Senescent-like border-associated macrophages regulate cognitive aging via migrasome-mediated induction of paracrine senescence in microglia.

Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging, possibly due to prolonged exposure to amyloid beta.

Mitochondria-associated condensates maintain mitochondrial homeostasis and promote lifespan.

Membraneless organelles assembled by liquid-liquid phase separation interact with diverse membranous organelles to regulate distinct cellular processes. It remains unknown how membraneless organelles are engaged in mitochondrial homeostasis. Here we demonstrate that mitochondria-associated translation organelles (MATOs) mediate local synthesis of proteins required for structural and functional maintenance of mitochondria.

Efficient sequence alignment against millions of prokaryotic genomes with LexicMap.

The size of microbial sequence databases continues to grow beyond the abilities of existing alignment tools. We introduce LexicMap, a nucleotide sequence alignment tool for efficiently querying moderate-length sequences (>250 bp) such as a gene, plasmid or long read against up to millions of prokaryotic genomes. We construct a small set of probe k-mers, which are selected to efficiently sample the entire database to be indexed such that every 250-bp window of each database genome contains multiple seed k-mers, each with a shared prefix with one of the probes.

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.

The STING/type I interferon axis drives the interplay between marginal zone B cells and T follicular helper cells in Sjögren's disease.

Type I interferon (IFN-I) is highly prevalent in autoimmune disorders and is intricately involved in disease pathogenesis, including Sjögren's disease (SjD), also known as Sjögren's syndrome. Although the T follicular helper (Tfh) cell response has been shown to drive SjD development in a mouse model of experimental Sjögren's syndrome (ESS), the connection between IFN-I and the Tfh cell response remains unclear. As the activation of stimulator of interferon genes (STING) induces IFN-I production, we first demonstrated that mice deficient in STING or IFN-I signaling presented diminished Tfh cells and were completely resistant to ESS development.

Endothelial cell-ILC3 crosstalk via the ET-1/EDNRA axis promotes NKp46ILC3 glycolysis to alleviate intestinal inflammation.

Communication between group 3 innate lymphoid cells (ILC3) and other immune cells, as well as intestinal epithelial cells, is pivotal in regulating intestinal inflammation. This study, for the first time, underscores the importance of crosstalk between intestinal endothelial cells (ECs) and ILC3. Our single-cell transcriptome analysis combined with protein expression detection revealed that ECs significantly increased the population of interleukin (IL)-22 ILC3 through interactions mediated by endothelin-1 (ET-1) and its receptor endothelin A receptor (EDNRA).

Minimally invasive versus open pancreaticoduodenectomy for periampullary tumors: a systematic review and meta-analysis of randomized controlled trials.

Background: Minimally invasive pancreaticoduodenectomy (MIPD) is used more commonly, but this surge is mostly based on observational data. This meta-analysis aimed to compare the short-term outcomes between MIPD and open pancreaticoduodenectomy (OPD) using data collected from randomized controlled trials (RCTs).

Methods: We searched PubMed, Cochrane Library, Embase, and Web of Science databases for RCTs comparing MIPD and OPD published before December 10, 2024.

Real-world treatment practices and survival outcomes of patients with de novo metastatic nasopharyngeal carcinoma after chemoimmunotherapy.

Objective: To evaluate the real-world treatment practices and survival outcomes of patients with de novo metastatic nasopharyngeal carcinoma (dnMNPC) after the combination of programmed death-1(PD-1) inhibitors with chemotherapy.

Methods: We retrospectively gathered data from patients with dnMNPC who were treated with a combination of chemotherapy and PD-1 inhibitors between August 2019 and August 2023. Kaplan-Meier analysis and Cox proportional hazards regression model were used for statistical analyses.

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.

Active use of latent tree-structured sentence representation in humans and large language models.

Understanding how sentences are represented in the human brain, as well as in large language models (LLMs), poses a substantial challenge for cognitive science. Here we develop a one-shot learning task to investigate whether humans and LLMs encode tree-structured constituents within sentences. Participants (total N = 372, native Chinese or English speakers, and bilingual in Chinese and English) and LLMs (for example, ChatGPT) were asked to infer which words should be deleted from a sentence.

Long-range PM pollution and health impacts from the 2023 Canadian wildfires.

Smoke from extreme wildfires in Canada adversely affected air quality in many regions in 2023. Here we use satellite observations, machine learning and a chemical transport model to quantify global and regional PM (particulate matter less than 2.5 μm in diameter) exposure and human health impacts related to the 2023 Canadian wildfires.

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.

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.

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.

Loss-of-function mutations in PLD4 lead to systemic lupus erythematosus.

Monogenic lupus offers valuable insights into the underlying mechanisms and therapeutic approaches for systemic lupus erythematosus (SLE). Here we report on five patients with SLE carrying recessive mutations in phospholipase D family member 4 (PLD4). Deleterious variants in PLD4 resulted in impaired single-stranded nucleic acid exonuclease activity in in vitro and ex vivo assays.

EMC2 promotes triple negative breast cancer growth by protecting FDFT1 from endoplasmic reticulum associated degradation to impair ferroptosis susceptibility.

Cholesterol biosynthesis is more activated in triple negative breast cancer (TNBC) than in other subtype breast cancer and plays essential role in facilitating TNBC. However, the regulatory network and how cholesterol biosynthesis contribute to TNBC development and progression are not well elucidated. Here, we found that reticulum membrane protein complex 2 (EMC2) is highly expressed in TNBC and predicts short survival of patients.

A novel FAP-targeting antibody-exatecan conjugate improves immune checkpoint blockade by reversing immunosuppressive microenvironment in pancreatic cancer.

Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, characterized by a complex tumor microenvironment that promotes immunosuppression and limits the efficacy of immune checkpoint blockade (ICB) therapy. Fibroblast activation protein (FAP) is overexpressed in the tumor stroma and represents a promising target for therapeutic intervention. Here, we developed a novel antibody-drug conjugate (ADC) targeting FAP, and investigated its anti-tumor activity and ability to enhance ICB efficacy in pancreatic cancer.

LEF1 confers resistance to DNA-damaging chemotherapies through upregulation of PARP1 and NUMA1 in ovarian cancer.

Resistance to platinum-based drugs and PARP inhibitors (PARPi) is the leading cause of treatment failure in epithelial ovarian cancer (EOC). This study aimed to identify resistance mechanisms shared by both. Using bioinformatic analyses, EOC tissues, primary tumor cells and organoids, and chemoresistant cell lines, we identified lymphoid enhancer-binding factor 1 (LEF1) as a candidate, whose expression was increased in both platinum-resistant and PARPi-resistant tumors.

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.