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Recent studies suggest that hypolimnetic respiration may be responsible for greenhouse gas (GHG) emissions from deep reservoirs. Currently, quantitative evaluation of aerobic vs. anaerobic processes and priming (enhanced processing of organic matter due to the addition of labile carbon) in regulating GHG production and emissions across the reservoir-downstream continuum remains largely unknown. High-resolution, annual time-series observations in a large, subtropical reservoir (Shuikou) experiencing seasonal hypoxia in southeast China indicate that aerobic hypolimnetic CO2 production dominated in most periods of the stratified spring/summer with higher rates at higher temperatures. In addition, anaerobic production of hypolimnetic CO2 occurred in the late stratified spring/summer period, which stimulated hypolimnetic production of CH4 and N2O. Incubation experiments showed that priming in spring enhanced both aerobic and anaerobic production of excess GHGs. A late spring flood event generated the highest daily efflux of CO2 through the flushing of GHG-enriched hypolimnion waters. Turbine degassing contributed 59%, 93%, and 63% of annual CO2, CH4, and N2O effluxes, respectively. Moreover, annual downstream GHG emissions were similar to those in the transition/lacustrine zone of the Shuikou reservoir. Diurnal variation observations revealed net CO2 emissions even during algal bloom seasons. The reservoir-downstream river continuum was a year-round source of GHGs (218.5 ± 18.9 Gg CO2-equivalent yr−1; CO2 contributed 91%). However, the loss of oxygen also leads to increased production and storage of recalcitrant dissolved organic carbon (RDOC). Thus, identifying mechanisms controlling both GHG emissions and RDOC production is crucial to constrain the carbon neutrality issue of hydroelectric reservoirs in the context of climate change miti

Wei Wei,1,2,* Haili Cao,2,* Di Shen,2 Xiyu Sun,2 Zhenzhen Jia,1 Mingzhen Zhang1 1School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Xi’an No.1 Hospital, Shaanxi Institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, First Affiliated Hospital of Northwestern University, Xi’an, Shaanxi, 710002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenzhen Jia; Mingzhen Zhang, Email jzz324716@stu.xjtu.edu.cn; mzhang21@xjtu.edu.cnPurpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment.Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED.Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells.Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.Keywords: dry eye disease, carbon dots nanozyme, thermosensitive in situ gel, composite ocular drug delivery system

Recent studies suggest that hypolimnetic respiration may be responsible for greenhouse gas (GHG) emissions from deep reservoirs. Currently, quantitative evaluation of aerobic vs. anaerobic processes and priming (enhanced processing of organic matter due to the addition of labile carbon) in regulating GHG production and emissions across the reservoir-downstream continuum remains largely unknown. High-resolution, annual time-series observations in a large, subtropical reservoir (Shuikou) experiencing seasonal hypoxia in southeast China indicate that aerobic hypolimnetic CO2 production dominated in most periods of the stratified spring/summer with higher rates at higher temperatures. In addition, anaerobic production of hypolimnetic CO2 occurred in the late stratified spring/summer period, which stimulated hypolimnetic production of CH4 and N2O. Incubation experiments showed that priming in spring enhanced both aerobic and anaerobic production of excess GHGs. A late spring flood event generated the highest daily efflux of CO2 through the flushing of GHG-enriched hypolimnion waters. Turbine degassing contributed 59%, 93%, and 63% of annual CO2, CH4, and N2O effluxes, respectively. Moreover, annual downstream GHG emissions were similar to those in the transition/lacustrine zone of the Shuikou reservoir. Diurnal variation observations revealed net CO2 emissions even during algal bloom seasons. The reservoir-downstream river continuum was a year-round source of GHGs (218.5 ± 18.9 Gg CO2-equivalent yr−1; CO2 contributed 91%). However, the loss of oxygen also leads to increased production and storage of recalcitrant dissolved organic carbon (RDOC). Thus, identifying mechanisms controlling both GHG emissions and RDOC production is crucial to constrain the carbon neutrality issue of hydroelectric reservoirs in the context of climate change mitigation strategies.

Wenfang He,1,* Siqiang Zheng,1,* Hua Zhang,2 Bowen Gao,3 Juan Jin,1 Mingzhen Zhang,3,4 Qiang He1 1Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3School of Basic Medical Sciences, Xi’an Key Laboratory of Immune Related Diseases, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 4Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, Shaanxi, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiang He; Mingzhen Zhang, Email qianghe1973@126.com; mzhang21@xjtu.edu.cnAbstract: The utilization of plant-derived vesicle-like nanoparticles (PDVLNs) has shown effectiveness in the prevention/treatment of inflammatory-mediated diseases, malignancies, and immune-related diseases, such as acute liver injury, allergic asthma, gastric cancer and so on. This highlights the promising potential of PDVLNs as biotherapeutics. Furthermore, it should be noted that PDVLNs possess the ability to function as both natural and engineered drug carriers, making them an appealing option. This review aims to present the appropriate extraction methods of PDVLNs, summarize the applications of PDVLNs in different diseases, and provide an outlook on the prospects of PDVLNs. At the same time, the authors also express their discussion on the current limitations of PDVLNs.Keywords: plant-derived vesicle-like nanoparticles, extraction methods, anti-inflammatory, immune regulation, antitumor

Wei Wei,1– 3 Yujie Zhang,1,2 Runqing Li,4 Yameng Cao,1,2 Xiangji Yan,1,2 Yana Ma,1,2 Yuanyuan Zhang,1,2 Mei Yang,1,2 Mingzhen Zhang1,2 1School of Basic Medical Sciences, Xi’an Key Laboratory of Immune Related Diseases, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Xi’an No.1 Hospital, Shaanxi Institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, First Affiliated Hospital of Northwestern University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Mei Yang; Mingzhen Zhang, Email yangmeimei528@stu.xjtu.edu.cn; mzhang21@xjtu.edu.cnBackground: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects.Materials and Methods: Herein, the hyaluronic acid (HA)-modified L-arginine CO2 nanoparticles (HA-L-Arg-CO2@NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO2 and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS.Results: HA-L-Arg-CO2@NPs show great biocompatibility and the excellent ability to target the colon. Usin

Wei Wei,1– 3 Yujie Zhang,1,2 Runqing Li,4 Yameng Cao,1,2 Xiangji Yan,1,2 Yana Ma,1,2 Yuanyuan Zhang,1,2 Mei Yang,1,2 Mingzhen Zhang1,2 1School of Basic Medical Sciences, Xi’an Key Laboratory of Immune Related Diseases, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Xi’an No.1 Hospital, Shaanxi Institute of Ophthalmology, Shaanxi Key Laboratory of Ophthalmology, Clinical Research Center for Ophthalmology Diseases of Shaanxi Province, First Affiliated Hospital of Northwestern University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Mei Yang; Mingzhen Zhang, Email yangmeimei528@stu.xjtu.edu.cn; mzhang21@xjtu.edu.cnBackground: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects.Materials and Methods: Herein, the hyaluronic acid (HA)-modified L-arginine CO2 nanoparticles (HA-L-Arg-CO2@NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO2 and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS.Results: HA-L-Arg-CO2@NPs show great biocompatibility and the excellent ability to target the colon. Usin

Gong L, Zhang Y, Liu C, Zhang M, Han S. Int J Nanomedicine. 2021;16:1083–1102. The authors have advised there is an error with the reference list on page 1100. Reference 160 should read as follows. 160. Gong LJ, Xie JN, Zhu S, Gu ZJ, Zhao YL. Application of multifunctional nanomaterials in tumor radiosensitization. Acta Phys Chim Sin. 2018;34(2):140–167. doi.org/10.3866/PKU.WHXB201707174 The updated reference should have also been cited in the additional following places: Page 1092, Heavy Metal Nanomaterials section, second sentence, the text should read “Based on this, numerous studies have focused on these heavy metal nanomaterials to investigate their radiotherapy sensitization.160” Page 1094, Nonmetallic Nanomaterials section, second sentence, the text should read “For example, C60, fullerene, has potent anticancer activities, however, the potential toxicity to normal tissues limits its further use.160” The authors apologize for these errors. Read the original article

Liuyun Gong, 1 Yujie Zhang, 2, 3 Chengcheng Liu, 2 Mingzhen Zhang, 2, 3 Suxia Han 1 1Department of Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 3Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Mingzhen Zhang; Suxia Han Email mzhang21@xjtu.edu.cn; shan87@xjtu.edu.cnAbstract: Radiotherapy (RT) is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Although great success has been achieved on radiotherapy, there is still an intractable challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are chemicals or pharmaceutical agents that can enhance the killing effect on tumor cells by accelerating DNA damage and producing free radicals indirectly. In most cases, radiosensitizers have less effect on normal tissues. In recent years, several strategies have been exploited to develop radiosensitizers that are highly effective and have low toxicity. In this review, we first summarized the applications of radiosensitizers including small molecules, macromolecules, and nanomaterials, especially those that have been used in clinical trials. Second, the development states of radiosensitizers and the possible mechanisms to improve radiosensitizers sensibility are reviewed. Third, the challenges and prospects for clinical translation of radiosensitizers in oncotherapy are presented.Keywords: radiosensitizers, cancer radiotherapy, therapeutics, nanomedicine, mechanismCorrigendum for this paper has been published

Gong L, Zhang Y, Liu C, Zhang M, Han S. Int J Nanomedicine. 2021;16:1083–1102. The authors have advised there is an error with the reference list on page 1100. Reference 160 should read as follows. 160. Gong LJ, Xie JN, Zhu S, Gu ZJ, Zhao YL. Application of multifunctional nanomaterials in tumor radiosensitization. Acta Phys Chim Sin. 2018;34(2):140–167. doi.org/10.3866/PKU.WHXB201707174 The updated reference should have also been cited in the additional following places: Page 1092, Heavy Metal Nanomaterials section, second sentence, the text should read “Based on this, numerous studies have focused on these heavy metal nanomaterials to investigate their radiotherapy sensitization.160” Page 1094, Nonmetallic Nanomaterials section, second sentence, the text should read “For example, C60, fullerene, has potent anticancer activities, however, the potential toxicity to normal tissues limits its further use.160” The authors apologize for these errors. Read the original article

Liuyun Gong, 1 Yujie Zhang, 2, 3 Chengcheng Liu, 2 Mingzhen Zhang, 2, 3 Suxia Han 1 1Department of Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 3Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Mingzhen Zhang; Suxia Han Email mzhang21@xjtu.edu.cn; shan87@xjtu.edu.cnAbstract: Radiotherapy (RT) is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Although great success has been achieved on radiotherapy, there is still an intractable challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are chemicals or pharmaceutical agents that can enhance the killing effect on tumor cells by accelerating DNA damage and producing free radicals indirectly. In most cases, radiosensitizers have less effect on normal tissues. In recent years, several strategies have been exploited to develop radiosensitizers that are highly effective and have low toxicity. In this review, we first summarized the applications of radiosensitizers including small molecules, macromolecules, and nanomaterials, especially those that have been used in clinical trials. Second, the development states of radiosensitizers and the possible mechanisms to improve radiosensitizers sensibility are reviewed. Third, the challenges and prospects for clinical translation of radiosensitizers in oncotherapy are presented.Keywords: radiosensitizers, cancer radiotherapy, therapeutics, nanomedicine, mechanismCorrigendum for this paper has been published

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p.D57A) in an Italian melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11,273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS. Differently from other RAS activating alterations, NRAS D57A expression is unable to activate MAPK-pathway both constitutively and after stimulation but enhances EGF-induced PI3K-pathway signaling in serum starved conditions in vitro. Consistent with in vitro data demonstrating that NRAS D57A does not enrich GTP binding, molecular modeling suggests that the D57A substitution would be expected to impair Mg2 + binding and decrease nucleotide-binding and GTPase activity of NRAS. While we cannot firmly establish NRAS c.170A > C (p.D57A) as a melanoma susceptibility variant, further investigation of NRAS as a familial melanoma gene is warranted.