作者机构：
[周敏] Geriatric Department, Chongqing Emergency Medical Center, The Fourth People's Hospital of Chongqing, Chongqing, 400030, China;[郑子光; 游宏宇] Western Investment Construction Co., LDT of CCTEB, Chengdu, 610041, China;[郭淼; 喻伟] School of Civil Engineering, Chongqing University, Chongqing, 400045, China;[杨旭] School of Life Sciences, Central China Normal University, Wuhan, 430079, China
通讯机构：
[Yu, W.] S;School of Civil Engineering, China
期刊：
Research in Microbiology,2023年:104173 ISSN：0923-2508
通讯作者：
Yang, Hong
作者机构：
[Qiu, Zhengyong; Mei, Cheng; Wang, Yu] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China;[Shi, Yu] College of Food and Biotechnology, Wuhan Institute of Design and Sciences, Wuhan 430079, PR China;[Yang, Hong] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China. Electronic address: hyang@ccnu.edu.cn
通讯机构：
[Yang, Hong] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China. Electronic address:
摘要：
Verrucomicrobiota is widely distributed in various habitats including insect guts. It was found to be prevalent in almost all investigated termite guts, whereas their physiological functions are not very clear. In this study we characterized the physiological and genomic properties of Verrucomicrobiota strain TSB47(T) isolated from Reticulitermes chinensis. The cells of strain TSB47(T) were Gram-stain-negative, non-motile, and non-spore-forming coccoid with one or more warts. 16S rRNA gene analysis showed that the closest relatives of strain TSB47(T) were Opitutaceae strain TAV1 and Ereboglobus luteus Ho45(T) (98.3% and 95.4% sequence similarity, respectively). Whole genome analysis revealed that there are a large number of glycoside hydrolase genes, amino acid metabolism genes, complete Mo-Fe nitrogenase and Fe-Fe nitrogenase gene clusters, as well as cbb(3)-type cytochrome oxidase gene in the genome of strain TSB47(T). Strain TSB47(T) grows well under anaerobic and microaerophilic conditions with a strong tolerance to oxygen. Physiological and genomic characters of strain TSB47(T) indicated its high adaptability to termite gut ecosystem. Based on phenotypic and phylogenetic evidence, we suggest strain TSB47(T) as the type species of a novel genus in the family Opitutaceae, for which the name Termitidicoccus mucosus sp. nov. is proposed. The type strain is TSB47(T) (CCTCC AB2022447(T); KCTC 102044(T)).
作者机构：
[Chen, Mingqing; Han, Qi; Wei, Zhaolan; Deng, Lingfu; Wang, Yunyi; Wang, Shuwei] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;[Chen, Mingqing] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Chen, Mingqing] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China. Electronic address:
摘要：
Previous studies suggest some link between formaldehyde exposure and harmful cardiovascular effects. But whether exposure to formaldehyde can cause blood pressure to rise, and if so, what the underlying mechanism is, remains unclear. In this study, C57BL/6 male mice were exposed to 0.1, 0.5, 2.5mg/m(3) of gaseous formaldehyde for 4hours daily over a three-week period. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) of the mice were measured by tail-cuff plethysmography, and any histopathological changes in the target organs of hypertension were investigated. The results showed that exposure to formaldehyde did cause a significant increase in blood pressure and heart rate, and resulted in varying degrees of damage to the heart, aortic vessels and kidneys. To explore the underlying mechanism, a specific inhibitor of angiotensin converting enzyme (ACE) was used to block the ACE/AT1R axis. We observed the levels of ACE and angiotensin II type 1 receptor (AT1R), as well as the bradykinin (BK) in cardiac cytoplasm. The data suggest that exposure to formaldehyde induced an increase in the expression of ACE and AT1R, and decreased the levels of BK. Strikingly, treatment with 5mg/kg/d ACE inhibitor can attenuate the increase in blood pressure and the pathological changes caused by formaldehyde exposure. This result has improved our understanding of whether, and how, formaldehyde exposure affects the development of hypertension.
摘要：
West of Beijing, Chinese white‐bellied rats (Niviventer confucianus, CWR) and Korean field mice (Apodemus peninsulae, KFM) are common and share similar habitat, diet, and activity, but differ in body size (CWR are bigger than KFM), food hoarding habit, and ability to protect caches. Intense asymmetric competition for food exists between the 2 rodent species, in that CWR have distinct advantage than KFM. However, how KFM coexists with CWR is less known. By tracking seed competition of 15 pairs of CWR–KFM over a 10‐day period for each under enclosure conditions, we found KFM could not compete over CWR at the seed source, but in terms of relative number (seed number/2) and relative energy of seeds (seed energy/3), they hoarded more seeds than CWR at the end of the trials. These results may promote their coexistence under the conditions of asymmetric competition. Abstract Asymmetric competition occurs when some species have distinct advantages over their competitors and is common in animals with overlapping habitats and diet. However, the mechanism allowing coexistence between asymmetric competitors is not fully clear. Chinese white‐bellied rats (Niviventer confucianus, CWR) and Korean field mice (Apodemus peninsulae, KFM) are common asymmetric competitors in shrublands and forests west of Beijing city. They share similar diet (e.g. plant seeds) and activity (nocturnal), but differ in body size (CWR are bigger than KFM), food hoarding habit (CWR: mainly larder hoarding; KFM: both larder and scatter hoarding), and ability to protect cached food (CWR are more aggressive than KFM). Here, we tested seed competition in 15 CWR–KFM pairs over a 10‐day period under semi‐natural enclosure conditions to uncover the differences in food hoarding, cache pilferage, and food protection between the 2 rodents, and discuss the implication for coexistence. Prior to pilferage, CWR harvested and ate more seeds than KFM. CWR tended to larder hoard seeds, whereas KFM preferred to scatter hoard seeds. Following pilferage, CWR increased consumption, decreased intensity of hoarding, and pilfered more caches from KFM than they lost, while KFM increased consumption more than they hoarded, and they preferred to hoard seeds in low and medium competition areas. Accordingly, both of the 2 rodent species increased their total energy consumption and hoarding following pilferage. Both rodent species tended to harvest seeds from the source, rather than pilfer caches from each other to compensate for cache loss via pilferage. Compared to CWR, KFM consumed fewer seeds when considering seed number, but hoarded more seeds when considering the seeds’ relative energy (energy of hoarded seeds/rodent body mass2/3) at the end of the trials. These results suggest that asymmetric competition for food exists between CWR and KFM, but differentiation in hoarding behavior could help the subordinate species (i.e. KFM) hoard more energy than the dominant species (i.e. CWR), and may contribute to their coexistence in the field.
摘要：
Hipposideros pratti called at higher intensities while keeping the constant frequencies of their echolocation pulses consistent under spectrally non-overlapping background noise conditions. The noise could decrease auditory sensitivity and sharp intensity tuning, suggesting an acoustic masking effect. These results provide further evidence of negative consequences of anthropogenic noise. The environment noise may disturb animal behavior and echolocation via three potential mechanisms: acoustic masking, reduced attention and noise avoidance. Compared with the mechanisms of reduced attention and noise avoidance, acoustic masking is thought to occur only when the signal and background noise overlap spectrally and temporally. In this study, we investigated the effects of spectrally non-overlapping noise on echolocation pulses and electrophysiological responses of a constant frequency-frequency modulation (CF-FM) bat, Hipposideros pratti. We found that H. pratti called at higher intensities while keeping the CFs of their echolocation pulses consistent. Electrophysiological tests indicated that the noise could decrease auditory sensitivity and sharp intensity tuning, suggesting that spectrally non-overlapping noise imparts an acoustic masking effect. Because anthropogenic noises are usually concentrated at low frequencies and are spectrally non-overlapping with the bat's echolocation pulses, our results provide further evidence of negative consequences of anthropogenic noise. On this basis, we sound a warning against noise in the foraging habitats of echolocating bats.
摘要：
The predation and/or dispersal of Quercus seeds by rodents play an important role in the creation of the tree species. The present study examined the effects of community habitats on the predation and dispersal of Quercus wutaishanica seeds by rodents. We released seeds with densities set at 2, 4, 8, 16, and 32 seed square meter with litter cover, soil burial, and bare ground in the Liupan Mountains National Nature Reserve in the Ningxia Hui Autonomous Region, northwest China. The results showed that (1) the litter cover and soil burial significantly increased the seed survival probability compared with bare ground treatments, especially the predation in situ (PIS) (p < 0.05). Both the scatter hoarding (SH) and larder hoarding (LH) for litter cover and soil burial were significantly increased compared with bare ground (p < 0.05). (2) The large seeds are preferentially predated after dispersal and their long-distance dispersal (>5 m) was significantly greater than that of small seeds (p < 0.05), while small seeds are more likely to be preyed on in situ or during short-distance dispersal (<3 m). (3) The Q. wutaishanica seed predation by rodents increased at a high density rather than at a low density, indicating a negative density-dependent predation. These findings provide insights into the ecological characteristics of Quercus tree regeneration and shed light on the coexistence between rodents and different-sized seeds.
期刊：
Journal of Advanced Research,2023年48:105-123 ISSN：2090-1232
通讯作者：
Xie, Na;Huang, CH;Chen, MQ
作者机构：
[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.;[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China.;[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.;[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China.;[Nice, Edouard C.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia.
通讯机构：
[Chen, MQ ] C;[Xie, N; Huang, CH ] W;West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.;West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.
关键词：
Long noncoding RNAs;Lipid metabolism;Lipid chaperones;Lipid receptors;Therapeutic target
摘要：
Background: The investigation of lncRNAs has provided a novel perspective for elucidating mechanisms underlying diverse physiological and pathological processes. Compelling evidence has revealed an intrin-sic link between lncRNAs and lipid metabolism, demonstrating that lncRNAs-induced disruption of lipid metabolism and signaling contribute to the development of multiple cancers and some other diseases, including obesity, fatty liver disease, and cardiovascular disease.Aimof Review: The current review summarizes the recent advances in basic research about lipid metabo-lism and lipid signaling-related lncRNAs. Meanwhile, the potential and challenges of targeting lncRNA for the therapy of cancers and other lipid metabolism-related diseases are also discussed.Key Scientific Concept of Review: Compared with the substantial number of lncRNA loci, we still know little about the role of lncRNAs in metabolism. A more comprehensive understanding of the function and mechanism of lncRNAs may provide a new standpoint for the study of lipid metabolism and signaling. Developing lncRNA-based therapeutic approaches is an effective strategy for lipid metabolism-related diseases.(c) 2023 Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
作者机构：
[Wang, Ruiqi; Li, Yingcan] Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau of the Ministry of Education, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China;[Jiao, Hengwu] School of Life Sciences, Central China Normal University, Wuhan 430079, China;[Sin, Simon Yung Wa] School of Biological Sciences, The University of Hong Kong, Hong Kong SAR 999077, China;[Rossiter, Stephen J] School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK;[Zhao, Huabin] Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau of the Ministry of Education, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: huabinzhao@whu.edu.cn
通讯机构：
[Huabin Zhao] K;Key Laboratory of Biodiversity and Environment on the Qinghai-Tibetan Plateau of Ministry of Education, Frontier Science Center for Immunology and Metabolism, College of Life Sciences, Wuhan University, Wuhan 430072, China
作者机构：
[Wang, P; Wang, Peng; Grimm, Bernhard; Ji, Shuiling] Humboldt Univ, Inst Biol Plant Physiol, Philippstr13, Bldg 12, D-10099 Berlin, Germany.;[Ji, Shuiling] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Wang, P; Wang, Peng] Univ Hong Kong, Sch Biol Sci, Hong Kong 999077, Peoples R China.;[Wang, P; Wang, Peng] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong 999077, Peoples R China.
通讯机构：
[Wang, P ; Grimm, B] H;Humboldt Univ, Inst Biol Plant Physiol, Philippstr13, Bldg 12, D-10099 Berlin, Germany.;Univ Hong Kong, Sch Biol Sci, Hong Kong 999077, Peoples R China.;Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong 999077, Peoples R China.
关键词：
chlorophyll biosynthesis;post-translational control;chloroplast signal recognition particle;protein stability;molecular chaperone;chloroplast development
摘要：
Protochlorophyllide oxidoreductase (POR), which converts protochlorophyllide into chlorophyllide, is the only light-dependent enzyme in chlorophyll biosynthesis. While its catalytic reaction and importance for chloroplast development are well understood, little is known about the post-translational control of PORs. Here, we show that cpSRP43 and cpSRP54, two components of the chloroplast signal recognition particle pathway, play distinct roles in optimizing the function of PORB, the predominant POR isoform in Arabidopsis. The chaperone cpSRP43 stabilizes the enzyme and provides appropriate amounts of PORB during leaf greening and heat shock, whereas cpSRP54 enhances its binding to the thylakoid membrane, thereby ensuring adequate levels of metabolic flux in late chlorophyll biosynthesis. Furthermore, cpSRP43 and the DnaJ-like protein CHAPERONE-LIKE PROTEIN of POR1 concurrently act to stabilize PORB. Overall, these findings enhance our understanding of the coordinating role of cpSPR43 and cpSRP54 in the post-translational control of chlorophyll synthesis and assembly of photosynthetic chlorophyll-binding proteins.
期刊：
JOURNAL OF PROTEOME RESEARCH,2023年22(10):3254-3263 ISSN：1535-3893
通讯作者：
Li, YZ;Zhu, H
作者机构：
[Yan, Songxin; Li, YZ; Liu, Chenxi; Li, Liubing; Li, Yongzhe; Wen, Xiaoting] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Clin Lab, Beijing 100730, Peoples R China.;[Liu, Chenxi] Sichuan Univ, West China Univ Hosp 2, Dept Clin Lab, Chengdu 610041, Peoples R China.;[Song, Guang] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.;[Song, Guang; Zhu, Heng; Zhu, H] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.;[He, Yangzhige] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Cent Res Lab, Beijing 100730, Peoples R China.
通讯机构：
[Li, YZ ] C;[Zhu, H ] J;Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Dept Clin Lab, Beijing 100730, Peoples R China.;Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
摘要：
Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.
期刊：
Frontiers in Microbiology,2023年13:1112301 ISSN：1664-302X
通讯作者：
Wang, Q.;Liu, L.-N.;Qiu, B.-S.;Duanmu, D.;Ma, W.
作者机构：
[Ma, Weimin] College of Life Sciences, Shanghai Normal University, Shanghai, China;[Liu, Lu-Ning] Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom;[Wang, Qiang] State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng, China;[Duanmu, Deqiang] State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan, China;[Qiu, Bao-Sheng] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
通讯机构：
[Ma, W.] C;[Liu, L.-N.] I;[Wang, Q.; Duanmu, D.] S;[Qiu, B.-S.] H;Institute of Systems, United Kingdom
关键词：
algae;antioxidant mechanism;carbon dioxide-concentrating mechanism;carbon fixation;evolution;light energy harvesting;photosynthetic electron transfer;photosynthetic membrane complexes
作者机构：
[Wang, Wen-Shu; Gao, Xiang; Lu, Ying-Tang; Zhu, Jiang; Yan, Da-Wei; Li, Ting-Ting; Yuan, Ting-Ting; Hong, Li-Wei] Wuhan Univ, Renmin Hosp Wuhan Univ, Coll Life Sci, State Key Lab Hybrid Rice, Wuhan 430072, Peoples R China.;[Yang, Yun-Huang; Zhu, Jiang] Chinese Acad Sci, Innovat Acad Precis Measurement Sci & Technol, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan 430071, Peoples R China.;[Ren, Feng] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Wang, Wen-Shu] Wuhan Acad Agr Sci, Inst Crop Sci, Wuhan 430345, Peoples R China.
通讯机构：
[Ying-Tang Lu; Ting-Ting Yuan] S;State Key Laboratory of Hybrid Rice, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan University , Wuhan 430072, China
摘要：
Jasmonic acid (JA) signaling plays a pivotal role in plant development and defense. MYC2 is a master transcription factor in JA signaling, and was found to be phosphorylated and negatively regulated by MAP kinase and receptor-like kinase. However, the kinases that positively regulate MYC2 through phosphorylation and promote MYC2-mediated activation of JA response have not been identified. Here, we identified CK2 as a kinase that phosphorylates MYC2 and thus regulates the JA signaling. CK2 holoenzyme can interact with MYC2 using its regulatory subunits and phosphorylate MYC2 at multiple sites with its catalytic subunits. Inhibition of CK2 activity in a dominant-negative plant line, CK2mut, repressed JA response. On the other hand, increasing CK2 activity by overexpression of CKB4, a regulatory subunit gene of CK2, enhanced JA response in a MYC2-dependent manner. Substitution of the Ser and Thr residues at phosphorylation sites of MYC2 by CK2 with Ala impaired MYC2 function in activating JA response. Further investigations evidenced that CK2 facilitated the JA-induced increase of MYC2 binding to the promoters of JA-responsive genes in vivo. Our study demonstrated that CK2 plays a positive role in JA signaling, and reveals a previously undiscovered mechanism that regulates MYC2 function.
摘要：
The toxicity of microplastics (MPs) to aquatic organisms has been extensively studied recently. However, few studies have investigated the effects of MPs in sediments on aquatic ecosystem functioning. In the present study, we conducted an in situ experiment to explore the concentration-dependent effects (0.025%, 0.25%, 2.5%) and size-dependent effects (150-300 μm and 500-1000 μm) of polypropylene microplastics (PP MPs) on Vallisneria natans litter decomposition dynamics, in particular, the process associated with macroinvertebrates, microorganisms, as well as microalgae and/or cyanobacteria. The results showed that exposure to high concentrations and large sizes of PP MPs can accelerate leaf litter biomass loss and nutrition release. Moreover, microbial respiration, microalgal and/or cyanobacteria chlorophyll-a were also significantly affected by PP MPs. However, PP MPs have no effect on the abundance of associated macroinvertebrate during the experiment, despite the collection of five macroinvertebrate taxa from two functional feeding groups (i.e., collectors and scrapers). Therefore, our experiment demonstrated that PP MPs may enhance leaf litter decomposition through effected microbial metabolic activity, microalgal and/or cyanobacteria biomass in the sedimentary lake. Overall, our findings highlight that PP MPs have the potential to interfere with the basic ecological functions such as plant litter decomposition in aquatic environments.
作者机构：
[Song, Hang; Zhou, Lei; Wang, Shenqi; Ge, Jing; Xu, Pengxin] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China.;[Wan, Ying; Tan, Ronghua] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan 430074, Peoples R China.;[Gao, Qian] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan 430074, Hubei, Peoples R China.;[Li, Rui] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Shenqi Wang; Lei Zhou; Shenqi Wang Shenqi Wang Shenqi Wang; Lei Zhou Lei Zhou Lei Zhou] C;[Ying Wan; Ying Wan Ying Wan Ying Wan] N;College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China<&wdkj&>National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China
摘要：
A new type of ketamine (KA)‐loaded nanoparticle (AC‐RM@HA‐MS‐KA) with specific targeting capabilities is developed to improve the efficacy of KA treatment. They can sustainably accumulate at the N‐methyl‐d‐aspartate receptor sites, effectively alleviate depressive symptoms, circumvent KA‐induced addiction, and significantly improve cognitive functions. Abstract Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)‐ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC‐RM@HA‐MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA‐loaded NPs (AC‐RM@HA‐MS‐KA) are constructed with a multilayer core–shell structure. KA‐loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC‐membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang‐2‐Con‐G, AC) to achieve specific targeting. One peptide (Ang‐2) is acted as a guide to facilitate the crossing of the blood–brain barrier (BBB), while the other (Con‐G) is functioned as a ligand for the targeted delivery of KA to the N‐methyl‐D‐aspartate receptor sites. Animal experiments reveal that AC‐RM@HA‐MS‐KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.
