Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

A Color-Reaction-Based Biochip Detection Assay for RIF and INH Resistance of Clinical Mycobacterial Specimens

( Wen Fei Xue ),( Jing Fu Peng ),( Xiao Li Yu ),( Shu Lin Zhang ),( Boping Zhou ),( Dan Qing Jiang ),( Jian Bo Chen ),( Bing Bing Ding ),( Bin Zhu ),( Yao Li ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.1

The widespread occurrence of drug-resistant Mycobacterium tuberculosis places importance on the detection of TB (tuberculosis) drug susceptibility. Conventional drug susceptibility testing (DST) is a lengthy process. We developed a rapid enzymatic color-reaction-based biochip assay. The process included asymmetric multiplex PCR/templex PCR, biochip hybridization, and an enzymatic color reaction, with specific software for data operating. Templex PCR (tem- PCR) was applied to avoid interference between different primers in conventional multiplex- PCR. We applied this assay to 276 clinical specimens (including 27 sputum, 4 alveolar lavage fluid, 2 pleural effusion, and 243 culture isolate specimens; 40 of the 276 were non-tuberculosis mycobacteria specimens and 236 were M. tuberculosis specimens). The testing process took 4.5 h. A sensitivity of 50 copies per PCR was achieved, while the sensitivity was 500 copies per PCR when tem-PCR was used. Allele sequences could be detected in mixed samples at aproportion of 10%. Detection results showed a concordance rate of 97.46% (230/236) in rifampicin resistance detection (sensitivity 95.40%, specificity 98.66%) and 96.19% (227/236) in isoniazid (sensitivity 93.59%, specificity 97.47%) detection with those of DST assay. Concordance rates of testing results for sputum, alveolar lavage fluid, and pleural effusion specimens were 100%. The assay provides a potential choice for TB diagnosis and treatment.

Adaptive Controller Design for Switched Stochastic Nonlinear Systems Subject to Unknown Dead-zone Input via New Type of Network Approach

Wen-Jing He,Shan-Liang Zhu,Na Li,Yu-Qun Han 제어·로봇·시스템학회 2023 International Journal of Control, Automation, and Vol.21 No.2

In this article, adaptive tracking control for a class of switched stochastic nonlinear systems subject to unknown dead-zone input using multi-dimensional Taylor network (MTN) is studied. Firstly, the characteristic function is introduced to convert the nonlinearity of the input dead-zone into a linear model. Secondly, a novel adaptive control method based on the backstepping recursive design technique is proposed, which combines MTN and common Lyapunov functions (CLFs). Significantly, a method to reduce the computational complexity of switched stochastic nonlinear systems is proposed for the first time, which introduces characteristic function and MTN technology. The result makes clear that the proposed controller can ensure all signals of the closed-loop system are bounded in probability, and the output of the system can track reference signal well. Finally, the effectiveness of proposed control method is verified by simulation results.

2-Hydroxydiplopterol, A New Cytotoxic Pentacyclic Triterpenoid from the Halotolerant Fungus Aspergillus variecolor B-17

Wen-Liang Wang,Pei-Pei Liu,Ya-Peng Zhang,Jing Li,Hong-Wen Tao,Qian-Qun Gu,Wei-Ming Zhu 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.9

A new hopane type pentacyclic triterpenoid, 2-hydroxydiplopterol (1) has been isolated from the metabolites produced by the halotolerant fungal strain Aspergillus variecolor B-17. The structure of 1 was determined by spectroscopic methods and single crystal X-Ray diffraction analysis. 2-Hydroxydiplopterol (1) exhibited cytotoxicity against K562 cells with an IC50 value of 22 μM.

Improvement of a Fingerprint-Based Remote User Authentication Scheme

Jing Xu,Wen-Tao Zhu,Deng-Guo Feng 보안공학연구지원센터 2008 International Journal of Security and Its Applicat Vol.2 No.3

Password authentication has been adopted as one of the most commonly used solutions in network environments to protect resources from unauthorized access. Recently, Khan et al. proposed an efficient fingerprint-based remote user authentication scheme with smart cards [15], in which a password/verification table is not required on the remote server, and users are allowed to choose and update their passwords freely. In this paper, we show that their scheme is vulnerable to the parallel session attack. Furthermore, their scheme is susceptible to the impersonation attack provided that the information stored in the smart card is disclosed by an adversary. We also propose an improved scheme which is immune to the presented attacks.

Aluminum speciation in drinking water distribution system: A case study in northeastern China

Wen-Dong Wang,Hong-Wei Yang,Jing Jiang,Zhen-Zhen Ding,Wan-Peng Zhu 한국화학공학회 2011 Korean Journal of Chemical Engineering Vol.28 No.5

This study aimed to investigate the variation of aluminum species in a drinking water distribution system in a city in northeastern China. The aluminum species were determined by fluorometric methods. Results showed that suspended aluminum (Sus-Al) was the major species in the drinking water supplied by plant B and accounted for about 42% of the total aluminum (Tol-Al). The concentrations of Sus-Al and Tol-Al could be controlled effectively by introducing reservoir water. In the water source switching process, the water quality variation led to the suddenly release of Sus-Al, especially in a cast iron pipeline that had been in service for more than 30 years, but the soluble aluminum varied little. In the plant A service areas, the average concentrations of the inorganic monomeric aluminum (IM-Al),monomeric aluminum (Mon-Al), and soluble aluminum (Sol-Al) were 0.008 mg L^−1, 0.03 mg L^−1, and 0.04 mg L^−1,respectively, and their concentrations in the plant B service areas were higher. The pH and fluoride were the major parameters affecting the soluble aluminum speciation. With a solution pH of 6.5-7.5 and fluoride below 0.3 mg L^−1,the Sol-Al could be controlled within 0.1 mg L^−1. Water quality regulation and terminal filtration were suggested for residual aluminum control.

LETTER TO THE EDITOR : One Mutation of the ED1 Gene in a Chinese Han Family with X-Linked Hypohidrotic Ectodermal Dysplasia

( Jing Wang ),( Wei Wei Ha ),( Wen Wang ),( Hua Yang Tang ),( Xian Fa Tang ),( Xian Dong Zheng ),( Jun Zhu ),( Xian Yong Yin ),( Sen Yang ),( Xue Jun Zhang ) 대한피부과학회 2014 Annals of Dermatology Vol.26 No.1

Predictive Value of Molecular Subtyping for Locoregional Recurrence in Early-Stage Breast Cancer with N1 without Postmastectomy Radiotherapy

Ge Wen,Jin-Shan Zhang,Yu-Jing Zhang,Yu-Jia Zhu,Xiao-Bo Huang,Xunxing Guan 한국유방암학회 2016 Journal of breast cancer Vol.19 No.2

Purpose: This study was designed to investigate the relationship between molecular subtype and locoregional recurrence (LRR) in patients with early-stage breast cancer with 1–3 positive axillary lymph nodes (ALNs) and improve the individualized indications for postmastectomy radiotherapy (PMRT). Methods: The records of 701 patients with pT1-2N1M0 breast cancer who did not undergo PMRT were retrospectively analyzed. Tumors were subclassified as follows: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and basal-like subtypes. Multivariate Cox analysis was used to determine the risk of LRR associated with the different subtypes and to adjust for clinicopathologic factors. Results: Luminal A, luminal B, HER2- enriched, and basal-like subtypes accounted for 51.2%, 28.0%, 8.1%, and 12.7% of cases, respectively. The median follow-up duration was 67 months (range, 9–156 months). Univariate analysis revealed that, compared with the luminal A subtype, the HER2-enriched and basal-like subtypes were associated with significantly higher 5-year LRR rates (5.6% vs. 21.6% and vs.15.7% respectively; p=0.002 each), lower 5-year LRR-free survival (LRFS) rates (90.6% vs. 73.8% and 78.5%, respectively; p=0.001 each), and poorer 5-year breast cancer-specific survival (BCSS) rates (93.7% vs. 82.2% [p=0.002] and 84.9% [p=0.001], respectively). Multivariate analysis revealed that the HER2-enriched and basal-like subtypes, age ≤35 years, a medial tumor, and pT2 stage were poor prognostic factors for LRR and LRFS; furthermore, 2 to 3 positive ALNs represented an independent prognostic factor affecting LRR. The 10-year LRR rates of patients with 0, 1, 2, 3, and 4 risk factors were 1.0%, 6.9%, 14.3%, 30.4%, and 54.3%, respectively (p<0.001); the 10-year BCSS rates were 86.6%, 88.5%, 84.4%, 79.7%, and 38.8%, respectively (p<0.001). Conclusion: Molecular subtyping allows for individualized evaluation of LRR risk in patients with pT1-2N1M0 breast cancer. PMRT should be recommended for patients with ≥3 LRR risk factors.

A Comparative Study of Camouflage Printing Color Matching Based on Monitor and Paper Card

Yu-wen Wang,Qing-zhu Yi,Yi Ding,Guang-xin Wu,Jing-bin Zhang,Ni Wang 한국섬유공학회 2021 Fibers and polymers Vol.22 No.4

To improve the accuracy of color reproduction for camouflage printing, a new color matching method, namedmonitor-paper-fabric, was proposed by importing color management into textiles, which matched the printing pastesaccording to the color of the paper card printed by the ink-jet printer after color management. Not like the traditional colormatching method, it matched the printing pastes according to the color from computer monitor after color correction. Twocolor matching methods were analyzed by comparing the color difference. It was found that the “monitor-paper-fabric” colormatching method could be considered as a convenient and feasible color matching method. Most color differences betweenthe monitor and the fabric in the camouflage pattern were reduced to lower than 4, except for color blocks 5 and 6. Inaddition, the color differences of six color blocks between the paper and the fabric were all less than 3.5, and were lower thanthose between the monitor and the fabric. The color consistency between the paper and the fabric was better than thatbetween the monitor and the fabric.

A Novel Hybrid Optimization Algorithm Based on GA and ACO for Solving Complex Problem

Bin Gao,Jing-Hua Zhu,Wen-chang Lang 보안공학연구지원센터 2015 International Journal of Multimedia and Ubiquitous Vol.10 No.8

In allusion to the deficiencies of the ant colony optimization algorithm for solving the complex problem, the genetic algorithm is introduced into the ant colony optimization algorithm in order to propose a novel hybrid optimization (NHGACO) algorithm in this paper. In the NHGACO algorithm, the genetic algorithm is used to update the global optimal solution and the ant colony optimization algorithm is used to dynamically balance the global search ability and local search ability in order to improve the convergence speed. Finally, some complex benchmark functions are selected to prove the validity of the proposed NHGACO algorithm. The experiment results show that the proposed NHGACO algorithm can obtain the global optimal solution and avoid the phenomena of the stagnation, and take on the fast convergence and the better robustness.