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The association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) has been known for decades, but mechanisms of gut-liver crosstalk are incompletely understood. Here, the authors show a colitis-triggered protective circuit suppressing cholestatic liver disease which encourages multi-organ treatment strategies for PSC.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Obesity and a high-fat diet can lead to insulin resistance in a process involving macrophage-mediated inflammation of adipose tissue. Here the authors show that glucocorticoid receptor-deficient macrophages have an elevated inflammatory response which aggravates insulin resistance implicating that glucocorticoids promote insulin-sensitizing actions via adipose tissue macrophages during obesity.

In summer 2022 an enormous fish kill was observed in the Oder River as a consequence of prymnesins produced by an algal bloom. An investigation of the exposure of aquatic life and human cells to the contaminated Oder water revealed the presence of neurotoxicants, which are attributed to B-type prymnesins, with minor contributions by organic micropollutants.

Measurements from the heavily shielded Orion spacecraft during the uncrewed Artemis I mission show dose-rate reductions due to shielding and orientation for Van Allen belt crossings and quantify the interplanetary cosmic-ray radiation in a human-rated spacecraft.

Steatohepatitis is a chronic hepatic inflammation associated with increased risk of hepatocellular carcinoma progression. Here the authors show that intestinal dysbiosis in mice lacking the inflammasome sensor molecule NLRP6 aggravates steatohepatitis and accelerates liver cancer progression, a process that can be delayed by antibiotic treatment.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

The new European X-Ray Free-Electron Laser (EuXFEL) is the first XFEL that generates X-ray pulses with a megahertz inter-pulse spacing. Here the authors demonstrate that high-quality and damage-free protein structures can be obtained with the currently available 1.1 MHz repetition rate pulses using lysozyme as a test case and furthermore present a β-lactamase structure.

Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.

Sunlight can change the composition of atmospheric aerosol particles, but the mechanisms through which this happens are not well known. Here, the authors show that fast radical reaction and slow diffusion near viscous organic particle surfaces can cause oxygen depletion, radical trapping and humidity dependent oxidation.

Necroptosis, a form of cell death, occurs in acute renal injury. Here, the authors show that ferroptosis—a form of cell death dependent on iron - also occurs during acute kidney injury, and show that an inhibitor of ferroptosis can improve survival in a mouse model of acute kidney damage.

Water availability is a major control of vegetation dynamics and terrestrial carbon cycling. Here, the authors show that vegetation sensitivity to soil moisture has been increasing in the last 36 years, especially in (semi)arid areas, and that state-of-the-art land surface models fail to capture this trend.

Children are less likely to be infected with SARS-CoV-2 and develop less severe disease than adults, which makes estimation of infection rates challenging. Here, the authors conduct seroprevalence surveys of children in Germany, describe changes in prevalence over time, and identify risk factors for infection.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

A disturbed microbial network characterizes relapsing refractory Crohn’s disease and antedates disease recurrence after surgical removal of the active disease segment.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.

Monitoring of western chimpanzee populations in Guinea-Bissau and Côte d’Ivoire reveals the presence of rare and different genotypes of Mycobacterium leprae, suggesting greater circulation in wild animals than previously thought.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Duquenne et al. show that tanycyte leptin receptor expression is required for leptin to enter the brain and regulate peripheral lipogenesis and pancreatic β-cell function.

Plasmodium malariae is a cause of malaria in humans and related species have been identified in non-human primates. Here, the authors use genomic analyses to establish that human P. malariae arose from a host switch of an ape parasite whilst a species infecting New World monkeys can be traced to a reverse zoonosis.

A chemical probe BI-9321 for the PWWP1 domain of NSD3 and its inactive analog were identified. BI-9321 binds to the methyl-lysine binding site, reduces the association of NSD3 with chromatin and inhibits proliferation of acute myeloid leukemia cells.

Affinity chromatography allows for the separation of biomolecules such as proteins, based on a change in the chemical solvent composition and the resulting impacts on ligand binding. Here, authors introduce a physical principle by exploiting the light-dependent interaction between the Azo-tag and an α- CD chromatography matrix.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Anders Molven and colleagues show that a recombined allele of the lipase gene CEL and its pseudogene CELP confers susceptibility to chronic pancreatitis. The hybrid allele is associated with approximately fivefold-higher risk of disease, and it encodes a protein with reduced lipolytic activity and prominent intracellular accumulation.

Standard of care for unfavorable-risk cancer of unknown primary (CUP) comprises platinum-based chemotherapy as first-line treatment, however therapeutic options remain limited. Here the authors report the results of a phase II trial of combined nivolumab (anti-PD1) and ipilimumab (anti-CTLA4) in patients with unfavorable CUP.

Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Common variable immunodeficiency disorder (CVID) is a primary immunodeficiency with autoimmune comorbidity. Here, Li et al. show shared genetic susceptibility with autoimmune diseases, identifying the first non HLA risk locus at CLEC16Ain the largest CVID genetic study to date.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Some aerosol particles—known as ice nuclei—initiate ice formation in clouds, thereby influencing precipitation, cloud dynamics and incoming and outgoing solar radiation. Measurements of the concentration and elemental composition of ice nuclei in the Amazon basin indicate that local bioparticles and Saharan dust could explain the presence of almost all ice nuclei during the wet season.

Climate change is expected to intensify the global hydrological cycle and to alter evapotranspiration, but direct observational constraints are lacking at the global scale. Now a data-driven, machine-learning technique and a suite of process-based models have been used to show that from 1982 to 1997 global evapotranspiration increased by about 7.1 millimetres per year per decade. But since 1998 this increase has ceased, probably because of moisture limitation in the Southern Hemisphere.

Ferroelectric oxides have emerged as candidate materials for non-volatile data-storage applications, but they can be difficult to process. Researchers have now used a high-temperature deposition process to fabricate arrays of metal–ferroelectric–metal nanocapacitors with a density of 176 gigabits per square inch.

Klaus Schwarz and colleagues report mutations in the gene encoding mitochondrial adenylate kinase 2 in reticular dysgenesis, the most severe form of inborn combined immunodeficiency, characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood.

Most of the low-energy electrons emitted from a material when it is subjected to ionization radiation are believed to be directly ionized secondary electrons. Coincidence measurements of the electrons ejected from water clusters suggests many are produced by a quantitatively new mechanism, known as intermolecular Coulombic decay.

Long-term stability of ecological communities is vital for maintaining ecosystem functioning. Here, Blüthgen et al. show that greater land-use intensity in grasslands and forests can have negative impacts on the stability of plant and animal communities, driven primarily by variation in asynchrony between species.

Vegetation resilience to drought is underlain by plant physiological responses. Here, the authors combine remote sensing data, explainable machine learning and model simulations to map global vegetation responses to drought linked to physiological processes such as stomatal regulation and light use efficiency.

Local pH alterations can be manifestations of pathologies such as cancer, inflammation and ischaemia. Here Düwelet al. show hyperpolarized ¹³C-labelled zymonic acid can be used as a non-invasive probe to map and measure pH in vivo, suggesting it as a candidate for clinical imaging and a diagnostic tool.

A driven-dissipative system of non-interacting bosons may form multiple condensates—a dynamics described by birth–death processes that also occur in evolutionary game theory. Here, the authors apply game theory to show how the vanishing of relative entropy production governs condensate selection.

Laser-produced plasma can be used for particle acceleration in different schemes. Here the authors demonstrate proton acceleration from the intense ultrashort laser pulse interaction with micron-sized cryogenic hydrogen jet.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

It is now established that pluripotent adult germline stem cells (haGSCs) are derived from spermatogonial cells of adult human testis and proposed that it may be possible to derive haGSCs from testicular biopsies to generate cells for individual cell-based therapy.