With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Objective: To understand the subjective and objective comfort evaluations of students from different age groups on desks and chairs, so as to provide reference for standardized allocation and use of desks and chairs. Methods: From January to April 2024, a total of 2 446 students were selected from 26 schools in 13 districts (counties/cities) in Shanghai, Tianjin, and Wuxi from Jiangsu Province by using cluster random method, including students in kindergartens, primary schools, junior high schools,senior high schools, colleges and universities. Standardized procedures were used to measure the height and weight of participants, and the matching desks and chairs models were selected according to the height. The subjective comfort of students on matching desks and chairs was investigated, and their objective comfort was evaluated by using a self designed questionnaire. The χ 2 test was used to analyze the differences of subjective perception and objective evaluation in comfort between different types of desks and chairs. Results: About 84.1% of the students subjectively thought that large desks and small chairs were very comfortable or relatively comfortable, followed by large desks and chairs (75.7%), and the proportion of small desks and chairs was the lowest among the three types (46.2%), and the difference was statistically significant ( χ 2=722.46, P <0.01). The reporting rates of primary school, junior high school and senior high school students who subjectively considered large desks and chairs to be very comfortable/relatively comfortable were higher than that of other types of desks and chairs, and the differences were statistically significant ( χ 2=297.49, 252.82, 343.67, P <0.01). However, there was no significant difference in the subjective comfort evaluation of different types of desks and chairs among kindergarten children ( χ 2=3.21, P >0.05), and 66.3% of the students in colleges and universities felt very comfortable/relatively comfortable when they used the matching standard desks and chairs. The objective evaluation results of the comfort for the three types of desks and chairs were consistent with the subjective evaluation, but the proportions of the objective evaluation as very comfortable/relatively comfortable were higher than that of the subjective evaluation ( χ 2=20.76- 813.47, P <0.01). Conclusions Large desks and chairs, as well as large desks with small chairs are perceived comfortable, while small desks and chairs are perceived less comfortable. It is recommended to match the large desks and chairs or large desks and small chairs that are suitable for them according to the "standard", to promote physical and mental health of students.

By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.
Adult ; Female ; Humans ; Young Adult ; Epilepsy ; Hippocampus ; Memory, Short-Term ; Mental Recall ; Prefrontal Cortex ; Theta Rhythm ; Male

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

Objective:To explore the mechanism of Mito-TEMPO inhibiting the activation of BV2 microglia induced by lead(Pb)exposure.Methods:Mouse microglia BV2 were cultured in vitro.The effects of different concentrations of lead exposure on the viability of BV2 cells were determined by MTT colorimetric method,and a model of lead expo-sure was developed and intervened with Mito-TEMPO antioxidant.Immunofluorescence staining was used to detect the expression of M1 activation marker CD86 protein.Enzyme-linked immunosorbent assay was used to detect the expression of pro-inflammatory factors interleukin-1 β(IL-1β),tumor necrosis factor α(TNF-α),interleukin-6(IL-6).Mito-chondrial superoxide indicator(MitoSOX)staining was used to detect the level of mitochondrial oxidative stress.JC-1 staining was used to detect mitochondrial membrane potential.The respiratory ability of mitochondria was detected by cell energy metabolism analysis system(O2k).Results:Compared with the control group,the expression of CD86 protein,the levels of pro-inflammatory cytokines IL-1β,TNF-α and IL-6 in BV2 cells increased significantly,the level of oxidative stress in mitochondria increased significantly,and the mitochondrial membrane potential and respiratory ability decreased significantly in lead exposed group.Mito-TEMPO treatment significantly reduced the oxidative stress and functional damage of mitochondria in BV2 cells,and significantly inhibited the M1 activation level of BV2 cells.Conclusion:The results show that Mito-TEMPO treatment can reverse the M1 activation of BV2 cells induced by lead exposure,and the specific mechanism may be related to the reduction of mitochondrial oxidative stress and dysfunction by Mito-TEMPO.

Objective To generate minichromosome maintenance protein 2(MCM2)gene knockout cervi-cal cancer HeLa cell lines using inducible CRISPR/Cas9 technology,and to explore the effect of MCM2 on DNA replication and replication stress.Methods The inducible CRISPR/Cas9 system,TLCV2,was used to construct MCM2 knockout HeLa cell lines.And the cell lines were divided into control group(Control),knockout group 1(KO1),and knockout group 2(KO2).Western blot,Edu incorporation experiment,real-time quantitative PCR(qPCR),immunofluorescence and MTT assay were used to analyze the effects of MCM2 knockout on DNA replica-tion and replication stress induced by hydroxyurea.Results The CRISPR/Cas9 system successfully knocked out the MCM2 gene after induction,and MCM2 knockout affected the stability of MCM2-7 complex.Compared with the control cells,MCM2 knockout cells had a dramatic decrease in the capacity of DNA replication,and the mRNA levels of Cyclin A1,Cyclin E1 and CDK4.Under DNA replication stress,MCM2 knockout cells decreased cell viability,DNA damage repair capacity,and increased genomic instability compared with control cells.Conclusion Knockout of MCM2 gene reduces the DNA replication capacity of HeLa cells under normal conditions and cell viability under replication stress.This study successfully generates MCM2 gene inducible knockout HeLa cell lines,laying the foundation for further research on the role and biological function of MCM2 gene in the occurrence and progression of cervical cancer.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

AIM To improve the quality standard for Guanxin Shengmai Pills.METHODS TLC was adopted in the qualitative identification of Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma,the analysis was performed on a silica G thin layer plate,along with the low layer solution of chloroform-methanol-water(13 : 7 : 2)stood at below 10℃ as a mobile phase,and 10％sulfuric acid ethanol solution as a derivatization reagent.HPLC was applied to determining the contents of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rd,the analysis was performed on a 20℃ thermostatic Thermo Accucore-C18 column(4.6 mm×150 mm,2.6 μm),with the mobile phase comprising of acetonitrile-water flowing at 0.8 mL/min in a gradient elution manner,and the detection wavelength was set at 203 nm.RESULTS The clear TLC bands present without negative interference.Four constituents showed good linear relationships within their own ranges(R2≥0.999 9),whose average recoveries were 91.21％-106.86％with the RSDs of 0.68％-1.43％.CONCLUSION This specific and reproducible method can provide a reference for the quality control of Guanxin Shengmai Pills.