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Purpose Lung injury associated with bronchopulmonary dysplasia (BPD) and its related neurodevelopmental disorders have garnered increasing attention in the context of premature infants. Establishing a reliable animal model is essential for delving into the underlying mechanisms of these conditions. Methods Newborn rats were randomly assigned to two groups: the hyperoxia-induced BPD group and the normoxia (NO) group. For the BPD group, they were nurtured in a hyperoxic environment with a high oxygen inspired fraction (0.85) from birth until day 14 within 28 days postnatally. In contrast, the NO group consisted of newborn rats that were nurtured in a normoxic environment with a standard oxygen inspired fraction (0.21) for 28 days postnatally. Various pathological sections of both lung and brain tissues were examined. TUNEL staining, immunofluorescence assays, and functional tests were performed, and the results were meticulously analyzed to assess the impact of hyperoxia environments on the developing organs. Results In the newborn rats of the BPD group, a significant reduction in alveolar number coupled with enlargement was observed, alongside severe fibrosis, collagen deposition, and constriction of bronchi and vascular lumens. This was accompanied by an accumulation of inflammatory cells and a marked deterioration in lung function compared to the NO group ( P < 0.05 ). Additionally, a decrease in neuronal count, an increase in neuronal apoptosis, proliferation of neuroglia cells, and demyelination were noted, and poorer performance in the Morris water maze test within the BPD group ( P < 0.05 ). Conclusion The BPD-rats model was established successfully. Lung injury in the BPD group evident across the bronchi to the alveoli and pulmonary vessels, which was associated with deteriorated lung function at postnatal day 14. Concurrently, brain injury extended from the cerebral cortex to the hippocampus, which was associated with impaired performance in orientation navigation and spatial probe tests at postnatal day 28.

Tumor angiogenesis is a crucial step in the further growth and metastasis of solid tumors. However, its regulatory mechanism remains unclear. Here, we showed that TARBP2, an RNA‐binding protein, played a role in promoting tumor‐induced angiogenesis both in vitro and in vivo through degrading the mRNAs of antiangiogenic factors, including thrombospondin1/2 (THBS1/2), tissue inhibitor of metalloproteinases 1 (TIMP1), and serpin family F member 1 (SERPINF1), by targeting their 3′untranslated regions (3′UTRs). Overexpression of TARBP2 promotes tumor cell–induced angiogenesis, while its knockdown inhibits tumor angiogenesis. Clinical cohort analysis revealed that high expression level of TARBP2 was associated with poor survival of lung cancer and breast cancer patients. Mechanistically, TARBP2 physically interacts with the stem‐loop structure located in the 3′UTR of antiangiogenic transcripts, leading to mRNA destabilization by the dsRNA‐binding domains 1/2 (dsRBDs1/2). Notably, the expression level of TARBP2 in human tumor tissue is negatively correlated with the expression of antiangiogenic factors, including THBS1/2, and brain‐specific angiogenesis inhibitor 1 (BAI1). Moreover, TARBP2 expression is strongly associated with tumor angiogenesis in a group of human lung cancer samples. Collectively, our results highlight that TARBP2 is a novel tumor angiogenesis regulator that could promote tumor angiogenesis by selectively downregulating antiangiogenic gene expression. We demonstrated that TARBP2 was able to promote tumor angiogenesis through selectively destabilizing the mRNAs of antiangiogenic factor genes via binding to the stem‐loop structure located in the 3′UTRs. Strikingly, our basic research findings have also been confirmed by analyzing the clinical samples and data from human breast and lung cancers. Thus, TARBP2 is likely to be a useful molecular target for antiangiogenic tumor therapy.

Tumor‐induced angiogenesis is important for further progression of solid tumors. The initiation of tumor angiogenesis is dictated by a shift in the balance between proangiogenic and antiangiogenic gene expression programs. However, the potential mechanism controlling the expression of angiogenesis‐related genes in the tumor cells, especially the process mediated by RNA‐binding protein (RBP) remains unclear. SAMD4A is a conserved RBP across fly to mammals, and is believed to play an important role in controlling gene translation and stability. In this study, we identified the potential role of SAMD4A in modulating angiogenesis‐related gene expression and tumor progression in breast cancer. SAMD4A expression was repressed in breast cancer tissues and cells and low SAMD4A expression in human breast tumor samples was strongly associated with poor survival of patients. Overexpression of SAMD4A inhibited breast tumor angiogenesis and caner progression, whereas knockdown of SAMD4A demonstrated a reversed effect. Mechanistically, SAMD4A was found to specifically destabilize the proangiogenic gene transcripts, including C‐X‐C motif chemokine ligand 5 (CXCL5), endoglin (ENG), interleukin 1β (IL1β), and angiopoietin 1 (ANGPT1), by directly interacting with the stem‐loop structure in the 3′ untranslated region (3′UTR) of these mRNAs through its sterile alpha motif (SAM) domain, resulting in the imbalance of angiogenic genes expression. Collectively, our results suggest that SAMD4A is a novel breast tumor suppressor that inhibits tumor angiogenesis by specifically downregulating the expression of proangiogenic genes, which might be a potential antiangiogenic target for breast cancer therapy. Here, we identified the expression pattern of RNA‐binding protein SAMD4A in breast cancers and its potential role in modulating angiogenesis‐related gene expression. Mechanistically, SAMD4A could suppress breast tumor angiogenesis and metastasis by selectively destabilizing proangiogenic mRNAs by targeting the stem‐loop structure in 3′UTR.

Background This study aimed to investigate the association between relative fat mass (RFM) and asthma, as well as to explore the mediating role of Systemic Immune-Inflammation Index (SII) and Systemic Inflammation Response Index (SIRI). Methods This cross-sectional study utilized data from the National Health and Nutrition Examination Survey from 2007 to 2018. Associations between RFM and asthma were tested using multivariable logistic regressions, restricted cubic splines, subgroup analyses, and interaction tests, with mediation analysis for SII and SIRI. The inflection point was determined by the two-piecewise linear regression. Sensitivity analysis and propensity score matching (PSM) was applied to validate the stability of the associations. Results Higher RFM was positively associated with asthma, with an inflection point at 34.08. Below this threshold, each unit increase in RFM was positively associated with a 2% increase in the odds of asthma (Odds ratio (OR) 1.02, 95% Confidence interval (CI): 1.00—1.03), while above it, the association strengthened, with a 5% increase in the odds per unit (OR 1.05, 95% CI: 1.04—1.07). The association was consistent across subgroups. The association between RFM and asthma is stronger in current asthma patients than in ever had asthma ones. Mediation analyses showed that SII and SIRI partially mediated 7.48% and 3.88% of the RFM-asthma association, respectively. The findings remained robust after sensitivity analyses and adjusting for confounding bias using PSM. Conclusions RFM is positively associated with the prevalence of asthma in the U.S., particularly among individuals with current asthma, with systemic inflammation partially mediating this relationship.

The accelerating threat from antimicrobial resistance (AMR) has become a global health issue. The properties of AMR in the gut microbiome of preterm infants and its clinical relevance with necrotizing enterocolitis (NEC) remain unknown. In‐depth integrative analyses of 5,684 gut metagenomes are performed to build an AMR genes (ARGs) landscape. A subset of 107 preterm infants who developed NEC is sampled to examine the trajectory and predictive potential of ARGs preceding NEC onset. The variation and core set of ARGs, their higher burden and diversity, and potential ARGs‐enriched gut bacteria in preterm infants compared to full‐term infants are comprehensively discovered, reflecting a strain shift in genomic functions. Moreover, the gut resistome converged over 9 days before NEC onset is observed, which is driven by 24 ARGs. Machine learning analysis reveals potential usage of the gut resistome as an indicator for predicting NEC onset in an external validation preterm birth cohort (the area under the receiver operating characteristic curve, AU‐ROC = 0.823), which is significantly higher than that based on the bacterial species (AU‐ROC = 0.727). Overall, the findings can be referenced to mitigate the burden and spread of ARGs, and specific ARGs have potential for disease risk stratification to improve clinical management. The gut resistome of preterm infants and its clinical relevance remain poorly understood. This study performs in‐depth integrative analyses of 5,684 gut metagenomes from preterm infants, uncovering distinct features that diverge from term infants. Notably, the gut resistome of preterm infants converges 9 days before necrotizing enterocolitis onset, highlighting its potential for early disease risk prediction.

Background This meta-analysis aimed to identify the near- and long-term neurodevelopmental prognoses of preterm or low birth weight (LBW) infants with different severities of intraventricular hemorrhage (IVH). Methods Four databases were searched for observational studies that were qualified using the Newcastle-Ottawa Scale. Results 37 studies involving 32,370 children were included. Compared to children without IVH, children with mild IVH had higher incidences of neurodevelopmental impairment (NDI), cerebral palsy (CP), motor/cognitive delay, hearing impairment and visual impairment, as well as lower scores of the mental development index (MDI) and psychomotor development (PDI). Moreover, compared to mild IVH, severe IVH increased susceptibilities of children to NDI, motor delay, CP, hearing impairment and visual impairment, with worse performances in MDI, PDI, motor score and IQ. Mild IVH was not associated with seizures or epilepsy. Conclusions Adverse neurodevelopmental outcomes positively associated with the occurrence and severity of IVH in preterm or LBW infants, providing evidence for counseling and further decisions regarding early therapeutic interventions. Impact Adverse neurodevelopmental outcomes later in life were closely associated with the occurrence and severity of IVH in preterm or LBW infants. Our results highlight the importance to make prediction of the neurodevelopmental outcomes of children born preterm or LBW with a history of IVH, which will guide affected parents when their children need clinical interventions to reach the full potential. We emphasize the importance of identifying specific developmental delays that may exist in children with IVH, providing detailed information for the development of comprehensive intervention measures.

Objective. To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population. Methods. Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group (n=198) and abnormal glucose tolerance group (n=358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISIM)) and insulin secretion indexes (HOMA-β, early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPARγ were selected. SNPs were genotyped on Sequenom MassARRAY platform. Results. The GG genotype of rs2920502 in PPARγ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526–0.969, P=0.042; GG: OR: 0.715, 95%CI: 0.527–0.97, P=0.031). The TT genotype of rs3856806 in PPARγ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055–2.017, P=0.022; TT: OR: 1.58, 95%CI: 1.104–2.761, P=0.032). The GG genotype of rs2920502 in PPARγ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes. Conclusion. It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPARγ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPARγ had an increased risk for diabetes.

Background Dysregulation of cell cycle progression is a common feature of human cancer cells; however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest in breast cancer. Methods Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and its association with patient survival. Quantitative real-time PCR and Western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assays, flow cytometry, and in vivo analyses were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA sequencing was applied to identify the differentially expressed genes regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1. Results We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse-free survival of patients with breast cancer. Roquin1 overexpression inhibited cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizes cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2), by targeting the stem–loop structure in the 3′ untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs. Conclusions Our findings demonstrated that Roquin1 is a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might be a potential molecular target for breast cancer treatment.

Background Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and β cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance. Methods Four hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes ( n  = 101), pre-diabetes ( n  = 186), and normal glucose tolerance ( n  = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-β, early-phase disposition index [DI 30 ], (ΔIns30/ΔGlu30)/HOMA-IR and total-phase index [DI 120 ]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate β cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained. Results In all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66–0.75) and 0.71 (95 % CI: 0.65–0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA-β, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal β cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and TG were significantly correlated with total-phase insulin secretion, but they also were not acceptable predictors of total-phase insulin secretion (0.60 < AUROC < 0.70). Conclusions In a Chinese population with different levels of glucose tolerance, TG/HDL-C and TG could be the predictors of IR. The lipid ratios could not be reliable makers of β cell function in the population.

Objectives To explore influence of carbohydrates/fat proportions, dietary ingredients on telomere length shortening, oxidative stress and inflammation in a Chinese population with different glucose tolerance status. Methods Five hundred and fifty-six Chinese subjects without diabetes history underwent a 75 g, 2 h Oral Glucose Tolerance Test (OGTT). Subjects with diabetes ( n  = 159), pre-diabetes ( n  = 197), and normal glucose tolerance ( n  = 200) were screened. Dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood leukocyte telomere length (LTL) was assessed using a real-time PCR assay. Blood lipid profile, levels of the oxidative stress indicators superoxide dismutase (SOD), glutathione reductase (GR), 8-oxo-2′-deoxyguanosine (8-oxo-dG) and inflammation indicators tumor necrosis factor (TNF-ɑ), interleukine-6 (IL-6) were measured. Levels of HbA1c, plasma glucose, insulin, and C peptide were also determined. Measurements were taken at 0 min, 30 min, 60 min, and 120 min after 75 g OGTT. Insulin sensitivity was evaluated by HOMA-IR. Basal insulin secretion index (HOMA-β), early phase disposition index (DI 30 ) and total phase disposition index (DI 120 ) indicate insulin levels at different phases of insulin secretion. Results In patients with newly diagnosed diabetes, LTL adjusted by age was longer in HbA1c < 7 % group (log (LTL):1.93 ± 0.25) than in HbA1c ≥ 7 % group (log (LTL):1.82 ± 0.29). LTL was not associated with daily energy intake, diet fat, carbohydrates and protein proportions. Multiple linear regression analysis indicated that legumes, nuts, fish and seaweeds were protective factors for LTL shortening, and sweetened carbonated beverage was a risk factor for LTL shortening ( legumes: β = 0.105, p  = 0.018; nuts: β = 0.110, p  = 0.011; fish: β = 0.118, p  = 0.007; seaweeds: β = 0.116, p  = 0.009; sweetened carbonated beverage: β = −0.120, p  = 0.004 ). Daily energy intake was positively associated with TNF-ɑ, IL-6 (TNF-ɑ: r  = 0.125, p  = 0.006;IL-6: r  = 0.092, p  = 0.04). Fat, carbohydrate proportions were positively associated with TNF-ɑ (fat: r  = 0.119, p  = 0.008 ; carbohydrate: r  = 0.094, p  = 0.043). Seaweeds and dairy intake were negatively associated with 8-oxo-dG (seaweed: r  = −0.496, p  = 0.001;dairy: r  = −0.246, p  = 0.046 ), vegetables and fruits were positively associated with GR ( vegetables: r  = 0.101, p  = 0.034;fruits: r  = 0.125, p  = 0.045). Cereal, meat were positively associated with TNF-ɑ ( cereal: r  = 0.091, p  = 0.048 ; meat: r  = 0.405, p  = 0.009). Conclusion Diabetes patients with better plasma glucose (HbA1c < 7 %) had longer LTL, LTL could reflect plasma glucose status in diabetes patients. LTL were probably not influenced by diet carbohydrates/fat proportions but was associated with diet ingredients. Diet ingredients significantly impacted on markers of inflammation and oxidative stress, which probably had an effect on LTL.