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Limited improvement of systemic therapy has been achieved in first line treatment for advanced Biliary tract cancer (BTC). In this randomized phase 2 trial on BTC, the combination of sintilimab, anlotinib, and gemcitabine/cisplatin demonstrated an improvement in progression - free survival (PFS) and objective response rate (ORR) while reducing the risk of disease progression compared to chemotherapy monotherapy.

Zhu et al. show that cAMP-dependent PKA phosphorylates Bora, enabling Aurora A binding and Plk1 activation. This modification ensures timely mitotic entry, unveiling a previously unrecognized interface between PKA signaling and cell cycle regulation.

Using experimental and atomistic simulations, the authors show that optical excitation lowers the energy barrier for domain wall motion. Combined with the imprint field, this effect enables subsecond optical control of domain switching in ferroelectric membranes.

The precise synthesis of functional polyarylamines based on a reactivity-regulated sequent cross-coupling carbon–nitrogen polycondensation method has been reported, with excellent batch-to-batch uniformity for perovskite solar cells.

A method making use of heavy water dissociation in bipolar membranes to synthesize deuterated acids and bases is described, which requires particularly mild conditions and inexpensive D₂O and K₂SO₄ and is also environmentally friendly.

Desmocollin 2 (DSC2) binds to the EBV glycoprotein H/glycoprotein L complex and allows for virus entry to epithelial cells, which could be blocked by DSC2-specific antibodies. DSC2 allowed for virus entry independent of Ephrin receptor A2.

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Pressure overload in the heart, such as from aortic stenosis, triggers early molecular changes before visible damage occurs. Here, the authors show that combining proteomics, transcriptomics, and genetic data reveals key drivers of heart failure, highlighting potential targets for treatment.

In this work, authors investigate how printing parameters like speed, temperature, and direction affect electrostatic charge in 3Dprinted polymers. They develop protocols for charge monitoring and control, demonstrating the potential to print quasi-electrets and offering insights into electrostatics during 3D printing.

Complex diseases often involve subtle subtypes, making their detection vital for personalized medicine. Here, the authors show that the PHet (Preserving Heterogeneity) method reliably uncovers disease-specific subtypes using small sets of features

Siltartoxatug, a first-in-class recombinant monoclonal antibody for tetanus prophylaxis, was shown to be safe and superior to plasma-derived human tetanus immunoglobulin in achieving anti-tetanus neutralizing antibody titers 12 hours after administration.

Polycystic ovary syndrome is a common cause of female infertility linked to metabolic and hormonal imbalances. Here, the authors show that androgen driven SLC1A5 upregulation increases glutamine uptake, leading to abnormal follicular development in PCOS via histone deacetylation.

In this phase 2 trial, YKYY017, a SARS-CoV-2 membrane fusion inhibitor, was tested against mild to moderate COVID-19. Inhaled YKYY017 at 20 mg produced a numerically higher viral load reduction compared with placebo on Day 4, suggesting potential antiviral activity. Both inhaled 10 mg and 20 mg YKYY017 were well-tolerated and had acceptable safety profiles.

Commonly used opioids for pain management primarily target the mu opioid receptor. However, mu opioid receptor agonists often come with harmful side effects. Here, the authors report the results of two phase 3 trials of HSK21542 (anrikefon), a highly selective activator of peripheral kappa opioid receptor agonists, for postoperative pain treatment following abdominal surgery.

How tree diversity effects on ecosystem functioning vary along climatic gradients is unclear. Here, analysing data from 15 experimental forest sites, the authors show that tree growth responses to neighbourhood species diversity are stronger in wetter climates but are unaffected by interannual climatic variation within sites.

Cells survive starvation by activating protective pathways. Here, the authors describe that kinase EFK-1/eEF2K defends against oxidative damage in long term starvation in C. elegans independently from its kinase activity and translation regulation.

The authors present PIONEAR–seq technology to assay in vitro binding of pioneer transcription factors to nucleosomes. The PIONEAR–seq data reveal that a nucleosome’s broader sequence context regulates the interactions of pioneer transcription factors via DNA bendability.

R9AP is a key receptor for entry of Epstein–Barr virus into human epithelial and B cells, and interacts directly with the viral glycoprotein gH/gL complex to mediate virus–host membrane fusion.

Lewis acid additive semicarbazide hydrochloride improves the formation of α-phase FAPbI₃-based films and promotes a homogeneous vertical distribution of A-site cations through a deprotonation–reprotonation process. The upgraded device performance reaches up to 26.12% with high stability, and mini-module perovskite solar cells achieving 21.47% (area, 11.52 cm²) demonstrate great scalability.

Single-cell transcriptomic profiling of immune cells in the blood and liver of a human decedent receiving a pig liver xenograft reveals impaired adaptive immunity and monocyte features that may induce T cell exhaustion and contribute to platelet activation.

Forming and steering a tight optical focus noninvasively in scattering media is a pivotal challenge in biomedical optics. The authors present an iterative time-reversal mechanism using nonlinearity to achieve this without a point-like guide star.

Quark–antiquark annihilation measurements provide a precise determination of the ratio of down and up antiquarks within protons as a function of momentum, which confirms the asymmetry between the abundance of down and up antiquarks.

Observations of SN 2021yfj reveal that its progenitor is a massive star stripped down to its O/Si/S core, which remarkably continued to expel vast quantities of silicon-, sulfur-, and argon-rich material before the explosion, informing us that current theories for how stars evolve are too narrow.

Combining antibody drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) targeting HER2 has been shown to improve efficacy in patients with advanced HER2+ breast cancer. Here, the authors report a randomised phase 2b trial comparing neoadjuvant ARX788 (HER2 ADC) plus pyrotinib (HER1, HER2 and HER4 TKI) against neoadjuvant standard of care (docetaxel, carboplatin, trastuzumab, and pertuzumab) for the treatment of HER2+ breast cancer.

A 2.5-billion-year record of oxygen isotopes in sedimentary sulfate reveals the transitional oxygenation of the Earth’s surface and provides constraints on the dynamic, lengthy co-oxygenation of Earth’s atmosphere and oceans.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

The use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

Here, the authors introduce carbon-to-carbon metal migration as a platform for dynamic association and show how such migrations, in combination with the incorporation of a simple hydrocarbon, can be harnessed to achieve autonomous directional translational motion of a metal centre along the length of a polyaromatic thread.

The mechanism underlying abnormal pain perception in autism remains unclear. Here authors show that histone lactylation decreases Dock4, an autism-related gene, to modulate heat pain by impairing Dynein-mediated Nav1.7 membrane trafficking, providing insights into thermosensor-independent mechanisms.

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

The impact of mercury (Hg) mitigation on microbe-mediated greenhouse gas (GHG) dynamics remains elusive. In this Perspective, the authors fill this gap by synthesizing fragmented evidence on the Hg-microbe-GHG nexus, proposing a roadmap to align Hg mitigation with climate action.

High-resolution FAST observations of a very-high-velocity cloud in the warm neutral medium reveal a network of hierarchical filaments formed by shock compression. These findings suggest a viable mechanism for early structure formation in the interstellar medium.

TUG protein localizes to the endoplasmic reticulum-Golgi intermediate compartment, forms biomolecular condensates, and organizes and stabilizes these membranes to support their function in diverse secretory and degradative trafficking pathways.