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.

The association of serum toxic metals and essential elements during early pregnancy with body mass index trajectory of infants during the first years: A prospective study.

To the best of our knowledge, prior research has yet to delve into the combined and interactive relationships between maternal exposure to essential elements and toxic metals and infancy's continuous growth and trajectories. This study aims to discern infant growth trajectories in the first year of life and to determine the associations of maternal serum levels of essential elements and toxic metals with growth trajectory. Within a Chinese prospective cohort in 2019 - 2021, 407 mother-infant pairs were included, and the serum levels of five essential elements (zinc, calcium, copper, magnesium and iron) and two toxic metals (cadmium and lead) in early pregnancy were assessed. The growth trajectory of infants was followed until age one year. Raw BMI and height values were transformed to age- and sex-specific BMI and height standard deviation (SD) scores. Latent-class group-based trajectory models and piecewise linear mixed regression were estimated to determine infant growth trajectories and growth velocity, respectively. The individual relationship between maternal metallic element levels and infant growth trajectory was examined using multinomial logistic regression models and linear mixed regression, while joint associations and interactive relationships were explored using Bayesian kernel machine regression (BKMR) following confounder adjustments. Four distinct trajectory patterns based on BMI-z score (low-rapid BMI gain group, normal-stable BMI group, very low-rapid BMI gain group and normal-rapid BMI gain group) and length-for-age (high-stable length group, low-stable length group, normal-rapid length gain group, very low-rapid length gain group) were identified during the first year post-birth, respectively. In single-metal and multiple-metal models, infants born to mothers with higher serum Zn and lower serum Cu levels were associated with a normal-rapid BMI gain trajectory during the first year. Serum Cu exhibited a positive correlation with the rate of BMI change solely in infants aged 6-12 months. Further, the BKMR analysis revealed a statistically significant and negative joint effect of the five essential elements on the likelihood of normal-rapid BMI/length gain trajectory when serum levels of these elements fell below the 70th percentile compared to median levels. In addition, high levels of serum copper and calcium interactively affect the rates of BMI change during 6-12 months old (ß: -0.21, 95% CI: -0.44, -0.03, P = 0.04, P-interaction=0.04). In conclusion, maternal trace elements at early pregnancy are linked to infant growth patterns and growth velocity in the first year of life.

A nutrient-wide association study for the risk of cardiovascular disease in the China Health and Nutrition Survey (CHNS) and the National Health and Nutrition Examination Survey (NHANES).

Evidence on the association between dietary nutrient-wide intake and cardiovascular disease (CVD) is inconclusive. Therefore, we systematically assessed the association between dietary intake of 29 nutrients and CVD risk using a nutrient-wide association study. Data were obtained from 7878 Chinese adults participating in the China Health and Nutrition Survey (CHNS) wave 2004-2015. We estimated the association of 29 nutrients with CVD risk. Significant findings were replicated in the National Health and Nutrition Examination Survey (NHANES). Four nutrients (selenium, vitamin A, carotenoids, and total protein) were significantly associated with CVD risk in the CHNS. The hazard ratio (HR) and 95% confidence interval (CI) for nutrient intake in the third tertile compared to the first tertile were 0.68 (0.51-0.90), 0.70 (0.54-0.91), 0.64 (0.50-0.83), and 0.54 (0.38-0.77), respectively. In the NHANES replication, selenium maintained a similar direction and strength of association, while the other nutrients were not replicated successfully. Our results provide support for a negative association between selenium intake and CVD risk, while the association of vitamin A, carotenoids and protein with CVD warrants further studies to confirm.

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.

Associations of obesity-related indices with prediabetes regression to normoglycemia among Chinese middle-aged and older adults: a prospective study.

Background: Prediabetes is associated with increased cardiovascular risk and all-cause mortality, while its regression will decrease the risks. This study investigated the associations of six obesity-related indices (waist-to-height ratio (WHtR), body roundness index (BRI), conicity index (CI), body shape index (ABSI), Chinese visceral adiposity index (CVAI), and triglyceride glucose (TyG) index) with prediabetes regression based on the China Health and Retirement Longitudinal Study (CHARLS), enrolling middle-aged and older adults. Methods: We included 2,601 participants with prediabetes from CHARLS, who were followed up from 2011-2012 to 2015-2016, with blood samples collected for measuring fasting plasma glucose and hemoglobin A1c. All the obesity-related indices at baseline and their dynamic changes were calculated and categorized into tertiles. Logistic regression analysis was applied to obtain the odds ratio (OR) and 95% confidence intervals (CIs). Attributable fractions (AFs) and 95% CIs of these indices and the dynamic changes were calculated with the AF package in R software, and the cutoff values of initial obesity-related indices were obtained by the receiver operating characteristic (ROC) analysis. Results: During the 4-year follow-up period, 562 (21.61%) participants regressed from prediabetes to normoglycemia. They had lower initial BRI, WHtR, CI, ABSI, CVAI, and TyG than those who did not (P < 0.05). After multivariable adjustment, participants in the first tertile of initial BRI (OR, 1.45, 95%CIs, 1.09-1.93), WHtR (OR, 1.46, 95%CIs, 1.10-1.95), and CVAI (OR, 1.47, 95%CIs, 1.11-1.93) had increased odds of prediabetes regression compared with those in the highest tertile. Participants with decreased TyG (OR, 2.08; 95%CIs, 1.61-2.70) also had increased odds of prediabetes regression compared with those with increased TyG. The cutoff values of initial obesity-related indices were 4.374 for BRI, 0.568 for WHtR, 8.621 for TyG, 1.320 for CI, 0.083 for ABSI, and 106.152 for CVAI, respectively. The AFs were 21.10% for BRI < 4.374, 20.85% for WHtR < 0.568, 17.48% for CVAI < 107.794, and 17.55% for ΔTyG < 0, respectively. Conclusion: Low initial BRI, WHtR, and CVAI, as well as TyG reduction, were significantly related to prediabetes regression to normoglycemia, and the AFs were around 20%. Less abdominal fat and insulin resistance reduction would benefit future health outcomes among people with prediabetes.

Influencing factors associated with quality of life and depression among COVID-19 survivors during convalescence.

This study aims to investigate influencing factors of quality of life (QoL) and depression among COVID-19 survivors during convalescence. A cross-sectional study was conducted in November 2020 in Wuhan, China. Information on social support, physical activity, QoL and depressive symptoms were assessed using self-administered questionnaires. Multivariate linear regression and multivariate logistic regression were used to assess the risk factors of subdomains of QoL (physical component score (PCS) and mental component score (MCS)) and depression, respectively. A total of 151 COVID-19 survivors (68 males) aged 53.21 (SD: 12.70) years participated in the study. Multivariate linear regression showed that age (ß=-0.241), history of chronic disease (ß=-0.4.774), physical activity (ß = 2.47) and social support (ß = 0.147) were significantly associated with PCS, while having a spouse (ß = 9.571), monthly income (ß = 0.043) and social support (ß = 0.337) were significantly associated with MCS. Logistic regression suggested that participants aged 40-60 years (OR = 10.20, 95%CI: 1.41-73.82) or above 60 years (OR = 15.63, 95%CI: 1.87-131.00), with high school or above education (OR = 5.81, 95%CI: 1.24-27.20), with low/moderate physical activity (low, OR = 2.97, 95%CI: 1.14-7.77; moderate, OR = 3.42, 95%CI: 1.07-10.91) and low/medium social support (low, OR = 4.81, 95% CI: 2.02-11.43; medium, OR = 9.70, 95%CI: 1.17-80.10) were more likely to be depressed, while higher monthly income (≥3000 Yuan RMB/month) was associated with lower risk for depression (OR = 0.27, 95%CI: 0.09-0.82). These findings indicate COVID-19 survivors with older age, having chronic conditions, without a spouse, low monthly income, low level of physical activity and social support had significantly increased risks for poor QoL and depression, and more attention should be given to this population.

The mediating effects of social support on the association between depression and life satisfaction among patients with schizophrenia or bipolar disorder.

Patients with schizophrenia or bipolar disorders in community had poor psychosocial functioning, social support, and life satisfaction. However, the interaction effects of social support and depression on life satisfaction remains unclear. Thus, we examined these associations among patients with schizophrenia or bipolar disorder. This cross-sectional study was conducted from October to December 2020 in Shenzhen, China. Information on social support, depression, and life satisfaction was assessed by standardized questionnaires through a face-to-face interview. Hierarchical multiple regression analysis was performed to estimate the associations of social support and depression with life satisfaction and to explore the mediation effect of social support. A total of 293 patients aged 39.7 ±â€…11.1 years (males: 47.1 %) were included in this study. Social support was positively associated with high life satisfaction (explaining 7.2% of the variance), while depression was negatively associated with life satisfaction (explaining 17.8% of the variance). Furthermore, social support mediated 12.5% of the association between depression and life satisfaction. Social support and depression were significantly associated with life satisfaction in patients with schizophrenia or bipolar disorders. Moreover, social support mediated the association between depression and life satisfaction in this population. Health interventions that benefit social support should be promoted to alleviate the negative impact of depression on their life satisfaction.

Dietary flavonoid intake is associated with a lower risk of diabetic nephropathy in US adults: data from NHANES 2007-2008, 2009-2010, and 2017-2018.

Few epidemiological studies have investigated the relationship between flavonoids and diabetic nephropathy (DN). Therefore, we explored the association between dietary flavonoid intake and DN among 1949 US adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018. Weighted logistic regression models demonstrated that the total flavonoid intake in the second (OR: 0.642; 95% CI: 0.456-0.906), third (OR: 0.665; 95% CI: 0.447-0.988), and the highest (OR: 0.551; 95% CI: 0.382-0.796) quantiles (versus the lowest) were associated with the decreased risk of DN. Restricted cubic spline (RCS) analyses showed that the total flavonoid intake had a negative linear association with DN (p-value for non-linearity was 0.003). Weighted quantile sum (WQS) regression analyses revealed that flavan-3-ols, flavones, and anthocyanidins were the main contributors for the combined effects of six flavonoid subclasses. Our findings suggested that higher dietary flavonoid intake was associated with a decreased risk of DN, with the greatest influence coming from flavan-3-ols, flavones, and anthocyanidins.

The biological functions of maternal-derived extracellular vesicles during pregnancy and lactation and its impact on offspring health.

During pregnancy and lactation, mothers provide not only nutrients, but also many bioactive components for their offspring through placenta and breast milk, which are essential for offspring development. Extracellular vesicles (EVs) are nanovesicles containing a variety of biologically active molecules and participate in the intercellular communication. In the past decade, an increasing number of studies have reported that maternal-derived EVs play a crucial role in offspring growth, development, and immune system establishment. Hereby, we summarized the characteristics of EVs; biological functions of maternal-derived EVs during pregnancy, including implantation, decidualization, placentation, embryo development and birth of offspring; biological function of breast milk-derived EVs (BMEs) on infant oral and intestinal diseases, immune system, neurodevelopment, and metabolism. In summary, emerging studies have revealed that maternal-derived EVs play a pivotal role in offspring health. As such, maternal-derived EVs may be used as promising biomarkers in offspring disease diagnosis and treatment. However, existing research on maternal-derived EVs and offspring health is largely limited to animal and cellular studies. Evidence from human studies is needed.

Severe fever with thrombocytopenia syndrome virus replicates in brain tissues and damages neurons in newborn mice.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate of 12-30%, which has an expanding endemic and caused thousands of infections every year. Central nervous system (CNS) manifestations are an important risk factor of SFTS outcome death. Further understanding of the process of how SFTSV invades the brain is critical for developing effective anti-SFTS encephalitis therapeutics. We obeserved changes of viral load in the brain at different time points after intraperitoneal infection of SFTSV in newborn C57/BL6 mice. The virus invaded the brain at 3 h post-infection (hpi). Notably, the viral load increased exponentially after 24 hpi. In addition, it was found that in addition to macrophages, SFTSV infected neurons and replicated in the brain. These findings provide insights into the CNS manifestations of severe SFTS, which may lead to drug development and encephalitis therapeutics.

Efficacy and safety of PD-1/PD-L1 inhibitors in triple-negative breast cancer: a systematic review and meta-analysis.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis that seriously threatens women's health. There is still a lack of effective therapeutic targets for TNBC treatment. We conducted a meta-analysis to evaluate the efficacy and safety of programmed cell death protein 1 (PD-1)/programmed death protein ligand 1 (PD-L1) inhibitors in combination with chemotherapy for TNBC patients. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) related to PD-1/PD-L1 inhibitors combined with chemotherapy. Literature conforming to the research content was identified according to the inclusion and exclusion criteria. The endpoints of efficacy were pathological complete response (pCR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). Safety outcomes included adverse events (AEs) of any grade, AEs of grade ≥3, serious AEs, and the incidence of various AEs. We obtained odds ratios (OR), hazard ratio (HR), and 95% confidence interval (CI) for the included studies. Data analysis was performed using Review Manager software (version 5.3). RESULTS: A total of 4468 patients from eight RCTs were analyzed. PD-1/PD-L1 inhibitors in combination with chemotherapy significantly improved pCR (OR, 1.59; 95% CI, 1.28 - 1.98, p < 0.0001), EFS (HR, 0.66; 95% CI, 0.48 - 0.91, p = 0.01), and OS (HR, 0.72; 95% CI, 0.52 - 0.99, p = 0.05) in patients with TNBC compared to chemotherapy alone or placebo in combination with chemotherapy. Furthermore, we found that the pCR rate was almost identical in the PD-L1 positive group (OR, 1.65; 95% CI, 1.26 - 2.16, p = 0.0002) and the PD-L1 negative group (OR, 1.56; 95% CI, 1.04 - 2.33, p = 0.03). Among patients with advanced-stage TNBC, PFS (HR, 0.82; 95% CI, 0.74 - 0.90, p < 0.0001) was longer in the combination therapy group than in the chemotherapy group. There were no statistically significant differences between the experimental and control groups in OS (HR, 1.03; 95% CI, 0.74 - 1.42, p = 0.87). In terms of safety, we found that the combination therapy group had a significantly higher incidence of hyperthyroidism in patients with early and advanced TNBC (OR, 5.76; 95% CI, 2.38 - 13.95, p = 0.0001) (OR, 7.86; 95% CI, 2.65 - 23.29, p = 0.0002). CONCLUSIONS: The combination of PD-1/PD-L1 inhibitors and chemotherapy could improve the survival and prognosis of patients with early and advanced TNBC. Combination treatment may be harmful to the thyroid; therefore, active surveillance and regular follow-up are necessary during treatment.

Risk Factors for Anthracycline-Induced Cardiotoxicity in Breast Cancer Treatment: A Meta-Analysis.

Background: Anthracyclines play an important role in the treatment of breast cancer (BC) and other malignant tumors. However, accompanied side-effects are non-ignorable. The purpose of this meta-analysis is to determine the risk factors for anthracycline-induced cardiotoxicity (ACT), so as to identify high-risk patients. Methods: The search for literature was conducted in PubMed, The Cochrane Library, Embase and Web of science. Records were selected with inclusion criteria and exclusion criteria. The newcastle-ottawa scale (NOS) was used to assess the quality of literature, and Review Manager 5.3 software was used for meta-analysis. Results: Thirteen studies met the inclusion criteria. Meta-analysis indicated that risk factors for ACT were use of trastuzumab (odds ratio [OR]: 2.84, 95% confidence interval [CI]: 2.49-3.22, p < 0.00001), cumulative dose of anthracyclines (OR: 1.45, 95%CI: 1.28-1.65, p < 0.00001), hypertension (OR: 2.95, 95%CI: 1.75-4.97, p < 0.0001), diabetes mellitus (DM) (OR: 1.39, 95%CI: 1.20-1.61, p < 0.0001), tumor metastasis (OR: 1.91, 95%CI: 1.17-3.11, p = 0.009) and coronary heart disease (CAD) (OR: 2.17, 95%CI: 1.50-3.15, p < 0.0001). In addition, our analysis revealed that body mass index (BMI) had no effect on ACT (OR: 1.18, 95%CI: 0.98-1.43, p = 0.08). Conclusions: Patients with high risk for ACT can be identified by these factors. For such patients, a higher level of monitoring and protection for the cardiac function should be performed by clinicians. Systematic Review Registration: INPLASY, identifier INPLASY202250140.

The association of adverse childhood experiences and its subtypes with adulthood sleep problems: A systematic review and meta-analysis of cohort studies.

Adverse childhood experience (ACE) is a powerful risk factor for long-term sleep health. However, the degree to which ACE and its subtypes contribute to adulthood sleep problems remains unknown. For this systematic review and meta-analysis, PubMed, Embase, Web of Sciences, Cochrane library, and CNKI (Chinese) were searched from inception to 1 December 2021. Cohort studies that examined the association between ACEs (aged <18 y) and adulthood sleep outcomes (aged ≥18 y) were included. The most fully adjusted odds ratios (ORs) were extracted and pooled using the random-effects model. A total of nine articles involving 108 330 participants from five high-income countries were identified. Individuals with at least one ACE subtype were more likely to report adulthood sleep problems (OR = 1.14, 1.09-1.20, I2 = 77.5%, n = 9 studies) compared with those without ACE. The pooled ORs were approximately 1.20 for sexual, physical, and emotional abuse with high heterogeneity (I2 > 80%), 1.09 (95% CI: 0.99-1.19, I2 = 0%, n = 2) for neglect, and 1.21 (95% CI: 1.14-1.30, I2 = 73.6%, n = 3) for family dysfunction. Individuals with multiple ACEs were associated with a higher magnitude of the risk for sleep problems (OR = 1.33, 95% CI: 1.18-1.49, I2 = 87.3%, n = 3). In conclusion, the magnitude of the risk for sleep problems was similar across ACE subtypes except for childhood neglect. ACE may have cumulative detrime ntal effects on sleep health. More longitudinal evidence regarding ACE-sleep relationships, particularly in low- and middle-income countries, is needed. Furthermore, more policy efforts and evidence-based preventions are warranted to address ACEs among children.

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.

Breast adenoid cystic carcinoma: a report of seven cases and literature review.

BACKGROUND: Primary adenoid cystic carcinoma (ACC) of breast is rarely seen clinically. It is a special subtype of triple-negative breast cancer characterized by low expression of Ki-67, low malignant potential, slow progression and favorable prognosis. To date, treatment for this disease is controversial and no consensus is reached. We analyzed clinical manifestations and pathological characteristics of seven primary breast ACC cases and reported in combination with literature review to promote understanding, diagnosis and treatment of this disease. CASE PRESENTATION: We collected seven breast ACC cases pathologically diagnosed and treated in Department of breast surgery of the First Affiliated Hospital of China Medical University from January 2015 to December 2018. We organized and summarized the clinical, imaging, pathological and prognostic information and performed statistical analysis. The median age was 60 years (ranging from 54 to 64 years). Tumors of all patients were detected by immunohistochemistry. Molecular types were mostly triple negative (4/7), and Ki-67 expression was low (5/7). Lymph node metastases were absent in all patients received axillary lymph node surgery. Median follow-up time was 39 months (ranging from 25 to 68 months). There was no occurrence of relapse, distant metastasis or death. CONCLUSION: Breast ACC is accompanied with favorable diagnosis, which is different from typical triple-negative breast cancer. Accurate diagnosis of ACC is particularly important.

Structural and Secondary Electron Yield Properties of Titanium-Palladium Films with Laser-Treated Copper Substrate for Application in Neutron Generators.

Secondary electron emission (SEE) of the oxygen-free high-conductivity copper (OFHC) target surface in neutron generators limits the stability and improvement of the neutron yield. A novel-type target of titanium-palladium films coated on laser-treated OFHC target substrate was proposed and explored in this work to obtain low secondary electron yield (SEY) without introducing any components. The combination of Ti-Pd films and laser-treated OFHC substrate can effectively suppress secondary electron emission and enhance the adsorption ability to hydrogen isotopes with the existence of Pd film. The surface morphologies, surface chemical states, and SEYs of Ti-Pd films with laser-treated OFHC substrate were studied systematically for the first time. The XPS results showed that the laser-treated OFHC substrate surface was basically covered by Pd film. However, the Pd film surface was partially oxidized, with percentages of 21.31 and 10.02% for PdO and PdO2, respectively. The SEYs of Ti-Pd films with laser-treated OFHC substrate were all below 1 within the investigated primary energy range of 100-3000 eV, which would be sufficient for application in neutron generators. Specifically, the maximum SEY (δmax) of laser-treated OFHC substrate coated by Ti-Pd films was 0.87 with corresponding incident electron energy of 400 eV.

20E-mediated regulation of BmKr-h1 by BmKRP promotes oocyte maturation.

BACKGROUND: Krüppel homolog 1 (Kr-h1) is a critical transcription factor for juvenile hormone (JH) signaling, known to play a key role in regulating metamorphosis and adult reproduction in insects. Kr-h1 can also be induced by molting hormone 20-hydroxyecdysone (20E), however, the underlying mechanism of 20E-induced Kr-h1 expression remains unclear. In the present study, we investigated the molecular mechanism of Kr-h1 induction by 20E in the reproductive system of a model lepidopteran insect, Bombyx mori. RESULTS: Developmental and tissue-specific expression analysis revealed that BmKr-h1 was highly expressed in ovaries during the late pupal and adult stages and the expression was induced by 20E. RNA interference (RNAi)-mediated depletion of BmKr-h1 in female pupae severely repressed the transcription of vitellogenin receptor (VgR), resulting in the reduction in vitellogenin (Vg) deposition in oocytes. BmKr-h1 specifically bound the Kr-h1 binding site (KBS) between - 2818 and - 2805 nt upstream of BmVgR and enhanced the transcription of BmVgR. A 20E cis-regulatory element (CRE) was identified in the promoter of BmKr-h1 and functionally verified using luciferase reporter assay, EMSA and DNA-ChIP. Using pull-down assays, we identified a novel transcription factor B. mori Kr-h1 regulatory protein (BmKRP) that specifically bound the BmKr-h1 CRE and activated its transcription. CRISPR/Cas9-mediated knockout of BmKRP in female pupae suppressed the transcription of BmKr-h1 and BmVgR, resulting in arrested oogenesis. CONCLUSION: We identified BmKRP as a new transcription factor mediating 20E regulation of B. mori oogenesis. Our data suggests that induction of BmKRP by 20E regulates BmKr-h1 expression, which in turn induces BmVgR expression to facilitate Vg uptake and oogenesis.

Transcriptomic analysis reveals the regulation network of BmKrüppel homolog 1 in the oocyte development of Bombyx mori.

Krüppel homolog 1 (Kr-h1), a zinc finger transcription factor, is involved in the metamorphosis and adult reproduction of insects. However, the role of Kr-h1 in reproduction of holometabolic insects remains to be elucidated. The regulation network of Kr-h1-associated genes in the reproduction in Bombyx mori was investigated in this study. The higher expression level of BmKr-h1 in the ovaries was detected during the late pupal stage and adults. RNA interference (RNAi)-mediated depletion of BmKr-h1 in the female at day 6 of pupae resulted in abnormal oocytes at 48 h post-double-stranded RNA treatment, which showed less yolk protein deposition and partially transparent chorion. RNA-seq and subsequent differentially expressed transcripts analysis showed that knockdown of BmKr-h1 caused a decrease in the expression of 2882 genes and an increase in the expression of 2565 genes in the oocytes at day 8 of pupae. Totally, 27 genes coding for transcription factors were down-regulated, while six genes coding for other transcription factors were up-regulated. BmKr-h1 bound to the Kr-h1 binding site of the transcription factors AP-1 (activating protein-1) and FOXG1 to increase their messenger RNA transcripts in the BmN cells, respectively. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of that positively co-expressed with AP-1 and FOXG1 transcripts showed mainly enrichment in the metabolic-related pathways, the nutrient absorption and the yolk protein absorption processes. These data suggested that BmKr-h1 might directly regulate the metabolic-related pathways, the nutrient absorption and the yolk protein absorption processes or probably through AP-1 and /or FOXG1 to regulate oocyte development.