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Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

During periods of stress, it is required to maintain the haematopoietic stem cell (HSC) pool. Here the authors show that Trim47 is important in the survival and function of HSCs after exposure to stress, and prevents haematopoietic failure by inhibiting MAVS-mediated excessive activation of the innate immune pathway.

While BH3-mimetics can be effective for treatment of haematological malignancies, their efficacy in solid tumours is limited. Here, using a range of patient-derived prostate cancer models, the authors demonstrate that increased replication stress induced by RB1 loss confers sensitivity to BH3 mimetics targeting BCL-XL.

The construction of vicinal stereocentres—particularly sterically bulky quaternary motifs—from racemic alkyl halides remains a formidable challenge. Here, a cobalt-catalysed enantioconvergent reductive addition of racemic alkyl halides to imines has been developed, enabling efficient synthesis of diverse contiguous stereocentres, including tertiary–tertiary, tertiary–quaternary and quaternary–quaternary stereocentres, with high diastereo- and enantioselectivities.

Stress urinary incontinence (SUI) is a significant clinical challenge where less invasive treatment strategies that also address the pathophysiology of SUI are desirable. Here, Fang et al. engineer an injectable, thermo-responsive composite hydrogel incorporated with programmed stem cells that provides structural support to the atrophic urethral sphincter and promotes urethral sphincter regeneration, angiogenesis, and neurogenesis as a treatment strategy for SUI.

Aberrant activation of Wnt/β-catenin signaling contributes to colorectal cancer (CRC) pathogenesis. Here the authors find that the cytoplasmic distribution of TRIM24 E3 ubiquitin ligase triggers ubiquitination and degradation of von Hippel-Lindau, resulting in the accumulation of β-catenin protein in CRC cells.

Li et al. show that the inner nuclear membrane protein LEMD3 organizes 3D chromatin architecture by anchoring heterochromatin at the nuclear periphery to maintain vascular smooth muscle cell contractile identity.

The O-alkylation of tertiary alcohols with racemic tertiary electrophiles to access chiral hindered dialkyl ethers has remained elusive. Now this synthetic challenge has been accomplished by copper-catalysed C–O cross-coupling between tertiary haloamides and alcohols using designed ligands.

CRISPR-based diagnostics are often limited by complex workflows and poor validation. Here the authors develop and validate a one-pot asymmetric CRISPR assay, which permits rapid and sensitive diagnosis of tuberculosis in a format which is suitable for resource-limited settings.

Two phase 2 trials, along with translational analysis of prospective cohorts and experimental analysis, indicate that immunosenescence as a mechanism of resistance to immunotherapy can be overcome with the senolytics dasatinib and quercetin in patients with head and neck squamous cell carcinoma.

Although miR-related mechanisms have been implicated in nasopharyngeal carcinoma (NPC), a precise role for miR-3188 has not been reported in this context. Here, Zhao et al. show that FOXO1-induced miR-3188 acts as a tumour suppressor in NPC by regulating the axis mTOR/PI3K/Akt/c-Jun.

This study introduces the Cattle Cell Atlas, a single-cell expression resource including 1,793,854 cells from 59 tissues. Integrative analyses leveraging this atlas provide insights into the biology underlying bovine monogenic and complex traits.

The authors realize a two-dimensional hybrid perovskite with robust multiaxial ferroelectricity and nonlinear optical response via molecular fluorination and lone pair expression of Ge²⁺, enabling prominent piezoelectric sensing in composite device

In urethral damage, exogenous implants designed for urethral repair are hindered by the open and harsh urethral microenvironments and the isotropic compression and swelling properties of the material. Here, Yang et al. develop a tri-layer hydrogel with anti-fouling and low-swelling properties for scarless urethral repair.

The role of cellular stress responses in ovarian aging remains incompletely understood. In this study, the authors identify NCOA7 as a facilitator of autophagic clearance of stress granules in granulosa cells, conveying protection against ovarian aging. Loss of NCOA7 promotes ovarian aging, whereas its expression via mRNA delivery delays aging.

This study presents LiteLoc, a lightweight and scalable AI model for efficient and accurate single molecule localization microscopy data analysis, bringing real-time deep-learning-based analysis to the era of high throughput super resolution imaging.

Genome and transcriptome analyses of 376 Gossypium hirsutum accessions uncover the regulation of gene expression during fiber development in allotetraploid cotton and highlight the potential for fiber quality improvement.

An asymmetric self-assembled monolayer improves the efficiency of perovskite/silicon tandem solar cells compared with symmetric self-assembled monolayers, resulting in a certified power conversion efficiency of up to 34.58%.

Lewis acid catalyzed tittle reaction of 1,3-dicycloalkenlidine ketones is recognized as so far the shortest and most effective 1-step method for construction of angular tricyclic scaffolds, which are extensively found in bioactive terpenoids. Here, the authors disclose the structure-reactivity relationship and a regioselectivity predicting model based on in situ IR technology, DFT calculations and machine leaning algorithms.

Sirtuin 5 (SIRT5) has been associated to colorectal cancer and metabolic regulation. Here, the authors show that SIRT5 silencing reduces nucleotide availability leading to DNA damage and tumor suppression in colorectal cancer models.

Here the authors identify the granin hormone SCG2 as a ligand for the inhibitory receptor LILRB4. They show that SCG2 released from tumors can suppress antitumor immune responses via this interaction, indicating possible therapeutic strategies.

Food waste is a global challenge that is strongly linked to climate change, resource consumption and human health. This study proposes a monetization approach based on a set of life-cycle assessment indicators that enables the comparison of food waste recycling technologies. The method was applied to food waste recycling in a Chinese province, revealing trade-offs and the effectiveness of different solutions.

‘Gastric cancer metastasis to the ovary is difficult to treat and is not fully understood. Here, the authors characterized mutations in a cohort of matched primary and metastatic disease, and found mutations, including in CLDN18, could predict treatment response to paclitaxel.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

In this work, authors elucidate the molecular mechanisms by which neonatal meningitis Escherichia coli facilitates bacterial invasion through inducing multiple programmed cell death pathways in brain microvascular endothelial cells.

Epstein-Barr virus is associated with increased cancer risk. Here, the authors analysed two population-based prospective cohorts in Southern China to examine the association between increased seropositivity and the risk of multiple cancer types.

The retention of galactose-deficient IgA1 (Gd-IgA1) in the mesangium leads to pathogenesis in IgA nephropathy. Here the authors report that Gd-IgA1 is internalized by mesangial cells potentially via transferrin receptor 1, forming aggregates that disrupt lysosomal function and elicit inflammation.

The sympathetic nervous system has been shown to respond to stress and activate haematopoietic stem cells. Here they show that cholinergic signals in the bone marrow preserve haematopoietic stem cell quiescence and self-renewal under proliferative stress.

An ex vivo organotypic and immunocompetent human leukaemia chip system is used for CAR T cell therapy modelling and screening of patient response.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Inhibitor of differentiation 1 (ID1) has been described as a cancer-promoting factor and also involved in the formation of an immunosuppressive tumor microenvironment. Here the authors report that ID1-expressing tumor associated macrophages favor colorectal cancer progression by promoting cancer cell stemness and CD8⁺ T cell exclusion.

The growing consumption of electronics is leading to the rapid accumulation of electronic waste, which has been a global concern for years. This work presents a closed-loop bio-recyclable cellulose-based dielectric film that can improve the circularity of electronics and could reduce electronic waste.

Significant efforts are needed to leap from the identification of trait-associated genetic variants to the revealing of the causal gene. Here, the authors translate genomic variants into gene-level functional haplotypes for GWAS and identify a gene encoding ferulic acid 5-hydroxylase 1 is responsible for superior cotton fiber quality.