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.

ObjectiveTo investigate the trend and influencing factors of newly reported human immunodeficiency virus (HIV) positivity rate among men who had sex with men (MSM) in Shanghai from 2021 to 2024, and to provide evidence for formulating scientific prevention and control measures of AIDS. MethodsMultiple rounds of cross-sectional questionnaire surveys were conducted among MSM by Shanghai Qing’ai Health Promotion Center. Pearson and Cochran-Armitage trend χ² tests were used to analyze the differences and changes in population characteristics and newly reported HIV positivity rates. A logistic regression model was applied for multivariate analyses of factors associated with newly reported HIV positivity. ResultsA total of 1 653 MSM who had not been previously diagnosed with HIV infection were surveyed. The newly reported HIV positivity rates in 2021, 2023, and 2024 were 7.87%, 3.91%, and 3.06%, respectively, showing a decreasing trend (χ²_trend=13.460, P_trend<0.001). Multivariate analyses revealed that MSM aged 18‒<25 years, residing locally for <1 year, identifying as bisexual, lacking HIV knowledge, and having ≥10 same-sex partners in the past 6 months exhibited higher newly reported HIV positivity rates. Conversely, MSM knowledgeable about HIV prevention, residing locally for 1‒5 years, and engaging in oral sex with male partners in the past 6 months demonstrated lower HIV positivity rates. Annual analyses revealed that MSM with HIV knowledge had lower newly reported HIV positivity rates in 2023 and 2024 (aOR=0.300, 95%CI: 0.811‒0.111; aOR=0.202, 95%CI: 0.085‒0.483). ConclusionThe newly reported HIV positivity rate among MSM in Shanghai from 2021 to 2024 showed a decline. Future interventions should focus on young and mobile MSM, strengthen HIV knowledge education through platforms such as the internet, promote safe sexual behaviors and regular testing, and further expand the coverage of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) to control HIV transmission within this population.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Objective To investigate the effects of methionine restriction(MR)on macrophages in lipopolysaccharide(LPS)-induced acute lung injury(ALI)and to explore the underlying mechanism.Methods According to the random number table method,36 male C57BL/6J mice(6～8 weeks old,23±2 g)were divided into 3 groups with 12 mice in each group:the sham group,the LPS group and the LPS+MR group.HE staining and pathological scoring of lung injury were performed in lung tissues.The expression of LPS-binding protein(LBP)and Toll-like receptor-4(TLR4)was detected by RT-qPCR and Western blotting.Macrophage-colony stimulating factor(M-CSF),granulocyte-macrophage-colony stimulating factor(GM-CSF)and chemokine C-C motif ligand 3(CCL3)which are all macrophage-associated chemokines were analyzed by immunohistochemistry.Results Compared with the sham group,the pathological score of lung injury in the LPS group was significantly increased(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were significantly increased;The number of positive cells of CD11b,F4/80,M-CSF,GM-CSF and CCL3 were significantly increased(P＜0.01).MR significantly improved LPS-induced ALI,and decreased the pathological score of lung injury(P＜0.01);The mRNA and protein expression levels of LBP and TLR4 were decreased;Compared with the LPS group,the number of positive cells of CD11 b,F4/80,M-CSF,GM-CSF and CCL3 were reduced in the LPS+MR group(P＜0.01).Conclusion MR could attenuate LPS-induced ALI by inhibiting the expression of macrophage chemokines and preventing infiltration and activation of macrophage to lungs.

BACKGROUND:Previous studies have shown that salidroside has an ameliorative effect on multi-organ fibrosis.However,the protective effect of salidroside on angiotensin ⅱ-induced fibrosis in cardiac fibroblasts is unclear. OBJECTIVE:To investigate the protective effects of salidroside on angiotensin ⅱ-induced oxidative stress and extracellular matrix deposition in cardiac fibroblasts of Sprague-Dawley rats and its mechanism of action. METHODS:Angiotensin Ⅱ was used to induce fibrosis in cardiac fibroblasts,and there were five experimental groups:normal control group,model group(final concentration of angiotensin Ⅱ in culture medium was 1 μmol/L),salidroside low and high dose groups(treatment with salidroside 50,100 μmol/L for 2 hours,followed by co-incubation with angiotensin Ⅱ for 48 hours),SIRT1 inhibitor group(treatment with SIRT1 inhibitor EX527 10 μmol/L for 2 hours,followed by high dose of salidroside for 2 hours and then co-incubation with angiotensin Ⅱ for 48 hours).The cell viability was detected using the cell counting kit-8 method,the cell migration rate was detected by Transwell,the intracellular reactive oxygen species level was detected by DCFH-DA fluorescent probe,and the intracellular malondialdehyde content,superoxide dismutase and catalase activities were detected by relevant kits.The protein and mRNA expression levels of SIRT1,LOXL2,α-SMA,type I collagen and type Ⅲ collagen were detected by western blot and qRT-PCR,respectively. RESULTS AND CONCLUSION:The cells were identified as cardiac fibroblasts by Vimentin fluorescence.Compared with the normal control group,cell viability,cell migration rate,reactive oxygen species level,and malondialdehyde content were significantly increased,superoxide dismutase and catalase activities were significantly decreased,LOXL2,α-SMA,type I collagen,type Ⅲ collagen mRNA and protein expression were significantly increased,and SIRT1 protein expression level was significantly decreased in the model group(all P＜0.01).Compared with the model group,the above indexes showed opposite changes in the salidroside low and high dose groups(all P＜0.05).Moreover,salidroside showed dose-dependent regulation.Compared with salidroside groups,cell migration rate and α-SMA protein expression level were significantly increased in the SIRT1 inhibitor group(both P＜0.001).To conclude,salidroside has a protective effect on angiotensin Ⅱ-induced cardiac fibroblasts and can dose-dependently inhibit oxidative stress and extracellular matrix deposition.

Objective To discuss the methods,efficacy,and safety of endovascular treatment for ruptured pseudoaneurysm hemorrhage of internal carotid artery(ICA)after radiotherapy for nasopharyngeal carcinoma(NPC).Methods The clinical data of 21 patients with ruptured pseudoaneurysm hemorrhage of ICA after radiotherapy for NPC,who were admitted to the Affiliated Union Hospital,Fujian Medical University of China,were retrospectively analyzed.The patient's surgical strategies were analyzed,the therapeutic results and the clinical and imaging follow-up results were summarized.Of the 21 patients,covered stent implantation was carried out in 8,stent-assisted coil embolization was employed in 6,and direct occlusion of parent artery was adopted in 7.Results Successful endovascular treatment was accomplished in all the 21 patients.Excellent hemostatic effect was obtained immediately after surgery.Aneurysm neck residue was observed in 2 patients,and aneurysm body residue was seen in one patients.Postoperative bleeding recurred in 5 patients,in 4 of them the bleeding stopped after once more occlusion of the parent artery,and one patient developed internal leakage after covered stent implantation and the bleeding stopped after balloon dilation,and this patient died of unknown cause one month later.One patient developed coma after covered stent implantation,CT scan demonstrated subarachnoid hemorrhage and brain swelling,and this patient showed no improvement after treatment and was self-discharged from hospital.ICA occlusion was seen in 3 patients during follow-up period,and 2 patients did not receive a postoperative follow-up visit.In the 19 patients who were followed up,the mRS score was 0 point(n=9),1 point(n=6),2 points(n=2),5 points(n=1),and 6 points(n=1).Conclusion For the ruptured pseudoaneurysm hemorrhage of ICA after radiotherapy for NPC,endovascular treatment is highly safe with reliable efficacy.The covered stent implantation carries good short-term efficacy,but there are also problems such as aneurysm recurrence,internal endoleak,etc.The direct occlusion of parent artery may have more reliable long-term efficacy.(J Intervent Radiol,2024,33:304-308)

Objective At present, the grading evaluation of patients with disorders of consciousness (DOC) is still a focus and difficulty in related fields. Electroencephalogram (EEG) can directly read and continuously reflect scalp electrical activity generated by brain tissue structure, with high temporal resolution. Auditory stimulation is easy to operate and has broad application prospects in clinical detection of DOC. The causal network can intuitively reflect the direction of information transmission through the causal relationship between time series, helping us better understand the information interaction between different regions of the brain of patients. This paper combines EEG and causal networks to explore the differences in brain functional connectivity between patients with unresponsive arousal syndrome (VS) and those with minimum state of consciousness (MCS) under auditory stimulation. MethodsA total of 23 DOC patients were included, including 11 MCS patients and 12 VS patients. Based on the Oddball paradigm, auditory naming stimulation was performed on DOC patients and EEG signals of DOC patients were synchronously collected. The brain functional networks were constructed using multivariate Granger causality method, and the differences in node degree, clustering coefficient, global efficiency, and causal flow of the brain networks between MCS patients and VS patients were calculated. The differences in network characteristics of patients with different levels of consciousness under auditory stimulation were compared from the perspective of cooperation between brain regions. ResultsThe causal connectivity between most brain regions in MCS patients was stronger than that in VS patients, and MCS patients had more brain network connectivity edges than VS patients. The average degree (P<0.05), average clustering coefficient, and global efficiency (P<0.05) of MCS patients under naming stimulation were higher than those of VS patients. The difference in out-degree between each node of VS patients was larger, and the difference in in-degree between each node of MCS patients was smaller. The difference in in-degree of MCS patients was more significant than that of VS patients, and the inflow and outflow of information in the brain functional network of MCS patients were stronger than those of VS patients. MCS and VS patients had differences of causal flow in the frontal and temporal lobes, the direction of information transmission in the parietal lobe and central region was not the same, and MCS patients had more electrodes as causal sources than VS patients. ConclusionThe information transmission ability of MCS patients is stronger than that of VS patients under auditory naming stimulation. Compared with VS patients, MCS patients have an increase in the number of electrode channels as the causal source, an increase in information output to other brain regions, and also an increase in the information output within brain regions, which may indicate a better state of consciousness in patients. MCS patients have more electrode channels for information output in the frontal lobe than VS patients, and the number of electrode channels for changing the direction of information transmission in the frontal lobe is the highest. The frontal lobe is closely related to the level of consciousness in patients with consciousness disorders. This study can provide a theoretical basis for the grading evaluation of consciousness levels in DOC patients.

Objective To investigate the impacts of wogonin on cardiac inflammation in pregnant hypertensive rats by regulating the monocyte chemotactic protein-1(MCP-1)/CC chemokine receptor 2(CCR2)signaling pathway.Methods Pregnancy hypertensive rat model was established by intragastric administration of nitroso L-arginine methyl ester.The rats were randomly divided into control group(0.9％NaCl),model group(0.9％NaCl),experimental-L,-H groups(3.33 and 13.32 mg·kg-1 Wogonin),magnesium sulfate group(intrabitoneal injection 100 mg·kg-1magnesium sulfate),recombinant rat MCP-1 protein(rRMCP-1)group(intraperitoneal injected 0.026 mg·kg-1 rRMCP-1),experimental-H+rRMCP-1 group(gavage 13.32 mg·kg-1 Wogonin+0.026 mg·kg-1 rRMCP-1),each group consisted of 12 animals.Each group was administered once a day for 7 days.The serum levels of tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay;the expression of M1 and M2 macrophages in rat myocardium was detected by immunofluorescence staining;the expression of MCP-1 protein in rat myocardium was detected by Western blot.Results Serum TNF-α levels in control group,model group,experimental-L,-H groups,magnesium sulfate group,rRMCP-1 group,experimental-H+rRMCP-1 group were(10.06±0.41),(23.39±0.57),(19.89±0.62),(13.64±0.51),(12.97±0.48),(28.84±1.05)and(17.15±0.69)pg·mL-1;the fluorescence intensities expressed by M1 type macrophages were 32.26±1.43,58.84±2.11,50.66±1.89,36.69±1.57,35.87±1.59,67.73±2.01 and 48.53±1.86;the fluorescence intensities expressed by M2 type macrophages were 31.15±1.20,46.56±1.03,51.92±1.04,59.11±0.82,59.26±0.83,40.26±1.12 and 45.53±1.65;the expression of MCP-1 protein were 0.58±0.03,1.86±0.11,1.62±0.09,0.76±0.07,0.78±0.06,2.16±0.13 and 1.34±0.12,respectively.The above indicators in the model group were compared with those in the control group,compare the above indicators with the model group in the experimental-L,-H groups,magnesium sulfate group and rRMCP-1 group,the above indicators in the experimental-H group were compared with those in the experimental-H+rRMCP-1 group,the differences were statistically significant(all P＜0.05).Conclusion Wogonin may inhibit cardiac inflammatory response in pregnant hypertensive rats by inhibiting the MCP-1/CCR2 signaling pathway.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

ObjectiveTo understand the characteristics of PM_2.5 pollution in the air of Pearl River Delta city in Guangdong Province under the COVID-19 epidemic and the health risks of inhaling elements in PM_2.5. MethodsIn 2022， 10 PM_2.5 monitoring points were set up in 10 districts in Guangzhou， Shenzhen， Foshan and Zhuhai， and air samples were collected for 7 consecutive days every month to analyze the concentration of PM_2.5 and the 12 elements in PM_2.5. The classic "four-step" method was used to evaluate the carcinogenic risk and chronic non-carcinogenic risk of the elements in air PM_2.5 on health. The age-sensitive characteristics of metal elements were combined in the carcinogenic risk assessment， and age-sensitive factors were introduced to analyze the impact of air pollution on population health. ResultsA total of818 samples were collected. and the average annual PM_2.5 concentration in the four cities of the Pearl River Delta was 30.17 （1.00-166.00， s=21.06） μg·m^-3， which was lower than the concentration limit of the secondary standard of the Ambient Air Quality Standard （GB 3095-2012）. The difference of PM_2.5 concentration in the four cities was statistically significant. The PM_2.5 concentrations in Zhuhai and Shenzhen， which were located near the sea， were lower than those in Guangzhou and Foshan. The monthly mean concentration of PM_2.5 in the four cities was the lowest at 13.70 （4.00-34.00， s=5.93） μg·m^-3 in July and the highest at 57.73 （14.00-146.00， s=27.96） μg·m^-3 in January， showing a low concentration from May to October and a high concentration from November to April of the following year. The average daily PM_2.5 concentration exceeded the secondary standard for 29 days， mainly distributed in January and November. The average annual mass concentration of elements in PM_2.5 in the four cities was Al>Mn>Pb>As>Ni>Cr>Se>Sb>Cd>Tl>Be>Hg. AS and Mn have chronic non-carcinogenic risk in population， while Cr， AS， Cd， Be and Ni have carcinogenic risk in population. ConclusionThe PM_2.5 pollution levels of the four cities in the Pearl River Delta are low and variable. Coastal cities are lower than non-coastal cities， which shows the characteristics of first decreasing and then increasing throughout the year. The order of mass concentration of metal elements of PM_2.5 in four cities is basically the same except Be and Ni. As and Mn in PM_2.5 show a certain degree of chronic non-carcinogenic risk， and As， Cr， Cd， Ni and Be have a certain degree of carcinogenic risk. The four cities need to take effective intervention measures to continue to strengthen the pollution control and health protection of Cr， As， Cd and Mn in the air， and control the health burden caused by air pollution.