Compound Shenma Jingfu granule alleviates cerebral ischemia via HIF-1α-mediated promotion of angiogenesis.

BACKGROUND: Shenma Jingfu Granule, a traditional Chinese medicine formula, has been used clinically for the treatment of cerebral circulation insufficiency. However, the mechanism involved in alleviating cerebral ischemia has not yet been fully elucidated. METHODS: An integrated approach involving network pharmacology and transcriptomics was utilized to clarify the potential mechanisms of SMJF Granule. Molecular docking and surface plasmon resonance (SPR) were employed to identify potential targets and ingredients of SMJF Granule. The anti-CI effect of SMJF Granule was determined on the middle cerebral artery occlusion (MCAO) model by using hematoxylin-eosin (H&E) and Nissl's staining, as well as triphenyl tetrazolium chloride (TTC) staining, and the potential targets involved in the mechanisms were validated by RT-qPCR and western blotting. RESULTS: Integrated analysis revealed the mechanism of SMJF Granule intervening in CI injury might be related to the HIF-1 signaling pathway and angiogenesis. Molecular docking and SPR assays demonstrated robust binding interactions between key compounds like salvianolic acid A and naringenin with the core target HIF-1α protein. The experiment confirmed that SMJF Granule lowered neurological scores, diminished infarct volume, and alleviated histopathological changes in vivo. The possible mechanism of SMJF Granule was due to regulating HIF-1 pathway, which contributed to up-regulating expression of VEGF and vWF in the penumbral region, showing a significant promotion of angiogenesis. CONCLUSION: SMJF Granule promoted angiogenesis through HIF-1α pathway, thereby alleviating cerebral ischemia injury. In addition, our findings provide some evidence that SMJF Granule is a candidate compound for further investigation in treating CI in the clinical.

Pulse buildup dynamics in a self-starting Mamyshev oscillator.

The Mamyshev oscillator (MO) can generate high-performance pulses. However, due to their non-resonant cavities, they usually are not self-starting, and there is almost no effort to reveal the pulse buildup dynamics of the MO. This paper investigates the dynamic of single pulse (SP) and multi-pulse formation in a self-starting MO. It indicated that both SP self-starting and multi-pulse self-starting can be obtained by adjusting the oscillator parameters. More importantly, increasing pump power could only result in bound state pulses (BSPs) if SP self-starting was formed. With the increase of the pump power, the pulse number in BSPs would increase. However, multiple pulses could not be formed only by increasing the pump power, and the BSPs obtained here underwent SP generated from noise, amplified, and then bounded, which is different from conventional passive mode-locked fiber lasers (CPMLFLs). On the other hand, if multiple pulses were self-initiated, BSPs, pulse bunch, and harmonic mode-locked pulses (HMLPs) could be obtained by adjusting the polarization state and pump power in the cavity. Furthermore, once any of the above states are formed, if the oscillator polarization state and filter interval are unchanged, only increasing the pump power from zero, the original state can still be obtained, which is consistent with the characteristics of the CPMLFLs. These findings will provide new insights into the pulse dynamics of self-starting MO, which will be significant for studying ultrafast laser technology and nonlinear optics.

Multi-field-driven optomechanical entanglement.

Cavity optomechanical (COM) entanglement, playing an essential role in building quantum networks and enhancing quantum sensors, is usually weak and easily destroyed by noises. As feasible and effective ways to overcome this obstacle, optical or mechanical parametric modulations have been used to improve the quality of quantum squeezing or entanglement in various COM systems. However, the possibility of combining these powerful means to enhance COM entanglement has yet to be explored. Here, we fill this gap by studying a COM system containing an intra-cavity optical parametric amplifier (OPA), driven optically and mechanically. By tuning the relative strength and the frequency mismatch of optical and mechanical driving fields, we find that constructive interference can emerge and significantly improve the strength of COM entanglement and its robustness to thermal noises. This work sheds what we believe to be a new light on preparing and protecting quantum states with multi-field driven COM systems for diverse applications.

Unveiling Optimal Synthesis and Structural Insights of Starch Ferulate via the Mechanoenzymatic Method.

In this study, starch ferulate was synthesized employing a mechanoenzymatic method, specifically based on the twin screw extrusion technique and lipase catalysis. The research then primarily centered on optimizing process parameters and conducting structural analysis. Optimal conditions were determined to be 8.2% ferulic acid addition, 66 °C extrusion temperature, and 3.2% lipase (N435) addition. The enzyme-catalyzed time was 30 s. The degree of substitution for starch ferulate was quantified at 0.005581 under these specific conditions. The presence of C=O bonds in the synthesized starch ferulate proved that the synthesis process was efficient. Additionally, the crystal structure underwent reconstruction. Observations through Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) demonstrated that the mechanoenzymatic method led to an augmentation in the specific surface area of starch molecules, thereby facilitating the exposure of active sites. This breakthrough underscores the vast potential of mechanoenzymatic techniques to revolutionize the rapid and sustainable synthesis of starch ferulate, marking a pioneering stride in ester synthesis. The insights garnered from this study transcend theory, offering a visionary roadmap for the development and real-world deployment of advanced modified starch esters.

Stability and Digestive Properties of a Dual-Protein Emulsion System Based on Soy Protein Isolate and Whey Protein Isolate.

The stability and digestive properties of a dual-protein emulsion consisting of soy protein isolate (SPI) and whey protein isolate (WPI) have been systematically studied. The results showed that the particle size and viscosity of the dual-protein emulsion system decreased continuously with the increase in WPI, and this might be related to the large amount of electric charge on the surface of the emulsion droplets. Dual-protein emulsions with ratios of 3:7 and 5:5 showed the highest emulsion activity, while emulsion stability increased with the increase in WPI. The thicker adsorption layer formed at the interface might have contributed to this phenomenon. After in-vitro-simulated digestion, the emulsion droplet particle size increased substantially due to the weakened electrostatic repulsion on the droplet surface, especially for the intestinal digestion phase. Meanwhile, WPI accelerated the release of free fatty acids in the digestion process, which played a positive role in the nutritional value of the dual-protein emulsion. In accelerated oxidation experiments, WPI also improved the antioxidant properties of the dual-protein emulsion system. This study will provide a new insight and necessary theoretical basis for the preparation of dual-protein emulsions.

Docking Design of the Different Microcapsules in Aqueous Solution and Its Quantitative On-Off Study.

To avoid risk, spacecraft docking technologies can transport batches of different astronauts or cargoes to a space station. Before now, spacecraft-docking multicarrier/multidrug delivery systems have not been reported on. Herein, inspired by spacecraft docking technology, a novel system including two different docking units, one made of polyamide (PAAM) and on of polyacrylic acid (PAAC), grafted respectively onto polyethersulfone (PES) microcapsules, is designed, based on intermolecular hydrogen bonds in aqueous solution. VB12 and vancomycin hydrochloride were chosen as the release drugs. The release results show that the docking system is perfect, and has a good responsiveness to temperature when the grafting ratio of PES-g-PAAM and PES-g-PAAC is close to 1:1. Below 25 °C, this system exhibited an "off" effect because the polymer chains on the microcapsule's surface produced intermolecular hydrogen bonds. Above 25 °C, when the hydrogen bonds were broken, the microcapsules separated from each other, and the system exhibited an "on" state. The results provide valuable guidance for improving the feasibility of multicarrier/multidrug delivery systems.

Effect of Corn Starch Granules on Stabilizing the Foam Structure of Ultrasonically Modified Whey Isolate Protein.

In this study, the mechanism of ultrasound combined with corn starch granules (CSG) treatment improved the foam properties of whey protein isolates (WPI) and was systematically investigated. The results showed that ultrasound combined with corn starch granules treatment increased foam capacity and stability by 15.38% and 41.40%, respectively. Compared with the control group, corn starch granules enhanced the surface charge (52.38%) and system turbidity (51.43%), which certainly provided the necessary conditions for the improvement of foam stabilization stability. In addition, corn starch granules as microgel particles increased the mechanical properties of the interfacial protein film, thus delaying the instability of foam. This research would provide new insights into the design of new protein-based foam foods in the future food industry.

Controllable Fabrication and Oil-Water Separation Properties of Polyethylene Terephthaloyl-Ethylenediamine-IPN-poly(N-Isopropylacrylamide) Microcapsules.

In this paper, we report a microcapsule embedded PNIPAN in P (TPC-EDA) shell and it can be regarded as an interpenetrating polymer network (IPN) structure, which can accelerate the penetration of oily substances at a certain temperature, and the microcapsules are highly monodisperse and dimensionally reproducible. The proposed microcapsules were fabricated in a three-step process. The first step was the optimization of the conditions for preparing oil in water emulsions by microfluidic device. In the second step, monodisperse polyethylene terephthaloyl-ethylenediamine (P(TPC-EDA)) microcapsules were prepared by interfacial polymerization. In the third step, the final microcapsules with poly(N-isopropylacrylamide) (PNIPAM)-based interpenetrating polymer network (IPN) structure in P(TPC-EDA) shells were finished by free radical polymerization. We conducted careful data analysis on the size of the emulsion prepared by microfluidic technology and used a very intuitive functional relationship to show the production characteristics of microfluidics, which is rarely seen in other literatures. The results show that when the IPN-structured system swelled for 6 h, the adsorption capacity of kerosene was the largest, which was promising for water-oil separation or extraction and separation of hydrophobic drugs. Because we used microfluidic technology, the products obtained have good monodispersity and are expected to be produced in large quantities in industry.

Network Pharmacology-Based Analysis on the Curative Effect of Kunxian Capsules against Rheumatoid Arthritis.

Kunxian capsules (KCs), a Chinese patent medicine, have been clinically proven to be effective in the treatment of rheumatoid arthritis (RA). However, the chemical profile of KC remains to be characterized, and the mechanism underlying the protective effect against RA is yet to be elucidated. Here, a network pharmacology-based approach was adopted, integrated with the chemical profiling of KC by UHPLC-Q-TOF/MS. As a result, a total of 67 compounds have been identified from KC extract, among which 43 were authenticated by comparison to the mass spectrum of standard chemicals. ADME behaviors of the chemical constituents of KC were predicted, resulting in 35 putative active ingredients. Through target prediction of both active ingredients of KC and RA and PPI analysis, core targets were screened out, followed by biological process and related pathway enrichment. Then, a TCM-herb-ingredient-target-pathway network was constructed and a multicomponent, multitarget, and multipathway synergistic mechanism was proposed, providing an information basis for further investigation. The active pharmaceutical ingredients included mainly terpenoids (such as triptolide and celastrol), sesquiterpene pyridines (such as wilforgine and wilforine), and flavonoids (such as icariin, epimedin A, B, and C, and 2″-O-rhamnosylicariside II).

Nonlinear THz radiation investigated by quantum simulations.

Terahertz (THz) waves can be generated by the nonlinear interaction between ultrashort laser pulses and air. The semiclassical photocurrent model is widely used. It is simple, but neglects the quantum effects. Some theoretical works are based on solving the time-dependent Schrödinger equation. However, it meets the difficulty of prohibitively large boxes in long-time evolution. Here we adopted the wave-function splitting algorithm to fully contain the information of photoelectrons. The contributions of the excited states and interference effects in electron wavepackets to THz radiation are studied numerically. We also theoretically investigated the THz generation from nitrogen molecules in a biased electric field. It is found that the THz yield enhancement as a function of the static field strength in experiments can be reproduced well by our method. In addition, the restriction of wavelength and phase difference in the two-color laser fields is less strict in the presence of the static field.

Transient receptor potential vanilloid 1 promotes EGFR ubiquitination and modulates EGFR/MAPK signalling in pancreatic cancer cells.

Transient receptor potential vanilloid-1 (TRPV1) was first identified in sensory neurons, where it was suggested as a therapeutic target for pain relief. Here, we show that TRPV1 is expressed in the pancreatic cancer cell line, PANC-1; that epidermal growth factor receptor (EGFR) expression is downregulated by overexpression or agonist-induced activation of TRPV1; and conversely, that EGFR expression is increased after silencing TRPV1. Furthermore, TRPV1 overexpression inhibits cell proliferation and significantly reduces the mRNA levels of two oncogenes, KRAS and AKT2. More importantly, TRPV1 downregulates EGFR levels by inducing EGFR ubiquitination and degradation, which modulate EGFR/MAPK signalling in pancreatic cancer cells. These results illustrate the regulation and mechanism of TRPV1 on EGFR in pancreatic cancer cells and may provide new ideas for the design of novel antitumor drugs targeting EGFR. SIGNIFICANCE OF THE STUDY: We investigated the effect and mechanism of TRPV1 on EGFR-mediated proliferation and transformation of pancreatic cancer cells, with the aim of providing new ideas and experimental evidence for the application of strategies that promote EGFR degradation to treat pancreatic cancer.

Functional analysis of amino acids at stalk/head interface of human parainfluenza virus type 3 hemagglutinin-neuraminidase protein in the membrane fusion process.

Human parainfluenza virus type 3 (hPIV3) is an important respiratory pathogen that causes the majority of viral pneumonia of infants and young children. hPIV3 can infect host cells through the synergistic action of hemagglutinin-neuraminidase (HN) protein and the homotypic fusion (F) protein on the viral surface. HN protein plays a variety of roles during the virus invasion process, such as promoting viral particles to bind to receptors, cleaving sialic acid, and activating the F protein. Crystal structure research shows that HN tetramer adopted a "heads-down" conformation, at least two heads dimmer on flank of the four-helix bundle stalk, which forms a symmetrical interaction interface. The stalk region determines interactions and activation of F protein in specificity, and the heads in down position statically shield these residues. In order to make further research on the function of these amino acids at the hPIV3 HN stalk/head interface, fifteen mutations (8 sites from stalk and 7 sites from head) were engineered into this interface by site-directed mutagenesis in this study. Alanine substitution in this region of hPIV3 HN had various effects on cell fusion promotion, receptor binding, and neuraminidase activity. Besides, L151A also affected surface protein expression efficiency. Moreover, I112A, D120A, and R122A mutations of the stalk region that were masked by global head in down position had influence on the interaction between F and HN proteins.