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.

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.

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.

Effects of Different Anesthetics on Perioperative Organ Protection and Postoperative Cognitive Function in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass.

In this paper, we have carried out an experimental study to investigate the effects of different anesthetics on perioperative organ protection and postoperative cognitive function in patients undergoing cardiac valve replacement with cardiopulmonary bypass. To realize this idea, a total of 90 patients with single valve replacement under general anesthesia and hypothermic cardiopulmonary bypass from January 2020 to October 2021 were enrolled. These patients were assigned into three groups, with 30 cases in each group by the digital table method. Group A was anesthetized with sufentanil combined with dexmedetomidine. Group B was anesthetized with sufentanil combined with etomidate. Group C was anesthetized with sufentanil combined with propofol. Perioperative organ protection and postoperative cognitive function of the three groups were compared. At T 0 time point, there was no significant difference in blood WBC, blood N, and CRP among groups A, B, and C (P > 0.05); At T 4 and T 5 time points, the indexes of blood WBC, blood N, and CRP in groups A, B, and C were higher compared to the T 0 time point. At T 4 and T 5 time points, the indexes of blood WBC, blood N, and CRP in group A were significantly lower compared to group B and group C. Before treatment, there was no significant difference in ALT and AST among groups A, B, and C (P > 0.05). After treatment, the indexes of ALT and AST in group A were significantly lower compared to group B and group C at T 4 and T 5 time points (P < 0.05). Before treatment, there was no significant difference in urea and creatinine among groups A, B, and C (P > 0.05). After treatment, the urea and creatinine indexes of group A were significantly lower compared to group B and group C at T 4 and T 5 time points (P < 0.05). Before treatment, there was no significant difference in CK-MB and CTnl among groups A, B, and C (P > 0.05); After treatment, the indexes of CK-MB and CTnl in group A were significantly lower compared to group B and group C at T 4 and T 5 time points (P < 0.05). Before treatment, there was no significant difference in MOCA scores among groups A, B, and C (P > 0.05). After treatment, the MOCA scores of group A were significantly higher compared to group B and group C at T 5 and T 6 time points (P < 0.05). Sufentanil combined with dexmedetomidine for heart valve replacement under cardiopulmonary bypass can reduce the dosage of anesthetics during the operation and have a certain perioperative protective effect on important organs such as the heart, lung, liver, and kidney, which may be related to reducing intraoperative hemodynamic fluctuations and inhibiting inflammatory stress response.

Hybrid laser precision engineering of transparent hard materials: challenges, solutions and applications.

Laser has been demonstrated to be a mature and versatile tool that presents great flexibility and applicability for the precision engineering of a wide range of materials over other established micromachining techniques. Past decades have witnessed its rapid development and extensive applications ranging from scientific researches to industrial manufacturing. Transparent hard materials remain several major technical challenges for conventional laser processing techniques due to their high hardness, great brittleness, and low optical absorption. A variety of hybrid laser processing technologies, such as laser-induced plasma-assisted ablation, laser-induced backside wet etching, and etching assisted laser micromachining, have been developed to overcome these barriers by introducing additional medium assistance or combining different process steps. This article reviews the basic principles and characteristics of these hybrid technologies. How these technologies are used to precisely process transparent hard materials and their recent advancements are introduced. These hybrid technologies show remarkable benefits in terms of efficiency, accuracy, and quality for the fabrication of microstructures and functional devices on the surface of or inside the transparent hard substrates, thus enabling widespread applications in the fields of microelectronics, bio-medicine, photonics, and microfluidics. A summary and outlook of the hybrid laser technologies are also highlighted.

One-step fabrication of metal nanoparticles on polymer film by femtosecond LIPAA method for SERS detection.

Flexible transparent SERS substrates have aroused great interest as a rapid and in situ detection method for trace chemicals. We demonstrate a one-step and environmentally friendly method to fabricate flexible fluorinated ethylene propylene (FEP) surface plasmon resonance film by femtosecond laser induced plasma assisted ablation (LIPAA) for in situ SERS detection. By tuning laser fluence, the distributions and sizes of silver and gold nanoparticles generated by femtosecond LIPAA are studied. Using a Rhodamine 6G (R6G) Raman probe with a 532 nm laser excitation, the proposed Ag NPs/FEP and Au NPs/FEP substrates show enhancement factors of 5.6 × 107 and 2.4 × 106, respectively, as compared to a bare FEP film without the metallic nanoparticles. The Raman signals show good uniformity and a linear relationship with the concentration of R6G solution. In addition, the detection limit of thiram on an apple for in situ measurement is 0.1 mg/Kg, corresponding to 7.96 ng/cm2. The proposed SERS detection approach has great potential to pave a new way in food safety applications, such as detecting pesticides in harvested fruits.

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.

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.

Corrigendum to "JAK2/STAT3 Pathway Was Associated with the Protective Effects of IL-22 on Aortic Dissection with Acute Lung Injury".

[This corrects the article DOI: 10.1155/2017/1917804.].

miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was closely involved in doxorubicin- (DOX-) induced cardiotoxicity. MicroRNA-200a (miR-200a) could target Keap1 mRNA and promote degradation of Keap1 mRNA, resulting in Nrf2 activation. However, the role of miR-200a in DOX-related cardiotoxicity remained unclear. Our study is aimed at investigating the effect of miR-200a on DOX-induced cardiotoxicity in mice. For cardiotropic expression, male mice received an injection of an adeno-associated virus 9 (AAV9) system carrying miR-200a or miR-scramble. Four weeks later, mice received a single intraperitoneal injection of DOX at 15 mg/kg. In our study, we found that miR-200a mRNA was the only microRNA that was significantly decreased in DOX-treated mice and H9c2 cells. miR-200a supplementation blocked whole-body wasting and heart atrophy caused by acute DOX injection, decreased the levels of cardiac troponin I and the N-terminal probrain natriuretic peptide, and improved cardiac and adult cardiomyocyte contractile function. Moreover, miR-200a reduced oxidative stress and cardiac apoptosis without affecting matrix metalloproteinase and inflammatory factors in mice with acute DOX injection. miR-200a also attenuated DOX-induced oxidative injury and cell loss in vitro. As expected, we found that miR-200a activated Nrf2 and Nrf2 deficiency abolished the protection provided by miR-200a supplementation in mice. miR-200a also provided cardiac benefits in a chronic model of DOX-induced cardiotoxicity. In conclusion, miR-200a protected against DOX-induced cardiotoxicity via activation of the Nrf2 signaling pathway. Our data suggest that miR-200a may represent a new cardioprotective strategy against DOX-induced cardiotoxicity.

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.

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.

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.

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.

Bindarit reduces the incidence of acute aortic dissection complicated lung injury via modulating NF-κB pathway.

The pathogenesis of acute aortic dissection (AAD) complicated acute lung injury (ALI) is not currently well defined. At present, no effective animal model has been established for AAD complicated ALI, which hinders research and development of an appropriate treatment regimen for the concurrent conditions. The aim of the present study was to evaluate the therapeutic effects of bindarit (Bnd), an indazolic derivative, on the production of monocyte chemoattractant protein (MCP)-1 in angiotensin II (AngII)-induced complicated ALI in rats. An AAD complicated ALI rat model was established using aminopropionitrile (BAPN) and AngII. The pathological features of AAD complicated ALI were assessed via biochemical and histopathological evaluations. AngII-stimulated human pulmonary microvascular endothelial cells (hPMVECs) were used to assess the effects of Bnd on MCP-1 expression. Western blot analysis was performed to analyze the expression of proteins that may be associated with the process. AAD complicated ALI was established following BAPN and AngII interference, and a massive accumulation of macrophages was observed in the lung tissues of the study rats. Bnd was able to significantly attenuate the incidence of AAD complicated ALI (P<0.05), and significantly inhibit the accumulation of macrophages (P<0.05). The overexpression of MCP-1 induced by AngII in hPMVECs was significantly inhibited by Bnd (P<0.05), which may be associated with downregulation of the classical nuclear factor-κB pathway. Bnd was able to attenuate the incidence of AAD complicated ALI, and inhibit the accumulation of macrophages in vivo. These findings provide a basis for future applications of Bnd as part of a therapeutic treatment schedule for aortic dissection complicated lung injury.

JAK2/STAT3 Pathway Was Associated with the Protective Effects of IL-22 On Aortic Dissection with Acute Lung Injury.

Patients with aortic dissection (AD) may present acute lung injury (ALI) that may affect the prognosis. In this study, we aim to investigate the roles and mechanism of IL-22 in the pathogenesis of AD complicated with ALI. Six hundred and twenty-one AD patients were included, and the incidence of ALI and pulmonary CT findings were analyzed. Mouse ALI model was established through AngII, and then IL-22 injection and AG490 were given. The pathological changes, infiltration of inflammatory cells, and expression of STAT3 were determined. For the in vitro experiment, cultivated pulmonary microvascular endothelial cells (PMVECs) were treated by angiotensin II (AngII), followed by treating with IL-22 and/or AG490. The expression and migration of STAT3 was determined. Flow cytometry was carried out to evaluate the apoptosis. IL-22 contributed to the expression of STAT3 in lung tissues and attenuation of ALI. IL-22 obviously inhibited the apoptosis of PMVECs mediated by AngII and downregulated the expression and intranuclear transmission of STAT3. Such phenomenon was completely inhibited upon administration of AG490, an inhibitor of JAK2. Our data showed IL-22 contributed to the inhibition of PMVEC apoptosis mediated by AngII through activating the JAK2/STAT3 signaling pathway, which may attenuate the ALI induced by AngII.

Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis.

The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated. Here we show that DAG could inhibit the migration and invasion of U251 cell line by inhibiting matrix metalloproteinase-2 (MMP2) expression. Furthermore, DAG could also inhibit tumor angiogenesis in vitro as well as in the zebrafish model. Mechanistic studies reveal that DAG inhibited both VEGFR2 and FGFR1 pathways. Our results suggest that DAG may be a potential multitarget agent that can inhibit tumor migration, invasion, and angiogenesis, and the anti-angiogenic effects may be involved in dual-suppression VEGF/VEGFR2 and FGF2/FGFR1 signal pathways.