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Researchers used explainable AI to analyze pancreas tissue from living donors, revealing that changes in fat cell clusters, nerve structures, and islet proximity to fat cells distinguish people with type 2 diabetes from those without the condition.

The authors propose and demonstrate the concept of photonic-electronic arbitrary-waveform generation, overcoming the bandwidth limitations of all-electronic systems. The idea is to exploit quadrature multiplexing of optical waveforms and opto-electronic conversion by phase-stabilized coherent detection.

Exhaustion is the functional deterioration of T cells following chronic stimulation. Here, Wu et al. show that mitochondrial dysfunction drives T cell exhaustion by inhibiting HIF-1α degradation and transcriptional metabolic reprogramming.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Detecting FGFR3-mutant muscle-invasive and metastatic urothelial cancers (MIBC/mUC) for targeted therapy remains challenging, but clinically important. Here, the authors develop a deep-learning model to detect FGFR3 mutations in MIBC/mUC from routine histopathology slides, allowing for highly sensitive, rapid, and cost-effective pre-screening.

Here, Urzi et al. pioneered a 2D self-organizing neuromuscular junction (soNMJ) model from human pluripotent stem cells, with implications for neuromuscular disease modeling and drug screening approaches.

In this phase 1 trial, patients with locally advanced or metastatic solid tumors were treated with the individualized mRNA neoantigen-specific immunotherapy (iNeST) autogene cevumeran alone or in combination with the anti-PD-L1 agent atezolizumab, showing long-lasting neoantigen-specific immune responses and preliminary clinical activity, supporting further development of this therapeutic approach.

Using bulk heart transcriptomics of rat models of right and left ventricle failure, Jurida et al. examined transcriptional changes in cardiomyocytes during the progression of heart failure and the overlap with transcriptomics from humans with chronic thromboembolic pulmonary hypertension (CTEPH), identifying more than 50 genes whose expression levels correlate with the severity of right heart disease.

Dewald et al. combine a non-invasive sampling approach (Lolli-Test) with an RT qPCR-pool testing strategy to screen for SARS-CoV-2 infections in children and use the method for surveillance and infection control in > 4000 school and daycare settings.

Proferroptotic activity of 7-dehydrocholesterol reductase is shown along with an unexpected prosurvival function of its substrate, 7-dehydrocholesterol, indicating a cell-intrinsic mechanism that could be used by cancer cells to protect phospholipids from oxidative damage and escape ferroptosis.

In the absence of GPX4, FSP1 regenerates ubiquinol from the oxidized form, ubiquinone, using NAD(P)H and suppresses phospholipid peroxidation and ferroptosis in cells.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4⁺ and CD8⁺ T-cell immunity.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

A study of patients with COVID-19 and healthy donors found CD4⁺ T cells that react to the spike protein of SARS-CoV-2 and human endemic coronaviruses; however, the effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined.

The scale and nature of energy investments under diverging technology and policy futures is of great importance to decision makers. Here, a multi-model study projects investment needs under countries’ nationally determined contributions and in pathways consistent with achieving the 2 °C and 1.5 °C targets as well as certain SDGs.

Theories of consciousness have a long and controversial history. One well-known proposal — integrated information theory — has recently been labeled as ‘pseudoscience’, which has caused a heated open debate. Here we discuss the case and argue that the theory is indeed unscientific because its core claims are untestable even in principle.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

Influenza A virus replication relies on host cell-derived ubiquitination of the viral polymerase. Here, Günl et al. show that site-specific ubiquitination of PB1-K578 is acquired during infection and facilitates spatiotemporal control of polymerase dimerization and NP binding.

Analyses of 2,083 globally distributed group A Streptococcus (GAS) genomes enable the development of a compendium of all GAS vaccine antigen sequences, providing a platform for population-genomics-informed vaccine design.

Several K+ channels control neuronal excitability, but the function of KCNQ5 (Kv7.5), which displays wide expression in the brain, is not known. Here the authors show that KCNQ5 controls excitability and function of hippocampal networks through modulation of synaptic inhibition.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

Genetic code expansion by ribosomal incorporation of non-natural amino acids has provided a useful approach for site-specific protein modification. This approach has now been extended to the model organism Drosophila melanogaster, permitting the introduction of non-standard amino acids into proteins within specific cell and tissue types and across developmental stages.

Mutations in the RNA-binding protein roquin-1 are known to result in humoral autoimmunity. Heissmeyer and colleagues show that MALT1 cleavage of roquin and regnase-1 downstream of TCR signaling releases cooperatively repressed targets to promote T_H17 cell differentiation

The role of IL-6 in obesity-associated inflammation remains controversial. Bruening and colleagues identify signaling by IL-6 as an important determinant for the alternative activation of macrophages during inflammation.

Enzymes that catalyse modifications of wobble uridine 34 tRNA are essential for the survival of melanoma cells that rely on HIF1α-dependent metabolism through codon-dependent regulation of the translation of HIF1A mRNA.

A light-oxygen-voltage photoreceptor was found to bind short RNA stem loops in a light-dependent manner, which can be harnessed to regulate gene expression in bacteria and mammalian cells.

The authors report the first-in-human application of personalized neo-antigen RNA vaccines in patients with melanoma.

In several human and mouse cancer cell lines and carcinomas, a sapienate biosynthesis pathway underpins metabolic plasticity by allowing these cells to bypass stearoyl-CoA desaturase-dependent fatty acid desaturation.