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Background: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). Methods: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using RNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. Results: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. Conclusion: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration: The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).

The longitudinal impact of perceived stress on the risk of cardiometabolic disease has not been comprehensively evaluated among children and young adults. We hypothesized that patterns of perceived stress from childhood to adulthood may predict cardiometabolic risk in early adulthood. As part of the Southern California Children’s Health Study (CHS), we examined perceived stress score (PSS) in adolescence (mean age, 13.3 years) and young adulthood (mean age, 23.6 years) among 276 participants. Based on PSS in adolescence and young adulthood, participants were categorized into 4 stress pattern groups: consistently high (n = 85), decreasing (n = 49), increasing (n = 59), and consistently low (n = 65). CHS participants were assessed for seven measures of cardiometabolic disease risk, namely carotid artery intima-media thickness (CIMT), systolic and diastolic blood pressure (SBP and DBP), obesity, percent body fat, android/gynoid ratio, and elevated HbA1c in their young adulthood. An overall cardiometabolic risk score was generated by summing the number of clinically elevated measures to indicate cumulative cardiometabolic risk. Using multivariate linear and logistic regression models, we examined PSS measured at single time points and change in PSS score across adolescence to young adulthood in relation to cardiometabolic disease risk. Results indicated that PSS in adulthood had significant positive associations with overall cardiometabolic risk score (Beta, 0.12: 95% CI, 0.01-0.22; p =0.031), CIMT (Beta, 0.01; 95% CI, 0.00-0.02; p =0.043), SBP (Beta, 1.27, 95% CI, 0.09-2.45; p =0.035), and DBP (Beta, 0.94; 95% CI, 0.13-1.76; p =0.024). Further, analyses of PSS patterns suggested that individuals with consistently high PSS had higher cardiometabolic risk scores (Beta, 0.26; 95% CI, -0.02-0.54; p =0.066), as well as significantly higher android/gynoid ratio (Beta, 0.09; 95% CI, 0.03-0.14; p =0.002), percent body fat (Beta, 0.96; 95% CI, 0.51-5.41; p =0.018), and greater odds of obesity (OR, 5.73; 95% CI, 1.96-16.78; p = 0.001), compared to individuals with consistently low PSS. Our work suggests that perceived stress from adolescence to adulthood may contribute to cardiometabolic disease risk in adulthood. Interventions to reduce stress earlier in life (e.g., in adolescence) should be investigated for their potential to reduce cardiometabolic disease risk factors in young adulthood.

Objective: Blood pressure (BP) typically drops to a nadir around 20 to 24 gestation weeks in a normal pregnancy. Distinct BP trajectories over pregnancy could reveal underlying cardiovascular function and predict future cardiovascular risk, but little is known about BP trajectories in Hispanic women. We aim to identify BP trajectories during pregnancy among low-income, Hispanic women. Methods: In the prospective Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, we abstracted clinic BP measures of 732 participants who had an average of 12 BP measures over pregnancy, ranging from 4 to 41 weeks. We used latent class mixture modeling to identify BP trajectories. We examined associations of population characteristics, pregnancy and birth outcomes, and 1-year postpartum BP with the identified trajectories. Results: We identified three distinct BP trajectories ( Figure ). Compared to the majority (class 1, n=569), the consistently high class 2 (14.8%, 108) was characterized by a higher pre-pregnancy BMI (ppBMI, 32.3±7.6 vs. 27.6 ±6.1 Kg/m 2 ) and a higher proportion of having college or above education (21.3% vs. 14.9%), while the high-low-high U-shape class 3 (7.5%, 55) had a higher ppBMI (32.0±7.9 Kg/m 2 ) but lower proportion of having college or above education (9.1%). Risk of preeclampsia was the highest in class 3 (43.6%), followed by class 2 (10.2%) and class 1 (6.0%), while the risk of gestational diabetes was the highest in class 2 (14.8%), followed by class 1 (7.9%) and class 3 (7.3%). Birthweight and gestational duration were both significantly lower in class 3 than classes 1 and 2. One-year postpartum systolic BP was significantly higher in class 2 (120.2±16.0 mmHg) and class 3 (122.4±16.0 mmHg) than class 1 (111.7±26.2 mmHg) after adjusting for maternal age, pre-pregnancy BMI, parity, and education. Conclusion: Elevated blood pressure may develop into district trajectories in pregnancy that further predict pregnancy and birth outcomes, as well as postpartum blood pressure.

Calmodulin (CaM) and calmodulin-like proteins (CML) act as significant Ca

Introduction People living in obesogenic environments, with limited access to healthful food outlets and exercise facilities, generally have poor health. Previous research suggests that behavioral risk factors and indicators of physiological functioning may mediate this link; however, no studies to date have had the requisite data to investigate multi-level behavioral and physiological risk factors simultaneously. The present study conducted serial and parallel mediation analyses to examine behavioral and physiological pathways explaining the association between environmental obesogenicity and cardiovascular disease (CVD). Methods This cross-sectional observational study used data from the 2012–2016 Health and Retirement Study, a representative survey of US older adults (n = 12,482, mean age 65.9). Environmental obesogenicity was operationalized as a combined score consisting of nine environmental measures of food and physical activity. CVD and health-compromising behaviors (diet, alcohol consumption, smoking, and exercise) were self-reported. Physiological dysregulation was assessed with measured blood pressure, heart rate, HbA1c, cholesterol levels, BMI, and C-reactive protein. The Hayes Process Macro was used to examine serial and parallel paths through health-compromising behaviors and physiological dysregulation in the environmental obesogenicity-CVD link. Results People living in more obesogenic environments had greater odds of self-reported CVD (odds ratio = 1.074, 95% confidence interval (CI): 1.028, 1.122), engaged in more health-compromising behaviors (β = 0.026, 95% CI: 0.008, 0.044), and had greater physiological dysregulation (β = 0.035, 95% CI: 0.017, 0.054). Combined, health-compromising behaviors and physiological dysregulation accounted for 7% of the total effects of environmental obesogenicity on CVD. Conclusion Behavioral and physiological pathways partially explain the environmental obesogenicity-CVD association. Obesogenic environments may stymie the success of cardiovascular health-promotion programs by reducing access to resources supporting healthy lifestyles.

Living in neighborhoods perceived as disordered exacerbates genetic risk for type 2 diabetes (T2D) among older adults. It is unknown whether this gene-neighborhood interaction extends to younger adults. The present study aims to investigate whether crime, an objectively measured indicator of neighborhood disorder, triggers genetic risk for T2D among younger adults, and whether this hypothesized triggering occurs through exposure to obesity.Data were from the Wave I (2008) National Longitudinal Study of Adolescent to Adult Health. A standardized T2D polygenic score was created using 2014 GWAS meta-analysis results. Weighted mediation analyses using generalized structural equation models were conducted in a final sample of 7606 adults (age range: 25-34) to test the overall association of T2D polygenic scores with T2D, and the mediating path through obesity exposure in low, moderate, and high county crime-rate groups. Age, sex, ancestry, educational degree, household income, five genetic principal components, and county-level concentrated advantage and population density were adjusted.The overall association between T2D polygenic score and T2D was not significant in low-crime areas (p = 0.453), marginally significant in moderate-crime areas (p = 0.064), and statistically significant in high-crime areas (p = 0.007). The mediating path through obesity was not significant in low or moderate crime areas (ps = 0.560 and 0.261, respectively), but was statistically significant in high-crime areas (p = 0.023). The indirect path through obesity accounted for 12% of the overall association in high-crime area.A gene-crime interaction in T2D was observed among younger adults, and this association was partially explained by exposure to obesity.

Eisenmenger syndrome is a life-threatening complication of congenital heart defects (CHD). Since Eisenmenger syndrome among children of repaired CHD is rare, very few studies have had the necessary data to investigate its distribution in children. The current study used data collected in rural China to investigate the prevalence of Eisenmenger syndrome in children with unrepaired CHD. Data were from the 2006 to 2016 patient medical records of China California Heart Watch, which is a traveling cardiology clinic in Yunnan Province, China. Patients were included if they (1) aged 18 or below, (2) had CHD(s), and (3) the defect was not repaired by the time of the clinic visit. The prevalence of Eisenmenger syndrome was calculated in each age and defect group. Using logistic regression models, we tested whether oxygen saturation, Down syndrome, sex, and age were significantly associated with Eisenmenger syndrome. Of the 1301 study participants, ventricular septum defect (VSD), atrial septal defect (ASD), and patent ductus arteriosus (PDA) were the most common CHD. About one-sixth of the patients had pulmonary hypertension and 1.5% had Eisenmenger syndrome. The percentages of Eisenmenger syndrome were 1.8% in VSD patients, 0 in ASD patients, and 0.9% in PDA patients. Patients in the age group between 15 and 18 years had the highest percentages of Eisenmenger syndrome (11.5%). Age and presence of Down syndrome were significantly associated with the presence of Eisenmenger syndrome. Our finding highlights the importance of early detection and correction of CHD.

Racial and ethnic health disparities are fundamentally connected to neighborhood quality. For example, racial and ethnic minorities are more likely to live in neighborhoods with signs of physical disorder (e.g., graffiti, vandalism), and physically disordered environments have been noted to associate with increased risk for chronic illness. Given that older adults may spend more time in their neighborhoods than younger adults as they transition out of the workforce, examining associations between neighborhood physical disorder and health among older minorities is of critical importance. Using 2016-2018 Health and Retirement Study (HRS) data, a representative sample of US adults aged 51 years and older (n= 9,080, mean age 68 years), we conducted a series of weighted linear regressions to examine links between neighborhood disorder as rated by third parties and both participant-perceived neighborhood safety and self-rated health. Study results indicated that higher neighborhood physical disorder was significantly related to more neighborhood safety concerns among non-Hispanic White and Hispanic residents, but not among non-Hispanic Blacks. On the other hand, neighborhood physical disorder was significantly associated with poorer health among all racial/ethnic groups. These patterns persisted after adjusting for education, sex, age, and census tract concentrated disadvantaged, population density, and racial/ethnic diversity. Our results indicate that community level interventions targeting neighborhood physical disorder may improve community health and minimize racial/ethnic health disparities.

Although congenital heart defects are the most common birth defects, occurring in nearly 1 in 100 births, many developing regions do not practice proper newborn cardiac screening, which uses pulse oximeter and stethoscope. We therefore designed and implemented an on-site training program of newborn cardiac screening for obstetric personnel in rural Yunnan province, China. The aims of this study were to evaluate whether the training improved trainees' knowledge on newborn cardiac screening and resulted in higher newborn cardiac screening rates. The training program, which started in July 2015 and lasted through 2016, trained 2,175 obstetric doctors and nurses from 104 rural hospitals. The trainees demonstrated significant knowledge improvement on the knowledge of cardiac screening. Additionally, before June 2016, the trained personnel performed proper cardiac screening on 44,614 (93.6%) newborn babies. Given the effectiveness and cost-efficiency of this program in Yunnan, we recommend similar programs be implemented in other developing areas.

Expansins are cell wall loosening proteins and involved in various developmental processes and abiotic stress. No systematic research, however, has been conducted on expansin genes family in barley. A total of 46 expansins were identified and could be classified into three subfamilies in Hordeum vulgare: HvEXPA, HvEXPB, and HvEXLA. All expansin proteins contained two conserved domains: DPBB_1 and Pollen_allerg_1. Expansins, in the same subfamily, share similar motifs composition and exon-intron organization; but greater differences were found among different subfamilies. Expansins are distributed unevenly on 7 barley chromosomes; tandem duplicates, including the collinear tandem array, contribute to the forming of the expansin genes family in barley with few whole-genome duplication events. Most HvEXPAs mainly expressed in embryonic and root tissues. HvEXPBs and HvEXLAs showed different expression patterns in 16 tissues during different developmental stages. In response to water deficit, expansins in wild barley were more sensitive than that in cultivated barley; the expressions of HvEXPB5 and HvEXPB6 were significantly induced in wild barley under drought stress. Our study provides a comprehensive and systematic analysis of the barley expansin genes in genome-wide level. This information will lay a solid foundation for further functional exploration of expansin genes in plant development and drought stress tolerance.

Aim The aim of this study was to determine reference values for oxygen saturation (SpO2 ) in neonates at mild and moderate altitudes. Methods Our study included 41 097 consecutively born, asymptomatic neonates from 35 hospitals, located in Yunnan, China, with altitudes ranging from 267 to 2202 m. Pre-and post-ductal SpO2 of each neonate was measured at 24 hours of age and before hospital discharge. All study participants, according to the altitude of birth, were categorised into three groups: low (0-500 m), mild (500-1500 m) and moderate altitude (1500-2500 m). Results Every 1000-m increase in altitude was associated with a 1.54 per cent decrease in mean SpO2 . The means of pre-ductal SpO2 at low, mild and moderate groups were 97.9%, 96.4% and 95.5%, respectively. We used the 2.5th percentile of SpO2 distribution as the cut-off for neonatal SpO2 screening and defined new cut-off values of ≤93% for mild altitudes, ≤92% for moderate altitudes and no adjustment for low altitudes. Conclusion We recommend revised cut-off values for neonatal SpO2 at mild and moderate altitudes and provide new values for paediatricians to refer to when screening neonates for severe congenital heart or lung diseases.

To reveal China's regional disparity both in research output and preferential research areas is the main purpose of this study. For this study, we investigated the research outputs of all 31 regions (27 provinces and 4 municipalities) in mainland China. The investigated dataset was sourced from CNKI, one of China's largest domestic academic databases. To measure research preferences between regions, we used the function of cosine distance rather than Euclidean distance. Clustering method was employed to classify the regions according to their similarity/disparity. In the end, six clusters were generated. Each cluster is different in research preferences. For example, Inner Mongolia in Cluster D is featured with the emphasis on animal handcraft; while Hubei province in Cluster A is characterized by a wide range of research areas.

The FLOWERING LOCUS T (FT) gene plays crucial roles in regulating the vegetative-to-reproductive phase transition. The FT-like gene of spring orchid (Cymbidium goeringii Rchb. f.), CgFT, was isolated and characterized. CgFT mRNA was detected in leaves, pseudobulb, and flowers. In flowers, CgFT was expressed more in young flower buds than in mature flowers, and was predominantly expressed in young ovary and sheath. Seasonal expression analysis in leaves of a three-year-old spring orchid showed that a large increase in transcription, which started on June 20 for CgFT. We propose that the increased transcription in the middle of June marks the beginning of flower induction in this species. The ectopic expression of CgFT in transgenic tobacco plants showed novel phenotypes by flowering earlier than wild-type plants. Further analysis of the flowering time-related genes indicated that the expression of LEAFY, APETALLA1, FRUITFULL and SEPALLATA1 were significantly upregulated in 35S::CgFT transgenic tobacco plants. These results indicated that CgFT is a putative FT homolog in spring orchid that regulates flower transition, similar to its homolog in Arabidopsis. This study provides the first information on the spring orchid floral gene to elucidate the regulation of the flowering transition in spring orchid.

The basic helix–loop–helix (bHLH) transcription factor Ptf1a plays stage-specific roles in the developing pancreas. During early pancreatic development, low levels of Ptf1a preferentially promote the differentiation of pancreatic progenitor cells into endocrine cells, whereas high levels of Ptf1a shift pancreatic progenitors towards an exocrine cell fate. In adults, Ptf1a is essential for the production of exocrine enzymes by pancreatic acinar cells. In this paper, we show that Ptf1a expression is repressed by miR-18a in pancreatic progenitors and acinar cells via its binding to the 3′UTR of Ptf1a mRNA. Furthermore, overexpression of miR-18a exerts little effect on pancreatic progenitors and acinar cells. These results indicate that miR-18a plays a fine-tuning role in regulating pancreatic progenitors and exocrine cells through the repression of Ptf1a expression.