Large-pore covalent organic framework as solid phase extraction absorbentforefficientdetermination of polypeptide antibiotics in animal-derived foods.

The precise determination of polypeptide antibiotics (PPTs) in foods has been always challenging because of the interference of various endogenous peptides in complex matrix. Herin, a novel large-pore covalent organic framework (TABPT-SPDA-COF) with accessible pore size of 7.9 nm was synthesized as a solid phase extraction (SPE) absorbent for efficiently enriching four PPTs existed in foods originating from animals. The parameters of SPE process were systematically optimized. Subsequently, four PPTs were determined by UHPLC-MS/MS. Under the optimal conditions, TABPT-SPDA-COF shows outstanding enrichment capacity for PPTs in contrast to commercial absorbents ascribed to size selectivity and multiple interaction effects. The method exhibits excellent linear range (0.005-100 ng mL-1), satisfactory limits of detection (0.1 pg mL-1) as well as relative recoveries (86.2-116 %). This work offers a practicable platform to monitor trace PPTs from complex animal-derived foodstuffs.

Exploring the Low-Dose Limit for Focal Hepatic Lesion Detection with a Deep Learning-Based CT Reconstruction Algorithm: A Simulation Study on Patient Images.

This study aims to investigate the maximum achievable dose reduction for applying a new deep learning-based reconstruction algorithm, namely the artificial intelligence iterative reconstruction (AIIR), in computed tomography (CT) for hepatic lesion detection. A total of 40 patients with 98 clinically confirmed hepatic lesions were retrospectively included. The mean volume CT dose index was 13.66 ± 1.73 mGy in routine-dose portal venous CT examinations, where the images were originally obtained with hybrid iterative reconstruction (HIR). Low-dose simulations were performed in projection domain for 40%-, 20%-, and 10%-dose levels, followed by reconstruction using both HIR and AIIR. Two radiologists were asked to detect hepatic lesion on each set of low-dose image in separate sessions. Qualitative metrics including lesion conspicuity, diagnostic confidence, and overall image quality were evaluated using a 5-point scale. The contrast-to-noise ratio (CNR) for lesion was also calculated for quantitative assessment. The lesion CNR on AIIR at reduced doses were significantly higher than that on routine-dose HIR (all p < 0.05). Lower qualitative image quality was observed as the radiation dose reduced, while there were no significant differences between 40%-dose AIIR and routine-dose HIR images. The lesion detection rate was 100%, 98% (96/98), and 73.5% (72/98) on 40%-, 20%-, and 10%-dose AIIR, respectively, whereas it was 98% (96/98), 73.5% (72/98), and 40% (39/98) on the corresponding low-dose HIR, respectively. AIIR outperformed HIR in simulated low-dose CT examinations of the liver. The use of AIIR allows up to 60% dose reduction for lesion detection while maintaining comparable image quality to routine-dose HIR.

A specific visual-volumetric sensor for mercury ions based on smart hydrogel.

On the basis of the "seeing is believing" concept and the existing theory of Hg2+ coordination chemistry, for the first time, we innovatively designed and synthesized a visual-volumetric sensor platform with fluorescein and uracil functionalized polyacrylamide hydrogel. Without the aid of any complicated instruments and power sources, the sensor-enabled quantitative µM-level Hg2+ detection Hg2+ by reading graduation on a pipette with the naked eye. The sensor undergoes volumetric response and shows a wide linear response range to Hg2+ (1.0 × 10-6-5.0 × 10-5 mol L-1) with 2.8 × 10-7 mol L-1 as the detection limit. The highly selective (easily distinguished Hg2+ from other common metal ions), rapid response (∼30 min), and acceptable repeatability (RSD < 5% in all cases) demonstrated that the developed sensor is suitable for onsite practical use for the determination of Hg2+ while being low-cost, simple, and portable. The design principles of the obtained materials and the construction techniques and methods of the sensors described in our study provide a new idea for the research and development of smart materials and a series of visual-volumetric sensors for other analytes.

The impact of sodium-glucose Cotransporter-2 inhibitors on lipid profile: A meta-analysis of 28 randomized controlled trials.

AIM: The present study aimed to evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on blood lipid profile. METHODS: We searched the PubMed, Cochrane Library, Medline, and EMBASE databases from the inception to July 2023 for randomized controlled trials (RCTs) comparing SGLT2i with placebo regarding lipid profile changes. The "Meta" package of R software was applied for data synthesis. RESULTS: A total of 28 RCTs were included and 5192 patients participated in the present study, including 2686 patients who received SGLT2is intervention and 2506 patients who were in the control group. SGLT2is significantly increased blood low density lipoprotein cholesterol (LDL-C) levels [mean difference (MD): 0.09 mmol/L, 95% confidence interval (CI) (0.03, 0.16), 95% prediction interval (PI) (-0.06, 0.24), P = 0.0046] and high density lipoprotein cholesterol (HDL-C) levels [MD: 0.08 mmol/L, 95% CI (0.06, 0.11), 95% PI (-0.00, 0.17), P < 0.0001]. However, we observed neutral effect of SGLT2is on total cholesterol (TC) [MD: 0.08 mmol/L, 95% CI (-0.08, 0.24), 95% PI (-0.24, 0.40), P = 0.3150] and triglyceride (TG) [MD: -0.03 mmol/L, 95% CI (-0.23, 0.16), 95% PI (-0.70, 0.63), P = 0.7382]. CONCLUSION: Our study determined that SGLT2is increase both LDL-C and HDL-C levels, but exerts not significant effect on TC and TG levels.

Full-sized realistic 3D printed models of liver and tumour anatomy: a useful tool for the clinical medicine education of beginning trainees.

BACKGROUND: Simulation-based medical education (SBME) and three-dimensional printed (3DP) models are increasingly used in continuing medical education and clinical training. However, our understanding of their role and value in improving trainees' understanding of the anatomical and surgical procedures associated with liver surgery remains limited. Furthermore, gender bias is also a potential factor in the evaluation of medical education. Therefore, the aim of this study was to evaluate the educational benefits trainees receive from the use of novel 3DP liver models while considering trainees' experience and gender. METHODS: Full-sized 3DP liver models were developed and printed using transparent material based on anonymous CT scans. We used printed 3D models and conventional 2D CT scans of the liver to investigate thirty trainees with various levels of experience and different genders in the context of both small group teaching and formative assessment. We adopted a mixed methods approach involving both questionnaires and focus groups to collect the views of different trainees and monitors to assess trainees' educational benefits and perceptions after progressing through different training programs. We used Objective Structured Clinical Examination (OSCE) and Likert scales to support thematic analysis of the responses to the questionnaires by trainees and monitors, respectively. Descriptive analyses were conducted using SPSS statistical software version 21.0. RESULTS: Overall, a 3DP model of the liver is of great significance for improving trainees' understanding of surgical procedures and cooperation during operation. After viewing the personalized full-sized 3DP liver model, all trainees at the various levels exhibited significant improvements in their understanding of the key points of surgery (p < 0.05), especially regarding the planned surgical procedure and key details of the surgical procedures. More importantly, the trainees exhibited higher levels of satisfaction and self-confidence during the operation regardless of gender. However, with regard to gender, the results showed that the improvement of male trainees after training with the 3DP liver model was more significant than that of female trainees in understanding and cooperation during the surgical procedure, while no such trend was found with regard to their understanding of the base knowledge. CONCLUSION: Trainees and monitors agreed that the use of 3DP liver models was acceptable. The improvement of the learning effect for practical skills and theoretical understanding after training with the 3DP liver models was significant. This study also indicated that training with personalized 3DP liver models can improve all trainees' presurgical understanding of liver tumours and surgery and males show more advantage in understanding and cooperation during the surgical procedure as compared to females. Full-sized realistic 3DP models of the liver are an effective auxiliary teaching tool for SBME teaching in Chinese continuing medical education.

Cord blood-derived Vδ2+ and Vδ2- T cells acquire differential cell state compositions upon in vitro expansion.

Human cord blood-derived γδ T cells (CBγδ) display a highly diverse TCRγδ repertoire and have a unique subtype composition different from fetal or adult peripheral blood counterparts. We expanded CBγδ in vitro using an irradiated Epstein-Barr virus-transformed feeder cell-based modified rapid expansion protocol (REP). Single-cell RNA sequencing tracked progressive differentiation of naïve CBγδ into cells expressing neoantigen-reactive tumor-infiltrating lymphocyte as well as tissue-resident memory precursor-like and antigen-presenting cell-like gene signatures. TCRγδ clonal tracing revealed a bias toward cytotoxic effector differentiation in a much larger proportion of Vδ2- clones compared to Vδ2+ clones, resulting in the former being more cytotoxic at the population level. These clonotype-specific differentiation dynamics were not restricted to REP and were recapitulated upon secondary nonviral antigen stimulations. Thus, our data showed intrinsic cellular differences between major subtypes of human γδ T cells already in operation at early postnatal stage and highlighted key areas of consideration in optimizing cell manufacturing processes.

The effect of sodium-glucose cotransporter-2 inhibitors on cardiac structure remodeling and function: A meta-analysis of randomized controlled trials.

BACKGROUND: It has been proven that sodium-glucose co-transporter 2 inhibitors (SGLT2is) improve the prognosis of patients with heart failure, independent of the presence of diabetes mellitus. Whether SGLT2 inhibitors affect cardiac structural remodeling and cardiac function is still uncertain. METHODS: We included published randomized controlled trials (RCTs) to compare the effect of SGLT2is and control therapy in patients with or without heart failure. The meta-analysis was performed using Review Manager 5.3 software. RESULTS: A total of 15 RCTs with a total of 1343 patients were selected for this meta-analysis, 663 of whom were on SGLT2is treatment and 680 of whom were in the control group. SGLT2is significantly improved heart rate (HR) [MD: -2.74, 95% CI (-4.71, -0.77), P = 0.006], left atrium volume index (LAVi) [MD: -1.99, 95% CI (-3.23,-0.75), P = 0.002], E/e' [MD: -1.47, 95% CI (-1.83,-1.10), P<0.00001], left ventricular mass index (LVMi) [MD: -2.38, 95% CI (-4.35, -0.40), P = 0.02], left ventricular end-systolic volume (LVESV) [MD: -6.50, 95% CI (-11.15,-1.84), P = 0.006], and left ventricular ejection fraction (LVEF) [MD: 1.78, 95% CI (0.56,3.01), P = 0.004] in the total population. Subgroup analysis indicated that compared with other SGLT2is, empagliflozin significantly decreased LVEDV, LVESV,LVMi, LAVi, E/e', and increased LVEF (P<0.05). In addition, the cardiac anti-remodeling effects of SGLT2 are particularly significant in patients with heart failure. CONCLUSION: Our study showed that SGLT2is, particularly empagliflozin, significantly reverse cardiac remodeling in patients with heart failure. Empagliflozin may be a potentially promising agent to reverse cardiac remodeling in clinical practice.

Online solid-phase extraction based on size-controllable spherical covalent organic framework for efficient determination of polybrominated diphenyl ethers in foods.

An analytical method of microspheric brominated covalent organic framework (Br-COF)-online solid-phase extraction integrated with high-performance liquid chromatography (online SPE-HPLC) was proposed for efficiently enriching six polybrominated diphenyl ethers (PBDEs) in foods. The Br-COF microspheres were facilely prepared with uniformity and dispersion by a size-controllable synthesis at the room temperature. Attributed to multiple interactions of the halogen bonding, Van der Waals forces, hydrophobic interaction along with size-matching effect, Br-COF performed satisfactory extraction capacity for PBDEs compared with commercial adsorbents. Five primary influencing factors were optimized, including loading solvent, loading flow rate, elution solvent, elution flow rate and elution volume. Under the optimal parameters, the implement displayed excellent linear ranges (0.5-500 ng mL-1) and low detection limits (0.01-0.05 ng mL-1). The relative recoveries in six spiked food samples ranged from 87.8 to 119.7 % with relative standard deviations below 10 %. This research estabished a promising platform for quantitatively determining trace PBDEs in complex foods.

Safety and efficacy of intracoronary recombinant human prourokinase administration in patients with acute myocardial infarction and ST­segment elevation: A meta­analysis of randomized controlled trials.

Slow blood flow or no reflow following percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) typically leads to an adverse prognosis. However, it is controversial whether to use prourokinase (Pro-UK) during PCI in patients with acute STEMI. The present meta-analysis compared the efficacy and safety of intracoronary Pro-UK administration in patients with acute STEMI. Published randomized controlled trials (RCTs) were analyzed to compare Pro-UK with non-Pro-UK treatment in patients with acute STEMI. PubMed, Cochrane Library and China National Knowledge Infrastructure were searched and meta-analysis was performed using Review Manager 5.3 software. A total of 13 RCTs were selected and 1,797 patients were considered in the meta-analysis, including 897 patients who received Pro-UK intervention and 900 patients who were in the control group. No significant heterogeneity was identified across these selected studies. Pro-UK therapy significantly decreased the incidence of major adverse cardiac events [risk ratio (RR), 0.68; 95% CI, 0.56-0.82, P<0.0001], left ventricular end-diastolic diameter [standardized mean difference (SMD), -0.26; 95% CI, -0.40 - -0.12; P=0.0003], corrected thrombolysis in myocardial infarction (TIMI) frame count [SMD, -0.45; 95% CI, -0.62 - -0.28; P<0.00001] and cardiac troponin I [SMD, -0.31; 95% CI, -0.46 - -0.17; P<0.0001]. In addition, Pro-UK administration increased TIMI grade 3 flow (RR, 1.16; 95% CI, 1.07-1.25; P=0.0003), TIMI myocardial perfusion grade 3 (RR: 1.39, 95% CI: 1.12-1.74, P=0.004), ST-segment resolution (RR, 1.23; 95% CI, 1.10-1.36; P=0.0002) and left ventricular ejection fraction (SMD, 0.38; 95% CI, 0.27-0.49; P<0.00001). No significant difference was identified in bleeding (RR, 1.12; 95% CI, 0.85-1.47; P=0.41). The present meta-analysis determined that intracoronary Pro-UK administration is efficacious and safe to decrease slow blood flow or no reflow phenomena following PCI and improve the prognosis of patients with acute STEMI.

Exosomal miR-590-5p in Serum as a Biomarker for the Diagnosis and Prognosis of Gastric Cancer.

The purpose of this study is to explore the expression of miRNA-590-5p, an exosome of gastric cancer (GC), and to evaluate the suitability of miR-590-5p, an exosome with its own clinical characteristics. Serum samples from 168 gastric cancer patients and 50 matched controls were collected and exosomal RNAs were extracted. After that, miR-590-5p is analyzed by quantitative polymerase chain reaction (qRT-PCR), which is more related to clinical and pathological parameters and patient monitoring data. MGC-803 and HGC-27 cells were treated by miR-590-5p mimics, and then the changes of cell fluidity and invasiveness were monitored. The results showed that the expression level of miR-590-5p in exosomes of healthy observation group, early (I and II) stage group, and late stage (III) group was 30.34 ± 6.35, 6.19 ± 0.81, and 2.9 ± 0.19, respectively (all p < 0.05). ROC (receiver-operating characteristic curve) showed that the AUC (area under the curve) of exosomal miR-590-5p was 0.810 with 63.7% sensitivity and 86% specificity. The expression of exosomal miR-590-5p in serum was related to clinical stage (p = 0.008), infiltration depth, and the expression level of ki-67 (p < 0.001). In addition, Kaplan-Meier analysis showed that the decrease of explicit level of exosomal miR-590-5p was related to the decrease of overall survival rate (p < 0.001). Cox regression analysis showed that miR-590-5p can be used as an independent predictor. Furthermore, upregulation of miR-590-5p inhibited cell migration and invasion in MGC-803 cells and HGC-27 cells. The serum expression level of exosomal miR-590-5p may be a biomarker, which is potentially useful and noninvasive for early detection and prediction of GC. In addition, miR-590-5p can play a role in eliminating carcinogens by actively regulating the malignant potential of gastric cancer.

A novel near-infrared optical and redox-active receptor for the multi-model detection of Hg2+ in water and living cells.

A key issue for constructing optical and redox-active receptors is how to conjugate a specific sensing kernel with a multi-signal-responsive system to carry out multi-feature analysis. Mercury is considered to be highly toxic to human health and ecological security. In this work, we present a novel near-infrared optical and redox-active receptor that can sense Hg2+ at ppb level in aqueous media via multi-model monitors with a low detection limit of 8.4 × 10-9 M (1.68 ppb). This receptor features a visible detection, 'off-on' fluorescence response, and efficient electrochemistry assessment, as well as pH-insensitivity to Hg2+ with high sensitivity. In view of its marked near-infrared emission and fluorescence enhancement, we successfully applied this receptor to visualize Hg2+ in live cells. Furthermore, a possible sensing model was established and rationalized with theoretical studies.

New Pyridine-Bridged Ferrocene-Rhodamine Receptor for the Multifeature Detection of Hg2+ in Water and Living Cells.

A challenge in the design of optical and redox-active receptors is how to combine a specific recognition center with an efficient responsive system to facilely achieve multifeature detection in biological and environmental analyses. Herein, a novel ferrocene-rhodamine receptor conjugated with a pyridine bridge was designed and synthesized. This receptor can sensitively sense Hg2+ in aqueous media via chromogenic, fluorogenic, and electrochemical multisignal outputs with a low detection limit and fast response time. Moreover, it can be qualified as a fluorescent probe for effectively monitoring Hg2+ in living cells. A plausible recognition mode was proposed and rationalized with theoretical calculations.

Ag@S-nitrosothiol core-shell nanoparticles for chemo and photothermal synergistic tumor targeted therapy.

Along with the development of controlled delivery systems for targeted therapy, 'single-strategy' therapy often fails to achieve the desired performance in real body internal environments. In such a case, it is necessary to develop synergistic therapy strategies. Herein, for the first time, we designed and synthesized hyaluronic acid (HA) modified Ag@S-nitrosothiol core-shell nanoparticles for synergistic tumor cell targeted therapy based on photothermal therapy (PTT) and nitric oxide (NO) based chemotherapy. Triggered by near-infrared irradiation (NIR), the Ag core nanoparticle would convert the light to cytotoxic heat via a surface plasmon resonance mechanism for cancer cell apoptosis. Meanwhile, responding to NIR as well as the generated heat, the S-nitrosothiol polymeric shells would give off free NO at high concentration, inducing NO based chemotherapy. Tumor cell selective cytotoxicity assay in vitro as well as tumor bearing mouse experiments in vivo demonstrated the effective photothermal and NO based chemical synergistic tumor targeted therapy. This spatiotemporally controllable system could provide a new option and era for tumor targeted therapy in the future.

Rapid microwave synthesis of dioxin-linked covalent organic framework for efficient micro-extraction of perfluorinated alkyl substances from water.

To synthesize covalent organic framework (COF) via irreversible reactions is more challenging than by reversible ones. In this work, microwave-assisted synthesis is used to facilitate the nucleophilic substitution of 2,3,5,6-tetrafluoro-4-pyridinecarbonitrile with 2,3,6,7,10,11-hexahydroxy triphenylene. The dioxin-linked COF, named TH-COF, was efficiently synthesized with extraordinarily large surface area of 1254 m2 g-1. With its high crystallinity, excellent thermal and chemical stabilities, TH-COF is used as the coating for the solid-phase micro-extraction (SPME) of perfluorinated alkyl substances (PFASs). The adsorptive mechanism was evaluated with adsorption isotherm and kinetic adsorption. Adsorption energies are calculated based on the density functional theory. Following SPME with TH-COF-coated fibers, PFASs were eluted using 1 mL of 0.6% trifluoroacetic acid/methanol and analyzed through the ultra-performance liquid chromatography equipped with triple quadrupole mass spectrometer (UPLC-MS/MS). When applied to spiked real water samples, this method demonstrates good linearity (0.01-1000 ng L-1) with R2 ≥ 0.9945. The TH-COF-SPME-UPLC-MS/MS technique provides low limits of detection (0.0020-0.0045 ng L-1), excellent precision (≤ 7.9%), and good fiber-to-fiber reproducibility (≤ 7.1%). The TH-COF-coated fibers can be reused at least 20 times without the loss of extraction performance. In addition, the relative recoveries from spiked real water samples are 89.5%-105%.

Oral delivery of a Lactococcus lactis strain secreting bovine lactoferricin-lactoferrampin alleviates the development of acute colitis in mice.

Ulcerative colitis (UC) is a chronic relapsing disease. Treatment of UC would benefit from specific targeting of therapeutics to the intestine. Previous studies have demonstrated that bovine lactoferricin and lactoferrampin have bactericidal, anti-inflammatory, and immunomodulatory effects. Here, we investigated whether oral administration of a bovine lactoferricin-lactoferrampin (LFCA)-encoding Lactococcus lactis (LL-LFCA) strain could alleviate experimental colitis. LFCA derived from LL-LFCA inhibited the growth of Escherichia coli and Staphylococcus aureus in vitro. In mice, administration of LL-LFCA decreased the disease activity index and attenuated dextran sulfate sodium (DSS)-induced body weight loss and colon shortening. LL-LFCA treatment also ameliorated DSS-induced colon damage, inhibited inflammatory cell infiltration, significantly decreased myeloperoxidase activity, and ameliorated DSS-induced disruption of intestinal permeability and tight junctions. In addition, 16S rDNA sequencing showed that LL-LFCA reversed DSS-induced gut dysbiosis. The production of proinflammatory mediators in serum and the colon was also reduced by administration of LL-LFCA. In vitro, LFCA derived from LL-LFCA decreased the messenger RNA expression of proinflammatory factors. The underlying mechanisms may involve inhibition of the nuclear factor kappa B (NF-κB) pathway. The results demonstrate that LL-LFCA ameliorates DSS-induced intestinal injury in mice, suggesting that LL-LFCA might be an effective drug for the treatment of inflammatory bowel diseases.

Elevated expression of TREK-TRAAK K2P channels in the retina of adult rd1 mice.

AIM: To examine the expression of Twik-related K+ channel 1 (TREK-1), Twik-related K+ channel 2 (TREK-2), and Twik-related arachidonic acid-stimulated K+ channel (TRAAK) in the retina of adult rd1 mice and to detect the protective roles of TREK-TRAAK two-pore-domain K+ (K2P) channels against retinal degeneration. METHODS: Twenty-eight-day-old C57BL/6J mice and 28-day-old rd1 mice were used in this study. Retinal protein, retinal RNA, and embedded eyeballs were prepared from these two groups of mice. Real-time quantitative polymerase chain reaction and Western blot analyses were used to assess the gene transcription and protein levels, respectively. Retinal structures were observed using hematoxylin and eosin (H&E) staining. Immunohistochemistry was utilized to observe the retinal localization of TREK-TRAAK channels. Current changes in retinal ganglion cells (RGCs) after activation of TREK-TRAAK channels were examined using a patch-clamp technique. RESULTS: Compared with C57BL/6J mice, rd1 mice exhibited significantly higher retinal mRNA and protein expression levels of TREK-1, TREK-2, and TRAAK channels. In both groups, immunohistochemistry showed expression of TREK-TRAAK channels in retinal layers. After addition of the TREK-TRAAK channel agonist arachidonic acid (AA), whole-cell voltage step evoked currents were significantly higher in RGCs from rd1 mice than in RGCs from control C57BL/6J mice, suggesting that TREK-TRAAK channels were opened in RGCs from rd1 mice. CONCLUSION: TREK-TRAAK K2P channels' expression is increased in adult rd1 mice. AA induced the opening of TREK-TRAAK K2P channels in adult rd1 mice and may thus counterbalance depolarization of RGCs and protect the retina from excitotoxicity. TREK-TRAAK channels may play a protective role against retinal degeneration.

Magnetic core-shell S-nitrosothiols nanoparticles as tumor dual-targeting theranostic platform.

The external force guided targeting strategy, as well as the in vivo active targeting strategy based on "ligands-receptors" on the targeting cells and tissues have attracted much research interest. Herein, a kind of hyaluronic acid (HA) and folic acid (FA) modified magnetic S-nitrosothiols core-shell nanoparticles for nitric oxide (NO) control release as dual-tumor targeting theranostic platform were described, combining the external guidance and internal active targeting properties. Confocal microscopy assay and cells cytotoxicity experiments confirmed the active tumor cells targeting recognition, cells uptake, and NO initiated cytotoxicity of the HA-FA external functional layer modified S-nitrosothiols nanoparticles in vitro. In vivo magnetic resonance imaging (MRI) characterization, bio-distribution assay in organs and tumor, significant tumor inhibition efficacy, survival units of the mice bearing tumor, as well as the systemic toxicity assay demonstrated the efficiency of cooperative tumor targeting diagnosis and controlled NO-releasing chemotherapy. To the best of our knowledge, this is the first time of the external magnet and HA-FA actively induced synergistic effect tumor targeting systems based on NO chemotherapy in vivo, serving as a new theranostic system.

Sensitization and synergistic anti-cancer effects of Furanodiene identified in zebrafish models.

Furanodiene is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anticancer effects in various types of cancer cell lines. In this study, we have successfully established zebrafish xenografts with 5 various human cancer cell lines; and validated these models with anti-cancer drugs used clinically for treating human cancer patients. We found that Furanodiene was therapeutically effective for human JF 305 pancreatic cancer cells and MCF-7 breast cancer cells xenotranplanted into zebrafish. Furanodiene showed a markedly synergistic anti-cancer effect when used in combination with 5-FU (5-Fluorouracil) for both human breast cancer MDA-MB-231 cells and human liver cancer BEL-7402 cells xenotransplanted into zebrafish. Unexpectedly, Furanodiene reversed multiple drug resistance in the zebrafish xenotransplanted with cis-Platinum-resistant human non-small cell lung cancer cells and Adriamycin-resistant human breast cancer cells. Furanodiene played its anti-cancer effects through anti-angiogenesis and inducing ROS production, DNA strand breaks and apoptosis. Furanodiene suppresseed efflux transporter Pgp (P-glycoprotein) function and reduced Pgp protein level, but no effect on Pgp related gene (MDR1) expression. These results suggest sensitizition and synergistic anti-cancer effects of Furanodiene that is worthy of a further investigation.

Amino-modified covalent organic framework as solid phase extraction absorbent for determination of carboxylic acid pesticides in environmental water samples.

The amino-modified covalent organic framework (NH2@COF) was synthesized via the thiol-ene click reaction of vinyl covalent organic framework (COF) with 4-aminobenzenethiol. The introduction of amino groups can interact with the anionic headgroup of carboxylic acid pesticides. Moreover, ample hydrophilic surface area can boost absorption in the water media. The NH2@COF was fully characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. Compared with vinyl COF and four commercial absorbents, the NH2@COF shows higher extraction efficiency for carboxylic acid pesticides. The solid phase extraction (SPE) conditions, involving flow rate, ionic strength, sample pH, desorption solvent, and desorption solvent volume, were optimized in details. Under the optimized conditions, the NH2@COF was successfully applied for the enrichment and determination of six carboxylic acid pesticides in environmental water samples combined with high performance liquid chromatography. The method features wide linearity (0.2-100 ng mL-1, r > 0.999), low limits of quantification (0.04-0.20 ng mL-1), and excellent precision (RSDs ≤ 8.7%). The recoveries range from 89.6% to 102.4% with RSDs ≤ 7.1%. Therefore, the NH2@COF-SPE method is an efficient pretreatment procedure and can be utilized for the selective extraction of carboxylic acid pesticides from environmental water samples.

Molecular imprinted S-nitrosothiols nanoparticles for nitric oxide control release as cancer target chemotherapy.

It is the goal for the development of cancer target chemotherapy with specific recognition, efficient killing the tumor cells and tissues to avoid the intolerable side effects. Molecular imprinted polymer (MIPs) nanoparticles could introduce kinds of specific bio-markers (template molecules) into the nanoparticles with the subsequent removal, leaving special holes in the structure with predictable recognition specificity with cells. Herein, we design and synthesize a kind of sialic acid (SA) over-expressed tumor target hollow double-layer imprinted polymer nanoparticles with S-nitrosothiols for nitric oxide (NO)-releasing as chemotherapy. Equilibrium/selective bindings properties and probe experimental results implies that the MIPs have an intelligently selective binding to cancer cells featuring high levels of SA glyans, providing precondition for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO-releasing. Cytotoxicity assay with kinds of cells demonstrates the intelligent in vitro SA over-expressed tumor cells targeting recognition, intracellular delivery and cytotoxicity. In vivo bio-distribution in tumor sites and major organs, significant suppression of tumor growth, tumor-bearing mice survival unit, and the systemic toxicity investigation experiments confirm the effective chemotherapy of the S-nitrosothiols MIPs nanoparticles for the target recognition and the controlled NO release for tumor treatment comparing to the results with S-nitrosothiols CPs as delivery system. The inevitable small amount of NO leakage from S-nitrosothiols MIPs would take part in normal physiological activities and not cause serious side effects. For the first time, this kind of nitric oxide based chemotherapy and molecular-imprinting cell recognition technique both in vitro and in vivo, might provide a solution for accurate therapy to various forms of cancer with specific markers and avoid the intolerable side effects of the traditional chemotherapy treatment.