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Transfer between the metro (underground railway system) and buses is standard in many cities, and the simultaneous arrival of these two modes can provide passengers with a smoother transfer experience. However, previous synchronous transfer studies rarely consider different public transport modes simultaneously. This paper presents an optimization model that maximizes the number of metro and bus network synchronizations considering the connection level. An improved algorithm that combines simulated annealing (SA) and artificial bee colony (ABC) is proposed. The best nectar source position in history is combined with the SA operation. The ABC and simulated annealing and improved artificial bee colony (SA–IABC) algorithms are used to solve the model using the Nanmendou metro station and the bus stations within 1.2 km around it in Fuzhou City, China. The results show that ABC and improved SA–IABC algorithms increase the synchronization times of the metro and bus network by 17% and 24% on average, respectively, without expanding the departure frequency.

The ordered membrane electrode assembly (MEA) is currently the frontier research field of proton exchange membrane fuel cells (PEMFCs). The ordered MEA is effective in increasing the utilization of...

Maintaining the balance of mitochondrial fission and mitochondrial autophagy on seizures is helpful to find a solution to control seizures and reduce brain injuries. The present study is to investigate the protective effect of inhibiting mitochondrial fission on brain injury in juvenile rat epilepsy induced by pentatetrazol (PTZ) by inhibiting the BCL2L13/LC3-mediated mitophagy pathway. PTZ was injected (40 mg/kg) to induce kindling once every other day, for a total of 15 times. In the PTZ + DMSO (DMSO), PTZ + Mdivi-1 (Mdivi-1), and PTZ + WY14643 (WY14643) groups, rats were pretreated with DMSO, Mdivi-1 and WY14643 for half an hour prior to PTZ injection. The seizure attacks of young rats were observed for 30 min after model establishment. The Morris water maze (MWM) was used to test the cognition of experimental rats. After the test, the numbers of NeuN(+) neurons and GFAP(+) astrocytes were observed and counted by immunofluorescence (IF). The protein expression levels of Drp1, BCL2L13, LC3 and caspase 3 in the hippocampus of young rats were detected by immunohistochemistry (IHC) and Western blotting (WB). Compared with the PTZ and DMSO groups, the seizure latency in the Mdivi-1 group was longer (P 0.01), and the severity degree and frequency of seizures were lower (P 0.01). The MWM test showed that the incubation periods of crossing the platform in the Mdivi-1 group was significantly shorter. The number of platform crossings, the platform stay time, and the ratio of residence time/total stay time were significantly increased in the Mdivi-1 group (P 0.01). The IF results showed that the number of NeuN(+) neurons in the Mdivi-1 group was greater, while the number of GFAP(+) astrocytes was lower. IHC and WB showed that the average optical density (AOD) and relative protein expression levels of Drp1, BCL2L13, LC3 and caspase 3 in the hippocampi of rats in the Mdivi-1 group were higher (P 0.05). The above results in the WY14643 group were opposite to those in the Mdivi-1 group. Inhibition of mitochondrial fission could reduce seizure attacks, protect injured neurons, and improve cognition following PTZ-induced epilepsy by inhibiting mitochondrial autophagy mediated by the BCL2L13/LC3 mitophagy pathway.

Smaller volume/weight and higher output power/energy density are always the goals of electrochemistry energy devices. Here, a simple strategy is proposed to prepare an integrated gas diffusion electrode (GDE) with high conductivity through skin electroplating. The skin electroplating is the combination of magnetron sputtering and spatial confinement electroplating. The electroplated metal obtained by skin electroplating is uniformly, continuously, and tightly attached to the surface of carbon paper like a layer of skin. Uniform and continuous electroplating metal layer endows the integrated electrode excellent conductivity with the square resistance as low as 27 mΩ sq

Proton exchange membrane fuel cells (PEMFCs) have potential applications in electric vehicles, laptops, and power stations. The catalyst layers in a membrane electrode assembly (MEA) are the core locations in PEMFCs in which to convert the chemical energy of fuels to electrical energy. For a catalyst layer with high performance, it must possess three fast transfer ways to transfer mass (reactants and products), electrons (e−) and protons (H+) quickly and simultaneously. In this work, we greatly improved the performance and lifetime of a fuel cell by constructing these three fast transfer pathways based on a well-ordered and cone-shaped Nafion array with a very high density (5.7 × 108 cones per cm2) using an anodic aluminum oxide (AAO) template. To build a fast pathway for electron transfer, well-dispersed graphene nanosheets were further filled into the Nafion array. After a series of efforts based on the above, the performance of the fuel cell with a cone array as an anode reached 1240 mW cm−2, which is 2.5 times higher than that without an array. Since Pt loading was as low as 17.6 μg cm−2, the mass specific power of Pt was as high as 70.5 kW gPt−1. Consequently, the Pt loading successfully reached the U.S. DOE 2020 target at the anode side, i.e. 25 μg cm−2. In addition, the lifetime of the PEMFC with the cone array is at least 300 h, which is much longer than the 150 h for a PEMFC without an array. Therefore, this work fully exhibits the great potential advantages of using an ordered Nafion array, and is promising to promote the development of the next generation of MEA for use in PEMFCs.

Flexible wearable electronics, including monitors, supercapacitors, sensors and batteries, especially stress or strain sensors, have attracted extensive discussion and attention, due to their distinctive characteristics such as high sensitivity and ultra-flexibility, and their broad application prospects in artificial intelligence (AI), robot sensing interfaces, and also high precision medical instruments. However, a narrower deformation rate, higher latency, and even counterfeit sensitivity severely limit their sensing performance and popularity in practical applications. Herein, a new bifunctional sensor based on excellent conductive and biocompatible porous copper nanowire (CuNW)/IonGel (PCI) composite films introducing a polystyrene (PS) microsphere template is developed. The sensor exhibits unparalleled mechanical properties (the maximum extension rate is 8000%), as well as omnidirectional, arbitrary angle/dimension extension, distortion and bending. This piezo-resistive sensor also features a convincing ultra-high sensitivity (S, 72.1 kPa−1) and gauge factor (Gf, 28.5) with negligible hysteresis under repeated cycle tests. Furthermore, compared to the same type of sensor, the limit of detection (LOD) is drastically reduced (merely 0.14 Pa). Undoubtedly, it is promising for high-resolution strain/stress-sensing electronic skin (e-skin) and green super-stretched electrodes.

BACKGROUND Wilms tumor (WT) is the most common type of pediatric renal malignancy, and is associated with poor prognosis. The aim of the present study was to identify microRNA (miRNA) signatures which might predict prognosis and categorize WTs into high- and low-risk subgroups. MATERIAL AND METHODS The miRNA expression profiles of WT patients and normal samples were obtained from the Therapeutically Applicable Research to Generate Effective Treatment database. Differentially expressed miRNAs between WT patients and normal samples were identified using the EdgeR package. Subsequently, correlations between differentially expressed miRNAs and the prognosis of overall survival were analyzed. Enrichment analyses for the targeted mRNAs were conducted via the Database for Annotation, Visualization, and Integration Discovery. RESULTS A total of 154 miRNAs were identified as differentially expressed in WT. Of those, 18 miRNAs were associated with overall survival (P

Background/aim: Hepatic stellate cells (HSCs) are critical determinants of liver tumor behavior such as vascular invasion, cell proliferation and migration. The apoptosis of HSCs can inhibit tumor growth and contribute to repressing hepatocellular carcinoma (HCC) progression. Our study aims to investigate the impact of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on HSCs under hypoxic conditions and the association of nuclear GAPDH with HCC patient outcomes and tumor progression. Patients and methods: Following stable cell passage, 0.3% O2 was used to induce hypoxia. Cell proliferation and apoptosis were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays and flow cytometry, respectively. Proteins expression were detected by extracting nuclear and cytoplasmic proteins and performing Western blots. GAPDH nuclear translocation was blocked by the agent deprenyl. Immunohistochemical staining for GAPDH was investigated in 137 HCC tissue samples from our center. An analysis of the clinicopathological features, Kaplan-Meier analysis and Cox proportional hazards regression analysis were applied. Results: MTT assays and flow cytometry analyses showed that the nuclear accumulation of GAPDH led to the apoptotic death of HSCs, while blockade of this process with deprenyl significantly decreased apoptosis. Western blots revealed that deprenyl inhibited the nuclear translocation of GAPDH. An analysis of the immunohistochemical staining of HSCs in HCC tissue samples (137) revealed that nuclear GAPDH expression was significantly positively correlated with HIF-1α expression. Overall survival (OS) and time-to-recurrence (TTR) estimated by Kaplan-Meier analyses showed that patients with high HIF-1α or low nuclear GAPDH levels in HSCs had significantly poorer prognosis compared with patients with low HIF-1α or high nuclear GAPDH expression in HSCs. Moreover, patients with combined high HIF-1α/low nuclear GAPDH expression in HSCs had the worst prognosis. The Cox regression analysis revealed that the combination of nuclear GAPDH/HIF-1α expression in HSCs was an independent prognostic factor for OS and TTR in HCC patients. Conclusions: These findings provide a novel mechanism underlying the involvement of intranuclear GAPDH in hypoxia-induced HSCs apoptosis and a correlation between nuclear GAPDH levels and the clinical prognosis, which may prompt the development of a novel therapeutic strategy for HCC.

Geometric errors such as inaccurate link length and assembly alignment are the primary sources of positioning errors for industrial robots. Besides, complex joint-dependent kinematic errors in the bearing system and harmonic drives are also non-negligible. The robot is regarded as an ideal rigid body in typical kinematic models, which can only describe the influence of geometric errors. This paper proposes a generalized kinematic error model based on product of exponentials (POE) formula, which contains constant geometric errors and complex joint-dependent kinematic errors. The unknown model parameters are identified with the Levenberg-Marquardt method. Experiments are implemented on an Efort ECR5 robot to validate the effectiveness of the proposed model. In these experiments, we use 250 measurements as the identification data set for parameter identification, and other 100 measurements are utilized to validate the accuracy of the proposed model. These experiments display that the proposed model can reduce the mean position error of the Efort ECR5 robot from 2.014 mm to 0.115 mm on the validation data set. Experimental results prove that the proposed model can describe the kinematics of industrial robots with high accuracy.

We report the growth of porous AlN films on C-face SiC substrates by hydride vapor phase epitaxy (HVPE). The influences of growth condition on surface morphology, residual strain and crystalline quality of AlN films have been investigated. With the increase of the V/III ratio, the growth mode of AlN grown on C-face 6H-SiC substrates changes from step-flow to pit-hole morphology. Atomic force microscopy (AFM), scanning electron microscopy (SEM) and Raman analysis show that cracks appear due to tensile stress in the films with the lowest V/III ratio and the highest V/III ratio with a thickness of about 3 μm. In contrast, under the medium V/III ratio growth condition, the porous film can be obtained. Even when the thickness of the porous AlN film is further increased to 8 μm, the film remains porous and crack-free, and the crystal quality is improved.

Humidity sensors have attracted intensive interest due to their significant air humidity monitoring values. But it is still a challenge in achieving highly sensitive and accurate humidity sensors with a rapid and convenient method. And only few studies examined the relationship between the sensing and the wetting behavior of sensing materials. Here, we propose a novel strategy for designing humidity sensor by using superhydrophilic ZnO nanoneedle array. Via this smart design, superhydrophilic ZnO nanoneedle array was first in-situ grown on the electrode of quartz crystal microbalance (QCM) transducers by a facile chemical deposition method in solution. The design admits the water molecule easily reach the internal and outer surface of the array, further form multi-molecular-layer adsorption mode on the surface based on a physical adsorption effect between water molecule and superhydrophilic ZnO nanoneedle array. The characterization and sensing results show that the sensors constructed from superhydrophilic ZnO nanoneedles with a defined morphology exhibit enhanced humidity sensing properties including high sensitivity (21.4 Hz/%RH, at 95%RH), fast response/recovery speed (2 s/2 s, at 33%RH), well reproducibility, and narrow hysteresis (Maximum 2%RH) compared with the hydrophilic ZnO seeds and the superhydrophobic ZnO nanoneedles. Finally, the humidity sensing mechanism was also discussed in detail.

Gas diffusion layer is one of the most important components of fuel cell, which supports the catalytic layer, collects the current and facilitates mass transfer. However, current carbon paper is mainly composed of long carbon fibers (CF), which brings drawbacks including rough surface, poor body homogeneity, excessive thickness, and preparation difficulty, etc. In this research, we invent a combination method to produce a highly flat, highly homogeneous, ultra-thin and high-performance carbon paper for proton exchange membrane fuel cell (PEMFC). The method combines the advantages of two materials, i.e. few-walled carbon nanotube (FWCNT) with high flatness and short CF with high porosity. And the combination method only contains three steps, material dispersion, carbon paper formation and heat treatment. The highest temperature for the heat treatment process is only 350 °C, which is much lower than the traditional 2000 °C. Due to the small size and fine distribution of FWCNT and CF, the new carbon paper exhibits highly flat (

Textile-based wearable devices have attracted much attention as they can improve the wearing comfort and safety of electronic products. This paper proposes a fabrication strategy for a multifunctional e-textile based on polypyrrole (PPy) and rose-like silver flower-decorated knitted cotton/spandex fabric (KCSF). The rose-like silver flower grown on the PPy surface by electrodeposition can further improve the surface roughness and pressure sensitivity of the fabric. PPy and rose-like silver flower-decorated KCSF can be used to construct a multi-layer pressure/strain sensor. The as-obtained sensor not only exhibits an ultra-wide working pressure range (0–900 kPa), but also achieves a high sensitivity (17.41 kPa−1 for low-pressure areas), which effectively balances the operating range and sensitivity. More importantly, the sensor can be used to accurately monitor different physiological signals, including the levels of swallowing, breathing rate, voice recognition, and sleep quality. In addition, an all-solid-state supercapacitor is fabricated using PPy-coated fabric electrodes, demonstrating a high areal capacitance of 978.9 mF cm−2 at 1 mA cm−2, an energy density of 80.3 µWh cm−2, and power density of 0.38 mW cm−2. The multifunctional e-textile with excellent sensing and energy storage behaviors is simple and easy to manufacture, with potential application prospects in the broad field of wearable technology.

Fibroblast activation protein (FAP) is a serine protease that has been reported in fibroblasts and some carcinoma cells, which correlates with poor patient outcomes. FAP can be induced under hypoxia which is also vital in the malignant behaviors of cancer cells. However, the role of FAP and its correlation with hypoxia has not been investigated in HCC cancer cells. In tissues from post-surgical HCC patients in our center, we adopted immunohistochemistry staining (IHC), western blot and quantitative RT-PCR to detect the expression levels of FAP and the hypoxia related marker, hypoxia inducible factor 1α (HIF-1α). X-tile software was used for the determination of high and low expression of FAP and HIF-1α after the IHC analysis. Clinicopathological analysis, Kaplan-Meier analysis and Cox regression model were performed. In-vitro experiments were performed to confirm the relationship between FAP and hypoxia in HCC cancer cell lines (HepG2, Huh7 and MHCC97H). Results revealed that expression levels of FAP and HIF-1α were significantly correlated (Pearson r2 = 0.2753, p < 0.0001) in IHC analysis of the 138-patient cohort. Western blot and quantity RT-PCR indicated parallel changes in 11 post-surgical fresh frozen tissues. The HIF-1α and FAP expression were associated with serum AFP, TNM, tumor size and vascular invasion. Cox regression analysis showed that HIF-1α/ FAP combination were the independent predictor for overall survival (OS) and time-to-recurrence (TTR) in post-surgical HCC patients. Kaplan-Meier analyses revealed that the patient with high levels of HIF-1α, FAP and combined HIF-1α/FAP had the shortest OS and TTR. In-vitro experiments showed that FAP was increased in hypoxic HCC cancer cell lines in parallel with that of HIF-1α and three EMT markers (E-cadherin, Snail and TWIST). In conclusion, the up-regulation of FAP in HCC cancer cells under hypoxia can be indicative of poor prognosis in patients.

Coronavirus disease 2019 (COVID-19) has threatened human health worldwide and could lead to multiple organs injury. However, the impact on the virus infecting the biliary system, especially the gallbladder, has remained unclear and no pathological evidence has been reported yet. A case of SARS-CoV-2 infection in a gallbladder with cholecystitis, which progressed rapidly to sepsis and required an emergency operation was investigated and reported. Clinical specimens of the COVID-19 patient including serum, oropharyngeal swabs, sputum, bile, abdominal drainage fluid, urine, stool, and gallbladder tissue were collected and tested for SARS-CoV-2 RNA using a quantitative polymerase chain reaction (qPCR) assay. Fresh normal gallbladder tissue and gangrenous gallbladder tissue were also collected for further research including hematoxylin and eosin (HE), immunohistochemistry (IHC), and immunofluorescent (IF) staining, and compared with the gallbladder from the COVID-19 patient. The bile, as well as the serum, oropharyngeal swabs, sputum, abdominal drainage fluid, urine, and rectal swabs were consecutively negative for SARS-CoV-2 RNA. The viral host receptor angiotensin-converting enzyme 2 (ACE2) was highly expressed in gallbladder epithelial cells, and viral nucleocapsid protein (NP) was visualized in the cytoplasm of gallbladder epithelial cells. Immune cells including CD2, CD3, CD4, CD8, CD20, CD38, CD68, and MPO were positive in gangrenous gallbladder tissues without SARS-CoV-2 infection, and were relatively downregulated in SARS-CoV-2 infective gallbladder tissue. This study provided evidence of SARS-CoV-2 infection in the gallbladder and verified that the gallbladder was one of the target organs that SARS-CoV-2 could attack and damage using ACE2 as a cell receptor. Due to the immune dysregulation involved, more vigilant management and early assessment is needed for COVID-19 patients with the comorbidity of cholecystitis.

Background The pathogenesis of non-cirrhotic hepatocellular carcinoma (HCC) with a high recurrence remains controversial, while microvascular invasion (MVI) is highly suggestive of tumor recurrence. This study aimed to investigate the effects of liver fibrosis on MVI and prognosis in HCC. Methods Based on the data of HCC in the Surveillance, Epidemiology, and End Results (SEER) database [2004-2015], multivariate logistic regression was used for correlation analysis. Survival was analyzed by Log-Rank test and Cox regression, and decision curve analysis and receiver operating characteristic curves were established to evaluate alternative diagnostic and prognostic strategies. Results The study included 1,492 patients with MVI (17.8%) or without MVI (82.2%) for HCC with a solitary nodule. Liver fibrosis was significantly correlated with the occurrence of MVI, and the risk of MVI in patients with a fibrosis score F5-6 was lower than in those with a score of F0-4 (OR =0.651, 95% CI: 0.492-0.860). Combining liver fibrosis could improve the prediction performance of MVI risk models, but liver fibrosis was less associated with survival outcomes in comparison with other tumor characteristics. Conclusions Lower liver fibrosis correlated with a higher risk of MVI in HCC with a solitary nodule and was a good indicator for improving the performance of MVI risk models. However, it was not a prognostic sensitive indicator.

In this work, through chemical vapor deposition (CVD) method, almost indistinguishable planar rose-like ZnO (PRZ) nanostructures could be prepared on the surface of honeycombed gallium nitride (HGaN) after more than ten deposition tests, and then constructed into PRZ/HGaN heterojunction gas sensor. Subsequent gas behaviors showed that the PRZ/HGaN heterostructure constructed by CVD greatly improved the selectivity and response value (32.5 at 100 ppm) to H2, and realized the improvement of the H2 sensing performance without noble metal modification. Importantly, fast response and recovery time was 47 s and 6 s, respectively. Meanwhile, this sensor presented excellent selectivity and stability. Ultimately, the dynamic monitoring of the sensor was performed for five consecutive months, and the fluctuation ratio of the response value (sensitivity) did not exceed ±2%. It could be predicted that the as-obtained sensor was expected to promote the substantial process of industrialization of highly stable metal oxide/HGaN heterojunction sensors.

Eu3+, Tm3+ co-doped AlN thin films have been prepared through ion implantation for the first time. The implanted samples were annealed at 1180 °C in N2 to recover implantation damages and activate the rare-earth ions. Luminescence properties were investigated by photoluminescence and cathodoluminescence spectra. Under 325 nm laser excitation, for both Eu3+-doped AlN and Eu3+, Tm3+ co-doped AlN, the sharp characteristic emission lines corresponding to intra-4fn-shell transitions of Eu3+ were observed, but no any emission peak associated to Tm3+ ion was observed. According to the cathodoluminescence spectra, both Eu3+ and Tm3+ ions can be excited efficiently under high-energy electron beam. For Eu3+, Tm3+ co-doped AlN, the cathodoluminescence emission intensity of Eu3+ and Tm3+ ions varies with the dose ratio of these two ions. A possible energy transfer mechanism between Tm3+ and Eu3+ is proposed. Through changing the dose ratio of Eu3+ respect to Tm3+ ions, the chromaticity coordinates and color temperatures could be effectively regulated.

Minority carrier lifetime and diffusion length are important parameters for GaN based material and devices. In this work, we obtained the minority carrier lifetime and diffusion length of p-GaN through the photoluminescence lifetime of the band edge peak, and analyzed the recombination behavior of carriers. Besides, the dependence of photoluminescence lifetime of GaN: Mg grown by MOCVD on annealing temperature (TA) and Mg concentration ([Mg]) has been investigated through Time-resolved Photoluminescence (TRPL) measurements. We increased the activated Mg acceptors ratio by increasing TA, analyzed the fast and slow decay of carrier recombination, and compared the effects of annealing on the lifetime of GaN band-edge emission with different Mg concentrations. And it is found that the minority carrier lifetime in p-GaN is not only related to Mg concentration, but also related to the activated Mg acceptors concentration / hole concentration. Meanwhile, we compared heteroepitaxial p-GaN with homoepitaxial p-GaN, and further analyzed the influence of dislocation as non-radiative recombination centers (NRCs) on carrier lifetime and recombination behavior.

Amino acid, taking the glycine (Gly) for example, was used for the first time as etchant to assemble honeycomb-like structure on gallium nitride (GaN) by photo-electrochemical etching (PECE) technique. Conspicuously, a novel dual-ion dissolution etching mechanism model was proposed, of which could extensively promote to almost all amino acids and their derivatives as well. Importantly, double ions of amino acids are of a synergistic effect with amino and carboxyl groups, which facilitate the generation and stabilization of the honeycomb-like structure with uniform pore size (~26.5 nm), high pore density and superior reusability, and the intermolecular hydrogen bonding can maintain the honeycomb-like structure without being destroyed. From the point of view of costs, scale-up production, biocompatibility and environmental friendliness, Gly has obvious advantages over the traditional strong acid and alkali etchant.

A low-temperature, highly sensitive H2S sensor based on Au-doped ZnO/Zn2SnO4 (AZZ) hierarchical structured composites was fabricated by using a screen printing craft. With the introduction of Au, the response of the AZZ-based sensor to H2S is improved from 2.1 to 15.92 at 150 °C for a [Au]/[Zn] molar ratio of 0.1%. Moreover, the as-prepared sensor has better selectivity to H2S. It is worth mentioning that the sensor shows a commendable ultra-fast recovery time (2 s). Importantly, the unique AZZ hierarchical structure is conducive to chemical adsorption, surfaces and interfaces reactions, gas diffusion and transmission, thereby enhancing the sensing performance.

The water chestnut-based carbon aerogel (WCA) that was directly in-situ prepared via a simple one-step hydrothermal method. The as-prepared WCA had excellent electrochemical properties as a binder-less electric double layer (EDL) electrode in SCs. Specifically, the WCA after annealing exhibited a superior mass specific capacitance of 343.4 F/g at 0.5 A/g in 3 M KOH. Also, the WCA displayed ultra-high capacitance retention rate, which significantly remained close to 100% after 20,000 cycles and still maintained 98.3% after 40,000 cycles. In addition, the green and sustainable WCA yet demonstrated ultra-high sensitivity (42.8 kPa−1) and recoverable performance, which had potential application value in flexible pressure sensors. After 3000 compression-release cycles, the recovery rate exceeded 90%.

The effects of displacement damage due to 1 MeV electron radiation on 680 nm and 850 nm vertical-cavity surface-emitting lasers (VCSELs) were experimentally investigated. The displacement damage dose was calculated using the MULASSIS tool, where it was found that radiation significantly affects the threshold current of VCSELs. The threshold current damage factor is 2.46 × 10−18 cm2/e for 680 nm VCSELs and 1.48 × 10−18 cm2/e for 850 nm VCSELs. In addition, the power intensity distribution and light output power degradation were characterized to evaluate the radiation hardness of VCSELs. An understanding of the performance degradation of VCSELs under electron exposure would be useful in optimizing their applications in hostile environments.

Background/aim: Hepatic stellate cells (HSCs) are critical determinants of liver tumor behavior such as vascular invasion, cell proliferation and migration. The apoptosis of HSCs can inhibit tumor growth and contribute to repressing hepatocellular carcinoma (HCC) progression. Our study aims to investigate the impact of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on HSCs under hypoxic conditions and the association of nuclear GAPDH with HCC patient outcomes and tumor progression. Patients and methods: Following stable cell passage, 0.3% O2 was used to induce hypoxia. Cell proliferation and apoptosis were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays and flow cytometry, respectively. Proteins expression were detected by extracting nuclear and cytoplasmic proteins and performing Western blots. GAPDH nuclear translocation was blocked by the agent deprenyl. Immunohistochemical staining for GAPDH was investigated in 137 HCC tissue samples from our center. An analysis of the clinicopathological features, Kaplan-Meier analysis and Cox proportional hazards regression analysis were applied. Results: MTT assays and flow cytometry analyses showed that the nuclear accumulation of GAPDH led to the apoptotic death of HSCs, while blockade of this process with deprenyl significantly decreased apoptosis. Western blots revealed that deprenyl inhibited the nuclear translocation of GAPDH. An analysis of the immunohistochemical staining of HSCs in HCC tissue samples (137) revealed that nuclear GAPDH expression was significantly positively correlated with HIF-1α expression. Overall survival (OS) and time-to-recurrence (TTR) estimated by Kaplan-Meier analyses showed that patients with high HIF-1α or low nuclear GAPDH levels in HSCs had significantly poorer prognosis compared with patients with low HIF-1α or high nuclear GAPDH expression in HSCs. Moreover, patients with combined high HIF-1α/low nuclear GAPDH expression in HSCs had the worst prognosis. The Cox regression analysis revealed that the combination of nuclear GAPDH/HIF-1α expression in HSCs was an independent prognostic factor for OS and TTR in HCC patients. Conclusions: These findings provide a novel mechanism underlying the involvement of intranuclear GAPDH in hypoxia-induced HSCs apoptosis and a correlation between nuclear GAPDH levels and the clinical prognosis, which may prompt the development of a novel therapeutic strategy for HCC.

An in situ electrochemical scanning electronic microscopy method is developed to systematically study the lithium plating/stripping processes in liquid electrolytes. The results demonstrate that the lithium dendrite growth speed and mechanism is greatly affected by the additives in the ether-based electrolyte.