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Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Background: Multidrug-resistance protein (MRP) 2 is a key membrane transporter that is expressed on hepatocytes and regulated by nuclear factor kappa B (NF-κB). Interestingly, endoplasmic reticulum (ER) stress is closely associated with liver injury and the activation of NF-κB signaling. Objective: Here, we investigated the impact of ER stress on MRP2 expression and the functional involvement of MRP2 in acute liver injury. Methods: ER stress, MRP2 expression, and hepatocyte injury were analyzed in a carbon tetrachloride (CCl4)-induced mouse model of acute liver injury and in a thapsigargin (TG)-induced model of ER stress. Results: CCl4 and TG induced significant ER stress, MRP2 protein expression and NF- κB activation in mice and LO2 cells (P Conclusion: ER stress enhances intrahepatic MRP2 protein expression by activating NF-κB. This increase in MRP2 expression mitigates ER stress and acute liver injury.

In recent years, two-photon excited (TPE) materials have attracted great attentions because of their excellent advantages over conventional one-photon excited (OPE) materials, such as deep tissue penetration, three-dimensional spatial selectivity and low phototoxicity. Also, they have been widely applied in lots of field, such as biosensing, imaging, photo-catalysis, photoelectric conversion, and therapy. In this article, we review recent advances in vibrant topic of two-photon fluorescent nanomaterials, including organic molecules, quantum dots (QDs), carbon dots (CDs) and metal nanoclus-ters (MNCs). The optical properties, synthetic methods and important applications of TPE nanomaterials in biomedical field, such as biosensing, imaging and therapy are introduced. Also, the probable challenges and perspectives in the forthcoming development of two-photon fluorescent nanomaterials are addressed.

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus (HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation (HD) and acute-on-chronic liver failure (ACLF) in patients with severe acute exacerbation (SAE) of chronic HBV infection remain unknown. AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection. METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation (AE model) and the model for end-stage liver disease (MELD) score in predicting the development of ACLF were evaluated. RESULTS Among 164 patients with SAE, 83 (50.6%) had compensated liver cirrhosis (LC), 43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase (AST) levels, and low prothrombin activity (PTA). The area under the receiver operating characteristic of the AE model [0.844, 95% confidence interval (CI): 0.779-0.896] was significantly higher than that of MELD score (0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF. CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

Hepatocyte nuclear factor alpha (HNF1α), endoplasmic reticulum (ER) stress, and hepatocyte apoptosis contribute to severe acute exacerbation (SAE) of liver injury. Here, we explore HNF1α–ER stress-hepatocyte apoptosis interaction in liver injury. LO2, HepG2 and SK-Hep1 cells were treated with thapsigargin (TG) or tunicamycin (TM) to induce ER stress. Carbon tetrachloride (CCl4) was used to induce acute liver injury in mice. Low-dose lipopolysaccharide (LPS) exacerbated liver injury in CCl4-induced mice. Significant apoptosis, HNF1α upregulation, and nuclear factor kappa B (NF-κB) activation were observed in human-derived hepatocytes during ER stress. Knockdown of Rela, NF-κB p65, inhibited the HNF1α upregulation. Following CCl4 treatment ER stress, apoptosis, HNF1α expression and RelA phosphorylation were significantly increased in mice. HNF1α knockdown reduced activating transcription factor 4 (ATF4) expression, and aggravated ER stress as well as hepatocyte apoptosis in vivo and in vitro. The double fluorescent reporter gene assay confirmed that HNF1α regulated the transcription of ATF4 promoter. LPS aggravated CCl4-induced liver injury and reduced HNF1α, and ATF4 expression. Therefore, in combination, HNF1α and ER stress could be mutually regulated forming a feedback loop, which helps in protecting the injured liver by down-regulating hepatocyte apoptosis. Low-dose LPS aggravates hepatocyte apoptosis and promotes the SAE of liver injury by interfering with the feedback regulation of HNF1α and ER stress in acute liver injury.

Background. Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods. In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results. TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression ( p < 0.05 ) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress ( p < 0.05 ). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers ( p < 0.05 ). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions. Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

Pitch has been used to prepare electrodes by high-temperature heat treatments for supercapacitors, lithium-ion batteries, on account of its rich aromatic ring structure. Here, the toluene-soluble component of pitch is used to prepare a kind of laminated carbon. This was realized by a template-free synthesis at low temperature with the addition of pressure. The toluene-soluble component has a small molecular weight, which makes the thermal deformation ability stronger and then enhances the orientation of the carbon layer with the help of pressure. The prepared anode exhibits a splendid electrochemical performance compared with the traditional graphite anode. A high stable capacity of approximately 550 mAh g-1 at 50 mA g-1 , which is much higher than graphite (372 mAh g-1 ), is obtained. Also, when the current density is up to 2 A g-1 , the capacity is about 150 mAh g-1 . Surprisingly, it also delivers a superior cycling performance. And when used as the anode/cathode electrode for lithium-ion capacitors, a high energy density can be obtained. The present work offers an opportunity to utilize the pitch source in lithium energy storage with promising cycle life, high energy/power density, and low cost.

Aim The aim of this study was to develop and validate a scoring system to predict the progression to acute-on-chronic liver failure (ACLF) in patients with acute exacerbation (AE) of chronic hepatitis B (CHB). Methods The baseline characteristics of 474 patients with AE of CHB were retrospectively reviewed; 280 and 194 patients were randomly assigned to the derivation and validation cohorts, respectively. Univariate risk factors associated with ACLF development were entered into a multivariate logistic regression. The score model was established, and its predictive value was evaluated by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC). Results Hepatitis B virus (HBV) DNA, international normalized ratio (INR) of prothrombin time, and patient age were identified as independent risk factors associated with progressing to ACLF. The prediction model was established as R = -13.323 + 0.553 × log HBV-DNA (copies/mL) + 3.631× INR + 0.053 × age. The AUROCs of our prediction model were higher than those of the Model for End-stage Liver Disease (MELD) and MELD-sodium (Na) for both cohorts. At the cut-off value of -2.43, our prediction model had higher sensitivity (87.5%), specificity (73.6%), positive predictive value (23.0%), positive likelihood ratio (3.30), and lower negative likelihood ratio (0.17) in the validation cohort than those of MELD and MELD-Na. Conclusion The independent risk factors associated with progressing to ACLF in patients with AE of CHB are HBV-DNA, INR, and age. Our risk prediction model is useful for predicting the development of ACLF.

AIM To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms. METHODS Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RT-PCR. Apoptotic index and cell viability of L02 cells and HepG2 cells were determined with flow cytometry and MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. RESULTS Pretreatment with 1 μmol/L PGE1 protected against TG-induced apoptosis in both L02 cells and HepG2 cells. PGE1 enhanced the TG-induced expression of C/EBP homologous protein (CHOP), glucose-regulated protein (GRP) 78 and spliced X box-binding protein 1 at 6 h. However, it attenuated their expressions after 24 h. PGE1 alone induced protein and mRNA expressions of GRP78; PGE1 also induced protein expression of DNA damage-inducible gene 34 and inhibited the expressions of phospho-PKR-like ER kinase, phospho-eukaryotic initiation factor 2α and CHOP. Treatment with protein kinase A (PKA)-inhibitor H89 or KT5720 blocked PGE1-induced up-regulation of GRP78. Further, the cytoprotective effect of PGE1 on hepatocytes was not observed after blockade of GRP78 expression by H89 or small interfering RNA specifically targeted against human GRP78. CONCLUSION Our study demonstrates that PGE1 protects against ER stress-induced hepatocyte apoptosis via PKA pathway-dependent induction of GRP78 expression.

Dry-wet spinning process was used to gain graphene oxide/polyimide composite fibers, then graphene/polyimide composite carbon and graphite fibers were obtained through carbonized and graphitized. Different graphene oxide contents of the composite carbon and graphite fibers were measured by thermal gravimetric analysis, Raman, mechanical properties, electrical properties,SEM and so on. The results show that when the GO content is 0.3%(mass fraction,the same below), the thermal property of the graphene oxide/polyimide composite fibers is the best. The mechanical and electrical properties are obriously improved by the addition of GO, graphitization degree also increases. When the composite carbon fibers are treated at 2800℃, GO content increases to 2.0%, the thermal conductivity of the composite graphite fibers reaches 435.57W·m-1·K-1 and cross-section structures of carbon fibers are more compact.

Aim To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration. Methods Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce liver injury. Human hepatocyte LO2 cells were incubated with thapsigargin to induce endoplasmic reticulum (ER) stress. Salubrinal, integrated stress response inhibitor (ISRIB), and DnaJC3 overexpression were used to alter eIF2α phosphorylation levels. Results CCl4 administration induced significant ER stress and eIF2α phosphorylation, and increased hepatocyte proliferation proportionally to the extent of injury. Inhibiting eIF2α dephosphorylation with salubrinal pretreatment significantly mitigated liver injury and hepatocyte proliferation. In LO2 cells, thapsigargin induced significant eIF2α phosphorylation and inhibited proliferation. Inhibiting eIF2α dephosphorylation partly restored cell proliferation during ER stress. Conclusions In acute liver injury, inhibiting eIF2α dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation.

Objectives. Protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α) is an important factor along the main pathways for endoplasmic reticulum (ER) stress-mediated apoptosis. In this study, we investigated the effects of eIF2α phosphorylation on hepatocyte apoptosis and the ER stress mechanisms in acute liver injury. Methods. eIF2α phosphorylation and apoptosis under ER stress were monitored and measured in male BALB/c mice with acute liver injury and human hepatocyte line LO2 cells. Results. Carbon tetrachloride (CCl4) administration triggered ER stress and hepatocyte apoptosis, as well as eIF2α phosphorylation in mice. Inhibition of eIF2α dephosphorylation, as the pretreatment with 4-phenylbutyric acid (chemical chaperone, ER stress inhibitor), mitigated CCl4-induced intrahepatic ER stress, apoptosis, and liver injury. In an ER stress model of LO2 cells induced by thapsigargin (disrupting ER calcium balance), inhibition of eIF2α dephosphorylation reduced ER stress and apoptosis, while PERK knockdown reduced eIF2α phosphorylation and exacerbated ER stress and apoptosis. Conclusions. eIF2α phosphorylation is one of the mechanisms employed by ER stress for restoring cellular homeostasis. Inhibition of eIF2α dephosphorylation mitigates hepatocyte apoptosis by alleviating ER stress in acute liver injuries.

In this study, a type of thiazolium-labeled 1,3,4-oxadiazole thioether bridged by diverse alkyl chain lengths was constructed. The antimicrobial activity of the fabricated thioether toward plant pathogenic bacteria and fungi was then screened. Antibacterial evaluation indicated that title compounds possess specific characteristics that enable them to severely attack three phytopathogens, namely

Objectives Protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α) is an important factor along the main pathways for endoplasmic reticulum (ER) stress-mediated apoptosis. In this study, we investigated the effects of eIF2α phosphorylation on hepatocyte apoptosis and the ER stress mechanisms in acute liver injury. Methods eIF2α phosphorylation and apoptosis under ER stress were monitored and measured in male BALB/c mice with acute liver injury and human hepatocyte line LO2 cells. Results Carbon tetrachloride (CCl4) administration triggered ER stress and hepatocyte apoptosis, as well as eIF2α phosphorylation in mice. Inhibition of eIF2α dephosphorylation, as the pretreatment with 4-phenylbutyric acid (chemical chaperone, ER stress inhibitor), mitigated CCl4-induced intrahepatic ER stress, apoptosis, and liver injury. In an ER stress model of LO2 cells induced by thapsigargin (disrupting ER calcium balance), inhibition of eIF2α dephosphorylation reduced ER stress and apoptosis, while PERK knockdown reduced eIF2α phosphorylation and exacerbated ER stress and apoptosis. Conclusions eIF2α phosphorylation is one of the mechanisms employed by ER stress for restoring cellular homeostasis. Inhibition of eIF2α dephosphorylation mitigates hepatocyte apoptosis by alleviating ER stress in acute liver injuries.

The transformation behavior of mesophase derived from three coal tar pitches with different softening-points was investigated. FTIR and XRD were used to analyze the compositions and molecular structures of pitches. The transformation behavior of the pitch to mesophase was observed in situ by a polarizing light microscope equipped with a heating stage. A correlation of the composition and molecular structure of the pitches to the development of the mesophase was obtained. Results indicate that the thermal conversion behavior of the three pitches to mesophase were different, and this was closely related to their aromaticity and quinolone insoluble fraction. The nucleation rate of mesocarbon microbeads was higher than the growth rate for the coal tar pitch with a high content of quinolone insolubles. A molecular lamellar structure with a high aromaticity benefitted the growth of microspheres and the formation of mesophase.