In this study, an engineered non-viral polymer based delivery systems with structural features mimicking that of viral vectors was developed and the potential of this carrier for siRNA delivery was assessed. The developed siRNA carrier was based on poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles decorated with integrin alphavbeta3 targeting peptide (RGD4C) and/or cell penetrating peptide (TAT) on the PEO shell, and modified with a polycation (spermine) in the PCL core for siRNA binding and protection. We observed increased cellular uptake and effective endosomal escape of siRNA delivered with the peptide-functionalized micelles especially those with dual functionality (RGD/TAT-micelles) compared to unmodified micelles (NON-micelles) in MDA435/LCC6 resistant cells. Transfection of mdr1 siRNA formulated in peptide-modified micelles led to P-gp down regulation both at the mRNA and protein level. Subsequent to P-gp down regulation, increased cellular accumulation of P-gp substrate, doxorubicin (DOX), in the cytoplasm and nucleus of resistant MDA435/LCC6 cells after treatment with peptide decorated polymeric micelle/mdr1 siRNA complexes was observed. As a result, resistance to DOX was successfully reversed. Interestingly, RGD/TAT-micellar siRNA complexes produced improved cellular uptake, P-gp silencing, DOX cellular accumulation, DOX nuclear localization and DOX induced cytotoxicity in MDA435/LCC6 cells when compared to micelles decorated with individual peptides. Results of this study indicated a potential for RGD/TAT-functionalized virus-like micelles as promising carriers for efficient delivery of mdr1 siRNA to MDA435/LCC6 resistant cells as means to reverse the P-gp mediated multidrug resistance to DOX.

We present results on the effects of various hydrophobic drugs and additives on the micellar structure of Pluronic F127 solutions. Small-angle neutron scattering experiments on 5wt% F127 solutions were used to measure micelle core size (R(1)), micelle corona size (R(2)), intermicellar interaction distance (R(int)), polydispersity (sigma), and aggregation number (N(agg)); dynamic light scattering was used to measure critical micelle concentration (CMC); and ultraviolet spectroscopy was used to measure drug solubility and apparent micelle-water partition coefficient (K(mw)). The core and corona size were found to generally increase in the presence of the drugs, as did R(int). Both sigma and N(agg) were found to decrease in the presence of most of the drugs, and the CMC was found to vary considerably with no clear correlation. A design of experiments (DOE) approach was used to analyze the results and build empirical correlations. All of the parameters from the SANS experiments were found to depend strongly on drug solubility, with a weak dependence on K(mw) in most cases. The aggregation number, however, was found to depend strongly on both K(mw) and solubility. The correlations can be used to roughly predict the structural parameters of F127 micelles for other hydrophobic drugs.

Covalently grafted poly(ethylene oxide) coatings have been widely studied for use in biomedical applications, particularly for the reduction of protein and other biomolecule adsorption. However, many of these studies have not characterized the hydrated structure of the coatings. This new study uses a combination of silica colloid probe interaction force measurements using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) in order to determine the grafting density and hydrated layer structure of monomethoxy poly(ethylene oxide) aldehyde layers, covalently grafted onto amine plasma polymer surfaces, and their interactions with silica surfaces. For high grafting densities, purely repulsive interactions were measured as expected for densely grafted polymer brushes. These interactions could be described by theoretical expectations for compression of one polymer brush layer. However, at lower grafting densities, attractive interactions were observed at larger separation distances, originating from bridging interactions due to adsorption of the PEO chains on the surface of the silica colloid probe. This is a new finding indicating that the coupled PEO molecules have sufficient conformational freedom to interact strongly with an adjacent surface or, for example, protein molecules for which there is an affinity. The attractive interactions could be removed by grafting an additional PEO layer onto the silica colloid probe. Protein adsorption measurements confirmed that at high grafting densities, the amount of adsorbed protein on the PEO grafted surfaces was greatly reduced, to the order of the detection limit for the XPS technique.

OBJECTIVE

To assess the effect of fatty acid substitution of a micelle-forming poly(ethylene oxide)-block-poly(N-hexyl stearate-L-aspartamide) (PEO-b-PHSA) on the encapsulation, hemolytic properties and antifungal activity of amphotericin B (AmB).

METHODS

PEO-b-PHSA with three levels of stearic acid substitution were synthesized and used to encapsulate AmB by a solvent evaporation method. Size exclusion chromatography and UV spectroscopy were used to confirm and measure levels of encapsulated AmB. The hemolytic activity of encapsulated AmB toward human red blood cells and its minimum inhibitory concentration against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans were obtained and compared to AmB alone.

RESULTS

An increase in the level of stearic acid substitution on PEO-b-PHSA improved the encapsulation of AmB while reducing its hemolytic activity. PEO-b-PHSA micelles having 50% and 70% stearic acid substitution (mol fatty acid: mol reacted and unreacted hydroxyls) were completely non-hemolytic at 22 microg/ml. At 11% stearic acid substitution, AmB caused 50% hemolysis at 1 microg/ml. AmB in PEO-b-PHSA micelles was as effective as AmB alone against pathogenic fungi.

CONCLUSIONS

PEO-b-PHSA micelles with a high level of stearic acid side chain substitution can effectively solubilize AmB, reduce its hemolytic activity yet retain its potent antifungal effects.

The dopamine receptor D2 (DRD2), a G-protein coupled receptor is expressed into PBd(22)-PEO(13) and PMOXA(20)-PDMS(54)-PMOXA(20) block copolymer vesicles. The conformational integrity of the receptor is confirmed by antibody- and ligand-binding assays. Replacement of bound dopamine is demonstrated on surface-immobilized polymersomes, thus making this a promising platform for drug screening.

The present work focused on the design of an assembled drug delivery system (DDS) to provide multifunctions, such as drug protection, self-regulated oscillatory release, and targeted uni-directional delivery by a bilayered self-folding gate and simple surface mucoadhesion. In this device, a pH-sensitive hydrogel together with a poly(hydroxyethyl methacrylate) (HEMA) barrier was used as a gate to control drug release. In addition, poly(HEMA) coated with poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO-PPO-PEO) surfactant was utilized to enhance mucoadhesion on the device surface. The release profiles of two model drugs, acid orange 8 (AO8) and bovine serum albumin (BSA) were studied in this assembled system, which compared with the conventional drug-entrapped carriers and enteric-coating systems. Furthermore, targeted uni-directional release was demonstrated in a side-by-side diffusion cell. In conclusion, for such an assembled device, the poly(HEMA) layer not only affects the folding direction but also serves as a barrier to protect the model drugs. The release time can be controlled by the thickness of the bilayered gate and the drug reservoir. Due to the reversible swelling behavior of poly(methyacrylic acid-g-ethylene glycol) (p(MAA-g-EG)) gels, the bilayered gate can sense the environmental pH change and achieve an oscillatory release pattern. Moreover, the local targeting and uni-directional release have been successfully demonstrated in vitro.

The prognosis for oral squamous cell carcinoma (OSCC) is not improving despite advances in surgical treatment. As with many cancers, there is a need to deliver therapeutic agents with greater efficiency into OSCC to improve treatment and patient outcome. The development of polymersomes offers a novel way to deliver therapy directly into tumor cells. Here we examined the internalization and biodistribution of two different fluorescently labeled polymersome formulations; polyethylene oxide (PEO)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) and poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-PDPA, into SCC4 OSCC cells in vitro and in vivo. In vitro SCC4 monolayers internalized PMPC-PDPA and PEO-PDPA at similar rates. However, in vivo PMPC-PDPA polymersomes penetrated deeper and were more widely dispersed in SCC4 tumors than PEO-PDPA polymersomes. In the liver and spleen PMPC-PDPA mainly accumulated in tissue macrophages. However, in tumors PMPC-PDPA was found extensively in the nucleus and cytoplasm of tumor cells as well as in tumor-associated macrophages. Use of PMPC-PDPA polymersomes may enhance polymersome-mediated antitumor therapy.

FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing.

Films containing hydroxypropylcellulose (HPC) and polyethylene oxide (PEO) were prepared using a Randcastle extruder (Model 750) with and without Vitamin E TPGS (TPGS, D-alpha-tocopheryl polyethylene glycol 1000 succinate) as an additive. Conventional plasticizers including polyethylene glycol 400 (PEG 400), triethyl citrate (TEC), and acetyltributyl citrate (ATBC) were also incorporated into films containing a 50:50 blend of HPC and PEO. The physical-mechanical properties including tensile strength (TS) and percent elongation (%E) were determined on an Instron according to the ASTM standards. Glass transition temperatures (T(g)) of the extruded films were determined utilizing a DSC 2920 Modulated differential scanning calorimeter and THERMAL ANALYST 2000 software. Gel permeation chromatography was used to study the stability of the polymer films under the processing conditions. The addition of 1, 3, and 5% Vitamin E TPGS, respectively, decreased the glass transition temperature of the extruded films containing either a 50:50 or 80:20 ratio of HPC to PEO in an almost linear fashion. In addition, the presence of 3% Vitamin E TPGS lowered the T(g) over 11 degrees C when compared with the HPC/PEO 50:50 blend film without TPGS, thus functioning as a plasticizer. The tensile strength decreased with increasing concentrations of TPGS, and the %E increased over 3-fold when compared with the HPC/PEO film that contained no additives. The film containing 3% Vitamin E TPGS had a similar tensile strength to that of the films containing 3% PEG 400, and a 3-fold increase in percent elongation when compared with the films containing 3% TEC and 3% ATBC. In addition, the Vitamin E TPGS facilitated the processing of the HPC/PEO films by decreasing the barrel pressure, drive amps, and torque of the extruder equipment.

The purpose of this study was to develop a buccal paclitaxel delivery system using the thermosensitive polymer Pluronic F127 (PF127) and the mucoadhesive polymer polyethylene oxide (PEO). The anticancer agent paclitaxel is usually used to treat ovarian, breast, and non-small-cell lung cancer. To improve its aqueous solubility, paclitaxel was incorporated into an inclusion complex with (2,6-di-O-methyl)-β-cyclodextrin (DMβCD). The formation of the paclitaxel inclusion complex was evaluated using various techniques, including x-ray diffractometry (XRD), Fourier-transform infrared (FT-IR) spectrophotometry, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Hydrogels were prepared using a cold method. Concentrations of 18, 20, and 23% (w/v) PF127 were dissolved in distilled water including paclitaxel and stored overnight in a refrigerator at 4 °C. PEO was added at concentrations of 0.1, 0.2, 0.4, 0.8, and 1% (w/v). Each formulation included paclitaxel (0.5 mg/mL). The sol-gel transition temperature of the hydrogels was measured using the tube-inverting method. Drug release from the hydrogels was measured using a Franz diffusion cell containing pH 7.4 phosphate-buffered solution (PBS) buffer at 37 °C. The cytotoxicity of each formulation was measured using the MTT assay with a human oral cancer cell (KB cell). The sol-gel transition temperature of the hydrogel decreased when PF127 was present and varied according to the presence of mucoadhesive polymers. The in vitro release was sustained and the release rate was slowed by the addition of the mucoadhesive polymer. The cytotoxicity of the blank formulation was low, although the drug-loaded hydrogel showed acceptable cytotoxicity. The results of our study suggest that the combination of a PF 127-based mucoadhesive hydrogel formulation and inclusion complexes improves the in vitro release and cytotoxic effect of paclitaxel.

Progressive external ophthalmoplegia (PEO), marked by progressive bilateral ptosis and diffuse reduction in ocular motility, represents a finding of mitochondrial myopathy rather than a true diagnosis. PEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality. Accurate and early recognition of PEO is paramount for the optimal care of these patients. We present an evidence-based review of the presenting neuro-ophthalmic features, differential diagnosis, diagnostic tools, systemic implications, and treatment options for isolated PEO and other PEO-associated mitochondrial syndromes.

A facile method to synthesize silver nanoparticles (AgNPs) using carboxymethyl chitosan (CMCTS), which act as reducing agent for silver ions as well as protecting agent for the formed AgNPs, is reported. CMCTS embedded AgNPs are mixed with polyethylene oxide (PEO). The blend polymers containing AgNPs are electrospun resulting in blend nano-fiber mats. The formation of AgNPs has been confirmed using UV-vis and TEM. The diameter range of 12-18 nm of well-dispersed AgNPs with a concentration of 100 ppm was obtained. The electrospun mats are characterized using SEM, EDX as well as TGA. Antimicrobial activity against different species of pathogenic/nonpathogenic; Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922 in addition to the fungus Candida albicans ATCC 10231 was studied. The results show excellent antimicrobial activity compared with nanofibers without AgNPs and AgNPs alone.

Apparent viscosities at different shear rates were measured for 3 types of saliva substitutes: (a) mucin-containing saliva; (b) substitutes based upon carboxymethylcellulose (CMC), and (c) solution of polyethylenoxide (PEO). The apparent viscosities were compared with those of human whole saliva. Human whole saliva and mucin-containing saliva substitutes appeared to be similar in their rheological properties. Both types of solution are viscoelastic solutions and adjust their apparent viscosities to their biological functions. Preparations containing CMC or PEO are non-Newtonian liquids. From this study it is concluded that mucin-containing saliva substitutes appear to be the best substitutes for natural saliva, as far as rheological properties are concerned.

OBJECTIVE

To demonstrate utility of folic acid-coated liposomes for enhancing the delivery of a poorly absorbed glycopeptide, vancomycin. via the oral route.

METHODS

Liposomes prepared as dehydration-rehydration vesicles (DRVs) containing vancomycin were optimized for encapsulation efficiency and stability. A folic acid-poly(ethylene oxide)-cholesterol construct was synthesized for adsorption at DRV surfaces. Liposomes were characterized by differential scanning calorimetry (DSC) and assessed in vitro in the Caco-2 cell model and in vivo in male Sprague-Dawley rats. Non-compartmental pharmacokinetic analysis of vancomycin was conducted after intravenous and oral administration of solution or liposome-encapsulated vancomycin with or without 0.05 mole ratio FA-PEO-Chol adsorbed at liposome surfaces.

RESULTS

Optimal loading of vancomycin (32%) was achieved in DRVs of DSPC:Chol:DCP, 3:1:0.25 mole ratio (m.r.) after liposome extrusion. Liposomes released less than 40% of the entrapped drug after 2 hours incubation in simulated gastrointestinal (GI) fluid and simulated intestinal fluid containing a 10 mM bile salt cocktail. Incorporation of FA-PEO-Chol in liposomes increased drug leakage by 20% but resulted in a 5.7-fold increase in Caco-2 cell uptake of vancomycin. Liposomal delivery significantly increased the area under the curve of oral vancomycin resulting in a mean 3.9-fold and 12.5-fold increase in relative bioavailability for uncoated and FA-PEO-Chol-coated liposomes, respectively, compared with an oral solution.

CONCLUSIONS

The design of FA-PEO-Chol-coated liposomes resulted in a dramatic increase in the oral delivery of a moderate-size glycopeptide in the rat compared with uncoated liposomes or oral solution. It is speculated that the cause of the observed effect was due to binding of liposome-surface folic acid to receptors in the GI tract with subsequent receptor-mediated endocytosis of entrapped vancomycin by enterocytes.

Background: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV) has been recently characterized, and soon spread around the world generating a pandemic. It has been suggested that men are more severely affected by the viral disease (COVID-19) than women.

Objective: the aim of the present Systematic Literature Review (SRL) and meta-analysis was to analyse the influence of gender on COVID-19 mortality, severity and disease outcomes. A SRL was performed in PubMed and Embase searching terms corresponding to the "PEO" format (Population = adult patients affected with COVID-19, Exposure = gender; Outcome = any available clinical outcomes by gender, including mortality and disease severity), search dates 01/01/2020-31/04/2020. Exclusion criteria were: case reports/series, reviews, commentaries, language other than English. We included full-text original articles. Data about study type, country, patients characteristics were extracted. Study quality was evaluated by Newcastle-Ottawa Scale (NOS). From a total of 950 hits generated by databases search, 85 articles fulfilling inclusion/exclusion criteria were selected.

Results: A random-effect meta-analysis was performed to compare mortality, recovery rates and disease severity in men versus women. Male to female ratio was 1: 0.8. A significant association between male sex and mortality (OR = 1.81; 95%CI: 1.25-2.62), as well as a lower chance of recovery in men (OR = 0.72; 95% CI: 0.55- 0.95). Male patients had a higher odd to present with a severe form of COVID-19 (OR = 1.46; 95%CI: 1.10-1.94).

Conclusions: male are more susceptible to COVID-19 infection, present with a more severe disease and have a worse prognosis. Further studies are warranted to unravel biological mechanisms underlying these observations.

Keywords: COVID-19; gender; systematic review and meta-analysis.

Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor) nanoparticles and DiI (acceptor) nanoparticles were coincubated with cancer cells for 2 h, increased FRET signals were observed from cell membranes, suggesting rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios were detected in nude mice after intravenous coadministration of DiD (donor) nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of nude mice i.v. administrated with DiD/DiR coloaded nanoparticles showed decreased FRET ratios. Based on the difference in FRET ratios between the two groups, in vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2 min. In addition, it was observed that the presence of cell membranes facilitated burst release of lipophilic cargos while incorporation of oleic acid-coated iron oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes. The developed in vitro and in vivo FRET imaging techniques can be used to screening stable nanoformulations for lipophilic drug delivery.

In this communication, the synthesis and characterization of thermo- and light responsive block copolymers is reported. PEO-b-PNIPAM polymers with azobenzene moieties were prepared and analyzed by turbidimetry, fluorescence, NMR and DLS measurements. A temperature controlled reversible formation as well as a light induced disruption and reformation of micellar structures in water was found.

A range of polyethylene oxide/polybutylene terephthalate (PEO/PBT) copolymers (70-30% PEO) was investigated for nonloadbearing bone replacement application. Porous PEO/PBT cylinders (d = 5 mm, h = 7 mm) were implanted transcortically in the diaphyseal femur of 10 goats, and the animals were sacrificed at 3, 6, 9, 12, and 26 weeks. Qualitative evaluation was performed using light and fluorescence microscopy, scanning electron microscopy, and back-scatter electron imaging with an attached X-ray microanalysis system. The percentage of bone ingrowth and the percentage of bone contact in the pore region were quantitatively assessed using undecalcified histological sections. The hydrogel properties of the PEO/PBT copolymers provided a rapid closure of the defect upon press-fit implantation, due to postoperative water uptake and subsequent swelling behavior of the materials. Bridging of the defect by bone and the occurrence of bone bonding were observed 6 weeks postoperatively for the material with the highest PEO content (70/30). For the 60/40 and 55/45 PEO/PBT proportions, union of the defect and bone bonding were observed at 9 and 12 weeks, respectively. The stiffer 40/60 and 30/70 PEO/PBT implants showed bridging of the 5-mm gap after 12 weeks, but did not reveal bone bonding up to 26 weeks. Peripheral fragmentation, mainly in the marrow cavity, was found for the 70/30 material at 12 weeks and had increased at 26 weeks. Degradation was not seen for the other materials. The histomorphometrical data confirmed the microscopical observations and demonstrated a direct relation between PEO content in the PEO/PBT co-polymers, the rate of bone ingrowth, and the amount of bone contact. Porous PEO/PBT copolymers are degradable, bone-bonding elastomeric substrates with favorable handling properties and a high percentage of bone ingrowth (69-78 at 26 weeks). It was therefore concluded that PEO/ PBT copolymers are highly promising materials for bone-replacement surgery.

We report a new mutation, a T->>C transition at nt.4285 in the mitochondrial tRNA(Ile) gene, in a sporadic case of progressive external ophtalmoplegia (PEO) and ragged-red fibers (RRF). The mutation, involving a highly conserved base-pair in the anticodon stem, was detected in high percentages (91%) in muscle, but not in blood. It has never been reported in literature in normal subjects and it was not found in any of 80 controls studied in our laboratory. The absence of the mutation in leukocytes in this case with pure muscle involvement confirms the importance of performing mtDNA studies in PEO patients preferentially on muscle rather than blood, which could give false negative results. Other mutations in the tRNA(Ile) gene associated with different phenotypes have been previously reported. Thus, tRNA(Ile) gene is confirmed to be another "hot spot" region for mtDNA mutations.

Screws for ligament reconstruction are nowadays mostly made of poly-L-lactide (PLLA). However, magnesium-based biomaterials are gathering increased interest in this research field because of their good mechanical property and osteoanabolic influence on bone metabolism. The aim of this pilot study was to evaluate the biocompatibility of an interference screw for ligament reconstruction made of magnesium alloy W4 by diecasting and milling and using different PEO-coatings with calcium phosphates. PLLA and titanium screws were used as control samples. The screws were implanted in the femur condyle of the hind leg of a merino sheep. The observation period was six and twelve weeks and one year. Histomorphometric, immunohistochemical, immunofluorescence, and molecular biological evaluation were conducted. Further TEM analysis was done. In all magnesium screws a clinically relevant gas formation in the vicinity of the biomaterial was observed. Except for the PLLA and titanium control samples, no screw was fully integrated in the surrounding bone tissue. Regarding the fabrication process, milling seems to produce less gas liberation and has a better influence on bone metabolism than diecasting. Coating by PEO with calcium phosphates could not reduce the initial gas liberation but rather reduced the bone metabolism in the vicinity of the biomaterial.

A facile method for imparting hydrolytic degradability to poly(ethylene oxide) (PEO), compatible with current PEGylation strategies, is presented. By incorporating methylene ethylene oxide (MEO) units into the parent PEO backbone, complete degradation was defined by the molar incorporation of MEO, and the structure of the degradation byproducts was consistent with an acid-catalyzed vinyl-ether hydrolysis mechanism. The hydrolytic degradation of poly[(ethylene oxide)-co-(methylene ethylene oxide)] was pH-sensitive, with degradation at pH 5 being significantly faster than at pH 7.4 at 37 °C in PBS buffer while long-term stability could be obtained in either the solid-state or at pH 7.4 at 6 °C.

Airborne particle filtration proposed for fibers requires their assembly into porous structures with small pore size and low packing density. The ability to maintain structural stability upon deformation stress in service is essential to ensure a highly porous packing material that functions reliably; however, it has proven extremely challenging. Here, we report a strategy to create anti-deformed poly(ethylene oxide)@polyacrylonitrile/polysulfone (PEO@PAN/PSU) composite membranes with binary structures for effective air filtration by combining multijet electrospinning and physical bonding process. Our approach allows the ambigenous fiber framework including thin PAN nanofibers and fluffy PSU microfibers, through which run interpenetrating PEO bonding structures, to assemble into stable filtration medium with tunable pore size and packing density by facilely optimizing the bimodal fiber construction and benefiting from the PEO inspiration. With the integrated features of small pore size, high porosity, and robust mechanical properties (8.2 MPa), the resultant composite membrane exhibits high filtration efficiency of 99.992%, low pressure drop of 95 Pa, and desirable quality factor of 0.1 Pa(-1); more significantly, it successfully gets rid of the potential safety hazards caused by unexpected structural collapsing under service stress. The synthesis of PEO@PAN/PSU medium would not only make it a promising candidate for PM2.5 governance but also provide a versatile strategy to design and develop stable porous membranes for various applications.

Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common manifestation of mitochondrial disease in adulthood, for which there is no curative therapy. In mice with MM, ketogenic diet significantly delayed progression of the disease. We asked in this pilot study what effects high-fat, low-carbohydrate "modified Atkins" diet (mAD) had for PEO/MM patients and control subjects and followed up the effects by clinical, morphological, transcriptomic, and metabolomic analyses. All of our five patients, irrespective of genotype, showed a subacute response after 1.5-2 weeks of diet, with progressive muscle pain and leakage of muscle enzymes, leading to premature discontinuation of the diet. Analysis of muscle ultrastructure revealed selective fiber damage, especially in the ragged-red-fibers (RRFs), a MM hallmark. Two years of follow-up showed improvement of muscle strength, suggesting activation of muscle regeneration. Our results indicate that (i) nutrition can modify mitochondrial disease progression, (ii) dietary counseling should be part of MM care, (iii) short mAD is a tool to induce targeted RRF lysis, and (iv) mAD, a common weight-loss method, may induce muscle damage in a population subgroup.

In this paper, we demonstrate a nanofiber patterning technique using field-enhanced electrospinning. Polyethylene oxide (PEO) nanofibers were electrospun on an elastomeric substrate with gold-coated pyramidal protrusions with the majority of fibers being deposited at the tips. The deposited nanofiber spots ranged from 8 x 8 microm(2) to 60 x 60 microm(2) in size, uniformly covering an area of 5 x 10 mm(2). Our experiments also indicate that nanofiber pattern selectivity is highly dependent on the separation/size ratio of the pyramidal protrusions with a ratio of <1, resulting in a superior selectivity.