Expression level of SOR1 is a bottleneck for efficient sorbitol utilization by yeast Komagataella kurtzmanii.

The yeast strain Komagataella kurtzmanii VKPM Y-727 shows a significant defect in sorbitol utilization compared to closely related yeast K. phaffii (including strains formerly identified as Pichia pastoris). Our aim was to investigate the factors that determine the phenotype of the wild-type strain and to obtain a K. kurtzmanii strain with an improved ability to utilize sorbitol. We sequenced and annotated the genome of K. kurtzmanii VKPM Y-727 and compared it with that of K. phaffii GS115. Five K. phaffii GS115 genes that might be involved in sorbitol metabolism were selected and transferred into K. kurtzmanii Y-727. The transfer of the modified SOR1 gene resulted in an increased growth rate of K. kurtzmanii in sorbitol, despite the fact that Y-727 already contains its own SOR1 gene without any apparent mutations. The enzymes encoded by the SOR1 genes were analyzed in vitro and found to have similar properties. Differences in promoter activity were assessed using lacZ as a reporter gene, and the PSDH727  (promoter of SOR1 (SDH727) from K. kurtzmanii Y-727) promoter was shown to be 1.5-2.0 times weaker than PSDH115  (promoter of SOR1 (SDH115) from K. phaffii GS115). Moreover, both promoters were less active in K. kurtzmanii than in K. phaffii when evaluated in cells grown in synthetic complete media with glucose or sorbitol. Thus, SOR1 gene expression was identified as a bottleneck in sorbitol metabolism in K. kurtzmanii. Also, the positive effect of additional modified SOR1 gene copies was observed in both yeasts, as K. kurtzmanii and K. phaffii could grow on synthetic complete media with sorbitol three times faster than the original K. phaffii GS115 strain.

Creation of a Composite Bioactive Coating with Antibacterial Effect Promising for Bone Implantation.

When creating titanium-containing bone implants, the bioactive coatings that promote their rapid engraftment are important. The engraftment rate of titanium implants with bone tissue depends significantly on the modification of the implant surface. It is achieved by changing either the relief or the chemical composition of the surface layer, as well as a combination of these two factors. In this work, we studied the creation of composite coatings with a two-level (the micro- and nanolevel) hierarchy of the surface relief, which have bioactive and bactericidal properties, which are promising for bone implantation. Using the developed non-lithographic template electrochemical synthesis, a composite coating on titanium with a controlled surface structure was created based on an island-type TiO2 film, silver and hydroxyapatite (HAp). This TiO2/Ag/HAp composite coating has a developed surface relief at the micro- and nanolevels and has a significant cytological response and the ability to accelerate osteosynthesis, and also has an antibacterial effect. Thus, the developed biomaterial is suitable for production of dental and orthopedic implants with improved biomedical properties.

Enantioselective Tail-to-Head Terpene Cyclizations by Optically Active Hexameric Resorcin[4]arene Capsule Derivatives.

Molecular capsules enable the conversion of substrates inside a closed cavity, mimicking to some extent enzymatic catalysis. Chirality transfer from the molecular capsule onto the encapsulated substrate has been only studied in a few cases. Here we demonstrate that chirality transfer is possible inside a rather large molecular container of approximately 1400 Å3 . Specifically, we present 1) the first examples of optically active hexameric resorcin[4]arene capsules, 2) their ability to enantioselectively catalyze tail-to-head terpene cyclizations, and 3) the surprisingly high sensitivity of enantioselectivity on the structural modifications.

Features of Fabrication of Titanium Dioxide Based Coatings for Non-Lithographic Template Electrochemical Synthesis of Micron Metal Particle Arrays.

This work is devoted to the development of non-lithographic template methods of synthesis. These methods have a significant advantage in terms of structure formation: there is no need to design and produce masks, which greatly simplifies the process, and more of them can work with nonplanar substrates. The purpose of this study was to reveal the conditions for the synthesis of titanium dioxide xerogel films of different topologies as well as to develop a technique for non-lithographic template electrochemical synthesis of micron metal particles arrays and to study the structure of the resulting coatings. The films were deposited on the surface of substrates via dip coating. Specific topology of the films was achieved by template sol-gel synthesis. Their structures were analyzed by SEM and XRD. Template synthesis of metal micro particles were realized by pulsed electrochemical deposition of metals into the perforations of xerogel films. Obtained materials were analyzed by SEM and XRD; the element distribution on the surface was determined by the EDS detector of SEM. Based on the analysis results, we suggest the mechanisms of formation of the xerogel topology and proved the efficiency of pulsed electrodeposition for template synthesis of micron particles arrays.

Optimized iminium-catalysed 1,4-reductions inside the resorcinarene capsule: achieving >90% ee with proline as catalyst.

In previous work, we demonstrated that iminium-catalysed 1,4-reductions inside the supramolecular resorcinarene capsule display increased enantioselectivities as compared to their regular solution counterparts. Utilizing proline as the chiral catalyst, enantioselectivities remained below 80% ee. In this study, the reaction conditions were optimized by determining the optimal capsule loading and HCl content. Additionally, it was found that alcohol additives increase the enantioselectivity of the capsule-catalysed reaction. As a result, we report enantioselectivities of up to 92% ee for iminium-catalysed 1,4-reductions relying on proline as the sole chiral source. This is of high interest, as proline is unable to deliver high enantioselectivities for 1,4-reductions in a regular solution setting. Investigations into the role of the alcohol additive revealed a dual role: it not only slowed down the background reaction but also increased the capsule-catalysed reaction rate.

Cosmetic Syndrome Correction with Calcium Hydroxylapatite-Based Filler in Patients with Connective Tissue Dysplasia.

Undifferentiated connective tissue dysplasia is one of the most common diseases of nowadays, which does not fit into the group of hereditary syndromes. This condition is diagnosed in 20-50% of the population at any age. The study aimed to correct the facial soft tissues of patients with undifferentiated connective tissue dysplasia through the cosmetic procedure of calcium hydroxylapatite injection. In 2018, a 36-year-old patient addressed the beauty salon with signs of undifferentiated connective tissue dysplasia, such as severe asymmetry of the face, infraorbital and nasolabial sulci, and thin and easily folding skin. Signs were observed from the age of 22, i.e., for 14 years. The therapy was performed using special features of the correction of facial soft tissue changes in patients with connective tissue dysplasia (CTD) using calcium hydroxylapatite-based products (Radiesse®, Merz North America, Inc., USA). Particular attention is given to the need for early correction to prevent premature skin aging related to this condition. After 14 days, a significant improvement of the patient's skin condition was noted after the passing of two procedures. Her condition was estimated as consistent with T1-2P0G0A1Zh1 P1M1K1 and corresponded to grade I age-related changes in the superficial soft tissues. The performed treatment showed high efficacy in case of mild connective tissue dysplasia diagnosis. The results showed that when collecting information from anamnesis, the diagnostic criteria for dysplasia should be considered. If the criteria are met, the cosmetological correction with collagen stimulators becomes possible.

The effectiveness of botulinum toxin type A (BTX-A) in the treatment of facial skin oily seborrhea, enlarged pores, and symptom complex of post-acne.

BACKGROUND: This study aimed to examine the effectiveness of botulinum toxin type A (BTX-A) in the treatment of acne. METHODS: The study was conducted in 2018 on 12 patients, 10 females and two males, aged 35 years on average. The injections with BTX-A were given during 2 weeks into the face skin in a dosage of 0.125-0.250 units. RESULTS: Skin moisture indexes increased during the therapy by 4% (P ≤ 0.05), and porosity decreased by 7% (P ≤ 0.01). Maximal changes were recorded for the sulci and pigmentation of the skin, namely, its values decreased by 10 and 9%, respectively (P ≤ 0.01). BTX-A is recommended for an application not only in plastic surgeries but also for local correction of acne on the patient's skin. CONCLUSION: A positive correlation was revealed between the duration of treatment and reduction of skin oiliness (0.87), pigmentation (0.78), skin sulci (0.84), and skin porosity (0.88), and negative correlation was established with increased skin moisture (-0.64). The obtained dependencies apply for the therapy period of up to 2 weeks. Pharmacological properties of BTX-A allow recommending it as a drug used in post-acne therapy.