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Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Selenoprotein P is secreted by the liver and when present in excess it promotes development of type 2 diabetes. Here the authors develop neutralizing antibodies to target human and mouse selenoprotein P, and show that they improve insulin secretion and glucose tolerance in mouse models.

Distinguishing biotic compounds from abiotic ones is critical to the search for life in the universe. Here, the authors demonstrate that the abiotic ethane has distinctively low 13C-13C abundances compared to biotic ethane.

Ketogenesis is critical for survival during the neonatal and perinatal periods. Arima et al. determine that hepatic ketogenesis prevents hyperacetylation of mitochondrial proteins and disruption of mitochondrial energetics.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Protoxylem and metaxylem vessels form banded and pitted cell walls, respectively. Here, the authors show that KNAT7 suppresses expression of the actin polymerizer, formin 11 (FH11), to determine the cell wall pattern of the metaxylem in Arabidopsis.

The sweetener D-allulose has beneficial metabolic effects in animal models, but its mechanism of action was unclear. Here the authors report that D-allulose triggers GLP-1 release in the gut and GLP-1R signaling on vagal afferents, counteracting arrhythmic overeating, obesity and diabetes.

Lithic cutting-edge productivity is a way of quantifying prehistoric human technological evolution. Here, the authors examine the Middle-to-Upper Paleolithic transition across eight assemblages in the eastern Mediterranean, finding the transition to be later than expected and associated with bladelet technology development.

In the phase III FLAURA study (NCT02296125), the third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) osimertinib provided superior progression-free survival versus comparator EGFR-TKIs in patients with NSCLC. Here, by next-generation sequencing of circulating tumor DNA, the authors assess candidate mechanisms of acquired resistance to first-line osimertinib in patients from the FLAURA trial.

Endothelin-1 regulates cardiovascular development by acting on neural crest cells. Here endothelin-1-deficient mice are studied, revealing that preotic neural crest cells differentiate into coronary artery smooth muscle cells through endothelin-1-dependent mechanisms.

Damaged mitochondria are removed from cells through a process called mitophagy. Here, Hoshino et al. show that the cytosolic fraction of the protein p53 inhibits mitophagy by sequestering the mitophagy regulator Parkin, leading to impaired mitochondrial integrity and cardiac function in aged or damaged mouse hearts.

Age-related macular degeneration (AMD) is a major cause of blindness. Now, the eosinophil/mast cell chemokine receptor CCR3 is shown to be specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and targeting CCR3 or its ligands in mice inhibits the choroidal neovascularization that underlies AMD. In the mouse model, CCR3 blockade was more effective and less toxic than VEGF-A neutralization, which is currently in clinical use.

The secreted ligand Angiopoietin-1 is essential for embryonic blood vessel development and adult vascular homeostasis. Here the authors show, using conditional knockout mice, that myocardium-derived Angiopoietin-1 is required for the formation of coronary veins, but not arteries.

Chemical and mechanical cues coordinately regulate angiogenesis. Here, the authors show that blood flow-driven intraluminal pressure regulates wound angiogenesis. Findings indicate that TOCA family of F-BAR proteins act as actin regulators required for endothelial cell migration and sense mechanical cell stretching to regulate wound angiogenesis.

How photosynthetic oxygen evolution is originated on ancient Earth is unknown. Here, the authors find that some amino acid residues at the ligand sites of the Mn cluster can be posttranslationally converted to the original carboxylate residues, which could have contributed to the evolutionary process of photosynthetic oxygen evolution.

Both poles of asteroid Ryugu, the target of space mission Hayabusa2, preserve the least processed material by space weathering. Here, the authors show detection of 700 nm absorption band in the polar spectra of Ryugu, that allows to constrain the hydrothermal history of its spectrally blue parent body.

Auxin-inducible degron systems can be leaky and require high doses of auxin. Here the authors establish AID2 which uses an OsTIR1 mutant and the ligand 5-Ph-IAA to overcome these problems and establish AID-mediated target depletion in mice.

In vivo delivery of CRISPR-Cas9 holds promise for treating muscular dystrophy, however, AAV delivery is known to be immunogenic. Here, the authors show that LNP delivery of CRISPR-Cas9 enables repeated injections into skeletal muscle and leads to restored dystrophin expression in multiple muscle groups.

Advanced colorectal cancers are characterised by intra-tumour heterogeneity dictated by neutral evolution. Here the authors analyse early colorectal tumours by whole-exome sequencing and find that Darwinian evolution determines the fate of early lesions in colorectal adenoma and carcinoma in situ.

Analysis of the kinase activity of 300 protein Ser/Thr kinases reveals that the substrate specificity of the kinome is substantially more diverse than expected and is driven extensively by negative selectivity

Functional and structural characterization of rhodopsin-bestrophin fusion proteins from marine algae unveils the existence of giant light-sensitive anion channels with unusual biophysical properties.

Solid electrolytes can improve the safety of the next generation of high-energy batteries, but they still suffer from low ionic conductivities and stability. Li₁₀GeP₂S₁₂ exhibits high lithium ionic conductivity at room temperature and should be practically advantageous with regard to device fabrication, stability and safety.

Incorporation of histone H3 variant H3.3 into chromatin regulates transcription. Here the authors find that H3.3 sub-variant H3mm7 is required for skeletal muscle regeneration and that H3mm7 nucleosomes are unstable and exhibit higher mobility, with H3mm7 promoting open chromatin around promoters.

Tardigrades are resistant to extreme environmental conditions including dehydration, radiation and the vacuum of space. Here the authors present a high-quality genome which displays minimal horizontal gene transfer, and identify the unique tardigrade protein Dsup which suppresses DNA damage.

Carbon-based materials are promising alternatives to noble metal catalysts, but their structures are typically disordered and difficult to control. Here, the authors obtain ordered carbonaceous frameworks with advantageous electrocatalytic properties via the carbonization of nickel-containing porphyrin dimer networks.

A monoclonal human T cell immunoreceptor with Ig and ITIM domains (TIGIT) agonistic antibody in a TIGIT knock-in mouse model suppresses follicular and peripheral helper T cell activation and enhances suppression effects of naive regulatory T cells.

Cofilin is a small actin-binding protein that accelerates actin turnover by disassembling actin filaments. Here the authors present the 3.8 Å cryo-EM structure of a cofilin-decorated actin filament and discuss mechanistic implications.

High-resolution X-ray spectra show near-solar abundances of chromium, manganese and nickel with respect to iron in the Perseus cluster, suggesting that the progenitors of type Ia supernovae could be near- and sub-Chandrasekhar-mass white dwarfs.

The Hayabusa2 spacecraft returned 5.4 g of material from the asteroid Ryugu. A first analysis of the samples found an estimated density of 1,282 ± 231 kg m⁻³, considerably lower than even the most porous meteorites. Together with preliminary spectral analysis, these results indicate that Ryugu is similar to CI chondrites, but darker, more porous and more brittle.

Masato Kasuga and colleagues and Shiro Maeda and colleagues each report the independent identification of SNPs in KCNQ1 associated with type 2 diabetes in the Japanese population. Each group replicated the associations in other populations of East Asian and European descent.