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The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

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.

Pancreatic ductal carcinoma is often diagnosed at a late stage due to challenges in detection. Here, the authors develop a serum metabolomics-based algorithm, which outperforms existing detection methods.

Electrocatalytic nitrate reduction in acidic wastewater offers a route to produce ammonia, but faces efficiency challenges. Here, the authors report a Ru/WO_3-x catalyst that uses a proton-management strategy to achieve high ammonia production and enables a device that recovers energy.

By combining satellite observations with ground-based data and expert validation, this analysis demonstrates considerable misestimation of grassland extent and thereby carbon stock estimates in previous global assessments based on remote sensing.

Methods of damaging cancer cells are of therapeutic interest. Here, the authors report on using gold nanoparticles as electron sinks with electroactive bacterial membranes to disrupt cancer cell redox balance, electron transfer induces oxidative stress and triggers cell death by apoptosis.

Graves’ disease is the leading cause of hyperthyroidism but treatment options can cause life-threatening complications. Chen et al. conduct two-stage direct HLA genotyping and genome-wide association studies to identify HLA-B*38:02 and HLA-DRB1*08:03 as major pharmacogenetic determinants.

NME3 is a member of NDPK family. Here, Chen et. al., discover that histidine phosphorylatable NME3 is required for hypoxia-induced mitophagy via PA-dependent interaction with Drp1, which is protected from MUL1-mediated ubiquitination for mitophagy.

The insertion of thin layers of cobalt can stabilize β-tungsten under back-end-of-line thermal constraints, allowing a 64-kb spin–orbit torque magnetic random-access memory to be fabricated that offers a spin–orbit torque switching of 1 ns, data retention of more than 10 years and a tunnelling magnetoresistance of 146%.

The red fluorescent protein mScarlet3-H is bright, photostable and very robust to high temperature, chaotropic conditions and oxidative environments. mScarlet3-H works well in correlative light and electron microscopy, tissue clearing and time-lapse super-resolution microscopy.

This study demonstrated that different types of HC-Pros from potyviruses exhibit varying capacities to inhibit HEN1. This results in distinct levels of autophagic AGO1 degradation, which in turn leads to differences in RNA silencing suppression efficiency.

Direct contact between tumour cells and fibroblasts influences tumour cell behaviour. Here the authors show that pancreatic cancer cells and fibroblasts directly interact via homophilic ATP1A1 binding, which induces fibroblasts to secrete activin A to promote epithelial-mesenchymal transition of tumour cells and myofibroblast activation.

Various forms of preconditioning can prevent ischemic-reperfusion injury after myocardial infarction. Here, the authors show that in mice, the presence of chronic neuropathic pain can have a cardioprotective effect, and that this is dependent on neural activation in the paraventricular thalamus.

The fluoroalkyl-containing organic molecules are widely used in drug discovery and material science. Herein, the authors report ligand regulated nickel(0)-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination.

Single-atom catalysts emerge as nanocatalytic medicine in chemodynamic therapy but suffer from inefficient kinetics for the production of reactive oxygen species because of the cell’s antioxidative mechanisms. Here, the authors employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatment.

The authors show that the Drosophila master regulator WAKE modulates the secretion of insulin-like peptides, triggering a decrease in 20-hydroxyecdysone levels. This lowers the perception of a male-specific sex pheromone and explains why WAKE-deficient Drosophila flies show male-male courtship behaviour.

Here the authors present the crystal structure of a bacterial STING. The structure shows that bacterial STING can modulate immune responses by forming anti-parallel dimers or, in certain species, through the presence of a long lid.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Developing multi-cancer early detection (MCED) tests based on cfDNA or protein markers holds great promise for effective cancer screening. Here, the authors show a sensitive, non-invasive pan-cancer detection method that concurrently detects the oncofetal chondroitin sulfate (ofCS) glycans and its protein backbone in plasma.

Evidence for the treatment of patients with mild-to-moderate COPD is limited. Here, the authors show that long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improve lung function in patients with mild-tomoderate COPD.

An analysis based on data from the Global Dietary Database shows mean animal-sourced food intakes among children and adolescents increased modestly from 1990 to two portions per day in 2018, but remain low in sub-Saharan Africa, India and Bangladesh.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

Dietary quality is reported at the global, regional and national level across 185 countries. Though diet quality increased modestly since 1990 at the global level, in South Asia and Sub-Saharan Africa it did not improve. In some regions, children’s dietary quality is lower than that of adults.

Heterozygous HNF1A mutations can give rise to maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. Here the authors show that MODY3-related HNF1A mutation in patient hiPSCderived pancreatic cells decreases glucose transporter GLUT2 expression due to compromised DNA binding.

TheArabidopsisCCA1 transcription factor is a core regulator of the circadian clock. Here, the authors show that the LWD1 protein, in complex with the TCP20 or TCP22 transcription factors, acts as a co-activator of CCA1 expression contributing to elevated CCA1 expression at dawn.

Modeling analysis from the Global Dietary Database estimated that 70% of new global cases of type 2 diabetes are attributable to suboptimal intake of 11 dietary factors, with substantial differences in dietary risks across world regions and nations.

The authors identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of elongation, segmentation, patterning and lineage allocation specifically within the trunk region of the mouse, acting downstream of the major signals known to control vertebral column formation.

The routes and lengths of migrations of Eurasian Arctic peregrine falcons have probably been shaped by climate change across the Last Glacial Maximum–Holocene transition and by selection for long-term memory acting on ADCY8, respectively.

The increased risk of mortality in patients with gout is increasingly recognized, and multiple guidelines call for better management of this disease and its comorbidities. A new study, however, has found that excess mortality in patients with gout has remained unchanged since 1999.

It is unclear how removal of axon debris and initiation of axon regeneration following nerve injury is co-regulated. In this study, the authors show that the extracellular domain (ECD) of the engulfment receptor, CED-1, functions as an adhesion molecule to promote axonal regeneration after injury, independent of its function in phagocytosis

Cdc42 activity is important for apical-basal epithelial polarity. Here, the authors show that Shp2 disrupts Cdc42 activation, and by reducing the expression of histone deactylase 6, restores epithelial lumen formation in a cdc42-independent manner.