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.

Auricular vagus nerve stimulation protects against postoperative cognitive dysfunction by attenuating neuroinflammation and neurodegeneration in aged rats.

Postoperative cognitive dysfunction (POCD) has been increasingly recognized as a significant complication after surgery, especially in senior patients. Vagus nerve stimulation (VNS) reportedly provides beneficial effects against various brain disorders, supporting a hypothesis of its protective role in POCD. However, direct stimulation of the vagus nerve is invasive, as it requires a surgical incision in the neck. Thus, we employed a non-invasive VNS method by stimulating the dermatome in the external ear, which is innervated by the vagus nerve (auricular vagus nerve stimulation; aVNS) and sought to investigate the efficacy of this method in treating surgery-induced cognitive dysfunction in an aged rat model of POCD. We observed that the treatment of aVNS alleviated postoperative memory impairment after exploratory laparotomy surgery, as demonstrated by the shorter swimming latency and distance in Morris water maze tests. Moreover, aVNS also reduced postoperative apoptosis in the hippocampus of the aged rats. Concomitant with these beneficial effects, we found that treatment with aVNS attenuated postoperative neuroinflammation (i.e., the protein level of interleukin-1ß and tumor necrosis factor-α, along with the nuclear protein expression of NF-κB) and Alzheimer's-related pathology (tau phosphorylation at AT-8 and Ser396, as well as the levels of Aß40 and Aß42) in the hippocampus of the aged rats. In conclusion, our study is the first to reveal the neuroprotective effect of aVNS against POCD. This effect might be attributed to the inhibition of neuroinflammation and Alzheimer's-related pathology. This study suggests non-invasive aVNS may serve as a promising method for clinical treatment of POCD.

Quantum dot vertical-cavity surface-emitting lasers covering the 'green gap'.

Semiconductor vertical-cavity surface-emitting lasers (VCSELs) with wavelengths from 491.8 to 565.7 nm, covering most of the 'green gap', are demonstrated. For these lasers, the same quantum dot (QD) active region was used, whereas the wavelength was controlled by adjusting the cavity length, which is difficult for edge-emitting lasers. Compared with reports in the literature for green VCSELs, our lasers have set a few world records for the lowest threshold, longest wavelength and continuous-wave (CW) lasing at room temperature. The nanoscale QDs contribute dominantly to the low threshold. The emitting wavelength depends on the electron-photon interaction or the coupling between the active layer and the optical field, which is modulated by the cavity length. The green VCSELs exhibit a low-thermal resistance of 915 kW-1, which benefits the CW lasing. Such VCSELs are important for small-size, low power consumption full-color displays and projectors.

KIAA0319 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

The gene KIAA0319 has been reported to be associated with developmental dyslexia (DD) in previous studies, although the results have not always been consistent. However, few studies have been conducted in Uyghur populations. In the present study, we aimed to investigate the association of KIAA0319 polymorphisms and DD in individuals of Uyghurian descent. We used a custom-by-design 48-Plex SNPscan Kit to genotype 18 single-nucleotide polymorphisms (SNPs) of KIAA0319 in a group of 196 children with dyslexia and 196 controls of Uyghur descent aged 8-12 years. As a result, 7 SNPs (Pmin=0.001) of KIAA0319 had nominal significant differences between the cases and controls under specific genotypic models. The two SNPs rs6935076 (P=0.020 under dominant model; P=0.028 under additive model) and rs3756821 (P=0.021 under additive model) remained significantly associated with dyslexia after Bonferroni correction. Linkage disequilibrium analysis showed three blocks within KIAA0319, and only a 10-SNP haplotype in block 3 was present at significantly different frequencies in the dyslexic children and controls. This study indicated that genetic polymorphisms of KIAA0319 are associated with an increased risk of DD in the Uyghur population.

Enhanced Light Emission due to Formation of Semi-polar InGaN/GaN Multi-quantum Wells.

InGaN/GaN multi-quantum wells (MQWs) are grown on (0001) sapphire substrates by metal organic chemical vapor deposition (MOCVD) with special growth parameters to form V-shaped pits simultaneously. Measurements by atomic force microscopy (AFM) and transmission electron microscopy (TEM) demonstrate the formation of MQWs on both (0001) and ([Formula: see text]) side surface of the V-shaped pits. The latter is known to be a semi-polar surface. Optical characterizations together with theoretical calculation enable us to identify the optical transitions from these MQWs. The layer thickness on ([Formula: see text]) surface is smaller than that on (0001) surface, and the energy level in the ([Formula: see text]) semi-polar quantum well (QW) is higher than in the (0001) QW. As the sample temperature is increased from 15 K, the integrated cathodoluminescence (CL) intensity of (0001) MQWs increases first and then decreases while that of the ([Formula: see text]) MQWs decreases monotonically. The integrated photoluminescence (PL) intensity of (0001) MQWs increases significantly from 15 to 70 K. These results are explained by carrier injection from ([Formula: see text]) to (0001) MQWs due to thermal excitation. It is therefore concluded that the emission efficiency of (0001) MQWs at high temperatures can be greatly improved due to the formation of semi-polar MQWs.

Strong localization effect and carrier relaxation dynamics in self-assembled InGaN quantum dots emitting in the green.

Strong localization effect in self-assembled InGaN quantum dots (QDs) grown by metalorganic chemical vapor deposition has been evidenced by temperature-dependent photoluminescence (PL) at different excitation power. The integrated emission intensity increases gradually in the range from 30 to 160 K and then decreases with a further increase in temperature at high excitation intensity, while this phenomenon disappeared at low excitation intensity. Under high excitation, about 40% emission enhancement at 160 K compared to that at low temperature, as well as a higher internal quantum efficiency (IQE) of 41.1%, was observed. A strong localization model is proposed to describe the possible processes of carrier transport, relaxation, and recombination. Using this model, the evolution of excitation-power-dependent emission intensity, shift of peak energy, and linewidth variation with elevating temperature is well explained. Finally, two-component decays of time-resolved PL (TRPL) with various excitation intensities are observed and analyzed with the biexponential model, which enables us to further understand the carrier relaxation dynamics in the InGaN QDs.

Rigorous microlens design using vector electromagnetic method combined with simulated annealing optimization.

In this paper, finite-aperture diffractive optical element with its critical dimension smaller than illumination wavelength is modeled and optimized using an integrated method. This method employs rigorous analysis model based on Finite Difference Time Domain (FDTD), and simulated annealing (SA) global search algorithm. Numerical results reveal that the diffraction efficiency of the 8-step microlens quickly climbs to its global optimum along with the optimization process, which manifests its global search ability. The design algorithm and implementation are discussed in details. Considering its time consuming efficiency and global search ability, our method provides valuable reference value in practical multistep microlens design.

Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signaling pathway in rat luteal cells.

OBJECTIVE: To observe the effect of kisspeptin on the endocrine function of rat luteal cells. DESIGN: Experimental animal study. SETTING: Research institute laboratory. ANIMAL(S): Immature Sprague-Dawley rats. INTERVENTION(S): The expression of kisspeptin and its receptor, GPR54, in immature rat ovaries treated with gonadotropin was observed via immunohistochemistry and real-time polymerase chain reaction. Then recombinant kisspeptin was used to examine the effect on the endocrine function of rat luteal cells. MAIN OUTCOME MEASURE(S): Expression and localization of kisspeptin, localization of GPR54, P and E2 secretion, expression of steroidogenic enzymes, and phosphorylation of Erk1/2. RESULT(S): Real-time polymerase chain reaction indicated that ovarian KiSS-1 mRNA levels increased significantly, showing a peak at the luteal period in gonadotropin-primed immature rats. Immunostaining analysis showed that after gonadotropin treatment, kisspeptin was strongly localized in theca cells, the interstitial compartment, and the corpus luteum and that GPR54 protein was clearly detected in the corpus luteum of rat ovaries. In cultured luteal cells, kisspeptin treatment augmented basal and hCG-induced P levels but not E2 production, with concomitant increases detected in the transcript levels of key steroidogenic enzymes (StAR, CYP11A, and 3ß-HSD). Furthermore, treatment with kisspeptin increased the phosphorylation of Erk1/2 mitogen-activated protein kinase in cultured luteal cells. CONCLUSION(S): The kisspeptin/GPR54 signaling system could stimulate P secretion in rat luteal cells via the Erk1/2 mitogen-activated protein kinase signaling pathway, suggesting an important role for the function of the corpus luteum.

[Toxicology and tissue distribution of Ruthenium (II) CO-releasing molecules and its interaction with endogenous substances].

Carbon monoxide has been proved to be an important signal molecule in body. Transition metal carbonyl compounds are solidified form of carbon monoxide. Numerous studies have shown that Ruthenium carbonyl carbon monoxide releasing molecules have a strong pharmacological activity. In this paper, five Ruthenium (II) carbonyl CORMs 1-5 were synthesized and their toxicology, tissue distribution and interaction with blood endogenous substances were investigated. The results showed CORMs' IC50 to fibroblasts are ranged from 212.9 to 2089.2 micromol x L(-1). Their oral LD50 to mouse is between 800 to 1600 mg x kg(-1). After repeated administration, CORMs 1 and CORMs 5 haven't shown an obvious influence to rats' liver and kidney function, but caused the injury to liver and kidney cells. The in vivo distribution result revealed the majority of CORMs were distributed in blood, liver and kidney, only a small part of CORMs distributed in lung, heart and spleen. They could scarcely cross the blood-brain barrier and distribute to brain. The non-CO ligands in structure have an obvious relevance to their in vivo absorption and distribution. Interestingly, CORMs could enhance the fluorescence of bovine serum albumin, and this enhancement was in direct proportion with the concentration of CORMs. Under different conditions, interaction of CORMs with glutathione got different type of products, one is Ruthenium (II) tricarbonyl complexes, and Ruthenium (II) dicarbonyl complexes.

Well-width dependence of the emission linewidth in ZnO/MgZnO quantum wells.

Photoluminescence (PL) spectra were measured as a function of well width (LW) and temperature in ZnO/Mg0.1Zn0.9O single quantum wells (QWs) with graded thickness. The emission linewidth (full width at half maximum) was extracted from the emission spectra, and its variation as a function of LW was studied. The inhomogeneous linewidth obtained at 5 K was found to decrease with increasing LW from 1.8 to 3.3 nm due to the reduced potential variation caused by the LW fluctuation. Above 3.3 nm, however, the linewidth became larger with increasing LW, which was explained by the effect related with defect generation due to strain relaxation and exciton expansion in the QW. For the homogenous linewidth broadening, longitudinal optical (LO) phonon scattering and impurity scattering were taken into account. The LO phonon scattering coefficient ΓLO and impurity scattering coefficient Γimp were deduced from the temperature dependence of the linewidth of the PL spectra. Evident reduction of ΓLO with decreasing LW was observed, which was ascribed to the confinement-induced enhancement of the exciton binding energy. Different from ΓLO, a monotonic increase in Γimp was observed with decreasing LW, which was attributed to the enhanced penetration of the exciton wave function into the barrier layers.

Performance enhancement of GaN-based light emitting diodes by transfer from sapphire to silicon substrate using double-transfer technique.

GaN-based light emitting diodes (LEDs) fabricated on sapphire substrates were successfully transferred onto silicon substrates using a double-transfer technique. Compared with the conventional LEDs on sapphire, the transferred LEDs showed a significant improvement in the light extraction and thermal dissipation, which should be mainly attributed to the removal of sapphire and the good thermal conductivity of silicon substrate. Benefited from the optimized wafer bonding process, the transfer processes had a negligible influence on electrical characteristics of the transferred LEDs. Thus, the transferred LEDs showed a similar current-voltage characteristic with the conventional LEDs, which is of crucial importance for practical applications. It is believed that the double-transfer technique offers an alternative way to fabricate high performance GaN-based thin-film LEDs.