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Graphical abstract Highlights • Rare ginsenosides were successfully bio-transformed by Aspergillus tubingensis. • Rh4 aglycone increased over 100 folds than that in the original TSSLG. • MCL-1 was explored as anticancer target of Rh4 and its aglycone. Abstract Rare ginsenoside Rh 4 and its aglycone are present in low levels in Panax ginseng. This study focused on achieving ginsenoside Rh 4 and its aglycone by microbial transformation of the total saponins of stems and leaves of P. ginseng (TSSLG). A total of 78 fungal strains isolated from the rhizosphere soil of P. ginseng , and one of them, Aspergillus tubingensis , was found to be capable of biotransformation of TSSLG to ginsenoside Rh4 and its aglycone with high efficiency, especially the content of ginsenoside Rh4 aglycone was enhanced 100 folds over than that in the original TSSLG. Compared with ginsenoside Rg3 (named ShenYi capsule as antitumor drug in China), ginsenoside Rh4 aglycone exhibited stronger antitumor activity against human cancer cell lines SGC-7901, KB-A-1 and HT-1080. The possible biotransformation pathways of ginsenoside Rh4 and its aglycone were speculated according to the chemical structures. The anticancer binding-target, myeloid cell leukemia 1 protein (MCL-1), was explored using molecular docking analysis and the possible combination mechanism was discussed. [ABSTRACT FROM AUTHOR]

In this Letter, we study a nonlocal vector nonlinear Schrödinger (NVNLS) equation with self-induced parity-time-symmetric potential. We construct the N -fold Darboux transformation in terms of compact determinant forms. Starting from the non-vanishing background, we give the general solution of spectral problem, which allows us to derive many different types of exact analytical solutions of the NVNLS equation, like the breathers, dark and anti-dark solitons. With three-component case as an example, we display three types of two-soliton elastic collision behaviors: breather and dark soliton, breather and anti-dark soliton, dark soliton and anti-dark soliton. [ABSTRACT FROM AUTHOR]

A total of 58 fungal isolates, belonging to 24 genera, were obtained from the leaves, stems and roots of Ginkgo biloba L.. Among them, one endophytic fungal strain, Penicillium cataractum SYPF 7131, displayed the strongest antibacterial activity. Four new compounds ( 1 – 4) were isolated from the strain fermentation broth together with four known compounds ( 5 – 8) . These structures were determined on the basis of 1D and 2D NMR and [Rh 2 (OCOCF 3 ) 4 ]-induced electronic circular dichroism (ECD) spectroscopic analyses. All the isolated compounds were screened for their in vitro antimicrobial activities. Compound 3 and 4 showed moderate inhibitory activity against Staphylococcus aureus . Compound 7 exhibited significant inhibitory activity against S. aureus with MIC value of 10 μg/mL. Further, the in silico molecular docking studies of the active compounds was used to explore the binding interactions with the active site of filamentous temperature-sensitive protein Z (FtsZ) from Staphylococcus aureus . The docking results revealed that compounds 3 , 4 and 7 showed high binding energies, strong H-bond interactions and hydrophobic interactions with FtsZ from S. aureus validating the observed antimicrobial activity. Based on antimicrobial activities and docking studies, compounds 3 , 4 and 7 were identified as promising antimicrobial lead molecules. [ABSTRACT FROM AUTHOR]

In this Letter, the Darboux transformation is first applied to the defocusing Sasa–Satsuma equation which describes the propagation dynamics of ultrashort light pulses in the normal dispersion regime of optical fibers. The N -fold iterative transformation is expressed in terms of the determinants. This transformation enables us to construct explicit analytical dark soliton solutions from non-vanishing background. In illustration, the single-dark soliton solution is presented from the once-iterated formula. [ABSTRACT FROM AUTHOR]

• SDH_1927 has the highest specific activity (56.72 ± 1.2 U/mg) among the eight L-sorbose dehydrogenases. • The 2-KGA production can be significantly increase by PMS under the condition of avoiding light. • The product 2-KGA could inhibit SDH activity by competing for the same hydrogen bonding sites with the substrate of L-sorbose. • The cell-recycling catalysis system is proposed to convert L-sorbose to 2-KGA, with the yield of 80.12 g/L and the productivity of 6.68 g/L/h. There are five L-sorbose dehydrogenases (SDH_2764, SDH_2744, SDH_0718, SDH_1927, SDH_0337) in Ketogulonicigenium vulgare SPU B805 and three L-sorbose dehydrogenases (SDH_02251, SDH_02271, SDH_P100164) in K. robustum SPU_B003, which play essential roles in the classical two-step fermentation for 2-keto-L-gulonic acid (2-KGA, the precursor of vitamin C) synthesis. In this work, the above eight SDH enzymes were cloned and purified, and their optimal pH values and reaction temperatures, kinetic properties (K m and K cat), thermal stabilities, substrate spectra, and effects of metal ions were determined. Eight SDH-harboring recombinant E.coli strains were verified to be capable to catalyze L-sorbose to 2-KGA. Additionally, the molecular docking results showed that the product 2-KGA could inhibit SDH activity by competing for the same hydrogen bonding sites with substrate L-sorbose. Finally, a novel and efficient whole-cell recycling catalysis system to overcome the product inhibition was proposed, the yield of 2-KGA reached up to 80.12 g/L with the productivity of 6.68 g/L/h. The results provide a promising prospect for selection and modification sorbose dehydrogenase for construction a one-step biotransformation system of 2-KGA. [Display omitted] [ABSTRACT FROM AUTHOR]

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N -atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC 50 = 0.55 μM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy. [Display omitted] • A series of isoquinolinone derivatives were designed, synthesized and evaluated for their inhibition on HIF-1 signaling. • 17q showed enhanced inhibition on HIF-1 signaling than its parent compound in inflammatory synovial cell line. • 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated the inflammation in vivo. [ABSTRACT FROM AUTHOR]

[Display omitted] • A one-step fermentation system was established in P. putida KT2440. • Enhanced electron transport efficiency increased the 2-KGA production. • The provision of a stable catalytic environment can enhance 2-KGA production. • Multi-strategy leads to a 15.48-fold enhancement in one-step fermentation. 2-KGA, a precursor for the synthesis of Vitamin C, is currently produced in China utilizing the "two-step fermentation" technique. Nevertheless, this method exhibits many inherent constraints. This study presents a comprehensive metabolic engineering strategy to establish and optimize a one-step 2-KGA fermentation process from D-sorbitol in Pseudomonas putida KT2440. In general, the endogenous promoters were screened to identify promoter P1 for subsequent heterologous gene expression in KT2440. Following the screening and confirmation of suitable heterologous gene elements such as sldh , sdh , cytc 551, pqq AB, and irr E, genetic recombination was performed in KT2440. In comparison to the initial achievement of expressing only sldh and sdh in KT2440, a yield of merely 0.42 g/L was obtained. However, by implementing four metabolic engineering strategies, the recombinant strain KT20 exhibited a significant enhancement in its ability to produce 2-KGA with a remarkable yield of up to 6.5 g/L – representing an impressive 15.48-fold improvement. [ABSTRACT FROM AUTHOR]

Highlights • Global brain ischemia caused delayed neuronal death(DND) in CA1 hippocampus in rats. • The ischemia led to GLT-1 down-regulation and p-p38 MAPK up-regulation in rats. • Lethal OGD decreased GLT-1 and increased p-p38 MAPK expression in astrocytes. • SB203580 or p38 MAPK siRNA reduced neuronal death and GLT-1 decreasing after OGD. • SB203580 alleviated the DND and GLT-1 down-regulation after brain ischemia in rats. Abstract The previous studies have shown that glial glutamate transporter-1 (GLT-1) participates in cerebral ischemic injury in rats. However, the mechanism involved remains to be elucidated. This study was undertaken to investigate whether p38 MAPK was involved in regulating GLT-1 in the process. At first, it was observed that global brain ischemia for 8 min led to obvious delayed neuronal death, GLT-1 down-regulation and p-p38 MAPK up-regulation in CA1 hippocampus in rats. Then, whether p-p38 MAPK was involved in regulating GLT-1 during cerebral ischemic injury was studied in vitro. Astrocyte-neuron co-cultures exposed to oxygen and glucose deprivation (OGD) were used to mimic brain ischemia. It was observed that lethal OGD (4-h OGD) decreased GLT-1 expression and increased p-p38 MAPK expression in astrocytes. The p-p38 MAPK protein rised from 0 min to 48 h that is the end time of the observation, and the peak value was at 12 h, which was 12.45 times of the control group. Moreover, pre-administration of p38 MAPK inhibitor SB203580 or its siRNA dose-dependently increased GLT-1 expression, and meanwhile alleviated the neuronal death induced by lethal OGD. The above results indicated that p38 MAPK signaling pathway participated in regulating GLT-1 during OGD injury in vitro. Finally, back to in vivo experiment, it was found that pre-administration of SB203580 by intracerebroventricular injection dose-dependently reversed the down-regulation of GLT-1 expression and attenuated the delayed neuronal death normally induced by global brain ischemia in CA1 hippocampus in rats. Taken together, it can be concluded that the mechanism of GLT-1 mediating cerebral ischemic injury depends on the activation of p38 MAPK. [ABSTRACT FROM AUTHOR]

Abstract A total of 180 fungal isolates, belonging to 20 genera and 47 species, were obtained from the roots, stems and leaves of Panax notoginseng. One isolate, the endophytic fungus Penicillium janthinellum SYPF 7899, displayed the strongest antibacterial activity and was studied for its production of secondary metabolites. In total, three new compounds, including rotational isomers 1a, 1b and 2 were isolated from the solid cultures of P. janthinellum , as well as eight known compounds (3 − 10). These structures were determined on the basis of 1D, 2D NMR and electronic circular dichroism (ECD) spectroscopic analyses as well as theoretical calculations. Compound 1 exhibited significant inhibitory activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 15 and 18 μg/ml, respectively. The other compounds showed moderate or weak activities. In addition, morphological observation showed the rod-shaped cells of B. subtilis growing into long filaments, which reached 1.5- to 2-fold of the length of the original cells after treatment with compound 1. The coccoid cells of S. aureus exhibited a similar response and swelled to a 2-fold volume after treatment with compound 1. In silico molecular docking was explored to study the binding interactions between the compounds and the active sites of filamentous temperature-sensitive protein Z (FtsZ) from B. subtilis and S. aureus. Compound 1a, 1b and 2 showed high binding energies, strong H-bond interactions and hydrophobic interactions with FtsZ. Based on the antimicrobial activities, cellular phenotype observation and docking studies, compound 1 is considered to be a promising antimicrobial inhibitor of FtsZ. Graphical Abstract Unlabelled Image [ABSTRACT FROM AUTHOR]