Disposable stainless steel working electrodes for sensitive and simultaneous detection of indole-3-acetic acid and salicylic acid in Arabidopsis thaliana leaves under biotic stresses.

The detection of phytohormones in real time has attracted increasing attention because of their critical roles in regulating the development and signaling of plants, especially in defense against biotic stresses. Herein, stainless steel sheet electrodes modified with carbon cement were coupled with paper-based analysis devices for direct and simultaneous detection of salicylic acid (SA) and indole-3-acetic acid (IAA) in plants. We demonstrated that the excellent conductivity of stainless steel sheet electrodes enabled us to simultaneously differentiate IAA and SA at a level of 10 nM. With our approach, the content of IAA and SA in Arabidopsis thaliana leaves infected or not infected with Pst DC3000 could be rapidly quantified at the same time. Our experimental results on differentiation of IAA and SA at different time points showed that there were antagonistic interactions between the IAA and SA after infection of Arabidopsis leaves with Pst DC3000. By offering a cost-effective approach for rapid and sensitive detection of IAA and SA, this study suggests that electrochemical detection can be used in the study and development of precision agriculture technology.

Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo.

Metal fluoride nanocrystals are widely used in biomedical studies owing to their unique physicochemical properties. The release of metal ions and fluorides from nanocrystals is intrinsic due to the solubility equilibrium. It used to be considered as a drawback because it is related to the decomposition and defunction of metal fluoride nanocrystals. Many strategies have been developed to stabilize the nanocrystals, and the equilibrium concentrations of fluoride are often <1 mM. Here we make good use of this minimum amount of fluoride and unveil that metal fluoride nanocrystals could effectively induce desilylation cleavage chemistry, enabling controlled release of fluorophores and drug molecules in test tubes, living cells, and tumor-bearing mice. Biocompatible PEG (polyethylene glycol)-coated CaF2 nanocrystals have been prepared to assay the efficiency of desilylation-induced controlled release of functional molecules. We apply the strategy to a prodrug activation of monomethyl auristatin E (MMAE), showing a remarkable anticancer effect, while side effects are almost negligible. In conclusion, this desilylation-induced cleavage chemistry avails the drawback on empowering metal fluoride nanocrystals with a new function of perturbing or activating for further biological applications.

A cohort study of factors that influence oral health-related quality of life from age 12 to 18 in Hong Kong.

BACKGROUND: There is a lack of cohort studies on the influence factors of oral health-related quality of life (OHRQoL). This study aimed to follow subjects from age 12 to 18 to analyse the sociodemographic and clinical factors that may influence OHRQoL. METHODS: This cohort study selected a representative sample from Hong Kong. Periodontal status and caries were examined according to WHO criteria. Four orthodontic indices were used to assess malocclusion. Child Perceptions Questionnaires (CPQ11-14) with 8 items (CPQ11-14-ISF: 8) and 37 items were used to assess OHRQoL at age 12 and age 15, respectively; Oral Health Impact Profile (OHIP-14) was used to assess OHRQoL at age 18. Wilcoxon signed ranks test and Friedman's test were used to analyse the age-related change of OHRQoL and malocclusion from age 12 to 18. Generalized estimating equations were used to analyse the influence factors of OHRQoL and to calculate adjusted risk ratio (RR). RESULTS: Subjects recruited in this study were 589 (305 females, 284 males), 364 (186 females, 178 males) and 300 (165 females, 135 males) at age 12, 15 and 18, respectively. Among them, 331 subjects (172 females, 159 males) were followed from age 12 to 15, and 118 subjects (106 females, 82 males) were followed from age 12 to 18. Subjects had less severe malocclusion at age 12 than at ages 15 and 18 (p = 0.000, measured by Dental Aesthetic Index). Age, periodontal status, and malocclusion had an effect on OHRQoL. When compared with OHRQoL at age 12, worse OHRQoL was observed at age 15 (adjusted RR = 1.06, 95%CI = 1.01-1.12, p = 0.032), but not at age 18 (adjusted RR = 1.01, 95%CI = 0.95-1.08, p = 0.759). Unhealthy periodontal conditions had a negative effect on OHRQoL (adjusted RR = 1.14, 95%CI = 1.04-1.25, p = 0.007). Only severe malocclusions had a negative effect on OHRQoL; a more severe malocclusion was associated with a higher effect on OHRQoL (adjusted RR = 1.09, 95%CI = 1.01-1.18, p = 0.032 for severe malocclusion, and adjusted RR = 1.17, 95%CI = 1.07-1.28, p = 0.001 for very severe malocclusion measured by Dental Aesthetic Index). CONCLUSION: Age, periodontal status, and malocclusion had an influence on OHRQoL from age 12 to 18. When clinicians attempt to improve subjects' OHRQoL, it is necessary to consider these factors.

The association between postpartum depression and early childhood caries.

Objective: To determine whether postnatal depression was associated with early childhood caries (ECC).Methods: This cross-sectional study was nested in a large cohort study named Born in Guangzhou Cohort Study (BIGCS). Mothers were invited to answer the Chinese version of Edinburgh Postpartum Depression Scale (EPDS) at 11-14 months postpartum. Children's ECC experience was assessed at 24-37 months old. Socio-demographic factors were collected by a self-completed questionnaire. Chi-square test was used for bivariate analysis, and binary logistic regression was used for multivariable analysis.Results: Totally 337 mother/children pairs were included into this study. Among them, 33 children had caries experience, accounting for 9.8% of the participants. Mothers with EPDS scores between 7 and 10 were associated with worse ECC experience of their children (adjusted OR = 2.948, 95% CI = 1.209-7.190), whereas mothers with EPDS scores higher than 10 were not associated with ECC experience of their children. Mother's education and the number of children living together were also associated with children's ECC experience (adjusted OR = 1.822, 95% CI = 1.013-3.275, and adjusted OR = 1.528, 95% CI = 1.086-2.150, respectively). Other factors such as maternal age at the time of conception, family income, mother's work status, duration of breastfeeding, and children's gender did not show effect on children's ECC experience.Conclusion: Postnatal depression could be associated with children's ECC experience. In this study, mothers with slightly depression symptoms were more likely to have adverse effects on their children's ECC experience.

The factors that influence oral health-related quality of life in young adults.

BACKGROUND: Young adulthood is a time when subjects transform their role from a dependent child to an independent social identity. This cross-sectional study aimed to analyze the sociodemographic and clinical factors that may influence the OHRQoL of 18-year-old young adults. METHODS: A representative sample was selected from Hong Kong. Periodontal status and caries were examined according to WHO criteria. Four orthodontic indices were used to assess malocclusion. The oral health impact profile (OHIP-14) was used to measure OHRQoL. Adjusted OR was calculated by ordinal logistic regression. RESULTS: A total of 300 eligible subjects (165 females, 135 males) were recruited. Females had more severe caries than males; however, gender was not a significant factor of OHRQoL. Household income affected OHRQoL more than parents' education did: household income had effects on physical pain, psychological discomfort, psychological disability, and the total OHIP; while parents' education had some effects on functional limitation, physical pain and psychological discomfort. As for clinical factors, unhealthy periodontal conditions were more prevalent than caries (94.67% vs. 59.00%); however, both of them showed no effect on OHRQoL. Malocclusion had a negative effect on OHRQoL; the most affected subscales were psychological discomfort and psychological disability. CONCLUSION: In this study, family ecosocial factors and malocclusion had an effect on OHRQoL. Among the family ecosocial factors, it was household income that had the most effect on OHRQoL. Malocclusion mainly affected the subscales of psychological discomfort and psychological disability. Gender, periodontal status and caries had no effect on young adults' OHRQoL.

The factors that influence oral health-related quality of life in 15-year-old children.

BACKGROUND: Several hypotheses on factors that influence oral health-related quality of life (OHRQoL) have been proposed but a consensus has not been reached. This cross-sectional study aimed to analyse the sociodemographic and clinical factors that may influence the OHRQoL of 15-year-old children. METHODS: A representative sample was selected from Hong Kong. Periodontal status and caries were examined according to WHO criteria. Four orthodontic indices were used to assess malocclusion. Child Perception Questionnaire (CPQ11-14, 37 items) including four domains, namely oral symptoms (OS), functional limitations (FL), emotional well-being (EWB), and social well-being (SWB), was used to measure OHRQoL. Adjusted OR was calculated by ordinal logistic regression. RESULTS: A total of 364 eligible subjects (186 girls, 178 boys) were recruited. The prevalence of caries was higher in girls than in boys (P = 0.013). Compared with girls, boys tended to have a better experience in the domains of EWB, SWB and the total CPQ (adjusted OR = 0.46, 0.59 and 0.61, respectively). Unhealthy periodontal conditions were more prevalent than caries (92.6% vs. 52.7%); moreover, periodontal conditions with CPI scores of 2 had a negative effect on the domain of SWB and the total CPQ (adjusted OR = 1.76 and 1.71, respectively). Only the most severe malocclusion showed an effect on the domain of FL and the total CPQ (adjusted OR = 1.55 and 2.10, respectively). Little effect of family ecosocial factors and caries was found on CPQ scores. CONCLUSION: In this study, gender, periodontal status, and malocclusion showed an effect on OHRQoL after adjusting for potential confounders. Boys had less caries and better OHRQoL than girls did. Unhealthy periodontal conditions led to worse social welfares and OHRQoL. The most severe level of malocclusion caused oral functional limitations, hence worse OHRQoL.

Association Between the Severity of Malocclusion, Assessed by Occlusal Indices, and Oral Health Related Quality of Life: A Systematic Review and Meta-Analysis.

PURPOSE: To assess whether different levels of malocclusion have different effects on the oral health-related quality of life (OHRQoL) and which domains of OHRQoL could be affected. MATERIALS AND METHODS: Nine electronic databases were searched. To make studies comparable, studies using the Child Perceptions Questionnaire (CPQ) to measure OHRQoL, and the Dental Aesthetic Index, Index of Orthodontic Treatment Need, and Index of Complexity, Outcome and Need to measure malocclusion were selected for systematic review. Meta-analysis was performed to calculate the weighted mean scores of CPQ. The two independent samples t-test was used to detect whether different severity groups of malocclusion have different CPQ scores. RESULTS: A total of 22 studies were included in this review and 6 were included in the meta-analysis. Most studies used a cross-sectional design and convenience sampling. Meta-analysis showed that the weighted mean scores of CPQ increased with malocclusion severity. The t-test showed nearly all levels of malocclusion affected the domains of functional limitation and social well-being; only very severe malocclusion affected the domains of oral symptoms, emotional well-being and the overall OHRQoL (p < 0.05). CONCLUSION: When OHRQoL was assessed by CPQ11-14 and malocclusion was assessed by orthodontic indices, children with malocclusion could have oral functional limitations and worse social lives; children with very severe malocclusion could further develop oral symptoms and had worse emotional experiences. Future longitudinal population-based studies would be helpful to confirm these results.

The factors that influence the oral health-related quality of life in 12-year-old children: baseline study of a longitudinal research.

BACKGROUND: Oral health-related quality of life (OHRQoL) could be affected not only by oral health but also by demographic and ecosocial factors. This research aimed to analyze the sociodemographic and clinical factors that may influence the OHRQoL of 12-year-old children. METHODS: A representative sample was selected from Hong Kong. Periodontal status and caries were examined according to WHO criteria. Four orthodontic indices were used to assess malocclusion. Child Perception Questionnaires (CPQ11-14-ISF:8 and CPQ11-14-RSF:8) including four domains, namely oral symptoms (OS), functional limitations (FL), emotional well-being (EWB), and social well-being (SWB), were used to measure OHRQoL. Adjusted OR was calculated by ordinal logistic regression. RESULTS: Totally 589 eligible subjects (305 females, 284 males) were recruited. Males tended to rank higher in OS domain but lower in EWB domain (adjusted OR = 1.89 and 0.67). Mother's education was linked more closely with children's CPQ scores. Higher education levels were associated with better quality of life (adjusted OR = 0.45 and 0.37). Household income showed no effect on CPQ scores. Unhealthy periodontal conditions had a negative effect on EWB and total CPQ (adjusted OR = 1.61 and 1.63). High caries experience only had a negative effect on SWB (adjusted OR = 1.60). Malocclusion affected FL, EWB, SWB and total CPQ: all malocclusion severities affected SWB; only severe malocclusions affected FL, EWB and total CPQ. CONCLUSION: Males were more tolerant of oral symptoms than females were. Higher levels of mother's education led to better OHRQoL of their children. Unhealthy periodontal conditions affected emotional well-being, while high caries experience affected social well-being. All malocclusion severities had an effect on social well-being; severe malocclusion further caused functional limitations, worse emotional well-being, and hence worse OHRQoL.

Relationship Between the Severity of Malocclusion and Oral Health Related Quality of Life: A Systematic Review and Meta-analysis.

PURPOSE: To investigate the impact of untreated malocclusion on different aspects of oral health-related quality of life (OHRQoL). MATERIALS AND METHODS: All relevant literature published up to February 18, 2016 was collected from nine electronic databases. To make studies comparable, studies that used the dental aesthetic index (DAI), index of orthodontic treatment need (IOTN), or index of complexity, outcome and need (ICON) to measure malocclusion and oral health impact profile (OHIP) to measure OHRQoL were selected for systematic review. Meta-analysis, two independent-samples t-test and binary logistic regression were used to test whether different malocclusion severity groups had different OHIP scores. RESULTS: A total of 564 non-duplicate publications were identified first. Of these, 13 studies were included in this review. All studies had a cross-sectional design and most of them used convenience samples. Eleven studies presented a significant result about the association of malocclusion and OHIP scores. Statistical analyses showed that malocclusion had an impact on all subscales scores, and more severe malocclusion indicated higher OHIP scores on the subscales of physical disability, physical pain, psychological discomfort, psychological disability, and social disability. CONCLUSION: Untreated malocclusion was significantly associated with OHRQoL. The more severe the malocclusion, the worse was the impact on some physical domains and all psychosocial domains of OHRQoL. There was a lack of longitudinal population-based studies to confirm this result.

A novel NTRK1 splice site variant causing congenital insensitivity to pain with anhidrosis in a Chinese family.

Background: Congenital insensitivity to pain with anhidrosis (CIPA, OMIM #256800), also known as hereditary sensory and autonomic neuropathy type Ⅳ (HSAN-IV), is a rare autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis, insensitivity to noxious stimuli, self-mutilating behavior and intellectual disability. CIPA can be caused by the variants in NTRK1 gene, which encodes a high-affinity tyrosine kinase receptor for nerve growth factor. To ascertain the hereditary cause of a patient with CIPA accompanied by the additional symptoms of mild growth retardation, prone to fracture, underdeveloped nails of fingers and toes, irregular tooth alignment, enamel hypoplasia, postoperative wound healing difficulty, hand and limb deformity, and dislocation of hip joint, whole exome sequencing was used and revealed a compound heterozygous variant in NTRK1. Methods: DNA was extracted from peripheral blood samples of pediatric patients and their parents, and subjected to comprehensive analysis using whole-exome sequencing (WES), followed by verification of variant sites in the NTRK1 gene through Sanger sequencing. To elucidate the functional impact of the newly discovered variants, an in vitro experimental system was established. Splicing analysis was conducted using PCR and Sanger sequencing, while expression levels were assessed through qPCR and Western blot techniques. Results: One hotspot variant c.851-33T>A(ClinVar ID: 21308) and a novel variant c.850 + 5G>A(ClinVar ID:3069176) was inherited from her father and mother, respectively, identified in the affected individuals. The c.850 + 5G>A variant in NTRK1 resulted in two forms of aberrant mRNA splicing: 13bp deletion (c.838_850del13, p. Val280Ser fs180) and 25bp deletion (826_850del25, p. Val276Ser fs180) in exon 7, both leading to a translational termination at a premature stop codon and forming a C-terminal truncated protein. The expression of two abnormal splicing isoforms was decreased both in the level of mRNA and protein. Conclusion: In conclusion, this study elucidated the genetic cause of a patient with CIPA and identified a novel variant c.850 + 5G>A in NTRK1, which broadened the and enriched the NTRK1 mutation spectrum.

Bio-based alginate and Si-, P- and N-containing compounds cooperate toward flame-retardant modification of polyester fabrics.

Imparting flame retardancy to polyester fabrics is still a pressing issue for the textile industry. To this end, a composite coating was developed by phosphite, pentamethyldisiloxane, urea and sodium alginate, and then applied together with calcium chloride to prepare flame-retardant polyester fabrics. The optimized polyester fabrics named PF-HUSC exhibited a rough surface with P, Si, N and Ca element distributions, as observed by scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDX). Flame retardancy evaluations showed that the damaged length of PF-HUSC with a limiting oxygen index (LOI) value of 35.3 ± 0.3 % was reduced from the contrastive 17.6 ± 0.4 cm to 4.6 ± 0.2 cm after vertical burning test. Thermogravimetric (TG) test confirmed that PF-HUSC retained a char residue as high as 35.1 % at 700 °C. Cone calorimetry test displayed that the total heat release (THR) and total smoke production (TSP) values of PF-HUSC were reduced to 3.1 MJ/m2 and 1.1 m2, respectively, as compared to those of pure polyester fabrics. More importantly, PF-HUSC still exhibited higher LOI value than that of pure polyester fabrics after 25 washing cycles. Hence, the coating scheme is considered as a new method to expand the preparation of flame-retardant polyester fabrics.

Asymmetric ionic bond shielding encountering with carboxylate capturing metal ions for enhancing the flame retardant durability of regenerated cellulose fibers.

Enhancing the flame retardancy and durability of cellulose fibers, particularly environmentally friendly regenerated cellulose fibers types like Lyocell fibers, is essential for advancing their broader application. This study introduced a novel approach to address this challenge. Cationic-modified Lyocell fibers (Lyocell@CAT) were prepared by introducing quaternary ammonium structures into the molecular chain of Lyocell fibers. Simultaneously, a flame retardant, APA, containing -COO-NH4+ and -P=O(O-NH4+)2 groups was synthesized. APA was then covalently bonded to Lyocell@CAT to prepare Lyocell@CAT@APA. Even after undergoing 30 laundering cycles (LCs), Lyocell@CAT@APA maintained a LOI value of 37.2 %, exhibiting outstanding flame retardant durability. The quaternary ammonium structure within Lyocell@CAT@APA formed asymmetric ionic bonds with the phosphate and carboxylate groups in APA, effectively shielding the binding of Na+ ions with phosphate groups during laundering, thereby enhancing the durability. Additionally, the consumption of Na+ ions by carboxylate groups further prevented their binding to phosphate groups, which contributed to enhance the durability properties. Flame retardant mechanism analysis revealed that both gas and condensed phase synergistically endowed excellent flame retardancy to Lyocell fibers. Overall, this innovative strategy presented a promising prospect for developing bio-safe, durable, and flame retardant cellulose textiles.

A novel splicing mutation in 5'UTR of GJB1 causes X-linked Charcot-Marie-tooth disease.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is the most frequent hereditary motor sensory neurological disease. GJB1 gene is the second most frequent cause of CMT, accounting for approximately 10% of CMT cases worldwide. We identified a large Han family with X-linked CMT disease. METHODS: In this study, the probands and his mother underwent electrophysiological examinations and other family members were assessed retrospectively. Whole-exome sequencing, Sanger sequencing, and SNP array linkage analysis were performed to find and confirm the variant. The functional effect of the identified variant was further investigated in HEK293 cells and MCF-7 cells by minigene splicing assay. RESULTS: The affected individuals had some clinical symptoms including symmetric atrophy and progressive weakness of the distal muscles in their twenties. Electrophysiological examinations result in peripheral nerve injury of the upper and lower limbs. Whole-exome sequencing identified a novel hemizygous deletion mutation (NM_000166: c.-16-8_-14del) in the GJB1 gene. SNP array linkage analysis and co-segregation analysis confirmed this mutation. Minigene splicing assay verified that this mutation leads to the activation of cryptic splicing sites in exon 2 which results in the deletion of exon 2. CONCLUSION: Our study provides theoretical guidance for prenatal diagnosis and subsequent fertility of this family. This result expands the spectrum of mutations in GJB1 known to be associated with CMTX and contributes to the diagnosis of CMT and clinical genetic counseling.

Combined effects of microplastics and excess boron on Microcystis aeruginosa.

Both microplastics (MPs) and excess boron (B) have adverse effects on microalgae. However, the combined toxic effects of MPs and excess B on microalgae have not been studied. The aim of this study was to investigate the combined effects of excess B and three types of surface-modified microplastics, including plain polystyrene (PS-Plain), amino-modified polystyrene (PS-NH2), and carboxyl-modified polystyrene (PS-COOH), on chlorophyll a content, oxidative damage, photosynthetic activity and microcystin (MC) production in Microcystis aeruginosa. The results showed that PS-NH2 inhibited the growth of M. aeruginosa, with the maximum inhibition rate of 18.84 %, while PS-COOH and PS-Plain showed stimulatory effects with the maximum inhibition rates of -2.56 % and - 8.03 % respectively. PS-NH2 aggravated the inhibition effects of B, while PS-COOH and PS-Plain alleviated the inhibition effects. Furthermore, the combined exposure of PS-NH2 and excess B had a much greater effect on oxidative damage, cell structure, and production of MCs in algal cells than the combined effects of PS-COOH and PS-Plain. The charges on microplastics affected both B adsorption on microplastics and the aggregation of microplastics with algal cells, indicating that the charge on microplastics is a dominant factor influencing the combined effects of microplastics and excess B on microalgae. Our findings can provide direct evidence for the combined effects of microplastics and B on freshwater algae and improve the understanding of the potential risks of microplastics in aquatic ecosystems.

Influence of relative humidity on the nanoscopic topography and dielectric constant of thin films of PPy:PSS.

The morphological, electric, and dielectric properties of water-based conjugated polymer blends, such as polypyrrole:polystyrene sulfonate (PPy:PSS) or poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), are known to be influenced by the water content. These properties also influence the macroscopic performance when the conjugated polymer blends are employed in a device. An in situ humidity-dependence study on thin films of PPy:PSS by Kelvin probe force microscopy (KPFM) is presented. A particular KPFM mode, dielectric imaging, is used, which detects the second harmonic electrostatic force. Thin PPy:PSS films are drop-coated on hydrophobic graphite substrates. Upon increasing the relative humidity, the hydrophilic PSS is swelled and dewetted on the substrate, while the hydrophobic PPy remains almost unchanged. The swelling and dewetting of PSS results in irreversible morphological changes in the thin films, as well as nanoscopic rearrangement on the surface of the PPy:PSS films. The nanoscopic rearrangement can only be detected by dielectric imaging. It is also observed that relative humidity affects unannealed and thermally annealed PPy:PSS thin films differently.

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer.

PURPOSE: As the deadliest gynecological malignancy, ovarian cancer ranks as a major cause of disease-related deaths to women worldwide and is treated with transurethral resection or systemic chemotherapy. However, traditional chemotherapeutic drug in antitumor therapy has shown unavoidable limitations, such as poor curative effects, systemic toxicity and development of drug resistance, leading to failure of tumor inhibition and recurrence. This study aims to explore an innovative method to enhance the clinical efficiency of ovarian cancer. MATERIALS AND METHODS: Using MTT assay, the cell viability was detected under different culture systems. Western blot was used to examine the expression of P-gp in doxorubicin-resistant and wild-type A2780/SKOV3 cells. We used confocal to examine the drug concentration under different culture conditions. Also, flow cytometry was used to detect the drug absorption at the determined time points under different culture systems. Using nude mice model, we evaluated the killing efficacy of chemotherapeutic drugs with or without nanoparticle encapsulation. ELISA was used to examine the levels of creatinine, alanine aminotransferase and aspartate aminotransferase in plasma. RESULTS: We found that pretreatment of chloroquine (CQ) as chemosensitizer markedly enhanced the anticancer effects in ovarian cancer. We also provided evidence that CQ efficiently increase the pH value of lysosomes in tumor cells, leading to the reverse of drug sequestration induced by lysosomes. To further improve the pharmacokinetics profiles and avoid the systemic toxicity caused by chemotherapeutic agents, we encapsulated CQ and chemotherapeutic drugs by polymeric nanoparticles methoxy poly(ethylene glycol)-poly(l-lactic acid). Codelivery of CQ and chemotherapeutic agents by nanocarrier revealed enhanced anticancer effects compared with the free drug delivery by tail vein injection. More importantly, accumulated drugs, prolonged drug circulation and reduced organic damages were observed in nanoparticles delivery. CONCLUSION: Codelivery of CQ and chemotherapeutic drugs by methoxy poly(ethylene glycol)-poly(l-lactic acid) could significantly improve the anticancer effects and might have important potency in clinical applications for ovarian cancer therapy.

Cross-Linked and Biodegradable Polymeric System as a Safe Magnetic Resonance Imaging Contrast Agent.

Owing to the low efficacy of clinically used small-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) agents, we designed and explored biodegradable macromolecular conjugates as MRI contrast agents. The linear polymeric structure and core-cross-linked formulation possessed different characteristics and features, so we prepared and comparatively studied the two kinds of Gd-based N-(2-hydroxypropyl) methacrylamide (HPMA) polymeric systems (the core-cross-linked pHPMA-DOTA-Gd and the linear one) using the clinical agent diethylene-triamine pentaacetic acid-Gd(III) (DTPA-Gd) as a control. This study was aimed to find the optimal polymeric formulation as a biocompatible and efficient MRI contrast agent. The high molecular weight (MW, 181 kDa) and core-cross-linked copolymer was obtained via the cross-linked block linear copolymer and could be degraded to low-MW segments (29 kDa) in the presence of glutathione (GSH) and cleaned from the body. Both core-cross-linked and linear pHPMA-DOTA-Gd copolymers displayed 2-3-fold increased relaxivity (r1 value) than that of DTPA-Gd. Animal studies demonstrated that two kinds of macromolecular systems led to much longer blood circulation time, higher tumor accumulation, and much higher signal intensity compared with the linear and clinical ones. Finally, in vivo and in vitro toxicity studies indicated that the two macromolecular agents had great biocompatibility. Therefore, we performed preliminary but important studies on the Gd-based HPMA polymeric systems as biocompatible and efficient MRI contrast agents and found that the biodegradable core-cross-linked pHPMA-DOTA-Gd copolymer might have greater benefits for the foreground.

Stimuli-Sensitive Biodegradable and Amphiphilic Block Copolymer-Gemcitabine Conjugates Self-Assemble into a Nanoscale Vehicle for Cancer Therapy.

The availability and the stability of current anticancer agents, particularly water-insoluble drugs, are still far from satisfactory. A widely used anticancer drug, gemcitabine (GEM), is so poorly stable in circulation that some polymeric drug-delivery systems have been under development for some time to improve its therapeutic index. Herein, we designed, prepared, and characterized a biodegradable amphiphilic block N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-GEM conjugate-based nanoscale and stimuli-sensitive drug-delivery vehicle. An enzyme-sensitive oligopeptide sequence glycylphenylalanylleucylglycine (GFLG) was introduced to the main chain with hydrophilic and hydrophobic blocks via the reversible addition-fragmentation chain transfer (RAFT) polymerization. Likewise, GEM was conjugated to the copolymer via the enzyme-sensitive peptide GFLG, producing a high molecular weight (MW) product (90 kDa) that can be degraded into smaller MW segments (<50 kDa), and ensuring potential rapid site-specific release and stability in vivo. The amphiphilic copolymer-GEM conjugate can self-assemble into compact nanoparticles. NIR fluorescent images demonstrated that the conjugate-based nanoparticles could accumulate and be retained within tumors, resulting in significant increased antitumor efficacy compared to free GEM. The conjugate was not toxic to organs of the mice as measured by body weight reductions and histological analysis. In summary, this biodegradable amphiphilic block HPMA copolymer-gemcitabine conjugate has the potential to be a stimuli-sensitive and nanoscale drug-delivery vehicle.

Extended duration versus standard duration of peginterferon alfa-2a in treatment of chronic hepatitis B: A systematic review and meta-analysis.

In the last decade, PEG-IFNa-2a has been widely used in the treatment of chronic hepatitis B (CHB). The current standard duration is 48 weeks; however, several studies based on small sample sizes have indicated that treatment extended beyond 48 weeks improved clinical outcomes than standard 48 weeks of therapy. Therefore, we performed a meta-analysis to compare the efficacy and safety of extended duration versus standard duration treatment with PEG-IFNa-2a monotherapy for patients with CHB. Four studies comprising of 350 patients were included in our study. Our analysis showed that extended treatment resulted in a higher HBsAg clearance rate compared with the standard treatment at the end of treatment, 24 and 48 weeks post-treatment [odds ratio (OR)=2.45, 95% confidence intervals (CI) (1.17-5.11), P=0.02; OR=3.17, 95% CI (1.62-6.21), P<0.01; OR=5.02, 95% CI (1.63-15.45), P<0.01, respectively]. Higher HBeAg seroconversion rates were also obtained in the extended treatment group than the standard treatment group at the end of treatment and 48 weeks post-treatment [OR=2.09, 95% CI (1.10-3.98), P=0.02, and OR=2.67, 95% CI (1.39-5.13), P<0.01, respectively]. In addition, extended treatment was superior to standard treatment in HBV-DNA inhibition rate at 48 weeks post-treatment [OR=3.15, 95% CI (1.51-6.57), P<0.01]. Therefore, extended treatment with PEG-IFNa-2a beyond 48 weeks may be a promising strategy to achieve higher rates of sustained HBV-DNA inhibition, HBeAg seroconversion and HBsAg clearance off-therapy for patients with CHB.

Stimuli-Responsive Biodegradable Hyperbranched Polymer-Gadolinium Conjugates as Efficient and Biocompatible Nanoscale Magnetic Resonance Imaging Contrast Agents.

The efficacy and biocompatibility of nanoscale magnetic resonance imaging (MRI) contrast agents depend on optimal molecular structures and compositions. Gadolinium [Gd(III)] based dendritic macromolecules with well-defined and tunable nanoscale sizes are excellent candidates as multivalent MRI contrast agents. Here, we propose a novel alternate preparation of biodegradable hyperbranched polymer-gadolinium conjugates via a simple strategy and report potentially efficient and biocompatible nanoscale MRI contrast agents for cancer diagnosis. The enzyme-responsive hyperbranched poly(oligo-(ethylene glycol) methacrylate)-gadolinium conjugate (HB-POEGMA-Gd) was prepared via one-step reversible addition-fragmentation chain transfer (RAFT) polymerization and Gd(III) chelating, and the cRGDyK functionalized polymer (HB-POEGMA-cRGD-Gd) was obtained via click chemistry. By using an enzyme similar to lysosomal cathepsin B, hyperbranched conjugates of high molecular weights (MW) (180 and 210 kDa) and nanoscale sizes (38 and 42 nm) were degraded into low MW (25 and 30 kDa) and smaller products (4.8 and 5.2 nm) below the renal threshold. Conjugate-based nanoscale systems had three-fold more T1 relaxivity compared to clinical agent diethylenediaminepentaacetic acid (DTPA)-Gd. Animal studies with the nanoscale system offered greater tumor accumulation and enhanced signal intensity (SI) in mouse U87 tumors of which the greatest activity was conferred by the cRGDyK moiety functionalized hyperbranched conjugate. In vitro cytotoxicity, hemocompatibility and in vivo toxicity studies confirmed no adverse events. This design strategy for multifunctional Gd(III)-labeled biodegradable dendritic macromolecules may have significant potential as future efficient, biocompatible polymeric nanoscale MRI diagnostic contrast agents for cancer.