lncRNA directs cooperative epigenetic regulation downstream of chemokine signals.

lncRNAs are known to regulate a number of different developmental and tumorigenic processes. Here, we report a role for lncRNA BCAR4 in breast cancer metastasis that is mediated by chemokine-induced binding of BCAR4 to two transcription factors with extended regulatory consequences. BCAR4 binding of SNIP1 and PNUTS in response to CCL21 releases the SNIP1's inhibition of p300-dependent histone acetylation, which in turn enables the BCAR4-recruited PNUTS to bind H3K18ac and relieve inhibition of RNA Pol II via activation of the PP1 phosphatase. This mechanism activates a noncanonical Hedgehog/GLI2 transcriptional program that promotes cell migration. BCAR4 expression correlates with advanced breast cancers, and therapeutic delivery of locked nucleic acids (LNAs) targeting BCAR4 strongly suppresses breast cancer metastasis in mouse models. The findings reveal a disease-relevant lncRNA mechanism consisting of both direct coordinated protein recruitment and indirect regulation of transcription factors.

Martian dunes indicative of wind regime shift in line with end of ice age.

Orbital observations suggest that Mars underwent a recent 'ice age' (roughly 0.4-2.1 million years ago), during which a latitude-dependent ice-dust mantle (LDM)1,2 was emplaced. A subsequent decrease in obliquity amplitude resulted in the emergence of an 'interglacial period'1,3 during which the lowermost latitude LDM ice4-6 was etched and removed, returning it to the polar cap. These observations are consistent with polar cap stratigraphy1,7, but lower- to mid-latitude in situ surface observations in support of a glacial-interglacial transition that can be reconciled with mesoscale and global atmospheric circulation models8 is lacking. Here we present a suite of measurements obtained by the Zhurong rover during its traverse across the southern LDM region in Utopia Planitia, Mars. We find evidence for a stratigraphic sequence involving initial barchan dune formation, indicative of north-easterly winds, cementation of dune sediments, followed by their erosion by north-westerly winds, eroding the barchan dunes and producing distinctive longitudinal dunes, with the transition in wind regime consistent with the end of the ice age. The results are compatible with the Martian polar stratigraphic record and will help improve our understanding of the ancient climate history of Mars9.

Two-billion-year-old volcanism on the Moon from Chang'e-5 basalts.

The Moon has a magmatic and thermal history that is distinct from that of the terrestrial planets1. Radioisotope dating of lunar samples suggests that most lunar basaltic magmatism ceased by around 2.9-2.8 billion years ago (Ga)2,3, although younger basalts between 3 Ga and 1 Ga have been suggested by crater-counting chronology, which has large uncertainties owing to the lack of returned samples for calibration4,5. Here we report a precise lead-lead age of 2,030 ± 4 million years ago for basalt clasts returned by the Chang'e-5 mission, and a 238U/204Pb ratio (µ value)6 of about 680 for a source that evolved through two stages of differentiation. This is the youngest crystallization age reported so far for lunar basalts by radiometric dating, extending the duration of lunar volcanism by approximately 800-900 million years. The µ value of the Chang'e-5 basalt mantle source is within the range of low-titanium and high-titanium basalts from Apollo sites (µ value of about 300-1,000), but notably lower than those of potassium, rare-earth elements and phosphorus (KREEP) and high-aluminium basalts7 (µ value of about 2,600-3,700), indicating that the Chang'e-5 basalts were produced by melting of a KREEP-poor source. This age provides a pivotal calibration point for crater-counting chronology in the inner Solar System and provides insight on the volcanic and thermal history of the Moon.

Chang'E-4 initial spectroscopic identification of lunar far-side mantle-derived materials.

Over 60 years of spacecraft exploration has revealed that the Earth's Moon is characterized by a lunar crust1 dominated by the mineral plagioclase, overlying a more mafic (richer in iron and magnesium) mantle of uncertain composition. Both crust and mantle formed during the earliest stages of lunar evolution when late-stage accretional energy caused a molten rock (magma) ocean, flotation of the light plagioclase, sinking of the denser iron-rich minerals, such as olivine and pyroxene, and eventually solidification2. Very large impact craters can potentially penetrate through the crust and sample the lunar mantle. The largest of these craters is the approximately 2,500-kilometre-diameter South Pole-Aitken (SPA) basin3 on the lunar far side. Evidence obtained from orbiting spacecraft shows that the floor of the SPA basin is rich in mafic minerals4, but their mantle origin is controversial and their in situ geologic settings are poorly known. China's Chang'E-4 lunar far-side lander recently touched down in the Von Kármán crater5,6 to explore the floor of the huge SPA basin and deployed its rover, Yutu-2. Here we report on the initial spectral observations of the Visible and Near Infrared Spectrometer (VNIS)7 onboard Yutu-2, which we interpret to represent the presence of low-calcium (ortho)pyroxene and olivine, materials that may originate from the lunar mantle. Geological context6 suggests that these materials were excavated from below the SPA floor by the nearby 72-km-diameter Finsen impact crater event, and transported to the landing site. Continued exploration by Yutu-2 will target these materials on the floor of the Von Kármán crater to understand their geologic context, origin and abundance, and to assess the possibility of sample-return scenarios.

Highly sensitive mid-infrared methane remote sensor using a deep neural network filter.

A novel mid-infrared methane remote sensor integrated on a movable platform based on a 3.291-µm interband cascade laser (ICL) and wavelength modulation spectroscopy (WMS) is proposed. A transmitting-receiving coaxial, visualized optical layout is employed to minimize laser energy loss. Using a hollow retro-reflector remotely deployed as a cooperative target, the atmospheric average methane concentration over a 100-meter optical range is measured with high sensitivity. A deep neural network (DNN) filter is used for second harmonic (2f) signal denoising to compensate for the performance shortcomings of conventional filtering. Allan deviation analysis indicated that after applying the DNN filter, the limit of detection (LOD) of methane was 86.62 ppb with an average time of 1 s, decreasing to 12.03 ppb with an average time of 229 s, which is a significant promotion compared to similar work reported. The high sensitivity and stability of the proposed sensor are shown through a 24-hour continuous monitoring experiment of atmospheric methane conducted outdoors, providing a new solution for high-sensitivity remote sensing of atmospheric methane.

Simulation evaluation of a single-photon laser methane remote sensor for leakage rate monitoring.

We propose a novel methane leakage rate remote sensor that combines a single-photon avalanche diode detector with a near-infrared 1653.7 nm low-power laser. The proposed M sequence and triangle wave signal modulation method simultaneously realizes the detection of methane leakage and target point clouds. Innovatively, the sensor's methane concentration and leakage rate quantification ability were simulated by combining the Gaussian plume diffusion model and the Risley prism. The effects of the prism rotation ratio, wind speed, leakage rate, atmospheric stability (AS), target reflectivity, signal averaging period, and concentration spatial interpolation method on leakage rate are discussed. When plume methane concentrations reduce from 10,000 to 500 ppm·m, the relative concentration bias rise from 1% to 30%, the absolute concentration bias is approximately 100 ppm·m. Two spatial concentration interpolation methods introduced leakage rate bias ranging from 6%-25%. For a low AS, the leakage rate bias under the cubic interpolation method was small (approximately 1.6%). In addition, when the initial leakage rate increased from 100 to 1,000 mg/s, the leakage rate bias was approximately 20% smaller.

Temperature-Automated Calibration Methods for a Large-Area Blackbody Radiation Source.

High-precision temperature control of large-area blackbodies has a pivotal role in temperature calibration and thermal imaging correction. Meanwhile, it is necessary to correct the temperature difference between the radiating (surface of use) and back surfaces (where the temperature sensor is installed) of the blackbody during the testing phase. Moreover, large-area blackbodies are usually composed of multiple temperature control channels, and manual correction in this scenario is error-prone and inefficient. At present, there is no method that can achieve temperature-automated calibration for a large-area blackbody radiation source. Therefore, this article is dedicated to achieving temperature-automated calibration for a large-area blackbody radiation source. First, utilizing two calibrated infrared thermometers, the optimal temperature measurement location was determined using a focusing algorithm. Then, a three-axis movement system was used to obtain the true temperature at the same measurement location on a large-area blackbody surface from different channels. This temperature was subtracted from the blackbody's back surface. The temperature difference was calculated employing a weighted algorithm to derive the parameters for calibration. Finally, regarding experimental verification, the consistency error of the temperature measurement point was reduced by 85.4%, the temperature uniformity of the surface source was improved by 40.4%, and the average temperature measurement deviation decreased by 43.8%. In addition, this system demonstrated the characteristics of strong environmental adaptability that was able to perform temperature calibration under the working conditions of a blackbody surface temperature from 100 K to 573 K, which decreased the calibration time by 9.82 times.

Adaptive Resolution Enhancement for Visual Attention Regions Based on Spatial Interpolation.

Resolution enhancement is crucial for human vision. However, it can be resource-consuming in the display pipeline. Therefore, there is a need to develop a lightweight resolution improvement algorithm specifically targeting visual attention regions. This paper presents a spatial-interpolation-based algorithm to improve the resolution of the visual attention area. The eye-tracking system consists of a near-infrared camera and an event camera is proposed to obtain the 3D gaze vector and eye moving trajectory. Secondly, the observation coordinates are obtained by gaze vectors, and the visual attention region is defined by the sensitive field-of-view angle. Then, interpolation-based adaptive spatial resolution enhancement and contrast enhancement adjustment are performed in the visual attention area. Finally, the feasibility of the proposed method is tested on both qualitative and quantitative dimensions. The experimental results demonstrate that the proposed method can significantly improve the visual effects.

Instrumental Neutron Activation Analysis of Chang'E-5 Lunar Regolith Samples.

The Chang'E-5 (CE-5) lunar samples were analyzed nondestructively for more than 40 elements by instrumental neutron activation analysis (INAA) with a strict quality assurance and quality control. Based on the INAA results, some new observations and discoveries were made. Major, minor, and trace elements in CE-5 are very different from those of the Earth and Apollo lunar samples. The rare earth element (REE) pattern indicated that the CE-5 lunar samples are mare basalts with a clear negative anomaly in Eu. Element correlations are a very interesting discovery; for example, the ratios of Ba/La and FeO/MnO in CE-5 are almost identical to those of the Apollo lunar samples. These observations and discoveries will enrich the understanding of the formation and evolution of the Moon.

A Snapshot Imaging Spectrometer Based on Uniformly Distributed-Slit Array (UDA).

Herein, we propose a system for a snapshot video hyperspectral imaging method based on a uniformly distributed-slit array (UDA) coding plate that not only effectively improves the scanning speed of spectrometers but also achieves a high spectral fidelity of snapshot videos. A mathematical model and optical link simulation of the new system are established. The analysis results show that the proposed method can more efficiently collect information and restore the spectral data cube, and the spectral smile of the system is less than 4.86 µm. The results of the spectral performance and external imaging tests of the system show that the system has the ability to collect spatial spectrum video information with a frame rate of 10 Hz and identify dynamic targets, laying a foundation for the design of a system with a higher frame rate and resolution.

Real-Time Hyperspectral Video Acquisition with Coded Slits.

We propose a real-time hyperspectral video acquisition system that uses coded slits. Conventional imaging spectrometers usually have scanning mechanisms that reduce the temporal resolution or sacrifice the spatial resolution to acquire spectral information instantly. Recently, computational spectral imaging has been applied to realize high-speed or high-performance spectral imaging. However, the most current computational spectral imaging systems take a long time to reconstruct spectral data cubes from limited measurements, which limits real-time hyperspectral video acquisition. In this work, we propose a new computational spectral imaging system. We substitute the slit in a conventional scanning-based imaging spectrometer with coded slits, which can achieve the parallel acquisition of spectral data and thus an imaging speed that is several times higher. We also apply an electronically controlled translation stage to use different codes at each exposure level. The larger amount of data allows for fast reconstruction through matrix inversion. To solve the problem of a trade-off between imaging speed and image quality in high-speed spectral imaging, we analyze the noise in the system. The severe readout noise in our system is suppressed with S-matrix coding. Finally, we build a practical prototype that can acquire hyperspectral video with a high spatial resolution and a high signal-to-noise ratio at 5 Hz in real time.

The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling.

BACKGROUND & AIMS: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic. METHODS: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2'-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients. RESULTS: High expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients. CONCLUSIONS: We found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.

Temperature and Emissivity Inversion Accuracy of Spectral Parameter Changes and Noise of Hyperspectral Thermal Infrared Imaging Spectrometers.

The emergence of hyperspectral thermal infrared imaging spectrometers makes it possible to retrieve both the land surface temperature (LST) and the land surface emissivity (LSE) simultaneously. However, few articles focus on the problem of how the instrument's spectral parameters and instrument noise level affect the LST and LSE inversion errors. In terms of instrument development, this article simulated three groups of hyperspectral thermal infrared data with three common spectral parameters and each group of data includes tens of millions of simulated radiances of 1525 emissivity curves with 17 center wavelength shift ratios, 6 full width at half maximum (FWHM) change ratios and 6 noise equivalent differential temperatures (NEDTs) under 15 atmospheric conditions with 6 object temperatures, inverted them by two temperature and emissivity separation methods (ISSTES and ARTEMISS), and analyzed quantitatively the effects of the spectral parameters change and noise of an instrument on the LST and LSE inversion errors. The results show that: (1) center wavelength shifts and noise affect the inversion errors strongly, while FWHM changes affect them weakly; (2) the LST and LSE inversion errors increase with the center wavelength shift ratio in a quadratic function and increase with FWHM change ratio slowly and linearly for both the inversion methods, however they increase with NEDT in an S-curve for ISSTES while they increase with NEDT slightly and linearly for ARTEMISS. During the design and development of a hyperspectral thermal infrared instrument, it is highly recommended to keep the potential center wavelength shift within 1 band and keep NEDT within 0.1K (corresponding LST error < 1K and LSE error < 0.015) for normal applications and within 0.03K (corresponding LST error < 0.5K and LSE error < 0.01) for better application effect and level.

The Scientific Information Model of Chang'e-4 Visible and Near-IR Imaging Spectrometer (VNIS) and In-Flight Verification.

The Chang'e-4 (CE-4) lunar rover, equipped with a visible and near-IR imaging spectrometer (VNIS) based on acousto-optic tunable filter spectroscopy, was launched to the far side of the moon on December 8, 2018. The detection band of the VNIS ranges from 0.45 to 2.4 µm. Because of the weak reflection of infrared radiation from the lunar surface, a static electronic phase-locked acquisition method is adopted in the infrared channel for signal amplification. In this paper, full-link simulations and modeling are conducted on the infrared channel information flow of the instrument. The signal characteristics of the VNIS are analyzed in depth, and the signal to noise ratio (SNR) prediction and laboratory verification are presented. On 4 January 2019, the VNIS started working successfully and acquired high-resolution spectrum data of the far side of the moon for the first time. Through analysis we have found that the SNR ratio is in line with our predictions, and the data obtained by VNIS in orbit are consistent with the information model proposed in this paper.

Volcanic history of the Imbrium basin: A close-up view from the lunar rover Yutu.

We report the surface exploration by the lunar rover Yutu that landed on the young lava flow in the northeastern part of the Mare Imbrium, which is the largest basin on the nearside of the Moon and is filled with several basalt units estimated to date from 3.5 to 2.0 Ga. The onboard lunar penetrating radar conducted a 114-m-long profile, which measured a thickness of ∼5 m of the lunar regolith layer and detected three underlying basalt units at depths of 195, 215, and 345 m. The radar measurements suggest underestimation of the global lunar regolith thickness by other methods and reveal a vast volume of the last volcano eruption. The in situ spectral reflectance and elemental analysis of the lunar soil at the landing site suggest that the young basalt could be derived from an ilmenite-rich mantle reservoir and then assimilated by 10-20% of the last residual melt of the lunar magma ocean.

Controlling chaotic spin-motion entanglement of ultracold atoms via spin-orbit coupling.

We study the spatially chaoticity-dependent spin-motion entanglement of a spin-orbit (SO) coupled Bose-Einstein condensate with a source of ultracold atoms held in an optical superlattice. In the case of phase synchronization, we analytically demonstrate that (a) the SO coupling (SOC) leads to the generation of spin-motion entanglement; (b) the area of the high-chaoticity parameter region inversely relates to the SOC strength which renormalizes the chemical potential; and (c) the high-chaoticity is associated with the lower chemical potential and the larger ratio of the short-lattice depth to the longer-lattice depth. Then, we numerically generate the Poincaré sections to pinpoint that the chaos probability is enhanced with the decrease in the SOC strength and/or the spin-dependent current components. The existence of chaos is confirmed by computing the corresponding largest Lyapunov exponents. For an appropriate lattice depth ratio, the complete stop of one of (or both) the current components is related to the full chaoticity. The results mean that the weak SOC and/or the small current components can enhance the chaoticity. Based on the insensitivity of chaos probability to initial conditions, we propose a feasible scheme to manipulate the ensemble of chaotic spin-motion entangled states, which may be useful in coherent atom optics with chaotic atom transport.

Infrared Image Super Resolution by Combining Compressive Sensing and Deep Learning.

Super resolution methods alleviate the high cost and high difficulty in applying high resolution infrared image sensors. In this paper we present a novel single image super resolution method for infrared images by combining compressive sensing theory and deep learning. Low resolution images can be regarded as the compressed sampling results of the high resolution ones in compressive sensing. With sparsity in this theory, higher resolution images can be reconstructed. However, because of diverse level of sparsity for different images, the output contains noise and loss of high frequency information. Deep convolutional neural network provides a solution to relieve the noise and supplement some missing high frequency information. By concatenating two methods, we manage to produce better results in super resolution tasks for infrared images than SRCNN and ScSR. PSNR and SSIM values are used to quantify the performance. Applying our method to open datasets and actual infrared imaging experiments, we also find better visual results are preserved.

Optical design, laboratory test, and calibration of airborne long wave infrared imaging spectrometer.

We discuss and evaluate a long wave infrared imaging spectrometer in terms of its opto-mechanical design and analysis, alignment, testing, and calibration. The instrument is a practical airborne sensor achieving high spectral resolution and sensitive noise equivalent delta temperature. The instrument operates in the 8 to 12.5 µm spectral region with 28.85 nm spectral sampling, 1 mrad instantaneous field of view, and >40° cross track field. The instrument comprises three uniform sub-modules with identical design parameters and performances. The sub-module design is based on a refractive foreoptics feeding an all-reflective spectrometer. The optical form of the spectrometer is a double-pass reflective triplet with a flat grating, which has a fast f/2 and high optical throughput. Cryogenic optics of 100 K is implemented only for the spectrometer. Assembly and thermal deformation and focusing adjustment design are particularly considered for this low temperature. All the mirrors of the spectrometer are opto-mechanical-integrated designed and manufactured by single-point diamond turning technology. We consider the center sub-module as an example, and we present its laboratory testing results and calibration; the results indicate the instrument's potential value in airborne sensing.

A rice plastidial nucleotide sugar epimerase is involved in galactolipid biosynthesis and improves photosynthetic efficiency.

Photosynthesis is the final determinator for crop yield. To gain insight into genes controlling photosynthetic capacity, we selected from our large T-DNA mutant population a rice stunted growth mutant with decreased carbon assimilate and yield production named photoassimilate defective1 (phd1). Molecular and biochemical analyses revealed that PHD1 encodes a novel chloroplast-localized UDP-glucose epimerase (UGE), which is conserved in the plant kingdom. The chloroplast localization of PHD1 was confirmed by immunoblots, immunocytochemistry, and UGE activity in isolated chloroplasts, which was approximately 50% lower in the phd1-1 mutant than in the wild type. In addition, the amounts of UDP-glucose and UDP-galactose substrates in chloroplasts were significantly higher and lower, respectively, indicating that PHD1 was responsible for a major part of UGE activity in plastids. The relative amount of monogalactosyldiacylglycerol (MGDG), a major chloroplast membrane galactolipid, was decreased in the mutant, while the digalactosyldiacylglycerol (DGDG) amount was not significantly altered, suggesting that PHD1 participates mainly in UDP-galactose supply for MGDG biosynthesis in chloroplasts. The phd1 mutant showed decreased chlorophyll content, photosynthetic activity, and altered chloroplast ultrastructure, suggesting that a correct amount of galactoglycerolipids and the ratio of glycolipids versus phospholipids are necessary for proper chloroplast function. Downregulated expression of starch biosynthesis genes and upregulated expression of sucrose cleavage genes might be a result of reduced photosynthetic activity and account for the decreased starch and sucrose levels seen in phd1 leaves. PHD1 overexpression increased photosynthetic efficiency, biomass, and grain production, suggesting that PHD1 plays an important role in supplying sufficient galactolipids to thylakoid membranes for proper chloroplast biogenesis and photosynthetic activity. These findings will be useful for improving crop yields and for bioenergy crop engineering.

GPX4 transcriptionally promotes liver cancer metastasis via GRHL3/PTEN/PI3K/AKT axis.

Hepatocellular carcinoma (HCC) is among the most fatal types of malignancy, with a high prevalence of relapse and limited treatment options. As a critical regulator of ferroptosis and redox homeostasis, glutathione peroxidase 4 (GPX4) is commonly upregulated in HCC and is hypothesized to facilitate cancer metastasis, but this has not been fully explored in HCC. Here, we report that up-regulated GPX4 expression in HCC is strongly associated with tumor metastasis. FACS-based in vivo and in vitro analysis revealed that a cell subpopulation featuring lower cellular reactive oxygen species levels and ferroptosis resistance were involved in GPX4-mediated HCC metastasis. Mechanistically, GPX4 overexpressed in HCC tumor cells was enriched in the nucleus and transcriptionally silenced GRHL3 expression, thereby activating PTEN/PI3K/AKT signaling and promoting HCC metastasis. Functional studies demonstrated that GPX4 amino acids 110-145 are a binding site that interacts with the GRHL3 promoter. As AKT is a downstream target of GPX4, we combined the AKT inhibitor, AKT-IN3, with lenvatinib to effectively inhibit HCC tumor cell metastasis. Overall, these results indicate that the GPX4/GRHL3/PTEN/PI3K/AKT axis controls HCC cell metastasis and lenvatinib combined with AKT-IN3 represents a potential therapeutic strategy for patients with metastatic HCC.