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In order to study the enzymatic properties of laccase derived from Lactobacillus and its potential application in biogenic amine degradation, the gene encoding laccase from Lactobacillus plantarum was heterologously expressed and the recombinant laccase was enzymatically characterized. The optimum reaction temperature and pH, the effects of metal ions and chelators on laccase activity, the tolerance of the recombinant laccase to different concentrations of ethanol and the degradation of biogenic amines by the recombinant laccase were determined. The results showed that the optimum reaction temperature and pH of the purified recombinant laccase was 40 ℃ and 4.0, respectively. Low concentrations of Mg2+, Zn2+ and Ca2+ could promote the activity of the recombinant laccase in different degrees, Zn2+ and Ca2+ being most effective. On the contrary, high concentrations of Mn2+, Fe2+ and ethylenediaminetetraacetic acid could inhibit the activity of recombinant laccase by 85% or more. Toward the substrate 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), the Michaelis constant and maximum reaction rate of the recombinant laccase were 2.49 mmol/L and 0.22 mmol/(L·min), respectively. In addition, the recombinant laccase had a good tolerance to ethanol at low concentration, and the residual activity was more than 75% after incubation in 20% (V/V) ethanol for 1 h. The degradation rates of tyramine and tryptamine by the recombinant laccase were both 100%, while the degradation rates of spermidine, phenethylamine and histamine were 49.60%, 25.27% and 21.80%, respectively. Based on the above results, the recombinant laccase from L. plantarum has great application potential in the degradation of biogenic amines in low-alcohol fermented beverages and fermented foods.

Supplemental Digital Content is Available in the Text. Background: Split-tendon medial transposition of lateral rectus (STMTLR) for complete oculomotor palsy can correct large angles of exotropia in adults, but outcomes are variable, and complications are frequent. Only a few pediatric cases have been reported, and further insight is needed to assess the child's alignment outcomes and ability for postsurgical gain of function. The aim of our study is to report the outcomes of this surgical procedure in pediatric cases of complete oculomotor palsy. Methods: A retrospective review of outcomes was conducted on 5 consecutive patients with complete oculomotor palsy treated with STMTLR by a single surgeon (V.S.S.) between 2015 and 2021 at tertiary referral centers. Primary outcome was postoperative horizontal alignment, and secondary outcome was demonstration of gain-of-function activity in the field of action of the paretic medial rectus muscle. Results: Five cases of pediatric complete oculomotor palsy underwent surgical treatment with STMTLR. Subjects averaged 5.3 years old (range 10 months-16 years). Two were female. Etiologies were heterogeneous, and all presented with unilateral (n = 2) or bilateral complete oculomotor palsy with exodeviations ranging from 45 to >120 prism diopters. Two subjects had bilateral disease secondary to military tuberculosis with CNS involvement. A third subject presented iatrogenically with complete bilateral third nerve palsies secondary to removal of a nongerminomatous germ cell tumor (NGGCT) of the pineal gland. The 2 remaining subjects had monocular involvement in their right eye, 1 from compressive neuropathy after a cavernoma midbrain hemorrhage, and 1 from a congenital right oculomotor palsy. All patients were observed to have stable ocular alignment for a period of at least 6 months before surgery. Unilateral STMTLR was performed in all cases except the subject with NGGCT, in which bilateral STMTLR was performed. Measurement of alignment permanence out to 1–3 years postop resulted in an average correction of 40.83 prism diopters (range 37.5–45 prism diopters) per operated eye. Four of 5 subjects regained limited but active adduction eye movements, and the 2 unilateral cases demonstrated improved convergence. None of the subjects experienced significant complications. Conclusions: STMTLR was a safe and effective approach for the surgical correction of complete pediatric oculomotor palsy in our case series. In addition, pediatric patients may benefit from STMTLR with immediate gain-of-function activity in the transposed lateral rectus muscle, which supports the hypothesis that children have a dynamic and adaptive neuroplasticity of visual target selection that predominates established agonist/antagonist neural signaling. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the rate and amount of cyclosporine A in cats following oral administration using intravenous administration as a reference. Twenty-four healthy cats were selected and randomly divided into four groups in this study. All animals were adapted in a convenient environment during the whole experiment and no adverse effect was observed. Each animal was given a respective dose only once. Blood samples were collected at scheduled time points and analyzed by the established method. The pharmacokinetic parameters were calculated by professional software used in the whole pharma industry of drug development. As a result, the amount of cyclosporine A absorbed in vivo is from one-fifth to one-third, demonstrating that the medium dose has great potential to get into the body. Due to its common side effects always being associated with the amount of cyclosporine in the blood, it is necessary to monitor the concentration of cyclosporine clinically. Practically, doctors draw blood before or 2 h after taking medicine. In this study, we concluded that taking a blood sample after 4 h has more power to estimate the extent of absorption and will be better at preventing the occurrence of side effects in clinical use. This study aimed to evaluate the absolute bioavailability of cyclosporine in cats by investigating the pharmacokinetic profile after intravenous and oral administration, respectively. Twenty-four clinically healthy cats were enrolled in this study and randomly divided into four groups, namely the intravenous group (3 mg/kg), low oral group (3.5 mg/kg), medium oral group (7 mg/kg), and high oral group (14 mg/kg). Whole blood was obtained at the scheduled time points after a single dose administration and cyclosporine was determined using ultra-performance liquid chromatography–tandem mass spectrometry technology (UPLC-MS/MS). Pharmacokinetic parameters were calculated using the WinNonlin 8.3.4 software via compartmental and non-compartmental models. As a result, the bioavailability values for the low, medium, and high oral groups were 14.64%, 36.98%, and 13.53%, respectively. The nonlinear pharmacokinetic profile was observed in the range from 3.5 mg/kg to 14 mg/kg in cats following oral administration. Whole blood concentrations taken 4 h after oral administration were better correlated with the area under the blood concentration–time curve AUC0–24 with a high regression coefficient (R2 = 0.896). This concentration would be a greater predictor in the following therapeutic drug monitoring. No adverse effect was observed in the whole study process. [ABSTRACT FROM AUTHOR]

The elastic properties of random and ordered ZrO2 nanotube- (ZrNT-) reinforced HA and β-TCP biocomposites were carried out by a numerical investigation with finite element approach. The elastic modulus, shear modulus, and Poisson's ratio affected by various ZrNT volume fractions (5.0 vol.%, 5.5 vol.%, 6.5 vol.%, 7.5 vol.%, 8.5 vol.%, and 10.0 vol.%) and aspect ratios (3, 5, 10 and 20) for both random and ordered reinforced composites were obtained and analysed. The advantages of random and ordered reinforced composites were further discussed. The random reinforced composite is suggested to be a proper candidate for ZrO2 nanotube-reinforced biocomposite on the application of bone repair and the substitute. [ABSTRACT FROM AUTHOR]

KPT-335 (Verdinexor) is a novel SINE that potently inhibits the nucleoprotein Exportin 1 (XPO1/CRM1) of tumor cell lines and reduces the replication level of the influenza virus. KPT-335 is mainly used for the treatment of canine tumors. Drugs for the effective treatment of feline tumors are currently unavailable in China. KPT-335 may have potential in the treatment of cat tumors. However, the effects of KPT-335 in cats are unreported, and no relevant methodology has been established for pharmacokinetic studies. In this study, a UPLC-MS/MS method was developed to determine KPT-335 concentrations in cat plasma, followed by pharmacokinetic studies. Briefly, plasma proteins are precipitated with acetonitrile, and the supernatant was collected for detection after centrifugation. The linearity for KPT-335 in cat plasma was in the range of 5-1,000 ng/mL. Satisfactory accuracy and precision were obtained. The intra-day accuracy was between -4.10% and 10.48%, the precision was ≤4.65%; the inter-day accuracy was between -0.11% and 8.09%, and the precision was ≤5.85%. Intra-day and inter-day accuracy and precision were within regulatory limits. The results of preliminary pharmacokinetic studies were as follows: T max was 1.46 ± 0.51 h; C max was 239.54 ± 190.60 ng·mL -1 ; T 1/2 was 5.16 ± 2.30 h; AUC 0-t was 1439.85 ± 964.64 ng·mL -1 ·h. The AUC 0-∞ was 1589.82 ± 1003.75 ng·mL -1 ·h. The purpose of this study was to develop a rapid and simple UPLC-MS/MS method to detect KPT-335 concentration in cat plasma and to conduct preliminary pharmacokinetic studies to support the future application of KPT-335 in felines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Qiu, Kong, Cao, Liu, Chen, Wen, Sun and Cao.)