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Background Kawasaki Disease (KD), which is mainly characterized by systemic small and medium vasculitis in children, can lead to coronary artery lesions (CALs). Our previous study identified that STAT3 signaling plays essential roles during the acute phase of KD patients. However, whether its interacted protein MDM2 (Murine double minute 2), which functions as an E3 ligase is likewise involved in KD pathogenesis still unknown and remains to be investigated. Methods The role of MDM2 was investigated using the whole-blood samples from KD patients with CALs before and after IVIG treatment. The plasma and peripheral blood mononuclear cells were respectively isolated and collected. Meanwhile, a Candida albicans cell wall extracts (CAWS)‑induced KD mouse model was used to analyze the in vivo functions of MDM2. Real-time PCR, western blotting, and enzyme-linked immunosorbent methods were used respectively in the HCAECs or other cells to investigate the molecular mechanism of MDM2 involved in KD. Results MDM2 levels were downregulated, and STAT3 and VEGFA levels were upregulated in clinical blood samples from KD patients with CAL in the acute stage and in the mouse model. In the mouse model and HCAECs, MDM2 co-located with STAT3 . In vitro, the endogenous STAT3 protein level in HCAECs was upregulated after MDM2knockdown. Overexpression of MDM2 increased STAT3 ubiquitination and endogenous STAT3 and VEGFA levels decreased significantly. Additionally, the E3 ubiquitin ligase MDM2 can target its endogenous substrate STAT3 for ubiquitination. Conclusions Decreased MDM2 levels can reduce STAT3 ubiquitination, leading to STAT3 activation and the induction of VEGFA transcription, which is involved in the vascular endothelial inflammatory injury process of KD.

Hepatocellular carcinoma (HCC) remains challenging due to the lack of efficient therapy. Promoting degradation of certain cancer drivers has become an innovative therapy. The nuclear transcription factor sine oculis homeobox 1 (SIX1) is a key driver for the progression of HCC. Here, we explored the molecular mechanisms of ubiquitination of SIX1 and whether targeting SIX1 degradation might represent a potential strategy for HCC therapy. Through detecting the ubiquitination level of SIX1 in clinical HCC tissues and analyzing TCGA and GEPIA databases, we found that ubiquitin specific peptidase 1 (USP1), a deubiquitinating enzyme, contributed to the lower ubiquitination and high protein level of SIX1 in HCC tissues. In HepG2 and Hep3B cells, activation of EGFR-AKT signaling pathway promoted the expression of USP1 and the stability of its substrates, including SIX1 and ribosomal protein S16 (RPS16). In contrast, suppression of EGFR with gefitinib or knockdown of USP1 restrained EGF-elevated levels of SIX1 and RPS16. We further revealed that SNS-023 (formerly known as BMS-387032) induced degradation of SIX1 and RPS16, whereas this process was reversed by reactivation of EGFR-AKT pathway or overexpression of USP1. Consequently, inactivation of the EGFR-AKT-USP1 axis with SNS-032 led to cell cycle arrest, apoptosis, and suppression of cell proliferation and migration in HCC. Moreover, we showed that sorafenib combined with SNS-032 or gefitinib synergistically inhibited the growth of Hep3B xenografts in vivo. Overall, we identify that both SIX1 and RPS16 are crucial substrates for the EGFR-AKT-USP1 axis-driven growth of HCC, suggesting a potential anti-HCC strategy from a novel perspective.

In this article, sensitivity analysis was performed using bidirectional single method with shell-and-tube heat exchanger as the basis and the entropy production in the working process of heat exchanger as target, to explore the optimizing direction for heat exchangers with the objective to reduce entropy production. First, the differential element analysis method was used in a case study of the entropy production of the heat transfer process - including the three heat transfer processes of convective heat exchange inside and outside the pipes and heat conduction across the pipe wall and the flow process - the fluid flowing process inside and outside the pipes, and the typical process parameter - dimensionless inlet heat exchange temperature difference, operation parameter - fluid flow rate inside the pipe and structural parameters - the heat transfer pipe inner diameter and length were used as characteristic parameters, to obtain the sensitivity coefficients under the conditions of the example, being respectively 0.95, 0.3, 0.3 and 0.38. The study in this article can provide some support to the energy efficiency evaluation of heat exchangers.

Entropy analysis method was adopted to analyze and optimize a jacketed pipes-type heat pipe steam generator. In the entropy analysis process, the entropy production resulted from the total temperature difference across the heat exchanger, the entropy production from main heat transfer element – heat pipes and the entropy production caused by the pressure drop due to working media flow on cold and hot sides were taken into consideration. In the calculation, the entropy production in all parts of the heat exchanger was analyzed row by row in a discrete pattern, except for the entropy production due to pressure drop on flue gas side. Analysis results show that for the heat exchanger in this case, the proportions of entropy production in the above-mentioned three parts are respectively 74.79%, 21.75% and 3.46%. On this basis, the article also made optimizing analysis with the cold and hot source temperature, heat pipe length and No. of heat pipe rows as parameters, to provide theoretical basis for further improving the energy efficiency of heat exchangers.

Objective: To investigate the new approach of two-step resection of primary massive liver cancer (PLC). Methods: 10 cases of primary massive liver cancer were treated with two-step resection after marked shrinkage of the tumor by integrating radiotherapy from June 1987 to December 1997. Step one: modified radiotherapy, including radiation of the whole liver by moving split fields and diminution field radiation, plus Traditional Chinese Medicine (TCM) of strengthening the spleen and regulating qi. The total dosage of the radiation was 50–60 Gy. Step two: 3–4 weeks after radiation, resecting the tumor. Results: the diameters of the masses shrinked from 11–15 cm to 6–8 cm after preoperative radiation and TCM. CT showed focus scan one hepatic portal lymph node (2 cm) and a satellite lesions around the tumor (1–3 cm) disappeared after treatment. In one AFP negative case survival cancerous cells was found. The operation did not cause death or serious postoperative complications.