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Objectives: To evaluate the difference of YAP-positive expression between GC and adjacent tissues, as well as the association of elevated YAP expression with clinicopathological features of GC. Methods: PubMed, Embase, Web of Science databases and the Chinese National Knowledge Infrastructure (CNKI) were searched from inception up to December 2018. The pooled ORs and corresponding 95% CIs were used to assess the strength of association. The heterogeneity among eligible studies was evaluated by the Q-test and I2 values. The sensitivity analysis was performed by sequential omission of individual studies. Moreover, Begg’s test and Egger’s test were used to evaluate publication bias. Results: A total of 2229 patients from 16 studies were included in this meta-analysis. The results showed that positive YAP expression was closely correlated with GC but not adjacent non-tumor tissue (OR = 8.08, 95% CI = 4.41 - 14.80). Additionally, YAP overexpression was found to be associated with more advanced TNM stage (OR = 2.68, 95% CI = 1.61 - 4.48), deeper invasion depth (OR = 2.05, 95% CI = 1.32 - 3.19), and lymph node metastasis (OR = 1.95, 95% CI = 1.29 - 2.96). No significant correlation was observed between YAP overexpression and degree of differentiation (OR = 1.17, 95% CI = 0.63 - 2.16), as well as gender of patients (OR = 1.12, 95% CI = 0.91 - 1.37) or tumor size (OR = 1.11, 95% CI = 0.82 - 1.49) of gastric cancer. Conclusions: This meta-analysis demonstrated that YAP might be a promising diagnostic marker and even a therapeutic target for gastric cancer.

This study aimed to elucidate the effect of a pellet feed containing fermented proteins on pond-raised Chinese mitten crabs, Eriocheir sinensis in a 7-month crab feeding experiment in Gucheng Lake, Jiangsu province, China. The results showed that fermented protein could significantly increase mean weight gain, crab size and total yield compared with control group. Moreover, the mean weight of male crabs and the number of large-sized male crabs improved over those of the control group. However, feed efficiency ratio did not differ significantly between the two groups. The amino acid content in the muscles of the female crabs of both the groups was higher than that in the muscles of the male crabs. The present study suggests that fermented compound protein may be one kind of potential protein sources for E. sinensis. Keywords: Chinese mitten crab, Fermented compound protein feed, Sex, Feed efficiency, Growth performance, Muscle amino acids

Monoclonal antibody (mAb), cytotoxins, and linker technology are three essential elements for developing a successful antibody-drug conjugate (ADC). In the research and development of ADCs industry, selected cytotoxins, such as auristatins and maytansines, are commonly tubulin inhibitors which are widely put into clinical use. Thereafter, with the booming development of ADCs, a large number of pharmaceutical companies have expanded a wide range of selectable cytotoxin product lines as well. Recently, the cytotoxic substance of 7-ethyl-10-hydroxycamptothecin (SN-38) conjugated to the monoclonal antibody by linker technology is developed as the second-generation ADCs. Here, the SN-38 families together with sacituzumab govitecan and labetuzumab govitecan are reviewed, whose features of metabolic pathway and toxicity in vivo are well-known. In sum, these methodology and technology would be convenient and flexible to be applied for developing the novel class of cytotoxins in ADCs industry.

Gambogic acid (GA) possesses good anti-tumor efficacy in preclinical studies, however, its poor hydrophilicity, short blood circulation time and side effect limited its clinical application. In this work, monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) copolymer was synthesized and used to encapsulate GA by a facile one-step solid dispersion and form nano-sized micelles (GA micelles). The GA micelles exhibited small average particle size (29±2 nm), high encapsulation efficiency (92.1±0.3%), and long drug release time-in vitro. Compared to free GA, GA micelles showed superior aqueous dispersity, better tumor cellular uptake, enhanced cytotoxicity and apoptosis induction effect against MCF-7 cells. Furthermore, in vivo studies demonstrated that GA micelles have better antitumor effect in the MCF-7 subcutaneous xenograft tumor model. Histopathological analysis of Ki-67 and TUNEL staining further proved that GA micelles could significantly suppress proliferation as well as increase the apoptosis of tumor cells. These results suggested that GA micelles could potentially improve therapeutic outcomes for breast cancer therapy.

Currently, the conventional atmospheric pressure-based and vacuum-based tumbling processes have a limited improvement on the chicken characteristic attributes during the marination process. In view of this, through a breathing (pressure change) tumbling strategy, ultrasonication (40 kHz, 140 W) was applied to improve tenderness, taste, and microstructure of chicken by a redesigned tumbler. The results showed that the tumbling with the breathing action and ultrasonication significantly enhanced the marinating absorptivity, tenderness and taste, and accelerated the degradation of myosin light chain. Free peptides (from 1465.9 ± 34.6 to 4725.7 ± 43.2 μg/mL) and amino acids (from 1.503 ± 0.096 to 2.593 ± 0.109 mg/mL) rose evidently for the control and the breathing tumbling treatment assisted by ultrasound respectively. Raman analysis revealed that strength of disulfide bonds declined from 0.731 ± 0.006 to 0.607 ± 0.011 a.u. and the conversion from α-helix (decreased by 67.23%) into β-fold (increased by 1573%) conformation occurred. Low field NMR analysis indicated that the content of immobilized water increased from 77385 ± 14 to 137011 ± 106 au·ms by integral calculus. Scanning and transmission electron microscopies clearly showed a prospective rupture of myofibers, myofibrils, and lysosomes. Overall, as a potential alternative, the breathing ultrasonic tumbling means improved the marinating efficiency and characteristics of marinated chicken breast.

Background Apoptosis is one of the pathways of programmed cell death (PCD), which leads to pathognomic cellular changes different from cellular necrosis. It includes the death receptor pathway and the mitochondrial pathway, both of which involve many key proteins abnormally expressed in apoptosis-related diseases, such as cancer. The majority of anti-cancer natural products promote apoptosis to induce cancer cell death. In this review, we aim to survey the current knowledge on key apoptotic proteins and some representative natural products that can induce cancer cell apoptosis by regulating these proteins. Method We reviewed the recent relative literatures using a structured search of bibliographic databases, and the keywords, such as natural products, cancer therapy, and apoptosis pathway, were used for inclusion/exclusion criteria. Results One hundred and seventy-one papers are included in this review. Numerous natural products have been reported to induce cell apoptosis by regulating the expression of key apoptotic proteins, leading to a variety of antitumor effects. This review identifies the major apoptotic proteins and elaborates the interaction between the apoptotic proteins and various natural anti-cancer products. Conclusion This review provides substantial evidences of apoptosis pathways in cancer cells and the apoptotic proteins modulated by active natural products, which may help to gain a comprehensive understanding for the development of natural drugs for better cancer treatment.

Cocktail treatment has become an effective multidrug medication therapy for many diseases, because of the additive or synergistic effect of each medicine and relief from adverse effects of drugs. Nanotechnology offers an unparalleled opportunity for co-delivery strategies with the ability to simultaneously release various drugs and controllably unify the pharmacokinetics. In this work, we formulated a cocktail composed of hydrogen sulfide-releasing aspirin (HS-ASP) and paclitaxel (PTX) in a single delivery system, which is fabricated by a biodegradable block copolymer (i.e., methoxy poly(ethylene glycol)–polycaprolactone). The resulting drug cocktail-loaded nanoparticles possess small and narrow size distribution (∼44 nm), high dual-drug encapsulation efficiency, pH-sensitivity and simultaneous drug release capability. The co-delivery of HS-ASP and PTX has significantly decreased the IC50 value of PTX on LL/2 cells by 17.7-fold compared with single free PTX and by 5.4-fold compared with PTX NPs. Meanwhile, its cellular uptake is improved by 2.67-fold compared with free HS-ASP/FITC-PTX, and it enhanced the cellular apoptosis (53.62%) as well as the cell cycle blocking at G2/M phase (47.9%) relative to other formulations. Confocal laser scanning results show that HS-ASP inhibited the mitosis of LL/2 cells, thereby sensitizing the cells to the tubulin disruption effect, which is a major apoptosis mechanism of PTX. Overall, such a combinational and controlled release strategy is expected to hold great potential for clinical use in cancer therapy.

Acute myeloid leukemia (AML) is a malignant disease characterized by abnormal growth and differentiation of hematopoietic stem cells. Although the pathogenesis has not been fully elucidated, many specific gene mutations have been found in AML. Fms-like tyrosine kinase 3 (FLT3) is recognized as a drug target for the treatment of AML, and the activation mutations of FLT3 were found in about 30% of AML patients. Targeted inhibition of FLT3 receptor tyrosine kinase has shown promising results in the treatment of FLT3 mutation AML. Unfortunately, the therapeutic effects of FLT3 tyrosine kinase inhibitors used as AML monotherapy are usually accompanied by the high risk of resistance development within a few months after treatment. FLT3 dual inhibitors were generated with the co-inhibition of FLT3 and another target, such as CDK4, JAK2, MEK, Mer, Pim, etc., to solve the problems mentioned above. As a result, the therapeutic effect of the drug is significantly improved, while the toxic and side effects are reduced. Besides, the life quality of AML patients with FLT3 mutation has been effectively improved. In this paper, we reviewed the studies of dual FLT3 inhibitors that have been discovered in recent years for the treatment of AML.

The systematic effects of temperatures and phosphates (single and compound forms) on gelling characteristics of myofibrillar proteins (MPs) extracted from chicken breast were investigated by texture analysis, Fourier-transform infrared spectroscopy, Raman spectroscopy, low-field nuclear magnetic resonance (NMR), scanning electron microscopy, and rheology. Heating to 60 °C and 80 °C induced the formation of an elastic and hard MP gel, and meanwhile compound phosphate (CP) enhanced gel elasticity and hardness. At 80 °C, the maximum elasticity and hardness of MP gels were determined as 0.81 ± 0.01 and 0.86 ± 0.02 N respectively. Compared to high temperature (100 and 120 °C) groups, the relative composition percentage of immobilized water reached a higher level for low temperature (60 and 80 °C) groups, determined as 95.15 ± 1.07% and 93.40 ± 1.02% respectively, indicating a better water-holding capacity. Raman and low field NMR analysis showed that low temperatures determined the affinity between moisture and MPs, while phosphates may help to protect gels from destruction caused by high temperatures. Hexametaphosphate and pyrophosphate as the composition of CP were liable to produce a desirable MP cross-linking network compared to tripolyphosphate. In addition, CP could strengthen the rheological viscoelasticity of MP gels formed at 80 °C.

The main objective of this paper is to investigate the pharmacokinetics of NM394 (an active metabolite of prulifloxacin) and evaluate the dose relationship and accumulation characteristics after single and multiple doses of prulifloxacin. Thirty healthy volunteers were given 132 mg, 264 mg, and 528 mg of prulifloxacin capsules in a randomized test corresponding to low, medium and high groups for single dose trial. With one-week washout period, 264 mg of prulifloxacin capsules were given to eight volunteers of the medium group for multiple doses trial. The concentration of NM394 in serum was determined by a sensitive HPLC method and its pharmacokinetic parameters were analyzed by DAS2.0.1 and evaluated by SPSS statistic software (version 13.0). Various parameters were determined. Numerical experiments show that the pharmacokinetic parameters of NM394 displayed first order linear pharmacokinetic character. There are no big differences in pharmacokinetic characteristics of NM394 between single and multiple doses. Almost no significant accumulation of drugs is observed after multiple doses of 264 mg per day for 7 d and chronopharmacokinetics were first observed.

This paper analyzes the existing algorithms of coverage of WSN, then proposes an algorithm of coverage of network base on the probability sensing model. First, the algorithm judges whether exists a sponsor set of the node i where node i is any node in the monitoring area. If the sponsor set is not existed, the node must keep working; else the algorithm executes the next steps. Determine whether the node would go to sleep taking into the probability of networks. The simulation results show that the agreement reduces the number of working nodes, extends the network's life cycle effectively, and achieve the desired network coverage.

The method was established to determine the level of isosorbide-5-nitrate in human plasma by reversed-phase high performance liquid chromatography (RP-HPLC). The sample preparation was carried by alkalizing the plasma sample followed by extraction with dichloromethane. The HPLC analysis was performed under the conditions as follows: a mixture of an aqueous buffer (pH adjusted to 7.8 by 0. 03 mol/L ammonia water) and acetonitrile (80: 20, v/v) as mobile phase, paracetamol as the internal standard, and the detection at 230 nm. The linear range was 20 - 1 000 microg/L using the ratio of peak areas; the detection limit was 12 microg/L; the average recovery was (97.11 +/- 2.45)% - (104.34 +/- 2.17)%, the intra-day relative standard deviations (RSDs) were less than 2.52%, and inter-day RSDs were less than 5.21%.