Dynamic evaluation of the prognostic value of 18F-FDG PET/CT in extranodal NK/T-cell lymphoma, nasal type.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.

Rhodoptilometrin, a Crinoid-Derived Anthraquinone, Induces Cell Regeneration by Promoting Wound Healing and Oxidative Phosphorylation in Human Gingival Fibroblast Cells.

Gingival recession (GR) potentially leads to the exposure of tooth root to the oral cavity microenvironment and increases susceptibility to dental caries, dentin hypersensitivity, and other dental diseases. Even though many etiological factors were reported, the specific mechanism of GR is yet to be elucidated. Given the species richness concerning marine biodiversity, it could be a treasure trove for drug discovery. In this study, we demonstrate the effects of a marine compound, (+)-rhodoptilometrin from crinoid, on gingival cell migration, wound healing, and oxidative phosphorylation (OXPHOS). Experimental results showed that (+)-rhodoptilometrin can significantly increase wound healing, migration, and proliferation of human gingival fibroblast cells, and it does not have effects on oral mucosa fibroblast cells. In addition, (+)-rhodoptilometrin increases the gene and protein expression levels of focal adhesion kinase (FAK), fibronectin, and type I collagen, changes the intracellular distribution of FAK and F-actin, and increases OXPHOS and the expression levels of complexes I~V in the mitochondria. Based on our results, we believe that (+)-rhodoptilometrin might increase FAK expression and promote mitochondrial function to affect cell migration and promote gingival regeneration. Therefore, (+)-rhodoptilometrin may be a promising therapeutic agent for GR.

Nanocarbon material-supported conducting poly(melamine) nanoparticle-modified screen-printed carbon electrodes for highly sensitive determination of nitrofuran drugs by adsorptive stripping voltammetry.

The toxicity of nitrofuran drugs has attracted great attention, and the reported electroanalytical methods suffered limited sensitivity. In this work, a sensitive electrochemical assay in the cathodic region is developed to determine four nitrofuran derivatives, including nitrofurantoin (NFT), nitrofurazone (NFZ), furaltadone (FTD), and furazolidone (FZD). The screen-printed carbon electrode (SPCE) was used as the electrode substrate, and the sensing surface was composed of multi-walled carbon nanotube (MWCNT) and conducting poly(melamine) (PME). The overoxidation-pretreated MWCNTs affect the surface morphology of the electrodeposited PME and, thus, the interaction with nitrofuran drugs. The characteristics of the nanocomposite-modified electrode surfaces were well characterized by field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and surface water contact angle experiments. The nanocomposite-modified electrodes exhibited excellent adsorption and electrochemical reduction of nitrofurans by cyclic voltammetry. The proposed assay exhibited a linear range of sub-micro to micro molar concentrations for the four drugs under the optimized differential pulse voltammetric (DPV) technique. The detection limits were found to be in the nanomolar ranges. The developed assay was applied to detect NFT in two real samples, and the results showed good recoveries that ranged from 99.0 to 104.8% and 98.0 to 103.2% for milk and lake water samples, respectively. Graphical abstract ᅟ.

Production and characterization of pellets using Avicel CL611 as spheronization aid.

PURPOSE: The study looked into the feasibility of producing pellet using Avicel CL611 as spheronization aid by the extrusion/spheronization technique. METHODS: Pellets were formulated to contain either 20% or 40% Avicel CL611 and lactose monohydrate as the other sole ingredient. Water is used as liquid binder. Quality of pellets and extrudates were analyzed for size distribution, shape, surface tensile strength and disintegration profile. RESULTS: More water was needed when higher Avicel CL611 fraction was used during the production of pellets. The pellets of larger size were obtained by increasing the water content. Pellets with aspect ratios of ∼1.1 were produced with high spheronization speed at short residence time. Higher tensile strength was achieved when increasing the water content and the fraction of Avicel CL611 during pellet production. These pellets also took longer time to disintegrate, nonetheless all the pellets disintegrated within 15 min. A positive linear relationship was obtained between the tensile strength and time for pellets to disintegrate. CONCLUSION: Strong but round pellets that disintegrate rapidly could be produced with Avicel CL611 as spheronization aid using moderately soluble compounds such as lactose.

Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma.

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24-74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43-79%) and 68% (95%CI, 47-84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45-83%) and 86% (95%CI, 63-95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

Preparation and characterization of enteric microparticles by coacervation.

The aim of this study was to produce cinnarizine loaded Eudragit(®) L100-55 microparticles by coacervation technique in order to achieve pH responsive drug release using hydroxypropyl methycellulose (HPMC) as stabilizer. The effect of enteric polymer: HPMC ratio on properties of microparticles was investigated with regard to particle size distribution, morphology, yield, encapsulation efficiency, in vitro drug release profiles and interaction between cinnarizine and Eudragit(®) L100-55. High drug encapsulation efficiency was seen in all microparticles. Particle diameter increased when the enteric polymer content was higher relative to HPMC. In vitro dissolution studies demonstrated that the drug release from the microparticles was dependent upon enteric polymer: HPMC ratio and particle size distribution. At the ratio of at least 3.75:1 of enteric polymer: HPMC, drug release was suppressed most significantly in low pH (hydrochloric acid as medium) while rapid drug release was observed in pH 7.4.

Effect of formulation compositions on niosomal preparations.

This study was aimed to investigate the effects of molar ratio of cholesterol to Span 60 and stabilizers (Solutol HS 15 or dicetyl phosphate (DCP)) on the entrapment of methylene blue, a model hydrophilic drug. The niosomes were prepared by the film hydration method and characterized for drug entrapment efficiency (EE), vesicle size, zeta potential and thermal properties of niosomal membrane. It was found that niosomal vesicles possessed median diameter ranging from 0.35 to 1.85 µm. The niosomes that were formulated with lower molar ratios of cholesterol to Span 60 of 0.33 and 0.50 produced significantly higher EE with both stabilizers when compared to cholesterol to Span 60 molar ratios of 1.0 and above (p < 0.05). The EE of niosomes stabilized with DCP was significantly higher (p < 0.05) than those prepared with Solutol HS 15 except at a molar ratio of cholesterol to Span 60 of 0.33. In conclusion, with low molar ratios of cholesterol to Span 60, more drugs could be entrapped within the niosomes regardless of the type of stabilizers. Furthermore, EE and median diameter of niosomes containing DCP were higher than those stabilized with Solutol HS 15.

Submucosal Injection of Activated Platelet-Rich Plasma for Treatment of Periodontal Disease in Dogs.

Periodontal disease is the most common oral disease seen in dogs, and its routine treatment usually involves dental scaling. Platelet-rich plasma (PRP) therapy may enhance the effectiveness of treatment of periodontal disease, delay the progression of the disease and decrease the time under anesthesia. However, its application in dogs is rarely discussed. The objective of this study was to evaluate the benefits of activated PRP for treatment of periodontal disease in dogs. 43 mL of whole blood was collected from six adult dogs and PRP extracted using the double centrifugation tube method. Subsequently, the PRP was activated using calcium chloride (A-PRP). Significantly elevated concentrations of PDGF-BB (7000.28 pg/mL), TGF-ß (378.98 pg/mL), and VEGF (7.14 pg/mL) were detected in the A-PRP. Additionally, three of the dogs with stage 2-3 periodontal disease were enrolled in the clinical trial. Periodontal pocket depth, stage of periodontal disease, gingival index, horizontal bone loss, and alveolar bone density involving the maxillary third and fourth premolar and first molar teeth (107, 108, 109, 207, 208, and 209) were evaluated. Teeth were treated by dental scaling alone (control group) or by dental scaling followed by submucosal injection of 0.1 mL A-PRP per site. After 56 days, significant improvement in periodontal pocket depth, stage of periodontal disease, gingival index, and horizontal bone loss was observed in dogs injected with A-PRP. The high concentrations of growth factors in A-PRP likely contributed to this effect. The use of submucosal injections of A-PRP to treat canine stage 2-3 periodontal disease appears safe and effective for clinical practice.

Engineered autologous bone marrow mesenchymal stem cells: alternative to cleft alveolar bone graft surgery.

Human recombinant bone morphogenetic protein 2 (rhBMP-2) accelerates bone regeneration but is associated with limited cementum and periodontal ligament regeneration, local root resorption, and ankylosis. This study assessed a new approach to the regeneration of the alveolar bone and periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication defective adenovirus to express the BMP-2 gene and pluronic F127 (PF127) in a large mammalian animal model. Bilateral maxillary periodontal defects were created over the premolar area in 9 mature male miniature swine. The 18 defects were randomly assigned to receive either BMP-2-expressing MSCs in the advBMP-2 group or MSCs alone in the MSC group. The regenerated periodontal attachment apparatus was evaluated histologically, and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis. Three months after implantation, significant bone volume was regenerated in the advBMP-2 group. Periodontal apparatus regeneration was significantly better in the advBMP-2 group. New cementum and Sharpey fibers were observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete healing with localized root surface resorption was noted in the control group. The use of ex vivo BMP-2-engineered autologous MSCs enhanced bone and periodontal apparatus regeneration in maxillary alveolar and periodontal defects in swine. This novel integrated approach might be suitable for clinical periodontal apparatus repair. This may be an alternative for cleft alveolar bone graft surgery.

Formulation and in vitro evaluation of self-emulsifying formulations of Cinnarizine.

The main objectives of this study were to improve the aqueous solubility and to modify in vitro dissolution profile of hydrophobic drug using self-emulsifying drug delivery systems (SEDDS). SEDDS were formulated using Capmul PG-12, Cremophor RH 40 and Tween 20 at different weight ratios and incorporated with Cinnarizine. The drug incorporation into pre-concentrate and drug solubility in phosphate buffer (pH 7.2) were investigated. In addition, the mean droplet size and drug release profile of the SEDDS were also determined. The drug incorporation was over 120 mg per 0.5 g pre-concentrate regardless of the composition of the formulations. The solubility of Cinnarizine in phosphate buffer (pH 7.2) was at least 1500 µM in the SEDDS. Formulations with only 10% w/w Capmul PG-12 were less than 20 nm in mean diameter while those produced with at least 20% w/w Capmul PG-12 were more than 100 nm regardless of the ratios of Cremophor RH 40 to Tween 20. SEDDS showed a significant increase of the mean percentage drug release than pure drug (p < 0.0001). In general, the SEDDS with 30% w/w of Capmul PG-12 provided the greatest enhancement in drug solubility in phosphate buffer as well as rapid drug release despite forming larger droplets upon emulsification. The combination of Capmul PG-12, Tween 20 and Cremophor RH 40 can produce SEDDS which can be used as an alternative dosage form for poorly water soluble drug.

[Characteristics, Sources, and Risk Assessment of Perlyfluoroalkyl Substances in Surface Water and Sediment of Luoma Lake].

Through the investigation and detection of the surface water and sediments of Luoma Lake, the structure and occurrence characteristics of PFASs (perlyfluoroalkyl substances) in the two types of media were analyzed, and the principal component analysis method was used to analyze the characteristics of such substances in the surface water. The source was analyzed, and the potential health risks of such substances were evaluated using the risk quotient method. The results showed that a total of 13 PFASs were detected in the surface sediments of Luoma Lake, and one more species was detected in the surface water (PFTeA); ρ(ΣPFASs) in the surface water ranged from 46.09 to 120.34 ng·L-1, and ω(ΣPFASs) in sediments ranged from 2.22 to 9.55 ng·g-1. PFPeA was the major component in surface water, and the mass fraction of PFPeA was 38%. PFBA was the major component in sediment, and the mass fraction of PFPeA was 61%. The multi-media PFASs in Luoma Lake were mainly short-chain substances; the high concentration area of PFASs in the surface water of Luoma Lake was concentrated and distributed at the mouth of the northern rivers. Its concentration showed a decreasing trend from north to south, and the content of PFASs in the sediments showed a decreasing trend from southwest to northeast. The distribution of ΣPFASs, PFBA, and PFOS in the sediments of Luoma Lake and the TOC content in the sediment were related; the principal component analysis showed that the PFASs in the surface water of Luoma Lake were mainly from textile flame retardant, rubber product emulsification, food packaging processes and paper surface treatment industries, the metal electroplating industry, and leather and textile manufacturing industries. PFASs in the surface water of Luoma Lake were at a relatively low health risk level.

Effect of thermocycling-induced stress on properties of orthodontic NiTi wires.

Background/purpose: In orthodontic applications, NiTi wires are under continuous bending stress and exposed to fluctuations in temperature over long durations. The sensitivity of NiTi to temperature can have a considerable influence on its mechanical properties. This study investigated the effects of deflected NiTi wire, presented in stress-induced (detwinned) martensite microstructure, combined with thermal cycle on the microstructure and mechanical properties. Materials and methods: We tested four types of as-received orthodontic NiTi: (1) Nitinol Classic (3 M Unitek), (2) Sentalloy (Tomy), (3) 27 °C CuNiTi (Ormco) and (4) 40 °C CuNiTi (Ormco). Each group of specimens was subjected to three different testing conditions: (1) temperature fluctuations (5000 cycles) between 5 and 55 °C, (2) continuous three-point bending force and (3) combination of thermal cycling and bending stress. Results: The specimens that underwent thermocycling as well as loading exhibited a substantial narrowing in stress hysteresis, which may be attributed to crystallinity lower than that of as-received NiTi wires. Reduced crystallinity can manifest in a number of imperfections, such as dislocations and internal stress, as well as a less-organized structure. Micro X-ray diffraction (XRD) analysis revealed the existence of martensite phase in Sentalloy wires subject to thermal and stress conditions. Under loading conditions, stress-induced martensite of NiTi wires exposed to temperature fluctuations of 5-55 °C also induced cyclic changes in bending stress. In a simulated intra-oral environment, the stability of austenite↔martensite transformation decreased. Conclusion: This study determined that bending stress in conjunction with repeated temperature fluctuations can greatly affect the microstructure and mechanical properties of NiTi wires.

The fusion peptide domain is the primary membrane-inserted region and enhances membrane interaction of the ectodomain of HIV-1 gp41.

To execute the membrane fusion function, it is necessary for the fusion protein of the virus to penetrate into the hydrophobic milieu of membrane bilayer. Hence identification of the region(s) of the ectodomain of viral fusion proteins involved in the membrane insertion and their interaction with the rest of the fusion protein in the membrane would be important for the mechanistic study of membrane fusion. To this end, we examined membrane activity of the fusion peptide, and the ectodomain protein with or without the fusion peptide domain of HIV-1 gp41 by several biophysical measurements. The results revealed that the ectodomain protein containing the fusion peptide domain had higher membrane-perturbing activity and deeper membrane insertion, while the construct lacking the fusion peptide domain had much lower membrane activity. Strikingly, the N-terminal heptad repeat region was found to be induced deeper into the membrane by the fusion peptide, consistent with the role of the latter in the membrane penetration. We concluded that the fusion peptide is the only stretch of gp41 ectodomain that embeds deeply in the membrane interior in the prefusion stage. The function of fusion peptide in terms of membrane interaction and the implications of its interplay with other domains of gp41 on the membrane fusion cascade were discussed.

PEGylated polymeric nanocapsules for oral delivery of trypsin targeted to the small intestines.

The lack of trypsin in the intestines may end up with malnutrition; thus, trypsin replacement therapy is required in such cases. The main objective of this study is to formulate and evaluate polymeric nanocapsule (PNC) systems able to deliver trypsin to the small intestines with the minimal release in the stomach with the maximum biological activity. Four nanocapsule formulations were prepared by double emulsion/evaporation method as w/o/w and s/o/w. Particle size, encapsulation efficiencies, drug release in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF), morphology, the biological activity of encapsulated trypsin and shelf-life stability were investigated for all formulations. All formulations had a spherical shape with submicron size, and encapsulation efficiency more than 80%. The biological activity of encapsulated trypsin was significantly affected by the amount of trehalose and whether the formulations were prepared as s/o/w or w/o/w (P < 0.05). Most of the encapsulated protein was released sustainedly at the target site (SIF) over 24 h with minimum amount release in the gastric fluids. Also, more than 90% of physical integrity trypsin encapsulated in all formulations was retained after storage under chilled conditions for six months. However, the enzymatic assay results show that with low trehalose content, the biological activity was low, while increasing the trehalose amount increased the shelf stability to reach around 100% after six months of the study. The results obtained in this research work clearly indicated a promising potential of controlled release polymeric nanocapsules containing trypsin to target the small intestine and protect trypsin from the harsh condition facing the proteins during the process of preparation or the period of storage.

Fabrication of bacteriochlorin shell/gold core nanoparticles for the sensitive determination of trichlosan using differential pulse voltammetry.

The triclosan contamination in daily life has attracted great attention, and there is rare electroanalytical assay based on π-system dyes. In this work, a facile preparation and electroanalytical application of an organic dispersion containing bacteriochlorin dyes (LS11) and gold nanoparticles (AuNPs) was proposed. The organic-inorganic hybrid nanocomposites were characterized by transmission electron microscope (TEM) showing a core-shell structure with a uniform layer of dye molecules. The as-prepared nanocomposites were successfully coated onto glassy carbon electrodes, and the surface characteristics of the top most layer of the modified electrodes were examined by atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM) and water contact angle experiments. The nanocomposite film-modified electrodes exhibited good electrochemical activity towards oxidation of triclosan. The oxidation of adsorbed triclosan occurred at a reduced overpotential, and the anodic current responses under a pre-concentration step prior to the potential scan were used for quantitative analysis. A good linear relationship from 0.01 µM to 0.5 µM was obtained using differential pulse voltammetry. The sensitivity and detection limit (S/N = 3) were 23.69 µA µM-1 and 0.03 µM, respectively. The proposed assay was applied to detect triclosan in two personal hygiene products using standard addition method, and the results showed good recoveries that ranged from 96.6% to 101.5% and from 99.3% to 103.8% for a toothpaste sample and a hand wash sample, respectively. A reference HPLC-UV method was used to evaluate the proposed electroanalytical method, and a good agreement was achieved.

Ciclosporin-loaded poly(lactide) microparticles: effect of TPGS.

The properties of spray dried PLA microparticles were affected by the choice of solvents, amount of ciclosporin and TPGS added. Ethyl acetate formed microparticle with smooth surface when compared to those produced by dichloromethane. The results of FTIR have not shown chemical interaction amongst PLA, ciclosporin and TPGS while thermal analysis showed physical interactions amongst these components. TPGS was found to lower Tg value of PLA by exerting a plasticizing effect while ciclosporin reverted this effect. When the content of TPGS increased from 2% (w/w) to 10% (w/w), the microparticles tended to agglomerate due to the lowering of the polymer Tg values at the employed spray drying temperature. In addition, a lesser amount of ciclosporin was found at the surface of the microparticle and resulted in smaller initial release of ciclosporin. When 2% (w/w) TPGS was used, the initial release of ciclosporin was enhanced and the microparticles formed were not agglomerated.

A novel electroanalytical assay for sulfamethazine determination in food samples based on conducting polymer nanocomposite-modified electrodes.

The toxicity of sulfa drugs has attracted great attention, and the reported electrochemical methods for sulfa drugs usually employ a high oxidation potential. In this work, a one-pot synthesized conducting polymer nanocomposite containing poly(3,4-ethylenedioxythiophene) (PEDOT) and MnO2 was cast on a screen-printed carbon electrode (SPCE), and the modified electrode showed superior electrochemical activity over a bare electrode for sulfamethazine (SMZ) determination. The SMZ detection was based on the electrochemical oxidation product, which showed an adsorptive property and exhibited a redox couple at 0.39V in pH 3 phosphate buffer solutions (PBS). The electrode surfaces were well characterized by the water contact angle technique, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and cyclic voltammetry. By the use of square wave voltammetry (SWV), a wide linear response to SMZ, from 1.0µM to 500µM, was obtained. The sensitivity and detection limits (S/N = 3) were 0.115µAµM-1 and 0.16µM, respectively. The proposed method and a reference high-performance liquid chromatographic method (HPLC) were applied for the determination of SMZ in two real samples using the standard addition method, and satisfactory recoveries and good agreement were obtained.

Highly sensitive and selective sensor for sunset yellow based on molecularly imprinted polydopamine-coated multi-walled carbon nanotubes.

Polydopamine (PDA) can be formed by monomeric self-polymerization in water. This convenient behavior was exploited to prepare a molecularly imprinted polymer (MIP) layer on the surface of multi-walled carbon nanotubes (MWCNTs) with sunset yellow (SY) as a template molecule. The prepared nanocomposites were characterized, and their electrochemical behavior towards SY was investigated. Under the optimized conditions, a glassy carbon electrode modified with the imprinted nanocomposite showed a highly selective and ultrasensitive electrochemical response to SY compared with the performance of control electrodes and previously reported electrochemical sensors for SY. The improved behavior of the developed sensor can be attributed to its superficial highly matched imprinted cavities on the excellent electrocatalytic matrix of MWCNTs and the electronic barrier of the non-imprinted PDA to outside molecules. The fabricated sensor expressed a linear relationship to SY concentrations from 2.2nM to 4.64µM with a detection limit of 1.4nM (S/N = 3). The sensor also exhibited excellent selectivity for SY over its structural analogs, good stability, and adequate reproducibility. The prepared sensor was successfully used to detect SY in real spiked samples. This methodology has potential application value and may be readily adapted to design other PDA-based MIP sensors.

Sensing capability of the localized surface plasmon resonance of gold nanorods.

We demonstrate the feasibility of using the longitudinal component of gold nanorod's surface plasmon resonance in biomolecular sensing. The sensitive dependence of the absorption maximum on the dielectric constant of the particle interfacial region makes gold nanorods a promise for constructing a biomolecular sensing scheme. The sensor containing gold nanorods, with a mean aspect ratio of 5.2, exhibits a sensitivity of ca. 366 nm/RIU (refractive index unit), which increases accordingly with the increase of the particle mean aspect ratios. Such a biosensor was further modified to demonstrate its effectiveness in quantitative detection for selective binding events, such as biotin/streptavidin pairs, through a process in which biotin molecules were chemically attached to the gold nanorods' surface prior to detection measurements. Results showed that the spectral lambda(max) shifts linearly to the concentrations of the streptavidin. The results from both experiment and model calculations strongly indicate the efficacy of the longitudinal surface plasmon absorption band in biosensing.

A Phase II Study of Methotrexate, Etoposide, Dexamethasone and Pegaspargase Sandwiched with Radiotherapy in the Treatment of Newly Diagnosed, Stage IE to IIE Extranodal Natural-Killer/T-Cell Lymphoma, Nasal-Type.

BACKGROUND: A phase II study of methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) sandwiched with radiotherapy for newly diagnosed, stage IE-IIE extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL) was conducted to explore its clinical efficacy and safety, as well as novel serum biomarkers upon anti-metabolic treatment. METHODS: Four cycles of MESA sandwiched with radiotherapy were administered. The primary end point was the overall response rate (ORR). Serum metabolomic profiles were assessed by liquid chromatography-mass spectrometry, with specific metabolites quantified by targeted metabolic analysis. FINDINGS: Forty patients were enrolled and the ORR was 92.1% (95%CI, 83.1%-100.0%). The 2-year progression-free survival (PFS) rate was 89.1% and overall survival (OS) rate was 92.0%. Grade 3/4 non-hematologic and hematologic toxicities were observed in 17 (42.5%) and 26 patients (65·0%) during chemotherapy, and in 9 (22.5%) and 0 (0.0%) patients during radiotherapy, respectively. Fifty-six significantly decreased and 59 increased metabolites were identified in ENKTL, as compared to healthy volunteers. A predictive principal components analysis model of asparaginase-associated metabolites, asparaginase-associated metabolic score (AspM), was established, including alanine, aspartate, glutamate, and succinic acid. Patients with high AspM score displayed superior survival and prognostic significance of AspM was validated in a historical cohort of early and advanced-stage ENKTL treated with asparaginase-based regimens. Multivariate analysis confirmed AspM as a prognostic score independent of PINK and PINK combined with Epstein-Barr virus DNA. INTERPRETATION: MESA sandwiched with radiotherapy is an effective and safe regimen for early-stage ENKTL. AspM score may be a promising prognostic index of serum metabolites in addition to clinical prognostic index in ENKTL.