Search

Compromised endothelial (EC) barrier function is a hallmark of inflammatory diseases. Mammalian target of rapamycin (mTOR) inhibitors, widely applied as clinical therapies, cause pneumonitis throug...

Vanadium pentoxide (V2O5) is one of the fundamental materials applied in the productions of batteries, vanadium-aluminium alloys, biomedicine, catalysis, etc. High purity V2O5 can be prepared from an intermediate product, namely ammonium polyvanadate (APV), using roasting after a drying process. In this paper, microwave heating was used as an alternative drying option for APV, which has advantages including selective heating, high heating efficiency, energy-saving, and environmental protection. The authors investigated the microwave heating characteristics of APV and discussed the effects of microwave power, the mass of APV, and initial water content on the efficiency of microwave drying. The dynamic analysis of the APV microwave drying process was also carried out. Four groups of thin-layer drying dynamic models, namely Modified-Page model, Verma model, Sickmplified-Fick's-diffusion model, and Two-term-exponential model, were fitted with the experimental data. Through comparison, the Modified Page model could better describe the microwave drying process of APV.

Background: Curcumin (CUR), a natural isolated compound from turmeric, helps in fighting many diseases, but the broad application of curcumin has been limited ascribed to low bioavailability. Objective: The aim of this study is to pursue the enhancement of curcumin bioavailability through coadministration of vitamin C. Methods: Such purpose was achieved through the analysis of curcumin pharmacokinetics by highperformance liquid chromatography coupled with electrospray ionization - tandem mass spectrometry (HPLC - ESI - MS/MS). The plasma was separated on a C18 reverse-phase column using acetonitrile and ammonium formate solution (pH 6.5; 2.0 mM) at 0.8 mL/min. MS/MS detection was carried out in negative mode using mass patterns of m/z 367.0 > 216.7 for curcumin and m/z 265.2 > 223.9 for internal standard (honokiol). Results: Successful application of the proposed method in the pharmacokinetic study presented clear changes in key pharmacokinetic parameters, including the growth of AUC (0-t) up to 2.4 times, a 2.2- fold increase of Cmax, 2.2-fold loss of CL, and 1.5-fold diminishment of t1/2. Conclusion: An HPLC-ESI-MS/MS method for the determination of curcumin in rat plasma and validated the improvement of bioavailability of curcumin through co-administration of vitamin C was determined. These changes were reasoned to the inhibition of lipid peroxidation induced by the use of vitamin C. Such a simple strategy is possible to become an alternative for enhancing curcumin efficiency in practice.

Single-atom catalysts have attracted numerous attention due to the high utilization of metallic atoms, abundant active sites, and highly catalytic activities. Herein, a single-atom ruthenium biomimetic enzyme (Ru-Ala-C3N4) is prepared by dispersing Ru atoms on a carbon nitride support for the simultaneous electrochemical detection of dopamine (DA) and uric acid (UA), which are coexisting important biological molecules involving in many physiological and pathological aspects. The morphology and elemental states of the single-atom Ru catalyst are studied by transmission electron microscopy, energy dispersive X-ray elemental mapping, high-angle annular dark field-scanning transmission electron microscopy, and high-resolution X-ray photoelectron spectroscopy. Results show that Ru atoms atomically disperse throughout the C3N4 support by Ru-N chemical bonds. The electrochemical characterizations indicate that the Ru-Ala-C3N4 biosensor can simultaneously detect the oxidation of DA and UA with a separation of peak potential of 180 mV with high sensitivity and excellent selectivity. The calibration curves for DA and UA range from 0.06 to 490 and 0.5 to 2135 μM with detection limits of 20 and 170 nM, respectively. Moreover, the biosensor was applied to detect DA and UA in real biological serum samples using the standard addition method with satisfactory results.

A few mode fiber temperature sensor filled with PDMS based on vernier effect is proposed. It uses single mode fiber (SMF), few mode fiber (FMF), and polydimethylsiloxane (PDMS) to form the SMF-air microcavity-FMF-PDMS-FMF structure. It is to slot the glass capillary tube, place the two FMFs in the slot at a suitable distance, and fill the slot with PDMS multiple times and seal it. The PDMS is used as a sensing microcavity. We insert the SMF from the other end of the glass capillary tube, adjust the distance, fix the SMF and seal the connection. Two end faces of the SMF and the first FMF form an air reference microcavity. Since the refractive index of each medium is different, multiple reflective surfaces are formed to reflect. Because the second FMF is infinitely long, whose right end is beveled, it is considered that the sensor has four reflected beams. When the temperature changes, the length and refractive index of the PDMS microcavity will change, which will cause a change in the interference spectrum of the sensor. And because the vernier effect is formed by the superposition of the two microcavities, the temperature sensitivity can be amplified and the temperature can be measured with high sensitivity. The experimental results show that in the range of 40–56°C, the transmission spectrum of the sensor appears red shift with the increase of temperature, and the temperature sensitivity can reach 3.89nm/°C. The sensor is simple to manufacture, has high sensitivity, and has good application prospects.

The mechanism and origins of ligand-controlled stereoselectivity of dirhodium (Rh2L4, L = OAc, S-tertPTTL)-catalysed intramolecular aliphatic C(sp3)–H aminations have been explored using DFT calculations. Both catalytic cycles occur via the formation of Rh2 = nitrene radical species, intramolecular H-abstraction and radical rebound. The origins of diastereoselectivity are revealed via distortion/interaction and noncovalent interaction analysis.

Because of the shortage of natural rutile, synthetic rutile is a widely used substitute welding materials for natural rutile owing to its excellent mechanical and thermal properties. In this work, rutile TiO2 was prepared from oxidation roasting titanium slag, which can be used as special welding materials. The phase microstructure characteristics of the raw materials and the roasted samples were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) spectroscopic analysis. Results indicated that the contents of sulfur (S) and carbon (C) in titanium slag decreased during oxidation roasting process, and the decreases of sulfur and carbon contents were mainly ascribed to the formation of corresponding oxides. XRD and FT-IR results revealed the formation of rutile TiO2 phase after titanium slag through oxidization roasting; additionally, observed from SEM patterns, the rutile TiO2 phase with a complex short rod-like crystal appeared in the products. Since the contents of sulfur (S), phosphorus (P) and carbon (C) element were all below 0.030% in the prepared rutile TiO2 with the recommended roasting approach (roasted at 1100 °C for 120 min), the present work highlights that Panzhihua titanium slag is a potential resource of titanium for the manufacture of high-quality rutile TiO2 applicable for special welding materials industry.

Aims Mammalian target of rapamycin (mTOR) inhibitors used in drug-eluting stents (DES) to control restenosis have been found to delay endothelialization and increase incidence of late-stent thrombosis through mechanisms not completely understood. We revealed that mTOR inhibition (mTORi) upregulated the expression of cell growth suppressor IRF-1 in primary human arterial endothelial cells (HAEC). This study aimed to examine how mTOR-regulated IRF-1 expression contributes to the suppressive effect of mTORi on arterial endothelial proliferation. Methods and results Western blotting, quantitative PCR, and a dual-luciferase reporter assay indicated that mTOR inhibitors rapamycin and torin 1 upregulated IRF-1 expression and increased its transcriptional activity. IRF-1 in turn contributed to the suppressive effect of mTORi by mediating HAEC apoptosis and cell cycle arrest in part through upregulation of caspase 1 and downregulation of cyclin D3, as revealed by CCK-8 assay, Annexin V binding assay, measurement of activated caspase 3, BrdU incorporation assay, and matrigel tube formation assay. In a mouse model of femoral artery wire injury, administration of rapamycin inhibited EC recovery, an effect alleviated by EC deficiency of IRF-1. Chromatin immunoprecipitation assay with HAEC and rescue expression of wild type or dominant-negative IRF-1 in EC isolated from Irf1−/− mice confirmed transcriptional regulation of IRF-1 on the expression of CASP1 and CCND3. Furthermore, mTORi activated multiple PKC members, among which PKCζ was responsible for the growth-inhibitory effect on HAEC. Activated PKCζ increased IRF1 transcription through JAK/STAT-1 and NF-κB signaling. Finally, overexpression of wild type or mutant raptor incapable of binding mTOR indicated that mTOR-free raptor contributed to PKCζ activation in mTOR-inhibited HAEC. Conclusions The study reveals an IRF-1-mediated mechanism that contributes to the suppressive effects of mTORi on HAEC proliferation. Further study may facilitate the development of effective strategies to reduce the side effects of DES used in coronary interventions.

Acrolein, a known toxin in tobacco smoke, has been demonstrated to be associated with inflammatory cardiovascular diseases, such as atherosclerosis. However, the definite mechanism of acrolein-induced inflammation remains unclear. Here, we report that acrolein induces reactive oxygen species (ROS) production in EAhy926 cells. Additionally, acrolein induces EAhy926 cells' inflammatory response and pyroptosis by activating NOD-like receptor protein 3 (NLRP3) inflammasome. Also, acrolein-induced cytotoxicity could be attenuated by N-acetyl-L-cysteine (NAC). Furthermore, acrolein upregulates the level of autophagy which can be reversed by NAC. Notably, the present study also indicates that autophagy inhibited by inhibitor 3-methyladenine (3MA) and siAtg7 exacerbate acrolein-induced NLRP3 inflammasome activation and pyroptosis. In summary, acrolein induced cytotoxicity by ROS-mediated NLRP3 inflammasome activation, and ROS upregulates the level of autophagy to inhibit the NLRP3 inflammasome excessive activation, indicating the bidirectional role of ROS in acrolein-induced cellular inflammation. Our results may provide novel mechanistic insights into acrolein-induced cardiovascular toxicity.

Given the complexity of injurious ingredients in practical wastewater, development of effective and low-cost multifunctional materials to decontaminate wastewater is of great necessity. Herein, polyacrylonitrile (PAN)/AgBr/Ag fibrous membranes are rationally designed and fabricated using combined electrospinning and wet-chemical methods. The surface AgBr/Ag Schottky junction is simply generated on hydrophilic PAN fibers by epitaxial growth approach, which simultaneously reveals superior photodegradation performance towards a variety of mimetic organic pollutions and excellent antibacterial activity due to their electron synergetic effect. Moreover, the stable porous structure of PAN/AgBr/Ag membranes and its good mechanic strength also ensures its good filtration performance. Overall, the PAN/AgBr/Ag fibrous membrane reveals water purification ability towards the simulated wastewater. In addition, benefit from the low content of Ag in PAN/AgBr/Ag membrane and easily scale-up, the self-standing PAN/AgBr/Ag membrane reveals great potential to practical wastewater treatment.

Utilizing surface polarization to improve the separation efficiency of photoinduced carriers is considered to be an effective strategy to enhance the photocatalytic activity. Herein, a novel nonprecious metal-based P-doped g-C3N4 (PCN)/polyaniline (PANI)/BaTiO3 (BTO) (PPB) ternary photocatalyst with a hollow architecture was rationally designed and prepared by a combined wet-chemical and thermal treatment strategy. Except for the Z-scheme involved in PCN and PANI, the vertical polarization provided by ferroelectric BTO further improved the separation efficiency of the photoinduced charge carrier, resulting in an enhanced visible-light photocatalytic hydrogen production activity of 602 μmol h−1 g−1, which was 21-fold higher than that of pristine g-C3N4, and an apparent quantum efficiency of 4.16% at 420 nm. In addition, benefitting from this ternary heterojunction, the photoinduced electrons were concentrated on the intermediate p-type PANI while holes were left on the lateral n-type PCN involved in the Z-scheme, resulting in the retention of high oxidation–reduction potentials. Moreover, this approach to enhance the photocatalytic activity by constructing a Z-scheme heterojunction and surface polarization could expand to other photosystems, which provides a new avenue for the rational design and the synthesis of novel photocatalysts.

Bornyl caffeate was initially discovered as a bioactive compound in medicinal plants. Despite the promising pharmacological activities including anti-tumor and antibacterial activities, the pharmacokinetics of the compound remain open. This work developed a high performance liquid chromatography-tandem mass spectrometric method for the determination of bornyl caffeate and caffeic acid (major metabolite and a main unit of bornyl caffeate) in vivo. Successful application of the method included identification of its metabolites and investigation on the drug pharmacokinetics. A total of 30 compounds were identified as the metabolites of bornyl caffeate in rats. We attributed these metabolites to phase I metabolic routes of reduction, oxidation, hydrolysis and phase II metabolic reactions of glucuronidation, sulfation, O-methylation and glycine. Glucuronidation, sulfation, O-methylation and reduction were the main metabolic pathways of bornyl caffeate. The method presented a linear range of 1–4000 ng mL−1. The pharmacokinetic profile of bornyl caffeate was found to be a three compartment open model, while caffeic acid fitted to a two compartment open model when it was administered alone or served as the main metabolite of bornyl caffeate. The time to peak concentration (Tmax) and the maximum plasma concentration (Cmax) of bornyl caffeate were 0.53 h and 409.33 ng mL−1. Compared with original caffeic acid, the compound displayed an increased half-life of elimination (T1/2β), area under the concentration time curve from 0 to t (AUC0–t) and area under the concentration time curve from 0 to ∞ (AUC0–∞), a decreased half-life of absorption (T1/2α) and an identical Cmax. Taking together, we concluded that bornyl caffeate is able to rapidly initiate therapeutic effect and last for a relatively long time in rats; metabolic pathways of O-methylation and reduction is key to interpret the mechanism and toxicity of bornyl caffeate.

Acrolein is a common environmental pollutant that has been linked to cardiovascular diseases, such as atherosclerosis (AS). Increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms haven't been completely elucidated. In human umbilical vein endothelial cells (HUVECs), we observed that acrolein treatment induced cell reactive oxygen species (ROS) generation, autophagy, pyroptosis and reduced cell migration. In addition, exposure to acrolein resulted in NLRP3 inflammasome activation as evidenced by cleavage of caspase-1 and downstream mature interleukin (IL)-1β and IL-18 secretion. Knockdown of NLRP3 by small interfering RNA remarkably suppressed acrolein-induced pyroptosis and increased cell migration. Moreover, the scavenging ROS relieved the autophagy, NLRP3 inflammasome activation and pyroptosis. Furthermore, the role of autophagy in the acrolein-medicated pyroptosis and cell migration was investigated. In our study, 3-methyladenine (3-MA), an autophagy inhibitor, aggravated NLRP3 inflammasome activation, pyroptosis and decreased cell migration, rapamycin (Rapa), an autophagy inducer, alleviated aforementioned phenomenon under acrolein stress. Besides, we found damaged mitochondrion accentuated NLRP3 inflammasome and pyroptosis in acrolein-treated cells. In conclusion, it is possible that acrolein induced cell pyroptosis and suppressed cell migration via ROS-dependent autophagy. What's more, NLRP3 inflammasome activation plays a key role in this process.

Acrolein, a highly reactive α,β-unsaturated aldehyde, is a toxic component of cigarette smoke. As a lipid peroxidation biomarker, acrolein plays an important role in a wide variety of disease states, such as neurodegenerative, Alzheimer's disease, diabetes and atherosclerosis. Endothelial cell injury is one of the initiating factors of atherosclerosis, but the underlying molecular mechanisms remain unclear. Our study primarily focused on acrolein-induced autophagy–dependent apoptosis and the possible molecular mechanism. The results showed that treatment with acrolein increased the number of intracellular GFP-LC3 II punctuates and the expression of autophagosome biomarker LC3-II, with the low dose (25 μM) or at the early stage of treatment (3 h). Following treatment of EAhy926 cells with acrolein for 6 h, lysosomal permeabilization changed, and cathepsin B (CB) was released. Additionally, acrolein induced the collapse of mitochondrial transmembrane potential, and cytochrome c was released. Furthermore, caspase-3 and caspase-9 activation showed that acrolein induced EAhy926 cell apoptosis. Autophagy inhibitor 3MA and CB inhibitor CA-074 Me (CA) attenuated acrolein-induced apoptosis. Collectively, our results suggested that acrolein-induced apoptosis is autophagy-dependent, occurring via injury to lysosomes and mitochondria. This study provides new mechanistic insight toward understanding the pathogenesis of acrolein-related disorders.

Insufficient neo-vascularization of in vivo implanted cell-seeded scaffold remains a major bottleneck for clinical translation of engineered bone formation. Demineralized bone matrix is an ideal bone scaffold for bone engineering due to its structural and biochemical components similar to those of native bone. We hypothesized that the microcarrier form of demineralized bone matrix favors ingrowth of vessels and bone regeneration upon in vivo implantation. In this study, a rat model of femoral vessel pedicle-based bone engineering was employed by filling the demineralized bone matrix scaffolds inside a silicone chamber that surrounded the vessel pedicles, and to compare the efficiency of vascularized bone regeneration between microcarrier demineralized bone matrix and block demineralized bone matrix. The results showed that bone marrow stem cells better adhered to microcarrier demineralized bone matrix and produced more extracellular matrices during in vitro culture. After in vivo implantation, microcarrier demineralized bone matrix seeded with bone marrow stem cells formed relatively more bone tissue than block demineralized bone matrix counterpart at three months upon histological examination. Furthermore, micro-computed tomography three-dimensional reconstruction showed that microcarrier demineralized bone matrix group regenerate significantly better and more bone tissues than block demineralized bone matrix both qualitatively and quantitatively (p

We investigated the protective effect and underlying molecular mechanism of nuclear factor-E2-related factor 2 (Nrf2) against mechanical-stretch-induced apoptosis in mouse fibroblasts. Normal cells, Nrf2 silencing cells, and Nrf2 overexpressing cells were respectively divided into two groups—nonintervention and cyclic mechanical strain (CMS)—subjected to CMS of 5333 μ (1.0 Hz for 4 h), six groups in total (control, CMS, shNfe212, shNfe212 + CMS, LV-shNfe212, and LV-shNfe212 + CMS). After treatment, cell apoptosis; cell-cycle distribution; expressions of Nrf2, Bax, Bcl-2, Cyt-C, caspase-3, caspase-9, cleaved-caspase-3, and cleaved-caspase-9; mitochondrial membrane potential (ΔΨm); reactive oxygen species (ROS); and malondialdehyde (MDA) levels were measured. Thirty virgin female C57BL/6 mice were divided into two groups: control (without intervention) and vaginal distension (VD) groups, which underwent VD for 1 h with an 8-mm dilator (0.3 ml saline). Leak-point pressure (LPP) was tested on day 7 after VD; Nrf2 expression, apoptosis, and MDA levels were then measured in urethra and anterior vaginal wall. Mechanical stretch decreased Nrf2 messenger RNA (mRNA) and protein expressions. Overexpression of Nrf2 alleviated mechanical-stretch-induced cell apoptosis; S-phase arrest of cell cycle; up-regulation of Bax, cytochrome C (Cyt-C), ROS, MDA, ratio of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9; and exacerbated the decrease of Bcl2 and ΔΨm in L929 cells. On the contrary, silencing of Nrf2 showed opposite effects. Besides, VD reduced LPP levels and Nrf2 expression and increased cell apoptosis and MDA generation in the urethra and anterior vaginal wall. Nrf2 exhibits a protective role against mechanical-stretch -induced apoptosis on mouse fibroblasts, which might indicate a potential therapeutic target of mechanical-trauma-induced stress urinary incontinence (SUI).

In this paper, a few mode fiber temperature sensor based on vernier effect is proposed. The sensor consists of two cascaded microcavities and realizes temperature sensing based on vernier effect. The single mode fiber(SMF) and few mode fiber(FMF) are fixed by a capillary glass tube to form an air reference microcavity. The end of the FMF is dipped with an appropriate amount of polydimethylsiloxane(PDMS) to form a sensing microcavity with a certain thickness, which is an air microcavity-FMF–PDMS structure. Due to the different refractive index of each medium, the light is reflected on the four critical surfaces, and the four reflected light beams interfere, the vernier effect is formed by adjusting the microcavity length to a suitable length. When the external temperature changes, the microcavity length and refractive index of PDMS change, which leads to the change of interference spectrum. Therefore, the high sensitivity measurement of temperature can be realized by the change of reflection spectrum. The temperature characteristics of the sensor are studied experimentally. The results show that the temperature sensitivity is significantly improved compared with the traditional single microcavity sensor. In the temperature range of 35°C ∼ 45°C, the temperature sensitivity can reach 4.7nm/°C, and the linearity is very good. The sensor has the advantages of compact structure, simple fabrication and high sensitivity, so it has wide application prospects in the field of temperature sensing.

With the growing concern about safety and environmental issues, amino acid-based surfactants have great potential as sustainable and eco-friendly substances. In the present study, six N-acyl oligopeptide surfactants were synthesized using fatty acid methyl esters (i.e., methyl caprate, methyl laurate, and methyl myristate) and glycyl oligopeptides (i.e., glycylglycine and glycylglycylglycine). Surface active properties and aggregation behaviors of these surfactants were investigated using surface tension, fluorescence probe, dynamic light scattering, and microscopy measurements. The adsorption at the air-water interface and aggregation in the aqueous solution depend on the structure of both hydrophilic head-groups and hydrophobic tails. Spherical vesicles were observed in the aqueous solutions of glycylglycine derivatives, whereas short tubular aggregates were found in that of corresponding glycylglycylglycine products. Intermolecular hydrogen-bonding interaction between the amide head-groups might be responsible for the different self-assembly behavior and microstructure of N-acyl oligopeptide surfactants in the aqueous solution.

The brazed grinding wheels were fabricated by high-frequency induction brazing with varying temperature from 900 to 1000 °C. The morphology and chemical composition of the brazing resultants around cubic boron nitride (cBN) grit were examined using scanning electron microscopy (SEM) and energy dispersion X-ray spectrometry (EDS) techniques. Grinding tests of titanium alloy Ti6Al4V were carried out. The results showed that the reaction layer composed of Ti-N and Ti-B compound was formed between the cBN grit and filler alloy. The specific grinding force and specific grinding energy of brazed cBN wheels were much lower than those of the electroplated counterpart during grinding of titanium. In particular, a good sharpness and bonding strength of brazed cBN wheel were obtained when the brazing temperature is 940 °C. With the brazing temperature increase, the main wear pattern of brazed cBN wheel is pullout, breakage, and crush, successively, while adhesion is dominant on the surface of the electroplated cBN wheel.

The increasing wall stress as is elicited by arterial hypertension promotes their reorganization in the vessel wall which may lead to arterial stiffening and contractile dysfunction. The nuclear factor of activated T cells 5 (NFAT5) pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the NFAT5 pathway was involved in the regulation of biomechanical stretch-induced human arterial smooth muscle cell (HUASMC) proliferation, inflammation, and migration. Herein, we showed that stretch promoted the expression of NFAT5 in human arterial smooth muscle cells and regulated through activation of c-Jun N-terminal kinase under these conditions. This may contribute to an improved activity of HUASMCs and thus promote reorganization in vascular remodeling processes such as hypertension-induced arterial stiffening and contractile dysfunction.

Aims Endothelial progenitor cell (EPC) dysfunction underlies a critical risk factor in diabetic vascular complications due to function defect in restoring endothelium injury. Crocetin has attracted increasing attention in several vascular-related diseases. In present study, we aimed to explore the role of crocetin in diabetic EPC dysfunction. Main methods EPCs were isolated from bone marrow in diabetic mice and identified using the fluorescence staining and flow cytometry. After exposure to various doses of crocetin, cell viability was detected by MTT assy. Then, colony formation, lactate dehydrogenase (LDH) release, cell apoptosis and caspase-3 activity were assessed. The underlying mechanism was also investigated by western blotting. Key findings EPCs from diabetic mice exhibited dysfunction under hyperglycemia condition. Interestingly, crocetin treatment alleviated the impairment in diabetic EPC proliferation and colony formation. Simultaneously, the increases in LDH release, cell apoptosis and caspase-3 activity were also restrained following crocetin stimulation. Additionally, EPC migration response to SDF-1 was also impaired under diabetic condition, which was partly restored by crocetin. Mechanism analysis manifested that administration with crocetin repaired the damage in the activation of PI3K/AKT-eNOS pathway and NO production, but attenuated ROS elevation in diabetic EPCs. Importantly, preconditioning with antagonist of LY294002 (for PI3K/AKT) or N G -monomethyl- l -arginine (for eNOS) antagonized the beneficial effect of crocetin on diabetic EPC dysfunction. Significance These data corroborated that crocetin could restore the dysfunction of diabetic EPCs by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways. Therefore, this research supports a potential promising therapeutic aspect for diabetic patients.

As a representative formulation of Radix Salviae miltiorrhizae (Danshen)-Lignum Dalbergiae odoriferae (Jiangxiang), Xiangdan injection is widely prescribed for cardio- and cerebrovascular diseases in practice. This necessitates a pharmacokinetic investigation of this formulation to make it safer and more broadly applicable. We developed and validated a sensitive, selective, and reliable high-performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of 11 phenolic compounds including danshensu plus two diterpenoid quinones like cryptotanshinone and tanshinone IIA in rat. We applied this method for the pharmacokinetic studies of the 13 compounds in a rat model of middle cerebral artery occlusion after intravenous injection of Xiangdan injection or Danshen injection. In sham-operated rats, the animals taking Xiangdan injection exhibited significant growth of the area under the curve for danshensu, protocatechuic aldehyde, and tanshinone IIA compared with the changes seen in the data of those administrated with Danshen injection. Such a pattern was also observed in middle cerebral artery occlusion rats, whereas increased the area under the curve values were observed for danshensu, protocatechuic aldehyde, caffeic acid, rosmarinic acid, and tanshinone IIA. These results demonstrated that synergistic interactions occurred between the components of Danshen and the active compounds of Jiangxiang both in sham-operated and middle cerebral artery occlusion rats, increasing the bioavailability of Danshen. The results presented herein can be used to determine a reference dose for the clinical application of Xiangdan injection, and to elucidate the synergistic mechanism of Danshen and Jiangxiang.

The cardiotoxicity of doxorubicin (DOX) limits its clinical use in the treatment of a variety of solid tumors and malignant hematologic disease. However, the mechanism by which it causes cardiotoxicity is not fully understood. Apoptosis has been regarded as one of mechanisms underlying the cardiotoxic effects of DOX. In our study, we found that treatment of human umbilical vein endothelial cells (HUVECs) with DOX induced autophagy and apoptosis in a dose- and time-dependent manner. Treatment with DOX induced autophagy at earlier time (3 h), then lysosomal membrane permeabilization (LMP) altered after treatment for 12 h which followed by the release of cathepsin D (CTSD). Lysosome-associated membrane proteins-1 and -2 (LAMP1 and LAMP2) were decreased in DOX-treated cells. Additionally, DOX induced the collapse of mitochondrial transmembrane potential, reduction of translocase of the outer mitochondrial membrane-20 (TOM-20), and release of cytochrome c. Furthermore, autophagy inhibitor 3-MA relieved DOX-induced apoptosis as assessed by the expression of cleaved caspase-3, cleaved caspase-9 and TUNEL assay. CTSD inhibitor, pepstatin A, upregulated TOM-20 and suppressed the mitochondria release of cytochrome c as well as apoptosis under DOX stress. Pyrroloquinoline quinine (PQQ), a new B vitamin, ameliorated aforementioned phenomenon. In conclusion, our results suggested that DOX-induced apoptosis was autophagy-dependent via lysosomal-mitochondrial axis. PQQ had an ability to protect cell from autophagy-dependent apoptosis induced by DOX via lysosomal-mitochondrial axis to some extent. This study provided new mechanistic insight toward understanding the pathogenesis of DOX-induced cardiotoxicity and the protection effect of PQQ.

Bifunctional rambutan-like nanosphere has been synthesised by combining the Au nanoparticles and polyluminol encapsulating with glucose oxidase using the one-pot hydrothermal redox protocol for the first time. Au nanoparticle/polyluminol/glucose oxidase (Au/PLUM/GOD) was developed via one step reaction through luminol solution redox reacted with HAuCl4 aqueous solution containing glucose oxidase protected from light at room temperature for 48 h. Highly luminescent luminol serves as a luminescent marker, while GOD possess high enzyme-catalytical charateristics when encapsulated in the bifunctional nanospheres. The synthetic method is easy, environmental friendly and high-productive. The prepared nanocomposites were used simply and effectively to develop highly sensitive solid-state electrochemiluminescent sensor for determination of glucose in human serum samples with wide linear range. Furthermore, it provided a promising approach for various biomolecule ECL sensors characterized by the parallel operative effects of both enzymic activities and the available concentrated surface luminescent molecules.

A highly binding dummy template molecularly imprinted polymers (Fe3O4-NH2@GO@MIPs) was synthesized used Fe3O4-NH2@GO as carrier by dummy surface molecular imprinting technique (DSMIT) for the first time. Fe3O4-NH2@GO@MIPs were characterized by fourier transform infrared (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), thermogravimetric analysis (TGA), brunauer emmett teller (BET) and vibrating specimen magnetometer (VSM). Adsorption and selectivity experiments of Fe3O4-NH2@GO@MIPs and non-imprinted polymers (Fe3O4-NH2@GO@NIPs) verified that the Fe3O4-NH2@GO@MIPs had a better selectivity and adsorption properties for five pyrethroids pesticides. Adsorption test results revealed that the adsorption behaviors of pyrethroids onto Fe3O4-NH2@GO@MIPs followed Langmuir equation adsorption isotherm and pseudo-second-order kinetic models. Fe3O4-NH2@GO@MIPs were used as sorbent in magnetic solid phase extraction (MSPE) to extract five pyrethroids from fruit juice samples, following desorption with acidified ethyl acetate, the pyrethroids were quantified by gas chromatography with electron capture detection (GC-ECD). The developed method MSPE coupled with GC-ECD achieved satisfactory recovery (72.1–106.8%) with RSD less than 10.8%, and the detection limits (LOD) for fenpropathrin (FENP), lambda-cyhalothrin (LC), cyfluthrin (CYF), fenvalerate (FEN) and deltamethrin (DEL) ranged from 0.007 to 0.015 μg/L. Compared to other methods, the procedure MSPE-GC-ECD based on Fe3O4-NH2@GO@MIPs in this work demonstrated to be a more convenient and practical method for the separation, enrichment, and detection of pyrethroids pesticides from fruit juice samples.

Tanshinol borneol ester (DBZ) is a potential drug candidate composed of danshensu and borneol. It shows anti-ischemic and anti-atherosclerosis activity. However, little is known about its metabolism in vivo. This research aimed to elucidate the metabolic profile of DBZ through analyzing its metabolites using high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. Chromatographic separation was performed on an Agilent TC-C18 column (150 × 4.6 mm, 5.0 μm) with gradient elution using methanol and water containing 0.2% (v/v) formic acid as the mobile phase. Metabolite identification involved analyzing the retention behaviors, changes in molecular weights and MS/MS fragment patterns of DBZ and its metabolites. As a result, 20 potential metabolites were detected and tentatively identified in rat plasma, urine and feces after administration of DBZ. DBZ could be metabolized to O-methylated DBZ, DBZ-O-glucuronide, O-methylated DBZ-O-glucuronide, hydroxylated DBZ and danshensu. Danshensu, a hydrolysis product of DBZ, could further be transformed into 12 metabolites. The proposed method was confirmed to be a reliable and sensitive alternative for characterizing metabolic pathways of DBZ and providing valuable information on its druggability.

Stress urinary incontinence (SUI) is a common hygienic problem affecting the quality of women’s life worldwide. In this research, we revealed the involvement and regulation of extracellular matrix (ECM) remodeling, oxidative damage, and TGF-β1 signaling in the pathological mechanisms of mechanical trauma-induced SUI. We found that excessive mechanical strain significantly increased apoptosis rate, decreased cell viability and ECM production, and broke the balance of MMPs/TIMPs compared with the nonstrain control (NC) group. The expression levels of TGFβ1, p-Smad3, Nrf2, GPx1, and CAT were downregulated, the production of ROS, 8-OHdG, 4-HNE, and MDA was increased, and the nuclear translocation of Smad2/3 was suppressed after 5333 μstrain’s treatment. Both mTGF-β1 pretreatment and Nrf2 overexpression could reverse mechanical injury-induced TGFβ1/Smad3 signaling inhibition and ECM remodeling, whereas mTGF-β1 had no effect on Nrf2 expression. Nrf2 overexpression significantly alleviated mechanical injury-induced ROS accumulation and oxidative damage; in contrast, Nrf2 silencing exhibited opposite effects. Besides, vaginal distention- (VD-) induced in vivo SUI model was used to confirm the in vitro results; Nrf2 knockout aggravates mechanical trauma-induced LPP reduction, ECM remodeling, oxidative damage, and TGF-β1/Smad3 suppression in mice. Therefore, we deduce that mechanical injury-induced ECM remodeling might be associated with Nrf2/ARE signaling suppression mediating TGF-β1/Smad3 signaling inhibition. This might reflect a new molecular target for SUI researches.

A two-stage titanium tetrachloride (TiCl 4 ) dosing strategy is applied for investigating the coagulation effect on simulated water containing humic acid (HA) and fulvic acid (FA) and these represent the dissolved organic matter (DOM). The influence of second TiCl 4 dose on coagulation efficiency, flock re-growth and the fractal dimension properties is studied for the beneficial effect of the second coagulant dose. Moreover, the impact of increased shear on the ultra filtration permeate flux in coagulation–ultra filtration (C–UF) hybrid process is explored. A small second dose essentially decreases the residual turbidity and improves the organic matter removal. Also, flocks with larger size and better recoverability result and having more compact structure than those obtained without the second TiCl 4 coagulant dose. At the same total TiCl 4 coagulant concentrations, the two-stage dosing mode reveals significant advantage over the single coagulant dosing in terms of turbidity removal, flock size and recoverability although organic matter removal and flock compactness degree are more or less deteriorated during the two-stage dosing process. The second TiCl 4 dose contributes to larger re-generated flocks with better re-growth ability than those obtained without the second dose within a wide range of high shear rate and even with prolonged breaking period. Two-stage dosing mode could improve the ultra filtration permeate flux under certain shear conditions. An extension in breakage time leads to much severer flux decline than short breakage periods. In case of FA simulated water, the ultra filtration permeate flux was less sensitive to increasing shear rate than in case of HA simulated water.

Curcumin is extracted from the rhizomes of the traditional Chinese herbCurcuma longaand has been proposed to function as a photosensitizer. The potential use of curcumin as a sonosensitizer for sonodynamic therapy (SDT) requires further exploration. This study investigated the sonodynamic effect of curcumin on macrophages, the pivotal inflammatory cells in atherosclerotic plaque. THP-1-derived macrophages were incubated with curcumin at a concentration of 40.7 μmol/L for 2 h and then exposed to pulse ultrasound irradiation (2 W/cm2with 0.86 MHz) for 5–15 min. Six hours later, cell viability was decreased in cells that had been treated with ultrasound for 10 and 15 min. After ultrasound irradiation for 15 min, the ratio of apoptotic and necrotic cells in SDT group was higher than that in ultrasound group, and the ratio of apoptotic cells was higher than that of necrotic cells. Both loss of mitochondrial membrane potential and morphological changes of cytoskeleton were apparent 2 h after treatment with curcumin SDT. These findings support that curcumin had sonodynamic effect on THP-1-derived macrophages and that curcumin SDT could be a promising treatment for atherosclerosis.

Aryl alkynoates (I) are coupled with β-keto acids (II) giving coumarin derivatives (III) in moderate to good yields.

A novel and convenient silver-mediated radical cyclization method for the synthesis of coumarin derivatives via the direct difunctionalization of alkynoates with α-keto acids through double C–C bond formation under mild conditions has been developed. This new method is highly efficient and practical, and the starting materials are readily prepared. The present method should provide a useful strategy for the construction of coumarin motifs.

A new microbial α-amylase inhibitor gene was cloned and characterized. The encoded, recombinant, α-amylase inhibitor protein was induced and expressed by isopropyl β-d-1-thiogalactopyranoside (IPTG) in Escherichia coli M15 cells. The effects of the α-amylase inhibitor protein on Helicoverpa armigera larvae were studied. Compared to the control, the weight of H. armigera larvae fed the diet with recombinant α-amylase inhibitor protein added at a concentration of 20 μg/g was reduced by 49.8%. The total soluble protein of H. armigera larvae fed the diet with the α-amylase inhibitor protein added was also reduced by 36.8% compared to the control. The recombinant α-amylase inhibitor protein showed inhibition activity against α-amylase of H. armigera. These results suggested that this α-amylase inhibitor protein may be a promising bioinsecticide candidate for controlling H. armigera.

Jiali Cheng,1,* Xin Sun,1,2,* Shuyuan Guo,1,* Wei Cao,1 Haibo Chen,1 Yinghua Jin,1 Bo Li,1 Qiannan Li,1 Huan Wang,1 Zhu Wang,3 Qi Zhou,3 Peng Wang,3 Zhiguo Zhang,3 Wenwu Cao,3,4 Ye Tian1,21Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People’s Republic of China; 3Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People’s Republic of China; 4Materials Research Institute, The Pennsylvania State University, University Park, PA, USA*These authors contributed equally to this workBackground: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX) after the administration of 5-aminolevulinic acid (ALA). Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX) on macrophages, which are the pivotal inflammatory cells in atherosclerosis.Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM) of ALA have no influence on cell viability (more than 90% of cells survived), but sonodynamic therapy (SDT) with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT) were measured using Hoechst 33258 and propidium iodide assay. ALA-SDT induced both cell apoptosis and necrosis, and the maximum apoptosis/necrosis ratio was observed at 6 hours after SDT with 1 mM of ALA and 5 minutes of ultrasound exposure. Flow cytometry analysis showed that ALA-SDT significantly increased late stage apoptotic cells (about 10-fold control). Furthermore, ALA-SDT induced reactive oxygen species generation in THP-1 macrophages immediately after the treatment and a conspicuous loss of mitochondrial membrane potential (MMP) at 6 hours compared with that of the control, ALA alone, and ultrasound alone groups.Conclusion: ALA-SDT exhibited synergistic apoptotic effects on THP-1 macrophages, involving excessive intracellular reactive oxygen species generation and MMP loss. Therefore, ALA-SDT is a potential treatment for atherosclerosis.Keywords: 5-aminolevulinic acid, protoporphyrin IX, sonodynamic therapy, macrophage, atherosclerosis

OBJECTIVE: To investigate relationships between serum levels of retinol binding protein 4 (RBP4) and clinical and metabolic variables in Chinese patients with type 2 diabetes mellitus. METHODS: A total of 513 patients (286 males/227 females) provided clinical and lifestyle data and blood and urine samples for analysis. Patients were stratified into four quartile groups according to serum RBP4 concentrations. RESULTS: RBP4 concentration was independently associated with gender, systolic blood pressure, serum triglyceride and creatinine levels, and estimated glomerular filtration rate (eGFR). Hypertension, dyslipidaemia, microalbuminuria and impaired eGFR (< 60 ml/min per 1.73 m2) were significantly more prevalent in patients with the highest RBP4 levels than in those with the lowest levels. Increased serum RBP4 was associated with increased risk of hypertension, dyslipidaemia, microalbuminuria and impaired eGFR after adjusting for gender, age, body mass index and duration of diabetes. CONCLUSION: Serum RBP4 may be a useful marker of overall metabolic control in Chinese patients with type 2 diabetes mellitus.

OBJECTIVE To study the antipyretic effect of baicalin in inhibiting yeast-induced fever in rats and the influence on inflammatory cytokine, then explore the possible mechanism of baicalin in inhibiting yeast-induced fever in rats. METHODS Rat modles of pyrexia were established by subcutaneous injection of yeast (2 g x kg(-1)); the rats of were divided into the normal control, model, baicalin high, medium and low-dose group and the effect of baicalin on the changes of the rats' temperature were observed. Dual antibody ELISA method was used to test the changes of IL-6, IL-1beta and TNF-alpha contents in in serum , hypothalamus and cerebral spinal fluid (CSF). Then analyze the correlation between the inhibition ratio of temperature heighten on three different dose of baicalin and the inhibition ratio of the contents heighten on IL-6, IL-1beta and TNF-alpha. RESULT The high dose of baicalin significantly inhibited the yeast-induced fever of rats, and decresesed IL-6, IL-1beta and TNF-alpha contents in serum, hypothalamus and CSF. The inhibition ratio of temperature heighten of baicalin had direct correlation with the inhibition ratio of the heighten on IL-1beta content in serum, hypothalamus and CSF (r = 0.873, P < 0.05), also dose TNF-alpha (r = 0.862, P < 0.01). CONCLUSION Baicalin may have obvious antipyretic effect by decreasing the increasing contents of IL-1beta and TNF-alpha in rats.