Omega-3 PUFA ameliorates hyperhomocysteinemia-induced hepatic steatosis in mice by inhibiting hepatic ceramide synthesis.

Hyperhomocysteinemia (HHcy) is a key risk factor in hepatic steatosis. In this study, we applied a metabolomic approach to investigate the changes in the metabolite profile due to HHcy-induced hepatic steatosis and the effects of omega-3 PUFA (polyunsaturated fatty acid) supplementation in mice. HHcy was induced in mice by giving DL-Hcy (1.8 g/L) in drinking water for 6 weeks, then the mice were sacrificed, and the metabolic profiles of the liver and plasma were analyzed through UPLC-ESI-QTOFMS-based lipidomics. Hepatic triglycerides and cholesterol were further assayed. The expression of ceramide metabolism-related genes was measured by quantitative PCR. Compared with control mice, HHcy mice exhibited hepatic steatosis with a notable increase in ceramide-related metabolites and subsequent upregulation of ceramide synthesis genes such as Sptlc3, Degs2, Cer4 and Smpd4. Omega-3 PUFA was simultaneously administered in HHcy mice through chow diet containing 3.3% omega-3 PUFA supplement for 6 weeks, which significantly ameliorated Hcy-induced hepatic steatosis. The decrease in hepatic lipid accumulation was mainly due to reduced hepatic levels of ceramides, which was partly the result of the lower expression of ceramide synthesis genes, Sptlc3 and Degs2. Similar beneficial effects of DHA were observed in Hcy-stimulated primary hepatocytes in vitro. In summary, Hcy-induced ceramide elevation in hepatocytes might contribute to the development of hepatic steatosis. Furthermore, downregulation of ceramide levels through omega-3 PUFA supplementation ameliorates hepatic lipid accumulation. Thus, ceramide is a potential therapeutic target for the treatment of hepatic steatosis.

Construction of Luminogen Exhibiting Multicolored Emission Switching through Combination of Twisted Conjugation Core and Donor-Acceptor Units.

Stimuli responsive luminescent materials, especially those exhibiting multicolor emission switching, have potential application in sensor, optical recording, security ink, and anti-counterfeit label. Through combination of twisted conjugation core and donor and acceptor units, a luminogen (2-(bis(4-(carbazol-9-yl)phenyl)methylene)malononitrile (1) was synthesized. Luminogen 1 can form three kinds of crystals emitting green (1GC, λem = 506 nm, ΦF = 19.8%), yellow-green (1YC, λem = 537 nm, ΦF = 17.8%), and orange (1OC, λem = 585 nm, ΦF = 30.0%) light upon 365 nm UV illumination. The emission of amorphous solid of 1 (1Am) overlaps with that of 1OC (λem = 585 nm), with quantum yield of 13.9%, which is seldom reported. Emission of 1 can be switched among green, yellow-green, and orange through morphology modulation upon exposure to thermal, solvent vapor, or mechanical stimuli. Finally, its potential application in optical recording was also investigated.

Surgical treatment of an invasive thymoma extending into the superior vena cava and right atrium.

Although invasive thymoma commonly infiltrates neighbouring mediastinal structures, its extension into the superior vena cava (SVC) and consequent SVC occlusion are rare. In such cases, the urgent removal of the thymoma and radical resection of the infiltrated SVC representreasonable options, since induction therapy is time-consuming and useless for symptom resolution. A case of invasive thymoma extending into the SVC and right atrium (RA) with SVC syndrome is reported. The patient underwent a combined resection of the invasive tumor and SVC under cardiopulmonary bypass (CPB), and the SVC and bilateral brachiocephalic vein (BCV) were reconstructed with an autologous pericardial 'Y' conduit. After 40 months of follow-up, the patient showed a patent graft and no tumor recurrence.

Surgical treatment of aortoesophageal fistula induced by a foreign body in the esophagus: 40 years of experience at a single hospital.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare but usually fatal complication of a foreign body in the esophagus. Little effective therapy exists to cure an AEF induced by esophageal foreign body. This report describes the authors' 40 years of experience treating patients with AEF caused by a foreign body and compares different treatments of patients and their clinical outcomes. METHODS: The treatments of five patients with AEF caused by esophageal foreign body impaction were recorded at Wuhan General Hospital of Guangzhou Command from 1970 to 2011. One of these five patients was managed with nonsurgical measures, whereas three were treated by surgery with cardiopulmonary bypass, and one was treated by surgery with endovascular stent-graft repair. RESULTS: All five AEF cases were confirmed by computed tomography, esophagogastroscopy, surgical findings, or two or both. The nonsurgically treated patient died of fatal hemorrhage. Another patient died during the postoperative period because of ventricular fibrillation (he had a history of coronary heart disease before the operation), and still another patient died of fatal hemorrhage during the surgery. The remaining two patients were completely cured by surgery: the one via traditional open thoracotomy with cardiopulmonary bypass and the other by surgery with endovascular stent-graft repair. CONCLUSIONS: The authors' experience indicates that early diagnosis and an aggressive surgical treatment without delay is the only form of effective therapy for AEF. Endovascular stent-graft repair may be a safe and feasible method for treating patients with AEF that has potential as an improved treatment option for AEF.

Role of FSCN1 in the tumor microenvironment of lung squamous cell carcinoma.

Tumor microenvironment (TME) regulated the development of the Lung squamous cell carcinoma (LUSC). To know more about the LUSC, this study tried to figure the role of fscin actin-bundling protein 1 (FSCN1) in the TME. We identified the FSCN1 as the hub immune gene in LUSC, with the use of weighted gene co-expression network analysis (WGCNA) and the Human Protein Atlas. Furthermore, we verified the higher expression of FSCN1 in LUSC compared with the normal tissues by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry. We then explored the associations among FSCN1, immune infiltrations, and inflammatory factors with the use of Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor IMmune Estimation Resource (TIMER). As a result, the expressions of FSCN1 was negatively related to the immune infiltrations, and positively related to the expressions of IL1A, IL1B, TGFB1 and TGFA. Moreover, we used the single-cell RNA-sequencing (scRNA-seq) data of LUSC to figure out the expressions level of FSCN1, IL1A, IL1B, TGFB1 and TGFA in the different cell type's of the TME. Finally, through the cytological experiments, we found that FSCN1 affected by TGFB1 contributes to the proliferation, anti-apoptotic effect, migration and invasion of the LUSC cells. In summary, this study Identified FSCN1 as the potential therapeutic target of LUSC, and reveals a complicated immune and inflammatory net in the TME.

Construction of a Luminogen Exhibiting High Contrast and Multicolored Emission Switching through Combination of a Bulky Conjugation Core and Tolyl Groups.

Stimuli-responsive luminogens may find application in highly sensitive sensors, memories and security inks. However, few examples exhibiting both high contrast and multi-colored emission switching have been reported due to the absence of a molecular design strategy. Through combination of large conjugation core and peripheral phenyl rings, we obtained ditolyldibenzofulvene (1). Luminogen 1 is AIE active and exhibits tetracolored emission depending on its morphology. Its three single crystals emit blue, yellow and dark orange light upon excitation, exhibiting a maximal emission of 461 nm, 545 nm and 586 nm, respectively, and its amorphous solid emits at 557 nm. All the four aggregates exhibit enhanced emission intensity at lower temperature, but only the orange-emissive crystals exhibit blue-shifted emission. The emission of 1 can be switched reversibly between any two of the four states through morphology tuning. Finally, the potential application of 1 in optical data storage was also investigated.

Adipocyte-derived Lysophosphatidylcholine Activates Adipocyte and Adipose Tissue Macrophage Nod-Like Receptor Protein 3 Inflammasomes Mediating Homocysteine-Induced Insulin Resistance.

The adipose Nod-like receptor protein 3 (NLRP3) inflammasome senses danger-associated molecular patterns (DAMPs) and initiates insulin resistance, but the mechanisms of adipose inflammasome activation remains elusive. In this study, Homocysteine (Hcy) is revealed to be a DAMP that activates adipocyte NLRP3 inflammasomes, participating in insulin resistance. Hcy-induced activation of NLRP3 inflammasomes were observed in both adipocytes and adipose tissue macrophages (ATMs) and mediated insulin resistance. Lysophosphatidylcholine (lyso-PC) acted as a second signal activator, mediating Hcy-induced adipocyte NLRP3 inflammasome activation. Hcy elevated adipocyte lyso-PC generation in a hypoxia-inducible factor 1 (HIF1)-phospholipase A2 group 16 (PLA2G16) axis-dependent manner. Lyso-PC derived from the Hcy-induced adipocyte also activated ATM NLRP3 inflammasomes in a paracrine manner. This study demonstrated that Hcy activates adipose NLRP3 inflammasomes in an adipocyte lyso-PC-dependent manner and highlights the importance of the adipocyte NLRP3 inflammasome in insulin resistance.

Hybridization of thiol-functionalized poly(phenylacetylene) with cadmium sulfide nanorods: improved miscibility and enhanced photoconductivity.

Molecules of a thiol-functionalized phenylacetylene derivative were assembled on the CdS nanorod surface and copolymerized with phenylacetylene, affording an inorganic semiconductor-conjugated polymer hybrid with excellent solubility and high photoconductivity.

Mechanochromic Luminescence of Aggregation-Induced Emission Luminogens.

Mechanochromic (MC) luminogens have found promising applications in mechanosensors, security papers, and optical storage for their change in emission behaviors in response to mechanical stimuli. Examples on MC luminescent materials are rare before the discovery of MC luminescence in aggregation-induced emission (AIE) luminogens. The twisted conformations of AIE luminogens (AIEgens) with appropriate crystallization capability afford loosely packing patterns, which facilitates their phase transformation in the solid state. The amorphous films of AIEgens exhibit enhanced emission intensity upon pressurization due to the increased molecular interactions, whereas crystals of AIEgens exhibit MC luminescence due to their amorphization by mechanical stimuli. AIEgens enrich the type of MC luminogens but those showing high emission contrast and multicolor emission switching and those working in a turn-on emission mode are seldom reported. Disclosure of the design strategy of high performance MC luminogens and exploration of their high-tech applications may be the future research directions for MC luminogens.

A unique fluorescence response of hexaphenylsilole to methyl parathion hydrolase: a new signal generating system for the enzyme label.

Methyl parathion hydrolase (MPH), an enzyme that catalyses the turnover of methyl parathion (MP) to p-nitrophenol (pNP), can be utilized as an enzyme label. In this paper, a unique fluorescence response of 1,1-bis[4-(diethylaminomethyl)phenyl]-2,3,4,5-tetraphenylsilole (A2HPS) to MPH whose gene was obtained from Pseudomonas sp. strain WBC-3 is described. In the absence of MP, A2HPS could only give a small fluorescence response to the enzyme (I/I0 = 1.1). The detection must be performed under low pH conditions, and the influence of BSA and hemoglobin (Hb) was high; upon addition of the enzyme's substrate, 1 × 10-5µg mL-1 or 2.85 × 10-13 M of the MPH could be reported by A2HPS with a higher I/I0 of 1.7. The detection limit was 105 times more sensitive than that given by a spectrophotometric method. In addition, the assay could be performed at a near neutral pH which was more biocompatible, and little influence was observed from BSA and Hb. The light-on response to the MPH was due to the different quenching effect of the MP and pNP on A2HPS and the improvement in the detection selectivity was due to combining the enzyme reaction with the detection. The findings of this work suggested that A2HPS and MP could form a new reporter system for the MPH enzyme label.

Cesium carbonate functionalized graphene quantum dots as stable electron-selective layer for improvement of inverted polymer solar cells.

Solution processable inverted bulk heterojunction (BHJ) polymer solar cells (PSCs) are promising alternatives to conventional silicon solar cells because of their low cost roll-to-roll production and flexible device applications. In this work, we demonstrated that Cs2CO3 functionalized graphene quantum dots (GQDs-Cs2CO3) could be used as efficient electron-selective layers in inverted PSCs. Compared with Cs2CO3 buffered devices, the GQDs-Cs2CO3 buffered devices show 56% improvement in power conversion efficiency, as well as 200% enhancement in stability, due to the better electron-extraction, suppression of leakage current, and inhibition of Cs(+) ion diffusion at the buffer/polymer interface by GQDs-Cs2CO3. This work provides a thermal-annealing-free, solution-processable method for fabricating electron-selective layer in inverted PSCs, which should be beneficial for the future development of high performance all-solution-processed or roll-to-roll processed PSCs.

Effect of 5-aza-2'-deoxycytidine on cell proliferation of non- small cell lung cancer cell line A549 cells and expression of the TFPI-2 gene.

OBJECTIVE: The present study employed 5-aza-2'-deoxycytidine (5-Aza-CdR) to treat non-small cell lung cancer (NSCLC) cell line A549 to investigate the effects on proliferation and expression of the TFPI-2 gene. METHODS: Proliferation was assessed by MTT assay after A549 cells were treated with 0, 1, 5, 10 µmol/L 5-Aza-CdR, a specific demethylating agent, for 24 ,48 and 72h. At the last time point cells were also analyzed by flow cytometry (FCM) to identify any change in their cell cycle profiles. Methylation-specific polymerase chain reaction (MSPCR), real time polymerase chain reaction(real-time PCR) and western blotting were carried out to determine TFPI-2 gene methylation status, mRNA expression and protein expression. RESULTS: MTT assay showed that the growth of A549 cells which were treated with 5-Aza-CdR was significantly suppressed as compared with the control group (0 µmol/L 5-Aza-CdR). After treatment with 0, 1, 5, 10 µmol/L 5-Aza-CdR for 72h, FCM showed their proportion in G0/G1 was 69.7±0.99%, 76.1±0.83%, 83.8±0.35%, 95.5±0.55% respectively (P<0.05), and the proportion in S was 29.8±0.43%, 23.7±0.96%, 15.7±0.75%, 1.73±0.45%, respectively (P<0.05), suggesting 5-Aza-CdR treatment induced G0/G1 phase arrest. MSPCR showed that hypermethylation in the promoter region of TFPI-2 gene was detected in control group (0 µmol/L 5-Aza-CdR), and demethylation appeared after treatment with 1, 5, 10 µmol/L 5-Aza-CdR for 72h. Real-time PCR showed that the expression levels of TFPI-2 gene mRNA were 1±0, 1.49±0.14, 1.86±0.09 and 5.80±0.15 (P<0.05) respectively. Western blotting analysis showed the relative expression levels of TFPI-2 protein were 0.12±0.01, 0.23±0.02, 0.31±0.02, 0.62±0.03 (P<0.05). TFPI-2 protein expression in A549 cells was gradually increased significantly with increase in the 5-Aza-CdR concentration. CONCLUSIONS: TFPI-2 gene promoter methylation results in the loss of TFPI-2 mRNA and protein expression in the non-small cell lung cancer cell line A549, and 5-Aza-CdR treatment could induce the demethylation of TFPI-2 gene promoter and restore TFPI-2 gene expression. These findings provide theoretic evidence for clinical treatment of advanced non-small cell lung cancer with the demethylation agent 5-Aza-CdR. TFPI-2 may be one molecular marker for effective treatment of advanced non-small cell lung cancer with 5-Aza-CdR.

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder.

OBJECTIVE: Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. METHODS: We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. RESULTS: Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. CONCLUSION: Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective.

Locking the phenyl rings of tetraphenylethene step by step: understanding the mechanism of aggregation-induced emission.

Stepwise locking of phenyl rings of tetraphenylethene increases the emission efficiency of luminogen solutions gradually, thus verifying the restriction of intramolecular rotation (RIR) mechanism of the aggregation induced emission phenomenon. The emission of the luminogen with one "O" bridge could be tuned reversibly in solid state through repeated heating and grinding.

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder

OBJECTIVE: Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder. METHODS: We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques. RESULTS: Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology. CONCLUSION: Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective.