Generating dual-wavelength VECSEL by selecting birefringence filter material and the application toward mid-infrared region via intracavity OPO.

A method for realizing a synchronized watt-level dual-wavelength vertical-external-cavity surface-emitting-laser (VECSEL) by using a tilted birefringence filter (BRF) is demonstrated. It is verified that by selecting suitable BRF material with different refractive index differences between extraordinary wave and ordinary wave, the dual-wavelength emission with a free spectrum range from sub-THz to tens of THz can be achieved. The output characteristics of such a dual-wavelength VECSEL are thoroughly investigated including its wavelength tunability and power difference. Finally, the intracavity optical parametric oscillator is applied to efficiently convert the dual-wavelength laser toward the mid-infrared region. The gain competition and longitudinal mode hopping performances for the multi-wavelength mid-infrared output are explored.

Low-threshold dual-wavelength CW mid-IR laser from shared intracavity quasi-phase-matched OPO.

A low-threshold continuous wave dual-wavelength mid-infrared laser is demonstrated by using an intracavity optical parametric oscillator (OPO) with a dual-wavelength pump wave. To realize a high-quality dual-wavelength pump wave, a composite Nd:YVO4/Nd:GdVO4 gain medium is applied for a linear polarized state and synchronization output. With the quasi-phase-matching OPO process, it is found that the dual-wavelength pump wave shares equal signal wave oscillation and leads to a lower OPO threshold. Finally, a diode threshold pumped power of barely 2 W can be achieved for the balanced intensity dual-wavelength watt-level mid-IR laser.

Ribose-5-phosphate isomerase A overexpression promotes liver cancer development in transgenic zebrafish via activation of ERK and ß-catenin pathways.

Dysregulation of the enzymes involved in the pentose phosphate pathway (PPP) is known to promote tumorigenesis. Our recent study demonstrated that ribose-5-phosphate isomerase (RPIA), a key regulator of the PPP, regulates hepatoma cell proliferation and colony formation. Our studies in zebrafish reveal that RPIA-mediated hepatocarcinogenesis requires extracellular signal-regulated kinase (ERK) and ß-catenin signaling. To further investigate RPIA-mediated hepatocarcinogenesis, two independent lines of transgenic zebrafish expressing human RPIA in the liver were generated. These studies reveal that RPIA overexpression triggers lipogenic factor/enzyme expression, steatosis, fibrosis and proliferation of the liver. In addition, the severity of fibrosis and the extent of proliferation are positively correlated with RPIA expression levels. Furthermore, RPIA-mediated induction of hepatocellular carcinoma (HCC) requires the ERK and ß-catenin signaling pathway but is not dependent upon transaldolase levels. Our study presents a mechanism for RPIA-mediated hepatocarcinogenesis and suggests that RPIA represents a valuable therapeutic target for the treatment of HCC.

Low Molecular Weight Fucoidan Prevents Radiation-Induced Fibrosis and Secondary Tumors in a Zebrafish Model.

Radiotherapy often causes unwanted side effects such as radiation-induced fibrosis and second malignancies. Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has many biological effects including anti-inflammation and anti-tumor. In the present study, we investigated the radioprotective effect of Oligo-Fucoidan (OF) using a zebrafish animal model. Adult zebrafish of wild-type and transgenic fish with hepatocellular carcinoma were orally fed with Oligo-Fucoidan before irradiation. Quantitative PCR, Sirius red stain, hematoxylin, and eosin stain were used for molecular and pathological analysis. Whole genomic microarrays were used to discover the global program of gene expression after Oligo-Fucoidan treatment and identified distinct classes of up- and downregulated genes/pathways during this process. Using Oligo-Fucoidan oral gavage in adult wild-type zebrafish, we found Oligo-Fucoidan pretreatment decreased irradiation-induced fibrosis in hepatocyte. Using hepatitis B virus X antigen (HBx), Src and HBx, Src, p53-/+ transgenic zebrafish liver cancer model, we found that Oligo-Fucoidan pretreatment before irradiation could lower the expression of lipogenic factors and enzymes, fibrosis, and cell cycle/proliferation markers, which eventually reduced formation of liver cancer compared to irradiation alone. Gene ontology analysis revealed that Oligo-Fucoidan pretreatment increased the expression of genes involved in oxidoreductase activity in zebrafish irradiation. Oligo-Fucoidan also decreased the expression of genes involved in transferase activity in wild-type fish without irradiation (WT), nuclear outer membrane-endoplasmic reticulum membrane network, and non-homologous end-joining (NHEJ) in hepatocellular carcinoma (HCC) transgenic fish. Rescue of those genes can prevent liver cancer formation. Conclusions: Our results provide evidence for the ability of Oligo-Fucoidan to prevent radiation-induced fibrosis and second malignancies in zebrafish.

Up-regulation of golgi α-mannosidase IA and down-regulation of golgi α-mannosidase IC activates unfolded protein response during hepatocarcinogenesis.

α-1,2 mannosidases, key enzymes in N-glycosylation, are required for the formation of mature glycoproteins in eukaryotes. Aberrant regulation of α-1,2 mannosidases can result in cancer, although the underlying mechanisms are unclear. Here, we report the distinct roles of α-1,2 mannosidase subtypes (MAN1A, MAN1B, ERMAN1, MAN1C) in the formation of hepatocellular carcinoma (HCC). Clinicopathological analyses revealed that the clinical stage, tumor size, α-fetoprotein level, and invasion status were positively correlated with the expression levels of MAN1A1, MAN1B1, and MAN1A2. In contrast, the expression of MAN1C1 was decreased as early as stage I of HCC. Survival analyses showed that high MAN1A1, MAN1A2, and MAN1B1 expression levels combined with low MAN1C1 expression levels were significantly correlated with shorter overall survival rates. Functionally, the overexpression of MAN1A1 promoted proliferation, migration, and transformation as well as in vivo migration in zebrafish. Conversely, overexpression of MAN1C1 reduced the migration ability both in vitro and in vivo, decreased the colony formation ability, and shortened the S phase of the cell cycle. Furthermore, the expression of genes involved in cell cycle/proliferation and migration was increased in MAN1A1-overexpressing cells but decreased in MAN1C1-overexpressing cells. MAN1A1 activated the expression of key regulators of the unfolded protein response (UPR), while treatment with endoplasmic reticulum stress inhibitors blocked the expression of MAN1A1-activated genes. Using the MAN1A1 liver-specific overexpression zebrafish model, we observed steatosis and inflammation at earlier stages and HCC formation at a later stage accompanied by the increased expression of the UPR modulator binding immunoglobulin protein (BiP). These data suggest that the up-regulation of MAN1A1 activates the UPR and might initiate metastasis. Conclusion: MAN1A1 represents a novel oncogene while MAN1C1 plays a role in tumor suppression in hepatocarcinogenesis. (Hepatology Communications 2017;1:230-247).

Augmentation cystoplasty and simultaneous ureteral reimplantation reduce high-grade vesicoureteral reflux in children with neurogenic bladder.

BACKGROUND: To compare the incidence of residual high-grade vesicoureteral reflux (HVUR) (≥Grade III) in neurogenic bladder patients receiving augmentation cystoplasty alone or with simultaneous ureteral reimplantation. Furthermore, we also tried to find the risk factors of residual VUR and febrile urinary tract infection. METHODS: Between 1999 and 2009, urinary bladder augmentation was performed in 21 children with neurogenic bladder. Seventeen of these patients had VUR on preoperative voiding cystourethrography, of whom 11 patients (14 ureters) received augmentation alone (Group A) and 6 patients (8 ureters) received simultaneously ureteral reimplantation (Group B). Univariate logistic regression analysis and Fisher exact test were used for statistical analysis. RESULTS: Six patients (8 ureters) had residual HVURs in Group A, but none in Group B. The incidences of residual HVUR were 57.14% and 0%, respectively. Seven patients had febrile UTIs after operation, 6 of them had residual HVURs. In risk factor analysis, postoperative follow-up duration less than 12 months and lack of anti-reflux operation were significant risk factors for residual HVUR; the residual HVUR was the significant risk factor for febrile urinary tract infection. CONCLUSION: Simultaneous ureteral reimplantation reduces postop HVUR significantly. We recommend augmentation and simultaneous ureteral reimplantation in children with HVUR and neurogenic bladder if technically feasible.