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Yucheng Fu, Guoyu He, Zhuochao Liu, Jun Wang, Zhusheng Zhang, Qiyuan Bao, Junxiang Wen, Zhijian Jin, Weibin Zhang Department of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaCorrespondence: Weibin ZhangDepartment of Orthopedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of ChinaTel +86-21-64370045, Ext 666983Fax +86-21-54660217Email zhangweibin10368@163.comBackground: Inflammatory response took part in the progression of tumor and was regarded as the hallmark of cancer. However, the prognostic relationship between osteosarcoma and inflammatory response-associated genes (IRGs) was unclear. This research aimed to explore the correlations between osteosarcoma prognosis and IRG signature.Methods: The inflammatory response-associated differentially expressed messenger RNAs (DEmRNAs) were screened out through Gene Expression Omnibus (GEO) and Molecular Signature Database (MSigDB) databases. Univariate and multivariate cox regression analyses were utilized to construct the IRG signature. The prognostic value of signature was investigated through Kaplan–Meier (KM) survival curve and nomogram. DEmRNAs among high and low inflammatory response-associated risks were identified and functional enrichment analyses were conducted. ESTIMATE, CIBERSORT and single-sample gene set enrichment analyses (ssGSEA) were implied to reveal the alterations in immune infiltration. All the above results were validated in Target database. The expression of IRGs was also validated in different cell lines by quantitative real-time PCR (qRT-PCR) and osteosarcoma patient samples by immunohistochemistry.Results: The IRG signature that consisted of two genes (MYC, CLEC5A) was established. In training and validation datasets, patients with lower risk scores survived longer and the IRG signature was confirmed as the independent prognostic factor in osteosarcoma. The nomogram was constructed and the calibration curves demonstrated the reliability of this model. Functional analysis of risk score-associated DEmRNAs indicated that immune-related pathways and functions were significantly enriched. ssGSEA revealed that 14 immune cells and 11 immune functions were significantly dysregulated. The qRT-PCR results indicated IRGs were significantly differently expressed in osteosarcoma and osteoblast cell lines. The immunohistochemistry analyses of patients’ samples revealed the same result.Conclusion: The novel osteosarcoma inflammatory response-associated prognostic signature was established and validated in this study. This model could serve as the biomarker and therapeutic target for osteosarcoma in the future.Keywords: osteosarcoma, inflammatory response, metastasis, prognosis, immune

Critical assessment of mega projects is emerging as a much-needed discipline in an era when, in many places, resource demands exceed environmental capacity. Using the Desalination Economic Evaluation Program developed by the International Atomic Energy Agency, we show that by 2030, China will have the capacity to produce 20.7 billion m3 of water annually, at $0.72/m3, as a coproduct of electricity generation through nuclear power, provided that the country favors desalination over water diversion. We calculate that the resulting production and supply chain can increase water resources in scarce regions by up to 228% while remaining affordable to poorest households. We then compare coal and nuclear desalination with the currently planned South-North Water Transfer mega project and show that, while the short-run cost of water diversion is lower, critical vulnerabilities and future resource demands favor nuclear desalination in coastal regions.

Xiaolong Zhao,1– 3,* Huajun Xu,1,3,* Chuan Dong,2,* Jiangang Fan,2 Gang He,2 Jianyin Zou,1,3 Lili Meng,1,3 Huaming Zhu,1,3 Kaiming Su,1,3 Mingpo Yang,4 Hongliang Yi,1,3 Jian Wang,5 Shankai Yin,1,3 Jian Guan1,3 1Department of Otolaryngology Head and Neck Surgery & Center of Sleep Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, People’s Republic of China; 4Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5School of Communication Science and Disorders/Physiol & Biophysics, Dalhousie University, Halifax, NS, Canada*These authors contributed equally to this workCorrespondence: Shankai Yin; Jian Guan Email skyin@sjtu.edu.cn; guanjian0606@sina.comBackground: Cardiac autonomic dysfunction (CAD) is a common pathology in cardiovascular diseases; however, the role of glycolipid metabolic disorders in CAD development in obstructive sleep apnea (OSA) remains poorly understood.Methods: In total, 4152 patients with suspected OSA were recruited in our sleep center. Metabolic characteristics including anthropometric and glycolipid data were collected. Heart rate variability (HRV) was measured to assess the risk of CAD; its dose–response relationship with OSA severity was evaluated via restricted cubic spline (RCS) analysis. A segmented multivariate linear regression (SMLR) model was used to evaluate the roles of metabolic variables in different stages of OSA.Results: The RCS showed that CAD risk increased in a nonlinear relationship pattern with OSA severity, from slow fluctuation at earlier stages to rapid change in later stages. After integrating the clinical definition and RCS selected knots, we obtained the new four OSA severity stages. SMLR model showed that the overall value of glycolipid variables for prediction of HRV abnormalities was greater than the value of OSA variables at earlier stages, while OSA variables were more effective predictors in more severe stages. The discordance in respective relationship of HRV with metabolic and OSA variables sheds the light how metabolic disorders promoted the development of CAD in OSA, the later further in turn deteriorates cardiac function.Conclusion: These results are indicative of stage-specific involvement of glycolipid metabolic factors underlying CAD nonlinear changes in patients with OSA. Early control glycolipid disorders may help the control of CAD development in patients with OSA.Keywords: obstructive sleep apnea, autonomic nervous system, cardiac autonomic neuropathy, metabolism, heart rate variability

Xuan Feng,1,2 Feng Xue,3 Guihua He,4 Suiping Huang,4 Qing Ni1,3 1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Jiangsu, People’s Republic of China; 2Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, 225001, Jiangsu, People’s Republic of China; 3Department of Surgery, Affiliated Hospital of Yangzhou University, Yangzhou, 225000, Jiangsu, People’s Republic of China; 4Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of ChinaCorrespondence: Suiping Huang; Qing Ni Email gzdoctorhsp@126.com; nqingnn@163.comPurpose: Banxia xiexin decoction (BXXX) is a classical Chinese herbal compound for the treatment of gastrointestinal diseases. Its ingredients are also considered helpful for cancer rehabilitation. Here, we will explore the regulatory mechanism of BXXX acting on PD-L1 in gastric cancer (GC).Methods: GC samples and the general baseline data of the patients were collated. Immunohistochemical (IHC) detected the expression of programmed cell death-ligand 1(PD-L1), hypoxia-inducible factor-1 (HIF-1), epidermal growth factor receptor (EGFR), interferon-γ receptor (IFNGR) and Toll-like receptor 4 (TLR4). ELISA detected the expressions of EGF, IFNG and IL-6 in serum samples. Network tools were used to analyze the potential molecules of BXXX. In the cell experiment, CCK-8 detected the cell proliferation. Tunel detected the apoptosis. Western blot detected the expression of related proteins. In animal experiments, the tumor volume of GC-bearing mice was observed. Expression of EGF, IFNG and IL-6 in the serum of tumor-bearing GC mice were detected by ELISA. Western blot detected the expression of related proteins.Results: The expressions of PD-L1, HIF-1, EGFR, IFNGR and TLR4 in the tissues of GC patients were significantly increased, and the expressions of EGF, IFNG and IL-6 in serum were increased. The molecular results of the network tools showed that BXXX and its main components have a targeting effect on the key molecules of each pathway in the PD-L1 regulatory network. Cell experiments showed that BXXX can inhibit the expression of PD-L1, HIF-1, EGFR and TLR4, but has no significant effect on the expression of IFNGR, thus inhibiting the proliferation and promoting the apoptosis of GC cells. The results were consistent with the animal experiments on tumor-bearing gastric cancer mice.Conclusion: BXXX inhibited the expression of PD-L1 through multi-target and multi-pathway regulation of major oncogenes in GC, thus effect cell proliferation and apoptosis.Keywords: banxia xiexin decoction, gastric cancer, PD-L1, multi-target and multi-pathway