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1.
Neural Regen Res ; 16(1): 143-149, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788469

RESUMO

Veins are easy to obtain, have low immunogenicity, and induce a relatively weak inflammatory response. Therefore, veins have the potential to be used as conduits for nerve regeneration. However, because of the presence of venous valves and the great elasticity of the venous wall, the vein is not conducive to nerve regeneration. In this study, a novel tissue engineered nerve graft was constructed by combining normal dissected nerve microtissue with an autologous vein graft for repairing 10-mm peripheral nerve defects in rats. Compared with rats given the vein graft alone, rats given the tissue engineered nerve graft had an improved sciatic static index, and a higher amplitude and shorter latency of compound muscle action potentials. Furthermore, rats implanted with the microtissue graft had a higher density and thickness of myelinated nerve fibers and reduced gastrocnemius muscle atrophy compared with rats implanted with the vein alone. However, the tissue engineered nerve graft had a lower ability to repair the defect than autogenous nerve transplantation. In summary, although the tissue engineered nerve graft constructed with autologous vein and nerve microtissue is not as effective as autologous nerve transplantation for repairing long-segment sciatic nerve defects, it may nonetheless have therapeutic potential for the clinical repair of long sciatic nerve defects. This study was approved by the Experimental Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2016-x9-07) on September 7, 2016.

2.
Food Chem ; 334: 127474, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32688175

RESUMO

Rapid and accurate detection of pesticide residues in food matrices are of great significance to food safety. This study aimed to characterize the fingerprint peaks of 2,4-dichlorophenoxyacetic acid (2,4-D) and to enhance its detection accuracy in food matrices by using terahertz (THz) time-domain spectroscopy. Density functional theory was used to simulate molecular dynamics of 2,4-D peaks (1.35, 1.60, 2.37 and 3.00 THz). Four baseline correction methods, including asymmetric least squares smoothing (AsLS), adaptive iteratively reweighted penalized least squares (AirPLS), background correction (Backcor), baseline estimation and denoising with sparsity (BEADS) were compared and used to eliminate spectral baselines of Zizania latifolia (ZIZLA), rice and maize containing 2,4-D residues, from 0.1 to 4 THz. Based on the peak information of 1.35 THz, the detection limit and accuracy of 2,4-D residues in these food matrices were significantly improved after THz spectral baseline correction, providing a new feasibility for food safety and agricultural applications.

3.
Biomed Res Int ; 2020: 8396429, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029525

RESUMO

Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK > 200 U/L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK > 200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.

4.
Mikrochim Acta ; 187(11): 596, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033870

RESUMO

A novel photoelectrochemical immunosensor has been constructed for the determination of methylated RNA. MoS2 nanosheets with large specific area were employed as photoactive material, gold nanoparticles were used as signal amplification unit and immobilization matrix of 4-mercaptophenylboronic acid, anti-m6A antibody was adopted as methylated RNA recognition reagent, and poly(U) polymerase-mediated RNA chain extension and Ru(NH3)63+ were used as assisted signal amplification unit. With the sensitization effect of Ru(NH3)63+, the photoactivity of WS2 nanosheets was improved greatly, which also improved the sensitivity. Using visible-light excitation and ascorbic acid as electron donor, the sensitive determination of methylated RNA was achieved by monitoring the photocurrent change with different concentrations of methylated RNA. This photoelectrochemical immunosensor has a wide linear relationship with methylated RNA concentration from 0.05 to 35 nM under optimal experimental conditions. The low detection limit of 14.5 pM was realized based on 3σ criterion. In addition to the good selectivity, this sensor also presents high reproducibility with a relative standard deviation of 1.4% for the photocurrent of seven electrodes. The applicability of the developed method was also investigated by detecting the level of methylated RNA in corn seedling leaves with and without sulfadiazine treatment. Graphical abstract A novel photoelectrochemical immunosensor was developed for methylated RNA detection using the photoactive material of MoS2 and poly(U) polymerase-mediated RNA chain extension.

5.
Front Immunol ; 11: 2027, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013860

RESUMO

Pleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namely that the lymphatics are only passive vessels, carrying antigenic fluid to secondary lymphoid sites. Rather, lymphatic vessels can be a selective barrier, efficiently coordinating egress of immune cells and factors within tissues, limiting tumor spread and immune pathology. An alternative explanation, offered here, is that damage associated molecular pattern molecules, released in excess, maintain a local milieu associated with recruitment and retention of immune cells associated with failed lymphatic clearance and functional lymphatic obstruction. We found that levels of high mobility group box 1 (HMGB1) were equally elevated in both benign and malignant pleural effusions (MPEs) and that limited diversity of T cell receptor expressing gamma and delta chain were inversely associated with these levels in MPEs. Acellular fluid from MPEs enhanced γδ T cell proliferation in vitro, while inhibiting cytokine production from γδ T cells and monocytes as well as restricting monocyte chemotaxis. Novel therapeutic strategies, targeting HMGB1 and its neutralization in such effusions as well as direct delivery of immune cells into the pleural space to reconstitute normal physiology should be considered.

6.
Br J Nutr ; : 1-26, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028452

RESUMO

The association between egg consumption and diabetes is inconclusive. We aimed to examine the association between long-term egg consumption and its trajectory with diabetes in Chinese adults. A total of 8 545 adults aged ≥ 18 years old who attended the China Health and Nutrition Survey from 1991 to 2009 were included in this analysis. Egg consumption at each survey was assessed by a three-day 24-hour recall and weighed food record methods. The consumption trajectories of egg were modelled with the latent class group approach. Diabetes was diagnosed based on fasting blood glucose in 2009. Logistic regression was used to examine the association. The mean age of the study population was 50.9 (SD 15.1) years. 11.1% had diabetes in 2009. Egg consumption nearly doubled in 2009 from 16 g/day in 1991. Compared with the first quartile of egg consumption (0-9.0 g/day), the adjusted OR (95% CI) of diabetes for the second (9.1-20.6 g/day), third (20.7-37.5 g/day), and fourth (≥ 37.6 g/day) quartiles were 1.29 (95% CI 1.03, 1.62), 1.37 (95% CI 1.09, 1.72), and 1.25 (95% CI 1.04, 1.64), respectively (P for trend = 0.029). Three trajectory groups of egg consumption were identified. Compared with Group 1 (30.7%, low baseline intake and slight increase), both Group 2 (62.2%, medium baseline intake and increase) and Group 3 (7.1%, high baseline intake and decrease) were associated with an increased odds ratio (OR) for diabetes. The results suggested that higher egg consumption was positively associated with the risk of diabetes in Chinese adults.

7.
Chem Commun (Camb) ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030170

RESUMO

We conceptually demonstrate single-cell infrared phenomics as a novel strategy of phenotypic screening with infrared microspectroscopy. Based on this development, the cancer cell HepG2 glycocalyx was first identified as a potential target of protopanaxadiol, an herbal medicine. These findings provide a powerful tool to accurately evaluate the cell stress response and to largely expand the phenotypic screening toolkit for drug discovery.

8.
Inorg Chem ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022177

RESUMO

A novel 3D luminescent coordination polymer (LCP) [Zn4(3-dpyb)2(odpa)2(H2O)3]·4H2O (1) (3-dpyb = N,N'-bis (3-pyridinecarboxamide)-1,4-butane, H4 odpa = 4, 4'-oxidiphthalic acid) was successfully synthesized under solvothermal conditions. LCP 1 displays remarkable fluorescent behavior and stability in a wide range of pH values and different pure organic solvents. More importantly, LCP 1 can become an outstanding candidate in the selective sensing of Fe3+, Bi3+, Cr2O72-, MnO4-, nitrobenzene (NB), acetaldehyde (AH), and acetylacetone (Hacac) under a lower detection limit. The change process of fluorescent intensity of these seven analytes in a diverse pH range indicates that LCP 1 can be an excellent luminescent sensor in multiple acid/base solutions. As far as we know, it is an infrequent example of a CP-based multiresponsive fluorescent sensor for metal cations, oxyanions, and toxic organic solvents under an acid or alkaline environment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33006481

RESUMO

Background: Circular RNAs (circRNAs) are regarded as important regulators in the tumorigenesis of multiple cancers. However, the characterization of circRNA exocyst complex component 6B (circEXOC6B) in ovarian cancer is barely known. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the enrichment of circEXOC6B, microRNA-376c-3p (miR-376c-3p), and forkhead box O3 (FOXO3). Cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay and colony formation assay. Cell metastasis was measured by transwell assays. Western blot assay was conducted to examine the expression of proliferation and metastasis-related proteins and FOXO3. The chemoresistance of ovarian cancer cells was analyzed by CCK8 assay. Flow cytometry was used to detect cell apoptosis. The activities of caspase3 and caspase9 were analyzed through using colorimetric assay kits. The direct interaction between miR-376c-3p and circEXOC6B or FOXO3 was predicted by StarBase software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft assay was conducted to verify the role of circEXOC6B on the paclitaxel (PTX) resistance of ovarian cancer cells in vivo. Results: The level of circEXOC6B was notably decreased in ovarian cancer tissues. Low level of circEXOC6B was associated with malignant pathological characteristics in ovarian cancer patients. CircEXOC6B suppressed the proliferation and motility and decreased the chemoresistance of ovarian cancer cells to PTX. CircEXOC6B functioned through directly targeting and downregulating miR-376c-3p. FOXO3 was a direct target of miR-376c-3p, and the abundance of FOXO3 was regulated by circEXOC6B/miR-376c-3p axis. CircEXOC6B accelerated the PTX sensitivity of ovarian cancer cells through acting as a decoy of miR-376c-3p to upregulate FOXO3 in vivo. Conclusion: CircEXOC6B suppressed the progression and PTX resistance of ovarian cancer cells through sequestering miR-376c-3p, thus enhancing FOXO3 level.

10.
Diabetes Metab Res Rev ; : e3414, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010796

RESUMO

Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide, and the limited availability of qualified ophthalmologists restricts its early diagnosis. For the past few years, artificial intelligence technology has developed rapidly and has been applied in DR screening. The upcoming technology provides support on DR screening and improves the identification of DR lesions with a high sensitivity and specificity. This review aims to summarize the progress on automatic detection and classification models for the diagnosis of DR. This article is protected by copyright. All rights reserved.

11.
J Pathol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044755

RESUMO

SETDB1 is a histone lysine methyltransferase that has critical roles in cancers. However, its potential role in gastric cancer (GC) remains obscure. Here, we mainly investigate the clinical significance and the possible role of SETDB1 in GC. We find that SETDB1 expression is upregulated in GC tissues and its high-level expression was a predictor of poor prognosis in patients. Overexpression of SETDB1 promoted cell proliferation and metastasis, while SETDB1 suppression had an opposite effect both in vitro and in vivo. Mechanistically, SETDB1 was shown to interact with ERG to promote the transcription of cyclinD1 (CCND1) and matrix metalloproteinase 9 (MMP9) through binding to their promoter regions. In addition, the expression of SETDB1 was also enhanced by the transcription factor TCF4 at the transcriptional level in GC. Furthermore, SETDB1 expression was found to be induced by Helicobacter pylori (H. pylori) infection in a TCF4-dependent manner. Taken together, our results indicate that SETDB1 is aberrantly overexpressed in GC and plays key roles in gastric carcinogenesis and metastasis via upregulation of CCND1 and MMP9. Our work also suggests that SETDB1 could be a potential oncogenic factor and a therapeutic target for GC. This article is protected by copyright. All rights reserved.

12.
BMJ Open ; 10(10): e032833, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046460

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between birth order and stereoacuity among Chinese children aged 60-72 months. DESIGN: Cross-sectional. PARTICIPANTS: 1342 children with complete data on the questionnaire, stereoacuity and refraction were included. RESULTS: The mean stereoacuity was 53.2±1.7, 56.9±1.9 and 60.9±1.5 s of arc in the first-born group, second-born group and third-born group, respectively. Lower birth order was significantly correlated with better stereoacuity (p=0.036). Third-borns (OR=3.02, p=0.027) were at higher risk of having subnormal stereoacuity compared with first-borns in the multivariate analysis. CONCLUSION: Later-borns had poorer stereoacuity than first-borns.

13.
Nanotechnology ; 32(2): 025302, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047676

RESUMO

Ambient humidity introduces water adsorption and intercalation at the surfaces and interfaces of low-dimensional materials. Our extensive molecular dynamics (MD) simulations reveal the completely opposite contributions of interfacial water to the peeling of monolayer graphene and hexagonal boron nitride (h-BN) sheets from graphite and BN substrates. For graphene, interfacial water decreases the peeling force, due to lower adhesion at the graphene/water interface. The peeling force of h-BN increases with an increase in the thickness of interfacial water, owing to stronger adhesion at the h-BN/water interface and the detachment of the water layer from the substrates. In this work, a theoretical model considering graphene/water and water/substrate interfacial adhesion energies is established, to predict the peeling forces of graphene and h-BN, which coincides well with the peeling forces predicted by the MD simulations. Our results should provide a deeper insight into the effect of interfacial water, induced by ambient humidity, on mechanical exfoliation and the transfer of two-dimensional van der Waals crystals.

14.
Nat Prod Res ; : 1-7, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33016123

RESUMO

One new piperazinedione derivative, nigerpiperazine A (1), along with six known compounds (2-7) were isolated from the fungus Aspergillus niger JX-5 from mangrove Ceriops tagal. Nigerpiperazine A (1) was elucidated by spectroscopic analyses and 13C NMR chemical shift calculations, compounds 4 and 5 were determined by X-ray and the CD spectra. The absolute configuration of 4 was identified by X-ray for the first time. Compounds 1 and 4 showed inhibitory activities against Helicoverpa armigera Hubner with the IC50 values of 200 and 100 µg/mL, respectively.

15.
J Tradit Chin Med ; 40(5): 812-819, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33000582

RESUMO

OBJECTIVE: To investigate effect of electroacupuncture (EA) with Bushen Jiannao on learning and memory ability in senescence-accelerated mouse prone 8 (SAMP8) mice and the related mechanisms. METHODS: 8-month-old senescence-accelerated-resistant (SAMR1) and SAMP8 mice were treated with EA at Baihui (GV 20), Shenshu (BL 23), and Taixi (KI 3) acupoint once a week for 8 weeks. The Morris water maze, enzyme linked immunosorbent assay, immunohistochemistry, and Western blot were used to assess Alzheimer's disease (AD)-associated cognitive and neuroinflammatory phenotypes. RESULTS: Our data showed that EA treatment decreased activation of microglia and astrocytes, decreased levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-17, and improved spatial memory deficits in SAMP8 mice. EA therapy with Bushen Jiannao exhibited anti-inflammatory properties and improved cognitive function. CONCLUSION: The present study indicates that EA treatment based on the interaction between kidney and brain can improve learning and memory ability by inhibiting activation of astrocytes and microglia and decreasing expression of pro-inflammatory cytokines, TNF-α and IL-17. EA treatment based on the interaction between kidney and brain may be an effective treatment for AD.

16.
Int J Mol Med ; 46(5): 1611-1632, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000182

RESUMO

Circular RNAs (circRNAs) are a type of endogenous non­coding RNAs that are connected at the 3' and 5' ends by exon or intron cyclization, which forms a covalently closed loop. They are stable, well conserved, exhibit specific expression in mammalian cells and can function as microRNA (miRNA or miR) sponges to regulate the target genes of miRNAs, which influences biological processes. Such as tumor proliferation, invasion, metastasis, apoptosis and tumor stage. circRNAs represent promising candidates for clinical diagnosis and treatment. In the present review, the biogenesis, classification and functions of circRNAs in tumors are briefly summarized and discussed. In addition, the participation of circRNAs in signal transduction pathways regulating gastrointestinal cancer cellular functions is highlighted.

17.
Chin Med J (Engl) ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33009021

RESUMO

BACKGROUND: Endometrial cancer is one of the most common malignancies of the reproductive system. Effective and cost-effective screening method for populations at high risk is not available. This study aimed to investigate specimen adequacy and the influencing factors in microscale endometrial sampling biopsy and to evaluate the diagnostic accuracy and medical cost of biopsy in endometrial cancer and atypical hyperplasia screenings in comparison with hysteroscopic endometrial biopsy. METHODS: A total of 1551 patients at high risk for endometrial lesions who required hysteroscopic endometrial biopsy from November 2017 to August 2018 were included. Microscale endometrial sampling biopsy was performed, followed by hysteroscopic endometrial biopsy. We evaluated the specimen adequacy and influencing factors of microscale endometrial sampling. Diagnostic consistency between microscale endometrial sampling biopsy and hysteroscopic endometrial biopsy was evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of microscale endometrial sampling biopsy in screening for endometrial cancer and atypical hyperplasia were analyzed, and the medical costs of the two procedures were compared. RESULTS: The specimen adequacy was 81.2%. Patient age, menopausal status, endometrial thickness, and endometrial lesion type were correlated with specimen adequacy. There was good consistency in distinguishing benign and malignant endometrial diseases between microscale endometrial sampling biopsy and hysteroscopic biopsy (kappa 0.950, 95% CI 0.925-0.975). The sensitivity, specificity, positive predictive value, and negative predictive value of microscale endometrial sampling biopsy were 91.7%, 100.0%, 100.0%, and 99.3% for endometrial cancer screening, respectively, and 82.0%, 100.0%, 100.0%, and 99.4% for atypical hyperplasia screening. The medical cost of endometrial sampling biopsy was only 22.1% of the cost of hysteroscopic biopsy. CONCLUSIONS: Microscale endometrial sampling biopsy is a minimally invasive alternative technique for obtaining adequate endometrial specimens for histopathological examination. It has the potential to be used in detecting endometrial cancer and atypical hyperplasia with high efficiency and low cost.

18.
Emerg Microbes Infect ; 9(1): 2289-2302, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33000989

RESUMO

Tissue-resident memory T (TRM) cells, located in the epithelium of most peripheral tissues, constitute the first-line defense against pathogen infections. Our previous study reported that gastric subserous layer (GSL) vaccination induced a "pool" of protective tissue-resident memory CD4+T (CD4+TRM) cells in the gastric epithelium. However, the mechanistic details how CD4+TRM cells form in the gastric epithelium are unknown. Here, our results suggested that the vaccine containing CCF in combination with Silk fibroin hydrogel (SF) broadened the distribution of gastric intraepithelial CD4+TRM cells. It was revealed that the gastric intraepithelial TRM cells were even more important than circulating memory T cells against infection by Helicobacter felis. It was also shown that gastric-infiltrating neutrophils were involved as indispensable mediators which secreted CXCL10 to chemoattract CXCR3+CD4+T cells into the gastric epithelium. Blocking of CXCR3 or neutrophils significantly decreased the number of gastric intraepithelial CD4+TRM cells due to reduced recruitment of CD4+T cells. This study demonstrated the protective efficacy of gastric CD4+TRM cells against H. felis infection, and highlighted the influence of neutrophils on gastric intraepithelial CD4+TRM cells formation.

19.
Int J Pediatr Otorhinolaryngol ; 139: 110228, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-33022554

RESUMO

BACKGROUND: Goldenhar Syndrome (GS) is a systematic polymalformational disease characterized by microtia, hemifacial microsomy, ocular anomalies, abnormal vertebra and other deformities. These congenital malformations brought severe physical and mental stress to the patients. Auricular reconstruction has always been the primary appeal of the patients and their families to achieve a better facial balance and harmony. However, multiple deformities made it a great challenge to perform this technique. In this study, we reported a modified expanded two-flap method of auricular reconstruction, which is more applicable for patients with Goldenhar Syndrome. METHODS: Between January of 2012 and September of 2019, 69 cases of Goldenhar Syndrome underwent auricular reconstruction with the modified expanded two-flap technique. Auricular reconstruction was performed in three surgical stages. In the first stage, a 50 ml kidney-shaped tissue expander was embedded in mastoid region and the retroauricular skin expanded. In the second stage, the autologous rib cartilage was harvested and the ear framework fabricated. The expander was further removed, and then enveloped by the expanded flap, retroauricular fascial flap and a free skin graft. In the third stage, the reconstructed ear was further trimmed, including lobule transposition and tragus reconstruction. RESULTS: The patients were followed for 6 months to 7 years. There were 63 cases (91.3%) responded satisfied outcomes in size, shape, position and bilateral symmetry. One case suffered expander leakage and tissue expansion accomplished after the expander was replaced. Hematoma was occurred in four cases and removed to complete the reconstruction. Complications of cartilage exposure were observed in one case. CONCLUSION: Modified expanded two-flap method is effective and safe in auricular reconstruction for patients of Goldenhar syndrome with long term satisfying results. Level of Evidence IV.

20.
Ecotoxicol Environ Saf ; 208: 111401, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038730

RESUMO

Dibromoacetic acid (DBA) is a by-product of disinfection in drinking water, which could cause many adverse effects in test animals. However, little research on its neurotoxicity has been conducted, and its mechanism has not been elucidated. In the present study, ninety Sprague-Dawley rats were administered DBA at doses of 0, 30, and 90 mg/kg body weight for 28 days via oral gavage. We found that DBA could induce obvious neurotoxicity in the pineal gland as indicated by histological changes and impaired rhythm of melatonin in pineal and serum. In the mechanism study, transcriptome data showed that DBA exposure could induce 732 differential expression genes. Besides, GO and KEGG analysis results indicated that these genes were enriched in circadian rhythms, among which CREB1 had the most significant fold change. And immunofluorescence staining (IF) and immunohistochemical staining (IHC) results showed that the number of amber-colored masculine neurons for the p-CREB1 in the 90 mg/kg group was markedly lower, and staining for the p-CREB1 was weaker. Moreover, the results of PCR and western blot showed that DBA exposure could down-regulate the expressions of CREB1 and p-CREB1, leading to the decreased expressions of gene and protein of arylalkylamine N-acetyltransferase (AANAT), and then resulting in the impaired melatonin synthesis in the pineal and serum. In conclusion, DBA exposure is associated with abnormal melatonin rhythm via inhibition of the p-CREB1-AANAT signalling pathway.

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