The Association Between Pre-Pregnancy and First-Trimester Hair Cortisol and Preterm Birth: A Causal Inference Model.

Background Adverse life events and chronic psychological distress before and during pregnancy have frequently been associated with preterm birth (PTB) but the biological underpinnings remain unclear. We investigated the association between corticosteroid levels in pre-pregnancy and first-trimester hair and the risk of PTB. Methods We followed 1,808 pregnant women from a prospective pre-birth cohort study in Lima, Perú. Hair samples were taken at the end of the first pregnancy trimester. The two most proximal 3cm segments to the scalp (representing pre-pregnancy and first-trimester) were analyzed to obtain hair cortisol and cortisone concentrations (HCC and HCNC). PTB was defined as birth < 37 completed gestational weeks. We constructed four generalized propensity scores for pre-pregnancy and first-trimester HCC and HCNC to create corresponding inverse probability weights before fitting marginal structural models for estimating the effect of HCC and HCNC on PTB risk. Results Pre-pregnancy Log HCC was not independently associated with PTB risk (RR = 0.97; 95%CI: 0.79, 1.19). In contrast, one SD increase from the mean first-trimester Log HCC was independently associated with a 37% (95%CI: 1.11, 1.69) increased risk of PTB. Although imprecise, pre-pregnancy Log HCNC was negatively associated with PTB risk (RR = 0.84; 95%CI: 0.58, 1.20), whereas the association between first-trimester Log HCNC and PTB risk was positive (RR = 1.20; 95%CI: 0.87, 1.65). Conclusions Our findings show that chronic corticosteroid levels in early pregnancy are causally linked to PTB risk in pregnant Peruvian women. This finding contributes to understanding the biological underpinnings of PTB better to enhance PTB prevention.

Diamond with Sp2-Sp3 composite phase for thermometry at Millikelvin temperatures.

Temperature is one of the seven fundamental physical quantities. The ability to measure temperatures approaching absolute zero has driven numerous advances in low-temperature physics and quantum physics. Currently, millikelvin temperatures and below are measured through the characterization of a certain thermal state of the system as there is no traditional thermometer capable of measuring temperatures at such low levels. In this study, we develop a kind of diamond with sp2-sp3 composite phase to tackle this problem. The synthesized composite phase diamond (CPD) exhibits a negative temperature coefficient, providing an excellent fit across a broad temperature range, and reaching a temperature measurement limit of 1 mK. Additionally, the CPD demonstrates low magnetic field sensitivity and excellent thermal stability, and can be fabricated into probes down to 1 micron in diameter, making it a promising candidate for the manufacture of next-generation cryogenic temperature sensors. This development is significant for the low-temperature physics researches, and can help facilitate the transition of quantum computing, quantum simulation, and other related technologies from research to practical applications.

Combinative effects of ß-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma.

Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the ß-adrenergic receptor. ß-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of ß-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of ß-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of ß-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with ß-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with ß-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and ß-elemene treatment alone groups. Our results suggest that ß-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects.

Indoleamine 2,3-dioxygenase 1 promotes osteosarcoma progression by regulating tumor-derived exosomal miRNA hsa-miR-23a-3p.

Background: Osteosarcoma (OS) is the most common primary malignant tumor originating in bone. Immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) participates in tumor immune tolerance and promotes tumor progression, while the study of IDO1 in OS is limited. Methods: Immunohistochemistry analysis was performed to test the expression of IDO1 and Ki67. The relationship between IDO1 or Ki67 positive count and clinical stage of the patient was analyzed. Laboratory test indexes including serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), white blood cell (WBC) count and C-reactive protein (CRP) at diagnosis of OS patients were collected. The relationship between positive count of IDO1 and Ki67 or laboratory test indexes was analyzed by Pearson's correlation analysis. IDO1 stably overexpressed cell lines of these cells (MG63 OE, 143B OE and hFOB1.19 OE) were constructed and validated by Western blot and Elisa. Exosomes were isolated from conditioned culture media of these cells and were identified by Zetaview nanoparticle tracking analyzer. Next-generation sequencing was conducted to identify miRNAs enriched in exosomes. Differentially expressed miRNAs (DE miRNAs) were verified in clinical samples and cell lines by qPCR. Biological processes and cell components analysis of DE miRNAs was conducted by GO enrichment analysis using the protein interaction network database. Results: Immunosuppressive enzyme IDO1 was highly expressed in tumor tissues. 66.7% (6/9) of the tissues showed moderately or strongly positive immunostaining signal of IDO1, and 33.3% (3/9) were weakly positive. The expression of IDO1 was positively related to Ki67 and associated with prognostic-related clinical features of OS patients. Overexpression of IDO1 significantly affected the exosome-derived miRNA subsets from MG63, 143B and hFOB1.19 cells. A total of 1244 DE miRNAs were identified, and hsa-miR-23a-3p was further screened as key DE miRNA involved in the progression of OS. GO analysis of target genes of the DE miRNA results showed that target enrichment in the functions of immune regulation and tumor progression. Discussion: Our results indicate that IDO1 has the potential to promote the progression of OS that is related to miRNAs mediated tumor immunity. Targeting IDO1-mediated hsa-miR-23a-3p may be a potential therapeutic strategy for OS treatment.

Association Between Child Abuse and Risk of Adult Coronary Heart Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to examine the association of child abuse with adult coronary heart disease risk and separately by abuse subtypes, including emotional abuse, sexual abuse, and physical abuse. METHODS: Data were extracted from studies published up through December 2021 and on the basis of research from PubMed, Embase, CINAHL, and PsycINFO. Studies were selected if they included adults with or without any type of child abuse and measured the risk of any type of coronary heart disease. Statistical analyses were conducted in 2022. The random effects model was used to pool the effect estimates presented by RRs with 95% CIs. Heterogeneity was assessed using Q and I2 statistics. RESULTS: The pooled estimates were synthesized using 24 effect sizes from 10 studies with a sample size of 343,371 adults. Adults with child abuse were associated with a higher risk of coronary heart disease than those without (RR=1.52; 95% CI=1.29, 1.79), and the association was similar for myocardial infarction (RR=1.50; 95 % CI=1.08, 2.10) and unspecified coronary heart disease (RR=1.58; 95% CI=1.23, 2.02). Moreover, emotional (RR=1.48; 95% CI=1.29, 1.71), sexual (RR=1.47; 95% CI=1.15, 1.88), and physical (RR=1.48; 95% CI=1.22, 1.79) abuse were associated with increased risk of coronary heart disease. DISCUSSION: Child abuse was associated with an increased risk of adult coronary heart disease. Results were generally consistent across abuse subtypes and sex. This study advocates further research on biological mechanisms linking child abuse to coronary heart disease as well as improvement in coronary heart disease risk prediction and targeted prevention approaches.

Personal and Work-Related Burnout Is Associated with Elevated Diastolic Blood Pressure and Diastolic Hypertension among Working Adults in Chile.

We aimed at investigating the association of personal and work-related burnout with blood pressure and hypertension among working adults in Chile. We conducted a cross-sectional study among 1872 working adults attending the Hospital del Trabajador in Santiago, Chile, between September 2015 and February 2018. The Copenhagen Burnout Inventory was used to assess personal and work-related burnout. Blood pressure was measured by medical practitioners. Multivariable linear and logistic regressions were used to estimate the association of burnout status with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension. After adjusting for confounders, participants with both types of burnout had a 1.66 (95% confidence interval [CI]: 0.02-3.30) mmHg higher mean DBP than those without burnout. The odds of isolated diastolic hypertension among the participants with only personal burnout and both types of burnout were 2.00-fold (odds ratio [OR] = 2.00; 95% CI: 1.21-3.31) and 2.08-fold (OR = 2.08; 95% CI: 1.15-3.78) higher than those without burnout. The odds of combined systolic/diastolic hypertension among the participants with only work-related burnout increased by 59% (OR = 1.59; 95% CI: 1.01-2.50) compared with those without burnout. Both work-related and personal burnouts were associated with increased DBP and odds of diastolic hypertension among working adults in Chile.

Circ_0000885 Enhances Osteosarcoma Progression by Increasing FGFR1 Expression via Sponging MiR-1294.

BACKGROUND: As a malignant tumor, the progression of osteosarcoma (OS) is mediated by multiple regulators, including circular RNAs (circRNAs). However, the role of circ_0000885 in OS is unclear. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ_0000885, miR-1294 and fibroblast growth factor receptor 1 (FGFR1). Cell proliferation was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Flow cytometry and transwell assay were employed to determine the cell cycle distribution, cell migration and invasion, respectively. Moreover, the relationship between miR-1294 and circ_0000885 or FGFR1 was confirmed by dual-luciferase reporter assay. The protein level of FGFR1 was assessed via Western blot (WB) analysis. Animal experiments were used to verify the effect of circ_0000885 silencing on OS tumor growth in vivo. RESULTS: Circ_0000885 level was increased in OS tissues and cells. Knockdown of circ_0000885 repressed the proliferation, migration, invasion and induced cell cycle arrest in OS cells. There was a binding relationship between miR-1294 and circ_0000885, and miR-1294 inhibitor could reverse the inhibitory effect of silenced circ_0000885 on OS progression. MiR-1294 could target FGFR1, and overexpressed FGFR1 could invert the suppression effect of miR-1294 mimic on OS progression. Silencing of circ_0000885 hindered FGFR1 expression, while this effect could be recovered by miR-1294 inhibitor. In addition, circ_0000885 knockdown reduced OS tumor growth via regulating the FGFR1 expression by sponging miR-1294 in vivo. CONCLUSION: Circ_0000885 played an active role in OS progression, indicating that it might be a potential target for OS therapy.