1.Surveillance of Oncomelania hupensis snails following interruption of schistosomiasis transmission in Yunnan Province
Siqi NING ; Yi DONG ; Chunhong DU ; Lifang WANG ; Yun ZHANG ; Yuhe HE ; Hua JIANG ; Jiayu SUN ; Chunqiong CHEN ; Jiaqi YAN ; Jihua ZHOU ; Zongya ZHANG ; Hongqiong WANG ; Meifen SHEN ; Jing SONG
Chinese Journal of Schistosomiasis Control 2026;38(2):200-206
Objective To investigate the distribution characteristics of Oncomelania hupensis snails in Yunnan Province fol-lowing interruption of schistosomiasis transmission, so as to provide the evidence for assessing the risk of schistosomiasis transmission and scientifically formulating the schistosomiasis surveillance program. Methods According to the requirements of the National Schistosomiasis Surveillance Scheme (2020 Edition), O. hupensis snail surveillance data were collected from 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province from 2020 to 2024, including area of snail survey, area of snail habitats, area of re-emerging snail habitats, number of frames surveyed, number of frames with O. hupensis snails, number of O. hupensis snails captured, and number of living snails, and the occurrence of frames with snails and mean density of living snails were calculated. Changes in snail status over the 5-year period from 2020 to 2024 and the differences in snail distributions specified by epidemic intensity, environmental type, and vegetation type were analyzed. Results The areas of snail survey increased from 1 727.96 hm2 in 2020 to 3 894.45 hm2 in 2024 (peak) across 18 schistosomiasis-endemic counties (cities, districts) in Yunnan Province during the period from 2020 through 2024. The areas of snail habitats increased from 70.36 hm2 in 2020 to a peak in 2023 (172.04 hm2), followed by a reduction to 132.36 hm2 in 2024, and the areas of re-emerging snail habitats increased from 42.71 hm2 in 2020 to a peak in 2022 (78.43 hm2), followed by a reduction to 40.21 hm2 in 2024. The occurrence of frames with snails and mean density of living snails increased from 1.24% (3 025/244 404) and (0.033 2 ± 0.038 7) snails/0.1 m2 in 2020 to peaks at 2.03% (6 231/307 563) and (0.066 9 ± 0.068 4) snails/0.1 m2 in 2023, followed by reductions to 1.04% (5 829/559 941) and (0.032 6 ± 0.057 7) snails/0.1 m2 in 2024, respectively. There was a significant difference in the occurrence of frames with snails over the 5-year study period (χ2 = 1 962.95, P < 0.05), and the occurrence of frames with snails reduced by 48.71% in 2024 relative to in 2023 (χ2 = 1 411.05, P < 0.005); however, there was no significant difference in the mean density of living snails over the 5 years (H = 5.310, P > 0.05). There were significant differences in the occurrence of frames with snails (χ2 = 481.27, P < 0.05) and mean density of living snails (H = 6.872, P < 0.05) in schistosomiasis-endemic areas with different epidemic intensities. The occurrence of frames with snails (χ2 = 25.32 and 38.70, both P values < 0.017) and mean density of living snails (Z = 28.55 and 49.96, both P values < 0.017) were higher in schistosomiasis transmission-interrupted and eliminated areas with snails than in schistosomiasis-eliminated areas without snails, and the occurrence of frames with snails (χ2 = 453.54, P < 0.017) and mean density of living snails (Z = −56.97, P < 0.017) were higher in schistosomiasis-eliminated areas with snails than in schistosomiasis transmission-interrupted areas with snails. O. hupensis snails were mainly distributed in paddy fields, dry farmlands and ditches; however, the occurrence of frames with snails (13.40%, 424/3 164) and mean density of living snails [(0.252 8 ± 0.158 7) snails/0.1 m2] were higher in ponds/weirs than in other types of environments (both P values < 0.05). Rice, dry farmland crops and weeds were main vegetations in which O. hupensis snails were distributed, and the occurrence of frames with snails (2.29%, 7 111/310 140) and mean density of living snails [(0.072 3 ± 0.018 9) snails/0.1 m2] were higher in weeds than in other types of environments (both P values < 0.05). Conclusions O. hupensis snails have been effectively controlled in Yunnan Province following implementation of integrated schistosomiasis control measures; however, there are still risk factors for schistosomiasis transmission, including reduced attention to schistosomiasis control and snail re-emergence. Improved control efforts and surveillance system construction and timely identification of risk factors of snail status and timely management are recommended to ensure the achievement of the target of schistosomiasis elimination as scheduled.
2.Identification and infection rate of densovirus in Culex pipiens pallens in Beijing in 2023
Xiu-yan XU ; Ting YAN ; Si-jie ZHU ; Jing LI ; Mei-de LIU ; Hong-jiang ZHANG ; Ting LIU ; Qiu-hong LI ; Xiao-jie ZHOU ; Ying TONG ; Yong ZHANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):25-30
Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.
3.A review of non-pharmacological interventions for lipid management in breast cancer survivors: a summary of the evidence
Jianxin TU ; Xiaomei HU ; Xintong DENG ; Ying TANG ; Yan JIANG ; Jing ZHOU
Chinese Journal of Practical Nursing 2025;41(17):1315-1322
Objective:To integrate the best evidence of non drug intervention for blood lipid management of breast cancer survivors used the evidence-based method, and provide evidence-based evidence for clinical medical staff to carry out dynamic monitoring and management of blood lipid abnormalities.Methods:According to the 6S model, the evidence summary, clinical decision, recommended practice, guidelines, systematic review, expert consensus, scientific position statement and other non-drug interventions on lipid management of breast cancer survivors were systematically searched from the evidence-based guidelines website and related databases from database establishment until June 10, 2024. The quality of the included literature was evaluated, and the evidence was extracted, summarized and formed.Results:A total of 14 literatures were included, including 7 guidelines, 5 expert consensus and 2 systematic reviews. Totally 21 best evidences were collected from the necessity of lipid management, lipid management objectives, individualized lipid monitoring and lipid management strategies.Conclusions:The quality and level of the best evidence collected in this study are generally high, which has reference significance for clinical medical staff to carry out scientific and effective non drug intervention in lipid management of breast cancer survivors. In the evidence transformation stage, it is necessary to fully consider the individual differences of patients, in order to improve the intervention effect and the quality of life of patients.
4.Comparative analysis of social skills and problem behaviors between children and adolescents with ASD and ADHD
Li SONG ; Xiaoru JIANG ; Qin ZHOU ; Zenghe YUE ; Jiaxue LIU ; Ke XU ; Yuxin QIAN ; Nana QIU ; Jing XU ; Xiaoyan KE
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(4):316-322
Objective:To explore the characteristics of social skills and problem behaviors of children and adolescents with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), as well as the association with core symptoms.Methods:A total of 409 patients aged 5-18 years old with ASD or ADHD in the outpatient department of Nanjing Brain Hospital from 2023 to 2024, and 344 children and adolescents with typical development(TD) were recruited.All participants were matched in a ratio of 1∶1∶1 (ASD∶ADHD∶TD) according to gender and age, and 97 participants were included in each group for analysis.The Chinese version of the social skills improvement system rating scales(SSIS-RS-C) was used to evaluate social skills and problem behaviors, and autistic child behavior checklist(ABC), childhood autism rating scale(CARS), the Chinese version of the social communication questionnaire(SCQ) and the Chinese version of Swanson, Nolan, and Pelham, version Ⅳ scale-parent form(SNAP-Ⅳ) were used to evaluate the core symptoms of ASD and ADHD, respectively. SPSS 26.0 software was used to perform variance, Chi-square test, Spearman correlation analysis and multivariate Logistic regression analysis.Results:The social skills score of ASD group was lower than ADHD group ((61.53±24.26) vs (80.89±15.19), P<0.05), while the problem behavior score of ASD group was higher than ADHD group ((38.82±11.92) vs (34.00±12.45), P<0.05). In ASD group, the scores of ABC, CARS and SCQ were negatively correlated with the score of social skills ( r=-0.26--0.55, P<0.05). In ADHD group, the total score and each subscale of SNAP-Ⅳ were positively correlated with the score of problem behavior ( r=0.25-0.65, P<0.05). Multivariate Logistic regression analysis showed that empathy was a negative influencing factor of ASD ( B=-0.246, OR=0.782, P<0.05), and hyperactivity/inattention was a positive influencing factor of ASD ( B=0.589, OR=1.802, P<0.01), while only hyperactivity/inattention was a positive influencing factor of ADHD( B=0.779, OR=2.180, P<0.01). Conclusion:Children and adolescents with ASD and ADHD both have defects in social skills and problem behaviors, and these defects are associated with the core characteristics of their respective diseases.
5.Research progress in effects and mechanisms of dietary pattern interventions in metabolic associated fatty liver disease
Jing SONG ; Shuo JIANG ; Fangyu WAN ; Juan LI ; MUHETA ADINA ; Xinying MIN ; Jingqi ZHOU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(7):926-933
Metabolic associated fatty liver disease(MAFLD)is a type of fatty liver disease associated with systemic metabolic disorders,and its prevalence has been increasing year by year,becoming a major challenge to global public health.The development of MAFLD is associated with various factors,including obesity,dyslipidemia,diabetes and other factors.Excessive body fat,particularly increased visceral adiposity,contributes to hepatic fat accumulation.Abnormal blood lipid levels can also disrupt liver fat metabolism.The risk of MAFLD in patients with diabetes is greatly increased due to insulin resistance and other problems.Dietary interventions are considered an effective strategy for the prevention and treatment of MAFLD.In recent years,several dietary patterns,such as low-carbohydrate diets,intermittent fasting,and the Mediterranean diet,have been applied in clinical practice.Their primary mechanisms include reducing oxidative stress,regulating gut microbiota,and inducing fat autophagy.However,the responses to different dietary patterns vary among individuals due to differences in genes,lifestyle,and disease severity.Therefore,systematically evaluating the effects and mechanisms of these dietary patterns in the prevention and treatment of MAFLD has significant clinical importance.This review compares the effects of different dietary patterns on improving liver function,hepatic fat content,blood glucose,and lipid levels,and analyzes their underlying mechanisms of intervention,to explore how to select personalized dietary strategies based on individual differences.It is intended to provide new insights for the precise prevention and treatment of MAFLD,thereby improving patients' outcomes and alleviating the burden on public health.
6.Study on biodistribution of mixed activated killer immune cells in immunodeficient mice after administration
Manman ZHAO ; Lijun JIANG ; Jing ZHAO ; Hua JIANG ; Ying HUANG ; Hairuo WEN ; Xiaobing ZHOU
Adverse Drug Reactions Journal 2025;27(5):274-280
Objective:To explore the biodistribution characteristics of mixed activated killer (MAK) immune cells in immunodeficient mice after administration.Methods:Ninety-six immune immunodeficient (NOG) mice (half male and half female) were equally divided into MAK cell group and solvent control group. The MAK cell group mice were injected with DiR-labeled MAK cells via the tail vein, while those in the solvent control group were injected with an equal amount of solvent via the tail vein. The number of MAK cells in the peripheral blood of mice was detected using a flow cytometry at 11 time points from 15 minutes to 84 days after administration. The distribution of MAK cells in mice was measured using in vivo bioluminescence imaging at 18 time points from 5 minutes to 84 days after administration. And at 8 time points from 3 hours to 84 days after administration, the heart, liver, spleen, lungs, kidneys, brain, stomach, duodenum, colon, bone marrow, fat, skeletal muscle, testes/uterus, epididymis/ovary, and blood were collected from corresponding mice. The DNA levels of MAK cells in blood and various organs of these mice were detected using fluorescence real-time quantitative polymerase chain reaction (qPCR) method.Results:The flow cytometry results showed that MAK cells could be detected in the peripheral blood of mice 15 minutes after administration, and the highest number of MAK cells in blood appeared during 3 hours to 1 day. By 14 days after administration, MAK cells were almost undetectable in peripheral blood of mice. In vivo bioluminescence imaging results showed that the fluorescence intensity of MAK cells in mice was strongest on days 1 and 2 after administration, and MAK cells were mostly distributed in the liver, spleen, lung, and leg bone of mouse. The qPCR detection results showed that MAK cells were mainly distributed in the spleen and lungs. High levels of MAK cell DNA amplification were observed in organs such as the spleen and lungs 28-56 days after administration, and a certain amount of MAK cell DNA could still be detected in organs of mice such as the spleen at 84 days.Conclusions:After administration, MAK cells were mainly distributed in the spleen, lung, liver and other organs of NOG mice. From 28 to 56 days after administration, MAK cells are significantly activated and proliferate, and a certain amount of MAK cell DNA can still be detected in the spleen and other organs after 84 days in mice.
7.Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
Haoyue LI ; Haitao ZHOU ; Lichun WEI ; Yinggang CHEN ; Wenjue ZHANG ; Feiyan DENG ; Ning LI ; Zheng JIANG ; Zheng LIU ; Jianwei LIANG ; Zhaoxu ZHENG ; Xianyu MENG ; Yufei LU ; Zifa LEI ; Xiaoge SUN ; Gong LI ; Yingjie WANG ; Yongwen SONG ; Shunan QI ; Hao JING ; Yirui ZHAI ; Shulian WANG ; Yexiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Oncology 2025;47(9):913-921
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
8.Changes in accommodative facility after posterior chamber implantation of V4c implantable collamer lens
Jing ZHOU ; Hao JIANG ; Xiu LONG ; Qiurong LONG ; Xin SHI ; Zhixuan CHEN ; Hao GU
Chinese Journal of Experimental Ophthalmology 2025;43(6):522-527
Objective:To investigate the changes in accommodative facility after implantation of V4c implantable collamer lens (ICL) using the intelligent flipper (iFLIP).Methods:A serial case-control study was conducted.Forty patients (80 eyes) who underwent ICL implantation of V4c for myopia correction and completed the follow-up were enrolled at the Affiliated Hospital of Guizhou Medical University from April 2022 to April 2023.Monocular and binocular accommodative facility, adjustment time, and relaxation time were measured with iFLIP before operation and at 1 week, 1 month, 3 months, and 6 months after operation.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University (No.2023-983).Written informed consent was obtained from each subject.Results:Monocular and binocular uncorrected visual acuity at 1 week, 1 month, 3 months and 6 months after surgery were significantly improved compared with before surgery, and the differences were statistically significant (all P<0.05).Monocular and binocular postoperative accommodative facility gradually increased over time, and the increase gradually decreased and gradually stabilized.Before operation and 1 week, 1 month, 3 months, and 6 months after operation, the monocular accommodative facility was (7.99±3.42), (10.19±4.25), (12.03±4.24), (13.10±4.66) and (13.64±4.40)cpm, and the binocular accommodative facility was (9.01±3.63), (9.56±3.38), (11.58±4.00), (13.31±3.64), and (14.03±3.72)cpm, respectively, with statistically significant overall differences ( F=24.02, 14.46; both P<0.001).Monocular accommodative facility was higher than before surgery at each time point after surgery, and was higher than 1 week after surgery at 1, 3, and 6 months after surgery, with statistically significant differences (all P<0.05).Binocular accommodative facility was higher at 1, 3, and 6 months after surgery than that before surgery and 1 week after surgery, and higher at 3 and 6 months after surgery than that at 1 month after surgery, with statistically significant differences (all P<0.05).With the extension of postoperative time, the monocular and binocular adjustment time and relaxation time gradually shortened, and the shortening gradually decreased and stabilized.Monocular adjustment time and relaxation time were shorter than before surgery at all time points after surgery.The monocular adjustment time was shorter at 1, 3 and 6 months after surgery than that at 1 week after surgery and shorter at 3 and 6 months after surgery than that at 1 month after surgery, and the monocular relaxation time was shorter at 3 and 6 months after surgery than that at 1 week after surgery, and the differences were statistically significant (all P<0.05).The binocular adjustment time was shorter at 1, 3 and 6 months after surgery than before surgery and at 1 week after surgery, shorter at 3 and 6 months after surgery than at 1 month after surgery and the binocular relaxation time was shorter at all time points after surgery than that before surgery, showing statistically significant differences (all P<0.05). Conclusions:After ICL implantation, uncorrected visual acuity, accommodative facility, adjustment time and relaxation time all improve throughout the preoperative period and eventually stabilize.
9.Construction and validation of a prognostic nomogram based on lipid parameters for pancreatic cancer patients undergoing postoperative adjuvant chemotherapy
Jinyue LIU ; Xue JING ; Shijin WANG ; Libin LIU ; Jianrui ZHOU ; Yueping JIANG
Chinese Journal of Pancreatology 2025;25(2):112-118
Objective:To establish and validate a lipid parameter-based prognostic model for predicting recurrence free survival (RFS) in pancreatic cancer patients receiving postoperative adjuvant chemotherapy.Methods:A retrospective analysis was conducted on the clinical and pathological data of 155 patients who underwent pancreatic cancer resection followed by adjuvant chemotherapy at Affiliated Hospital of Qingdao University between January 2019 and December 2022. The patients were randomly divided into a training set ( n=108) and a validation set ( n=47) in a 7∶3 ratio. X-tile software was used to determine cutoff values for lipid parameters. Univariate and multivariate Cox regression analyses were performed to construct a model predicting RFS, which was then visualized using a nomogram. The model's predictive performance, accuracy and stability, and clinical application value were evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. Individual risk scores for recurrence were calculated based on the nomogram model, and X-tile software was employed to identify optimal cutoff values for risk stratification, which was used to divide patients into low-risk and high-risk groups. Survival differences between two groups were analyzed using survival curves. Results:Among lipid parameters, patients with higher apolipoprotein A1 level had obviously longer RFS than those with low apolipoprotein A1 level (10.17 months vs 8.92 months, HR=0.397, 95% CI 0.237~0.664); patients with high total cholesterol level had obviously shorter RFS than those with low total cholesterol level (8.33 months vs 16.27months, HR=3.382, 95% CI 1.901~5.824) ; patients with high low-density lipoprotein level had obviously shorter RFS than those with low low-density lipoprotein level (8.53 months vs 11.43 months, HR=1.617, 95% CI 1.013~2.582) ; patients with high lipoprotein(a) had shorter RFS than those with low lipoprotein(a) (8.53 months vs 14.43 months, HR=2.640, 95% CI 1.514-4.604) ; and all the differences were statistical significant (all P value <0.05). Univariate Cox regression analysis identified advanced T stage, advanced N stage, high total cholesterol level, high low-density lipoprotein level, low apolipoprotein A1 level, high apolipoprotein B level, and high lipoprotein(a) level as risk factors for RFS. Multivariate Cox regression analysis revealed that tumors located in the pancreatic body or tail ( HR=0.63, 95% CI 0.36-0.86, P=0.042), advanced T stage ( HR=4.85, 95% CI 1.47-16.04, P=0.010), advanced N stage ( HR=0.48, 95% CI 0.26-0.87, P=0.015), elevated total cholesterol levels ( HR=3.61, 95% CI 1.46-8.91, P=0.005), high density lipoprotein levels ( HR=0.48, 95% CI 0.26-0.87, P=0.015), and elevated lipoprotein(a) levels ( HR=3.17, 95% CI 1.61-6.24, P<0.001) were independent risk factors for RFS. The nomogram model incorporating these six factors above demonstrated an AUC of 0.78 (95% CI 0.70-0.87) in the training set and 0.75 (95% CI 0.59-0.91) in the validation set. Calibration curves indicated a high degree of agreement between predicted and observed outcomes. DCA suggested that the model provides substantial clinical benefit. Kaplan-Meier survival curve analysis showed that patients in the high-recurrence risk group from training set and validation set both had significantly shorter RFS compared to those in the low-recurrence risk group (6.93 months vs 12.13 months, HR=4.024, 95% CI 2.594-6.243; 6.85 months vs 11.93 months, HR=2.314, 95% CI 1.227-4.362); and all the differences were statistical significant (all P value <0.05). Conclusions:The nomogram model based on lipid parameters can effectively predict recurrence free survival in patients undergoing adjuvant chemotherapy after pancreatic cancer surgery.
10.A proximity-induced chimera platform for targeted protein arginine methylation.
Yanlin JIAN ; Tianyang ZHOU ; Chendong GUO ; Yibo GAO ; Chen YAO ; Zixi WANG ; Xuehan JIANG ; Ke WANG ; Jian MA ; Yang GAO ; Yizeng FAN ; Jing LIU ; Bohan MA ; Lei LI
Acta Pharmaceutica Sinica B 2025;15(5):2625-2639
Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.


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