Water-Templated Growth of Interfacial Superglue Polymers for Tunable Thin Films and In Situ Fluid Encapsulation.

Thin polymer films (TPFs) are indispensable elements in numerous technologies ranging from liquid encapsulation to biotechnology to electronics. However, their production typically relies on wet chemistry involving organic solvents or chemical vapor deposition, necessitating elaborate equipment and often harsh conditions. Here, an eco-friendly, fast, and facile synthesis of water-templated interfacial polymers based on cyanoacrylates (superglues, CAs) that yield thin films with tailored properties is demonstrated. Specifically, by exposing a cationic surfactant-laden water surface to cyanoacrylate vapors, surfactant-modulated anionic polymerization produces a manipulable thin polymer film with a thickness growth rate of 8 nm min-1. Furthermore, the shape and color of the film are precisely controlled by the polymerization kinetics, wetting conditions, and/or exposure to patterned light. Using various interfaces as templates for film growth, including the free surface of drops and soap bubbles, the developed method advantageously enables in situ packaging of chemical and biological cargos in liquid phase as well as the encapsulation of gases within solidified bubbles. Simple, versatile, and biocompatible, this technology constitutes a potent platform for programmable coating and soft/smart encapsulation of fluids.

Removal of Cyanoacrylate Glue From the External Auditory Canal With Hydrogen Peroxide and Acetic Acid: A Case Report.

Ear canal foreign bodies are commonly encountered in the field of otolaryngology. This is especially common in the pediatric otolaryngology discipline. As a foreign body, cyanoacrylate glue (also called "super glue") can be difficult to remove and cause significant patient distress. Multiple solvents can be described as aiding in removing such foreign bodies. Here, a case is described in which hydrogen peroxide and acetic acid were used sequentially to remove cyanoacrylate glue from the external auditory canal. We describe a technique allowing en bloc removal of the cyanoacrylate glue. Thankfully, the patient's hearing returned to baseline post-operatively with minimal complications. Overall, cyanoacrylate glue can be a very difficult foreign body to remove from the ear canal. In this case, the sequential use of hydrogen peroxide and acetic acid to soak the glue was a safe and successful method to facilitate glue removal from the ear canal.

Snoopligase-catalyzed molecular glue enables efficient generation of hyperoligomerized TRAIL variant with enhanced antitumor effect.

Clinical application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is predominantly limited by its inefficient apoptosis induction in tumor cells, which might be improved by using molecular superglue-mediated hyperoligomerization to increase its valency. Here, the minimal superglue peptide pairs, including Snoopligase-catalyzed SnoopTagJr/SnoopDogTag and SpyStapler-catalyzed SpyTag/SpyBDTag, were individually fused at the N- or C-terminus of the TRAIL promoter to produce superglue-fusion TRAIL variants. Similar to native trivalent TRAIL, these superglue-fusion TRAIL variants were highly expressed in Escherichia coli (E. coli) and spontaneously trimerized. In the presence of Snoopligase or SpyStapler, the trivalent superglue-fusion TRAIL variants were predominantly crosslinked into hexavalent TRAIL variants. Nevertheless, Snoopligase was more efficient than SpyStapler in the production of hexavalent TRAIL variants. In particular, Snoopligase-catalyzed trivalent TRAIL variants with N-terminal fusion of SnoopTagJr/SnoopDogTag produced hexavalent SnHexaTR with the highest yield (∼70%). The in vitro cytotoxicity of SnHexaTR was 10-40 times greater than that of TRAIL in several tumor cells. In addition, compared to trivalent TRAIL, hexavalent SnHexaTR showed a longer serum half-life and greater tumor uptake, which resulted in eradication of 50% of tumor xenografts of TRAIL-sensitive COLO 205. In mice bearing TRAIL-resistant HT-29 tumor xenografts, hexavalent SnHexaTR combined with bortezomib encapsulated in liposomes also showed robust tumor growth suppression, indicating that hyperoligomerization mediated by minimal molecular superglue significantly increased the cytotoxicity and antitumor effect of TRAIL. As a novel anticancer agent candidate, the hexavalent SnHexaTR has great potential for clinical application in cancer therapy.

Demographic profile and clinical characteristics of patients presenting with acute ocular burns.

Purpose: To study and compare the demographic and clinical profile of acute ocular burns (AOB) in children and adults. Methods: This retrospective case series included 271 children (338 eyes) and 1300 adults (1809 eyes) who presented to two tertiary eye care centers within one month of sustaining AOB. Data regarding demographics, causative agents, severity of injury, visual acuity (VA), and treatment were collected and analyzed. Results: Males were more commonly affected particularly among adults (81% versus 64%, P < 0.00001). Among children, 79% sustained domestic injuries, whereas 59% of adults had work-place injuries (P < 0.0001). Most cases were due to alkali (38%) and acids (22%). Edible lime (chuna, 32%), superglue (14%), and firecrackers (12%) in children, and chuna (7%), insecticides, lye, superglue (6% each), toilet cleaner (4%) and battery acid (3%) in adults, were the main causative agents. The percentage of cases with Dua grade IV-VI was greater in children (16% versus 9%; P = 0.0001). Amniotic membrane grafting and/or tarsorrhaphy were needed in 36% and 14% of affected eyes in children and adults, respectively (P < 0.00001). The median presenting VA was logMAR 0.5 in children and logMAR 0.3 in adults (P = 0.0001), which improved significantly with treatment in both groups (P < 0.0001), but the final VA in eyes with Dua grade IV-VI burns was poorer in children (logMAR 1.3 versus logMAR 0.8, P = 0.04). Conclusion: The findings clearly delineate the at-risk groups, causative agents, clinical severity, and treatment outcomes of AOB. Increased awareness and data-driven targeted preventive strategies are needed to reduce the avoidable ocular morbidity in AOB.

A Real-Time Registration Algorithm of UAV Aerial Images Based on Feature Matching.

This study aimed to achieve the accurate and real-time geographic positioning of UAV aerial image targets. We verified a method of registering UAV camera images on a map (with the geographic location) through feature matching. The UAV is usually in rapid motion and involves changes in the camera head, and the map is high-resolution and has sparse features. These reasons make it difficult for the current feature-matching algorithm to accurately register the two (camera image and map) in real time, meaning that there will be a large number of mismatches. To solve this problem, we used the SuperGlue algorithm, which has a better performance, to match the features. The layer and block strategy, combined with the prior data of the UAV, was introduced to improve the accuracy and speed of feature matching, and the matching information obtained between frames was introduced to solve the problem of uneven registration. Here, we propose the concept of updating map features with UAV image features to enhance the robustness and applicability of UAV aerial image and map registration. After numerous experiments, it was proved that the proposed method is feasible and can adapt to the changes in the camera head, environment, etc. The UAV aerial image is stably and accurately registered on the map, and the frame rate reaches 12 frames per second, which provides a basis for the geo-positioning of UAV aerial image targets.

Molecular superglue-mediated higher-order assembly of TRAIL variants with superior apoptosis induction and antitumor activity.

Prompting higher-order death receptor (DR) clustering by increasing the valency of DR agonist is efficient to induce apoptosis of tumor cells. As an attractive DR agonist with superior biosafety, the trimeric tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts limited antitumor effect in patients, which is predominantly attributed to its low DR clustering ability and short serum half-life. Previous antibody scaffolds-based engineering strategies to increase the valency and/or prolong the serum half-life of TRAIL improve apoptosis induction, however, often produce large proteins with poor tumor penetration. Covalent protein ligation mediated by small molecular superglues such as SpyTag/SpyCatcher might be a novel strategy to assemble higher-order TRAIL variants. Upon fusion to TRAIL promotor, SpyTag/SpyCatcher molecular superglue preferentially ligated two trimeric TRAIL to produce a hexameric TRAIL variant, HexaTR, exhibiting a significantly increased apoptosis induction. In addition, an albumin-binding HexaTR, ABD-HexaTR, with a prolonged serum half-life by binding to endogenous albumin was also produced using the same strategy. Compared to the trimeric TRAIL, the hexameric HexaTR and ABD-HexaTR showed 20-50 times greater in vivo antitumor effect, resulting in eradication of several types of large (150-300 mm3) tumor xenografts. Combination with bortezomib carried by liposome further improved the antitumor effects of the hexavalent HexaTR and ABD-HexaTR in refractory cancer. Our results indicate that the superglue-mediated higher-order assembly is promising to improve the DR clustering and proapoptotic signaling of TRAIL, showing great advantages in constructing the next generation of DR agonists for cancer therapy.

Protein superglue inspired in-situ one-step site-specific immobilization of beta2-adrenoceptor and its application in bioactive compound screening from Cortex Magnoliae Officinalis.

The platforms based on immobilization of transmembrane proteins have become an effective way to study drug-protein interaction and identify new leads for drug discovery. Herein, we exploited the protein superglue (i.e. SpyTag-SpyCatcher chemistry) for site-specific, oriented, and in-situ one-step beta2-adrenoceptor (ß2-AR) immobilization. SpyCatcher was used as a fusion tag at the C-terminal of ß2-AR and the macroporous silica gels were functionalized with the SpyTag peptide. Immobilization was realized by immersing the gels into the E.coli cell lysate containing ß2-AR-SpyCatcher. Characterization of the functionalized gels was performed by X-ray photoelectron spectroscopy and fluorescence microscopy. Adsorption energy distribution calculation, injection amount dependent analysis (IADA) and nonlinear chromatographic were used for receptor-ligand interaction analysis. The affinity rank order of four ligands to the receptor was tulobuterol> chlorprenaline> salbutamol> terbutaline, which showed highly consistent with data from the radioligand binding assay and the ß2-AR column prepared by HaloTag technology. Magnolol and honokiol were screened from Cortex Magnoliae Officinalis and proved to promote the expression of the receptor in human airway smooth muscle cells. Our work unraveled the great potential to generate good bioactivity of the immobilized ß2-AR through Spy toolbox. This technology can be extended to the immobilization of other functional proteins, providing a better alternative in the field of bioanalysis, biosensing, and separation science.

Tooth adornment among siblings living in an urban slum in Nigeria: Health implications for a vulnerable population.

Tooth jewelry boosts the appearance and confidence of wearers. However, its use may carry adverse health consequences. This paper creates awareness about a practice not previously reported in Nigeria, to prevent negative health consequences while appropriate measures are taken to quantify and describe the determinants and plan appropriate interventions.

Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.

Creation of Multimeric Single-Domain Antibodies Using Bacterial Superglues.

Multimerization of single-domain antibodies (sdAbs) is instrumental for construction of antibody molecules with high avidity, extended in vivo half-life, and tailor-made biological activity. Two-component superglues, based on bacterium-derived peptides (Tags) and small protein domains (Catchers) that form isopeptide bonds when in close proximity, enable the creation of multimers by simply mixing of the individual components. Here, we provide detailed methods for the construction of sdAbs and scaffolds bearing genetically fused superglue components and their assembly into multimeric complexes.

Zoonoses Anticipation and Preparedness Initiative, stakeholders conference, February 4 & 5, 2021.

The Zoonoses Anticipation and Preparedness Initiative (ZAPI) was set up to prepare for future outbreaks and to develop and implement new technologies to accelerate development and manufacturing of vaccines and monoclonal antibodies. To be able to achieve surge capacity, an easy deployment and production at multiple sites is needed. This requires a straightforward manufacturing system with a limited number of steps in upstream and downstream processes, a minimum number of in vitro Quality Control assays, and robust and consistent platforms. Three viruses were selected as prototypes: Middle East Respiratory Syndrome (MERS) coronavirus, Rift Valley fever virus, and Schmallenberg virus. Selected antibodies against the viral surface antigens were manufactured by transient gene expression in Chinese Hamster Ovary (CHO) cells, scaling up to 200 L. For vaccine production, viral antigens were fused to multimeric protein scaffold particles using the SpyCatcher/SpyTag system. In vivo models demonstrated the efficacy of both antibodies and vaccines. The final step in speeding up vaccine (and antibody) development is the regulatory appraisal of new platform technologies. Towards this end, within ZAPI, a Platform Master File (PfMF) was developed, as part of a licensing dossier, to facilitate and accelerate the scientific assessment by avoiding repeated discussion of already accepted platforms. The veterinary PfMF was accepted, whereas the human PfMF is currently under review by the European Medicines Agency, aiming for publication of the guideline by January 2022.

Vaccine Efficacy of Self-Assembled Multimeric Protein Scaffold Particles Displaying the Glycoprotein Gn Head Domain of Rift Valley Fever Virus.

Compared to free antigens, antigens immobilized on scaffolds, such as nanoparticles, generally show improved immunogenicity. Conventionally, antigens are conjugated to scaffolds through genetic fusion or chemical conjugation, which may result in impaired assembly or heterogeneous binding and orientation of the antigens. By combining two emerging technologies-i.e., self-assembling multimeric protein scaffold particles (MPSPs) and bacterial superglue-these shortcomings can be overcome and antigens can be bound on particles in their native conformation. In the present work, we assessed whether this technology could improve the immunogenicity of a candidate subunit vaccine against the zoonotic Rift Valley fever virus (RVFV). For this, the head domain of glycoprotein Gn, a known target of neutralizing antibodies, was coupled on various MPSPs to further assess immunogenicity and efficacy in vivo. The results showed that the Gn head domain, when bound to the lumazine synthase-based MPSP, reduced mortality in a lethal mouse model and protected lambs, the most susceptible RVFV target animals, from viremia and clinical signs after immunization. Furthermore, the same subunit coupled to two other MPSPs (Geobacillus stearothermophilus E2 or a modified KDPG Aldolase) provided full protection in lambs as well.

Pediatric Aural Foreign Body Extraction: Comparison of Efficacies Among Clinical Settings and Retrieval Methods.

OBJECTIVES: To compare the efficacy of aural foreign body (FB) extractions among medical care settings and determine if certain methods of extraction resulted in higher failure rates and procedural complications. STUDY DESIGN: Case series with chart review. SETTING: Emergency departments (EDs), urgent cares (UCs), pediatric primary care providers (PCPs), and otolaryngologists (ENTs). METHODS: A total of 366 pediatric patients with EAC foreign bodies at a tertiary children's hospital and associated satellite clinics. RESULTS: The ED/UCs (17.46%), PCPs (75.22%), and ENTs (94.54%) exhibited highly variable success rates for pediatric aural FB extractions. Complications were considerably higher for attempts by ED/UCs (22.22%) as compared with PCPs (2.61%) and those of unclear etiology (2.73% of all attempts). Use of balloon-tipped catheters and adhesive-tipped probes (eg, cyanoacrylate/superglue) for FB extraction exhibited 0% success rates with high severity of complications. CONCLUSION: Our statistics provide an example in which ED/UCs had higher failure rates at pediatric aural FB removals when compared with PCPs and ENTs. If a single provider (PCP or ED/UC) fails to retrieve an aural FB or if the provider is not comfortable conducting the procedure, then referral to an ENT is preferable to another PCP or ED/UC. Our evidence reveals that balloon-tipped catheters and adhesive-tipped probes for FB removal in the pediatric population are prone to failure and higher rates/severity of complications.

A Case of Pediatric Cyanoacrylate Adhesive Injury to the Eye.

A 5-year-old Japanese boy presented to the emergency room of our hospital because his right eye had been glued shut for 2 h following instillation of cyanoacrylate adhesive. The clinical examination showed redness of the right upper and lower lid skin; the right eyelid margins adhered to each other because of matting of the eyelashes, and crystallized glue was found within the matted eyelashes. The "hook" technique, which separates the eyelids using a blunt-tip device, was performed to separate the lids. The technique seems to be simple and safe for physicians such as ophthalmology residents to use to treat cyanoacrylate-induced adhesion of the eyelids of patients who often first present to their local emergency room as in our case.

Superglue self-insertion into the male urethra - A rare case report.

BACKGROUND: Foreign body insertion in the urethra and bladder are relatively rare. These patients usually insert foreign body in urethra for eroticism, inquisitiveness, or as a consequence of disinhibited or disturbed behavior. CASE PRESENTATION: Herein, we report a case of 41-year-old man presented with weak stream and suprapubic pain. Due to incontinence, he instilled superglue into his urethra. On perineal examination, a foreign body was palpable in the penile urethra. A 10 cm dried superglue block got out with incision at glance. CONCLUSION: Urethral foreign bodies are mostly found on physical examination and clinical history. Although imaging modalities are commonly used for FBs detection, the necessity of imaging modalities are still a controversy.

The optimisation of fingermark enhancement by VMD and Lumicyano™ on thermal paper.

The enhancement of fingermarks on thermal paper can be challenging due to background staining caused by polar solvents used in fingermark enhancement techniques such as ninhydrin. This study explored a commercial one-step superglue fuming process, Lumicyano™, and Vacuum Metal Deposition (VMD) to develop fingermarks on this substrate and overcome this issue. Different sequential treatments involving Lumicyano™ and a combination of VMD methods were investigated with varying degrees of success with some sequences being highly sensitive. The VMD processes, however, were observed to generally be more effective at enhancing marks, whereas Lumicyano™ provided little or no benefit on this paper type. The results indicate that Lumicyano™ is only beneficial as a pre-treatment when the entire sequence of gold/zinc and silver/zinc is taken to completion. The gold/zinc and silver/zinc VMD processes were optimised on five different thermal papers, and the optimised techniques were then directly compared to determine which was more successful on each thermal paper type as a single treatment.

Further Pseudo-Operational Trials with the Lumicyano Double- and Co-Fuming Process for the Detection of Latent Fingermarks.

This study presents a number of pseudo-operational trials on plastic bags investigating the double- and co-fuming process of a one-step fluorescent cyanoacrylate (LumicyanoTM ) in comparisons with the two-step process with basic yellow 40 (BY40) staining for the detection of latent fingermarks. The results demonstrate that both Lumicyano solution and dye contribute to the increased detection of latent fingermarks during the double-fuming process (trial 1). Co-fuming the Lumicyano solution and dye separately (at a concentration of 8%) but simultaneously was less effective than 8% Lumicyano (trial 2). Co-fuming Lumicyano 8% and an additional 8% Lumicyano dye by weight was more effective than Lumicyano 8% (trial 3), possibly due to increased fluorescent material deposition during co-fuming allowing for better visualization. The use of BY40 after Lumicyano resulted in a considerable increase in detected fingermarks.

Molecular Superglues: Discovery and Engineering Orthogonalization.

Molecular superglues covalently ligate two or more macromolecules together into super stable, covalently linked assemblies. The discovery of intramolecular isopeptide and ester bond crosslinks in bacterial adhesin proteins, inspired the development of two distinct protein ligating technologies based on split protein domains. These chemically distinct technologies could be combined as orthogonal (non-cross-reacting) technologies to make complex assemblies. Here we provide simple practical instructions in the discovery, characterisation, and application of orthogonal ester bond crosslinks as molecular superglues. A large toolkit of diverse, orthogonal molecular superglues will expand our assembly repertoire, and afford increasingly more complex one-, two-, and three-dimensional protein nanomaterials with exquisite control over the final molecular architecture.

An assessment of a portable cyanoacrylate fuming system (LumiFume™) for the development of latent fingermarks.

The effectiveness and suitability of a portable cyanoacrylate fuming system (LumiFume™) with Lumicyano™ at detecting latent fingermarks was assessed. The first phase of the study compared the LumiFume™ system with traditional cabinet fuming and black/white powder suspension for the development of latent fingermarks on a variety of surfaces (glass, plastic bin bag, laminated wood and tile) by means of depletion series' from 10 donors and four ageing periods (1, 7, 14 and 28 days). The portable fuming system provided superior quality of developed marks on glass and laminated wood whereas powder suspension was better on bin bags and all three techniques were comparable on tile. A decrease in mark quality was recorded from 1 to 14 days for the fuming techniques before an increase at 28 days. Lumicyano™ fluorescence stability studies over a 28 day period by means of depletion series' on glass slides and plastic bin bags revealed better quality marks for the portable system LumiFume™; however, storing marks under light conditions expedited deterioration for both systems. All marks developed with Lumicyano™ were subsequently treated with BY40 resulting in further improvement in mark quality for all substrates and ageing periods, with the exception of laminated wood which absorbed the fluorescent stain reducing the contrast in the process. The second phase of the study consisted of a pseudo-operational trial on 300 various substrates (e.g. glass bottles, aluminium cans, plastic bags) recovered from recycling bins. LumiFume™ and Lumicyano™ yielded 1469 marks whereas Lumicyano™ cabinet fuming and powder suspension yielded 1026 and 641 marks respectively. Similar to the first phase of the study, further treatment of the Lumicyano™ treated marks with BY40 resulted in further quality improvement as well as additional new marks. The LumiFume™ system produced results at least equivalent to the traditional cabinet fuming with Lumicyano™ highlighting its potential for implementation into casework to process crime scenes.