LncRNA NRON promotes tumorigenesis by enhancing MDM2 activity toward tumor suppressor substrates.

The E3 ligase MDM2 promotes tumor growth and progression by inducing ubiquitin-mediated degradation of P53 and other tumor-suppressing proteins. Here, we identified an MDM2-interacting lncRNA NRON, which promotes tumor formation by suppressing both P53-dependent and independent pathways. NRON binds to MDM2 and MDMX (MDM4) via two different stem-loops, respectively, and induces their heterogenous dimerization, thereby enhancing the E3 ligase activity of MDM2 toward its tumor-suppressing substrates, including P53, RB1, and NFAT1. NRON knockdown dramatically inhibits tumor cell growth in vitro and in vivo. More importantly, NRON overexpression promotes oncogenic transformation by inducing anchorage-independent growth in vitro and facilitating tumor formation in immunocompromised mice. Clinically, NRON expression is significantly associated with poor clinical outcome in breast cancer patients. Together, our data uncover a pivotal role of lncRNA that induces malignant transformation of epithelial cells by inhibiting multiple tumor suppressor proteins.

Curvilinear relationship was found between visceral adiposity index and stress urinary incontinence among US adult women: A cross-sectional study.

AIMS: The purpose of this study was to find out the relation between visceral adipose index (VAI) levels and stress urinary incontinence (SUI) in adult women. METHODS: From the National Health and Nutrition Examination Survey (NHANES) 2007-2020, females aged 20 or above were identified for this study. Visceral adiposity was determined using the VAI score, and the assessment of urinary incontinence was carried out through a correlation questionnaire. Logistic regression models and restricted cubic spline (RCS) regression were employed to analyze the relationship between VAI levels and SUI. RESULTS: Among the 6522 participants, 2672 (41.0%) were reported SUI. Multivariate logistic regression revealed significantly higher odds of SUI with increasing VAI levels (Q4 vs. Q1), adjusted odds ratio (aOR) = 1.53 (CI: 1.29-1.81, p < 0.001). RCS regression indicated a curvilinear relationship between VAI and SUI (p = 0.003). In threshold analysis, aOR for developing SUI was 1.18 (CI: 1.11-1.26, p < 0.001) for participants with VAI < 4.73, suggesting an 18% increased risk of SUI with each unit increase in VAI. No association between VAI and SUI was observed when VAI was ≥4.73. CONCLUSIONS: Our study has revealed a significant curvilinear relationship between VAI and SUI within a large and representative sample of women. Future research is necessary to evaluate the relationship between the two and explicate the underlying mechanisms of this relationship.

Maternal dietary patterns during pregnancy and birth weight: a prospective cohort study.

BACKGROUND: Existing data on maternal dietary patterns and birth weight remains limited and inconsistent, especially in non-Western populations. We aimed to examine the relationship between maternal dietary patterns and birth weight among a cohort of Chinese. METHODS: In this study, 4,184 mother-child pairs were included from the Iodine Status in Pregnancy and Offspring Health Cohort. Maternal diet during pregnancy was evaluated using a self-administered food frequency questionnaire with 69 food items. Principal component analysis was used to identify dietary patterns. Information on birth weight and gestational age was obtained through medical records. Adverse outcomes of birth weight were defined according to standard clinical cutoffs, including low birth weight, macrosomia, small for gestational age, and large for gestational age. RESULTS: Three maternal dietary patterns were identified: plant-based, animal-based, and processed food and beverage dietary patterns, which explained 23.7% variance in the diet. In the multivariate-adjusted model, women with higher adherence to the plant-based dietary patten had a significantly higher risk of macrosomia (middle tertile vs. low tertile: odds ratio (OR) 1.45, 95% CI 1.00-2.10; high tertile vs. low tertile: OR 1.55, 95% CI 1.03-2.34; P-trend = 0.039). For individual food groups, potato intake showed positive association with macrosomia (high tertile vs. low tertile: OR 1.72, 95% CI 1.20-2.47; P-trend = 0.002). Excluding potatoes from the plant-based dietary pattern attenuated its association with macrosomia risk. No significant associations was observed for the animal-based or processed food and beverage dietary pattern with birth weight outcomes. CONCLUSIONS: Adherence to a plant-based diet high in carbohydrate intake was associated with higher macrosomia risk among Chinese women. Future studies are required to replicate these findings and explore the potential mechanisms involved.

Prenatal features and postnatal follow-up of congenital ventricular outpouching: A retrospective study of two centers in China.

OBJECTIVES: Congenital ventricular outpouching (CVO) is a rare cardiac malformation that can manifest as congenital ventricular aneurysm (CVA) and/or congenital ventricular diverticula (CVD). In this study, we describe the prenatal features and postnatal follow-up of 27 cases of CVO. METHODS: The clinical data of 27 patients with CVO who attended Sir Run Run Shaw Hospital Affiliated to the Medical College of Zhejiang University (Zhejiang Province, China) and Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Zhejiang Province, China) from April 2013 to October 2022 were retrospectively analyzed. The patients were also followed up by telephone. The prenatal characteristics and postnatal outcomes of the patients with CVO were evaluated. RESULTS: CVO was detected in 26 cases prenatally, 14 (51.85%) were diagnosed with CVA, nine (33.33%) were diagnosed with CVD, three (11.11%) were equivocal for CVA/CVD, and one (3.70%) was detected with CVA postnatally. Six patients underwent follow-up fetal echocardiography approximately 4 weeks after the initial echocardiography examination, and a significant difference in CVO size was observed between the two examinations (P = .02). Eight patients (29.63%) demonstrated cardiovascular dysfunction, and the median CVO size in fetuses with and without cardiovascular dysfunction was 205 (range: 169-396) mm2 and 124 (range: 92-154.5) mm2 , respectively (P = .01). Correlation was found between CVO size and fetal cardiac dysfunction (p = .000, r = .778). Eight patients (29.63%) had cardiac/extracardiac defects. Thirteen patients were live born, 12 were terminated pregnancies, and two were lost to follow-up. The postpartum size of the CVOs remained stable in six patients, decreased in two patients, dissolved in three patients, and were surgically removed in two patients. With the exception of one patient with CVA complicated with complex congenital cardiac malformation who underwent surgical treatment after birth and who had postoperative left ventricular dysfunction (Case 1), the prognosis of all of the patients was good. CONCLUSION: CVO is often associated with cardiac malformations. The size of prenatal CVOs can increase with gestational development, and cardiovascular dysfunction is significantly related to CVO size. The postpartum prognosis of patients with CVO is good. Echocardiography plays a key role in the diagnosis of congenital ventricular outpouching. Prenatal counseling should be cautious regarding the diagnosis and the prognosis although our cases had a favorable prognosis.

The infection rates of HBV and HCV decreased significantly in Zhejiang Province, China: A comparative study based on the data of two sero-epidemiological surveys in 1992 and 2020.

In 2020, China conducted a nationwide, sero-epidemiological, cross-sectional survey of viral hepatitis. The stratified multi-stage cluster random sampling method was used to select the permanent population aged 1-69 years, followed by questionnaire survey and sample collection and detection of the serological markers of hepatitis B (HBV) and hepatitis C viruses (HCV). A total of 4747 individuals aged 1-69 years were investigated in Zhejiang Province. The positive rates of hepatitis B surface antigen and anti-HCV were 4.3% and 0%, respectively. Compared to a similar sero-epidemiological survey in 1992, the 2020 survey showed that the HBV infection rate in Zhejiang Province decreased by 56.5%. In both surveys, HBV infection rate increased with age (in 1992, χ2  = 185.866, p = .000; in 2020, χ2  = 1383.836, p = .000). Compared with 1992, the positive anti-HCV rate in those aged 1-69 years in 2020 decreased by 100.0%. This result showed that the HBV vaccine and blood screening to prevent HBV and HCV infection significantly decreased the infection rate of HBV and HCV in the younger generation of Zhejiang province. However, the rate of HBV carriers aged 30-69 years was still high, which underscores the need to strengthen the management and treatment of chronic HBV infection. Hence, Zhejiang province can eliminate the public health threat of viral hepatitis.

Rice Cell Division Cycle 20s are required for faithful chromosome segregation and cytokinesis during meiosis.

Chromosome segregation must be under strict regulation to maintain chromosome euploidy and stability. Cell Division Cycle 20 (CDC20) is an essential cell cycle regulator that promotes the metaphase-to-anaphase transition and functions in the spindle assembly checkpoint, a surveillance pathway that ensures the fidelity of chromosome segregation. Plant CDC20 genes are present in multiple copies, and whether CDC20s have the same functions in plants as in yeast and animals is unclear, given the potential for divergence or redundancy among the multiple copies. Here, we studied all three CDC20 genes in rice (Oryza sativa) and constructed two triple mutants by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated genome editing to explore their roles in development. Knocking out all three CDC20 genes led to total sterility but did not affect vegetative development. Loss of the three CDC20 proteins did not alter mitotic division but severely disrupted meiosis as a result of asynchronous and unequal chromosome segregation, chromosome lagging, and premature separation of chromatids. Immunofluorescence of tubulin revealed malformed meiotic spindles in microsporocytes of the triple mutants. Furthermore, cytokinesis of meiosis I was absent or abnormal, and cytokinesis II was completely prevented in all mutant microsporocytes; thus, no tetrads or pollen formed in either cdc20 triple mutant. Finally, the subcellular structures and functions of the tapetum were disturbed by the lack of CDC20 proteins. These findings demonstrate that the three rice CDC20s play redundant roles but are indispensable for faithful meiotic chromosome segregation and cytokinesis, which are required for the production of fertile microspores.

Oxytocin Receptor in Cerebellar Purkinje Cells Does Not Engage in Autism-Related Behaviors.

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.

Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer.

Colorectal cancer (CRC) is a common malignant cancer worldwide. Although the molecular mechanism of CRC carcinogenesis has been studied extensively, the details remain unclear. Small nucleolar RNAs (snoRNAs) have recently been reported to have essential functions in carcinogenesis, although their roles in CRC pathogenesis are largely unknown. In this study, we found that the H/ACA snoRNA SNORA24 was upregulated in various cancers, including CRC. SNORA24 expression was significantly associated with age and history of colon polyps in CRC patient cohorts, with high expression associated with a decreased 5-year overall survival. Our results indicated that the oncogenic function of SNORA24 is mediated by promoting G1/S phase transformation, cell proliferation, colony formation, and growth of xenograft tumors. Furthermore, SNORA24 knockdown induced massive apoptosis. RNA-sequencing and gene ontology (GO) enrichment analyses were performed to explore its downstream targets. Finally, we confirmed that SNORA24 regulates p53 protein stability in a proteasomal degradation pathway. Our study clarifies the oncogenic role of SNORA24 in CRC and advance the current model of the role of the p53 pathway in this process.

Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors.

Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL- and not BLA- and vHipp-NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL-NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.

[Survey on the awareness rate of nutrition and health knowledge among residents aged 18-64 in Shanghai in 2021].

OBJECTIVE: To analyze the nutrition and health knowledge of residents aged 18-64 in Shanghai, and to understand the level of nutrition and health knowledge and its influencing factors. METHODS: The total of 6518 residents aged 18-64 years old in Shanghai were selected by stratified random sampling in 2021. The subjects were grouped by gender, age, education levels, occupations, and regions. The awareness rate of nutrition and health knowledge and its influencing factors were investigated using the questionnaire and scoring standard designed by National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention. Household survey, face-to-face questioning by surveyors and help to fill in the options. RESULTS: The score of nutrition and health knowledge of residents aged 18-64 in Shanghai was 68.43±12.82, and the awareness rate was 35.78%. The average score(t=-5.04, P<0.01) and awareness rate(χ~2=14.06, P<0.01) of women were significantly higher than men. Significant differences in average scores and awareness rates were found among different groups of ages(F=15.02, P<0.01;χ~2=23.46, P<0.01), education levels(F=191.45, P<0.01;χ~2=210.29, P<0.01), occupations(F=99.17, P<0.01;χ~2=224.12, P<0.01) and regions(F=22.11, P<0.01;χ~2=44.61, P<0.01). The female(OR=1.13, 95%CI 1.02-1.25), high school education and above(OR=1.68-2.85) had better knowledge of nutrition and health. While 18-34 years(OR=0.69-0.74), people engaged in non-medical health institutions(OR=0.46-0.70) and living in non-urban central areas(OR=0.74-0.81) had poorer awareness of nutrition and health knowledge. CONCLUSION: The awareness rate of nutrition and health knowledge among residents aged 18-64 in Shanghai is still upside potential.

Changing Epidemiology of Hepatitis A in China: Evidence From Three National Serological Surveys and the National Notifiable Disease Reporting System.

BACKGROUND AND AIMS: China has conducted surveillance for hepatitis A since 1990, and hepatitis A was highly-to-intermediately endemic in 1992 when a Chinese hepatitis A vaccine (HepA) was licensed and introduced as a family-pay vaccine. In 2008, HepA was introduced into the Expanded Program on Immunization as a free childhood vaccine. APPROACH AND RESULTS: Three nationally representative surveys conducted in 1992, 2006, and 2014 assessed hepatitis B serology. The 1992 survey included hepatitis A virus (HAV) serology, and we tested sera from the 2006 and 2014 surveys for HAV antibodies. We used surveillance, seroprevalence, and vaccination status data to describe the changing epidemiology of hepatitis A in China from 1990 through 2014. Before HepA licensure, anti-HAV seroprevalence was 60% at 4 years of age, 70% at 10 years, and 90% at 59 years; incidence was 52/100,000 and peaked at 4 years. In 2006, after >10 years of private sector vaccination, HepA coverage was <30% among children <5 years, and incidence was 5.4/100,000 with a peak at 10 years. In 2014, coverage was >90% among children under 5 years; incidence was 1.9/100,000. Individuals born before the national introduction of HepA (1988-2004) had lower anti-HAV seroprevalence than earlier and later birth cohorts. CONCLUSIONS: The incidence of hepatitis A declined markedly following HepA introduction and improvement of sanitation and hygiene. The emerging epidemiology is consistent with disease-induced immunity having been replaced by vaccine-induced immunity, resulting in a low incidence of hepatitis A. Catch-up HepA campaigns to close the immunity gap among the 1998-2004 birth cohorts should be considered.

Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.

BACKGROUND: Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). METHODS: Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-ß, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups. RESULTS: Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-ß, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota. CONCLUSIONS: Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.

[Association between timing for introducing complementary foods and body composition of children aged 3-5 years in five provinces of China].

OBJECTIVE: To explore the association between different timing of introducing complementary foods during infancy and the body composition of children aged 3-5 years. METHODS: The data was from National Nutrition and Health Systematic Survey for 0-18 Years Old Children in China. A face-to-face interview to caregivers of children was conducted to retrospectively collect timing of introducing complementary foods of children aged 3-5 years. The bioelectrical impedance analysis was used to measure the body composition of children by professionally trained investigators. The exposure variable of the study was the timing of introducing complementary foods(≤5 months old, 6 months old and ≥7 months old). The outcome variables were the fat-free mass, fat-free mass index, body fat mass, body fat mass index, and percentage of body fat. According to age stratification, a multivariate linear regression model was used to calculate the mean, mean difference and 95% CI after adjusting for potential confounders. RESULTS: After adjusting for potential confounders, there were no statistically significant difference in body fat mass, body fat mass index, percentage of body fat and fat-free mass index among different groups of timing for introducing complementary foods for children aged 3-5 years old. For children aged 3-5 years, after adjusting for potential confounders, the difference of fat free mass was statistically significant among children with different timing for introducing of complementary foods(3 years old: 12.89 kg vs. 12.66 kg vs. 12.94 kg, F=4.42, P=0.013; 5 years old: 16.27 kg vs. 16.23 kg vs. 16.66 kg, F=5.40, P=0.005). The fat free mass of children aged 3 years was lower when introducing complementary foods during 6 months of age than at ≤5 months of age(mean difference=-0.23 kg(95% CI-0.45--0.02 kg)). The fat free mass of children aged 5 years was higher when introducing complementary foods at ≥7 months of age than at≤5 months of age(mean difference=0.39 kg(95% CI 0.08-0.70 kg)). CONCLUSION: It is found that the association between timing for introducing complementary foods during infancy and the fat mass indicators of children aged 3 to 5 years was not statistically significant, and the association between timing for introducing complementary foods and fat-free mass may be inconsistent for different fat-free mass indicators.

Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies.

BACKGROUND: The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China. METHODS: During 2014-2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed. RESULTS: (1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group. CONCLUSIONS: HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

Long noncoding RNA lnc-RI regulates DNA damage repair and radiation sensitivity of CRC cells through NHEJ pathway.

A percentage of colorectal cancer (CRC) patients display low sensitivity to radiotherapy, which affects its therapeutic effect. Cancer cells DNA double-strand breaks (DSBs) repair capacity is crucial for radiosensitivity, but the roles of long noncoding RNAs (lncRNAs) in this process are largely uncharacterized. This study aims to explore whether lnc-RI regulates CRC cell growth and radiosensitivity by regulating the nonhomologous end-joining (NHEJ) repair pathway. CRC cells in which lnc-RI has been silenced showed lower cell growth and higher apoptosis rates due to increased DSBs and cell cycle arrest. We found that miR-4727-5p targets both lnc-RI and LIG4 mRNA and inhibit their expression. CRC cells showed increased radiosensitivity when lnc-RI was silenced. These results reveal novel roles for lnc-RI in both DNA damage repair and radiosensitivity regulation in CRC cells. Our study revealed that lnc-RI regulates LIG4 expression through lnc-RI/miR-4727-5p/LIG4 axis and regulates NHEJ repair efficiency to participate in DNA damage repair. The level of lnc-RI was negatively correlated with the radiosensitivity of CRC cells, indicates that lnc-RI may be a potential target for CRC therapy. We also present the first report of the function of miR-4727-5p.

LncRNA lnc-RI regulates homologous recombination repair of DNA double-strand breaks by stabilizing RAD51 mRNA as a competitive endogenous RNA.

DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. The current models of the mechanism of DSB repair are based on studies of DNA repair proteins. Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules, with diverse functions in biological processes. In the present study, we found that expression of the ionizing radiation-inducible lncRNA, lnc-RI, was correlate negatively with micronucleus frequencies in human peripheral blood lymphocytes. Knockdown of lnc-RI significantly increased spontaneous DSBs levels, which was confirmed to be associated with the decreased efficiency of homologous recombination (HR) repair of DSBs. The expression of RAD51, a key recombinase in the HR pathway, decreased sharply in lnc-RI-depressed cells. In a further investigation, we demonstrated that miR-193a-3p could bind with both lnc-RI and RAD51 mRNA and depressed the expression of lnc-RI and RAD51 mRNA. Lnc-RI acted as a competitive endogenous RNA (ceRNA) to stabilize RAD51 mRNA via competitive binding with miR-193a-3p and release of its inhibition of RAD51 expression. To our knowledge, this is the first study to demonstrate the role of lnc-RI in regulating HR repair of DSBs. The feedback loop established in the current study suggests that lnc-RI is critical for the maintenance of genomic stability.

A rapid and sensitive recombinase aided amplification assay to detect hepatitis B virus without DNA extraction.

BACKGROUND: Hepatitis B virus (HBV) infection is the major public health problem worldwide. In clinical practice, serological and molecular assays are the most commonly used diagnostic methods to detect HBV infection in clinical practices. METHODS: Here we present a rapid and sensitive recombinase aided amplification assay (RAA) to detect HBV at 39.0 °C for 30 min without DNA extraction from serum samples. The analytical sensitivity of RAA assay was 100 copies per reaction and showed no cross reaction with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The universality of RAA assay was validated by testing of 41 archived serum samples with predefined HBV genotypes (B, C and D). RESULTS: A total of 130 archived suspected HBV infected serum samples were detected by commercial qPCR with DNA extraction and RAA assay without DNA extraction (heat-treatment). Compared with qPCR assay as a reference, the RAA assay obtained 95.7% sensitivity and 100% specificity and a kappa value of 0.818. CONCLUSIONS: We developed a rapid, convenient, highly sensitive and specific method to detect HBV without DNA extraction in clinical samples. This RAA method of HBV detection is very suitable for clinical testing.

A Novel Approach for Imaging of Thoracic Outlet Syndrome Using Contrast-Enhanced Magnetic Resonance Angiography (CE-MRA), Short Inversion Time Inversion Recovery Sampling Perfection with Application-Optimized Contrasts Using Different Flip Angle Evolutions (T2-STIR-SPACE), and Volumetric Interpolated Breath-Hold Examination (VIBE).

BACKGROUND The aim of this study was to introduce a novel method combining contrast-enhanced magnetic resonance angiography (CE-MRA), short inversion time inversion recovery sampling perfection with application-optimized contrasts using different flip angle evolutions (T2-STIR-SPACE) and volumetric interpolated breath-hold examination (VIBE) sequences in the assessment of thoracic outlet syndrome (TOS). MATERIAL AND METHODS CE-MRA, T2-STIR-SPACE, and VIBE techniques were employed to evaluate neurovascular bundles in 27 patients clinically suspected of TOS. Images were evaluated to determine the cause of neurovascular bundle compression. Surgical exploration was performed in patients with abnormal magnetic resonance imaging (MRI) results. RESULTS Twenty patients were found to be abnormal: 6 cases showed only neurogenic TOS and the correlates included infraclavicular hemangiomas (n=1) and transverse cervical artery (n=5). Arterial-neurogenic TOS was found in 4 cases, including subclavian lymph node metastasis from breast cancer (n=3) and schwannoma (n=1). Arterial-venous-neurogenic TOS was found in 1 subject, and the correlates included a fibrous band from the cervical rib and elongated C7 transverse process. In this case, the subclavian artery/vein was compressed dynamically. Venous-neurogenic TOS was noted in one subject. Nine patients were considered as post-traumatic TOS, including brachial plexus edema (n=3), the brachial plexus rupture (n=2), peri-brachial plexus effusion (n=3), and stenosis of the SCA (n=1). In the remaining 7 patients, MRI did not detect abnormalities. CONCLUSIONS TOS can be evaluated by CE-MRA, T2-STIR-SPACE, and VIBE during a single examination, with a reduced contrast material dose. This imaging modality performs well in showing the anatomical structure of the neurovascular bundle and the cause of the compression.

Expression and potential roles of IL-33/ST2 in the immune regulation during Clonorchis sinensis infection.

During clonorchiasis, immune responses of hosts are responsible for the removal of the worms and also are involved in the progress of the pathological damage caused by Clonorchis sinensis. Interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, has emerged as a potent inducer to bile duct proliferation and fibrosis; however, little is known of this signaling in the pathogen-caused periductal inflammation and fibrosis. In the present study, using immunohistochemistry, real-time PCR, enzyme-linked immunosorbent assay (ELISA), and flow cytometry, we studied the expression of IL-33/ST2 during C. sinensis infection, as well as their potential roles in C. sinensis-induced host immune responses. The results showed that a higher level of IL-33 was detected in the sera of patients of clonorchiasis (n = 45), compared with in those of healthy donors (n = 16). Similarly, in FVB mice experimentally infected with C. sinensis, a higher level of IL-33 was detected at latent stage both in the serum and in the liver, as well as the up-regulated expression of ST2 receptor on the inflammatory cells, especially on CD4(+) T cells in the liver of infected mice. Our results, for the first time, indicated that the increased IL-33/ST2 may be involved in the regulation of immunopathology induced by C. sinensis.

[The genetic toxicity and toxicology mechanism of metal nano materials].

Although metal nano materials have been widely used in various fields, the potential risks of it still could not be neglected. In this paper, the effects and mechanisms of genotoxicity caused by different nano materials were discussed. Human body can be exposed to metal nano materials through multiple pathways, metals nano follow the blood stream in circulatory system and distribute to organs. Metal nano particles are mainly uptaken into cells by endocytosis, and direct or indirect damages to genes can be induced by these particles after metabolism in cells. These damages would affect the course of cell cycle and the stability of the genome, resulting in gene mutation or chromosome aberration, and even leading to the death or malignant transformation of cells.