Fraxin Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation and TLR4/NF-κB and MAPK Signaling Pathways.

Objective: UC is a chronic gastrointestinal disorder of uncertain etiology. However, effective therapeutic drug options for UC are relatively limited. Fraxin represents a principal active constituent within the traditional Chinese medicinal herb known as Cortex Fraxini or Qinpi. Nevertheless, the impact of Fraxin on UC remains uncharted. This study aims to explore the potential of Fraxin, a key component of Cortex Fraxini, in inhibiting DSS-induced intestinal inflammation in mice and to unravel the underlying mechanisms. Methods: In vitro experiment,the RAW264. 7 cells were induced by LPS as the model.In vivo experiment,the mice were induced by DSS as the animal model for a ten day experiment.The ELISA, western blots, measurement of oxidative stress markers and other relevant methods were used to discuss the effect of Fraxin on LPS-induced RAW264.7 cells and the inhibitory effect of Fraxin on intestinal inflammation induced by DSS in mice and underlying mechanisms. Results: Our findings indicated that Fraxin significantly reduced symptoms of UC, such as body weight loss, colonic length shortening, and histological damage. At the molecular level, it inhibited ROS generation, reduced pro-inflammatory cytokines, and regulated key pathways including TLR4/NF-κB and MAPK.The findings indicated that Fraxin diminished the expression of p-NF-κB and p-IκB, downregulated iNOS and COX-2 expression, and lessened p38, JNK and ERK phosphorylation. Conclusion: Taken together, Fraxin ameliorates UC by regulating oxidative stress, inflammation, and TLR4/NF-κB and MAPK pathways, and Fraxin may be a new treatment for UC. Our findings suggest that Fraxin could offer a novel therapeutic approach for UC, targeting oxidative stress and key inflammatory pathways.

Enhanced Plastic Stability: Achieving High Performance in a Al6xxx Alloy Fabricated by Additive Manufacturing.

Additive manufacturing (AM) facilitates the creation of materials with unique microstructural features and distinctive phenomena as compared to conventional manufacturing methods. Among the various well-fabricated AM alloys, aluminum alloys garner substantial attention due to their extensive applications in the automotive and aerospace industries. In this work, an Al6xxx alloy is successfully fabricated with outstanding performance. A nucleation agent is introduced to diminish the susceptibility to cracking during the AM process, thereby inducing a heterogeneous microstructure in this alloy. However, the introduction of ultrafine grains induces plastic instability, evidenced by the presence of Lüders band. This work investigates the evolution of the Lüders band and the strategy to reduce their undesirable effect. The heterogeneity destabilizes the band propagation and thus deteriorates the ductility. Through a T6 heat treatment, the local Lüders strain decreases from 10.0% to 6.2%, leading to a substantial enhancement in plastic stability. With the increase in grain growth and the enlargement of coarse grain regions, the mismatch between the local and macroscopic Lüders strain disappears. Importantly, the strength and the thermal conductivity are concurrently increased. The findings demonstrate the significance of ensuring plastic stability to achieve improved strength-ductility trade-off in AM alloys with heterogeneous microstructures.

Injectable hydrogels as promising in situ therapeutic platform for cartilage tissue engineering.

Injectable hydrogels are gaining prominence as a biocompatible, minimally invasive, and adaptable platform for cartilage tissue engineering. Commencing with their synthesis, this review accentuates the tailored matrix formulations and cross-linking techniques essential for fostering three-dimensional cell culture and melding with complex tissue structures. Subsequently, it spotlights the hydrogels' enhanced properties, highlighting their augmented functionalities and broadened scope in cartilage tissue repair applications. Furthermore, future perspectives are advocated, urging continuous innovation and exploration to surmount existing challenges and harness the full clinical potential of hydrogels in regenerative medicine. Such advancements are crucial for validating the long-term efficacy and safety of hydrogels, positioning them as a promising direction in regenerative medicine to address cartilage-related ailments.

Reaction of cyclamate with hypochlorous acid in vitro and formation of chlorcyclohexylamine and cyclohexylamine.

In this work, we investigated the reaction of cyclamate with hypochlorous acid (HOCl) in simulated gastric juice. The reaction products were detected by high-performance liquid chromatography diode array detection (HPLC-DAD) and ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). We also explored the changes in product concentration as a function of reaction time, cyclamate and HOCl concentrations. Cyclamate reacted with hypochlorous acid instantly in the simulated gastric fluid. N, N-dichlorcyclohexylamine and cyclohexylamine were both detected when the HOCl concentration was at millimole. Cyclohexylamine can only be found when HOCl concentration was at micromole. N, N-dichlorcyclohexylamine and cyclohexylamine concentrations both increased when cyclamate concentration increased under the millimole level of HOCl. As an important reactive oxygen species, hypochlorous acid (HClO) is produced in various physiological processes. The abnormal rise of the HClO level is associated with many inflammatory diseases. Chronic gastritis associated with Helicobacter pylori is a multistep, progressive, life-long inflammation. So, chronic gastritis infected with H. pylori may cause cyclamate metabolizing into cyclohexylamine in vivo.

Additive manufacturing of alloys with programmable microstructure and properties.

In metallurgy, mechanical deformation is essential to engineer the microstructure of metals and to tailor their mechanical properties. However, this practice is inapplicable to near-net-shape metal parts produced by additive manufacturing (AM), since it would irremediably compromise their carefully designed geometries. In this work, we show how to circumvent this limitation by controlling the dislocation density and thermal stability of a steel alloy produced by laser powder bed fusion (LPBF) technology. We show that by manipulating the alloy's solidification structure, we can 'program' recrystallization upon heat treatment without using mechanical deformation. When employed site-specifically, our strategy enables designing and creating complex microstructure architectures that combine recrystallized and non-recrystallized regions with different microstructural features and properties. We show how this heterogeneity may be conducive to materials with superior performance compared to those with monolithic microstructure. Our work inspires the design of high-performance metal parts with artificially engineered microstructures by AM.

Recommendations and considerations for speeding the collapse of the non-ventilated lung during single-lung ventilation in thoracoscopic surgery: a literature review.

Video-assisted thoracoscopic thoracic surgery has the advantages of less physical damage, less postoperative pain, and a rapid recovery. Therefore, it is widely used in the clinic. The quality of nonventilated lung collapse is the key point of thoracoscopic surgery. Poor lung collapse on the operative side damages surgical exposure and prolongs the process of surgery. Therefore, it is important to achieve good lung collapse as soon as possible after opening the pleura. Over the past two decades, there have been reports of advances in research on the physiological mechanism of lung collapse and several kinds of techniques for speeding up lung collapse. This review will inform the advances of each technique, make recommendations for reasonable implementation and discuss their controversies and considerations.

Changes of mercury and methylmercury content and mercury methylation in Suaeda salsa soil under different salinity.

In this paper, we studied the changes of Hg and MeHg contents in Liaohe estuarine Suaeda salsa soils under anaerobic conditions by simulated indoor incubation at constant temperature and whether the changes of salinity (CK, 0.5%, 1.0%, 1.5%, 2.0%) affected SRB and dominated the formation of MeHg. The lowest Hg content is found in the subsurface Suaeda salsa soils at 2.0% salinity. The MeHg content in the soil also showed a general trend of increasing and then decreasing with increasing flooding salinity, and the MeHg content was higher at 0.5-1.0% flooding salinity. SRB was present in the soil under all salinity conditions and reached the maximum value at 15 days of incubation. The SRB content was higher under CK, S1 and S2 conditions, and the soil MeHg content showed a significant positive correlation with the number of SRB bacteria, indicating that the formation of MeHg was related to SRB which is of great significance to the study of estuarine wetlands.

Influence Mechanism of Energy Efficiency Label on Consumers' Purchasing Behavior of Energy-Saving Household Appliances.

Mandatory energy efficiency label is an effective way to change consumers' consumption habits and guide them to buy energy-saving appliances. However, few studies concerned about the impact of energy efficiency label on consumers' purchasing behavior. Based on the theory of planned behavior (TPB), social cognitive theory and signaling theory, this paper constructs a theoretical model of the effect of the energy label on consumers' purchasing behavior of energy-saving household appliances. The survey data of 396 household appliance consumers in Mianyang City, China, are collected by the interception method, and the theoretical model is tested by structural equation modeling (SEM). Empirical results of this study indicate that consumers' cognition and perceived value of energy efficiency label significantly affect label trust. Perceived value has a significant impact on consumers' purchasing behavior of energy-saving appliances, while label cognition and label trust indirectly influence consumers' purchasing behavior through the intermediary variable of purchase intention. External environmental factors such as publicity and education as well as subjective norms affect consumers' actual purchasing behavior through the intermediary effect of purchase intention. This study provides important insights into the policy intervention measures to promote consumers' purchasing behavior of energy-saving appliances.

Evaluation and analysis on suitability of human settlement environment in Qingdao.

Human settlement environment is space places closely related to human production and life, and also surface spaces inseparable from human activities. As a coastal city in the east of China, Qingdao has a relatively high level of urbanization. However, it also along with many urban problems at the same time, among which the problem of human settlement environment has attracted more and more general attention from people. According to the characteristics of human settlement environment in Qingdao, the research constructs an index system with 10 index factors from natural factors and humanity factors, and proposes a comprehensive evaluation model. Evaluate and grade suitability of human settlement environment in Qingdao, explore the spatial aggregation and differentiation of the quality of human settlement environment, and reveal the internal connection of spatial evolution. The results indicate that the overall livability of Qingdao is relatively good, showing a multi-center and radial driving development. The distribution of livability is uneven, showing a decreasing spatial distribution law from the coast to the inland, and the quality of human settlement environment in Jiaozhou Bay and the coastal areas is relatively high. Qingdao is mainly based on natural livability, supplemented by humanity livability, compared with natural suitability, the spatio-temporal evolution characteristics of humanity livability have experienced three stages: rising-contradictory rising-harmonious rising. The quality of human settlement environment has obvious spatial correlation and is positively correlated with the degree of agglomeration, and the agglomeration of blocks with a higher quality of human settlement environment is higher than that of blocks with a lower level. The rule of human settlement environment changing over time is that areas with high quality of human settlement environment begin to shift from the city center to the north and the south, transforming into multi-point development, and overall environmental suitability has been improved. According to the results of the comprehensive evaluation, combined with its local development status and policies, the research puts forward developmental suggestions for the construction of human settlement environment in Qingdao, and provides decision-making basis for relevant departments to solve the problem of deterioration of human settlement environment.

Determination of semicarbazide residue in human urine samples using liquid chromatography-tandem mass spectrometry.

An ultra-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry (UPLC-ESI-MS/MS) with pre-column derivatisation was developed and validated for the determination of semicarbazide in human urine. Urine samples were derivatised with 2-nitrobenzaldehyde and subsequently extracted with acetonitrile. Extracts were concentrated and then analysed by UPLC-MS/MS. The time per run was 7 min. Good results were observed for the linearity of matrix-matched calibration curves (R2 > 0.99) in the concentration range of 1-100 µg/L. The absolute recovery ranged from 98.7% to 108.6%, with the relative standard deviations (RSDs) of 2.2%-3.6%. The limit of detection and quantification for the semicarbazide was 0.5 µg/L and 1 µg/L, respectively. The method showed good extraction efficiency, high sensitivity, and good reproducibility. It was suitable for the detection of semicarbazide in human urine. Residues of semicarbazide were between 1.0 and 41.5 µg/L in children's 24-h urine. This work is the first report on the quantitative analysis of SEM in 24-h human urine samples.

Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy.

Oxidative stress is a critical factor in the pathology of age-related macular degeneration (AMD). Apigenin (AP) is a flavonoid with an outstanding antioxidant activity. We had previously observed that AP protected APRE-19 cells against oxidative injury in vitro. However, AP has poor water and fat solubility, which determines its low oral bioavailability. In this study, we prepared the solid dispersion of apigenin (AP-SD). The solubility and dissolution of AP-SD was significantly better than that of the original drug, so the oral bioavailability in rats was better than that of the original drug. Then, the effects of AP-SD on the retina of a model mouse with dry AMD were assessed by fundus autofluorescence (FAF), optical coherence tomography (OCT), and electron microscopy; the results revealed that AP-SD alleviated retinopathy. Further research found that AP-SD promoted the nuclear translocation of Nrf2 and increased expression levels of the Nrf2 and target genes HO-1 and NQO-1. AP-SD enhanced the activities of SOD and GSH-Px and decreased the levels of ROS and MDA. Furthermore, AP-SD upregulated the expressions of p62 and LC3II in an Nrf2-dependent manner. However, these effects of AP-SD were observed only in the retina of Nrf2 WT mice, not in Nrf2 KO mice. In addition, the therapeutic effect of AP-SD was dose dependent, and AP did not work. In conclusion, AP-SD significantly enhanced the bioavailability of the original drug and reduced retinal oxidative injury in the model mouse of dry AMD in vivo. The results of the underlying mechanism showed that AP-SD upregulated the expression of antioxidant enzymes through the Nrf2 pathway and upregulated autophagy, thus inhibiting retinal oxidative damage. AP-SD may be a potential compound for the treatment of dry AMD.

Optical needles with arbitrary homogeneous three-dimensional polarization.

We propose a new method to generate optical needles by focusing vector beams comprised of radially polarized component and azimuthally polarized vortex components. The radial part can generate longitudinal polarization, while the azimuthal parts can generate left- and right-handed polarization. Hence, an arbitrary 3D polarization can be obtained. To our knowledge, it may be the first time that arbitrarily polarized optical needles whose transverse sizes are under 0.5λ have been achieved. The polarized homogeneity of the needles is beyond 0.97.

Evidence of the involvement of spinal αB-crystallin in the maintenance of bone cancer pain in rats.

BACKGROUND: αB-crystallin (CRYAB) is a small heat shock protein that is able to inhibit neuroinflammatory responses under various pathological conditions. Some studies have proven that neuroinflammatory mechanisms play important roles in bone cancer pain (BCP). However, whether CRYAB participates in the maintenance of BCP has not yet been examined. METHODS: Walker256 tumour cells were inoculated into the tibia to induce a rat model of BCP. Von Frey hairs were used to measure mechanical allodynia. Immunohistochemistry and western blotting were used to examine the expression level of CRYAB in the spinal dorsal horn. RESULTS: The gradual development of mechanical allodynia was induced by the injection of Walker256 cells into the tibia. The downregulation of spinal CRYAB expression was found in BCP rats. The intrathecal administration of CRYAB (from days 9 to 15 post-inoculation) dose-dependently alleviated mechanical allodynia in BCP rats. Additionally, there were concomitant increases in spinal CRYAB expression and decreases in TNF-α expression. CONCLUSIONS: Spinal CRYAB may participate in the maintenance of BCP in rats. The findings will help to identify new drugs for the management of BCP.

A Solid Dispersion of Quercetin Shows Enhanced Nrf2 Activation and Protective Effects against Oxidative Injury in a Mouse Model of Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 µg/mL in water and 2.3×104 µg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 µg/mL and AUC of 12.015 µg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch's membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.

Symmetry of electric spin angular momentum density in the tight focusing of linearly polarized vortex beams.

Symmetry of electric spin angular momentum (SAM) density in the tight focusing of linearly polarized vortex beams is investigated in this paper. By calculating analytic expressions of SAM density, reflection symmetry and rotation symmetry of SAM density are found in the focal region. The vortex phase can break some symmetry, leading to non-zero longitudinal SAM. When the vortex phase vanishes, more symmetry will occur. It is proved that longitudinal SAM is zero when the topological charge is zero, and that transverse SAM is always zero. This paper is expected to advance our understanding of distribution of SAM density and optical spin-orbit coupling.

Synergistic Effect of Retinoic Acid Polymeric Micelles and Prodrug for the Pharmacodynamic Evaluation of Tumor Suppression.

All-trans retinoic acid (ATRA) is an effective agent that induces differentiation, inhibits cell proliferation, and acts as an anticancer agent. ATRA was successfully conjugated with Pluronic F127 via esterification to enhance its anticancer effects. Pluronic-ATRA showed high cytotoxicity and inhibitory concentrations (IC50) 50% lower than those of ATRA in various breast cancer cell lines (4T1:31.16-8.57 µg/mL; EMT6: 50.48-7.08 µg/mL; MDA-MB-231:37.58-8.99 µg/mL; BT474:25.27-9.09 µg/mL). In combination with chemotherapy, Pluronic-ATRA synergistically enhanced the cytotoxic effects of cisplatin (CDDP). Pluronic-ATRA combined with CDDP effectively suppressed breast tumor growth in vivo. The results of this study demonstrate the potential of Pluronic-ATRA as an anticancer agent that can be used in combination therapy against solid tumors.

Au nanoparticles with enzyme-mimicking activity-ornamented ZIF-8 for highly efficient photodynamic therapy.

The tumor hypoxic microenvironment (THME) has a profound impact on tumor progression, and modulation of the THME has become an essential strategy to promote photodynamic therapy (PDT). Here, an oxygen self-supplied nanodelivery system that is based on nanometal-organic frameworks (nMOFs) with embedded AuNPs (Au@ZIF-8) on the nMOF surface as a catalase (CAT)-like nanozyme and encapsulating Ce6 inside as a photosensitizer was found to mitigate tumor hypoxia and reinforce PDT. As soon as Au@ZIF-8 reaches the tumor site, the AuNP nanozyme can catalyze excessive H2O2 to produce O2 to alleviate tumor hypoxia, promoting the production of 1O2 with strong toxicity toward tumor cells under irradiation. Our study demonstrates that nMOFs embellished with a nanozyme have great potential for overcoming the THME for cancer therapeutics, which provides a facile strategy for accurate bioimaging and cancer therapy in vivo.

Theoretical generation of arbitrarily homogeneously 3D spin-orientated optical needles and chains.

The generation of homogeneously 3D spin-orientated optical needles and optical chains is investigated by focusing the annular collimated beam composed of radially polarized component and azimuthally polarized vortex components with aplanatic focusing systems. Using the Richards-Wolf vector diffraction theory, analytic expressions of focal electric fields and target spin-orientation are given. The results show that the spin-orientation is tunable by changing two parameters of the incident beam while keeping the mean size of the focal spot under 0.5λ. Spin-orientation homogeneity purity is introduced to evaluate spin-orientation homogeneity quantitatively and the results present that spin-orientation homogeneity purity is always beyond 0.996 when spin-orientation varies.

Fangchinoline supplementation attenuates inflammatory markers in experimental rheumatoid arthritis-induced rats.

The present study evaluated the anti-inflammatory activity of fangchinoline in rheumatoid arthritis-induced rats. Rats were grouped into sham (group I), rheumatoid arthritis (group II, control), fangchinoline (2 µM, group III), and fangchinoline (4 µM, group IV) groups. The serum levels of lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMPs), prostaglandin-E2 (PGE2), nitric oxide (NO), zinc, ceruloplasmin, uric acid, and copper were determined. Chondrocyte cell proliferation, reactive oxygen species (ROS), and cellular levels of TNF-α and IL-6 were assessed. Lipid peroxidation, GSH, SOD, catalase, and Gpx levels recovered to near normal levels by fangchinoline treatment. Fangchinoline treatment significantly reduced the TNF-α level by 17.8% and 40.8% in groups III and IV respectively, whereas IL-6 was significantly decreased by 23.2% and 45%, respectively. Fangchinoline treatment significantly decreased the MMP-3 level by 23.1% and 65.1% in groups III and IV respectively, whereas PGE2 was significantly decreased by 31.8% and 63.8%, respectively. Fangchinoline treatment decreased NO, uric acid, ceruloplasmin, and copper levels, whereas the zinc content was increased. Chondrocyte proliferation was significantly reduced to 73.3%, 51.3%, and 42.4% at 2 µM, 4 µM, and 6 µM fangchinoline treatment respectively. Intracellular ROS, TNF-α, and IL-6 levels were significantly reduced in the chondrocytes. Protein expression of TNF-α was significantly decreased by 0.27-, 0.53-, and 0.67-fold at 2 µM, 4 µM, and 6 µM fangchinoline treatment respectively. In conclusion, fangchinoline is effective as an anti-inflammatory agent in rheumatoid arthritis-induced rats.

Ultra-long magnetization needle induced by focusing azimuthally polarized beams with a spherical mirror.

Based on extended Richards-Wolf theory for axisymmetric surfaces and the inverse Faraday effect, we propose the generation of a purely longitudinal magnetization needle by focusing Gaussian annular azimuthally polarized beams with a spherical mirror. The needle obtained has a longitudinal length varying hundreds to thousands of wavelengths while keeping the lateral size under 0.4λ, and the corresponding aspect ratio can easily reach more than 2000. It may be the first time that a magnetization needle whose aspect ratio is over 500 has been achieved. The approximate analytical expressions of the magnetization needle are given, and the longitudinal length is tunable by changing the value of the angular thickness and the position of the annular beams.