Forming a Double-Helix Phase of Single Polymer Chains by the Cooperation between Local Structure and Nonlocal Attraction.

Double-helix structures, such as DNA, are formed in nature to realize many unique functions. Inspired by this, researchers are pursuing strategies to design such structures from polymers. A key question is whether the double helix can be formed from the self-folding of a single polymer chain without specific interactions. Here, using Langevin dynamics simulation and theoretical analysis, we find that a stable double-helix phase can be achieved by the self-folding of single semiflexible polymers as a result of the cooperation between local structure and nonlocal attraction. The critical temperature of double-helix formation approximately follows T^{cri}∼ln(k_{θ}) and T^{cri}∼ln(k_{τ}), where k_{θ} and k_{τ} are the polymer bending and torsion stiffness, respectively. Furthermore, the double helix can exhibit major and minor grooves due to symmetric break for better packing. Our results provide a novel guide to the experimental design of the double helix.

pH-Triggered Surface Charge Reversed Nanoparticle with Active Targeting To Enhance the Antitumor Activity of Doxorubicin.

PLGA nanoparticles are widely used in tumor targeting drug delivery systems. However, the naked PLGA nanoparticles (NNPs) not only have low drug loading but also can be rapidly removed from blood circulation by the immune system. The aim of this study was to prepare pH-triggered surface charge reversed lipid hybrid PLGA nanoparticles (LNPs) to enhance drug loading and drug delivery efficiency. CHO-Arg-His-OMe and FA-PEG-DSPE were synthesized to modify PLGA nanoparticles to prepare LNPs. The drug loading and encapsulation rate of LNPs were greatly improved as compared with NNPs. In pH 7.4 medium, doxorubicin (DOX)-loaded LNPs showed negative charge and released DOX slowly. In pH 5.0 medium, DOX-loaded LNPs exhibited positive charge and released DOX quickly. DOX-loaded LNPs delivered more DOX to the nucleus of KB cells and MBA-MD-231/ADR cells than did free DOX. In addition, DOX-loaded LNPs significantly inhibited the proliferation of KB cells and MBA-MD-231/ADR cells. Compared with free DOX, the same dose of the DOX-loaded LNPs delivered more DOX to tumor tissue. Thus, DOX-loaded LNPs significantly inhibited the growth of tumor in tumor-bearing nude mice and obviously reduced the systemic toxicity of DOX. In conclusion, pH-triggered surface charge reversed DOX-loaded LNPs significantly enhanced the antitumor activity of DOX in vitro and in vivo. DOX-loaded LNPs had great potential in tumor targeted chemotherapy.

High-resolution morphologic and ultrashort time-to-echo quantitative magnetic resonance imaging of the temporomandibular joint.

OBJECTIVE: To implement high-resolution morphologic and quantitative magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) using ultrashort time-to-echo (UTE) techniques in cadavers and volunteers. METHODS: This study was approved by the institutional review board. TMJs of cadavers and volunteers were imaged on a 3-T MR system. High-resolution morphologic and quantitative sequences using conventional and UTE techniques were performed in cadaveric TMJs. Morphologic and UTE quantitative sequences were performed in asymptomatic and symptomatic volunteers. RESULTS: Morphologic evaluation demonstrated the TMJ structures in open- and closed-mouth position. UTE techniques facilitated the visualization of the disc and fibrocartilage. Quantitative UTE MRI was successfully performed ex vivo and in vivo, reflecting the degree of degeneration. There was a difference in the mean UTE T2* values between asymptomatic and symptomatic volunteers. CONCLUSIONS: MRI evaluation of the TMJ using UTE techniques allows characterization of the internal structure and quantification of the MR properties of the disc. Quantitative UTE MRI can be performed in vivo with short scan times.

PEG-detachable lipid-polymer hybrid nanoparticle for delivery of chemotherapy drugs to cancer cells.

The experiment aimed to increase the drug-delivery efficiency of poly-lactic-co-glycolic acid (PLGA) nanoparticles. Lipid-polymer hybrid nanoparticles (LPNs-1) were prepared using PLGA as a hydrophobic core and FA-PEG-hyd-DSPE as an amphiphilic shell. Uniform and spherical nanoparticles with an average size of 185 nm were obtained using the emulsification solvent evaporation method. The results indicated that LPNs-1 showed higher drug loading compared with naked PLGA nanoparticles (NNPs). Drug release from LPNs-1 was faster in an acidic environment than in a neutral environment. LPNs-1 showed higher cytotoxicity on KB cells, A549 cells, MDA-MB-231 cells, and MDA-MB-231/ADR cells compared with free doxorubicin (DOX) and NNPs. The results also showed that, compared with free DOX and NNPs, LPNs-1 delivered more DOX to the nuclear of KB cells and MDA-MB-231/ADR cells. LPNs-1 induced apoptosis in KB cells and MDA-MB-231/ADR cells in a dose-dependent manner. The above data indicated that DOX-loaded LPNs-1 could kill not only normal tumor cells but also drug-resistant tumor cells. These results indicated that modification of PLGA nanoparticles with FA-PEG-hyd-DSPE could considerably increase the drug-delivery efficiency and LPNs-1 had potential in the delivery of chemotherapeutic agents in the treatment of cancer.

Quantitative 3D ultrashort time-to-echo (UTE) MRI and micro-CT (µCT) evaluation of the temporomandibular joint (TMJ) condylar morphology.

OBJECTIVE: Temporomandibular dysfunction involves osteoarthritis of the TMJ, including degeneration and morphologic changes of the mandibular condyle. The purpose of this study was to determine the accuracy of novel 3D-UTE MRI versus micro-CT (µCT) for quantitative evaluation of mandibular condyle morphology. MATERIALS AND METHODS: Nine TMJ condyle specimens were harvested from cadavers (2 M, 3 F; age 85 ± 10 years, mean ± SD). 3D-UTE MRI (TR = 50 ms, TE = 0.05 ms, 104-µm isotropic-voxel) was performed using a 3-T MR scanner and µCT (18-µm isotropic-voxel) was also performed. MR datasets were spatially registered with a µCT dataset. Two observers segmented bony contours of the condyles. Fibrocartilage was segmented on the MR dataset. Using a custom program, bone and fibrocartilage surface coordinates, Gaussian curvature, volume of segmented regions, and fibrocartilage thickness were determined for quantitative evaluation of joint morphology. Agreement between techniques (MRI vs. µCT) and observers (MRI vs. MRI) for Gaussian curvature, mean curvature, and segmented volume of the bone were determined using intraclass correlation coefficient (ICC) analysis. RESULTS: Between MRI and µCT, the average deviation of surface coordinates was 0.19 ± 0.15 mm, slightly higher than the spatial resolution of MRI. Average deviation of the Gaussian curvature and volume of segmented regions, from MRI to µCT, was 5.7 ± 6.5% and 6.6 ± 6.2%, respectively. ICC coefficients (MRI vs. µCT) for Gaussian curvature, mean curvature, and segmented volumes were 0.892, 0.893, and 0.972, respectively. Between observers (MRI vs. MRI), the ICC coefficients were 0.998, 0.999, and 0.997, respectively. Fibrocartilage thickness was 0.55 ± 0.11 mm, as previously described in the literature for grossly normal TMJ samples. CONCLUSIONS: 3D-UTE MR quantitative evaluation of TMJ condyle morphology ex-vivo, including surface, curvature, and segmented volume, shows high correlation against µCT and between observers. In addition, UTE MRI allows quantitative evaluation of the fibrocartilaginous condylar component.

Efficacy of spray flushing in the reprocessing of flexible endoscopes: A randomized controlled trial.

BACKGROUND: Commonly used cleaning brushes in the reprocessing of flexible endoscopes often cause damage within the working channels. AIM: To develop a spray flushing system to achieving effective cleaning of the working channels while minimizing damage. METHODS: This prospective study included 60 used endoscopes and 60 Teflon tubes randomly divided into a control group (n = 30) and an experimental group (n = 30). The material of Teflon tubes was the same as that of the endoscope working channel. Endoscopes in the control group were manually cleaned using traditional cleaning brushes, while those in the experimental group were cleaned using the newly developed spray flushing system. ATP levels, cleanliness, and microbiological testing of the working channels were measured. Additionally, Teflon tubes in the control group underwent 500 passes with a cleaning brush, while those in the experimental group were subjected to the spray flushing system, and channel damage was evaluated. RESULTS: The ATP levels (RLU) in the two groups were 32.5 (13-66) and 26 (16-40), respectively (P > 0.05). Cleanliness scores were 1.5 (1-2) and 1 (1-2), respectively (P > 0.05). Debris was found in 73.3% of the control group, which was significantly higher than 46.7% in the experimental group (P < 0.05). Microbiological tests for both groups yielded negative results. Teflon tube damage in the control group was rated at 4 (4-5.25), which was significantly higher than in the experimental group 4 (3-4) (P < 0.01). CONCLUSION: The spray flushing system demonstrated superior efficacy in removing debris and resulted in less damage to the endoscope working channels compared with traditional cleaning brushes.

Recombinant human coxsackievirus B3 from children with acute myocarditis in China.

Recombination events were found in two human coxsackievirus B3 strains, Beijing0811 and SD2012CHN. The strains were isolated separately from five newborns diagnosed with severe hospital-acquired acute myocarditis in Beijing in 2008 and from two children diagnosed with hand, foot, and mouth disease with concurrent acute myocarditis in Shandong in 2012.

MR imaging near metal with undersampled 3D radial UTE-MAVRIC sequences.

Recently developed techniques such as the multiple acquisition with variable resonance image combination and slice encoding for metal artifact correction techniques have improved the ability of clinical magnetic resonance scanners to image near metal implants. These sequences are based on fast spin echo sequences which preclude detection of short T(2) tissues such as tendons, ligaments, and cortical bone. Ultrashort echo time sequences have the potential to detect signals from these tissues. In this study, we investigate the potential of combining ultrashort echo time with multiple acquisition with variable resonance image combination to image short T(2) musculoskeletal tissues adjacent to metallic implants. Different radio frequency excitation pulse types and spectral binning strategies were studied. We found that ultrashort echo time-multiple acquisition with variable resonance image combination sequences were able to significantly reduce typical artifacts near metal, as well as detect very short T(2) signals that are usually not visualized using clinical pulse sequences.

One-pot construction of epoxy resin nanocarrier delivering abamectin and its efficacy on plant root-knot nematodes.

BACKGROUND: The complex preparation process and storage instability of nanoformulations hinders their development and commercialization. In this study, nanocapsules loaded with abamectin were prepared by interfacial polymerization at room temperature and ordinary pressure using the monomers of epoxy resin (ER) and diamine. The potential mechanisms of primary amine and tertiary amine in influencing the shell strength of the nanocapsules and the dynamic stability of abamectin nanocapsules (Aba@ER) in the suspension system were systematically researched. RESULTS: The tertiary amine catalyzed the self-polymerization of epoxy resin into linear macromolecules with unstable structures. The structural stability of the diamine curing agent with a primary amine group played a key role in enhancing the structural stability of the polymers. The intramolecular structure of the nanocapsule shell formed by isophorondiamine (IPDA) crosslinked epoxy resin has multiple spatial conformations and a rigid saturated six-membered ring. Its structure was stable, and the shell strength was strong. The formulation had stable dynamic changes during storage and maintained excellent biological activity. Compared with emulsifiable concentrate (EC), Aba@ER/IPDA had superior biological activity, and the field efficacy on tomato root-knot nematode was enhanced by approximately 31.28% at 150 days after transplanting. CONCLUSION: Aba@ER/IPDA, which has excellent storage stability and simple preparation technology, can provide a nanoplatform with industrial prospects for efficient pesticide delivery. © 2023 Society of Chemical Industry.

Survey of enterovirus infections from hand, foot and mouth disease outbreak in China, 2009.

BACKGROUND: In China, a rapid expansion of Hand, foot, and mouth disease (HFMD) outbreaks has occurred since 2004 and HFMD has become an important issue for China. However, people are still only concerned with human enterovirus 71(HEV-71) and coxsackie virus A16 (CV-A16). Much of what is known about the other enterovirus infections relies on fractional evidence and old epidemic data, with little knowledge concerning their distribution. To alert potential threatens of the other enteroviruses, our study genetically characterized specimens from different regions of China and yielded novel information concerning the circulating and phylogenetic characteristics of enteroviral strains from HFMD cases. FINDINGS: A total of 301 clinical throat swabs were randomly obtained from patients suffering from HFMD from the southern, northern and central regions of China during outbreaks in 2009. 266 of 301 (88.4%) HFMD cases were found positive for HEV and seven genotypes, HEV-71, CV-A16, -B5, -A4, -A6, -A10, and -A12, were detected. CONCLUSIONS: The HFMD pathogen compositions in the different regions of China were significantly different. HFMD epidemics might persist for a long time in China due to the multiple pathogen compositions, the enteroviral characteristic of recombination and co-infection, the ever-increasing travel and migration and the deficiency of effective vaccine. Our study deserves the attention on HFMD control and vaccine development.

Layer-by-layer coated hybrid nanoparticles with pH-sensitivity for drug delivery to treat acute lung infection.

Bacteria-induced acute lung infection (ALI) is a severe burden to human health, which could cause acute respiratory distress syndrome (ARDS) and kill the patient rapidly. Therefore, it is of great significance to develop effective nanomedicine and therapeutic approach to eliminate the invading bacteria in the lung and manage ALI. In this study, we design a layer-by-layer (LbL) liposome-polymer hybrid nanoparticle (HNP) with a pH-triggered drug release profile to deliver antibiotics for the eradication of bacteria to treat ALI. The liposome is prepared by the lipid film hydration method with a homogenous hydrodynamic diameter and low polydispersity index (PDI). The antibiotic spectinomycin is efficiently loaded into the liposomal core through the pH-gradient method. The pH-sensitive polycationic polymer poly(ß-amino ester) (PBAE) and polyanionic sodium alginate (NaAIg) layers are decorated on the surface of liposome in sequence via electrostatic interaction, resulting in spectinomycin-loaded layer-by-layer hybrid nanoparticles (denoted as Spe@HNPs) which have reasonable particle size, high stability, prolonged circulation time, and pH-triggered drug release profile. The in vitro results demonstrate that Spe@HNPs can efficiently induce the death of bacteria with low minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) and drug-resistant MRSA BAA40 strains. The in vivo results reveal that Spe@HNPs can eradicate the invading MRSA BAA40 with improved antimicrobial efficacy and low side-effect for ALI treatment. This study not only reports a promising nanomedicine but also provides an effective method to prepare nanoplatforms for drug delivery and controlled release.

Negative-Pressure Isolation Mask for Endoscopic Examination During the Coronavirus Disease 2019 Pandemic: A Randomized Controlled Trial.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, endoscopists have high risks of exposure to exhaled air from patients during gastroscopy. To minimize this risk, we transformed the oxygen mask into a fully closed negative-pressure gastroscope isolation mask. This study aimed to evaluate the effectiveness, safety, and feasibility of use of this mask during gastroscopy. METHODS: From February 28, 2020, to March 10, 2020, 320 patients undergoing gastroscopy were randomly assigned into the mask group (n = 160) or conventional group (n = 160). Patients in the mask group wore the isolation mask during gastroscopy, whereas patients in the conventional group did not wear the mask. The adenosine triphosphate fluorescence and carbon dioxide (CO2) concentration in patients' exhaled air were measured to reflect the degree of environmental pollution by exhaled air. Patients' vital signs, operation time, and adverse events during endoscopy were also evaluated. RESULTS: Four patients were excluded because of noncooperation or incomplete data. A total of 316 patients were included in the final analysis. The difference between the highest CO2 concentration around patients' mouth and CO2 concentration in the environment was significantly decreased in the mask group compared with the conventional group. There was no significant difference in the adenosine triphosphate fluorescence, vital signs, and operation time between the 2 groups. No severe adverse events related to the isolation mask, endoscopy failure, or new coronavirus infection during follow-up were recorded. DISCUSSION: This new isolation mask showed excellent feasibility of use and safety compared with routine gastroscopy during the COVID-19 pandemic.

Facile and eco-friendly preparation of super-amphiphilic porous polycaprolactone.

Super-amphiphilic (highly oleophilic and hydrophilic) materials have attracted tremendous interest for fundamental research and potential applications, owing to their unique affinity for both oil and water. In this work, a novel super-amphiphilic porous polycaprolactone (PCL) was fabricated via an efficient and eco-friendly method, in which stearic acid (SA) was used as both a porogen and a dopant precursor. The porous PCL had an interconnected hierarchical pore structure and was capable of absorbing oil and water rapidly. The complementary cooperation of the oleophilic and hydrophilic domains on the pore surface induced the amphiphilicity, while the capillary forces caused a wicking action. The synergy of the two effects gave rise to the super-wetting property. The special amphiphilic feature of the porous PCL had a positive effect on its biocompatibility and the material can be considered as a promising candidate for tissue engineering applications.

Reduction-responsive shell cross-linked micelles derived from amphiphilic triblock copolymer as anticancer drug delivery carrier.

Stimuli-responsive crosslinked micelles are attractive carriers for in vivo delivery of water-insoluble therapeutic drugs due to their excellent stability during the blood circulation and high therapeutic effect resulting from the intelligent break-up of the crosslinked structure triggered by intracellular conditions as well as the subsequent fast drug release. Herein, novel amphiphilic triblock copolymer poly(l-lactide)-b-poly(allyl glycidyl ether/propanedithiol)-b-poly(ethylene glycol) (PLLA-b-P(AGE-SH)-b-PEG) was designed and synthesized by combining two successive ring-opening polymerizations and subsequent "thio-ene" reaction. Due to their unique amphiphilic architecture, copolymer PLLA-b-P(AGE-SH)-b-PEG could self-assemble into core-shell micelles, and the stimuli-responsive crosslinked micelles (SCMs) were obtained by crosslinking the P(AGE-SH) segments in the micellar shell under redox condition. The SCMs exhibited good stability against extensive dilution and slow sustained drug release in a simulated normal physiologycal environment, but fast release in the presence of GSH. As revealed by the cytotoxicity assay, the micelles from the copolymer PLLA-b-P(AGE-SH)-b-PEG showed excellent biocompatibility against HEK293T cells. Due to these combined good properties, the stimuli-responsive crosslinked micelles from PLLA-b-P(AGE-SH)-b-PEG are proposed to be an ideal carrier for the in vivo delivery of water-insoluble therapeutics.

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study.

In this paper, we aimed to investigate the feasibility of direct visualization of myelin, including myelin lipid and myelin basic protein (MBP), using two-dimensional ultrashort echo time (2D UTE) sequences and utilize phase information as a contrast mechanism in phantoms and in volunteers. The standard UTE sequence was used to detect both myelin and long T2 signal. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to selectively detect myelin by suppressing signal from long T2 water protons. Magnitude and phase imaging and T2* were investigated on myelin lipid and MBP in the forms of lyophilized powders as well as paste-like phantoms with the powder mixed with D2O, and rubber phantoms as well as healthy volunteers. Contrast to noise ratio (CNR) between white and gray matter was measured. Both magnitude and phase images were generated for myelin and rubber phantoms as well white matter in vivo using the IR-UTE sequence. T2* values of ~300µs were comparable for myelin paste phantoms and the short T2* component in white matter of the brain in vivo. Mean CNR between white and gray matter in IR-UTE imaging was increased from -7.3 for the magnitude images to 57.4 for the phase images. The preliminary results suggest that the IR-UTE sequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.

[Therapeutic effect of conservative treatment of refracture in cemented vertebrae after percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

OBJECTIVE: To evaluate the therapeutic effects of conservative treatment of refracture in cemented vertebrae after percutaneous vertebroplasty for osteoporotic vertebral compression fractures in elderly patients. METHODS: Between January, 2012 and August, 2014, a total of 324 elderly patients (381 vertebrae) received percutaneous vertebroplasty for osteoporotic vertebral compression fractures. Of these patients, 12 patients (14 vertebrae) complained of recurrence of back pain and were confirmed to have refracture in the cemented vertebrae by imaging examination. Seven of these 12 patients (9 vertebrae), who were all female with an average refracture time of 8±6.7 weeks (range 2-20 weeks), received conservative treatments with analgesics, osteoporosis medication, bracing and physical therapy, and their visual analogue scale (VAS) scores and Oswestry disability index (ODI) at 7 days and 1, 3 and 12 months after the treatment were measured. RESULTS: The 7 patients were followed up for 21.3±11.2 months (range 13-29 months) after conservative treatments. Their VAS score and ODI decreased significantly over time after the treatment (P<0.05) and showed significant differences between the measurements at 7 days, 1 and 3 months (P<0.05) but not between 3 and 12 months (P>0.05). The average VAS score and ODI before treatments were 8.3±0.8 and (88.3±3.2)%, 3.1±1.2 and (56.3±7.7)% at 1 month, and 0.8±0.7 and (5.9±2.8)% at 3 months during the follow-up, respectively.No such complications as phlebothrombosis of the leg, decubitus, or hypostatic pneumonia occurred in these cases. CONCLUSION: Though with a relatively low incidence rate, refracture in the cemented vertebrae is one of the important causes of recurrence of back pain following percutaneous vertebroplasty. Conservative treatment is effective in relieving pain and improving the spine function in such cases without obvious complications.

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

ETHNOPHARMACOLOGICAL RELEVANCE: Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. AIM OF THE STUDY: The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. MATERIALS AND METHODS: The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. RESULTS: Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8µg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5µg/mL. CONCLUSIONS: Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.

Class I ADP-ribosylation factors are involved in enterovirus 71 replication.

Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.