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In a large single-arm phase 2 trial, the anti-PD-1 inhibitor tislelizumab combined with the next-generation BTK inhibitor zanubrutinib had an overall response rate of 58.3% and was well tolerated in patients with Richter’s transformation.

Ceremonial feasting in Early Neolithic Asiab, western Iran, involved transport of animals over substantial distances to celebrate far-flung social networks, according to analysis of microscopic tooth growth patterns and geochemistry.

Rare mutations in the high requirement temperature protein A1 (HTRA1) cause cerebral vasculopathy. Here, authors establish mechanistically distinct protein repair approaches to reverse the deleterious effects of pathogenic mutations interfering with the assembly and protease function of HTRA1.

Conserved microbiome features across clinical and geographical variations may enable microbiome-based predictions of outcomes in CD19-targeted CAR-T cell immunotherapy

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Understanding how biosilica forms is crucial to our knowledge of this important biomaterial. Now, the role of collagen as structuring agent for the metre-long spicules of a primitive glass sponge has been revealed and found to have an unusual peptide motif.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Sinonasal tumour diagnosis can be complicated by the heterogeneity of disease and classification systems. Here, the authors use machine learning to classify sinonasal undifferentiated carcinomas into 4 molecular classe with differences in differentiation state and clinical outcome.

SNURPORTIN-1, encoded by the SNUPN gene, plays a key role in the nuclear import of spliceosomal small nuclear ribonucleoproteins, however its physiological function remains unclear. Here the authors report that recessive SNUPN mutations cause a distinct subtype of childhood muscular dystrophy and reveal SNURPORTIN-1’s role in muscle homeostasis, offering insights for new therapeutic strategies.

Mimicking high-level abstraction of the brain to achieve energy advantages is a fundamental issue in neuromorphic computing. Here, the authors fabricate an asynchronous chip and demonstrate a high-accuracy neuromorphic system with power consumption of 0.7mW.

The Moon formed around 50 Myr after the Solar System, suggests a lunar silicate Hf/W ratio higher than that of Earth, from high-precision compositional analysis of lunar rock samples.

Small heat shock proteins (sHsps) form large spherical assemblies and their regulation is not well understood. Here, the authors provide insights into the mechanism of Hsp26 activation by characterising phospho-mimetic mutants of yeast Hsp26. They present cryo-EM structures of the wild-type Hsp26 40mer and its phospho-mimetic mutants that reveal the ___location of the thermosensor in the oligomer, and the authors also show that the thermosensor ___domain is targeted by phosphorylation, which relieves the intrinsic inhibition of chaperone activity.

It is a challenge to measure changes in the crystal structures in picometer scale and the associated phase. Here the authors demonstrate the lattice expansion and polar distortions of oxygen deficient SrTiO₃ using a resonance X-ray scattering technique.

Recently, the first orally-administered ultra-long acting insulin was shown to have clinical efficacy. Here, the authors report the molecular engineering, as well as the biological and pharmacological properties of these insulin analogues.

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.

In Greenlandic Inuit, a TBC1D4 loss-of-function mutation increases type 2 diabetes risk by tenfold. Carriers show severe muscle insulin resistance, impaired glucose disposal and reduced muscle GLUT4, yet exercise mitigates these defects, offering potential for personalized lifestyle interventions.

The emergence of conductivity at the {001} interface of LaAlO₃ and SrTiO₃ is one of the more celebrated examples of interface engineering. Using a microscopy approach based on a sensitive magnetometry probe, it is now shown that narrow paths of enhanced conductivity occur along the crystallographic axes of the oxide structures.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Proteomics can be used to refine cancer classification. Here, the authors characterise chronic lymphocytic leukaemia patients by proteogenomics, and identified a subtype of patients with poor prognosis associated with aberrant B cell receptor signalling.

Niche crosstalk with Haematopoietic cells underlies normal haematopoiesis and myeloid disorders. Here the authors report a Stabilin2-Cre driver mouse with Cre-activity restricted to bone marrow sinusoidal endothelial cells, and that Stabilin2-Cre driven overactivation of b-catenin leads to erythroid differentiation defects and anaemia.

Inhibition of the fatty acid oxidation metabolic pathway through inactivation of Cpt1b enhances cardiomyocyte survival and proliferation and allows heart regeneration in adult mice.

The authors here look into the phase transitions in Li-/Mn-rich layered cathode materials during synthesis and cycling. It is revealed that the Li-rich layered structure tends to transform to a Li-poor spinel phase via an intermediate Li-containing rock salt phase, with release of lithium/oxygen.

Adipocyte plasticity during injury repair is debated. Here, the authors find that injury causes temporary adipocyte migration, but without lineage conversion to myofibroblasts. Distinct migration patterns, transcriptomics and ECM depositions indicate that adipocytes, unlike fibroblasts, do not contribute to fibrotic scars.

Smooth muscle cell-specific knockout of Tet3 in mice leads to loss of intragenic 5-hydroxymethylcytosine, accumulation of spurious transcripts and TLR7/8-mediated lung inflammation resembling asthma in human lung samples.

Utrophin is a dystrophin-related protein stabilizing the sarcolemma in absence of dystrophin. Here the authors report that inactivation of the protein deacetylase SIRT6, involved in the deacetylation of the epigenetic mark H3K56ac in muscle cells, increases expression of utrophin and ameliorates dystrophic muscle pathology in mice.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

The authors report that neddylation is required for dendritic spine development and stability, and loss of neddylation in excitatory forebrain neurons leads to synaptic loss, impaired neurotransmission, and learning and memory deficits. The roles of neddylation in spine maturation and synaptic transmission could be attributed to neddylation of PSD-95.

Rhabdopeptides are synthesized by non-ribosomal peptide synthetases (NRPSs) and the multiple NRPS subunits interact through docking domains (DD). Here the authors provide insights into DD interaction patterns and present the structures of three N-terminal docking domains (^NDD) and a ^NDD-^CDD complex and derive a set of recognition rules for DD interactions.

The scope of patents covering SARS-CoV-2 and diagnostics, vaccines and treatments related to the virus remains unclear, but the pandemic may have created a permanent demand for SARS-CoV-2-related products and spark long-term interest in relevant intellectual property rights.

iCLiPSpy is a simple assay to identify residues important for substrate binding and activity of intramembrane-cleaving proteases (I-CLiPs) in vivo and can be adapted to a screening assay for I-CLiP inhibitor or activator discovery.

Transcriptional alterations demonstrate that adipose tissue responded to exercise completely distinct from skeletal muscle in the same human subjects. Adipose tissue showed acute and repeated reduction in transcripts of lipid uptake, synthesis and storage. The data also suggest the restoration of a healthier circadian rhythm in adipose tissue of subjects with obesity after regularly performed exercise. The interconnection of circadian rhythm with lipid metabolism possibly contributes to improved metabolic health and prevention of diabetes.