Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer.

OBJECTIVE: Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention. DESIGN: We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies. RESULTS: The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion. CONCLUSION: These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC.

Reconstruction Filters Improving the Spatial Resolution and Signal-to-Noise Ratio of Surface Plasmon Resonance Microscopy.

Benefitting from high sensitivity, real-time, and label-free imaging, surface plasmon resonance microscopy (SPRM) has become a powerful tool for dynamic detection of nanoparticles. However, the evanescent propagation of surface plasmon polaritons (SPPs) induces interference between scattered and launched SPPs, which deteriorates the spatial resolution and signal-to-noise ratio (SNR). Due to the simplicity and fast processing, image reconstruction based on deconvolution has shown the feasibility of improving the spatial resolution of SPRM imaging. Retrieving the particle scattering from SPRM interference imaging by filters is crucial for reconstruction. In this work, we illustrate the effect of filters extracting SPP scattering of nanoparticles with different sizes and shapes for reconstruction. The results indicate that the optimum filters are determined by the material of nanoparticles instead of particle sizes. The reconstruction of single Au and PS nanospheres as well as Ag nanowires with optimum filters is achieved. The reconstructed spatial resolution is improved to 254 nm, and the SNR is increased by 8.1 times. Our research improves the quality of SPRM imaging and provides a reliable method for fast detection of particles with diverse sizes and shapes.

Unveiling the impact of low-frequency electrical stimulation on network synchronization and learning behavior in cultured hippocampal neural networks.

Understanding the dynamics of neural networks and their response to external stimuli is crucial for unraveling the mechanisms associated with learning processes. In this study, we hypothesized that electrical stimulation (ES) would lead to significant alterations in the activity patterns of hippocampal neuronal networks and investigated the effects of low-frequency ES on hippocampal neuronal populations using the microelectrode arrays (MEAs). Our findings revealed significant alterations in the activity of hippocampal neuronal networks following low-frequency ES trainings. Post-stimulation, the neural activity exhibited an organized burst firing pattern characterized by increased spike and burst firings, increased synchronization, and enhanced learning behaviors. Analysis of peri-stimulus time histograms (PSTHs) further revealed that low-frequency ES (1Hz) significantly enhanced neural plasticity, thereby facilitating the learning process of cultured neurons, whereas high-frequency ES (>10Hz) impeded this process. Moreover, we observed a substantial increase in correlations and connectivity within neuronal networks following ES trainings. These alterations in network properties indicated enhanced synaptic plasticity and emphasized the positive impact of low-frequency ES on hippocampal neural activities, contributing to the brain's capacity for learning and memory.

In Situ Growth of Wafer-Scale Patterned Graphene and Fabrication of Optoelectronic Artificial Synaptic Device Array Based on Graphene/n-AlGaN Heterojunction for Visual Learning.

The unique optical and electrical properties of graphene-based heterojunctions make them significant for artificial synaptic devices, promoting the advancement of biomimetic vision systems. However, mass production and integration of device arrays are necessary for visual imaging, which is still challenging due to the difficulty in direct growth of wafer-scale graphene patterns. Here, a novel strategy is proposed using photosensitive polymer as a solid carbon source for in situ growth of patterned graphene on diverse substrates. The growth mechanism during high-temperature annealing is elucidated, leading to wafer-scale graphene patterns with exceptional uniformity, ideal crystalline quality, and precise control over layer number by eliminating the release of volatile from oxygen-containing resin. The growth strategy enables the fabrication of two-inch optoelectronic artificial synaptic device array based on graphene/n-AlGaN heterojunction, which emulates key functionalities of biological synapses, including short-term plasticity, long-term plasticity, and spike-rate-dependent plasticity. Moreover, the mimicry of visual learning in the human brain is attributed to the regulation of excitatory and inhibitory post-synapse currents, following a learning rule that prioritizes initial recognition before memory formation. The duration of long-term memory reaches 10 min. The in situ growth strategy for patterned graphene represents the novelty for fabricating fundamental hardware of an artificial neuromorphic system.

Architecting the metabolic reprogramming survival risk framework in LUAD through single-cell landscape analysis: three-stage ensemble learning with genetic algorithm optimization.

Recent studies have increasingly revealed the connection between metabolic reprogramming and tumor progression. However, the specific impact of metabolic reprogramming on inter-patient heterogeneity and prognosis in lung adenocarcinoma (LUAD) still requires further exploration. Here, we introduced a cellular hierarchy framework according to a malignant and metabolic gene set, named malignant & metabolism reprogramming (MMR), to reanalyze 178,739 single-cell reference profiles. Furthermore, we proposed a three-stage ensemble learning pipeline, aided by genetic algorithm (GA), for survival prediction across 9 LUAD cohorts (n = 2066). Throughout the pipeline of developing the three stage-MMR (3 S-MMR) score, double training sets were implemented to avoid over-fitting; the gene-pairing method was utilized to remove batch effect; GA was harnessed to pinpoint the optimal basic learner combination. The novel 3 S-MMR score reflects various aspects of LUAD biology, provides new insights into precision medicine for patients, and may serve as a generalizable predictor of prognosis and immunotherapy response. To facilitate the clinical adoption of the 3 S-MMR score, we developed an easy-to-use web tool for risk scoring as well as therapy stratification in LUAD patients. In summary, we have proposed and validated an ensemble learning model pipeline within the framework of metabolic reprogramming, offering potential insights for LUAD treatment and an effective approach for developing prognostic models for other diseases.

Heterojunction polarization enhancement and shielding for AlGaN-based solar-blind ultraviolet avalanche detectors.

AlGaN-based solar-blind ultraviolet avalanche detectors have huge potentials in the fields of corona discharge monitoring, biological imaging, etc. Here, we study the impact of the heterojunction polarization-related effects on the AlGaN-based solar-blind ultraviolet avalanche detectors. Our work confirms that the polarization heterojunction is beneficial to reducing avalanche bias and lifting avalanche gain by improving the electric field in the depletion region, while the polarization-induced fixed charges will lead to a redistribution of the electrons, in turn shielding the charges and weakening the electric field enhancement effect. This shielding effect will need external bias to eliminate, and that is why the polarization heterojunction cannot work at relatively low bias but has an enhancement effect at high bias. Controlling the doping level between the hetero-interface can affect the shielding effect. An unintentionally doped polarization heterojunction can effectively reduce the shielding effect, thus reducing the avalanche bias. The conclusions also hold true for the negative polarization regime. We believe our findings can provide some useful insights for the design of the AlGaN-based solar-blind ultraviolet detectors.

Highly reflective Ni/Pt/Al p-electrode for improving the efficiency of an AlGaN-based deep ultraviolet light-emitting diode.

In this work, we propose a highly reflective Ni/Pt/Al p-electrode for AlGaN-based deep ultraviolet (DUV) light-emitting diodes (LEDs) with a wavelength of 276 nm. AlGaN-based DUV LEDs with traditional Al-based reflectivity electrodes suffer from device degradation and wall-plug efficiency (WPE) droop due to the Al diffusion during electrode annealing. By inserting a Pt layer between the Ni contact layer and the Al reflective layer, the contact characteristics of the p-electrode can be optimized by blocking the diffusion of the O and Al atoms, maintaining a high reflectivity of over 80% near 280 nm. Compared to the AlGaN-based DUV LEDs with Ni/Au traditional p-electrodes and Ni/Al traditional reflective p-electrodes, the WPE of the LED with a highly reflective Ni/Pt/Al p-electrode is improved by 10.3% and 30.5%, respectively. Besides, compared to the other novel reflective p-electrodes using multiple annealing or evaporation processes reported for the AlGaN-based DUV LEDs, we provide a new, to the best of our knowledge, optimization method for single evaporation and annealing p-type reflective electrodes, featured with a simpler and more convenient process flow.

Directional surface plasmon polariton scattering using single magnetic nanoparticles.

Directional surface plasmon polaritons (SPPs) are expected to promote the energy efficiency of plasmonic devices, via limiting the energy in a given spatial domain. The directional scattering of dielectric nanoparticles induced by the interference between electric and magnetic responses presents a potential candidate for directional SPPs. Magnetic nanoparticles can introduce permeability as an extra manipulation, whose directional scattered SPPs have not been investigated yet. In this work, we demonstrated the directional scattered SPPs by using single magnetic nanoparticles via simulation and experiment. By increasing the permeability and particle size, the high-order TEM modes are excited inside the particle and induce more forward directional SPPs. It indicated that the particle size manifests larger tuning range compared with the permeability. Experimentally, the maximum forward-to-backward (F-to-B) SPP scattering intensity ratio of 118.52:1 is visualized by using a single 1 µm Fe3O4 magnetic nanoparticle. The directional scattered SPPs of magnetic nanoparticles are hopeful to improve the efficiency of plasmonic devices and pave the way for plasmonic circuits on-chip.

Tissue-engineered bone construct promotes early osseointegration of implants with low primary stability in oversized osteotomy.

OBJECTIVES: To evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy. MATERIALS AND METHODS: An oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate ß (TCP-ß); B: autologous adipose derived-stem cells with TCP-ß (ASCs/TCP-ß); C: ASCs transfected with the enhanced-GFP gene with TCP-ß (EGFP-ASCs/TCP-ß); D: ASCs transfected with the BMP-2 gene with TCP-ß (BMP2-ASCs/TCP-ß). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed. RESULTS: ASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D. CONCLUSION: The low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.

Nanoscale phase separation on an AlGaN surface characterized by scanning diffusion microscopy.

AlGaN is an important material for deep ultraviolet optoelectronic devices and electronic devices. The phase separation on the AlGaN surface means small-scale compositional fluctuations of Al, which is prone to degrade the performance of devices. In order to study the mechanism of the surface phase separation, the Al0.3Ga0.7N wafer was investigated by the scanning diffusion microscopy method based on the photo-assisted Kelvin force probe microscope. The response of the surface photovoltage near the bandgap was quite different for the edge and the center of the island on the AlGaN surface. We utilize the theoretical model of scanning diffusion microscopy to fit the local absorption coefficients from the measured surface photovoltage spectrum. During the fitting process, we introduce as and ab parameters (bandgap shift and broadening) to describe the local variation of absorption coefficients α(as, ab, λ). The local bandgap and Al composition can be calculated quantitatively from the absorption coefficients. The results show that there is lower bandgap (about 305 nm) and lower Al composition (about 0.31) at the edge of the island, compared with those at the center of the island (about 300 nm for bandgap and 0.34 for Al composition). Similar to the edge of the island, there is a lower bandgap at the V-pit defect which is about 306 nm corresponding to the Al composition of about 0.30. These results mean Ga enrichment both at the edge of the island and the V-pit defect position. It proves that scanning diffusion microscopy is an effective method to review the micro-mechanism of AlGaN phase separation.

Plasmonic-enhanced efficiency of AlGaN-based deep ultraviolet LED by graphene/Al nanoparticles/graphene hybrid structure.

The AlGaN-based deep ultraviolet light-emitting diode (DUV LED) has advantages of environmentally friendly materials, tunable emission wavelength, and easy miniaturization. However, the light extraction efficiency (LEE) of an AlGaN-based DUV LED is low, which hinders its applications. Here, we design a graphene/Al nanoparticles/graphene (Gra/Al NPs/Gra) hybrid plasmonic structure, where the strong resonant coupling of local surface plasmons (LSPs) induces a 2.9-times enhancement for the LEE of the DUV LED according to the photoluminescence (PL). The dewetting of Al NPs on a graphene layer by annealing is optimized, resulting in better formation and uniform distribution. The near-field coupling of Gra/Al NPs/Gra is enhanced via charge transfer among graphene and Al NPs. In addition, the skin depth increment results in more excitons being coupled out of multiple quantum wells (MQWs). An enhanced mechanism is proposed, revealing that the Gra/metal NPs/Gra offers a reliable strategy for improving the optoelectronic device performance, which might trigger the advances of LEDs and lasers with high brightness and power density.

Selective detection of nitrofurantoin by histidine-capped silver nanoclusters with blue luminescence.

In view of the significance of nitrofurantoin, there is an urgent need for efficient analytical methods for accurate detection of nitrofurantoin. Considering their superior fluorescence performance and rarity of reports regarding nitrofurantoin detection by fluorescent silver nanoclusters (Ag NCs), Ag NCs with good stability and uniform size were synthesized through a simple method by protection of histidine (His) and reduction of ascorbic acid (AA). Based on the quenching by nitrofurantoin, Ag NCs were applied successfully in the detection of nitrofurantoin with high sensitivity. In the range of 0.5-150 µM, a linear relationship was found between ln(F0 /F) and nitrofurantoin amounts. Static quenching and inner filter effect were proved to be the main quenching mechanisms. Significantly superior selectivity and satisfactory recovery results in bovine serum indicate that Ag NCs provide a better choice for nitrofurantoin detection.

The important role of glial transmitters released by astrocytes in Alzheimer's disease: A perspective from dynamical modeling.

This paper aims to establish a coupling model of neuronal populations and astrocytes and, on this basis, explore the possible mechanism of electroencephalography (EEG) slowing in Alzheimer's disease (AD) from the viewpoint of dynamical modeling. First and foremost, excitatory and inhibitory time constants are shown to induce the early symptoms of AD. The corresponding dynamic nature is mainly due to changes in the amplitude and frequency of the oscillatory behavior. However, there are also a few cases that can be attributed to the change of the oscillation mode caused by the limit cycle bifurcation and birhythmicity. Then, an improved neural mass model influenced by astrocytes is proposed, considering the important effects of glutamate and adenosine triphosphate (ATP) released by astrocytes on the synaptic transmission process reported in experiments. The results show that a dysfunctional astrocyte disrupts the physiological state, causing three typical EEG slowing phenomena reported clinically: the decreased dominant frequency, the decreased rhythmic activity in the α band, and the increased rhythmic activity in the δ+θ band. In addition, astrocytes may control AD when the effect of ATP on synaptic connections is greater than that of glutamate. The control rate depends on the ratio of the effect of glutamate on excitatory and inhibitory synaptic connections. These modeling results can not only reproduce some experimental and clinical results, but, more importantly, may offer a prediction of some underlying phenomena, helping to inspire the disease mechanisms and therapeutic methods of targeting astrocytes.

Study on Chemical Constituents of Panax notoginseng Leaves.

Panax notoginseng (Burk.) F. H. is a genuine medicinal material in Yunnan Province. As accessories, P. notoginseng leaves mainly contain protopanaxadiol saponins. The preliminary findings have indicated that P. notoginseng leaves contribute to its significant pharmacological effects and have been administrated to tranquilize and treat cancer and nerve injury. Saponins from P. notoginseng leaves were isolated and purified by different chromatographic methods, and the structures of 1-22 were elucidated mainly through comprehensive analyses of spectroscopic data. Moreover, the SH-SY5Y cells protection bioactivities of all isolated compounds were tested by establishing L-glutamate models for nerve cell injury. As a result, twenty-two saponins, including eight dammarane saponins, namely notoginsenosides SL1-SL8 (1-8), were identified as new compounds, together with fourteen known compounds, namely notoginsenoside NL-A3 (9), ginsenoside Rc (10), gypenoside IX (11), gypenoside XVII (12), notoginsenoside Fc (13), quinquenoside L3 (14), notoginsenoside NL-B1 (15), notoginsenoside NL-C2 (16), notoginsenoside NL-H2 (17), notoginsenoside NL-H1 (18), vina-ginsenoside R13 (19), ginsenoside II (20), majoroside F4 (21), and notoginsenoside LK4 (22). Among them, notoginsenoside SL1 (1), notoginsenoside SL3 (3), notoginsenoside NL-A3 (9), and ginsenoside Rc (10) showed slight protective effects against L-glutamate-induced nerve cell injury (30 µM).

All-type optical logic gates using plasmonic coding metamaterials and multi-objective optimization.

In this article, we propose a multiport plasmonic system (MPS) for implementing all-type logic gates based on coding metamaterials and inverse design technology. Compared to traditional plasmonic logic gates, the coding metamaterials based on metal-dielectric-metal (MDM) structures provide powerful programmability for manipulating electromagnetic (EM) waves and have a compact footprint (0.8 µm × 1.1 µm) for integration. To improve the performance of logic gates, the nondominated sorting genetic algorithm version II (NSGA-II) are used to optimize the distributions of coding metamaterials. After the optimization, the simulation results show that all types of logic gates (AND, OR, NOT, NAND, NOR, XNOR, and XOR) can be obtained with an operating wavelength of 1.31 µm. The maximum extinction ratios between logic states "1" and "0" reach 10.15 dB, 57.54 dB, 43.25 dB, 20.76 dB, 10.42 dB, 24.04 dB, and 27.74 dB for the AND, OR, NOT, NAND, NOR, XNOR, and XOR gates, respectively. Moreover, wavelength-tunable logic operations are also demonstrated to work within a wide spectrum. Our proposed plasmonic system not only provides a universal scheme for implementing all-type compact logic gates for optical processing and computing but also demonstrates effective applications of inverse design in nanophotonic devices.

Effects of nanoparticle sizes, shapes, and permittivity on plasmonic imaging.

Plasmonic imaging has exhibited superiority in label-free and fast detection to single nanoparticles due to its high sensitivity and high temporal resolution, which plays an important role in environmental monitoring and biomedical research. As containing plenty of information associated with particle features, plasmonic imaging has been used for identifying the particle sizes, shapes, and permittivity. Yet, the effects of the nanoparticle features on plasmonic imaging are not investigated, which hinders the in-depth understanding to plasmonic imaging and its applications in particle identification. In this work, we analyzed five types of nanoparticles, including polystyrene (PS), Au, silicon nanospheres as well as PS and Ag nanowires. We illustrated the effects of nanoparticle sizes, shapes, and permittivity on spatial resolution, imaging contrast, and interference fringes. We found that nanoparticle sizes and permittivity influenced the imaging contrast. Via introducing size parameter relevant to interference fringes, the connection between particle shape and reduction rate of size parameter is built, and the effects of particle shapes on the interference patterns are revealed. Our research provides a basis for improving the plasmonic imaging and presents guidance for applications on particle identification in nano-detection, biosensor, and environmental monitoring.

Hybrid metal/Ga2O3/GaN ultraviolet detector for obtaining low dark current and high responsivity.

In this work, we have proposed and fabricated a metal/Ga2O3/GaN hybrid structure metal-semiconductor-metal ultraviolet photodetector with low dark current and high responsivity. The Schottky contact of Ni/Ga2O3 makes the Ga2O3 layer fully depleted. The strong electric field in the Ga2O3 depletion region can push the photo-induced electrons from the Ga2O3 layer into the GaN layer for more efficient carrier transport. Therefore, the hybrid structure simultaneously utilizes the advantage of the absorption to solar-blind ultraviolet light by the Ga2O3 layer and the high electron mobility of the GaN layer. Thus, the dark current and the photocurrent for the proposed device can be greatly improved. As a result, an extremely high photo-to-dark-current ratio of 1.46 × 106 can be achieved. Furthermore, quick rise and fall times of 0.213 s and 0.027 s at the applied bias of 6 V are also obtained, respectively.

Regulating the valence level arrangement of high-Al-content AlGaN quantum wells using additional potentials with Mg doping.

Quantum states and arrangement of valence levels determine most of the electronic and optical properties of semiconductors. Since the crystal field split-off hole (CH) band is the top valence band in high-Al-content AlGaN, TM-polarized optical anisotropy has become the limiting factor for efficient deep-ultraviolet (DUV) light emission. Additional potentials, including on-site Coulomb interaction and orbital state coupling induced by magnesium (Mg) doping, are proposed in this work to regulate the valence level arrangement of AlN/Al0.75Ga0.25N quantum wells (QWs). Diverse responses of valence quantum states |pi〉 (i = x, y, or z) of AlGaN to additional potentials due to different configurations and interactions of orbitals revealed by first-principles simulations are understood in terms of the linear combination of atomic orbital states. A positive charge and large Mg dopant in QWs introduce an additional Coulomb potential and modulate the orbital coupling distance. For the CH band (pz orbital), the Mg-induced Coulomb potential compensates the orbital coupling energy. Meanwhile, the heavy/light hole (HH/LH) bands (px and py orbitals) are elevated by the Mg-induced Coulomb potential. Consequently, HH/LH energy levels are relatively shifted upward and replace the CH level to be the top of the valence band. The inversion of optical anisotropy and enhancement of TE-polarized emission are further confirmed experimentally via spectroscopic ellipsometry.

EPS8 supports pancreatic cancer growth by inhibiting BMI1 mediated proteasomal degradation of ALDH7A1.

Aldehyde dehydrogenase 7 family member A1 (ALDH7A1) is an enzyme catalyzing lipid peroxidation of fatty aldehydes. It plays a critical role in sustaining high oxygen consumption rate (OCR) and ATP production in pancreatic ductal adenocarcinoma (PADC). However, why PADC cells maintain a relatively high level of ALDH7A1 concentration is still not well understood. In the current study, we explored the interplay between epidermal growth factor receptor kinase substrate 8 (EPS8) and ALDH7A1 in PADC cells. PADC cell lines MIA PaCa-2 and AsPANC-1 were used for in vitro and in vivo studies. The co-IP assay showed mutual interactions between Flag-EPS8 and Myc-ALDH7A1 in both MIA PaCa-2 and AsPANC-1 cells. EPS8 knockdown resulted in decreased ALDH7A1 protein levels and increased poly-ubiquitination. An interaction was observed between ALDH7A1 and BMI1 but not between BMI1 and EPS8. BMI1 knockdown reduced ALDH7A1 poly-ubiquitination and degradation caused by EPS8 knockdown. Dual EPS8 and ALDH7A1 knockdown had a synergistic effect on suppressing PADC cell proliferation in vitro and in vivo. In conclusion, this study revealed that EPS8 supports PADC growth by interacting with ALDH7A1 and inhibiting BMI1 mediated proteasomal degradation of ALDH7A1.