Herein, we report a simple and facile strategy to prepare one kind of smart chiral magnetic nanoparticles (Fe
3
O
4
@PDA@PNG-CD) with high enantioselectivity via combining mussel-inspired ...polydopamine (PDA) chemistry with surface-initiated atom transfer radical polymerization for effective enantioseparation of tryptophan enantiomers (
dl
-Trp). The PDA thin layer plays a pivotal role in fabricating high-density poly(
N
-isopropylacrylamide-
co
-glycidyl methacrylate)-
β
-cyclodextrin (PNG-CD) smart polymer brushes onto the Fe
3
O
4
NPs. The grafted PNG-CD plays a significant role in greatly boosting the enantioselectivity of the Fe
3
O
4
@PDA@PNG-CD, which is composed of the poly(
N
-isopropylacrylamide-
co
-glycidyl methacrylate) (PNG) copolymer chains with numerous appended
β
-cyclodextrin (
β
-CD) units. The
β
-CD units serve as chiral selectors capable of selectively recognizing and binding
l
-tryptophan (
l
-Trp) into their cavities by forming stable host–guest inclusion complexes of
β
-CD/
l
-Trp, and the PNIPAM chains act as microenvironmental adjustors for the inclusion constants of
β
-CD/
l
-Trp complexes. Operating temperature and initial concentrations of
dl
-Trp are two important factors that significantly affect the separation efficiency of
dl
-Trp and the enantioselectivity of the Fe
3
O
4
@PDA@PNG-CD. Furthermore, the Fe
3
O
4
@PDA@PNG-CD also demonstrates satisfactory recycling and excellent magnetic separability from enantiomeric solution. Such smart chiral magnetic NPs with high enantioselectivity developed in this study show great potentials in direct enantioseparation of various chiral compounds.
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•An easy-to-get and low-cost Cs+-recognizable polymeric hydrogel has been developed.•The hydrogel displays rapid and selective adsorption towards Cs+.•Synergistic effect of AAc units ...and Cs+(B18C6)2 host-guest complexes is good for adsorption.•The hydrogel shows great potential for decontamination of Cs+ from radioactive contaminants.
At present, selective and efficient removal of cesium ions (Cs+) from nuclear waste is of significant importance but still challenging. In this study, an easy-to-get and low-cost hydrogel adsorbent has been developed for effective adsorption and removal of Cs+ from aqueous environment. The novel Cs+-recognizable poly(acrylic acid-co-benzo-18-crown-6-acrylamide) (poly(AAc-co-B18C6Am)) hydrogel is specifically designed with a synergistic effect, in which the AAc units are designed to attract Cs+ via electrostatic attraction and the B18C6Am units are designed to capture the attracted Cs+ by forming stable 2:1 “sandwich” complexes. The poly(AAc-co-B18C6Am) hydrogels are simply synthesized by thermally initiated free-radical copolymerization and display excellent Cs+ adsorption from commonly coexisting metal ions. Important parameters affecting the adsorption are investigated comprehensively, and the adsorption kinetics and adsorption isotherms are also discussed systematically. The poly(AAc-co-B18C6Am) hydrogels exhibit rapid Cs+ adsorption within 30min and the adsorption process is governed by the pseudo-second order model. Adsorption isotherm results demonstrate that the equilibrium data are well fitted by the Langmuir isotherm model, indicating that the Cs+ adsorption is probably a monolayer adsorption process. Such Cs+-recognizable hydrogel materials based on the host-guest complexation are promising as efficient and feasible candidates for adsorption and removal of radioactive Cs+ from nuclear contaminants.
•Recent progress on reaction-based fluorescent probes for biomolecules in brain.•Focusing on central nervous system diseases-related biomarkers.•Design principles for specific analytes and the ...challenges were discussed.
Central nervous system (CNS)-related pathologies have been historically recognized as one of the hotspots in medical research. Extensive evidences have shown that biomolecules including small molecules and enzymes are tightly linked to diverse of disorders in human brain. To decipher the pathological roles of these molecules in closely linked mental illness, it is of great significance to develop effective approaches for imaging the associated biomarkers in CNS. Owning to its unique advantages, such as non-invasiveness and real-time imaging, fluorescence imaging (FI) has been developed as a robust tool for tracking various molecules in brain. Notably, an increasing number of fluorescent probes have been proposed to track the molecules in brain in vivo over the past decades. In this review, we systematically summarized the methods for the designs and applications of reaction-based fluorescent probes according to the intrinsic characteristic of biomarkers in CNS. Furthermore, the potential challenges for monitoring biomolecules and the suggestions for developing new reaction-based fluorescent probes in this field were also discussed. We hope that the information herein can help break the dilemmas such as the sensitivity requirement and limited bioapplications.
Antibiotics are widely used for treating bacterial infections. However, excessive or improper use of antibiotics can pose a serious threat to human health and water environments, and thus, developing ...cost-effective, portable and effective strategies to analyze and detect antibiotics is highly desired. Herein, we reported a responsive photonic hydrogel (RPH)-based optical biosensor (PPNAH) with superior recyclability for sensitive and colorimetric determination of a typical β-lactam antibiotic penicillin G (PG) in water. This sensor was composed of poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel with incorporated penicillinase and Fe3O4@SiO2 colloidal photonic crystals (CPCs). The sensor could translate PG concentration signals into changes in the diffraction wavelength and structural color of the hydrogel. It possessed high sensitivity and selectivity to PG and excellent detection performances for other two typical β-lactam antibiotics. Most importantly, due to the unique thermosensitivity of the poly(N-isopropylacrylamide) moieties in the hydrogel, the PG-responded PPNAH sensor could be facilely regenerated via a simple physical method at least fifty times while without compromising its response performance. Besides, our sensor was suitable for monitoring the PG-contaminated environmental water and displayed satisfactory detection performances. Such a sensor possessed obvious advantages of superior recyclability, highly chemical stability, low production cost, easy fabrication, wide range of visual detection, simple and intuitive operation for PG detection, and environmental-friendliness, which holds great potential in sensitive and colorimetric detection of the PG residues in polluted water.
Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for ...information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV‐infected human vascular endothelial cells (HUVECs) (Exo‐HV) and found the antiviral properties of Exo‐HV in the uninfected recipient cells. High‐throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo‐HV. MiR‐145‐5p, one of the abundant miRNAs packaged into Exo‐HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76‐118 and inducing type I interferon (IFN‐I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV‐infected HUVECs were able to transfer active molecules, miR‐145‐5p as a proving sample, to mediate novel anti‐HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.
Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children.
The present study aimed to investigate the influence of delayed or missed ...dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.
A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.
For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.
It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.
Four β-cyclodextrin (β-CD)/benzene derivatives gels were developed as temporary plugging agent for different formation temperature ranges. The gel was composed of β-CD as the host, benzene ...derivatives as the guest and 1,2-propylene glycol as solvent. The systems undergo a "sol-gel" phase transition when the temperature rises. By adding different benzene derivatives (toluene/phenol/benzoic acid) in the system, the gel temperature could be controlled between 70 and 130 ℃. And the gel turns into a solution again upon further heating. Further, FT-IR, X-ray diffractometer (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used to analyze the micromorphology and phase transformation mechanism of the gel. The results confirmed that the gelling process of the four systems mainly depends on non-covalent bond action. Furthermore, the degradation rate and the plugging and permeability recovery rate were tested. The results showed that the degradation rate of the four systems were finally greater than 98%, the plugging rate was greater than 85%, and permeability recovery value was more than 98%, which can meet the requirements of fracturing temporary plugging with the formation temperature of 70 ∼ 130 ℃.
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•The binding ability of benzene derivatives to β-cyclodextrin affects the gelation temperature.•As the temperature increases, the system is self-assembly into a three-dimensional network structure.•The “sol-gel” phase transformation mainly depends on supramolecular force rather than chemical change.•Supramolecular gel based on cyclodextrin has good temporary plugging and self-degradation effect in tight oil reservoirs.
Influenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can ...cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses.
We did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime–boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050.
Between Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2–5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis.
The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed.
Bill & Melinda Gates Foundation.
The objective of this study was to establish a nomogram model to predict SI in patients with cancer and further evaluate its performance.
This study was performed among 390 patients in oncology ...departments of Affiliated Hospital of Nantong University from April 2020 to January 2021. Of these, eligible patients who were diagnosed with cancer were split into training and validation cohorts according the ratio of 2:1 randomly. In the training cohort, multivariate regression was performed to determine the independent variables related to SI. A nomogram was built incorporating these variables. The model performance was evaluated by an independent validation cohort.
The prevalence of SI in patients with cancer was 22.31% and 19.23% in training and validation cohorts, respectively. The nomogram model suggested independent variables for SI, including depression, emotional function, time after diagnosis, family function and educational status. The area under the curve (AUC) was 0.93 (95%CI, 0.90-0.97) and 0.82 (95%CI, 0.74-0.90) in training and validation cohorts respectively, which indicated good discrimination of the nomogram in predicting SI in cancer patients. The p-value of the goodness of fit (GOF) test was 0.197 and 0.974 in training and validation cohorts respectively, suggesting our nomogram model has acceptable calibration power, and the calibration curves further indicated good calibration power.
In conclusion, the nomogram model for predicting individualized probability of SI could help clinical caregivers estimate the risk of SI in patients with cancer and provide appropriate management.
Systemic lupus erythematosus (SLE) is an inflammatory disease caused by autoantibodies, with high morbidity and mortality. It involves multiple systems, particularly the renal, which can lead to ...lupus nephritis (LN); its multi-system effects have a significant impact on the physical and mental health of patients. Exosomes are vesicles that are secreted during cell activity and carry a variety of nucleic acids, proteins, and lipids. They are distributed through body fluids for cellular communication. MicroRNAs (miRNAs) are nucleic acids that are packaged within the exosome that are taken up and released in response to changes in plasma membrane structure. MiRNAs are potential participants in immune and inflammatory responses, which are transported to target cells and can inhibit gene expression in receptor cells. It has been suggested that exosomal miRNA can regulate the pathogenesis of SLE and, as such, they are of value in diagnosis and treatment. In this paper, we focus on the research progress into exosomal miRNA in SLE and inspire new directions for SLE related research.
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