67 research outputs found

    Optimization of HiPSCs differentiating into PPs and mechanism study of gene expression noise

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    Human induced pluripotent stem cells (hiPSCs) hold significant potential for cell replacement therapy due to their capacity to differentiate into various cell types. Pancreatic progenitors (PPs) are key intermediate cells in the differentiation of hiPSCs into pancreas cells. However, obtaining uniformly mature PPs remains challenging. Moreover, gene expression is also influenced by gene noise, which can result in stochastic gene expression and subsequent cell heterogeneity. Therefore, it is both essential to develop a universal platform for optimizing hiPSCs differentiation into PPs and to uncover the generation mechanisms of gene noise. In the first part, we established an hiPS cell line with four-reporter genes to monitor marker gene expression and developed a microwell array to mimic the in vivo environment. Based on these two achievements, we could track and analyze cells in real-time or in situ during differentiation. Finally, we successfully optimized the factor combination for hiPSCs differentiation into PPs in 3D environment and efficiently obtained homogeneous Pdx1+ pancreatic organoids. We believe this research can contribute to the development of cell replacement therapy for diabetes. In the second part, we established light-inducible cell lines and developed illumination devices. We observed large noise generated by amplitude modulation (AM) light with intermediate intensity, while this noise could be regulated by pulse-width modulation (PWM) light. We proposed that the noise was induced by the interaction of p65AD and CBP/p300. To validate this hypothesis, we conducted various experiments, including disrupting CBP/P300 HAT activities, assessing histone acetylation and chromatin accessibility through next-generation sequencing (NGS), and evaluating transcriptional noise via mRNA counts, and so on. All these experiments supported our hypothesis. Furthermore, we found that this hypothesis might be also universal in endogenous genes expression in mammalian cells. This research can offer a mechanism-based approach to modulate gene expression noise and is beneficial for studying cell-fate control.</p

    Some results for special families of channels with memory

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    The main concerns of this thesis are some special families of channels with memory, which are of great importance both in theory and in practical applications. Unlike discrete memoryless channels, the capacity of channels with memory generally admits no single-letter characterization and it is difficult to numerically evaluate the channel capacity. As prominent examples of channels with memory, finite-state channels have attracted much interest. However, the numerical computation of the channel capacity of a finite-state channel is still an open problem. Recently, two algorithms have been proposed to numerically compute the channel capacity for a special family of finite-state channels with Markovian inputs. One sufficient condition for the convergence of the proposed algorithms is the concavity of mutual information rate with respect to some chosen parameters of the input Markov chains. In this thesis, under mild positivity conditions, concavity is proved at the high signal-to-noise ratio and counterexamples are given to show that concavity may fail in general. The input-constrained discrete erasure channels are examples of channels with memory and the channel capacity is unknown and has been a long-standing open problem in information theory. In this thesis, an \explicit" formula of the mutual information rate for a discrete erasure channel with a Markovian input is derived. Moreover, if the input Markov chain is of first-order and supported on the (1; ∞)- run length limited constraint, the mutual information rate is shown to be strictly concave with respect to the transition probability of the input Markov chain. By comparing the asymptotics in the high SNR regime, feedback capacity is shown to be strictly larger than the non-feedback capacity, which disproves a statement of Shannon. The other example of channels with memory is the recently proposed ash memory channel model, which possesses both input and output memory. In this thesis, the ash memory channels are shown to be indecomposable under rather weak conditions. Then the channel capacity is shown to be achievable by a stationary process and consequently, as its order tends to infinity, the Markov capacity converges to the real channel capacity. This result suggests that it is highly possible to apply the ideas and techniques in the computation of the capacity of finite-state channels, which are relatively better explored, to that of the capacity of ash memory channels.published_or_final_versionMathematicsDoctoralDoctor of Philosoph

    Author Correction: Climate-driven connectivity loss impedes species adaptation to warming in the deep ocean (Nature Climate Change, (2025), 15, 3, (315-320), 10.1038/s41558-025-02256-7)

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    Correction to: Nature Climate Changehttps://doi.org/10.1038/s41558-025-02256-7, published online 4 March 2025. In the version of this article initially published, four authors, including Yi Li, were listed as corresponding authors. Yi Li is the sole corresponding author, as in now amended in the HTML and PDF versions of the article

    Table_1_Global research trends and focus on the link between colorectal cancer and gut flora: a bibliometric analysis from 2001 to 2021.DOCX

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    BackgroundColorectal cancer (CRC) is a highly prevalent cancer, and the global healthcare system bears a significant burden due to its incidence. Modulating the gut microbiota is a promising approach to enhance the efficacy of CRC treatment and reduce its adverse effects. The causal relationship between specific microorganisms’ presence and CRC development has been widely validated. However, few studies have investigated this relationship using bibliometric methods. Therefore, this study analyzed the research hotspots and trends in human gut microbiology and CRC over the last two decades from a bibliometric perspective. The study aims to provide novel insights into basic and clinical research in this field.MethodsThe articles and reviews on gut microbiota in CRC were obtained from the Web of Science Core Collection (WOSCC) on November 2, 2022. CiteSpace and VOSviewer were used to conduct the bibliometric and knowledge-map analysis.ResultsA total of 2,707 publications were obtained, with a rapid increase in the number of publications since 2015. The United States and China are the main contributors in this field and have established a network of partnerships in several countries. 414 academic journals have published articles on this topic. The author with the highest number of publications is Jun Yu from the Chinese University of Hong Kong. In addition to “intestinal flora” and “colorectal cancer,” high frequency terms in the keyword co-occurrence network analysis included inflammatory bowel disease, Fusobacterium nucleatum, inflammation, long-chain fatty acids, ulcerative colitis, bile acids, and resistant starch. Analysis of keyword trends using burst testing revealed that biomarkers, abnormal crypt foci, bifidobacteria, β-glucuronidase, short-chain fatty acids, bile acids, and DNA methylation are at the forefront of research in this area.ConclusionThe findings of this study provide a bibliometric analysis and visualization of the key research areas in gut microbiota and CRC over the past 20 years. The results suggest that the role of gut microbiota in CRC and its underlying mechanisms should be closely monitored, particularly in the areas of biomarkers, metabolic pathways, and DNA methylation, which may emerge as hot topics in this field.</p

    Identification of sources of elevated concentrations of polycyclic aromatic hydrocarbons in an industrial area in Tianjin, China

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    The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined by gas chromatography equipped with a mass spectrometry detector in 105 topsoil samples from an industrial area around Bohai Bay, Tianjin in the North of China. Results demonstrated that concentrations of PAHs in 104 soil samples from this area ranged from 68.7 to 5,590 ng g (-aEuro parts per thousand 1) dry weight with a mean of a16PAHs 814 +/- 813 ng g (-aEuro parts per thousand 1), which suggests that there exists mid to high levels of PAH contamination. The concentration of a16PAHs in one soil sample from Tianjin Port was exceptionally high (48,700 ng g (-aEuro parts per thousand 1)). Ninety-three of the 105 soil samples were considered to be contaminated with PAHs (> 200 ng g (-aEuro parts per thousand 1)), and 25 were heavily polluted (> 1,000 ng g (-aEuro parts per thousand 1)). The sites with high PAHs concentration are mainly distributed around chemical industry parks and near highways. Two low molecular weight PAHs, naphthalene and phenanthrene, were the dominant components in the soil samples, which accounted for 22.1% and 10.7% of the a16PAHs concentration, respectively. According to the observed molecular indices, house heating in winter, straw stalk combustion in open areas after harvest, and petroleum input were common sources of PAHs in this area, while factory discharge and vehicle exhaust were the major sources around chemical industrial parks and near highways. Biological processes were probably another main source of low molecular weight PAHs
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