Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China.

BACKGROUND: Folic acid supplementation is recommended for reducing the risk of birth defects. We aimed to assess the protective association of periconception folic acid supplements with birth defects in real-world setting. METHODS: This prospective, population-based cohort study utilized national preconception registered data of married Chinese couples planning a pregnancy within 6 months between 2010 and 2012 in Mainland China. Participated women are freely provided folic acid starting 3 months before conception till 3 months after conception. Birth defects were self-reported at 42 days postpartumn followup. R software (v4.0.2) was applied for statistical analyses. RESULTS: Complete data of 567,547 couples with pregnancy outcomes and folic acid supplementation were extracted for final analysis. A total of 74.7% women were with folic acid supplementation, and 599 birth defects were self-reported. The odd of birth defects was lower among women taking folic acid compared to their counterparts not taking (0.102% vs 0.116%, P < 0.001). In the multiple logistic regression analyses, the odd of birth defects was lower among couples with maternal folic acid supplementation (OR = 0.78, 95%CI: 0.66-0.95, P = 0.011), especially decreased odd of neural tube defects (NTDs) (OR = 0.56, 95%CI: 0.39-0.82, P = 0.003). This association was confirmed by 1:4 and 1:10 case control analysis. Odds of birth defects were significantly lower among women with folic acid supplementation more than 3 months before pregnancy (P < 0.001), and moreover, the odds of cleft (P = 0.007) and NTDs (P = 0.007) were of notable decrease. CONCLUSION: This retrospective case cohort study provides programmatic evidence for public health strategy-making to for reducing the risk of NTDs and clefts.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.

Effects of exercise therapy on disability, mobility, and quality of life in the elderly with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise is an effective treatment in chronic low back pain (CLBP), but there are few studies on CLBP in the elderly, and the intervention effect is controversial. We aimed to compare the efficacy of different exercises therapy on CLBP, dysfunction, quality of life, and mobility in the elderly. METHODS: We searched Web of Science, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure, EMBASE, and PubMed from the database inception till December 31, 2022. The publication languages were Chinese and English. Randomized controlled trials (RCTs) of exercise intervention in the elderly (≥ 60 years) with CLBP were included. Two reviewers independently extracted the data and evaluated them using the Revised Cochrane Risk of Bias Tool for Randomized Trials 2 (RoB2). The pooled effect sizes on different aspects of outcome measures were calculated. RESULTS: Sixteen articles (18 RCTs) were included, comprising a total of 989 participants. The quality of included studies was relatively high. Meta-analysis results indicated that exercise therapy could improve visual analog scale (VAS) (WMD = - 1.75, 95% CI - 2.59, - 0.92, p < 0.05), Oswestry disability index (ODI) (WMD = - 9.42, 95% CI - 15.04, - 3.79, p < 0,005), short-form 36-item health survey physical composite summary (SF-36PCS) (WMD = 7.07, 95% CI 1.01, 13.14, p < 0.05), short-form 36-item health survey mental composite summary (SF-36MCS) (WMD = 7.88, 95% CI 0.09, 15.67, p < 0.05), and timed up and go test (TUG) (WMD = - 0.92, 95% CI - 2.22, 0.38, p < 0.005). CONCLUSION: Exercise therapy effectively improved VAS, ODI, and SF-36 indexes in the elderly. Based on the subgroup, when designing the exercise therapy regimen, aerobics, strength, and mind-body exercise (≥ 12 weeks, ≥ 3 times/week, ≥ 60 min) should be considered carefully, to ensure the safety and effectiveness for the rehabilitation of CLBP patients. More high-quality trials are needed in future to confirm the effect of exercise on SF-36 and TUG indexes.

[Application of metronidazole combined with minocycline in reducing infection after dental implant in patients with localized periodontitis].

PURPOSE: To explore the value of metronidazole combined with minocycline in reducing infection after dental implant in patients with localized periodontitis. METHODS: A total of 120 patients with localized periodontitis who underwent dental implantation in the Department of Stomatological, Shanghai Pudong New Area People's Hospital from August 2021 to September 2022 were selected. According to the way of postoperative infection prevention, the patients were divided into control group and experimental group, with 60 patients in each group. The control group was orally given roxithromycin capsules, and the experimental group was locally coated with minocycline hydrochloride ointment and metronidazole gel. The incidence of postoperative infection and complications was compared between the two groups. The modified gingival creval bleeding index (mSBI), periodontal probing depth (PD) and modified plaque index (mPLI) of the patients were examined by periodontal probe. Serum C-reactive protein (CRP) level was determined by immunoturbidimetry and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) level was determined by ELISA. SPSS 25.0 software package was used for statistical analysis of the data. RESULTS: Good healing rate of the experimental group was 91.67% higher than that of the control group 73.33%, postoperative infection rate was 8.33% and complication rate was 6.67% in the experimental group, significantly lower than that of the control group (26.67% and 20.00%), respectively (P＜0.05). After treatment, the level of CRP, TNF-α and IL-6 in the experimental group were significantly lower than those in the control group (P＜0.05). At 3 and 6 months after treatment, mSBI, mPLI and PD in the experimental group were significantly lower than those in the control group(P＜0.05). CONCLUSIONS: The administration of minocycline hydrochloride and metronidazole in patients with localized periodontitis undergoing implantation can reduce oral inflammatory response, reduce postoperative infection and other complications, and improve periodontal health.

The "Matrisome" reveals the characterization of skin keloid microenvironment.

Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large-scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

Effects of Sevoflurane on Apoptosis of Myocardial Cells in IRI Rats.

BACKGROUND: Cardiomyocyte apoptosis functions essentially in ischemia/reperfusion- (I/R-) induced myocardial injury. It is suggested that autophagy is widely implicated in the regulation of cell survival and death. Sevoflurane, as a largely used inhalational general anesthetic, has been shown to have a protective effect on cardiomyocytes. However, it was yet elusive on the underlying mechanisms. AIM: The objective of this study is to investigate the association of sevoflurane-mediated cardioprotective effects with autophagy regulation. METHODS: An in vitro hypoxia model was established in primary cardiomyocytes from fresh myocardial tissue of the rats. The apoptosis rate of myocardial cells treated with hypoxia and treated with sevoflurane was measured. Western blot and immunocytochemical assay were used to measure the protein expression. The cell proliferation rate and cell apoptosis were measured using the MTT assay and flow cytometry, respectively. RESULTS: The expression of apoptotic proteins including B cell lymphoma-2 (Bcl-2), CCAAT/enhancer-binding protein homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and Bcl-2-associated X protein (BAX) in myocardium treated with sevoflurane was significantly lower than that in myocardium treated with hypoxia. The expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in myocardium treated with sevoflurane was higher than that in myocardium treated with hypoxia, suggesting better connectivity of the myocardium. CONCLUSION: Sevoflurane treatment reduced the apoptosis of myocardial cells after hypoxia treatment.

Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples.

The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

Antimicrobial peptide AR-23 derivatives with high endosomal disrupting ability enhance poly(l-lysine)-mediated gene transfer.

BACKGROUND: pH-sensitive peptides are a relatively new strategy for conquering the poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides by exchanging positively-charged residues with negatively-charged glutamic acid residues (Glu) greatly improves its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection. METHODS: In the present study, we investigated the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 with respect to enhancing cationic polymer-mediated transfection. Three analogs were synthesized by replacing the positively-charged residues in the AR-23 sequence with Glu one-by-one. RESULTS: The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking, the transfection efficiency and the cytotoxicity of the polyplexes were determined. Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in the AR-23 sequence greatly improved poly(l-lysine)-mediated gene transfection efficiency at the same time as maintaining low cytotoxicity. CONCLUSIONS: The results indicate that replacement of positively-charged residues with sufficient Glu residues may be considered as a method for designing pH-sensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.

Exposure to tobacco smoke and stillbirth: a national prospective cohort study in rural China.

INTRODUCTION: Parental exposure to tobacco smoke has been associated with an increased risk of stillbirth, while only a few studies took the overall parental tobacco exposure status into consideration. We aim to explore the relationship of parental smoking and passive smoking before and during pregnancy with stillbirth in a large Chinese rural cohort. DESIGN: 248 501 couples were enrolled in a national prospective cohort study conducted in rural China. Parental exposure to tobacco smoke before and during pregnancy, along with other risk factors, was ascertained by questionnaires. Pregnancy outcomes were recorded by physicians. RESULTS: The ORs (Odds Ratios) of maternal active smoking, maternal passive smoking, paternal active smoking and paternal passive smoking were 2.07 (95% CI 1.25 to 3.41), 1.22 (95% CI 1.01 to 1.47), 1.36 (95% CI 1.13 to 1.63) and 1.10 (95% CI 0.87 to 1.39), respectively. The rates of stillbirth increased from 0.31% for the maternal non-smoking group to 0.43% for the smoking cessation during pregnancy group, to 0.64% for the decreased smoking group and 1.28% for the continuing smoking group. A similar pattern was found in the change in paternal smoking status and stillbirth. Stratified by maternal passive smoking, the OR of paternal smoking was 1.35 (95% CI 1.13 to 1.61) in the maternal non-smoking group and 1.67 (95% CI 1.09 to 2.56) in the maternal passive smoking group. CONCLUSIONS: Parental exposure to tobacco smoke increased the risk of stillbirth, especially for those continuing smoking during pregnancy. Paternal smoking is an independent risk factor for stillbirth despite maternal passive smoking status.

Computer-Aided Diagnosis (CAD) of Pulmonary Nodule of Thoracic CT Image Using Transfer Learning.

Computer-aided diagnosis (CAD) has already been widely used in medical image processing. We recently make another trial to implement convolutional neural network (CNN) on the classification of pulmonary nodules of thoracic CT images. The biggest challenge in medical image classification with the help of CNN is the difficulty of acquiring enough samples, and overfitting is a common problem when there are not enough images for training. Transfer learning has been verified as reasonable in dealing with such problems with an acceptable loss value. We use the classic LeNet-5 model to classify pulmonary nodules of thoracic CT images, including benign and malignant pulmonary nodules, and different malignancies of the malignant nodules. The CT images are obtained from Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) where both pulmonary nodule scanning and nodule annotations are available. These images are labeled and stored in a medical images knowledge base (KB), which is designed and implemented in our previous work. We implement the 10-folder cross validation (CV) to testify the robustness of the classification model we trained. The result demonstrates that the transfer learning of the LeNet-5 is good for classifying pulmonary nodules of thoracic CT images, and the average values of Top-1 accuracy are 97.041% and 96.685% respectively. We believe that our work is beneficial and has potential for practical diagnosis of lung nodules.

Heparanase Promotes Tumor Growth and Liver Metastasis of Colorectal Cancer Cells by Activating the p38/MMP1 Axis.

Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. In this study, we examined the expression of HPSE in different colorectal cancer (CRC) cell lines. Gene manipulation was applied to reveal the effect of HPSE on proliferation, invasion, and metastasis of CRC. Knockdown of HPSE resulted in decreased cell proliferation in vitro, whereas overexpression of HPSE resulted in the opposite phenomenon. Consistently, in vivo data showed that knockdown of HPSE suppressed tumor growth of CRC. Furthermore, knockdown of HPSE inhibited invasion and liver metastasis in vitro and in vivo. RNA-sequencing analysis was performed upon knockdown of HPSE, and several pathways were identified that are closely associated with invasion and metastasis. In addition, HPSE is positively correlated with MMP1 expression in CRC, and HPSE regulates MMP1 expression via p38 MAPK signaling pathway. In conclusion, our data demonstrate that HPSE knockdown attenuated tumor growth and liver metastasis in CRC, implying that HPSE might serve as a potential therapeutic target in the treatment of CRC.

Papillary cystadenoma of the parotid gland: A case report.

BACKGROUND: Papillary cystadenoma is a rare benign epithelial tumor of the salivary gland, which is characterized by papillary structures and oncocytic cells with rich eosinophilic cytoplasm. We found only one case of papillary cystadenoma in nearly 700 cases of salivary gland tumors. Our case was initially mistaken for a tumor of the right temporomandibular joint (TMJ) capsule rather than of parotid gland origin. Preoperative magnetic resonance imaging (MRI) and computed tomography (CT) should be carefully studied, which allows for appropriate preoperative counseling and operative planning. CASE SUMMARY: Here, we report an unusual case of a 54-year-old woman with a parotid gland papillary cystadenoma (PGPC) that was misdiagnosed as a tumor of the right TMJ capsule. She was initially admitted to our hospital due to a mass anterior to her right ear inadvertently found 5 d ago. Preoperative CT and MRI revealed a well circumscribed tumor that was attached to the right TMJ capsule. The patient underwent a resection through an incision for TMJ, but evaluation of an intraoperative frozen section revealed a benign tumor of the parotid gland. Then we removed part of the parotid gland above the temporal facial trunk. The facial nerve was preserved. Postoperative histopathological findings revealed that the tumor was PGPC. No additional treatment was performed. There was no recurrence during a 20-mo follow-up period. CONCLUSION: The integrity of the interstitial space around the condyle in MRI or CT should be carefully evaluated for parotid gland or TMJ tumors.

Risk factors of stillbirth in rural China: A national cohort study.

People living in rural China are more frequently exposed to some specific risk factors which made stillbirth rate higher than urban areas. National Free Preconception Health Examination Project was launched to investigate these risk factors and collected a representative sample of 248501 participants from 31 provinces in China from 2010 to 2013. Parental risk factors were ascertained twice before and during pregnancy respectively by questionnaires. Stillbirth or live birth were recorded by trained physicians. In the analysis, nested case-control study was conducted, and propensity score matching method was used to adjust the confounding. Multi-level logistic regression was used to fit for multi-level sampling. The overall stillbirth rate was 0.35% in rural China, it was higher in North (0.42%) and West (0.64%) areas. Maternal exposure to pesticide (OR (95%CI 1.06, 3.39)), hypertension (OR = 1.58 (95%CI 1.07, 2.34)), lack of appetite for vegetables (OR = 1.99 (95%CI 1.00, 3.93)), stress (compared with no pressure, OR of a little pressure was 1.34(95% CI 1.02, 1.76)); paternal exposure to smoking (OR = 1.22 (95% CI 1.02, 1.46)), organic solvents (OR = 1.64 (95% CI 1.01, 2.69)) were found independent risk factors of stillbirth. Folacin intake 3 months before pregnancy (OR = 0.72 (95%) CI 0.59, 0.89), folacin intake 1-2 months before pregnancy (OR = 0.71 (95% CI 0.55, 0.92)), folacin intake after pregnancy (OR = 0.81 (95% CI 0.65, 1.02) for) were protect factors of stillbirth. Maternal pesticide exposure, lack of vegetables, stress, paternal smoking and exposure to organic solvents were risk factors of stillbirth. Folic acid intake was protective factor of stillbirth, no matter when the intake began.

Reference Range and Sociodemographic Characteristics of TSH among Reproductive Age Women in Rural China.

Appropriate reference range of thyroid-stimulating hormone (TSH) is important to interpreting the results of thyroid functional tests. However, the reference range and sociodemographic characteristics of TSH based on large-scale studies are yet to be declared in rural China. To clarify reference range and sociodemographic characteristics of TSH in reproductive age of women from rural China. A nationwide population-based study was conducted as The National Free Preconception Health Examination Project (NFPHEP). Nearly 400,000 (n = 392,659) of Chinese rural women aged 15-55 years were randomly recruited. Predetermined strict exclusion criteria made a number of 359,895 as the reference population. Serum TSH was evaluated with enzyme-linked immunosorbent assay (ELISA). The reference range of TSH on overall and reference population was 0.39-5.20 and 0.39-5.13 uIU/ml (2.5th-97.5th percentiles), respectively. In the reference population, the range (2.5th to 97.5th percentile) of serum TSH in different age groups was 0.40-5.03 uIU/ml, 0.39-5.15 uIU/ml, 0.37-6.10 uIU/ml, and 0.44-7.03 uIU/ml, respectively. The mean TSH value in women aged 26-35 years was 2.26 uIU/ml, significantly lower than those aged 36-45 (p < 0.001). The mean TSH values for eastern, central, and western regions were 2.28 uIU/ml, 2.29 uIU/ml, and 2.24 uIU/ml respectively. The mean of serum TSH concentration was significantly higher in central region than that in western region (p ≤ 0.001). The TSH value 0.39-5.13 uIU/ml (2.5th-97.5th percentiles) was derived as a reference range of reproductive age women from rural China. We use the TSH ranges from reference population to diagnose hyperthyrotropinemia or hypothyroidism in different areas in China. The reference ranges for eastern, central, and western regions were 0.33-5.61 uIU/ml, 0.40-5.04 uIU/ml, and 0.40-4.98 uIU/ml (2.5th-97.5th percentiles) respectively. The value of serum TSH was associated with age, living region, smoking, drinking, educational level, and interpersonal tension, as well as life and economic pressure, but irrelevant to ethnicity or occupation.

[Effects of Dnmt1 and Dnmt3b in mucoepidermoid carcinoma of salivary glands].

PURPOSE: To investigate the effects of DNA methyltransferase in mucoepidermoid carcinoma of human salivary glands tissues. METHODS: Forty-three samples from mucoepidermoid carcinoma of salivary glands and 17 normal salivary gland tissues were collected from January 2010 to September 2013. Immunohistochemistry and Western blot were used to detect the expression of Dnmt1 and Dnmt3b in normal tissues and specimen of mucoepidermoid carcinoma of salivary glands. The data were analysed with SPSS 22.0 software package. RESULTS: The positive expression rate of Dnmt1 in mucoepidermoid carcinoma tissue was 37.21%, and that in normal salivary gland tissues was 17.65%, there was no significant difference between them; the positive expression rate of Dnmt3b in mucoepidermoid carcinoma tissue was 83.72%, which was significantly higher than that in normal salivary gland tissue (11.76%, P<0.01). However, there was no significant correlation between high expression of Dnmt1 and Dnmt3b and clinicopathological parameters. CONCLUSIONS: Dnmt3b may play a role in the tumorigenesis of mucoepidermoid carcinoma in salivary glands.

Both maternal and paternal risk factors for term singleton low birthweight infants in rural Chinese population: a population-based, retrospective cohort study.

No large population-based study has focused on both maternal paternal risk factors for low birthweight (LBW) in China. We aimed to identify parental risk factors associated with LBW.A population-based, retrospective cohort study was conducted on 202,725 singleton infants at 37-42 weeks. These term singleton newborns were classified as LBW with birthweight ≤2500 g(TLBW) and normal birthweight between 50th to 97th percentile (TNBW 50th-97th) according to Chinese singleton norms. Multiple logistic regression analyses were used to find those parental risk factors of LBW by comparing two groups. TLBW and TNBW(50th-97th) occupied 4.8% and 70.8% of the study population, respectively. Logistic regression showed a significant association with positive maternal hepatitis B surface antigen (RR = 1.979, P = 0.047), irregular folic acid intake (RR = 1.152, P = 0.003), paternal history of varicocele (RR = 2.404, P = 0.003) and female babies (RR = 1.072, P = 0.046). Maternal smoking, hypertension and history of stillbirth were found related to LBW but no statistically significant. Positive maternal hepatitis B surface antigen, irregular folic acid intake, paternal history of varicocele had a negative effect on birth weight. Measures are necessarily taken to avoid them to improve pregnancy outcomes. Further studies should be done to investigate each detailed risk factors on LBW.

Self-Recognition of an Inducible Host lncRNA by RIG-I Feedback Restricts Innate Immune Response.

The innate RNA sensor RIG-I is critical in the initiation of antiviral type I interferons (IFNs) production upon recognition of "non-self" viral RNAs. Here, we identify a host-derived, IFN-inducible long noncoding RNA, lnc-Lsm3b, that can compete with viral RNAs in the binding of RIG-I monomers and feedback inactivate the RIG-I innate function at late stage of innate response. Mechanistically, binding of lnc-Lsm3b restricts RIG-I protein's conformational shift and prevents downstream signaling, thereby terminating type I IFNs production. Multivalent structural motifs and long-stem structure are critical features of lnc-Lsm3b for RIG-I binding and inhibition. These data reveal a non-canonical self-recognition mode in the regulation of immune response and demonstrate an important role of an inducible "self" lncRNA acting as a potent molecular decoy actively saturating RIG-I binding sites to restrict the duration of "non-self" RNA-induced innate immune response and maintaining immune homeostasis, with potential utility in inflammatory disease management.

CPEB4 regulates glioblastoma cell proliferation and predicts poor outcome of patients.

OBJECTIVE: Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene expression at transcriptional level and has been reported to be associated with biological malignancy in cancers. However, little was known about the correlation between CPEB4 and glioblastoma cell proliferation and the prognostic significance in patients. Our aim was to investigate the functional role and prognostic value of CPEB4 in glioblastoma. PATIENTS AND METHODS: We determined the expression of CPEB4 protein using immunohistochemistry in tissue microarrays containing 278 glioma patients (including 98 primary glioblastomas) and evaluated its association with pathological grades and clinical outcome by univariate and multivariate analyses. And then, lentiviral-mediated RNAi targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell proliferation. RESULTS: In our cohort, CPEB4 expression was positively related to glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01). High expression of CPEB4 was associated with significantly poor prognosis, and could be identified as an independent risk factor for overall survival (OS) and progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) = 1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies further showed that downregulation of CPEB4 significantly reduced the growth rate of T98G and U251 cells comparing with the controls. CONCLUSION: Our study indicated that increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients and suppression of CPEB4 inhibit tumor cell proliferation, suggesting a potential therapeutic target for glioblastoma.

Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA.

Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus.