Ionic Liquids in Pharmaceutical and Biomedical Applications: A Review.

The unique properties of ionic liquids (ILs), such as structural tunability, good solubility, chemical/thermal stability, favorable biocompatibility, and simplicity of preparation, have led to a wide range of applications in the pharmaceutical and biomedical fields. ILs can not only speed up the chemical reaction process, improve the yield, and reduce environmental pollution but also improve many problems in the field of medicine, such as the poor drug solubility, product crystal instability, poor biological activity, and low drug delivery efficiency. This paper presents a systematic and concise analysis of the recent advancements and further applications of ILs in the pharmaceutical field from the aspects of drug synthesis, drug analysis, drug solubilization, and drug crystal engineering. Additionally, it explores the biomedical field, covering aspects such as drug carriers, stabilization of proteins, antimicrobials, and bioactive ionic liquids.

Preparation and application of nano petal-shaped covalent organic frameworks modified polystyrene-divinylbenzene- glycidylmethacrylate microspheres for the extraction of illicit drugs from wastewater.

A novel nano petal-shaped covalent organic frameworks modified magnetic polystyrene-divinylbenzene-glycidylmethacrylate (NP-COF@Mag-PS/DVB/GMA) microsphere has been synthesized. It is a perfect combination of high productivity of PS/DVB/GMA microspheres and excellent enrichment efficiency of COF particles, and the excellent properties of NP-COF@Mag-PS/DVB/GMA microspheres are characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) and X-ray photoelectron spectroscopy (XPS). The sorbent can extract illicit drugs via the reverse-phase interactions provided by benzene ring on the polymer backbone and the hydrogen bonding interactions provided by functional group (-NH-) on the COF particles. Based on using NP-COF@Mag-PS/DVB/GMA as sorbents, an easiness-to-handle of magnetic dispersive solid phase extraction (Mag-dSPE) procedure is proposed for the simultaneous preconcentration of 12 illicit drugs from wastewater. The obtained results show high extraction efficiency of NP-COF@Mag-PS/DVB/GMA to illicit drugs with recoveries between 81.6 and 116%. Furthermore, a liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) method for the determination of 12 illicit drugs from wastewater at sub-ppt levels has been proposed and validated with the pretreatment of samples by Mag-dSPE. The limits of quantification (LOQs) for the 12 illicit drugs are between 0.40 and 4.90 ng/L. Validation results on linearity, specificity, trueness and precision, as well as on application to the analysis of 12 illicit drugs in ten real samples demonstrate the applicability to environment monitoring analysis.

Preparation of sheet-like covalent organic frameworks and their application for efficient preconcentration of 4-(tert-octyl)-phenol and 4-nonylphenol in textiles.

In the design of highly ordered (covalent organic frameworks) COFs with "ordered domains size and orientation" construction in a well-defined arrangement, the molecular monomers are the key factors. Here, the effect of molecular monomers on the construction of COFs has been studied, and two kinds of molecular monomers, i.e., ethanediamine (flexible amine ligand) and 4,4'-diaminobiphenyl (rigid amine ligand) have been used for developing sheet-like COFs-I and sheet-like COFs-II, respectively. Furthermore, they have been evaluated in the dispersive solid phase extraction (dSPE) procedure for textiles prior to the analysis of alkylphenol by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). The results showed that, the optimal usage amount of sheet-like COFs-II used in the dSPE procedure was less than that of sheet-like COFs-I, which may be explained by much higher adsorption capacity of sheet-like COFs via hydrogen-bonding and π-π stacking interactions. Rectilinear calibration graphs were obtained for 4-(tert-octyl)-phenol (4-tOP) and 4-nonylphenol (4-NP) in the range 0.2-20 µg/kg with determination coefficient (r2) higher than 0.9990, and the limits of detection (LODs) of 4-tOP and 4-NP were 0.039 µg/kg and 0.048 µg/kg, respectively. The developed method has been successfully applied to analysis of 50 textile samples, in which 4-tOP and 4-NP were found in six samples with concentrations in the range of 1.6 µg/kg-20.9 µg/kg.

Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis.

In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9-21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI 16.5-25.7%) was higher compared to China (12.9%, 95% CI 8-17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95% CI 3.2-79.4%) compared to areas outside Wuhan in China (7.1%, 95% CI 4.0-10.3%). The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days. Conclusions and relevance: gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.

Assessment of the risk of musculoskeletal adverse events associated with fluoroquinolone use in children: A meta-analysis.

BACKGROUND: The use of fluoroquinolone antibiotics has been restricted in children because of their potential to cause adverse musculoskeletal events. This study was performed to systematically evaluate whether there is a difference between fluoroquinolone and non-fluoroquinolone antibiotics in terms of their associated risk of adverse musculoskeletal events in children. METHODS: Cochrane Library, Embase, and PubMed databases were used to retrieve studies related to fluoroquinolone and non-fluoroquinolone-induced musculoskeletal adverse events in children. A meta-analysis was performed using Stata 11. RESULTS: A total of 10 studies were included in the analysis. The combined results showed that there was no statistical difference between fluoroquinolone and non-fluoroquinolone groups in terms of musculoskeletal adverse events in children (risk ratio = 1.145, 95% confidence interval = 0.974 - 1.345, P = .101). Subgroup analysis was performed using a random-effects model. Here, the effects on the trovafloxacin and levofloxacin groups were significantly different from that of the control group. However, musculoskeletal adverse events due to either drug was not reported after long-term follow-up. CONCLUSIONS: The results showed that fluoroquinolone and non-fluoroquinolone antibiotics were not different in terms of their ability to cause musculoskeletal adverse events in children. For this reason, fluoroquinolone antibiotics can be used in children as appropriate. PROSPERO REGISTRATION NUMBER: CRD42019133900.

Two symptomatic cases of dysfibrinogenemia in China: one with gamma-chain Arg275Cys mutation and another without detectable mutation in fibrinogen genes.

The aim of this study was to investigate causative mutations of two unrelated symptomatic Chinese children with dysfibrinogenemia and their family members.Fibrinogen genes, including FGA, FGB and FGG of all participants were PCR-amplified, followed by direct sequencing. Precipitated plasma fibrinogen of some family members was analyzed by western blotting, fibrin polymerization and scanning electron microscopy (SEM).Proband 1 associated with frequent epistaxis was identified to harbor a heterozygous Arg275Cys mutation in FGG, along with a polymorphism Arg448Lys in FGB. Proband 2 with apparently prolonged thrombin time and very low functional fibrinogen had undergone both spontaneous intracranial hemorrhages and deep venous thrombosis. Sequencing of all proximal promoters, coding regions, introns and 3'-untranslated region using genomic DNA of Proband 2 yielded no mutation in three fibrinogen genes. Western blotting of this patient's precipitated plasma fibrinogen detected no truncated protein. Fibrinogen polymerization curve showed prolonged lag phase and severely decreased final turbidity, and SEM observations of fibrin clots made from Proband 2 revealed an abnormal sponge-like mass with large pores. We speculate that other underlying mechanisms responsible for dysfibrinogenemia such as abnormal posttranscriptional processing or posttranslational modification, which are independent of detectable mutations in the genomic DNA sequence, may exist.

Systemicity of chlorantraniliprole in velvetleaf (Abutilon theophrasti).

The systemicity of chlorantraniliprole was investigated and evidence was collected for formulating strategies in controlling vegetable or rice pests. Systemicity of chlorantraniliprole was investigated through chlorantraniliprole application on velvetleaf (Abutilon theophrasti) leaves as well as through hydroponic experiments. The roots of velvetleaf were incubated in chlorantraniliprole solution with a concentration of 50 microg/mL; the concentrations of chlorantraniliprole in xylem above the solution parts were 3.14, 5.67, and 6.89 microg/g at 24, 48, and 72 h after treatment. When the roots were incubated in chlorantraniliprole solution with a concentration of 200 microg/mL, the concentrations of chlorantraniliprole in xylem above the solution reached 6.48, 8.76, and 10.55 microg/g at 24, 48, and 72 h after treatment. Chlorantraniliprole was not detected in the phloem above the solution after these two treatments. When chlorantraniliprole solution with a concentration of 100 microg/mL was applied on mature leaves, chlorantraniliprole was found in xylem above the mature leaves at concentrations of 0.55, 0.74, and 0.92 microg/g at 24, 48, and 72 h after the treatment. No chlorantraniliprole was detected in the leaves below the mature leaves or the phloem above them. When chlorantraniliprole solution with a concentration of 100 microg/mL was applied on apical leaves, no chlorantraniliprole was detected in the xylem or phloem below them. These results indicated that chlorantraniliprole can be transported through xylem only upward, but chlorantraniliprole has no phloem mobility in velvetleaf.

Quaternary ammonium chitosan derivative dynamic coating for the separation of veterinary sulfonamide residues by CE with field-amplified sample injection.

A quaternary ammonium chitosan, 2-hydroxypropyltrimethylammonium chloride chitosan (HACC), has been developed for the dynamic coating material in CE for the first time. It presented many advantages such as favorable water solubility, satisfactory coating efficiency, and EOF toward the anode at pH >7.0. Using the modified fused-silica capillary, sulfonamides (SAs), an important group of veterinary drugs, were separated and detected by CE combined with field-amplified sample injection (FASI). The LODs of sulfonamides with UV detection were less than 0.5 ng/mL. The proposed method has been applied to the determination of veterinary sulfonamide residues in samples such as chicken, beef, and honey with fast separation (15 sulfonamides within 20 min), low LODs (0.1-0.5 ng/mL), and good reliability compared to the criteria of China (GB/T 18932.17-2003).