Second-Sphere Polyhedron-Distortion-Induced Broadened and Red-Shifted Emission in Lu3(MgxAl2-x)(Al3-xSix)O12:Ce3+ for Warm WLED.

Orange-yellow phosphors with extended broadband emission are highly desirable for warmer white-light-emitting diodes (WLED) with a higher color-rendering index. Targeted phosphors Ce3+-doped Lu3(MgxAl2-x)(Al3-xSix)O12 (x = 0, 0.25, 0.50, 0.75, and 1.00) were developed by chemical composition modification for luminescent tuning from green to orange-yellow with spectral broadening. The correlation between structure evolution and luminescent properties was elucidated by the local structure, fluorescence lifetime, and Eu3+ luminescence as a structural probe. The polyhedron distortion in the second-sphere coordination leads to the site differentiation and symmetry degradation of Ce3+ with the accommodation of (MgSi)6+ pairs, comprehensively resulting in the red shift (540 → 564 nm) and broadening in emission spectra. The WLED fabrication results demonstrate that the red shift and broadening in the emission of Lu3(MgxAl2-x)(Al3-xSix)O12:Ce3+ make it more suitable for the single-phosphor converted warm WLED.

Cyan-Green Phosphor (Lu2M)(Al4Si)O12:Ce3+ for High-Quality LED Lamp: Tunable Photoluminescence Properties and Enhanced Thermal Stability.

High-quality white light-emitting diodes (w-LEDs) are mainly determined by conversion phosphors and the enhancement of cyan component that dominates the high color rendering index. New phosphors (Lu2M)(Al4Si)O12:Ce3+ (M = Mg, Ca, Sr and Ba), showing a cyan-green emission, have been achieved via the co-substitution of Lu3+-Al3+ by M2+-Si4+ pair in Lu3Al5O12:Ce3+ to compensate for the lack of cyan region and avoid using multiple phosphors. The excitation bands of (Lu2M)(Al4Si)O12:Ce3+ (M = Mg, Ca, Sr and Ba) show a red-shift from 434 to 445 nm which is attributed to the larger centroid shift and crystal field splitting. The enhanced structural rigidity associated with the accommodation of larger M2+ leads to a decreasing Stokes shift and the corresponding blue-shift (533 → 511 nm) in emission spectra, along with an improvement in thermal stability (keeping ∼93% at 150 °C). The cyan-green phosphor Lu2BaAl4SiO12:Ce3+ enables to fabricate a superhigh color rendering w-LED ( Ra = 96.6), verifying its superiority and application prospect in high-quality solid-state lightings.

Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion.

Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal-fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta.

Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway.

The cytostatic drug from traditional Chinese medicinal herb has acted as a chemotherapeutic agent used in treatment of a wide variety of cancers. Oxymatrine, classified as a quinolizidine alkaloid, is a phytochemical product derived from Sophora flavescens, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma MNNG/HOS cell have not been well studied. In the present study, the cytotoxic effects of oxymatrine on MNNG/HOS cells were examined by MTT and bromodeoxyuridine (BrdU) incorporation assays. The percentage of apoptotic cells and the level of mitochondrial membrane potential (Δψ m) were assayed by flow cytometry. The levels of apoptosis-related proteins were measured by Western blot analysis or enzyme assay Kit. Our results showed that treatment with oxymatrine resulted in a significant inhibition of cell proliferation and DNA synthesis in a dose-dependent manner, which has been attributed to apoptosis. Furthermore, we found that oxymatrine considerably inhibited the expression of Bcl-2 whilst increasing that of Bax. This promoted mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the activation of caspase-9 and -3. Moreover, addition of oxymatrine to MNNG/HOS cells also attenuated phosphatidylinositol 3-kinase (PI3K) /Akt signaling pathway cascade, evidenced by the dephosphorylation of P13K and Akt. Likewise, oxymatrine significantly suppressed tumor growth in female BALB/C nude mice bearing MNNG/HOS xenograft tumors. In addition, no evidence of drug-related toxicity was identified in the treated animals by comparing the body weight increase and mortality. Therefore, these findings should be useful for understanding the apoptotic cellular mechanism mediated by oxymatrine and might offer a therapeutic potential advantage for human osteosarcoma chemoprevention or chemotherapy.

p21 overexpression sensitizes osteosarcoma U2OS cells to cisplatin via evoking caspase-3 and Bax/Bcl-2 cascade.

Osteosarcoma is the most common form of primary malignant bone tumor that mainly occurs in juvenile patients. The mechanisms of formation and development of osteosarcoma have been studied for a long time. Recently, more and more evidence showed that p21 plays important roles in regulating tumor growth. To study the effects of p21 on the chemosensitivity of human osteosarcoma U2OS cells to cisplatin and its relevant mechanisms, we stably transfect the pC-21-SN3 vector containing P21 to U2O3 cells (U2O3-p21), which was identified by RT-PCR and Western blot. The results showed that no p21 was expressed in U2OS and U2OS-vec cells, but it was highly expressed in U2O3-p21 cells at mRNA and protein levels. The growth of U2OS cells was almost not influenced by p21 alone. However, U2O3-p21 cells underwent more obvious apoptotic morphological changes than U2OS and U2OS-vec cells after being treated with cisplatin (5 µg) for 72 h. Besides, increased expression of cleaved caspase-3 and Bax/Bcl-2 ratio was observed in cisplatin-treated U2O3-p21 cells. These data clearly indicated that exogenous p21 gene transfection could enhance the cisplatin-induced cytotoxicity against human osteosarcoma U2OS cells, at least in part, by activating caspase-3 cascade and increasing Bax/Bcl-2 ratio.

Wogonin Restrains the Malignant Progression of Lung Cancer Through Modulating MMP1 and PI3K/AKT Signaling Pathway.

BACKGROUND: Wogonin, a natural flavonoid compound, represses cancer cell growth and induces cancer cell apoptosis in diverse malignancies. However, the function of Wogonin in lung cancer cells and its regulatory mechanism deserve to be identified. METHODS: A549 and H460 cells were treated with Wogonin, and the cell growth, apoptosis, migration and invasion were measured by CCK-8 and EdU, flow cytometry and Transwell assays. The targeted genes of Wogonin and lung cancer were identified from the TCMSP and Genecards databases, respectively. The STRING database and Cytoscape software were used to establish a PPI network and screen hub genes. GO and KEGG analysis was conducted to explore the functions and signal pathways related to the hub genes. MMP1 expression in lung cancer was analyzed using the UALCAN databases, and GSEA was performed utilizing LinkedOmics. Gelatin zymography assay was used to detect MMP1 activity. MMP1 mRNA expression was detected by qRT-PCR. Besides, MMP1, p-AKT and c-Myc protein were detected by Western Blot assay. RESULTS: Wogonin could suppress the proliferation, migration and invasion of A549 and H460 cells and induce apoptosis. GO and KEGG enrichment analysis revealed the hub genes were mostly enriched in re-entry into the mitotic cell cycle and apoptosis. The expression of MMP1 was markedly upregulated in lung squamous cell carcinoma, lung adenocarcinoma tissues, and lung cancer cell lines. Wogonin could significantly inhibit MMP1 expression and activity, and overexpression of MMP1 significantly reversed the effect of Wogonin on the malignant phenotypes of A549 and H460 cells. Wogonin inhibited the expression of p-AKT and c-Myc protein by regulating MMP1. CONCLUSION: Wogonin can repress lung cancer cells' growth and metastatic potential and promote cell apoptosis via repressing MMP1 expression and modulating PI3K/AKT signaling pathway.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Long noncoding RNA regulatory factor X3- antisense RNA 1 promotes non-small cell lung cancer via the microRNA-577/signal transducer and activator of transcription 3 axis.

Lung cancer is the most frequent malignancy, and non-small cell lung cancer (NSCLC) is its most common pathological type. Molecular targeted therapy has been testified to be effective in intervening in the occurrence and development of malignancies. This study investigates the effect of lncRNA Regulatory Factor X3- antisense RNA 1 (RFX3-AS1) in NSCLC progression. The RFX3-AS1 profile in NSCLC tissues and cells was measured by quantitative reverse transcription PCR (qRT-PCR). The RFX3-AS1 overexpression model was constructed. The cell counting kit-8 (CCK-8) experiment and cell colony formation assay were adopted to test cell viability. The cell apoptosis was determined by flow cytometry (FCM). Cell migration and invasion were monitored by the Transwell assay, and Western blot was implemented to verify the protein profiles of signal transducer and activator of transcription 3 (STAT3), E-cadherin, Vimentin and N-cadherin. In vivo, we validated the impact of RFX3-AS1 overexpression on the NSCLC xenograft mouse model. The targeting relationships between RFX3-AS1 and miR-577, miR-577 and STAT3 were confirmed by the dual-luciferase reporter assay. The results manifested that overexpressing RFX3-AS1 markedly facilitated NSCLC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and suppressed cell apoptosis. In contrast, miR-577, which was a downstream target of RFX3-AS1, dramatically impeded the malignant biological behaviors of NSCLC cells. STAT3 was a direct target of miR-577, and it was negatively regulated by the latter. STAT3 activation reversed miR-577-mediated anti-tumor roles. In brief, RFX3-AS1 aggravated NSCLC progression by regulating the miR-577/STAT3 axis.

Association between TGFBR1*6A and osteosarcoma: a Chinese case-control study.

BACKGROUND: TGFBR1*6A is a common hypomorphic variant of transforming growth factor beta receptor 1 (TGFBR1). TGFBR1*6A is associated with an increased cancer risk, but the association of this polymorphism with osteosarcoma remains unknown. We have measured the frequency of TGFBR1*6A variants in osteosarcoma cases and controls. METHODS: Our case-control study is based on 168 osteosarcoma patients and 168 age- and gender-matched controls. Blood samples were obtained and the TGFBR1*6A variant determined by PCR amplification and DNA sequencing. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated by unconditional logistic regression, adjusted for both age and gender. Three models - dominant, additive and recessive - were used to analyze the contribution of the TGFBR1*6A variant to osteosarcoma susceptibility. RESULTS: Heterozygotic and homozygotic TGFBR1*6A variants represented 50.4% and 6.0% of the 168 cases, whereas the controls had 18. 5% and 1.3%, respectively. ORs for homozygosity and heterozygosity of the TGFBR1*6A allele were 4.6 [95% CI, 2.33-7.97] and 2.9 [95% CI, 1.59-5.34] in the additive model. There were significant increases in the TGFBR1*6A variants in osteosarcoma cases compared to control in all 3 models. Further analysis showed that TGFBR1*6A genotypes were not associated with gender, age, or tumor location. However, TGFBR1*6A was significantly associated with less metastasis. CONCLUSIONS: TGFBR1*6A, a dominant polymorphism of TGFBR1, is associated with increased susceptibility and metastasis spread of osteosarcoma.

[Comparison between Gd-DTPA-enhanced MRI and USPIO-enhanced MRI in diagnosing benign and metastatic cervical lymph nodes in rabbit models].

OBJECTIVE: To compare the diagnostic value of gadolinium diethylenetriaminepenta-acetic acid (Gd-DTPA)-enhanced MRI with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI in differentiating reactive hyperplastic lymph nodes from metastatic lymph nodes in rabbit models. METHODS: Reactive hyperplastic cervical lymph node model was established in 18 rabbits as hyperplasia group, and tumor-bearing lymph node model was established in another 18 rabbits as tumor group. For Gd-DTPA-enhanced MRI, T1WI and T2WI were performed on 9 animals of each model, and T1WI was acquired 80 seconds after administration of Gd-DTPA. For USPIO-enhanced MRI, T1WI, T2WI and T2*WI were performed on another 9 animals of each model before and 24 hours after administration of USPIO. MRI images were analyzed and correlated with surgical specimens and pathological results. RESULTS: In the tumor group, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Gd-DTPA-enhanced MRI were 62.5%, 91.3%, 88.2%, 70.0% and 76.6%, respectively. The corresponding values of USPIO-enhanced MRI were 95.0%, 90.9%, 90.5%, 95.2% and 92.9%, respectively. The sensitivity and accuracy of USPIO-enhanced MRI differ significantly from those of Gd-DTPA-enhanced MRI. In the hyperplasia group, the accuracy of Gd-DTPA-enhanced MRI was 74.2%, while 87.1% for USPIO-enhanced MRI. CONCLUSION: USPIO-enhanced MRI has higher accuracy in diagnosing metastatic lymph nodes than Gd-DTPA-enhanced MRI.

Influence of hot water treatment and O-carboxymethyl chitosan coating on postharvest quality and ripening in Hami melons (Cucumis melo var. saccharinus) under long-term simulated transport vibration.

Hami melon (Cucumis melo var. saccharinus) is famous in China because of its delicious taste. The fast post-harvest metabolism of Hami melon, which is harvested in summer, creates challenges for preservation during storage. In this study, the ripening-related changes in Hami melon were monitored throughout postharvest storage, including transport. The effects of hot water (HW) treatment and HW treatment in combination with O-carboxymethyl chitosan (CMC) coating on ripening were evaluated based on the changes in membrane leakage; respiration rates; malondialdehyde (MDA) content; superoxide dismutase, catalase, and peroxidase activities; total antioxidant capacity (TAC); and total phenolic content during storage. Transmission electron microscopy and magnetic resonance imaging were also used to monitor changes in the quality of Hami melons during storage. The results indicate that transport vibration can accelerate ripening-related changes in Hami melon. Transport vibration increased membrane leakage and microstructural changes in the melon tissue; enhanced the respiration rate and MDA content; suppressed the activities of antioxidant enzymes; and decreased the TAC and total phenolic contents. Compared to HW treatment alone, HW treatment combined with the coating with 1% (w/v) CMC more effectively delayed the ripening-related changes in Hami melons under transport vibration. PRACTICAL APPLICATIONS: The results of this study show that transport vibration can accelerate ripening in Hami melons. Both hot water (HW) treatment and a combination of HW treatment and O-carboxymethyl chitosan (CMC) coating were effective in delaying ripening in Hami melons under simulated long-term transport vibration. Compared with HW treatment alone, HW treatment combined with CMC coating was more effective in preserving Hami melons, as indicated by lower respiration rates; better integrity of the plasma membrane and cell wall in the parenchyma tissue; lower membrane leakage and malondialdehyde content; greater antioxidant enzyme activities, total antioxidant capacity, and total phenolic content; and improved magnetic resonance imaging T2 relaxation values. Thus, HW treatment combined with CMC coating provides a useful way for the Hami melon industry to maintain postharvest quality, extend the shelf life, and improve the marketing of Hami melon.

[MRI monitoring of cerebral spinal fluid metastasis in rabbit model].

OBJECTIVE: To establish a rabbit model of cerebral spinal flow metastasis, to analyze the growth rate of tumor, and to investigate the value of MRI in monitoring the biology of tumor compared with pathology. METHODS: Twenty-four New Zealand white rabbits were inoculated with suspension of VX(2) tumor cells in the subarachnoid space via the foramen magnum (experimental group), and 6 rabbits were inoculated with normal saline (control group). MRI examination, including non-enhanced T(1)WI, T(2)WI, and FLAIR sequences and then T(1)WI, FLAIR after dynamic contrast enhanced with Gd-DTPA were done 7 approximately 22 days after inoculation with a 3-day interval. The rabbits were killed after the last MRI scan with their spinal cords, spinal meninges, and tumor taken out to undergo microscopy. RESULTS: (1) MRI plain scan showed that in the experimental group 2 nodi in the medulla and 1 nodes in the cervical spinal cord were found with low signal on T(1)WI and high signal on T(2)WI; and FLAIR imaging showed local lesions with medial signal in 6 rabbits (25%). And no abnormal signs were seen in the control group. (2) MRI enhancement showed that in the experimental group the images of 15 rabbit models were enhanced markedly with irregular thickening of meninges or nodules at the subarachnoid space on T(1)WI, positive signs were confirmed on FLAIR sequence in 16 of the 24 rabbits, and positive signs were noted on DCE-MRI scanning in 18 of the 24 rabbits (75%). In the control group 5 of the 6 rabbits were negative in images. Microscopy showed thickened of meninges and spinal meninges in 20 of the 24 rabbits of the experimental group and spinal cord metastasis in 22 rabbits. No pathological changes were seen in the control group. Statistics showed a CSF metastasis rate of 91.67%. There were significant difference between the plain scan and T(1)WI with enhancement (P < 0.01) and between FLAIR scan and FLAIR enhancement scans. There was a significant difference between T(1)WI and FLAIR enhancement and pathological findings (P < 0.05). There was no significant difference between DCE-MRI method and pathological results (P > 0.05). CONCLUSION: Gd-DTPA enhanced MRI scan sequences has a high sensitivity and specificity and can be used in monitoring the growth of CSF metastasis. There is a disparity between the MRI signs and pathological findings. It is a key that to improve the spatial resolution of machine and to investigate the best method for detecting early metastasis.

Grifolic acid causes osteosarcoma cell death in vitro and in tumor-bearing mice.

Grifolic acid is a natural compound isolated from the fungus Albatrellus confluens. In the present study, we assessed the effects of grifolic acid on human osteosarcoma cells. We found that grifolic acid dose- and time-dependently induced cell death in the U-2 OS, MG-63, Saos-2, and 143B human osteosarcoma cell lines. Grifolic acid decreased osteosarcoma cell mitochondrial membrane potential, ATP production, and cellular NADH levels, but did not impact mitochondrial membrane potential in isolated mitochondria from human osteosarcoma cells. Intratumoral injection of grifolic acid also promoted tumor cell death and prolonged survival in nude mice bearing human osteosarcoma xenografts. Grifolic acid had no obvious toxicity in mice, with no histological changes in liver, kidney, lung, or heart, and no changes in blood cell counts or levels of plasma total protein, alanine aminotransferase, or aspartate aminotransferase. These results show that grifolic acid induces osteosarcoma cell death by inhibiting NADH generation and ATP production without obvious toxicity. Intratumoral injection of grifolic acid may be a promising anti-osteosarcoma therapeutic option in patients.

[MRI monitoring ultra-small superparamagnetic iron oxide (USPIO) particle labeling C6 rat glioma cells].

OBJECTIVE: To monitor the effects of labeling C6 rat glioma cells with different concentrations of USPIO in vivo and in vitro. METHODS: C6 rat glioma cells of 1 x 10(6), 2 x 10(6) and 1 x 10(7) were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO, The signal intensity of cells were evaluated by MRI with T(1)WI, T(2)WI and GRE/30 degrees sequences in vitro. 1 x 10(6) of C6 glioma cells were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO and inoculated into the right frontal lobe of 2 rats under stereotaxis apparatus respectively (total 6 rats), Same MRI parameters were used just as above. Iron particle density and cells was measured by HE and Prussian blue stain under microscopy. RESULTS: Different cell population was cultured with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO about 12 hours. The MR signal intensity of labeling cells were inversely correlated with the different concentration of USPIO groups in T(2)W and GRE/30 degrees imaging (t = 4.19, 3.38, P < 0.05) in vitro. There was an inversely correlation between the labeling cell population and the signal intensity at the same concentration of USPIO (t = 5.16, 2.35, 4.41; P < 0.05). Dyeing degree of labeling cells stained by Prussian blue gradually deepened from 25 microg/ml to 50 microg/ml by microscopy. In vivo MRI can clearly show the cells labeled with 25 microg/ml USPIO. CONCLUSIONS: Iron particle density in the rat glioma cells were gradually increased with the concentration of USPIO. The MR signal intensity was inversely correlated with the cell population at the same condition. 25 microg/ml USPIO labeling rat glioma cells were enough for in vivo monitoring by MRI.

[The value of MR dynamic time-resolved subtracted imaging in evaluating the blood supply by systemic artery in patients with lung cancer].

BACKGROUND: To explore the application value of MR dynamic time-resolved subtracted imaging in qualitative and quantitative assessment of blood supply by systemic artery in patients with lung cancer. METHODS: A prospective study using MR FSPGR pulse sequence dynamic scan after contrast enhancement was undertaken in fifty-one patients with lung cancer which were proved by cytology or/and histology. The time-resolved subtracted imaging were acquired using the pre- and post-enhanced images in different phases of pulmonary circulation during the first-pass period (FPP) of contrast agent. The time-signal curves of FPP at four ROI placed on pulmonary artery (PA), descending aorta (DA), mass (M) and contralateral pulmonary parenchyma (PP), and the ST (start-time) and PT (peak-time) of those four ROI were measured. The enhancement ratio of the signals of M/PP at PA/DA peak time (E MP , E MA , E PP , E PA ) were calculated. RESULTS: According to the time-resolved subtracted imaging during PA phase, intensity of the signal was low in 7 cases, medium in 2, but not enhanced in other 42 cases. All the 51 cancer masses were remarkably enhanced during DA phase. During FPP, the ST [(5.90±0.51)s] and PT [(12.75±0.67)s] of PP were slightly later than the ST [(4.19±0.43)s] and PT [(10.59±0.66)s] of PA, while the ST [(11.03±0.80)s] and PT [(33.62±3.06)s] of cancer masses were later than ST [(9.43±0.59)s] and PT [(19.81±4.14)s] of DA. E MA was significantly higher than E MP (91.47%±18.83% vs 15.38%±11.03%, P < 0.001), while E PP were remarkably higher than E PA (273.83%±48.60% vs 140.65%±24.40%, P < 0.001). CONCLUSIONS: MR dynamic time-resolved subtracted imaging is feasible to be a non-invasive technique in qualitative and relatively quantitative assessment of blood supply by systemic artery in patients with lung cancer.

[A preliminary application of MR dynamic time-resolved subtracted perfusion imaging to qualitative and partial quantitative evaluation of the blood supply by pulmonary artery in peripheral type lung cancer].

BACKGROUND: To explore the application of MR time-resolved subtracted perfusion imaging to qualitatively and partially quantitatively evaluate blood supply by pulmonary artery in patients with peripheral type lung cancer. METHODS: Twenty-three patients with peripheral type lung cancer proved cytologically or/and histologically underwent MR perfusion study. The time-resolved subtracted imaging which provided the perfusion images in different phases were performed. First-pass time-signal intensity curves of pulmonary artery, descending aorta, lung mass were obtained respectively, and start-time and peak-time of them were compared. The signal enhanced ratio of the masses in pulmonary artery and aorta perfusion phases were calculated respectively. RESULTS: Fourteen masses began to enhance during pulmonary circulation phase and reached peak value during systematic-circulation phase, and the average signal change ratio during pulmonary circulation phase was much smaller than that during systematic-circulation phase, indicating their blood supply came both from pulmonary and systematic blood circulation, but mainly from the latter. Seven masses began to enhance and reached peak value during systematic-circulation phase, indicating their blood supply came mainly from systematic blood circulation. Two masses began to enhance and reached peak value during pulmonary-circulation phase, indicating their blood supply came mainly from pulmonary blood circulation. CONCLUSIONS: MR dynamic time-resolved subtracted perfusion imaging is feasible to qualitatively and relatively quantitatively evaluate blood supply of pulmonary artery for peripheral type lung cancer.

Rab27A regulates exosome secretion from lung adenocarcinoma cells A549: involvement of EPI64.

Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis. The unique composition of exosomes can be transported to other cells which allow cells to exert biological functions at distant sites. However, in lung cancer, the regulation of exosome secretion was poorly understood. In this study, we employed human lung adenocarcinoma A549 cells to determine the exosome secretion and involved regulation mechanism. We found that Rab27A was expressed in A549 cells and the reduction of Rab27A by Rab27A-specific shRNA could significantly decrease the secretion of exosome by A549 cells. EPI64, a candidate GAP that is specific for Rab27, was also detected in A549 cells. By pull-down assay, we found that EPI64 participated in the exosome secretion of A549 cells by acting as a specific GAP for Rab27A, not Rab27B. Overexpression of EPI64 enhanced exosome secretion. Taken together, in A549 cells, EPI64 could regulate the exosome secretion by functioning as a GAP specific for Rab27A.

Hypoxia promotes migration and induces CXCR4 expression via HIF-1α activation in human osteosarcoma.

BACKGROUND: Cellular adaptation to a hypoxic microenvironment is essential for tumor progression and is largely mediated by HIF-1α through coordinated regulation of hypoxia-responsive genes. The chemokine SDF-1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers. In this study, we investigated the response of osteosarcoma cells to hypoxia and the expression of CXCR4 and HIF-1α in human osteosarcoma specimens and explored the roles of CXCR4 and HIF-1α in the cell migration process. METHODOLOGY/PRINCIPAL FINDINGS: We performed immunohistochemistry, immunocytochemistry, quantitative real-time PCR, Western blots and fluorescent reporter assays to evaluate the correlation between CXCR4 and HIF-1α expression in human osteosarcoma specimens or SOSP-9607 cells under normoxic and hypoxic conditions. Transwell assays were used to assess cell migration under different conditions. Exposure of SOSP-9607 cells to hypoxic conditions resulted in significantly increased migration. When SOSP-9607 cells were subjected to hypoxic conditions, the mRNA and protein levels of CXCR4 were significantly increased in a time-dependent manner. Moreover, siHIF-1α significantly decreased the mRNA and protein levels of CXCR4 under hypoxia, whereas pcDNA-HIF-1α significantly increased the mRNA and protein levels of CXCR4 under normoxia. A luciferase reporter gene study showed that siHIF-1α reduced pGL3-CXCR4 luciferase activity. Furthermore, coexpression of HIF-1α and CXCR4 was significantly higher in patients with distant metastasis compared with those without metastasis. CONCLUSIONS/SIGNIFICANCE: The hypoxia-HIF-1α-CXCR4 pathway plays a crucial role during the migration of human osteosarcoma cells, and targeting this pathway might represent a novel therapeutic strategy for patients suffering from osteosarcoma.

Exosomes derived from Rab27a­overexpressing tumor cells elicit efficient induction of antitumor immunity.

Lung cancer is the leading cause of mortality worldwide. However, there is a lack of effective therapeutic strategies. Currently, tumor immunotherapy based on exosomes, which are secreted by a variety of cell types including tumor cells, has drawn particular attention and are suggested to have the potential for exploitation in tumor therapy. Nevertheless, the therapeutic efficacy mediated via tumor cell-derived exosomes is not satisfactory. Rab27a, one of the Rab family of small GTPases, has been suggested to be important in exosome secretion. Thus, the purpose of the present study was to examine whether exosomes derived from Rab27a­overexpressing cells elicited more potent antitumor immunity. A Rab27a­overexpressing line was established via transfection of a Rab27a overexpression vector into the human non-small-cell lung cancer cell line, A549. Exosomes were isolated and the typical exosomal protein markers, CD9, CD63, heat shock protein (Hsp) 70 and Hsp90, were found to be enriched in the exosomes derived from Rab27a­overexpressing cells. Subsequently, these exosomes were demonstrated to be capable of upregulating major histocompatibility complex class II molecules as well as the co-stimulatory molecules CD80 and CD86 on dendritic cells (DCs), suggesting that more potent maturation of DCs was induced. Furthermore, DCs loaded with exosomes derived from Rab27-overexpressing cells significantly promoted CD4+ T cell proliferation in vitro. In addition, in vivo immunization of exosomes derived from Rab27a­overexpressing cells inhibited tumor growth in a mouse model. It was also demonstrated that splenocytes from mice immunized with exosomes derived from Rab27-overexpressing cells expressed high levels of type I cytokines, including IL-2 and IFN-γ, which are important in the regulation of cell-mediated antitumor immunity. Collectively, it was demonstrated that exosomes derived from Rab27a­overexpressing cancer cells elicited more potent antitumor immune effects, which may provide novel insights for the development of efficient exosome-based cancer vaccines.

Reductions in flesh discolouration and internal morphological changes in Nanhui peaches (Prunus persica (L.) Batsch, cv. Nanhui) by electrolysed water and 1-methylcyclopropene treatment during refrigerated storage.

The effects of electrolysed water (EW) and EW in combination with 1-methylcyclopropene (EW/MCP) on flesh discolouration of Nanhui peaches (Prunus persica (L.) Batsch, cv. Nanhui) were examined during storage at 2°C. Changes in flesh colour, ethylene production, membrane permeability, malondialdehyde (MDA), total phenolic contents and the activities of polyphenol oxidase (PPO) and peroxidase (POD) were assayed periodically after harvest and during 44days of storage. The internal morphological characteristics of Nanhui peaches were monitored using magnetic resonance imaging (MRI) at the beginning and end of storage. These data revealed that the EW/MCP treatment is more effective than the EW treatment for decreasing ethylene production and maintaining fruit cell membrane integrity, delaying increases in MDA and total phenolic contents, and lessening changes in PPO and POD activities and the internal morphology of peaches. Each of these effects contributes to suppressing flesh discolouration and maintaining the quality of Nanhui peaches during storage.