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Abstract Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.

Covalent organic frameworks (COFs) are an emerging type of crystalline and porous photocatalysts for hydrogen evolution. Here, the authors report a β-ketoamine COF by systematically engineering N-sites, architecture, and morphology for improved water splitting activity.

Structured Illumination Microscopy allows for the visualization of biological structures at resolutions below the diffraction limit, but this imaging modality is still hampered by high experimental complexity. Here, the authors present a combination of interferometry and machine learning to construct a structured illumination microscope for super resolution imaging of dynamic sub-cellular biological structures in multiple colors.

Biomass allocation in plants is fundamental for understanding and predicting terrestrial carbon storage. Here, the authors conduct a meta-analysis showing that warming effect on plant root:shoot is influenced by precipitation and the type of mycorrhizal fungi associated.

The study of covalent organic frameworks (COFs) in electrocatalytic CO2 reduction reaction (CO2RR) has drawn much attention. Here the authors show a series of tetrathiafulvalene based COFs designed and exfoliated into nanosheets which exhibit high electrocatalytic CO2RR performance.

It is unclear whether CO2-stimulation of photosynthesis can propagate through slower ecosystem processes and lead to long-term increases in terrestrial carbon. Here the authors show that CO2-stimulation of photosynthesis leads to a 30% increase in forest regrowth over a decade of CO2 enrichment.

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCAphl) and peripheral small duct type (iCCApps). S100P + SPP1− iCCAphl has significantly reduced levels of infiltrating CD4+ T cells, CD56+ NK cells, and increased CCL18+ macrophages and PD1+CD8+ T cells compared to S100P-SPP1 + iCCApps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCApps has significantly more SPP1+ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1− iCCAphl. Moreover, S100P-SPP1 + iCCApps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA. The molecular classification and tumour microenvironment in intrahepatic cholangiocarcinoma (iCCA) need further characterisation. Here, the authors perform single cell RNA-sequencing from 14 pairs of iCCA tumours and non-tumour liver tissues and propose S100P and SPP1 as markers for patient classification. [ABSTRACT FROM AUTHOR]