Circular RNA Pum_0014 Targets miR-146a-5p/NF2 Axis to Regulate VEGF/PAK1 Pathway and Reduce H2O2-induced Cardiomyocyte Apoptosis.

Circular RNAs (circRNAs) have emerged as essential regulators in cardiovascular disease, including acute myocardial infarction (AMI). This study investigated the role of circRNA Pum1_0014 in myocardial infarction (MI) and its underlying mechanisms using an H9C2 cell model. Through Sanger sequencing, nucleic acid electrophoresis, RNase R, and transcriptional inhibition experiments, Pum1_0014 was identified as a novel circRNA. The cell localization of circRNA Pum1_0014 was detected by qPCR and fluorescence in situ hybridization, and the results revealed that circRNA Pum1_0014 is predominantly located in the cytoplasm. StarBase (URL: http://starbase.sysu.edu.cn/) and TargetScan (URL: https://www.targetscan.org/vert_80/) were used to predict circRNA Pum1_0014 targeting miRNAs and miRNA targeting mRNA, and the results identified miR-146a-5p as a potential target of Pum1_0014, which in turn targets NF2. The plasmid encoding the mutant circRNA Pum1_0014 or the 3'UTR mutant NF2 was constructed, and the interaction between Pum1_0014 and miR-146a-5p or miR-146a-5p and NF2 was detected by luciferase reporter gene assay. The results confirmed the interactions between Pum1_0014, miR-146a-5p, and NF2. In the MI cell model, upregulation of circRNA Pum1_0014 and NF2 and downregulation of miR-146a-5p were observed. Knockdown of circRNA Pum1_0014 inhibited NF2 expression and activated the VEGF/PAK1 pathway, reducing cardiomyocyte apoptosis. Conversely, inhibition of miR-146a-5p and overexpression of NF2 had opposite effects. These findings suggest that circRNA Pum1_0014 acts through the miR-146a-5p/NF2 axis to reduce cardiomyocyte apoptosis in MI via the VEGF/PAK1/NF2 pathway.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Shijiazhuang in Spring].

Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O3） and PM2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 µg·m-3 and 122.18 µg·m-3, respectively. Meanwhile, the OFP was 361.23 µg·m-3 during the polluted period and 266.96 µg·m-3 during the clean period, whereas the SOAFP was 1.98 µg·m-3 and 1.61 µg·m-3, respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM2.5 and O3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

Ano1 regulates embryo transport by modulating intracellular calcium levels in oviduct smooth muscle.

Oviductal smooth muscle exhibits spontaneous rhythmic contraction (SRC) and controls the passage of the ova at the exact time, but its mechanistic regulation remains to be determined. In this study, female mice with Ano1SMKO (smooth muscle-specific deletion of Ano1) had reduced fertility. Deficiency of Ano1 in mice resulted in impaired oviductal SRC function and reduced calcium signaling in individual smooth muscle cells in the oviduct. The Ano1 antagonist T16Ainh-A01 dose-dependently inhibited SRCs and [Ca2+]i in the oviducts of humans and mice. A similar inhibitory effect of SRCs and [Ca2+]i was observed after treatment with nifedipine. In our study, ANO1 acted primarily as an activator or amplifier in [Ca2+]i and contraction of tubal smooth muscle cells. We found that tubal SRC was markedly attenuated in patients with ectopic pregnancy. Then, our study was designed to determine whether chloride channel Ano1-mediated smooth muscle motility is associated with tubal SRC. Our findings reveal a new mechanism for the regulation of tubal motility that may be associated with abnormal pregnancies such as ectopic pregnancies.

HMGB1 in depression: An overview of microglial HMBG1 in the pathogenesis of depression.

Depression is a prevalent psychiatric disorder with elusive pathogenesis. Studies have proposed that enhancement and persistence of aseptic inflammation in the central nervous system (CNS) may be closely associated with the development of depressive disorder. High mobility group box 1 (HMGB1) has obtained significant attention as an evoking and regulating factor in various inflammation-related diseases. It is a non-histone DNA-binding protein that can be released as a pro-inflammatory cytokine by glial cells and neurons in the CNS. Microglia, as the immune cell of the brain, interacts with HMGB1 and induces neuroinflammation and neurodegeneration in the CNS. Therefore, in the current review, we aim to investigate the role of microglial HMGB1 in the pathogenetic process of depression.

[Anatomical structure and physiological characteristics of Robinia pseudoacacia of different stand ages]. / 不同林龄刺槐解剖结构及生理特性.

Drought intensity and frequency have been increased as a result of global warming. Exploring the drought resistance mechanism of Robinia pseudoacacia plantations of different stand ages on the Loess Plateau is crucial for understanding the stability of forest productivity in the region. We investigated anatomical traits, hydraulic function, and non-structural carbohydrate content of the xylem, as well as their association, in R. pseudoacacia plantations of different stand ages in a semi-arid region. The results showed that the vessel diameter, total pit membrane area, pit membrane area, vesture area, and vestured overlap of young and middle-aged stands were larger than those of mature stands, and the pit density was significantly lower in mature stands. Hydraulic conductivity was significantly related to vessel diameter, pit membrane area, and vesture area. Hydraulic conductivities of branches in young, middle-aged, and mature stands were 2.30, 2.12, and 0.76 kg·m-1·s-1·MPa-1, respectively, with embolism values of 54.5%, 53.8%, and 45.1%. Hydraulic conductivity was significantly related to soluble sugar and starch contents. The soluble sugar contents of branches in young, middle-aged and mature stands were 4.9%, 4.2%, and 3.8%, respectively. Xylem growth capacity of R. pseudoacacia in mature stand declined, resulting in the formation of small vessels with many small pits, which reduced hydraulic conductivity while maintaining hydraulic safety, resulting in a decrease of non-structural carbohydrates content. This study revealed the drought response mechanism of R. pseudoacacia plantations with different ages, providing a scientific foundation for the management and nurturing of R. pseudoacacia plantations on the Loess Plateau.

Influences of fresh and frozen embryo transfer on neonatal birthweight and the expression of imprinted genes PEG10 /L3MBTL1 in placenta.

To investigate the influences of fresh embryo transfer (ET) and frozen embryo transfer (FET) on neonatal birthweight and the expression of imprinted genes PEG10 and L3MBTL1 in the placenta after in vitro fertilization-embryo transfer (IVF-ET), we analyzed the neonatal birthweight between fresh ET and FET transfer cycles. Then, we collected placentas delivered by fresh ET and FET, and real-time quantitative PCR, Western blotting and immunohistochemistry were used to detect the expression of PEG10 and L3MBTL1. The mean neonatal birthweight of fresh ET was lower than that of FET(3348.48 ± 521.05 vs. 3450.34 ± 524.13, P < 0.001). The risks of low birthweight (LBW) and small-for-gestational age (SGA) were lower after FET (3.9 % vs. 5.4 %; 7.2 % vs. 10.3 %), with adjusted rate ratios of 0.74 (95 % CI, 0.59-0.93; P = 0.003) and 0.70 (95 % CI, 0.59-0.84; P < 0.001), respectively. FET resulted in higher frequencies of macrosomia and large-for-gestational age (LGA) (14.2 % vs. 10.3; 11.0 % vs. 7.1 %) than fresh ET, with adjusted rate ratios of 1.45 (95 % CI, 1.26-1.68; P < 0.001) and 1.62 (95 % CI, 1.37-1.91; P < 0.001), respectively. We also observed PEG10 mRNA and protein expression levels in placentas delivered by fresh ET and FET were significantly different, but there were no significant differences in L3MBTL1 between the two groups. Fresh ET may affect the expression of the imprinted gene PEG10 in the placenta and adverse to placental implantation and development, resulting to increasing incidences of LBW and SGA.

Discovery of a novel nonsteroidal selective glucocorticoid receptor modulator by virtual screening and bioassays.

Synthetic glucocorticoids (GCs) have been widely used in the treatment of a broad range of inflammatory diseases, but their clinic use is limited by undesired side effects such as metabolic disorders, osteoporosis, skin and muscle atrophies, mood disorders and hypothalamic-pituitary-adrenal (HPA) axis suppression. Selective glucocorticoid receptor modulators (SGRMs) are expected to have promising anti-inflammatory efficacy but with fewer side effects caused by GCs. Here, we reported HT-15, a prospective SGRM discovered by structure-based virtual screening (VS) and bioassays. HT-15 can selectively act on the NF-κB/AP1-mediated transrepression function of glucocorticoid receptor (GR) and repress the expression of pro-inflammation cytokines (i.e., IL-1ß, IL-6, COX-2, and CCL-2) as effectively as dexamethasone (Dex). Compared with Dex, HT-15 shows less transactivation potency that is associated with the main adverse effects of synthetic GCs, and no cross activities with other nuclear receptors. Furthermore, HT-15 exhibits very weak inhibition on the ratio of OPG/RANKL. Therefore, it may reduce the side effects induced by normal GCs. The bioactive compound HT-15 can serve as a starting point for the development of novel therapeutics for high dose or long-term anti-inflammatory treatment.

Inhibition of Connexin 36 attenuates HMGB1-mediated depressive-like behaviors induced by chronic unpredictable mild stress.

BACKGROUND: High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1. METHODS: After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping. RESULTS: The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1ß (IL-1ß) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine. CONCLUSIONS: Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1-mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.

Discovery of novel antagonists targeting the DNA binding domain of androgen receptor by integrated docking-based virtual screening and bioassays.

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.

Quantitative Estimation of the Hydrogen-Atom-Donating Ability of 4-Substituted Hantzsch Ester Radical Cations.

The purpose of this study is to investigate thermodynamic and kinetic properties on the hydrogen-atom-donating ability of 4-substituted Hantzsch ester radical cations (XRH•+), which are excellent NADH coenzyme models. Gibbs free energy changes and activation free energies of 17 XRH•+ releasing H• [denoted as ΔG HD o(XRH•+) and ΔG HD ≠(XRH•+)] were calculated using density functional theory (DFT) and compared with that of Hantzsch ester (HEH2) and NADH. ΔG HD o(XRH•+) range from 19.35 to 31.25 kcal/mol, significantly lower than that of common antioxidants (such as ascorbic acid, BHT, the NADH coenzyme, and so forth). ΔG HD ≠(XRH•+) range from 29.81 to 39.00 kcal/mol, indicating that XRH•+ spontaneously releasing H• are extremely slow unless catalysts or active intermediate radicals exist. According to the computed data, it can be inferred that the Gibbs free energies and activation free energies of the core 1,4-dihydropyridine radical cation structure (DPH•+) releasing H• [ΔG HD o(DPH•+) and ΔG HD ≠(DPH•+)] should be 19-32 kcal/mol and 29-39 kcal/mol in acetonitrile, respectively. The correlations between the thermodynamic driving force [ΔG HD o(XRH•+)] and the activation free energy [ΔG HD ≠(XRH•+)] are also explored. Gibbs free energy is the important and decisive parameter, and ΔG HD ≠(XRH•+) increases in company with the increase of ΔG HD o(XRH•+), but no simple linear correlations are found. Even though all XRH•+ are judged as excellent antioxidants from the thermodynamic view, the computed data indicate that whether XRH•+ is an excellent antioxidant in reaction is decided by the R substituents in 4-position. XRH•+ with nonaromatic substituents tend to release R• instead of H• to quench radicals. XRH•+ with aromatic substituents tend to release H• and be used as antioxidants, but not all aromatic substituted Hantzsch esters are excellent antioxidants.

Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common types of malignancy and accounts for >3 million deaths worldwide each year. The present study aimed to evaluate the role of notum palmitoleoyl-protein carboxylesterase (NOTUM) in in vivo and in vitro, and to identify the relationship between NOTUM and the apoptosis of COAD. Moreover, the present study aimed to investigate whether NOTUM regulated Fas cell surface death receptor (FAS)-mediated apoptosis was affected by the Wnt signaling pathway. Gene expression profiling interactive analysis (GEPIA) was used to predict the potential function of NOTUM. Western blotting and reverse transcription-quantitative PCR were conducted to detect the protein and mRNA expression levels of NOTUM in different tissues or cell lines. The occurrence and development of COAD was detected after NOTUM knockdown lentivirus administration. The apoptosis of COAD was also observed. SKL2001 was applied to examine whether the role of NOTUM was regulated by Wnt. GEPIA analysis demonstrated that NOTUM expression in COAD tumor tissue was higher compared with in normal tissues. Pair-wise gene correlation analysis identified a potential relationship between NOTUM and Wnt. NOTUM protein and mRNA expression levels in colon carcinoma tissues and RKO cells were increased. NOTUM knockdown lentivirus serves a role in inhibiting COAD development by reducing tumor proliferation, reducing tumor size, and increasing the level of apoptosis in vitro and in vivo. Moreover, NOTUM could increase apoptosis in COAD, which was regulated by FAS, and SKL2001 blocked the progress of apoptosis after NOTUM regulation by NOTUM knockdown lentivirus in vitro and in vivo. Collectively, the present results suggested that NOTUM may be able to regulate the apoptosis of COAD, and that Wnt may be the down-stream target signaling of NOTUM in apoptosis.

Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5.

BACKGROUND: Pathophysiological vascular remodeling in response to disturbed flow with low and oscillatory shear stress (OSS) plays important roles in atherosclerosis progression. Pomegranate extraction (PE) was reported having anti-atherogenic effects. However, whether it can exert a beneficial effect against disturbed flow-induced pathophysiological vascular remodeling to inhibit atherosclerosis remains unclear. The present study aims at investigating the anti-atherogenic effects of pomegranate peel polyphenols (PPP) extraction and its purified compound punicalagin (PU), as well as their protective effects on disturbed flow-induced vascular dysfunction and their underlying molecular mechanisms. METHODS: The anti-atherogenic effects of PPP/PU were examined on low-density lipoprotein receptor knockout mice fed with a high fat diet. The vaso-protective effects of PPP/PU were examined in rat aortas using myograph assay. A combination of in vivo experiments on rats and in vitro flow system with human endothelial cells (ECs) was used to investigate the pharmacological actions of PPP/PU on EC dysfunction induced by disturbed flow. In addition, the effects of PPP/PU on vascular smooth muscle cell (VSMC) dysfunction were also examined. RESULTS: PU is the effective component in PPP against atherosclerosis. PPP/PU evoked endothelium-dependent relaxation in rat aortas. PPP/PU inhibited the activation of Smad1/5 in the EC layers at post-stenotic regions of rat aortas exposed to disturbed flow with OSS. PPP/PU suppressed OSS-induced expression of cell cycle regulatory and pro-inflammatory genes in ECs. Moreover, PPP/PU inhibited inflammation-induced VSMC dysfunction. CONCLUSION: PPP/PU protect against OSS-induced vascular remodeling through inhibiting force-specific activation of Smad1/5 in ECs and this mechanism contributes to their anti-atherogenic effects.

Exercise training in patients with corrected tetralogy of Fallot: A protocol for systematic review and meta-analysis.

BACKGROUND: The arrival of transcatheter mitral valve therapies has provided feasible and safe alternatives to medical and surgical treatments for mitral regurgitation. The aim of this study is to estimate the relative efficacy and safety of exercise training in patients with corrected tetralogy of Fallot through meta-analysis. METHODS: : A systematic search will be performed using PubMed, EMBASE, the Cochrane Library, Web of Science, CBM, CNKI, WanFang Data, and VIP to include random controlled trials or nonrandom controlled trials comparing the efficacy and safety of exercise training in corrected tetralogy of Fallot patients. The risk of bias for the included nonrandom controlled studies will be evaluated according to Risk of Bias in Nonrandomized Studies of Interventions. We will use the Cochrane Collaboration's tool (version 2 of the Cochrane risk of bias tool for randomized trials) to assess risk of bias of included random controlled trials. Revman 5.4 and STATA 15.0 will be used to complete the meta-analysis and generate forest plots. Grading of recommendations assessment, development, and evaluation will be used to assess the quality of evidence. RESULTS: : The results of this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: : This study will provide broad evidence of efficacy and safety of exercise training in patients with corrected tetralogy of Fallot and provide suggestions for clinical practice and future research. PROTOCOL REGISTRATION NUMBER: INPLASY202150006.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch.

Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

Expert consensus of the Chinese Association for the Study of Pain on ion channel drugs for neuropathic pain.

Neuropathic pain (NPP) is a kind of pain caused by disease or damage impacting the somatosensory system. Ion channel drugs are the main treatment for NPP; however, their irregular usage leads to unsatisfactory pain relief. To regulate the treatment of NPP with ion channel drugs in clinical practice, the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs . Here, we reviewed the mechanism and characteristics of sodium and calcium channel drugs, and developed recommendations for the therapeutic principles and clinical practice for carbamazepine, oxcarbazepine, lidocaine, bulleyaconitine A, pregabalin, and gabapentin. We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.

[Progress in Gene Therapy of Sickle Cell Disease Based on Hemoglobin F--Review].

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for ß- like hemoglobin diseases, such as sickle cell disease and ß- thalassemia.

More Depression-Related Public Concern After the Suicide of a Pop Star in China: Evidence From the Online Big Data Platform.

Background: In China, we have seen dramatic increases in public concern over depression and mental health after the suicide of some famous persons. The objective of this study is to investigate the changes of search-engine query patterns to monitor this phenomenon based on the tragic suicide of a young Chinese pop star, Kimi Qiao. Methods: The daily search volume for depression was retrieved from both the Baidu Index (BDI) and the Sina MicroBlog Index (SMI). Besides, the daily BDI for suicide, schizophrenia, obsessive-compulsive disorder, common cold, stomach cancer, and liver cancer were collected for comparison. According to the time of Qiao's suicide, all data were divided into two periods (i.e., Period One from 1 September 2015 to 31 August 2016 while Period Two ranged from 1 October 2016 to 30 September 2017). The paired t-test was used to compare the differences in search volumes between two periods. The Pearson correlation analysis was used to estimate correlations between the BDI and SMI for depression. Results: The average BDI for depression, BDI for suicide, and SMI for depression in Period Two were significantly higher than in Period One (p < 0.05). There was a strong positive correlation between the BDI and SMI for depression (r = 0.97, p < 0.001). And no significant difference in BDI for other diseases between the two periods was found. Conclusions: The changes of search-engine query patterns indicated that the celebrity's suicide might be able to improve the netizens' concern about depression in China. The study suggests publishing more practical knowledge and advice on depression through the Internet and social media, to improve the public's mental health literacy and help people to cope with their depressive symptoms appropriately.

Expression and DNA Methylation Status of the Imprinted Genes PEG10 and L3MBTL1 in the Umbilical Cord Blood and Placenta of the Offspring of Assisted Reproductive Technology.

The aim of this study is to investigate the expression and DNA methylation status of the imprinted genes PEG10 and L3MBTL1 in the offspring of assisted reproductive technology (ART). The ART group consists of 30 cases of placenta and umbilical cord blood from ART full-term, uncomplicated singleton pregnancy progeny, and the normal control group consists of 30 cases of placenta and umbilical cord blood from natural full-term, uncomplicated singleton pregnancy progeny. The imprinted genes PEG10 and L3MBTL1 are analyzed, and the expression and methylation status of the two genes are detected using real-time quantitative polymerase chain reaction (QRT-PCR), immunohistochemistry (IHC), Western blotting (WB), and methylation-specific polymerase chain reaction (MSP). Compared with the normal control group, the PEG10 mRNA relative quantity (RQ) value in the placenta is 0.994 ± 0.458, with its RQ value up-regulated (P = 0.015). The PEG10 mRNA RQ value in the umbilical cord blood is 0.875 ± 0.452, with its RQ value up-regulated (P = 0.002). However, the L3MBTL1 mRNA RQ value in the placenta is 0.404 ± 0.234, with its RQ value down-regulated (P = 0.024). The L3MBTL1 mRNA RQ value in the umbilical cord blood is 0.337 ± 0.213, and there is no difference in the umbilical cord blood (P = 0.081). Compared with the normal control group, the expression of PEGl0 protein in the placenta of the ART progeny is up-regulated (P = 0.000), while the expression of L3MBTLl protein is down-regulated (P = 0.000). The methylation status of the PEGl0 promoter region in the placenta in the ART group is lower than that in the normal control group (P = 0.037), and that of the promoter region of the umbilical cord blood is lower than that of the natural pregnancy group (P = 0.032). The methylation status of the L3MBTLl promoter region is higher in the placenta than in the normal control group (P = 0.038), and there is no difference between the two groups in the umbilical cord blood (P = 0.301). In the ART group, the values of PEGl0 and L3MBTLl RQ in the placenta and the umbilical cord blood of the hypermethylated group are lower than in those of the hypomethylated group. ART may increase the risk of the abnormal expression of PEG10 and L3MBTL1 in offspring imprinted genes. The methylation of the promoter region may be the mechanism that regulates the expression of PEGl0 and L3MBTL1.

SH3PXD2A-AS1/miR-330-5p/UBA2 ceRNA network mediates the progression of colorectal cancer through regulating the activity of the Wnt/ß-catenin signaling pathway.

Long non-coding RNAs have important roles in the occurrence and progression of various cancers. However, the molecular mechanism of lncRNAs in colorectal cancer (CRC) is not well illustrated. Thus, we used bioinformatics methods to find potential lncRNAs associated with CRC progression, and chose SH3PXD2A-AS1 as a candidate for further analysis. The roles of SH3PXD2A-AS1 in CRC cells were determined by CCK-8, transwell invasion, wound healing and flow cytometry assays. Besides, we established the CRC tumor models in nude mice to study the effect of SH3PXD2A-AS1 on the tumor growth. Based on the ceRNA hypothesis, we used miRDB and miRTarBase websites to identify the SH3PXD2A-AS1-related ceRNA regulatory network, and measured the roles of this network in CRC cells. The results revealed that the expression profiles of SH3PXD2A-AS1 from GEO and TCGA databases showed an aberrant high level in CRC tissues compared with colorectal normal tissues. SH3PXD2A-AS1 over-expression was also found in CRC cells. SH3PXD2A-AS1 knockdown inhibited the CRC cellular proliferation, invasion and migration but induced apoptosis. Besides, SH3PXD2A-AS1 knockdown also suppressed the growth of CRC tumors. Furthermore, SH3PXD2A-AS1 could function as a ceRNA of miR-330-5p. Additionally, UBA2 was proved to be a target gene of miR-330-5p. Moreover, SH3PXD2A-AS1 knockdown downregulated UBA2 expression through sponging miR-330-5p to inactivate the Wnt/ß-catenin signaling pathway, thereby inhibiting the cell growth and promoting apoptosis. Therefore, the SH3PXD2A-AS1/miR-330-5p/UBA2 network could regulate the progression of CRC through the Wnt/ß-catenin pathway. These findings offer new sights for understanding the pathogenesis of CRC and provide potential biomarkers for CRC treatment.