Inverse design of Bézier curve-based mechanical metamaterials with programmable negative thermal expansion and negative Poisson's ratio via a data augmented deep autoencoder.

Controlling stress and deformation induced by thermo-mechanical stimulation in high-precision mechanical systems can be achieved by mechanical metamaterials (MM) exhibiting negative thermal expansion (NTE) and negative Poisson's ratio (NPR). However, the inverse design of MM exhibiting a wide range of arbitrary target NTEs and NPRs is a challenging task due to the low design flexibility of analytical methods and parametric studies based on numerical simulation. In this study, we propose Bézier curve-based programmable chiral mechanical metamaterials (BPCMs) and a deep autoencoder-based inverse design model (DAIM) for the inverse design of BPCMs. Through iterative transfer learning with data augmentation, DAIM can generate BPCMs with a curved rib shape inaccessible with the Bézier curve, which improves the inverse design performance of the DAIM in the data sparse domain. This approach decreases the mean absolute error of NTE and NPR between the inverse design target and the numerical simulation results of inverse designed BPCMs on the data-sparse domain by 79.25% and 83.33% on average, respectively. A 3D-printed BPCM is validated experimentally and exhibits good coincidence with the target NTE and NPR. Our proposed BPCM and the corresponding inverse design framework enable the inverse design of BPCMs with NTE in the range of -1100 to 0 ppm K-1 and NPR in the range of -0.6 to -0.1. Furthermore, programmable thermal deformation modes with a fixed Poisson's ratio are realized by combining various inverse designed BPCM unit cells. BPCMs and the DAIM for their inverse design are expected to improve the mechanical robustness of high-precision mechanical systems through tunable modulation of thermo-mechanical stimulation.

Anti-biofilm and anti-virulence effects of zerumbone against Acinetobacter baumannii.

Acinetobacter baumannii is a multidrug-resistant opportunistic pathogen that affects patients with a compromised immune system and is becoming increasingly important as a hospital-derived infection. This pathogen is difficult to treat owing to its intrinsic multidrug resistance and ability to form antimicrobial-tolerant biofilms. In the present study, we aimed to assess the potential use of zerumbone as a novel anti-biofilm and/or anti-virulence agent against A. baumannii. The results showed that zerumbone at sub-inhibitory doses decreased biofilm formation and disrupted established A. baumannii biofilms. The zerumbone-induced decrease in biofilm formation was dose-dependent based on the results of microtitre plate biofilm assays and confocal laser scanning microscopy. In addition, our data validated the anti-virulence efficacy of zerumbone, wherein it significantly interfered with the motility of A. baumannii. To support these phenotypic results, transcriptional analysis revealed that zerumbone downregulated the expression of biofilm- and virulence-associated genes (adeA, adeB, adeC and bap) in A. baumannii. Overall, our findings suggested that zerumbone might be a promising bioactive agent for the treatment of biofilm- and virulence-related infections caused by multidrug-resistant A. baumannii.

Antimicrobial and antibiofilm activities of Clostridium butyricum supernatant against Acinetobacter baumannii.

Acinetobacter baumannii is the major nosocomial pathogen that causes serious infections such as ventilator-associated pneumonia and bacteremia due to its biofilms. Hence, this study investigated the antimicrobial and antibiofilm potentials of cell-free supernatants (CFS) obtained from Clostridium butyricum, as probiotic, against A. baumannii. Our results demonstrated that C. butyricum CFS inhibited A. baumannii cell growth in planktonic culture. Also, C. butyricum CFS not only inhibited the biofilm development and dispersed mature biofilms, but also suppressed the metabolic activity of biofilm cells, showing antibiofilm activity. The biofilm components reduced by C. butyricum CFS were observed via confocal laser scanning microscopy. In addition, C. butyricum CFS exhibited antivirulence effect by inhibiting the motility of A. baumannii. Furthermore, C. butyricum CFS significantly downregulated the expression of efflux pump-related genes including adeA, adeB and adeC in A. baumannii. Our data demonstrate that C. butyricum CFS showed antimicrobial and antibiofilm effects on A. baumannii. These effects are closely associated with suppression of motility and efflux pump-related genes in A. baumannii. The findings suggest that C. butyricum CFS can be used as a new therapeutic alternative against biofilm-associated infection caused by multidrug-resistant A. baumannii.

Effect of Probiotic Clostridium butyricum NCTC 7423 Supernatant on Biofilm Formation and Gene Expression of Bacteroides fragilis.

Enterotoxigenic Bacteroides fragilis (ETBF) is the main pathogen causing severe inflammatory diseases and colorectal cancer. Its biofilm plays a key role in the development of colorectal cancer. The objective of this study was to determine the antagonistic effects of cell-free supernatants (CFS) derived from Clostridium butyricum against the growth and biofilm of ETBF. Our data showed that C. butyricum CFS inhibited the growth of B. fragilis in planktonic culture. In addition, C. butyricum CFS exhibited an antibiofilm effect by inhibiting biofilm development, disassembling preformed biofilms and reducing the metabolic activity of cells in biofilms. Using confocal laser scanning microscopy, we found that C. butyricum CFS significantly suppressed the proteins and extracellular nucleic acids among the basic biofilm components. Furthermore, C. butyricum CFS significantly downregulated the expression of virulence- and efflux pump-related genes including ompA and bmeB3 in B. fragilis. Our findings suggest that C. butyricum can be used as biotherapeutic agent by inhibiting the growth and biofilm of ETBF.

Efficacy of zerumbone against dual-species biofilms of Candida albicans and Staphylococcus aureus.

Candida albicans and Staphylococcus aureus are the most common opportunistic pathogens that co-exist as mixed biofilms. Dual-species biofilms of C. albicans and S. aureus cause nosocomial medical device-related infections that are strongly resistant to antibiotics and host immune responses compared with mono-species biofilms. The purpose of this study was to describe the efficacy of zerumbone derived from Zingiber zerumbet (L.) Smith, on dual-species biofilm formation. This study examined the inhibitory effects of zerumbone on planktonic cell growth, adhesion and biofilm formation. The results demonstrated that zerumbone remarkably inhibited mono- and dual-species biofilms formed by C. albicans and S. aureus using the XTT [2,3-bis(2-smethoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide]-reduction assay. Furthermore, a significant decrease in biomass and cell density of dual-species biofilms following zerumbone treatment was confirmed using confocal laser scanning microscopy (CLSM). Therefore, our study suggests that zerumbone is a potential antimicrobial and antibiofilm agent indicated for the therapeutic management of nosocomial medical device-related infections induced by dual-species biofilms of C. albicans and S. aureus.

Zerumbone inhibits Candida albicans biofilm formation and hyphal growth.

Candida albicans biofilm formation is considered an important matter because it can lead to strong resistance to conventional antifungal agents. Hyphae formed by C. albicans can also act as an important virulence factor related to its biofilm. The objective of this study was to determine the effect of zerumbone, a monocyclic sesquiterpene extracted from Zingiber zerumbet (L.) Smith, against C. albicans biofilm formation. Our results suggest that zerumbone possesses antifungal and antibiofilm activity that inhibits biofilm formation and eradicates preformed biofilm. Notably, zerumbone considerably reduced carbohydrate and DNA contents of biofilm matrix. In addition, zerumbone showed antivirulence effects by decreasing the growth of hyphae and inhibiting morphologic changes of C. albicans. Furthermore, zerumbone significantly downregulated expression levels of biofilm-related and hyphae-specific genes, including HWP1 and ALS3. Since zerumbone suppresses biofilm formation and hyphae growth, these results indicate that zerumbone could be used as a potential candidate to treat and prevent C. albicans biofilm-related infections.

Fabrication of Tapered Micropillars with High Aspect-Ratio Based on Deep X-ray Lithography.

In this study, a fabrication method of tapered microstructures with high aspect ratio was proposed by deep X-ray lithography. Tapered microstructures with several hundred micrometers and high aspect ratio are demanded owing to the high applicability in the fields of various microelectromechanical systems (MEMS) such as optical components and microfluidic channels. However, as the pattern and gap size were downsized to smaller micro-scale with higher aspect ratio over 5, microstructures were easily deformed or clustered together due to capillary force during the drying process. Here, we describe a novel manufacturing process of tapered microstructures with high aspect ratio. To selectively block the deep X-ray irradiation, an X-ray mask was prepared via conventional ultraviolet (UV) lithography. A double X-ray exposure process with and without X-ray mask was applied to impose a two-step dose distribution on a photoresist. For the clear removal of the exposed region, the product was developed in the downward direction, which encourages a gravity-induced pulling force as well as a convective transport of the developer. After a drying process with the surface additive, tapered microstructures were successfully fabricated with a pattern size of 130 µm, gap size of 40 µm, and aspect ratio over 7.