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Ping, Z.

Publications and source records attributed to Ping, Z..

6 recordsLinked to original sources

Fibrotic lung-derived sphingosine-1-phosphate drives emotion-like disorders by regulating hippocampal neuroinflammation and cell death

The incidence of emotional disorders in patients with idiopathic pulmonary fibrosis (IPF) is substantially higher than that in the general population, severely compromising their quality of life. However, the underlying mechanisms remain poorly understood. In this study with multi-omics, we demonstrated that sphingosine-1-phosphate (S1P) derived from IPF lungs drive anxiety and depressive-like behaviors. Mechanistically, circulating S1P in the blood bound to hippocampal S1PR1 to regulate the PI3K/PKA/CREB signaling pathway, leading to synapse damage, the activation of microglia and astrocytes, neuroinflammation and ferroptosis in the hippocampus. Pharmacological inhibition of Sphk1, a key enzyme in S1P synthesis, reduced serum S1P levels and alleviated IPF-induced anxiety and depressive-like behaviors. Similarly, selective inhibition of hippocampal S1P receptor signaling using Fingolimod also attenuated neuroinflammation and ferroptosis and ameliorated mood disorders in IPF models. Collectively, these findings demonstrate that metabolite S1P from fibrotic lungs serves as a mediator of lung-to-brain functional influence, providing new insights into the IPF comorbid mood disorders and potential therapeutic targets.

neuroscience↗

A practical DNA data storage using expanded alphabet introducing 5-methylcytosine

DNA molecular is a promising next-generation data storage medium. Recently, it has been theoretically proposed that non-natural or modified bases can serve as extra molecular letters to increase the information density. However, the feasibility of the strategy is challenging due to the difficulty in synthesizing and the complex structure of non-natural DNA sequences. Here, we described a practical DNA data storage transcoding scheme named R+ based on expanded molecular alphabet by introducing 5-methlcytosine(5mC). We also demonstrated the experimental validation by encoding one representative file into several 1.3~1.6 kbps in vitro DNA fragments for nanopore sequencing. The results show an average data recovery rate of 98.97% and 86.91% with and without reference respectively. This work validates the practicability of 5mC in DNA storage systems, with a potentially wide range of applications. Availability & ImplementationR+ is implemented in Python and the code is available under the MIT license at https://github.com/Incpink-Liu/DNA-storage-R_plus

synthetic biology↗

Pooled genetic screens identify breast cancer risk genes involved in evasion from T cell-mediated killing

Genome-wide association studies have identified more than 220 loci associated with breast cancer susceptibility. A major challenge is now to identify the effector genes with plausible functions in the context of breast cancer risk. We have previously performed pooled CRISPR screens to identify target genes at risk loci that drive cancer hallmarks including proliferation or modulating DNA damage response. We now extend these screens to identify genes involved in response to cytotoxic T lymphocyte (CTL) killing. We performed knockout and inhibition screens to identify genes that affect the response of the MCF7 human breast cancer cell line to CTL killing in an in vitro co-culture system. We identified 33 candidate risk genes associated with resistance or sensitisation to T cell-mediated killing. Using single gene perturbation, we showed that deletion of candidate risk genes IRF1, ATF7IP, CCDC170 and CASP8 induced resistance, while ablation of CFLAR, CREBBP, and PRMT7 sensitized cells to CTL killing. We used reporter assays to show that the risk-associated alleles at rs736801 and rs3769821 reduced transactivation of the IRF1 and CASP8 promoters, respectively. We showed that pharmacological inhibition of PRMT7 rendered breast cells sensitive to CTL killing and PRMT7 levels were negatively correlated with CD8+ infiltration and patient survival in luminal A breast cancer patient cohorts. Our results demonstrate that phenotypic pooled CRISPR screens are a useful approach for high throughput functional follow-up of GWAS findings, identifying genes which alter immune responses to breast cancer which offer opportunities to enhance immunotherapy.

genetics↗

Unveiling the Intricate Sinking behavior of Large Diatoms: Insights from Time-Frequency Analysis of Palmerina hardmaniana Sinking under Silicate-Depleted Conditions

Nutrient limits impact diatom sinking in time domain, but response in time-frequency domain is unclear. Studying the response of large diatoms to nutrients exclusively in the time domain fails to fully capture the complete impact of nutrient limitations on sinking behavior due to the absence of crucial information, including period and frequency. Wavelet analysis provides valuable insights into the period and frequency of signals and unveils their positions in the time. This study investigated the sinking behavior response of the large diatom Palmerina hardmaniana to silicate-depleted conditions in the time-frequency domain using wavelet analysis. The results showed that P. hardmaniana was capable of regulating its sinking speed, and this regulation occurred intermittently in time. The predominant frequency of intermittent regulation fell within the range of 0.13-0.50 Hz (equivalent to a period of 2-8 s) for both control and silicate-depleted conditions. The similarity in the frequency range of regulation between the two groups suggests the involvement of shared physiological mechanisms. P. hardmaniana responded to silicate depletion by intensifying the regulation of 0.13-0.50 Hz, which was reflected in the time domain as a change in the proportion of different instantaneous sinking speeds and consequently lead to a significant increase or decrease in the mean sinking speed (p<0.05). Additionally, the regulation of P. hardmaniana sinking behavior was also influenced by the physiological state of the cells. Short-term silicate stress (30 min) enhanced the oscillation power of sinking regulation, while prolonged silicate stress ([&ge;] 3 d) led to a decline in oscillation power.

plant biology↗

Chamaeleo: a robust library for DNA storage coding schemes

Chamaeleo is currently the only collection library that focuses on adapting multiple well-established coding schemes for DNA storage. It provides a tool for researchers to study various coding schemes and apply them in practice. Chamaeleo adheres to the concept of high aggregation and low coupling for software design which will enhance the performance efficiency. Here, we describe the working pipeline of Chamaeleo, and demonstrate its advantages over the implementation of existing single coding schemes. The source code is available at https://github.com/ntpz870817/Chamaeleo, it can be also installed by the command of pip.exe, "pip install chamaeleo". Alternatively, the wheel file can be downloaded at https://pypi.org/project/Chamaeleo/. Detailed documentation is available at https://chamaeleo.readthedocs.io/en/latest/. Author SummaryDNA is now considered to be a promising candidate media for future digital information storage in order to tackle the global issue of data explosion. Transcoding between binary digital data and quanternary DNA information is one of the most important steps in the whole process of DNA digital storage. Although several coding schemes have been reported, researchers are still investigating better strategies. Moreover, the scripts of these coding schemes use different programming languages, software architectures and optimization contents. Therefore, we here introduce Chamaeleo, a library in which several classical coding schemes are collected, to reconstruct and optimize them. One of the key features of this tool is that we modulize the functions and make it feasible for more customized way of usage. Meanwhile, developers can also incorporate their new algorithms according to the framework expediently. Based on the benchmark tests we conducted, Chamaeleo shows better flexibility and expandability compared to original packages and we hope that it will help the further study and applications in DNA digital storage.

bioinformatics↗

Towards Practical and Robust DNA-based Data Archiving by Codec System Named ‘Yin-Yang’

DNA is a promising data storage medium due to its remarkable durability and space-efficient storage. Early bit-to-base transcoding schemes have primarily pursued information density, at the expense however of introducing biocompatibility challenges or at the risk of decoding failure. Here, we propose a robust transcoding algorithm named the "Yin-Yang Codec" (YYC), using two rules to encode two binary bits into one nucleotide, to generate DNA sequences highly compatible with synthesis and sequencing technologies. We encoded two representative file formats and stored them in vitro as 200-nt oligo pools and in vivo as an ~54-kb DNA fragment in yeast cells. Sequencing results show that YYC exhibits high robustness and reliability for a wide variety of data types, with an average recovery rate of 99.94% at 104 molecule copies and an achieved recovery rate of 87.53% at 100 copies. In addition, the in vivo storage demonstration achieved for the first time an experimentally measured physical information density of 198.8 EB per gram of DNA (44% of the theoretical maximum for DNA).

synthetic biology↗