Dynamics of respiratory infectious diseases under rapid urbanization and COVID-19 pandemic in the subcenter of Beijing during 2014-2022.

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014-2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China. Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014-2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases. Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014-2022, and the incidence rate of NRIDs was higher during 2017-2019 (153/100 000) than during 2014-2016 (930/100 000) and during 2020-2022 (371/100 000), respectively (both P < 0.001). The CIU constantly increased with slight fluctuation in 2016 and 2018, respectively. The incidence rate of NRIDs showed an increase along with the CIU during 2014-2019 (r = 0.95, P = 0.004), while the incidence rate's tendency was interrupted by COVID-19 during 2020 with slight decrease in 2020-2021 and rebounded in 2022. For the patients aged <15 years, the incidence rate of NRIDs revealed a very sharp rise at the urbanization period without COVID-19 pandemic compared with that under pre-urbanization period (RR = 7.93, 95 % CI 7.63-8.24), and dropped off to the similar level as of pre-urbanization period when COVID-19 pandemic spread. Conclusions: Urbanization process may increase the incidence of NRIDs but constrained by COVID-19. Certain measures should be taken to prevent and control the effects by urbanization process, such as good natural environment with less population density, ecological environment with good air quality, promoted hand hygiene, mask wearing, keeping interpersonal distance, vaccination, media publicity for NRIDs' prevention and control.

Accuracy Assessment of Geometric-Distortion Identification Methods for Sentinel-1 Synthetic Aperture Radar Imagery in Highland Mountainous Regions.

SAR imagery plays a crucial role in geological and environmental monitoring, particularly in highland mountainous regions. However, inherent geometric distortions in SAR images often undermine the precision of remote sensing analyses. Accurately identifying and classifying these distortions is key to analyzing their origins and enhancing the quality and accuracy of monitoring efforts. While the layover and shadow map (LSM) approach is commonly utilized to identify distortions, it falls short in classifying subtle ones. This study introduces a novel LSM ground-range slope (LG) method, tailored for the refined identification of minor distortions to augment the LSM approach. We implemented the LG method on Sentinel-1 SAR imagery from the tri-junction area where the Xiaojiang, Pudu, and Jinsha rivers converge at the Yunnan-Sichuan border. By comparing effective monitoring-point densities, we evaluated and validated traditional methods-LSM, R-Index, and P-NG-against the LG method. The LG method demonstrates superior performance in discriminating subtle distortions within complex terrains through its secondary classification process, which allows for precise and comprehensive recognition of geometric distortions. Furthermore, our research examines the impact of varying slope parameters during the classification process on the accuracy of distortion identification. This study addresses significant gaps in recognizing geometric distortions and lays a foundation for more precise SAR imagery analysis in complex geographic settings.

Metal-Organic Framework Nanomaterials as a Medicine for Catalytic Tumor Therapy: Recent Advances.

Nanomaterials, with unique physical, chemical, and biocompatible properties, have attracted significant attention as an emerging active platform in cancer diagnosis and treatment. Amongst them, metal-organic framework (MOF) nanostructures are particularly promising as a nanomedicine due to their exceptional surface functionalities, adsorption properties, and organo-inorganic hybrid characteristics. Furthermore, when bioactive substances are integrated into the structure of MOFs, these materials can be used as anti-tumor agents with superior performance compared to traditional nanomaterials. In this review, we highlight the most recent advances in MOFs-based materials for tumor therapy, including their application in cancer treatment and the underlying mechanisms.

Magnetostrictive-piezocatalytic CoFe2O4@UiO-66 nanohybrid and its potential for deep-seated tumor treatment.

Magnetostrictive CoFe2O4 (CFO) nanoparticles were encapsulated within a UiO-66 metal-organic-framework layer to form a CFO@UiO-66 nanohybrid. The deforming of CFO, in response to a high-frequency AC magnetic field, initiates the piezocatalytic property of UiO-66 to generate ˙OH radicals, which can kill cancer cells buried in thick tissues, showcasing bright potential for deep-seated tumor treatment.

Genome-wide identification of toll-like receptors in Octopus sinensis and expression analysis in response to different PAMPs stimulation.

Toll-like receptors (TLRs) are one of the extensively studied pattern recognition receptors (PRRs) and play crucial roles in the immune responses of vertebrates and invertebrates. In this study, 14 TLR genes were identified from the genome-wide data of Octopus sinensis. Protein structural domain analysis showed that most TLR proteins had three main structural domains: extracellular leucine-rich repeats (LRR), transmembrane structural domains, and intracellular Toll/IL-1 receptor domain (TIR). The results of subcellular localization prediction showed that the TLRs of O. sinensis were mainly located on the plasma membrane. The results of quantitative real-time PCR (qPCR) showed that the detected TLR genes were differentially expressed in the hemolymph, white bodies, hepatopancreas, gills, gill heart, intestine, kidney, and salivary gland of O. sinensis. Furthermore, the present study investigated the expression changes of O. sinensis TLR genes in hemolymph, white bodies, gills, and hepatopancreas in different phases (6 h, 12 h, 24 h, 48 h) after stimulation with PGN, poly(I: C) and Vibrio parahaemolyticus. The expression of most of the TLR genes was upregulated at different time points after infection with pathogens or stimulation with PAMPs, a few genes were unchanged or even down-regulated, and many of the TLR genes were much higher after V. parahaemolyticus infection than after PGN and poly(I:C) stimulation. The results of this study contribute to a better understanding of the molecular immune mechanisms of O. sinensis TLRs genes in resistance to pathogen stimulation.

Therapeutic potential of targeting Nrf2 by panobinostat in pituitary neuroendocrine tumors.

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.

Trends of the prevalence rate of central lymph node metastasis and multifocality in patients with low-risk papillary thyroid carcinoma after delayed thyroid surgery.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients.

3D-Printed Fluorescent Hydrogel Consisting of Conjugated Polymer and Biomacromolecule for Fast and Sensitive Detection of Cr(VI) in Vegetables.

Portable fluorescent film sensors offer a solution to the contamination issue in homogeneous sensor detection systems. However, their special structure leads to low sensitivity and a long response time, resulting in a significant scientific challenge limiting their development and application. In this work, we propose a dual design strategy to prepare highly sensitive film sensors for rapidly detecting Cr2O72-. Specifically, P(Fmoc-Osu)-SA hydrogel films were developed by integrating the biological macromolecule sodium alginate (SA) with the conjugated polymer poly(N-(9-Fluorenylmethoxycarbonyloxy)succinimide) (P(Fmoc-Osu)), using both mold and inkjet 3D printing methods. The "molecular wire effect" of the sensing unit P(Fmoc-Osu) and the water channel within the film substrate are responsible for the improved sensitivity and the reduced response time of this thin film sensor. P(Fmoc-Osu)-SA hydrogel films prepared by these two methods can rapidly detect Cr2O72- with limits of detection of 1.18 and 0.078 nM, respectively. Considering that 3D-printed hydrogel films can be tailored to different shapes according to detection needs, the P(Fmoc-Osu)-SA hydrogel films produced from this method were effectively applied in vegetable samples. This study provides an innovative and effective strategy for the development of biocompatible hydrogel sensors that offer the potential for determining trace amounts of Cr2O72- in agriculture.

Structure-Guided Image Completion with Image-level and Object-level Semantic Discriminators.

Structure-guided image completion aims to inpaint a local region of an image according to an input guidance map from users. While such a task enables many practical applications for interactive editing, existing methods often struggle to hallucinate realistic object instances in complex natural scenes. Such a limitation is partially due to the lack of semantic-level constraints inside the hole region as well as the lack of a mechanism to enforce realistic object generation. In this work, we propose a learning paradigm that consists of semantic discriminators and object-level discriminators for improving the generation of complex semantics and objects. Specifically, the semantic discriminators leverage pretrained visual features to improve the realism of the generated visual concepts. Moreover, the object-level discriminators take aligned instances as inputs to enforce the realism of individual objects. Our proposed scheme significantly improves the generation quality and achieves state-of-the-art results on various tasks, including segmentation-guided completion, edge-guided manipulation and panoptically-guided manipulation on Places2 datasets. Furthermore, our trained model is flexible and can support multiple editing use cases, such as object insertion, replacement, removal and standard inpainting. In particular, our trained model combined with a novel automatic image completion pipeline achieves state-of-the-art results on the standard inpainting task.

Self-assembly behavior and adhesive performance of imidazolium cation grafted cellulose nanocrystals in confined space.

Confined evaporation-induced self-assembly (C-EISA) is a powerful technique to guide disordered nanoparticles into long-range organized structures. Herein, we investigate the C-EISA behavior of 1-butyl-3-vinylimidazolium cation ([VBIm]+) grafted cellulose nanocrystals (CNC-C) in a parallel-plates confined geometry. Interestingly, CNC-C can spontaneously assemble into maze-like patterns with branch dimensions on the micrometer scale and uniformly distributed throughout the confined space, which is completely different from the lamellar self-assembly patterns of unmodified CNCs. Combining in situ observations and microscopic characterization, we speculate that the formation of maze-like patterns originates from the reduction of colloidal stability induced by the grafted imidazolium cations. The electrostatic attraction between CNC-C aggregated bundles and glass substrates acts as anchor points, thereby leading to the unstable motion of the liquid-air menisci during the inward intrusion of air. Due to the physicochemical properties and unique C-EISA behavior, the CNC-C based adhesive can maintain adhesion at temperatures of ca. 200 °C, while rapidly debonding when immersed in water, demonstrating the potential to be used as stimuli-responsive temporary or removable adhesives. Furthermore, the strategy proposed in this work for achieving CNCs patterning is also promising to be extended to other anisotropic rod-shaped nanoparticles.

Hydroxylation of the indium tin oxide electrode promoted by surface bubbles.

Adherent bubbles at electrodes are generally treated as reaction penalties. Herein, in situ hydroxylation of indium tin oxide surfaces can be easily achieved by applying a constant potential of +1.0 V in the presence of bubbles. Its successful hydroxylation is further demonstrated by preparing a ferrocene-terminated film, which is confirmed by cyclic voltammetry and X-ray photoelectron spectroscopy.

Thermoelectrocatalysis: an emerging strategy for converting waste heat into chemical energy.

This perspective defines and explores an innovative waste heat harvesting strategy, thermoelectrocatalysis (TECatal), emphasizing materials design and potential applications in clean energy, environmental, and biomedical technologies.

EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway.

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma (UM). Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions. In search of genetic vulnerability for UM, we found that inhibition of euchromatic histone lysine methyltransferase 2 (EHMT2) expression or activity significantly reduced the proliferation and migration capacity of cancer cells. Notably, elevated expression of EHMT2 had been validated in UM samples. Furthermore, Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage. Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2. Its transcription was suppressed by EHMT2 in a methyltransferase-dependent pattern in GNAQ/11-mutant UM cells, leading to elevated RhoA activity. Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes. Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth, suggesting the driver role of these two key molecules. In summary, our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

Adenoid Cystic Carcinoma of Esophagus with Lung Metastasis: Case Report.

Adenoid cystic carcinoma (ACC) is a malignant tumor originating in the salivary glands. It most commonly affects the salivary and lacrimal glands, with less frequent occurrences in the esophagus. Esophageal ACC (EACC) typically manifests in the middle or lower parts of the esophagus, with exceedingly rare instances in the upper part. Lung metastasis in EACC is uncommon, and understanding its clinical features and treatment strategies remains challenging. In this study, we present a case of ACC originating in the upper esophagus with lung metastasis. The patient, a middle-aged female, was admitted to the Department of Respiratory and Critical Care Medicine due to an esophageal mass discovered during physical examination that had been present for 4.5 years, along with a newly identified pulmonary nodule for 2 weeks. An X-ray barium meal revealed the presence of a benign esophageal cervical mass. Gastroscopy revealed elevated lesions below the esophageal inlet, and a pathological biopsy confirmed the diagnosis of EACC. The aim of this case report is to enhance understanding of this rare condition and improve clinicians' awareness of the disease. By providing details of the patient's diagnosis, clinical presentation, imaging features and pathological features, we aim to improve diagnostic accuracy and clinical management of similar cases in the future.

Dynamic functional network connectivity analysis in schizophrenia based on a spatiotemporal CPD framework.

Objective.Dynamic functional network connectivity (dFNC), based on data-driven group independent component (IC) analysis, is an important avenue for investigating underlying patterns of certain brain diseases such as schizophrenia. Canonical polyadic decomposition (CPD) of a higher-way dynamic functional connectivity tensor, can offer an innovative spatiotemporal framework to accurately characterize potential dynamic spatial and temporal fluctuations. Since multi-subject dFNC data from sliding-window analysis are also naturally a higher-order tensor, we propose an innovative sparse and low-rank CPD (SLRCPD) for the three-way dFNC tensor to excavate significant dynamic spatiotemporal aberrant changes in schizophrenia.Approach.The proposed SLRCPD approach imposes two constraints. First, the L1regularization on spatial modules is applied to extract sparse but significant dynamic connectivity and avoid overfitting the model. Second, low-rank constraint is added on time-varying weights to enhance the temporal state clustering quality. Shared dynamic spatial modules, group-specific dynamic spatial modules and time-varying weights can be extracted by SLRCPD. The strength of connections within- and between-IC networks and connection contribution are proposed to inspect the spatial modules. K-means clustering and classification are further conducted to explore temporal group difference.Main results.82 subject resting-state functional magnetic resonance imaging (fMRI) dataset and opening Center for Biomedical Research Excellence (COBRE) schizophrenia dataset both containing schizophrenia patients (SZs) and healthy controls (HCs) were utilized in our work. Three typical dFNC patterns between different brain functional regions were obtained. Compared to the spatial modules of HCs, the aberrant connections among auditory network, somatomotor, visual, cognitive control and cerebellar networks in 82 subject dataset and COBRE dataset were detected. Four temporal states reveal significant differences between SZs and HCs for these two datasets. Additionally, the accuracy values for SZs and HCs classification based on time-varying weights are larger than 0.96.Significance.This study significantly excavates spatio-temporal patterns for schizophrenia disease.

Biomimetic Multiscale Oriented PVA/NRL Hydrogel Enabled Multistimulus Responsive and Smart Shape Memory Actuator.

Shape memory hydrogels provide a worldwide scope for functional soft materials. However, most shape memory hydrogels exhibit poor mechanical properties, leading to low actuation strength, which severely limits their applications in smart biomimetic devices. Herein, a strategy for muscle-inspired shape memory-oriented polyvinyl alcohol (PVA)-natural rubber latex (NRL) hydrogel (OPNH) with multiscale oriented structure is demonstrated. The shape memory function comes from the stretch-induced crystallization of natural rubber (NR), while PVA forms strong hydrogen bonding interactions with proteins and phospholipids on the surface of NRL particles. Meanwhile, the reconfigurable interactions of PVA and NR produce a multiscale-oriented structure during stretch-drying, improving the mechanical and shape memory properties. The resultant OPNH shows excellent interfacial compatibility, exhibiting outstanding mechanical performance (3.2 MPa), high shape fixity (≈80%) and shape recovery ratio (≈92%), high actuation strength (206 kPa), working capacity (105 kJ m- 3 ), extremely short response time (≈2 s), low response temperature (28 °C) and smart thermal responsiveness. It can even maintain muscle-like working capacity when lifting a load equivalent to 372 times its weight, providing a new class shape memory material for the application in smart biomimetic muscles and multistimulus responsive devices.

Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin's lymphomas varying in clinical, phenotypic, and genetic features. The molecular pathogenesis and the role of the tumor microenvironment in PTCL are poorly understood, with limited biomarkers available for genetic subtyping and targeted therapies. Through an integrated genomic and transcriptomic study of 221 PTCL patients, we delineate the genetic landscape of PTCL, enabling molecular and microenvironment classification. According to the mutational status of RHOA, TET2, histone-modifying, and immune-related genes, PTCL is divided into 4 molecular subtypes with discrete patterns of gene expression, biological aberrations, and vulnerabilities to targeted agents. We also perform an unsupervised clustering on the microenvironment transcriptional signatures and categorize PTCL into 4 lymphoma microenvironment subtypes based on characteristic activation of oncogenic pathways and composition of immune communities. Our findings highlight the potential clinical rationale of future precision medicine strategies that target both molecular and microenvironment alterations in PTCL.

Root microbiota of tea plants regulate nitrogen homeostasis and theanine synthesis to influence tea quality.

The flavor profile of tea is influenced not only by different tea varieties but also by the surrounding soil environment. Recent studies have indicated the regulatory role of soil microbes residing in plant roots in nutrient uptake and metabolism. However, the impact of this regulatory mechanism on tea quality remains unclear. In this study, we showed that a consortium of microbes isolated from tea roots enhanced ammonia uptake and facilitated the synthesis of theanine, a key determinant of tea taste. Variations were observed in the composition of microbial populations colonizing tea roots and the rhizosphere across different seasons and tea varieties. By comparing the root microorganisms of the high-theanine tea variety Rougui with the low-theanine variety Maoxie, we identified a specific group of microbes that potentially modulate nitrogen metabolism, subsequently influencing the theanine levels in tea. Furthermore, we constructed a synthetic microbial community (SynCom) mirroring the microbe population composition found in Rougui roots. Remarkably, applying SynCom resulted in a significant increase in the theanine content of tea plants and imparted greater tolerance to nitrogen deficiency in Arabidopsis. Our study provides compelling evidence supporting the use of root microorganisms as functional microbial fertilizers to enhance tea quality.

Artemisia argyi extract exerts antioxidant properties and extends the lifespan of Drosophila melanogaster.

BACKGROUND: Chinese mugwort (Artemisia argyi) possesses extensive pharmacological activities associated with anti-tumour, antioxidative and anti-inflammatory effects. The present study aimed to investigate the antioxidant and anti-ageing effects of A. argyi extract (AAE) on the fruit fly (Drosophila melanogaster) ageing model by detecting antioxidant enzyme activities and the mRNA level of antioxidant genes. RESULTS: AAE could significantly lengthen the mean lifespan, 50% survival days, and maximum lifespan of D. melanogaster, especially when the amount of AAE added reached 6.68 mg mL-1, the mean lifespan of both female and male flies increased by 23.74% and 22.30%, respectively, indicating the effective life extension effect of AAE. At the same time, AAE could improve the climbing ability and tolerance to hydrogen peroxide in D. melanogaster. In addition, the addition of AAE effectively increased the activities of copper-zinc-containing superoxide dismutase, manganese-containing superoxide dismutase and catalase in D. melanogaster and reduced the contents of malondialdehyde. Moreover, when reared with diets containing AAE, the expression of antioxidant-related genes SOD1, SOD2 and CAT was up-regulated in D. melanogaster and down-regulated for MTH genes. CONCLUSION: The study indicates that AAE effectively enhances the antioxidant capacity of D. melanogaster and has potential applications as an antioxidant and anti-ageing agent in the nutraceutical industry. © 2024 Society of Chemical Industry.

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs.

BACKGROUND & AIMS: Despite the increasing number of treatment options available for liver cancer, only a small proportion of patients achieve long-term clinical benefits. Here, we aim to develop new therapeutic approaches for liver cancer. METHODS: A compound screen was conducted to identify inhibitors that could synergistically induce senescence when combined with cyclin-dependent kinase (CDK) 4/6 inhibitor. The combination effects of CDK4/6 inhibitor and exportin 1 (XPO1) inhibitor on cellular senescence were investigated in a panel of human liver cancer cell lines and multiple liver cancer models. A senolytic drug screen was performed to identify drugs that selectively killed senescent liver cancer cells. RESULTS: The combination of CDK4/6 inhibitor and XPO1 inhibitor synergistically induces senescence of liver cancer cells in vitro and in vivo. The XPO1 inhibitor acts by causing accumulation of RB1 in the nucleus, leading to decreased E2F signaling and promoting senescence induction by the CDK4/6 inhibitor. Through a senolytic drug screen, cereblon (CRBN)-based proteolysis targeting chimera (PROTAC) ARV-825 was identified as an agent that can selectively kill senescent liver cancer cells. Up-regulation of CRBN was a vulnerability of senescent liver cancer cells, making them sensitive to CRBN-based PROTAC drugs. Mechanistically, we find that ubiquitin specific peptidase 2 (USP2) directly interacts with CRBN, leading to the deubiquitination and stabilization of CRBN in senescent liver cancer cells. CONCLUSIONS: Our study demonstrates a striking synergy in senescence induction of liver cancer cells through the combination of CDK4/6 inhibitor and XPO1 inhibitor. These findings also shed light on the molecular processes underlying the vulnerability of senescent liver cancer cells to CRBN-based PROTAC therapy.