Immune checkpoint inhibitors combined with chemotherapy in conversion therapy for stage IV gastric cancer: a multicenter retrospective cohort study.

Objectives: To evaluate the efficacy of combining PD-1 inhibitors with chemotherapy in conversion therapy for patients with stage IV gastric cancer and to determine the populations most likely to benefit from this regimen.

Methods: Data from patients with stage IV gastric cancer who received conversion therapy with PD-1 inhibitors combined with chemotherapy between January 2018 and December 2022 at multiple centers were retrospectively reviewed. Patients who underwent conversion surgery were categorized into a surgery group, while those who did not were placed into a palliative group.

Changes in food choices and dietary patterns during the lifestyle intervention and their association with type 2 diabetes risk in participants with high or low genetic risk for type 2 diabetes.

Purpose: To investigate how a group-based lifestyle intervention affects food choices and if the dietary patterns at the end of the intervention are associated with incidence type 2 diabetes (T2D). We also investigated if the possible associations between diet and T2D risk were modified by the genetic risk for T2D.

Methods: Participants in the T2D-GENE study were men with prediabetes aged 50-75 years, body mass index  ≥ 25 kg/m, belonging in either low or high genetic risk score (GRS) tertile for T2D.

A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2.

Targeted protein degraders hold potential as therapeutic agents to target conventionally 'undruggable' proteins. Here, we develop a high-throughput screen, DEath FUSion Escaper (DEFUSE), to identify small-molecule protein degraders. By conjugating the protein of interest to a fast-acting triggerable death protein, this approach translates target protein degradation into a cell survival phenotype to illustrate the presence of degraders.

A neuronal correlate for time interval estimation in the crow's telencephalon.

Interval timing, the ability to perceive and estimate durations between events, is essential for many animal behaviors. In mammals, it is linked to specific cortical and sub-cortical brain regions, but its neural basis in birds remains unclear. We trained two male carrion crows on a time estimation task using visual stimuli, cueing them to wait for a minimum duration of 1500 ms, 3000 ms, or 6000 ms before responding to receive a reward.

ABO blood group antigens influence host-microbe interactions and risk of early spontaneous preterm birth.

The mechanisms by which vaginal microbiota shape spontaneous preterm birth (sPTB) risk remain poorly defined. Using electronic clinical records data from 74,913 maternities in conjunction with metaxanomic (n = 596) and immune profiling (n = 314) data, we show that the B blood group phenotype associates with increased risk of sPTB and adverse vaginal microbiota composition. The O blood group associates with sPTB in women who have a combination of a previous history of sPTB, an adverse vaginal microbial composition and pro-inflammatory cervicovaginal milieu.

Monatomic glass formation through competing order balance.

The phase transformation of single-element systems is a fundamental natural process with broad implications, yet many aspects remain puzzling despite their simplicity. For instance, transition metals, Tantalum (Ta) and Zirconium (Zr), commonly form body-centred cubic crystals when supercooled. However, according to large-scale computer simulations, their crystallisation rates can differ by over 100 times.

Pleistocene terrestrial warming trend in East Asia linked to Antarctic ice sheets growth.

How terrestrial mean annual temperature (MAT) evolved throughout the past 2 million years (Myr) remains elusive, limiting our understanding of the patterns, mechanisms, and impacts of past temperature changes. Here we report a ~2-Myr terrestrial MAT record based on fossil microbial lipids preserved in the Heqing paleolake, East Asia. The increased amplitude and periodicity shift of glacial-interglacial changes in our record align with those in sea surface temperature (SST) records.

Improved GVHD-free relapse-free survival when rATG/ATLG is used in allo-HCT from matched sibling donors - an EBMT registry study by the Transplant Complications Working Party.

The EBMT recommends rabbit anti-thymocyte or anti-T-lymphocyte globulin (rATG/ATLG) as GVHD prophylaxis in matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). However, discrepancies between recommendations and clinical practice were reflected in the EBMT survey. Therefore, we performed retrospective EBMT registry analysis from 2014 to 2021 to reinforce the real-world evidence context of rATG/ATLG impact on post-transplantation outcomes.

Functional synapses between neurons and small cell lung cancer.

Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate. Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer. Cancer-to-neuron synapses have been reported in gliomas, but whether peripheral tumours can form such structures is unknown.

Late fluid flow in a primitive asteroid revealed by Lu-Hf isotopes in Ryugu.

Carbonaceous asteroids are the source of the most primitive meteorites and represent leftover planetesimals that formed from ice and dust in the outer Solar System and may have delivered volatiles to the terrestrial planets. Understanding the aqueous activity of asteroids is key to deciphering their thermal, chemical and orbital evolution, with implications for the origin of water on the terrestrial planets. Analyses of the objects, in particular pristine samples returned from asteroid Ryugu, have provided detailed information on fluid-rock interactions within a few million years after parent-body formation.

Human gastroids to model regional patterning in early stomach development.

The human stomach features distinct, regionalized functionalities along the anterior-posterior axis. Historically, studies on stomach patterning have used animal models to identify the underlying principles. Recently, human pluripotent stem (hPS)-cell-based gastric organoids for modelling domain-specific development of the fundic and antral epithelium are emerging.

Observing differential spin currents by resonant inelastic X-ray scattering.

Controlling spin currents, that is, the flow of spin angular momentum, in small magnetic devices, is the principal objective of spin electronics, a main contender for future energy-efficient information technologies. A pure spin current has never been measured directly because the associated electric stray fields and/or shifts in the non-equilibrium spin-dependent distribution functions are too small for conventional experimental detection methods optimized for charge transport. Here we report that resonant inelastic X-ray scattering (RIXS) can bridge this gap by measuring the spin current carried by magnons-the quanta of the spin wave excitations of the magnetic order-in the presence of temperature gradients across a magnetic insulator.

Stabilizing effect of amino acids on protein and colloidal dispersions.

Amino acids (AAs) have a long history of being used as stabilizers for biological media. For example, they are important components in biomedical formulations. The effect of AAs on biological systems is also starting to be appreciated.

The oldest known lepidosaur and origins of lepidosaur feeding adaptations.

The Lepidosauria is the most species-rich group of land-dwelling vertebrates. The group includes around 12,000 species of lizards and snakes (Squamata) and one species of Rhynchocephalia, the tuatara Sphenodon punctatus from New Zealand. Squamates owe their success to their generally small size, but also to their highly mobile skull that enables them to manipulate large prey.

Amplifying antigen-induced cellular responses with proximity labelling.

Antigen-induced clustering of cell surface receptors, including T cell receptors and Fc receptors, represents a widespread mechanism in cell signalling activation. However, most naturally occurring antigens, such as tumour-associated antigens, stimulate limited receptor clustering and on-target responses owing to insufficient density. Here we repurpose proximity labelling, a method used to biotinylate and identify spatially proximal proteins, to amplify designed probes as synthetic antigen clusters on the cell surface.

ABCA7 variants impact phosphatidylcholine and mitochondria in neurons.

Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.

Probing the heterogeneous nature of LiF in solid-electrolyte interphases.

The electrolyte-electrode interface serves as the foundation for a myriad of chemical and physical processes. In battery chemistry, the formation of a well-known solid-electrolyte interphase (SEI) plays a pivotal role in ensuring the reversible operations of rechargeable lithium-ion batteries (LIBs). However, characterizing the precise chemical composition of the low crystallinity and highly sensitive SEI presents a formidable challenge.

Fluctuating DNA methylation tracks cancer evolution at clinical scale.

Cancer development and response to treatment are evolutionary processes, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types.

Giant two-photon upconversion from 2D exciton in doubly-resonant plasmonic nanocavity.

Photon upconversion through high harmonic generation, multiphoton absorption, Auger recombination and phonon scattering performs a vital role in energy conversion and renormalization. Considering the reduced dielectric screening and enhanced Coulomb interactions, semiconductor monolayers provide a promising platform to explore photon upconversion at room temperature. Additionally, two-photon upconversion was recently demonstrated as an emerging technique to probe the excitonic dark states due to the extraordinary selection rule compared with conventional excitation.

Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML.

Pediatric acute myeloid leukemia (pAML) is a heterogeneous malignancy driven by diverse cytogenetic mutations. While identification of cytogenetic lesions improved risk stratification, prognostication remains inadequate with 30% of standard-risk patients experiencing relapse within 5 years. To deeply characterize pAML heterogeneity and identify poor outcome-associated blast cell profiles, we performed an analysis on 708,285 cells from 164 bone marrow biopsies of 95 patients and 11 healthy controls.

A three-dimensional ex vivo model recapitulates in vivo features and drug resistance phenotypes in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) preferentially localizes in the bone marrow (BM) and displays recurrent patterns of medullary and extra-medullary involvement. Leukemic cells exploit their niche for propagation and survive selective pressure by chemotherapy in the BM microenvironment, suggesting the existence of protective mechanisms. Here, we established a three-dimensional (3D) BM mimic with human mesenchymal stromal cells and endothelial cells that resemble vasculature-like structures to explore the interdependence of leukemic cells with their microenvironment.