Author Correction: Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.
Explore the source record for details and available documents.
Published Erratum↗
Biomedical subjects
Peng Du
Publications and source records attributed to Peng Du.
From population to individual: advocating personalised digital tools for heat-health early warning in a changing climate.
Escalating heat extremes under climate change are imposing substantial health burdens, with 2023 and 2024 consecutively breaking global temperature records. Mounting evidence suggests that heatwaves elevate the risks of hospitalisation and mortality across multiple disease categories, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and acute kidney injury. Nonetheless, most existing heat-health warning systems remain primarily reliant on population-level predictions, and considering individual differences and disease-specific considerations when defining warning levels would benefit the effectiveness of early prevention for high-risk groups. In this Viewpoint, which is based on the framework of precision public health-delivering the right intervention to the right population at the right time-we propose a framework for personalised digital heat-health early warning tools comprising three dimensions: individualised, risk-stratified prediction models that generate tiered early warnings; personalised health prompts coupled with theory-informed behavioural interventions; and adaptive, equity-oriented alert delivery mechanisms tailored to diverse populations. Such tools have the potential to bridge precision disease prevention and climate adaptation, thereby helping to mitigate heat exposure risks and disease burdens, particularly among high-risk populations. Future implementation research will be essential to address substantial challenges related to feasibility, validation, and equity.
Journal Article↗
Targeting MondoA-TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment.
In the tumour microenvironment, accumulated lactic acid (LA) promotes tumour immune evasion by facilitating regulatory T cell (Treg) immunosuppressive function and restraining CD8+ T cell cytotoxicity, but the underlying mechanism remains elusive. Here we report that transcriptional factor MondoA-induced thioredoxin interacting protein (TXNIP) transcription is a common feature of both Treg and CD8+ T cells in response to lactic acid. In contrast to reduction in immunosuppressive capacity in MondoA-deficient Treg cells, loss of MondoA enhanced CD8+ T cell cytotoxic function in the lactic-acid-induced immunosuppressive microenvironment, by restoring glucose uptake and glycolysis. Mechanistically, lactic acid relied on sentrin/SUMO-specific protease 1 (SENP1) to stimulate the MondoA-TXNIP axis, which impaired TCR/CD28-signal-induced CD8+ T cell activation. Importantly, targeting the MondoA-TXNIP axis potentiated antitumour immunity in multiple cancer types and synergized with anti-PD-1 therapy to promote effective T cell responses in colorectal cancer. Our results demonstrate that the MondoA-TXNIP axis is a promising therapeutic target for improving cancer immunotherapy.
Tumor Microenvironment↗
Mouse totipotent blastomere-like cells model embryogenesis from zygotic genome activation to post implantation.
Embryo development begins with zygotic genome activation (ZGA), eventually generating blastocysts for implantation. However, in vitro systems modeling the pre-implantation development are still absent and challenging. Here, we used mouse totipotent blastomere-like cells (TBLCs) to develop spontaneous differentiation and blastoid formation systems, respectively. We found Wnt signaling enabled the rapid expansion of TBLCs and the optimization of their culture medium. We successfully developed a TBLC-spontaneous differentiation system in which mouse TBLCs (mTBLCs) firstly converted into two types of ZGA-like cells (ZLCs) distinguished by Zscan4 expression. Surprisingly, Zscan4-, but not Zscan4+, ZLCs further passed through intermediate 4-cell and then 8-cell/morula stages to produce epiblast, primitive endoderm, and trophectoderm lineages. Significantly, single TBLCs underwent expansion, compaction, and polarization to efficiently generate blastocyst-like structures and even post-implantation egg-cylinder-like structures. Conclusively, we established TBLC-based differentiation and embryo-like structure formation systems to model early embryonic development, offering criteria for evaluating and understanding totipotency.
Animals↗