Biology subjects

CHEN, J.

Publications and source records attributed to CHEN, J..

6 recordsLinked to original sources

bioRxiv2026

In vivo programming of stem-like CAR T cells by lymphatic-selective lipid nanoparticle enables durable anti-tumour efficacy in orthotopic model

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in hematological malignancies, yet its efficacy in solid tumours remains limited by poor persistence and progressive exhaustion within the tumour microenvironment. These barriers may be particularly pronounced in emerging in vivo CAR-T therapies, in which transient transgene expression and insufficient control over T-cell differentiation restrict the generation of durable antitumour immunity. Here, we report a primary lymphoid tissue-targeting lipid nanoparticle (pLNP), that directs in vivo CAR-T programming to the thymus and lymphoid tissues, thereby increasing the proportion of stem-like CAR-T cells and promoting durable, exhaustion-resistant antitumour responses. After antibody conjugation, pLNP enabled in vivo CAR expression in developing T cells, generating CAR-T cells enriched in naive and stem cell-like memory phenotypes with prolonged persistence. To reinforce this, we co-administered interleukin-7 (IL-7) mRNA, which increased stem-like CAR-T populations, favoured progenitor exhausted T (Tpex) cells over terminally exhausted states, and enhanced cytotoxic function without overt inflammatory amplification. This stemness-promoting strategy also improved responsiveness to immune checkpoint blockade, producing synergistic antitumour effects with anti-PD-1 therapy, reducing LNP dose requirements, and inducing durable tumour regression with prolonged survival in both subcutaneous and orthotopic DLL3-positive small-cell lung cancer models. Similar enhancement of in vivo CAR-T efficacy was also observed in aged mice with thymic involution. Together, these findings illustrated that primary lymphoid tissue-directed in vivo CAR-T programming is a potential strategy to overcome insufficient persistence and progressive exhaustion in solid tumours.

bioengineering↗

bioRxiv2025

Rapid Identification of Metal Resistance Genes Using an Enhanced ResNet Deep Learning Model Trained on a largely Expanded BacMet-Based Database

Heavy metal pollution poses significant risks to both the environment and public health. Effective management requires not only reducing contaminants but also understanding microbial adaptation, which could be achieved through the comprehensive identification and classification of metal resistance genes. This study expanded the existing BacMet database by incorporating 1,219,137 unique amino acid sequences through BLASTp analysis, thereby increasing the number of metal resistance-related acid sequences by more than 1,600-fold compared to the 753 sequences included in the previous version. We employed various deep learning models for our proposed multi-label framework which could effectively overcome the well-recognized challenging issue of strict classification among metal translocating proteins such as CopA, ZntA, SilA, CadA, and CzcA due to their high sequence similarity and overlapping metal specificities, including AlexNet, VGG, GoogleNet, ResNet, BERT, ViT, and Mamba2, with ResNet demonstrating superior performance in terms of accuracy, robustness, and computational efficiency. The ResNet model achieved a Jaccard score of 98.91%, significantly higher than BLASTp (98.19%) and DIAMOND (98.16%), and was approximately 6,500 times faster in inference speed than these traditional alignment-based methods. Furthermore, the predictive performance of the model and the reliability of the expanded gene library were experimentally validated through overexpression and metal resistance assays of selected genes. Additionally, we developed the Predicting Metal Resistance Amino Acid Sequences (PMRAAS, https://s3.v100.vip:16165) website, facilitating online predictions of gene metal resistance. Our findings provided deeper insights into microbial adaptation mechanisms in metal-polluted environments and offered a robust tool for advancing heavy metal pollution management through enhanced bioremediation strategies.

genomics↗

bioRxiv2025

Neural circuits between nodose ganglion and pulmonary neuroendocrine cells regulate lung inflammatory responses

The lungs are organs exposed to the external environment, and the air we inhale contains various pathogens, such as endotoxins. The vagus nerve, which innervates the lungs, may play a role in detecting pathogens that invade the lungs. Through transcriptome analysis, tissue clearance imaging, electrical excitability recording, and gene- and cell-specific knockout experiments, we found that vagus nerve endings innervate pulmonary neuroendocrine cells (PNECs). These nerve endings sense bacterial endotoxins via pain receptors (TRPA1) rather than toll-like receptors (TLR4), eliciting electrical excitation and enhancing the production of neuropeptides (CGRP) in the nodose ganglia. In turn, CGRP released by sensory neurons from the nodose ganglia promotes both neuropeptide production and the proliferation of PNECs, thereby amplifying endotoxin-induced lung inflammatory responses. This reveals that the neural circuits between the nodose ganglion and PNECs play a critical role in regulating lung inflammatory responses.

neuroscience↗

bioRxiv2024

Catalytic-independent functions of INTAC in conferring sensitivity to BET inhibition

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs with poorly understood mechanisms. Using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary module of the INTAC complex, a global regulator of polymerase pause-release dynamics. This process bypasses a requirement for INTACs catalytic activities and instead leverages direct engagement of the auxiliary module with the RACK7/ZMYND8-KDM5C complex to remove histone H3K4 methylation. Targeted degradation of the COMPASS subunit WDR5 to attenuate H3K4 methylation restores sensitivity to BET inhibitors, highlighting how simultaneously targeting coordinated chromatin and transcription regulators can circumvent drug-resistant tumors.

molecular biology↗

bioRxiv2020

ABCB-mediated auxin transport in outer root tissues regulates lateral root spacing in Arabidopsis

Root branching is an important strategy to explore efficiently large volumes of soil. To economize this process, lateral roots (LR) are formed along the growing root at discrete positions that are instructed by oscillating auxin signals derived from the lateral root cap (LRC). This assumes that auxin moves from the LRC across multiple layers to accumulate in the pericycle. Here, we identified, using gene silencing and CRISPR based approaches, a group of five genetically linked, closely related ABCBs that control LR spacing by modulating the amplitude of the auxin oscillation. The transporters localize to the plasma membrane and reveal significant auxin export activity. These ABCBs are mainly expressed in the LRC and epidermis where they contribute to auxin transport towards the root oscillation zone. Our findings highlight the importance of auxin transport in the outer tissues of the root meristem to regulate LR spacing.

plant biology↗

bioRxiv2019

Genome-wide DNA polymorphisms in four Actinidia arguta genotypes based on whole-genome re-sequencing

Among the genus Actinidia, Actinidia arguta possesses the strongest cold resistance and produces fresh fruit with an intense flavor. To investigate genomic variation that may contribute to variation in phenotypic traits, we performed whole-genome re-sequencing of four A. arguta genotypes originating from different regions in China and identified the polymorphisms using InDel markers. In total, 4,710,650, 4,787,750, 4,646,026, and 4,590,616 SNPs and 1,481,002, 1,534,198, 1,471,304, and 1,425,393 InDels were detected in the Ruby-3, Yongfeng male, Kuilv male, and Hongbei male genomes, respectively, compared with the reference genome sequence of Hongyang. A subset of 120 InDels were selected for re-sequencing validation. Additionally, genes related to non-synonymous SNPs and InDels in coding domain sequences were screened for functional analysis. The analysis of GO and KEGG showed that genes involved in cellular responses to water deprivation, sucrose transport, decreased oxygen levels and plant hormone signal transduction were significantly enriched in A. arguta. The results of this study provide insight into the genomic variation of kiwifruit and can inform future research on molecular breeding to improve cold resistance in kiwifruit.

plant biology↗