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Background: Chiari-like malformation in dogs and Chiari malformation type 1 in humans are conditions characterized by a relatively small caudal cranial fossa, leading to cerebellar herniation. This study aimed to develop a rat model of Chiari-like malformation using surgical techniques based on morphological characteristics observed in dogs. Methods: Endocranial magnetic resonance images of both normal dogs and dogs diagnosed with Chiari-like malformation were retrospectively analyzed. Measurements of the caudal cranial fossa volume, rostral and medial fossa volume, and volume index were taken. The differences in caudal cranial fossa volume and volume index between normal dogs and those diagnosed with Chiari-like malformation were then utilized to create a rat model of Chiari-like malformation through surgical intervention. The measurements were conducted on both the rat Chiari-like malformation models and normal rats, with each measurement taken twice and the mean values calculated. Results: Significant differences were found between normal dogs and dogs diagnosed with Chiari-like malformation in terms of the volume of the caudal cranial fossa (27.62% reduction) and the volume index (23.36% reduction) (p<0.05). These differences were used to develop a rat model, which also showed significant reductions in both caudal cranial fossa volume (29.52%) and volume index (28.30%) compared to normal rats (p<0.05). The condition in the rat model was confirmed through magnetic resonance imaging, which revealed cerebellar herniation into the foramen magnum. Conclusions: The study successfully established a rat model of Chiari-like malformation that accurately reproduces the morphological features observed in dogs. This model potentially serves as a valuable tool for investigating the pathological mechanisms and potential therapeutic approaches for Chiari-like malformation in veterinary medicine. [ABSTRACT FROM AUTHOR]

A 15‐year‐old Cocker Spaniel was referred to for the evaluation of left forelimb lameness. Radiographic and computed tomography examinations revealed osteolysis of the proximal left third, fourth and fifth metacarpal bones and pathological fractures of the proximal left fourth metacarpal bone. Histopathological examination via bone biopsy did not provide a definitive diagnosis, and the owner elected limb‐sparing surgery. The fourth metacarpal bone and digits were amputated. Subsequently, autologous bone grafts were performed on the lytic area of the third and fifth metacarpal bones. The dog showed improvement in gait 7 weeks after reconstructive surgery. Chronic non‐bacterial osteomyelitis (CNO) was diagnosed by exclusion. To the best of our knowledge, CNO has not been previously reported in dogs. [ABSTRACT FROM AUTHOR]

Topical delivery to treat dermatological disease is constrained by low skin permeability to most drugs due to the stratum corneum barrier. STAR particles containing microneedle protrusions can be topically applied on the skin to create micropores that dramatically increase skin permeability, even to water‐soluble compounds and macromolecules. This study addresses the tolerability, acceptability, and reproducibility of STAR particles rubbed on the skin at multiple pressures and after multiple applications to human subjects. One‐time STAR particle application at pressures between 40 and 80 kPa showed that skin microporation and erythema directly correlated with increased pressure, and 83% of subjects reported STAR particles to be comfortable at all pressures. Repeated application of STAR particles for 10 consecutive days at 80 kPa showed that skin microporation (~0.5% of skin area), erythema (low‐to‐moderate), and comfort with self‐administration (75%) were similar over the course of the study. Comfort of sensations associated with STAR particles increased from 58% to 71% during the study, and familiarity with STAR particles increased from 12.5% to 50% of subjects reporting STAR particle application not feeling different from other skin products. This study demonstrates that topically applied STAR particles were well tolerated and highly acceptable after application at various pressures and repeated daily use. These findings further suggest that STAR particles offer a safe and reliable platform to enhance cutaneous drug delivery. [ABSTRACT FROM AUTHOR]

Patients with wet age-related macular degeneration (AMD) require intravitreal injections of bevacizumab (Bev) or other drugs, often on a monthly basis, which is a burden on the healthcare system. Here, we developed an in-situ forming hydrogel comprised of Bev and hyaluronic acid (HA) crosslinked with poly(ethylene glycol) diacrylate for slow release of Bev after injection into the suprachoroidal space (SCS) of the eye using a microneedle. Liquid Bev formulations were cleared from SCS within 5 days, even when formulated with high viscosity, unless Bev was conjugated to a high molecular-weight HA (2.6 MDa), which delayed clearance until 1 month. To extend release to 6 months, we synthesized in-situ forming Bev-HA hydrogel initially as a low-viscosity mixture suitable for injection and flow in the SCS to cover a large area extending to the posterior pole of the eye where the macula is located in humans. Within 1 h after injection, Bev and HA were crosslinked, which retained Bev for slow release as the hydrogel biodegraded. In vivo studies in the rabbit eye reported Bev release for >6 months, depending on gel formulation and Bev assay. The in-situ forming Bev-HA hydrogel was well tolerated, as assessed by clinical exam, fundus imaging, histological analysis, and intraocular pressure measurement. We conclude that Bev released from an in-situ forming hydrogel may enable long-acting treatments of AMD and other posterior ocular indications. [Display omitted] • Anti-VEGF released for 6 months from in-situ forming hydrogel in the suprachoroidal space. • Bevacizumab and hyaluronic acid crosslinked with poly(ethylene glycol) diacrylate. • Hydrogel formulation covered a large area extending to the posterior retina. • Hydrogel delivery system was well tolerated by the rabbit eye in vivo. [ABSTRACT FROM AUTHOR]

Microneedle (MN) is a minimally invasive drug delivery method that is directly inserted into the skin without pain to improve the efficiency of transdermal administration and is a drug delivery system used to treat various diseases. Furthermore, nanoparticle (NP)‐based drug delivery methods suggest therapeutic strategies to improve drug solubility and increase drug delivery efficiency. Therefore, the drug delivery system in which NPs and MNs are integrated is a promising alternative to the existing delivery methods of poorly soluble and hydrophobic drugs and nucleic acid therapeutics. This system can increase the solubility of drugs and biocompatibility in the body and improve the therapeutic efficacy with sustained drug release. In this review, we investigated recent studies of NPs designed for drug delivery, sustained‐release drug delivery MNs based on these NPs, and the applications for clinical treatments. [ABSTRACT FROM AUTHOR]

Recombinant Escherichia coli (E. coli) strain that produces phytochelatin (PC) and/or metallothionein (MT) can synthesize various metal nanoparticles (NPs) by reducing metal ions. Here we report in vivo biosynthesis of iron oxide nanocomposites (NCs) using recombinant E. coli. We designed a strategy of biosynthesizing iron oxide NCs by first internalizing chemically synthesized iron oxide NPs, followed by the reduction of added metal ions on the surface of internalized NPs by PC and/or MT in E. coli. For this, chemically synthesized Fe3O4 NPs were internalized by recombinant E. coli, and then, Au and Ag ions were added for the biosynthesis of AuFe3O4 and AgFe3O4 NCs, respectively. The NCs synthesized were analyzed by transmission electron microscopy, UV–vis spectrophotometry, and X-ray diffractometry to characterize their shape, optical property, and crystallinity. The Fe3O4 NPs in the biosynthesized NCs allowed easy purification of the biosynthesized NCs by applying a magnetic field. The AuFe3O4 NCs were used for enzyme-linked immunosorbent assay to detect prostate-specific antigen protein, while AgFe3O4 NCs were utilized for the antimicrobial application with low minimum inhibitory concentration. As recombinant E. coli can uptake and reduce various NPs and metal ions, biosynthesis of a wide range of NCs as new nanomaterials will be possible for diverse applications. Key points: • AuFe3O4 and AgFe3O4 nanocomposites were synthesized by recombinant E. coli. • Escherichia coli synthesized different iron oxide NCs depending on the metal ions to be added. • Biosynthesized AuFe3O4 NC was used for ELISA and AgFe3O4 NC for antimicrobial tests. [ABSTRACT FROM AUTHOR]

Glaucoma is the leading cause of irreversible blindness. Current treatments use drugs or surgery to reduce intraocular pressure (IOP). In this study, a drug‐free, nonsurgical method is developed that lowers IOP for 4 months without requiring daily patient adherence. The approach involves expanding the suprachoroidal space (SCS) of the eye with an in situ‐forming hydrogel injected using a microneedle. This study tests the hypothesis that SCS expansion increases the drainage of aqueous humor from the eye via the unconventional pathway, which thereby lowers IOP. SCS injection of a commercial hyaluronic acid (HA) hydrogel reduces the IOP of normotensive rabbits for more than 1 month and an optimized HA hydrogel formulation enables IOP reduction for 4 months. Safety assessment by clinical ophthalmic examinations indicate the treatment is well tolerated. Histopathology shows minor hemorrhage and fibrosis at the site of injection. Further analysis by ultrasound biomicroscopy demonstrates a strong correlation of IOP reduction with SCS expansion. Outflow facility measurements show no difference in pressure‐dependent outflow by the conventional pathway between treated and untreated eyes, supporting the hypothesis. In conclusion, SCS expansion with an in situ‐forming hydrogel can enable extended IOP reduction for treating ocular hypertension and glaucoma without drugs or surgery. [ABSTRACT FROM AUTHOR]

• The suprachoroidal space (SCS) is a novel route for ocular drug delivery. • The safety and efficacy of SCS delivery have been demonstrated in clinical trials. • SCS delivery targeting chorioretina limits drug exposure in the anterior segment. • SCS delivery has been demonstrated using novel drug formulations and devices. The suprachoroidal space (SCS), a potential anatomical space between the sclera and choroid, is a novel route for drug delivery targeting the chorioretinal layers of the eye. The safety and efficacy of SCS drug delivery have been shown in multiple clinical trials. Recent studies have developed methods for more precise targeting within the SCS at sites of action at the posterior pole (e.g., macula), near the limbus (e.g., ciliary body), and throughout the SCS using iontophoresis, swollen hydrogels, high-density particle emulsions, highly viscous and non-Newtonian fluids, and microstents. Here, we review novel technologies targeting the posterior, anterior, or entire SCS. [ABSTRACT FROM AUTHOR]

Treatment of many posterior-segment ocular indications would benefit from improved targeting of drug delivery to the back of the eye. Here, we propose the use of iontophoresis to direct delivery of negatively charged nanoparticles through the suprachoroidal space (SCS) toward the posterior pole of the eye. Injection of nanoparticles into the SCS of the rabbit eye ex vivo without iontophoresis led to a nanoparticle distribution mostly localized at the site of injection near the limbus and <15% of nanoparticles delivered to the most posterior region of SCS (>9 mm from the limbus). Iontophoresis using a novel microneedle-based device increased posterior targeting with >30% of nanoparticles in the most posterior region of SCS. Posterior targeting increased with increasing iontophoresis current and increasing application time up to 3 min, but further increasing to 5 min was not better, probably due to the observed collapse of the SCS within 5 min after injection ex vivo. Reversing the direction of iontophoretic flow inhibited posterior targeting, with just ~5% of nanoparticles reaching the most posterior region of SCS. In the rabbit eye in vivo, iontophoresis at 0.14 mA for 3 min after injection of a 100 μL suspension of nanoparticles resulted in ~30% of nanoparticles delivered to the most posterior region of the SCS, which was consistent with ex vivo findings. The procedure was well tolerated, with only mild, transient tissue effects at the site of injection. We conclude that iontophoresis in the SCS using a microneedle has promise as a method to target ocular drug delivery within the eye, especially toward the posterior pole. [ABSTRACT FROM AUTHOR]

The suprachoroidal space (SCS) is a potential space between the sclera and choroid that traverses the circumference of the posterior segment of the eye. The SCS is an attractive site for drug delivery because it targets the choroid, retinal pigment epithelium, and retina with high bioavailability, while maintaining low levels elsewhere in the eye. Indeed, phase III clinical trials are investigating the safety and efficacy of SCS drug delivery. Here, we review the anatomy and physiology of the SCS; methods to access the SCS; kinetics of SCS drug delivery; strategies to target within the SCS; current and potential clinical indications; and the safety and efficacy of this approach in preclinical animal studies and clinical trials. [ABSTRACT FROM AUTHOR]

In this study, we developed a centrifugal direct recombinase polymerase amplification (direct-RPA) microdevice for multiplex and real-time identification of food poisoning bacteria contaminated milk samples. The microdevice was designed to contain identical triplicate functional units and each unit has four reaction chambers, thereby making it possible to perform twelve direct-RPA reactions simultaneously. The integrated microdevice consisted of two layers: RPA reagents were injected in the top layer, while spiked milk samples with food poisoning bacteria were loaded into sample reservoirs in the bottom layer. For multiplex bacterial detection, the target gene-specific primers and probes were dried in each reaction chamber. The introduced samples and reagents could be equally aliquoted and dispensed into each reaction chamber by centrifugal force, and then the multiplex direct-RPA reaction was executed. The target genes of bacteria spiked in milk could be amplified at 39 °C without a DNA extraction step by using the direct-RPA cocktails, which were a combination of a direct PCR buffer and RPA enzymes. As the target gene amplification proceeded, the increased fluorescence signals coming from the reaction chambers were recorded in real-time at an interval of 2 min. The entire process, including the sample distribution, the direct-RPA reaction, and the real-time analysis, was accomplished with a custom-made portable genetic analyzer and a miniaturized optical detector. Monoplex, duplex, and triplex food poisoning bacteria (Salmonella enterica, Escherichia coli O157:H7, and Vibrio parahaemolyticus) detection was successfully performed with a detection sensitivity of 4 cells per 3.2 μL of milk samples within 30 min. By implementing the direct-PRA on the miniaturized centrifugal microsystem, the on-site food poisoning bacteria analysis would be feasible with high speed, sensitivity, and multiplicity. [ABSTRACT FROM AUTHOR]

An integrated reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) microdevice which consists of microbead-assisted RNA purification and RT-LAMP with real-time monitoring by a miniaturized optical detector was demonstrated. The integrated RT-LAMP microdevice includes four reservoirs for a viral RNA sample (purified influenza A viral RNA or lysates), a washing solution (70% ethanol), an elution solution (RNase-free water), and an RT-LAMP cocktail, and two chambers (a waste chamber and an RT-LAMP reaction chamber). The separate reservoirs for a washing solution, an elution solution, and an RT-LAMP cocktail were designed with capillary valves for stable storage. Three influenza A virus strains (A/H1N1, A/H3N2, and A/H5N1) were used for RNA templates, and RT-LAMP primer sets were designed to detect hemagglutinin (HA) and conserved M gene. Sequential sample flow to the microbeads for RNA purification was achieved by centrifugal force with optimization of capillary valves and a siphon channel. Furthermore, the purified RNA solution was successfully isolated from the waste solution by changing the rotational direction, and combined with the RT-LAMP cocktail in the RT-LAMP reaction chamber for target gene amplification. Total process from the sample injection to the result was completed in 47 min. Influenza A H1N1 virus was confirmed on the integrated RT-LAMP microdevice even with 10 copies of viral RNAs, which revealed 10-fold higher sensitivity than that of a conventional RT-PCR. Subtyping and specificity test of influenza A H1N1 viral lysates were also performed and clinical samples were successfully genotyped to confirm influenza A virus on our proposed integrated microdevice. [ABSTRACT FROM AUTHOR]

Considering the fatal human victims and economic loss by the annual epidemic influenza virus, the development of a rapid and convenient genetic analysis methodology is demanding for timely on-site pathogen detection. In this study, we utilized reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for multiplex target gene amplification, and the resultant amplicons were analyzed on the immunochromatographic strip (ICS) for subtyping influenza A virus. Through the optimized primer design, reaction temperature and time, and concentration of enzymes ( Bst DNA polymerase and AMV reverse transcriptase) and dNTP, the HA (H1, H3, and H5 gene) and conserved M gene were amplified. The ICS contains two test lines in addition to a control line in order to detect the presence of the HA and M gene, thereby informing us of influenza virus A type as well as its subtype (H1N1, H3N2, and H5N1). The combination of the multiplex RT-LAMP with the ICS could be complete in 40 min and the pathotyping and subtyping of influenza A virus were performed even with 10 copies of viral RNA templates. Moreover, the subtyping of clinical samples, which were obtained from patients infected by influenza A virus was successfully confirmed using the multiplex RT-LAMP and ICS techniques, showing great feasibility of our methodology for real sample analysis with high speed, simplicity and sensitivity. [ABSTRACT FROM AUTHOR]

Pathotyping and subtyping of influenza A virus were performed with a packaged paper fluidic-based analytical microdevice (PFAM) after one-step reverse transcription-polymerase chain reaction (RT-PCR). The PFAM contains two test lines: one for detecting M gene to identify the influenza A virus and another for haemagglutinin subtyping to determine the viral strain among H1N1, H3N2, and H5N1. The M gene and the haemagglutinin gene (H1, H3, and H5 genes) were amplified by using the Digoxigenin and the Texas Red modified primers, respectively, in the multiplex RT-PCR. The amplicon products were loaded in the conjugate pad of the PFAM in which the streptavidin coated gold nanoparticles were linked with the biotin moieties that were incorporated in the middle of the DNA strands, and then captured by the anti-Digoxigenin and anti-Texas Red immobilized on the test lines. Influenza A H1N1, H3N2, and H5N1 could be identified with a limit of detection of 102 copies of RNA templates in 10min. Pathotyping and subtyping of the clinical nasopharyngeal swab samples were also analyzed whose results were confirmed by real-time RT-PCR. [ABSTRACT FROM AUTHOR]

There is continuing interest in the synthesis of polyhydroxy-terminated molecular species for diverse applications ranging from photolithographic materials to intermediates in the synthesis of porous, crosslinked polymers as media for molecular separations, drug delivery etc. We describe here the use of [vinylSiO1.5]8 and [vinylSiO1.5]10/12 mixtures to synthesize first- and second-generation acetoxyphenyl compounds via metathesis with p-acetoxystyrene (generation 1, GEN1) or metathesis with p-bromostyrene followed by Heck coupling with p-acetoxystyrene (generation 2, GEN2). The resulting acetoxy compounds were then hydrolyzed to produce octa-, deca- and dodecahydroxy GEN1 and GEN2 compounds. These compounds were purified and then reacted with adipic acid chloride to form the first examples of highly crosslinked polyesters based on silsesquioxanes. The coupling products, their hydrolyzed products and the crosslinked polymers were characterized using a variety of spectroscopic methods. In general, the observed specific surface areas were less than 5 m2 g−1; however, the T8 GEN1 derivative gave a surface area of 25 m2 g−1 and was the only crosslinked polymer with a TGA ceramic yield that matched theory for 'perfect' crosslinking. This crosslinked polyester has the shortest organic linker between cages and despite the highly flexible C6 linker provides continuing evidence that it is possible to use the cubic symmetry in these materials to build well-ordered 3-D nanocomposite structures. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Spherical 3D graphite microballs (3D GMs) and their nanohybrids (3D GM–Fe3O4 nanoparticles) were synthesized by using a microfluidic droplet generator and a thermal evaporation-induced capillary compression method. Using the 3D GM–Fe3O4 nanoparticle as a support for polymerization, 3D GM–polypyrrole composites were produced with a unique core–shell structure. [ABSTRACT FROM AUTHOR]

In this paper, we assess the utilityof complementary routes tosilsesquioxane based compounds using F–catalyzedcoupling to synthesize [vinylSiO1.5]xPhSiO1.5]10-x/12-xmixtures followed by copolymerization with divinylbenzene(via ADMET), or using reverse Heck coupling with 1,4-dibromobenzeneand 4,4′-dibromo-stilbene to prepare lightly branched, nonlinearBOC systems. In another paper, we describe the use of Heck and Suzukicoupling to synthesize model conjugated p-R-stilbeneSQBOCs starting from [p-IPh8SiO1.5]8and coupling with divinylbenzene (DVB) and 1,4-diethynylbenzene(DEB) finding extended 3-D conjugation in the DEB polymers. We findthat the reverse Heck coupling (where the linker contains the bromomoieties) works best for these systems giving BoC oligomers with Mnof ∼6 kDa, in which extended excitedstate conjugation is observed for 1,4-dibromobenzene linked systemsthrough ∼50+ nm red shifts in the emission spectra comparedwith DVB linked systems and model compounds. We compare and contrastthe photophysical properties of the two sets of BOCs and the systemwhere the conjugation length of the linker changes from divinylbenzeneto divinylstilbene. We find that for a linker with a longer conjugationlength, a red-shifted absorption and emission is observed; however,the difference in emission is much larger for the 1,4-dibromobenzene-linkedsystem as compared to the model compounds, suggesting that a morerigid linker contributes to better orbital overlap with the cage and/orphenyl groups, increasing excited state conjugation interactions. [ABSTRACT FROM AUTHOR]

The general objectives of the workreported here and in accompanying papers are to identify optimal toolsfor the synthesis of silsesquioxane (SQ)-based BoC oligomers and polymers,especially those that show 3-D, through-chain (cage) conjugation inthe excited state. Here we first examine the utility of polymerizing(p-IPhSiO1.5)8with divinylbenzene(DVB) using Heck catalytic cross-coupling as baseline systems forBoCs with model dendrons. Thereafter, we functionalize the remainingIPh groups by cross-coupling with 4-MeOC6H4CHCH2or 4-NH2C6H4CHCH2. As an alternate approach, we first functionalize (p-IPhSiO1.5)8with 4-MeOC6H4CHCH2or 4-NH2C6H4CHCH2by catalytic cross-couplingsuch that only an average of two iodophenyls remain and then polymerizedwith DVB or 1,4-diethynylbenzne (DEB). This latter approach permitssynthesis of copolymers as demonstrated using 1:1 mixtures of thetwo SQs with R = NH2or OMe. Here we assess the utilityof two different routes to conjugated BoC polymers. Investigationof the UV–vis absorption and emission properties of these BoCsindicates the DVB polymers exhibit no emission red-shifts becausea significant portion of the DVB used is the 1,3-isomer. However,the DEB polymers reveal ∼40 nm red-shifts and charge transfer(CT) behavior, suggesting electronic interactions between SQ cagesthrough the conjugated, bridging moieties. DEB copolymers with R =NH2– and MeO–stilbene functional groups onthe cages show red-shifts intermediate between the red-shifts of thesimple homopolymers, rather than independent emissionsfrom both units as would obtain with a physical mixture again supportingelectronic communication along the polymer chains and throughthe cagesvia the conjugated linkers. [ABSTRACT FROM AUTHOR]

In this study, we present a novel bead-incorporated centrifugal sample pretreatment microdevice to purify influenza A H3N2 viral RNA. Simple revolution per minute (RPM) control can lead to RNA capture on a bead-bed, and the sequential loading of a washing solution and an elution solution. Tetraethoxy orthosilicate (TEOS)-treated glass microbeads were utilized as a capture matrix. The sample pretreatment microdevice consists of four reservoirs for storing an RNA sample, a washing solution, an elution solution, and a collected sample, and they were merged at the microbead-bed microchannel. The washing solution reservoir and the elution solution reservoir were connected to the bead-bed microchannel through a capillary valve and a siphon channel, respectively. An RNA sample (a lysed influenza A H3N2 virus), a washing solution (70% ethanol) and an elution solution (water or a reverse transcription-polymerase chain reaction (RT-PCR) cocktail) were loaded into the designated reservoirs, and they were successively transported to the bead-bed by RPM control owing to the optimized channel design. Purified RNAs could be obtained in 440 s. Then, a target H3 gene was amplified by an off-chip based real-time RT-PCR to evaluate the capture efficiency of RNA on our proposed microdevice. 81% of RNAs were successfully captured and purified. Interestingly, the use of the RT-PCR cocktail itself as an elution solution resulted in a 76% capture yield. Furthermore, we successfully performed RNA purification from the clinical nasopharyngeal swabs to identify the subtype of the influenza A virus. This platform provides high potential for the direct integration of the sample pretreatment microdevice into the downstream micro-PCR unit to create a total genetic analysis microsystem. [ABSTRACT FROM AUTHOR]

Abstract: Poly(propylene carbonate) (PPC) was synthesized by the zinc glutarate catalyzed copolymerization of carbon dioxide and propylene oxide (PO). Hydrolytic degradability of the PPC polymer was examined in tetrahydrofuran solutions containing 10wt.% acidic or basic aqueous solutions of varying pH using viscometry and GPC analysis. Further, the hydrolysis behaviors of all PPC solutions were compared with those of poly(ɛ-caprolactone) (PCL) and poly(d,l-lactic acid) (PLA). All polymers studied show higher degradability in strong basic conditions than in strong acidic conditions, but very low degradability in moderate acidic, basic and neutral conditions. Moreover, PPC is degraded less in strong acidic conditions than the polyesters, while in strong basic conditions, the polycarbonate is more easily degraded. The difference in degradabilities of these polymers in acidic conditions is associated with the different nucleophilicities of their carbonyl oxygen atoms, while in basic conditions the differences are associated with the different electrophilicities of the corresponding carbonyl carbon atoms. With regard to the hydrolysis results and the structural and chemical nature of the polymer backbones, degradation mechanisms are proposed for the acid- and base-catalyzed hydrolyses of PPC, PCL and PLA. [Copyright &y& Elsevier]

Diabetes is a chronic disease with significant complications, necessitating regular treatment and checkups, which can be costly and time-consuming for patients. To address this, we developed the Sliding Microneedle (MN)-Lateral flow immunoassay strip (LFIAs) device that combines the advantages of MNs and LFIAs to detect IL-6, an independent biomarker for diabetes complications. This device offers rapid and highly sensitive detection of IL-6 by extracting interstitial fluid (ISF) through MNs and transferring it to LFIAs. The stainless MN, embedded in the 3D-printed Sliding MN-LFIAs device, was inserted into the skin at a 20° angle, minimizing blood contamination risk. With a filter paper attached to the MN surface, the device collected 4.65 ± 0.05 μL of ISF containing IL-6 within 90 s. The ISF was then transferred to the LFIAs using a running buffer. After a 15-min reaction, silver enhancement (SE) treatment was applied, allowing for the highly sensitive and specific detection of IL-6 at 102 pg/mL concentrations. The Sliding MN-LFIAs device successfully distinguished between normal and diabetic rat models, demonstrating its potential as an effective tool for detecting diabetes complications quickly and affordably. [ABSTRACT FROM AUTHOR]

Injection into the suprachoroidal space (SCS) allows drug delivery targeted to sclera, choroid, and retina. Here, we studied SCS injection formulated with collagenase to expand drug delivery coverage and increase posterior drug targeting within SCS by breaking down collagen fibrils that link sclera and choroid in the SCS. When 1 μm latex microparticles were injected with a collagenase formulation using microneedles into the SCS of rabbit eyes ex vivo and incubated at 37 °C for 4 h, microparticle delivery coverage increased from 20% to 45% and enhanced posterior drug targeting. Collagenase concentration was optimized to 0.5 mg/mL to maximize expanded posterior delivery and minimize tissue damage. Effects of collagenase injection within SCS increased and then plateaued 4 h after injection. Simultaneous injection of collagenase and microparticles had a greater effect on expanded delivery in the SCS compared to sequential injection. Collagenase injection into the SCS of rabbit eyes in vivo was also effective to expand delivery and was generally well-tolerated, showing transiently lowered IOP, but no apparent lasting adverse effects on ocular tissues such as sclera, choroid, and retina, as determined by analyzing histology, sclera tensile strength, and fundus imaging. We conclude that addition of collagenase during SCS injection can expand drug delivery coverage and increase posterior drug targeting. Image 1 • Drug delivery in the suprachoroidal space (SCS) can target chorioretinal tissue. • The sclera and choroid, which bound SCS, are connected by loose collagen fibrils. • Collagenase delivery to SCS expanded drug delivery coverage by digesting collagen. • Collagenase delivery to SCS increased drug targeting to the posterior SCS. • Collagenase formulation was well tolerated by the rabbit eye in vivo. [ABSTRACT FROM AUTHOR]

Point-of-care (POC) molecular diagnostics plays a pivotal role for the prevention and treatment of infectious diseases. In spite of recent advancement in microfluidic based POC devices, there are still rooms for development to realize rapid, automatic and cost-effective sample-to-result genetic analysis. In this study, we propose an integrated rotary microfluidic system that is capable of performing glass microbead based DNA extraction, loop mediated isothermal amplification (LAMP), and colorimetric lateral flow strip based detection in a sequential manner with an optimized microfluidic design and a rotational speed control. Rotation direction-dependent coriolis force and siphon valving structures enable us to perform the fluidic control and metering, and the use of the lateral flow strip as a detection method renders all the analytical processes for nucleic acid test simplified and integrated without the need of expensive instruments or human intervention. As a proof of concept for point-of-care DNA diagnostics, we identified the food-borne bacterial pathogen which was contaminated in water or milk. Not only monoplex Salmonella Typhimurium but also multiplex Salmonella Typhimurium and Vibrio parahaemolyticus were analysed on the integrated rotary genetic analysis microsystem with a limit of detection of 50 CFU in 80 min. In addition, three multiple samples were simultaneously analysed on a single device. The sample-to-result capability of the proposed microdevice provides great usefulness in the fields of clinical diagnostics, food safety and environment monitoring. [ABSTRACT FROM AUTHOR]

We present a centrifugal microfluidic device which enables multiplex foodborne pathogen identification by loop-mediated isothermal amplification (LAMP) and colorimetric detection using Eriochrome Black T (EBT). Five identical structures were designed in the centrifugal microfluidic system to perform the genetic analysis of 25 pathogen samples in a high-throughput manner. The sequential loading and aliquoting of the LAMP cocktail, the primer mixtures, and the DNA sample solutions were accomplished by the optimized zigzag-shaped microchannels and RPM control. We targeted three kinds of pathogenic bacteria ( Escherichia coli O157:H7 , Salmonella typhimurium and Vibrio parahaemolyticus ) and detected the amplicons of the LAMP reaction by the EBT-mediated colorimetric method. For the limit-of-detection (LOD) test, we carried out the LAMP reaction on a chip with serially diluted DNA templates of E. coli O157:H7 , and could observe the color change with 380 copies. The used primer sets in the LAMP reaction were specific only to the genomic DNA of E. coli O157:H7 , enabling the on-chip selective, sensitive, and high-throughput pathogen identification with the naked eyes. The entire process was completed in 60 min. Since the proposed microsystem does not require any bulky and expensive instrumentation for end-point detection, our microdevice would be adequate for point-of-care (POC) testing with high simplicity and high speed, providing an advanced genetic analysis microsystem for foodborne pathogen detection. [ABSTRACT FROM AUTHOR]

The application of unsteady incompressible flow phenomenon over the bluff bodies has received the attention of many researchers due to the rich and complex physics underpinning these flows, and thus requiring special attention in their modelling and numerical simulations. The wake that forms at the leeside of the bluff body is of particular interest. Reynolds number and geometry are in turn two prominent parameters that govern the formation and subsequent behaviour of this wake. This paper reviews the wake formations for different cylindrical bluff bodies cross-sections such as circular, elliptical, helically twisted elliptical, symmetric wavy, asymmetric wavy, and harbor seal vibrissae cylinders. Alongside the Reynolds number and geometrical shape, the impacts of rotational rate, aspect ratio, angle of attack, and gap ratio between the cylinder and the bottom wall on the hydrodynamic coefficients, Strouhal number, recirculation length and suppression of vortex shedding in the cylinder wake are investigated. In addition, the variation of hydrodynamic coefficients for different cylindrical shapes are compared. Finally, concluding remarks are drawn based on recent advances in understanding the flow features and predictions with CFD methods. • The passive flow control methods over different cross-sectional bluff bodies are reviewed. • The wide range of flow regimes: laminar to supercritical are considered to review the flow characteristics of cylinders. • The impact of Reynolds number and geometry of the cylinder on hydrodynamic coefficients and wake formations are investigated. • The detailed characteristics of the wakes have been identified and summarised. • Comparison between the hydrodynamic coefficients of the different geometric shapes of the cylinders are summarised. [ABSTRACT FROM AUTHOR]

An advanced centrifugal microsystem is developed which has capability of automatic and programmed chemical reagent loading and reactions to screen the colloidal nanocrystal synthesis in a high-throughput manner. As a proof of concept, triplicate synthetic reactions for water-soluble multi-color CdS nanocrystals are executed under ten different conditions on a chip. The proposed disk-shaped microdevice contains a top layer for distributing the reagents through zig-zag continuous channels and a bottom layer for 30 functional units, each of which is composed of a reaction chamber and three reservoirs connected with a control, a precursor, and a basic solution, respectively. All the reservoirs are linked to the main channel via different microfluidic channel dimension, and the main channel is directed to the reaction chamber. Through rotational speed control, the three solutions are sequentially loaded to the reaction chamber with precise volume, and the multiplex CdS nanocrystals synthesis is processed. By tuning the concentration of sulfur in a control solution, multi-color CdS nanocrystals are produced from green to red depending on the molar ratios of Cd 2+ to S 2− . [ABSTRACT FROM AUTHOR]

Interstitial fluid (ISF) is a body fluid that fills, surrounds cells and contains various biomarkers, but it has been challenging to extract ISF in a reliable and sufficient amount with high speed. To address the issues, we developed the tilted microneedle ISF collecting system (TMICS) fabricated by 3D printing. In this system, the microneedle (MN) was inserted at 66° to the skin by TMICS so that the MN length could be extended within a safe range of skin penetration. Moreover, TMICS incorporating three MN patches created reliable ISF collecting conditions by penetrating the skin at consistent angle and force, 4.9 N. Due to the MN length increase and the patch number expansion, the surface area of the penetrated tissue was increased, thereby confirming that ISF extraction efficiency was improved. Skin ISF was collected into the paper reservoir on the patch, and the absorbed area was converted into a volume. ISF extraction from the rat skin in vivo by TMICS was well tolerated, and the 2.9 μL of ISF was obtained within 30 s. Therefore, TMICS is promising to apply in the diagnosis of multiple biomarkers in ISF with high speed and stability. [ABSTRACT FROM AUTHOR]

Diverse touch experiences offer a path toward greater human–machine interaction, which is essential for the development of haptic technology. Recent advances in triboelectricity‐based touch sensors provide great advantages in terms of cost, simplicity of design, and use of a broader range of materials. Since performance solely relies on the level of contact electrification between materials, triboelectricity‐based touch sensors cannot effectively be used to measure the extent of deformation of materials under a given mechanical force. Here, an ion‐doped gelatin hydrogel (IGH)‐based touch sensor is reported to identify not only contact with an object but also deformation under a certain level of force. Switchable ionic polarization of the gelatin hydrogel is found to be instrumental in allowing for different sensing mechanisms when it is contacted and deformed. The results show that ionic polarization relies on conductivity of the hydrogels. Quantitative studies using voltage sweeps demonstrate that higher ion mobility and shorter Debye length serve to improve the performance of the mechanical stimuli‐perceptible sensor. It is successfully demonstrated that this sensor offers dynamic deformation‐responsive signals that can be used to control the motion of a miniature car. This study broadens the potential applications for ionic hydrogel‐based sensors in a human–machine communication system. [ABSTRACT FROM AUTHOR]

Abstract Herein, a photo-crosslinkable coumarin-containing polymer, poly(7-(4-vinyl-benzyloxyl)-4-methylcoumarin) or PVBMC, was prepared, and its physicochemical and electrical properties as a gate dielectric in organic electronic devices, such as organic thin-film transistor (OTFT) and inverter, was evaluated. The crosslinking of PVBMC by exposure to UV light (365 nm) over time was characterized using Fourier-transform IR and UV–visible spectroscopy. The measured capacitance of the cross-linked PVBMC thin film in a metal-insulator-metal-type capacitor was as high as 36.4 pF/mm2. Pentacene-based OTFT and load-type inverter with the cross-linked PVBMC gate dielectric were prepared, and their electrical responses were evaluated under ambient conditions. The OTFT showed dominant hole charge carrier transport behavior with a field-effect mobility of 1.52 × 10−1 cm2/Vs and negligible hysteresis. The load-type inverter based on the OTFT exhibited moderate static and dynamic switching responses to the applied electrical pulse. These results suggest the potential application of photo-crosslinked PVBMC as a gate dielectric in the fabrication of high-performance OTFT-based devices. Graphical abstract Image 1 Highlights • Photo-crosslinkable coumarin-based polymer (PVBMC) gate dielectric was synthesized. • Cross-linking of PVBMC involved [2 + 2] cycloaddition. • Cross-linked PVBMC high-density chain packing and increased hydrophobicity. • Device with cross-linked PVBMC gate dielectric had 30 × higher field-effect mobility with bias stability. [ABSTRACT FROM AUTHOR]

Intramuscular (IM) vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) failed in clinical trials due to vaccine-enhanced respiratory disease. To test the efficacy of skin vaccination against respiratory syncytial virus (RSV), we investigated the immunogenicity, efficacy, and inflammatory disease after microneedle (MN) patch delivery of FI-RSV vaccine (FI-RSV MN) to the mouse skin with or without an adjuvant of monophosphoryl lipid A (MPL). Compared to IM vaccination, MN patch delivery of FI-RSV was more effective in clearing lung viral loads and preventing weight loss, and in diminishing inflammation, infiltrating immune cells, and T helper type 2 (Th2) CD4 T cell responses after RSV challenge. With MPL adjuvant, MN patch delivery of FI-RSV significantly increased the immunogenicity and efficacy as well as preventing RSV disease as evidenced by lung viral clearance and avoiding pulmonary histopathology. Improved efficacy and prevention of disease by FI-RSV MN with MPL were correlated with no sign of airway resistance, lower levels of Th2 cytokines and infiltrating innate inflammatory cells, and higher levels of Th1 T cell responses into the lung. This study suggests that MN patch delivery of RSV vaccines to the skin with MPL adjuvant would be a promising vaccination method. [ABSTRACT FROM AUTHOR]

This work describes fully automated and colorimetric foodborne pathogen detection on an integrated centrifugal microfluidic device, which is called a lab-on-a-disc. All the processes for molecular diagnostics including DNA extraction and purification, DNA amplification and amplicon detection were integrated on a single disc. Silica microbeads incorporated in the disc enabled extraction and purification of bacterial genomic DNA from bacteria-contaminated milk samples. We targeted four kinds of foodborne pathogens (Escherichia coli O157:H7, Salmonella typhimurium, Vibrio parahaemolyticus and Listeria monocytogenes) and performed loop-mediated isothermal amplification (LAMP) to amplify the specific genes of the targets. Colorimetric detection mediated by a metal indicator confirmed the results of the LAMP reactions with the colour change of the LAMP mixtures from purple to sky blue. The whole process was conducted in an automated manner using the lab-on-a-disc and a miniaturized rotary instrument equipped with three heating blocks. We demonstrated that a milk sample contaminated with foodborne pathogens can be automatically analysed on the centrifugal disc even at the 10 bacterial cell level in 65 min. The simplicity and portability of the proposed microdevice would provide an advanced platform for point-of-care diagnostics of foodborne pathogens, where prompt confirmation of food quality is needed. [ABSTRACT FROM AUTHOR]

An integrated microdevice, consisting of a micropump, a passive mixer, a magnetic separation chamber, and a microcapillary electrophoretic channel, was constructed for biobarcode assay based multiplex biological agent detection in a sample-to-answer-out manner within 30 min with high sensitivity. [ABSTRACT FROM AUTHOR]