iTRAQ-based quantitative proteomic analysis in liver of Pomacea canaliculata induced by oleanolic acid stress.

BACKGROUND: Triterpene acid is one of the typical active constituents of Eucalyptus bark, which is the main by-product of the Eucalyptus wood industry. Our studies have demonstrated that triterpene acid stress could inhibit climbing and increase mortality in Pomacea canaliculata (Lamarck). However, limited attention has been paid to the proteomic responses of this snail under triterpene acid stress. RESULT: Using iTRAQ-based quantitative proteomics, we elucidated the regulatory mechanism in the livers of P. canaliculata held in chlorine-free water and exposed to 100 mg L-1 oleanolic acid (OA) for 24 h. A total of 4308 proteins were identified, of which 274 were differentially expressed proteins (DEPs) including 168 (61.31%) differentially upregulated proteins and 106 (38.69%) differentially downregulated proteins. Bioinformatics analysis revealed that P. canaliculata responses to OA stress are mainly involved in glucose metabolism, energy synthesis, immune response, stress response, protein synthesis, and apoptosis. According to KEGG analysis, the 274 DEPs were mapped to 168 KEGG pathways and 10 KEGG pathways were significantly enriched (P < 0.05). Furthermore, qRT-PCR was performed for histone H4, catalase, isocitrate dehydrogenase, superoxide dismutase, ferritin, lipase, and tropomyosin to validate the iTRAQ results. CONCLUSION: Proteomic analysis suggested that OA stress led to the disruption of glucose metabolism, energy synthesis, and protein synthesis, and triggered a series of molecular pathways containing many key proteins involved in the immune process, thereby helping P. canaliculata resist OA stress. © 2022 Society of Chemical Industry.

The COVID-19 Pandemic and Economic Growth: Theory and Simulation.

The outbreak of COVID-19 pandemic has caused profound consequences on world economy. In order to explore the long-term impact of the pandemic on economic growth and the effects of different policy responses, this paper combines economic theory with epidemiological model to construct an interdisciplinary model, in which labor supply is dynamically constrained by pandemic conditions. Analysis of model equilibrium suggests that outbreaks of infectious disease reduce labor supply and negatively affect economic output. The accumulation of health capital can suppress the spread of disease and improve the recovery rate of infected individuals, which will alleviate the labor supply constraint caused by the pandemic and lead to an increase in output and consumption. The model is then calibrated to Chinese economy. The simulation results imply that government's public health policy can enhance the role of health capital in promoting economic growth. But the marginal effect of certain policies is diminishing. Therefore, the government needs to balance pandemic prevention and control costs and marginal benefits when formulating public health policies. When the pandemic is under control, the resumption of production is feasible and the economic stimulus package could lead to economic recovery.

Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis.

Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16. B16 preferentially inhibited Btk (IC50 = 21.70 ±â€¯0.82 nM) over closely related kinases with moderate selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk Y223 auto-phosphorylation and PLCγ2 Y1217 phosphorylation. MTT revealed that B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines with IC50 values over 30 µM. Moreover, B16 showed very weak potential to block the hERG channel (IC50 = 11.10 µM) in comparison to ibrutinib (IC50 = 0.97 µM). Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous solubility ≈ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t1/2 = 7.02 h) and reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the potential to a safe and efficacious treatment for arthritis.

Enhancement of chitosanase production by cell immobilization of Gongronella sp. JG.

Chitosanase production of Gongronella sp. JG cells immobilized in calcium alginate gel and polyurethane foam was compared with that of the free cells, there was a 60% increase in the enzyme yield (2429 U/L) compared to the highest yield obtained from free cells (1513 U/L). The optimal immobilization parameters (concentrations of sodium alginate, calcium chloride, bead inoculums, bead diameter, etc) for the enhanced production of chitosanase were determined as: sodium alginate 2% (w/v), 0.1 M calcium chloride, inoculum 10 mL beads to 100 mL production media and 2.7 mm bead diameter. Maximum chitosanase production was achieved with initial pH of 5.5 and temperature of 30 °C. The alginate beads had well stability, retained 85% ability of enzyme production even after 7 cycles of repeated batch fermentation. These results showed the immobilization technique was a feasible and economical method for chitosansase production by Gongronella sp. JG.

Enhancement of chitosanase production by cell immobilization of Gongronella sp. JG

Chitosanase production of Gongronella sp. JG cells immobilized in calcium alginate gel and polyurethane foam was compared with that of the free cells, there was a 60% increase in the enzyme yield (2429 U/L) compared to the highest yield obtained from free cells (1513 U/L). The optimal immobilization parameters (concentrations of sodium alginate, calcium chloride, bead inoculums, bead diameter, etc) for the enhanced production of chitosanase were determined as: sodium alginate 2% (w/v), 0.1 M calcium chloride, inoculum 10 mL beads to 100 mL production media and 2.7 mm bead diameter. Maximum chitosanase production was achieved with initial pH of 5.5 and temperature of 30 ºC. The alginate beads had well stability, retained 85% ability of enzyme production even after 7 cycles of repeated batch fermentation. These results showed the immobilization technique was a feasible and economical method for chitosansase production by Gongronella sp. JG.

L(+)-lactic acid production by co-fermentation of glucose and xylose with Rhizopus oryzae obtained by low-energy ion beam irradiation.

Low-energy ion beam irradiation (10-200 keV) has been proved to have a wide range of biological effects in recent years. When Rhizopus oryzae PW352 was irradiated with a 15-keV low-energy ion beam an L(+)-lactic acid high-yield mutant, RQ4015, was obtained. When 150 g/l glucose was used as the sole carbon source, L(+)-lactic acid of RQ4015 reached 121 g/l after 36 h shake-flask cultivation. However, the highest lactic acid concentration 74 g/l was obtained when 100 g/l xylose was present in the medium as the sole carbon source. When mixed xylose (25 g/l) and glucose (75 g/l) were present in a bubble column, L(+)-lactic acid production of RQ4015 reached 83 g. A high mutation rate and a wide mutation spectrum of low-energy ion implantation were observed in the experiment, suggesting that ion implantation can be a highly efficient mutagenic means for microorganism breeding in many commercial applications.

Induction of germline cell cycle arrest and apoptosis by sodium arsenite in Caenorhabditis elegans.

The nematode Caenorhabditis elegans has been shown to be a model organism in studying aquatic toxicity. Although epidemiological studies have shown that arsenic is teratogenic and carcinogenic to humans, the lethality assay indicated that C. elegans is less sensitive to inorganic arsenic than any other organisms that have been tested thus far. In the present study, we used the more malleable germline of C. elegans as an in vivo system to investigate the genotoxic effects of arsenite. After animals were exposed to sodium arsenite at concentrations ranging from 1 microM to 0.5 mM, mitotic germ cells and germline apoptosis were scored after DAPI staining and acridine orange vital staining, respectively. DMSO rescue experiments were performed by exposing C. elegans to 0.01 mM arsenite in the presence of DMSO (0.1%) for 24 h, and reactive oxygen species (ROS) were semiquantified by CM-H(2)DCFDA vital staining. The results indicated that arsenic exposure reduced the brood size of C. elegans and caused mitotic cell cycle arrest and germline apoptosis, which, to some extent, exhibited a concentration- and time-dependent manner. The addition of 0.1% DMSO completely rescued arsenic-induced cell cycle arrest and partially suppressed germline apoptosis. Furthermore, treatment of animals with arsenite at a dose of 0.01 mM significantly increased ROS production in the intestine, which could be reduced by DMSO treatment. The present study also indicated that C. elegans might be used as an in vivo model system to study the mechanisms of arsenic-induced genotoxic effects.