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Solid‐Phase Engineered Metal‐Free Carbonized Polymer Dots With Auto‐Generated Rigid Amorphous Network Enabled High‐Temperature Liquid‐Phase Phosphorescence
ABSTRACT While organic phosphorescent materials hold immense promise, their application is severely hampered by limited emission tunability, short lifetimes, and environmental instability. Herein, we report a facile solid‐phase engineering strategy to achieve the large‐scale synthesis of metal‐free carbonized polymer dots (CPDs) from a single precursor. These CPDs feature tunable phosphorescence wavelengths (∼472 to 545 nm) and lifetimes (∼646.49 µs to 65.56 ms), coupled with extraordinary resilience to thermal and moisture stress. Experimental surveys and theoretical calculations reveal that high‐temperature solid‐phase reaction drive the structural evolution of CPDs from amorphous molecules to ordered heptazine structures, enabling the CPDs with progressive singlet‐triplet energy splitting for tunable phosphorescence wavelengths. Concurrently, the auto‐generated rigid amorphous network and hydrophobic groups of CPDs synergistically mitigate triplet exciton quenching triggered by dissolved oxygen and thermal deactivation, endowing the tunable high‐temperature liquid‐phase phosphorescence. With the unique optical characteristics, these CPDs show great promise for applications in aqueous‐phase illumination, displays under harsh conditions, and three‐dimensional information encryption. This work paves a new approach to polymeric phosphorescent materials, significantly contributing to the advanced lighting and information technologies.
Total Synthesis of <i>ent</i> ‐Kaurenoic Acid Diterpenoids Enabled by Distal Conformational Control in Photoredox Radical Polyene Cyclization
ABSTRACT We report a divergent synthesis of ent ‐kaurenoic acid‐derived diterpenoids enabled by a stereoselective photoredox radical polyene cyclization directed by distal conformational control. A chiral bicyclo[3.2.1]octane unit biases the reactive polyene conformation and controls stereochemical outcome remotely during cascade cyclization. This substrate‐encoded process enables highly diastereoselective construction of the 6/6/6/5 ent ‐kaurenoic acid framework under visible‐light conditions. A convergent nickel‐catalyzed reductive cross‐electrophile coupling rapidly assembles the cyclization precursor. Late‐stage oxidation‐state and stereochemical editing from a common intermediate provide access to seven structurally distinct diterpenoids, including the first total synthesis of noueinsiancin D.
Dynamic Dual‐Site Relay Catalysis Enables Selective Solar‐Driven CO <sub>2</sub> Reduction Toward Ethanol
ABSTRACT Photocatalytic CO 2 reduction to ethanol (C 2 H 5 OH) offers a sustainable carbon recycling route but is limited by inefficient C−C coupling under visible light irradiation. Here, we report a defect‐engineered WO 3‐x /In SAs (SAs, single atoms) photocatalyst with a dynamic dual‐site relay mechanism, where electron‐rich W−V O (V O , oxygen‐vacancy) and electron‐deficient In single atom sites cooperatively drive selective ethanol synthesis. The W−V O site acts as a persistent *CO supply hub for CO 2 ‐to‐*CO conversion, while In site functions as an ethanol‐selective coupling center for targeted *CO−*CO coupling. This relay enables exceptional ethanol production and high selectivity (97.43% electrons selectivity and 86.35% yield‐based selectivity). Notably, the photocatalyst maintains efficient CO 2 ‐to‐ethanol conversion efficiency under natural sunlight illumination in scaled‐up experiments using a reactor equipped with a 20 × 20 cm 2 plate coated with WO 3‐x /In SAs . Combined in situ spectroscopy and DFT calculations reveal that W−V O orchestrates CO 2 ‐to‐*CO feeding and relays electrons to In SAs , reducing the C−C coupling barrier via asymmetric electron distribution. Electron‐trapping at oxyphilic In stabilizes *CO via O‐lone‐pair donation; subsequent W d‐orbital hybridization anchors *OCCO, dictating ethanol selectivity. Our work provides a design strategy for efficient photogenerated carrier utilization in CO 2 ‐to‐ethanol conversion, with implications for scalable solar fuel synthesis.
MOF‐Derived Hollow CoFe@NC Nanocages for Highly Efficient Degradation of Textile Fibers
ABSTRACT The accelerated accumulation of synthetic textile fibers, particularly 100% polyester (PET), poses a persistent environmental challenge due to their chemical inertness and resistance to degradation. Herein, hollow CoFe@NC nanocages were synthesized through a cyanometalate‐assisted transformation of ZIF‐67 nanocubes followed by reductive calcination, producing metallic CoFe alloy domains confined within an N‐doped graphitic carbon framework. The optimized CoFe@NC‐600 catalyst exhibited a hollow architecture, abundant accessible active sites, and strong metal–carbon interfacial coupling for efficient peroxymonosulfate (PMS) activation. Under visible‐light irradiation, the CoFe@NC‐600/PMS system achieved 99.2% degradation efficiency toward real PET textile substrates, confirmed by gravimetric analysis, total organic carbon (TOC) measurement, and degradation product identification. Beyond conventional semiconductor photocatalysis, this work demonstrates that metallic alloy–carbon interfaces can efficiently utilize visible light through coupled photothermal conversion, interfacial electronic activation and CoFe redox mediation to drive PMS oxidation. X‐ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy (EIS), radical quenching experiments and density functional theory (DFT) calculations reveal that the CoFe/N‐doped carbon interface facilitates PMS adsorption, electron transfer and O─O bond activation, promoting the generation of radical and nonradical reactive species. This study provides new insights into metal–carbon hybrid catalysts for advanced oxidation processes and offers a sustainable approach for the remediation of persistent polymer wastes.
Sulfur‐Modulated Covalent Organic Framework Superstructures With Highly Dense and Fully Accessible Protophilic Sites for High‐Performance All‐Organic Proton Batteries
ABSTRACT Covalent organic frameworks (COFs) have emerged as competitive battery materials by solving the solubility and/or kinetics limitations of small molecules and polymers, while offering structure‐function merits over inorganics. However, a tricky trade‐off remains between active‐site density and accessibility. Here we describe a trade‐off‐breaking design of sulfur‐modulated COF superstructures (TD‐COFS) via synergistic geometric‐electronic structure engineering. Flower‐shaped TD‐COFS is constructed by intermolecular H‐bonding and π‐π stacking self‐assembly of tricarbonyl‐benzothiazole motifs, maximizing exposure of well‐organized multi‐protophilic active sites and π‐electron delocalization routes. Electron‐rich S‐heterocyclic benzothiazole (replacing N‐containing bipyridine, TM‐COFS) increases the electronegativity of TD‐COFS and reduces the redox barrier (S < N), enabling synchronous optimization of molecular charge distribution and electronic bandgap (−0.75/1.82 vs. −0.52/2.47 eV of TM‐COFS). Furthermore, sulfur modulation boosts proton‐transfer redox activity with a low activation energy (0.23 eV), and achieves full accessibility of highly dense protophilic sites in TD‐COFS (99.3% vs. 0.34 eV/84.7% of TM‐COFS), liberating high capacity (356 mAh g −1 ) and cycling stability (70 000 cycles). Besides, the assembled soft‐packed all‐organic proton batteries deliver state‐of‐the‐art capacity (161 mAh g −1 ), energy density (81 Wh kg −1 cell ), and life (3000 cycles). This work broadens the design philosophy of structured‐tailored COFs with highly dense and accessible protophilic sites for better proton batteries.
Upcycling Poly(ethylene terephthalate) Into High‐Efficient Epoxy Toughener: Hyperbranched Oligomer Induced Nano‐Structural Heterogeneities
ABSTRACT The post‐consumer recycling efficacy of poly(ethylene terephthalate) (PET) has attracted considerable attention. Current chemical recycling of PET predominantly targets monomers, specialty chemicals, and functional materials, yet faces hurdles of costly purification/decolorization and limited market capacity. Here, we report an upcycling paradigm to directly transfer waste PET into highly efficient epoxy tougheners. Through a one‐pot process, PET is converted into hyperbranched oligomers (HBO) bearing a compact architecture and abundant terminal hydroxyl groups. This unique structure enables uniform dispersion and covalent integration into the epoxy network during curing, resulting in the formation of chemically seamless and homogeneous rigid nano‐structural heterogeneities. And these nano‐structural heterogeneities act as stress concentrators that activate localized plastic deformation, promote crack deflection and bridging, and induce microcracking, collectively establishing a multi‐scale energy dissipation network, rather than the cavity‐induced shear deformation process characteristic of conventional hyperbranched polymers. Remarkably, merely 0.3 wt.% incorporation enhances impact strength by 98.9% without compromising intrinsic processability, mechanical and thermal stability. Moreover, this method demonstrates strong feedstock versatility and has been validated at the kilogram scale, offering a viable and integrated pathway for high‐value plastic circularity.
Decoding Atypical G‐Quadruplexes and Their Interactome in Liquid Biopsies via Integrated Electroanalytical–Proteomic Technologies
ABSTRACT A multipurpose electroanalytical biotechnology to advance the role of atypical G‐quadruplex (G4) structures as emerging, multifunctional DNA biomarkers is reported. The technology presented enables determination, selective isolation, and in‐depth characterization of G4 motifs from liquid and solid biopsy samples obtained from oncology patients. The strategy relies on magnetic immunocaptors operating in a competitive assay between endogenous G4 targets and a homologous biotinylated G4 sequence labeled with an enzyme conjugate, coupled with amperometric transduction at screen‐printed electrodes. Beyond G4 determination and evaluation of the interaction of G4‐ligands using electroanalytical transduction, the strategy allows efficient G4 capture, facilitating their downstream structural and molecular characterization using complementary omics techniques. The analytical performance is validated in synthetic models and clinically relevant samples from colorectal cancer (CRC) patients, demonstrating the direct detection of G4 structures in plasma from oncology patients without prior nucleic acid extraction. Furthermore, by integrating magnetic immunocapture with PCR and DNA sequencing, and advanced proteomics, we confirm the selective isolation of endogenous G4‐forming DNA regions and show that CRC induces a stage‐dependent remodeling of the plasma G4 protein interactome beyond global G4 level changes, respectively. Notably, we identified a CRC‐associated G4‐binding protein linked to poor survival.
Separation and Valorization of Chlorine From Tail Gas Streams
ABSTRACT The chemical industry generates chlorine‐containing tail gas streams on a million‐ton scale. Following the established linear approach, these streams are neutralized, consuming large quantities of caustic soda (NaOH), thereby producing waste streams of lower value. To overcome this unsustainable linear approach, we developed a circular process to recycle chlorine from tail gas streams. The process is enabled by an ion exchange resin [IEx]Cl that selectively adsorbs chlorine in the presence of other gases, including oxygen, nitrogen, carbon dioxide, and hydrogen, while forming the corresponding trichloride [IEx][Cl 3 ] by halogen bonding. Upon application of heat (80°C) and reduced pressure the adsorbed chlorine is efficiently released, and the ion exchange resin [IEx]Cl is regenerated. Importantly, the adsorbed chlorine can also be directly converted with ethylene or carbon monoxide into the base chemicals 1,2‐dichloroethane or phosgene, respectively. In this way, chlorine from tail gas streams can be recycled and valorized in an integrated process supporting the transformation of the chemical industry toward a more circular economy.
Chemoenzymatic Radiosynthesis of a Gluconate Transporter‐Targeted In Vivo Bacterial Sensor From Clinical [ <sup>18</sup> F]FDG
ABSTRACT Many bacteria, but not mammalian cells, can directly import and metabolize extracellular gluconate via gluconate permease (GntP) and kinase (GntK). We hypothesized that fluorine‐18 labeled gluconic acid ([ 18 F]FGA) could leverage unique bacterial gluconate metabolism for pathogen‐specific PET imaging. Here, we report [ 18 F]FGA as a new PET tracer targeting bacterial gluconate metabolism. The chemoenzymatic radiosynthesis of [ 18 F]FGA was simple, only requiring readily available [ 18 F]FDG and glucose oxidase. [ 18 F]FGA showed broad detection sensitivity across multiple bacterial species, including multidrug‐resistant clinical isolates. Staphylococcus aureus transposon mutant studies showed substantial loss of [ 18 F]FGA uptake in GntP and GntK mutants, supporting high specificity for bacterial gluconate metabolism. [ 18 F]FGA PET selectively highlighted live bacterial infection, with high target‐to‐nontarget ratios in S. aureus (36‐fold) and Escherichia coli (30‐fold) in a murine model of myositis. Unlike [ 18 F]FDG, no appreciable uptake of [ 18 F]FGA was detected at sites of sterile inflammation. In a Klebsiella pneumoniae pneumonia model, [ 18 F]FGA showed significantly higher accumulation in the infected lung (5.2 ± 0.8%IA/cc) than in the uninfected lung (0.1 ± 0.0%IA/cc), further supporting its potential for imaging challenging clinical infections. Taken together, [ 18 F]FGA PET may be a useful tool for pathogen‐targeted imaging in clinical practice.
Hierarchical Surface‐to‐Bulk Architecture for High‐Performance O3‐Type Sodium Cathodes
ABSTRACT O3‐type layered oxide cathodes suffer from surface chemical instability and sluggish Na + transport within the O‐type framework, limitations that are aggravated by humid‐air exposure and fast‐charging operation, leading to severe interfacial degradation and rapid capacity decay. Herein, we propose a mild ethylene‐glycol–assisted treatment that in situ constructs a coherent surface‐to‐bulk architecture within NaNi 1/3 Fe 1/3 Mn 1/3 O 2 (NFM) particles, comprising a nanoscale surface rock‐salt layer, a depth‐dependent Na‐vacancy gradient, and a Na‐deficient bulk. This hierarchical configuration locks the surface chemistry while opening continuous Na + percolation pathways across the surface–bulk junction, thereby flattening radial (de)sodiation heterogeneity and steering a more uniform, highly reversible phase evolution during prolonged cycling. As a result, the modified sample exhibits outstanding fast‐charging performance, delivering 107.6 mAh g −1 at 5C (600 mA g −1 ) with 81.6% capacity retention after 400 cycles. This work highlights gradient interphase coupled with Na‐vacancy engineering as an effective strategy to develop high‐performance layered oxide cathodes for sodium‐ion batteries.
Harnessing Secondary Nucleation–Driven Supramolecular Bundled Fibers for Long‐Range One‐Dimensional Assembly of Semiconductor Nanocrystals
ABSTRACT Achieving long‐range 1D organization of semiconductor nanocrystals without altering their inherent optical properties is highly challenging, yet crucial for their applications. Herein, we report on the secondary‐nucleation‐triggered supramolecular polymerization of an alkyl chain‐tethered tetraphenylethylene derivative ( TPE‐A ) in dodecane, leading to the formation of ultralong, rigid, bundled and straight 1D fibers. Supramolecular polymerization of TPE‐A in dodecane proceeds through a nucleation–elongation mechanism, resulting in non‐emissive 1D nanofibers as the primary kinetic aggregates ( Aggr KP ). The non‐emissive characteristic of Aggr KP suggests that the tetraphenylethylene (TPE) units within Aggr KP are in a “monomer‐like” state. The TPE units and alkyl chains in Aggr KP enable their interaction with free monomers in solution, thereby acting as “seed” for catalyzing secondary nucleation. This process leads to the temporal evolution of highly fluorescent, ultralong, rigid bundled fibers as the stable thermodynamic product ( Aggr TP ). The enhanced fluorescence of Aggr TP is attributed to the aggregation‐induced emission from the TPE during the bundling of the nanofibers. As a result of secondary‐nucleation‐triggered bundling, Aggr TP creates multiple micrometer‐long, straight, parallel, 1D hydrophobic lanes. The potential of the hydrophobic lanes in Aggr TP to serve as a supramolecular template for the long‐range 1D organization of semiconductor nanocrystals without compromising their inherent optical properties is demonstrated.
Introducing Diradicaloid Thiele's Hydrocarbon Derivatives as Ligand in Transition Metal Chemistry
ABSTRACT Thiele's hydrocarbon (TH) derivatives, or p ‐quinodimethanes, are prototypical members of the organic diradicaloid family, predominantly explored in organic and main‐group organometallic chemistry. Herein, we introduce them to transition‐metal coordination by employing N‐doped TH derivatives as ligands. Pyridine‐ and pyrazine‐substituted p ‐quinodimethane ligands were synthesized, enabling the formation of mono‐ and dinuclear rhodium and cyclometalated iridium complexes ( Py∙Rh , Pz∙Rh , Py∙Ir , and Pz∙Ir ). We show the strong effects that simple metalation, and more importantly, orthometalation can have on the photophysical and electrochemical properties, as well as on singlet‐triplet gaps of these diradicaloids. Additionally, the metalated mixed‐valent forms are strongly electrochromic NIR absorbing dyes. Spectro‐electrochemical studies reveal distinct electronic interactions between the diradicaloid backbone and the metal centers, highlighting the potential of N‐doped TH derivatives as versatile redox‐active ligands in transition‐metal chemistry.
Nature’s antivenom: Combinations of conserved rattlesnake serum metalloproteinase inhibitors block the lethal action of viper venoms
Snakebite maims or kills several hundred thousand people each year. For more than a century, treatment has relied on antivenoms derived from animals immunized with whole venoms, but their efficacy, safety, and availability are highly variable, and it is often not well understood which specific venom components must be inhibited to prevent mortality and major morbidities. New therapeutic approaches are needed. Here, we take an evolutionary approach to antivenom design inspired by the longstanding observation that vipers have evolved serum-borne toxin inhibitors that confer resistance to their own venoms. We have investigated the abilities of a family of four rattlesnake metalloproteinase (MP) inhibitors derived from the ancestral serum glycoprotein Fetuin-A (FETUAs) to neutralize the enzymatic, hemorrhagic, and lethal activities of viper venoms. We find that while certain individual FETUA proteins are able to inhibit enzymatic or hemorrhagic activity, they are unable or only partially able to inhibit venom lethality. However, we show that specific combinations of FETUA proteins complement one another’s activities and are sufficient to fully neutralize rattlesnake venom lethality with approximately 10 times greater potency than commercial antivenom. Moreover, we demonstrate that FETUA proteins are well conserved among viper subfamilies and that rattlesnake FETUAs are able to inhibit the MPs and neutralize the lethality of several evolutionarily distant pit viper or true viper venoms. Our results highlight the critical importance of inhibiting MPs in hemorrhagic venoms and the potential general utility of combinations of naturally evolved, recombinant MP inhibitors in the treatment of viper snakebite.
Thermodynamically Driven Multi‐Site Photoswitching in Tetraoxindole Cavitands Controlled by Hydrogen Bonding and Mechanochemistry
ABSTRACT Integration of multiple photoswitches into a single multi‐responsive system is a promising strategy toward achieving high information density, complex logic operations, and large‐amplitude motion. However, such systems typically suffer from poor efficiency. In this study, we present a strategy for efficient multi‐site photoswitching that is based on realizing forward and reverse transformations along thermodynamically favorable pathways. We show that tetra‐ E ‐oxindole‐resorcinarene undergoes effective multi‐site photoswitching to form a tetra‐ Z ‐isomer, which is more stable due to the intramolecular hydrogen‐bonding network. To achieve a reverse transformation, modulation of the relative stability of the isomers is required. Here, deprotonation under mechanochemical conditions effectively swaps stability, enabling effective back transformation to the tetra‐ E ‐isomer. Mechanochemistry is indispensable for this transformation, as swapping the stability of isomers is ineffective in solutions. By DFT calculations, we demonstrate that a network of hydrogen bonds is crucial for the modulation of isomers’ stability and multiplication of energetic effects. Finally, gas‐phase ion mobility mass spectrometry provided a complementary picture, confirming the all‐ E ↔ all‐ Z interconversions and their charge‐dependent direction.
Designing Novel Solar‐Blind Ultraviolet Nonlinear Optical Crystals Based on Local Proton Distribution Complementary Effect
ABSTRACT Dipolar π‐conjugated groups with large polarizability anisotropy and hyperpolarizability are generally regarded as important nonlinear optical (NLO) active building units. However, their strong dipole‐dipole interactions remain a key challenge in designing non‐centrosymmetric structures. To overcome this, we proposed a novel non‐centrosymmetric structure design strategy based on the local proton distribution complementary effect. Importantly, it could induce the groups to form a zigzag ordered arrangement along the direction perpendicular to the π‐conjugated plane, thereby significantly increasing the probability of forming non‐centrosymmetric structures. Based on this strategy, we successfully designed and synthesized two novel solar‐blind ultraviolet non‐centrosymmetric crystals, (C 3 N 2 H 5 )Na 3 (S 2 O 3 ) 2 ·2H 2 O and (C 3 N 2 H 5 )ClO 4 ·(C 3 N 2 H 4 ), with imidazolium/imidazole groups. Both crystals exhibit excellent optical performances, with a large birefringence of 0.158 @ 546 nm in (C 3 N 2 H 5 )ClO 4 ·(C 3 N 2 H 4 ) and a strong NLO effect approximately 2.6 times that of KH 2 PO 4 in (C 3 N 2 H 5 )Na 3 (S 2 O 3 ) 2 ·2H 2 O, which mainly result from the intrinsic characteristics of imidazolium/imidazole groups and their ordered arrangement. Consequently, this work not only develops two promising solar‐blind UV NLO crystals but also offers a novel structure design strategy that is expected to promote the development of NLO materials.
Accelerating <i>Campylobacter</i> zoonosis in the Anthropocene
Intensive poultry farming has transformed global bird populations, concentrating billions of chickens into dense industrial systems that fundamentally reshape ecological space. As birds are important pathogen reservoirs, these changes can have important consequences for the spread of zoonoses including Campylobacter jejuni —the leading cause of bacterial gastroenteritis. Analyzing 2,747 genomes from chickens and wild birds, we show that poultry intensification has eroded historic host–strain associations and created a new and expanding ecological niche. Phylogenetic reconstructions reveal an estimated 100-fold increase in chicken-to-wild-bird host transitions since 1900 compared to predomestication levels, alongside dramatic post-1960 expansions of chicken-associated lineages and rising pathogen effective population sizes. Model simulations further indicate that expanding, high-density chicken populations could act as ecological “pathogen sponges,” absorbing and amplifying diverse strains while sustaining high prevalence and coinfection rates. Genome-wide association analyses show that strains adapted to the chicken niche frequently acquire genes linked to oxidative stress, metal homeostasis, motility, and antimicrobial resistance. Together, these findings demonstrate that intensive poultry farming is reshaping pathogen ecology and accelerating the evolution and spread of a major zoonotic bacterium, with direct implications for human health.
Global threat exposure of islands in a changing world
Islands are at the forefront of global environmental change. Biological invasions, land-use change, and climate change are driving population declines and causing irreversible losses in island ecosystems. Although global threat exposure maps have been developed in recent years, they are mostly designed for coarse-grained, continental-extent analyses, often overlooking islands. Here, we assessed the cumulative exposure to biological invasion, land-use change, and climate change by 2050, for more than 16,000 islands worldwide using multiple threat markers. Climate change emerged as a ubiquitous threat, being the dominant threat for 65% of all islands, followed by land-use change (22%) and biological invasions (13%). Islands with the highest cumulative exposure were more likely to be isolated, without historical connection with the mainland. Small and low-elevation islands at low latitudes exhibited greater exposure to climate change, whereas larger, high-elevation islands tended to be more exposed to land-use change. Certain countries and subdivisions, such as Seychelles, Bangladesh, China, French Polynesia, and Micronesia, harbored statistically disproportionate numbers of highly exposed islands, highlighting geographic hotspots of cumulative exposure where conservation efforts might be particularly urgent. Our study indicates that by 2050, most islands will be simultaneously exposed to a triple threat arising from the combined impacts of land-use change, climate change, and biological invasions. This study provides robust quantification of island cumulative exposure to three key drivers of biodiversity loss, making a crucial step toward assessing global biodiversity vulnerability.
A wearable patch for continuous levodopa monitoring in sweat: Towards exertion and power-free pharmacodynamic assessment in Parkinson’s disease
Precision management of Parkinson’s disease (PD) requires frequent levodopa (L-dopa) dose adjustments, yet current monitoring relies on subjective symptom reporting and infrequent blood testing. Here, we present a soft, fingertip-mounted wearable platform for continuous, noninvasive L-dopa monitoring. By combining osmotically harvested passive sweat with soft hydrogels, a potentiometric sensing strategy, and individualized calibration, the platform estimates blood L-dopa information from sweat without external power or iontophoresis. Strong correlations between sweat and high-performance liquid chromatography (HPLC)-measured blood L-dopa concentrations were observed in healthy ( P r = 0.85 ) and PD subjects ( P r = 0.88 ) following a single immediate-release L-dopa/carbidopa dose. Low motor symptom scores aligned with peak L-dopa levels, confirming pharmacodynamic relevance. L-dopa cleared faster in PD patients despite similar bioavailability to healthy subjects, while recorded hemodynamic responses showed short hypotensive trends for both groups. Machine learning identified sweat and blood pressure as key contributors toward accurate estimation of blood L-dopa levels (mean absolute error = 2.02 µM vs. ground truth). Overall, our easy-to-use, energy-efficient wearable supports real-time, stimulation-free monitoring, potentially enabling at-home dosage adjustments and paving the way for future autonomous closed-loop L-dopa therapeutic system development.
Energy prioritization and neurometabolic scaling in a social insect brain
Brains are metabolically costly and due to their high energetic demands may receive priority under conditions of reduced energy availability. Such preferential energy allocation to the brain has been described for humans and other mammals, but previous studies have not directly quantified brain metabolic rate or simultaneously considered whole-body metabolism. We recorded brain metabolic rate ex vivo, brain mass, body mass, and whole-body metabolic rate in workers of the ant Tetramorium immigrans and found the proportion of whole-body energy allocated to the brain nearly doubled to 45% when nutritionally stressed. Body metabolic rate was significantly reduced without a comparable decrease in brain metabolic rate. The ability of nutritionally compromised workers to recognize and aggressively respond to a sympatric competitor was not affected, indicating that sensory perception and neural processing necessary for this critical behavior are maintained during energy limitation. Our finding that similar patterns of brain energy prioritization occur across remotely related clades with exceptionally different body sizes, respiratory systems, and brain allometries suggests conservation of ancient neurohormonal mechanisms or functional convergence of processes to protect the brain. Furthermore, although the worker brain was 5% of body mass, brain metabolic rate was 24 to 30% of body metabolic rate under unstressed conditions, remarkably similar to the pattern of humans and other mammals. Brain metabolic rate of T. immigrans was predictable from the scaling of brain metabolic rate in mammals, suggesting ecological, physiological, and evolutionary effects of body size on brain metabolic rate are common.
Biomarker-Stratified Phase II Trial of Trastuzumab Rezetecan in Advanced Salivary Gland Carcinoma Across Cohorts With High and Low Human Epidermal Growth Factor Receptor 2 Expression
PURPOSE Systemic treatment options for advanced salivary gland carcinoma (SGC) are limited, and prospective data for human epidermal growth factor receptor 2 (HER2)–directed therapy remain sparse, particularly in HER2-low disease. We evaluated trastuzumab rezetecan (SHR-A1811), a HER2-directed antibody-drug conjugate, in prospectively defined HER2-high and HER2-low cohorts. PATIENTS AND METHODS In this phase II trial, patients with unresectable locally advanced or recurrent/metastatic SGC were enrolled in separate HER2-high (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) and HER2-low (IHC 1+ or IHC 2+/ISH–) cohorts. Each cohort was independently evaluated using Simon's optimal two-stage design. SHR-A1811 was administered intravenously once every 3 weeks at a recommended starting dose of 4.8 mg/kg. The primary end point was confirmed objective response rate (ORR) per RECIST version 1.1. RESULTS Forty-six patients were enrolled and treated, including 24 in the HER2-high cohort and 22 in the HER2-low cohort. The median follow-up was 21.9 months (95% CI, 16.9 to 26.9) and 11.3 months (95% CI, 6.9 to 15.7), respectively. The confirmed ORR was 91.7% (95% CI, 73.0 to 99.0), including four complete responses, in the HER2-high cohort and 45.5% (95% CI, 24.4 to 67.8) in the HER2-low cohort. Median progression-free survival (PFS) and overall survival (OS) were not reached in the HER2-high cohort. In the HER2-low cohort, the median PFS was 12.7 months and the median OS was 21.3 months. Grade 3 or higher treatment-related adverse events occurred in 41.3% of patients, most commonly neutrophil count decreased (32.6%). Interstitial lung disease occurred in 6.5% of patients, all grade 1. No treatment-related deaths occurred. CONCLUSION SHR-A1811 showed high antitumor activity in HER2-high SGC and promising activity in HER2-low SGC, with a manageable safety profile.