Carbazolyl-Modified Neutral Ir(III) Complexes for Efficient Detection of Picric Acid in Aqueous Media.

Based on the electron-deficient property of picric acid (PA), two neutral Ir(III) complexes 1 and 2 modified with the electron-rich carbazolyl groups were synthesized and characterized. Both 1 and 2 exhibit aggregation-induced phosphorescence emission (AIPE) properties in THF/H2O. Among them, 2 is extremely sensitive for detecting PA with a limit of detection of 0.15 µM in THF/H2O. Furthermore, the selectivity for PA is significantly higher compared to other analytes, enabling the efficient detection of PA in four common water samples. The density functional theory calculations and the spectroscopic results confirm that the sensing mechanism is photo-induced electron transfer (PET).

Early diagnosis and staging of paraquat-induced pulmonary fibrosis using [18F]F-FAPI-42 PET/CT imaging.

BACKGROUND: Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [18F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis. METHODS: After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [18F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [18F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUVmean) was calculated. RESULTS: PET signals revealed that in areas with evident lesions on CT, the SUVmean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUVmean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [18F]F-FAPI-42 binding to activated fibroblasts. CONCLUSION: [18F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.

Modifying Proton Relay into Bioinspired Dye-based Coordination Polymer for Photocatalytic Proton-Coupled Electron Transfer.

Proton-coupled electron transfer (PCET) imparts an energetic advantage over solo electron transfer in activating inert substances. Natural PCET enzyme catalysis generally requires tripartite preorganization of proton relay, substrate-bound active center, and redox mediator, making the processes efficient and precluding side reactions. Inspired by this, a heterogeneous photocatalytic PCET system was established to achieve higher PCET driving forces by modifying proton relays into anthraquinone-based anionic coordination polymers. The proximally separated proton relays and photoredox-mediating anthraquinone moiety allowed pre-assembly of inert substrate between them, merging proton and electron into unsaturated bond by photoreductive PCET, which enhanced reaction kinetics than the counter catalyst without proton relay. This photocatalytic PCET method was applied to a broad-scoped reduction of aryl ketones, unsaturated carbonyls, and aromatic compounds. The distinctive regioselectivities for the reduction of isoquinoline derivatives were found to occur on the carbon-ring sides. PCET-hydrogenated radical intermediate of quinoline could be trapped by alkene for proton relay-assisted Minisci addition, forming the pharmaceutical aza-acenaphthene scaffold within one step. When using heteroatom(X)-H/C-H compounds as proton-electron donors, this protocol could activate these inert bonds through photooxidative PCET to afford radicals and trap them by electron-deficient unsaturated compounds, furnishing the direct X-H/C-H functionalization.

AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation.

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

Melatonin Mitigates Atrazine-Induced Renal Tubular Epithelial Cell Senescence by Promoting Parkin-Mediated Mitophagy.

The accumulation of senescent cells in kidneys is considered to contribute to age-related diseases and organismal aging. Mitochondria are considered a regulator of cell senescence process. Atrazine as a triazine herbicide poses a threat to renal health by disrupting mitochondrial homeostasis. Melatonin plays a critical role in maintaining mitochondrial homeostasis. The present study aims to explore the mechanism by which melatonin alleviates atrazine-induced renal injury and whether parkin-mediated mitophagy contributes to mitigating cell senescence. The study found that the level of parkin was decreased after atrazine exposure and negatively correlated with senescent markers. Melatonin treatment increased serum melatonin levels and mitigates atrazine-induced renal tubular epithelial cell senescence. Mechanistically, melatonin maintains the integrity of mitochondrial crista structure by increasing the levels of mitochondrial contact site and cristae organizing system, mitochondrial transcription factor A (TFAM), adenosine triphosphatase family AAA domain-containing protein 3A (ATAD3A), and sorting and assembly machinery 50 (Sam50) to prevent mitochondrial DNA release and subsequent activation of cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase pathway. Furthermore, melatonin activates Sirtuin 3-superoxide dismutase 2 axis to eliminate the accumulation of reactive oxygen species in the kidney. More importantly, the antisenescence role of melatonin is largely determined by the activation of parkin-dependent mitophagy. These results offer novel insights into measures against cell senescence. Parkin-mediated mitophagy is a promising drug target for alleviating renal tubular epithelial cell senescence.

Chiral Iridium-Based TLD-1433 Analogues: Exploration of Enantiomer-Dependent Behavior in Photodynamic Cancer Therapy.

Metallodrug-based photodynamic therapy (PDT) agents have demonstrated significant superiority against cancers, while their different chirality-induced biological activities remain largely unexplored. In this work, we successfully developed a pair of enantiopure mononuclear Ir(III)-based TLD-1433 analogues, Δ-Ir-3T and Λ-Ir-3T, and their enantiomer-dependent anticancer behaviors were investigated. Photophysical measurements revealed that they display high photostability and chemical stability, strong absorption at 400 nm with high molar extinction coefficients (ε = 5.03 × 104 M-1 cm-1), and good 1O2 relative quantum yields (ΦΔ ≈ 47%). Δ- and Λ-Ir-3T showed potent efficacy against MCF-7 cancer cells, with a photocytotoxicity index of ≤44 238. This impressive result, to the best of our knowledge, represents the highest value among reported mononuclear Ir(III)-based PDT agents. Remarkably, Λ-Ir-3T tended to be more potent than Δ-Ir-3T when tested against SK-MEL-28, HepG2, and LO2 cells, with consistent results across multiple test repetitions.

Confinement Effect in Metal-Organic Framework Cu3(BTC)2 for Enhancing Shape Selectivity of Radical Difunctionalization of Alkenes.

The radical difunctionalization of alkenes plays a vital role in pharmacy, but the conventional homogeneous catalytic systems are challenging in selectivity and sustainability to afford the target molecules. Herein, the famous readily available metal-organic framework (MOF), Cu3(BTC)2, has been applied to cyano-trifluoromethylation of alkenes as a high-performance and recyclable heterogeneous catalyst, which possesses copper(II) active sites residing in funnel-like cavities. Under mild conditions, styrene derivatives and various unactivated olefins could be smoothly transformed into the corresponding cyano-trifluoromethylation products. Moreover, the transformation brought about by the active copper center in confined environments achieved regio- and shape selectivity. To understand the enhanced selectivity, the activation manner of the MOF catalyst was studied with control catalytic experiments such as FT-IR and UV-vis absorption spectroscopy of substrate-incorporated Cu3(BTC)2, which elucidated that the catalyst underwent a radical transformation with the intermediates confined in the MOF cavity, and the confinement effect endowed the method with pronounced selectivities.

A rationally designed nuclei-targeting FAPI 04-based molecular probe with enhanced tumor uptake for PET/CT and fluorescence imaging.

PURPOSE: Fibroblast activation protein inhibitor (FAPI) -based probes have been widely studied in the diagnosis of various malignant tumors with positron emission tomography/computed tomography (PET/CT). However, current imaging studies of FAPI-based probes face challenges in rapid clearance rate and potential false-negative results. Furthermore, FAPI has been rarely explored in optical imaging. Considering this, further modifications are imperative to improve the properties of FAPI-based probes to address existing limitations and broaden their application scenarios. In this study, we rationally introduced methylene blue (MB) to FAPIs, thereby imparting nuclei-targeting and fluorescence imaging capabilities to the probes. Furthermore, we evaluated the added value of FAPI-based fluorescence imaging to traditional PET/CT, exploring the potential application of FAPI-based probes in intraoperative fluorescence imaging. METHODS: A new FAPI-based probe, namely NOTA-FAPI-MB, was designed for both PET/CT and fluorescence imaging by conjugation of MB. The targeting efficacy of the probe was evaluated on fibroblast activation protein (FAP)-transfected cell line and human primary cancer-associated fibroblasts (CAFs). Subsequently, PET/CT and fluorescence imaging were conducted on tumor-bearing mice. The tumor detection and boundary delineation were assessed by fluorescence imaging of tissues from hepatocellular carcinoma (HCC) patients. RESULTS: NOTA-FAPI-MB demonstrated exceptional targeting ability towards FAP-transfected cells and CAFs in comparison to NOTA-FAPI. This benefit arises from the cationic methylene blue (MB) affinity for anionic nucleic acids. PET/CT imaging of tumor-bearing mice revealed significantly higher tumor uptake of [18F]F-NOTA-FAPI-MB (standard uptake value of 2.20 ± 0.31) compared to [18F]F-FDG (standard uptake value of 1.66 ± 0.14). In vivo fluorescence imaging indicated prolonged retention at the tumor site, with retention lasting up to 24 h. In addition, the fluorescent probes enabled more precise lesion detection and tumor margin delineation than clinically used indocyanine green (ICG), achieving a 100.0% (6/6) tumor-positive rate for NOTA-FAPI-MB while 33.3% (2/6) for ICG. These findings highlighted the potential of NOTA-FAPI-MB in guiding intraoperative surgical procedures. CONCLUSIONS: The NOTA-FAPI-MB was successfully synthesized, in which FAPI and MB simultaneously contributed to the targeting effect. Notably, the nuclear delivery mechanism of the probes improved intracellular retention time and targeting efficacy, broadening the imaging time window for fluorescence imaging. In vivo PET/CT demonstrated favorable performance of NOTA-FAPI-MB compared to [18F]F-FDG. This study highlights the significance of fluorescence imaging as an adjunct technique to PET/CT. Furthermore, the encouraging results obtained from the imaging of human HCC tissues hold promise for the potential application of NOTA-FAPI-MB in intraoperative fluorescent surgery guidance within clinical settings.

Efficient automated high dynamic range 3D measurement via deep reinforcement learning.

High dynamic range 3D measurement technology, utilizing multiple exposures, is pivotal in industrial metrology. However, selecting the optimal exposure sequence to balance measurement efficiency and quality remains challenging. This study reinterprets this challenge as a Markov decision problem and presents an innovative exposure selection method rooted in deep reinforcement learning. Our approach's foundation is the exposure image prediction network (EIPN), designed to predict images under specific exposures, thereby simulating a virtual environment. Concurrently, we establish a reward function that amalgamates considerations of exposure number, exposure time, coverage, and accuracy, providing a comprehensive task definition and precise feedback. Building upon these foundational elements, the exposure selection network (ESN) emerges as the centerpiece of our strategy, acting decisively as an agent to derive the optimal exposure sequence selection. Experiments prove that the proposed method can obtain similar coverage (0.997 vs. 1) and precision (0.0263 mm vs. 0.0230 mm) with fewer exposures (generally 4) compared to the results of 20 exposures.

Wood-inspired metamaterial catalyst for robust and high-throughput water purification.

Continuous industrialization and other human activities have led to severe water quality deterioration by harmful pollutants. Achieving robust and high-throughput water purification is challenging due to the coupling between mechanical strength, mass transportation and catalytic efficiency. Here, a structure-function integrated system is developed by Douglas fir wood-inspired metamaterial catalysts featuring overlapping microlattices with bimodal pores to decouple the mechanical, transport and catalytic performances. The metamaterial catalyst is prepared by metal 3D printing (316 L stainless steel, mainly Fe) and electrochemically decorated with Co to further boost catalytic functionality. Combining the flexibility of 3D printing and theoretical simulation, the metamaterial catalyst demonstrates a wide range of mechanical-transport-catalysis capabilities while a 70% overlap rate has 3X more strength and surface area per unit volume, and 4X normalized reaction kinetics than those of traditional microlattices. This work demonstrates the rational and harmonious integration of structural and functional design in robust and high throughput water purification, and can inspire the development of various flow catalysts, flow batteries, and functional 3D-printed materials.

Recent Advances in 4D Printing of Advanced Materials and Structures for Functional Applications.

4D printing has attracted tremendous worldwide attention during the past decade. This technology enables the shape, property, or functionality of printed structures to change with time in response to diverse external stimuli, making the original static structures alive. The revolutionary 4D-printing technology offers remarkable benefits in controlling geometric and functional reconfiguration, thereby showcasing immense potential across diverse fields, including biomedical engineering, electronics, robotics, and photonics. Here, a comprehensive review of the latest achievements in 4D printing using various types of materials and different additive manufacturing techniques is presented. The state-of-the-art strategies implemented in harnessing various 4D-printed structures are highlighted, which involve materials design, stimuli, functionalities, and applications. The machine learning approach explored for 4D printing is also discussed. Finally, the perspectives on the current challenges and future trends toward further development in 4D printing are summarized.

Hepatocellular carcinoma: signaling pathways, targeted therapy, and immunotherapy.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a high mortality rate. It is regarded as a significant public health issue because of its complicated pathophysiology, high metastasis, and recurrence rates. There are no obvious symptoms in the early stage of HCC, which often leads to delays in diagnosis. Traditional treatment methods such as surgical resection, radiotherapy, chemotherapy, and interventional therapies have limited therapeutic effects for HCC patients with recurrence or metastasis. With the development of molecular biology and immunology, molecular signaling pathways and immune checkpoint were identified as the main mechanism of HCC progression. Targeting these molecules has become a new direction for the treatment of HCC. At present, the combination of targeted drugs and immune checkpoint inhibitors is the first choice for advanced HCC patients. In this review, we mainly focus on the cutting-edge research of signaling pathways and corresponding targeted therapy and immunotherapy in HCC. It is of great significance to comprehensively understand the pathogenesis of HCC, search for potential therapeutic targets, and optimize the treatment strategies of HCC.

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum-Mitochondria Interaction.

Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER-mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood-brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER-mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.

Short-term and Long-term Outcomes of Robotic Enucleation of Tumors Located in the Pancreatic Head and Uncinate Process.

OBJECTIVE: To assess short-term and long-term outcomes following robotic enucleation (REn) of tumors in the proximal pancreas. BACKGROUND: Despite the advantages of preserving function via pancreatic enucleation, controversies persist, since this can be associated with severe complications, such as clinically relevant postoperative pancreatic fistula, especially when performed near the main pancreatic duct. The safety and efficacy of REn in this context remain largely unknown. METHODS: A retrospective analysis was performed of all patients who underwent REn for benign and low-grade malignant neoplasms in the pancreatic head and uncinate process between January 2005 and December 2021. Clinicopathologic, perioperative, and long-term outcomes were compared with a similar open enucleation (OEn) group. RESULTS: Of 146 patients, 92 underwent REn with a zero conversion-to-open rate. REn was superior to OEn in terms of shorter operative time (90.0 minutes vs 120.0 minutes, P<0.001), decreased blood loss (20.0 mL vs 100.0 min, P=0.001), and lower clinically relevant postoperative pancreatic fistula rate (43.5% vs 61.1%, P=0.040). Bile leakage rate, major morbidity, 90-day mortality, and length of hospital stay were comparable between groups. No post-REn grade C POPF or grade IV/V complication was identified. Subgroup analyses for uncinate process tumors and proximity to the main pancreatic duct did not demonstrate inferior postoperative outcomes. In a median follow-up period of 50 months, REn outcomes were comparable to OEn regarding recurrence rate and pancreatic endocrine or exocrine function. CONCLUSIONS: REn for pancreatic head and uncinate process tumors improved clinically relevant outcomes without increased major complications compared to OEn, while demonstrating comparable long-term oncological and functional outcomes.

Electric Power Generated from Magnetic Nanofluid Droplets Sliding upon Superslippery Surfaces.

An enduring challenge in the field of electric power generation employing magnetic nanofluids pertains to the inherent issue of solid-liquid adhesion, which results in random residue deposition of magnetic nanofluids on solid substrates during motion. Superslippery surfaces, characterized by their exceptional repellent properties and ultralow adhesion characteristics toward an extensive spectrum of fluids, offer an effective approach to ameliorate the aforementioned adhesive problem. Herein, it is demonstrated that electric power can be generated through the sliding of magnetic nanofluid droplets on superslippery surfaces. The electric power generation can be attributed to the change in magnetic flux caused by the magnetic nanofluid droplet passing or leaving a bottom coil associated with a magnet. By tailoring system parameters, such as the volume of the magnetic nanofluid or the vibration speed, the resulting maximal current can exceed 6 µA. An integrated device, featuring enclosed superslippery inner surfaces, can be securely attached to the arm of a volunteer, allowing for the conversion of mechanical energy into electricity. When the volunteer's arm moves, the electrical energy generated by the device can be utilized to light an LED lamp bead. The proposed strategy using superslippery surfaces facilitates low-adhesion transport of magnetic nanofluids, presenting an alternative solution to the development of next-generation solid/liquid energy harvesting devices.

Robust Superhydrophobicity through Surface Defects from Laser Powder Bed Fusion Additive Manufacturing.

The robustness of superhydrophobic objects conflicts with both the inevitable introduction of fragile micro/nanoscale surfaces and three-dimensional (3D) complex structures. The popular metal 3D printing technology can manufacture robust metal 3D complex components, but the hydrophily and mass surface defects restrict its diverse application. Herein, we proposed a strategy that takes the inherent ridges and grooves' surface defects from laser powder bed fusion additive manufacturing (LPBF-AM), a metal 3D printing process, as storage spaces for hydrophobic silica (HS) nanoparticles to obtain superhydrophobic capacity and superior robustness. The HS nanoparticles stored in the grooves among the laser-melted tracks serve as the hydrophobic guests, while the ridges' metal network provides the mechanical strength, leading to robust superhydrophobic objects with desired 3D structures. Moreover, HS nanoparticles coated on the LPBF-AM-printed surface can inhibit corrosion behavior caused by surface defects. It was found that LPBF-AM-printed objects with HS nanoparticles retained superior hydrophobicity after 150 abrasion cycles (~12.5 KPa) or 50 cycles (~37.5 KPa). Furthermore, LPBF-AM-printed ships with superhydrophobic coating maintained great water repellency even after 10,000 cycles of seawater swashing, preventing dynamic corrosion upon surfaces. Our proposed strategy, therefore, provides a low-cost, highly efficient, and robust superhydrophobic coating, which is applicable to metal 3D architectures toward corrosion-resistant requirements.

Additively Manufactured Flexible Liquid Metal-Coated Self-Powered Magnetoelectric Sensors with High Design Freedom.

Although additive manufacturing enables controllable structural design and customized performance for magnetoelectric sensors, their design and fabrication still require careful matching of the size and modulus between the magnetic and conductive components. Achieving magnetoelectric integration remains challenging, and the rigid coils limit the flexibility of the sensors. To overcome these obstacles, this study proposes a composite process combining selective laser sintering (SLS) and 3D transfer printing for fabricating flexible liquid metal-coated magnetoelectric sensors. The liquid metal forms a conformal conductive network on the SLS-printed magnetic lattice structure. Deformation of the structure alters the magnetic flux passing through it, thereby generating voltage. A reverse model segmentation and summation method is established to calculate the theoretical magnetic flux. The impact of the volume fraction, unit size, and height of the sensors on the voltage is studied, and optimization of these factors yields a maximum voltage of 45.6 µV. The sensor has excellent sensing performance with a sensitivity of 10.9 kPa-1 and a minimum detection pressure of 0.1 kPa. The voltage can be generated through various external forces. This work presents a significant advancement in fabricating liquid metal-based magnetoelectric sensors by improving their structural flexibility, magnetoelectric integration, and design freedom.

Hypoxia-induced long non-coding RNA LINC00460 promotes p53 mediated proliferation and metastasis of pancreatic cancer by regulating the miR-4689/UBE2V1 axis and sequestering USP10.

Long non-coding RNAs are considered to be key regulatory factors of oncogenesis and tumor progression. It is reported that LINC00460 plays the role of oncogene in some tumors. However, LINC00460's role and mechanism of action in pancreatic cancer have not yet been fully elucidated. We identified LINC00460 by analyzing data from the Gene Expression Omnibus database. The role of LINC00460 in proliferation and metastasis was examined using CCK8, colony formation, wound healing, and transwell assays. The potential mechanisms of LINC00460 in regulating mRNA levels were elucidated by RNA pull-down, RNA immunoprecipitation, Chromatin immunoprecipitation, Co-immunoprecipitation, and Immunofluorescence assays. The results showed that LINC00460 was upregulated in pancreatic cancer cells and tissues. Highly expressed LINC00460 is significantly related to short survival of pancreatic cancer patients. Inhibition of LINC00460 attenuated pancreatic cancer cell proliferation and metastasis, whereas its overexpression reversed this effect. Mechanically, LINC00460 is induced by hypoxia, through binding of the hypoxia-inducible factor 1-α in the promoter region of LINC00460. Furthermore, LINC00460 functioned as an miR-4689 sponge to regulate the downstream target gene UBE2V1, enhancing the stability of mutant p53 in pancreatic cancer cells. LINC00460 also further promotes pancreatic cancer development by sequestering USP10, a cytoplasmic ubiquitin-specific protease that deubiquitinates p53 and enhances its stability. Collectively, our study demonstrated that LINC00460 is a hypoxia-induced lncRNA that plays the role of oncogene in pancreatic cancer by modulating the miR-4689/UBE2V1 axis, sequestering USP10, and ultimately enhancing the stability of mutant p53.