Biology subjects

Ji, Z.-L.

Publications and source records attributed to Ji, Z.-L..

5 recordsLinked to original sources

bioRxiv2026

A Selective Multivalent NET-Associated Chromatin Neutralizer Resolves Infection-Associated Inflammation in Severe Sepsis

Targeting the overwhelming inflammation driven by neutrophil extracellular traps (NETs) during infection provides an opportunity to manage severe sepsis. This potential needs to be realized by exploring selective NET-neutralization materials, which remains a challenge. Herein, we report a multivalent macromolecular strategy that targets NET-associated DNA-histone chromatin complexes while preserving antibacterial activity of aminoglycoside. We identify 8-arm PEG-conjugated netilmicin (8-arm Netil) as a lead NETs-neutralizer from a library of multivalent aminoglycoside-displayed materials. When compared with 2- and 4-arm counterparts, 8-arm Netil exhibits potent antibacterial activity and high-affinity binding to DNA-histone chromatin complexes through stable multivalent noncovalent interactions, thereby suppressing NET-induced TLR4/TLR9 activation and macrophage inflammatory responses. In severe septic mice, intravenously administered 8-arm Netil preferentially accumulates in inflamed tissues, leading to improved survival protection, owing to the reduction of bacterial dissemination, NET accumulation, systemic cytokine production, and multiple-organ injury. These findings establish NET-associated DNA-histone chromatin complexes as actionable extracellular targets and demonstrate multivalent chromatin targeting as a rational material design strategy for selective NET neutralization and inflammation control in severe sepsis.

bioengineering↗

bioRxiv2025

3' to 5' Translation of Circular RNAs?

For decades, the 5[->]3 direction of translation has been a central dogma of molecular biology(1). Here we present evidence that eukaryotic circular RNAs (circRNAs) can serve as templates for 3[->]5 backward translation (BT), yielding polypeptides with distinct sequence and structural features not found in canonical proteomes. Mining of more than 6,000 multi-omics datasets identified [~]1 million candidate BT proteins across eukaryotes, including 59,000 high-confidence human BT proteins supported by mass spectrometry. Genetic combinatorial experiments (KO and KI) and cell-free translation of synthetic circRNAs establish BT as a conserved mechanism. Loss-of-function studies of hs.circCAPN15 in human and dm.circROLS in Drosophila underscore the functional importance of BT-derived proteins. Our work challenges the long-standing unidirectional translation paradigm, expands the functional landscape of the genetic code, and reveals a hitherto hidden layer of proteomic complexity with broad implications for biology and therapeutics.

molecular biology↗

bioRxiv2023

Nphos: Database and Predictor of Protein N-phosphorylation

Protein N-phosphorylation widely present in nature and participates in various biological functions. However, current knowledge on N-phosphorylation is extremely limited compared to that on O-phosphorylation. In this study, we collected 11,710 experimentally verified N-phosphosites of 7344 proteins from 39 species and subsequently constructed the database Nphos to share up-to-date information on protein N-phosphorylation. Upon these substantial data, we characterized the sequential and structural features of protein N-phosphorylation. Moreover, after comparing of hundreds of learning models, we chose and optimized gradient boosting decision tree (GBDT) models to predict three types of human N-phosphorylation, achieving mean areas under the receiver operating characteristic curve (AUC) of 90.56%, 91.24%, and 92.01% for pHis, pLys, and pArg, respectively. Meanwhile, we discovered 488,825 distinct N-phosphosites in the human proteome. The models were also deployed in Nphos for interactive N-phosphosite prediction. In summary, this work provides new insights and points for both flexible and focused investigations of N-phosphorylation. It will also facilitate a deeper and more systematic understanding of protein N-phosphorylation modification by providing a data and technical foundation. Nphos is freely available at http://www.bio-add.org and http://ppodd.org.cn/Nphos/.

bioinformatics↗

bioRxiv2020

Integrate Heterogeneous NGS and TGS Data to Boost Genome-free Transcriptome Research

It is a long-term challenge to undertake reliable transcriptomic research under different circumstances of genome availability. Here, we newly developed a genome-free computational method to aid accurate transcriptome assembly, using the amphioxus as the example. Via integrating ten next generation sequencing (NGS) transcriptome datasets and one third-generation sequencing (TGS) dataset, we built a sequence library of non-redundant expressed transcripts for the amphioxus. The library consisted of overall 91,915 distinct transcripts, 51,549 protein-coding transcripts, and 16,923 novel extragenic transcripts. This substantially improved current amphioxus genome annotation by expanding the distinct gene number from 21,954 to 38,777. We consolidated the library significantly outperformed the genome, as well as de novo method, in transcriptome assembly from multiple aspects. For convenience, we curated the Integrative Transcript Library database of the amphioxus (http://www.bio-add.org/InTrans/). In summary, this work provides a practical solution for most organisms to alleviate the heavy dependence on good quality genome in transcriptome research. It also ensures the amphioxus transcriptome research grounding on reliable data.

bioinformatics↗

bioRxiv2020

Reference-free and de novo Identification of Circular RNAs

BackgroundEarly studies have unveiled multiple regulatory functions of circular RNAs (circRNAs); however, accurate detection and quantification of circRNAs, especially in understudied organisms, is unsolved yet. ResultsIn this study, we developed a new reference-free method, namely Cirit, to de novo detect circRNAs with sequence support from the next generation sequencing (NGS) transcriptome. The Cirit showed remarkable performance in accurate detection and quantification of circRNAs via comparing with current methods from different aspects. Using Cirit, we detected 28,813 nonredundant human circRNAs from 91 transcriptome datasets, as well as 2,385 circRNAs from four understudied organisms. Subsequent analyses found that the majority of human circRNAs expressed spatiotemporally; only a very small portion of circRNAs were back-splice junction (BSJ)-consistent (maximally 5.17%) or sequence-consistent (under 2%). Furthermore, circRNA genesis were relatively flexible that only about 60% of human circRNAs used the canonical GT-AG pattern for back-splice. The inconsistent expression of circRNAs challenges their roles as precise transcriptional regulators. ConclusionsIn summary, the reference-free method provides a straightforward and universal way for reliable circRNA research. It will largely boost the successful rate in designing highly specific probes to monitor circRNA behavior in cell. In particular, it brings circRNA research to the organisms that have no genome or draft genome.

bioinformatics↗