Single-nucleus ribonucleic acid-sequencing and spatial transcriptomics reveal the cardioprotection of Shexiang Baoxin Pill (SBP) in mice with myocardial ischemia-reperfusion injury

Aim: The Shexiang Baoxin Pill (SBP) has been extensively used to treat cardiovascular diseases in China for four decades, and its clinical efficacy has been widely approved. However, the mechanism by which this is achieved remains largely unexplored. Research attempting to understand the underlying mechanism is ongoing, but the findings are controversial. Here, we aimed to explore the possible mechanism of SBP in myocardial ischemia-reperfusion (I/R) injury using heart single-nucleus and spatial ribonucleic acid (RNA) sequencing.Methods: We established a murine myocardial I/R injury model in C57BL/6 mice by ligating and recanalizing the left coronary artery anterior descending branch. Subsequently, single-nucleus RNA-seq and spatial transcriptomics were performed on mice cardiac tissue. We initially assessed the status of cell types and subsets in the model administered with or without SBP.Results: We used single-nucleus RNA sequencing to comprehensively analyze cell types in the cardiac tissue of sham, I/R, and SBP mice. Nine samples from nine individuals were analyzed, and 75,546 cells were obtained. We classified the cells into 28 clusters based on their expression characteristics and annotated them into seven cell types: cardiomyocytes, endothelial cells, fibroblasts, myeloid cells, smooth muscle cells, B cells, and T cells. The SBP group had distinct cellular compositions and features than the I/R group. Furthermore, SBP-induced cardioprotection against I/R was associated with enhanced cardiac contractility, reduced endocardial cell injury, increased endocardial-mediated angiogenesis, and inhibited fibroblast proliferation. In addition, macrophages had active properties.Conclusion: SBP improves the early LVEF of I/R mice and has a cardioprotective effect. Through sequencing analysis, we observed that SBP can increase the gene expression of Nppb and Npr3 in the infarct area of the heart. Npr3 is related to vascular generation mediated by endocardial cells and requires further research. In addition, SBP increases the number of fibroblasts, inhibits the expression of genes related to fibroblast activation and proliferation, and increases the transformation of endothelial cells into fibroblasts. These findings will help to indicate directions for further research

Association between EGF +61 G/A and glioma risk in a Chinese population

Abstract Background Epidermal growth factor (EGF) is critical in cancer process. EGF and EGF receptor (EGFR) interaction plays a pivotal role in cell proliferation, differentiation, and tumorigenesis of epithelial tissues. Variations of the EGF +61G/A (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to brain glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population. Methods In this study, we analyzed single nucleotide polymorphism of EGF +61G/A in 677 patients with glioma and 698 gender- and age-matched controls. Genotyping was performed by polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Results The A allele (minor Allele) was 33.0% in cases and 27.3% in controls. The additive model was more powerful to reveal the association in our study than that of recessive and dominant model. Our data showed the genotype G/A and A/A was associated with increased risk for glioma (adjusted OR = 1.48, 95%CI: 1.17-1.87, p = 0.001 for G/A, adjusted OR = 1.81, 95%CI: 1.20-2.72, p = 0.005 for A/A, respectively), and for glioblastoma (adjusted OR = 1.51, 95%CI: 1.06-2.17, p = 0.024 and adjusted OR = 2.35, 95%CI: 1.34-4.15, p = 0.003, respectively). The A allele significantly increased glioma risk (OR = 1.31, 95%CI: 1.11-1.55, p = 0.001). The additive model (G/G vs G/A vs A/A) showed that both G/A and A/A genotype increased glioma risk (adjusted OR = 1.40, 95% CI: 1.17-1.66, p = 0.0002).G/A and A/A genotypes or EGF +61 A allele increased risk in both low and high WHO grade glioma. Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers. Conclusions Our study indicated that G/A and A/A genotypes or EGF +61 A allele were associated with higher glioma risk in Chinese. This is in contrast with previous studies which reported G allele as a risk factor of glioma in Caucasian. The role of EGF +61 A/G polymorphism in glioma susceptibility needs further investigation.</p

Single nucleotide polymorphisms in DNA repair genes and risk of cervical cancer: A case-control study

In this report, we describe a case control study in a Chinese population aimed at identifying possible associations between susceptibility to cervical cancer and single nucleotide polymorphisms in XRCC1 194C>T, XRCC1 280G>A, XRCC1 399G>A, ERCC2 751A>C, ERCC2 156C>A, ERCC1 118C>T, PARP1 762T>C, RAD51 135G>C and HER2 655A>G. The cases comprised 154 patients: 80 cervical squamous cell carcinomas (SCCs), 2 adenocarcinomas and 72 cervical intraepithelial neoplasias (CINs). A total of 177 healthy women were recruited as the controls. A significant association was found between ERCC1 118C>T and SCC in the additive genetic model [odds ratio (OR)=1.711; 95% confidence interval (CI), 1.089–2.880; p=0.021] and the dominant genetic model (OR=1.947; 95% CI, 1.056–3.590; p=0.033). Among women with a smoking family member, ERCC1 118C>T increased SCC risk in the additive model (OR=2.800; 95% CI, 1.314–5.968; p=0.008). For women who had first intercourse before 22 years of age, XRCC1 280G>A was found to act as a protective factor for SCC under the additive model (OR=0.228; 95% CI, 0.058–0.900; p=0.035), while RAD51 135G>C was a risk factor for CIN (OR=4.246; 95% CI, 1.335–13.502; p=0.014). For women who had first intercourse after 22 years of age, the additive genetic model showed RAD51 135G>C (OR=0.359; 95% CI, 0.138–0.934; p=0.036) and HER2 655A>G (OR=0.309; 95% CI, 0.098–0.972; p=0.045) to be protective factors for SCC. XRCC1 399G>A increased CIN risk among women who first gave birth before the age of 22 in the additive genetic model (OR=4.459; 95% CI, 1.139–17.453; p=0.032). For those who first gave birth after age 22, ERCC1 118C>T was found to be a risk factor for SCC in the additive genetic model (OR=1.884; 95% CI, 1.088–3.264; p=0.024). A significant interaction was observed between RAD51 135G>C and age at first intercourse (pinteraction=0.033 for SCC, pinteraction=0.021 for CIN), as well with sexual partner number (pinteraction=0.001 for SCC). The interaction between HER2 655A>G and age at first intercourse, ERCC2 156C>A and family smoking status and XRCC1 280G>A and alcohol consumption were significant, with pinteraction=0.023 for SCC, pinteraction=0.021 for CIN and pinteraction=0.025 for SCC, respectively

Systematic genome editing of the genes on zebrafish Chromosome 1 by CRISPR/Cas9

Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes. Meanwhile, by high-throughput bioinformatics analysis, we found that sequence features play pivotal roles in effective gRNA targeting at specific genes of interest, while the success rate of gene targeting positively correlates with GC content of the target sites. Moreover, we found that nearly one-fourth of all mutants are related to human diseases, and several representative CRISPR/Cas9-generated mutants are described here. Furthermore, we tried to identify the underlying mechanisms leading to distinct phenotypes between genetic mutants and antisense morpholino-mediated knockdown embryos. Altogether, this work has generated the first chromosome-wide collection of zebrafish genetic mutants by the CRISPR/Cas9 technology, which will serve as a valuable resource for the community, and our bioinformatics analysis also provides some useful guidance to design gene-specific gRNAs for successful gene editing

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios

CEPC Conceptual Design Report: Volume 2 - Physics & Detector

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios

CEPC Technical Design Report -- Accelerator

International audienceThe Circular Electron Positron Collider (CEPC) is a large scientific project initiated and hosted by China, fostered through extensive collaboration with international partners. The complex comprises four accelerators: a 30 GeV Linac, a 1.1 GeV Damping Ring, a Booster capable of achieving energies up to 180 GeV, and a Collider operating at varying energy modes (Z, W, H, and ttbar). The Linac and Damping Ring are situated on the surface, while the Booster and Collider are housed in a 100 km circumference underground tunnel, strategically accommodating future expansion with provisions for a Super Proton Proton Collider (SPPC). The CEPC primarily serves as a Higgs factory. In its baseline design with synchrotron radiation (SR) power of 30 MW per beam, it can achieve a luminosity of 5e34 /cm^2/s^1, resulting in an integrated luminosity of 13 /ab for two interaction points over a decade, producing 2.6 million Higgs bosons. Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons, facilitating precise measurements of Higgs coupling at sub-percent levels, exceeding the precision expected from the HL-LHC by an order of magnitude. This Technical Design Report (TDR) follows the Preliminary Conceptual Design Report (Pre-CDR, 2015) and the Conceptual Design Report (CDR, 2018), comprehensively detailing the machine's layout and performance, physical design and analysis, technical systems design, R&D and prototyping efforts, and associated civil engineering aspects. Additionally, it includes a cost estimate and a preliminary construction timeline, establishing a framework for forthcoming engineering design phase and site selection procedures. Construction is anticipated to begin around 2027-2028, pending government approval, with an estimated duration of 8 years. The commencement of experiments could potentially initiate in the mid-2030s