tbuckley/cabot-search huggingface dataset:
Bioeliminable Pt@Bi<sub>2</sub>Se<sub>3</sub>-RGD Nanoassembly for Enhancing Photoacoustic Imaging-Guided Tumor Immuno-Radiotherapy by Inducing Apoptosis via the Areg Pathway
Authors: Huanhuan Tan, Shiyan Fu, Li Shen, Qinyang Lin, Wenrun Li, Yonghong Ran, Yazhen Zhao, Longfei Tan, Yuhui Hao
Journal: Theranostics (2025)

Background: Nanoradiosensitizers containing high Z-group elements have been reported widely as potential candidates for radiotherapy. However, the specific regulatory mechanism is unclear, and biodegradability needs to be addressed urgently. Methods: We synthesized a silk sericin-containing nano assembly, Pt@Bi2Se3-RGD (PBR). PBR's antitumor and bioeliminable effects were demonstrated in 4T1 tumor cells in vitro and in vivo. The immuno-radiotherapy effects of PBR were evaluated using a bilateral tumor model. Results: Combining photoacoustic imaging-guided PBR with radiotherapy improved the efficiency of anti-PD-L1 treatment, eliciting a robust immune response. Importantly, silk sericin-containing PBR could respond to the local intracellular environment in the tumor with acidic pH and overexpressed MMP-9, collapsing into Bi, Se, and scattered Pt nanoparticles (NPs) and finally be cleared from the body. The results also suggested that PBR may act on the Areg/Egfr/Bcl-2 pathway, inducing apoptosis for radiosensitization. Conclusion: The multifunctional, bioeliminable PBR nanoassembly synthesized in this study demonstrated radiosensitization, which, in conjunction with the PD-L1 immune blockade, could suppress primary and distal tumors. Thus, as a sensitizer for synergistic radiotherapy and immunotherapy, PBR could have wide-ranging clinical applications in oncology.
Recent advances in the mechanisms, current treatment status, and application of multifunctional biomaterials for radiation-induced skin injury
Authors: Yang Xu, Quanying Liu, Wenfeng Li, Zhihe Hu, Chunmeng Shi
Journal: Theranostics (2025)

Radiation-induced skin injury (RISI) is a prevalent complication following nuclear accidents and radiotherapy for tumors. The associated side effects may include erythema, desquamation, ulceration, and in severe cases, necrosis of certain skin tissues. These adverse reactions significantly impact the quality of life for patients and contribute to both psychological distress and economic burdens. However, there is currently no standardized protocol for the treatment and management of RISI. In comparison to traditional pharmaceuticals, the utilization of biomaterials in addressing radiation-induced diseases has garnered increasing attention due to their superior biocompatibility and outstanding functionality. Nevertheless, comprehensive reviews on this topic remain scarce. In this context, this paper systematically elucidates the pathogenesis of RISI, subsequently introducing the clinical manifestations and advancements in treatment for RISI. It emphasizes a comprehensive discussion on the design and innovation of novel biomaterials aimed at treating and protecting against RISI, while also illustrating the mechanisms by which multifunctional biomaterials enhance both treatment efficacy and protective measures for radiation-induced skin conditions. Finally, it addresses the challenges encountered by multifunctional biomaterials in managing radiation-related diseases and outlines potential directions for future research efforts. The objective of this review is to investigate the therapeutic and protective effects of multifunctional biomaterials in relation to radiation-induced skin injury, thereby providing significant reference value for the design and clinical application of innovative materials.
Glucose homeostasis controls N-acetyltransferase 10-mediated ac4C modification of HK2 to drive gastric tumorigenesis
Authors: Qiang Wang, Mengmeng Li, Chen Chen, Lei Xu, Yao Fu, Jiawen Xu, Chuanjun Shu, Bo Wang, Zhangding Wang, Changyu Chen, Tao Song, Shouyu Wang
Journal: Theranostics (2025)

Rationale: Abnormal metabolic states contribute to a variety of diseases, including cancer. RNA modifications have diverse biological functions and are implicated in cancer development, including gastric cancer (GC). However, the direct relationship between glucose homeostasis and 4-acetylcytosine (ac4C) modification in GC remains unclear. Methods: The prognostic value of RNA acetyltransferase NAT10 expression was evaluated in a human GC cohort. Additionally, preoperative PET/CT data from GC patients and Micro-PET/CT imaging of mice were employed to assess the relationship between NAT10 and glucose metabolism. The biological role of NAT10 in GC was investigated through various experiments, including GC xenografts, organoids, and a conditional knockout (cKO) mouse model. The underlying mechanisms were examined using dot blotting, immunofluorescence staining, co-immunoprecipitation, and high-throughput sequencing, among other techniques. Results: Glucose deprivation activates the autophagy-lysosome pathway, leading to the degradation of NAT10 by enhancing its interaction with the sequestosome 1 (SQSTM1)/microtubule-associated protein 1 light chain 3 alpha (LC3) complex, ultimately resulting in a reduction of ac4C modification. Furthermore, the levels of ac4C and NAT10 are elevated in GC tissues and correlate with poor prognosis. A strong correlation exists between NAT10 levels and 18F-FDG uptake in GC patients. Furthermore, NAT10 drives glycolytic metabolism and gastric carcinogenesis in vitro and in vivo. Mechanistically, NAT10 stimulates ac4C modification at the intersection of the coding sequence (CDS) and 3' untranslated region (3'UTR) of hexokinase 2 (HK2) mRNA, enhancing its stability and activating the glycolytic pathway, thereby driving gastric tumorigenesis. Conclusion: Our findings highlight the critical crosstalk between glucose homeostasis and the ac4C epitranscriptome in gastric carcinogenesis. This finding offers a potential strategy of targeting NAT10/HK2 axis for the treatment of GC patients, especially those with highly active glucose metabolism.
Nsun2 controls cardiac homeostasis and hypertrophic response by regulating PRKACA expression
Authors: Dongdong Jian, Xiaolei Cheng, Datun Qi, Shixing Wang, Chenqiu Wang, Yingchao Shi, Zhen Li, Shouyi Jin, Zhen Jia, Peng Teng, Zhen Pei, Xiaoping Gu, Liguo Jian, Wengong Wang, Xia Yi, Junyue Xing, Hao Tang
Journal: Theranostics (2025)

Rationale: Internal modifications of mammalian RNA have been suggested to be essential for the maintenance of cardiac homeostasis. However, the role of RNA cytosine methylation (m5C) in the heart remains largely unknown. Methods: Bulk and single cell RNA sequencing data and tissues from the human hearts were exploited for analyzing the expression of RNA m5C modifying proteins. Neonatal rat and adult mouse cardiomyocytes were isolated to assess the impact of Nsun2 on cellular hypertrophic response. Cre/LoxP-mediated gene knockout and recombinant adeno-associated virus serotype 9 (rAAV9) were employed respectively to achieve cardiac-specific interference of the expression of related genes in mice that were subjected to heart stresses from aging, aortic constriction, and angiotensin II stimulation. RNA m5C immunoprecipitation sequencing (m5C-RIP-seq), RNA pull-down, polysome profiling, reporter gene analysis, and IonOptix measurement were conducted to elucidate the involved regulatory mechanisms. Results: Nsun2 expression was significantly elevated in human, rat, and mouse hypertrophic myocardial cells. Knockout of Nsun2 (αMHC-CreERT2, Nsun2 flox+/+) abolished the hypertrophic response of mice to diverse stresses, while accelerating the progression of heart failure. Mechanistically, Nsun2 specifically methylates PKA catalytic subunit alpha (PRKACA) mRNA, which substantially promotes PRKACA translation in a YBX1-dependent manner. Nsun2 ablation markedly attenuated the activation of PKA signaling, as evidenced by the reduced PKA activity and protein phosphorylation levels of PKA substrates, impaired myocyte contraction and relaxation, and disturbed calcium transients. Overexpressing Nsun2 and PRKACA-3'UTR transcripts in the myocardia sensitized and desensitized heart hypertrophic responses, respectively, whereas co-administration of the PKA inhibitor H-89 or overexpressing PRKACA-3'UTR transcript lacking Nsun2 methylating regions failed to produce corresponding responses, reiterating the significance of Nsun2-PRKACA regulation in the cardiac hypertrophic program. Conclusion: These observations reveal the importance of Nsun2-PRKACA regulation in cardiac homeostasis, which provides novel insights into heart function modulation and sheds light on future treatments for hypertrophic remodeling associated heart diseases.
Molecular simulation-aided self-adjuvanting nanoamplifier for cancer photoimmunotherapy
Authors: Junmou Gu, Rongtao Zhu, Ruopeng Liang, Weijie Wang, Jian Li, Senfeng Zhao, Yahui Wu, Jiahui Cao, Shihua Yang, Yuling Sun
Journal: Theranostics (2025)

Background: By leveraging the power of photodynamic therapy (PDT), photosensitizers eliminate cancer cells under specific laser irradiation and trigger systemic immune responses, a potent strategy in tumor immunotherapy. However, the accompanying tumor microenvironment induces immunosuppression, restricting the efficacy of PDT. Methods: Computer-aided screening was used to identify adjuvants, followed by flow cytometry analysis to assess the activation levels of various immune cells in both in vitro and in vivo experiments. Cytotoxicity assays were conducted to evaluate the impact of the nanomaterials on tumor cells. Pharmacokinetic studies were performed to observe the drug concentration in vivo. The efficacy of the nanomaterials was further tested using in situ tumor, metastasis, and organoid models. Results: we first utilized computational simulations and experimental validations to identify Vit K2 as an adjuvant with a high affinity for Toll-like receptor (TLR) agonist ligands; Vit K2 effectively activated antigen-presenting cells, including dendritic cells (DCs) and macrophages, and promoted their maturation through the TLR pathways. The precisely engineered nanoamplifier with on-demand pyropheophorbide a (PPA) release ability could notably kill the primary tumor. Vit K2-activated macrophages and DCs matured, promoting antigen presentation and CD8+ T cell activation. As anticipated, the nanoamplifier exhibited significant anti-tumor effects in primary/distal breast tumors, lung metastatic breast cancer, and patient-derived organoid models. Conclusion: Our research findings demonstrate that the nanoparticles formed by the computer-aided screened adjuvant, Vit K2, and the photosensitizer PPA achieved significant anti-tumor activity and immune microenvironment remodeling.
Loss of SGK1 supports metastatic colonization in hepatocellular carcinoma by promoting resistance to T cell-mediated immunity
Authors: Zefan Zhang, Chenlu Geng, Minfang Song, Hengbin Liang, Kaiqian Zhou, Yang Liu, Jing Wu, Xingxu Huang, Jian Zhou, Jia Fan, David H Peng, Liye Zhang, Yong Cang, Yunfan Sun
Journal: Journal of Hepatology (2025)
The ins and outs of unpacking the black box: Understanding motivation using a multi-level approach
Authors: F Wurm, I J M van der Ham, J Schomaker
Journal: Behavioral and Brain Sciences (2025)

Abstract Although higher-level constructs often fail to explain the mechanisms underlying motivation, we argue that purely mechanistic approaches have limitations. Lower-level neural data help us identify “biologically plausible” mechanisms, while higher-level constructs are critical to formulate measurable behavioral outcomes when constructing computational models. Therefore, we propose that a multi-level, multi-measure approach is required to fully unpack the black box of motivated behavior.
Response to the critiques (and encouragements) on our critique of motivation constructs
Authors: Kou Murayama, Hayley Jach
Journal: Behavioral and Brain Sciences (2025)

Abstract The target article argued that motivation constructs are treated as black boxes and called for work that specifies the mental computational processes underlying motivated behavior. In response to critical commentaries, we clarify our philosophical standpoint, elaborate on the meaning of mental computational processes and why past work was not sufficient, and discuss the opportunities to expand the scope of the framework.
There's no such thing as a free lunch: A computational perspective on the costs of motivation
Authors: Eliana Vassena, Jacqueline Gottlieb
Journal: Behavioral and Brain Sciences (2025)

Abstract Understanding the psychological computations underlying motivation can shed light onto motivational constructs as emergent phenomena. According to Murayama and Jach, reward-learning is a key candidate mechanism. However, there's no such thing as a free lunch: Not only benefits (like reward), but also costs inherent to motivated behaviors (like effort, or uncertainty) are an essential part of the picture.
Definitional devils and detail: On identifying motivation as an animating dynamic
Authors: Rex A Wright, Simona Sciara, Giuseppe Pantaleo
Journal: Behavioral and Brain Sciences (2025)

Abstract Murayama and Jach critically evaluate the idea that motivation is a dynamic that determines behavior and propose alternatively that it might be an emergent property that people construe through perceived regularities in experience and action. The critique has value but fails to appreciate the progress that has been made in moving beyond the idea of which the authors are critical.
Predictive processing: Shedding light on the computational processes underlying motivated behavior
Authors: Lieke L F van Lieshout, Zhaoqi Zhang, Karl J Friston, Harold Bekkering
Journal: Behavioral and Brain Sciences (2025)

Abstract Integrating the predictive processing framework into our understanding of motivation offers promising avenues for theoretical development, while shedding light on the computational processes underlying motivated behavior. Here we decompose expected free energy into intrinsic value (i.e., epistemic affordance) and extrinsic value (i.e., instrumental affordance) to provide insights into how individuals adapt to and interact with their environment.
Connecting theories of personality dynamics and mental computational processes
Authors: Juliette L Ratchford, Eranda Jayawickreme
Journal: Behavioral and Brain Sciences (2025)

Abstract Whole Trait Theory (and other dynamic theories of personality) can illuminate the process by which motivational states become traits. Mental computational processes constitute part of the explanatory mechanisms that drive trait manifestations. Empirical work on Whole Trait Theory may inform future research directions on mental computational processes.
Mental computational processes have always been an integral part of motivation science
Authors: Michael Richter, Guido H E Gendolla
Journal: Behavioral and Brain Sciences (2025)

Abstract Some constructs in motivation science are certainly underdeveloped and some motivation researchers may work with underspecified constructs, as suggested by Murayama and Jach (M&amp;J). However, this is not indicative of a general problem in motivation science. Many motivation theories focus on specific mechanisms underlying motivated behavior and thus have already adopted the computational process perspective that M&amp;J call for.
The role of metacognitive feelings in motivation
Authors: Rolf Reber, Josefine Haugen, Liva J Martinussen
Journal: Behavioral and Brain Sciences (2025)

Abstract Metacognitive feelings are an integral part of mental computational processes and influence the outcome of computations. We review supporting evidence on affect inherent in perceptual processes, fluency in study decisions, metacognitive feelings in aha-experiences and intuition, and affect in early phases of interest development. These findings connect to recent theories that combine metacognitive feelings with computational models.
Adopt process-oriented models (if they're more useful)
Authors: Brendan A Schuetze, Luke D Rutten
Journal: Behavioral and Brain Sciences (2025)

Abstract Though we see the potential for benefits from the development of process-oriented approaches, we argue that it falls prey to many of the same critiques raised about the existing construct level of analysis. The construct-level approach will likely dominate motivation research until we develop computational models that are not only accurate, but also broadly usable.
Motivational constructs: Real, causally powerful, not psychologically constructed
Authors: Andrea Scarantino
Journal: Behavioral and Brain Sciences (2025)

Abstract Murayama and Jach criticize the use of high-level motivational constructs in psychology, urging psychologists to “unpack” the black box. These constructs are alleged to be “psychological constructions” with no causal powers of their own. I argue that this view is mistaken, and that high-level motivational constructs are causal even when unpacked in terms of underlying computational, algorithmic, and implementational processes.
Beyond reductionism: Understanding motivational energization requires higher-order constructs
Authors: Kennon M Sheldon, Richard M Ryan
Journal: Behavioral and Brain Sciences (2025)

Abstract We argue that the target article's computational/reductionistic approach to motivation is insufficient to explain the energization of human behavior, because such explanation requires broad consideration of “what people are trying to do.” We illustrate what is gained by retaining (rather than jettisoning) higher-order motivation constructs and show that the authors’ approach assumes, but fails to name, such constructs.
Human papillomavirus-related squamous cell carcinomas after blood or marrow transplantation—a BMTSS report
Authors: Anna Sällfors Holmqvist, Qingrui Meng, Wendy Landier, Lindsey Hageman, Liton F Francisco, Elizabeth Schlichting Ross, Nora Balas, Alysia Bosworth, Hok Sreng Te, Ravi Bhatia, F Lennie Wong, Daniel Weisdorf, Saro H Armenian, Smita Bhatia
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Human papillomavirus (HPV) is associated with an increased risk for a variety of squamous cell carcinomas (SCCs) in the general population. The risk for subsequent SCCs in BMT survivors that are potentially related to HPV (cervical, oropharyngeal, vulvar, vaginal, anal, and penile cancer; HPV-related SCCs) remains unknown. Methods We determined the risk of HPV-related SCCs in 7,936 2 y-survivors of autologous or allogeneic BMT performed between 1974 and 2014 and identified the role of demographic and clinical factors associated with HPV-related SCCs using proportional subdistribution hazards model for competing risks. Standardized incidence ratio (SIR) was used to compare the risk of HPV-related SCC with age-, sex-, and calendar-specific incidence in the general population. Results The median age at transplantation was 46 y (range, 0-78 y); 58.5% (n = 4,642) were males, and 72.2% (n = 5,727) were non-Hispanic White. Half of the patients (50.3%, n = 3,991) had received an allogeneic BMT. The SIR for oropharyngeal SCC (n = 53) was 1.8 (95%CI = 1.3-2.3) and for cervical SCC among female BMT recipients (n = 26) was 9.4 (95%CI = 6.3-13.6), compared to the general US population. The hazard of an HPV-related SCC was higher among allogeneic BMT recipients with chronic graft vs host disease (cGvHD) (any HPV-related SCC: HR = 6.24, 95%CI = 3.11-12.50; oropharyngeal: HR = 4.85, 95%CI = 2.11-11.15; cervical: HR = 4.98, 95%CI = 1.65-15.00; reference=autologous BMT). Pre-BMT radiation increased the risk of oropharyngeal SCC (HR = 2.98, 95%CI = 1.57-5.65). Conclusion These findings underscore the importance of risk-based HPV vaccination and surveillance after BMT.
NF2 loss-of-function and hypoxia drive radiation resistance in grade 2 meningiomas
Authors: Bhuvic Patel, Sangami Pugazenthi, Collin W English, Vijay Nitturi, Shree S Pari, Tatenda Mahlokozera, William A Leidig, Hsiang-Chih Lu, Alicia Yang, Kaleigh Roberts, Patrick DeSouza, Kyle P McGeehan, Diane D Mao, Namita Sinha, Joseph E Ippolito, Sonika Dahiya, Allegra Petti, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background World Health Organization Grade 2 meningiomas (G2Ms) often recur and resist therapies. G2Ms with histopathological necrosis have been associated with worse local control (LC) following radiation therapy, but the drivers and biomarkers of radiation resistance in G2Ms remain unknown. Methods We performed genetic sequencing and histopathological analysis of 113 G2Ms and investigated the role of genetic and microenvironmental factors on clonogenic survival following ionizing radiation. We performed transcriptional profiling of our in vitro model and 18 human G2M tumors by bulk RNA sequencing as well as eight G2Ms by single nuclei RNA sequencing. Results NF2 loss-of-function (LOF) mutations were associated with necrosis in G2Ms (p = .0127). Tumors with NF2 mutation and necrosis had worse post-radiation LC compared to NF2 wildtype tumors without necrosis (p = .035). Under hypoxic conditions, NF2 knockdown increased radiation resistance in vitro (p &amp;lt; .001). Bulk RNA sequencing revealed NF2- and hypoxia-specific changes and a 50-gene set signature specific to radiation resistant, NF2 knockdown and hypoxic cells, which distinguished NF2 mutant/necrotic patient G2Ms by unsupervised clustering. Enrichment analysis revealed downregulation of apoptosis pathway genes and upregulation of proliferation-associated genes and genes normally downregulated after UV radiation exposure in NF2-mutant/necrotic tumor cells, which were validated with functional assays. Conclusions NF2 LOF in the setting of hypoxia confers radiation resistance through transcriptional programs that reduce apoptosis and promote proliferation. These pathways may identify tumors resistant to radiation and represent therapeutic targets that in the future could improve LC in patients with radiation resistant G2Ms.