tbuckley/cabot-search huggingface dataset:
The common HAQ STING allele prevents clinical penetrance of COPA syndrome
Authors: Noa Simchoni, Shogo Koide, Maryel Likhite, Yoshihiko Kuchitsu, Senkottuvelan Kadirvel, Christopher S. Law, Brett M. Elicker, Santosh Kurra, Margaret Mei-Kay Wong, Bo Yuan, Alice Grossi, Ronald M. Laxer, Stefano Volpi, Dilan Dissanayake, Tomohiko Taguchi, David B. Beck, Tiphanie P. Vogel, Anthony K. Shum
Journal: The Journal of Experimental Medicine (2025)

COPA syndrome, an autosomal-dominant inborn error of immunity, is nonpenetrant in ∼20% of individuals, with no known mediators of protection. Recent studies implicate STING in the pathogenesis of COPA syndrome. We show that the common HAQ STING allele mediates complete clinical protection. We sequenced 35 individuals with COPA mutations, 26 affected patients and 9 unaffected carriers, finding HAQ STING co-segregation with clinical nonpenetrance. Exome sequencing identified only the mutations comprising HAQ STING as variants shared by unaffected carriers and absent in patients. Experimentally, we found that HAQ STING acts dominantly to dampen COPA-dependent STING signaling. Expressing HAQ STING in patient cells rescued the molecular phenotype of COPA syndrome. Our study is the first report of a common and well-tolerated allele mediating complete clinical protection from a severe genetic disorder. Our findings redefine the diagnostic criteria for COPA syndrome, expose functional differences among STING alleles with broad scientific and clinical implications, and reveal a potential universal gene therapy approach for patients.
Left ventricular dysfunction in potential heart donors after brain death: When is it reversible?
Authors: Brian Wayda, Helen Luikart, Yingjie Weng, Shiqi Zhang, Bruce Nicely, Javier Nieto, John Belcher, Thomas Pearson, Nikole Neidlinger, John Nguyen, Tahnee Groat, Darren Malinoski, Jonathan Zaroff, Kiran K. Khush
Journal: European Journal of Heart Failure (2025)
Targeting WDPF domain of Hsp27 achieves a broad spectrum of antiviral
Authors: Mandi Wu, Wei Li, Houying Leung, Yiran Wang, Qianya Wan, Peiran Chen, Cien Chen, Yichen Li, Xi Yao, Ming‐Liang He
Journal: MedComm (2025)

Abstract Enterovirus A71 (EV‐A71) is a positive‐sense single‐stranded RNA virus, which hijacks host proteins to benefit viral internal ribosome entry site (IRES)‐dependent protein translation and further propagation. We demonstrated that serine 78 (S78) phosphorylation of Hsp27 is critical for Hsp27/hnRNP A1 relocalization upon EV‐A71 infection. Here, we report that the deletion of WDPF and ACD domains disturbs subcellular localization of Hsp27, resulting in partial nuclear translocation. The domain deletion‐induced Hsp27 nuclear translocation fails to direct hnRNP A1 translocation. The 2A pro ‐induced IRES activity and viral replication are suppressed by the deletion of WDPF or ACD domain. Surprisingly, a peptide (WDPF) dramatically inhibits S78 phosphorylation. Therefore, hnRNP A1 translocation, viral IRES activity, and viral protein translation and propagation are all strongly suppressed by the WDPF peptide, but not by peptide without WDPFR sequence (ΔWDPF). Moreover, the WDPF peptide also has potent antiviral activity on other RNA virus (e.g., coronavirus HCoV‐OC43) and DNA virus (e.g., HSV‐1 and HBV). Peptide treatment with kinase inhibitor Sorafenib brings an additional inhibitory effect on HCoV‐OC43 and HSV‐1. Taken together, we uncover a crucial role of WDPF domain in S78 phosphorylation for EV‐A71‐induced hnRNP A1 nuclear translocation, IRES‐dependent viral protein translation, and EV‐A71 propagation. Our results explore a new path for target‐based pan‐antiviral strategy.
An Activatable Long‐Fluorescence‐Lifetime Probe for Exploring the Dual Function of StrH in Biofilm Formation and Necroptosis
Authors: Xiangchuan Meng, Qian Liu, Xiang Wang, Xiaowan Han, Qingyang Zhang, Hai‐Yu Hu
Journal: Advanced Healthcare Materials (2025)

Abstract Streptococcus pneumoniae infections, particularly those associated with biofilm formation, pose significant therapeutic challenges due to their increased resistance to antibiotics and immune evasion. Identifying new biomarkers is crucial for accurate diagnosis and the development of innovative treatment strategies. StrH is recognized as a key enzyme in S. pneumoniae carbohydrate metabolism, however, its specific role in biofilm formation and its interactions with the host remain poorly understood. In this study, a highly sensitive and selective turn‐on long‐lifetime fluorescence probe, “HBT‐PXZ‐St,” is designed to detect StrH activity and to reveal its functions. Using fluorescence lifetime imaging microscopy (FLIM), “HBT‐PXZ‐St” can quantify StrH activity and image live S. pneumoniae cells, achieving a fluorescence lifetime of ≈2 µs, which effectively minimizes background short‐lived fluorescence interference. Additionally, the findings suggest that StrH activity significantly contributes to biofilm development and induces necroptosis in A549 host cells via the receptor‐interacting serine/threonine‐protein kinase 1 (RIPK1) pathway, thereby promoting bacterial colonization and invasion. This study provides insight into StrH's dual role as both a “sword and shield” during colonization and invasion, suggesting its potential as a therapeutic target for novel treatments against S. pneumoniae infections.
Disrupting Biofilms on Human Kidney Stones–A Path Toward Reducing Infectious Complications During Stone Surgery
Authors: Daniel Massana Roquero, Grace H. Holton, T. Jessie Ge, Zachary Kornberg, Kathleen E. Mach, Gabriella Rodriguez, Vinh La, Hubert Lau, Ryan Sun, Timothy C. Chang, Simon Conti, Joseph C. Liao
Journal: Advanced Healthcare Materials (2025)

Kidney stones are a common disorder associated with significant morbidity and often requires surgical intervention. Pathogenic bacteria are found in almost 40% of stones, where they form biofilms that are protected from systemic antibiotic treatments. Stone surgeries disperse biofilms resulting in up to 30% of patients developing postoperative urinary tract infections and 15% developing sepsis. This work is based on the hypothesis that chitosan, an antimicrobial polymer, can eradicate bacterial biofilms present in the stone and potentially serve as an adjunct to irrigation during stone surgery. First, fresh patient-derived kidney stone fragments (n = 56) are collected from stone surgeries. A total of 32% of stones are colonized, predominantly with Enterococcus faecalis, Escherichia coli, and Proteus mirabilis. A short, clinically relevant, chitosan treatment reduces the bacterial burden on colonized stones by over 90% in all specimens tested, regardless of stone composition and bacterial strain. To assess this approach toxicity, ex vivo human ureters and in vivo porcine bladders are exposed to topical chitosan irrigation. No toxic or pathological abnormalities other than urothelial exfoliation are noted. In conclusion, chitosan effectively disrupts kidney stone-associated bacterial biofilms with minimal urothelial toxicity and may provide an effective and safe approach to reducing postoperative complications.
Living Microalgae‐Based Magnetic Microrobots for Calcium Overload and Photodynamic Synergetic Cancer Therapy
Authors: Shuai Jiang, Bo Hao, Xin Song, Yihang Jiang, Junjia Guo, Yuqiong Wang, Qinglong Wang, Xin Wang, Tiantian Xu, Xinyu Wu, Kai Fung Chan, Philip Wai Yan Chiu, Li Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract The combination of Ca 2+ overload and reactive oxygen species (ROS) production for cancer therapy offers a superior solution to the lack of specificity in traditional antitumor strategies. However, current therapeutic platforms for this strategy are primarily based on non‐targeting nanomaterials, leading to undesirable off‐target side effects. Additionally, resistance to ROS and apoptosis induced by the hypoxic tumor microenvironment (TME) further limits therapeutic efficiency. Herein, a magnetic microrobot based on living Spirulina Platensis (SP), which is coated with a double layer of Fe 3 O 4 nanoparticles (NPs) and CaCO 3 NPs. The microrobots can accumulate in tumor regions under magnetic attraction, which produces a high‐Ca 2+ environment under the acidic TME and facilitates Ca 2+ overload under ultrasound (US) stimulation. Meanwhile, sufficient oxygen (O 2 ) production by photosynthesis helps alleviate hypoxia and promotes in situ ROS production by chlorophyll‐mediated photodynamic therapy (PDT), which can coordinate with Ca 2+ overload to induce cell apoptosis. With these unique properties, the SP‐based microrobots offer a promising microrobotics‐based strategy for in situ Ca 2+ accumulation and ROS production, contributing to a precise and effective way for cancer treatment.
Flexible Short Silica Fibers and Tricalcium Phosphate Synergistically Promote Bone Fracture Healing in Composite Cryogel Scaffolds
Authors: Xinyi Wang, Zhengchao Yuan, Guangfang Cai, Yifan Lu, Shasha Zhou, Panpan Shang, Cheng Li, Zewen Wang, Zhenchao Liu, Muhammad Shafiq, Mohamed EL‐Newehy, Meera Moydeen Abdulhameed, Xiao Lu, Yuan Xu, Xiumei Mo
Journal: Advanced Healthcare Materials (2025)

Bone tissue engineering is a critical area of research focused on enhancing the regeneration of bone tissue, particularly in cases of complex defects. Despite inherent self-healing capabilities of bone, irregularly-shaped defects pose significant challenges for complete regeneration, thereby necessitating innovative therapeutic strategies. This study addresses these challenges by exploring the development of advanced tissue regeneration scaffolds. Here, tricalcium phosphate (TCP) is integrated with short silica (SiO2) fibers to develop 3D cryogel scaffolds, designated as SSFx@TCP. These cryogel scaffolds exhibit low density (<2 mg cm- 3), high water absorption (>3500%), and favorable sustained release properties, enabling effective cellular interactions. Notably, the SSFx@TCP cryogels support cell attachment, proliferation, and differentiation, while also regulate gene expression associated with angiogenesis and osteogenesis. Furthermore, in vivo assays demonstrated that these scaffolds can effectively promote de novo bone production in a rat calvarial defect model 8 weeks post-operatively, thereby indicating their potential to mimic the natural extracellular matrix. The successful integration of bioactive components in these cryogels may be beneficial for improved clinical outcomes in bone regeneration therapies and ultimately enhancing patient care in reconstructive surgery.
Cerium‐Containing Mesoporous Bioactive Glass Nanoparticles Reinforced 3D‐Printed Bioceramic Scaffolds toward Enhanced Mechanical, Antioxidant, and Osteogenic Activities for Bone Regeneration
Authors: Zihan Zhao, Xueying Chen, Heming Chen, Jue Zhang, Liting Du, Fei Jiang, Kai Zheng
Journal: Advanced Healthcare Materials (2025)

Abstract The repair of critical‐sized bone defects remains a substantial clinical challenge. While 3D printing of bioceramics has emerged as a promising strategy to address this issue, conventional bioceramics often exhibit limited antioxidant and osteogenic activities. To address these limitations, a novel approach is introduced to enhance 3D‐printed hydroxyapatite (HA) scaffolds by incorporating cerium‐containing mesoporous bioactive glass nanoparticles (Ce‐MBGNs) into the digital light processing. The nanocomposite bioceramic scaffolds are systematically optimized by varying the weight concentrations of Ce‐MBGNs (1, 3, and 5 wt%). The results demonstrate that the incorporation of Ce‐MBGNs significantly enhances the mechanical properties, mineralization, antioxidant capacity, and osteogenic potential of the HA scaffolds when compared to pure HA scaffolds and the HA scaffolds containing Ce‐free MBGNs. In vivo bone repair effects of the optimized HA scaffolds containing 5 wt% Ce‐MBGNs (5Ce‐MBGs) group are further assessed in a rat calvarial critical‐sized defect model. The results indicate that the 5Ce‐MBGs effectively facilitate the repair of critical‐sized bone defects. This study highlights the potential of integrating Ce‐MBGNs with bioceramics in 3D printing to significantly improve scaffold performance. Such an approach holds promise for developing personalized and more effective therapeutic strategies for bone defect repair, particularly in challenging clinical scenarios involving inflammation.
An open‐label, single‐arm, multicenter, phase II trial of bireociclib as monotherapy for heavily pretreated HR‐positive, HER2‐negative advanced breast cancer patients: BRIGHT‐1 trial
Authors: Jiayu Wang, Qingyuan Zhang, Tao Sun, Huiping Li, Ying Cheng, Zhongsheng Tong, Huihui Li, Wei Li, Jingfen Wang, Yuee Teng, Xinhong Wu, Jing Cheng, Zhendong Chen, Zhengqiu Zhu, Li Wang, Mingming Liu, Xianghui Duan, Lingmei Xu, Binghe Xu
Journal: Cancer Communications (2025)

Abstract Background Bireociclib (XZP‐3287) is a novel selective cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor, with a favorable safety profile demonstrated in preclinical and phase I studies. BRIGHT‐1 aimed to further explore the efficacy and safety of bireociclib monotherapy in patients with locally advanced, recurrent or metastatic, hormone receptor‐positive and human epidermal growth factor receptor 2‐negative (HR + /HER2 − ) breast cancer who had progressed on or after prior chemotherapy and endocrine therapy in advanced settings, without previous exposure to CDK4/6 inhibitors. Methods In this open‐label phase II trial, eligible patients received bireociclib 480 mg twice daily (BID) until disease progression or intolerable toxicities. The primary endpoint was the confirmed objective response rate (ORR) assessed by an independent review committee (IRC). The secondary endpoints included progression‐free survival (PFS), investigator‐assessed ORR, disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), overall survival (OS), safety and the pharmacokinetic properties of bireociclib. Results A total of 131 patients were enrolled. At data cutoff (July 31, 2023), the IRC‐assessed ORR was 29.8% (95% confidence interval [CI], 22.1% to 38.4%), with a DCR of 73.3% (95% CI, 64.8% to 80.6%), CBR of 42.0% (95% CI, 33.4% to 50.9%) and a median DoR of 15.2 months (95% CI, 9.5 months to not reached). The median PFS was 11.0 months (95% CI, 7.3 months to 12.9 months) assessed by the IRC, and the median OS was 29.0 months (95% CI, 24.9 months to not reached). The most frequently reported treatment‐emergent adverse events (TEAEs) of any grade were diarrhea (93.1%), neutrophil count decreased (87.0%), white blood cell decreased (86.3%), vomiting (78.6%), anemia (72.5%), and platelet count decreased (72.5%). The grade ≥3 TEAEs occurred in 109 (83.2%) patients. The most common grade ≥3 TEAEs were neutrophil count decreased (43.5%), white blood cell decreased (32.8%), hypokalemia (20.6%), and diarrhea (19.1%). Conclusions Bireociclib monotherapy at 480 mg BID exhibited promising and sustained clinical activity, with no unexpected and acceptable toxicity in patients with recurrent or metastatic HR + /HER2 − breast cancer who had progressed on or after previous therapy. Trial registration Clinicaltrials.gov ID, NCT04539496.
Clinical management and therapeutic optimization of patients with heart failure with reduced ejection fraction and low blood pressure. A clinical consensus statement of the Heart Failure Association (<scp>HFA</scp>) of the <scp>ESC</scp>
Authors: Hadi Skouri, Nicolas Girerd, Luca Monzo, Mark C. Petrie, Michael Böhm, Marianna Adamo, Wilfried Mullens, Gianluigi Savarese, Mehmet Birhan Yilmaz, Offer Amir, Antoni Bayes‐Genis, Biykem Bozkurt, Javed Butler, Ovidiu Chioncel, Alexandre Mebazaa, Jose L. Merino, Brenda Moura, Piotr Ponikowski, Petar Seferovic, Giuseppe M.C. Rosano, Marco Metra
Journal: European Journal of Heart Failure (2025)
Responsiveness of systemic lupus erythematosus subjects to iberdomide based on molecular endotypes
Authors: Prathyusha Bachali, Andrea Daamen, Shimon Korish, Yanhua Hu, Peter Schafer, Amrie Grammer, Peter E Lipsky
Journal: Annals of the Rheumatic Diseases (2025)

Iberdomide is a cereblon E3-ligase modulator that promotes proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) and was shown to be efficacious among subjects with generalised systemic lupus erythematosus (SLE). This study sought to identify baseline gene expression profiles of SLE subjects responsive to iberdomide and analyse the impact of this agent on gene expression. Whole blood samples obtained from 276 female SLE subjects in the phase 2b iberdomide trial (NCT03161483) were assessed by RNA sequencing followed by gene set variation analysis (GSVA) using 32 informative gene modules. Unsupervised K-means clustering categorised subjects according to molecular endotypes at baseline. Each endotype was compared for treatment related gene expression changes. K-means clustering of GSVA scores from whole blood yielded 5 patient subsets (endotypes A-E) with increases in molecular abnormalities indicative of enhanced immune activity. Significant clinical responses to iberdomide, determined using the SLE Responder Index 4, were confined to endotypes C and E. The most important treatment related gene modules in responders in endotype E were Treg cells, B cells, and interferon, whereas unfolded proteins, oxidative phosphorylation and anergic/activated T cells were associated with responsiveness in endotype C. Molecular profiles of SLE subjects identified pharmacodynamic effects of iberdomide that occurred in all endotypes as well as changes in specific gene modules altered in endotypes associated with a significant clinical response. Thus, gene expression-based molecular profiling may be useful to enrich clinical trials for treatment-responsive subjects and also monitor the pharmacodynamic impact of therapy.
Corrigendum to ‘A sandwiched microarray platform for benchtop cell-based high throughput screening’ [Biomaterials Volume 32 Issue 3 (2011) 12500]
Authors: Jinhui Wu, Ian Wheeldon, Yuqi Guo, Tingli Lu, Yanan Du, Ben Wang, Jiankang He, Yiqiao Hu, Ali Khademhosseini
Journal: Biomaterials (2025)
Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis
Authors: Yuxin Zhang, Yuchao Jing, Juan He, Rui Dong, Tongyang Li, Fang Li, Xiaoqing Zheng, Gaoyu Liu, Ran Jia, Jin Xu, Fan Wu, Chunhong Jia, Jin Song, Lijuan Zhang, Pan Zhou, Haitao Wang, Zhi Yao, Qiang Liu, Ying Yu, Jie Zhou
Journal: Immunity (2025)
Outer radial glia promotes white matter regeneration after neonatal brain injury
Authors: Hideo Jinnou, Lauren M Rosko, Satoshi Yamashita, Soichiro Henmi, Jaya Prasad, Van K Lam, Artur Agaronyan, Tsang-Wei Tu, Yuka Imamura, Kazuya Kuboyama, Kazunobu Sawamoto, Kazue Hashimoto-Torii, Nobuyuki Ishibashi, Vittorio Gallo
Journal: Cell Reports Medicine (2025)

The developing gyrencephalic brain contains a large population of neural stem cells in the ventricular zone and outer subventricular zone (OSVZ), the latter populated by outer radial glia (oRG). The role of oRG during postnatal development is not well understood. We show that oRG cells increase proliferative capacity and contribute to oligodendrocyte precursor cell (OPC) production following brain injury in human infants and neonatal piglets, whose brains resemble the human brain in structure and development. RNA sequencing revealed oRG-specific transcriptional responses to injury in piglets and showed that the activating transcription factor 5 (ATF5) pathway positively regulates oRG proliferation. Intranasal activation of ATF5 using salubrinal enhanced OSVZ-derived oligodendrogenesis in the injured periventricular white matter and improved functional recovery. These results reveal a key role for postnatal oRG in brain injury recovery and identify ATF5 as a potential therapeutic target for treating white matter injury in infants.
Differential modification of ascending spinal outputs in acute and chronic pain states
Authors: David A Yarmolinsky, Xiangsunze Zeng, Natalie MacKinnon-Booth, Caitlin A Greene, Chloe Kim, Yu-Ting Cheng, Bruna Lenfers Turnes, Clifford J Woolf
Journal: Neuron (2025)

Pain hypersensitivity arises from the induction of plasticity in peripheral and spinal somatosensory neurons, which modifies nociceptive input to the brain, altering pain perception. We applied longitudinal calcium imaging of spinal dorsal projection neurons to determine whether and how the representation of somatosensory stimuli in the anterolateral tract, the principal pathway transmitting nociceptive signals to the brain, changes between distinct pain states. In healthy mice, we identified stable outputs selective for cooling or warming and a neuronal ensemble activated by noxious thermal and mechanical stimuli. Induction of acute peripheral sensitization by topical capsaicin transiently re-tuned nociceptive output neurons to encode low-intensity stimuli. In contrast, peripheral nerve injury resulted in a persistent suppression of innocuous spinal outputs coupled with persistent activation of a normally silent population of high-threshold neurons. These results demonstrate differential modulation of spinal outputs to the brain during nociceptive and neuropathic pain states.
Bio-Orthogonal-Labeled Exosomes Reveals Specific Distribution in Vivo and Provides Potential Application in ARDS Therapy
Authors: Song Yang, Haomiao Zhu, Hongzhen Jin, Kun Wang, Junna Song, Na Sun, Yonghui Liu, Xiaona Yin, Rui Wang, Xiao Wu, Huadong Liu, Chunling Zhang, Wei Zhao, Fan Yu
Journal: Biomaterials (2025)
Health-related quality of life in patients with HR+/HER2− early breast cancer treated with ribociclib plus a nonsteroidal aromatase inhibitor: results from the NATALEE trial
Authors: Peter A. Fasching, Dennis Slamon, Zbigniew Nowecki, Bozena Kukielka-Budny, Daniil Stroyakovskiy, Denise A. Yardley, Chiun-Sheng Huang, Arlene Chan, Stephen Chia, Miguel Martín, Hope S. Rugo, Sherene Loi, Sara Hurvitz, Michael Untch, Karen Afenjar, Rodrigo Fresco, Andriy Danyliv, Ilia Ferrusi, Zheng Li, Gabriel Hortobagyi
Journal: Clinical Cancer Research (2025)

Abstract Purpose: The phase 3 NATALEE trial reported a statistically significant invasive disease-free survival benefit with ribociclib plus nonsteroidal aromatase inhibitor (NSAI) versus an NSAI alone in stage II/III hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) early breast cancer (EBC). Here we report health-related quality of life (HRQOL) data from NATALEE. Patients and methods: Patients were randomized to receive ribociclib plus NSAI or NSAI alone. Patient-reported outcome scores (EORTC QLQ-C30 global health status and physical, social, and emotional functioning domains; EORTC QLQ-BR23 breast-symptoms scale; health on a visual analog scale of EQ-5D-5L; and the Hospital Anxiety and Depression Scale) were assessed. The prespecified primary HRQOL endpoint was physical functioning. Mean scores and time-categorical and prespecified linear-time repeated-measure models were used to evaluate HRQOL changes during treatment. Results: HRQOL was evaluated in all patients in the ribociclib plus NSAI (n = 2549) and NSAI alone (n = 2552) arms. Compliance was high in both arms (≈93%-97%). Mean scores did not differ meaningfully from baseline for any analyzed domain. Likewise, neither a meaningful change from baseline (in either treatment arm) nor a difference between arms was observed during treatment in the time-categorical, model-adjusted mean scores for any HRQOL domains—using published thresholds for interpreting longitudinal and between-group differences, with all values being within 0.5 SD of their baseline values. Linear-time regression analysis confirmed these findings. Conclusions: These analyses of NATALEE show that adding adjuvant ribociclib to an NSAI does not negatively impact HRQOL in patients with HR+/HER2− EBC.