Impact of Nutritional Tea Polyphenols on Growth, Feed Efficiency, Biochemical Traits, Antioxidant Capacity, Haematological Parameters and Immunity in Coho Salmon ().

To evaluate the impact of nutritional tea polyphenols (TPs) on body composition, growth, biochemical markers, antioxidant capacity, and hemato-immunological levels, a ten-week feeding experiment was carried out on coho salmon (, 180.51 ± 0.15 g).

Optimistic effects of galaxolide and polystyrene microplastic stress on the physio-biochemical characteristics and metabolic profiles of an ornamental plant.

Galaxolide (HHCB) and polystyrene (PS) microplastics or nanoplastics have been widely recognized as emerging pollutants. However, very few efforts have been made to remove these contaminants from the environment using eco-friendly materials such as plant materials. Therefore, this study sought to investigate the physiological and biochemical effects and tolerance mechanisms of Mirabilis jalapa L.

Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers.

Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple studies of PAM pathway-driven tumors.

Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors.

Activation of the PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K and Akt enzymatic assays.

The G2A Receptor Deficiency Aggravates Atherosclerosis in Rats by Regulating Macrophages and Lipid Metabolism.

The orphan G protein-coupled receptor G2A has been linked to atherosclerosis development. However, available data from mouse models are controversial. Rat G2A receptor bears more similarities with its human homolog.

Synthesis and SAR development of quinoline analogs as novel P2X7 receptor antagonists.

The P2X7 receptor (P2X7R) plays an important role in diverse conditions associated with tissue damage and inflammation, suggesting that the human P2X7R (hP2X7R) is an attractive therapeutic target. In the present study, the synthesis and structure-activity relationship (SAR) of a novel series of quinoline derivatives as P2X7R antagonists are described herein. These compounds exhibited mechanistic activity (YO PRO) in an engineered HEK293 expressing hP2X7R as well as a functional response (IL-1β) in human THP-1 (hTHP-1) cellular assays.

Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats.

Background And Aims: Low-density lipoprotein receptor (Ldlr) and apolipoprotein E (Apoe) knockout (KO) mice have been widely used as animal models of atherosclerosis. However, data suggested that it is difficult to develop typical atherosclerosis in rats. To this end, Ldlr and Apoe KO rats were generated and the potential to develop novel atherosclerosis models was evaluated.

[Expression of recombinant human ZP3 protein using the baculovirus expression system].

Objective: To investigate the methods and solve the technical bottlenecks in the preparation of recombinant human protein hZP3 using the baculovirus expression system and pave the technical ground for the production and application of recombinant hZP3.

Methods: The recombinant vector pFASTBAC HTa-hZP3 was constructed and transferred to competent E. coli cells carrying bacmid to produce recombinant bacmid by homologous recombination.

SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors.

Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2.

[Reference values of semen parameters for normal fertile men in Shanghai].

Objective: To analyze the distribution characteristics of the main semen parameters of healthy semen donors and normal fertile men in Shanghai, compare the semen quality between the two groups, and investigate the normal reference values of the semen parameters of the fertile population in Shanghai.

Methods: We obtained semen samples from 100 healthy donors and 41 fertile men, performed semen analyses according to the WHO (2010) guidelines, and determined the semen volume, sperm concentration, sperm progressive motility, total sperm count and total progressively motile sperm count. We analyzed the distribution of the semen parameters of the normal fertile men, and obtained the lower limits of their normal reference values.

[Direct fumigation for freeze-thawing of human sperm: an experimental study].

Objective: To study the effect of direct fumigation on the post-thaw recovery rate of cryopreserved spermatozoa, and to search for a best method for human sperm cryopreservation.

Methods: We collected semen samples from 100 donors conforming to the normal reference values in WHO Laboratory Manual for the Examination and Processing of Human Semen (5th Ed), divided them into two groups, and subjected them to cryopreservation by programmable freezing (Group A) and direct fumigation (Group B), respectively. We detected the progressive motility of pre-freezing and post-thaw sperm with a computer-assisted semen analyzer, and compared the effects of the two methods on the functional integrity of sperm membrane and the rate of abnormal sperm using the percentage of hypo-osmotic swelling sperm and modified Papanicolaou staining.

Direct determination of trace cadmium in environmental samples by dynamic reaction cell inductively coupled plasma mass spectrometry.

Cadmium is subject to significant Zr and Mo based oxide/hydroxide interferences in ICP-MS analysis of environmental samples. In this work, a dynamic reaction cell (DRC) technology was used to eliminate these metal oxide/hydroxide interferences. The potentially interfering ions (94)Zr(16)OH(+), (94)Mo(16)OH(+) and (95)Mo(16)O(+) on (111)Cd(+) were oxidized to higher oxides (94)ZrO(2)H(+)/(94)ZrO(3)H(+), (94)MoO(2)H(+)/(94)MoO(3)H(+), and (95)MoO(2)(+)/(95)MoO(3)(+) by O(2) as the reaction gas in DRC.

Synthesis and evaluation of a gamma-lactam as a highly selective EP2 and EP4 receptor agonist.

Gamma-lactam analogs (2) of EP(4) receptor agonists were identified by substitution of the pyrazolidinone ring (1) with a pyrrolidinone ring. Several compounds (such as 2a, 2h) with high potency, selectivity and acceptable PK profiles were discovered. These were assessed in animal models of ovulation induction and bronchoconstriction.

Synthesis and evaluation of novel pyrazolidinone analogs of PGE2 as EP2 and EP4 receptors agonists.

Replacement of the hydroxy cyclopentanone ring in PGE(2) with chemically more stable heterocyclic rings and substitution of the unsaturated alpha-alkenyl chain with a metabolically more stable phenethyl chain led to the development of potent and selective analogs of PGE(2). Compound 10f showed the highest potency and selectivity for EP(4) the receptor.

Discovery of novel prostaglandin analogs of PGE2 as potent and selective EP2 and EP4 receptor agonists.

Analogs of PGE(2) with introduction of diene groups at the omega-side chain have been synthesized and evaluated for their binding affinity for EP(2) and EP(4) receptors. An optimized analog (compound 9b) showed high potency and selectivity for the EP(4) receptor over other known receptors.

Steady-state kinetics and inhibition of anaerobically purified human homogentisate 1,2-dioxygenase.

HGO (homogentisate 1,2-dioxygenase; EC 1.13.11.

[Study on the influence of medical abortion and surgical abortion on subsequent pregnancy].

Objective: To evaluate and compare medical abortion versus surgical abortion in respect of their influence on the safety of the mother and baby in the subsequent pregnancy and parturition.

Methods: Based on the principle of informed consent of subjects, 150 healthy pregnant women with a past history of having experienced medical abortion once were included in the study group (also called medical abortion group), and in the same period, 150 healthy pregnant women with a past history of having experienced surgical abortion once were enrolled into the comparison group (also called surgical abortion group). From then on, all the pregnant women in the two groups were followed up till a week after labor.