tbuckley/cabot-search huggingface dataset:
Semiconducting Perylene Diimide J‐aggregates Cross‐linked Hydrogel Enables High‐Efficiency Photothermal Controlled Release of Nitric Oxide for Antibiofilm Therapy
Authors: Kangxin Zhang, Bo Wang, Fengwei Sun, Zhen Yang
Journal: Advanced Healthcare Materials (2025)

Antibiofilm treatment, particularly drug-containing wound healing dressings, does not typically penetrate the robust protective extracellular polymeric substance of biofilm and eradicate the bacteria. Here, a rational design of nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6)-based injectable hydrogel, is reported in which the NO release can be triggered by a photothermal effect owing to semiconducting perylene diimide (PDI) J-aggregation fibers. The synthetic PDI derivatives self-assembling into 0D nanoparticles and then aggregating to 1D J fiber is accompanied by absorbance red-shifting from 700 to 790 nm and then to 852 nm. After encapsulating BNN6, a "sandwich roll" (SR) like structure is evenly crosslinked into an injectable hydrogel (SRH) exhibiting a high photothermal convenience efficiency of 72%, which enables the SRH to achieve highly efficient photocontrol NO release. The SRH shows excellent injectability, shape adaptability, and effective antibacterial efficacy over 99% to the E.coli and S. aureus. and remarkable in vivo antibiofilm efficiency of 99.58% by laser irradiation. Furthermore, the synergistic treatment displays the ability to eliminate inflammation, facilitate angiogenesis, and promote collagen deposition, thereby significantly stimulating the healing process of wounds. The semiconducting J-aggregation injectable hydrogel can be a versatile strategy for the treatment of biofilm.
Nano Copper‐chelate Triggers Cuproptosis‐like Death in Fungi and Synergizes with Microneedles for Enhanced Biofilm Removal
Authors: Xing Ge, Shuyue Deng, Lilin Chen, Feng Feng, Tianye Fang, Yu Ding, Hui Jiang, Jun Yang, Xinmei Liu, Jianjun Dai, Lei Yang, Yanmin Ju
Journal: Advanced Healthcare Materials (2025)

Fungal infections pose a significant global public health threat, particularly candidemia and biofilm formation. Current antifungal drugs have limitations due to their toxicity and drug resistance. Ion interference therapy, particularly cuproptosis, shows significant potential for disease treatment. Herein, nano copper-chelate Cu(DDC)2@BSA (CDB) is synthesized for antifungal research and the mechanism of cuproptosis-like death is investigated. Initially, CDB demonstrates a strong inhibitory effect on multiple fungi and exhibits strong antifungal activity against two fluconazole-resistant clinical isolates. The decrease in ATPase activity and mitochondrial membrane potential indicates that the antifungal mechanism may involve mitochondrial dysfunction. Subsequently, transcriptome analysis reveals significant alterations in genes related to copper ions transport and regulation, oxidative phosphorylation, and mitochondrial function. Additionally, copper ions overload is observed, along with an increase in heat shock protein 70 levels and a decrease in lipoic acid synthetase protein expression. Given that biofilms hinder drug penetration, quaternary ammonium chitosan microneedles are employed in combination with CDB to penetrate the biofilm barrier and enhance the antifungal effect. Overall, this study provides new insight into the cuproptosis-like death mechanism in fungi and presents a promising strategy for fungal infection treatment through the combination of nano copper-chelate and microneedle delivery system.
Variation Between Imaging and Non‐Imaging Transcranial Doppler Systems Versus a Phantom Doppler Generated Velocity
Authors: Mustapha Shu’aibu Hikima, Nura Idris, Muhammad Abba Suwaid, Mark Rodeghier, Ibrahim Musa Idris, Khadija Alkali Bulama, Ahmed Usman, Ted Lynch, Michael R. DeBaun
Journal: American Journal of Hematology (2025)

Stroke in children with sickle cell disease (SCD) is associated with significant morbidity and mortality. Transcranial Doppler (TCD) velocities, specifically time-averaged maximum mean velocity (TAMMV), are critical for stroke risk stratification. Variability in TCD velocity measurements across different machines and ultrasonographers complicates clinical decision-making. Using a phantom Doppler flow machine generating a fixed flow, we evaluated four non-imaging and one imaging TCD machine against a reference TAMMV of 191 cm/s. All machines demonstrated high precision but varied accuracy, with mean velocities ranging from 169 to 189 cm/s. All non-imaging machines underestimated the TAMMV (p < 0.001). The imaging TCD machine also underestimated the velocity, even after a standard adjustment of adding 15 cm/s to the velocity (p < 0.001). Based on the results of the local non-imaging TCD machines accuracy, the northern Nigerian pediatricians agreed on the following threshold for primary stroke prevention for all non-imaging TCD machines: two independent ultrasonographers' velocities for any velocity ≥ 180 cm/sec and < 220 cm/sec or one TCD velocity > 200 cm/sec.
Correspondence: “Challenging the Frontier: Bridging Systemic Biomarkers and Small Airway Dynamics in Severe Asthma Management”
Authors: Ourania S. Kotsiou, Paraskevi Kirgou, Dimitra Siachpazidou, Konstantinos Bartziokas, Konstantinos Tourlakopoulos, Foteini Malli, Maria Pinaka, Zoe Daniil, Konstantinos I. Gourgoulianis
Journal: Allergy (2025)
Co‐Delivery of Multiple Toll‐Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy
Authors: Aaron Ramirez, Jenny E. Hernandez‐Davies, Aarti Jain, Lu Wang, Erwin Strahsburger, D. Huw Davies, Szu‐Wen Wang
Journal: Advanced Healthcare Materials (2025)

Most seasonal and pandemic influenza vaccines are derived from inactivated or attenuated virus propagated in chicken eggs, while more advanced delivery technologies, such as the use of recombinant proteins and adjuvants, are under-utilized. In this study, the E2 protein nanoparticle (NP) platform is engineered to synthesize vaccines that simultaneously co-deliver influenza hemagglutinin (H5) antigen, TLR5 agonist flagellin (FliCc), and TLR9 agonist CpG 1826 (CpG) all on one particle (termed H5-FliCc-CpG-E2), with uniform molecular orientation significant for immunomodulation. Antigen-bound NP formulations elicit higher IgG antibody responses and broader homosubtypic cross-reactivity against different H5 variants than unconjugated antigen alone. IgG1/IgG2c skewing is modulated by adjuvant type and NP attachment. Conjugation of flagellin to the NP causes significant IgG1 (Th2) skewing while attachment of CpG yields significant IgG2c (Th1) skewing, and simultaneous conjugation of both flagellin and CpG results in a balanced IgG1/IgG2c (Th2/Th1) response. Animals immunized with E2-based NP vaccines and subsequently challenged with H5N1 influenza show 100% survival, and only animals that receive adjuvanted NP formulations are also protected against morbidity. This investigation highlights that NP-based delivery of antigen and multiple adjuvants can be designed to effectively modulate the strength, breadth toward variants, and bias of an immune response against influenza viruses.
Fluorescence‐Switchable Iron‐Doped Nanodot Assembly as a Robust Redox Dyshomeostasis Amplifier for Noninvasive Treatment of Deep‐Seated Tumors
Authors: Haiyan Xing, Minyu Han, Tao Zhang, Guicheng Zeng, Jie He, Zhigang Xu, Yuejun Kang, Peng Xue
Journal: Advanced Healthcare Materials (2025)

Carbon dots (CDs) have been recognized as promising candidates for cancer diagnosis and therapy, owing to their intrinsic fluorescence properties and facile functionalization pathways. However, such tiny-sized CDs tend to be rapidly excreted by the kidney and/or hepatobiliary system before reaching the tumor site, which may significantly weaken their performance in tumor theranostics. Here, fluorescence switchable iron-doped carbon dot assemblies (FCDDs) are developed with an average size of ≈120 nm for passive tumor targeting. After lesional enrichment, FCDDs can be dissembled into Fe-doped CDs (FCDs) with fluorescence switched on, in response to the upregulated glutathione (GSH) in the tumor microenvironment. The ultrasmall FCDs are able to penetrate into the deep region of solid tumors and generate reactive oxygen species (ROS) through the Fenton reaction. Such ROS accumulation and GSH deprivation caused by FCDDs can effectively trigger the irreversible apoptosis and ferroptosis of tumor cells. Meanwhile, the resultant intracellular redox dyshomeostasis induces prominent immunogenic cell death to prevent metastasis. Tumor-specific fluorescence imaging not only enables cancerous tissue probing but also assists in monitoring the treatment effectiveness. Taken together, this paradigm exemplifies a practical approach to improve the functionality of CDs toward clinical applications and may inspire more facile designs toward upcoming translational medicines.
Response to kratz, plon, and lupo
Authors: Shuai Li, Laura Madanat-Harjuoja, Timothy R Rebbeck, Lisa R Diller
Journal: JNCI Journal of the National Cancer Institute (2025)

Journal Article Accepted manuscript Response to Kratz, Plon, and Lupo Get access Shuai Li, PhD, Shuai Li, PhD Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, 3010, AustraliaPrecision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, 3168, Victoria, AustraliaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Laura Madanat-Harjuoja, MD, PhD, Laura Madanat-Harjuoja, MD, PhD Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, 00029, FinlandFinnish Cancer Registry, Helsinki, 00130, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy R Rebbeck, PhD, Timothy R Rebbeck, PhD Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USADana-Farber Cancer Institute, Boston, 02115, MA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Lisa R Diller, MD, PhD, Lisa R Diller, MD, PhD Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, 02115, MA, USADepartment of Pediatrics, Harvard Medical School, Boston, 02115, MA, USA Corresponding Authors: Lisa R. Diller, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, Tel: 617-632-5642, Email: [email protected]. Search for other works by this author on: Oxford Academic PubMed Google Scholar On Behalf Of The Consortium Of Investigators Of Modifiers Of BRCA1/2 (CIMBA) On Behalf Of The Consortium Of Investigators Of Modifiers Of BRCA1/2 (CIMBA) Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, djaf028, https://doi.org/10.1093/jnci/djaf028 Published: 11 February 2025 Article history Received: 16 January 2025 Accepted: 18 January 2025 Published: 11 February 2025
Emerging mechanisms and therapeutics in inflammatory muscle diseases
Authors: Sven Wischnewski, Hans-Werner Rausch, Chiseko Ikenaga, Jan Leipe, Thomas E Lloyd, Lucas Schirmer
Journal: Trends in Pharmacological Sciences (2025)

Idiopathic inflammatory myopathies (IIMs), or myositis, are rare diseases marked by immune-driven muscle damage and complications like skin lesions and interstitial lung disease (ILD). Despite advances, challenges in diagnosis and treatment persist, particularly in inclusion body myositis (IBM), where no effective therapy exists. Recent breakthroughs, including transcriptomics and insights into antibody-mediated immunity and interferon (IFN) signaling, have clarified IIM pathophysiology and spurred the development of new therapies, such as chimeric antigen receptor (CAR) T cells and Janus kinase (JAK) inhibitors. We explore the latest findings on the mechanisms underlying adult-onset IIMs, emphasizing IBM pathobiology and its unique immune and degenerative pathways, such as a selective type 2 myofiber damage and severe cell stress. Finally, we highlight the recent advances in transcriptomics, single-cell analysis, and machine learning in transforming IIM research by improving diagnostic accuracy, uncovering therapeutic targets, and supporting the development of personalized treatment strategies.
Therapeutic Targeting of the Activin Receptor Signaling Pathway: Proof of Concept in Myeloid Neoplasms
Authors: Ayalew Tefferi, Naseema Gangat
Journal: American Journal of Hematology (2025)

Both authors are listed as co-investigators in a multicenter clinical trial involving DISC 0974 for the treatment of anemia associated with myelofibrosis or myelodysplastic syndromes (Disc Medicine Inc.; NCT05320198). The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Effect of high flow nasal cannula oxygenation on incidence of hypoxia during sedated gastrointestinal endoscopy in patients with obesity: multicentre randomised controlled trial
Authors: Leilei Wang, Yuanyuan Zhang, Dan Han, Mengyun Wei, Jie Zhang, Xiangyang Cheng, Yizhe Zhang, Muyan Shi, Zijian Song, Xiangrui Wang, Xiaoqing Zhang, Diansan Su
Journal: BMJ (2025)

Abstract Objective To determine whether high flow nasal cannula (HFNC) oxygenation can reduce the incidence of hypoxia during sedated gastrointestinal endoscopy in patients with obesity. Design Multicentre, randomised, parallel group trial. Setting Three tertiary hospitals in Shanghai, China. Participants 1000 adult patients with obesity (body mass index ≥28) who were scheduled for gastrointestinal endoscopy. Interventions Participants were randomly allocated to receive regular nasal cannula oxygenation or HFNC oxygenation during a sedated procedure with propofol and low dose sufentanil. Main outcome measures The primary outcome was the incidence of hypoxia (75%≤SpO 2 &lt;90% for &lt;60 s) during the procedure. Secondary outcomes included the incidences of subclinical respiratory depression (90%≤SpO 2 &lt;95% for any duration) and severe hypoxia (SpO 2 &lt;75% for any duration or 75%≤SPO 2 &lt;90% for &gt;60 s) during the procedure. Results From 6 May 2021 to 26 May 2023, 984 patients (mean age 49.2 years; 36.9% (n=363) female) completed the study and were analysed. Compared with regular nasal cannula oxygenation, HFNC oxygenation reduced the incidence of hypoxia from 21.2% (103/487) to 2.0% (10/497) (difference −19.14, 95% confidence interval −23.09 to −15.36; P&lt;0.001), subclinical respiratory depression from 36.3% (177/487) to 5.6% (28/497) (difference −30.71, −35.40 to −25.92; P&lt;0.001), and severe hypoxia from 4.1% (20/487) to 0% (0/497) (difference −4.11%, −6.26 to −2.48; P&lt;0.001). Other sedation related adverse events did not differ between the two groups. Conclusions In patients with obesity, oxygenation via HFNC during sedated gastrointestinal endoscopy significantly reduced the incidences of hypoxia, subclinical respiratory depression, and severe hypoxia without increasing other adverse events. Trial registration ClinicalTrials.gov NCT04500392 .
Potential Clinical and Economic Impacts of Cutbacks in the President’s Emergency Plan for AIDS Relief Program in South Africa
Authors: Aditya R. Gandhi, Linda-Gail Bekker, A. David Paltiel, Emily P. Hyle, Andrea L. Ciaranello, Yogan Pillay, Kenneth A. Freedberg, Anne M. Neilan
Journal: Annals of Internal Medicine (2025)

Future U.S. congressional funding for the President's Emergency Plan for AIDS Relief (PEPFAR) program is uncertain. To evaluate the clinical and economic impacts of abruptly scaling back PEPFAR funding ($460 million) from South Africa's total HIV budget ($2.56 billion) in 2024. Model-based analysis of 100%, 50%, and 0% PEPFAR funding with proportional decreases in HIV diagnosis rates (26.0, 24.3, 22.6 per 100 person-years [PY]), 1-year treatment engagement (people with HIV [PWH] receiving/initiating antiretroviral therapy: 92.2%/80.4%, 87.1%/76.0%, 82.0%/71.5%), and primary prevention (4.0%, 2.2%, 0.5% reduction in incidence with no programming [1.24 per 100 PY]). Published HIV care continuum; PEPFAR funding estimates. South African adults (HIV prevalence, 16.2%; incidence, 0.32 per 100 PY). Lifetime. Health care sector. PEPFAR funded 100% (PEPFAR_100%), 50% (PEPFAR_50%), or 0% (PEPFAR_0%). HIV infections, life expectancy, and lifetime costs (2023 U.S. dollars). With current HIV programming (PEPFAR_100%), 1 190 000 new infections are projected over 10 years; life expectancy would be 61.42 years for PWH, with lifetime costs of $11 180 per PWH. Reduced PEPFAR funding (PEPFAR_50% and PEPFAR_0%) would add 286 000 and 565 000 new infections, respectively. PWH would lose 2.02 and 3.71 life-years with nominal lifetime cost reductions of $620 per PWH and $1140 per PWH that would be offset at the population level by more PWH requiring treatment for infection. Countries with similar HIV prevalence and greater reliance on PEPFAR funding could experience disproportionately higher incremental infections and survival losses. Budget fungibility and exact programmatic implications of reducing PEPFAR funding are unknown. Abrupt PEPFAR cutbacks would have immediate and long-term detrimental effects on epidemiologic and clinical HIV outcomes in South Africa. National Institutes of Health.
The Brain-Penetrant Pan ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases
Authors: Danyyl Ippolitov, Yi-Han Lin, Jeremy Spence, Aleksandra Glogowska, Thatchawan Thanasupawat, Jason Beiko, Marc R. Del Bigio, Xin Xu, Amy Q. Wang, Darian Williams, Raul Calvo, Abhijeet Kapoor, Juan J. Marugan, Mark J. Henderson, Thomas Klonisch, Sabine Hombach-Klonisch
Journal: Cancer Research (2025)

Abstract Brain metastasis occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with trastuzumab and HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in vivo models for HER2+ BCBM has curtailed the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis. Here, we generated and characterized a luminal B HER2+ BCBM cell model (BCBM94) isolated from a patient HER2+ brain metastasis. Repeated hematogenic xenografting of BCBM94 consistently generated BCBM in mice. The clinical receptor tyrosine kinase inhibitor (RTKi) lapatinib blocked phosphorylation of all ErbB receptors (ErbB1-4) and induced the intrinsic apoptosis pathway in BCBM94. Neuregulin-1 (NRG1), an ErbB3/ErbB4 ligand that is abundantly expressed in the brain, abrogated lapatinib-induced apoptosis in HER2+ BCBM94 and BT474 models. ErbB3 signaling pathways that involved PI3K-AKT and the phosphorylation of BAD at serine 136 to prevent apoptosis were essential for NRG1-induced survival. High throughput RTKi screening identified the brain-penetrant pan-ErbB inhibitor poziotinib as a highly potent compound that reduced cell viability in HER2+ BCBM in the presence of NRG1. Two weeks of poziotinib treatment successfully ablated BCBM94 and BT474 HER2+ brain tumors in vivo. In conclusion, this study established a patient-derived HER2+ BCBM model and identified poziotinib as highly efficacious RTKi with excellent brain penetrability that eliminated HER2+ BCBM.
PIEZO1-Mediated Calcium Signaling and Podocyte Injury in Diabetic Kidney Disease
Authors: Weiwei Li, Zongwei Zhang, Zhuan Peng, Hongtu Hu, Xiaofei Cui, Zijing Zhu, Yue Qi, Wenjie Chen, Hongyan Liu, Wei Liang, Guohua Ding, Zhaowei Chen
Journal: Journal of the American Society of Nephrology (2025)

Background: Diabetic kidney disease (DKD) is characterized by progressive injury to glomerular podocytes due to sustained mechanical stress within the glomerulus. Piezo proteins, acting as cellular mechanosensors, play a pivotal role in mechanotransduction by sensing mechanical forces and regulating intracellular ion flux. This study investigates the role of Piezo1 in the progression of DKD and its mechanistic involvement in podocyte injury. Methods: Podocyte-specific Piezo1 knockout mice were generated using the streptozotocin plus high-fat diet model of DKD. In vitro studies included the use of Piezo1 inhibitors to assess calcium influx, podocyte cytoskeletal rearrangement, and apoptosis under stiff matrix conditions. Additionally, nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and transient receptor potential cation channel 6 (TRPC6) signaling pathways were explored to establish their role in Piezo1-mediated podocyte injury. Adeno-associated virus -TRPC6 was utilized to overexpress TRPC6 in podocyte-specific Piezo1 knockout mice to assess the in vivo interaction between Piezo1 and TRPC6. Results: Podocyte-specific deletion of Piezo1 significantly ameliorated the progression of DKD in diabetic mice. Inhibition of Piezo1 reduced calcium influx, cytoskeletal rearrangement, and podocyte apoptosis in vitro . Mechanistically, Piezo1 activation triggered a signaling loop involving NFATc1 and TRPC6, leading to increased calcium influx, perpetuating podocyte injury. TRPC6 overexpression in vivo counteracted the protective effects of Piezo1 deletion, confirming the critical role of the Piezo1/NFATc1/TRPC6 axis in DKD progression. Conclusions: Piezo1 plays a key mechanosensory role in podocyte injury during DKD progression by mediating calcium influx and activating the NFATc1/TRPC6 signaling pathway.
Long-Term Physical Exercise for Preventing CKD in Older Adults
Authors: Stein I. Hallan, Marius A. Øvrehus, Michael G. Shlipak, O. Alison Potok, Solfrid Romundstad, Nils P. Aspvik, Ulrik Wisløff, Joachim H. Ix, Dorthe Stensvold, Knut A. Langlo
Journal: Journal of the American Society of Nephrology (2025)

Background: Chronic kidney disease (CKD) is a growing global public health issue. Physical exercise mitigates several kidney-related pathophysiological pathways, yet its impact on kidney function remains underexplored. We investigated the dose-response effect of physical exercise on kidney function preservation in older adults. Methods: Post-hoc analysis of the Generation 100 Study, a 5-year open-label, randomized, parallel-arm clinical trial conducted from 2012 to 2018 in Trondheim, Norway. All inhabitants aged 70-77 years were invited (n=6,966). Main exclusion criteria were dementia; severe, uncontrolled cardiovascular disease or hypertension; or conditions precluding exercise. The control group (n=385) received information on national physical activity recommendations. Intervention groups underwent supervised moderate-intensity continuous training (70% of peak heart rate) for 50 minutes (n=380) twice weekly for five years or high-intensity interval training (90% of peak heart rate) for 4 minutes x4 (n=391) twice weekly for five years. The primary outcome was cystatin C-based rapid eGFR decline (&gt;5mL/min/1.73m 2 per year). Results: A total of 1,156 participants were randomized with median (interquartile range) age 72 (3) years and eGFR 95 (20) mL/min/1.73 m 2 . Oxygen uptake increased by 1.8, 2.3, and 3.3 mL/kg/min in the control, moderate-intensity, and high-intensity groups. Rapid eGFR decline occurred in 117 (30%), 108 (28%), and 92 (23%) participants, respectively. Compared to controls, relative risk (RR) was 0.93 (0.75-1.16) for moderate-intensity and 0.75 (95% CI 0.59-0.95) for high-intensity, demonstrating a significant dose-response relationship (P for trend 0.02). In observational analyses, participants with decreasing moderate-vigorous activity (&gt; -20 minute/week) had RR 1.30 (95% CI 0.93-1.83) for rapid eGFR decline, while those with increasing activity (&gt; +20 minutes/week) had RR 0.73 (0.53-0.99) compared to stable activity after adjusting for baseline age, sex, VO 2peak and eGFR. Conclusions: High-intensity interval training significantly reduced the risk of rapid eGFR decline in older adults.