Preliminary analysis of global column-averaged CO2 concentration data from the spaceborne aerosol and carbon dioxide detection lidar onboard AEMS.

In contrast to the passive remote sensing of global CO2 column concentrations (XCO2), active remote sensing with a lidar enables continuous XCO2 measurements throughout the entire atmosphere in daytime and nighttime. The lidar could penetrate most cirrus and is almost unaffected by aerosols. Atmospheric environment monitoring satellite (AEMS, also named DQ-1) aerosol and carbon dioxide detection Lidar (ACDL) is a novel spaceborne lidar that implements a 1572 nm integrated path differential absorption (IPDA) method to measure the global XCO2 for the first time. In this study, special methods have been developed for ACDL data processing and XCO2 retrieval. The CO2 measurement data products of ACDL, including the differential absorption optical depth between the online and offline wavelengths, the integral weighting function, and XCO2, are presented. The results of XCO2 measurements over the period from 1st June 2022 to 30th June 2022 (first month data of ACDL) are analyzed to demonstrate the measurement capabilities of the spaceborne ACDL system.

Airborne atmospheric carbon dioxide measurement using 1.5 µm laser double-pulse IPDA lidar over a desert area.

An integrated path differential absorption (IPDA) lidar can accurately measure regional C O 2 weighted column average concentrations (X C O 2), which are crucial for understanding the carbon cycle in climate change studies. To verify the performance and data inversion methods of space-borne IPDA lidar, in July 2021, we conducted an airborne lidar validation experiment in Dunhuang, Gansu Province, China. An aircraft was equipped with a lidar system developed to measure X C O 2 and an in situ greenhouse gas analyzer (GGA). To minimize measurement errors, energy monitoring was optimized. The system bias error of the DAOD was determined by changing the laser output mode from the off/on to the on/on mode. The X C O 2 inversion results obtained through comparing the schemes of averaging signals before "log (logarithm)" and averaging after "log" indicate that the former performs better. The IPDA lidar measured X C O 2 over the validation site at 405.57 ppm, and both the IPDA lidar and GGA measured sudden changes in the C O 2 concentration. The assimilation data showed a similar trend according to the altitude to the data measured by the in situ instrument. A comparison of the mean X C O 2 derived from the GGA results and assimilation data with the IPDA lidar measurements showed biases of 0.80 and 1.12 ppm, respectively.

Robust algorithm for precise XCO2 retrieval using single observation of IPDA LIDAR.

CO2 column-weighted dry-air mixing ratio (XCO2) products with high precision and spatial resolution are essential for inverting CO2 fluxes and promoting our understanding of global climate change. Compared with passive remote sensing methods, IPDA LIDAR, as an active remote sensing technique, offers many advantages in measuring XCO2. However, a significant random error in IPDA LIDAR measurements causes XCO2 values calculated directly from LIDAR signals to be unqualified as the final XCO2 products. Hence, we propose an efficient particle filter-based inversion of CO2 for single observation (EPICSO) algorithm to precisely retrieve the XCO2 of every LIDAR observation while preserving the high spatial resolution of LIDAR measurements. The EPICSO algorithm adopts the sliding average results as the first estimate of the local XCO2; subsequently, it estimates the difference between two adjacent XCO2 points and calculates the posterior probability of XCO2 based on particle filter theory. To evaluate the performance of the EPICSO algorithm numerically, we perform an EPICSO to process pseudo-observation data. The simulation results show that the results retrieved by the EPICSO algorithm satisfy the required high precision and that the algorithm is robust to a significant amount of random errors. In addition, we utilize LIDAR observation data from actual experiments in Hebei, China, to validate the performance of the EPICSO algorithm. The results retrieved by the EPICSO algorithm are more consistent with the actual local XCO2 than those of the conventional method, indicating that the EPICSO algorithm is efficient and practical for retrieving XCO2 with high precision and spatial resolution.

Diagnostic Value of the Combination of Ultrasonographic Optic Nerve Sheath Diameter and Width of Crural Cistern with Respect to the Intracranial Pressure in Patients Treated with Decompressive Craniotomy.

BACKGROUND: The monitoring of intracranial pressure (ICP) and detection of increased ICP are crucial because such increases may cause secondary brain injury and a poor prognosis. Although numerous ultrasound parameters, including optic nerve sheath diameter (ONSD), width of the crural cistern (WCC), and the flow velocities of the central retinal artery and middle cerebral artery, can be measured in patients after hemicraniectomy, researchers have yet to determine which of these is better for evaluating ICP. This study aimed to analyze the correlation between ICP and ultrasound parameters and investigate the best noninvasive estimator of ICP. METHODS: This observational study enrolled 50 patients with brain injury after hemicraniectomy from January 2021 to December 2021. All patients underwent invasive ICP monitoring with microsensor, transcranial, and ocular ultrasound postoperatively. We measured the ONSD including the dura mater (ONSDI), the ONSD excluding the dura mater, the optic nerve diameter (OND), the eyeball transverse diameter (ETD), the WCC, and the flow velocities in the central retinal artery and middle cerebral artery. Then, we calculated the ONSDI-OND (the difference between ONSDI and OND) and ONSDI/ETD (the ratio of ONSDI to ETD). Patients were divided into a normal ICP group (n = 35) and an increased ICP group (≥ 20 mm Hg, n = 15) according to the ICP measurements. Correlations were then assessed between the values of the ultrasound parameters and ICP. RESULTS: The ONSDI, ONSDI-OND, and ONSDI/ETD were positively associated with ICP (r = 0.455, 0.482, 0.423 and p = 0.001, < 0.001, 0.002, respectively), whereas the WCC was negatively associated with ICP (r = - 0.586, p < 0.001). The WCC showed the highest predictive power for increased ICP (area under the receiver operating characteristic curve [AUC] = 0.904), whereas the ONSDI-OND and ONSDI also presented with acceptable predictive power among the ONSD-related parameters (AUC = 0.831, 0.803, respectively). The cutoff values for increased ICP prediction for ONSDI, ONSDI-OND, and WCC were 6.29, 3.03, and 3.68 mm, respectively. The AUC of the combination of ONSDI-OND and WCC was 0.952 (95% confidence interval 0.896-1.0, p < 0.001). CONCLUSIONS: The ONSDI, ONSDI-OND, and WCC were correlated with ICP and had acceptable accuracy levels in estimating ICP in patients after hemicraniectomy. Furthermore, WCC showed a higher diagnostic value than ONSD-related parameters, and the combination of ONSDI-OND and WCC was a satisfactory predictor of increased ICP.

Calibration experiments based on a CO2 absorption cell for the 1.57-µm spaceborne IPDA LIDAR.

The spaceborne IPDA LIDAR has the potential to measure the global atmosphere CO2 column concentrations with high accuracy. For this kind of LIDAR, system calibration experiments in the laboratory are of high importance. In this study, a specially-customized CO2 absorption cell is employed to simulate the CO2 column absorption of the spaceborne platform. Then calibration experiments are constructed for the receiving system and the entire LIDAR system. The absorption of several different XCO2 concentrations from 400 to 415 ppm in the atmosphere is equivalent to that of the absorption cell charged with different pressures of pure CO2. Under the zero pressure of the absorption cell, the calculated equivalent column average concentration (XCO2) is 12.53 ppm, which acts as system bias. In the calibration experiments, the absolute errors are all less than 1 ppm. And the standard deviations (STDs) are less than 1.1 ppm (148-shot averaging) and 0.8 ppm (296-shot averaging) for receiving system and less than 1.2 ppm and 0.9 ppm for the IPDA LIDAR system. All the results of different average times are close to each other and less than 1 ppm, which proves the high accuracy of the IPDA LIDAR system. In addition, the XCO2 concentrations Allan deviation of 0.25 ppm and 0.35 ppm at 100 s shows that the receiving system and IPDA LIDAR system function with long-term stability. Using a CO2 absorption cell as a standard calibration device in the laboratory validates the measurement accuracy and stability of the spaceborne IPDA LIDAR prototype. Furthermore, the proposed absorption cell may serve as a standard calibration device for related atmosphere trace gases sounding research.

Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis.

BACKGROUND: Tumor cells detachment from primary lesions is an early event for hepatocellular carcinoma (HCC) metastasis, in which cell adhesion molecules play an important role. The role of mechanical crowding has attracted increasing attention. Previous studies have found that overcrowding can induce live cells extrusion to maintain epithelial cell homeostasis, and normally, live extruded cells eventually die through a process termed anoikis, suggesting the potential of tumor cells resistant to anoikis might initiate metastasis from primary tumors by cell extrusion. We have demonstrated transmembrane adhesion molecule blood vessel epicardial substance (BVES) suppression as an early event in HCC metastasis. However, whether its suppression is involved in HCC cell extrusion, especially in HCC metastasis, remains unknown. This study aims to investigate the role of BVES in tumor cells extrusion in HCC metastasis, as well as the underlying mechanisms. METHODS: Cells extrusion was observed by silicone chamber, petri dish inversion, and three-dimensional cell culture model. Polymerase chain reaction, western blotting, immunohistochemistry, immunofluorescence, co-immunoprecipitation, and RhoA activity assays were used to explore the underlying mechanisms of cell extrusion regulated by BVES. An orthotopic xenograft model was established to investigate the effects of BVES and cell extrusion in HCC metastasis in vivo. RESULTS: Tumor cell extrusion was observed in HCC cells and tissues. BVES expression was decreased both in HCC and extruded tumor cells. BVES overexpression led to the decrease in HCC cells extrusion in vitro and in vivo. Moreover, our data showed that BVES co-localized with ZO-1 and GEFT, regulating ZO-1 expression and localization, and GEFT distribution, thus modulating RhoA activity. CONCLUSION: The present study revealed that BVES downregulation in HCC enhanced tumor cells extrusion, thus promoting HCC metastasis, which contributed to a more comprehensive understanding of tumor metastasis, and provided clues for developing novel HCC therapy strategies. Video abstract.

Validation of an airborne high spectral resolution Lidar and its measurement for aerosol optical properties over Qinhuangdao, China.

Compared with ground-based lidar, airborne lidar has a wider observation area, which is useful for studying aerosol distribution and transportation. A dual-wavelength high spectral resolution Lidar (HSRL) was developed for the validation and calibration of an upcoming satellite payload. The HSRL was installed on an airplane, and field campaigns were conducted in Qinhuangdao, China. Meanwhile, four observation sites were established at different locations on the ground to verify the results of the airborne lidar. This article compares the HSRL measurements with those from ground-based micro-pulse lidar (MPL), Mie-scattering lidar, sun photometer, and spaceborne cloud-aerosol Lidar and infrared pathfinder satellite observations (CALIPSO), and Moderate Resolution Imaging Spectroradiometer (MODIS). The stability and reliability of the HSRL system were fully verified. The flight area covered several surface types, including ocean, town, mountain, and forest, which strongly affect the AOD above them. The boundary layer AOD was analyzed in different regions, based on the impact of human activities. The results demonstrated that the AOD in urban area was the largest, and smallest in marine areas, a result ascribed to the influence of industrial activities.

Sensitivity analysis and correction algorithms for atmospheric CO2 measurements with 1.57-µm airborne double-pulse IPDA LIDAR.

In this study, a 1.57-µm airborne double-pulse integrated-path differential absorption (IPDA) light detection and ranging (LIDAR) system was developed for CO2 measurements. This airborne IPDA LIDAR is integrated with a real-time frequency monitoring system, an integrated sensor for temperature, pressure, and humidity, an inertial navigation system, and a global positioning system. The random errors of the LIDAR system, which are caused by the signal noise, background noise, and detector noise, among other factors, are analyzed for different target reflectivities at a flight altitude of 8 km. After parametric optimization, the signal is unsaturated at high target reflectivity. Further, it can be detected at low target reflectivity by adjusting the detector gain. After the averaging of 148 shots, the relative random error (RRE) was 0.057% for a typical target reflectivity of 0.1 sr-1. Moreover, the systematic errors caused by the laser pulse energy, linewidth, spectral purity, and frequency drift, as well as the atmospheric parameters related to the flight experiments are also investigated. The relative system error (RSE) was 0.214% as determined based on an analysis of the systematic errors, which are primarily caused by the frequency drift. Two methods are proposed to reduce the RSE caused by the frequency drift. The first is the averaging of 148 shots, which can reduce the RSE to 0.096%. The other method involves calculating the integral weight function (IWF) using real-time frequency. However, this is a time-consuming and computationally intensive process. Hence, look-up tables for the absorption cross-section were created to overcome this issue, resulting in a decrease in the RSE to 0.096%. Using actual aircraft attitude angles, velocity, and position data from flight experiments, the relative errors (REs) in the IWF caused by the uncorrected integral path and Doppler shift were determined to be 0.273% and 0.479%, respectively. However, it was found that corrections to the integral path and Doppler shift based on accurate calculations of the IWF cause the airborne platform to turn in such a way that the REs are eliminated. Hence, this study confirms the validity of system parameters and provides a reference for other researchers who study similar IPDA LIDAR systems. Further, the sensitivity analysis of the airborne IPDA LIDAR system can provide a reference to future data inversions. Moreover, the proposed correction algorithms for the integral path and Doppler shift contribute to more accurate inversion results.

Analysis of energy monitoring for a double-pulsed CO2 integrated path differential absorption lidar at 1.57 µm.

For double-pulsed 1.57 µm integrated path differential absorption lidar, the transmitted pulse energy measurement is an important factor that can influence the uncertainty of CO2 concentration measurement. An energy monitoring experiment was performed to determine how to improve the measurement precision of the transmitted pulse energy. Ground glass diffusers were used to reduce the speckle effect during energy monitoring. The roughness and rotational speed of the ground glass diffusers were considered and compared. The normalized energy ratios between on-line and off-line echo pulses and on-line and off-line energy monitoring pulses were analyzed, and the Allan deviation was used to evaluate the energy monitoring results. Averaging 148 shots, the standard deviation of the normalized energy ratio reached 0.0757%, whereas the correlation between the energy ratio of the on-line and off-line energy monitoring pulses and the energy ratio of the on-line and off-line echo pulses was higher than 90%.

Optimal iodine absorption line applied for spaceborne high spectral resolution lidar.

Spaceborne high spectral resolution lidar (HSRL) provides a wide range of observations, e.g., measurements of aerosol backscattering and extinction coefficients and aerosol depolarization ratio with high accuracy, which are of great significance to the study of air pollution monitoring and climate change. With different cells and finger temperatures, the transmittance of the different absorption lines of the iodine vapor filter at 532 nm wavelength was measured. The 1064 nm fundamental frequency pulse energy and the 532 nm frequency-doubled pulse energy output of different seeder laser wavelengths were measured. Based on the relationship among the laser output power, the absorption line shape of the iodine vapor filter, and the atmospheric model, the echo power was calculated and compared. The 1110 iodine absorption line was selected as the optimized filter for the HSRL, which could increase in 22% and 14% efficiency compared with the traditional 1109 line, and a new proposed 1105 line at the 532 nm HSRL channel at 5 km altitude with an enhanced aerosol model, respectively.

Double-pulse 1.57 µm integrated path differential absorption lidar ground validation for atmospheric carbon dioxide measurement.

A ground-based double-pulse integrated path differential absorption (IPDA) instrument for carbon dioxide (CO2) concentration measurements at 1572 nm has been developed. A ground experiment was implemented under different conditions with a known wall located about 1.17 km away acting as the scattering hard target. Off-/offline testing of a laser transmitter was conducted to estimate the instrument systematic and random errors. Results showed a differential absorption optical depth (DAOD) offset of 0.0046 existing in the instrument. On-/offline testing was done to achieve the actual DAOD resulting from the CO2 absorption. With 18 s pulses average, it demonstrated that a CO2 concentration measurement of 432.71±2.42 ppm with 0.56% uncertainty was achieved. The IPDA ranging led to a measurement uncertainty of 1.5 m.

Design and simulation of a biconic multipass absorption cell for the frequency stabilization of the reference seeder laser in IPDA lidar.

The design process and simulation method of a multipass absorption cell used for the frequency stabilization of the reference seeder laser in integrated path differential absorption (IPDA) lidar are presented. On the basis of the fundamental theory of the Herriott multipass cell comprising two spherical mirrors, the initial parameters of the multipass cell, which has an optical path greater than 10 m and consists of two biconic mirrors, were calculated. More than 30 light spots were distributed on each mirror, and the distance between adjacent spots was mostly optimized to greater than six times the beam waist. After optimization, the simulated transmittance spectrum and associated differential signal were obtained. The interference induced by surface scattering was also simulated, and its influence on the differential signal was analyzed. A correspondence between the simulated results and the testing data was observed.

Histidine-rich calcium binding protein promotes growth of hepatocellular carcinoma in vitro and in vivo.

We have recently shown that the histidine-rich calcium binding protein (HRC) promotes the invasion and metastasis of hepatocellular carcinoma (HCC). In the current study, we evaluated whether HRC may also affect the growth of HCC. We found that ectopic expression of HRC obviously enhanced proliferation and colony formation, while suppression of HRC exhibited inhibitory effects. Furthermore, we demonstrated that HRC promoted tumor growth in nude mice. These effects may result from the ability of HRC to upregulate cyclinD1 and cyclin-dependent kinase 2 (CDK2) expressions and promote G1/S transition. Further study showed that MEK/ERK signaling pathway was involved in HRC-induced cell proliferation. Interestingly, overexpression or depletion of HRC revealed its regulation on endoplasmic reticulum stress (ERS) and apoptosis, which was partially dependent on PERK/ATF4/CHOP signaling pathway. In addition, blocking ERS using 4-phenylbutyric acid (4-PBA) not only downregulated the expression of PERK, ATF4 and CHOP, but also significantly decreased apoptosis induced by HRC silence, whereas ERS inducer thapsigargin (TG) exerted the opposite effects. Our study thus demonstrates a role of HRC in promoting HCC growth, besides its role in inducing HCC metastasis, and highlights HRC as a promising intervention target for HCC.

Sodium Ferulate Reduces Portal Pressure Through Inhibition of RhoA/Rho-Kinase and Activation of Endothelial Nitric Oxide Synthase in Cirrhotic Rats.

BACKGROUND AND AIMS: Recent studies have demonstrated that increased RhoA/Rho-kinase activity and reduced nitric oxide activity have the necessary machinery to induce cirrhosis. However, it is unclear whether this regulates the functions of hepatic stellate cells (HSCs). In this study, we used sodium ferulate (SF) in a cirrhotic rat model and examined its roles in regulating RhoA activation in HSCs and the subsequent effects on contraction of HSCs. METHODS: Bile duct ligation method was used to induce cirrhosis in rats. Intrahepatic resistance was investigated in in situ perfused livers. Hepatic RhoA, Rho-kinase and eNOS expressions were studied by RT-PCR and Western blot. RhoA pull-down assay and collagen gel contraction assay of HSCs were performed by incubation with SF in the absence or presence of GGPP. RESULTS: We showed that in cirrhotic liver, SF can efficiently affect RhoA activation via lowering the synthesis of GGPP in HSCs. These actions effectively reduced basal intrahepatic resistance in cirrhotic rats. Our study further suggested that SF effectively decreased Rho-kinase activity and increased activity of eNOS at both the mRNA and protein levels. SF treatment of HSCs reduced RhoA GTP without affecting the total RhoA protein level, and GGPP had the ability to block SF-induced protein expression. Furthermore, SF inhibited the contraction of activated HSCs and this inhibition was efficiently reversed by addition of GGPP. CONCLUSIONS: SF inhibits hepatic RhoA/Rho-kinase signaling and activates the NO/PKG pathway in cirrhotic rats. This may serve as a mechanism for reducing the contraction of activated HSCs upon SF treatment.

Eye-safe single-frequency single-mode polarized all-fiber pulsed laser with peak power of 361 W.

An all-fiber, single-frequency, single-mode linearly polarized, high peak power pulsed laser at 1540 nm for coherent Doppler wind lidar is demonstrated. A narrow-linewidth seed laser is pulse modulated by an acousto-optic modulator and then amplified by two-stage cascade amplifiers. An 0.8 m long erbium/ytterbium co-doped polarization-maintaining fiber with a core diameter of 10 µm is used as the gain fiber of a power amplifier, and longitudinally varied strains are applied on the gain fiber to realize approximately 3.4 times enhancement of the stimulated Brillouin scattering threshold. Peak power of 361 W pulse width of 200 ns at 10 kHz repetition rate is achieved with transform-limited linewidth and diffraction-limited beam quality. To the best of our knowledge, it is the highest peak power of an eye-safe, single-mode narrow-linewidth pulsed fiber laser based on 10 µm core diameter silica fiber.

Colon Metastasis from Pancreatic Cancer: A Case Report.

Pancreatic cancer commonly metastasizes to the liver, lung or adrenal glands, but rarely spreads to the colon. We describe a case of a 65-year-old man with operation history of endoscopic submucosal dissection for rectal adenoma, who visited our department with a lesion in the sigmoid colon. A biopsy of the sigmoid pathologic lesion found heterologous cells in the muscularis mucosa, which indicated that this lesion did not originate in the colon. Abdominal enhanced CT results revealed a soft tissue mass in pancreatic tail and several masses in the liver and rectovesical pouch. 18-FDG PET-scan results showed pancreatic neoplastic mass. Biopsy result of pancreatic pathologic area was positive for ductal pancreatic adenocarcinoma. Immunohistochemical staining confirmed that the sigmoid lesion was a metastasis from a primary pancreatic adenocarcinoma-an unusual pattern of spread. The patient accepted chemotherapy after an oncologic evaluation. To our knowledge, there were only nine reported cases of metastatic pancreatic cancer spreading to the colon. This was a rare route of metastasis for pancreatic cancer. It is important to keep this possibility in mind when patients present with a colon lesion. Furthermore, our case highlights the importance of considering metastases when a colon mass is found in patients with a history of colon cancer, although primary colon cancer is still more likely.

Single-frequency pulsed laser source with hybrid MOPA configuration.

A unique approach with a hybrid master oscillator power amplifier configuration to obtain single-frequency, high-energy laser pulses at 1064 nm is presented. The setup consists of a single-frequency seed laser, a multistage fiber amplifier, and a four-pass crystal rod amplifier. Pulse energy of 10 mJ is obtained at the repetition rate of 100 Hz. The pulse width is about 110 ns with a transform-limited linewidth of 3.2 MHz. The M(2) factor of the output beam is about 1.5. To our knowledge, this is the first report of using a hybrid amplifier to obtain 10 mJ pulses with long pulse width and transform-limited linewidth.

Ultrasound-based artificial intelligence in gastroenterology and hepatology.

Artificial intelligence (AI), especially deep learning, is gaining extensive attention for its excellent performance in medical image analysis. It can automatically make a quantitative assessment of complex medical images and help doctors to make more accurate diagnoses. In recent years, AI based on ultrasound has been shown to be very helpful in diffuse liver diseases and focal liver lesions, such as analyzing the severity of nonalcoholic fatty liver and the stage of liver fibrosis, identifying benign and malignant liver lesions, predicting the microvascular invasion of hepatocellular carcinoma, curative transarterial chemoembolization effect, and prognoses after thermal ablation. Moreover, AI based on endoscopic ultrasonography has been applied in some gastrointestinal diseases, such as distinguishing gastric mesenchymal tumors, detection of pancreatic cancer and intraductal papillary mucinous neoplasms, and predicting the preoperative tumor deposits in rectal cancer. This review focused on the basic technical knowledge about AI and the clinical application of AI in ultrasound of liver and gastroenterology diseases. Lastly, we discuss the challenges and future perspectives of AI.

Netrin-1 promotes cell migration and invasion by down-regulation of BVES expression in human hepatocellular carcinoma.

The axon guidance cues netrin-1 has been reported to be associated with cancer progression in various types of human cancers. However, the underlying molecular mechanism of netrin-1-mediated metastasis remains obscure. In this study, we found that overexpression of netrin-1 promoted HCC cell migration and invasion as determined by transwell assay and 3D cell culture assay. However, netrin-1 knockdown inhibited these processes. Further investigation indicated that netrin-1 decreased the expression of Blood Vessel Epicardial Substance (BVES), which was down-regulated in HCC. Interestingly, LY294002, a special inhibitor to PI3K/AKT signaling which was determined as a downstream pathway of netrin-1, restored the reduction in BVES caused by netrin-1. In addition, BVES exhibited an opposite effect on HCC cell metastasis to that of netrin-1. Importantly, up-regulating BVES expression significantly attenuated netrin-1-enhanced migration and invasion, whereas silencing BVES expression rescued the metastatic phenotype in netrin-1 knockdown cells. Moreover, netrin-1 expression was negatively correlated with BVES in HCC tissues and cell lines with different metastatic potential. Taken together, these results reveal that netrin-1 promotes HCC cell metastasis by regulating BVES expression via AKT activation.

The histidine-rich calcium binding protein (HRC) promotes tumor metastasis in hepatocellular carcinoma and is upregulated by SATB1.

The histidine-rich calcium binding protein (HRC) is a regulator of Ca2+-homeostasis. Herein, we found that HRC was frequently upregulated in human hepatocellular carcinoma (HCC) tissues, and its expression was correlated with tumor size and metastasis. Moreover, HRC expression was positively related to the metastatic potential of HCC cell lines. Knockdown of HRC suppressed cell invasion and migration in vitro, whereas ectopic expression of HRC resulted in increased cell invasion and migration in vitro and intrahepatic and lung metastasis in vivo. Interestingly, the pro-invasion and pro-migration effects of HRC were associated with focal adhesion turnover, which was a consequence of FAK phosphorylation. Further experiments showed that HRC induced phospho-FAK, focal adhesion turnover and cell migration through Ca2+/CaM singaling. We found that HRC increased [Ca2+]i by inhibiting the expression of SERCA2. In addition, upregulation of HRC in HCC was attributed to SATB1, which is known to promote HCC metastasis. Ectopic expression of SATB1 enhanced HRC gene transcription by activating AP-1 in mainly a JNK-dependent manner. Our findings highlight HRC as a potential therapeutic target for HCC treatment.