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.

A new Schiff base modified MCM-41 molecular sieve(N-MCM-41)was synthesized via post-grafting method with 2-pyridine formaldehyde for efficient removal of lead ions(Pb2+)from aqueous solution.X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),Fourier transform-infrared(FT-IR)spectroscopy,thermogravimetric analysis(TGA),and X-ray photoelectron spectroscopy(XPS)were employed to characterize the structure,morphology,surface functional groups and chemical states of N-MCM-41.Moreover,the adsorption behavior of Pb2+by N-MCM-41 was systematically studied.Batch adsorption studies revealed that N-MCM-41 showed the maximal adsorption capacity of 101.3 mg/g at 45℃and pH=5.5 under the initial Pb2+ concentration of 80 mg/L after 180 min adsorption.The adsorption process conformed to the Langmuir isotherm model and the pseudo-second-order kinetics model.The adsorption of Pb2+by N-MCM-41 was a spontaneous and endothermic process.Adsorption mechanism analyses suggested that functional groups on N-MCM-41 had strong coordination ability with Pb2+to improve the adsorption capacity.The synthesized N-MCM-41 adsorbent exhibited excellent reusability in five regeneration cycles.Overall,this study showed that the N-MCM-41 had good application prospect to remove Pb2+ from aqueous solution.

Polyunsaturated fatty acids (PUFAs) have diverse health-promoting effects, such as potentially protecting in immune, nervous, and cardiovascular systems by targeting a variety of sites, including most ion channels. Voltage-gated potassium channels of the K_V7 family and large-conductance Ca²⁺- and voltage-activated K⁺ (BK_Ca) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional K_V7 channels and BK_Ca channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on K_V7 channels and BK_Ca channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on K_V7 and BK_Ca channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In K_V7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in K_V7 channels, while in BK_Ca channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of K_V7 and BK_Ca channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate K_V7 and BK_Ca channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.

Objective To explore the prognostic value of long non-coding RNAs(lncRNAs)as novel biomarkers for stomach adenocarcinoma(STAD).Methods RNA-seq transcriptome data and clinical details for STAD were downloaded from the The Cancer Genome Atlas(TCGA)database.Differentially expressed lncRNAs were identified by bioinformatics analysis.Survival analysis,independent prognostic analysis and receiver operating characteristic(ROC)curve were used to identify lncRNAs with independent prognostic value.Then,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to evaluate the biological profiles of the co-expressed genes.Finally,oncoPredict R package was used to predict the drug sensitivity.Results A total of 1 583 differentially expressed lncRNAs were identified from STAD tumor tissues.A lncRNAs AP000695.1 with survival and independent prognostic value was screened.The area under 5-year survival ROCs was 0.836.AP000695.1 was co-expressed with 16 genes involved in tumor cell invasion,metastasis and diffusion.Finally,anti-tumor drug sensitivity prediction revealed that patients in the low expression group were more sensitive to anti-tumor drugs.Conclusion This study discovered a risk factor lncRNAs AP000695.1 with independent prognostic value,may provide insight for individualized antitumor therapy and prognosis prediction for STAD patients.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the clinical efficacy and safety of cattle encephalon glycoside and ignotin injection combined with reduced glutathione injection and levodopa and benserazide hydrochloride tablets in the treatment of elderly patients with Parkinson's disease complicated with mild cognitive impairment(PD-MCI).Methods Elderly patients with PD-MCI were randomly divided into control group and treatment group.Two groups were treated with levodopa and benserazide hydrochloride tablet for anti-Parkinson's disease therapy,and on this basis,the control group was given intravenous drip of reduced glutathione 1.2 g(qd),and the treatment group was given intravenous drip of cattle encephalon glycoside and ignotin injection 10 mL(qd)on the basis of the control group.Both groups of patients were treated continuously for 4 weeks.The clinical efficacy,serum regulated upon activation,normal T cell expressed and secreted(RANTES),α-synuclein(α-syn),brain-derived neurotrophic factor precursor protein(pro-BDNF),catalase(CAT),total superoxide dismutase(T-SOD),cognitive function and quality of life were compared between both groups,and the adverse drug reactions were observed.Results In treatment group,48 cases were enrolled but 3 cases were lost,thus 45 cases were finally included in the analysis.In control group,48 cases were enrolled but 6 cases were lost,thus 42 cases were included in the analysis.After treatment,the total effective rates in treatment and control groups were 93.33％(42 cases/45 cases)and 76.19％(32 cases/42 cases)respectively(P＜0.05).After treatment,RANTES levels in treatment group and control group were(25.57±4.62)and(30.29±4.92)pg·mL-1;α-syn levels were(3.08±0.76)and(3.74±1.09)μg·L-1;pro-BDNF levels were(144.65±17.54)and(182.26±15.75)ng·mL-1;CAT levels were(168.54±10.64)and(160.48±9.74)kU·L-1;T-SOD levels were(123.75±20.54)and(110.18±22.66)kU·L-1;Montreal Cognitive Assessment Scale scores were(25.08±2.75)and(23.14±2.64)points;and 39-item Parkinson's Disease Quality of Life Questionnaire scores were(45.84±8.42)and(50.34±7.62)points,respectively.The differences of above indexes were statistically significant between two groups(all P＜0.05).The adverse drug reactions in treatment group were arrhythmia,dizziness,chills and gastrointestinal discomfort.The adverse drug reactions in control group were transient thrombocytopenia and arrhythmia.The total incidences of adverse drug reactions in treatment group and control group were 8.89％and 4.76％wthout significant difference(P＞0.05).Conclusion Cattle encephalon glycoside and ignotin injection combined with reduced glutathione injection and levodopa and benserazide hydrochloride tablets has exact clinical efficacy in the treatment of elderly patients with PD-MCI,and it can significantly enhance the neuroprotective and antioxidant effects and improve the cognitive function and quality of life of patients,and it does not increase the incidence rate of adverse drug reactions.

Objective To summarize the acupoints and parameters commonly used in the treatment of vascular cognitive impairment(VCI)by electro-acupuncture(EA)through the visual data mining technique to provide a reference basis for clinical treatment.Methods The clinical studies of EA on the treatment of VCI were searched in CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases.The literature is managed by Note Express and the database is established by Excel.The frequency of selected acupoints,frequency,meridian tropism,parameter frequency and frequency of used acupoints are counted.Factor analysis is carried out by SPSS 21.0 software.SPSS Modeler 18.3 software is used to analyze association rules and co-occurrence network,and the analysis results are visualized by Cytoscape 3.9.1 software.Results Finally,155 papers were included,containing 155 acupoint prescriptions and 157 parameter prescriptions.Acupoint prescriptions involved 100 acupoints with a total frequency of 856 times;parameter prescriptions involved 33 parameters with a total frequency of 788 times.Conclusion At present,there is a big difference between the clinical studies,and there is no recognized acupoint and parameter for EA treatment of VCI.By further summarizing the law of EA acupuncture point and parameter,the study has sorted out the law of commonly used acupoints,meridian tropism,compounding and parameter selection for EA treatment of VCI.It was concluded that the selection of acupoints mainly started from the three aspects of deficiency,phlegm and stasis,focusing on the combination of local and distal selection of acupoints,through the identification of internal organs and meridians,to achieve the simultaneous regulation of the heart,spleen and kidney,and to take into account both the symptoms and the root cause,and to play the roles of opening the orifices to wake up mind,calming mind and benefiting intellect,strengthening the spleen and tonifying the kidneys,and invigorating blood circulation to remove stasis.The parameters of EA are recommended to be sparse and dense wave,low frequency,as tolerated by the patient,30 minutes/times,1 time/day,5 times/week as the main combinations,which can provide a certain reference basis for clinical decision-making.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.

After entering the body from the drug delivery site, antitumor nanomedicines need to cross a series of physiopathological barriers to reach the target site of action to effectively exert antitumor therapeutic effects. The ligand modification strategy is a classic method to enhance the efficiency of nanomedicine delivery in vivo, but the contradiction between the single ligand modification strategy, which is characterized by unity and stage, and the in vivo delivery process, which is characterized by versatility and whole-process characteristics, determines that nanomedicines modified by a single ligand alone cannot satisfy the target efficacy requirements. Therefore, the use of multiligand combinatorial modification strategies by virtue of nanomedicine surface area advantages is key to advancing the next generation of smart nanomedicines. In this paper, on the basis of summarizing and classifying the commonly used functional ligands for in vivo delivery, the advantages and research progress of multiligand combination modification of antitumor nanomedicines are discussed with special focus, and the multiligand combination modification is classified as synergistic and complementary according to the combination of the ligands, which is of great significance to ensure that antitumor nanomedicines can overcome the multiple physiopathological barriers to achieve precise delivery.

The presence of food-borne pathogenic bacteria poses a severe threat to human health. Therefore,it is essential to develop effective methods for bacteria detection. Herein,a method based on digital polymerase chain reaction (PCR) chip was developed for rapid and effective detection of three kinds of common food-borne bacteria (Staphylococcus aureus,Salmonella typhimurium and Listeria monocytogenes). Driven by centrifugal force,samples could be easily loaded and digitized in 15 min. PCR results showed that the positive microchambers in the chip could be identified after 25 thermal cycles. The chip had advantages in the quantitative detection of bacterial nucleic acid at low concentration,which could effectively avoid false negative results. Multiple detection of bacterial samples with concentration of 105-108 CFU/mL could also be realized using this chip. Compared with fluorescent quantitative PCR,this method had higher accuracy and sensitivity,especially for detection of targets at low concentration.