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Although the majority of the population will be protected due to the advent and widespread use of the HPV vaccine, the treatment of cervical cancer for all causes, including HPV-negative cervical cancer, is still worthy of further research. The focal point of this study was Canadine's inhibition of epithelial-mesenchymal transformation (EMT) in cervical cancer. Immunoblotting, wound healing and tumor invasion experiments showed that low concentration of Canadine could inhibit the EMT process, proliferation and migration of HT-3 cells (HPV-negative cell line). Combined with GEO database, it was found that the expression levels of several genes highly expressed in cervical tumor tissues could be inhibited by Canadine, especially MAGEA3. Further experiments confirmed that the inhibition of Canadine on MAGEA3 protein increased with time. The small interference and overexpression plasmid of MAGEA3 were designed and verified. In HT-3 cells, when MAGEA3 levels were directly decreased, mesenchymal phenotypic markers were decreased and epithelial phenotypic markers were increased. The opposite result was obtained by overexpression of MAGEA3. In addition, the inhibition of EMT due to the reduction of endogenous MAGEA3 by Canadine was also offset by the overexpression of exogenous MAGEA3. The study concludes that Canadine inhibits EMT of cervical cancer by inhibiting MAGEA3. [ABSTRACT FROM AUTHOR]

Background: Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. Objective: We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. Method: From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter [less than or equal to]2.5 [micro]m (P[M.sub.2.5]), PM with aerodynamic diameter [less than or equal to] 10 [micro]m (P[M.sub.10]), sulfur dioxide (S[O.sub.2]), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. Results: We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of P[M.sub.2.5], P[M.sub.10], S[O.sub.2] and CO were the 21th to 24th weeks of pregnancy. Every 10-[micro]g/[m.sup.3] increase in P[M.sub.2.5] and P[M.sub.10], 5-[micro]g/[m.sup.3] increase in S[O.sub.2], and 0.1-mg/[m.sup.3] increase in CO was associated with low maternal hemoglobin levels [-0.94 g/L (95% confidence interval (CI): -1.15, -0.73), -1.31 g/L (95% CI: -1.55, -1.07), -2.96 g/L (95% CI: -3.32, -2.61), and -1.11 g/L (95% CI: - 1.31, -0.92), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. Conclusions: Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134, Introduction Air pollution is associated with health problems, including pregnancy-associated complications and increased adverse pregnancy outcomes. (1-3) Prelabor rupture of membranes (PROM) affects 3% to 21% of all pregnant women [...]

Purposes: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma‐CpGs island methylator phenotype (G‐CIMP) but have an unmethylated promoter of O‐6‐methylguanine‐DNA methyltransferase (unMGMT). Methods: The discovery‐validation approach was planned incorporating a series of G‐CIMP−/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi‐CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. Results: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy‐related CpGs, from which a 10‐CpG risk signature was further constructed. Both the 64‐CpG panel and the 10‐CpG risk signature were validated showing significant correlations with overall survival of G‐CIMP−/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10‐CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. Conclusions: The 64 TMZ efficacy‐related CpGs and in particular the 10‐CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G‐CIMP−/unMGMT GBMs. [ABSTRACT FROM AUTHOR]

Aims: To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ). Methods: Fifty of 71 patients completed this double‐blind placebo‐controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments. The Positive and Negative Symptom Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and PM test were assessed before and after treatment. Results: Both Event‐based PM (EBPM) and Time‐based PM (TBPM) scores at baseline were significantly lower in patients with SCZ than that in HCs. After rTMS treatments, the scores of EBPM in patients with SCZ was significantly improved and had no differences from that in HCs, while the scores of TBPM did not improved. The negative symptom scores on PANSS and the scores of almost all subscales and total scores of SANS were significantly improved in both groups. Conclusions: Our findings indicated that bilateral high‐frequency rTMS treatment can alleviate EBPM but not TBPM in patients with SCZ, as well as improve the negative symptoms. Significance: Our results provide one therapeutic option for PM in patients with SCZ. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of compound Chai Jin Jie Yu Tablets (CJJYT) in ameliorating cognitive impairment associated with depression and its potential mechanism of action. Methods: In vitro experiments, the hippocampus was isolated from the whole brain of the fetal rat and cultured into hippocampal neuron cells. 50 μM corticosterone (CORT) was added to each group 18 h before the experiment for modeling depression, with the exception of the control group. After modeling, the blank serum group was added with 10% blank serum, the CJJYT group and the venlafaxine group were added with the corresponding 10% drug-containing serum, and the control group and the model group were added with equal volumes of culture medium. The intracellular Ca2+ mean fluorescence intensity, miniature excitatory postsynaptic current (mEPSC) current amplitude, and frequency of different hippocampal neurons were evaluated as indicators of synaptic function in the hippocampal neurons. In addition, the expression of synaptic plasticity related proteins, synaptophysin-α (SYN-α), N-methyl-D-aspartate receptor 2A (NR2A), N-methyl-D- aspartate receptor 2B (NR2B), post synaptic density 95 protein (PSD-95), calcium/calmodulin dependent protein kinaseⅡ (CaMKⅡ) and synaptic associated protein (SynGAP) were detected in the hippocampal neurons by immunofluorescence staining and high content analysis (HCA) system. Then, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of SYN-α, NR2A, NR2B, PSD- 95, CaMKⅡ and SynGAP. For in vivo experiments, except for those in the blank control group, all rats were treated within a single cage for chronic unpredictable stress-induced depression modeling and subjected to corresponding drug interventions. Behavioral tests were used to detect depressive behavior and determine learning, memory and other cognitive abilities, whereas enzyme-linked immunosorbent assay (ELISA) was used to detect the CORT levels. Golgi-Cox staining was used to observe changes in the synaptic morphology of parahippocampal gyrus CA1 area (CA1) and dentategyrus (DG). Results: In vitro, CJJYT treatment reduced the intracellular Ca2+ mean flurorescence intensity in the hippocampal neurons (P < 0.05), causing a reduction in the frequency and current amplitude of mEPSC (P < 0.05), and thus inhibited the excessive activation of post-synaptic receptors. CJJYT treatment reduced the protein and mRNA expression of SYN-α, NR2A, NR2B and PSD-95 in the hippocampal neurons (P < 0.05), increased the mRNA and protein expression of CaMKⅡ and SynGAP (P < 0.05), and thereby improved the synaptic plasticity of the hippocampal neurons. In vivo, CJJYT intervention improved sucrose preference, voluntary activity , learning and memory ability of Morris water maze test, and suppressed appetite (P < 0.05), and increased the despair feeling of forced swimming test (P < 0.05). The CORT level was reduced (P < 0.05), leading to the repair of synaptic damage in the hippocampal neurons. Conclusions: CJJYT can improve the synaptic function of hippocampal neurons and has obvious protective effects on neurons. It can repair the structural damage in the hippocampal neurons, improving the cognitive ability of the depressed model rats. The mechanism of CJJYT improving cognition in depressed rats may be related to the transmission and function of SYN-α/NR and its downstream neurotransmitters.

Aiming at the fuzzy operation commonly used in image tampering,a new fuzzy detection scheme using smooth filter preserving edges and mathematical morphological methods was studied.By using the sharpening function and denoising function of both methods,tampering and location of tampering position can be pointed out without embedding information such as watermarking technique.The method can not only determine whether an image has been virtualized,but also detect the extent of the image blur.Experimental results confirm the effectiveness of the scheme.

Background: Depression is a neuropsychiatric disease resulting from deteriorations of molecular networks and synaptic injury induced by stress. Traditional Chinese formula Xiaoyaosan (XYS) exert antidepressant effect, which was demonstrated by a great many of clinical and basic investigation. However, the exact mechanism of XYS has not yet been fully elucidated. Methods: In this study, chronic unpredictable mild stress (CUMS) rats were used as a model of depression. Behavioral test and HE staining were used to detect the anti-depressant effects of XYS. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. The biological functions and potential mechanisms of XYS for depression were gathered from the GO and KEGG pathway. Then, constructed the competing endogenous RNA (ceRNA) networks to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Additionally, longest dendrite length, total length of dendrites, number of intersections, and density of dendritic spines were detected by Golgi staining. MAP2, PSD-95, SYN were detected by immunofluorescence respectively. BDNF, TrkB, p-TrkB, PI3K, Akt, p-Akt were measured by Western Blotting. Results: The results showed that XYS could increase the locomotor activity and sugar preference, decreased swimming immobility time as well as attenuate hippocampal pathological damage. A total of 753 differentially expressed lncRNAs (DElncRNAs), 28 circRNAs (DEcircRNAs), 101 miRNAs (DEmiRNAs), and 477 mRNAs (DEmRNAs) were identified after the treatment of XYS in whole transcriptome sequencing analysis. Enrichment results revealed that XYS could regulate multiple aspects of depression through different synapse or synaptic associated signal, such as neurotrophin signaling and PI3K/Akt signaling pathways. Then, vivo experiments indicated that XYS could promote length, density, intersections of synapses and also increase the expression of MAP2 in hippocampal CA1, CA3 regions. Meanwhile, XYS could increase the expression of PSD-95, SYN in the CA1, CA3 regions of hippocampal by regulating the BDNF/trkB/PI3K signal axis. Conclusion: The possible mechanism on synapse of XYS in depression was successfully predicted. BDNF/trkB/PI3K signal axis were the potential mechanism of XYS on synapse loss for its antidepressant. Collectively, our results provided novel information about the molecular basis of XYS in treating depression. [ABSTRACT FROM AUTHOR]