Hippo dictates signaling for cellular homeostasis and immune defense in Crassostrea hongkongensis hemocytes

IntroductionThe Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution.MethodThe complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes.ResultThe results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis.DiscussionThis study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution

Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study

Contextualizing legal norms: a multi-dimensional view of the 2014 legal capital reform in China

This paper intends to shed light on the contentious theme of the reception of legal transplantation in the host environment, by examining the 2014 legislative reform of legal capital in China, which at least on paper imitates the enabling settings of US Revised Model Business Corporation Act (RMBCA). The paper looks at the interconnections between national-specific contextual elements, the resultant complexities, and the spillover effects of transplanted configurations in the unique Chinese socio-cultural setting, implicating the discrepancy between the ‘law in practice’ and the borrowed words ‘on the books’, and suggesting the importance of gaining a holistic understanding of ‘law’ involving the legal traditions in both the donor country and the recipient nation

How to Improve the Business Achievement of Seven Stars Hotel in Nanchang

Nowadays in the hotel industry there exists a fierce market competition by the rapid development of China’s economy. China’s hotel industry has used a planned economy hostel mode in the past, however, the mode has changed into a star formation hotel. There are more and more luxurious and comfortable four or five star standard hotels than before. This kind of hotel is a suitable selection for the business people, tourists and any other groups. Seven Stars Hotel is a four- star standard business hotel which will be the case hotel in the thesis. Nanchang Seven Stars Hotel is a four-star standard business hotel which was invested by Glorious Construction Engineering Company of Japan and Jiang Xi Botai Group Company. Under the situation in China’s economy and China’s hotel industry, Seven Stars Hotel needs to improve the business achievement and to get an effective strategy to keep A steady position in the market. The starting part of the thesis work introduces the general introduction and background information. In the theoretical part, the internal management part includes the knowledge on human resource management and supply chain management. The external management part includes marketing management and competitive advantage. In empirical part the hotel’s strengths, weaknesses, opportunities and threats are introduced by using the information from interviews and the data collected about the hotel. The section includes interviews with the manager of the hotel, the human resource department manager of the hotel and the marketing department manager. The information from interviews include the general information, the advantages, the goals, the situation of employees, the promotion strategy of the hotel and also some annual reports. By using the information analysis, the hotel has been given some approaches of improving the business achievement. According to the whole analysis and research, the problems that exist have been defined with the internal part and external part. The marketing methods and marketing ability, the draining rate of the employees, the cost of hotel operation have to be considered. The core of the thesis work is that by making innovations and changes on the hotel’s management and so on to help Seven Star Hotel to improve the business achievement and keep steady in the market

How do family firms cope with economic crisis? : Case studies about Chinese family firms

Introduction:The current economic crisis started in 2007 warned many business pro-fessions how important it is to react to the crisis quickly and properly. Many studies have been conducted on family businesses about their special resources environment, succession, governance etc. There are barely literature has ever mentioned about how family business cope with economic crisis. Thus, the author conducted such a study on this topic to explore more in family business study.Purpose:To enhance the understanding of economic crisis management in fam-ily business, this thesis will analyze the actions of family firms during the economic crisis. This research aims to investigate how unique fam-ily firm resources influence the way they cope with the economic crisis.Method:A qualitative research has been conducted in this study. In-depth inter-views were conducted in two family business firms with the business owners and other high level position staff who have clear picture about the management during economic crisis. Tele-interview was adopted due to the distance limit.Conclusions:During economic crisis, family firms do not use layoff as a major means to cost down. They keep relative stable relationship with their employ-ees as well as other business partners. They seek financial and other help from the family members or in the family network rather than other external resources such as bank etc. The governance also con-cerns more on employee benefits

Impact of Molecular Modification on the Efficiency of Recombinant Baculovirus Vector Invasion to Mammalian Cells and Its Immunogenicity in Mice

The baculovirus display system (BDS), an excellent eukaryotic surface display technology that offers the advantages of safety, efficiency, and economy, is widely used in biomedicine. A previous study using rBacmid-Δgp64-ires-gp64 expressed in low copy numbers of the gp64 gene achieved high-efficiency expression and co-display of three fluorescent proteins (GFP, YFP, and mCherry). However, low expression of GP64 in recombinant baculoviruses also reduces the efficiency of recombinant baculovirus transduction into mammalian cells. In addition, the baculovirus promoter has no expression activity in mammalian cells and thus cannot meet the application requirements of baculoviral vectors for the BDS. Based on previous research, this study first determined the expression activity of promoters in insect Spodoptera frugiperda 9 cells and mammalian cells and successfully screened the very early promoter pie1 to mediate the co-expression of multiple genes. Second, utilizing the envelope display effect of the INVASIN and VSVG proteins, the efficiency of transduction of recombinant baculovirus particles into non-host cells was significantly improved. Finally, based on the above improvement, a recombinant baculovirus vector displaying four antigen proteins with high efficiency was constructed. Compared with traditional BDSs, the rBacmid-Δgp64 system exhibited increased display efficiency of the target protein by approximately 3-fold and induced an approximately 4-fold increase in the titer of serum antibodies to target antigens in Bal B/c mice. This study systematically explored the application of a new multi-gene co-display technology applicable to multi-vaccine research, and the results provide a foundation for the development of novel BDS technologies