Spatiotemporally sequential delivery of biomimetic liposomes potentiates glioma chemotherapy.

As one of the most challenging cancers, glioma still lacks efficient therapeutic treatment in clinics. The dilemmas of nanodrug-based therapies for glioma are due not only the limited permeability of the blood-brain barrier (BBB) but also the deficiency of targeting tumor lesions. Thus, spatiotemporally sequential delivery of therapeutics from BBB-crossing to glioma accumulation is considered a strategy to obtain better outcomes. Here, we developed a biomimetic chemotherapy nanodrug composed of the hybrid membrane envelope of U87 cell membranes and RAW264.7 cell membranes, and the core of paclitaxel (PTX)-loaded liposome (PTX@C-MMCL). In the research, PTX@C-MMCL showed superior ability to cross the BBB via RAW264.7 cell membranes and accurate targeting to the brain tumor lesions relying on the homotypic targeting capacity of U87 cell membranes. Furthermore, PTX@C-MMCL can maintain a prolonged circulation in vivo. Importantly, PTX@C-MMCL effectively inhibited the development of glioma. Conclusively, our biomimetic nanodrug holds great potential for brain tumor targeting therapy.

Evaluation of poly(N-isopropylacrylamide)/tetraphenylethylene/amphotericin B-based visualized antimicrobial nanofiber wound dressing for whole skin wound healing in rats.

The aim of this work is to develop a novel nanofiber wound dressing with multiple functional properties that combines suitable mechanical properties, slow and controlled drug release, antifungal activity, and visual drug monitoring to accelerate wound healing while reducing systemic circulation of the drug, achieving reduced dose and side effects, and achieving patient satisfaction and compliance. In this paper, visualized nanofiber films were prepared using electrostatic spinning technology. This nanofiber wound dressing has soft tissue-like mechanical and antifungal properties and is biocompatible. In particular, the poly(N-isopropylacrylamide) (PNIPAAm)/tetraphenylethylene (TPE)/amphotericin B (AMB) nanofiber films showed good performance in terms of antifungal activity and cytocompatibility compared with medical gauze, and significantly accelerated the wound healing process in a mouse total wound defect model with PCL+PVP+TPE+AMB+PNIPAAm. The wound healing rate of nanofibrous membrane group was 100% at 14 days. In addition, histological analysis, collagen deposition and immunohistochemistry showed, for example, fewer inflammatory cells, more fibroblasts around the damaged area, increased wound epithelial atrophy, reduced granulation tissue, connective tissue reconstruction, epithelial tissue formation, and abundant small angiogenesis in the dermis near the epidermis; a higher level of collagen deposition fraction of 49.97%; and a simultaneous reduction in HIF-1α production and upregulated the expression of CD31. In conclusion, this antifungal nanofiber film showed promising applications throughout the skin wound healing process.

Sequentially sustained release of anticarcinogens for postsurgical chemoimmunotherapy.

Postsurgical treatment is of great importance to combat tumor recurrence and metastasis. Anti-CD47 antibodies (aCD47) can block the CD47-signal regulatory protein-alpha (CD47-SIRPα) pathway to restore immunity. Here, an in-situ gel implantation was engineered by crosslinking chitosan (CS) and pullulan (Pul) for postsurgical treatment. A highly selected chemotherapeutic, cyclopamine (Cyc), encapsulated in liposomes (Cyc-Lip) was co-loaded with aCD47 in gels for chemoimmunotherapy. Importantly, a sequential drug release kinetics can be achieved. Nanotherapeutics were confirmed to be released prior to aCD47 in a burst-release manner, which was benefit for immediately killing residual tumor cells followed by releasing tumor antigens. Meanwhile, aCD47 was released in a sustained-release manner to restore macrophage functions and exert anti-tumor immune responses. Afterwards, the efficacy of in-situ chemoimmunotherapy was confirmed on 4T1 mouse breast cancer models, which could not only efficiently augment anti-tumor effect to inhibit tumor recurrence but also establish a long-term immune memory to combat tumor metastasis.

Fabrication of a hierarchical nanoreactor based on COFs for cascade enzyme catalysis.

A hierarchical nanoreactor based on covalent organic frameworks (COFs) was fabricated using polystyrene spheres (PSs) as a template. When applied in cascade catalysis, the nanoreactor significantly improved the catalytic activity of internal enzymes, and showed protection for the enzyme in harsh environments. Moreover, glucose can be sensitively detected (detection sensitivity: 10 µM) by the nanoreactor.

Deeply Infiltrating iRGD-Graphene Oxide for the Intensive Treatment of Metastatic Tumors through PTT-Mediated Chemosensitization and Strengthened Integrin Targeting-Based Antimigration.

A limited infiltration and the subsequent low effective drug concentration result in poor chemotherapeutic outcomes against tumors, and even further promote tumor resistance and metastatic. Herein, iRGD-modified graphene oxide (GO) nanosheets (IPHG) are developed for the intensive treatment of metastatic tumors using focus-specific penetrated delivery together with photothermal therapy-mediated chemosensitization and photothermal therapy-strengthened integrin targeting-based antimigration. In vitro and in vivo data verified the mechanism of the tumor-selective infiltration of IPHG is based on a rigid 2D structure-associated advantage regarding hemodynamics and endothelial contact, followed by iRGD-endowed transendothelial and intratumoral transport. Once IPHG-DOX-penetrated 4T1 tumors are exposed to near-infrared irradiation, hyperthermia stress and photothermal therapy-elevated effective drug concentrations result in chemosensitization and prominent tumor suppression. Meanwhile, the specific binding of iRGD to integrins and photothermal therapy leads to the synergistic perturbation of cytoskeleton remodeling and subsequent impairment of cell motility and metastasis. The tailored design of IPHG validates a promising paradigm for drug delivery to combat tumor resistance and metastasis resulting from poor target access for single chemotherapy.

Study of the isomeric Maillard degradants, glycosylamine and Amadori rearrangement products, and their differentiation via MS2 fingerprinting from collision-induced decomposition of protonated ions.

RATIONALE: The focus of this work was to study glycosylamine and Amadori rearrangement products (ARPs), the two major degradants in the Maillard reactions of pharmaceutical interest, and utilize their MS2 fingerprints by liquid chromatography/high-resolution tandem mass spectrometry (LC/HRMS2 ) to quickly distinguish the two isomeric degradants. These two types of degradants are frequently encountered in the compatibility and stability studies of drug products containing primary or secondary amine active pharmaceutical ingredients (APIs), which are formulated with excipients consisting of reducing sugar functionalities. METHODS: Vortioxetine was employed as the primary model compound to react with lactose to obtain the glycosylamine and ARP degradants of the Maillard reaction, and their MS2 spectra (MS2 fingerprints) were obtained by LC/MS2 . Subsequently, the two degradants were isolated via preparative HPLC and their structures were confirmed by one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) determination. RESULTS: The MS2 fingerprints of the two degradants display significantly different profiles, despite the fact that many common fragments are observed. Specifically, protonated glycosylamine shows a prominent characteristic fragment of [Mvort + C2 H3 O]+ at m/z 341 (Mvort is the vortioxetine core), while protonated ARP shows a prominent characteristic fragment of [Mvort + CH]+ at m/z 311. Further study of the Maillard reactions between several other structurally diverse primary/secondary amines and lactose produced similar patterns. CONCLUSIONS: The study suggests that the characteristic MS2 fragment peaks and their ratios may be used to differentiate the glycosylamine and ARP degradants, the two isomeric degradants of the Maillard reaction, which are commonly encountered in finished dosage forms of pharmaceutical products containing primary and secondary amine APIs.

Effects of Morphologies of Thermosensitive Electrospun Nanofibers on Controllable Drug Release.

Electrospun nanofibers is a promising and versatile avenue for building controlled drug release system because of the facile fabrication and the broad range of polymer materials. This research systematically studied the morphological effect of thermosensitive electrospun nanofibers, including porous and coaxial structures, on controllable drug release. Three types of drugs, nicotinamide, paracetamol, and ibuprofen, with different hydrophilicity were applied in this study. The data of drug release were all fitted to the first-order kinetic model regardless of the drug properties, and the release rates paralleled with their hydrophilicity. Sol-gel phase transition of the thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel led to slower drug release at 37°C compared with those at 25°C. Regarding morphology, coaxial nanofibers could provide higher loading efficiency and slower drug release rather than porous nanofibers. Our research highlighted the overall effects of compound property, temperature, and the morphological structures of thermosensitive electrospun nanofibers on the controlled drug release. Our results concluded that hydrophobic drug encapsulated in the core-shell PNIPAAm nanofibers could perform excellent sustained release and also controllable release under temperature stumuli. Impact statement The behaviors for the controlled release of drugs loaded in the thermosensitive electrospun nanofibers could be affected by various factors including the properties of loaded drug, morphologies of nanofibrous, and lower critical solution temperatures of thermosensitive hydrogels. However, few systematical investigations have been performed in this area. In this article, we designed and fabricated porous and coaxial thermosensitive poly(N-isopropylacrylamide) electrospun nanofibers with different drug loading to study the comprehensive effect. This study suggested when adopting thermosensitive electrospun hydrogel nanofibers as the controllable drug release carrier, the hydrophilicity of loaded compounds and the morphologies of nanofibers are necessary to be optimized.

Iron (III)-mediated degradation of α-asarone and characterization of its major degradation products by UPLC-MS/MS and NMR.

α-Asarone, the main bioactive phytochemicals of Acorus species, is widely used in the treatment of respiratory disorders. The solution stability study of α-asarone was investigated in the presence of various metal ions. α-Asarone was found to be unstable in the presence of the metal ions Fe3+, Cu2+ and Al3+, in which the induction of Fe3+ was highly prone to the degradation of α-asarone. Thus, an iron (III)-mediated forced degradation study of α-asarone was carried out. One oxidative and four dimeric products were formed after the degradation of α-asarone. The complete mass fragmentation patterns for α-asarone and its degradation products (DPs) were established by UPLC-MS/MS in the positive ionization mode, and their structural confirmation was accomplished with 1H and 13C NMR. Then, the mechanistic pathways for the formation of all DPs were postulated. Finally, the oxidation degradation behavior and mechanism of α-asarone in the presence of oxidative stressors viz., hydrogen peroxide and azobisisobutyronitrile were explored.

JLX001 attenuates blood-brain barrier dysfunction in MCAO/R rats via activating the Wnt/ß-catenin signaling pathway.

JLX001, a new dihydrochloride of Cyclovirobuxine D (CVB-D), has bioactivities against ischemia injury. The blood-brain barrier (BBB) disruption is involved in the pathogeneses of ischemic stroke. This study was designed to explore the effect and potential mechanism of JLX001 on the BBB after ischemic stroke. Rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) to mimic cerebral ischemia in vivo. In vitro, rat primary brain microvascular endothelial cells (PBMECs) were cultured and exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). Posttreatment of JLX001 for 15 days after MCAO/R improved the behavior, learning and memory ability. Pretreatment of JLX001 for 3 days significantly attenuated infarct volume, lessened brain edema, mitigated BBB disruption and decreased the neurological deficit score in MCAO/R rats. Moreover, JLX001 increased cell viability and reduced sodium fluorescein leakage after OGD/R injury. In addition, JLX001 increased the expressions of Claudin-5 and Occludin, decreased the expression of MMP-9 both in vivo and in vitro. Moreover, immunofluorescence staining and western immunoblotting results showed that JLX001 increased the expressions of tight junction proteins via activating Wnt/ß-catenin signal pathway in vivo and in vitro, which may be associated with the activation of PI3K/Akt signaling. Besides, XAV939 (an inhibitor of the Wnt/ß-catenin pathway) proved the connection of JLX001 and Wnt/ß-catenin pathway. These results suggest that JLX001 alleviates BBB disruption after MCAO/R and OGD/R possibly by alleviating MMP-9 and activating the Wnt/ß-catenin signaling pathway.

Structure Elucidation and Mechanistic Study of a New Dimeric Degradant in Ropinirole Hydrochloride Extended-Release Tablets.

PURPOSE: The goal of the study was to elucidate the structure of a new degradant (1,3'-Dimer), generated in the stability testing of ropinirole extended-release tablets, and the formation mechanism of 1,3'-Dimer and its isomer (3,3'-Dimer). METHODS: The strategy of combining LC-PDA/UV-MSn (n = 1, 2) and NMR in conjunction with mechanism-based forced degradation study was employed to identify the structure of the unknown degradant and the formation mechanism of this dimeric degradant as well as its isomer, 3,3'-Dimer. The forced degradation was conducted by treating ropinirole API with formaldehyde under alkaline catalysis. A compatibility study between ropinirole and lactose was also performed. RESULTS: The degradant was isolated from the forced degradation sample and characterized by LC-PDA/UV-MSn as well as NMR measurement. The impurity was identified as a new dimeric degradant of ropinirole connected by a methylene bridge via the 1- and 3'-position of each ropinirole unit (i.e., 1,3'-Dimer of ropinirole), which is an isomer of a known dimeric degradant of ropinirole, namely 3,3'-Dimer. CONCLUSIONS: The newly occurred unknown degradant in ropinirole extended-release tablets was elucidated as the methylene-bridged 1,3'-Dimer of ropinirole. Based on the mechanistic study, 1,3'-Dimer and its isomer (3,3'-Dimer) were both formed by the reaction of ropinirole with residual formaldehyde present or formed in lactose, a main excipient of the formulation.

JLX001 improves myocardial ischemia-reperfusion injury by activating Jak2-Stat3 pathway.

AIMS: To investigate the preclinical pharmacodynamics and mechanism of JLX001 against myocardial ischemia reperfusion (MI/R) for clinical application. MATERIALS AND METHODS: In vivo, SD rats were given intragastric administration for 5 days, and the MI/R model was established by ligating/releasing the left anterior descending coronary artery. In vitro, the oxygen-glucose deprivation/reperfusion (OGD/R) model was established after the drug was pre-incubated for 24 h in H9C2 cells. The infract size was determined by TTC staining. Left ventricular function of MI/R rats was detected by echocardiography. The level of histopathological score was determined by hematoxylin-eosin (HE) staining. The level of superoxide dismutase (SOD), malondialdehyde (MDA), creatine kinase (CK), lactic dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were determined by relevant kits. The level of apoptosis was measured by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Hoechst staining. The expression of p-Jak2, p-Stat3, Bax, Bcl-2, TNF-α, IL-1ß protein were determined by western blot. KEY FINDINGS: JLX001 can significantly improve left ventricular function, reduce myocardial infract size, histopathological score, the level of MDA, CK, LDH, TNF-α, IL-1ß and the expression of Bax protein, significantly increase the activity of SOD, Bcl-2 protein expression, p-Jak2 protein expression, p-Stat3 protein expression in rat heart tissues and H9C2 cells. These effects can be reversed by AG490 which is a specific inhibitor of Jak2-Stat3 pathway. SIGNIFICANCE: JLX001 can alleviate MI/R injury by inhibiting myocardial apoptosis, inflammation, and oxidative stress via Jak2-Stat3 pathway in vivo and in vitro.

JLX001 Ameliorates Ischemia/Reperfusion Injury by Reducing Neuronal Apoptosis via Down-Regulating JNK Signaling Pathway.

JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The pharmacodynamic tests demonstrated that JLX001 ameliorated I/R injury by reducing infarct sizes and brain edema. The results of Morris water maze, neurological scores, cylinder test and posture reflex test implied that JLX001 improved the learning, memory and motor ability after MCAO/R in the long term. Anti-apoptotic effects of JLX001 and its regulation of cytosolic c-Jun N-terminal Kinases (JNKs) signal pathway were confirmed in vivo by co-immunofluorescence staining and western immunoblotting. Furthermore, primary cortical neuron cultures were prepared and exposed to oxygen glucose deprivation/reoxygenation (OGD/R) for in vitro studies. Cytotoxicity test and mitochondrial membrane potential (MMP) test showed that JLX001 enhanced cell survival rate and maintained MMP. Flow cytometry and TdT-mediated dUTP-X nick end labeling (TUNEL) staining demonstrated the anti-apoptotic effects of JLX001 in vitro. Likewise, JLX001 regulated JNK signal pathway in vivo, which was also confirmed by western immunoblotting. Collectively, this study presents the first evidence that JLX001 exerted protective effects against I/R injury by reducing neuronal apoptosis via down-regulating JNK signaling pathway.

Therapeutic effects of JLX-001 on ischemic stroke by inducing autophagy via AMPK-ULK1 signaling pathway in rats.

(3ß,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX-001), a structural analogue of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effects of JLX001 on ischemic stroke (IS) and research its induction of autophagy function via 5'-AMP-activated protein kinase (AMPK)-Human Serine/threonine-protein kinase (ULK1) signaling pathway activation. The therapeutic effects of JLX001 were evaluated by infarct sizes, brain edema, neurological scores and proportion of apoptotic neurons in Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R). The number of autophagosomes was obtained by transmission electron microscopy. The expression of LC3-II was measured by immunofluorescence. p-AMPK and activated ULK1 were detected by western blots. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, neurological scores and proportion of apoptotic neurons in MCAO/R rats. The number of autophagosomes was increased, accompanying with the increased expressions of LC3-II, p-AMPK and ULK1. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms may relate to inducing autophagy via AMPK-ULK1 signaling pathway activation.

JLX001 Modulated the Inflammatory Reaction and Oxidative Stress in pMCAO Rats via Inhibiting the TLR2/4-NF-κB Signaling Pathway.

Inflammatory reactions and oxidative stress play critical roles in cerebral ischemic injuries. Microglia are activated after ischemic injury. Activated microglia produce neurotoxic proinflammatory factors and reactive oxygen species (ROS), which have been demonstrated closely related TLR2/4-NF-κB signal pathways. This study was to evaluate the effect of JLX001 against ischemic injury and investigate the mechanisms. The permanent middle cerebral artery occlusion (pMCAO) model was employed in rats. The neurobehavioral score, brain infarction rate, brain water content, pathological changes, immunohistochemical staining, biochemical index (T-AOC, SOD, and MDA), proinflammatory factors (IL-1ß, TNF-α, and NO), expression of TLR2/4 and nuclear translocation of NF-κB p65 were determined. To explore probable underlying mechanism of the neuroprotective effect of JLX001, BV-2 cells were exposed to in oxygen-glucose deprivation (OGD) for 4 h to mimic ischemic injury in vitro. The result showed that JLX001 significantly decreased neurological deficit score, infarct size, and brain edema, attenuated pathological changes, inhibited the activation of microglia, improved the process of oxidative stress, reduced the release of proinflammatory cytokines and downregulated TLR2/4-NF-κB signal pathway. Moreover, OGD reduced BV2 cell viability, induced oxidative damage, increased the release of proinflammatory factors and activated TLR2/4-NF-κB signal pathway, which was significantly reversed by the intervention of JLX001. This study demonstrates that JLX001 is effective in protecting the brain from ischemic injury, which may be mediated by regulating oxidative stress, inflammation and inhibiting TLR2/4-NFκB signal pathway.

Therapeutic effects of JLX001 on cerebral ischemia through inhibiting platelet activation and thrombus formation in rats.

(3ß,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX001), a derivative of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effect of JLX001 on cerebral ischemia and researchits antiplatelet and antithrombosis activities via thromboxane (TXA2)/phospholipase C-ß-3(PLCß3)/protein kinase C (PKC) pathway suppression. The therapeutic effects of JLX001 was evaluated by infarct sizes, brain edema and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Brain TXA2 and prostacyclin (PGI2) were measured by enzyme-linked immunosorbentassay (ELISA). P-PLCß3and activated PKC were detected by immunohistochemical method. Adenosine diphosphate (ADP) or 9, 11-dieoxy-11α, 9α-epoxymethanoeprostaglandin F2α (U46619) was used as platelet agonist in the in vivo and in vitro platelet aggregation experiments. Clotting time and bleeding time were determined. Besides, two whole-animal experiments including arteriovenous shunt thrombosis and pulmonary thromboembolism model were conducted. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, and neurological scores in permanent middle cerebral artery occlusion (pMCAO) rats. Brain TXA2 level, p-PLCß3and activated PKC were decreased, while PGI2level had no significant change. Besides, JLX001 inhibited platelet aggregation induced by ADP or U46619 and exhibited anti-coagulation effects with a minor bleeding risk. In the two whole-animal experiments, JLX001 inhibited thrombus formation. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms relate to inhibiting platelet activation and thrombus formation via TXA2/PLCß3/PKC pathway suppression.

DNA-functionalized photonic crystal microspheres for multiplex detection of toxic metal ions.

A novel type of suspension array for multiplex detection of heavy metal ions with photonic crystal hydrogel microspheres was reported. The photonic crystal hydrogel microspheres have close-packed photonic crystal particles as their encoding units and ssDNA-functionalized hydrogel as the sensing units. The developed microspheres were successfully applied in multiplex detection of heavy metal ions.

Rapid determination of sulfonamide residues in pork by surface-modified hydrophilic electrospun nanofibrous membrane solid-phase extraction combined with ultra-performance liquid chromatography.

This study aimed to rapidly determine 13 representative sulfonamide (SA) residues in pork by using a surface-modified hydrophilic polystyrene sulfonic acid (PSSA) electrospun nanofibrous membrane as the solid-phase extraction (SPE) pretreatment sorbent, followed by ultra-performance liquid chromatography (UPLC) analysis. The highly hydrophilic nature of PSSA nanofibrous membrane created by vacuum plasma treatment was characterized using Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), water contact angle, and X-ray photoelectron spectroscopy (XPS) measurements. In the pretreatment procedures, 13 SA standards, which were spiked in the fatty pork samples, were extracted, enriched, and purified by the SPE procedure based on the principle of ion exchange with the sulfonic groups on the PSSA chains. Under the optimized conditions, the calibration curves of 13 SA compounds showed good linearities with correlation coefficients (r) of more than 0.99 in the range of 50.0-200 µg kg(-1). The mean recoveries of 13 SAs at the spiked concentrations of 50, 100, and 200 µg kg(-1) were in the range of 70.3-92.5 % with average RSDs (n = 6) of less than 15 % (except for sulfacetamide, 56.9-61.6 %). Compared with other pretreatment methods reported previously, less organic solvent (especially without degreasing the extract with n-hexane) was used in this time-saving SPE procedure, which avoids the possibility of emulsification and therefore enhances the recoveries. The developed and validated analysis method was sensitive, accurate, rapid, convenient, environmentally friendly, and was successfully applied for the detection of 13 SA residues in commercially available pork samples.

Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking.

Pidotimod, a synthetic dipeptide, has two chiral centers with biological and immunological activity. Its enantiomers were characterized by x-ray crystallographic analysis. A chiral stationary phase (CSP) Chiralpak-IA based on amylose derivatized with tris-(3, 5-dimethylphenyl carbamate) was used to separate pidotimod enantiomers. The mobile phase was prepared in a ratio of 35:65:0.2 of methyl-tert-butyl-ether and acetonitrile trifluoroaceticacid. In addition, thermodynamics and molecular docking methods were used to explain the enantioseparation mechanism by Chiralpak-IA. Thermodynamic studies were carried out from 10 to 45 °C. In general, both retention and enantioselectivity decreased as the temperature increased. Thermodynamic parameters indicate that the interaction force between the pidotimod enantiomer (4S, 2'R) and IA CSP is stronger and their complex model is more stable. According to GOLD molecular docking simulation, Van der Waals force is the leading cause of pidotimod enantiomers separation by IA CSP.

Application of packed porous nanofibers-solid-phase extraction for the detection of sulfonamide residues from environmental water samples by ultra high performance liquid chromatography with mass spectrometry.

Porous electrospun nanofibers, as new materials for solid-phase extraction, were synthesized by electrospinning and coupled with ultra high performance liquid chromatography and mass spectrometry to determine sulfonamide residues in environmental water. Aligned porous polystyrene electrospun nanofibers were fabricated under the mechanism of phase separation. The high-specific surface of these nanofibers (70 m(2)/g) could improve recoveries of the target sulfonamides 4-10 times compared with that of polystyrene nonporous material (3.8 m(2)/g). Under the optimized conditions, 13 sulfonamide residues showed an excellent linear relationship in the range of 0.125-12.5 ng/mL with a linear correlation coefficient (r(2)) greater than 0.99, and the detection limits of sulfonamides were as low as 0.80-5.0 ng/L. Compared to the commercial C18 and HLB columns, the homemade porous nanofibers columns had some merits including simple fabrication and extraction process, short process time and environmental friendliness. The optimized method was applied to eight water samples collected from different livestock farms (Xuzhou, China). The results showed that polystyrene porous nanofibers were promising to preconcentrate sulfonamides of different polarities in the waste water.