Physicochemical, structural and functional properties of low methoxyl pectin­iron (III) complex and its effect on rats with iron deficiency anemia.

Iron deficiency anemia (IDA) is the most common nutritional disease worldwide. In this study, a low methoxyl pectin (LMP)­iron(III) complex was prepared. The physicochemical and structural properties were characterized by HPSEC, HPIC, CV, FTIR, 1H NMR, XRD, SEM and CD. The results showed that iron increased the molecular weight of the LMP­iron(III) from 11.50 ± 0.32 to 12.70 ± 0.45 kDa and improved its crystallinity. Moreover, the findings demonstrated that -OH and -COOH groups in LMP coordinate with Fe3+ to form ß-FeOOH. The water-holding capacity, emulsion stability, and antioxidant activities of the LMP­iron(III) were lower than those of LMP. Furthermore, the therapeutic effects of LMP­iron(III) on IDA were investigated in rats. Following LMP­iron(III) supplementation, compared with the model group, the administration of LMP­iron(III) significantly increased the body weight, hemoglobin concentration, and serum iron concentration as well as decreased free erythrocyte protoporphyrin concentration. Therefore, the LMP­iron(III) can potentially treat IDA in rats experiments, providing a theoretical basis for the development of a promising iron supplement.

Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.

High-Efficiency Corrosion Inhibitor of Biomass-Derived High-Yield Carbon Quantum Dots for Q235 Carbon Steel in 1 M HCl Solution.

Eco-friendly self-doped carbon quantum dots (ZCQDs) with excellent corrosion inhibition ability were prepared via solid-phase pyrolysis only using Zanthoxylum bungeanum leaves as the raw material. Compared with the relevant research, a simpler and higher yield (25%) preparation process for carbon quantum dots was proposed. ZCQDs were characterized by transmission electron microscopy and X-ray photoelectron spectroscopy, and the average size of ZCQDs with multitudes of O- and N-containing functional groups was about 2.53 nm. The prepared ZCQDs were used to inhibit the corrosion of Q235 steel in HCl solution, and the inhibition behavior was investigated through weight loss, electrochemical test, surface analysis, and adsorption thermodynamic analyses. The results showed that the ZCQDs, acted as a mixed corrosion inhibitor, have an effective corrosion inhibition for Q235, the corrosion inhibition efficiency reached 95.98% at 200 mg/L, and at this concentration, effective protection of at least 132h (IE > 90%) is provided. Moreover, the adsorption mechanism of ZCQDs was consistent with that of Redlich-Peterson adsorption, including chemisorption and physisorption. A new corrosion inhibition mechanism of ZCQDs has been thoroughly studied and proposed; ZCQDs have functional groups containing O and N, which can form a protective barrier through physical adsorption and chemisorption, but the coverage of the protective film is low at low concentrations. With the increase of concentration, the protective film formed by ZCQDs on the metal surface will first increase the coverage and then adsorb more ZCQDs on the protective film to form a thicker and denser protective film to protect the metal. The carbon quantum dots prepared in this paper have advantages including a green, renewable precursor, a fast method, high yield, and excellent corrosion inhibition. Therefore, this work can inspire and facilitate, to a certain extent, the future application of doped carbon quantum dots as efficient corrosion inhibitors in HCl solutions.

Fabrication of Anatase TiO2/PVDF Composite Membrane for Oil-in-Water Emulsion Separation and Dye Photocatalytic Degradation.

At present, the types of pollutants in wastewater are more and more complicated, however, the multifunctional membrane materials are in short supply. To prepare a membrane with both high efficient oil-in-water emulsion separation performance and photocatalytic degradation performance of organic dyes, the bifunctional separation membrane was successfully prepared by electrostatic spinning technology of PVDF/PEMA and in situ deposition of anatase TiO2 nanoparticles containing Ti3+ and oxygen vacancies (Ov). The prepared composite membrane has excellent hydrophilic properties (WCA = 15.65), underwater oleophobic properties (UOCA = 156.69), and photocatalytic performance. These composite membranes have high separation efficiency and outstanding anti-fouling performance, the oil removal efficiency reaches 98.95%, and the flux recovery rate (FRR) reaches 99.19% for soybean oil-in-water emulsion. In addition, the composite membrane has outstanding photocatalytic degradation performance, with 97% and 90.2% degradation of RhB and AG-25 under UV conditions, respectively. Several oil-in-water separation and dye degradation experiments show that the PVDF composite membrane has excellent reuse performance. Based on these results, this study opens new avenues for the preparation of multifunctional reusable membranes for the water treatment field.

Fabrication of photo-Fenton self-cleaning PVDF composite membrane for highly efficient oil-in-water emulsion separation.

The anti-fouling performance of membranes is an important performance in the separation of oil/water. However, the membrane with anti-fouling performance will also have surface scaling phenomenon when it runs for a long time. Therefore, there is still a great demand for stain-resistant membranes with good self-cleaning ability and high flux recovery rate. Based on this, this paper firstly prepared a hydrophilic membrane with carboxyl group and carboxyl ion by blending poly(ethylene-alt-maleic anhydride) (PEMA) and polyvinylidene fluoride (PVDF), and then prepared a self-cleaning composite membrane by in situ mineralization of ß-FeOOH particles on the surface of the membrane for efficient oil-in-water emulsion separation. A large number of -COOH/COO- and ß-FeOOH particles on the membrane surface make the composite membrane have strong hydrophilic properties (WCA = 20.34°) and underwater superoleophobicity (UOCA = 155.10°). These composite membranes have high separation efficiency (98.8%) and high flux (694.56 L m-2 h-1 bar-1) for soybean oil-in-water emulsion. Importantly, the as-prepared membrane shows excellent flux recovery rate (over 99.93%) attributed to the robust photo-Fenton catalytic activity of ß-FeOOH, and the ß-FeOOH is chemically bonded to the as-prepared membrane, which makes the as-prepared membrane have good reusability. This work provides hope for the application of self-cleaning membranes in the construction of anti-fouling membranes for wastewater remediation.

Efficiency of Gemini surfactant containing semi-rigid spacer as microbial corrosion inhibitor for carbon steel in simulated seawater.

SRB is one of the main bacteria causing marine microbial corrosion. In order to reduce the loss of microbial corrosion, a Gemini surfactant (12-B-12) containing semi-rigid spacer was used to investigate the anti-bacterial and anti-corrosion performances of carbon steel in simulated seawater by weight-loss test, electrochemical method and surface morphology analysis. The results showed that the inhibition efficiency of 0.01 mM 12-B-12 was as high as 98.3% after 30 days of incubation in simulated seawater with SRB, and the planktonic and sessile SRB on the carbon steel surface can be reduced to undetectable level. Quantum chemical calculation and molecular dynamics simulation were used to study the structure-activity relationship.

Operating Transverse Aortic Constriction with Absorbable Suture to Obtain Transient Myocardial Hypertrophy.

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate cardiomyocyte hypertrophy and slow down progression to heart failure. For novices, however, the MHP model is usually quite difficult to establish because of the technical obstacles in ventilator operation, opening the chest repeatedly, and bleeding caused by debanding. To facilitate this model, to increase the surgical success rate and to reduce the incidence of bleeding, we switched to absorbable sutures for the first TAC combing with a ventilator-free technique. Using a 2-week absorbable suture, we demonstrated that this procedure could cause significant myocardial hypertrophy in 2 weeks; and 4 weeks after surgery, myocardial hypertrophy was almost completely regressed to the baseline. Using this protocol, the operators could master the MHP model easily with a lower operation mortality.

Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway.

Vortioxetine is a potent antagonist of the 5-hydroxytryptamine receptor and serotonin transporter and has been reported to function as an antidepressant in the treatment of major depressive disorder. However, its antitumor effects remain unclear. Here, we examined whether vortioxetine affects the characteristics of GC cells. Cell viability was measured by a colony formation assay and, in addition, cell invasion, migration and apoptosis assays were performed with a transwell assay and a flow cytometry assay. Protein levels were measured by western blotting. We found that vortioxetine inhibited the proliferation, invasion and migration abilities of AGS cells. Additionally, vortioxetine could induce apoptosis and autophagy by increasing the levels of Bax, active caspase-3/-9, Beclin-1 and light chain 3, as well as by downregulating Bcl-2 and P62. Further investigations indicated that vortioxetine regulated apoptosis and autophagy via activation of the phosphoinositide 3-kinase/AKT pathway. Taken together, our data suggest that vortioxetine has cytotoxic effects against GC AGS cells as a result of inhibiting proliferation, invasion and migration, as well as by inducing apoptosis and autophagy through the phosphoinositide 3-kinase/AKT pathway.

Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of ß-catenin.

AIMS: Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. METHODS AND RESULTS: Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3ß, and active ß-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active ß-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. CONCLUSION: Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3ß/ß-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

Sunflower Head Pectin with Different Molecular Weights as Promising Green Corrosion Inhibitors of Carbon Steel in Hydrochloric Acid Solution.

Three sunflower head pectin (SFHP) with different molecular weights (M w = 4.50, 97.23, and 254.64 kDa) were obtained by enzyme-assisted extraction and characterized by FTIR and 1H NMR spectroscopy. The corrosion inhibition of mild steel in 1 M HCl solution was evaluated by the weight loss measurement. The inhibition efficiency (IE%) increased as its concentration increases and decreased as the temperature increases. The SFHP with the lowest M w of 4.50 kDa exhibited an IEmax of 92.05% at the medium concentration (2.0 g L-1). The inhibition properties of SFHP (M w = 4.50 kDa) were investigated electrochemically and theoretically. The electrochemical impedance spectroscopy (EIS) revealed that the charge-transfer resistance increased as its concentration increases, the double-layer capacitance decreased as concentration increases, and the IE% also increased as concentration increases. The potentiodynamic polarization (PP) revealed that the SFHP acted as mixed-type inhibitor. The IE% reached 90.3% at the medium concentration (2.0 g L-1) of SHFP. The three-dimensional super depth digital microscopy and scanning electron microscopy tests confirmed the formation of inhibitor films on the surface of mild steel. The adsorption of SFHP on the mild steel surface was proved to obey the Langmuir adsorption isotherm. The theoretical studies via density functional theory and molecular dynamics simulation further revealed the mechanism of corrosion inhibition.

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice.

The mechanism of right ventricular failure (RVF) requires clarification due to the uniqueness, high morbidity, high mortality, and refractory nature of RVF. Previous rat models imitating RVF progression have been described. Compared with rats, mice are more accessible, economical, and widely used in animal experiments. We developed a pulmonary artery constriction (PAC) approach which is comprised of banding the pulmonary trunk in mice to induce right ventricular (RV) hypertrophy. A special surgical latch needle was designed that allows for easier separation of the aorta and the pulmonary trunk. In our experiments, the use of this fabricated latch needle reduced the risk of arteriorrhexis and improved the surgical success rate to 90%. We used different padding needle diameters to precisely create quantitative constriction, which can induce different degrees of RV hypertrophy. We quantified the degree of constriction by evaluating the blood flow velocity of the PA, which was measured by noninvasive transthoracic echocardiography. RV function was precisely evaluated by right heart catheterization at 8 weeks after surgery. The surgical instruments made inhouse were composed of common materials using a simple process that is easy to master. Therefore, the PAC approach described here is easy to imitate using instruments made in the lab and can be widely used in other labs. This study presents a modified PAC approach that has a higher success rate than other models and an 8-week postsurgery survival rate of 97.8%. This PAC approach provides a useful technique for studying the mechanism of RVF and will enable an increased understanding of RVF.

UPLC-QTOF-MS-guided isolation of anti-COPD ginsenosides from wild ginseng.

Four previously undescribed ginsenosides, along with five known analogues were isolated from wild ginseng by a UPLC-QTOF-MS-guided fractionation procedure. Their structures were elucidated on the basis of spectroscopic and spectrometric data (1D and 2D NMR, HR-ESI-MS). The isolated compounds could significantly inhibit the cigarette smoke extract (CSE)-induced inflammatory reaction in A549 cells. The HDAC2 pathway might be involved in the protective effect against the CSE-mediated inflammatory response in A549 cells.

Pharmacokinetic and Metabolism Studies of Curculigoside C by UPLC-MS/MS and UPLC-QTOF-MS.

Pharmacokinetic and metabolism studies were carried out on curculigoside C (CC), a natural product with good antioxidant and neuroprotective effects, with the purpose of investigating the effects of the hydroxyl group at C-3' in curculigoside. A rapid and sensitive method with UPLC-MS was developed and fully validated for the first time in the pharmacokinetic analysis for quantification of CC in rat plasma. The assay was linear (R² > 0.9984) over the concentration range of 1⁻2500 ng/mL, with the lower limit of quantification (LLOQ) being 1 ng/mL. The intra-day and inter-day precision (expressed as relative standard deviation, RSD) ranged from 4.10% to 5.51% and 5.24% to 6.81%, respectively. The accuracy (relative error, RE) ranged from -3.28% to 0.56% and -5.83% to -1.44%, respectively. The recoveries ranged from 92.14% to 95.22%. This method was then applied to a pharmacokinetic study of rats after intragastric administration of 15, 30 and 60 mg/kg CC. The results revealed that CC exhibited rapid oral absorption (Tmax = 0.106 h, 0.111 h, and 0.111 h, respectively), high elimination (t1/2 = 2.022 h, 2.061 h, and 2.048 h, respectively) and low absolute bioavailability (2.01, 2.13, and 2.39%, respectively). Furthermore, an investigation on the metabolism of CC was performed by UPLC-QTOF-MSE. Twelve metabolites of CC from plasma, bile, urine and faeces of rats were confirmed. The main metabolic pathways of CC, which involve dehydration, glucosylation, desaturation, formylation, cysteine conjugation, demethylation and sulfonation, were profiled. In conclusion, this research has developed a sensitive quantitative method and demonstrated the metabolism of CC in vivo.

Pharmacokinetic and Metabolism Studies of 12-Riboside-Pseudoginsengenin DQ by UPLC-MS/MS and UPLC-QTOF-MSE.

Pharmacokinetic and metabolism studies of 12-riboside-pseudoginsengenin DQ (RPDQ), a novel ginsenoside with an anti-cancer effect, were carried out, aiming at discussing the characteristics of the ginsenoside with glycosylation site at C-12. In the pharmacokinetic analysis, we developed and validated a method by UPLC-MS to quantify RPDQ in rat plasma. In the range of 5⁻1000 ng/mL, the assay was linear (R² > 0.9966), with the LLOQ (lower limit of quantification) being 5 ng/mL. The LOD (limit of detection) was 1.5 ng/mL. The deviations of intra-day and inter-day, expressed as relative standard deviation (RSD), were ≤ 3.51% and ≤ 5.41% respectively. The accuracy, expressed as relative error (RE), was in the range ⁻8.82~3.47% and ⁻5.61~2.87%, respectively. The recoveries were in the range 85.66~92.90%. The method was then applied to a pharmacokinetic study in rats intragastrically administrated with 6, 12, and 24 mg/kg RPDQ. The results showed that RPDQ exhibited slow oral absorption (Tmax = 7.0 h, 7.5 h, and 7.0 h, respectively), low elimination (t1/2 = 12.59 h, 12.83 h, and 13.74 h, respectively) and poor absolute bioavailability (5.55, 5.15, and 6.08%, respectively). Moreover, the investigation of metabolites were carried out by UPLC-QTOF-MS. Thirteen metabolites of RPDQ were characterized from plasma, bile, urine, and feces of rats. Some metabolic pathways, including oxidation, acetylation, hydration, reduction, hydroxylation, glycine conjugation, sulfation, phosphorylation, glucuronidation, glutathione conjugation, and deglycosylation, were profiled. In general, both the rapid quantitative method and a good understanding of the characteristics of RPDQ in vivo were provided in this study.

[Dose-effect relationship of DMSO and Tween 80 influencing the growth and viability of murine bone marrow-derived cells in vitro].

This study was purpose to examine the effect of dimethyl sulfoxide (DMSO) and Tween 80 on the growth and viability of stromal cells (BMSC), colony-forming units for granulocytes and macrophages (CFU-GM) and bone marrow endothelial cell line (BMEC) from murine bone marrow in vitro, and to analyze the concentration-effect relationship. The colony yields of colony-forming units fibroblastic (CFU-F) and CFU-GM were assessed in the murine bone marrow cell cultures at various concentrations of DMSO or Tween 80 and in the control groups. The MTT assay and trypan blue exclusion were used to determine the cell viability and percentage of survival in BMSC and BMEC cultures with or without either of these organic solvents. The results showed that the colony yields of both CFU-F and CFU-GM were decreased significantly (p<0.05 or <0.01) at the concentrations (v/v final) of 2% DMSO or 0.005%-0.01% Tween 80 respectively, as compared with control. The cell viability and percentage of survival of BMSC and BMEC cultures were significantly reduced (p<0.05 or <0.01) at 0.5%-1.0% DMSO or 0.002%-0.005% Tween 80, as compared with control. With the increase of volume fractions of these solvents, the decreased percentages of corresponding measurements were increased by degrees. It is concluded that when the concentration of DMSO or Tween 80 goes to a certain level in cell culture medium, either of the organic solvents has an inhibitory action or/and cytotoxicity on the growth and viability of BMSCs, CFU-GM and BMECs. The growth inhibition and cytotoxic response are more significant at higher concentrations of these solvents.