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YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation.
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Transporte Activo de Núcleo Celular , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Poro Nuclear/metabolismo , Fosfoproteínas/metabolismo , Animales , Fenómenos Biomecánicos , Proteínas de Ciclo Celular , Línea Celular Tumoral , Núcleo Celular/metabolismo , Humanos , Ratones , Factores de Transcripción , Transcripción Genética , Proteínas Señalizadoras YAPRESUMEN
Proteins can spontaneously tie a variety of intricate topological knots through twisting and threading of the polypeptide chains. Recently developed artificial intelligence algorithms have predicted several new classes of topological knotted proteins, but the predictions remain to be authenticated experimentally. Here, we showed by X-ray crystallography and solution-state NMR spectroscopy that Q9PR55, an 89-residue protein from Ureaplasma urealyticum, possesses a novel 71 knotted topology that is accurately predicted by AlphaFold 2, except for the flexible N terminus. Q9PR55 is monomeric in solution, making it the smallest and most complex knotted protein known to date. In addition to its exceptional chemical stability against urea-induced unfolding, Q9PR55 is remarkably robust to resist the mechanical unfolding-coupled proteolysis by a bacterial proteasome, ClpXP. Our results suggest that the mechanical resistance against pulling-induced unfolding is determined by the complexity of the knotted topology rather than the size of the molecule.
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Inteligencia Artificial , Proteínas Bacterianas , Pliegue de Proteína , Ureaplasma urealyticum , Modelos Moleculares , Péptidos , Proteínas Bacterianas/química , Estructura Terciaria de ProteínaRESUMEN
SignificanceMany protocols used in material design and training have a common theme: they introduce new degrees of freedom, often by relaxing away existing constraints, and then evolve these degrees of freedom based on a rule that leads the material to a desired state at which point these new degrees of freedom are frozen out. By creating a unifying framework for these protocols, we can now understand that some protocols work better than others because the choice of new degrees of freedom matters. For instance, introducing particle sizes as degrees of freedom to the minimization of a jammed particle packing can lead to a highly stable state, whereas particle stiffnesses do not have nearly the same impact.
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Metal halide perovskites are crystalline materials with a sharp increase in popularity and rapidly becoming a major contender for optoelectronic device applications. In this work, we provide the optoelectronic features of a possible novel candidate, ZSnCl3 (Z = Na/K) Sn-based on a detailed numerical simulation. The output of the current computations is compared to the results that are currently available, and a respectable agreement is noted. The studied compounds were cubic in nature and structurally stabe. The mechanical properties reflect the mechanical stability and ductility of the proposed materials. The Sn-based single perovskite compounds proposed in this study are mechanically stable and ductile. The narrow direct band gap for NaSnCl3 and KSnCl3 are 1.36 eV and 1.47 eV, respectively, using the HSE06 hybrid function with the Boltztrp2 integrated in Quantum ESPRESSO (QE) software. The effective use of these compounds in perovskite solar cells and other optoelectronic applications was confirmed by optical absorption spectral measurements conducted in the photon energy range of 0-20 eV.
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Hybrid metal halide perovskite (MHP) materials, while being promising for photovoltaic technology, also encounter challenges related to material stability. Combining 2D MHPs with 3D MHPs offers a viable solution, yet there is a gap in the understanding of the stability among various 2D materials. The mechanical, ionic, and environmental stability of various 2D MHP ligands are reported, and an improvement with the use of a quater-thiophene-based organic cation (4TmI) that forms an organic-semiconductor incorporated MHP structure is demonstrated. It is shown that the best balance of mechanical robustness, environmental stability, ion activation energy, and reduced mobile ion concentration under accelerated aging is achieved with the usage of 4TmI. It is believed that by addressing mechanical and ion-based degradation modes using this built-in barrier concept with a material system that also shows improvements in charge extraction and device performance, MHP solar devices can be designed for both reliability and efficiency.
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8-oxoguanines (8-oxoG) in cells form compromised G-quadruplexes (GQs), which may vary GQ mediated gene regulations. By mimicking molecularly crowded cellular environment using 40% DMSO or sucrose, here it is found that oxidized human telomeric GQs have stabilities close to the wild-type (WT) GQs. Surprisingly, while WT GQs show negative formation cooperativity between a Pt(II) binder and molecularly crowded environment, positive cooperativity is observed for oxidized GQ formation. Single-molecule mechanical unfolding reveals that 8-oxoG sequence formed more diverse and flexible structures with faster folding/unfolding transition kinetics, which facilitates the Pt(II) ligand to bind the best-fit structures with positive cooperativity. These findings offer new understanding on structures and properties of oxidized G-rich species in crowded environments. They also provide insights into the design of better ligands to target oxidized G-rich structures formed under oxidative cell stress.
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G-Cuádruplex , Oxidación-Reducción , Cinética , Humanos , Telómero/química , Telómero/metabolismoRESUMEN
Flexible electronics have revolutionized the field by overcoming the rigid limitations of traditional devices, offering superior flexibility and adaptability. Conductive ink performance is crucial, directly impacting the stability of flexible electronics. While metal filler-based inks exhibit excellent conductivity, they often lack mechanical stability. To address this challenge, we present a novel conductive ink utilizing a ternary composite filler system: liquid metal and two micron-sized silver morphologies (particles and flakes). We systematically investigated the influence of filler type, mass ratio, and sintering process parameters on the composite ink's conductivity and mechanical stability. Our results demonstrate that flexible wires fabricated with the liquid metal/micron silver particle/micron silver flake composite filler exhibit remarkable conductivity and exceptional bending stability. Interestingly, increasing the liquid metal content results in a trade-off, compromising conductivity while enhancing mechanical performance. After enduring 5000 bending cycles, the resistance change in wires formulated with a 4:1 mass ratio of micron silver particles to flakes is only half that of wires with a 1:1 ratio. This study further investigates the mechanism governing resistance variations during flexible wire bending. Additionally, we observed a positive correlation between sintering temperature and pressure with the conductivity of flexible wires. The significance of the sintering parameters on conductivity follows a descending order: sintering temperature, sintering pressure, and sintering time. Finally, we demonstrate the practical application of this technology by integrating the composite ink-based flexible wires with conductive polymer-based strain sensors. This combination successfully achieved the detection of human movements, including finger and wrist bending.
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Conductividad Eléctrica , Dispositivos Electrónicos Vestibles , Humanos , Plata/química , Movimiento (Física) , ElectrónicaRESUMEN
Two-dimensional fullerene networks have been synthesized in several forms, and it is unknown which monolayer form is stable under ambient conditions. Using first-principles calculations, I show that the believed stability of the quasi-tetragonal phases is challenged by mechanical, dynamic, or thermodynamic stability. For all temperatures, the quasi-hexagonal phase is thermodynamically the least stable. However, the relatively high dynamic and mechanical stabilities suggest that the quasi-hexagonal phase is intrinsically stronger than the other phases under various strains. The origin of the high stability and strength of the quasi-hexagonal phase can be attributed to the strong covalent C-C bonds that strongly hold the linked C60 clusters together, enabling the closely packed hexagonal network. These results rationalize the experimental observations that so far only the quasi-hexagonal phase has been exfoliated experimentally as monolayers.
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The double perovskites are become the emerging aspirant to fulfill the demand of energy. Therefore, the optoelectronic, elastic and transport characteristics of Ba2 XMoO6 (X = Zn, Cd) are addressed systemically. The elastic constants show the mechanical stability. The nature of Ba2 ZnMoO6 is brittle and Ba2 CdMoO6 is ductile with large values of Debye temperature covalent bonding. The electronic band structures exhibit band gaps of 2.81 and 2.98 eV, which increase their importance for optoelectronic applications. The absorption of light energy, optical loss, refractive index, polarization of light energy are addressed in the energy range zero to 14 eV. Furthermore, thermoelectric characteristics are computed against chemical potentials at 300, 600, and 900 K. The chemical potential decides the p-type nature, with holes as majority carriers. The increasing temperature increases the power factor and figure of merit. Therefore, the optoelectronic and thermoelectric characteristics reveals the importance of studied DPs for energy applications.
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Flexible solid-state Zn-ion batteries (ZIBs) have garnered considerable attention for next-generation power sources, but the corrosion, dendrite growth, and interfacial problems severely hinder their practical applications. Herein, a high-performance flexible solid-state ZIB with a unique heterostructure electrolyte is facilely fabricated through ultraviolet-assisted printing strategy. The solid polymer/hydrogel heterostructure matrix not only isolates water molecules and optimizes electric field distribution for dendrite-free anode, but also facilitates fast and in-depth Zn2+ transport in the cathode. The in situ ultraviolet-assisted printing creates cross-linked and well-bonded interfaces between the electrodes and the electrolyte, enabling low ionic transfer resistance and high mechanical stability. As a result, the heterostructure electrolyte based ZIB outperforms single-electrolyte based cells. It not only delivers a high capacity of 442.2 mAh g-1 with long cycling life of 900 cycles at 2 A g-1 , but also maintains stable operation under mechanical bending and high-pressure compression in a wide temperature range (-20 °C to 100 °C).
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How to mildly structure a high intrinsic activity and stable catalytic electrode to realize long-term catalytic water splitting to produce hydrogen at a wide range of pH values at industrial high current is a challenge. Herein, this work creatively proposes to prepare industrial-grade catalytic electrodes with high efficiency and stability at high current density through carbon quantum dots (CDs) modification nickel sulfide on hydrophilic flexible filter paper via one-step mild chemical plating (denoted as CDs-Ni3 S2 @HFP). The intrinsic activity and surface area, electron transfer ability, and corrosion resistance of Ni3 S2 material are increased due to the regulation, homogenous, and high concentration doping of CDs. The overpotential of the flexible catalytic electrode is only 30, 35, and 87 mV in 1 m KOH, simulated seawater (1 m KOH + 0.5 m NaCl), and neutral electrolyte (0.5 m PBS) at a current density of 10 mA cm-2 . More attractively, the CDs-Ni3 S2 @HFP electrode achieves over 500 h of efficient and stable catalysis at industrial high current density (500 mA cm-2 ). Due to the advantages of mild, universal, and large-area preparation of catalytic materials, this work provides technical support for flexible catalytic electrodes in efficient catalysis toward water splitting, energy storage, and device preparation.
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OBJECTIVE: The insufficient stability of alginate-chitosan (ALG-CS) microcapsules in biorelevant media limits their applications in the biomedical field. Attempts were made to improve the membrane stability of ALG-CS microcapsules by noncovalent crosslinking with tannic acid. RESULTS: The membrane stability of ALG-CS microcapsules in culture medium and serum was significantly improved by crosslinking with tannic acid. Moreover, the reason for the significant improvement in membrane stability had been demonstrated to be that the stability of chitosan-tannic acid (CS-TA) polyelectrolyte complexes was less affected by the competitive binding of those weak acid ions such as HCO3-. In addition, the optimal conditions for preparing alginate-chitosan-tannic acid (ALG-CS-TA) microcapsules were tannic acid concentration of 0.5% (w/v) and pH = 7. CONCLUSION: The study provides a novel approach for improving the stability of the ALG-CS microcapsules in biorelevant media to expand their scope of application in the biological field.
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Quitosano , Quitosano/química , Alginatos/química , CápsulasRESUMEN
The graphene-based aerogels with good electrical conductivity and compressibility have been reported. However, it is challenging to fabricate the graphene aerogel to have excellent mechanical stability for its application in wearable devices. Thus, inspired by macroscale arch-shaped elastic structures and the importance of crosslinking in microstructural stability, we synthesized the mechanically stable reduced graphene oxide aerogels with small elastic modulus by optimizing the reducing agent to make the aligned wrinkled microstructure in which physical crosslinking is dominant. We used L-ascorbic acid, urea, and hydrazine hydrate as reducing agents to synthesize the graphene aerogels rGO-LAA, rGO-Urea, and rGO-HH, respectively. Hydrazine hydrate was found to be best in enhancing the physical and ionic interaction among graphene nanoflakes to achieve a wavy structure with excellent fatigue resistance. Notably, the optimized rGO-HH aerogel maintained structural stability even after 1000 cycles of compression of 50% strain and decompression, showing 98.7% stress retention and 98.1% height retention. We also studied the piezoresistive properties of the rGO-HH aerogel and showed that the rGO-HH-based pressure sensor exhibited excellent sensitivity (~5.7 kPa-1) with good repeatability. Hence, a super-compressible and mechanically stable piezoresistive material for wearable functional devices was demonstrated by controlling the microstructure and surface chemistry of the reduced graphene oxide aerogel.
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Phosphate (PO43-) is an essential nutrient in agriculture; however, it is hazardous to the environment if discharged in excess as in wastewater discharge and runoff from agriculture. Moreover, the stability of chitosan under acidic conditions remains a concern. To address these problems, CS-ZL/ZrO/Fe3O4 was synthesized using a crosslinking method as a novel adsorbent for the removal of phosphate (PO43-) from water and to increase the stability of chitosan. The response surface methodology (RSM) with a Box-Behnken design (BBD)-based analysis of variance (ANOVA) was implemented. The ANOVA results clearly showed that the adsorption of PO43- onto CS-ZL/ZrO/Fe3O4 was significant (p ≤ 0.05), with good mechanical stability. pH, dosage, and time were the three most important factors for the removal of PO43-. Freundlich isotherm and pseudo-second-order kinetic models generated the best equivalents for PO43- adsorption. The presence of coexisting ions for PO43- removal was also studied. The results indicated no significant effect on PO43- removal (p ≤ 0.05). After adsorption, PO43- was easily released by 1 M NaOH, reaching 95.77% and exhibiting a good capability over three cycles. Thus, this concept is effective for increasing the stability of chitosan and is an alternative adsorbent for the removal of PO43- from water.
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Quitosano , Contaminantes Químicos del Agua , Adsorción , Quitosano/química , Fosfatos , Agua/química , Cinética , Contaminantes Químicos del Agua/química , Concentración de Iones de HidrógenoRESUMEN
Practical lithium-sulfur (Li-S) batteries are severely plagued by the instability of solid electrolyte interphase (SEI) formed in routine ether electrolytes. Herein, an electrolyte with 1,3,5-trioxane (TO) and 1,2-dimethoxyethane (DME) as co-solvents is proposed to construct a high-mechanical-stability SEI by enriching organic components in Li-S batteries. The high-mechanical-stability SEI works compatibly in Li-S batteries. TO with high polymerization capability can preferentially decompose and form organic-rich SEI, strengthening mechanical stability of SEI, which mitigates crack and regeneration of SEI and reduces the consumption rate of active Li, Li polysulfides, and electrolytes. Meanwhile, DME ensures high specific capacity of S cathodes. Accordingly, the lifespan of Li-S batteries increases from 75â cycles in routine ether electrolyte to 216â cycles in TO-based electrolyte. Furthermore, a 417â Wh kg-1 Li-S pouch cell undergoes 20â cycles. This work provides an emerging electrolyte design for practical Li-S batteries.
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The maturation process that occurs in most viruses is evolutionarily driven, as it resolves several conflicting virion assembly requirements. During herpesvirus assembly in a host cell nucleus, micron-long double-stranded herpes DNA is packaged into a nanometer-sized procapsid. This leads to strong confinement of the viral genome, resulting in tens of atmospheres of intracapsid DNA pressure. Yet, the procapsid is unstable due to weak reversible interactions between its protein subunits, which ensures free energy minimization and reduces assembly errors. In this work, we show that herpesviruses resolve these contradictory capsid requirements through a mechanical capsid maturation process facilitated by multifunctional auxiliary protein UL25. Through mechanical interrogation of herpes simplex virus 1 (HSV-1) capsid with atomic force microscopy nano-indentation, we show that UL25 binding at capsid vertices post-assembly provides the critical capsid reinforcement required for stable DNA encapsidation; the absence of UL25 binding leads to capsid rupture. Furthermore, we demonstrate that gradual capsid reinforcement is a feasible maturation mechanism facilitated by progressive UL25 capsid binding, which is likely correlated with DNA packaging progression. This work provides insight into elegantly programmed viral assembly machinery, where targeting of capsid assembly mechanics presents a new antiviral strategy that is resilient to the development of drug resistance. IMPORTANCE Most viruses undergo a maturation process from a weakly assembled particle to a stable virion. Herpesvirus capsid undergoes mechanical maturation to withstand tens of atmospheres of DNA pressure. We demonstrate that this mechanical capsid maturation is mainly facilitated through binding of auxiliary protein UL25 in herpes simplex virus 1 (HSV-1) capsid vertices. We show that UL25 binding provides the critical capsid reinforcement required for stable DNA encapsidation. Our data also suggest that gradual capsid reinforcement by progressive UL25 binding is a feasible capsid maturation mechanism, correlated with DNA packaging progression.
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Proteínas de la Cápside/genética , Herpesvirus Humano 1/metabolismo , Animales , Cápside/metabolismo , Proteínas de la Cápside/metabolismo , Chlorocebus aethiops , ADN Viral/genética , Genoma Viral , Herpesviridae/genética , Herpesvirus Humano 1/genética , Células Vero , Proteínas Virales/metabolismo , Virión/metabolismo , Ensamble de VirusRESUMEN
Core-shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core-shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core-shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core-shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness.
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Sistemas de Liberación de Medicamentos , Agua , Microesferas , Reproducibilidad de los Resultados , PolimerizacionRESUMEN
The starch composite films (SCFs) will be one of the best alternative packaging materials to petroleum based plastic films, which mitigates white pollution and energy consumption. However, weak mechanical stability, water resistance, and dyeability has hindered the application of SCFs. Herein, a bioinspired robust SCFs with super-hydrophobicity and excellent structural colors were prepared by fiber-reinforcement and assembling SiO2/Polydimethylsiloxane (PDMS) amorphous arrays on the surface of SCFs. The properties of the designed SCFs were investigated by various methods including scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), a tensile test, contact angle (CA) test, and an optical test. The results showed that the obtained SCFs possessed a higher tensile strength (55.17 MPa) attributed to the formed abundant hydrogen bonds between the molecular chains of the starch, cellulose fiber, and polyvinyl alcohol. Benefiting from the nanostructure with rough surface which were modified by materials with low surface free energy, the contact angle and sliding angle of the film reached up to 154° and 2°, respectively. The colors which were produced by the constructive interference of the coherent scattered light could cover all of the visible regions by tuning the diameters of the SiO2 nanoparticles. The strategy in the present study not only reinforces the mechanical strength and water resistance of SCFs but also provides an environmentally friendly way to color the them, which shows unprecedented application potential in packaging materials of the starch composite films.
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Biomimética , Almidón , Color , Interacciones Hidrofóbicas e Hidrofílicas , Dióxido de Silicio , Espectroscopía Infrarroja por Transformada de Fourier , Almidón/química , AguaRESUMEN
OBJECTIVES: To assess the mechanical stability of implants after implantoplasty and thermocyclic loading, the residual thickness of the instrumented areas and neighbouring tooth injury due to implantoplasty. MATERIALS AND METHODS: Using a phantom head simulator and maxillary model implants were subjected to an implantoplasty procedure. Thirty implants were randomly assigned to receive one of three instrumentation sequences. After instrumentation, injury on neighbouring teeth was assessed. Instrumented implants and non-instrumented controls were subjected to 1.2 million cycles of thermo-mechanical loading in a chewing machine. Afterwards, maximum fracture load for all implants and an additional five pristine control implants was tested. RESULTS: Generally, damage of neighbour teeth was a frequent finding (33 ± 56% of all cases) with considerable inter-group differences. No considerable inter-group difference for the residual implant thickness was found for different areas assessed. No implant fractured during cyclic loading. Fracture load was reduced after cyclic loading of uninstrumented implants from 2,724 ± 70 N to 2,299 ± 127 N, and after implantoplasty to 1,737 ± 165 N, while no effect by the instrumentation sequence could be observed. CONCLUSIONS: Both implantoplasty and cyclic loading were shown to reduce the implants' maximum bending strength. Cyclic loading in a laboratory masticator, simulating a five-year equivalent of chewing, did not result in fractured implants. Since neighbouring tooth injury was assessed often, care should be taken with the selection of suitable instruments.
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Implantes Dentales , Fracaso de la Restauración Dental , Análisis del Estrés Dental , Humanos , Masticación , Ensayo de MaterialesRESUMEN
BACKGROUND: A newly developed multiple use applicator for vaginal tablets/vaginal inserts* was evaluated for its general suitability. There are no standard procedures described in guidelines or general accepted publications as to how this kind of product should be tested for suitability of purpose. METHODS: Due to the lack of existing standard procedures, three separate tests were designed and successful executed: (a) First, a patient acceptability evaluation was carried out as part of a phase III trial (registered in EudraCT on 9 Jan 2017, number 2017-000142-22 2. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number%3A2017-000142-22 ). (b) Secondly, a cleaning procedure for the applicator after simulated multiple use was developed and verified in order to prove a minimized risk of microbiological contamination of the device. A newly developed vaginal fluid to simulate multiple applications was applied for this trial. (c) Lastly, a third trial evaluated the mechanical stability and proper functionality of the applicator after multiple simulated uses. Even potential abrasion of material of the device was checked. RESULTS: Acceptable patient compliance of the new multiple use applicator was verified after 2 weeks of daily use. Furthermore, diary data assessments of patients participating in the Pharmacodynamic part of the trial were evaluated as well. Overall, patient acceptability of the new applicator was proven. The easy-to-use cleaning procedure for the applicator, which can even be carried out in a domestic environment, was developed and successfully verified for effectiveness, meeting all microbiological acceptance criteria for vaginal products of the European Pharmacopeia. The mechanical stability and proper functionality of the applicator after 50 simulated uses was also evaluated. All tested applicator batches (fresh and aged) passed the final evaluation, with no limitations in functionality. CONCLUSION: The tests developed and executed consider various compliance aspects of the newly developed applicator. Results of these individual tests met the expectations and/or the predefined acceptance criteria. All included trials performed produced results justifying and qualifying the applicator for the intended multiple-use. The procedures outlined may also be a guide as to how this kind of medical device can be tested for suitability. Trial registration Registered in EudraCT, number 2017-000142-22, start date 24 May 2017.