Thirteen novel (E)-alpha-(methoxyimino)benzeneacetate derivatives, the analogues of strobilurins, which contain two pharmacophoric substructures of the methyl (E)-methoxyiminoacetate moiety and 1,3,5-substituted pyrazole ring, were stereoselectively synthesized. It was found that the coupling reaction could give stereoselectively (E:Z ca. 14:1) the key intermediate material (E)-methyl 2-(hydroxyimino)-2-o-tolyl acetate (2). An X-ray crystallographic structure determination was carried out in a representative product. The preliminary bioassays indicated that all of the compounds 1 showed potent fungicidal activity against Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Physalospora piricola, and Bipolaris mayclis.

Click-through rate (CTR) prediction is a critical task in online advertising systems. A large body of research considers each ad independently, but ignores its relationship to other ads that may impact the CTR. In this paper, we investigate various types of auxiliary ads for improving the CTR prediction of the target ad. In particular, we explore auxiliary ads from two viewpoints: one is from the spatial domain, where we consider the contextual ads shown above the target ad on the same page; the other is from the temporal domain, where we consider historically clicked and unclicked ads of the user. The intuitions are that ads shown together may influence each other, clicked ads reflect a user's preferences, and unclicked ads may indicate what a user dislikes to certain extent. In order to effectively utilize these auxiliary data, we propose the Deep Spatio-Temporal neural Networks (DSTNs) for CTR prediction. Our model is able to learn the interactions between each type of auxiliary data and the target ad, to emphasize more important hidden information, and to fuse heterogeneous data in a unified framework. Offline experiments on one public dataset and two industrial datasets show that DSTNs outperform several state-of-the-art methods for CTR prediction. We have deployed the best-performing DSTN in Shenma Search, which is the second largest search engine in China. The A/B test results show that the online CTR is also significantly improved compared to our last serving model.

Objective To explore whether bone turnover biomarkers (BTMs), i.e., C-terminal telopeptide of type I collagen (CTX) and procollagen type I aminoterminal propeptide (PINP), are associated with fracture. Methods We searched electronic database including PubMed, Embase and Cochrane Library, and the reference lists of relevant articles published from inception to August 22, 2018. An updated meta-analysis was performed to assess the prediction value of CTX and PINP in fracture. Results Nine articles met our inclusion criteria and were included in the meta-analysis. The crude and adjusted effect size between PINP and fracture were extracted from two and five studies, respectively. PINP was not associated with fracture incidence without adjusting covariates (crude GR, 1.03; 95% CI, 0.91–1.17). After adjusting for potential confounders, PINP demonstrated a significant positive association with fracture (adjusted GR, 1.28; 95% CI, 1.15–1.42). In the subgroup analysis of studies after adjusting covariates, there were significant associations in women. Both the crude (1.16, 95%CI, 1.04–1.20) and adjusted GR (1.20, 95%CI, 1.05–1.37) shown positive relationships between CTX and fracture, which were extracted from four and six studies, separately. The sensitivity analysis confirmed the stability of the results. In the subgroup analysis of studies after adjusting covariates, there were significant associations in the subgroups of elderly, female, and hip fracture patients. Conclusions Our results indicate a statistically significant but modest association between BTMs (s-PINP or s-CTX) and future fracture risk after adjusting for BMD and clinical risk factors. The causal relationship between the two clinical conditions requires future validation with more standardized studies. Registration number CRD42018107879 Electronic supplementary material The online version of this article (10.1186/s13018-019-1100-6) contains supplementary material, which is available to authorized users.

Emodin (EMD) is an anthraquinone derivative extracted from the root and rhizome of Rheum palmatum L. which exhibits a range of activities, including anti-bacterial, antitumor, diuretic and vasorelaxant effects. The ability to inhibit metastasis and angiogenesis was shown in previous pharmacological studies, but clear information to address EMD affecting angiogenesis and metastasis in human breast cancer is still lacking. In the present study, we evaluated a possible role for EMD in angiogenesis and metastasis induced by breast cancer cells. It was revealed here that EMD attenuated tumor cell-induced metastasis and angiogenesis both in vitro and in vivo. Furthermore, it was found that these inhibitory effects were caused by MMPs and VEGFR-2 inhibition in metastatic breast cancer cells and endothelial cells, respectively. Western blot analysis showed reduction of Runx2 activation in the EMD-treated cells. ELISA based Runx2 transcription factor assay showed that the interaction between Runx2 and target sequences was inhibited by EMD. Our findings suggested that the inhibitory effects of EMD on tumor-induced metastasis and angiogenesis were caused by MMPs and VEGFR-2 inhibition, which may be associated with the downregulation of Runx2 transcriptional activity.

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Abstract. Fucoidan is a type of sulfated polysaccharide isolated from seaweed. The present study used ovariectomized Sprague-Dawley rats, which were treated with fucoidan. The effects of fucoidan on bone metabolism, density and microarchitecture were assessed using micro-computed tomography (CT), histomorphometric analysis, biochemical markers of bone metabolism (Serum procollagen type I N propeptide and C-terminal telopeptide-1) and tests of mechanical competence of the femur. In addition, the effects of low-molecular weight fucoidan (LMWF) on in vitro cultured osteoclasts were examined, in order to determine the mechanisms underlying LMWF-induced osteoclastic inhibition. In ovariectomized rats, LMWF increased femoral bone density. Micro-CT scan also revealed that LMWF prevented microarchitectural deterioration and histomorphometric analysis determined that LMWF increased trabecular bone number and reduced the surface of bone resorption. In addition, LMWF reduced the high bone turnover rate, and improved the mechanical properties of the femur in ovariectomized rats. In vitro experiments revealed that LMWF inhibited the receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor-induced differentiation of RAW264.7 cells into tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and reduced the bone resorption surface of the osteoclasts. Reverse transcription-quantitative polymerase chain reaction demonstrated that LMWF inhibited mRNA expression of TRAP, matrix metallopeptidase-9, nuclear activator of activated T-cells 1, and osteoclast-associated immunoglobulin-like receptor, which are components of the signaling pathway for osteoclast differentiation. LMWF had no effect on RANK mRNA expression. In conclusion, the present study confirmed that LMWF inhibited osteoclast differentiation and bone resorption, and may be a potential treatment for osteoporosis in ovariectomized rats.

At present, the increasing trend of medical disputes has become a serious problem in the work of medical institutions, and directly affects the social stability and orderly development of the institutions. We searched the literature on medical disputes and crisis management in China and Australia within PubMed (2010-2019), China Knowledge Network (CNKI, 2010-2019), and Wanfang Data Knowledge Service Platform (2010-2019). There are several drawbacks in the management of hospital medical disputes in China: 1) the knowledge of crisis is unilateral and not systematic; 2) there are too much stereotype thoughts in crisis management; 3) the crisis attribution is too simple; the crisis impact assessment is insufficient. It is worth learning from Australia’s system, including the legal system, relevant non-governmental organizations, and doctor-patient communication. In view of the malpractice existing in China's medical dispute management, Australia's legal system for handling disputes, doctor-patient communication and other aspects are worthy of our reference. In particular, the construction of third-party supervision and mediation institutions and the prevention of doctor-patient disputes should be optimized.