FURIN suppresses the progression of atherosclerosis by promoting macrophage autophagy.

FURIN, a member of the mammalian proprotein convertases (PCs) family, can promote the proteolytic maturation of proproteins. It has been shown that FURIN plays an important role in the progression of atherosclerosis (AS). Current evidence indicates that autophagy widely participates in atherogenesis. This study aimed to explore whether FURIN could affect atherogenesis via autophagy. The effect of FURIN on autophagy was studied using aortic tissues from aortic dissection patients who had BENTALL surgery, as well as macrophages and ApoE-/- mice. In atherosclerotic plaques of aortic tissues from patients, FURIN expression and autophagy were elevated. In macrophages, FURIN-shRNA and FURIN-overexpression lentivirus were used to intervene in FURIN expression. The results showed that FURIN overexpression accelerated LC3 formation in macrophages during the autophagosome formation phase. Furthermore, FURIN-induced autophagy resulted in lower lipid droplet concentrations in macrophages. The western blot revealed that FURIN regulated autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway. In vivo, FURIN overexpression resulted in increased macrophage LC3 formation in ApoE-/- mice atherosclerotic plaques, confirming that FURIN could inhibit the progression of AS by promoting macrophage autophagy. The present study demonstrated that FURIN suppressed the progression of AS by promoting macrophage autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway, which attenuated atherosclerotic lesion formation. Based on this data, current findings add to our understanding of the complexity of AS.

Probing the Spin-Orbit Time Delay of Multiphoton Ionization of Kr by Bicircular Fields.

We study multiphoton ionization of Kr atoms by circular 400-nm laser fields and probe its photoelectron circular dichroism with the weak corotating and counterrotating circular fields at 800 nm. The unusual momentum- and energy-resolved photoelectron circular dichroisms from the ^{2}P_{1/2} ionic state are observed as compared with those from ^{2}P_{3/2} ionic state. We identify an anomalous ionization enhancement at sidebands related to the ^{2}P_{1/2} ionic state on photoelectron momentum distribution when switching the relative helicity of the two fields from corotating to counterrotating. By performing the two-color intensity-continuously-varying experiments and the pump-probe experiment, we find a specific mixed-photon populated resonant transition channel in counterrotating fields that contributes to the ionization enhancement. We then probe the time delay between the two spin-orbit coupled ionic states (^{2}P_{1/2} and ^{2}P_{3/2}) using bicircular fields and reveal that the resonant transition has an insignificant effect on the relative spin-orbit time delay.

Universal Description of the Attoclock with Two-Color Corotating Circular Fields.

We experimentally measure the laser-intensity-dependent photoelectron momentum distributions (PMDs) of Ar atoms with two-color (ω+2ω) corotating circularly polarized fields. The interference patterns on PMDs reveal complex structures with respect to the laser intensity ratio. The main above-threshold ionization peaks and sidebands on PMD distribute oppositely when the fundamental field is much weaker than the second-harmonic field, and the PMD reveals a characteristic single-lobe distribution when the two colors have comparable intensities. Using strong-field approximation, we analytically explain how the interference pattern on PMD evolves with respect to the relative laser intensity. By analyzing the interference pattern, we reveal the phase difference and the temporal evolution of the emitting electron wave packets. We show that, when monitoring the intensity ratio, the double-pointer attoclock geometry with corotating circular fields can be universally mimicked as the spatially rotating temporal double-slit experiments with the variable slit width, which can be used to probe and control strong-field ionization.

Unifying Tunneling Pictures of Strong-Field Ionization with an Improved Attoclock.

We demonstrate a novel attoclock, in which we add a perturbative linearly polarized light field at 400 nm to calibrate the attoclock constructed by an intense circularly polarized field at 800 nm. This approach can be directly implemented to analyze the recent hot and controversial topics involving strong-field tunneling ionization. The generally accepted picture is that tunneling ionization is instantaneous and that the tunneling probability synchronizes with the laser electric field. Alternatively, recently it was described in the Wigner picture that tunneling ionization would occur with a certain of time delay. We unify the two seemingly opposite viewpoints within one theoretical framework, i.e., the strong-field approximation (SFA). We illustrate that both the instantaneous tunneling picture and the Wigner time delay picture that are derived from the SFA can interpret the measurement well. Our results show that the finite tunneling delay will accompany nonzero exit longitudinal momenta. This is not the case for the instantaneous tunneling picture, where the most probable exit longitudinal momentum would be zero.

Attoclock Photoelectron Interferometry with Two-Color Corotating Circular Fields to Probe the Phase and the Amplitude of Emitting Wave Packets.

We employ attosecond angular streaking with photoelectron interferometric metrology to reveal electron sub-Coulomb-barrier dynamics. We use a weak perturbative corotating circularly polarized field (800 nm) to probe the strong-field ionization by an intense circularly polarized field (400 nm). In this double-pointer attoclock photoelectron interferometry, we introduce a spatially rotating temporal Young's two-slit interferometer, in which the oppositely modulated wave packets originating from consecutive laser cycles are dynamically prepared and interfered. Developing a Fourier-transform algorithm on energy-resolved photoelectron interferograms, we can directly extract the amplitude and the phase of emitting electron wave packets from strong-field ionization.

Energy- and Momentum-Resolved Photoelectron Spin Polarization in Multiphoton Ionization of Xe by Circularly Polarized Fields.

We perform a joint experimental and theoretical study on momentum- and energy-resolved photoelectron spin polarization in multiphoton ionization of Xe atoms by circularly polarized fields. We experimentally measure the photoelectron momentum distributions of Xe atoms in circularly polarized near-infrared (800 nm) and ultraviolet (400 nm) light, respectively. We analyze the momentum- and energy-resolved photoelectron spin polarization by comparing the experimental photoelectron momentum distributions with the simulations, although we cannot derive the spin polarization solely from the experiment. We show that the use of circularly polarized ultraviolet light at 400 nm can create better than 90% spin polarization with focal volume effect considered, which enables the separation of the spin states by momentum gating. This paves the way to produce high-degree spin-polarized electron sources from strong-field multiphoton ionization.

Revealing the Sub-Barrier Phase using a Spatiotemporal Interferometer with Orthogonal Two-Color Laser Fields of Comparable Intensity.

We measure photoelectron momentum distributions of Ar atoms in orthogonally polarized two-color laser fields with comparable intensities. The synthesized laser field is used to manipulate the oscillating tunneling barrier and the subsequent motion of electrons onto two spatial dimensions. The subcycle structures associated with the temporal double-slit interference are spatially separated and enhanced. We use such a spatiotemporal interferometer to reveal sub-barrier phase of strong-field tunneling ionization. This study shows that the tunneling process transfers the initial phase onto momentum distribution. Our work has the implication that the sub-barrier phase plays an indispensable role in photoelectron interference processes.

Spatiotemporal imaging and shaping of electron wave functions using novel attoclock interferometry.

Electrons detached from atoms by photoionization carry valuable information about light-atom interactions. Characterizing and shaping the electron wave function on its natural timescale is of paramount importance for understanding and controlling ultrafast electron dynamics in atoms, molecules and condensed matter. Here we propose a novel attoclock interferometry to shape and image the electron wave function in atomic photoionization. Using a combination of a strong circularly polarized second harmonic and a weak linearly polarized fundamental field, we spatiotemporally modulate the atomic potential barrier and shape the electron wave functions, which are mapped into a temporal interferometry. By analyzing the two-color phase-resolved and angle-resolved photoelectron interference, we are able to reconstruct the spatiotemporal evolution of the shaping on the amplitude and phase of electron wave function in momentum space within the optical cycle, from which we identify the quantum nature of strong-field ionization and reveal the effect of the spatiotemporal properties of atomic potential on the departing electron. This study provides a new approach for spatiotemporal shaping and imaging of electron wave function in intense light-matter interactions and holds great potential for resolving ultrafast electronic dynamics in molecules, solids, and liquids.

Malat1 promotes macrophage-associated inflammation by increasing PPAR-γ methylation through binding to EZH2 in acute myocardial infarction.

The inflammatory microenvironment of macrophage plays an important role in acute myocardial infarction (AMI), but the regulatory mechanism is unknown. Here, we aimed to investigate the role of Malat1 on inflammation microenvironment of macrophage in AMI. Our study found that Malat1 expression was increased in AMI, which mainly expressed in macrophages. Malat1 inhibition improved collagen deposition and inflammation in infarcted heart. In vitro, Malat1 inhibition evidently reduced macrophage-associated inflammation. The results from ribonucleic acid pull-down (RNA pull-down) and RNA Immunoprecipitation (RIP) assay demonstrated that Malat1 directly binds to EZH2. Malat1 and EZH2 complex could increase histone H3K27me3 expression and further inhibit the production of PPAR-γ. In vivo, inhibition of Malat1 also leaded to the down-regulation of both EZH2 and H3K27me3, as well as up-regulation of PPAR-γ in infarcted heart. Therefore, these findings demonstrate a novel mechanism of Malat1 on inflammation microenvironment of macrophage in AMI, which provide a new target for its treatment.

Probing the orbital angular momentum of intense vortex pulses with strong-field ionization.

With the rapid development of femtosecond lasers, the generation and application of optical vortices have been extended to the regime of intense-light-matter interaction. The characterization of the orbital angular momentum (OAM) of intense vortex pulses is very critical. Here, we propose and demonstrate a novel photoelectron-based scheme that can in situ distinguish the OAM of the focused intense femtosecond optical vortices without the modification of light helical phase. We employ two-color co-rotating intense circular fields in the strong-field photoionization experiment, in which one color light field is a plane wave serving as the probing pulses and the other one is the vortex pulses whose OAM needs to be characterized. We show that by controlling the spatial profile of the probing pulses, the OAM of the vortex pulses can be clearly identified by measuring the corresponding photoelectron momentum distributions or angle-resolved yields. This work provides a novel in situ detection scenario for the light pulse vorticity and has implications for the studies of ultrafast and intense complex light fields with optical OAM.

Biogenetic nanocarriers with enhanced pH stability formed by zein and selectively depolymerized mushroom hyperbranched ß-glucans.

Hyperbranched polysaccharide from Pleurotus tuber-regium (PTR-HBPS) is a ß-glucan with high degree of branching (DB, 0.69) and a molecular weight (Mw) of 31.2 × 105 g/mol with mixed ß-1, 4/ß-1, 4, 6/ß-1, 6 glucosidic linkages. PTR-HBPS was depolymerized by cellulase and ß-glucosidase under optimized conditions to form PC (PTR-HBPS depolymerized by cellulase) and PG (PTR-HBPS depolymerized by ß-glucosidase) fractions with a minimum Mw of 2.74 × 105 and 3.98 × 105 g/mol, respectively. PC fractions had no significant changes for its primary structure in terms of glycosidic linkages, DB, and triple helical structure, while the DB of PG fractions was reduced to 0.63 with the loss of triple helical structure. Nanoparticles fabricated by PC fractions with zein showed better stability under different pH conditions. Enzymatic depolymerized low Mw ß-glucan derived from PTR-HBPS with similar structural characteristics as the native one has potential as nanocarriers for food bioactive substances.

Downregulation of microRNA-512-3p enhances the viability and suppresses the apoptosis of vascular endothelial cells, alleviates autophagy and endoplasmic reticulum stress as well as represses atherosclerotic lesions in atherosclerosis by adjusting spliced/unspliced ratio of X-box binding protein 1 (XBP-1S/XBP-1U).

AS is an important pathological basis of cardiovascular disease. miRNAs are involved in almost all steps of AS, including the injury and dysfunction of endothelial cells and vascular smooth muscle cells. This work elucidated the biological functions of miR-512-3p in AS and probed into the underlying molecular mechanism. In the present work, ox-LDL-treated HUVECs served as the in vitro model of AS and ApoE-/- mice were nourished with a high-fat diet to establish an in vivo model of AS. Proliferation, apoptosis, and migration of HUVECs were evaluated by CCK-8, TUNEL staining, Western blot, and transwell assays. Immunofluorescence examined LC3 expression and levels of autophagy-related and ER stress-related proteins were determined by Western blot assay. In addition, starBase predicted the complementary binding sites of XBP-1 to miR-512-3p and luciferase reporter assay confirmed the interaction between miR-512-3p and XBP-1. Moreover, H&E staining was employed to evaluate atherosclerotic lesions in AS model mice. Results revealed that ox-LDL treatment decreased the proliferative and migrative activities and promoted the apoptosis of HUVECs as well as induced autophagy and ER stress, which were abrogated by miR-512-3p silencing. Importantly, ox-LDL treatment elevated miR-512-3p expression and XBP-1 was a direct target of miR-512-3p. Mechanistically, knockdown of miR-512-3p enhanced the viability, suppressed the apoptosis, and promoted the migration of ox-LDL-treated HUVECs, alleviated atherosclerotic lesions in AS model mice as well as repressed autophagy and ER stress by targeting XBP-1 to manipulate the ratio of XBP-1S/XBP-1 U.

Effects of SGLT2 inhibitors on cardiovascular, renal, and major safety outcomes in heart failure: A meta-analysis of randomized controlled trials.

AIMS: Sodium-glucose co-transporter 2 inhibitor (SGLT2i), initially introduced for the treatment of diabetes mellitus (DM), demonstrates cardiovascular and renal benefits in patients with heart failure (HF). We aimed to conduct a meta-analysis of its effects on cardiovascular, renal, and major safety outcomes in HF. METHODS AND RESULTS: PubMed, Embase, Cochrane Library, and Web of Science were searched using the terms of "SGLT2i and HF" or "SGLT2i *". Seven randomized, placebo-controlled trials comprising 14,113 HF patients (mean age, 66.0 years; female, 27.6%; DM, 58.9%) were included. SGLT2i treatment was associated with lower incidences (compared with placebo) of the composite outcomes of cardiovascular death or hospitalization for HF (HHF) (ratio risk [RR] 0.773; 95% confidence interval [CI], 0.719-0.831; p < 0.001; I2 = 8.1%), cardiovascular death (RR 0.872; 95% CI, 0.788-0.964; p = 0.008; I2 = 0.0%), HHF (RR 0.722; 95% CI, 0.657-0.793; p < 0.001; I2 = 15.4%) and serious decrease in renal function (RR 0.673; 95% CI, 0.549-0.825; p < 0.001; I2 = 17.7%). SGLT2i treatment was associated with a lower incidence of serious adverse events (SAEs) (RR 0.867; 95% CI, 0.808-0.930; p < 0.001; I2 = 60.1%), but a higher incidence of volume depletion (RR 1.177; 95% CI, 1.040-1.333; p = 0.010; I2 = 0.0%). Analysis on patients without DM showed consistent results, except for cardiovascular death. CONCLUSION: SGLT2i treatment contributed to better cardiovascular and renal outcomes in patients with HF, regardless of the presence or absence of DM. SGLT2i also resulted in a lower incidence of SAEs, although a higher incidence of volume depletion was observed.

Encapsulation and release behavior of curcumin based on nanoemulsions-filled alginate hydrogel beads.

To provide the bilateral advantages of emulsions and hydrogels, a facile approach was used to fabricate nanoemulsions filled hydrogel beads through combining the method of self-emulsification and sodium alginate (SA) ionic gelation. The encapsulation and release behavior of curcumin (Cur) were further investigated. The results indicated that Cur packaged nanoemulsions were with the size of 24.26 ±â€¯0.22 nm. The nanoemulsions filled SA hydrogel beads were spherical shell with the diameter of 0.46 ±â€¯0.02 mm. For Cur, the EE and LC of emulsion filled SA hydrogel beads were 99.15 ±â€¯0.85% and 7.25 ±â€¯3.16 mg/g respectively. The release behavior could be regulated by external pH condition. The release behavior at pH 9.0 displayed a higher release rate than that at pH 7.0. Cur released behavior well followed the Hixcon-Crowell model which indicated that Cur was released in a diffusion-controlled model. Comparatively investigation of microstructure using field emission scanning electron microscope (FE-SEM) further investigates the corrosion behavior of SA gel beads during Cur release. The worth-while endeavor provided a practical combined technique of emulsions and ionic gelation to fabricate hybrid hydrogel beads that have potential in delivery system for hydrophobic composition.