The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence (Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box

Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis

Background and AimsPatients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism.MethodsChanges in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry.ResultsThe proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway.ConclusionsB cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines

Material Cost Advantage and Development of Small Printing Industry: Based on the Case of Xinhua Phenomenon

Based on the survey of small printing industry in Beijing, Xi’an and Zhengzhou, this paper analyses the development of Xinhua Phenomenon as one case of Rural Migration Entrepreneurship and find that group culture is an important factor to promote the development of Xinhua Phenomenon. Through the econometric analysis, the research finds that Xinhua printing group offers better services than non-Xinhua group to gain the material cost advantage and promote the development of Xinhua Phenomenon

Material Cost Advantage and Development of Small Printing Industry: Based on the Case of Xinhua Phenomenon

Based on the survey of small printing industry in Beijing, Xi’an and Zhengzhou, this paper analyses the development of Xinhua Phenomenon as one case of Rural Migration Entrepreneurship and find that group culture is an important factor to promote the development of Xinhua Phenomenon. Through the econometric analysis, the research finds that Xinhua printing group offers better services than non-Xinhua group to gain the material cost advantage and promote the development of Xinhua Phenomenon

Investigating the “One Farm Household, Two Production systems” in Rural China: The Case of Vegetable and Fruit Farmers

Food safety receives an escalating attention since the 2008 milk scandal in China. Chinese government faces a great challenge to safeguard the safety of food supply chain due to the significant fermentation of producers and weak institutional resources to monitor and enforce food safety standards. Chinese farm households often practice two separate production systems for the same crop for the market and self-consumption separately and, thus the so called “One Farm Household, Two Production Systems” (OFH-TPS) gain the popularity in the recent years. This study provides both a theoretical framework to model the OFH-TPS decision and an empirical analysis to identify factors affecting the OFH-TPS decision using household survey data. We find that information asymmetry of product quality and measures to reduce the asymmetry such as product inspections and certifications play an important role in the OFH-TPS decision. In particular, product inspections conducted by industry associations, agricultural cooperatives, or farmer themselves curb the adoption of the TFH-TPS, whereas government inspection has no statistically significant effect. Farmers who sell green foods are less likely but organic farmers are more likely to adopt the OFH-TPS, which echoes the expectation based on the theoretical model. We also find that training of pesticide applications reduce the adoption of the OFH-TPS, but the perceived adverse effects of pesticide applications have no statistical effects. Furthermore, farmers who uses highly toxic and banned pesticides and/or who perceive poor food safety of the local markets are more likely to adopt the OFH-TPS. This study provides rich policy implications. First, calling the engagement of private sector to safeguard food safety and improving the efficacy of government inspection are critical to improve food safety. Second, education on pesticide applications is critical, especially among retailers of pesticides

Problems and Suggestions on the Blacklist Policy of Food Safety

In order to increase the illegal credit cost and social cost of companies, blacklist policies for food factories came into being. According to international experiences, blacklist policy, as a systematic project, is compatible with law and regulations, social credit system, and social observation movement. This paper reviewed the international experiences in blacklist policies and analyzed the existing problems in blacklist policies. In addition, three constructive suggestions were proposed in this paper

Background, Current Situation and International Experience of Food and Drug Police System

Establishing the food and drug police system is particularly important for effectively striking at illegal and criminal activities related to food and drug. This study firstly revealed actual background of establishment of the food and drug police system. Taking the high profile gutter oil case in 2013 as an example, it analyzed advantages of the police in food safety supervision. Then, it summarized some pilot projects in China and analyzed characteristics of the Office of Criminal Investigations of FDA. Finally, it came up with problems and recommendations for improving food and drug police system

Targeting the <i>MIR34C-5p</i>-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

<p>Pirarubicin (THP) is a newer generation anthracycline anticancer drug. In the clinic, THP and THP-based combination therapies have been demonstrated to be effective against various tumors without severe side effects. However, previous clinical studies have shown that most patients with cervical cancer are not sensitive to THP treatment, and the associated mechanisms are not clear. Consistent with the clinical study, we confirmed that cervical cancer cells were resistant to THP in vitro and in vivo. Our data demonstrated that THP induced a protective macroautophagy/autophagy response in cervical cancer cells, and suppression of this autophagy dramatically enhanced the cytotoxicity of THP. By scanning the mRNA level change of autophagy-related genes, we found that the upregulation of <i>ATG4B</i> (autophagy-related 4B cysteine peptidase) plays an important role in THP-induced autophagy. Moreover, THP increased the mRNA level of <i>ATG4B</i> in cervical cancer cells by promoting mRNA stability without influencing its transcription. Furthermore, THP triggered a downregulation of <i>MIR34C-5p</i>, which was associated with the upregulation of <i>ATG4B</i> and autophagy induction. Overexpression of <i>MIR34C-5p</i> significantly decreased the level of ATG4B and attenuated autophagy, accompanied by enhanced cell death and apoptosis in THP-treated cervical cancer cells. These results for the first time reveal the presence of a <i>MIR34C-5p</i>-ATG4B-autophagy signaling axis in THP-treated cervical cancer cells in vitro and in vivo, and the axis, at least partially, accounts for the THP nonsensitivity in cervical cancer patients. This study may provide a new insight for improving the chemotherapeutic effect of THP, which may be beneficial to the further clinical application of THP in cervical cancer treatment.</p