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Renhui Huang,1,2,* Qi Shi,1,* Shutian Zhang,1,2 Hong Lin,1,2 Chengzhi Han,1,2 Xinyi Qian,1 Yijun Huang,1 Xiaorong Ren,1 Jiayuan Sun,3 Nana Feng,4 Chunmei Xia,1 Meng Shi5 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 4Department of Respiratory and Critical Medicine, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, People’s Republic of China; 5Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Affiliated with Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meng Shi, Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Affiliated with Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, People’s Republic of China, Tel +86 15921527577, Email huashan_heart@sina.cn Chunmei Xia, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 13917406439, Email cmxia@fudan.edu.cnPurpose: Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis of lung ischemia/reperfusion (I/R) injury. Cyclic GMP-AMP synthase (cGAS) is a cytosol dsDNA sensor, coupling with downstream stimulator of interferon genes (STING) located in the ER, which involves innate immune responses. The aim of our present study was to investigate the effects of cGAS on lung I/R injury via regulating ERS.Methods: We used Sprague-Dawley rats to make the lung I/R model by

Shutian Zhang,1,* Li Hu,2,* Chengzhi Han,1 Renhui Huang,1 Kokwin Ooi,1 Xinyi Qian,1 Xiaorong Ren,1 Dechang Chu,3 Haili Zhang,3 Dongshu Du,4 Chunmei Xia1 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200240, People’s Republic of China; 3College of Agriculture and Bioengineering, Heze University, Heze, 274000, People’s Republic of China; 4School of Life Science, Shanghai University, Shanghai, 200444, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunmei XiaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 54237612-805Email cmxia@fudan.edu.cnDongshu DuSchool of Life Science, Shanghai University, Shanghai, 200444, People’s Republic of ChinaEmail sdhzdds@163.comPurpose: Oxidative/nitrosative stress, neuroinflammation and their intimate interactions mediate sympathetic overactivation in hypertension. An immoderate inflammatory response is characterized not only by elevated proinflammatory cytokines (PICs) but by increases in mitochondrial dysfunction, reactive oxygen species (ROS), and nitric oxide (NO). Recent data pinpoint that both the phospholipid and lipid droplets (LDs) are potent modulators of microglia physiology.Methods: Stress rats underwent compound stressors for 15 days with PLIN2-siRNA or scrambled-siRNA (SC-siRNA) administrated into the rostral ventrolateral medulla (RVLM). Lipids were analyzed by mass spectroscopy-based quantitative lipidomics. The phenotypes and proliferation of microglia, LDs, in the RVLM of rats were detected; blood pressure (BP) and myocardial injury in rats were evaluated. The anti-oxidative/nitrosative stress effect of phosphatidylethanolamine (PE) was explo

Shutian Zhang,1,2,* Yufeng Yan,3,* Yongze Wang,1,2 Zhaodong Sun,1,2 Chengzhi Han,1,2 Xinyi Qian,1,2 Xiaorong Ren,1,2 Yi Feng,4 Jian Cai,5 Chunmei Xia1 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Clinical Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China; 3Experimental Teaching Center of Basic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 4Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China; 5Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200240, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunmei XiaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 54237612-805Email cmxia@fudan.edu.cnJian CaiDepartment of Neurology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200240, People’s Republic of ChinaEmail feele@sina.comPurpose: Glial activation and the disorders of cytokine secretion induced by endoplasmic reticulum stress (ERS) are crucial pathogenic processes in establishing ischemia/reperfusion (I/R) injury of the brain and spinal cord. This present study aimed to investigate the effects of mucous-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) on spinal cord ischemia/reperfusion (SCI/R) injury via regulating glial ERS.Methods: SCI/R was induced by thoracic aorta occlusion-reperfusion in rats. The MALT1-specific inhibitor MI-2 or human recombinant MALT1 protein (hrMALT1) was administrated for three consecutive days after the surgery. Immunofluorescent staining was

Sparse code multiple access (SCMA) is a promising multiplexing approach to achieve high system capacity. In this paper, we develop a novel iterative detection and decoding scheme for SCMA systems combined with Low-density Parity-check (LDPC) decoding. In particular, we decompose the output of the message passing algorithm (MPA) based SCMA multiuser detection into intrinsic part and prior part. Then we design a joint detection and decoding scheme which iteratively exchanges the intrinsic information between the detector and the decoder, yielding a satisfied performance gain. Moreover, the proposed scheme has almost the same complexity compared to the traditional receiver for LDPC-coded SCMA systems. As numerical results demonstrate, the proposed scheme has a substantial gain over the traditional SCMA receiver on AWGN channels and Rayleigh fading channels.

Sparse code multiple access (SCMA) is a novel non-orthogonal multiple access technique, which fully exploits the shaping gain of multi-dimensional codewords. However, the lack of simplified multiuser detection algorithm prevents further implementation due to the inherently high computation complexity. In this paper, general SCMA detector algorithms based on Sum-product algorithm are elaborated. Then two improved algorithms are proposed, which simplify the detection structure and curtail exponent operations quantitatively in logarithm domain. Furthermore, to analyze these detection algorithms fairly, we derive theoretical expression of the average mutual information (AMI) of SCMA (SCMA-AMI), and employ a statistical method to calculate SCMA-AMI based specific detection algorithm. Simulation results show that the performance is almost as well as the based message passing algorithm in terms of both BER and AMI while the complexity is significantly decreased, compared to the traditional Max-Log approximation method.

BACKGROUND: Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissue releases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Even though blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI) at 9 h time point, the later time points are not studied and the role of HMGB1 in APAP overdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyte regeneration. This study aims to test whether blockade of HMGB1 improves hepatocyte regeneration after APAP overdose. METHODS: Male C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAP administration, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 hours for a total of 2 doses. RESULTS: 24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantly improved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the sham IgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1 significantly decreased serum transaminases (ALT and AST), markedly reduced the number of hepatic inflammatory cells infiltration and restored liver structure to nearly normal; this beneficial effect was associated with enhanced hepatic NF-κB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration. CONCLUSION: HMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.

BACKGROUND: Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissue releases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Even though blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI) at 9 h time point, the later time points are not studied and the role of HMGB1 in APAP overdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyte regeneration. This study aims to test whether blockade of HMGB1 improves hepatocyte regeneration after APAP overdose. METHODS: Male C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAP administration, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 hours for a total of 2 doses. RESULTS: 24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantly improved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the sham IgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1 significantly decreased serum transaminases (ALT and AST), markedly reduced the number of hepatic inflammatory cells infiltration and restored liver structure to nearly normal; this beneficial effect was associated with enhanced hepatic NF-κB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration. CONCLUSION: HMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.

BACKGROUND: Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Necrotic tissue releases high mobility group B1 (HMGB1), and HMGB1 contributes to liver injury. Even though blockade of HMGB1 does not protect against APAP-induced acute liver injury (ALI) at 9 h time point, the later time points are not studied and the role of HMGB1 in APAP overdose is unknown, it is possible that neutralization of HMGB1 might improve hepatocyte regeneration. This study aims to test whether blockade of HMGB1 improves hepatocyte regeneration after APAP overdose. METHODS: Male C57BL/6 mice were treated with a single dose of APAP (350 mg/kg). 2 hrs after APAP administration, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 μg per dose) or non-immune (sham) IgG every 24 hours for a total of 2 doses. RESULTS: 24 hrs after APAP injection, anti-HMGB1 therapy instead of sham IgG therapy significantly improved hepatocyte regeneration microscopically; 48 hrs after APAP challenge, the sham IgG treated mice showed 14.6% hepatic necrosis; in contrast, blockade of HMGB1 significantly decreased serum transaminases (ALT and AST), markedly reduced the number of hepatic inflammatory cells infiltration and restored liver structure to nearly normal; this beneficial effect was associated with enhanced hepatic NF-κB DNA binding and increased the expression of cyclin D1, two important factors related to hepatocyte regeneration. CONCLUSION: HMGB1 impairs hepatocyte regeneration after APAP overdose; Blockade of HMGB1 enhances liver recovery and may present a novel therapy to treat APAP overdose.

BACKGROUND: Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G0), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-α and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-α and IL-6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose. METHODS: C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours. RESULTS: 72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-α concentration, enhanced hepatic NF-κB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration. CONCLUSION: RLS improves liver recovery from APAP hepatotoxicity.