Enhanced d-π overlap in a graphene supported Ni/PtNi heterojunction for efficient seawater hydrogen evolution.

d-π overlap, which represents overlap between metal-d and graphene-π orbitals to facilitate electron transfer, has rarely been reported. Ni/PtNi-G2 exhibits exceptional performance in seawater hydrogen evolution due to the electron-rich surface on Pt resulting from enhanced d-π overlap and subsequent electron transfer from graphene and Ni to Pt.

Comments on "Effect of type 2 diabetes mellitus in the prognosis of acute-on-chronic liver failure patients in China".

A study addressing the influence of type 2 diabetes on the prognosis of acute-on-chronic liver failure patients was reviewed. Some statistical deficiencies were found in the reviewed article, and the sample size was too small to support the study. In addition, age should have been considered as one of the prognostic factors.

Piperlongumine Inhibits Akt Phosphorylation to Reverse Resistance to Cisplatin in Human Non-Small Cell Lung Cancer Cells via ROS Regulation.

Resistance is a major concern when administering chemotherapy to patients with non-small cell lung cancer (NSCLC). Chemosensitizer are agents that can reverse resistance to chemotherapeutic drugs, thereby enhancing the chemosensitivity of tumor cells. Thus, their development will improve therapeutic efficacy in cancer. However, few effective chemosensitizer have been identified to date. Piperlongumine (PL) has been shown to effectively reverse resistance to chemotherapeutic drugs in several types of cancers. However, the mechanisms associated with the chemotherapy resistance reversal effect of PL and its regulation of target factors in chemotherapy resistance cells are still unclear. This study investigated the reversal effect of PL both in vitro and in vivo, and provided evidence that PL inhibited the phosphorylation of Akt via the accumulation of reactive oxygen species in chemotherapy resistance cells. Consequently, various Akt activation-dependent genes caused a reduction of drug efflux and induction of apoptosis in cisplatin-resistant A549 NSCLC cells. Our results indicate that Akt phosphorylation may play a functional role in the reversal effect of PL and contribute, at least in part, to the treatment outcomes of patients with chemotherapy resistance.

Nucleocapsid protein of porcine reproductive and respiratory syndrome virus antagonizes the antiviral activity of TRIM25 by interfering with TRIM25-mediated RIG-I ubiquitination.

Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), and is characterized by respiratory diseases in piglet and reproductive disorders in sow. Identification of sustainable and effective measures to mitigate PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV plays a crucial role in inhibiting host innate immunity during PRRSV infection. In the current study, a new host-restricted factor, tripartite motif protein 25 (TRIM25), was identified as an inhibitor of PRRSV replication. Co-immunoprecipitation assay indicated that the PRRSV N protein interferes with TRIM25-RIG-I interactions by competitively interacting with TRIM25. Furthermore, N protein inhibits the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress interferon ß production. Furthermore, with increasing TRIM25 expression, the inhibitory effect of N protein on the ubiquitination of RIG-I diminished. These results indicate for the first time that TRIM25 inhibits PRRSV replication and that the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination. This not only provides a theoretical basis for the development of drugs to control PRRSV replication, but also better explains the mechanism through which the PRRSV N protein inhibits innate immune responses of the host.

Determination of alkaline phosphatase activity and of carcinoembryonic antigen by using a multicolor liquid crystal biosensor based on the controlled growth of silver nanoparticles.

An ultrasensitive liquid crystal biosensor is described for multicolor visualization of the activity of alkaline phosphatase (ALP) based on the controlled growth of silver nanoparticles. The enzymatic product is accumulated on the surface of the LC sensing film by means of silver deposition, and the birefringent signal (observed with a polarizing microscope) is strongly enhanced as a result. The presence of AuNPs also enhances the sensitivity by about 4 orders of magnitude. The bright spots in polarized optical microscopy (POM) images increase with increasing activities of ALP. The signal intensities of the spots are then calculated by using Photoshop software and by multiplying the average brightness of the spots by the pixel value. The detection limit for ALP is 1.2 nU·mL-1, which is 5-7 orders of magnitude lower than other colorimetric or fluorometric methods. The method was applied to a highly sensitive immunoassay for the carcinoembryonic antigen (CEA) by integrating immunomagnetic separation. The immunoassay was applied to the analysis of complex samples without tedious sample pretreatment, and a detection limit as low as 0.35 pg·mL-1 of CEA was achieved. The method has attractive features in that it provides an ultrasensitive multicolor visualization approach for enzymes such as ALP, but also paves the way to a new kind of immunoassay coupled to immunomagnetic separation. Graphical abstract A signal enhanced liquid crystal (LC)-based multicolor immunosensor is described that is based on immunomagnetic separation and biometallization. Alkaline phosphatase (ALP) and carcinoembryonic antigen (CEA) can be easily visualized by bare eyes using the polarized optical microscopy (POM) images of LCs.

MOV10 inhibits replication of porcine reproductive and respiratory syndrome virus by retaining viral nucleocapsid protein in the cytoplasm of Marc-145 cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) has been a major threat to global industrial pig farming ever since its emergence in the late 1980s. Identification of sustainable and effective control measures against PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV is specifically localized in the cytoplasm and nucleus of virus-infected cells which is important for PRRSV replication. In the current study, a new host restricted factor, Moloney leukemia virus 10-like protein (MOV10), was identified as an inhibitor of PRRSV replication. N protein levels and viral replication were significantly reduced in Marc-145 cells stably overexpressing MOV10 compared with those in wild-type Marc-145 cells. Adsorption experiments revealed that MOV10 did not affect the attachment and internalization of PRRSV. Co-immunoprecipitation and immunofluorescence co-localization analyses showed that MOV10 interacted and co-localized with the PRRSV N protein in the cytoplasm. Notably, MOV10 affected the distribution of N protein in the cytoplasm and nucleus, leading to the retention of N protein in the former. Taken together, these findings demonstrate for the first time that MOV10 inhibits PRRSV replication by restricting the nuclear import of N protein. These observations have great implications for the development of anti-PRRSV drugs and provide new insight into the role of N protein in PRRSV biology.

Reverse effect of curcumin on CDDP-induced drug-resistance via Keap1/p62-Nrf2 signaling in A549/CDDP cell.

OBJECTIVE: To assess the effect of curcumin on CDDP-induced drug resistance and explore the underlying molecular mechanism through Nrf2 system and autophagy pathway. METHODS: A drug-resistant cell model was established by exposing A549/CDDP cell to 2 µg/mL CDDP. A549/CDDP cell was treated with 20 µg/mL CDDP and 10 µM curcumin. The cell viability and apoptosis level, the signals of Keap1/P62-Nrf2 and autophagy pathway were analyzed. RESULTS: CDDP induction promoted drug-resistant phenotype in A549/CDDP cell and activated autophagy as well as Nrf2 signals in A549/CDDP cell. Meanwhile, curcumin combination attenuated autophagy and Nrf2 activation induced by CDDP, and reversed the drug-resistant phenotype. Notably, curcumin combination augmented Keap1 transcription. Furthermore, Keap1 ablation with short hairpin RNAs hampered the efficacy of curcumin, suggesting Keap1 played a crucial role on reversal effect of curcumin. CONCLUSIONS: The present findings demonstrate that CDDP promotes abnormal activation of Nrf2 pathway and autophagy, leading to drug resistance of A549/CDDP cell. Curcumin attenuates this process and combat drug-resistance through its potent activation on Keap1 transcription, which is essential for interplay between oxidative stress induced Nrf2 activation and autophagy/apoptosis switch.

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Effects of intracavitary administration of Endostar combined with cisplatin in malignant pleural effusion and ascites.

This study evaluated the efficacy and safety of intracavitary administration of recombinant human endostatin (Endostar) combined with cisplatin chemotherapy in treating malignant pleural effusion and ascites. Forty-five patients with malignant pleural effusion and ascites were divided into the EP group (n = 23), who received Endostar and cisplatin intracavitarily, and P group (n = 22), who were intracavitarily treated with cisplatin only. Pleural effusion and ascites were completely drained before treatments. The treatment was administered once a week; two treatments were considered as one course. The outcome quality of life as well as toxicity were evaluated. The objective overall response and disease control rates were, respectively, 78.3 % (18/23) and 87.0 % (20/23) in EP group. In contrast, these parameters were significantly (p < 0.05) lower in P groups: 40.9 % (9/22) and 59.1 % (13/22), respectively. The improvement rate of Karnofsky Performance Status was 87.0 % (20/23) in EP group versus 59.1 % (13/22) in P group (p < 0.05). All patients tolerated the combined treatment well, and no severe adverse effects were observed. Intracavitary injection of Endostar combined with cisplatin is effective and safe to treat malignant pleural effusion and ascites.

[A prospective randomized controlled clinical trial of irinotecan plus cisplatin versus gemcitabine plus cisplatin as a first-line treatment for advanced non-small cell lung cancer].

OBJECTIVE: To prospectively evaluate the efficacy and toxicity of irinotecan plus cisplatin (IP regimen) compared with gemcitabine plus cisplatin (GP regimen) as a first-line treatment for advanced non-small cell lung cancer (NSCLC). METHODS: A total of 63 patients were randomly assigned to two regimens. IP Group (31 patients): irinotecan 100 mg/m(2), iv, d1 and d8; cisplatin 25 mg/m(2), iv, d1 to d3, and 3 weeks a cycle. GP Group (32 patients): gemcitabine 1000 mg/m(2), d1 and d8; cisplatin 25 mg/m(2), iv, d1 to d3, and 3 weeks a cycle. All the patients at least received two cycles of therapy. The response rate (RR), disease control rate (DCR), median time to tumor progression (TTP), median survival time (MST), l-year survival rate, and side effects were observed. RESULTS: Among the 31 cases of IP group, 8 patients had PR, 17 patients had SD and 6 patients had PD. The RR and DCR were 25.8% (8/31) and 80.6% (25/31), respectively. The TTP was 6.7 months, MST was 11.2 months and the 1-year survival rate was 45.2% (14/31). Among 32 cases in the GP group, 11 patients had PR, 18 patients had SD and 3 patients had PD. The RR and DCR were 34.4% (11/32) and 90.6% (29/32), respectively. The TTP was 6.5 months, MST was 11.0 months and the 1-year survival rate was 43.7% (14/32). The main side effects of the two groups included hematologic toxicities, digestive tract reaction and hair loss. The incidence of diarrhea in the IP group was significantly higher than that in the GP group (P < 0.05), but the incidence of thrombocytopenia in the GP group was significantly higher than that in the IP group (P < 0.01). CONCLUSIONS: Our findings demonstrate that the two regimens have similar efficacy as a first-line treatment for advanced NSCLC. The major toxicities of the two regimens are well tolerable.

[Comparison between the effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer].

OBJECTIVE: To observe and compare the response rate and toxicity of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer. METHODS: Sixty-three patients with advanced gastric cancer were randomly divided into two groups. The CPT-11 + CAP group consisted of 32 patients who received irinotecan plus capecitabine: CPT-11 100 mg/m(2) was injected in 90 minutes on d 1, 8;capecitabine 2000 mg/m(2), bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days. The L-OHP + CAP group consisted of 31 patients who received oxaliplatin plus capecitabine: oxaliplatin 100 mg/m(2) on day 1, capecitabine 2000 mg/m(2), bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days. Two or more cycle chemotherapy was completed in each group. RESULTS: In the CPT-11 + CAP group, no patient achieved complete response and 13 patients achieved partia1 response. The overall response rate was 40.6% (13/32), and the median progression-free survival time was 6.3 months. In the L-OHP + CAP group, no patient achieved complete response and 12 patients achieved partial response. The overall response rate was 38.7% (12/31), and the median progression-free survival time was 6.1 months. There was no significant difference between them (P > 0.05). The most common toxicities were gastrointestinal reaction, peripheral neuropathy and myelosuppression in the two groups. Patients in CPT-11 + CAP group experienced more III/IV diarrhea (28.1%/3.2%, P = 0.018). On the contrary, the rate of III/IV neurotoxicity in the group B was higher (25.8%/3.1%, P = 0.027). No chemotherapy-related death occurred. CONCLUSION: The therapeutic effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer are good and comparable, and their toxicities are tolerable.

Three new dioxopiperazine metabolites from a marine-derived fungus Aspergillus fumigatus Fres.

Three new dioxopiperazine metabolites (1-3), together with two known compounds, N-acetyltyramine (4) and cyclo-(Ala-Val) (5), were isolated from a marine-derived fungus Aspergillus fumigatus Fres. Their structures were established by spectroscopic methods. Their cytotoxic activities against the K562 cell line were preliminarily evaluated by the sulphorhodamine B (SRB) method.

A new gliotoxin analogue from a marine-derived fungus Aspergillus fumigatus Fres.

A new gliotoxin analogue (1), as well as four known compounds gliotoxin (2), bisdethiobis (methylthio) gliotoxin (3), bis-N-norgliovictin (4) and didehydrobisdethiobis (methylthio) gliotoxin (5), were isolated from a culture of marine-derived fungus Aspergillus fumigatus Fres. The structure of 1 was determined on the basis of spectroscopic methods. All five compounds were evaluated for the cytotoxic effects on tsFT210 cell line by the SRB method.

Enantiopure double-helical phenylene ethynylene cyclophynes with the 2,2'-binaphthyl template.

New types of enantiopure compounds were synthesized to gain better insight into the structural features of phenylene ethynylene cyclophynes. Besides the previously obtained meta-substituted arylene ethynylenes, 1, ortho-connected phenylene ethynylene units were incorporated to give cyclophynes with ortho/meta and ortho/ortho connection modes, 2 and 3. Furthermore, a diphenylethyne component was also accommodated in 4. Both ab initio calculations and NMR spectra suggest a large amount of strain for 2 but less strain for 3 and 1 a, the latter having the smallest ring size among cyclophynes with the meta/meta connection mode. The CD spectra of 2 and 3 showed a characteristic shoulder at around 340 nm, similar to the case of 1 a. This implies that the aromatic acetylene bonds cross over each other in the double-helical structure. These results indicate that chirality information is useful for probing the persistency of molecular shape.

[Apoptosis gene expression profiling of placental trophoblast cells in patients with pregnancy induced hypertension].

OBJECTIVE: To explore the function of placental trophoblast cell apoptosis on the pathogenetic mechanism of pregnancy induced hypertension (PIH). METHODS: Apoptosis of trophoblast cells in 20 cases of PIH (PIH group) and in 10 cases of normal pregnancy (control group) were directly observed using the terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL) method. Apoptosis gene expression patterns were screened with gene chip provided by Poxing Company, Shanghai. Standards for differently expressed genes were: (1) An absolute value of the natural logarithm of cy5 (PIH group)/cy3 (control group) greater than 0.69 with a difference of signal of cy5 2 times over that of cy3. (2) The signal value either cy3 or cy5 must be greater than 800. RESULTS: (1) TUNEL test showed that the number of trophoblast cells apoptosis per ten thousand micro m(2) was 1.584 in the PIH group and 0.032 in the control group with significant difference between the two groups (P < 0.01). (2) Ten differently expressed apoptosis genes were obtained through gene chip test (occupy 5% of total apoptosis gene in the gene chip). There was a significant decrease of apoptosis gene expression in all of PIH patient placental tissues (i.e a ratio of cy5/cy3 less than 1). Among them, there were genes that possess significant anti-apoptosis functions (including SFRP(2), IAP(2), DHCY24 and ATPIA1). CONCLUSIONS: Remarkable apoptosis was found in placental trophoblast cells of PIH patients. Significant decrease in genes with anti-apoptosis functions can result in the apoptosis of placental trophoblast cells and thus contributes to the pathogenesis of PIH.