Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Objective:To characterize and compare the polysaccharide components of Panax japonicus with its common counterfeits (Dysosma versipellis, Lycopus lucidus and Dysosma pleiantha); To provide a scientific basis for the quality evaluation of polysaccharides of Panax japonicu.Methods:Crude polysaccharides were extracted using water and subsequently precipitated with ethanol. Three batches of total polysaccharides from Panax japonicus, Dysosma versipellis, Lycopus lucidus and Dysosma pleiantha were prepared using the savage deproteinization method. The molecular weight distribution, functional group characteristics and monosaccharide composition of each batch were analyzed using high performance gel filtration chromatography (HPGFC), fourier-transform infrared spectroscopy (FT-IR) and derivatization of 1-phenyl-3-methyl-5-pyrazolinone with high performance liquid chromatography (PMP-HPLC). Using DEAE column chromatography purification and specific enzymolysis, combined with high performance thin layer chromatography and carbohydrate gel electrophoresis, the saccharide profiles of polysaccharides of Panax japonicus and its counterfeits were analyzed and compared.Results:The molecular weight distribution of total polysaccharides from three batches of Panax japonicus exhibited high similarity, with a concentrated distribution ranging from 2.05×10 4 - 1.87×10 3 Da. However, the molecular weight distribution of total polysaccharides from Dysosma versipellis was scattered in regions 5.08×10 6-6.47×10 5 Da and 6.47×10 5-2.05×10 4 Da, while Lycopus lucidus and Dysosma pleiantha was scattered in regions 6.47×10 5-2.05×10 4 Da and 2.05×10 4-1.87×10 3 Da; the infrared spectra of all samples exhibited similarity, indicating that the sugar chains of each polysaccharide were predominantly linked by α-glycosidic bonds, with no significant differences was observed. In terms of monosaccharide composition, the polysaccharides from Panax japonicus, Dysosma versipellis and Dysosma pleiantha were mainly composed of glucose, galactose, arabinose, galacturonic acid, rhamnose and mannose. In contrast, the polysaccharides from Lycopus lucidus were distinct, primarily consisting of galactose and glucose; glycosidic linkage analysis revealed that the polysaccharides purified by DEAE column chromatography from Panax japonicus and its counterfeits were resistant to hydrolysis by β- galactosidase, but could be hydrolyzed by α-amylase and pectinase (except for Lycopus lucidus). The oligosaccharides produced by α-amylase hydrolysis of three batches of Panax japonicus polysaccharides were similar, showing clear differences from those of the counterfeits. The results of pectinase hydrolysis were correlated with the content of uronic acids. Conclusions:The total polysaccharides from Panax japonicus, Dysosma versipellis, Lycopus lucidus and Dysosma pleiantha exhibit significant differences in their molecular weight distributions. The monosaccharide composition of Lycopus lucidus polysaccharides is notably distinct, making it easily distinguishable from other species; purification using DEAE column chromatography, combined with HPTLC and polysaccharide analysis using carbohydrate gel electrophoresis (PACE), effectively differentiates the polysaccharides of Panax japonicus from its counterfeits. This approach provides a valuable reference for the quality analysis of polysaccharides in TCM. Additionally, it lays a foundation for the development and utilization of Panax japonicus polysaccharides.

Objective:To analyze the epidemiological characteristics and pathogen spectrum of influenza outbreaks in Shaanxi Province from 2014 to 2023 and provide basis reference for strengthening regional influenza prevention and control.Methods:The data were collected from the Public Health Emergency Management Information System of the China Disease Prevention and Control Information System and the China Influenza Surveillance Information System. On-site epidemiological investigation information and etiological test results of influenza network laboratories reported in Shaanxi Province during 2014-2023 were collected, and descriptive analysis was conducted on the time, region, and location distribution of influenza outbreaks. SPSS 25.0 software was used for statistical analysis.Results:A total of 386 influenza outbreaks were reported in Shaanxi from 2014 to 2023, with a total attack rate of 1.81% (14 880/821 001). The epidemic peaks mainly occurred in winter and spring (November to March of the following year), and there was an alternating pattern of epidemic peaks in different years (the early peak was in December, and the late peak was in March of the following year). The epidemic areas were mainly concentrated in the Qinba Mountains of southern Shaanxi (209, 54.15%) and Guanzhong Plain (173, 44.82%). The epidemic places were mainly distributed in primary schools (239, 61.92%), and the differences of epidemic areas and places were statistically significant (all P<0.001). Influenza A(H3N2) viruses were the predominant pathogen in the outbreak (849, 57.76%), and influenza A(H3N2), B (Victoria) lineage and A(H1N1)pdm09 virus alternately dominated the epidemic peak in different years. Conclusions:The peak of influenza outbreaks in Shaanxi Province was winter and spring during 2014-2023. Primary schools in the Qinba Mountains of southern Shaanxi and Guanzhong Plain should be targeted for prevention and control. In the prevention and control programs, close attention should be paid to the changing trend of dominant strains. Effective intervention measures should be targeted to the high-incidence areas and seasons.

Objective:To establish an HPLC fingerprint of Shenling Baizhu Powder and Shenling Baizhu Pills; To evaluate the quality consistency of commercial Shenling Baizhu Powder and Shenling Baizhu Pills.Methods:HPLC method was adopted with Agilent TC-C18 column (250 mm×4.6 mm, 5 μm). The mobile phase was 0.05% phosphoric acid-acetonitrile with gradient elution; the flow rate was 1.0 ml/min; the detection wavelength was 203 nm; the column temperature was 25 ℃. The HPLC fingerprints of Shenling Baizhu Powder and Shenling Baizhu Pills from different manufacturing enterprises were established and analyzed by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM (Version 2012) software for similarity evaluation, and the main chromatographic peaks were identified.Results:The control fingerprints of Shenling Baizhu Powder and Shenling Baizhu Pills were obtained. 73 common peaks and 79 common peaks were identified respectively. The similar degrees of all samples were over 0.92. The quality consistency of drugs different batches of different production enterprises was good. A total of 10 components were identified, including Liquiritin, Ginsenoside Rg1, Ginsenoside Rb1, Glycyrrhizin, Isoliquiritin, Ginsenoside Rd, Glycyrrhizic acid, AtractylenolideⅠ, AtractylenolideⅡ and AtractylenolideⅢ.Conclusions:The established HPLC fingerprints can quickly evaluate the formulation quality of Shenling Baizhu Powder and Shenling Baizhu Pills, providing basis the quality control.

Objective:To explore the distribution and characteristics of microbiota in the lower reproductive tract of patients with cervical squamous cell carcinoma infected by human papilloma virus (HPV) 16 subtype.Methods:A prospective, cross-sectional study was conducted. A total of 6 patients with HPV16 single subtype positive cervical squamous cell carcinoma admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from August 2019 to June 2020 were selected as cervical carcinoma group, and 6 healthy women who did not indicate abnormalities in thin-based layer cytology test (TCT) during the same period among the physical examination population and had HPV negative test result were selected as the healthy control group. A sterile cotton swab was used to collect secretions from the posterior cervical fornix in patients before antitumor treatment and healthy controls during physical examination. The high variable region of the 16S rRNA gene V1-V2 of the bacteria was amplified by using next generation sequencing (NGS), and then the distribution and characteristics of the bacteria were analyzed.Results:The age of cervical cancer group and the healthy control group was (51±8) years and (48±3) years, respectively, and the difference in age between the both groups was statistically significant ( t= 0.63, P= 0.540). The patients of both groups had reproductive history and no smoking experience. Alpha diversity analysis showed that compared with the healthy control group, the sobs ( t= 3.25, P= 0.009) and chao ( t= 2.91, P= 0.016) indexes were higher in cervical cancer group, and the differences were statistically significant. The shannon index was higher ( t= 2.07, P= 0.065) and simpson index was lower ( t= 1.74, P= 0.113) in cervical cancer group, while the difference was not statistically different. Data dimensionality reduction analysis in principal coordinate analysis (PCoA) based on bray-curtis distance showed that the difference in Beta diversity between the healthy control group and cervical cancer group was statistically significant ( R2= 0.154, P = 0.018). At the phylum level, the proportion of Firmicutes in cervical cancer group was lower than that in the healthy control group (30.21% vs. 68.28%), while the proportion of Bacteroidetes in cervical cancer group decreased slightly (6.87% vs. 8.11%); and the proportion of Actinobacteria (26.91% vs. 14.42%) and Proteobacteria (27.33% vs. 0.67%) had an increase in cervical cancer group. At the genus level, compared with the healthy control group, the proportion of Lactobacillus and Corynebacterium decreased in cervical cancer group, and loss of dominant flora could be detected; while Rhodococcus, Klebsiella and Aerococcus increased significantly in cervical cancer group. The bacteria species in cervical cancer group was increased compared with the healthy control group. Linear discriminant analysis (LDA) showed that Rhodococcus (LDA = 5.04), Klebsiella (LDA = 4.71), Enterobacter (LDA = 4.29), Ralstonia (LDA = 4.28), Ochrobactrum (LDA = 4.23) and Veillonella (LDA = 4.14) were the distinctive microbiota of cervical cancer group at the genus level. At the phylum level, Firmicutes (LDA = 5.23) in the healthy control group could be considered as a marker species. At the species level, the proportions of Rhodococcus ( P = 0.025), Ralstonia ( P = 0.045), Veillonella ( P = 0.044), Paraburkholderia ( P = 0.045), Pseudomonas ( P = 0.043) in cervical cancer group were increased compared with the healthy control group, and the differences were statistically significant. Conclusions:HPV16 single positive patients with cervical squamous cell carcinoma show the characteristics such as the increased diversity and richness of the lower reproductive tract microbiota compared with the healthy controls, while the abundance of Lactobacillus decreases. Rhodococcus and Klebsiella could serve as symbolic microbial in the lower reproductive tract. However, further studies still need to be verified.

Olfactory bulb is a critical component in encoding and processing olfactory signals, characterized by its intricate neural projections and networks dedicated to this function. It has been found that descending neural projections from the olfactory cortex and other advanced brain regions can modulate the excitability of olfactory bulb output neurons in the olfactory bulb, either directly or indirectly, which can further influence olfactory discrimination, learning, and other abilities. In recent years, advancements in optogenetic technology have facilitated extensive application of neuron manipulation for studying neural circuits, thereby greatly accelerating research into olfactory mechanisms. This review summarizes the latest research progress on the regulatory effects of neural projections from the olfactory cortex, basal forebrain, raphe nucleus, and locus coeruleus on olfactory bulb function. Furthermore, the important role that photogenetic technology plays in olfactory mechanism research is evaluated. Finally, the existing problems and future development trends in current research are preliminarily proposed and explained. This review aims to provide new insights into the mechanisms underlying olfactory neural regulation as well as applications of optogenetic technology, which are crucial for advancing the research on olfactory mechanism and the application of optogenetic technology.
Olfactory Bulb/physiology* ; Optogenetics/methods* ; Animals ; Humans ; Olfactory Pathways/physiology* ; Olfactory Cortex/physiology* ; Smell/physiology*

Changes in cardiac structure and function such as myocardial aging,valve alterations,alterations in the cardiac conduction system and vascular aging are crucial for studying therapeutic methods for age-related cardiovascular diseases.Histone methylation modification is involved in the regulation of gene expression and closely related to the occurrence and development of age-related car-diovascular diseases.This paper provided a comprehensive review on the role of histone methylation modification in cardiac structural and functional changes,providing new theoretical basis for age-relat-ed cardiovascular diseases.

Changes in cardiac structure and function such as myocardial aging,valve alterations,alterations in the cardiac conduction system and vascular aging are crucial for studying therapeutic methods for age-related cardiovascular diseases.Histone methylation modification is involved in the regulation of gene expression and closely related to the occurrence and development of age-related car-diovascular diseases.This paper provided a comprehensive review on the role of histone methylation modification in cardiac structural and functional changes,providing new theoretical basis for age-relat-ed cardiovascular diseases.

Eosinophil extracellular traps (EETs), an important pathway of eosinophil to exert its effects, are composed of DNA fibers, histone and eosinophil granule proteins. Recently, many researches have shown that EETs play an important role in the genesis and development of respiratory diseases including asthma, allergic bronchopulmonary aspergillosis and chronic obstructive pulmonary disease. EETs can directly damage airway epithelial cells, promote airway inflammation and airway hypersecretion, increase the stickiness of secretions and induce the generation of autoantibody, helping eosinophils and their products participate in a cascade of events leading to inflammation and disease. Researches on EETs can also be helpful in investigating new targets for the treatment of chronic airway diseases.