Search

The zoonotic parasite Toxoplasma has complex developmental programs to accommodate different lifestyles that are important for parasite transmission and pathogenesis. Here, the authors discover a novel chromatin remodeling complex containing SNF2L in Toxoplasma and report its crucial roles in regulating the parasite’s developmental programs.

Treatment selection for recurrent hepatocellular carcinoma (rHCC) after hepatectomy remains challenging. Here, the authors develop HEROVision, a Vision Transformer-based model for personalised prognosis prediction and treatment optimisation in rHCC based on clinical and imaging data, outperforming other guideline staging systems and revealing patients who would benefit from changing treatments.

CNS injuries cause persistent deficits. Here, the authors show that regenerated axons in an optic tract injury model form functional synapses, restoring the pupillary light reflex, and highlight neuronal types and presynaptic activity in recovery.

Zhang, Jiang and colleagues demonstrate that, independent of its role in innate immunity, STING can target and inhibit HK2 activity, thereby blocking tumour aerobic glycolysis and enhancing antitumour immune responses.

Zhang and colleagues found that Omicron RBD binding to Siglec-9 impaired phagocytosis and antigen presentation in macrophages, an effect abrogated by an F375S mutation in the spike protein of Omicron.

Fluorescence microscopy can be exploited to visualize and study T cell mediated cytotoxicity. Here the authors describe a high-throughput Bessel oblique plane microscopy platform for 3D imaging and phenotyping of cytotoxic CAR-T cells in co-culture with cancer cells.

Hypercompact CRISPR-Cas12f systems have been engineered to generate miniABEs but these have limitations. Here the authors generate Cas12f-derived miniCBEs and develop miniABEs with improved editing and targeting scopes; they use these to correct pathogenic mutations in cell lines and introduce mutations in vivo.

Multivalent antigen display on nanoparticles can enhance the immunogenicity of vaccines targeting viral moieties. Here the authors employ DNA origami to rationally design and assemble nanovaccines against SARS-CoV-2 and characterize cellular and humoral immune response in female mice.

Disease-related premature stop codons are efficiently corrected by harnessing near-cognate tRNAs.

High-quality genomes of two cultivated tetraploid cottons Gossypium hirsutum cv. NDM8 and Gossypium barbadense acc. Pima90 and resequencing of 1,081 G. hirsutum accessions provide insights into the role of structural variations.

Eosinophils are innate immune cells critical for protection from parasites, but their developmental origin remains under studied. Here they analyze development of eosinophils in zebrafish and find that eosinophilic lineage commitment and differentiation are regulated by the Cebp1-Cebpβ axis.

sp³ amorphous carbon exhibits exceptional mechanical, thermal, and optical properties, but cannot be synthesized using traditional processes. Here authors report a nearly pure sp³−hybridized amorphous carbon synthesized from C₇₀ which shows more short/medium-range order and enhanced thermal conductivity compared to C₆₀.

Retrieval of a new starting active compound with a novel scaffold during early drug development is an important but challenging task. Here, the authors propose a generative deep learning model and by applying this model they discover a potent and highly selective RIPK1 inhibitor with a previously unreported scaffold.

Many solid microstructures have limited sensitivity over a wide pressure range due to their inherent structural compressibility. Xiong et al. propose a Marangoni-driven deterministic formation approach for creating hollow microstructures, enabling greater deformation while hindering structural stiffening.

Species-rich plant communities often have higher productivity than monocultures. Here, the authors analyse biodiversity-ecosystem functioning experiments in grasslands and forests and find that the biodiversity effects on community productivity strengthen over time thanks to shifts in contributions of species with different resource acquisition traits.

LUBAC is involved in adding linear ubiquitin chains to important immune signaling proteins. Here the authors show that this mechanism is effective in inhibiting STAT1-mediated interferon signaling, and that the deubiquitinase OTULIN can remove these linear ubiquitins from STAT1 to reactivate this antiviral signaling pathway.

Circumsporozoite protein (CSP), the major surface protein of Plasmodium sporozoites, is important for parasite targeting to mosquito salivary glands and the mammalian liver. Here, Zhu et al. show that CSP is required for rodent malaria oocysts to evade mosquito immunity by inducing hemocyte nitration and causing subsequent defects in sporozoite-release from oocysts.

Properties of cytidine and adenosine deaminases lead to off-target effects for cytosine base editors (CBEs) and adenine base editors (ABEs). Here the authors report that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single/double mutations with minimised off-targets.

Na et al. identify KMT2C deficiency as a driver of small cell lung cancer metastasis and demonstrate that it leads to epigenetic reprogramming through histone and DNA hypomethylation by upregulating DNMT3A.

Ferroptosis is a promising therapeutic target for a variety of diseases, but a majority of known ferroptosis inhibitors belong to either antioxidants or iron chelators. Here, the authors discover a new non-classical small molecule inhibitor that is a PHB2 binder and show it ameliorates liver damage in an acute liver injury model.

Understanding the molecular changes in the transition from esophageal squamous precancerous lesions (ESPL) to esophageal squamous cell carcinoma (ESCC) remains essential. Here, the authors analyze ESPL samples using spatial transcriptomics and reveal expression changes in TAGLN2 and CRNN during progression to ESCC.

Photoelectrochemical systems have emerged as a sustainable technology for wastewater treatment. Here, Tang et.al report a bias-free driven ion assisted photoelectrochemical system that can utilize sodium chloride in seawater as a cost-effective additive for wastewater treatment.

Naive T cells are quiescent but undergo dynamic changes upon antigenic activation. Li and colleagues show that upregulation of tRNA methyltransferase complex TRMT61A–TRMT6 and N¹-methyladenosine modification of tRNAs contribute to accelerated mRNA translation efficiency, in particular that of MYC protein, and are required for rapid T cell proliferation.

Using Lorentz transmission electron microscopy, one of the first direct observations of topological spin texture is described, in the pseudogap phase of a high-temperature cuprate superconductor based on YBa₂Cu₃O_6+x.

Beta cell dysfunction and reduction in beta cell mass are hallmark events in the pathogenesis of diabetes mellitus. We identify focal adhesion protein Kindlin-2 as a key factor that controls insulin synthesis and secretion and beta cell mass by modulating MafA and beta-catenin proteins in pancreatic beta cells.

The Montreal Protocol globally phased out ozone-layer depleting CCl₄ by 2010. However, atmospheric measurements show eastern China emitted ~7.6 gigagrams/year in 2021–2022. Further, industrial sources of ongoing CCL₄ emissions are identified.

Here, using proteomics, molecular biology and sequencing, the authors demonstrate that OGT-dependent O-GlcNAcylation of H4S47 is important for replication-origin activation, presumably through regulating DDK-induced phosphorylation of the MCM complex.

The ADP-ribosyltransferase PARP11 promotes ubiquitination and degradation of the interferon type I (IFN-I) receptor IFNAR1 by mono-ADP-ribosylating the ubiquitin E3 ligase β-TrCP, thus suppressing the IFN-I-mediated antiviral responses both in vitro and in vivo.

This study reveals an unrecognized role of ABHD5 in regulating colon cancer stemness via controlling YAP methylation and nuclear localization, further explaining the molecular mechanism through which ABHD5 functions as a tumour suppressor gene in colon cancer.

The study of cross-catenated metallacages could provide facile insights into achieving more precise control over low-symmetry/high-complexity hierarchical assembly systems but is currently lacking. Here, the authors report a cross-catenane formed between two position-isomeric Pt(II) metallacages in the solid state.

Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1^+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

The mechanisms underlying differential chemotherapeutic response to 5-fluorouracil are not fully known. Here, the authors show that ABDH5 regulates sensitivity to 5-fluorouracil in colorectal cancer by regulating lysosome function.

Robust protocols for the synthesis of chiral α-tertiary amino acids remain scarce due to the challenge of constructing congested tetrasubstituted stereocentres. Now a cobalt-catalysed enantioselective aza-Barbier reaction of ketimines with various unactivated alkyl halides has been developed, forming diverse chiral α-tertiary amino esters with high enantioselectivity and excellent functional group tolerance.

Rad5 is a hub connecting three replication stress tolerance pathways. Here, the authors present the 3.3 Å crystal structure of a N-terminal truncated K.lactis Rad5 construct that reveals the spatial arrangement of the HIRAN, Snf2 and RING domains and structure-guided in vitro and in vivo experiments reveal multiple activities of the yeast Rad5 HIRAN ___domain among them a role in binding PCNA and supporting its ubiquitination.

Debranching of glycogen is an important step in its use as an energy source. Here, the authors describe the crystal structures of glycogen debranching enzyme alone and in complex with oligosaccharides and provide molecular insights into the function, and into associated diseases.

UTX is a tumor suppressor gene located on the X-chromosome so it could potentially contribute to the cancer gender bias. Here the authors, using a mouse model of B cell lymphoma, show that UTX is a dosage sensitive tumor suppressor and may be responsible for some of the increased incidence and possibly aggressiveness of male cancers that harbour UTX mutations.

Analysis of data from the Born in Guangzhou Cohort Study comprising mainly of trios and mother–infant pairs reveals novel East Asian-specific genetic associations with maternal bile acid, gestational weight gain and infant cord blood traits.

Xu, Liu, Pen, Zhang et al. demonstrate that the SEL1L–HRD1 complex, which is part of the ERAD protein quality control machinery, safeguards haematopoietic stem cell identity and niche ___location by ensuring the haematopoietic stem cell surface expression of MPL.

Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Here, the authors identify 2 compounds that target the binding of STAT3/5 specifically to the TET1 promoter, inhibiting its expression and AML cell viability.

Mechanistic exploration of PDE4DIP in the progression of non-small cell lung cancer (NSCLC) demonstrates that PDE4DIP coordinates with AKAP9 to promotes NSCLC growth via regulating PKA/CREB signaling pathway.