1.The Structure and Function of The YopJ Family Effectors in The Bacterial Type III Secretion System
Ao-Ning LI ; Wen-Bo LI ; Yu-Ying LU ; Min-Hui ZHU ; Yu-Long QIN ; Yong ZHAO ; Zhao-Huan ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):516-533
The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP6), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP6-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.
2.Exploring Biological Characteristics of Rat Model of Atrial Fibrillation with Phlegm-heat and Blood Stasis Pattern Based on Metabolomics
Ailin HOU ; Yuxuan LIU ; Wenxi YU ; Xing JI ; Chan WU ; Dazhuo SHI ; Ying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):245-255
ObjectiveTo establish an animal model of atrial fibrillation(AF) that accurately reflects the phlegm-heat and blood stasis(TRYZ) pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups:the control group, the TRYZ+AF group,the AF group and the TRYZ group, with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide(LPS) injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride(Ach-CaCl2) via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration, echocardiography evaluated left atrial dimensions and cardiac function, fully automated biochemical analyzer measured the levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C), hemoreometer analyzed the whole blood viscosity, plasma viscosity, and whole blood reduced viscosity, a coagulation analyzer assessed prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), and fibrinogen(FIB), enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of C-reactive protein(CRP), interleukin(IL)-1β, IL-6, IL-17, tumour necrosis factor(TNF)-α, matrix metalloproteinase-9(MMP-9), galectin-3(Gal-3), Collagen Ⅰ, and α-smooth muscle actin(α-SMA). Hematoxylin-eosin(HE) staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium, Western blot was employed to detect MMP-9, Collagen Ⅰ and α-SMA protein expression in myocardial tissue, real-time quantitative polymerase chain reaction(Real-time PCR) evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight, tongue color[red(R), green(G), and blue(B)], and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling, compared with the control group, rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight, dry faeces, elevated rectal temperature, dark red tongue, decreased RGB values on the tongue surface, and markedly elevated TC and LDL-C levels(P<0.05, P<0.01). The TRYZ+AF, TRYZ, and AF groups exhibited significantly decreased TT, APTT and PT, along with markedly elevated whole blood viscosity and FIB(P<0.05, P<0.01). Rats in the TRYZ+AF and AF groups exhibited AF rhythm, markedly decreased heart rate, prolonged RR intervals, enlarged left atrium, and significantly reduced ejection fraction and shortening fraction(P<0.05, P<0.01). Serum levels of CRP, IL-1β, IL-6, IL-17, TNF-α, MMP-9, Gal-3, Collagen Ⅰ, and α-SMA were elevated in rats from the TRYZ+AF, TRYZ, and AF groups compared to the control group, with the most pronounced increase observed in the TRYZ+AF group(P<0.05, P<0.01). Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF, TRYZ and AF groups was higher than that in the control group(P<0.05, P<0.01). Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9, Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups(P<0.05, P<0.01). Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group, primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome, demonstrating the pathological process where the interactions of phlegm, heat and stasis jointly trigger tremor, this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.
3.Empirical study of input, output, outcome and impact of community-based rehabilitation stations
Xiayao CHEN ; Ying DONG ; Xue DONG ; Zhongxiang MI ; Jun CHENG ; Aimin ZHANG ; Didi LU ; Jun WANG ; Jude LIU ; Qianmo AN ; Hui GUO ; Xiaochen LIU ; Zefeng YU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):83-89
ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.
4.Herbal Textual Research on Quisqualis Fructus in Famous Classical Formulas
Xiuping WEN ; Shiying CHEN ; Ying TAN ; Guanwen ZHENG ; Huilong XU ; Wen XU ; Chengzi YANG ; Zehao HUANG ; Yu LIN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):225-237
This article systematically analyzed the historical evolution of the origin, scientific name, producing area, quality evaluation, harvesting and processing, and other aspects of Quisqualis Fructus by consulting the ancient materia medica, medical books, prescription books, local literature and combining with the modern literature and standards, summarized and explored the development rules of its medicinal properties and efficacy along with their underlying causes, in order to provide support for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shijunzi was first recorded as Liuqiuzi in Nanfang Caomuzhuang of the Jin dynasty, and the name of Shijunzi was first used in Kaibao Bencao of the Song dynasty, which has been consistently used throughout subsequent dynasties, and there were also aliases such as Junziren, Sijunzi, and Dujilizi. The mainstream source of Quisqualis Fructus used in the past dynasties has been the dried mature fruits of Quisqualis indica, a plant belonging to the family Combretaceae. In modern times, its variety Q. indica var. villosa has also been recorded as the medicinal material of Quisqualis Fructus. In 2007, the Flora of China(English edition) designated Q. indica var. villosa as a synonym of Q. indica. Today, the accepted name of Shijunzi is updated to Combretum indicum. According to ancient herbal records, the producing areas of Quisqualis Fructus were Guangdong, Hong Kong, Macao, Guangxi, Hainan, Sichuan and Fujian, and then gradually expanded to Yunnan, Taiwan, Jiangxi and Guizhou. Since the Song dynasty, two major production regions have gradually emerged in Sichuan, Chongqing and Fujian. Currently, it is primarily cultivated in Chongqing, Guangxi and other areas, with Chongqing yielding the highest output. Since modern times, superior quality has been defined by large size, a purple-black surface, plump grains, and a yellowish-white kernel. According to ancient herbal records, the harvesting period of Quisqualis Fructus was the July and August of the lunar calendar, mostly used raw after shelling or with the shell intact, it underwent processing methods such as cleaning, slicing, mixing, steaming, roasting, stewing, and frying. Currently, the harvesting period is autumn, followed by sun-drying or low-heat drying, with processing methods including cleaning, stir-frying, and stewing. In ancient and modern literature, the records of the properties, functions and indications of Quisqualis Fructus are basically the same, that is, sweet in taste, warm in nature, predominantly non-toxic, belonging to the spleen and stomach meridians. It possesses effects of insecticide, decontamination and invigorating spleen for ascariasis, enterobiasis, abdominal pain due to worm accumulation and infantile malnutrition.The contraindications for use primarily include avoiding consumption by individuals without parasitic infestations, limiting use for those with spleen-stomach deficiency-cold, refraining from drinking hot tea during medication, and avoiding excessive intake. Based on the textual research, it is suggested that the dried mature fruits of Q. indica should be used as the medicinal material for the development of famous classical formulas containing Quisqualis Fructus. Processing methods may be chosen according to prescription requirements, and the raw products is recommended for medicinal use if not specified.
5.Epidemiological characteristics and disease burden of liver cancer in Guangdong Province
Ying ZHANG ; Yixuan CHEN ; Rong CAO ; Yue GAO ; Yutong HAN ; Ye WANG ; Ruilin MENG ; Xueyan ZHENG ; Yu LIAO ; Zhuanping ZENG
Journal of Public Health and Preventive Medicine 2026;37(1):68-72
Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000,respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.
6.Effects of Modified Buyang Huanwu Tang on Mice with Cerebral Ischemia-reperfusion Injury by Regulating PINK1/Parkin Signaling Pathway-mediated Mitochondrial Autophagy
Li GUO ; Hengwen CHEN ; Cun ZHAN ; Zhenzhen YING ; Zuomin WU ; Shaoju JIN ; Shangmei CAO ; Shengming HUANG ; Jin WANG ; Xiaotao YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):34-43
ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury (CI/RI) in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase (PINK1/Parkin) signaling pathway-mediated mitophagy, and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups (n = 12 per group): Sham-operated group, middle cerebral artery occlusion/reperfusion (MCAO/R) model group, low-, medium-, and high-dose modified Buyang Huanwu Tang groups (8.84, 17.68, 35.36 g·kg-1·d-1), and an aspirin group (13.00 mg·kg-1·d-1). Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy (TEM). Serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression levels of PINK1, Parkin, microtubule-associated protein 1 light chain 3B (LC3B, LC3Ⅱ/Ⅰ), and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR (Real-time PCR) and Western blot, respectively. ResultsCompared with the sham-operated group, the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Severe cortical injury on the infarct side was observed, characterized by decreased neuronal density, cytoplasmic vacuolation, nuclear pyknosis, a marked reduction in Nissl bodies, dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons, and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly (P<0.01). Mitochondria exhibited cristae membrane rupture and matrix vacuolation, with rupture of the outer mitochondrial membrane and formation of autophagosomes, the number of which increased significantly. Serum SOD activity decreased significantly (P<0.01), while MDA content increased significantly (P<0.01). In infarcted brain tissues of model mice, the relative mRNA expression and protein levels of PINK1, Parkin and LC3B were significantly increased (P<0.05, P<0.01), whereas p62 mRNA and protein expression were significantly decreased (P<0.05, P<0.01), showing statistical significance. Compared with the model group, all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios (P<0.01). Neuronal density increased significantly, cytoplasmic vacuolation was alleviated, nuclear morphology tended to be more regular and clearer, Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored, with some mitochondria showing autophagosome encapsulation, and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly (P<0.01), while MDA content decreased significantly. The mRNA and protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ were significantly increased (P<0.05, P<0.01), while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased (P<0.05, P<0.01), showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1, Parkin, and LC3Ⅱ/Ⅰ and downregulate p62 protein expression, suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.
7.The role of shed syndecan-4 in temporomandibular joint osteoarthritis in rats
HE Kangping ; CHEN Xiaohua ; LI Jinru ; ZHAN Ying ; HE Feng ; JIANG Tianlu ; LI Feifei ; YU Shibin
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(5):443-455
Objective:
To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment.
Methods:
This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA.
Results:
Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01).
Conclusion
During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.
8.Correlation Between "Pathological Accumulation from Collateral Obstruction" and Gap Junction Communication Dysfunction and Its Application in Tumor Prevention and Treatment
Hongtai XIONG ; Ying SONG ; Yanyuan DU ; Peiyi YU ; Honggang ZHENG
Journal of Traditional Chinese Medicine 2025;66(13):1311-1316
By reviewing modern research and integrating clinical practice, this paper elucidates the correlation between the traditional Chinese medicine theory of pathological accumulation from collateral obstruction and gap junction intercellular communication (GJIC), as well as its theoretical connotation and clinical application in tumor prevention and treatment. Physiologically, gap junction and collateral channels share similarities in structural distribution, substance exchange and information transmission. Pathologically, metabolic coupling mediated by dysfunctional gap junction resembles collaterals stagnation, forming the basis of tumor pathogenesis. The establishment of heterotypic gap junction parallels collateral hyperactivity, contributing to tumor metastasis. The post-translational modifications (PTMs) disorder of connexins is similar to the deficiency of collaterals, serving as a driver of tumor progression. Clinically, tumor treatment should follow the pathomechanism of collateral obstruction leading to pathological accumulation. In the early stage, detoxifying and unblocking collaterals can restore intercellular communication and inhibit tumorigenesis; in the progressive stage, calming hyperactivity and suppressing aberrant collateral pathways can prevent metastasis by interrupting heterotypic gap junction formation; and in the terminal stage, supporting vital qi and modulating PTMs of connexins can help delay tumor progression.
9.Impact of prenatal triclosan exposure on ADHD-like symptoms in school-aged children
Jingjing LI ; Xiaomeng CHENG ; Yan ZHANG ; Luanluan LI ; Xiaodan YU ; Ying TIAN ; Yu GAO
Journal of Environmental and Occupational Medicine 2025;42(6):645-651
Background Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder in children, often diagnosed during school age. The etiology of ADHD remains unclear; however, existing studies suggest that environmental factors, such as exposure to triclosan (TCS), may be associated with the occurrence of ADHD-like symptoms in offspring. Nevertheless, relevant research in China remains limited. Objective To investigate the impact of early pregnancy TCS exposure on ADHD-like symptoms in 7-year-old children. Methods This study was based on the Shanghai Birth Cohort (SBC) and included 662 mother-child pairs. TCS concentrations in early pregnancy urine samples were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Demographic information was collected via questionnaires and medical record abstraction. ADHD-like symptoms in 7-year-old children were first assessed using the Strengths and Difficulties Questionnaire (SDQ). Further differentiation of ADHD-like symptom subtypes (inattentive and hyperactive/impulsive) was conducted using the SNAP-IV, a clinically validated ADHD screening tool. Negative binomial regression models were applied to evaluate the associations between prenatal TCS exposure and hyperactive behavior (SDQ assessment) as well as ADHD-like symptom subtypes (SNAP-IV assessment) in 7-year-old children. Results The positive rate of TCS in early pregnancy urine samples was 91.39%, with median concentrations of 0.69 μg·L−1 and 0.63 μg·g−1 before and after the creatinine adjustment, respectively. The modeling results indicated that prenatal TCS exposure was associated with an increased risk of hyperactive symptoms (SDQ assessment) in 7-year-old children (RR=1.04, 95%CI: 1.02, 1.06); the stratified analyses by children sex revealed similar effects for both boys (RR=1.04, 95%CI: 1.02, 1.07) and girls (RR=1.04, 95%CI: 1.01, 1.07). Further analysis of ADHD-like symptom subtypes showed that prenatal TCS exposure increased the risk of inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.05); the sex-stratified analyses indicated associations between TCS exposure and inattentive symptoms (RR=1.03, 95%CI: 1.00, 1.07) as well as hyperactive/impulsive symptoms (RR=1.04, 95%CI: 1.01, 1.08) in girls. Conclusion Prenatal TCS exposure is associated with an increased risk of ADHD-like symptoms in 7-year-old children, primarily contributing to the risk of the inattention subtype. The impact is more pronounced in girls.
10.Impacts of pre-pregnancy exposure to per- and polyfluoroalkyl substances on menstrual characteristics among women undergoing assisted reproductive technology
Huyi TAO ; Yujie CAO ; Yitao PAN ; Jiuru ZHAO ; Zhiwei LIU ; Yu GAO ; Ying TIAN
Journal of Environmental and Occupational Medicine 2025;42(6):652-660
Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely used in various products, leading to population exposure and long-term accumulation. At present, there is a lack of research on the relationships between pre-pregnancy PFAS and menstrual characteristics among women undergoing assisted reproductive technology (ART) in China. Objective To explore the relationships between pre-pregnancy PFAS exposure among women undergoing ART and menstrual characteristics prior to assisted reproductive treatment. Methods This study employed a cross-sectional research design, recruiting women undergoing ART treatment at the Reproductive Clinic of the International Peace Maternity & Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, from 2017 to 2020 as study participants. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to detect 42 types of PFAS in pre-pregnancy serum samples. Questionnaires were administered to collect information on demographic characteristics, lifestyle habits, and menstrual characteristics (average menstrual cycle length, average menstrual period length, menstrual irregularities, and menstrual bleeding volume) of women undergoing ART. Multiple linear regression, binary logistic regression, and multinomial logistic regression analyses were performed to investigate the relationships between individual PFAS exposure before pregnancy and menstrual characteristics among ART women. Additionally, weighted quantile sum (WQS) model was applied to analyze the association between PFAS mixtures and menstrual characteristics. Results In the pre-pregnancy serum samples of the study population, 15 PFAS were detected in more than 60% of the samples, including perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), perfluoro-2-propoxypropanoic acid (HFPO-DA), perfluoro-2-methoxyacetic acid (PFMOAA), and perfluoro-(3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA). Among them, PFOA had the highest median concentration of 9.160 ng·mL−1. The single PFAS exposure analysis revealed a positive correlation between PFAS and irregular menstrual cycles. Specifically, for every natural-log unit (e) increase in PFOA, PFBS, or PFHxS level, the incidence of irregular menstrual cycles increased by 57%, 42%, or 39%, respectively. Most PFAS were positively correlated with the average number of menstrual cycle days, such as PFHpA (b=1.08, 95%CI: 0.11, 2.05), PFOA (b=1.69, 95%CI: 0.39, 3.00), PFBS (b=1.23, 95%CI: 0.25, 2.22), PFHxS (b=1.47, 95%CI: 0.61, 2.32), PFHpS (b=1.48, 95%CI: 0.35, 2.61), and 6:2 Cl-PFESA (b=0.90, 95%CI: 0.08, 1.72). Furthermore, levels of PFHpA (OR=1.39, 95%CI: 1.06, 1.82), PFOA (OR=1.58, 95%CI: 1.09, 2.30), PFBS (OR=1.37, 95%CI: 1.04, 1.80), PFHxS (OR=1.34, 95%CI: 1.05, 1.71), PFHpS (OR=1.53, 95%CI: 1.10, 2.14), and 6:2 Cl-PFESA (OR=1.34, 95%CI: 1.06, 1.70) were positively correlated with low menstrual blood volume, while PFOA (OR=0.40, 95%CI: 0.23, 0.71), PFHpS (OR=0.45, 95%CI: 0.29, 0.71), and HFPO-DA (OR=0.68, 95%CI: 0.48, 0.97) were negatively correlated with high menstrual blood volume. The mixed exposure model showed that PFAS mixtures were positively correlated with the average number of menstrual cycle days (b=1.60, 95%CI: 0.49, 2.71), irregular menstrual cycles (OR=1.77, 95%CI: 1.19, 2.63), and low menstrual blood volume (OR=1.59, 95%CI: 1.08, 2.35), but negatively correlated with high menstrual blood volume (OR=0.40, 95%CI: 0.22, 0.73). Conclusion Women undergoing ART in Shanghai are widely exposed to PFAS prior to conception. Exposure to PFAS before pregnancy may be related to menstrual characteristics among women seeking ART before undergoing fertility treatments, but additional data from larger populations are required to validate the findings of this study.


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