Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

The diagnostic value of narrow-band imaging for early and invasive lung cancer: a meta-analysis

This study aimed to compare the ability of narrow-band imaging to detect early and invasive lung cancer with that of conventional pathological analysis and white-light bronchoscopy. We searched the PubMed, EMBASE, Sinomed, and China National Knowledge Infrastructure databases for relevant studies. Meta-disc software was used to perform data analysis, meta-regression analysis, sensitivity analysis, and heterogeneity testing, and STATA software was used to determine if publication bias was present, as well as to calculate the relative risks for the sensitivity and specificity of narrow-band imaging vs those of white-light bronchoscopy for the detection of early and invasive lung cancer. A random-effects model was used to assess the diagnostic efficacy of the above modalities in cases in which a high degree of between-study heterogeneity was noted with respect to their diagnostic efficacies. The database search identified six studies including 578 patients. The pooled sensitivity and specificity of narrow-band imaging were 86% (95% confidence interval: 83-88%) and 81% (95% confidence interval: 77-84%), respectively, and the pooled sensitivity and specificity of white-light bronchoscopy were 70% (95% confidence interval: 66-74%) and 66% (95% confidence interval: 62-70%), respectively. The pooled relative risks for the sensitivity and specificity of narrow-band imaging vs the sensitivity and specificity of white-light bronchoscopy for the detection of early and invasive lung cancer were 1.33 (95% confidence interval: 1.07-1.67) and 1.09 (95% confidence interval: 0.84-1.42), respectively, and sensitivity analysis showed that narrow-band imaging exhibited good diagnostic efficacy with respect to detecting early and invasive lung cancer and that the results of the study were stable. Narrow-band imaging was superior to white light bronchoscopy with respect to detecting early and invasive lung cancer; however, the specificities of the two modalities did not differ significantly

Immune Checkpoint B7-H3 Is a Therapeutic Vulnerability in Prostate Cancer Harboring Pten and TP53 Deficiencies

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3\u27s role in cancer progression, predictive biomarkers for B7-H3-targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate cancer. We found that loss of PTEN and TP53 induced B7-H3 expression by activating transcriptional factor Sp1. Prostate-specific deletion of Cd276 resulted in delayed tumor progression and reversed the suppression of tumor-infiltrating T cells and NK cells in Pten/Trp53 genetically engineered mouse models. Furthermore, we tested the efficacy of the B7-H3 inhibitor in preclinical models of castration-resistant prostate cancer (CRPC). We demonstrated that enriched regulatory T cells and elevated programmed cell death ligand 1 (PD-L1) in myeloid cells hinder the therapeutic efficacy of B7-H3 inhibition in prostate tumors. Last, we showed that B7-H3 inhibition combined with blockade of PD-L1 or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) achieved durable antitumor effects and had curative potential in a PTEN/TP53-deficient CRPC model. Given that B7-H3-targeted therapies have been evaluated in early clinical trials, our studies provide insights into the potential of biomarker-driven combinatorial immunotherapy targeting B7-H3 in prostate cancer, among other malignancies

Effects of solar wind density and velocity variations on the Martian ionosphere and plasma transport - a MHD model study

Solar wind dynamic pressure, consisting solar wind density and velocity , is an important external driver that controls Martian plasma environment. In this study, a 3D magnetohydrodynamic model is applied to investigate the separate influences of solar wind density and velocity on the Martian ionosphere. The spatial distributions of ions in the dayside and near nightside ionosphere under different and are analyzed, as well as the ion transport process. We find that for the same dynamic pressure condition, the ionosphere extends to higher altitudes under higher solar wind density, indicating that a solar wind velocity enhancement event is more efficient at compressing the Martian ionosphere. A higher will result in a stronger induced magnetic field, shielding the Martian ionosphere, preventing the penetration of solar wind particles. For the same dynamic pressure, increasing (decreasing ) leads to a higher horizontal ion velocity, facilitating day-to-night plasma transport. As a result, the ionosphere extends farther into the nightside. Also, the ion outflow flux is larger for high , which may lead to a higher escape rate. Moreover, the strong crustal fields in the southern hemisphere also cause significant effect to the ionosphere, hindering horizontal ion transport. An additional outflow channel is also provided by the crustal field on the southern dayside, causing different responses of flow pattern between local and global scale while the solar wind condition is varied

Author Correction: Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results

Correction to "Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results

UHPLC-HRMS-Based Untargeted Lipidomics Reveal Mechanism of Antifungal Activity of Carvacrol against <i>Aspergillus flavus</i>

Aspergillus flavus is a common contaminant in grain, oil and their products. Its metabolite aflatoxin B1 (AFB1) has been proved to be highly carcinogenic. Therefore, it is of great importance to find possible antifungal substances to inhibit the growth and toxin production of Aspergillus flavus. Carvacrol (CV) was reported as a potent antifungal monoterpene derived from plants. In this paper, the antifungal effects and mechanism of CV on Aspergillus flavus were investigated. CV was shown good inhibition on the growth of Aspergillus flavus and the production of AFB1. CV used in concentrations ranging from 0, 50, 100 and 200 μg/mL inhibited the germination of spores, mycelia growth and AFB1 production dose-dependently. To explore the antifungal mechanism of CV on Aspergillus flavus, we also detected the ergosterol content of Aspergillus flavus mycelia, employed Scanning Electron Microscopy (SEM) to observe mycelia morphology and utilized Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS) to explore the lipidome profiles of Aspergillus flavus. The results showed that the production of ergosterol of mycelia was reduced as the CV treatment concentration increased. SEM photographs demonstrated a rough surface and a reduction in the thickness of hyphae in Aspergillus flavus treated with CV (200 µg/mL). In positive ion mode, 21 lipids of Aspergillus flavus mycelium were downregulated, and 11 lipids were upregulated after treatment with 200-µg/mL CV. In negative ion mode, nine lipids of Aspergillus flavus mycelium were downregulated, and seven lipids upregulated after treatment with 200-µg/mL CV. In addition, the analysis of different lipid metabolic pathways between the control and 200-µg/mL CV-treated groups demonstrated that glycerophospholipid metabolism was the most enriched pathway related to CV treatment

A Wearable Combined Wrist Pulse Measurement System Using Airbags for Pressurization

The pulse measurement instrument is based on traditional Chinese medicine (TCM) and is used to collect the pulse of patients to assist in diagnosis and treatment. In the existing pulse measurement system, desktop devices have large volumes, complex pressure adjusting operations, and unstable pressurization. Wearable devices tend to have no pressurization function or the function to pressurize three channels separately, which are not consistent with the diagnostic method in TCM. This study constructs a wearable pulse measurement system using airbags for pressurization. This system uses guide plates, guide grooves, and positioning screws to adjust the relative position of the wristband and locate Cun, Guan and Chi regions. The pulse signal measured by the sensor is collected and sent to a computer by microcontroller unit. In experiments, this system successfully obtains the best pulse-taking pressure, its pulse waveform under continuous decompression, and the pulse waveform of three regions under light, medium, and heavy pressure. Compared with the existing technology, the system has the advantages of supporting single-region and three-region pulse acquisition, independent pressure adjustment, and position adjustment. It meets the needs of home, medical, and experimental research, and it is convenient and comfortable to wear and easy to carry

Associations of CYP24A1 Copy Number Variation with Vitamin D Deficiency and Insulin Secretion

Vitamin D plays an important role in insulin secretion. As the enzyme that initiates degradation of the active metabolite of vitamin D (1,25-(OH)2 vitamin D), 24-hydroxylase encoded by CYP24A1 may be associated with insulin secretion. In this study, we aimed at investigating the association between copy number of CYP24A1 and the concentration of insulin. Included in the study were 1528 rural people from Henan Province of China. The copy number of CYP24A1 and the concentrations of serum 25(OH) vitamin D3 and insulin were determined. Association between copy number of CYP24A1 and vitamin D deficiency was investigated with logistic regression model. Correlation between copy number of CYP24A1 and serum insulin was observed by Spearman correlation. The results suggested that copy number variation of CYP24A1 was associated with vitamin D deficiency. Higher copy number of CYP24A1 was a risk factor for vitamin D deficiency (adjusted odds ratio: 1.199; 95% confidence interval: 1.028–1.397; P = 0.021). Furthermore, copy number of CYP24A1 was positive correlated with the concentration of serum insulin (r = 0.115; P < 0.001), regardless of vitamin D status, age, and body mass index (BMI). Increased copy number of CYP24A1 is associated with not only vitamin D deficiency but also increased serum insulin. Vitamin D supplement may be beneficial to individuals with high copy number of CYP24A1. Novelty Increased copy number of CYP24A1 was a risk factor of vitamin D deficiency. Increased copy number of CYP24A1 was associated with increased serum concentration of insulin independent of age, BMI, and vitamin D status.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Characteristics of Urban Flood Resilience Evolution and Analysis of Influencing Factors: A Case Study of Yingtan City, China

Intense climate change and rapid urbanization have increased the risk of urban flooding, seriously affecting urban economic and social stability. Enhancing urban flood resilience (UFR) has required a new solution to cope with urban flood disasters. In this study, taking Yingtan city as an example, a system of indicators for evaluating UFR was constructed, with 17 representative indicators, comprising three subsystems: socio-economic, ecological, and infrastructural. A hybrid model combining Fuzzy Analytic Hierarchy Process (FAHP), Entropy Weight Method (EWM), and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was applied, to develop an index-based measurement to compare and evaluate UFR, and Gray Relational Analysis (GRA) was used to discover the main factors affecting UFR. In addition, the natural discontinuous method was innovatively used to divide the UFR grade interval into levels, and the grade change was evaluated based on the TOPSIS method. The results showed that (1) From 2010 to 2022, the UFR in Yingtan City increased by 80.69%, and the factors affecting UFR were highly correlated with urban infrastructure development; however, the ecological resilience in the subsystem showed a fluctuating downward trend because of the influence of the surface area of lakes and rivers; (2) The grades of UFR for Yingtan City increased from Level III (2010 and 2016) to Level IV (2022), with local financial expenditures and the age structure of the population being the main factors currently limiting the development of UFR. The study provides a theoretical basis for the construction of an indicator system for assessing the UFR of Yingtan and proposes practical improvement directions for UFR