Bioactive secondary metabolites from tomato-derived bacterium Bacillus velezensis Hnu24.

A series of secondary metabolites have been isolated from the genus of Bacillus velezensis, most of which show antibacterial and insecticidal activities. In order to find more bioactive secondary metabolites from B. velezensis, one new natural component aminoindole dimer baciindole A (1), together with seven known compounds (2-8) were isolated from the tomato-derived bacterium Bacillus velezensis Hnu24. The structure of compound 1 was elucidated by its HR-ESI-MS spectral data and 1 D/2D NMR spectroscopic analysis. Compound 3 showed antibacterial activity against Staphylococcus aureus, S. epidermidis and Ralstonia solanacearum with the MIC values of 3.125, 12.5 and 50 µg/mL, respectively. Compound 4 showed antibacterial activity against S. aureus with the MIC value of 12.5 µg/mL. Compound 3 showed cytotoxic activity for human colon cancer HTC116 cancer cells with the IC50 value of 8.42 ± 0.48 µM. Five compounds (1-4 and 8) were obtained from the strain of B. velezensis for the first time. These results indicated that 3 will be useful in developing antimicrobial and treatment of colon cancer agents.

Talaromarins A-F: Six New Isocoumarins from Mangrove-Derived Fungus Talaromyces flavus TGGP35.

Six new isocoumarin derivative talaromarins A-F (1-6), along with 17 known analogues (7-23), were isolated from the mangrove-derived fungus Talaromyces flavus (Eurotiales: Trichocomaceae) TGGP35. Their structures were identified by detailed IR, UV, 1D/2D NMR and HR-ESI-MS spectra. The absolute configurations of new compounds were determined by the modified Mosher's method and a comparison of their CD spectra with dihydroisocoumarins described in the literature. The antioxidant, antibacterial, anti-phytopathogenic and inhibitory activity against α-glucosidase of all the isolated compounds were tested. Compounds 6-11, 17-19 and 21-22 showed similar or better antioxidant activity than the IC50 values ranging from 0.009 to 0.27 mM, compared with the positive control trolox (IC50 = 0.29 mM). Compounds 10, 18, 21 and 23 exhibited strong inhibitory activities against α-glucosidase with IC50 values ranging from 0.10 to 0.62 mM, while the positive control acarbose had an IC50 value of 0.5 mM. All compounds showed no antibacterial or anti-phytopathogenic activity at the concentrations of 50 µg/mL and 1 mg/mL, respectively. These results indicated that isocoumarins will be useful to developing antioxidants and as diabetes control agents.

Effect of High-Voltage Additives on Formation of Solid Electrolyte Interphases in Lithium-Ion Batteries.

Solid electrolyte interphase (SEI) formed at the interface in lithium-ion batteries plays an important role in isolating electrons and permeating ions during charging/discharging processes. Therefore, the formation of a good interface is crucial for better battery performance. In this study, additives based on adiponitrile (ADN) and trimethyl borate (TMB) were employed to broaden the electrochemical window and form a good SEI layer. Electrochemical Atomic force microscopy (EC-AFM) was used for in situ studies of film-formation mechanisms in high-voltage electrolytes on high-temperature pyrolytic graphite (HOPG), as well as Li- and Mn-rich (LMR) materials. X-ray photoelectron spectroscopy (XPS) combined with electrochemical methods revealed a synergistic reaction between the two additives to form a more stable interfacial film during charging/discharging processes to yield assembled batteries with improved cycle performance, its capacity increased from below 100 mAh/g to 200 mAh/g after 50 cycles. In sum, these findings would have great significance for the development of high voltage lithium-ion batteries with enhanced performance.

Indication of Strongly Correlated Electron Transport and Mott Insulator in Disordered Multilayer Ferritin Structures (DMFS).

Electron tunneling in ferritin and between ferritin cores (a transition metal (iron) oxide storage protein) in disordered arrays has been extensively documented, but the electrical behavior of those structures in circuits with more than two electrodes has not been studied. Tests of devices using a layer-by-layer deposition process for forming multilayer arrays of ferritin that have been previously reported indicate that strongly correlated electron transport is occurring, consistent with models of electron transport in quantum dots. Strongly correlated electrons (electrons that engage in strong electron-electron interactions) have been observed in transition metal oxides and quantum dots and can create unusual material behavior that is difficult to model, such as switching between a low resistance metal state and a high resistance Mott insulator state. This paper reports the results of the effect of various degrees of structural homogeneity on the electrical characteristics of these ferritin arrays. These results demonstrate for the first time that these structures can provide a switching function associated with the circuit that they are contained within, consistent with the observed behavior of strongly correlated electrons and Mott insulators.

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus-Scorpion against prostate cancer.

The present study aimed to investigate the molecular mechanism of the Astragalus-Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus-Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the 'active ingredient-target disease' network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus-Scorpion drug pair. The core targets of the protein-protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.

A LHFPL3-AS1/miR-580-3p/STAT3 Feedback Loop Promotes the Malignancy in Melanoma via Activation of JAK2/STAT3 Signaling.

Melanoma is one of the severe skin cancers, accounting for three fourths of all deaths caused by skin cancers and gathering attention from researchers. Previous studies have elucidated that long noncoding RNAs (lncRNA) engage actively in tissue physiology and disease development, especially in tumorigenesis. LncRNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) has rarely been mentioned in researches regarding cancers; therefore, the underlying role and function of LHFPL3-AS1 in melanoma arouse our interest. Data from our work suggested that LHFPL3-AS1 expression was markedly elevated in melanoma tissues and cells. Of note, patients with melanoma with high level of LHFPL3-AS1 were burdened with unfavorable prognosis. Functionally, it has been revealed that LHFPL3-AS1 exerted pro-growth, pro-invasion, and pro-EMT functions in melanoma. Mechanistically, it was figured out that LHFPL3-AS1 could be transcriptionally activated by STAT3. In turn, LHFPL3-AS1 served as a sponge of miR-580-3p to augment STAT3 expression, resulting in activated JAK2/STAT3 signaling pathway in melanoma. IMPLICATIONS: Our study revealed a novel positive feedback loop LHFPL3-AS1/miR-580-3p/STAT3 in melanoma, which might contribute to finding potential therapeutic targets for melanoma.

Overexpression of microRNA-612 Restrains the Growth, Invasion, and Tumorigenesis of Melanoma Cells by Targeting Espin.

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

Construction and identification of an RNA interference lentivirus vector targeting the Ras homology C gene of melanoma cells.

BACKGROUND: Melanoma has the highest mortality among all superficial malignant tumors. The poor prognosis is due to its high metastasis rate and the lack of therapeutic targets. As a molecular switch that controls tumor metastasis, Ras homology C (RhoC) has been correlated with tumor progression, especially tumor invasion and metastasis. However, little research has been done about the effects of RNA interference (RNAi) targeting RhoC on the invasion and metastasis of melanoma. In this study, we constructed an RNAi lentivirus vector targeting the RhoC gene of melanoma cells and identified its silencing effects on the RhoC gene. METHODS: Based on the RhoC gene encoding information, three pGPU6/GFP/Neo-short hairpin (shRNA) plasmids were constructed. After detecting their silencing effects on the RhoC gene of A375 cells, the most effective pGPU6/GFP/Neo-shRNA plasmid was packed with lentivirus to construct the recombinant pLenti6.3-EGFP-453 targeting RhoC. The lentivirus vector was used to infect A375 cells, and then the expression of RhoC mRNA and protein were determined with real-time PCR and Western blotting. RESULTS: The plasmids pGPU6/GFP/Neo-shRNA 336, pGPU6/GFP/Neo-shRNA 453, and pGPU6/GFP/Neo-shRNA 680 were constructed. After they were transfected into A375 cells, the expressions of RhoC mRNA and protein were 1.47 ± 0.26, 1.13 ± 0.16, 1.39 ± 0.11 and 70.98 ± 9.21, 50.67 ± 6.06, 65.77 ± 4.06, respectively. pGPU6/GFP/Neo-shRNA 453 was the most effective sequence, and was used to successfully construct the pLenti6.3-EGFP-453 lentiviral vector targeting RhoC. pLenti6.3-EGFP-453 was used to infect A375 cells. The expression of RhoC mRNA and protein were 1.05 ± 0.05 and 62.04 ± 15.86 in the lentivirus group, 4.21 ± 0.24 and 220.86 ± 24.07 in the negative lentivirus control group, and 4.63 ± 0.32 and 257.39 ± 12.30 in the normal control group respectively with the difference between the lentivirus group and the control groups being statistically significant (P < 0.05). CONCLUSION: The successfully constructed pLenti6.3-EGFP-453 vector targeting the RhoC can effectively infect human melanoma A375 cells in vitro, and significantly inhibit the RhoC mRNA and protein expression.

Reconstruction of singular eyelid defects in aging individuals based on facial aesthetic subunits.

BACKGROUND: In consideration of the distinctive structural characteristics of the eyelid, the optimally matching donor site to the original recipient site skin should be selected when a full-thickness skin graft is anticipated in a small-sized or medium-sized eyelid defect in middle-aged or elderly patients. METHODS: Eight patients ranging in age from 47 to 71 years suffered singular eyelid defects of different causes. Based on the location, shape, and degree of the defects, we removed the redundant skin as a skin graft from the same side in the contralateral eyelid in a routine blepharoplasty procedure and transferred the graft to repair the defect. RESULTS: The skin grafts survived in all cases, and the incisions healed primarily. The eyelid laxity improved, and no complications occurred. All cases were followed up for 3 months to 2 years, the quality of skin grafts was similar to that of the surrounding skin, and the activity was ideal. CONCLUSIONS: When an eyelid defect is not amenable to direct closure and skin grafting is selected, the proper donor site is vital to the final outcome. The same facial aesthetic subunits, such as sufficient laxity in the contralateral eyelid skin in middle-aged and elderly patients, can provide the best match with the recipient skin and represent the best donor site for defect reconstruction.

[Reshaping the nasal tip with autologous nasal septum cartilage combined with ePTFE grafts and autologous auricular cartilage grafts].

OBJECTIVE: To evaluate the clinical effects of reshaping the nasal tip with autologous nasal septum cartilage combined with expanded polytetrafluoroethylene (ePTFE) and autologous auricular cartilage grafts. METHODS: The nasal septal cartilage combined with ePTFE (group A, 70 cases) and autologous auricular cartilage grafts (group B, 48 cases) were used separately. The therapeutic effect and operation time were compared using the t-test or the χ²-test by the SPSS 12.0 software. RESULTS: The mean operation time (x(-) ± s) in group A was less than those in group B and the difference was significant (t = 13.258, P = 0.000). The width of nasal tip equal to (6 - 8) mm was found in 67 cases (95.7%) in group A, and 46 cases (95.8%) in group B. There was no statistically significant difference between group A and group B (χ² = 0.001, P = 0.996). The correction result of the nasal tip projection, angle of ration, the included angle of nasal dorsum and nasal columella and the height of the nasal tip did not show statistically significant difference between group A and group B (χ² value were 0.001, 0.069, 0.149, 0.073, respectively, all P > 0.05). CONCLUSION: The autologous nasal septal cartilage combined with ePTFE and autologous auricular cartilage grafts showed similar clinical effect.

Effect of Chinese herbal medicine for calming Gan (肝) and suppressing hyperactive yang on arterial elasticity function and circadian rhythm of blood pressure in patients with essential hypertension.

OBJECTIVE: To observe the effect of Chinese herbal medicine for calming Gan (肝) and suppressing hyperactive yang (平肝潜阳, CGSHY) on arterial elasticity function and the circadian rhythm of blood pressure in patients with essential hypertension (EH). METHODS: Adopting a parallel, randomized design, sixty-four patients with EH of stages I and II were randomly divided into two groups according to a random number table, with 32 in each group. The patients in the treatment group were treated with CGSHY and those in the control group were treated with Enalapril. All patients were given 24-h ambulatory blood pressure monitoring (ABPM) before and after a 12-week treatment. Trough/peak (T/P) ratios of systolic and diastolic blood pressure (SBP & DBP) of each group were calculated. The circadian rhythm of their blood pressure was observed at the same time. The changes in elasticity of the carotid artery in the patients, including stiffness parameter (ß), pressure-strain elastic modulus (Ep), arterial compliance (AC), augmentation index (AI), and pulse wave velocity (PVWß) were determined by the echo-tracking technique before and after a 12-week treatment. In the meantime, their levels of nitric oxide (NO) and endothelin-1 (ET-1) were measured respectively. RESULTS: After treatment, all parameters in the 24-h ABPM and the elasticity of the carotid artery (ß, Ep, AC and PVWß) were markedly improved, the level of NO was increased, and ET-1 was decreased in both groups as compared with values before treatment (P<0.05 or P<0.01). Further, the improvements in the ratio of T/P of SBP & DBP and in the level of NO and ET-1 in the treatment group were more significant than those in the control group (P<0.05). There were no significant differences in all parameters in the ABPM monitoring and the elasticity of the carotid artery, the recovery of blood pressure circadian rhythm, and the therapeutic effect of antihypertension in EH patients between the two groups (P>0.05). CONCLUSIONS: Chinese herbal medicine for CGSHY may lower the blood pressure smoothly and recover the circadian rhythm of blood pressure in EH patients. They may also improve the carotid elasticity of EH patients similar to that of Enalapril. The mechanism of action of Chinese herbs on EH might be related to the regulation of vascular endothelium function.

Malignant cutaneous tumors of the scalp: a study of demographic characteristics and histologic distributions of 398 Taiwanese patients.

BACKGROUND: The scalp is a unique anatomic region, in which pilosebaceous follicles are concentrated. OBJECTIVE: We sought to investigate demographic characteristics and histologic distributions of malignant scalp tumors. METHODS: Primary and metastatic scalp malignancies diagnosed histopathologically between 1983 and 2003 were reviewed. Age at diagnosis, sex, and histologic types were analyzed. RESULTS: A total of 398 Taiwanese patients (200 males, 198 females) were selected. Age at diagnosis ranged from 3 to 103 years. Most malignant scalp tumors (69.8%) occurred in those 50 years or older. Basal (41.2%) and squamous (16.6%) cell carcinomas were the most common histologic types. Surprisingly, metastatic tumors (12.8%) came in third, in which lung cancers were the most frequent primary tumor in both male and female patients. LIMITATIONS: In our series, the case number of metastatic scalp malignancies was underestimated because not all patients with metastatic scalp tumors received a scalp skin biopsy. CONCLUSION: Because a wide spectrum of primary and metastatic malignancies can occur on the scalp, scalp inspection should be included in general screening for either skin or internal cancers.