Browse Articles

Sequence-defined donor-acceptor-donor oligo(para-phenylene ethynylene)s with emission across the visible spectrum

Abstract Donor-acceptor engineering is a widely employed strategy for π-conjugated molecules to modulate their electronic structure and photophysical behavior. Oligo( para -phenylene ethynylene)s (OPEs) provide a rigid and modular π-conjugated scaffold that is particularly well suited for the systematic incorporation of donor and acceptor units. In this work, a symmetric donor-acceptor-donor (D-A-D) sequence was adopted to tune the electronic structure of the OPE molecular rods. By varying the acceptor unit, two series of OPE emitters, OPE- x (3-mers) and OPE- x ’ (5-mers), were synthesized via Sonogashira cross-coupling reactions. With increasing acceptor strength, the emission wavelength could be tuned from the blue to the red spectral region for both applied conjugation lengths, while preserving high photoluminescence quantum yields (PLQY). By extending the degree of conjugation by a defined number of repeating units, a decrease was observed for both the Stokes shift and the emission full width at half maximum (FWHM) across the series. Further analysis aided by quantum-chemical calculations provides a molecular-level understanding of the observed photophysical trends.

Sulfur Vacancy‐Enriched Cu ₄ SnS _4−x Nanosheets Enable Synergistic Cuproptosis, Photothermoelectric Catalytic and Immunotherapy

ABSTRACT Photothermoelectric catalytic therapy (PTECT) faces challenges like restricted thermoelectric activity and tumor recurrence. In this study, we introduce a defect engineering strategy to synthesize sulfur vacancies (S v ) enriched Cu 4 SnS 4−x nanosheets with promising thermoelectric properties, followed by loading small‐molecule inhibitor NLG919. Spherical aberration corrected transmission electron microscopy and X‐ray absorption fine structure reveal the fine structural characteristics of S v , which make the nanosheets possess an ultra‐high photothermal conversion efficiency of 64.7% under 808 nm laser irradiation. This generates a localized temperature gradient that induces an internal electric field, which enhances carrier separation, boosts peroxidase‐ and catalase‐like activities, and produces substantial amounts of reactive oxygen species (ROS), enabling cooperative PTECT and multi‐enzymatic catalytic therapy. Density functional theory calculations show that S v reduces the thermal conductivity, thus enhancing the figure of merit value and the PTECT effect. Accumulation of Cu ions, ROS, and heat triggers cuproptosis, mitochondrial apoptosis, and endoplasmic reticulum‐based immunogenic cell death. The released NLG919 disrupts the IDO‐induced Trp/Kyn metabolic pathway, reversing the tumor immune suppressive microenvironment. This integrated approach achieves high efficiency (96%) and long‐term anticancer efficacy. These findings may provide valuable insights for advancing thermoelectric materials in tumor therapy.

GIS-integrated multi-criteria decision framework for waste-to-energy plant site selection in Beni Suef governorate, Egypt

Abstract This study presents the first comprehensive GIS-MCDM site suitability model for a Waste-to-Energy (WTE) facility in Upper Egypt. A sixteen-criterion analytical framework encompassing environmental protection, geological safety, infrastructure accessibility, and social proximity constraints was developed through a structured expert consultation process involving 42 specialists from academic, governmental, and environmental sectors. Criterion weights were derived using the Analytical Hierarchy Process (AHP) and validated with a Consistency Ratio of 2.6% (well below the 10% threshold). Spatial data layers were derived from Landsat-9 imagery (SVM classification), ASTER GDEM (30 m), ERA5-Land wind reanalysis, World population grids, OpenStreetMap infrastructure networks, and the Conoco–EGPC geological map of Egypt. Across the 10,698.5 km² study area, the integrated suitability map reveals that zones classified as high or very high suitability together constitute only 2.02% of the total area (59.5 km²; very high: 0.19%, 6.3 km²; high: 1.83%, 53.2 km²). The dominant land constraint, 69.3% classified as very low suitability, reflects strict environmental exclusion buffers around protected areas (PA; weight 11.4%), sensitive land uses (SU; 11.2%), surface water bodies (SW; 9.4%), and steep terrain (SP; 9.4%). Three candidate sites with high suitability scores were delineated, with the most favorable located east of Beni Suef city (coordinates: 29°01′ N, 31°07′ E; area: 22.75 km²), proximate to the governorate’s largest existing landfill (~ 2.6 km) and with favorable north-westerly wind alignment relative to populated zones. This study advances the GIS-MCDM literature by integrating geological (faults, lithology, soil bearing capacity) and environmental safety criteria within an arid-region planning context, an approach insufficiently addressed in prior Egypt-focused or MENA (WTE) siting studies. The resulting suitability model constitutes a reproducible, evidence-based decision-support tool for Egyptian environmental planners and aligns with Egypt’s Sustainable Development Strategy 2030 goals for renewable energy diversification and circular economy promotion. The selected site shows potential logistical and economic advantages due to its proximity to existing landfill infrastructure and regional road networks; however, these advantages represent spatial screening indicators and require further techno-economic and network-based transport assessment before implementation. Model validation using ROC–AUC analysis confirmed good discriminatory performance, with an AUC of 0.829, overall accuracy of 90.0%, and Kappa coefficient of 0.801.

Achieving 1.0‐s Thermally Activated Delayed Fluorescence via Synergistic Control of Reverse Intersystem Crossing and Exciton Cycling

ABSTRACT Persistent thermally activated delayed fluorescence (p‐TADF) is fundamentally constrained by the kinetic trade‐off between reverse intersystem crossing (rISC) and triplet exciton decay, including phosphorescence and non‐radiative processes, which intrinsically limits its lifetime ( τ DF ). Here we present a synergistic strategy that overcomes this limitation by concurrently slowing the rISC rate ( k rISC ) while preserving the condition k rISC ≫ k Ph + k nr,T and deliberately promoting multiple intersystem crossing (ISC)/rISC exciton cycles. The efficacy of this approach is validated by o ‐TFBCz, which achieves an unprecedented τ DF of 1.00 s even in unannealed poly(methyl methacrylate), despite originating from a phosphorescence core with a lifetime ( τ Ph ) of only 1.92 s. This system exhibits bluish‐green afterglow under blue‐light excitation and outstanding thermal stability. Quantitative photophysical analysis reveals an average of 2.1 ISC/rISC cycles per exciton in this material, enabled by an ISC rate ( k ISC ) that dominates over fluorescence ( k Fl ) and internal conversion ( k IC ) rates ( k ISC > k Fl + k IC ). These results establish a clear, generalizable blueprint for breaking the lifetime ceiling of pure organic p‐TADF materials.

Computational validation of a wearable biomechanical sensor network framework for real-time fatigue monitoring and performance prediction in gymnastic training

Programming Bio–Bio Electronic Interfaces for Light‐Driven Interspecies Electron Transfer

ABSTRACT Living systems organize electron flow through continuous, spatially and energetically structured redox networks, whereas most synthetic light‐driven bioelectronic platforms rely on abiotic materials to generate and inject electrons into cells, limiting selective coupling between living partners. Here, we report programmable living electronic interfaces that enable direct, light‐driven interspecies electron transfer (IET) between two living microorganisms. A conformal poly(3,4‐ethylenedioxythiophene) network integrated into the envelope of Synechococcus elongatus intercepts and relays photosynthetic electron flux, while supramolecular cucurbit[7]uril host–guest interactions program defined cell–cell assembly with engineered Escherichia coli . Redox‐active mediators embedded within the interface establish energetically matched electron‐transfer pathways across species boundaries. Redox‐potential matching identifies neutral red as an optimal mediator, enabling selective delivery of photosynthetic electrons into E. coli with an IET efficiency of 83.7%, thereby enhancing light‐driven biocatalysis. This work establishes an integrated bio–bio electronic architecture that embeds electronic conduction within living redox networks, defining a paradigm for constructing light‐powered microbial consortia distinct from conventional abiotic–bio hybrid systems.

Direct Deaminative Alkynylation of Aliphatic Primary Amines

ABSTRACT Alkyl‐substituted internal alkynes are useful motifs in organic synthesis and medicinal chemistry, but their preparation from common amine precursors remains challenging. Aliphatic primary amines are widespread functional groups, yet their direct use as alkylating reagents is limited by the strength of the C(sp 3 )─N bond. Herein, we describe a direct deaminative alkynylation of aliphatic primary amines using alkynyl bromides as coupling partners. The transformation proceeds under metal‐free conditions with an N ‐anomeric amide as a nitrogen‐deletion reagent, enabling formation of C(sp 3 )─C(sp) bonds without prior amine prefunctionalization. The reaction shows good functional‐group tolerance and accommodates a range of aliphatic amines, including substrates derived from pharmaceuticals and natural products. This study demonstrates the feasibility of converting aliphatic primary amines into internal alkynes and expands the scope of deaminative C─C bond‐forming reactions.

A Diammonium‐Based Non‐Dion‐Jacobson Phase 2D Perovskite With High Durability for Efficient and Stable 2D/3D Perovskite Solar Modules

ABSTRACT Dion‐Jacobson (DJ) phase 2D perovskites have attracted much interest in photovoltaic community owing to their potential higher stability relative to 3D counterparts. The conventional wisdom has been that organic diammoniums certainly generate DJ 2D perovskites by forming bilateral hydrogen bonds with two layers of inorganic [PbI 6 ] 4− slabs. However, we herein report a diammonium‐based non‐DJ phase 2D perovskite, composed of 3 , 3′ ‐methylenediphenyldiammonium ( 3,3 ‐MDPDA 2+ ). Single‐crystal structure of the resultant 2D perovskite has a formula of ( 3,3‐ MDPDA)PbI 4 as the DJ phase, but reveals that there are two layers of 3,3 ‐MDPDA 2+ between adjacent inorganic layers and two ammonium groups of each 3,3 ‐MDPDA 2+ link to a single inorganic [PbI 6 ] 4− slab. Moreover, the 3,3 ‐MDPDA 2+ cations in the organic bilayer present unique π‐π interactions, including intralayered edge‐to‐face and interlayered parallel‐displaced configurations, respectively, leading to high stability of the diammonium‐based non‐DJ 2D perovskite. When introducing it into the 3D perovskite film to construct 2D/3D structures, resulting perovskite solar cells and modules (effective area: 50 cm 2 ) demonstrate efficiencies of 26.52% and 23.34%, respectively, with outstanding operational stability retaining 94% of initial efficiency under continuous maximum power point tracking for 1200 h.

A predisposing effect of HLA class II genes in celiac disease by skewing the naive CD4 ⁺ T cell receptor repertoire

Polymorphisms of human leukocyte antigen (HLA) genes confer risks for human diseases. Predisposing effects related to T cell receptor (TCR) recognition of peptide–HLA can be selection of TCR repertoire and/or preferential presentation of disease-driving epitopes. In celiac disease (CeD), HLA-DQ2.5 predisposes by presenting gluten peptides to CD4 + T cells that typically employ stereotyped TCRs. Here, we analyzed whether genetic variants within the HLA and TR loci shape the naive TCR repertoire. We sequenced the αβ TCR repertoires of naive CD4 + T cells of 103 CeD subjects and 103 controls and performed gene usage quantitative trait loci analyses. The naive CD4 + TCR repertoire was significantly affected by TRA, TRB, and in particular HLA polymorphisms. The presence of HLA-DQ2.5 influenced the TCR repertoire, resulting in significant enrichment of TCR genes being involved in recognition of gluten epitopes in the repertoires of CeD subjects versus controls. HLA thus affects disease risk by selection of a disease-relevant TCR repertoire.

Wave propagation in fluid-saturated nanoporous media: Upscaling molecular mechanics into continuum-level description

Understanding how mechanical, thermodynamic, and acoustic properties emerge in fluid-saturated nanoporous materials remains a major challenge due to the breakdown of classical continuum assumptions at molecular length scales. Here, we present a multiscale framework that extends linear chemo-poroelasticity theory to describe the coupled response of nanoporous solids and confined fluids to mechanical wave excitation. The effective poromechanical parameters—elasticity and stress-chemistry coupling tensors, scalar chemistry modulus, and fluid mobility tensor—are computed from atomistic simulations of methane adsorption and transport in a prototypical zeolite. These simulation-informed parameters are then embedded in a continuum model of mechanical wave propagation. This integrated approach enables the prediction of the effective wave speeds and attenuation as a function of frequency, fluid loading, and nanopore-scale structure. The methodology provides a physically grounded path for linking molecular interactions to macroscopic acoustic and elastic response. In turn, this framework offers opportunities for designing nanoporous materials with tailored transport, mechanical, and acoustical properties—particularly in the emerging field of nanoscale acoustics.

Biophysical fitness landscape design traps viral evolution

Evolutionary adaptation is often visualized as a population’s stochastic climb toward the top of a fitness landscape. While there exist approaches to design or synthetically evolve proteins into desired structures, there is a lack of methodology for designing, tuning, and quantitatively reshaping the fitness landscapes themselves on which protein evolution takes place. Here, we introduce foundational principles of fitness landscape design (FLD) to customize the structural peaks and valleys of biophysical fitness landscapes with quantitative accuracy, offering robust control of long-term evolutionary outcomes. Our FLD algorithms use stochastic optimization of a chemically derived biophysical fitness model to consistently discover optimal antibody ensembles which force a target protein to evolve according to a user-specified target fitness landscape. We then apply FLD to suppress the fitnesses of two SARS-CoV-2 genotype neutral networks and to discover proactive vaccines that preemptively restrict escape variant fitness trajectories before they arise.

Cryo-EM of the eukaryotic purine transporter UapA demonstrates intramolecular and lipid regulation of transport

Members of the nucleobase ascorbate transporter (NAT) family (SLC23) are elevator-type transporters that are responsible for the uptake of nucleobases and ascorbate. In fungi, NAT members are also responsible for the specific uptake of antifungal nucleobase analogues, such as oxypurinol, allopurinol, or 8-azaguanine. Here, we report nearly full-length cryo-EM structures of UapA, a high-affinity purine transporter from the model fungus Aspergillus nidulans , in inward-facing apo- and substrate-loaded conformations at 2.06 to 3.5 Å in detergent and lipid nanodiscs. The high-resolution structures reveal the role of water molecules and lipids in substrate binding, specificity, transporter dimerization, and activity. Notably, the N-tail of UapA is found to be structured, interacting with both the core and scaffold domains, which in combination with functional data suggests a dual role in trafficking and transport dynamics. Overall, our study provides unprecedented structural and functional insights into an elevator-type fungal transporter, which may well contribute to the exploitation of NAT transporters as specific gateways for targeted pharmacological antifungal approaches.

Knotted solid tori in contact manifolds

In this paper, we study solid tori in contact manifolds. Specifically, we study the contact width of a knot type and give criteria for when it can be explicitly computed. We also prove there are many “nonthickenable” tori in many knot types. These tori are frequently essential in the study of Legendrian and transverse knot theory and tight contact structures on manifolds obtained by surgery on the knot. Previously, nonthickenable tori have only been observed for iterated torus knots in S 3 and were thought to be rare. We show that they are quite common, exist in other manifolds, and even for a hyperbolic knot in S 3 . We also make and highlight several conjectures about the general nature of knots in contact manifolds.

Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease

Fibrosis is the end-stage of a maladaptive process that occurs when the body’s normal wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage of neovascular age-related macular degeneration (nAMD), the most common cause of central vision loss in people over the age of 50. The cellular sources of excess extracellular matrix (ECM) contributing to subretinal fibrosis are unknown, as is the heterogeneity of cells involved in the fibrotic process. Here we identify cells contributing to subretinal fibrosis by using Col1a1 -YFP reporter mice to noninvasively image collagen production in real-time in vivo in two disease models, 1) a resolving retinal injury model and 2) a fibrotic model of subretinal disease. We create a collagen-producing eye cell atlas for subretinal injury and demonstrate subretinal fibroblast heterogeneity in healthy, resolving, and fibrotic tissue. We identify distinct molecular characteristics of general repair/resolving fibroblast populations versus pathogenic pro-fibrotic collagen-producing fibroblasts. Integration of this collagen-producing eye cell atlas with a published collagen-producing lung cell atlas shows conserved pro-fibrotic fibroblasts in both organs, yet also uncovers tissue-specific fibroblast populations unique to subretinal fibrosis. A Fap + Fgl2 + fibroblast population significantly expands in subretinal fibrosis that expresses the highest levels of collagens and distinctively expresses ECM components Periostin , Col15a1 and Col6a5 . Immunolabeling of mouse and human-donor eye tissue support the fibroblastic expression and perivascular location of periostin as clearly distinguishing between bona fide fibrosis and early disease in nAMD. Our collagen-producing eye cell atlas is a valuable resource for studying distinct fibroblast subsets in homeostasis, early injury, and fibrosis.

Exploring memory effects: Sparse identification in vector-borne diseases

Predicting the human burden of vector-borne diseases from limited surveillance data remains a major challenge, particularly in the presence of nonlinear transmission dynamics and delayed effects arising from vector ecology and human behavior. We develop a data-driven framework based on an extension of Sparse Identification of Nonlinear Dynamics to systems with distributed memory, enabling discovery of transmission mechanisms directly from time series data. Using severe fever with thrombocytopenia syndrome as a case study, we show that this approach can uncover key features of tick-borne disease dynamics using only human incidence and local temperature data, without imposing predefined assumptions on human case reporting. We further ascertain the robustness of the recovered incidence-temperature model by integrating it with mechanistically derived tick–host covariates, showing that the forecasting ability does not improve. This suggests that the proposed core data-driven model already delivers strong predictions. The framework also allows for systematic sensitivity analysis of memory kernels and behavioral parameters. Although the approach prioritizes predictive accuracy over mechanistic transparency, it yields sparse, interpretable integral representations suitable for epidemiological forecasting. This methodology provides a scalable strategy for forecasting vector-borne disease risk and informing public health decision-making under data limitations.

On the origin of PRDM9-guided recombination hotspots

Meiotic recombination is highly conserved across vertebrates and plays an essential role in ensuring chromosomal segmentation and generating genomic variation. However, species employ two strikingly different mechanisms to guide recombination. In most mammals, recombination hotspot locations are determined by the protein PRDM9, which binds specific DNA sequence motifs. These motifs are rapidly eroded by biased gene conversion, rendering this mechanism self-destructive and evolutionarily transient. In contrast, birds initiate recombination at open chromatin regions independently of sequence motifs, producing self-preserving and evolutionarily stable recombination hotspots. Some species use both types of hotspots simultaneously, raising the unresolved question of why PRDM9-guided hotspots persist alongside a robust alternative. Here, we address this problem using a population genetic model that explicitly considers competition between PRDM9-guided and non-PRDM9-guided recombination hotspots. We show that non-PRDM9-guided hotspots are generally favored because, lacking sequence specificity, they generate more crossovers required for proper chromosome segregation. However, PRDM9-guided hotspots can overcome this disadvantage when simultaneous binding of both homologous chromosomes (symmetric binding) is more likely to resolve as crossovers than binding of a single homolog (asymmetric binding). Although PRDM9 reduces overall crossover rate, its sequence specificity increases the probability of symmetric binding within hotspots, creating a trade-off that can favor PRDM9 under specific selection regimes. Our model predicts that PRDM9-dependent species are particularly sensitive to disruptions of symmetric binding, whereas species lacking PRDM9 are more vulnerable to complete crossover failure. Intermediate regimes allow stable coexistence of both hotspot types.

Rheologic controls on the depth dependence of megathrust earthquakes

The various slip behaviors of the subduction megathrust fault, including deadly megathrust earthquakes, are depth-dependent. Yet, we do not know what causes this depth dependence, in part due to variability between subduction zone thermal structures and lithological inputs. Here, we investigate controls on the nucleation depths of great earthquakes (Mw ≳ 8) and the deeper extent of seismogenesis. To do so, we create rheologic strength envelopes for six subduction zones using published constitutive relations for subducting lithologies and regional thermal models. We then compare the strength envelopes to local plate interface earthquake depths. Our synthesis shows that subducted sediments undergo a transition from frictional to predominantly viscous deformation near 300 ± 60 ° C a transition that correlates with the maximum nucleation depths of great earthquakes at 20 to 30 km. However, smaller plate interface earthquakes ( 5 ≤ Mw < 8) continue to nucleate below this depth, and the maximum earthquake size decreases until the base of the seismogenic zone at 40 to 60 km depth and ∼ 500 °C. We evaluate potential causes of seismicity below the onset of viscous deformation in these now metasediments, and conclude that the presence of lithologic heterogeneities that are loaded to frictional failure by viscously deforming metasediments is most plausible. Thus, we propose that great earthquakes can nucleate and grow into large events where all lithologies are frictional. However, the base of the seismogenic zone is deeper than the onset of viscous deformation in metasediments, which limits the growth of earthquakes into large events, and here seismicity reflects the existence and size of heterogeneity along the plate interface.

HDAC inhibition sensitizes pancreatic tumors to DNA damage by global redistribution of the transcriptional machinery

The DNA damage response (DDR) is critical for pancreatic ductal adenocarcinoma (PDAC) development and therapeutic responses, including to genotoxic agents. While epigenetic modulators have been shown to contribute to the DDR, how chromatin regulation dictates responses to DNA damage in PDAC remains incompletely understood. Here, we identify Class I histone deacetylases (HDACs) as critical regulators of the DDR. HDAC1/2 direct the genomic distribution of H3K27ac, ensuring sufficient BRD4 and RNA polymerase II (Pol II) occupancy at DDR gene promoters. HDAC inhibition by entinostat shifts the balance of H3K27 acetylation preferentially toward intergenic regions, diverting BRD4 and Pol II from promoters, thereby suppressing DDR gene expression. In line with this, HDAC inhibition heightens DNA damage and sensitizes PDAC to diverse DNA-damaging and DDR-targeting agents. Since the clinical development of HDAC inhibitors has been limited by systemic toxicity, we developed bottlebrush prodrug (BPD) nanoparticles for tumor-selective entinostat delivery. Entinostat-BPD achieved tumor-specific HDAC inhibition while displaying potent efficacy and reduced systemic toxicity. These findings reveal an HDAC-dependent DDR vulnerability and offer combinational and precision targeting strategies to facilitate clinical translation and improve PDAC patient outcomes.

Large cities lose their growth advantage as countries urbanize

The share of the world population living in cities with more than one million people rose from 11% in 1975 to 24% in 2025 (our estimates). Will this trend toward greater concentration in large cities continue or level off? We introduce two new city population datasets that use consistent city definitions across countries and over time. The first covers the world between 1975 and 2025, using satellite imagery. The second covers the United States between 1850 and 2020, using census microdata. We find that urban growth follows a characteristic life cycle. In the early stages of a country’s urbanization process, large cities grow faster than smaller ones. At later stages, growth rates equalize across sizes. We use this life cycle to project future population concentration in large cities. Our projections suggest that 38% of the world population will be living in cities with more than one million people by 2100. This estimate is higher than the 33% implied by the well-known theory of proportional growth, but lower than the 42% obtained by extrapolating current trends.

Chemical ecology and convergent evolution of natural hallucinogens: From ecological defense to conserved neural targets

Natural hallucinogenic compounds have arisen independently across plants, fungi, and animals, evolving into a diverse chemical arsenal that includes phenethylamines, indolealkylamines, and terpenoid scaffolds. Beyond clinical and cultural frameworks, their ecological origins and evolutionary trajectories may help explain why such potent modulators of perception, emotion, and cognition persist in nature. Here, integrating chemical ecology, comparative genomics, biosynthetic logic, and evolutionary biology, we propose that these molecules may function as defensive agents or symbiosis-associated manipulators of herbivore and pollinator behavior. A “building-block” biosynthetic logic links primary metabolism to convergent psychotropic scaffolds via a recurrent set of tailoring reactions, including decarboxylations and methylations. Recent advances illuminate mescaline biosynthesis in cacti, horizontal gene transfer of psilocybin clusters in fungi, and symbiont-derived alkaloids in grasses. We also assess the debate surrounding endogenous mammalian tryptamines, arguing that the leading hypothesis points toward sigma-1 receptor-mediated cytoprotection and stress responses, supported by convergent pharmacological and cellular evidence, rather than inherent hallucinogenic functions. Across kingdoms, natural hallucinogens appear to converge on conserved neural targets, including serotonergic and other neuromodulatory systems that are shared across phyla. From this perspective, human psychoactivity is likely an evolutionary by-product of molecules selected for ecological interactions with animals possessing deeply conserved receptor architectures. Framing hallucinogens through chemical ecology not only clarifies their origins but also highlights translational opportunities in target discovery, pathway engineering, and sustainable production, while emphasizing the need to integrate conservation, ethical sourcing, and benefit-sharing into the current hallucinogenic renaissance.