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Regulations of m^(6)A and other RNA modifications and their roles in cancer

Frontiers of Medicine 2024年第4期18卷 622-648页

作者： Xin-Hui Chen Kun-Xiong Guo Jing Li Shu-Hui Xu Huifang Zhu Guang-Rong Yan Biomedicine research Center Guangdong Provincial Key Laboratory of Major Obstetric DiseaseGuangdong Provincial Clinical Research Center for Obstetrics and GynecologyState Key Laboratory of Respiratory Diseasethe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhou510150China

RNA modification is an essential component of the epitranscriptome,regulating RNA metabolism and cellular *** types of RNA modifications have been identified to date;they include N^(6)-methyladenosine(m^(6)A),N^(1)-methyladenosine(m1A),5-methylcytosine(m5C),N^(7)-methylguanosine(m^(7)G),N^(6),2′-O-dimethyladenosine(m^(6)Am),N4-acetylcytidine(ac^(4)C),*** modifications,mediated by regulators including writers,erasers,and readers,are associated with carcinogenesis,tumor microenvironment,metabolic reprogramming,immunosuppression,immunotherapy,chemotherapy,etc.A novel perspective indicates that regulatory subunits and post-translational modifications(PTMs)are involved in the regulation of writer,eraser,and reader functions in mediating RNA modifications,tumorigenesis,and anticancer *** this review,we summarize the advances made in the knowledge of different RNA modifications(especially m^(6)A)and focus on RNA modification regulators with functions modulated by a series of factors in cancer,including regulatory subunits(proteins,noncoding RNA or peptides encoded by long noncoding RNA)and PTMs(acetylation,SUMOylation,lactylation,phosphorylation,etc.).We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer ***,inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

关键词： RNA modification writers erasers readers regulatory subunits PTMs cancer

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Magnitude and direction of temperature variability affect hospitalization for myocardial infarction and stroke:population-based evidence from Guangzhou,China

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 1-11页

作者： Zhou Yang Murui Zheng Ze-Lin Yan Hui Liu Xiangyi Liu Jie-Qi Jin Jiagang Wu Chun-Quan Ou State key laboratory of Organ Failure research Department of BiostatisticsGuangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou 510515China Guangzhou Center for disease Control and Prevention Guangzhou 510440China

Relationships between nonoptimal temperatures and cardiovascular disease(CVD)mortality have been well ***,evidence of the association between temperature variability(TV)and CVD morbidity is *** study aimed to quantify the risk and burden of CVD-related hospitalization associated with the magnitude and direction of *** on meteorology and population-based hospitalizations for myocardial infarction(MI)and stroke were collected in Guangzhou,China,from 2013 to *** temperature variability(HTV)was measured as the standard deviation of hourly temperature records over specific exposure *** direction(upward or downward)of HTV was defined as the average daily mean temperature change relative to that of the previous day during the exposure ***-Poisson regression was applied to assess the impact of HTV after adjusting for the daily mean temperature,and the hospitalization fractions attributable to HTV were calculated.A 1℃-increase in HTV was significantly associated with a 2.24%and 1.72%increase in hospitalizations for MI and hemorrhagic stroke(HS)at lag 0–1 d,respectively,and a 1.55%increase in hospitalizations for ischemic stroke(IS)at lag 0–3 *** the study period,5.99%,4.64%,and 4.53%of MI,HS,and IS hospitalizations,respectively,were attributable to *** upward TV exerts acute effects on CVD hospital admissions,whereas the impact of downward TV generally *** findings highlight the importance of the magnitude and direction of temperature fluctuations,in addition to the mean level,in assessing the adverse health impacts of temperature variations.

关键词： Hourly temperature variability Cardiovascular Hospitalization Direction China

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Dopamine Inhibits the Expression of Hepatitis B Virus Surface and e Antigens by Activating the JAK/STAT Pathway and Upregulating Interferon-stimulated Gene 15 Expression

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Journal of Clinical and Translational Hepatology 2024年第5期12卷 443-456页

作者： Xiaoquan Liu Xiuqing Pang Zhiping Wan Jinhua Zhao Zhiliang Gao Hong Deng Department of Infectious diseases Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina guangdong key laboratory of liver disease research Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou GuangdongChina key laboratory of Tropical disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouGuangdongChina

Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be *** previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into *** present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying ***:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression *** analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated *** knocked down ISG15 and then monitored HBsAg and HBeAg expression *** analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated *** used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg *** virus was collected from HepAD38.7 cell culture ***:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell ***15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 ***-treated cells activated the JAK/STAT pathway,which upregulated ISG15 *** the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 ***:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.

关键词： Hepatitis B virus Dopamine JAK-STAT/ISG15 axis HBV surface antigen HBV e antigen HepG2.2.15 cell line Human NTCP-expressing HepG2 cell line HepAD38 cell line

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Viral hepatitis E:Clinical manifestations,treatment,and prevention

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肝脏研究（英文） 2024年第1期8卷 11-21页

作者： Qiumin Luo Jia Chen Yeqiong Zhang Wenxiong Xu Ying Liu Chan Xie Liang Peng Department of Infectious disease The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina guangdong key laboratory of liver disease research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing *** the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)*** acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver ***,some immunocompromised patients are at risk of developing chronic HEV infection and *** screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis *** review focused on the clinical presentation,management,and prevention of hepatitis E.

关键词： Hepatitis E Chronic hepatitis Screening Antiviral therapy Vaccination

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Effects of hydroxyproline supplementation in low fish meal diets on collagen synthesis, myofiber development and muscular texture of juvenile Pacific white shrimp(Litopenaeus vannamei)

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Animal Nutrition 2024年第2期17卷 428-437页

作者： Menglin Shi Haoming Li Tianyu Chen Bocheng Huang Xiaoyue Li Xiaohui Dong Shuyan Chi Qihui Yang Hongyu Liu Junming Deng Beiping Tan Shuang Zhang Shiwei Xie laboratory of Aquatic Nutrition and Feed College of Fisheries Guangdong Ocean University Aquatic Animals Precision Nutrition and High-Efficiency Feed Engineering research Centre of guangdong Province key laboratory of Aquatic Livestock and Poultry Feed Science and Technology in South China Ministry of Agriculture guangdong provincial key Lab of Aquatic Animals disease Control and Healthy Culture

This experiment aimed to evaluate the impact of dietary hydroxyproline(Hyp) supplementation on the muscle quality of juvenile Pacific white shrimp(Litopenaeus vannamei) fed a low fishmeal diet. Six formulated diets included one high fishmeal(HF; 25% fishmeal content) and five low fishmeal diets(10%fishmeal content) with 0%, 0.2%, 0.4%, 0.6% and 0.8% Hyp(LF0, LF2, LF4, LF6 and LF8, respectively). Each diet was assigned to four replicates, and 40 shrimp(0.32 ± 0.00 g) per replicate were fed four times a day for 8 weeks. Dietary Hyp supplementation had little effects on growth performance, but increased the contents of Hyp, prolyl 4-hydroxylases(P4Hs), and collagen. The meat yield, springiness, hardness,chewiness, and cohesiveness of muscle were the highest in the LF4 group among the low fishmeal groups(P < 0.05). Cooking loss and freezing loss of muscle were the lowest in the LF4 group(P < 0.05). Dietary supplementation with 0.4% Hyp increased the myofiber density and decreased the myofiber diameter of muscle(P < 0.05). Supplementation of Hyp in the diet up-regulated the mRNA expression of smyhc5,smyhc15, col1a1, col1a2, igf-1f, tgf-β and tor and down-regulated the mRNA expression of smyhc1, smyhc2,smyhc6a(P < 0.05). Supplementation of Hyp in the diet up-regulated the protein expression of P-4E-BP1,P-AKT, AKT and P-AKT/AKT(P < 0.05). These results suggested that the addition of 0.4% Hyp to low fishmeal diets improved the muscle quality of L. vannamei.

关键词： Hydroxyproline Collagen Muscle quality Litopenaeus vannamei

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Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma

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肝脏研究（英文） 2024年第2期8卷 105-117页

作者： Huan Wei Songhao Luo Yanhua Bi Chunhong Liao Yifan Lian Jiajun Zhang Yuehua Huang guangdong provincial key laboratory of liver disease research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina School of Mathematics Sun Yat-sen UniversityGuangzhouChina guangdong provincial key laboratory of liver disease research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina School of Public Health Sun Yat-sen UniversityGuangzhouChina School of Mathematics Sun Yat-sen UniversityGuangzhouChina guangdong Province key laboratory of Computational Science Sun Yat-sen UniversityGuangzhouChina guangdong provincial key laboratory of liver disease research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Infectious diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively *** aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning *** study was the first large-scale investigation of these two miRNAs in HCC plasma samples.Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with *** diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC.Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P＜0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3％,AP=0.80)and miR-16(AUC=0.83,79.0％,AP=0.83)than for AFP(AUC=0.74,61.7％,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9％)and the AP to 0.85 and was significantly superior to the other markers in this study(P＜0.05 for all),as further demonstrated by the detection error tradeoff ***,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these ***,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16.Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

关键词： Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) microRNA-15a microRNA-16-1 Biomarker Machine learning Pseudotemporal ordering

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Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B

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liver research 2024年第3期8卷 179-187页

作者： Lina Wu Jiadi Lai Qiumin Luo Yeqiong Zhang Chaoshuang Lin Dongying Xie Youming Chen Hong Deng Zhiliang Gao Liang Peng Wenxiong Xu Department of Infectious diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina guangdong key laboratory of liver disease research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina key laboratory of Tropical disease Control Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdongChina

Background and aim Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA *** Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation ***,clinical,and laboratory data were collected and analyzed after NA *** Ninety-six patients who finished 5 years of follow-up were *** remained undetectable in 29 patients with end of treatment(EOT)HBsAg *** 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9%)patients with an estimated annual incidence of HBsAg seroclearance of 3.6%.Patients with EOT HBsAg levels of≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of>1000 IU/mL(33.3%vs.5.4%).The proportion of patients with HBsAg≤1000 IU/mL increased during *** regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/*** optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/*** Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of≤1000 IU/mL during 5 years of follow-up after NA *** monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

关键词： Hepatitis B virus(HBV) Chronic hepatitis B(CHB) Hepatitis B surface antigen(HBsAg) Nucleos(t)ide analogs(NAs) Quantitative HBsAg Kinetics

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Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients

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World Journal of Gastroenterology 2024年第23期30卷 3005-3015页

作者： Yan-Fen Xu Hui-Yun Ma Gui-Ling Huang Yu-Ting Zhang Xue-Yan Wang Ming-Jie Wei Xiao-Qing Pei Department of Ultrasound State Key Laboratory of Oncology in South ChinaGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of Radiology State Key Laboratory of Oncology in South ChinaGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of Medical Ultrasound State Key Laboratory of Oncology in South ChinaGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the *** disease poses a serious public health problem in China,ranking fifth for incidence and third for *** of the invasive depth of the tumor is vital to treatment *** To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March *** underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T *** of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging *** diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold *** A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were *** accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of *** DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

关键词： Double contrast-enhanced ultrasonography Multi-detector computed tomography Gastric cancer T staging

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Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3467-3482页

作者： Zhan-Li Chen Chen Xie Wei Zeng Rui-Qi Huang Jin-E Yang Jin-Yu Liu Ya-Jing Chen Shi-Mei Zhuang MOE key laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional GenesSchool of Life SciencesState Key Laboratory of Oncology in Southern ChinaSun Yat-sen UniversityGuangzhouPR China key laboratory of liver disease of guangdong Province The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630PR China

Mitotic catastrophe(MC),which occurs under dysregulated mitosis,represents a fascinating tactic to specifically eradicate tumor *** pyroptosis can be a death form of MC remains ***-mediated protein degradation is crucial for ***(BTZ),which inhibits the 20S catalytic particle of proteasome,is approved to treat multiple myeloma and mantle cell lymphoma,but not solid tumors due to primary *** date,whether and how proteasome inhibitor affected the fates of cells in M-phase remains ***,we show that BTZ treatment,or silencing of PSMC5,a subunit of 19S regulatory particle of proteasome,causes G2-and M-phase arrest,multi-polar spindle formation,and consequent caspase-3/GSDME-mediated pyroptosis in M-phase(designated as mitotic pyroptosis).Further investigations reveal that inhibitor of WEE1/PKMYT1(PD0166285),but not inhibitor of ATR,CHK1 or CHK2,abrogates the BTZ-induced G2-phase arrest,thus exacerbates the BTZ-induced mitotic arrest and *** BTZ and PD0166285 treatment(named BP-Combo)selectively kills various types of solid tumor cells,and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 *** using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment,and no obvious toxicity is observed in BP-Combo-treated *** findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase,characterize pyroptosis as a new death form of mitotic catastrophe,and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

关键词： proteasome inhibiting catastrophe

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Dietary black soldier fly oil enhances growth performance,flesh quality,and health status of largemouth bass(Micropterus salmoides)

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Animal Nutrition 2024年第3期18卷 234-245页

作者： Hailin Yuan Junru Hu Xiangce Li Qiuxuan Sun Xiaohong Tan Cuihong You Yewei Dong Yanhua Huang Meng Zhou Innovative Institute of Animal Healthy Breeding College of Animal Sciences and TechnologyZhongkai University of Agriculture and EngineeringGuangzhouGuangdong 510225China Guangzhou key laboratory of Aquatic Animal diseases and Waterfowl Breeding GuangzhouGuangdong 510225China guangdong provincial Water Environment and Aquatic Products Security Engineering Technology research Center GuangzhouGuangdong 510225China guangdong provincial key laboratory of Animal Breeding and Nutrition research GuangzhouGuangdong 510640China

The study aimed to assess the effects of dietary black soldier fly oil(BSFO)on the growth performance,flesh quality,and health status of largemouth bass(Micropterus salmoides).Six iso-nitrogenous and isolipid diets were formulated by substituting fish oil and soybean oil(1/2,wt/wt)with BSFO in percentages of 0%,20%,40%,60%,80%,and 100%,*** diets were fed to 960 fish(initial body weight=16.5 g)in four replicates for 8 *** related to growth performance,body composition,hematology,flesh quality,expression of genes related to inflammatory cytokines and apoptosis,and the response of fish to Aeromonas veronii challenge were *** results showed that the weight gain rate was numerically improved in all BSFO substitution groups,ranging from 9.3%to 44.0%compared to the control *** highest survival rate and the lowest hepatosomatic index and condition factor were observed in the BFSO20 *** terms of flesh quality,the water-holding capacity of the dorsal muscle was elevated with higher levels of dietary ***,significant changes in texture properties(cohesiveness,gluing,and chewiness)were observed in the BSFO20 group(Pliver function were optimized in most of the BFSO substitution ***,the expressions of six inflammation-and apoptosis-related genes(IL-1β,Bcl-xl,BAX,caspase8,TNF-α,and IL-10)were significantly affected by dietary BSFO(P<0.05).Following bacterial challenge,the seven-day cumulative survival rates of fish were considerably increased from 10.0%in the control group to 60.0%and 66.7%in the BSFO80 and BSFO100 groups,***-variable linear regression analysis revealed that various parameters related to fish growth,flesh quality,and health status were significantly influenced by dietary BSFO substitution levels in a dose-dependent manner(P<0.05).In conclusion,substituting around 20%of dietary fish oil and soybean oil with BSFO is promisin

关键词： Micropterus salmoides Black soldier fly oil(BSFO) Growth performance Flesh quality Health status

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