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Changes in physical fitness in Chinese primary schools following the “double reduction” policy based on Policy Instrument Theory
Static-dynamic-thermal characteristic analysis and experimental study of motorized spindle
Creatinine assay interferences compromises MELD accuracy and may bias liver allocation
Abstract The Model for End-Stage Liver Disease (MELD) score is widely used to prioritize patients for liver transplantation and to estimate short-term mortality in end-stage liver disease. Inaccuracies in serum creatinine measurements, particularly interference from bilirubin, both key components of the MELD, may influence clinical decision-making. However, standardized approaches to address such analytical bias are lacking. Here we show that bilirubin-related interference leads to clinically relevant MELD distortions and associated outcomes. We developed a correction model using controlled in vitro matrices and validated it against representative patient samples. The model was applied to a large cohort from registry data and a separate clinical population. After correction, clinically meaningful score shifts occurred in a substantial proportion of patients, with lower corrected scores associated with altered transplantation probability and mortality estimates. These findings highlight the importance of harmonized, interference-resistant creatinine assays to improve fairness and accuracy in liver transplant allocation.
Encapsulation of pomegranate peel bioactive phenolic extract: laboratory proof-of-concept experiment, scale-up computer-aided batch process design, techno-economic feasibility and life cycle analysis
Antioxidant malic-acid-derived lipid nanoparticles delivering secretory uricase circRNA for hyperuricemia and complication management in mice
Residual multi-scale attention and deformable learning for lumbar spine MRI segmentation
Lab-grown sperm: scientists inch closer to fertility breakthrough
Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features
Abstract Cancer arises from genetic and epigenetic alterations that reshape chromatin, transcriptional regulation, and malignant cell states. To chart cancer-intrinsic regulatory programs, we build a pan-cancer single-cell atlas of 60 cancer cell lines spanning 16 tissue origins and 20 cancer types, comprising 240,957 snRNA-seq and 223,347 snATAC-seq profiles. Integrative analyses reveal cell-state heterogeneity, core gene-regulatory networks, and a conserved EMT axis transcending tissue of origin; copy-number analysis identifies transcription factor amplification and hyperactivation as drivers of state reprogramming. Comparing cutaneous melanoma with acral melanoma, a rare subtype underrepresented in previous studies, uncovers a universal inflammation-suppressive program in acral and an inflamed landscape in cutaneous melanoma, with JAK-STAT activity as the central discriminator. Integrating data across models and patient cohorts links tumor-intrinsic regulation to microenvironmental composition and therapeutic response. By profiling rare alongside common subtypes, this atlas offers a resource for mapping pan-cancer and subtype-specific regulatory programs shaping cell-state plasticity.
Strict ontogenetic control rather than environmental plasticity drives colour morph stability in the common wall lizard
Deciphering the initiation pathway of CagT4SS assembly by in vitro reconstitution of subcomplexes
Abstract Cag type IV secretion system (CagT4SS) mediates the translocation of diverse substrates and is critical for the Helicobacter pylori pathogenesis. Its assembly is initiated by the central cylinder comprising CagX, CagY and CagM, however, the order and detailed mechanism remain unclear. Here, we characterize their respective self-oligomerizing properties and in vitro reconstitute subcomplexes that recapitulate features of the native nanomachine. By integrating multiple biophysical analyses, the structures, binding kinetics and conformational dynamics of assembly intermediates are shown. The assembly begins with self-oligomerization of CagX, followed by CagY association to form a stable periplasmic ring complex (PRC). CagM is subsequently coupled with CagX through multimerization of dimers, with CagY enhancing both the stability and cooperativity of its association. Our findings show the spatial and temporal nature of the assembly process, in particular the significance of PRC substructure, providing mechanistic insights into the biogenesis of bacterial T4SSs beyond static models.
Bone health in patients with IL-6 receptor deficiency
Which ‘AI scientist’ suits your lab? A guide for the perplexed
Molecular basis of polyadenylated RNA fate determination in the nucleus
Abstract Eukaryotic genomes generate a plethora of polyadenylated (pA + ) RNAs 1,2 , which are packaged into ribonucleoprotein particles (RNPs). To ensure faithful gene expression, functional pA + RNPs, including protein-coding RNPs, are exported to the cytoplasm, whereas transcripts within non-functional pA + RNPs are degraded in the nucleus 1–4 . How cells distinguish these opposing fates remains unknown. The DExD-box ATPase UAP56 (also known as DDX39B) is a central component of functional pA + RNPs, and promotes their docking to the nuclear pore complex-anchored TREX-2 5,6 , which triggers transcript release from UAP56 to facilitate export 7 . Here we reveal that the poly(A) tail exosome targeting (PAXT) connection 8 binds a TREX-2-like module, which releases pA + RNAs from UAP56 for decay by the nuclear exosome. The core of this module consists of a LENG8–PCID2–SEM1 trimer, which we show is structurally and biochemically equivalent to the central GANP–PCID2–SEM1 trimer of TREX-2. Mutagenesis and transcriptomic data demonstrate that the nuclear fate of pA + RNPs is governed by the contending actions of nucleoplasmic PAXT and nuclear pore complex-associated TREX-2, which interpret RNA-bound UAP56 as a signal for RNA decay or export, respectively. As RNA targets of PAXT are generally short and intron-poor, we propose an overall model for pA + RNP fate determination whereby the distinct sub-nuclear localizations of PAXT and TREX-2 govern the degradation of short non-functional pA + RNAs while allowing export of their longer and functional counterparts.
HELZ-BRCA2 complex resolves R-loops to drive transcription-coupled homologous recombination
Abstract R-loops are transcription-induced, three-stranded nucleic acid structures that, if not properly resolved, can disrupt DNA repair and compromise genome stability. BRCA2, a tumor suppressor vital for homologous recombination (HR), also contributes to R-loop regulation, though the underlying mechanisms remain poorly understood. Here, we identify HELZ as a direct BRCA2 interactor and characterize it as an ssRNA-specific R-loop resolvase. BRCA2 enhances HELZ helicase activity and promotes its recruitment to R-loops. Importantly, HELZ resolves R-loops at DNA double-strand breaks, enabling efficient DNA end resection and HR, particularly within transcriptionally active genomic regions. We further demonstrate that HELZ is critical for R-loop clearance in cancers with elevated transcriptional activity and R-loop accumulation, such as estrogen receptor-positive breast cancer, where it becomes essential for cell survival under estrogen-induced transcriptional stress. These findings establish HELZ as a BRCA2-dependent regulator of R-loop homeostasis and identify it as a potential biomarker and therapeutic target in R-loop-driven malignancies.
Advanced AGC of multi-area interconnected power systems using SBOA-tuned parallel fuzzy logic controller with energy storage
Concept2Brain: an AI model for predicting neurophysiological responses to text and pictures
Abstract Evolving methods rooted in artificial intelligence (AI) offer new opportunities for linking human behavior and experience to brain function. Here, we introduce the Concept2Brain model, a deep network designed to generate synthetic electrophysiological responses to semantic/emotional information conveyed through pictures or text. Leveraging AI solutions like CLIP from OpenAI, the model generates a representation of a stimulus and maps it into an electrophysiological latent space. We demonstrate that this openly available resource generates synthetic neural responses that closely resemble those observed empirically. The Concept2Brain model is provided as a web service tool for creating open and reproducible EEG datasets by predicting brain responses to any semantic concept or picture. Beyond its practical applications, it also paves the way for AI-driven brain activity modeling, offering new possibilities for studying how the brain represents the world.
Adsorptive elimination of Cr(VI) from wastewater using benzalkonium chloride modified Egyptian bentonite
Abstract In this study, Egyptian sodium bentonite (NaB) was modified with the cationic surfactant benzalkonium chloride (BAC) to prepare organo-modified bentonite (OMB), which altered the surface chemistry and introduced positively charged adsorption sites, thereby enhancing the adsorption performance. NaB and OMB were characterized by (FTIR), (XRD), (BET), and zero charge point ( pH pzc ) measurements. After the modification, the OMB was used to remove highly toxic Cr(VI), commonly found in industrial effluents, from aqueous solutions via batch adsorption. The impacts of BAC loading, pH, exposure time, clay dose, initial Cr(VI) concentration, temperature, and shaking speed were systematically investigated in relation to the sorption process. The optimal conditions for removal were found to be 150% BAC loading (w/w relative to NaB), pH = 2, clay dose = 4 g L − 1 , 60 min contact time for NaB and 70 min for OMB, 10 mg L − 1 initial concentration of Cr (VI) ions, and shaking speed of 200 rpm. Under these conditions, OMB achieved 99.6 ± 0.4% removal ( $$\:{Q}_{\text{e}}$$ ≈ 2.27 ± 0.05 mg g − 1 ), whereas NaB removed only 6.6 ± 0.06% of Cr(VI) ions. Adsorption kinetics followed the pseudo-second-order model, while equilibrium data followed the Langmuir isotherm, indicating surface interactions on the clay surface. Thermodynamic parameters indicated that Cr(VI) adsorption on NaB was endothermic and nonspontaneous, whereas adsorption on OMB was spontaneous and exothermic. These results demonstrate that BAC-modified bentonite is an efficient and low-cost adsorbent for Cr(VI) removal from heavy metal-contaminated water.
A blastoporal organizer in a ctenophore
Abstract In an iconic experiment in 1924, Hilde Mangold and Hans Spemann established that the dorsal blastopore lip of amphibian embryos functions as an organizer and induces a secondary body axis when transplanted into a host embryo 1 . This discovery demonstrated that specific embryonic regions can regulate embryonic patterning and lead to the establishment of an entire body axis. Subsequent studies have revealed that cnidarians, the sister group to Bilateria, also possess a blastoporal embryonic organizer 2,3 . However, the evolutionary origin of the organizer remains unclear. Here we report that the blastopore lip of the ctenophore Mnemiopsis leidyi , a member of the evolutionary sister group to all other metazoans 4,5 , exhibits organizer activity. We show that transplanted fragments of blastopore lip tissue from M. leidyi gastrula induce secondary pharynx and mouth formation. Moreover, transphyletic transplantation experiments show that the blastopore lip of M. leidyi leads to the generation of a secondary body axis in embryos of the cnidarian Nematostella vectensis . Organizer function in M. leidyi requires both β-catenin and TGFβ signalling, and the TGFβ-family ligands probably provide this inductive capacity. These findings reveal the deep homology of the blastoporal organizer in ctenophores, cnidarians and vertebrates, implying the ancestral organizer role of the blastopore lip. We propose that the emergence of the organizer was an essential innovation that facilitated the change from the temporal cell differentiation of unicellular relatives to the spatial cell differentiation of the first multicellular embryo.