (4) although traditional ecological evaluation techniques were essential early on, remote sensing and modeling have become the primary methods for assessment; (5) keyword clustering allows the classification of the research into six relatively independent subtopics: climate change and terrestrial ecosystems, sequestration and organic-carbon, ecosystem services, nitrogen and carbon cycling, biomass and forest, and blue carbon, which provides a reference for further research on ecological carbon sequestration and carbon neutrality

Ex vivo cultivated retinal pigment epithelial cell transplantation for the treatment of rabbit corneal endothelial dysfunction

Abstract Objective Stem cell therapy is a promising strategy for the treatment of corneal endothelial dysfunction, and the need to find functional alternative seed cells of corneal endothelial cells (CECs) is urgent. Here, we determined the feasibility of using the retinal pigment epithelium (RPE) as an equivalent substitute for the treatment of corneal endothelial dysfunction. Methods RPE cells and CECs in situ were obtained from healthy New Zealand male rabbits, and the similarities and differences between them were analyzed by electron microscopy, immunofluorescent staining, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Rabbit primary RPE cells and CECs were isolated and cultivated ex vivo, and Na+/K+-ATPase activity and cellular permeability were detected at passage 2. The injection of cultivated rabbit primary RPE cells, CECs and human embryonic stem cell (hESC)-derived RPE cells was performed on rabbits with corneal endothelial dysfunction. Then, the therapeutic effects were evaluated by corneal transparency, central corneal thickness, enzyme linked immunosorbent assay (ELISA), qRT-PCR and immunofluorescent staining. Results The rabbit RPE cells were similar in form to CECs in situ and ex vivo, showing a larger regular hexagonal shape and a lower cell density, with numerous tightly formed cell junctions and hemidesmosomes. Moreover, RPE cells presented a stronger barrier and ionic pumping capacity than CECs. When intracamerally injected into the rabbits, the transplanted primary RPE cells could dissolve corneal edema and decrease corneal thickness, with effects similar to those of CECs. In addition, the transplantation of hESC-derived RPE cells exhibited a similar therapeutic effect and restored corneal transparency and thickness within seven days. qRT-PCR results showed that the expressions of CEC markers, like CD200 and S100A4, increased, and the RPE markers OTX2, BEST1 and MITF significantly decreased in the transplanted RPE cells. Furthermore, we have demonstrated that rabbits transplanted with hESC-derived RPE cells maintained normal corneal thickness and exhibited slight pigmentation in the central cornea one month after surgery. Immunostaining results showed that the HuNu-positive transplanted cells survived and expressed ZO1, ATP1A1 and MITF. Conclusion RPE cells and CECs showed high structural and functional similarities in barrier and pump characteristics. Intracameral injection of primary RPE cells and hESC-derived RPE cells can effectively restore rabbit corneal clarity and thickness and maintain normal corneal function. This study is the first to report the effectiveness of RPE cells for corneal endothelial dysfunction, suggesting the feasibility of hESC-derived RPE cells as an equivalent substitute for CECs

EGCG promotes the sensory function recovery in rats after dorsal root crush injury by upregulating KAT6A and inhibiting pyroptosis

Dorsal root injury usually leads to irreversible sensory function loss and lacks effective treatments. (−)-epigallocatechin-3-gallate (EGCG) is reported to exert neuroprotective roles in the nervous systems. However, the function of EGCG in treating dorsal root injury remains unclear. Hence, we built the dorsal root crush injury (DRCI) rat model to be treated with EGCG, followed by the western blot, Enzyme-linked immunosorbent assay, and sensory behavior tests. We observed that EGCG can upregulate the Lysine acetyltransferase 6A (KAT6A) level and inhibit the pyroptosis, indicated by downregulated gasdermin-D, caspase-1, and interleukin 18 protein levels, and alleviate the neuropathic pain, indicated by the decreased paw withdraw threshold in Plantar test and decreased paw withdraw latency in von Frey test, and downregulated calcitonin gene-related peptide, nerve growth factor, and c-Fos protein levels. But EGCG cannot alleviate the neuropathic pain when the KAT6A was inhibited by CTX-0124143 and pyroptosis was activated by Miltirone. These combined results indicated that EGCG can promote the sensory function recovery in rats after DRCI via upregulating KAT6A and inhibiting pyroptosis, laying the foundation for EGCG to be a novel candidate for the treatment of dorsal root injury

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Abstract Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Results Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4. Conclusion We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo

Additional file 1 of Sialic acid exacerbates gut dysbiosis-associated mastitis through the microbiota-gut-mammary axis by fueling gut microbiota disruption

Additional file 1: Figure S1. SARA induces mastitis in cows. Cows were treated with a standard or high-grain diet for two months and ruminal, serum, milk and mammary gland tissues were harvested for analysis. A. Ruminal PH at day 60 from Health and SARA cows (n=6). B-C. Ruminal and serum LPS levels were detected using ELISA (n=6). D. Somatic cell count was performed in Health and SARA cows (n=6). E. Representative images of H&E-stained sections from Health and SARA samples. Red arrows indicate leukocyte infiltration. Blue arrows show the structure injury of mammary gland. Black arrows indicate edema. F. Histological score based on H&E-stained sections (n=6). Mammary TNF-α (G) and IL-1β (H) from Health and SARA groups were measured by ELISA (n=6). Each dot represents an individual cow (A-D and F-H) and Student’s t test was performed (A-D and F-H). **p < 0.01, ***p < 0.001 indicate significance. Figure S2. Data quality checks. A. The Pearson correlation of ruminal QC samples. B-C. The PCA score plots for Health and SARA samples containing QC samples (n=6). QC, quality control; PCA, Principal component analysis. Figure S3. Classification and functional annotation of metabolites. A. KEGG pathway annotation for Health and SARA ruminal samples. B. HMDB classification annotation. C. Lipid maps annotation for Health and SARA groups. HMDB, Human Metabolome Database; KEGG, Kyoto Encyclopedia of Genes and Genomes. Figure S4. SARA induced ruminal metabolic changes. A. PLS-DA score plots for ruminal samples (n=6). B. Cross-validation plot with a permutation test repeated 200 times. The intercepts of R2 (0.0, 0.57) and Q2 (0.0,–1.09) indicate that the PLS-DA model was not overfitting. C. Pathway enrichment analysis of significantly elevated metabolites in SARA sample according to the KEGG pathway. Figure S5. Spearman correlation between metabolites and inflammatory parameters. The red color denotes a positive correlation, while green color denotes a negative correlation. The intensity of the color is proportional to the strength of Spearman correlation. *p < 0.05, **p < 0.01, ***p < 0.001 indicate significance. Figure S6. Spearman correlation among metabolites. The top 20 correlated metabolites were showed based on the P value. The red color denotes a positive correlation, while blue color denotes a negative correlation. Figure S7. SA and FMT change the intestinal SA levels. A-B. The intestinal SA levels from different treatment groups (n=6-8). Data are expressed as the mean ± SD (A-B) and one-way ANOVA was performed, followed by Tukey test (A-B). *p < 0.05, **p < 0.01, ***p < 0.001 indicate significant difference. Figure S8. Sialic acid treatment has minimum effects on the synthesis of milk proteins and ileum histology. A-D. Relative mammary gene expressions associated with the synthesis of milk proteins from indicated groups, including Csn1, Csn2, Csn3, and Wap (n=7-8). E. The average weight changes of litters from different treatment groups (n=6). F. Representative images of H&E-stained ileum sections from indicated mice. G. Histological score based on H&E-stained sections (n=7-8). Figure S9. Composition of the gut microbiota in different groups. A. Chao1 index in different groups (n=7-8). B. Ace index (n=7-8). C. Bacterial composition at the family level in the gut were displayed (n=7-8). Each dot represents an individual mouse (A and B) and one-way ANOVA was performed, followed by Tukey test (A and B). ***p < 0.001 indicate significance. ns, no significance. Figure S10. Top 50 metabolism pathways enriched in different groups using Tax4Fun. Figure S11. Sodium tungstate treatment reduces intestinal Enterobacteriaceae abundance. A. The gut microbial compositions at the family level from different treatment groups (n=4). B. A Wilcoxon rank-sum test was performed to identify the differential bacterial taxa in the AN and AN+T groups (FDR < 0.05) (n=4). Figure S12. The ruminal and intestinal microbial compositions in the donor and recipient mice, and the effect of RMT on systemic inflammation in mice. A-D. Alpha diversity indices, including observed species (A), Shannon (B), Chao1 (C) and Simpson index (D), from Health and SARA groups (n=6). E. The ruminal microbial compositions at the family level from the indicated groups (n=6). F. Venn diagram showed the observed OTUs in different RMT groups. G-I. Alpha diversity indices, including Shannon (G), Chao1 (H) and Simpson index (I), from different treatment groups (n=7). J. The gut microbial compositions at the family level from different RMT groups (n=7). K-L. Serum TNF-α (K) and IL-1β (L) levels by ELISA (n=7). Data are expressed as boxplot (A-D and G-I) or the mean ± SD (K-L). A Student’s t test (A-D) or one-way ANOVA was performed, followed by Tukey test (G-I and K-L). *p < 0.05, **p < 0.01, ***p < 0.001 indicate significant difference. Figure S13. A high-starch diet promotes SA production and mastitis in SRMT mice. A. Neu5Ac levels from different treatment groups (n=5). B. Representative images of H&E-stained mammary sections. C. Histological scores based on H&E-stained mammary sections (n=5). D-F. Mammary TNF-α (D), IL-1β (E), MPO activity (F) were assessed (n=5). Data are expressed as the mean ± SD (C-F) and one-way ANOVA was performed, followed by Tukey test (C-F). **p < 0.01, ***p < 0.001 indicate significant difference. Table S1. Identified number of differential metabolites in Health and SARA samples. Table S2. Metabolites significantly upregulated in SARA cows and ranked according to the P-value. Table S3. Metabolites significantly downregulated in SARA cows and ranked according to the P-value. Table S4. The oligonucleotides used in this study