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Na Zhang,1,* Hui Wu,2,* Yingzhi Liang,1,* Jianming Ye,1 Huan Zhang,3 Yuqing Miao,3 Yane Luo,1 Haiming Fan,3 Tianli Yue1,4 1College of Food Science and Technology, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 2State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 4Laboratory of Quality and Safety Risk Assessment for Agro-Products (Yangling), Ministry of Agriculture, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yane Luo Email luoyane@nwu.edu.cnPurpose: Superparamagnetic iron oxide nanoparticles (SPIONs) have exhibited preeminent diagnosis and treatment performances, but their low internalization severely limits predesigned functions. The low cell internalization is now an urgent bottleneck problem for almost all nanomaterials. To achieve more internalization of SPIONS, recombinant M13 phage was designed for targeted delivery and smart release.Methods: M13 phages were designed to co-express exogenous SPARC binding peptide (SBP) and cathepsin B cleavage peptide (DFK), formed recombinant DFK-SBP-M13. 3.37± 0.06 nm of SPIONs were modified by 3, 4-dihydroxyhydrocinnamic acid (DHCA) to gain 10.80 ± 0.21 nm of DHCA-coated SPIONs, i.e., DHCA@SPIONs. Upon adjusting the proportions of DHCA@SPIONs and DFK-SBP-M13, the multi-carboxyl SPIONs assembled onto recombinant M13 phages via covalent bonding. The assemblies were co-cultured with MDA-MB-231 cells to interpret their internalization and smart release.Results: The “corn-like” SPIONs@DFK-SBP-M13 (261.47± 3.30 nm) assemblies have not been reported previously. The assembly was stable, dispersible

Metal contamination from base metal sulphide mines is a major environmental challenge that poses many ecological and health risks. We examined the metal concentrations in the Dabaoshan mine in South China in water, sediments, and aquatic organisms and their specific characteristics (i.e. size, body tissue, species, and habitat) along the Hengshi and Wengjiang River courses to assess acid mine drainage remediation efforts. Metal concentrations of arsenic, cadmium, chromium, copper, lead, nickel, thallium, and zinc were examined in tissues (i.e. gills, intestines, and muscles) of 17 freshwater species of fish, shrimps, and crabs. Metals in tissues followed the trend: intestines > gills > muscles; nearly all intestine samples exceeded the safe limits of metals analysed in this study. There is a positive correlation between distance from the mine and metal concentrations related to the flow of surface water and the habitat of aquatic organisms. The concentrations of arsenic, copper, and zinc were the highest in aquatic organisms, and the distribution was influenced by physical (distance from mine, currents, and seasonality), chemical (pH and competing ions), and biological (species, habitat, and predator-prey relation) factors. Large demersal fish and benthic fauna had higher concentrations of metals. Bioaccumulation and biomagnification of metals, as well as the high metal pollution index and target hazard quotient (arsenic, cadmium, copper, lead, thallium, and zinc), occurred in bottom feeders (C. aumtus, X. argentea) and fish belonging to higher trophic levels (P. fulvidraco, O. mossambicus). Lead and cadmium indicated the highest level of biomagnification from prey to predator. Health risks exist from the dietary intake of common aquatic species such as tilapia and carp besides crustaceans due to high arsenic, cadmium, lead, and thallium levels. Further reduction of metals is necessary to improve the effects of acid mine drainage in the catchment., Funding Agencies|Linkoping University-Guangzhou University Research Center on Urban Sustainable Development; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2018A030310309]; Joshua Wat proofread the thesis for WSC

Metal contamination from base metal sulphide mines is a major environmental challenge that poses many ecological and health risks. We examined the metal concentrations in the Dabaoshan mine in South China in water, sediments, and aquatic organisms and their specific characteristics (i.e. size, body tissue, species, and habitat) along the Hengshi and Wengjiang River courses to assess acid mine drainage remediation efforts. Metal concentrations of arsenic, cadmium, chromium, copper, lead, nickel, thallium, and zinc were examined in tissues (i.e. gills, intestines, and muscles) of 17 freshwater species of fish, shrimps, and crabs. Metals in tissues followed the trend: intestines > gills > muscles; nearly all intestine samples exceeded the safe limits of metals analysed in this study. There is a positive correlation between distance from the mine and metal concentrations related to the flow of surface water and the habitat of aquatic organisms. The concentrations of arsenic, copper, and zinc were the highest in aquatic organisms, and the distribution was influenced by physical (distance from mine, currents, and seasonality), chemical (pH and competing ions), and biological (species, habitat, and predator-prey relation) factors. Large demersal fish and benthic fauna had higher concentrations of metals. Bioaccumulation and biomagnification of metals, as well as the high metal pollution index and target hazard quotient (arsenic, cadmium, copper, lead, thallium, and zinc), occurred in bottom feeders (C. aumtus, X. argentea) and fish belonging to higher trophic levels (P. fulvidraco, O. mossambicus). Lead and cadmium indicated the highest level of biomagnification from prey to predator. Health risks exist from the dietary intake of common aquatic species such as tilapia and carp besides crustaceans due to high arsenic, cadmium, lead, and thallium levels. Further reduction of metals is necessary to improve the effects of acid mine drainage in the catchment., Funding Agencies|Linkoping University-Guangzhou University Research Center on Urban Sustainable Development; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2018A030310309]; Joshua Wat proofread the thesis for WSC

Metal contamination from base metal sulphide mines is a major environmental challenge that poses many ecological and health risks. We examined the metal concentrations in the Dabaoshan mine in South China in water, sediments, and aquatic organisms and their specific characteristics (i.e. size, body tissue, species, and habitat) along the Hengshi and Wengjiang River courses to assess acid mine drainage remediation efforts. Metal concentrations of arsenic, cadmium, chromium, copper, lead, nickel, thallium, and zinc were examined in tissues (i.e. gills, intestines, and muscles) of 17 freshwater species of fish, shrimps, and crabs. Metals in tissues followed the trend: intestines > gills > muscles; nearly all intestine samples exceeded the safe limits of metals analysed in this study. There is a positive correlation between distance from the mine and metal concentrations related to the flow of surface water and the habitat of aquatic organisms. The concentrations of arsenic, copper, and zinc were the highest in aquatic organisms, and the distribution was influenced by physical (distance from mine, currents, and seasonality), chemical (pH and competing ions), and biological (species, habitat, and predator-prey relation) factors. Large demersal fish and benthic fauna had higher concentrations of metals. Bioaccumulation and biomagnification of metals, as well as the high metal pollution index and target hazard quotient (arsenic, cadmium, copper, lead, thallium, and zinc), occurred in bottom feeders (C. aumtus, X. argentea) and fish belonging to higher trophic levels (P. fulvidraco, O. mossambicus). Lead and cadmium indicated the highest level of biomagnification from prey to predator. Health risks exist from the dietary intake of common aquatic species such as tilapia and carp besides crustaceans due to high arsenic, cadmium, lead, and thallium levels. Further reduction of metals is necessary to improve the effects of acid mine drainage in the catchment., Funding Agencies|Linkoping University-Guangzhou University Research Center on Urban Sustainable Development; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2018A030310309]; Joshua Wat proofread the thesis for WSC

Ziyuan Shen,1,* Fei Wang,2,* Chenlu He,1,* Dashan Li,3 Shanlin Nie,3 Zhenzhen Bian,3 Mingkang Yao,4 Yuhao Xue,5 Ying Wang,6 Weiying Gu,2 Taigang Zhu,7 Yuye Shi,5 Hao Zhang,4 Shuiping Huang,1,8 Yuqing Miao,9 Wei Sang3 On behalf of the Huaihai Lymphoma Working Group1Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Hematology, The First People’s Hospital of Huaian, Huaian, Jiangsu, People’s Republic of China; 6Department of Personnel, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 7Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, People’s Republic of China; 8Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei SangDepartment of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8613645207648Email xyfylbl515@xzhmu.edu.cnYuqing MiaoDepartment of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of ChinaTel +8613851342032Email miaomiaomyq@163.comIntroduction: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analy

Metal contamination from base metal sulphide mines is a major environmental challenge that poses many ecological and health risks. We examined the metal concentrations in the Dabaoshan mine in South China in water, sediments, and aquatic organisms and their specific characteristics (i.e. size, body tissue, species, and habitat) along the Hengshi and Wengjiang River courses to assess acid mine drainage remediation efforts. Metal concentrations of arsenic, cadmium, chromium, copper, lead, nickel, thallium, and zinc were examined in tissues (i.e. gills, intestines, and muscles) of 17 freshwater species of fish, shrimps, and crabs. Metals in tissues followed the trend: intestines > gills > muscles; nearly all intestine samples exceeded the safe limits of metals analysed in this study. There is a positive correlation between distance from the mine and metal concentrations related to the flow of surface water and the habitat of aquatic organisms. The concentrations of arsenic, copper, and zinc were the highest in aquatic organisms, and the distribution was influenced by physical (distance from mine, currents, and seasonality), chemical (pH and competing ions), and biological (species, habitat, and predator-prey relation) factors. Large demersal fish and benthic fauna had higher concentrations of metals. Bioaccumulation and biomagnification of metals, as well as the high metal pollution index and target hazard quotient (arsenic, cadmium, copper, lead, thallium, and zinc), occurred in bottom feeders (C. aumtus, X. argentea) and fish belonging to higher trophic levels (P. fulvidraco, O. mossambicus). Lead and cadmium indicated the highest level of biomagnification from prey to predator. Health risks exist from the dietary intake of common aquatic species such as tilapia and carp besides crustaceans due to high arsenic, cadmium, lead, and thallium levels. Further reduction of metals is necessary to improve the effects of acid mine drainage in the catchment., Funding Agencies|Linkoping University-Guangzhou University Research Center on Urban Sustainable Development; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2018A030310309]; Joshua Wat proofread the thesis for WSC

Na Zhang,1,* Hui Wu,2,* Yingzhi Liang,1,* Jianming Ye,1 Huan Zhang,3 Yuqing Miao,3 Yane Luo,1 Haiming Fan,3 Tianli Yue1,4 1College of Food Science and Technology, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 2State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China; 3Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi, 710069, People’s Republic of China; 4Laboratory of Quality and Safety Risk Assessment for Agro-Products (Yangling), Ministry of Agriculture, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yane Luo Email luoyane@nwu.edu.cnPurpose: Superparamagnetic iron oxide nanoparticles (SPIONs) have exhibited preeminent diagnosis and treatment performances, but their low internalization severely limits predesigned functions. The low cell internalization is now an urgent bottleneck problem for almost all nanomaterials. To achieve more internalization of SPIONS, recombinant M13 phage was designed for targeted delivery and smart release.Methods: M13 phages were designed to co-express exogenous SPARC binding peptide (SBP) and cathepsin B cleavage peptide (DFK), formed recombinant DFK-SBP-M13. 3.37± 0.06 nm of SPIONs were modified by 3, 4-dihydroxyhydrocinnamic acid (DHCA) to gain 10.80 ± 0.21 nm of DHCA-coated SPIONs, i.e., DHCA@SPIONs. Upon adjusting the proportions of DHCA@SPIONs and DFK-SBP-M13, the multi-carboxyl SPIONs assembled onto recombinant M13 phages via covalent bonding. The assemblies were co-cultured with MDA-MB-231 cells to interpret their internalization and smart release.Results: The “corn-like” SPIONs@DFK-SBP-M13 (261.47± 3.30 nm) assemblies have not been reported previously. The assembly was stable, dispersible

Metal contamination from base metal sulphide mines is a major environmental challenge that poses many ecological and health risks. We examined the metal concentrations in the Dabaoshan mine in South China in water, sediments, and aquatic organisms and their specific characteristics (i.e. size, body tissue, species, and habitat) along the Hengshi and Wengjiang River courses to assess acid mine drainage remediation efforts. Metal concentrations of arsenic, cadmium, chromium, copper, lead, nickel, thallium, and zinc were examined in tissues (i.e. gills, intestines, and muscles) of 17 freshwater species of fish, shrimps, and crabs. Metals in tissues followed the trend: intestines > gills > muscles; nearly all intestine samples exceeded the safe limits of metals analysed in this study. There is a positive correlation between distance from the mine and metal concentrations related to the flow of surface water and the habitat of aquatic organisms. The concentrations of arsenic, copper, and zinc were the highest in aquatic organisms, and the distribution was influenced by physical (distance from mine, currents, and seasonality), chemical (pH and competing ions), and biological (species, habitat, and predator-prey relation) factors. Large demersal fish and benthic fauna had higher concentrations of metals. Bioaccumulation and biomagnification of metals, as well as the high metal pollution index and target hazard quotient (arsenic, cadmium, copper, lead, thallium, and zinc), occurred in bottom feeders (C. aumtus, X. argentea) and fish belonging to higher trophic levels (P. fulvidraco, O. mossambicus). Lead and cadmium indicated the highest level of biomagnification from prey to predator. Health risks exist from the dietary intake of common aquatic species such as tilapia and carp besides crustaceans due to high arsenic, cadmium, lead, and thallium levels. Further reduction of metals is necessary to improve the effects of acid mine drainage in the catchment., Funding Agencies|Linkoping University-Guangzhou University Research Center on Urban Sustainable Development; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2018A030310309]; Joshua Wat proofread the thesis for WSC

Metal contamination from base metal sulphide mines is a major environmental challenge that poses many ecological and health risks. We examined the metal concentrations in the Dabaoshan mine in South China in water, sediments, and aquatic organisms and their specific characteristics (i.e. size, body tissue, species, and habitat) along the Hengshi and Wengjiang River courses to assess acid mine drainage remediation efforts. Metal concentrations of arsenic, cadmium, chromium, copper, lead, nickel, thallium, and zinc were examined in tissues (i.e. gills, intestines, and muscles) of 17 freshwater species of fish, shrimps, and crabs. Metals in tissues followed the trend: intestines > gills > muscles; nearly all intestine samples exceeded the safe limits of metals analysed in this study. There is a positive correlation between distance from the mine and metal concentrations related to the flow of surface water and the habitat of aquatic organisms. The concentrations of arsenic, copper, and zinc were the highest in aquatic organisms, and the distribution was influenced by physical (distance from mine, currents, and seasonality), chemical (pH and competing ions), and biological (species, habitat, and predator-prey relation) factors. Large demersal fish and benthic fauna had higher concentrations of metals. Bioaccumulation and biomagnification of metals, as well as the high metal pollution index and target hazard quotient (arsenic, cadmium, copper, lead, thallium, and zinc), occurred in bottom feeders (C. aumtus, X. argentea) and fish belonging to higher trophic levels (P. fulvidraco, O. mossambicus). Lead and cadmium indicated the highest level of biomagnification from prey to predator. Health risks exist from the dietary intake of common aquatic species such as tilapia and carp besides crustaceans due to high arsenic, cadmium, lead, and thallium levels. Further reduction of metals is necessary to improve the effects of acid mine drainage in the catchment., Funding Agencies|Linkoping University-Guangzhou University Research Center on Urban Sustainable Development; Natural Science Foundation of Guangdong Province, ChinaNational Natural Science Foundation of Guangdong Province [2018A030310309]; Joshua Wat proofread the thesis for WSC

Le Chang,1 Xiao Li Liu,1,2 Dai Di Fan,1 Yu Qing Miao,1 Huan Zhang,1 He Ping Ma,1 Qiu Ying Liu,1 Pei Ma,1 Wei Ming Xue,1 Yan E Luo,1 Hai Ming Fan1,3 1Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Materials Science and Engineering, Faculty of Engineering, National University of Singapore, Singapore; 3Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China Abstract: Magnetic hyperthermia is a promising technique for the minimally invasive elimination of solid tumors. In this study, uniform magnetite nanoparticles (MNPs) with different particle sizes were used as a model system to investigate the size and surface effects of human-like collagen protein-coated MNPs (HLC-MNPs) on specific absorption rate and biocompatibility. It was found that these HLC-MNPs possess rapid heating capacity upon alternating magnetic field exposure compared to that of MNPs without HLC coating, irrespective of the size of MNPs. The significant enhancement of specific absorption rate is favorable for larger sized nanoparticles. Such behavior is attributed to the reduced aggregation and increased stability of the HLC-MNPs. By coating HLC on the surface of certain sized MNPs, a significant increase in cell viability (up to 2.5-fold) can be achieved. After subcutaneous injection of HLC-MNPs into the back of Kunming mice, it was observed that the inflammatory reaction hardly occurred in the injection site. However, there was a significant presence of phagocytes and endocytosis after the injection of nonconjugated counterparts. The overall strategy to fabricate HLC-MNPs can serve as a general guideline to address the current challenges in clinical magnetic hyperthermia, improved biocomp

Le Chang,1 Xiao Li Liu,1,2 Dai Di Fan,1 Yu Qing Miao,1 Huan Zhang,1 He Ping Ma,1 Qiu Ying Liu,1 Pei Ma,1 Wei Ming Xue,1 Yan E Luo,1 Hai Ming Fan1,3 1Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Materials Science and Engineering, Faculty of Engineering, National University of Singapore, Singapore; 3Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China Abstract: Magnetic hyperthermia is a promising technique for the minimally invasive elimination of solid tumors. In this study, uniform magnetite nanoparticles (MNPs) with different particle sizes were used as a model system to investigate the size and surface effects of human-like collagen protein-coated MNPs (HLC-MNPs) on specific absorption rate and biocompatibility. It was found that these HLC-MNPs possess rapid heating capacity upon alternating magnetic field exposure compared to that of MNPs without HLC coating, irrespective of the size of MNPs. The significant enhancement of specific absorption rate is favorable for larger sized nanoparticles. Such behavior is attributed to the reduced aggregation and increased stability of the HLC-MNPs. By coating HLC on the surface of certain sized MNPs, a significant increase in cell viability (up to 2.5-fold) can be achieved. After subcutaneous injection of HLC-MNPs into the back of Kunming mice, it was observed that the inflammatory reaction hardly occurred in the injection site. However, there was a significant presence of phagocytes and endocytosis after the injection of nonconjugated counterparts. The overall strategy to fabricate HLC-MNPs can serve as a general guideline to address the current challenges in clinical magnetic hyperthermia, improved biocomp