1.Herbal Cake-separated Moxibustion Improves Cognitive Function in Rat Model of Chronic Fatigue Syndrome via PI3K/Beclin1 Signaling Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):149-158
ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome (CFS) by regulating autophagy via phosphatidylinosiol 3-kinase (PI3K)/autophagy key molecule yeast Atg6 homologue 1 (Beclin1) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows: control, model, sham cake-separated moxibustion, intragastric administration with Chinese herbs, and herbal cake-separated moxibustion, each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days, and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14). The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days, rat behaviors were observed and the levels of interleukin (IL)-4, IL-10, blood urine nitrogen (BUN), and malondiadehyde (MDA) in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultsCompared with the normal group, the model group showed reduced crossings, shortened residence time in the target quadrant, and prolonged average escape latency on days 1, 2, 3, and 4 (P<0.01) in the Morris water maze test. In the new object recognition test, the model group showed decreased recognition index of exploration time and recognition index of exploration times (P<0.01), lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus (P<0.01), and down-regulated mRNA and protein levels of PI3K and Beclin1 (P<0.01). After treatment, compared with the model group, each treatment group showed increased crossings, prolonged residence time in the target quadrant, and shortened average escape latency on days 1, 2, 3, and 4 (P<0.05, P<0.01). In addition, the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus (P<0.05, P<0.01), and up-regulated the mRNA and protein levels of PI3K and Beclin1 (P<0.05, P<0.01). Compared with the sham cake-separated moxibustion group, the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings, prolonged residence time in the target quadrant (P<0.05), elevated level of IL-4, lowered level of MDA, and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus (P<0.05, P<0.01). The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 (P<0.05, P<0.01). In addition, this group showed elevated serum level of IL-4, lowered serum level of MDA, and declined BUN level in the hippocampus (P<0.05, P<0.01). Compared with the intragastric administration with Chinese herbs group, the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 (P<0.05) and relative protein levels of PI3K and Beclin1 (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory, reduce inflammatory response and oxidative stress, and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.
2.Herbal Cake-separated Moxibustion Improves Cognitive Function in Rat Model of Chronic Fatigue Syndrome via PI3K/Beclin1 Signaling Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):149-158
ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome (CFS) by regulating autophagy via phosphatidylinosiol 3-kinase (PI3K)/autophagy key molecule yeast Atg6 homologue 1 (Beclin1) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows: control, model, sham cake-separated moxibustion, intragastric administration with Chinese herbs, and herbal cake-separated moxibustion, each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days, and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14). The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days, rat behaviors were observed and the levels of interleukin (IL)-4, IL-10, blood urine nitrogen (BUN), and malondiadehyde (MDA) in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultsCompared with the normal group, the model group showed reduced crossings, shortened residence time in the target quadrant, and prolonged average escape latency on days 1, 2, 3, and 4 (P<0.01) in the Morris water maze test. In the new object recognition test, the model group showed decreased recognition index of exploration time and recognition index of exploration times (P<0.01), lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus (P<0.01), and down-regulated mRNA and protein levels of PI3K and Beclin1 (P<0.01). After treatment, compared with the model group, each treatment group showed increased crossings, prolonged residence time in the target quadrant, and shortened average escape latency on days 1, 2, 3, and 4 (P<0.05, P<0.01). In addition, the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus (P<0.05, P<0.01), and up-regulated the mRNA and protein levels of PI3K and Beclin1 (P<0.05, P<0.01). Compared with the sham cake-separated moxibustion group, the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings, prolonged residence time in the target quadrant (P<0.05), elevated level of IL-4, lowered level of MDA, and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus (P<0.05, P<0.01). The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 (P<0.05, P<0.01). In addition, this group showed elevated serum level of IL-4, lowered serum level of MDA, and declined BUN level in the hippocampus (P<0.05, P<0.01). Compared with the intragastric administration with Chinese herbs group, the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 (P<0.05) and relative protein levels of PI3K and Beclin1 (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory, reduce inflammatory response and oxidative stress, and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.
3.Mechanism of Herbal Cake-separated Moxibustion in Improving Neuroimmune Inflammation in Rats with Chronic Fatigue Syndrome by Interfering TLR4/MyD88/NF-κB Pathway
Chuntao ZHAI ; Yawei HOU ; Linjuan SHI ; Yixiao WANG ; Wei LI ; Yuefeng TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):140-149
ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome (CFS) rats, based on the regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups: Normal group, model group, sham herbal cake moxibustion group, Chinese medicine intragastric administration group, and herbal cake-separated moxibustion group, with 10 rats in each group. Except for the normal group, all other groups underwent a 21-day modeling process, followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque (CV8), Guanyuan (CV4), Zusanli (ST36), and Qimen (LR14) acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), as well as hippocampal levels of IL-1β, IL-6, TNF-α, and NF-κB, were detected by enzyme-linked immunosorbent assay (ELISA). Morphological changes in the hippocampus were observed using hematoxylin-eosin (HE) staining. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of TLR4, MyD88, and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4, MyD88, NF-κB, and p65 proteins in the hippocampus. ResultsCompared with the normal group, the model group showed a significant decrease in upright times during the open field test (P<0.01), as well as significant reductions in total movement distance, resting time, and center region duration (P<0.01). In the tail suspension test, immobility time increased (P<0.01), and struggle times decreased (P<0.01). Serum and hippocampal levels of IL-1β, IL-6, and TNF-α, as well as hippocampal NF-κB levels and TLR4, MyD88, and NF-κB mRNA expression, were significantly elevated (P<0.01). After treatment, compared with the model group, the total movement distance and upright times in the open field test were significantly increased in all treatment groups (P<0.01), while resting time and center region duration were notably prolonged (P<0.05, P<0.01). Immobility time in the tail suspension test was significantly shortened (P<0.01), and struggle times significantly increased (P<0.05). Serum and hippocampal levels of IL-1β, IL-6, TNF-α, hippocampal NF-κB levels, and TLR4 and NF-κB mRNA expression were significantly reduced (P<0.05, P<0.01). Compared with the sham herbal cake moxibustion group, the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test (P<0.05) and a significant increase in upright times (P<0.01). In the tail suspension test, immobility time was reduced (P<0.01), and struggle times increased (P<0.01). Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced (P<0.01), while serum IL-6 levels, as well as hippocampal levels of IL-1β, TNF-α, NF-κB, and TLR4, MyD88, and NF-κB mRNA expression, were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group (P<0.05, P<0.01). Compared with the Chinese medicine intragastric administration group, the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test (P<0.01). In the tail suspension test, immobility time was reduced (P<0.01), and struggle times increased (P<0.01). Serum IL-1β, hippocampal TNF-α levels, and TLR4, MyD88, and NF-κB mRNA expression were significantly decreased (P<0.05, P<0.01). ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats, regulates neuroimmune inflammatory responses, and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.
4.Correlation between soluble α-Klotho levels with diabetic kidney disease and blood glucose control during continuous blood glucose monitoring
Linjuan LI ; Junchen ZHENG ; Mei ZHANG ; Rui WANG ; Ning YANG
Chinese Journal of Diabetes 2024;32(5):343-346
Objective To analyze the relationship between soluble α-Klotho(SKL)levels and continuous glucose monitoring(CGMS)-derived measures of glycemic management in diabetic kidney disease(DKD)patients.Methods A total of 140 T2DM patients admitted to the Department of General Medicine Affiliated Hospital of Yan'an University from May 2020 to May 2022 were selected and divided into two groups according to the levels of UACR:T2DM group(UACR<30 mg/g,n=60),DKD group(UACR≥30 mg/g,n=80)and 45 healthy persons(NC group)who received physical examination in the hospital during the same period were the NC group.Results The SKL level of DKD group was lower than that of T2DM group and NC group(P<0.05).Spearman correlation analysis showed that SKL was positively correlated with eGRF and TIR(P<0.01),and negatively correlated with Scr,UACR,CysC,β2-MG,FPG,HbA1c,MG,TAR and GMI(P<0.01).Multiple linear regression analysis showed that HbA1c and GMI were the influencing factors of SKL.Conclusion The level of SKL in DKD patients is correlated with HbA1c and GMI.
5.Summary of the best evidence for peripheral arterial catheters placement and management in pediatric intensive care unit
Min ZHOU ; Qin FU ; Linjuan WANG ; Zerui ZHENG ; Chuhao ZHANG ; Xiaozhen ZHENG ; Jing JING
Chinese Journal of Nursing 2024;59(10):1255-1262
Objective To retrieve,evaluate and summarize the best pertinent evidence on the placement and management of peripheral arterial catheters in critically ill children at home and abroad for clinical references.Methods A systematic search was conducted in related databases on the evidence of the placement and management of peripheral arterial catheters in critically ill children.The spectrum of eligible documents included clinical decisions,guidelines,evidence summaries,systematic reviews,expert consensuses,and norms.The search period was from the establishment of the databases to April 30,2023.The included literature was limited to English and Chinese languages.The quality of the literature was independently evaluated by evidence-based trained investigators and combined with professional judgment to extract information from the literature that met the quality standards.Results A total of 18 articles were included,including 3 guidelines,3 clinical decisions,8 evidence summaries,3 systematic reviews and 1 expert consensus.The best evidence included a total of 27 pieces of evidence in 4 areas,namely the assessment of indwelling peripheral arterial catheters,placement of peripheral arterial catheters,maintenance during the duration of indwelling peripheral arterial catheters,and removal.Conclusion This study summarized the most robust evidence pertaining to the management of peripheral arterial catheters in critically ill children,and provided an evidence-based basis for the standardized placement and management of peripheral arterial catheters in critically ill children.Nursing staff should carefully select and apply evidence according to the actual clinical situation,the wishes of children and parents.
6.The effects rehabilitation timing on the motor functioning of children with a traumatic brain injury
Zerui ZHENG ; Qin FU ; Min ZHOU ; Jianguo CAO ; Linjuan WANG ; Fanling MENG
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(11):983-987
Objective:To document any impact of the timing of rehabilitation interventions on the recovery of motor function among children after a traumatic brain injury (TBI).Methods:Seventy-one children with a TBI were randomly divided into a control group ( n=36) and an observation group ( n=35). All received comprehensive rehabilitation-15 to 30 days after admission for those in the control group and 2 to 14 days after admission for the observation group. It included joint range-of-motion training, multi-sensory stimulation training, low-frequency electrical stimulation, and acupuncture. Before the experiment and 4, 12 and 24 weeks afterward, everyone′s motor functioning, muscle tone, and functional independence were quantified using the Fugl-Meyer Assessment (FMA), the Modified Ashworth Scale (MAS), and the WeeFIM pediatric functional independence measure. Results:Four weeks after the intervention the average FMA and WeeFIM scores of both groups had already increased significantly. At 12 and 24 weeks the average FMA and WeeFIM scores of the observation group were significantly higher than the control group′s averages. Muscle tone was then also significantly better on average. There was no significant difference in the incidence of rehabilitation interruptions between the two groups.Conclusion:Early comprehensive rehabilitation intervention within 2 to 14 days of admission can effectively better the motor functioning and functional independence of pediatric TBI patients.
7.Reliability and Validity Analysis on Symptom Identification Scale for Vascular Cognitive Impairment with Kidney Yang Deficiency
Chunyan GUO ; Chen FU ; Zhenmin XU ; Min WANG ; Ying ZHANG ; Xiaobing HOU ; Tao LI ; Huanmin NIU ; Linjuan SUN ; Yunling ZHANG ; Baoxin CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):153-157
Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.
8.A multicenter survey on nurses'knowledge and practice of children's sleep management in pediatric ICU
Xiaorui FAN ; Ying GU ; Jing HU ; Shaodan QI ; Linxi HE ; Wenlan ZHANG ; Linjuan WANG ; Weijie SHEN ; Yuxia YANG
Chinese Journal of Nursing 2024;59(4):447-454
Objective To investigate the current status of nurses'knowledge,attitude and practice regarding sleep management of critically ill children in pediatric ICU,and to analyze its impact factors.Methods A self-designed questionnaire on general information and a questionnaire on knowledge and practical behaviors of pediatric ICU nurses on child's sleep management were used.In March 2023,902 pediatric ICU nurses from 24 hospitals in China were surveyed using a convenient sampling method,and the impact factors were analyzed using multiple stepwise linear regression.Results 893 valid questionnaires were collected and the recovery rate of valid questionnaires was 99.00%.Nurses in pediatric ICU scored(33.71±7.76)in knowledge dimension,(37.38±4.86)in attitude dimension and(80.60±16.78)in practice dimension,with a total score of(151.78±24.27).The scores of knowledge and attitude,knowledge and practice,attitude and practice are all positively correlated(r=0.393,P<0.001;r=0.495,P<0.001;r=0.320,P<0.001).The results of multiple stepwise linear regression analysis showed that gender,region,whether they had received sleep management training were the influencing factors of pediatric ICU nurses'total score of knowledge,attitude and practice towards children's sleep management(P<0.05).Conclusion Nurses in pediatric ICU are positive about sleep management for critically ill children,but their knowledge and practice levels need to improve.Nursing managers should strengthen the theoretical knowledge and practical behavioral training of pediatric ICU nurses on child sleep management,develop scientific sleep management plans,and guide nurses to make reasonable evaluation and interventions to improve children's sleep quality.
9.Correlation between the varicella incidence and temperature in Minhang District, Shanghai
Xia ZHAO ; Linjuan DONG ; Yibin ZHOU ; Zhaowen ZHANG ; Jinsong CUI ; Jialei FAN ; Chenxi XU ; Dunjia WANG
Shanghai Journal of Preventive Medicine 2024;36(8):753-759
ObjectiveTo explore the exposure-lag-response relationship between temperature and risk of varicella incidence,and to provide a scientific evidence for early warning and precise prevention and control of varicella epidemic. MethodsDaily varicella cases and daily meteorological data were collected in Minhang District, Shanghai from 2010 to 2022. A distributed lag nonlinear model was used to determine the exposure-lag-response relationship between temperature and risk of varicella incidence. Furthermore, effect of temperature on the incidence risk was determined across different age groups. ResultsIn 2010‒2022, the total number of notified varicella cases was 26 207 in Minhang District, with the highest incidence in the group aged 3‒14 years (50.35%). The seasonal pattern of daily varicella cases showed a double peak. The large peak was found in November and December, followed by a smaller peak in May and June. Moreover, the distributed lag nonlinear model showed a unimodal curve in the relationship between temperature and varicella incidence. The RR value reached its maximum peak of 1.90 (95%CI: 1.25‒2.87) at 7 ℃. A reverse U-shape was found in the lag-response curves between temperature and varicella incidence. Furthermore, the effect of temperature on the varicella incidence showed a unimodal pattern in the varicella cases aged 3‒14 years. The RR value reached its peak at 11 ℃ (RR=2.89, 95%CI: 1.33‒6.24). In contrast, the effect of temperature on the varicella incidence in the cases aged 15 years and above showed a unimodal pattern, with RR value reaching the peak at 5 ℃ (RR=2.14, 95%CI: 1.33‒3.44). ConclusionThe unimodal curve is found in the relationship between temperature and varicella incidence. Low temperature is associated with increased risk of varicella incidence. Children aged 3‒14 years are more susceptible to the effect of temperature on the varicella incidence.
10.The two-stage interaction of Ebola virus VP40 with nucleoprotein results in a switch from viral RNA synthesis to virion assembly/budding.
Linjuan WU ; Dongning JIN ; Dan WANG ; Xuping JING ; Peng GONG ; Yali QIN ; Mingzhou CHEN
Protein & Cell 2022;13(2):120-140
Ebola virus (EBOV) is an enveloped negative-sense RNA virus and a member of the filovirus family. Nucleoprotein (NP) expression alone leads to the formation of inclusion bodies (IBs), which are critical for viral RNA synthesis. The matrix protein, VP40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. However, the molecular mechanism by which VP40 regulates viral RNA synthesis and virion assembly/budding is unknown. Here, we show that within IBs the N-terminus of NP recruits VP40 and is required for VLP-containing NP release. Furthermore, we find four point mutations (L692A, P697A, P698A and W699A) within the C-terminal hydrophobic core of NP result in a stronger VP40-NP interaction within IBs, sequestering VP40 within IBs, reducing VP40-VLP egress, abolishing the incorporation of NC-like structures into VP40-VLP, and inhibiting viral RNA synthesis, suggesting that the interaction of N-terminus of NP with VP40 induces a conformational change in the C-terminus of NP. Consequently, the C-terminal hydrophobic core of NP is exposed and binds VP40, thereby inhibiting RNA synthesis and initiating virion assembly/budding.
Ebolavirus/physiology*
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HEK293 Cells
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HeLa Cells
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Humans
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Nucleocapsid Proteins/metabolism*
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RNA, Viral/metabolism*
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Viral Matrix Proteins/metabolism*
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Virion/metabolism*
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Virus Assembly

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