Browse Articles

Elastase and myeloperoxidase participate in neutrophil extracellular trap release stimulated by SARS-CoV-2

Abstract COVID-19 is a disease triggered by SARS-CoV-2 and some individuals develop a severe form that can progress to multiple organ failure. Neutrophils have been described as responsible for the release of neutrophil extracellular traps (NETs). The role of the elastase and myeloperoxidase (MPO) in NET release by neutrophils stimulated by SARS-CoV-2 infection was not addressed, and it was the aim of the present study. The NET release by human neutrophils infected with SARS-CoV-2 depends on elastase/MPO migration to the nucleus. Moreover, elastase/MPO migration is a consequence of PKC and PI3K kinase activation, leading to reactive oxygen species generation by the neutrophil mitochondria and NOX-2. We also reanalyzed the single-cell RNA sequencing data available in a database and demonstrated that neutrophils from bronchoalveolar lavage (BAL) fluid of patients with COVID-19 present increased expression of genes involved in the formation of the NOX2 complex, PKC delta and members of the PI3K family. In summary, the release of NETs by neutrophils in response to SARS-CoV-2 infection depends on the sequential activation of the PKC/PI3K/ROS pathway, inducing elastase/MPO migration to the nucleus triggering the NET formation. Thus, our study demonstrates new insights into the signaling pathways that induce NETs in response to SARS-CoV-2, highlighting new targets for studies and therapies for COVID-19.

Covalent Interfacial Anchoring of 1D‐2D Hybrid Nanofillers to Poly(Vinyl Alcohol) Networks Enables High‐Strength, High‐Stiffness Hydrogel Fibers

ABSTRACT Hydrogels with high strength, stiffness, and toughness under full hydration are essential for load‐transfer applications such as artificial tendons, ligaments, and soft robotics. Yet achieving such performance remains difficult because conventional polymer networks are intrinsically soft and transfer stress inefficiently. Here, a covalent interfacial anchoring (CIA) strategy is introduced to enable high‐strength, high‐stiffness hydrogel microfibers under full hydration by chemically anchoring carbon nanotubes (CNTs) and graphene oxide (GO) within poly(vinyl alcohol) networks. In this network, CNTs contribute to axial load transfer, whereas GO forms glutaraldehyde‐mediated PVA–GO acetal linkages that suppress nanofiller mobility during deformation and promote efficient stress transfer. The resulting hydrogel fibers achieve tensile strength of 132 MPa, modulus of 1.1 GPa and toughness of 25 MJ m −3 under full hydration and maintain ∼88% displacement after 100 tendon‐mimetic loading cycles. These findings highlight covalent interfacial anchoring as an effective strategy for engineering strong and stiff hydrogel fibers for tendon‐like load‐transfer applications.

Mathematical modelling of plasmodium vivax control strategies in the high endemic Chittagong district of Bangladesh

Isotype-specific antibody secreting plasma cells harbor epigenetic and transcription factor architectures defining distinct cell lineages

Abstract Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense. Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype-specific gene regulation are largely unaddressed. Here, we performed an integrated multiomics analysis (RNA sequencing, ATAC-seq [assay for transposase-accessible chromatin using sequencing], DNA methylation) on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection. Although conclusions regarding temporal and spatial specific programs could not be determined, we observed isotype-enriched expression patterns mapping to TLR signaling, cell cycle, cholesterol metabolism, cell adhesion, and homing. ETS:IRF, NFAT, REL, RUNX, SMAD, and STAT5 binding motifs differentially mapped to isotype-enriched gene expression programs. Additionally, DNA hypomethylation patterns in class-switched ASCs correlate with transcription factor–specific programming. The unique transcriptional and epigenetic programs among the 3 ASC isotypes suggest that each is a distinct lineage that dictates isotype-specific functional characteristics important for humoral immunity.

Lighting up Metal Nanoclusters as Promising Molecular Emitters

ABSTRACT Atomically precise metal nanoclusters (NCs) have emerged as promising optical materials in recent years. At the transition size between metal atoms and plasmonic metal nanoparticles, metal NCs exhibit elusive mechanisms underlying their photoluminescence (PL) properties. This fundamental understanding not only requires establishing a correlation with charge carrier dynamics, but can shed light on the design of metal NCs with desired optical properties. This Review discusses the charge carrier dynamics contributing to PL, including excitation, transition, and relaxation, highlighting the critical roles of the structure and active surface of metal NCs. Additionally, metal NCs can serve as building blocks or precursors to tailor PL properties through intermolecular interactions. Finally, we summarize emergent applications and highlight the challenges and opportunities for photoluminescent metal NCs, hoping that this work will stimulate more research on fundamental understanding and applications.

The microbiological spectrum and clinical course of adolescents and adults with peritonsillar abscesses

Abstract A peritonsillar abscess (PTA) displays a purulent infection arising from acute tonsillitis, involving a variety of aerobic and anaerobic bacteria. Fusobacterium necrophorum , a gram-negative anaerobe, is considered a significant risk factor for complications like Lemierre’s syndrome. This study aimed to analyze the microbiological spectrum of PTA and its impact on the clinical course and outcomes. This retrospective study included all patients diagnosed with PTA at a tertiary care center between January 2018 and June 2023. Data on patient demographics, inflammatory markers, microbiological aspects (including species identification and antibiotic therapy), and clinical management were collected. Overall, 321 patients with a mean age of 34.1 years were included. Most patients (80.1%) underwent tonsillectomy, while others received surgical incision and drainage (18.1%) or no surgical treatment (1.9%). Patients with tonsillectomy had a significantly longer hospital stay compared to those with incision and drainage (5.4 ± 2.5 days vs. 4.4 ± 1.3 days; adjusted p  = 0.004). Surgical complications were more frequent in patients with tonsillectomy (13.6% vs. 1.7%; adjusted p  = 0.048), whereas ipsilateral recurrence was more common in patients with incision and drainage (8.6% vs. 0.0%; adjusted p  = 0.004). Higher CRP levels at admission ( p  = 0.002) were predictive for a higher risk of infection-related complications. Streptococcus pyogenes was the most frequently identified pathogen (25.9%), followed by Streptococci of the anginosus group (15.3%), and Fusobacterium necrophorum (FN; 11.5%), which was significantly more common in adolescents (age < 18 years; 25.3%) than in adult patients (9.5%; adjusted p  = 0.020) and had high antibiotic susceptibility rates with 100% to clindamycin and 96.6% to penicillin or aminopenicillin with beta-lactamase inhibitor, the latter being administered to the majority (87.2%) of patients as empiric antibiotic treatment. This study provides insights into the demographic, clinical, and microbiological characteristics of PTAs. Consistent with previous literature, this study shows a higher frequency of FN in PTAs in adolescents and young adults. However, unlike previous reports, this was not associated with increased complication rates.

CD151 identifies a cytotoxic CD4 T cell population enriched in people with HIV that later develop cancer

Abstract People with HIV (PWH) exhibit persistent immune activation despite effective antiretroviral therapy, contributing to risk of non-AIDS-associated comorbidities such as cancer. Cell populations reflecting immune remodeling trajectories preceding malignancy are poorly characterized. Using peripheral blood mononuclear cells from an adult cohort (25–65 yr), we quantified the tetraspanin CD151 on T cells in people without HIV (PWOH), PWH without documented cancer during follow-up, and PWH who subsequently developed a non-AIDS-defining cancer (PWHc), with samples collected a median of 5 yr prior to cancer diagnosis. In PWOH, CD4+CD151+ T cell frequencies increased with age, consistent with physiologic immune aging. In contrast, elevated CD4+CD151+ frequencies were observed at younger ages in both HIV-positive groups, with the typical age-associated increase attenuated. Notably, frequencies were highest in PWHc. CD151 expression was not associated with increased CD25 or CD69, indicating that expansion was not explained by generalized T cell activation. Instead, CD4+CD151+ T cells were enriched for granzyme B and localized predominantly to CD28− effector memory (CD45RA−CCR7−) compartments, consistent with a cytotoxic CD4+ (cCD4) phenotype. Single-cell RNA sequencing of 1 participant per group identified a cCD4+ transcriptional cluster enriched in the PWHc sample. Here, we report that CD151 identifies a cCD4 T cell lineage that accumulates with age in PWOH but appears prematurely expanded in virally suppressed PWH, particularly in PWHc. These findings support CD151+cCD4 T cell expansion as a feature of altered immune remodeling detectable years before cancer diagnosis, suggesting a potential role in mechanisms linking chronic immune dysregulation to malignancy risk in PWH.

Origin of Suppressed Photovoltage Loss in Organic Solar Cells With Additive Engineering

ABSTRACT Additive engineering has become widely adopted for tuning morphology and photovoltaic behaviors of organic solar cells (OSCs), while the resultant increase in delocalization of charge transfer (CT) excitons is often accompanied by a reduced CT‐state energy of additive‐processed blend films, which impairs photovoltage and restrains further improvements of photovoltaic efficiencies. Here, we achieve mitigation of photovoltage loss ( V loss ) over 30 meV while remaining high charge generation/transport efficiencies in a range of OSCs with A‐D‐A’‐D‐A type acceptors after additive treatment. Combined experimental and molecular dynamics simulation analyses reveal that additive treatments suppress voltage loss primarily by increasing the dielectric constant ( ε r ) in the CT state and reducing energetic disorder. These changes help inhibit back charge transfer from charge‐separated states to CT states, thereby decreasing non‐radiative recombination (Δ V non‐rad ) and improving device open‐circuit voltage. We further establish a universal ε r ‐dependent relationship for voltage loss, showing that both the increase in photovoltage and the reduction in Δ V non‐rad scale linearly with the enhancement of the blend dielectric constant. These findings deepen our insights into the voltage loss in organic solar cells, paving a way for surpassing the current photovoltage limits toward higher‐performance devices.

Hypoxia-related gene signatures and PRMT5 define radiation resistance and prognosis in head and neck squamous cell carcinoma

A latency-aware multispectral image processing framework for real-time band compression and spectral-spatial optimization

Bond Exchange‐Driven Interfacial Relay Redox Enables Ultrahigh‐Rate Zn Batteries With High Iodine Utilization

ABSTRACT Aqueous Zn || iodine batteries are promising for multiple application scenarios but suffer from severe “dead iodine” issues, leading to limited iodine utilization and areal capacity, especially at high rates. Here, we design an interfacial relay redox strategy driven by halogen‐bond exchange to address this challenge. Using electrochemically generated polyiodides (e.g., I 3 − ) from sulfonium iodides on the current collector as redox anchors, our approach enables iodine relay conversion at the electrolyte–electrode interface with uniform polyiodide deposition/dissolution. The formed hydrophobic organic cation‐polyiodide pairs suppress shuttling, while halogen‐bond exchange promotes rapid ion/electron transport and further conversion from I 3 − to I 5 − , effectively eliminating “dead iodine.” Consequently, the Zn || iodine battery demonstrates exceptional rate capability (up to 100 mA cm −2 ), high iodine utilization (51%–80% at 1–40 mA cm −2 ), and long‐term cyclability (> 1,200 cycles at 7.04 mA h cm −2 ), far beyond most of the state‐of‐the‐art systems. A pouch cell validates its practicality. This work establishes a new paradigm for designing static halogen batteries with high energy/power density and extended lifespan, offering broader insights for energy storage systems.

Diagnostic value of [68Ga]Ga-FAPI-46 PET in comparison to [18F]FDG PET in triple-negative breast cancer and potential for theranostic application

Abstract This single-center subgroup analysis of a prospective trial (NCT04571086) at University Hospital Essen investigated tumor uptake and detection rates of [ 68 Ga]Ga-FAPI-46- versus [ 18 F]FDG PET in triple-negative breast cancer (TNBC) patients undergoing initial or follow-up staging. Lesions were recorded across anatomical regions, with detection efficacy, uptake values, tumor-to-liver ratios, and tumor volumes assessed. 22 patients were included (initial- n  = 10, follow-up staging n  = 12). No significant difference in region-based detection rates was observed between [ 18 F]FDG- (93%, 53/57 regions) and [ 68 Ga]Ga-FAPI-46 PET (93%, 53/57 regions) (McNemar p  = 1.0). Three patients (25%) at follow-up staging showed an average tumor SUV mean ≥5 on [ 68 Ga]Ga-FAPI-46 PET; 2/3 showed SUV max >10 in most lesions. Mean tumor volume was higher for [ 68 Ga]Ga-FAPI-46, though not statistically significant at initial- (50.1 ± 120.8 mL vs. 11.9 ± 18.5 mL) and follow-up staging (102.2 ± 122.3 mL vs. 79.0 ± 90.4 mL). [⁶⁸Ga]Ga-FAPI-46 PET demonstrated comparable detection in TNBC; high tumor uptake in a subset, supporting its theranostic potential.

Metal–Phenolic Coatings Enable Universal Design of Spherical Nucleic Acids

ABSTRACT Spherical nucleic acids (SNAs), structures consisting of a nanoparticle core chemically modified with a dense shell of nucleic acids, are central to the fields of structural nanomedicine and colloidal crystal engineering with DNA. However, the synthetic methods used to prepare them often require different oligonucleotide immobilization chemistries for each type of core. Here, a general strategy to construct SNAs using metal–phenolic (MP) coatings is introduced. The polymeric shell formed through coordination bonds between polyphenols and metal ions (e.g., Fe 3+ ) can be used to modify the surfaces of a wide variety of particles, spanning a diverse range of sizes, shapes, compositions, and surface charges (e.g., gold spheres and cubes, silica, polystyrene, and melamine resin). Importantly, these shells, regardless of nanoparticle core, can be conjugated to thiolated DNA via Michael addition chemistry. MP‐SNAs retain many of the hallmark properties of conventional SNAs, including enhanced cellular uptake, and serve as versatile building blocks for the programmable assembly of a diverse library of nanoparticles and microparticles into larger and more sophisticated superstructures.

Access to C─N and N─N Axially Chiral Pyridinones via NHC‐Catalyzed Dynamic Kinetic Resolution of Rotationally Restricted Cyclic Imides

ABSTRACT Atropisomers bearing C─N or N─N axes are an important class of chiral molecules, yet stereoconvergent strategies for accessing these compounds using organocatalytic techniques remain limited. Herein, we report the N‐heterocyclic carbene (NHC)‐catalyzed dynamic kinetic resolution (DKR) of rotationally restricted cyclic imides via (3 + 3) annulation with enals under oxidative conditions for the synthesis of C─N or N─N axially chiral pyridinones. Mechanistic experiments shed light on keto‐enol tautomerism in cyclic imides, which serves as the operative mode of enantiomer interconversion. This transformation furnishes C─N/N─N axially chiral frameworks bearing a remote stereogenic center in high yields with excellent enantioselectivity (up to 99:1 er) and good diastereocontrol. Rotation barrier studies confirm the high configurational stability of the products. Reactions conducted using pre‐formed carbenes provide information on DKR operating in the present case over the competing desymmetrization pathway.

HEGFT-UNet: a hybrid transformer–CNN UNet architecture for thyroid ultrasound image segmentation

Impact of Tumor Genomic Profile on Adjuvant Chemotherapy Efficacy in Resected Pancreatic Adenocarcinoma: Results From the PRODIGE-24/CCTG PA6 Study

PURPOSE Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes. PATIENTS AND METHODS Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)–associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively. RESULTS In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among KRAS- mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; P < .001), while no benefit was observed in KRAS wild-type tumors (interaction test, P int. = 0.010). HRR and BRCA status were not predictive ( P int. = .568 and P int. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups. CONCLUSION Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in KRAS wild-type tumors should be considered hypothesis-generating and warrants further investigation.

Erratum: Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials

Force Reveals Hidden Conformations and Dissociation Pathways in Individual π‐Interacting Dimers

ABSTRACT Harnessing mechanical force to control molecular structure is a central strategy in the design of mechano‐responsive materials. Noncovalent interactions are particularly attractive in this context because of their reversibility and tunable mechanical stability, yet the conformational energy landscapes of such motifs often remain inaccessible to conventional ensemble techniques. Here, we use atomic force microscopy‐based force spectroscopy to probe individual π‐interactions within a perylene diimide dimer. Single‐molecule pulling experiments combined with molecular dynamics simulations reveal two distinct long‐lived conformers with parallel and anti‐parallel perylene diimide orientations that are indistinguishable by ensemble techniques. The parallel conformer exhibits greater mechanical stability and ruptures through a sequential pathway in which the dimer converts to an anti‐parallel arrangement before π–π dissociation. Passive force spectroscopy resolves both conformers in real‐time, validates the force‐induced interconversion pathway predicted by steered molecular dynamics simulations, and quantifies their mechanical resistance and lifetime under constant load. Together, these results show that combining passive force spectroscopy with molecular simulations can reveal hidden conformational states in noncovalent assemblies and map their force‐dependent energy landscape. Our findings provide molecular‐level insight into the mechanics of π–π interactions and highlight single‐molecule force spectroscopy as a powerful approach to uncover hidden structural states in supramolecular systems.

Quaternized Engineered Hydrogels for Subsaturated Moisture‐Driven CO ₂ Capture

ABSTRACT Net zero emissions will require atmospheric carbon dioxide removal to counterbalance unavoidable emissions while sustaining human life. Moisture‐swing direct air capture (DAC) uses humidity for regeneration of a material that absorbs CO 2 , enabling cyclic operation without large thermal swings or vacuum. However, many reported systems require near‐saturated humidification for CO 2 release, narrowing the passive operating window and increasing water management demands. Here, we present passive diurnal moisture‐swing hydrogels (PDMHs) that are regenerated under subsaturated RH conditions, thereby broadening the climatic window for passive CO 2 capture. Specifically, we develop a quaternized poly(2‐(diethylamino)ethyl methacrylate) (PDEAEMA) hydrogel that combines humidity‐responsive quaternary ammonium sites with a phase‐transition temperature (lower critical solution temperature) that governs hydration behavior. Using air containing 400 ppm CO 2 , PDMH achieves a CO 2 uptake of 1.06 mmol g −1 at 40°C and 30% relative humidity (RH). Humidification at 25°C enables regeneration efficiencies of 92% at 90% RH and 79% at 80% RH. Under a two‐step, 24 h diurnal protocol, PDMH shows >90% CO 2 release during desorption and a stable working capacity of 0.97–1.05 mmol g −1 over 40 cycles. Comparative energy analysis shows that PDMH outperforms the other sorbents evaluated in terms of energy efficiency.

Darolutamide Alone and in Combination With Goserelin in Androgen Receptor–Positive Salivary Gland Carcinoma: Results From the Phase II DISCOVARY Trial

PURPOSE Salivary gland carcinoma (SGC), particularly salivary duct carcinoma (SDC), is a rare and aggressive malignancy with no standard systemic treatment. Androgen receptor (AR) expression is frequently detected in SDC, which suggests inhibition of the AR pathway as a therapeutic strategy. We conducted a prospective phase II trial of the efficacy and safety of darolutamide, a second-generation AR signaling inhibitor, as monotherapy or in combination with goserelin, in patients with AR-positive unresectable locally advanced (LA) or recurrent/metastatic (R/M) SGC. METHODS DISCOVARY was a multicenter, single-arm, phase II trial conducted in Japan. Patients with unresectable LA or R/M AR-positive SGC were enrolled into two sequential cohorts, a monotherapy cohort (darolutamide 600 mg orally twice daily) and a combination cohort (darolutamide plus goserelin 3.6 mg subcutaneously once every 28 days). The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life. RESULTS Fifty-seven patients were enrolled (monotherapy, n = 24; combination, n = 33). In the monotherapy cohort, the confirmed ORR was 8.3% (90% CI, 1.5 to 24.0) and the median PFS was 5.7 months. In the combination cohort, ORR was 45.2% (90% CI, 29.7 to 61.3) and the median PFS was 13.1 months. Twelve-month OS rates were 91.3% and 87.0%, respectively. Most adverse events were grade 1 or 2 in severity, with no treatment-related deaths. Quality of life was preserved. No clear association between AR expression level or Ki-67 index and treatment response was evident in exploratory analysis. CONCLUSION Darolutamide demonstrated antitumor activity in AR-positive SGC, with numerically more favorable outcomes with goserelin. Darolutamide plus goserelin may represent a chemotherapy-sparing option in this rare malignancy.