1.Analysis of T7 RNA Polymerase: From Structure-function Relationship to dsRNA Challenge and Biotechnological Applications
Wei-Chen NING ; Yu HUA ; Hui-Ling YOU ; Qiu-Shi LI ; Yao WU ; Yun-Long LIU ; Zhen-Xin HU
Progress in Biochemistry and Biophysics 2025;52(9):2280-2294
T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.
2. Analysis of cerebral gray matter structure in multiple sclerosis and neuromyelitis optica
Xiao-Li LIU ; Ai-Xue WU ; Ru-Hua LI ; An-Ting WU ; Cheng-Chun CHEN ; Lin XU ; Cai-Yun WEN ; Dai-Qian CHEN
Acta Anatomica Sinica 2024;55(1):17-24
Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.
3.Progress of interruption of schistosomiasis transmission and prospects in Yunnan Province
Yun ZHANG ; Lifang WANG ; Xiguang FENG ; Mingshou WU ; Meifen SHEN ; Hua JIANG ; Jing SONG ; Jiayu SUN ; Chunqiong CHEN ; Jiaqi YAN ; Zongya ZHANG ; Jihua ZHOU ; Yi DONG ; Chunhong DU
Chinese Journal of Schistosomiasis Control 2024;36(4):422-427
Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.
4.Immunotherapy of pancreatic cancer with triptolide combined with ginsenoside Rg3
Wen-wen ZHAO ; Ting-ting JIANG ; Zhi-rong WANG ; Yun-yun WANG ; Xiang-xiang WU ; Hua-hui ZENG
Acta Pharmaceutica Sinica 2024;59(6):1794-1803
Liposome was used as carrier to carry triptolide and ginsenoside Rg3 in the treatment of pancreatic cancer tumor mice. The effects of liposome on the levels of CD4+ and CD8+ microenvironmental immune factors of pancreatic cancer tumor were investigated, and the tumor inhibitory effect and safety were evaluated. In this study, Pan02 cells were used to construct a tumor-bearing C57BL/6 mouse model. After 14 days of treatment, the changes in tumor volume and body weight of tumor-bearing mice were observed. The results showed that the high and low doses of liposome had significant therapeutic effect on tumor volume in the model group (
5.Advances of artificial intelligence technology in the discovery and optimization of lead compounds
Zi-yue LI ; Kai-yuan CONG ; Shi-qi WU ; Qi-hua ZHU ; Yun-gen XU ; Yi ZOU
Acta Pharmaceutica Sinica 2024;59(9):2443-2453
In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.
6.Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture (version 2024)
Yun HAN ; Feifei JIA ; Qing LU ; Xingling XIAO ; Hua LIN ; Ying YING ; Junqin DING ; Min GUI ; Xiaojing SU ; Yaping CHEN ; Ping ZHANG ; Yun XU ; Tianwen HUANG ; Jiali CHEN ; Yi WANG ; Luo FAN ; Fanghui DONG ; Wenjuan ZHOU ; Wanxia LUO ; Xiaoyan XU ; Chunhua DENG ; Xiaohua CHEN ; Yuliu ZHENG ; Dekun YI ; Lin ZHANG ; Hanli PAN ; Jie CHEN ; Kaipeng ZHUANG ; Yang ZHOU ; Sui WENJIE ; Ning NING ; Songmei WU ; Jinli GUO ; Sanlian HU ; Lunlan LI ; Xiangyan KONG ; Hui YU ; Yifei ZHU ; Xifen YU ; Chen CHEN ; Shuixia LI ; Yuan GAO ; Xiuting LI ; Leling FENG
Chinese Journal of Trauma 2024;40(9):769-780
Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.
7.Treatment of Acetabular Anterior Column Fractures With Antegrade Percutaneous Screw Fixation Under Robot Navigation
Zuzhou WEN ; Yun YE ; Xizhi WU ; Hua ZHOU ; Ang LUO ; Hongqiang CHEN
Chinese Journal of Minimally Invasive Surgery 2024;24(5):350-354
Objective To investigate the clinical effect of anterograde percutaneous screw fixation under robot navigation in the treatment of acetabular anterior column fractures.Methods A retrospective analysis was made on 7 cases of anterior acetabular column fractures from April 2021 to January 2023.The traction reduction was conducted by using pelvic"double reverse"traction table,the orthopedic robot-assisted design was carried out to plan the screw entry point and direction,and the antegrade channel cannulated screw was used for internal fixation.Results The operation time was 60-95 min(mean,78 min).The intraoperative blood loss was 5-20 ml(mean,8.6 ml).The number of fluoroscopy was7-11(mean,8.7).The guide needle was unadjusted in 3 cases and adjusted for 1-2 times in 4 cases(once in 2 cases and twice in 2 cases).The actual path deviated from the planned by 0.65-1.50 mm(mean,0.98±0.30 mm).The excellent and good rate of screw position was 100%.X-ray and CT examinations were performed at 48 h after the operation.According to the Matta reduction standard,anatomical reduction was achieved in 6 cases and satisfactory reduction in 1 case.All the 7 cases were followed up for 6-28 months(mean,15 months).At the last follow-up,the Harris score of the hip joint was85-96 points(mean,91.6 points)and the pain of visual analogue scale(VAS)was0.There were no complications such as infection,loosening of internal fixation,or neurological dysfunction.Conclusion Anterograde percutaneous screw fixation under robot navigation in the treatment of acetabular anterior column fractures is safe,effective,and satisfactory.
8.Analysis of Learning Curve of Bikini Incision Direct Anterior Approach Total Hip Arthroplasty
Zuzhou WEN ; Hongqiang CHEN ; Xizhi WU ; Ang LUO ; Hua ZHOU ; Junzhao QIAO ; Yun YE
Chinese Journal of Minimally Invasive Surgery 2024;24(9):604-609
Objective To explore the learning curve of Bikini incision direct anterior approach total hip arthroplasty(Bikini-THA).Methods Clinical data of 80 cases of Bikini-THA initially completed by an operator skilled in posterolateral approach and direct anterior approach total hip arthroplasty from March 2020 to March 2023 were retrospectively analyzed,and the learning curve was observed by scatter plots of operative time and intraoperative bleeding.They were divided into groups A to D according to the order of surgery,with 20 cases in each group.The operative time,intraoperative bleeding,acetabular abduction angle,anteversion angle,angle between stem and femoral axis,postoperative hip Harris score and complications were compared among the 4 groups.Results After about 40 cases,the decreasing trend of operative time and intraoperative bleeding slowed down and stabilized.The operative time and intraoperative bleeding in the 4 groups were group A>group B>groups C and D(P<0.05),and the differences between the group C and group D were not statistically significant(P>0.05).The acetabular prosthesis was well-positioned in the 4 groups(abduction angle of 30°-50°,anteversion angle of 5°-25°).The femoral prosthesis center fixation rate(angle between stem and femoral axis ≤3°)was group A<groups C and D(P=0.003,0.003).The differences in the Harris scores of the hip joints at 2 weeks,1 month,3 months,and 12 months postoperatively of the 4 groups were not statistically significant(P>0.05),and the efficacy evaluations of the hip joints at 12 months postoperatively were all excellent.There were 5 cases of complications in the group A(2 cases of greater trochanter fracture and 3 cases of lateral femoral cutaneous nerve injury),3 cases of complications in the group B(1 case of greater trochanteric fracture,1 case of lateral femoral cutaneous nerve injury,and 1 case of incision infection),1 case of complications in the group C(lateral femoral cutaneous nerve injury),and no complications in the group D.The follow-up period lasted for 12-26 months,with a mean of(19.4±4.7)months.There were no complications such as dislocation or loosening of the prosthesis.Conclusion The Bikini-THA learning curve was approximately 40 cases.
9.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]
10.Single mini-incision combined with honeycomb titanium plate in treatment of acute acromioclavicular joint disloca-tion
Yu-Chen WANG ; Wei-Zhong YU ; Yun-Feng LI ; Wen-Ke ZHU ; Chuan JIA ; Jun-Qi WU ; Hua GAO ; Lin JI
China Journal of Orthopaedics and Traumatology 2024;37(6):576-582
Objective To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation.Methods The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods.Among them,20 patients were fixed with single small incision with honeycomb titanium plate(titanium plate group),including 11 males and 9 females,aged from 23 to 65 years old with an average of(47.40±12.58)years old;12 patients on the left side,8 patients on the right side;11 patients with type Ⅲ,3 patients with type Ⅳ,and 6 patients with type Ⅴ according to Rockwood classification.Twenty patients were fixed with clavicular hook plate(clavicular hook group),including 8 males and 12 females,aged from 24 to 65 years old with an average of(48.40±12.08)years old;12 patients on the left side,8 patients on the right side;10 patients with type Ⅲ,2 patients with type Ⅳ,and 8 patients with type V according to Rockwood classifica-tion.Operative time,incision length,intraoperative blood loss,hospital stay,visual analogue scale(VAS)and Constant-Murley score of shoulder joint function were compared between two groups.Anteroposterior radiographs of the affected shoulder joint were recorded before,immediately and 6 months after surgery,and the coracoclavicular distance was measured and compared.Results Both groups of patients were successfully completed operation without serious complications.All patients were fol-lowed up for 6 to 15 months with an average of(11.9±4.8)months.There were no incisional infection,internal plant fracture or failure,bone tunnel fracture and other complications occurred.The incision length of titanium plate group(35.90±3.14)mm was significantly shorter than that of clavicular hook group(49.30±3.79)mm(P<0.05).There were no significant difference in operative time,intraoperative blood loss and hospital stay between two groups(P>0.05).At 1 and 3 months after operation,VAS of titanium plate group was lower than that of clavicular hook group(P<0.05).Connstant-Murley scores in titanium plate group at 1,3 and 6 months after operation were(86.80±1.36),(91.60±2.32)and(94.90±2.22),respectively;and in clavicular hook group were(78.45±5.47),(85.55±2.01)and(90.25±1.92),which were higher than that of clavicular hook group(P<0.05).There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after op-eration(P>0.05).Conclusion For the treatment of acute acromioclavicular joint dislocation,single small incision combined with honeycomb titanium plate have advantages of shorter incision,fast recovery of shoulder joint function without the second operation,and has good satisfaction of patient.

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