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461 papers

Designing polymer-peptide conjugates to target dipeptide repeat aggregates implicated in amyotrophic lateral sclerosis.

Gray VP et al. · Jul 8, 2026

Toxic dipeptide repeats such as the aggregating glycine-alanine (GA) n peptide are implicated in the progression of amyotrophic lateral sclerosis (ALS), a lethal neuromuscular disease with an urgent need for new therapeutics. Here, we report polymer-peptide conjugates that prevent aggregation of (GA) 10 . Optical density measurements and transmission electron microscopy demonstrate that conjugates prevent aggregation when co-incubated with (GA) 10 and disperse pre-aggregated (GA) 10 . These results represent an important step toward a new generation of therapeutics for ALS and contribute to a growing body of literature demonstrating the potential of polymer-peptide conjugates as therapeutics.

Medicine

The Newton-X platform for mixed quantum-classical dynamics.

Barbatti M et al. · Jul 8, 2026

Mixed quantum-classical dynamics (MQCD) methods are effective models for excited-state processes in quasi-classical molecular systems, in which nuclear motion is described by classical trajectories while electronic populations undergo quantum nonadiabatic transitions. This article presents Newton-X 26, a new generation of the Newton-X platform that consolidates two decades of development into a modular ecosystem for generating spectra and initial conditions, propagating dynamics, and analyzing, postprocessing, and archiving data. Newton-X 26 supports multiple MQCD strategies, including surface hopping, decoherence-corrected Ehrenfest dynamics, and ab initio multiple spawning, and connects to a range of electronic-structure engines through dedicated interfaces. The platform emphasizes efficient execution for large trajectory ensembles, enabling systematic convergence analyses and uncertainty estimation. Complementary tools support automated data curation, machine-learning-assisted workflows, and reproducible FAIR-oriented reporting and sharing. Taken together, Newton-X 26 provides an open-source environment for routine MQCD applications and continued method development across multiple electronic-structure levels.

Physics and Astronomy

Enzymatic 1,4-addition of 2-hydroxy-3-keto-glucal for β-selective aryl-C-glycosylation of polyphenols.

Kastner K et al. · Jul 7, 2026

3-Ketoglycals are versatile Michael acceptors widely used in chemical C -glycosylation. Here, we report the enzymatic equivalent of this transformation, catalysed by a 3-keto- C -glycoside lyase, enabling selective C -glycosylation of polyphenolic natural products. The reaction proceeds with remarkable chemo- and stereo-selectivity, affording aryl- C -β-glycosides.

Chemistry

CO homologation and isocyanide activation by a trisilyl alane radical anion.

Zhu Y et al. · Jul 7, 2026

We report the divergent reactivities of a trisilyl-substituted alane and its radical anionic species towards isocyanides and carbon monoxide. While the neutral Al(III) species forms coordination complexes, the Al(II) radical promotes cyanide formation. Notably, the radical anion mediates CO homologation to yield a C 3 fragment, which provides new insight into main-group CO homologation.

Chemistry

Synthesis and pyroelectric response of disperse red 1 functionalized silicones: cyclic monomer, homopolymer, and block copolymer derivatives.

Beccard MS et al. · Jul 6, 2026

Pyroelectric materials enable the direct conversion of thermal fluctuations into electrical energy, offering a promising approach to waste heat recovery. While pyroelectric polymers are highly valued for their scalable synthesis, mechanical flexibility, and tunable properties, the field is currently dominated by poly(vinylidene fluoride) (PVDF)-based materials, which present environmental and processing challenges. To develop fluorine-free alternatives and elucidate the influence of molecular architecture on thermal-to-electrical conversion, we synthesized a series of siloxane-based materials functionalized with Disperse Red 1 (DR1) moieties, including a cyclic siloxane monomer, a homopolysiloxane, and a block copolysiloxane. Differential scanning calorimetry confirms the semicrystalline nature of these siloxanes, with glass transitions ( T g ) near room temperature and melting temperatures of about 80 °C. Notably, even unpoled samples exhibit a measurable pyroelectric response at elevated temperatures. The pyroelectric response at low temperatures is significantly enhanced by poling the crystalline domains in an electric field above the melting transitions ( T m ). Among the synthesized materials, the homopolymer exhibited the highest pyroelectric response (0.66 µC m -2 K -1 at 60 °C). While this value is significantly lower than the typical values for PVDF (>20 µC m -2 K -1 ), it should be noted that the processing and poling steps differ substantially. Under similar conditions, the PVDF value was only twice that of the homopolymer. Even more interesting, in an unpoled sample, the homopolymer shows a response similar to that of the poled sample, while PVDF shows almost no response. The superior response for the unpoled sample is attributed to the synergistic effects of DR1 self-ordering and secondary pyroelectricity-the strain-induced changes in dipole density resulting from thermal expansion. These findings provide a framework for designing high-performance, silicone-based pyroelectric transducers through precise structural control.

Materials Science

Bioorthogonal tuning of nanosurface opsonisation via click coupling of a complement fusion protein inhibitor.

Jacques S et al. · Jul 3, 2026

Complement opsonisation contributes to immune clearance of nanopharmaceuticals, but complement activation has some undesirable effects. Herein, we show that tethering the fusion complement receptor 2-complement receptor 1 (CR2-CR1) regulator to cross-linked iron oxide nanoworms via a PEG spacer and copper-free click chemistry overcomes complement opsonisation. Furthermore, CR2-CR1-conjugated nanoworms reduce complement opsonisation of unmodified nanoparticles.

Medicine

Water adsorption on a model silicate surface: wollastonite (100).

Lezuo L et al. · Jul 2, 2026

Water adsorption on silicate surfaces is a critical yet poorly understood process relevant to, e.g. , mineral weathering and cement hydration. This study investigates the structure of water overlayers on a model calcium silicate, the lowest-energy (100) surface of wollastonite (CaSiO 3 ). It combines atomically resolved non-contact atomic force microscopy (nc-AFM), acquired with qPlus sensors and functionalized tips in ultrahigh vacuum (UHV), with density functional theory (DFT) calculations employing the metaGGA r 2 SCAN + rVV10 functional. Adding incremental doses of water to the sample at cryogenic temperatures produces distinct structures governed by the competition between water-surface and water-water interactions. With two water molecules per surface unit cell, water-surface interactions dominate: In line with previous theoretical predictions, adsorbates follow the surface lattice. As the coverage increases, intermolecular hydrogen bonding competes with bonding to the surface, leading to the emergence of complex, coexisting patterns. While their small energy differences prevent an unambiguous identification of the most stable structure by DFT, the experimentally observed symmetries help constrain plausible structural models. Above a critical density of four water molecules per unit cell, water-water interactions prevail, and water clusters are formed. The results provide an atomic-scale framework for understanding water interactions with calcium silicate surfaces.

Earth and Planetary Sciences

Ectonucleotidases CD39 and CD73 expression levels are independent and inverse predictors of survival in muscle-invasive bladder cancer.

Ledderose S et al. · Jul 1, 2026

Bladder cancer is one of the leading causes of cancer-related mortality worldwide. Long-term survival is particularly poor in patients with muscle-invasive bladder cancer (MIBC). Modulation of purinergic signaling through the ectonucleotidases CD39 and CD73 has emerged as a promising therapeutic strategy in cancer medicine. Altered expression patterns of these molecules have been linked to prognosis in various malignancies. In this study, we assessed the value of CD39 and CD73 expression as prognostic markers and potential therapeutic targets in MIBC. CD39 and CD73 expression was determined by immunohistochemistry using tissue microarrays from 180 patients with MIBC. Associations between tumoral and stromal expression and clinicopathological variables, including overall survival (OS), tumor-specific survival (TSS) and disease-free survival (DFS), were analyzed. Tumor cells did not express CD39. High stromal CD39 expression was significantly associated with a lower T category and UICC stage as well as prolonged median OS, TSS, and DFS. High CD73 expression by tumor cells was significantly associated with poorer OS and TSS. Stromal CD73 expression was not significantly correlated with survival outcomes. Our findings indicate distinct and compartment-specific roles for CD39 and CD73 in MIBC. They suggest that high CD73 expression in tumor cells and low CD39 expression in stromal cells are negative prognostic indicators and potential therapeutic targets in MIBC.

Biochemistry, Genetics and Molecular Biology

Polygenic Risk Scores for Incident Dementia in the Multi-Ethnic Study of Atherosclerosis.

Xue D et al. · Jul 1, 2026

Over 75 Alzheimer's disease (AD) and dementia-associated variants have been identified through genome-wide association studies, but the utility of polygenic risk scores (PRS) for predicting AD and dementia in diverse and admixed populations remains unclear. We compared how PRS approaches differing in p-value thresholds, variant weights, and source ancestry perform in predicting dementia in 6338 African American, Chinese, Hispanic, and White individuals from the Multi-Ethnic Study of Atherosclerosis. We tested clumping and thresholding (C+T) methods with varying parameters against Bayesian approaches (PRS-CS, PRS-CSx). We compared the ability of each method to predict incident dementia in all participants and in groups stratified by self-reported race/ethnicity. We additionally analyzed performance across groups stratified by estimated proportion of non-Finnish European (NFE)-like ancestry. Including more variants does not improve performance. We found comparable associations between dementia and PRS when comparing a C+T method with only 15 SNPs and PRS derived from Bayesian models that include > 800,000 SNPs (HR 5e-08 = 1.18, 95% CI: 1.08-1.28; HR CSx = 1.17, 95% CI: 1.07-1.27). The p lowNFE _ 5e-08 = 1.27, 95% CI: 1.08-1.50; HR lowNFE _ CSx = 1.12, 95% CI: 0.94-1.33). More selective PRS models using genome-wide significant SNPs may be preferable for dementia prediction in diverse populations.

Biochemistry, Genetics and Molecular Biology

Initiation of High-Potency Benzodiazepine Prescriptions Among Survivors of Severe Trauma.

Oldner A et al. · Jul 1, 2026

Background Trauma is a major public health concern that often leads to long-term psychological distress and chronic pain. Benzodiazepines (BZDs) are sometimes prescribed for anxiety, insomnia, or acute stress-related symptoms, but long-term use is associated with dependence and adverse outcomes. The extent to which BZDs are initiated after trauma, and their implications for long-term health, remain poorly understood. This study aimed to assess the association between trauma exposure and initiation of high-potency BZDs, identify risk factors within the trauma cohort and examine the association between new BZD use and long-term mortality. Methods We conducted a population-based cohort study using data from a regional trauma registry linked to Swedish national health registers. New initiation of BZD prescriptions was defined as filling at least one prescription within 6 months after trauma. Multivariable logistic regression was used to assess associations between trauma exposure and BZD initiation and to identify risk factors within the trauma cohort. Cox proportional hazards regression evaluated the association between new BZD use and 6-18-month mortality. Results The study included 12,206 BZD-naive trauma patients and 66,801 matched controls. Trauma exposure was independently associated with new high-potency BZD use. Within the trauma cohort, risk factors included older age, psychiatric comorbidity, substance abuse, pre-traumatic opioid or sedative-hypnotic drug use, penetrating trauma, and higher injury severity. New BZD use was associated with markedly elevated 6-18-month mortality (adjusted HR 2.9, 95% CI 2.0-4.2, p Conclusions Trauma exposure independently predicted initiation of high-potency BZDs among previously BZD-naive patients. Psychiatric comorbidity, substance use, and greater injury severity were important risk factors. The association between new BZD use and increased long-term mortality underscores the need for cautious prescribing and structured follow-up after trauma. Editorial comment This study examines initiation of high-potency benzodiazepines among previously naive survivors of severe trauma using linked registry data. It shows that trauma exposure is strongly associated with new benzodiazepine use, particularly in older, comorbid, and vulnerable patients. Initiation is also associated with higher subsequent mortality, likely reflecting underlying clinical and psychosocial risk rather than a causal drug effect.

Psychology