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DNA damage from chemotherapy can activate cGAS–STING and interferon pathways. Here, the authors show that cGAS–STING signaling is specific to DNA rich in CA repeats, whereas DNA not rich in CA repeats is detected by AIM2, resulting in opposing tumor immune responses.

Nie et al. show that myocardial CCDC25 detects doxorubicin-induced neutrophil extracellular trap DNA and activates reactive oxygen species production and autophagy, leading to cardiotoxicity. Targeting CCDC25 exerts a cardioprotective effect without impacting the antitumor activity of doxorubicin in lymphoma and breast cancer models.

Fixing CO₂ into value-added solid carbon such as carbon nanofibres is a promising process but poses substantial challenges. Now a tandem strategy is proposed where CO₂ and water are electrocatalytically converted into syngas to subsequently form carbon nanofibres via a thermocatalytic process.

Engineered TadA variants in cytosine base editors (CBEs) offer advantages like smaller size and reduced off-target effects. Here, authors develop an advanced CBE (aTdCBE) through ortholog screening and protein engineering, successfully enabling exon skipping in Duchenne muscular dystrophy model.

Using a thermal Rb-Xe hybrid spin maser the authors report the observation of a time crystal. The formation of time crystal is caused by a strong retarded interaction and the new oscillation frequency scales with the delay time characterized by the phase lag of the original oscillations.

Cyclin D1 is involved in tamoxifen resistance in breast cancer (BC) but how it is regulated is unclear. Here, the authors demonstrate that the LncRNA DILA1 contributes to tamoxifen resistance in breast cancer by binding to Cyclin D1 and preventing its degradation.

C->G transversions can be highly desirable editing outcomes. Here the authors optimise CGBEs and provide a deep learning model for predicting editing outcomes based on sequence context.

Analysis of CRISPR-Cas off-targets is important. Here the authors incorporate molecular dynamics simulations in the computational analysis of CRISPR editing and report the CRISOT tool suite and apply this to genome-wide CRISPR off-target prediction and sgRNA optimisation.

Song and colleagues report that in breast cancer, chemotherapy induces the IRENA lncRNA, which reprograms tumor suppressive macrophages to protumorigenic phenotypes and promotes chemoresistance.

Therapeutic options for patients with triple-negative breast cancer (TNBC) in later-line setting are limited. Here the authors report the results of a phase 2 clinical trial to evaluate efficacy and safety of the combination of camrelizumab (anti-PD1), apatinib (VEGFR2 inhibitor), and eribulin in patients with heavily pre-treated advanced TNBC.

Altered lipid metabolism has been associated with tumour malignancy, but underlying mechanisms are not clear. Here the authors show that proto-oncogene Src interacts and phosphorylates metabolic enzyme phosphatidic acid phosphatase LPIN1 (lipin-1) to promote growth and metastasis in breast cancer.

Chemoresistance and metastasis are tightly associated features in non-small cell lung cancer (NSCLC). Here, the authors show that resistant NSCLCs have high levels of miR-128-3p which promotes EMT and cancer stem cell survival through the modulation of both Wnt/B-catenin and TGF-β pathway.

The potential off-target effects of long-term expression of base editors in vivo are unclear. Here the authors report SAFETI, Systematic evaluation Approach For gene Editing tools by Transgenic mIce, to examine off-target effects of base editors over time in mice, and see abnormal side effects.

Here the authors show that, when phosphorylated at Tyr34, THEMIS behaves as an allosteric activator to phosphatase SHP1, ensuring appropriate negative regulation of T cell antigen receptor signaling and thus assisting in T cell maturation and expansion.

It is known that genotoxic stress induces high levels of ROS and deplete cellular glutathione stores. Here, Cao et al. uncover a β-catenin-dependent TCF/LEF-independent mechanism that promotes histone-mediated transcriptional activation of glutathione synthesis.

Cytidine deaminases with high editing efficiencies, diverse editing windows and increased ratios of on-target to off-target effects can be discovered via structure-based generative machine learning.

Most breast cancer patients are estrogen receptor positive and thus benefit from treatments that inhibit estrogen production; however, one third of tamoxifen-treated patients develops resistance and relapse. Here the authors show that tamoxifen resistant cells are resistant to chemotherapy because of BARD1 and BRCA1 upregulation.

Oxytocin derived from peripheral sympathetic neurons is shown to regulate lipolysis and systemic metabolism.

Effective control of tumors requires the presence of inflammatory helper and cytotoxic T cells. Song and colleagues demonstrate that the protein RGS1 cell-intrinsically regulates effector T cell homing to tumors and thereby impairs tumor control.

Resistance to therapy is a significant issue for patients with metastatic breast cancer (MBC). Here the authors analyze total miRNA from serum samples of 386 MBC patients before treatment with a follow up of 31 months and define a four miRNA signature that predicts the therapeutic benefit of trastuzumab.

Cai et al. show that CK1α suppresses lung cancer growth by inducing autophagy through a PTEN–AKT–FOXO3a pathway that ultimately leads to ATG7 expression.

Acquired resistance to chemotherapy can lead to multi-drug resistance and poor prognosis in cancer. Here, the authors show that Rac1 increases glycolysis and non-oxidative pentose phosphate pathway activity leading to neoadjuvant chemotherapy (NAC) resistance, thus its inhibition sensitizes resistant breast cancer PDXs to NAC.

DNA from neutrophil extracellular traps interacts with the transmembrane receptor CCDC25 on cancer cells, activating the ILK-β-parvin pathway to enhance cell motility and promote distant metastases.

While aromatase inhibitors (AI) are an effective treatment for patients with estrogen receptor positive breast cancer, resistance presents a major obstacle. Here, the authors identify DIO3OS, a long noncoding RNA, as a driver of AI-resistance in breast cancer through the enhancement of aerobic glycolysis.

HIF1alpha is reported to drive tumourigenesis through activating glycolysis. Here, the authors show that HIFAL, the HIF1alpha antisense long non-coding RNA, and HIF1alpha form a positive feed-forward loop which is essential for HIF1a-mediated metabolic reprogramming and oncogenic role.

Studies in mice reveal that CREB regulated transcription coactivator 2 (CRTC2) acts as a mediator of mTOR signalling in the liver to regulate SREBP1-controlled lipid homeostasis during feeding and diabetes; overexpression of a CRTC2 mutant defective for mTOR regulation improves the lipogenic program and insulin sensitivity in obese mice.

lncRNAs can regulate immune responses at a number of levels. Song and colleagues demonstrate that the lncRNA NKILA is expressed by tumor-associated cytotoxic T cells, and this predisposes them to activation-induced cell death and escape of tumors from immunologically mediated destruction.

Chen et al. show that tumour-associated macrophages transmit HIF-1α-stabilizing long noncoding RNA through extracellular vesicles to breast cancer cells, thereby enhancing tumour glycolysis and chemoresistance.

We introduce a major scientific endeavour called π-HuB (proteomic navigator of the human body), its aim being to generate and harness multimodality proteomic datasets to enhance our understanding of human biology.

Cytosine and adenine base editors have undesired off-target effects on RNA, but this activity can be reduced in deaminase-engineered variants while preserving on-target DNA editing.

Structural and biochemical insights help engineer a cytosine base editor variant that possesses improved on-target activity with minimal DNA and RNA off-target editing.

GOTI (genome-wide off-target analysis by two-cell embryo injection) detects off-target mutations of CRISPR–Cas9-based genome editing and base editing. One blastomere of a two-cell mouse embryo is edited so that edited and unedited cells from the same genetic background can be compared.

Human umbilical cord mesenchymal stem cells and their extracellular vesicles protect neuronal cells from ischemia-reperfusion injury by enhancing cell viability and reducing damage through mechanisms involving the stabilization of FUNDC1 by USP35.