1.Brain Aperiodic Dynamics
Zhi-Cai HU ; Zhen ZHANG ; Jiang WANG ; Gui-Ping LI ; Shan LIU ; Hai-Tao YU
Progress in Biochemistry and Biophysics 2025;52(1):99-118
Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.
2.Expression of indoleamin 2, 3-dioxygenase 1 in different types of breast cancer and its relationship with patient prognosis and immune cell infiltration
LI Xiaopiao1 ; LI Jie1 ; XIAO Jun2 ; DONG Yuhua2 ; HE Xun1 ; ZHANG Jinjuan2,3
Chinese Journal of Cancer Biotherapy 2025;32(6):620-627
[摘 要] 目的:探究吲哚胺2,3-双加氧酶1(IDO1)在不同类型乳腺癌组织中的表达及其与患者预后和免疫细胞浸润的关系。方法:收集 TCGA 数据库中乳腺癌RNA测序数据和相应临床资料,分析IDO1 mRNA在不同亚型、不同分期、不同绝经阶段及不同年龄等各类型乳腺癌组织与癌旁组织中的表达差异。将IDO1 mRNA表达有明显差异的乳腺癌类型的患者分为IDO1高、低表达组,比较3组间的疾病特异性生存率(DSS),分析IDO1 mRNA在DSS有明显差异的癌组织中的表达水平与免疫细胞浸润的关系。采用免疫组化法检测IDO1蛋白在ER阴性、PR阴性、HER2阳性及Ⅱ期乳腺癌组织中的表达情况,对数据库数据进行验证。结果:IDO1 mRNA在乳腺癌组织中呈高表达,但在不同类型乳腺癌中的表达不同。IDO1 mRNA在ER阴性、PR阴性、HER2阳性、HER2阴性亚型、Ⅱ期、T2期、N0期和M0期分期、绝经前、绝经后和年龄≤ 60岁患者的乳腺癌组织中呈高表达(P < 0.05或P < 0.01或P < 0.001)。ER阴性、PR阴性、HER2阳性和Ⅱ期亚组中,IDO1 mRNA高表达患者的DSS明显高于低表达患者(P < 0.05或P < 0.01)。ER阴性、PR阴性、HER2阳性和Ⅱ期乳腺癌组织中IDO1 mRNA表达与活化的树突状细胞(aDC)、Th1细胞、T细胞、CD56dim NK细胞、CTL和Treg细胞等免疫细胞浸润有关联(均P < 0.001)。IDO1蛋白在ER阴性、PR阴性、HER2阳性及Ⅱ期乳腺癌组织中均呈高表达(均P < 0.001),与数据库数据分析结果一致。结论:IDO1在不同类型的乳腺癌组织中的表达不同,IDO1表达与ER阴性、PR阴性、HER2阳性和Ⅱ期乳腺癌患者的预后和免疫细胞浸润有关联。
3.Research progress on impacts of air pollutants, gut microbiota, and seminal microbiota on semen quality
Wenchao XIA ; Jiahua SUN ; Yuya JIN ; Ruixin LUO ; Ruyan YAN ; Yuming GUI ; Yongbin WANG ; Fengquan ZHANG ; Wei WU ; Weidong WU ; Huijun LI
Journal of Environmental and Occupational Medicine 2025;42(8):1003-1008
In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.
4.Effect of Dihuang Yinzi Decoction (地黄饮子)on Retinal Insulin Content and Insulin Signaling Pathway Related Protein Expression in Alzheimer's Disease Model Mice
Dongyan WU ; Wanwei GUI ; Xiaodan WANG ; Qinqing LI ; Jinmiao CHAI ; Junlong ZHANG
Journal of Traditional Chinese Medicine 2024;65(15):1593-1601
ObjectiveTo observe the possible mechanism of Dihuang Yinzi Decoction (地黄饮子) for improving cognitive dysfunction in Alzheimer's disease (AD) from the perspective of retina. MethodsForty-five APP/PS1 mice (AD model mice) were randomly divided into model group, Dihuang Yinzi Decoction group, and memantine group, with 15 mice in each group, while 15 wild-type C57BL/6J mice from the same litter were used as blank group. Mice in Dihuang Yinzi Decoction group were given Dihuang Yinzi Decoction 30.03 g/(kg·d) by gavage, mice in the memantine group were given memantine hydrochloride 6.1 mg/(kg·d) by gavage, and mice in the blank group and the model group were given normal saline 2 ml/(kg·d) by gavage for 4 consecutive weeks. Fasting blood glucose was measured weekly. After 4 weeks of intervention, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed; Morris water maze was used to detect the changes in spatial memory ability of mice; glucose oxidase method was used to detect retinal glucose content of mice; enzyme-linked immunosorbent assay (ELISA) was used to detect serum and retinal insulin content of mice, and Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the retina, and the retinal thickness and ganglion cell number were counted; protein immunoblotting was performed to detect the retinal pathway-associated proteins [insulin receptor substrate 1 (IRS1), phosphorylated insulin receptor substrate 1 (pIRS1), phosphatidylinositol-3-hydroxykinase (PI3K), protein kinase B (Akt1), phosphorylated protein kinase B (pAkt1)] expression; retinal glucose transporter protein 4 (GLUT4) expression was detected by immunohistochemistry. ResultsCompared with the blank group, fasting blood glucose of mice in the model group at weeks 1, 2, 3, and 4, blood glucose and area under the curve (AUC) at different time point of OGTT and ITT test, fasting serum insulin, and HOMA-IR increased (P<0.05, P<0.01); in the Morris water maze experiment, the escape latency increased from day 3 to day 5, and the number of crossing platforms, the percentage of target quadrant distance, and the percentage of target quadrant time decreased (P<0.05, P<0.01); the outer nuclear layer of the retina became sparse, thinner, and the number of ganglion cells decreases (P<0.01); the expression level of retinal glucose increased, while the expression levels of insulin, pIRS1/IRS1, PI3K/β-Actin, pAkt1/Akt1, and GLUT4 proteins decreased (P<0.01). Compared with the model group, fasting blood glucose at week 4, blood glucose at each time point of the OGTT and ITT tests AUC decreased (P<0.05, P<0.01), and fasting serum insulin and HOMA-IR decreased (P<0.05) in Dihuang Yinzi Decoction group; In the Morris water maze test, the escape latency shortened on day 4 and day 5, number of platform crossings, target quadrant distance as a proportion of total distance, and target quadrant movement time as a proportion of total time decreased (P<0.05, P<0.01); retinal pathological changes alleviated, and retinal thickness and ganglion cell number increased (P<0.01); retinal glucose content decreased, and retinal pIRS1/IRS1, PI3K/β-Actin, and GLUT4 protein expression elevated (P<0.05 or P<0.01). ConclusionsDihuang Yinzi Decoction can improve cognitive dysfunction of Alzheimer's disease, which may be related to regulating retinal insulin content and insulin signaling pathway.
5.Investigation on a suspected outbreak of carbapenem-resistant Acinetobacter baumannii nosocomial infection in an intensive care unit
Mei HUANG ; Xiaobo GUI ; Ya YANG ; Feng LU ; Juanxiu QIN ; Yan LI ; Shuyi ZHANG ; Wenqin ZHOU ; Xiaofang FU ; Haiqun BAN
Shanghai Journal of Preventive Medicine 2024;36(5):435-438
ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) nosocomial infection in an intensive care unit (ICU) and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection. MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing (MLST) were conducted and intervention measures were taken. ResultsA total of 4 cases with CRAB infection were identified, among which 1 case was determined to be community-acquired and3 cases were hospital-acquired. The isolated strains shared the same drug resistance, and were all classified into ST368 type. In the surface and hand samples (n=40), 2 CRAB strains were detected in the air filter beside the bed of the first case, with a detection rate of 5%. After adopting comprehensive prevention and control strategies, including environmental cleaning and disinfection, hand hygiene, staff management and training, and supervision, no similar case with CRAB infection was found. ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection, and inadequate implementation of hand hygiene. Timely identification, investigation, and targeted measures remain crucial to effective control of possible nosocomial infection.
6.Pathogenic spectrum and molecular characteristics of infectious diarrhea among children in Putuo District, Shanghai
Wenchao GU ; Huansheng ZHANG ; Haifeng TANG ; Hao YAN ; Tingting WU ; Yilin GUI ; Qiang LI ; Yong LI
Shanghai Journal of Preventive Medicine 2024;36(6):543-550
ObjectiveTo investigate the pathogenic spectrum and molecular characteristics of infectious diarrhea among children in Putuo District of Shanghai from 2018 to 2023, and to provide scientific basis for the prevention and control of infectious diarrhea in children. MethodsFecal samples from the cases visited sentinel hospitals for children’s diarrheal disease in Putuo District, Shanghai, were collected from January 2018 to December 2023. A total of 11 species of bacteria were isolated and cultured, and 5 species of viruses were detected by real-time fluorescent polymerase chain reaction (PCR). The molecular typing of some positive strains was analyzed by the standard pulsed-field gel electrophoresis (PFGE) method. The polymerase-capsid protein linkage region of some norovirus-positive samples was amplified by reverse transcription PCR, and was sequenced and analyzed by bioinformatics software. The Chi-square test and Fisher’s exact probability test were used to compare the pathogen-positive rates in 2018‒2019 and 2020‒2023. ResultsOf the 707 cases of children with infectious diarrhea, the total positive rate was 47.67%, with a single bacterial positivity rate of 16.27%, a single viral positivity rate of 22.63%, and a mixed positivity rate of 8.77%, respectively. The dominant pathogens were rotavirus (10.75%), norovirus (10.33%), enteropathogenic Escherichia coli (8.06%), Salmonella (6.36%), enteroaggregative Escherichia coli (5.52%), and Campylobacter (5.23%). Bacterial infections were predominant in summer and fall, and viral infections were predominant in winter and spring. The total positive rate decreased in 2020‒2023 compared with that of 2018‒2019 (χ2=5.753,P<0.05). Thirty-seven strains of Salmonella, 81 strains of diarrheagenic Escherichia coli, and 19 strains of Campylobacter were completed for the molecular typing analysis by PFGE, which were classified into 28, 80 and 18 banding types, respectively, with a wide range of banding similarity. Nineteen copies of norovirus GⅡ group gene sequences were analyzed and classified into 5 genotypes, which were mainly GⅡ.Pe-GⅡ.4 and GⅡ.P16-GⅡ.2 types. ConclusionRotavirus, norovirus, diarrheagenic Escherichia coli, Salmonella, and Campylobacter are the dominant pathogens of infectious diarrhea in children in Putuo District of Shanghai. The pathogen spectrum shows a trend of seasonal epidemic characteristics, with a diversity of molecular characteristics of some pathogens. Surveillance and monitoring on molecular characteristics of the pathogens of infectious diarrhea in children should be strengthened in different seasons, so as to provide a laboratory basis for the prevention and control of infectious diarrhea.
7.Endo-beta-N-acetylglucosaminidase: Possible Functions and Mechanisms
Xin-Rong LU ; Yong-Liang TONG ; Wei-Li KONG ; Lin ZOU ; Dan-Feng SHEN ; Shao-Xian LÜ ; Rui-Jie LIU ; Shao-Xing ZHANG ; Yu-Xin ZHANG ; Lin-Lin HOU ; Gui-Qin SUN ; Li CHEN
Progress in Biochemistry and Biophysics 2024;51(5):985-999
Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.
8.Allergy Associated With N-glycans on Glycoprotein Allergens
Yu-Xin ZHANG ; Rui-Jie LIU ; Shao-Xing ZHANG ; Shu-Ying YUAN ; Yan-Wen CHEN ; Yi-Lin YE ; Qian-Ge LIN ; Xin-Rong LU ; Yong-Liang TONG ; Li CHEN ; Gui-Qin SUN
Progress in Biochemistry and Biophysics 2024;51(5):1023-1033
Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.
9.Pollution status and distribution characteristics of indoor air bacteria in subway stations and compartments in a city of Central South China
Shuyan CHENG ; Zhuojia GUI ; Liqin SU ; Guozhong TIAN ; Tanxi GE ; Jiao LUO ; Ranqi SHAO ; Feng LI ; Weihao XI ; Chunliang ZHOU ; Wei PENG ; Minlan PENG ; Min YANG ; Bike ZHANG ; Xianliang WANG ; Xiaoyuan YAO
Journal of Environmental and Occupational Medicine 2024;41(7):801-806
Background Bacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. Objective To understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. Methods Three subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO2), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min−1, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO2 concentration and total bacterial count. Results The pass rates were 100.0% for airborne total bacteria count, PM2.5, and PM10 in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO2, but 0% for humidity. The overall median (P25, P75) total bacteria count was 177 (138,262) CFU·m−3. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P<0.05). A total of 874 strains and 82 species were identified by automatic microbial mass spectrometry. The results of identification were all over 9 points, and the predominant bacteria in the air were Micrococcus luteus (52.2%) and Staphylococcus hominis (9.8%). Three pathogens, Acinetobacter baumannii (0.3%), Corynebacterium striatum (0.1%), and Staphylococcus epidermidis bacilli (2.2%) were detected in 23 samples (2.6%), and the associated locations were mainly distributed in train compartments during evening rush hours. Conclusion The total bacteria count in indoor air varies by monitoring sites of subway stations and time periods, and there is a risk of opportunistic bacterial infection. Attention should be paid to cleaning and disinfection during peak passenger flow hours in all areas.
10.Determination concentration of methotrexate and its polyglutamates in human erythrocyte by high-performance liquid chromatographic fluorescence method
Gui-Jie ZHANG ; Ting LIAO ; Hong-Yu JIE ; Wen-Ying CHEN ; Qiang LI
The Chinese Journal of Clinical Pharmacology 2024;40(1):117-120
Objective To establish a sensitive,accurate and simple method for the determination of methotrexate and methotrexate polyglutamates(MTXPG2 and MTXPG3)in human erythrocytes.Methods A dual three element gradient liquid chromatograph with a fluorescence detector was used,the C18-WP column(20 mm ×4 mm,5μm)was used as the online SPE column,and the Athena C18-WP column(150 mm x4.6 mm,3 μm)was used as the analytical column.Erythrocyte lysate was precipitated with zinc sulphate-10%formic acid methanol(100:90,v/v),and postcolumn photo-oxidation of MTXPGs to fluorescent analytes using H2O2.The fluorescence excitation wavelength was 274 nm,the emission wavelength was 470 nm,the column temperature was 40 ℃,and the injection volume was 100 μL.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.Results MTX,MTXPG2 and MTXPG3 had good linearity in the range of 12.5-400.0 nmol·L-1.The standard curve of MTX was y=763.8x-2 961.1(R2=0.999 5),and the extraction recovery rate was 60.7%-66.1%;the standard curve of MTXPG2 was y=1 017.8x-239.8(R2=0.998 4),and the extraction recovery rate was 67.2%-67.3%;the standard curve of MTXPG3 was y=1 069.1x-819.6(R2=0.999 4),the extraction recovery rate was 62.9%-70.1%.Intra-day precision RSD<8.8%,inter-day precision RSD<10.8%.Conclusion This method is accurate and reproducibility,and the online solid-phose extraction enrichment and separation of target compounds simplify the sample pretreatment steps,improve the analysis efficiency,and is suitable for detecting the concentration of MTX,MTXPG2 and MTXPG3 in erythrocytes of patients with rheumatoid arthritis.

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