[99mTc]Tc-PSMA-T4—Novel SPECT Tracer for Metastatic PCa: From Bench to Clinic

Despite significant advances in nuclear medicine for diagnosing and treating prostate cancer (PCa), research into new ligands with increasingly better biological properties is still ongoing. Prostate-specific membrane antigen (PSMA) ligands show great potential as radioisotope carriers for the diagnosis and therapy of patients with metastatic PCa. PSMA is expressed in most types of prostate cancer, and its expression is increased in poorly differentiated, metastatic, and hormone-refractory cancers; therefore, it may be a valuable target for the development of radiopharmaceuticals and radioligands, such as urea PSMA inhibitors, for the precise diagnosis, staging, and treatment of prostate cancer. Four developed PSMA-HYNIC inhibitors for technetium-99m labeling and subsequent diagnosis were subjected to preclinical in vitro and in vivo studies to evaluate and compare their diagnostic properties. Among the studied compounds, the PSMA-T4 (Glu-CO-Lys-L-Trp-4-Amc-HYNIC) inhibitor showed the best biological properties for the diagnosis of PCa metastases. [^99mTc]Tc-PSMA-T4 also showed effectiveness in single-photon emission computed tomography (SPECT) studies in humans, and soon, its usefulness will be extensively evaluated in phase 2/3 clinical trials.     

The Influence of NH4NO3 and NH4ClO4 on Porous Structure Development of Activated Carbons Produced from Furfuryl Alcohol

The influence of NH₄NO₃ and NH₄ClO₄ on the porous texture and structure development of activated carbons produced from a non-porous polymeric precursor synthesized from furfuryl alcohol has been studied. The non-doped counterparts were prepared and studied for comparison purposes. NH₄NO₃ and NH₄ClO₄-doped polymers were carbonized under N₂ atmosphere at 600 °C, followed by CO₂ activation at 1000 °C and the obtained carbon materials and activated carbons were thoroughly characterized. The porosity characterization data have shown that NH₄NO₃-derived ACs present the highest specific surface area (up to 1523 m²/g in the experimental conditions studied), and the resulting porosity distributions are strongly dependent on the activation conditions. Thus, 1 h activation is optimum for the microporosity development, whereas larger activation times lead to micropores enlargement and conversion into mesopores. The type of doping salts used also has a substantial impact on the surface chemical composition, i.e., C=O groups. Moreover, NH₄NO₃ and NH₄ClO₄ constitute good sources of nitrogen. The type and contribution of nitrogen species are dependent on the preparation conditions. Quaternary nitrogen only appears in doped samples prepared by carbonization and pyrrolic, pyrydinic, and nitrogen oxide groups appear in the NH₄NO₃ -series. NH₄NO₃ incorporation has led to optimized materials towards CO₂ and C₂H₄ sorption with just 1 h activation time.     

Organic Acids Secreted by Lactobacillus spp. Isolated from Urine and Their Antimicrobial Activity against Uropathogenic Proteus mirabilis

The natural microbiota of the urinary tract includes Lactobacillus spp., which secrete molecules with antimicrobial properties and have antagonistic activity against many pathogens. This paper focuses on the antibacterial effect of Lactobacillus strains isolated from urine against clinical strains of Proteus mirabilis isolated from kidney stones and from urine with coexisting urolithiasis. The study involved analyzing the main antimicrobial molecules secreted by Lactobacillus. In order to indicate which agent had the strongest antimicrobial effect, the supernatants were made alkaline and treated with catalase and high temperature. Both treated and untreated supernatants were analyzed for their activity. Exposing uropathogens to all untreated cell-free supernatants of Lactobacillus significantly reduced their growth, and it was established that these properties were related to organic acid secretion by these strains. Using LC–MS/MS and spectrophotometric techniques, lactic, citric, and succinic acids were determined qualitatively and quantitatively. The influence of these acids on the P. mirabilis growth and biofilm formation and their influence on membrane permeability were also investigated. The results indicate that organic acids secreted by Lactobacillus strains have a high antibacterial potential and could be used as novel agents in the treatment of urinary tract infections caused by P. mirabilis.     

The Impact of Formulation on the Content of Phenolic Compounds in Snacks Enriched with Dracocephalum moldavica L. Seeds: Introduction to Receiving a New Functional Food Product

A new type of multigrain snack has been designed containing varied additions of Moldavian dragonhead (Dracocephalum moldavica L.) seeds. The antioxidant properties and the general health benefits of this plant material have already been widely acknowledged. The research discussed herein aimed to investigate the influence of the formulation and expansion method (frying) on the content of polyphenolic compounds, individual phenolic acids, and antiradical properties of innovative snacks enriched with dragonhead seeds. The highest content of polyphenols (0.685 mg GAE/mL), free phenolic acids (47.052 µg/g of dry matter), and highest radical scavenging activity (96.23% towards DPPH) were found in the fried snacks enriched with 22% of seeds. In these samples, 11 phenolic acids were detected. Strong positive correlations were seen between the addition of dragonhead and the polyphenol content (r = 0.989) and between the quantity of the enriching additive and the content of free phenolic acids (r = 0.953). The research has shown that such innovative snacks have the potential to supply health-benefiting free phenolic acids, e.g., salicylic, isoferulic, ferulic, p-coumaric, vanillic. Our studies provide an introduction to the development of a new range of functional foods.     

The Expression Profiles of the Salvia miltiorrhiza 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase 4 Gene and Its Influence on the Biosynthesis of Tanshinones

Salvia miltiorrhiza is a medicinal plant that synthesises biologically-active tanshinones with numerous therapeutic properties. An important rate-limiting enzyme in the biosynthesis of their precursors is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). This study presents the organ-specific expression profile of the S. miltiorrhiza HMGR4 gene and its sensitivity to potential regulators, viz. gibberellic acid (GA₃), indole-3-acetic acid (IAA) and salicylic acid (SA). In addition, it demonstrates the importance of the HMGR4 gene, the hormone used, the plant organ, and the culture environment for the biosynthesis of tanshinones. HMGR4 overexpression was found to significantly boost the accumulation of dihydrotanshinone I (DHTI), cryptotanshinone (CT), tanshinone I (TI) and tanshinone IIA (TIIA) in roots by 0.44 to 5.39 mg/g dry weight (DW), as well as TIIA in stems and leaves. S. miltiorrhiza roots cultivated in soil demonstrated higher concentrations of the examined metabolites than those grown in vitro. GA₃ caused a considerable increase in the quantity of CT (by 794.2 µg/g DW) and TIIA (by 88.1 µg/g DW) in roots. In turn, IAA significantly inhibited the biosynthesis of the studied tanshinones in root material.     

Optimality conditions for the calculus of variations with higher-order delta derivatives

We prove the Euler–Lagrange delta-differential equations for problems of the calculus of variations on arbitrary time scales with delta-integral functionals depending on higher-order delta derivatives.     

Second Noether’s theorem with time delay

In this paper, we consider variational problems with delayed argument. Simple proofs of the first and second Noether theorems are given. Applying our results to some concrete problems we obtain conservation laws for systems with delay.     

Discrete leader‐following consensus

In this paper, a leader‐following consensus of discrete‐time multi‐agent systems with nonlinear intrinsic dynamics is investigated. We propose and prove conditions ensuring a leader‐following consensus. Numerical examples are given to illustrate our results.     

Undiscovered Potential: Ge Catalysts for Lactide Polymerization

Polylactide (PLA) is a high potential bioplastic that can replace oil-based plastics in a number of applications. To date, in spite of its known toxicity, a tin catalyst is used on industrial scale which should be replaced by a benign catalyst in the long run. Germanium is known to be unharmful while having similar properties as tin. Only few germylene catalysts are known so far and none has shown the potential for industrial application. We herein present Ge complexes in combination with zinc and copper, which show amazingly high polymerization activities for lactide in bulk at 150 °C. By systematical variation of the complex structure, proven by single-crystal XRD and DFT calculations, structure–property relationships are found regarding the polymerization activity. Even in the presence of zinc and copper, germanium acts as the active site for polymerizing probably through the coordination–insertion mechanism to high molar mass polymers.