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Circulating epigenetic and epitranscriptomic biomarkers identify EGFR status, predict TKI response and reveal therapeutic vulnerabilities in NSCLC
Safety and Clinical Outcomes of Pooled Donor, Nonengrafting Expanded Progenitor Cells in Single-Unit Cord Blood Transplantation
PURPOSE Cord blood transplantation (CBT) is limited by delayed hematopoietic recovery leading to frequent use of double-unit grafts. This phase II study evaluated the safety of adding dilanubicel, a cryopreserved, cord blood (CB)–derived, non–human leukocyte antigen-matched expanded progenitor cell product generated from pooled donors to single-unit CBT. MATERIALS AND METHODS Between March 2022 and July 2025, we enrolled 28 patients with hematologic malignancies in this single-center phase II trial. The infusion of a matched single CB unit was followed by a target dose of 800 × 10 6 CD34 + cells of dilanubicel. All patients received a myeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine and mycophenolate mofetil. RESULTS The median age was 36 years (range, 10-63). Underlying diagnoses included acute leukemias (n = 25) and other hematologic malignancies (n = 3). All patients engrafted neutrophils (median, 18 days; range, 14-30) and platelets (median, 31 days; range, 26-43). Dilanubicel induced transient myelomonocytic recovery, peaking on day 7 and absent by day 14. An early lymphocyte expansion, derived exclusively from the CB graft, occurred by day 9 and peaked by day 11. No grade 3 to 4 acute or chronic GVHD was observed. At a median follow-up of 1.4 years, 27 patients remain alive and disease-free. When evaluated alongside a contemporaneous institutional cohort receiving standard single- or double-unit CBT, patients treated with dilanubicel demonstrated faster hematopoietic recovery and a markedly lower incidence of severe acute GVHD. CONCLUSION The addition of dilanubicel to single-unit CBT demonstrated a favorable safety profile, with no severe acute or chronic GVHD, and was associated with excellent clinical outcomes. These findings support further investigation of this strategy.
Strain‐Tunable Phonon Coupling and Polarization Optoelectronics in Supersaturation‐Grown Boron Phosphide Nanowires
ABSTRACT Boron phosphide (BP) nanowires represent a rare 1D semiconductor, combining outstanding chemical stability, ultrahigh hardness, and high thermal conductivity. However, their controlled growth and optical functionality remain largely unexplored due to irregular morphologies, toxic precursors, and complex synthesis routes. Here, we develop a supersaturation‐engineered chemical vapor transport (CVT) strategy to synthesize air‐stable, single‐crystalline cubic BP nanowires with tunable diameters. Strain‐engineered Raman spectroscopy reveals pronounced phonon broadening and symmetry‐selective frequency shifts, uncovering strong strain–phonon coupling. The inherent noncentrosymmetry and nanoscale confinement further induce highly anisotropic Raman and polarization‐resolved SHG responses. The BP nanowires show remarkable environmental stability over 12 months and competitive photodetector performance, with a responsivity of 5.2 × 10 4 A/W and detectivity exceeding 6.4 × 10 11 Jones under 595 nm illumination. The device also shows good ambient‐storage stability and flexible‐substrate compatibility. Integration with MoS 2 amplifies polarization discrimination, achieving an anisotropy ratio of 2.87 at 532 nm, surpassing previously reported low‐dimensional systems. This work establishes strain–phonon coupling‐mediated polarization control as a new paradigm for BP‐based optoelectronic and photonic platforms.
Damage evolution and microscopic failure characteristics of dense sandstone at different water contents
Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data
PURPOSE Integrating external control data into clinical trial designs and analyses has the potential to accelerate drug development processes. We reanalyzed the three experimental arms of the Individual Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a randomized phase II platform trial in newly diagnosed O 6 -methylguanine-DNA methyltransferase-unmethylated glioblastoma (ClinicalTrials.gov identifier: NCT02977780 ). To evaluate the validity of using external data sets, we compared treatment effect estimates based on internal INSIGhT control data and matched external control data. METHODS The three experimental arms of INSIGhT (abemaciclib [n = 72], neratinib [n = 80], and CC-115 [n = 12]) did not improve survival compared with internal controls (standard chemoradiation [n = 70]). We derived external control patient-level data from multiple real-world and clinical trial data sets. We applied propensity score matching and Cox proportional hazards models to estimate treatment effects with external controls. Additionally, using this glioblastoma (GBM) data collection, we specified simulation scenarios to evaluate trial designs that integrate external controls. RESULTS After matching to external controls, no survival benefit was observed for patients receiving abemaciclib (hazard ratio [HR], 1.00 [95% CI, 0.75 to 1.34]), neratinib (HR, 0.93 [95% CI, 0.70 to 1.24]), or CC-115 (HR, 0.88 [95% CI, 0.41 to 1.88]). Simulations, together with the INSIGhT data and a collection of GBM data sets, allowed us to examine efficiencies and risks of clinical trial designs that leverage external control data. CONCLUSION The use of carefully matched external controls, to replace or augment the internal controls of INSIGhT, produced treatment effect estimates that were similar to previously published analyses. Single-arm trial designs and hybrid randomized designs incorporating propensity score–matched external control data evaluated treatment effects in the early-phase testing of experimental therapies in newly diagnosed GBM. The validity of this approach and risks of bias depended on the availability of comprehensive and accurate data on all potential confounders, in the absence of unmeasured confounding.
Steering CO <sub>2</sub> Electroreduction to Methane and Deuterated Methane via Hydrogen‐Bond Engineering on Copper–Phenolic Networks
ABSTRACT Electrochemical CO 2 reduction (eCO 2 R) powered by renewable electricity offers a sustainable route for carbon cycling and value‐added chemical synthesis. Among possible products, methane (CH 4 ) is particularly attractive due to its high energy density and direct compatibility with existing natural gas infrastructure. However, it remains challenging to selectively produce CH 4 with conventional copper catalysts. Herein, we developed a copper–phenolic network catalyst featuring atomically dispersed Cu─O 4 sites, where adjacent uncoordinated hydroxyl groups from tannic acid (TA) act as intrinsic hydrogen‐bond donors to stabilize the oxygen‐bound formate intermediate (*OCHO). This hydrogen‐bond‐enabled microenvironment redirects eCO 2 R from the conventional *CO‐mediated pathway toward a formate‐derived route, while simultaneously suppressing the competing hydrogen evolution reaction. As a result, the optimized Cu‐PTA catalyst delivers a high CH 4 Faradaic efficiency of 75.5% with a partial current density of 302.0 mA cm −2 in aqueous electrolyte. Notably, this pathway‐steering strategy is readily applicable to deuterated electrolytes, enabling efficient production of deuterated methane (CD 4 ) with a record‐high Faradaic efficiency of 83.1% and a partial current density of 415.6 mA cm −2 . This work establishes hydrogen‐bond engineering as a general approach for manipulating reaction pathways through local stabilization of oxygen‐bound intermediates toward sustainable synthesis of high‐value chemicals.
Computational insights into the 5-fluorouracil loading efficiency of chitosan-PLGA nanocarrier in water
Abstract The therapeutic application of 5-fluorouracil (5-FU) is limited by its rapid metabolism, systemic toxicity, and drug resistance, which motivates the development of efficient polymer-based nanocarriers. In this study, the non-covalent interactions between 5-FU and a chitosan-conjugated poly(lactic-co-glycolic acid) (CS–PLGA) hybrid nanocarrier were investigated using density functional theory (DFT) at the PBE-D3/6–311 + G** level in an aqueous environment modeled via the Polarizable Continuum Model (PCM). Structural analysis indicates that adsorption of 5-FU induces minor elongations in PLGA carbonyl and ester bonds (up to ~ 0.01 Å), along with slight angular distortions, suggesting weak to moderate hydrogen bonding and electrostatic interactions while preserving the structural integrity of the polymer backbone. Adsorption energies ranging from -0.87 to -1.16 eV suggest energetically favorable adsorption of 5-FU on the CS–PLGA surface. Frontier molecular orbital analysis shows a moderate reduction in the HOMO–LUMO gap upon complex formation (ΔE g ≈ 15–17%), accompanied by an increase in dipole moment, indicating enhanced polarity of the drug–carrier system. UV–Vis simulations reveal bathochromic shifts in the absorption maxima (271–295 nm), reflecting electronic perturbations induced by drug adsorption, consistent with excited-state stabilization through hydrogen bonding and local electrostatic interactions. Charge transfer, ESP, and NBO analyses indicate partial electron redistribution from CS–PLGA to 5-FU, particularly in selected configurations, consistent with non-covalent adsorption. Infrared (IR) spectral shifts further support hydrogen-bond-mediated interactions between functional groups of the drug and polymer. Therefore, the results suggest that CS–PLGA provides a stable and responsive environment for 5-FU adsorption, supporting its potential application as a nanocarrier for controlled drug delivery.
Less Isn't Simple: Insights From Postmastectomy Radiotherapy Deintensification Trials
Interfacial Fluorinated Ion Crowding Enables Reversible Zinc Metal Batteries
ABSTRACT Aqueous zinc metal batteries (AZMBs) are promising candidates for large‐scale energy storage owing to their intrinsic safety. However, their lifespan is severely limited by side reactions such as dendrite growth and hydrogen evolution at the Zn‐electrolyte interface. Conventional single‐electrolyte‐additive approaches are thermodynamically constrained, yielding only insufficient coverage of the inner‐Helmholtz plane (IHP) and poor control of interfacial reactions. Here, we report an interfacial fluorinated‐ion crowding strategy by simultaneously introducing multiple low‐concentration fluorinated additives. Computational and spectroscopic analyses reveal that various‐sized F‐groups densely occupy the IHP, displacing water molecules and homogenizing Zn 2+ flux. This emergent crowding effect, inaccessible to single‐additive strategies, enables unprecedented interfacial regulation. Electrochemical tests demonstrate ultrastable Zn plating/stripping over 1200 h at 5 mA cm −2 and 1800 h at 10 mA cm −2 , more than tenfold longer than the baseline electrolyte. This work establishes interfacial ion crowding as a powerful design principle, rooted in fundamental electrochemistry, offering a pathway toward high‐performance and durable AZMBs.
Distinct conformational dynamics of the type-2 Angiotensin II receptor bound to Angiotensin II and Angiotensin (1–7)
Abstract The Angiotensin II type-2 receptor (AGTR2) is a G protein-coupled receptor (GPCR) that mediates vasodilatory, anti-proliferative, and cardioprotective responses as part of the renin–angiotensin system (RAS). However, the precise structural dynamics underlying its ligand-specific activation remain incompletely understood. In this study, we performed long-timescale molecular dynamics (MD) simulations to investigate how Angiotensin peptides differentially modulate the structural dynamics of AGTR2 in both inactive- and active-like conformations and to elucidate ligand-specific modulation of AGTR2 in the RAS protective arm. Ang II stabilized a ‘Locked Active State’ through compact TM3–TM6 distances, persistent hydrogen bonding (PHE8–LYS215 5.42 ), salt bridges (ARG2-ASP279 6.58 , ARG2-ASP297 7.32 ), hydrophobic contacts (TRP100 2.60 , MET128 3.36 ), and rotameric locking of micro-switches. These interactions stabilized Helix 8, enhancing dynamic network connectivity and supporting ligand-dependent activation-related conformational tendencies rather than a full canonical GPCR activation transition. Conversely, Ang1–7 induced a ‘Flexible Intermediate State’ characterized by weaker interactions (PRO7–THR125 3.33 ), dynamic instability at the Helix 8 interface, and increased conformational sampling. Activation motif analyses (CWxP, PIF, E/DRY, NPxxY), DCC maps, CP, DRIN metrics, and PCA confirmed distinct signaling features for each ligand. This study provides a dual functional profile for AGTR2, where Ang II acts as a strong conformational stabilizer promoting activation-related dynamic features, while Ang 1–7 serves as a dynamic modulator. These findings contribute to a structural and dynamic framework for understanding AGTR2 signaling and supporting its therapeutic potential in fine-tuning cardiovascular responses within the RAS.
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Chelation Drives Surface Substitution in Hybrid‐MXenes
ABSTRACT Hybrid organic–inorganic MXenes ( h ‐MXenes) offer a versatile platform for tailoring the surface chemistry of two‐dimensional transition‐metal carbides and nitrides through covalently bound organic ligands. Although monodentate amido/imido functionalization has been demonstrated previously, chelating ligand binding has remained unexplored. Here, we report the synthesis of Ti 3 C 2 (en) x h ‐MXenes via substitution of Br terminations in Ti 3 C 2 Br 2 with deprotonated ethylenediamine (en). By varying the amount of n‐BuLi used for en deprotonation, the surface coordination evolves from predominantly monodentate to bidentate binding. This transition is evidenced by a contraction of the interlayer spacing and attenuation of the ─NH 2 signal in x‐ray photoelectron spectroscopy. Solid‐state NMR reveals that bidentate coordination dominates when 4 equiv. of n‐BuLi is employed, while inelastic neutron scattering, supported by simulated vibrational spectra, provides independent confirmation of the bidentate binding motif. Density functional theory calculations show that bidentate en is significantly more stable than monodentate configurations for replacing Br terminations. Ab initio molecular dynamics further reveal dynamic surface chemistry involving proton transfer, β‐H elimination, surface imine–Ti bond formation, and partial reversion to monodentate coordination. These findings establish ligand denticity as a new design parameter for engineering MXene surface chemistry and tuning material properties.
π‐Enlargement in Porphyrin Macrocycles at Interfaces
ABSTRACT Porphyrins are essential heteroatomic macrocycles, fundamental to both biological systems and advanced technology. Their unique molecular architecture enables key functions in nature, such as oxygen transport in hemoglobin and light harvesting in chlorophyll, and inspires cutting‐edge applications in chemical sensing, catalysis, renewable energy conversion, and optoelectronics. Consequently, significant efforts are dedicated to develop their solution‐phase chemistry, particularly by strategically modifying the macrocyclic structure to tailor their properties. Inspired by the field of on‐surface covalent synthesis, we introduce a pioneering strategy to tailor porphyrin macrocycles at interfaces, specifically expanding an 18‐π porphyrin into a 20‐π system. Such transformation is achieved by depositing a porphyrin precursor, equipped with two trifluoromethyl (‐CF 3 ) functional groups in a trans configuration, onto a hot Ag(111) surface. By combining scanning probe microscopy and spectroscopy, complemented with density‐functional theory calculations, we confirm the successful formation of the 20‐π free‐base expanded porphyrin, exhibiting potential high antiaromaticity attributed to the preservation of planar conformation at the interface according to theoretical calculations. The transformation occurs through precursor dehalogenation and subsequent insertion of two carbon atoms into the macrocycle, driving its expansion, and affording a narrow bandgap of ∼0.2 eV. Furthermore, we demonstrate its coordinative capabilities toward cobalt, forming a unique two‐fold coordination node within the expanded core. Our findings pave the way for engineering expanded porphyrins at interfaces enabling enhanced antiaromaticity and narrow bandgaps, while affording the design of novel coordination motifs, and, simultaneously, demonstrating the capabilities of surface science in exploring such expanded macrocyclic architectures at the atomic scale.
PureChain web-based energy predictor with federated learning Dirichlet for real-time energy consumption forecasting
Guanylyl Cyclase 2C–Targeted Chimeric Antigen Receptor T-Cell Therapy in Patients With Metastatic Colorectal Cancer
PURPOSE The clinical efficacies of third- or later-line therapies for metastatic colorectal cancer (CRC) are extremely limited. The purpose of this study was to evaluate the safety and efficacy of a chimeric antigen receptor T (CAR T) cell targeting guanylyl cyclase 2C (GUCY2C) that was steadily expressed in all stages of CRC in a phase I study. PATIENTS AND METHODS This was an open-label, single-center, phase I study, consisting of a 3 + 3 pattern dose-escalation phase and a dose-expansion investigation. Tumor tissues were histologically confirmed positive for GUCY2C expression. Four dose levels were tested in the dose-escalation phase, including 3 × 10 8 (DL1), 6 × 10 8 (DL2), 12 × 10 8 (DL3), and 20 × 10 8 (DL4) CAR T cells. The primary end points were safety and tolerability within 28 days after the first infusion. RESULTS In the dose-escalation phase, dose-limiting toxicity was not observed. DL3 was chosen for dose-expansion study. A total of 20 patients with metastatic CRC were infused with GUCY2C CAR T after lymphodepletion, and only one patient (5.0%) showed grade 3 cytokine release syndrome and neurotoxicity. Grade 3 diarrhea occurred in 11 patients (55.0%). Of 19 evaluable patients, the objective response rate (ORR) was 26.3%, with all responding patients in DL3 and DL4 groups. Of 10 patients in the DL3 group, the ORR was 40.0% and the median progression-free survival time (mPFS) was 7.0 months. Among patients showing medium-to-high GUCY2C expression in the DL3 group, the ORR achieved 50.0% and the mPFS was 9.0 months. CONCLUSION GUCY2C CAR T showed acceptable safety profile and high response rate in patients with third- or later-line CRC, and the clinical efficacy was associated with CAR T dose level.
Flexible, Biocompatible Supercapacitors Weaved From Layered Phyllosilicates and Zwitterions via Ionicity
ABSTRACT Phyllosilicates, for example, bentonite clay, are among the most abundant natural minerals, yet their brittleness and poor conductivity have limited their use in energy storage applications, typically requiring harmful solvents and synthetic binders to form functional membranes. Here, we report a polymer‐free, aqueous‐based approach in which betaine, a naturally occurring zwitterion, is intercalated into bentonite clay galleries through ionic interactions between its cationic trimethylammonium group and the negatively charged clay surface. This intercalation bridges the clay galleries, creating ion‐conductive pathways within free‐standing, mechanically robust membranes, as confirmed by molecular dynamics simulations, rheo‐impedance, and electrochemical impedance spectroscopy. Incorporation of transition‐metal ions (Fe 3 + , Mn 2 + ) introduces redox‐active sites that contribute to pseudocapacitive charge storage. The resulting membranes function as both electrodes (113 mAh/g vs. NMC811) and separators in all‐clay supercapacitor devices, delivering an energy density of 158 mWh/cm 3 and a power density of 5688 mW/cm 3 , with ∼75% capacitance retention after 30000 cycles. The devices are biocompatible and can power LEDs up to 2.2 V after brief charging. We show, for the first time, that zwitterions and clay provide a simple, scalable, and sustainable route to biocompatible, flexible supercapacitors for low‐power applications requiring mechanical flexibility and material sustainability.
A geospatial machine-learning framework for regional electrification estimation mapping and trend analysis using demographic and infrastructure features
Abstract Many rural communities in Ethiopia’s Amhara region lack electricity access despite substantial urban-rural disparities. Traditional surveys are costly and inconsistent, while Nighttime Light (NTL)-population threshold methods suffer from arbitrary thresholds, off-grid detection failures, and light-access conflation. This study develops a geospatial machine learning framework using Visible Infrared Imaging Radiometer Suite—Day/Night Band (VIIRS-DNB) nighttime lights, population density, and distances to grid lines and roads. Random Forest (RF) outperforms Support Vector Machine (SVM) and Decision Tree (DT), achieving 86.8% overall accuracy and a 71.3% Kappa coefficient for operational mapping of electrification status and estimation of regional electrification rates from 2018 to 2024. Validation against GPS-recorded transformer locations demonstrates that the Random Forest model reconstructs a realistic, corridor-type electrified network and outperforms a calibrated NTL–population threshold approach, which tends to miss grid-connected rural corridors and overestimate urban brightness effects. The resulting maps reveal zone-level disparities and steady growth to 41% electrification by 2024, with population density (27.49% importance) emerging as the leading predictor among balanced variables. This framework supports SDG 7 planning and investment prioritization in underserved areas.