First report on establishment and characterization of the extrahepatic cholangiocarcinoma sarcoma cell line CBC2T-2.

BACKGROUND: Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice. These cells consist of both epithelial and mesenchymal cells. Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma. However, cholangiocarcinoma sarcoma cell lines are not available in cell banks. AIM: To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line, namely CBC2T-2. METHODS: We conducted a short tandem repeat (STR) test to confirm the identity of the CBC2T-2 cell line. Furthermore, we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies. The tumorigenic potential of CBC2T-2 cells was tested in vivo using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The cells were injected subcutaneously and tumor formation was observed. In addition, immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts. The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma. Lastly, whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line. RESULTS: The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue. The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology. The cells exhibited a high proliferation ratio with a doubling time of 47.11 h. This cell line has migratory, invasive, and clonogenic abilities. The chromosomes in the CBC2T-2 cells were polyploidy, with numbers ranging from 69 to 79. The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice. CBC2T-2 cells and xenografts were positive for both the epithelial marker, CK19, and the mesenchymal marker, vimentin. These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics. The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma, and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option. CONCLUSION: We established the first human cholangiocarcinoma sarcoma cell line, CBC2T-2, with stable biogenetic traits. This cell line, as a research model, has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.

Green Vertical-Cavity Surface-Emitting Lasers Based on InGaN Quantum Dots and Short Cavity.

Room temperature low threshold lasing of green GaN-based vertical cavity surface emitting laser (VCSEL) was demonstrated under continuous wave (CW) operation. By using self-formed InGaN quantum dots (QDs) as the active region, the VCSEL emitting at 524.0 nm has a threshold current density of 51.97 A cm-2, the lowest ever reported. The QD epitaxial wafer featured with a high IQE of 69.94% and the δ-function-like density of states plays an important role in achieving low threshold current. Besides, a short cavity of the device (~ 4.0 λ) is vital to enhance the spontaneous emission coupling factor to 0.094, increase the gain coefficient factor, and decrease the optical loss. To improve heat dissipation, AlN layer was used as the current confinement layer and electroplated copper plate was used to replace metal bonding. The results provide important guidance to achieving high performance GaN-based VCSELs.

[Observation of the therapeutic effect on acute ankle sprain treated with surrounding needling and cold compression].

OBJECTIVE: To observe the difference in the therapeutic effect on acute ankle sprain treated with the combination of surrounding needling and cold compression in comparison of the conventional cold compression. METHODS: The patients with acute ankle sprain were randomly divided into control group (33 cases) and observation group (35 cases). In the first 3 days of treatment, the conventional cold compression was used in the control group, while the surrounding needling technique of acupuncture was combined with cold compression in the observation group. Separately, along the distal-lateral side of the leg, and the lateral sides of the heel and the dorsal part of the foot, 3 or 4 needles were inserted in each part，total 9 to 12 needles, toward the center of swelling and pain site, and distributed in a fan shape. The needles were retained for 30 min and the acupuncture therapy was delivered once daily. Since the 4th day of treatment, the hot compress and the static stretching exercise of the ankle joint were adopted in the two groups, once daily for 1 week. The visual analogue scale (VAS) score for ankle pain and ankle swelling degree were compared between the two groups before and after 3-day treatment, as well as the score of American orthopedic foot and ankle society (AOFAS) ankle-hindfoot scale was evaluated. RESULTS: After 3-day treatment, VAS score was decreased in both groups (P<0.01), and the score in the observation group was lower than that of the control group (P<0.01). Ankle swelling degree was relieved in both groups (P<0.01), and there was no significant difference between the two groups. After 1 week of treatment, the scores of AOFAS ankle-hindfoot scale were improved in both groups (P<0.01), and the score in the observation group was higher than the control group (P<0.05). CONCLUSION: Either the combined therapy of surrounding needling and cold compression or the conventional cold compression can effectively relieve pain and swelling induced by acute ankle sprain. The therapeutic effect of the combined therapy is superior to the conventional cold compression for the motor function improvement of ankle joint.

Improvement of optical properties of InGaN-based red multiple quantum wells.

The realization of red-emitting InGaN quantum well (QW) is a hot issue in current nitride semiconductor research. It has been shown that using a low-Indium (In)-content pre-well layer is an effective method to improve the crystal quality of red QWs. On the other hand, keeping uniform composition distribution at higher In content in red QWs is an urgent problem to be solved. In this work, the optical properties of blue pre-QW and red QWs with different well width and growth conditions are investigated by photoluminescence (PL). The results prove that the higher-In-content blue pre-QW is beneficial to effectively relieve the residual stress. Meanwhile, higher growth temperature and growth rate can improve the uniformity of In content and the crystal quality of red QWs, enhancing the PL emission intensity. Possible physical process of stress evolution and the model of In fluctuation in the subsequent red QW are discussed. This study provides a useful reference for the development of InGaN-based red emission materials and devices.

Dual-wavelength switching in InGaN quantum dot micro-cavity light-emitting diodes.

Dual-wavelength switchable emission has been demonstrated in InGaN quantum dot (QD) micro-cavity light-emitting diodes (MCLEDs). By simply modulating the injected current levels, the output of the device can be dynamically tuned between the two distinct cavity modes at 498.5 and 541.7 nm, exhibiting deterministic mode switching in the green spectral range. Owing to the microcavity effect, high spectral purity with a narrow linewidth of 0.21 nm was obtained. According to the experimental and theoretical results, it can be concluded that the dual-wavelength switching for the investigated MCLEDs is ascribed to the broad and tunable gain of a thin InGaN QD active region, together with the mode selection and enhancement effect of the cavity. To provide additional guidelines for controllable dual-wavelength switchable operation in nitride-based light-emitting devices, detailed design and fabrication strategies are discussed. This work presents an effective method to achieve mode switching for practical applications such as multi-wavelength optical recording, frequency mixing, flip-flop and optical switches.

Dexmedetomidine protects against degeneration of dopaminergic neurons and improves motor activity in Parkinson's disease mice model.

Parkinson's disease (PD) is the result of dopaminergic (DA) neuronal death in the substantianigra pars compacta (SNc). Current treatments for PD such as L-dopa are limited in effectiveness and fail to address the cause. Targeted anti-inflammatory therapies, particularly directed at nuclear factor kappa B (NF-κB) activity in alleviating degeneration of DA-neurons is of evolving interest. In the present study, we hypothesised that dexmedetomidine (DEX), an alpha-2 receptor adrenergic agonist, suppress the inflammatory responses associated with PD and restores dopaminergic levels by alleviating substantia nigral degeneration. Male mice (C57Bl/10, 8-11 months old and of 34-40 g of weight) were divided into: the control, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and MPTP + dexmedetomidine (MPTP + DEX) (n = 26 each group). Dex restored dopamine levels in SNpc of MPTP-induced PD mice model. Results of immunohisto staining revealed that Dex treatment post-MPTP induction restored TH-positive cells, with only 12.37% increase (##p < 0.01 vs MPTP) on the third day and a steep 55% increase (###p < 0.001 vs MPTP) following the seventh day of Dex treatment. Moreover, the expressions of proinflammatory markers regulated by NF-κB were diminished in Dex + MPTP group. In addition, cylinder test revealed that Dex treatment improved asymmetric limb usage pattern in MPTP induced mice over the course of 7 days. Hence, in this study, we provided insight on the effect of Dex in the inhibition of NF-κB1 regulated proinflammatory mediators to improve dopamine levels and reduce SNpc dopaminergic neuronal degeneration.

Marinobacter alexandrii sp. nov., a novel yellow-pigmented and algae growth-promoting bacterium isolated from marine phycosphere microbiota.

The marine phycosphere harbors unique cross-kingdom associations with ecological relevance. During investigating the diversity of phycosphere microbiota of marine harmful algal blooms dinoflagellates, a faint yellow-pigmented bacterium, designated as strain LZ-8, was isolated from paralytic shellfish poisoning toxin-producing dinoflagellate Alexandrium catenella LZT09. The new isolate appeared to have growth-promoting potential toward its algal host. Molecular analysis using 16S rRNA gene, housekeeping rpoD gene and whole-genome sequence comparison indicated that strain LZ-8T was a novel gammaproteobacterium of the family Alteromonadaceae. The major fatty acids of strain LZ-8T were C16:0, C18:1 ω9c, C12:0 3-OH, summed feature 3, C16:1 ω9c, C12:0 and summed feature 9. The major isoprenoid quinone was Q-9. Polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipid, two unidentified aminolipids and six unidentified polar lipids. The genomic DNA G+C content was 57.36 mol%. Based on genome sequencing, several biosynthetic gene clusters responsible for bacterial biosynthesis of carotenoids and siderophores that may involve in algae-bacterial interactions were identified in the genome of strain LZ-8T. The polyphasic characterization indicated that strain LZ-8T represents a novel Marinobacter species. The name Marinobacter alexandrii sp. nov., type strain LZ-8T (= CCTCC AB 2018386T = KCTC 72198T) is proposed.

Efficacy of a new oncolytic adenovirus armed with IL-13 against oral carcinoma models.

PURPOSE: The efficacy of traditional therapies for oral carcinoma (OC) is limited. Oncolytic adenovirus, a novel strategy of cancer therapy, shows potential use in OC treatment. However, its clinical application is limited by pre-existing neutralizing antibodies. Thus, this study aimed to examine the efficacy of a new modified adenovirus against OC in vitro and in vivo. MATERIALS AND METHODS: A multiple modified adenovirus (MMAD) armed with IL-13 (MMAD-IL-13) was constructed, and its effect on Cal-27 cells was examined. The potency of MMAD-IL-13 was examined in vitro and in vivo. For in vitro experiment, CCK-8 kit was used to determine the IC50 of MMAD-IL-3 in OC cell lines. For in vivo experiment, Cal-27 xenograft models were used to determine the antitumor effect of MMAD-IL-13. Apoptosis was measured in Cal-27 cells by Western blotting assay. Immunity response was detected in Cal-27 xenograft models 7 days after intratumoral injection with MMAD-IL-13. The potency of MMAD and MMAD-IL-13 was compared in Cal-27 peripheral blood mononuclear cells (PBMCs) models. RESULTS: MMAD-IL-13 was successfully constructed; the harvested virus could be replicated and they overexpressed human IL-13 in Cal-27 cells. Compared with MMAD, MMAD-IL-13 showed enhanced antitumor effect in vitro by inducing apoptosis and reducing percentage of M2 macrophages in tumor environment in vivo. MMAD-IL-13 also showed potent antitumor effect in Cal-27, SCC-4, and Tca8113 cells in vitro and in Cal-27 xenograft models in vivo. However, MMAD-IL13 did not harm normal human oral epithelial cells in vitro and exhibited no effect on body weight in Cal-27 xenograft models. In Cal-27 PBMC models, MMAD-IL-13 showed stronger antitumor effect than MMAD. CONCLUSION: A new oncolytic adenovirus carrying the human IL-13 gene was constructed. This virus effectively led to remission of tumor development and death of OC cells in vivo and in vitro, showing its potential as a clinical cancer therapy.