Deep insight on Li interlayer migration in O3-type NaLi1/3Mn2/3O2 as a cathode material for Na-ion batteries.

Layered manganese transition metal oxides, such as NaMnO2, have attracted great interest due to the low cost and high capacity. However, complex phase transitions in NaMnO2 lead to poor cycling stability. The introduction of Li doping has been confirmed to improve the performance of NaMnO2. O3-type NaLi1/3Mn2/3O2 (NLMO), synthesized in 2021, has demonstrated excellent electrochemical performance. Notably, irreversible Li interlayer migration (Li migrates from the transition metal layer to the alkali metal layer) has been observed during cycling, which is related to the electrochemical performance. Therefore, it is crucial to understand the mechanism underlying Li interlayer migration in O3-NLMO. However, the environment of Li interlayer migration on cycling is complex and involves interlayer spacing, Na-ion concentration, the degree of O-ion oxidation, and phase transition. Here, in this work, we utilized the first-principles method to decouple the coupling factors influencing the Li interlayer migration. Through analyzing the impact of the single-factor on Li interlayer migration, we aim to identify the crucial factors affecting this process. Our results show that a decrease in Na-ion concentration and an increase in O-ion oxidation degree promote the Li interlayer migration, while the O-P phase transition suppresses the Li interlayer migration. Interlayer spacing was found to play a less influential role in Li interlayer migration. Our investigations provide effective strategies for the subsequent regulation of Li interlayer migration.

Structural and Na-ion diffusion behavior of O3/P3/P2-type NaNi1/3Mn1/3Fe1/3O2 cathode for Na-ion batteries from first-principles study.

A layered sodium-ion battery cathode, O3/P3/P2-type NaNi1/3Mn1/3Fe1/3O2, has been systematically investigated by first-principles density functional theory to explore the detailed structural and Na-ion diffusion behavior during desodiation. Our results suggest that the (NaO6) spacing is greatest in the P3 phase and lowest in the O3 phase, with the P2 phase exhibiting intermediate spacing. During desodiation, the intermediate stages have a greater (NaO6) spacing than the initial and final stages. The great (NaO6) spacing facilitates the formation of the P3 phase, resulting in the structural evolution of NaxNi1/3Mn1/3Fe1/3O2 from the O3 to the P3 phase at x ≈ 0.59, finally reaching the O3 structure again at x ≈ 0.12. The electronic structure clearly proves that both Ni and Fe are active in O3/P3/P2-type NaxNi1/3Mn1/3Fe1/3O2. Ni2+ is oxidized to Ni3+ as Na content decreases from x = 1 to x = 0.66, then further oxidized to Ni4+ at x = 0.33, and finally, Fe3+ → Fe4+ oxidation occurs at x = 0. In the Na ion diffusion behavior, the order of the barrier is O3 (0.82 eV) > P2 (0.53 eV) > P3 (0.35 eV) at the initial stage, whereas it is O3 (0.53 eV) > P3 (0.21 eV) > P2 (0.16 eV) at a highly desodiated stage. The former can be traced back to the (NaO6) spacing, but the latter is related to the different Na sites. Our results thus provide a factor of the structural evolution and Na ion diffusion barrier by considering (NaO6) width and Na site changes during desodiation.

Vv-circSIZ1 mediated by pre-mRNA processing machinery contributes to salt tolerance.

CircRNAs exist widely in plants, but the regulatory mechanisms for the biogenesis and function of plant circRNAs remain largely unknown. Using extensive mutagenesis of expression plasmids and genetic transformation methods, we analyzed the biogenesis and anti-salt functions of a new grape circRNA Vv-circSIZ1. We identified Vv-circSIZ1 that is mainly expressed in the cytoplasm of xylem. CircSIZ1 is species-specific, and genomic circSIZ1-forming region of seven tested species could be backspliced in Nicotiana benthamiana, but not in Arabidopsis. The retention length of Vv-circSIZ1 flanking introns was significantly positively correlated with its generation efficiency. The precise splicing of Vv-circSIZ1 does not depend on its mature exon sequence or internal intron sequences, but on the AG/GT splicing signal sites and branch site of the flanking introns. The spliceosome activity was inversely proportional to the expression level of Vv-circSIZ1. Furthermore, RNA-binding proteins can regulate the expression of Vv-circSIZ1. The overexpression of Vv-circSIZ1 improved salt tolerance of grape and N. benthamiana. Additionally, Vv-circSIZ1 could relieve the repressive effect of VvmiR3631 on its target VvVHAc1. Vv-circSIZ1 also promoted transcription of its parental gene. Overall, these results broaden our understanding of circRNAs in plants.

Dissociation of (Li2O2)0,+ on graphene and boron-doped graphene: insights from first-principles calculations.

Reducing charge overpotential is of great significance to enhance the efficiency and cyclability of Li-O2 batteries. Here, a dramatically reduced charge overpotential via boron-doped graphene as a catalytic substrate is successfully predicted. By first-principles calculations, from the perspective of reaction thermodynamics and kinetics, the results show that the electrochemical oxidation of the Li2O2+ cation is easier than the chemical oxidation of the neutral Li2O2 molecule, and the oxidation of (Li2O2)0,+ is facilitated by boron-doping in pristine graphene. More importantly, the results reveal the oxidation mechanism of (Li2O2)0,+: two-step dissociation with the LiO2 molecule as a reactive intermediate has advantages over one-step dissociation; the rate-determining step for the dissociation of (Li2O2+)G is the oxygen evolution process, while the lithium removal process is the rate-determining step for the dissociation of (Li2O20)G, (Li2O20)BG, and (Li2O2+)BG.

The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder cancer.

Chemotherapy drug resistance frequently happens in more than 50% of bladder cancer patients and is the major obstacle for the bladder cancer therapy. Recent studies have shown that long noncoding RNA (lncRNA) is involved in the development of chemoresistance. In this study, we reported hypoxia inducible factor 1α-antisense RNA 2 (HIF1A-AS2), as a subtype-specific hypoxia inducible lncRNA, is upregulated in bladder cancer cells and tissue after cisplatin (Cis) treatment. The induction of HIF1A-AS2 in bladder cancer cells rendered resistance to Cis-induced apoptosis. Silencing HIF1A-AS2 in Cis-resistant bladder cancer cells was re-sensitized to Cis-induced apoptosis. Mechanically, we found that HIF1A-AS2 suppressed the transcription activity of p53 family proteins by promoting the expression of high-mobility group A1 (HMGA1). The induction of HMGA1 physically interacts with p53, p63, and p73, and therefore constrains their transcriptional activity on Bax. Knockdown of HIF1A-AS2 or HMGA1 rescued the expression of Bax, which therefore enhanced the killing effect of Cis. Furthermore, we also found that the expression of HIF1A-AS2 was higher in the human bladder tumor tissues after Cis treatment, and was positive correlated to the expression of HIF1α and HMGA1. This study suggests that upregulated HIF1A-AS2 hampers the p53 family proteins dependent apoptotic pathway to promote Cis resistance in bladder cancer. Our data suggested that HIF1A-AS2 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer.

Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression.

Long noncoding RNAs (lncRNAs) have been acknowledged as vital regulators in tumorigenesis of human cancers, including hepatocellular carcinoma (HCC). LINC00461 has been found to promote progression of glioma and breast cancer. Nevertheless, the function of LINC00461 in HCC is still unknown. Here, we found that LINC00461 was upregulated in HCC tissues and positively correlated with advanced stage and metastasis. Furthermore, LINC00461 overexpression in HCC patients predicts unfavorable prognosis. Loss-of-function assays showed that LINC00461 silencing suppressed the proliferation, migration and invasion of HCC cells in vitro, and impeded tumor growth in vivo. Mechanistically, LINC00461 inversely regulates miR-149-5p abundance in HCC. Further investigation indicated that LINC00461 was a competing endogenous RNA (ceRNA) by directly sponging miR-149-5p in HCC cells. Moreover, LRIG2 was identified as the downstream target of miR-149-5p and its expression was regulated by LINC00461/miR-149-5p axis. Restoration of LRIG2 reversed LINC00461 knockdown attenuated HCC cell proliferation, migration and invasion. In summary, our findings revealed that LINC00461 is an oncogene in HCC through regulating miR-149-5p/LRIG2 pathway.

Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis.

Long noncoding RNAs (lncRNAs) are involved in tumorigenesis. Previously, lncRNA MNX1-AS1 was reported to increase the malignancy of ovarian cancer, cervical cancer and lung cancer. However, the potential function of MNX1-AS1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that MNX1-AS1 was remarkably upregulated in HCC tissues and cell lines. Furthermore, MNX1-AS1 overexpression was related to advanced stage and metastasis, and predicted poor prognosis. Loss-of-function assays showed that MNX1-AS1 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro. Further investigation indicated that MNX1-AS1 silencing delayed HCC growth in vivo. Mechanistically, we identified that MNX1-AS1 was a competing endogenous RNA (ceRNA) for miR-218-5p. We demonstrated that MNX1-AS1 promoted COMMD8 expression through sponging miR-218-5p, and then contributed to HCC progression. Restoration of COMMD8 significantly reversed the effects of MNX1-AS1 knockdown. Taken together, our findings demonstrated that MNX1-AS1 promoted the malignant properties of HCC through targeting miR-218-5p/COMMD8 pathway.

The crab Relish plays an important role in white spot syndrome virus and Vibrio alginolyticus infection.

Relish is a transcription factor and forms an important part of the immune deficiency signaling pathway. In the current study, a Relish homolog was cloned from the hemolymph of Scylla paramamosain using RT-PCR and RACE. The full length cDNA of Relish consists of 4263 base pairs (bp), including a 3552 bp open reading frame encoding a 1184 amino acid protein. The data showed that Relish was highly expressed in the gonad and digestive organs of S. paramamosain. Furthermore, the expression of Relish was up-regulated by infection with white spot syndrome virus (WSSV) or Vibrio alginolyticus. When Relish was knocked down, immune genes such as Janus Kinase, signal transducer and activator of transcription, crustin antimicrobial peptide, prophenoloxidase, C-type-lectin and myosin-II-essential-light-chain-like-protein were significantly down-regulated (P < 0.01), and Toll-like receptor was significantly up-regulated (P < 0.01) in hemocytes. The mortality of WSSV-infected or V. alginolyticus-infected crabs was enhanced following Relish knockdown. Thus, Relish is very important in the progression of WSSV and V. alginolyticus infection. It was found that Relish knockdown caused the highest level of apoptosis in the disease-free group, and higher levels of apoptosis in the WSSV group and V. alginolyticus group compared with that in the control group. Knockdown of Relish influenced the activity of phenoloxidase (PO) and superoxide dismutase (SOD), and total hemocyte count (THC) following WSSV or V. alginolyticus infection, indicating that Relish plays a regulatory role in the immune response to WSSV or V. alginolyticus infection in crabs. Thus, we conclude that Relish may anticipate host defense mechanisms against pathogen infection by affecting apoptosis, THC, PO activity and SOD activity.

Up-regulation of miR-10b-3p promotes the progression of hepatocellular carcinoma cells via targeting CMTM5.

In this study, we investigated how miR-10b-3p regulated the proliferation, migration, invasion in hepatocellular carcinoma (HCC) at both in vitro and in vivo levels. CMTM5 was among the differentially expressed genes (data from TCGA). The expression of miR-10b-3p and CMTM5 was detected by qRT-PCR and Western blot (WB). TargetScan was used to acquire the binding sites. Dual-luciferase reporter gene assay was used to verify the direct target relationship between miR-10b-3p and CMTM5. WB analysis proved that miR-10b-3p suppressed CMTM5 expression. Furthermore, proliferation, invasion and migration of HCC cells were measured by MTT assay, colony formation assay, transwell assay and wound-healing assay, respectively. Kaplan-Meier plotter valued the overall survival of CMTM5. Finally, xenograft assay was also conducted to verify the effects of miR-10b-3p/CMTM5 axis in vivo. Up-regulation of miR-10b-3p and down-regulation of CMTM5 were detected in HCC tissues and cell lines. CMTM5 was verified as a target gene of miR-10b-3p. The overexpression of CMTM5 contributed to the suppression of the proliferative, migratory and invasive abilities of HCC cells. Moreover, the up-regulation of miR-10b-3p and down-regulation of CMTM5 were observed to be associated with worse overall survival. Lastly, we have confirmed the carcinogenesis-related roles of miR-10b-3p and CMTM5 in vivo. We concluded that the up-regulation of miR-10b-3p promoted the progression of HCC cells via targeting CMTM5.

The shrimp hormone receptor acts as an anti-apoptosis and anti-inflammatory factor in innate immunity.

Previously, we found that the expression of several genes, including HR, varied in Drosophila melanogaster after white spot syndrome virus (WSSV) infection. In this present study, we further investigated the role of HR in Kuruma shrimp, Marsupenaeus japonicus and determined its anti-apoptosis and anti-inflammation role in the innate immune system. We successfully identified a partial sequence (866 bp in length) of the M. japonicus hormone receptor ligand binding domain (mjHR_LBD/mjHR). The 5' end of mjHR was successfully obtained; the open reading frame (ORF) ran from 33 to 701 bp, and encoded a protein containing 222 amino acids. mjHR belonged to the ligand binding domain of hormone receptors, was most likely part of a nuclear hormone receptor, and shared a close evolutionary relationship with other arthropods, such as insects. mjHR was expressed predominantly in immunity tissues such as gills, hemolymph and the hepatopancreas. WSSV infection could cause the down-regulation of mjHR, while infection with Vibrio alginolyticus could cause significant up-regulation of mjHR. The expression of mjHR was knocked down by dsRNA expressed by an engineered LITMUS 38i-HR plasmid. Virus and bacteria challenge experiment showed that the mortality of WSSV-infected shrimps was elevated in the absence of HR while the mortality of shrimps infected with V. alginolyticus was slightly reduced. Phenoloxidase (PO) activity, phagocytosis and apoptosis were promoted, while superoxide dismutase (SOD) activity was impaired, indicating that mjHR functions in an anti-apoptosis and anti-inflammation manner to prevent shrimp death caused by an over-load of immunity responses. Differences between mjHR expression and mortality change after WSSV or V. alginolyticus infection indicated that there was a different strategy for viruses or bacteria when confronted with the innate immune system.

Epigallocatechin-3-gallate protects Kuruma shrimp Marsupeneaus japonicus from white spot syndrome virus and Vibrio alginolyticus.

Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and exhibits potential antibacterial and anticancer activities. In this study, EGCG was used in pathogen-challenge experiments in shrimp to discover its effect on the innate immune system of an invertebrate. Kuruma shrimp Marsupeneaus japonicus was used as an experimental model and challenged with white spot syndrome virus (WSSV) and the Gram-negative bacterium Vibrio alginolyticus. Pathogen-challenge experiments showed that EGCG pretreatment significantly delayed and reduced mortality upon WSSV and V. alginolyticus infection, with VP-28 copies of WSSV also reduced. Quantitative reverse transcription polymerase chain reaction revealed the positive influence of EGCG on several innate immune-related genes, including IMD, proPO, QM, myosin, Rho, Rab7, p53, TNF-alpha, MAPK, and NOS, and we observed positive influences on three immune parameters, including total hemocyte count and phenoloxidase and superoxide dismutase activities, by EGCG treatment. Additionally, results showed that EGCG treatment significantly reduced apoptosis upon V. alginolyticus challenge. These results indicated the positive role of EGCG in the shrimp innate immune system as an enhancer of immune parameters and an inhibitor of apoptosis, thereby delaying and reducing mortality upon pathogen challenge. Our findings provide insight into potential therapeutic or preventive functions associated with EGCG to enhance shrimp immunity and protect shrimp from pathogen infection.

Molecular characterization of glutaminyl-peptide cyclotransferase(QPCT)in Scylla paramamosain and its role in Vibrio alginolyticus and white spot syndrome virus (WSSV) infection.

Glutaminyl-peptide cyclotransferase (QPCT) catalyzes the posttranslational modification of an N-terminal glutamate of proteins to pyroglutamate. This renders the protein more resistant to protease degradation, more susceptible to hydrophobic interactions, aggregation, and neurotoxic. In this study, we evaluated the influence of QPCT in the crab Scylla paramamosain infected with white spot syndrome virus (WSSV) or with Vibrio alginolyticus. A cDNA clone, encompassing the entire 2445 bp of the S. paramamosain QPCT gene, containing a 1113 bp open reading frame (ORF) encoding a 370 amino acid protein was cloned from S. paramamosain. Real-time PCR indicated that QPCT was primarily expressed in the digestive tract of S. paramamosain, was up-regulated in hemocytes after infection with V. alginolyticus, and down-regulated in hemocytes after infection with WSSV. Knockdown of QPCT expression by double-stranded RNA (QPCT-dsRNA) resulted in down-regulation of prophenoloxidase (proPO) and crustin antimicrobial peptide, whereas myosin-II-essential-light-chain-like-protein was significantly up-regulated in hemocytes at 24 h post QPCT-dsRNA treatment. WSSV challenge in crabs treated with QPCT-dsRNA resulted in a reduction in viral burden and in the apoptotic rate of crab hemocytes, while the phagocytic activity of crab hemocytes and overall mortality rate were increased. This suggests that WSSV might take advantage of QPCT to benefit its replication. In contrast, V. alginolyticus infection in crabs treated with QPCT-dsRNA indicated that the apoptotic rate and phagocytic activity of hemocytes, and overall incidence of mortality, were increased compared to mock-treated animals, indicating that QPCT might be a resistance factor in bacterial infection. These results increase our understanding of the function of QPCT and its role in the innate immunity of S. paramamosain.

Molecular characterization of shrimp harbinger transposase derived 1 (HARBI1)-like and its role in white spot syndrome virus and Vibrio alginolyticus infection.

The role of the nuclease, HARBI1-like protein (mjHARBI1-like) in the innate immunity of Marsupenaeus japonicus was explored in this study. The 1361 bp cDNA sequence of mjHARBI1-like was cloned from M. japonicus using RACE. RT-qPCR analysis results showed that the gills and hepatopancreas of M. japonicus were the main tissues where mjHARBI1-like is expressed. In addition, it was also found that white spot syndrome virus (WSSV) or Vibrio alginolyticus challenge could stimulate mjHARBI1-like expression. After mjHARBI1-likewas inhibited, expression of immune genes such as toll, p53, myosin, and proPO were significantly downregulated (P < 0.01). However, in shrimp hemocytes, hemocyanin and tumor necrosis factor-α (TNF-α) were up-regulated significantly (P < 0.01). This study demonstrated that mjHARBI1-like plays a key role in the progression of WSSV and V. alginolyticus infection. Specifically, the cumulative mortality of WSSV-infected and V. alginolyticus-infected shrimp was significantly advanced by double-strand RNA interference (dsRNAi) of mjHARBI1-like. Apoptosis studies indicated that mjHARBI1-dsRNA treatment caused a reduction in hemocyte apoptosis in bacterial and viral groups. In addition, phagocytosis experiments illustrated that mjHARBI1-dsRNA treatment led to a lower phagocytosis rate in hemocytes of V. alginolyticus-challenged shrimp. It was also found that knockdown of mjHARBI1-like inhibited shrimp phenoloxidase (PO) activity, superoxide dismutase (SOD) activity, and total hemocyte count (THC) after WSSV or V. alginolyticus infection. These data indicate a regulative role of mjHARBI1-likein the immunity of shrimp in response to pathogen infection. Resultantly, it was concluded that mjHARBI1-like might have a positive effect on the anti-WSSV immune response of shrimp by regulating apoptosis, THC, PO activity, and SOD activity. Additionally, mjHARBI1-like might promote anti-V. alginolyticus infection by participating in regulating phagocytosis, apoptosis, SOD activity, PO activity, and THC.

Molecular characterization of diphthamide biosynthesis protein 7 in Marsupenaeus japonicus and its role in white spot syndrome virus infection.

Diphthamide biosynthesis protein 7 (Dph7) is a vital protein for diphthamide biosynthesis in archaea and eukaryotes. The 1143 bp cDNA sequence of Dph7 was cloned from the gills of Marsupenaeus japonicus using RT-PCR and RACE. Data showed that Dph7 was highly expressed in the gills and digestive gland of M. japonicus. Furthermore, the expression of dph7 was induced by infection with white spot syndrome virus (WSSV). When Dph7 was knocked down, immune genes such as toll, prophenoloxidase (proPO), p53, tumor necrosis factor-α (TNF-α) and signal transducer and activator of transcription (STAT) were significantly down-regulated (P < 0.01) in hemocytes. First, we demonstrated that Dph7 is very important in the progression of WSSV infection and that the time of death for WSSV-infected shrimp was significantly advanced following RNAi targeting of Dph7. We also investigated the effect of Dph7 on apoptosis rate in M. japonicas and found that Dph7-dsRNA treatment caused lower levels of apoptosis in hemocytes, both in the disease-free group and the WSSV group. Knock-down of Dph7 affected the activity of both phenoloxidase (PO) and superoxide dismutase (SOD), and total hemocyte count (THC) after infection with WSSV, indicating that Dph7 plays a regulatory role in the immunological reaction of shrimp in response to WSSV infection. Thus, we conclude that Dph7 may promote the anti-WSSV immune response of shrimp by regulating apoptosis, SOD and PO activity, and can influence the progression of WSSV infection.

Molecular cloning of Kuruma shrimp Marsupenaeus japonicus endonuclease-reverse transcriptase and its positive role in white spot syndrome virus and Vibrio alginolyticus infection.

This study investigated the function of endonuclease-reverse transcriptase (mjERT) in Marsupenaeus japonicus. The 1129 bp cDNA sequence of mjERT was cloned from M. japonicus using rapid amplification of cDNA ends (RACE) PCR, and RT-qPCR analysis indicated that mjERT was highly expressed in the gills and hepatopancreas of M. japonicus. We also found that white spot syndrome virus (WSSV) or Vibrio alginolyticus challenge could enhance the expression of mjERT. When mjERT was inhibited, immune genes such as toll, p53, hemocyanin and tumor necrosis factor-α (TNF-α) were significantly down-regulated (P < .01) in the hemocytes of shrimp, while myosin was significantly up-regulated (P < .01). We demonstrated that mjERT is very important for the progression of WSSV infection and that the cumulative mortality of WSSV-infected and V. alginolyticus-infected shrimps was significantly increased following mjERT RNA interfere (RNAi). Apoptosis data provided information to suggest that mjERT-dsRNA challenge caused less apoptosis in hemocytes in both the disease-free and viral group. We also revealed that mjERT-dsRNA treatment resulted in a lower phagocytosis rate in the hemocytes of V. alginolyticus-challenged shrimp. Finally, we found that the absence of mjERT had an significantly negative impact upon shrimp phenoloxidase (PO) activity, superoxide dismutase (SOD) activity and total hemocyte count (THC) following WSSV or V. alginolyticus infection, indicating a regulative role for mjERT in the innate immunity of shrimp in response to pathogenic infection. In summary, we concluded that mjERT might promote the anti-WSSV immune response of shrimp by regulating apoptosis, PO activity, THC and SOD activity, and also exert a positive role in the immune response against V. alginolyticus by regulating phagocytosis, SOD activity, PO activity and THC.

Bandgap tuning in MoSSe bilayers: synergistic effects of dipole moment and interlayer distance.

From first principles calculations, the lowest energy structures of bilayer MoSSe with different combination patterns (S-S, Se-Se, and S-Se bilayers) have been confirmed. The results demonstrate that the band gap of bilayer MoSSe can be tuned by interlayer distance and dipole moment. A larger interlayer distance increases the band gap, while a larger dipole moment reduces the band gap. That is, the gap is affected by the synergistic effects of dipole moment and interlayer distance in a MoSSe bilayer. Our results provide a new way to realize band gap modulation by changing the dipole moment or the interlayer distance. Impressively, another important finding is that the S-Se bilayer has a type-II band alignment, which makes it a good candidate for applications in optoelectronics.

Asymmetric Nitrone Synthesis via Ligand-Enabled Copper-Catalyzed Cope-Type Hydroamination of Cyclopropene with Oxime.

We report realization of the first enantioselective Cope-type hydroamination of oximes for asymmetric nitrone synthesis. The ligand promoted asymmetric cyclopropene "hydronitronylation" process employs a Cu-based catalytic system and readily available starting materials, operates under mild conditions and displays broad scope and exceptionally high enantio- and diastereocontrol. Preliminary mechanistic studies corroborate a CuI-catalytic profile featuring an olefin metalla-retro-Cope aminocupration process as the key C-N bond forming event. This conceptually novel reactivity enables the first example of highly enantioselective catalytic nitrone formation process and will likely spur further developments that may significantly expedite chiral nitrone synthesis.

B-cell lymphoma 2 inhibitor ABT-737 induces Beclin1- and reactive oxygen species-dependent autophagy in Adriamycin-resistant human hepatocellular carcinoma cells.

ABT-737, a B-cell lymphoma 2 homology 3 mimetic, not only induces cell apoptosis by inhibiting the interaction of B-cell lymphoma 2 and Bax but also induces cell autophagy by interrupting the interaction of B-cell lymphoma 2 and Beclin1. Several recent studies have reported that ABT-737 has antitumor efficacy in diverse cancers. However, another study showed that hepatocellular carcinoma cells with high B-cell lymphoma 2 expression were resistant to ABT-737 compared to hepatocellular carcinoma cells with low B-cell lymphoma 2 expression. It was also found that ABT-737-induced autophagy is crucial for drug resistance. Here, we observed that of B-cell lymphoma 2 expression in Adriamycin-resistant human hepatocellular carcinoma HepG2/ADM cells is higher than that in human hepatocellular carcinoma HepG2 cells. Therefore, we further confirmed the mechanism and effect of autophagy induced by ABT-737 on apoptosis in HepG2/ADM cells with high B-cell lymphoma 2 expression. Our results showed that ABT-737 induced apoptosis and autophagy in time- and dose-dependent manner in HepG2/ADM cells, and this ABT-737-induced autophagy was Beclin1-dependent. In addition, we demonstrated that ABT-737 induced reactive oxygen species-mediated autophagy, and the reactive oxygen species-inhibitor N-acetyl-l-cysteine suppressed the reactive oxygen species-induced autophagy and ABT-737-induced increase in HepG2/ADM cell apoptosis. Furthermore, autophagy inhibitors increased HepG2/ADM cell apoptosis. In conclusion, our study further confirms that Beclin1- and reactive oxygen species-dependent autophagy induced by ABT-737 also plays a protective function in HepG2/ADM cells, which show B-cell lymphoma 2 expression higher than that in HepG2 cells.

The crustin-like peptide plays opposite role in shrimp immune response to Vibrio alginolyticus and white spot syndrome virus (WSSV) infection.

Crustin is an antimicrobial peptide (AMP) that plays a key role in innate immunity of crustaceans. In this study, we cloned the entire 660 bp crustin-like sequence with a 507 bp open reading frame encoding a 168 amino acid from Marsupenaeus japonicus. The crustin-like gene was primarily expressed in gills and over-expressed in shrimp hemocytes after challenge with WSSV or Vibrio alginolyticus. After knockdown crustin-like gene using specific double-stranded RNA (CRU-dsRNA), IMD, Rab7, L-lectin, mitogen-activated protein kinase, p53, prophenoloxidase and Rho were down-regulated and nitric oxide synthase, myosin and tumor necrosis factor-α were up-regulated in hemocytes at 24 h post dsRNA treatment. After WSSV challenge, The mortality, WSSV copy number and expressions of WSSV immediate early genes (IE1, IE2, DNA polymerase, VP28) were both decreased but the apoptosis rate was increased in CRU-dsRNA-treated shrimps, indicating that WSSV may take advantage of crustin-like to benefit its replication. After silenced the crustin-like, the results of phagocytosis showed that the phagocytic rate of shrimp hemocytes on WSSV decreased significantly. In contrast, the absence of crustin-like in shrimps increased the mortality following V. alginolyticus challenge, indicating that crustin-like may play a positive role in the antibacterial process. The phagocytosis experiment showed there was a higher phagocytosis rate of hemocytes after CRU-dsRNA treatment. The result indicated that V. alginolyticus may be able to use crustin-like to avoid phagocytosis of shrimp hemocytes. These results further added to our understanding of the function of crustin-like peptide and also provided its potential role in innate immunity in shrimp.

Epigallocatechin-3-gallate inhibit replication of white spot syndrome virus in Scylla paramamosain.

Epigallocatechin-3-gallate (EGCG) has exhibited potential antibacterial and anticancer activities. In this study, we tested whether EGCG can protect the mud crab Scylla paramamosain against white spot syndrome virus (WSSV). Treatment with 1.5 mg/kg EGCG killed crab hemocytes but treatment with 1 mg/kg EGCG did not. Results of the virus challenge experiment confirmed that EGCG could enhance the survival rate of WSSV-challenged crabs, and treatment with 1 mg/kg EGCG significantly increased their resistance to WSSV compared with the control. Thus, 1 mg/kg EGCG was used as the experimental dose in subsequent analyses. EGCG treatment may induce certain immune pathways, such as the phenoloxidase and JAK-STAT pathways, and it also can enhance the activity of prophenoloxidase. EGCG + WSSV treatment significantly reduced the number of WSSV copies at 24, 48, and 72 h post-challenge compared with the control (WSSV challenge without EGCG treatment). These results demonstrate that EGCG may effectively improve innate immunity and survival of WSSV-challenged S. paramamosain and inhibit WSSV replication by blocking the expression of late stage WSSV genes. Therefore, our study presented that EGCG might represent a new potential therapeutic or preventive approach to control white spot syndrome.