4-Dimensional printing: exploring current and future capabilities in biomedical and healthcare systems-a Concise review.

4-Dimensional Printing (4DP) is the latest concept in the pharmacy and biomedical segment with enormous potential in dosage from personalization and medication designing, which adopts time as the fourth dimension, giving printed structures the flexibility to modify their morphology. It can be defined as the fabrication in morphology with the help of smart/intelligent materials like polymers that permit the final object to alter its properties, shape, or function in response to external stimuli such as heat, light, pH, and moisture. The applications of 4DP in biomedicines and healthcare are explored with a focus on tissue engineering, artificial organs, drug delivery, pharmaceutical and biomedical field, etc. In the medical treatments and pharmaceutical field 4DP is paving the way with unlimited potential applications; however, its mainstream use in healthcare and medical treatments is highly dependent on future developments and thorough research findings. Therefore, previous innovations with smart materials are likely to act as precursors of 4DP in many industries. This review highlights the most recent applications of 4DP technology and smart materials in biomedical and healthcare fields which can show a better perspective of 4DP applications in the future. However, in view of the existing limitations, major challenges of this technology must be addressed along with some suggestions for future research. We believe that the application of proper regulatory constraints with 4DP technology would pave the way for the next technological revolution in the biomedical and healthcare sectors.

Solvent sensitivity of ortho substituent effect on 13C NMR chemical shift of the carboxyl carbon (δco) in benzoic acid.

A reverse ortho effect is observed for the (13)C NMR chemical shifts of the carboxyl carbon (δ(co)) in benzoic acids measured in aprotic solvents of varying polarity. The ortho effect on δ(co) is best described by a combination of the reverse field and steric accelerating effects of the substituent in an 80: 20 pattern in apolar aprotic solvents and a 60: 40 pattern in dipolar aprotic ones. Interestingly, no good enough correlation was found between δ(co) and log k(1) of the acids measured in similar solvents. A critical analysis of the results clearly indicates the use of an apolar aprotic solvent and not a dipolar aprotic one as the solvent of choice for investigating intrinsic substituent effects on δ(c) in an aromatic system.

Virulence factor secretion and translocation by Bordetella species.

Here we review the Bordetella virulence secretome with an emphasis on factors that translocate into target cells. Recent advances in understanding the functions of adenylate cyclase toxin, a type 1 secretion system (T1SS) substrate, and pertussis toxin, a type IV secretion system (T4SS) substrate, are briefly described and a compilation of additional secretion systems and secreted factors is provided. Particular attention is devoted to the Bsc type III secretion system (T3SS) and controversies surrounding it. Efforts to identify effector proteins, characterize in vitro and in vivo phenotypes, and the potential role of type III secretion during human infections are discussed.

Bordetella Bsp22 forms a filamentous type III secretion system tip complex and is immunoprotective in vitro and in vivo.

Type III secretion system (T3SS) tip complexes serve as adaptors that bridge the T3SS needle and the pore-forming translocation apparatus. In this report we demonstrate that Bsp22, the most abundantly secreted substrate of the Bordetella T3SS, self-polymerizes to form the Bordetella bronchiseptica tip complex. Bsp22 is required for both T3SS-mediated cytotoxicity against eukaryotic cells and haemoglobin release from erythrocytes. Bacterial two-hybrid analysis and protein pull-down assays demonstrated the ability of Bsp22 to associate with itself and to bind BopD, a component of the Bordetella translocation pore. Immunoblot and cross-linking analysis of secreted proteins or purified Bsp22 showed extensive multimerization which was shown by transmission electron microscopy to lead to the formation of variable length flexible filaments. Immunoelectron microscopy revealed Bsp22 filaments on the surface of bacterial cells. Given its required role in secretion and cell-surface exposure, we tested the protective effects of antibodies against Bsp22 in vitro and in vivo. Polyclonal antisera against Bsp22 fully protected epithelial cells from T3SS-dependent killing and immunization with Bsp22 protected mice against Bordetella infection. Of the approximately 30 genes which encode the Bordetella T3SS apparatus, bsp22 is the only one without characterized orthologues in other well-characterized T3SS loci. A maximum likelihood phylogenetic analysis indicated that Bsp22 defines a new subfamily of T3SS tip complex proteins. Given its immunogenic and immunoprotective properties and high degree of conservation among Bordetella species, Bsp22 and its homologues may prove useful for diagnostics and next-generation subunit vaccines.

Kinetics and mechanism of proton transfer between disubstituted benzoic acids and carbinol base of crystal violet in chlorobenzene.

An investigation on the detailed kinetics of proton transfer between a set of di- and monofluoro- and chloro- (2,3-, 2,5-, 2,6-, 3,5-, 2-, and 3-) benzoic acids (HA) and Crystal Violet carbinol base in chlorobenzene favors a mechanism in terms of fast equilibrium between HA and D to form a H-bonded complex, D...HA, followed by rate-limiting proton transfer along the H-bond to form the colored ion pair DH+A- under the combined influence of monomer HA catalyst, nonreactive cyclic dimer (HA)2 inhibitor, and hyperacidic homoconjugated complex H(HA2) catalyst through a transition state with nearly 60% charge separation.

Chemometric analysis of disubstituent effects on the 13C chemical shifts of the carboxyl carbons (deltaCO) of benzoic acids. A comparative study of the substituent effects on the strength of benzoic acids in apolar aprotic media.

The results of measurements of substituent induced chemical shifts of carboxyl carbons (deltaCO) of dichloro- and difluorobenzoic acids, including the monosubstituted ones with substituents at meta- and/or ortho- positions, in chloroform-d and strengths of these acids (log K) in chlorobenzene show an anomalous reverse trend between deltaCO and log K, while the electron density at carboxyl carbons should influence similarly both deltaCO and log K. A detailed chemometric analysis of comparison of disubstituent effects between deltaCO and log K on the basis of Fujita-Nishioka's multiparameter approach and assumption of additivity of substituent effects shows a dominance of the localized pi-polarization mechanism relative to simple electrostatic effects upon deltaCO. Further, steric factors play a significant role in determining deltaCO whereas with respect to log K they were insignificant. The overall anomaly has been rationalized keeping in mind that, while log K is a gross measure of energy differences between the ionized and unionized forms of the acids, deltaCO is a very sensitive probe for determining changes in electron density at the carboxyl carbon of the unionized acid.