Sex-specific differences in the associations between adiposity indices and incident hyperuricemia among middle-aged and older adults: a nationwide longitudinal study.

Objective: Although obesity is a known risk for hyperuricemia (HUA), the associations between adiposity indices and incident HUA and whether sex-specific differences exist is still unknown. We aimed to investigate the associations between adiposity indices and incident HUA in a longitudinal study. Methods: Data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011-2012 and 2015-2016 were used to conduct a cohort study. Participants aged ≥45 years without HUA at baseline were included in this study. Adiposity indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio body roundness index (BRI), conicity index (CI), lipid accumulation product (LAP) index, waist-to-height ratio (WHtR), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI), were calculated. Logistic analysis was used to analyze the association between adiposity indices and incident HUA risk stratified by gender. Receiver operating characteristic curve analysis was performed to evaluate the power of predictions for incident HUA. Results: Of 5,873 participants aged 59.0 ± 8.7 years enrolled in this study, 578 (9.8%) participants developed HUA during the 4-year follow-up period. After adjusting for confounding variables, LAP, VAI, and CVAI showed significant association with incident HUA. BMI, WC, WHtR, BRI, and CI were significantly associated with incident HUA in women but not in men. LAP had the highest area under the curve (AUC) (0.612) followed by CVAI (0.596) in men, while CVAI had the highest AUC (0.707) followed by LAP (0.691) in women. All indices showed better predictive ability in women than in men. Conclusion: Our findings indicated that adiposity indices were effective predictors of incident HUA and showed better predictive power in women than men. In clinical practice, adiposity indices could be used to assess and prevent incident HUA among Chinese middle-aged and older adults.

DNA Robots for CRISPR/Cas12a Activity Management and Universal Platforms for Biosensing.

The CRISPR/Cas12a system is a revolutionary genome editing technique that is widely employed in biosensing and molecular diagnostics. However, there are few reports on precisely managing the trans-cleavage activity of Cas12a by simple modification since the traditional methods to manage Cas12a often require difficult and rigorous regulation of core components. Hence, we developed a novel CRISPR/Cas12a regulatory mechanism, named DNA Robots for Enzyme Activity Management (DREAM), by introducing two simple DNA robots, apurinic/apyrimidinic site (AP site) or nick on target activator. First, we revealed the mechanism of how the DREAM strategy precisely regulated Cas12a through different binding affinities. Second, the DREAM strategy was found to improve the selectivity of Cas12a for identifying base mismatch. Third, a modular biosensor for base excision repair enzymes based on the DREAM strategy was developed by utilizing diversified generation ways of DNA robots, and a multi-signal output platform such as fluorescence, colorimetry, and visual lateral flow strip was constructed. Furthermore, we extended logic sensing circuits to overcome the barrier that Cas12a could not detect simultaneously in a single tube. Overall, the DREAM strategy not only provided new prospects for programmable Cas12a biosensing systems but also enabled portable, specific, and humanized detection with great potential for molecular diagnostics.

Self-Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit.

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg2+ . Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.

CRISPR/Cas12a-based fluorescence aptasensor integrated with two-dimensional cobalt oxyhydroxide nanosheets for IFN-γ detection.

Cytokine storm (CS) is a risky immune overreaction accompanied by significant elevations of pro-inflammatory cytokines including interferon-γ (IFN-γ), interleukin and tumor necrosis factor. Sensitive detection of cytokine is conducive to studying CS progress and diagnosing infectious diseases. In this study, we developed a tandem system combining aptamer, strand displacement amplification (SDA), CRISPR/Cas12a, and cobalt oxyhydroxide nanosheets (termed Apt-SCN tandem system) as a signal-amplified platform for IFN-γ detection. Owing to the stronger affinity, target IFN-γ bound specifically to the aptamer from aptamer-complementary DNA (Apt-cDNA) duplex. The cDNA released from the Apt-cDNA duplex initiated SDA, resulting in the generation of double-stranded DNA products that could activate the trans-cleavage activity of CRISPR/Cas12a. The activated CRISPR/Cas12a further cleaved FAM-labeled single-stranded DNA probe, preventing it from adhering to the cobalt oxyhydroxide nanosheets and recovering the fluorescence signal. Sensitive fluorometric analysis of IFN-γ was successfully performed with detection limit as low as 0.37 nM. Unlike traditional protein analysis methods, Apt-SCN tandem system incorporates multiple signal amplification techniques and may also be applicable for other cytokines assay. This study was the initial study to utilize SDA and CRISPR/Cas12a to detect IFN-γ, showing great potential for cytokines clinical assay and CS prevention.

Weekend warrior physical activity pattern is associated with lower depression risk: Findings from NHANES 2007-2018.

OBJECTIVE: This study aimed to explore the association between weekend warrior physical activity (PA) pattern and depression risk in American adults. METHODS: Data of adults (n = 21,125) from NHANES 2007-2018 were used. Adults were categorized into 4 PA patterns (inactive, insufficiently active, weekend warrior, and regularly active) by self-reported PA levels. Participant characteristics in different groups were tested using the Rao & Scott adjusted χ2 test. Multivariate logistic regression models with adjustment for demographics data, behavioral factors and health condition were used to explore the association between PA patterns and depression risk. Finally, interaction analyses were conducted to test if the associations differ by gender, age, race, education level, income level and marital status. RESULTS: Multivariate logistic regression models showed that insufficiently active, weekend warrior and regularly active adults had 31% (OR: 0.69, 95%CI:0.54-0.88), 57% (OR: 0.43, 95%CI:0.25-0.74) and 54% (OR: 0.46, 95%CI:0.39-0.54) reduced depression risk when compared with inactive adults, respectively. When compared with regularly active adults, inactive (OR: 2.188, 95%CI:1.842-2.600) and insufficiently active (OR: 1.505, 95%CI:1.159-1.955) adults had elevated depression risk, but no significant difference was found between weekend warrior (OR: 0.949, 95%CI:0.538-1.675) and regularly active adults. Moreover, the associations did not differ by demographic variables. CONCLUSIONS: This study showed that adults who engaged in either regularly active pattern or weekend warrior pattern, experienced lower risk of depression compared to inactive adults. Weekend warrior and regularly active patterns showed similar benefits for lowering depression risk in adults, encouraging adults to take up PA in limited sessions.

Dysregulation of MicroRNAs Derived from Plasma Extracellular Vesicles in Schizoaffective Disorder.

The association between peripheral blood extracellular vesicles (EVs)-derived miRNAs (EVs-miRNAs) and neuropsychiatric diseases has been extensively studied. However, it remains largely unclear about the expression profile of EVs-miRNAs in schizoaffective disorder (SAD) patients. In our study, we isolated the EVs from plasma samples of patients and healthy controls, and then analyzed the expression profiles of EVs-miRNAs through small RNA sequencing. Our results identified 32 differentially expressed (DE) miRNAs (25 upregulated and 7 downregulated) in SAD patients. A module containing 42 miRNAs closely related to SAD was identified by weighted gene co-expression network analysis (WGCNA), among which has-miR-15b-5p, has-miR-301a-3p, has-miR-342-3p, has-miR-219b-5p, and has-miR-145-5p were identified as hub miRNAs. The enrichment analysis showed that the target genes of these 42 miRNAs were significantly enriched in multiple pathways related to neuropathology and located at synapses. A total of 6 DE miRNAs (has-miR-7-5p, has-miR-144-3p, has-miR-155-5p, has-miR-342-3p, has-miR-342-5p, and has-miR-487b-3p) associated with SAD were selected for qRT-PCR verification. The level of has-miR-342-3p in SAD patients was downregulated, and hsa-miR-155-5p was upregulated. Our findings support the hypothesis that dysregulation of EVs-miRNAs in plasma might be involved in the underlying neuropathology of SAD through several biological pathways and provide important preliminary evidence supporting the use of EVs-miRNAs as potential novel biomarkers in SAD.

Sleep duration and depressive symptoms in Chinese middle-aged and older adults: The moderating effects of grip strength.

BACKGROUND: Evidence on the combined effect of sleep duration and grip strength on depressive symptoms is scarce. This study aimed to explore the moderating effect of grip strength on the association between sleep duration and depressive symptoms in a large cohort of middle-aged and older adults. METHOD: Data were extracted from the China Health and Retirement Longitudinal Study (CHARLS) 2011-2018 wave. Grip strength and sleep duration were assessed by dynamometer and self-report, respectively. Depressive symptoms were determined by the Centre for Epidemiological Studies Depression scale (CESD-10). Multivariable cox regression model was used to explore the associations between sleep duration, and depressive symptoms, and assess moderation by grip strength. RESULTS: A total of 4337 participants aged 57.0 ± 8.1 years (45.1 % females) were included in this study. During the 7-year follow up period, 1508 participants developed depressive symptoms. Short sleep duration (<6 h/d) was significantly associated with an increased risk of depressive symptoms [Hazard ratio (HR):1.24, 95 % confidence interval (CI):1.09, 1.40)]. This association remained in individuals with the low (HR:1.22, 95%CI:1.00, 1.49) and middle grip strength (HR:1.32, 95%CI: 1.07, 1.63), but attenuated in individuals with high grip strength (HR:1.11, 95%CI: 0.86, 1.43). CONCLUSIONS: High grip strength mitigated the association between short sleep duration and higher risk of depressive symptoms. Thus, improving sleep duration and strengthening muscle strength are recommended to prevent depressive symptoms in middle-aged and older adults.

The non-specific lipid transfer protein McLTPII.9 of Mentha canadensis is involved in peltate glandular trichome density and volatile compound metabolism.

Mentha canadensis L. is an important spice crop and medicinal herb with high economic value. The plant is covered with peltate glandular trichomes, which are responsible for the biosynthesis and secretion of volatile oils. Plant non-specific lipid transfer proteins (nsLTPs) belong to a complex multigenic family involved in various plant physiological processes. Here, we cloned and identified a non-specific lipid transfer protein gene (McLTPII.9) from M. canadensis, which may positively regulate peltate glandular trichome density and monoterpene metabolism. McLTPII.9 was expressed in most M. canadensis tissues. The GUS signal driven by the McLTPII.9 promoter in transgenic Nicotiana tabacum was observed in stems, leaves, and roots; it was also expressed in trichomes. McLTPII.9 was associated with the plasma membrane. Overexpression of McLTPII.9 in peppermint (Mentha piperita. L) significantly increased the peltate glandular trichome density and total volatile compound content compared with wild-type peppermint; it also altered the volatile oil composition. In McLTPII.9-overexpressing (OE) peppermint, the expression levels of several monoterpenoid synthase genes and glandular trichome development-related transcription factors-such as limonene synthase (LS), limonene-3-hydroxylase (L3OH), geranyl diphosphate synthase (GPPS), HD-ZIP3, and MIXTA-exhibited varying degrees of alteration. McLTPII.9 overexpression resulted in both a change in expression of genes for terpenoid biosynthetic pathways which corresponded with an altered terpenoid profile in OE plants. In addition, peltate glandular trichome density was altered in the OE plants as well as the expression of genes for transcription factors that were shown to be involved in trichome development in plants.

Programmable CRISPR-Cas12a and self-recruiting crRNA assisted dual biosensing platform for simultaneous detection of lung cancer biomarkers hOGG1 and FEN1.

Human 8-oxoguanine DNA glycosylase (hOGG1) and flap endonuclease 1 (FEN1) are recognized as potential biomarkers in lung cancer investigations. Developing analytical platforms of simultaneously targeting hOGG1 and FEN1 with high selectivity, sensitivity, especially programmability and universality is highly valuable for clinical research. Herein, we established a signal-amplified platform for simultaneously detecting hOGG1 and FEN1 on the basis of cleavage-induced ligation of DNA dumbbell probes, rolling circle transcription (RCT) and CRISPR-Cas12a. A hOGG1 cleavable site and FEN1 cleavable flap were dexterously designed at the 5' end of DNA flapped dumbbell probes (FDP) for hOGG1 and FEN1. After cleavage, the resulting nick sites with juxtaposition of 5' phosphate and 3' hydroxyl terminus could be linked to closed DNA dumbbell probes (CDP) by DNA ligase. The CDP served as a template for RCT, producing plentiful crRNA repeats to activate the trans-cleavage activity of CRISPR-Cas12a which could cleave fluorophores (TAMRA and FAM) and quenchers (BHQ2 and BHQ1) double-labeled ssDNA reporters. Then, hOGG1 and FEN1 could be detected by the recovered fluorescence signal, allowing for the highly sensitive calculated detection limits of 0.0013 and 0.0052 U/mL, respectively. Additionally, this method made it possible to evaluate the inhibitory effects, even to measure hOGG1 and FEN1 activities at the single-cell level. This novel target enzyme-initiated, circles-transcription without promoters, real-time generation, and self-assembly features of FDP-RCT-Cas12a system suppressed nonspecific background remarkably and relieved rigorous requirement of protospacer adjacent motif site. Hence, the universality of FDP-RCT-Cas12a system toward various disease-related non-nucleic acid targets which are tested without using aptamers was extremely improved.

Maternal obesity induces liver lipid accumulation of offspring through the lncRNA Lockd/mTOR autophagy pathway.

Maternal obesity increases the risk of obesity and metabolic diseases in the offspring in early life, but the underlying mechanism has not been elucidated. The aim of this study is to explore whether lncRNA and autophagy are involved in the regulation of maternal obesity on the liver lipid metabolism of the offspring. C57BL/6 mice were fed high-fat diet (HFD) or standard chow diet (CD) for 12 weeks before the start of mating and continued until the end of the lactation period. The lipid metabolism indexes of the three-week-old offspring were detected. The RNA sequencing (RNA-seq) and western blot analysis for autophagy-related protein were performed on the offspring's liver to determine the comprehensive expression profile of lncRNA and autophagy level. In addition, AML12 cells were treated with small interfering RNA (siRNA) and rapamycin. Western blot, qRT-PCR and Oil Red O staining were used to detect protein expression, mRNA expression and lipid accumulation levels. As a result, maternal obesity leads to low expression of lncRNA Lockd and autophagy inhibition in the offspring's liver. Knockdown of lncRNA Lockd could further inhibit autophagy and aggravate lipid accumulation. Rapamycin treatment could improve lipid accumulation in AML12 cells. Our study revealed that maternal obesity caused low expression of lncRNA Lockd in the offspring's liver, and lncRNA Lockd positively regulates autophagy through the mTOR signaling pathway. This study provides new insights into the occurrence of lipid accumulation in the liver of offspring.

Associations of health-risk behaviors with mental health among Chinese children.

The study aimed to investigate the individual and combined association of health-risk behaviors with mental health among Chinese children. A cross-sectional study was conducted in Wuhan, China, from May to June 2018. Participants self-reported the information on physical activity (PA), screen time (ST), fruit and vegetable (FV) intake, and sleep duration. Mental health, including depression, social anxiety and self-esteem, was assessed using standard questionnaires. A total of 1296 children (704 males and 592 females) aged 9.2 ± 0.4 years were included in the present study. The prevalence of low PA, high ST, low FV intake, and inadequate sleep duration was 45.6%, 18.0%, 69.7%, and 64.7%, respectively. Overall, significant associations were found between individual health-risk behavior and increased risks of mental health. Furthermore, children with three or four health-risk behaviors showed significantly increased risks of anxiety (OR: 3.18, 95%CI: 1.63-6.21), depression (OR: 4.55, 95%CI: 2.28-9.09) and low self-esteem (OR: 3.59, 95%CI: 2.20-5.88) compared with those without health-risk behavior. Results of this study revealed a high prevalence of health-risk behaviors among Chinese children. Furthermore, the clustering of health-risk behavior was associated with significantly increased risks of mental health in this population. Considering these findings, it is important to perform early interventions to reduce children's health-risk behavior and prevent mental health problems.

Characterization of the Glehnia littoralis Non-specific Phospholipase C Gene GlNPC3 and Its Involvement in the Salt Stress Response.

Glehnia littoralis is a medicinal halophyte that inhabits sandy beaches and has high ecological and commercial value. However, the molecular mechanism of salt adaptation in G. littoralis remains largely unknown. Here, we cloned and identified a non-specific phospholipase C gene (GlNPC3) from G. littoralis, which conferred lipid-mediated signaling during the salt stress response. The expression of GlNPC3 was induced continuously by salt treatment. Overexpression of GlNPC3 in Arabidopsis thaliana increased salt tolerance compared to wild-type (WT) plants. GlNPC3-overexpressing plants had longer roots and higher fresh and dry masses under the salt treatment. The GlNPC3 expression pattern revealed that the gene was expressed in most G. littoralis tissues, particularly in roots. The subcellular localization of GlNPC3 was mainly at the plasma membrane, and partially at the tonoplast. GlNPC3 hydrolyzed common membrane phospholipids, such as phosphotidylserine (PS), phosphoethanolamine (PE), and phosphocholine (PC). In vitro enzymatic assay showed salt-induced total non-specific phospholipase C (NPC) activation in A. thaliana GlNPC3-overexpressing plants. Plant lipid profiling showed a significant change in the membrane-lipid composition of A. thaliana GlNPC3-overexpressing plants compared to WT after the salt treatment. Furthermore, downregulation of GlNPC3 expression by virus-induced gene silencing in G. littoralis reduced the expression levels of some stress-related genes, such as SnRK2, P5SC5, TPC1, and SOS1. Together, these results indicated that GlNPC3 and GlNPC3-mediated membrane lipid change played a positive role in the response of G. littoralis to a saline environment.

The association of child neglect with lifestyles, depression, and self-esteem: Cross-lagged analyses in Chinese primary schoolchildren.

Child neglect robustly predicts many behavioral problems and adulthood mental disorders, but little is known about its association with daily lifestyles and psychological development during childhood, particularly in the longitudinal study. We aimed to examine the association of child neglect with physical activity (PA), screen time (ST), eating habits (EHs), and depression/self-esteem using a two-wave follow-up study of primary schoolchildren in Wuhan, China. Data of 1085 schoolchildren aged 8-10 years (boys: 53.5%) were analyzed. Child neglect, lifestyles, and depression/self-esteem were collected in 2018 (T1) and 2019 (T2). Autoregressive cross-lagged models (ARCLMs) were fitted to explore the interrelationships among these variables. In ARCLM including child neglect and lifestyles, higher child neglect at T1 was significantly associated with higher ST and more risky EHs at T2, while insignificantly associated with PA. In ARCLM including child neglect and depression/self-esteem, lower T1 child neglect significantly predicted a higher T2 depression, but insignificantly for T2 self-esteem. In ARCLM including all variables, child neglect still significantly predicted later ST and depression, but insignificantly predicted EHs. Our study underscores that child neglect is strongly intertwined with ST, EHs, and depression during childhood. The prevention of child neglect may promote some healthy lifestyles and depression in children.

AMPK/mTOR downregulated autophagy enhances aberrant endometrial decidualization in folate-deficient pregnant mice.

Existing evidence suggests that adverse pregnancy outcomes are closely related to dietary factors. Folate plays an important role in neural tube formation and fetal growth, folate deficiency is a major risk factor of birth defects. Our early studies showed that folate deficiency could impair enddecidualization, however, the mechanism is still unclear. Dysfunctional autophagy is associated with many diseases. Here, we aimed to evaluate the adverse effect of folate deficiency on endometrial decidualization, with a particular focus on endometrial cell autophagy. Mice were fed with no folate diet in vivo and the mouse endometrial stromal cell was cultured in a folate-free medium in vitro. The decrease of the number of endometrial autophagosomes and the protein expressions of autophagy in the folate-deficient group indicated that autophagosome formation, autophagosome-lysosome fusion, and lysosomal degradation were inhibited. Autophagic flux examination using mCherry-GFP-LC3 transfection showed that the fusion of autophagosomes with lysosomes was inhibited by folate deficiency. Autophagy inducer rapamycin could reverse the impairment of folate deficiency on endometrial decidualization. Moreover, folate deficiency could reduce autophagy by disrupting AMPK/mTOR signaling, resulting in aberrant endometrial decidualization and adverse pregnancy outcomes. Further co-immunoprecipitation examination showed that decidual marker protein Hoxa10 could interact with autophagic marker protein Cathepsin L, and the interaction was notably reduced by folate deficiency. In conclusion, AMPK/mTOR downregulated autophagy was essential for aberrant endometrial decidualization in early pregnant mice, which could result in adverse pregnancy outcomes. This provided some new clues for understanding the causal mechanisms of birth defects induced by folate deficiency.

Association Between Diet Quality and Cardiometabolic Risk Factor Clustering Stratified by Socioeconomic Status Among Chinese Children.

BACKGROUND: Few studies have evaluated the long-term relationship between diet quality and cardiometabolic risk factor clustering among children. The moderating effect of socio-economic status (SES) is of interest. OBJECTIVE: To investigate the association between diet quality with cardiometabolic risk among Chinese children and to explore the moderating effect of SES. DESIGN: In this cohort study, 5 waves (1997-2009) of the China Health and Nutrition Survey were used. Diet quality was measured by a modified version of the Chinese Children Dietary Index (mCCDI) based on Dietary Guidelines for Chinese. PARTICIPANTS: Children between the ages of 7 and 17 (n = 2903) who completed at least 2 surveys were included. Those who missed measures or had hypertension or diabetes at baseline were excluded. MAIN OUTCOME MEASURES: The fasting blood samples were collected in 2009. Waist circumference (WC) and blood pressure (BP) were measured in each survey. STATISTICAL ANALYSIS PERFORMED: A continuous cardiometabolic risk score (MetScore) was derived by a confirmatory factor analysis of 5 components: WC, BP, glucose, triglycerides, and high-density lipoprotein cholesterol. Considering the latency period of the effect of behaviors, the mCCDI was lagged by the period between surveys. Linear regression was used to analyze the association of mCCDI with MetScore and its components. Mixed effect linear regression and lagged mCCDI were used for WC and BP models. RESULTS: Higher mCCDI was independently associated with a lower MetScore at follow-up (ß: -.11; 95% CI: -.18 to -.04). Higher lagged mCCDI over time was associated with a lower WC z score overall (ß: -.05; 95% CI: -.08 to -.01) and among children in the low SES group (ß: -.09; 95% CI: -.14 to -.04) but not those in the high SES group. When examining the 15 mCDDI components separately, scores for 5 components: more grains, vegetables, soybeans and its products; less sugar-sweetened beverages; and more diet variety were significantly associated with a lower MetScore. CONCLUSIONS: Among Chinese children, higher diet quality measured by mCCDI was independently associated with a lower MetScore at follow-up.

Microwave-assisted synthesis of ruthenium(ii) complexes containing levofloxacin-induced G2/M phase arrest by triggering DNA damage.

Ru(ii) complexes have attracted increasing attention as promising antitumor agents for their relatively low toxicity, high affinity to DNA molecules, and correlation with multiple targets. Meanwhile, quinolones are synthetic antibacterial agents widely used in the clinical practice. In this paper, two novel Ru(ii) complexes coordinated by levofloxacin (LOFLX), [Ru(bpy)2(LOFLX)]·2ClO4 (1), and [Ru(dmbpy)2(LOFLX)]·2ClO4 (2) (bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine) were synthesized with high efficiency under microwave irradiation and characterized by ESI-MS, 1H NMR, and 13C NMR. The binding behavior of these complexes with double-strand calf thymus DNA(CT-DNA) was investigated using spectroscopy, molecular docking, and density functional theory calculations. Results showed that 2 exhibited higher binding affinity than 1 and LOFLX. Further studies showed that 2 could induce the G2/M phase arrest of A549 cells via DNA damage. In summary, these results indicated that 2 could be developed as a potential anticancer agent in treatment of lung cancer through the induction of cell cycle arrest at G2/M phase by triggering DNA damage.

Maternal obesity alters circRNA expression and the potential role of mmu_circRNA_0000660 via sponging miR_693 in offspring liver at weaning age.

BACKGROUND AND AIMS: Maternal obesity predispose offspring to metabolic disorders and obesity, but the mechanisms are not fully understood, especially during early life. Circular RNA (circRNA) can regulate the expression of target genes through the regulatory pathways of competing endogenous RNA (ceRNA). We hypothesized that the offspring of obese dams exhibit impaired metabolic health through the dysregulated expression of hepatic circRNA. METHODS AND RESULTS: A high-fat diet (HFD) or standard chow diet (CD) were randomized to dams for 12 weeks before mating. Specific diets continued for each dam throughout pregnancy and lactation. Then, lipid metabolic parameters were assessed in dams and female offspring. We performed liver RNA sequencing (RNA-seq) for the offspring of HFD- and CD-dams to comprehensively identify differentially expressed (DE) circRNA and messenger RNA (mRNA). Further, ceRNA networks combining DE circRNA, mRNA, and microRNA were predicted based on MiRanda and TargetScan databases combined with the lipid metabolism-related pathway. As a result, the circRNA_0000660-miR_693-Igfbp1 regulatory pathway was selected from liver and AML12 cell line. Quantitative real-time polymerase chain reaction, dual luciferase reporter gene system, and Small interfering RNA for circRNA_0000660 transfection experiment were applied to validate. CONCLUSIONS: Our work investigated new mechanisms of the effect of maternal obesity on offspring's lipid metabolism. Several novel targets were uncovered to reverse the effect.

Fruit and vegetable intake in relation to depressive and anxiety symptoms among adolescents in 25 low- and middle-income countries.

BACKGROUND: Fruit and vegetable intake (FVI) has been inversely associated with the risk of depression. However, there is a gap in evidence from low- and middle-income countries (LMICs) and among adolescents. Further, little is known about FVI in relation to the risk of anxiety. Therefore, we examined these associations among adolescents in 25 LMICs. METHODS: Data from the Global School-based Student Health Survey were analyzed in 65267 adolescents aged 12-15 years (mostly nationally representative). Depressive and anxiety symptoms during the past 12 months were self-reported. Frequencies of FVI during the past 30 days were collected. Multivariable logistic regression and meta-analyses of country-wise estimates were undertaken. RESULTS: The prevalence of depressive and anxiety symptoms were 30.3% and 9.8%, respectively. A meta-analysis indicated that FVI of <5 times/d (vs. higher) was associated with an increased risk of depressive symptoms (OR = 1.10; 95% CI = 1.02-1.18). The pooled estimate for anxiety symptoms was insignificant. When examined separately, fruit intake was significantly associated with both lower risks of depressive and anxiety symptoms; vegetable intake was significantly associated with a lower risk of depressive symptoms, but not with anxiety. LIMITATIONS: Only adolescents attending school were included; the cross-sectional design cannot reveal causality; outcomes were not measured against the gold-standard diagnostic criteria. CONCLUSIONS: Our study provides multi-national evidence of the protective effect of FVI against depressive and anxiety symptoms among adolescents in LMICs, enabling key stakeholders to address mental health issues among adolescents globally.

Discovery of aromatic amides with triazole-core as potent reversal agents against P-glycoprotein-mediated multidrug resistance.

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major impediment for clinical cancer therapy. 19 novel aromatic amides with triazole-core as MDR reversal agents were designed and synthesized via click chemistry to reverse MDR. Among them, compound 42 was identified as the most promising candidate with high potency (EC50 = 78.1 ±â€¯5.4 nM), low cytotoxity (SI > 1282) and persistent duration in reversing doxorubicin (DOX) resistance in K562/A02 cells. 42 also enhanced the potency of other P-gp associated cytotoxic agents with different structures. In further study, remarkably increased intracellular accumulation of Rh123 and DOX in K562/A02 cells was achieved by compound 42, while CYP3A4 activity had no change by compound 42. These results indicate that compound 42 as a relatively safe modulator of P-gp-mediated MDR has good potential for further development.

Acupuncture for radiotherapy-induced nausea and vomiting: A systematic review protocol.

BACKGROUND: Assessing the effectiveness and safety of acupuncture therapy for treating patients with radiotherapy-induced nausea and vomiting (RINV) is the main purpose of this systematic review protocol. METHODS: The following electronic databases will be searched from inception to Sep 2019: Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, Traditional Chinese Medicine, Chinese Biomedical Literature Database, Wan-Fang Database, and Chinese Scientific Journal Database. All published randomized controlled trials in English or Chinese related to acupuncture for RINV will be included. The primary outcome is the severity and frequency of RINV during radiotherapy. The secondary outcomes is the physical condition and quality of life after radiotherapy. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be conducted with Review Manager Software V.5.2. RESULTS: The results will provide a high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: The conclusion of our study will provide evidence to judge whether acupuncture is an effective intervention for patients suffered from RINV. PROSPERO REGISTRATION NUMBER: CRD42019130952.