Dapagliflozin alleviates high glucose-induced injury of endothelial cells via inducing autophagy.

Hyperglycaemia is a key factor in the progression of diabetes complications. Dapagliflozin (DAPA), a new type of hypoglycaemic agent, has been shown to play an important role in anti-apoptotic, anti-inflammatory and antioxidant activities. Previous studies have demonstrated an endothelial protective effect of DAPA, but the underlying mechanism was still unclear. Autophagy is a homeostatic cellular mechanism that circulates unfolded proteins and damaged organelles through lysosomal dependent degradation. In this study, we aimed to investigate whether DAPA plays a protective role against high glucose (HG)-induced endothelial injury through regulating autophagy. The results showed that DAPA treatment resulted in increased cell viability. Additionally, DAPA treatment decreased interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α levels in endothelial cells subjected to HG conditions. We observed that HG inhibited autophagy, and DAPA increased the autophagy level by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway. Chloroquine reversed all of these beneficial effects as an autophagy inhibitor. In summary, the endothelial protective effect of DAPA in HG can be attributed in part to its role in activating of autophagy via the AKT/mTOR signalling pathway. Therefore, suggesting that the activation of autophagy by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.

Realization of ∼10 nm Features on Semiconductor Surfaces via Femtosecond Laser Direct Patterning in Far Field and in Ambient Air.

Direct fabrication of ∼10 nm features by optical means in far field and in ambient air on semiconductor surfaces is significant for next-generation advances nanomanufacturing. We report here a new method that enables the direct formation of 12 nm (λ/66) features on silicon surfaces. It is processed in far field and in ambient air via the irradiation of orthogonally polarized double femtosecond laser beams. The coupling of orthogonally polarized double femtosecond laser beams and the incubation effect due to multiple femtosecond laser pulses irradiation under high repetition rate enable the 12 nm nanostructures creation parallel to the scanning direction, regardless of scanning path.

High-quality sapphire microprocessing by dual-beam laser induced plasma assisted ablation.

Sapphire is a kind of ultrahard transparent material with good chemical resistance. These great properties also make sapphire functional device fabrication a big challenge. We propose a novel dual-beam laser induced plasma assisted ablation (LIPAA) for high-quality sapphire microprocessing. One laser beam is focused on a sacrificial target for nano-particle generation by LIPAA to assist the sapphire ablation by the other laser beam. The new technology can reduce the ablation threshold of sapphire and the roughness of the fabricated structures. The laser fluence for particle generation is optimized. Furthermore, we demonstrate a sapphire Dammann grating and an OAM generator fabricated by this method. This method can be expanded to arbitrary transparent material precision machining for various applications.

The Role of the Gut Microbiota in Coronary Heart Disease.

PURPOSE OF REVIEW: This review focuses on recent evidence examining the role gut microbiota play in coronary heart disease. It also provides a succinct overview of current and future therapies targeting the gut microbiota for coronary heart disease risk reduction. RECENT FINDINGS: A consensus has been reached that differences exist in the gut microbiotas of patients with coronary heart disease. Studies have shown that the gut microbiota is associated with obesity, diabetes, dyslipidemia, and hypertension, which are risk factors for coronary heart disease. The gut microbiota is involved in mediating basic metabolic processes, such as cholesterol metabolism, uric acid metabolism, oxidative stress, and inflammatory reactions, through its metabolites, which can induce the development of atherosclerosis and coronary heart disease. Interfering with the composition of gut microbiota, supplementing probiotics, and fecal donation are active areas of research to potentially prevent and treat coronary heart disease. Gut microbiota are causally associated with coronary heart disease. We analyzed the gut microbiota's effects on risk factors for coronary heart disease and studied the effects of gut microbiota metabolites on coronary heart disease. Gut microbiota is a potential target for preventing and treating coronary heart disease.

Dynamically tunable multi-lobe laser generation via multifocal curved beam.

Beams with curved properties, represented by Airy beam, have already shown potential applications in various fields. Here we propose a simple method to achieve a multifocal curved beam (MCB). The scheme is based on the ability of microspheres to control the distribution of the light field. Combined with the caustic effect, the dynamic control of the beam curvature and the foci can be realized. The simulation results confirm the mechanism behind this phenomenon. Furthermore, MCB is applied experimentally into the end-pumped microchip laser. This work has verified the theory of MCB and achieved a dynamically tunable multi-lobe laser, which has a wide application prospect.

Manipulating the wavelength-drift of a Tm laser for resonance enhancement in an intra-cavity pumped Ho laser.

We demonstrate an enhancement mechanism and thermal model for intra-cavity pumped lasers, where resonance enhancement in intra-cavity pumped Ho laser was achieved by manipulating the wavelength-drift nature of the Tm laser for the first time. Optical conversion efficiency of 37.5% from an absorbed 785 nm diode laser to a Ho laser was obtained with a maximum output power of 7.51 W at 2122 nm, which is comparable to the conversion efficiency in 1.9 µm LD pumped Ho lasers. Meanwhile, more severe thermal effects in the Ho-doped gain medium than the Tm-doped one at high power operation were verified based on the built thermal model. This work benefits the design or evaluation of intra-cavity pumped lasers, and the resonance enhancement originated from the difference in reabsorption loss between stark levels at the lasing manifolds of quasi-three-level rare-earth ions has great interest to improve the existing intra-cavity pumped lasers or explore novel lasers.

Passively Q-switched solid-state Tm:YAG laser using topological insulator Bi2Te3 as a saturable absorber.

We demonstrated a passively Q-switched solid-state Tm:YAG laser using topological insulator (TI) Bi2Te3 as the saturable absorber (SA) for the first time, to the best of our knowledge. The Q-switched laser pulses were obtained with the minimum pulse width of 382 ns, the maximum pulse energy of 4.8 µJ, the maximum average output power of 272 mW, and a pulse repetition rate of 57.67 kHz. The results indicate that Bi2Te3 can be a promising kind of saturable absorber in the 2 µm wavelength region.

Spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of Curcuma aromatica.

Curcuma aromatica is used as a traditional Chinese medicine, and it is mainly distributed in Guangxi, China. In this study, 10 batches of C. aromatica were collected from different origins in Guangxi. The fingerprints were established by HPLC technique to investigate the quality stability of C. aromatica. The spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica was assessed by similarity analysis, gray relational analysis and multiple linear regression analysis. From the results, the similarity values between each batch of C. aromatica and reference fingerprint were >0.880, indicating the good quality stability of the 10 batches of C. aromatica. Twenty common peaks were selected as the fingerprints to evaluate the quality and hypolipidemic effect of C. aromatica. The results of spectrum-effect relationship showed that peaks 10, 18, 13, 15 and 17 in the fingerprints were closely related to hypolipidemic effect. This study successfully established the spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica, which provided methods for quality control and more effectively studies on bioactive compounds of C. aromatica. It could also provide a new simple and effective method for utilizing the fingerprints to optimize the Chinese prescription and develop traditional Chinese medicine.

Evaluation of Different Minimally Invasive Techniques in Surgical Treatment for Ventricular Septal Defect.

BACKGROUND: Minimally invasive cardiac surgery is becoming a safe and cosmetic alternative to standard median sternotomy (SMS). This retrospective study reviews our results and experience with the lower mini-sternotomy (LMS) technique and the right lateral thoracotomy (RLT) technique for ventricular septal defect (VSD) closure compared with SMS. METHODS: Between January 2013 and Dec 2015, 198 patients underwent repair VSD through lower mini-sternotomy (LMS Group, n=66), right lateral thoracotomy (RLT Group, n=59), standard median sternotomy (SMS Group, n=73). Cardiopulmonary bypass was achieved directly in the three different approaches. RESULTS: Procedures were performed successfully in all patients among the three groups and no in-hospital mortality occurred. No patient was reverted to standard median sternotomy in the LMS Group and RLT Group. The CPB time was 37.73±11.46 mins in the LMS Group, 41.3±13.97 mins in the RLT Group and 36.99±10.84 mins in the SMS Group (p=0.078); the cross-clamp times were 23.85±9.78 mins in the LMS Group, 22.54±9.08 mins in the RLT Group and 19.23±6.92 mins in the SMS Group (p=0.009). The total incision length of the procedure in the SMS Group (7.45±1.54cm) was longer than the other groups (LMS Group, 5.58±0.8cm and RLT Group, 5.96±1.48cm) and the difference was significant (p<0.001). CONCLUSIONS: Both the LMS and RLT approach can be performed with favourable cosmetic and acceptable clinical results for closing VSD. They are the promising alternatives to standard median sternotomy and merit further study.

Efficient 2122 nm Ho:YAG laser intra-cavity pumped by a narrowband-diode-pumped Tm:YAG laser.

We first demonstrate an efficient Ho:YAG laser intra-cavity pumped by a narrowband-diode-pumped Tm:YAG laser. The pump wavelength of the laser diode was selected according to the excitation peak which is also one of the absorption peaks of a 3.5 at. % Tm:YAG crystal and was locked by volume Bragg gratings. In the Tm laser experiment, a maximum output power of 11.12 W, corresponding to a slope efficiency of 51.6%, was obtained. In the Ho laser experiment, a maximum output power of 8.03 W at 2122 nm with a slope efficiency of 38% was obtained for 24.96 W of diode pump power incident on the Tm:YAG rod.

Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II.

Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement.

Concordance between cardio-protective effect on isoproterenol-induced acute myocardial ischemia and phenolic content of different extracts of Curcuma aromatica.

CONTEXT: A classic traditional Chinese medicine Curcuma aromatica Salisb. (Zingiberaceae) has been reported to have favourable effects on the cardiovascular system. OBJECTIVE: To research the cardio-protective effect of different C. aromatica hydroalcoholic extracts on isoproterenol (ISO)-induced acute myocardial ischemia (AMI) in rats. The total phenols in different extracts were detected simultaneously. MATERIALS AND METHODS: The rhizomes of C. aromatica dry powder were refluxed with 30%, 50%, 70% and 90% hydroalcoholic solvents to obtain different extracts. Rats were pretreated with four C. aromatica extracts (150 mg/kg/day, i.g.) for 9 days and then given ISO (30 mg/kg/day, s.c.) for 2 consecutive days, respectively. Heart rate, ST-segment, T-wave and serum levels of CK-MB, LDH, TAC, SOD, NO and MDA were measured. Total phenols of the different extracts were determined using the Folin-Ciocalteu assay. RESULTS: Pretreatment with C. aromatica significantly decreased the elevated levels of serum specific cardiac injury biomarkers (CK-MB and LDH), the serum level of MDA, the ST-segment and T-wave. In addition, C. aromatica increased the heart rate, as well as the levels of TAC, SOD and NO, compared to ISO-induced controls. The total phenols in the 70% extract were higher than in the other extracts reaching 5.629 ± 0.037 mg/g, crude drug. DISCUSSION AND CONCLUSION: Curcuma aromatica hydroalcoholic extracts exhibited remarkable cardio-protective effects against AMI in rats. The 70% extracts showed the strongest bioactivity. These results indicate that ethanol concentration in preparation of extracts of C. aromatica plays an important role in the protective effect against AMI.

[Apoptosis of hepatocellular induced by active ingredients of Zanthoxyli Radix by Raman spectroscopy].

The apoptosis of mono-hepatocellular induced by the active ingredients of the Zanthoxyli Radix was investigated using laser Raman spectroscopy. Hepatoma cells (BEL-7404) were treated with 10 mg•L⁻¹ nitidine chloride and 3 g•L⁻¹ the extracts of Zanthoxyli Radix, respectively, then were divided into two parts, one for fluorescence staining, the other for determination of Raman spectroscopy. The acquired spectra were then processed by background elimination, smoothing, and normalization. Fluorescence staining results showed that the nucleuses from untreated group were uniformly stained, while those from the group treated for 48 hours were densely stained and broken. The spectra results revealed that the intensity of peaks associated with nucleic acid and protein decreased after the cells were incubated with the extracts of Zanthoxyli Radix for 12, 24, 36 and 48 hours. The intensity of peaks at 785,1 002,1 175,1 660 cm⁻¹ was decreased with the time of the cells were incubated by the extracts of Zanthoxyli Radix. The results indicated that the extracts of Zanthoxyli Radix could induce the apoptosis of hepatoma cells and reduce the amount of nucleic acid and protein in the cells. There is a certain relevance between the drug treatment time and the efficacy. The above results suggest that Raman spectra can provide abundant information about the changes in biological macromolecules within the cells after incubated by the extracts of Zanthoxyli Radix and serve as an effective method for the real time measurement of apoptosis.

New C13 lipids from the marine-derived fungus Trichoderma harzianum.

Chemical examination of the fermentation broth of a sponge-associated fungus Trichoderma harzinum HMS-15-3 led to the isolation of four pairs of new C13 lipid enantiomers namely harzianumols A-H (1a-4b). Their structures were elucidated on the basis of extensive spectroscopic (IR, MS, 1D, and 2D NMR) data analysis, including the modified Mosher's method for the assignment of their absolute configurations. The new compounds were evaluated for antihyperlipidemic effects in HepG2 cells.

Optimization of the extraction conditions and quantification by RP-LC analysis of three alkaloids in Zanthoxylum nitidum roots.

CONTEXT: A classic traditional Chinese medicine, Zanthoxylum nitidum (Roxb.) DC. widely used in China, exhibits anticancer, anti-inflammatory and antianalgesic activities. Alkaloids are one of the main bioactive components. It is urgent to develop a simple and reliable method to determine the main alkaloids in Z. nitidum roots. OBJECTIVE: To determine the three alkaloids in Z. nitidum roots, a reversed-phase liquid chromatographic (RP-LC) method combined with an optimum extraction condition was established. MATERIALS AND METHODS: A method involving four-factor-three-level orthogonal array design including the extracting solvent and the RP-LC condition was assayed. Twenty batches were collected from different areas of the Guangxi Province at different harvesting times. The determined alkaloids were nitidine chloride (NC, 1), ethoxychelerythrine (2) and liriodenine (3). The stable mobile phase was a C18 packing, and the mobile phase was acetonitril-aqueous phosphoric acid-triethylamine-buffer solution. RESULTS: The optimum extraction and detection conditions have been determined in the process of quantification of Z. nitidum root alkaloids. The three alkaloids were detected simultaneously in the 20 batches of samples. The results clearly showed that alkaloid concentrations differed significantly among Z. nitidum collected from various collection areas. DISCUSSION AND CONCLUSION: We have established an optimum extraction and detection conditions in the process of quantification the three alkaloids in Z. nitidum roots. From this research, the most influenced factor on Z. nitidum roots was the collecting location, and the next factor was the harvesting time. The collecting location and the harvesting time should be considered as the high-quality medicinal herbs factors.

Major depressive disorder and aneurysm: A genetic study of association and causality.

BACKGROUND: Association between depression and aneurysm has been implicated but the specific role of depression in aneurysm remains unclear. We aimed to comprehensively characterize the relation of major depressive disorder (MDD) with aneurysm by subtype. METHODS: Harnessing summary statistics from genome-wide association studies (Ncase/Ncontrol = 7603/317,899 for aortic aneurysm; 7321/317,899 for thoracic aortic aneurysm; 3201/317,899 for abdominal aortic aneurysm; 1788/317,899 for cerebral aneurysm; and 246,363/561,190 for major depressive disorder), we estimated the genetic correlation between MDD and each of four aneurysm subtypes via LD Score Regression and tested the causality via various estimators under the bi-directional Mendelian randomization (MR) framework. RESULTS: Positive genetic correlation of statistical significance, ranging between 0.15 (with thoracic aortic aneurysm, P = 0.005) and 0.25 (with abdominal aortic aneurysm, P = 0.001), was consistently observed for MDD with each aneurysm subtype. In the MR analysis of MDD as an exposure, genetic liability to MDD causally increased the risk of cerebral (odds ratio: 1.71; 95 % confidence interval: 1.26-2.34) but not aortic aneurysm. Replication analysis of an independent dataset (Ncase/Ncontrol = 6242/59,418) corroborated this signal. In contrast, causal effect was not evident for any neurysm subtype on susceptibility to MDD. LIMITATIONS: Aneurysm could have been underdiagnosed if asymptomatic, leading to an underestimated causal impact on MDD. Non-linearity of the causal effect was not tested due to the lack of individual-level data. CONCLUSIONS: Depression and aneurysm may share common pathomechanisms. Screening depressed population and improving the clinical management for depression may benefit the primary prevention of cerebral aneurysm.

Simultaneous determination of flavonoids, isochlorogenic acids and triterpenoids in Ilex hainanensis Using high performance liquid chromatography coupled with diode array and evaporative light scattering detection.

A high performance liquid chromatography coupled with diode array and evaporative light scattering detection (HPLC-DAD-ELSD) method for simultaneous determination of eight major bioactive compounds including two flavonoids (rutin and eriodictyol-7-O-ß-D-glucopyranoside), two isochlorogenic acids (isochlorogenic acid A and isochlorogenic acid C) and four triterpenoids (ilexhainanoside D, ilexsaponin A1, ilexgenin A and ursolic acid) in Ilex hainanensis has been developed for the first time. The 283 nm wavelength was chosen for determination of two flavonoids and two isochlorogenic acids. ELSD was applied to determine four triterpenoids. The analysis was performed on an Agilent Zorbax SB-C18 column (250 × 4.6 mm i.d., 5 µm) with gradient elution of 0.2% formic acid in water and acetonitrile. The method was validated for linearity, limit of detection, limit of quantification, precision, repeatability and accuracy. The proposed method has been successfully applied for simultaneous quantification of the analytes in four samples of Ilex hainanensis, which is helpful for quality control of this plant.

[GC-MS analysis of essential oil from Curcuma aromatica rhizome of different growth periods].

OBJECTIVE: To analyze the essential oil from the rhizome of Curcuma aromatica of different growth periods, and to provide the scientific reference for reasonable cultivation and quality control of this plant. METHODS: The essential oil was extracted by hydrodistillation and analyzed with GC-MS. The relative contents were determined with area normalization method. RESULTS: The main volatile constituents in the rhizome of Curcuma aromatica were basically the same. Among these volatile constituents, curdione was the major. The relative content of curdione was 16.35% in the rhizome of wild plant in Hengxian county, and 15.81% in the rhizome of one-year-old plant in Mingyang farm, Nanning city. The relative content of eucalyptol in the 2-year-old cultivated rhizome in Hengxian county was 15.40%, and 14.59% in the rhizome of wild plant in Hengxian county. beta-Elemene, beta-caryophyllene,eugenol and germacrone were also the main constituents in the rhizome essential oil. CONCLUSION: Volatile constituents in the rhizome of Curcuma aromatica are similar to each other,but the relative content of each component is different. This result can provide the scientific foundation for the cultivation of Curcuma aromatica.

Depletion of lncRNA MEG3 Ameliorates Imatinib-Induced Injury of Cardiomyocytes via Regulating miR-129-5p/HMGB1 Axis.

Imatinib is a classical targeted drug to treat chronic myeloid leukemia (CML). However, it shows cardiotoxicity, which limits its clinical application. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) shows proapoptotic properties in human cells. This study is performed to investigate whether targeting MEG3 can attenuate imatinib-mediated cardiotoxicity to cardiomyocytes. In this work, H9c2 cells were divided into four groups: control group, hypoxia group, hypoxia + imatinib, and hypoxia + imatinib + MEG3 knockdown group. MEG3 and microRNA-129-5p (miR-129-5p) expression levels were detected by the quantitative real-time PCR (qRT-PCR). The viability and apoptosis of H9c2 cells were then evaluated by cell counting kit-8 (CCK-8), flow cytometry, and TUNEL assays. The targeting relationships between MEG3 and miR-129-5p, between miR-129-5p and high-mobility group box 1 (HMBG1), were validated by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. The protein expression level of HMGB1 was detected by western blot. It was revealed that, Imatinib-inhibited cell viability and aggravated the apoptosis of H9c2 cells cultured in hypoxic condition, and MEG3 knockdown significantly counteracted this effect. MiR-129-5p was a downstream target of MEG3 and it directly targeted HMGB1, and knockdown of MEG3 inhibited HMGB1 expression in H9c2 cells. In conclusion, targeting MEG3 ameliorates imatinib-induced injury of cardiomyocytes via regulating miR-129-5p/HMGB1 axis.

PCSK9, a novel immune and ferroptosis related gene in abdominal aortic aneurysm neck.

The gene expression profile of abdominal aortic aneurysm (AAA) neck is not fully understood. The etiology of AAA is considered to be related to atherosclerosis and the inflammatory response, involving congenital, genetic, metabolic, and other factors. The level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to those of cholesterol, oxidized low-density lipoprotein, and triglycerides. PCSK9 inhibitors have significant effects on lowering LDL-cholesterol, reversing atherosclerotic plaques, and reducing the risk of cardiovascular events and have been approved by several lipid-lowering guidelines. This work was aimed to investigate the potential role of PCSK9 in the neck of AAA. We extracted the expression dataset (GSE47472) containing 14 AAA patients and 8 donors and single-cell RNAseq (scRNA-seq) data (GSE164678) of CaCl2-induced (AAA) samples from the Gene Expression Omnibus dataset. Through bioinformatics methods, we found that PCSK9 was up-regulated in the proximal neck of human AAA. In AAA, PCSK9 was mainly expressed in fibroblasts. Additionally, immune check-point PDCD1LG2 was also expressed higher in AAA neck than donor, while CTLA4, PDCD1, and SIGLEC15 were down-regulated in AAA neck. The expression of PCSK was correlated with PDCD1LG2, LAG3, and CTLA4 in AAA neck. Additionally, some ferroptosis-related genes were also down-regulated in AAA neck. PCSK9 was also correlated with ferroptosis-related genes in AAA neck. In conclusion, PCSK9 was highly expressed in AAA neck, and may exert its role through interacting with immune check-points and ferroptosis-related genes.