Browse Articles

The number of phosphorus loss events will increase with variability and seasonality in far future climate scenarios

A PHF19-YTHDC1 condensate switches EZH2-mediated gene suppression to activation for prostate cancer progression

EZH2, a core component of PRC2 complex, silences global gene expression by tri-methylating histone H3K27. It remains an elusive question that EZH2 hyperexpression discords with its H3K27me3 activity of gene suppression in advanced prostate cancer. Here, we report a nascent RNA-dependent PHF19-YTHDC1 condensate capable of switching EZH2-mediated gene suppression to activation during prostate cancer progression. We found that the long isoform of PRC2 accessory subunit PHF19, PHF19L, was highly expressed in advanced prostate cancer that promoted the tumor progression and hormonal therapy resistance. Mechanistically, PHF19L was recruited to the m 6 A modified nascent RNA through YTHDC1 and formed a liquid-like YTHDC1-PHF19L condensate that pulled the EZH2 away from chromatin, resulting in reduced H3K27me3 deposition and the activated expression of EZH2-repressed genes. Therefore, our study reveals a biomolecular condensate that modulates the switch from EZH2-mediated epigenetic gene silence to activation during the progression of prostate cancer.

Introducing a hybrid intrusion detection method for IoT-cloud environments based on ResNeXt and improved Ebola optimization search algorithm

Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release

In Alzheimer’s disease (AD), hyperactivated microglia produce inflammatory mediators that contribute to neuroinflammation and neuronal damage. Amyloid precursor protein (APP), a transmembrane protein expressed in many cell types, including neurons and microglia, plays a critical role in AD pathogenesis via its secretase-mediated processing to release the C-terminal 99-residue transmembrane fragment (C99) that is further cleaved to yield amyloid-β peptides. Voltage-gated proton channels (Hv1) have been implicated in microglial activation and release of inflammatory mediators, but the potential role of these channels in human microglia and AD pathogenesis remains unclear. Here, we demonstrate that human induced pluripotent stem cell–derived microglia (iMG) express native Hv1 channels with biophysical and pharmacological attributes determined by their coassembly with APP and that APP knockdown decreases Hv1 currents, suppressing cytokine and reactive oxygen species release. In HEK293T cells, APP is shown to increase current by favoring channel opening at more negative membrane potentials. C99 is sufficient to assemble with Hv1 and alters channel function even more significantly than APP. Coimmunoprecipitation, total internal reflection fluorescence microscopy, and altered pharmacology further demonstrate that C99 forms stable complexes with Hv1 in the plasma membrane. In addition, we find that two early-onset AD mutations in APP (E682K and D694N) that reside within C99 significantly increase voltage-dependent channel activity beyond that induced by wild type C99, rationalizing their enhanced mediation of neuroinflammation.

Ticagrelor versus clopidogrel in Chinese patients with coronary artery disease: a retrospective real-world study

Differential <i>O</i> -glucose elongation on a specific EGF repeat within the canonical ligand–binding domain regulates DLL1/4-NOTCH1 signaling

Three types of O -linked glycosylation— O -glucose, O -fucose, and O - N -acetylglucosamine— are crucial for the function of Notch receptors, which regulate critical cell fate determination processes in a wide variety of contexts. O -Glucose glycans are transferred to serine residues located between the first and second conserved cysteines within the epidermal growth factor-like (EGF) repeats in the Notch extracellular domain. Previously, O -glucose glycans were shown to be extended to a trisaccharide structure with two xyloses via α1-3 linkages. Our recent studies, however, indicated that the O -glucose glycan on NOTCH1 EGF10 can be extended by hexose and Neu5Ac. Here, we demonstrated that this hexose- and Neu5Ac-extended glycan has a 3’-sialyllactose-like structure synthesized by specific members of two isoenzyme families, B4GALT1 and ST3GAL4. Using mass spectrometry, we identified this modification exclusively on NOTCH1 EGF10 and the analogous NOTCH3 EGF9 domain, with no detection in any other EGF domains in NOTCH1, NOTCH2, and NOTCH3. Sequence comparison and mutagenesis experiments identified one amino acid at position -2 of the fourth cysteine (C 4 -2) in the EGF domain as crucial for the galactose elongation of O -glucose glycans. We further demonstrated that this site-specific elongation of O -glucose on NOTCH1 EGF10 significantly impacts ligand binding and signal transduction of NOTCH1. In the context of early T cell development, the C 4 -2 mutants NOTCH1 A396Y and A396F enhance T cell differentiation through DLL1- and DLL4-dependent NOTCH1 signaling. Our findings contribute to the understanding of the intricate regulatory mechanisms of Notch receptor function mediated by distinct positions and structures of O -glycans.

A hybrid stellar mass black-hole optimization framework for finding significant biclusters using average Kendall rank correlation

Abstract Microarray gene expression data are high-dimensional and complex, with patterns that may appear only under specific conditions. Traditional clustering often misses these local patterns, whereas biclustering can reveal groups of genes with coordinated expression across particular conditions. In this paper, we propose a biclustering approach using average Kendall correlation, which captures nonlinear and monotonic relationships often overlooked by standard measures like Euclidean distance or Pearson correlation. To efficiently search for optimal biclusters, we implement a modified stellar mass black-hole optimization (MSBO) approach that integrates the Nelder–Mead simplex method with Lévy flight to enhance both local and global search capabilities. The proposed technique is validated on couple of widely used benchmark gene expression datasets, namely the yeast cell cycle and lymphoma. The biological importance of the identified biclusters is evaluated with the help of the gene ontology (GO) database. Experimental results demonstrate that our method outperforms traditional approaches in identifying statistically significant and biologically relevant biclusters, achieving a p-value of 3.73 × 10 −16 . These findings address the pressing need for more effective biclustering techniques in the study of microarray data.

Nir2 crystal structures reveal a phosphatidic acid–sensing mechanism at ER–PM contact sites

Agonist-induced activation of phosphoinositide-specific phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] to diacylglycerol (DAG) at the inner leaflet of the plasma membrane (PM). DAG can be enzymatically transformed into phosphatidic acid (PA) and accumulated at the PM. PYK2 N-terminal domain-interacting receptor 2 (Nir2) mediates the formation of ER–PM membrane contact sites (MCSs) by specifically recognizing PA at the PM and directly interacting with ER membrane protein vesicle-associated membrane protein-associated proteins (VAPs). The N-terminal phosphatidylinositol transfer protein domain of Nir2 facilitates PI/PA exchange at ER–PM MCSs to maintain PI and PA levels. Here, we reveal the mechanisms by which Nir2 senses phosphatidic acid (PA) and associates with membranes, based on three crystal structures of its C-terminal Lipin/Ned1/Smp2 (LNS2) domain bound to PA, the diphenylalanine [FF]–containing acidic tract (FFAT) motif complexed with vesicle-associated membrane protein–associated protein B/C (VAPB), and the Asp-Asp-His-Asp (DDHD) domain. The C-terminal LNS2 domain of Nir2 directly interacts with the phosphate in the headgroup of PA via hydrogen bonds involving S1025, T1065, K1103, and K1126. Formation of a salt bridge between E355 in Nir2 and R55 in VAPB is essential for Nir2 FFAT–VAPB interaction. The central DDHD domain of Nir2 forms a twofold symmetric dimer, and this self-association contributes to stable and tight membrane association. These findings reveal how Nir2-mediated ER–PM MCS formation maintains continued PI(4,5)P 2 -dependent PLC signaling.

Population genetic structure reveals asymmetric hybridization between Pinus pumila and P. parviflora var. Pentaphylla in the Hakkoda Mountains, Northern Japan

Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM

Pentameric ligand-gated ion channels (pLGICs) are vital neurotransmitter receptors that are key therapeutic targets for neurological disorders. Although the high-resolution structures of these channels have been elucidated, capturing their dynamic conformational transitions remains challenging due to the transient nature of intermediate states. In this study, we investigated a prokaryotic proton-gated pLGIC, GLIC. In our cryo-EM data at pH 4.0, we identified and segregated asymmetric particles, which we precisely aligned to resolve high-resolution structures of several previously unresolved asymmetric intermediate states, in addition to symmetric closed and open states. Detailed structural analysis revealed systematic conformational changes at individual subunits driving the channel opening. Molecular dynamics simulations were used to assign the functional states. We further examined the roles of the F116 and Y251 residues, located at the domain interface, playing a central role in interdomain communication. In addition, patch-clamp experiments on GLIC I240A and L241A mutants, located in the M2 helix, demonstrated their importance in channel gating. Together, these results shed light on the sequential and asymmetric conformational transitions that occur during GLIC activation, offering a deeper mechanistic understanding of asymmetric gating in pLGICs.

Joint analysis of sQTL and Hi-C reveals spatial proximity between sQTLs and target genes in cancer tissues

Logarithmic coding leads to adaptive stabilization in the presence of sensorimotor delays

Animals respond to sensory stimuli with motor actions, which in turn generate new sensory inputs. This sensorimotor loop is constrained by time delays that impose a trade-off between responsiveness and stability. Additionally, as the relationship between a motor command and the corresponding sensory feedback is context-dependent, the response must be adapted in real time. It is generally believed that this adaptation process relies on an internal model that is continuously updated through prediction error minimization. Here, we experimentally reveal an alternative strategy based on a simpler feedback mechanism that does not require any internal model. We developed a virtual reality system for the miniature transparent fish Danionella cerebrum that enables in vivo brain-wide imaging during fictive navigation. By systematically manipulating the feedback parameters, we dissected the motor control process that allows the animal to stabilize its position using optic flow. The sensorimotor loop can be fully described by a single delay differential equation, whose solutions quantitatively capture the observed behavior across all experimental conditions. Both behavioral and neural data indicate that the observed adaptive response arises from logarithmic nonlinearities at the sensory (Weber–Fechner law) and motor (Henneman’s size principle) ends. These fundamental properties of the nervous system, conserved across species and sensory modalities, have traditionally been interpreted in terms of efficient coding. Our findings unveil a distinct functional role for such nonlinear transformations: ensuring stability in sensorimotor control despite inherent delays and sensory uncertainty.

Analysis of thermal and dynamic mechanical properties of epoxy bio-composites reinforced with sisal fibers and carbon nanotubes

Abstract The present study focuses on the fabrication and analysis of thermal and dynamic mechanical properties of epoxy bio-composites reinforced with 15 wt.% sisal fibers and varying carbon nanotube (CNT) content (0–2.0 wt.%). As per the results, incorporation of 1.0 wt.% CNT significantly enhances thermal and mechanical properties of the composite. Compared to the baseline composite without CNTs, thermal degradation onset has been improved by approximately 13%, while crystallinity and thermal resilience also increased. The storage modulus and loss modulus rose by approximately 79% and 197% respectively, indicating greater stiffness and energy absorption capacity. The damping factor (tan δ) decreased by over 56%, implying enhanced load-bearing capability with reduced energy dissipation. These improvements are attributed to better interfacial bonding and uniform CNT dispersion at 1.0 wt.%. The SEM analysis of epoxy bio-composites also revealed that the optimal dispersion and strong interfacial bonding are achieved at 1.0 wt.% CNT. Overall, the findings demonstrate that optimal thermal stability and viscoelastic properties occur at low CNT content in natural fiber composites, making them suitable for advanced structural applications in automotive, aerospace, and packaging sectors.

All the world’s a phage

A renewed interest in bacteriophages has emerged from the explosive discovery of the complex pan-immune bacterial defense system and a revival of the therapeutic potential of phages in the age of widespread antimicrobial resistance to antibiotics. However, the road ahead is daunting because of the huge genetic diversity of phages and the vast numbers of genes of unknown function. A fully integrated approach that includes curiosity-driven exploration of phage biology, the development of integrated and inclusive research-education programs based on phage discovery and genomics (SEA-PHAGES), and the advancement of phage therapeutics provides a holistic structure for advancing the field. The phages of mycobacteria illustrate this model and a large mycobacteriophage collection reveals the enormous diversity of phages infecting a single bacterial strain and illuminates the evolutionary mechanisms giving rise to genomes with mosaic architectures. A set of 2,600 fully sequenced and annotated mycobacteriophage genomes and the development of tools for engineering them with desirable properties enable phage therapies for treating Mycobacterium infections for which antibiotics frequently fail. Technological advances in synthetic genomics and structural biology promise to rapidly advance this field and powerfully stimulate developments in all aspects of bacteriophage investigation and application. Here I describe what we have learned from the study of mycobacteriophages and how a holistic approach—integrating curiosity-driven research, inclusive education, and medicine—can serve as a model for advancing microbiology broadly.

Synergistic role of potassium fertilizer and kinetin in mitigating iron toxicity and enhancing yield in lowland rice

Spatial gene expression analysis reveals pathological niches in Japanese encephalitis virus neuroinvasion

Japanese encephalitis virus (JEV) infection causes encephalitis in humans and animals. Following intradermal infection, JEV crosses the blood–brain barrier (BBB) and reaches target cells in the brain parenchyma. However, the cellular dynamics and pathological niches involved in JEV neuroinvasion remain poorly understood. In this study, we investigated the early stages of JEV infection in the mouse brain employing a highly multiplexed spatial transcriptomics platform to map viral RNA and host gene expressions in intact brain sections at a single-cell resolution. Although JEV RNA was undetectable in brain sections at 1-day postinfection (dpi), innate immune responses were transiently activated across the brain. At 4 dpi, we detected limited viral RNA and mapped its spatial distribution, identifying glial cells surrounding microvessels as early targets of brain infection. We further characterized transcriptional changes in infected and surrounding bystander cells, revealing cell-type–specific antiviral responses. Notably, JEV neuroinvasion led to the downregulation of endothelial tight junction genes, indicative of an early event that precedes BBB impairment during subsequent disease progression. Our spatial transcriptomic analysis provides insights into cell-type– and region-specific responses to JEV infection, and highlights the early role of glial cells in shaping the immune response landscape of the brain. These findings greatly improve our understanding of JEV pathogenesis before the onset of clinical encephalitis.

Tuning photoluminescence in Gd2O3 via lattice engineering for advanced barcode and LEDs applications

Abstract The utilization of luminescent phosphors in barcode technology can enhance the security feature. Using NaOH as a reducing agent, we have prepared Gd 2 O 3 :Eu 3+ /Er 3+ for luminescent phosphor. The cubic structure of Gd 2 O 3 phosphor is confirmed by the structural analysis conducted using XRD. Dopant Eu and Er induce lattice contraction and expansion in the host lattice, respectively. Based on SEM analysis, porous and irregular particles with an average size of 401 nm were observed. In Tem analysis of prepared phosphor have some particle are in spherical in shape. The formation of Gd 2 O 3 was confirmed by Gd-O band stretching as shown in the FTIR analysis. The emission in the red and green regions is emitted by Gd 2 O 3 :Eu 3+ and Gd 2 O 3 :Er 3+ , respectively. The emission peaks of Gd 2 O 3 :Eu 3+ /Er 3+ are observed at 524 nm, 539 nm, 549 nm, 563 nm, 593 nm, 612 nm, and 629 nm when it is triggered by 363 nm, with a maximum energy transfer efficiency of 95.93%. Enhancing the security of barcodes can be achieved through the use of color-tunable Gd 2 O 3 :Eu 3+ /Er 3+ phosphor. Gd 2 O 3 :Er 3+ (1.5 mol%) is a prominent candidate for LED bulbs due to its CCT (5765 K).

Squamous cell carcinoma antigen-1/SerpinB3 is an endogenous skin injury response element

The squamous cell carcinoma antigen SerpinB3 is a serum-circulating biomarker of epithelial cancers associated with high metastasis, treatment resistance, and poor prognosis. Despite its clinical significance, the endogenous role of SerpinB3 has remained undefined. Here, we identify SerpinB3 as a mediator of epithelial wound healing. Injury induces SerpinB3 expression in vitro and in vivo in the migrating epidermal tongue; overexpression of the protein promotes epithelial-to-mesenchymal transition–like changes. Recombinant Serpinb3a, the mouse ortholog, enhances re-epithelialization in vitro and accelerates wound closure and collagen remodeling in vivo. These findings reveal a physiological function for SerpinB3 in epithelial repair and suggest that its expression in cancer, chronic wounds, and inflammatory diseases may reflect reactivation of a conserved wound response program—positioning SerpinB3 as a compelling therapeutic target.

Intelligent power control using deep neural networks and regularized learning for shipboard microgrid

Magnon-induced electric polarization and magnon Nernst effects

Magnons offer a promising path toward energy-efficient information transmission and the development of next-generation classical and quantum computing technologies. However, efficiently exciting, manipulating, and detecting magnons remains a critical need. We show that magnons, despite their charge-neutrality, can induce electric polarization through their spin and orbital moments. This effect is governed by system symmetry, magnon band hybridization, and interactions with other quasiparticles. We calculate the electric polarization induced by magnons in two-dimensional collinear honeycomb and noncollinear antiferromagnets (AFMs), showing that the presence of the Dzyaloshinskii–Moriya interaction yields a finite net electric polarization. In NiPSe 3 , a collinear honeycomb AFM with Zigzag order, the induced net electric polarization is about three orders of magnitude greater than in MnPS 3 , a collinear honeycomb AFM with Néel phase. In the noncollinear AFM KFe 3 (OH) 6 (SO 4 ) 2 , the net electric polarization can be tuned via magnon hybridization, which can be controlled by external magnetic fields. These findings reveal that electric fields could be used to both detect and manipulate magnons under certain conditions by leveraging their spin and orbital angular moment. They also suggest that the discovery or engineering of materials with substantial magnon orbital moments could enhance practical uses of magnons for future computing and information transmission applications.