Sex-specific associations between maternal thyroid peroxidase antibodies and cognitive development in preschool children: A prospective cohort study.

BACKGROUND: An association between maternal thyroid dysfunction throughout pregnancy and subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. METHODS: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition. A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. RESULTS: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06-4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10-5.05). Maternal TPOAb positivity in the third trimester was associated with below-average working memory (WMI) (OR: 2.51; 95% CI: 1.02-6.20) in girls. In girls, the WMI (ß = -3.17, 95% CI: -5.82--0.52), fluid reasoning index (FRI) (ß = -4.49, 95% CI: -7.18--1.80), and FSIQ score (ß = -2.43, 95% CI: -4.77--0.08) decreased, whereas in mothers, the level of lgTPOAb increased during pregnancy. CONCLUSIONS: Positive maternal thyroid peroxidase antibody levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Association between maternal fasting glucose levels throughout pregnancy and preschoolers' refractive errors.

PURPOSE: We aimed to investigate the association between maternal fasting plasma glucose (FPG) trajectories during pregnancy and children's refractive errors at 6 years old. DESIGN: Based on the Ma'anshan Birth Cohort (MABC) in China, a total of 1987 mother-child pairs were included in this study. METHODS: Using the group-based trajectory model, trajectory fitting was performed on fasting blood glucose levels during the first, second, and third trimesters of pregnancy. Children's vision was measured at 6 years of age using the standard logarithmic visual acuity E-chart and cycloplegic refraction examination. Logistic regression models and multi-informant generalized estimating equations were used to analyze the association between maternal blood glucose level and 6-year-old children's visual acuity. RESULTS: Children born of mothers with high level FPG trajectory had a higher risk of developing refractive error [OR=1.46 (95% CI 1.08 1.97)], hypermetropia [OR=1.64 (95% CI 1.09, 2.46)] and astigmatism [OR=1.60 (95% CI 1.06, 2.41)] at age six compared to those with low level trajectory. Maternal blood glucose level in the first [ß=-0.012 (95% CI -0.024, -0.001)] and the second [ß=-0.016 (95% CI -0.025, -0.006)] trimesters was associated with 6 year children's distance vision value. CONCLUSIONS: High level of fasting plasma glucose trajectories during pregnancy has been observed to be associated with 6-year-old children's refractive error, hypermetropia and astigmatism. The first and the second trimesters may be critical periods for the effects of maternal blood glucose on children's vision. The long-term effect of maternal glucose metabolism on children's visual development deserves further study.

Sex-specific association between maternal mild anemia and children's behavioral development: a birth cohort study.

There has been limited research on maternal anemia affecting children's behavioral development, with a lack of studies focusing on sex differences in this association. Based on the Ma'anshan Birth Cohort, 2132 mother-child pairs were included. Maternal anemia was evaluated based on the hemoglobin concentration and children's behavioral development was assessed by Achenbach Child Behavior Checklist 1.5-5. Binary logistic regression models indicated that compared with children born of mothers without anemia throughout pregnancy, maternal mild anemia during pregnancy or only anemia in the 3rd trimester was associated with increased risks of aggressive behaviors in boys. Maternal mild anemia only in the 2nd trimester was associated with increased risks of attention problems in boys. In girls, maternal mild anemia during pregnancy was associated with increased risks of withdrawn, internalizing problems and total problems. Girls born of mothers with mild anemia only in the 2nd trimester had higher risks of total problems. Maternal mild anemia in both 2nd and 3rd trimesters was associated with increased risks of internalizing problems in girls. Our study identified sex-specific effects of maternal mild anemia during pregnancy on children's behavioral development problems.

A distinctive subcortical functional connectivity pattern linking negative affect and treatment outcome in major depressive disorder.

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.

Association between hyperglycemia during pregnancy and offspring's refractive error: A focused review.

This review article explores the relationship between hyperglycemia during pregnancy and the visual development of offspring, specifically focusing on refractive error. The authors conducted a comprehensive search for relevant articles in various databases and assessed the methodological quality of the included studies. The findings consistently indicate that hyperglycemia during pregnancy can have a detrimental impact on the structural and functional aspects of visual development in offspring. The intrauterine hyperglycemic environment appears to negatively affect the retina and lens, leading to refractive errors. In conclusion, there is likely an association between hyperglycemia during pregnancy and the development of refractive errors in offspring.

USP36-mediated PARP1 deubiquitination in doxorubicin-induced cardiomyopathy.

Doxorubicin (Dox) is a potent antineoplastic agent, but its use is curtailed by severe cardiotoxicity, known as Dox-induced cardiomyopathy (DIC). The molecular mechanism underlying this cardiotoxicity remains unclear. Our current study investigates the role of Ubiquitin-Specific Protease 36 (USP36), a nucleolar deubiquitinating enzyme (DUB), in the progression of DIC and its mechanism. We found increased USP36 expression in neonatal rat cardiomyocytes and H9C2 cells exposed to Dox. Silencing USP36 significantly mitigated Dox-induced oxidative stress injury and apoptosis in vitro. Mechanistically, USP36 upregulation positively correlated with Poly (ADP-ribose) polymerase 1 (PARP1) expression, and its knockdown led to a reduction in PARP1 levels. Further investigation revealed that USP36 could bind to and mediate the deubiquitination of PARP1, thereby increasing its protein stability in cardiomyocytes upon Dox exposure. Moreover, overexpression of wild-type (WT) USP36 plasmid, but not its catalytically inactive mutant (C131A), stabilized PARP1 in HEK293T cells. We also established a DIC model in mice and observed significant upregulation of USP36 in the heart. Cardiac knockdown of USP36 in mice using a type 9 recombinant adeno-associated virus (rAAV9)-shUSP36 significantly preserved cardiac function after Dox treatment and protected against Dox-induced structural changes within the myocardium. In conclusion, these findings suggest that Dox promotes DIC progression by activating USP36-mediated PARP1 deubiquitination. This novel USP36/PARP1 axis may play a significant regulatory role in the pathogenesis of DIC.

Are there bidirectional associations between maternal thyroid function and glucose metabolism in singleton live births? A birth cohort study.

(1) Aims: To examine the associations between maternal thyroid function and glucose metabolism during pregnancy. (2) Methods: This study was based on Ma' anshan Birth Cohort in China. Totally 2375 pregnant women were included in data analysis. Maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb) and fasting plasma glucose (FPG) levels during the first, second and third trimesters of pregnancy were measured retrospectively. Mplus 8.0 was used to construct a cross-lagged panel model to examine the potential bidirectional association between thyroid function and FPG levels throughout pregnancy. (3) Results: FT4 levels were positively correlated with FPG levels in the first trimester and negatively correlated with FPG levels in the second trimester. TSH levels were negatively associated with FPG levels in the second trimester, and in the first trimester, it could positively predict FPG levels in the second trimester. No significant association was found between TPOAb levels and FPG levels during pregnancy. (4) Conclusions: There was a non-bidirectional association between maternal thyroid function and glucose metabolism during pregnancy. FT4 and TSH levels influence FPG concentrations in the first and second trimesters of pregnancy.

Low-Shear Stress Promotes Atherosclerosis via Inducing Endothelial Cell Pyroptosis Mediated by IKKε/STAT1/NLRP3 Pathway.

Atherosclerosis is initiated by vascular endothelial dysfunction, and low-shear stress (LSS) of blood flow is a key factor leading to endothelial dysfunction. Growing evidence suggests that endothelial cell pyroptosis plays an important role in the development of atherosclerosis. Studies have shown that low-shear stress can induce endothelial cell pyroptosis, but the exact mechanism remains unclear. Our experiments demonstrated that low-shear stress induced endothelial cell pyroptosis and the phosphorylation of IκB kinase ε (IKKε). IKKε knockdown not only significantly attenuated atherosclerosis lesions of aortic arch areas in ApoE-/- mice fed with high cholesterol diets, but also markedly reduced endothelial cell pyroptosis and NLRP3 expression triggered by low-shear stress. Further mechanism studies showed that IKKε promoted the expression of NLRP3 via activating signal transducer and activator of transcription 1 (STAT1) and the subsequent binding of STAT1 to NLRP3 promoter region. These results suggest that low-shear stress plays a pro-atherosclerotic role by promoting endothelial cell pyroptosis through the IKKε/STAT1/NLRP3 pathway, which provides new insights into the formation of atherosclerosis.

Hyperactivation and enhanced cytotoxicity of reduced CD8+ gamma delta T cells in the intestine of patients with Crohn's disease correlates with disease activity.

BACKGROUND AND AIMS: We aimed to investigate the immune characteristics of intestinal CD8+ gamma delta T (CD8+ γδ T) cells in Crohn's disease (CD) and their correlation with disease activity. METHODS: The study cohorts included 21 CD patients and 21 healthy individuals. CD8+ γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis. RESULTS: The study revealed a reduction in intestinal CD8+ γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8+ γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8+ γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR+ CD8+ γδT cell ratio, CD8+ γδT ratio, and CD8+ γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B+ CD8+ γδT cell and Perforin+ CD8+ γδT cell were identified as indicators that distinguish mildly moderately active CD cases. CONCLUSIONS: Intestinal CD8+ γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8+ γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8+ γδ T cells can be used as indicators to assist in diagnosing CD patients.

Association of gestational weight gain rate in pregnant women with children's cognitive and behavioral development: A birth cohort study.

BACKGROUND: The evidences on the relationship between gestational weight gain rate (GWGR) and children's cognitive and behavioral development have been limited. METHODS: A total of 3273 singleton live birth mother-child pairs from the Ma'anshan Birth Cohort in China were included in the study. Maternal GWGR was calculated based on the weights measured at multiple antenatal checkups. Children's cognitive and behavioral development were assessed by Chinese version of Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition and Achenbach Child Behavior Checklist 1.5-5. Then generalized linear models were performed for analyses. RESULTS: In the field of children's cognitive development, excessive GWGR in the second trimester was associated with increased visual space index (VSI), fluid reasoning index (FRI) and full scale intelligence quotient (FSIQ) scores, while excessive GWGR in the third trimester was associated with decreased VSI, working memory index (WMI) and FSIQ scores. In the field of children's behavioral development, excessive GWGR in the second trimester was associated with decreased aggressive behaviors and externalizing problems scores. LIMITATIONS: Children's behavioral development was assessed by main caregivers and might cause a certain degree of bias. There might be other potential confounders that we did not take into account. CONCLUSIONS: A high GWGR in the second trimester might be beneficial for children's cognitive and behavioral development, while a high GWGR in the third trimester might be harmful.

Effectiveness of preoperative ultrasonography in predicting metachronous contralateral inguinal hernia in children: a single-arm prospective study using a historical control for comparison.

PURPOSE: To analyze the value of ultrasonography in predicting metachronous contralateral inguinal hernia (MCIH) and diagnosing contralateral persistent processus vaginalis (CPPV) in children with unilateral inguinal hernia, a prospective study was conducted. METHODS: All participants underwent a preoperative ultrasound on the contralateral groin. Patients in group A1 received operating procedure according to ultrasound results (patients with negative contralateral US results received hernia repair on the affected side), and patients in group A2 received operation according to laparoscopic results (patients received hernia repair and CPPV ligation). All patients were followed up 2 years and compared to a historical control (group B) who underwent open hernia repair only on the affected side regardless of contralateral US results. RESULTS: In groups A1 and A2, laparoscopic exploration revealed the presence of a CPPV in 490 cases. Ultrasound was found to be accurate in 104 out of the 490 cases with four false-positive and 386 false-negative results. This yielded an accuracy of 59.3%, a sensitivity of 21.2%, and a specificity of 99.2%. 10 patients in group A1, and 74 patients in group B developed MCIH. The accuracy, sensitivity, and specificity of the value of ultrasonography in predicting MCIH were 89.3%, 52.4%, and 92.5%, respectively. CONCLUSIONS: Preoperative ultrasonography of the contralateral groin is currently unable to accurately detect CPPV, but it appears to be a promising method in predicting MCIH by using rigorous diagnosing criteria.

Advances in functional MRI research in bipolar disorder: from the perspective of mood states.

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression. Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder. However, the pathophysiology underlying mood instability, mood switching and the development of extreme mood states is less well understood. This review presents a comprehensive overview of current evidence from functional MRI studies from the perspective of mood states. We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder, irrespective of the mood state. We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects. Finally, we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research. A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

Dual/Multi-Modal Image-Guided Diagnosis and Therapy Based on Luminogens with Aggregation-Induced Emission.

The combination of multiple imaging methods has made an indelible contribution to the diagnosis, surgical navigation, treatment, and prognostic evaluation of various diseases. Due to the unique advantages of luminogens with aggregation-induced emission (AIE), their progress has been significant in the field of organic fluorescent contrast agents. Herein, this manuscript summarizes the recent advancements in AIE molecules as contrast agents for optical image-based dual/multi-modal imaging. We particularly focus on the exceptional properties of each material and the corresponding application in the diagnosis and treatment of diseases.

Copublication promotes dissemination hypertension guidelines: a retrospective cohort study.

To evaluate the impact of copublication on hypertension-related clinical practice guidelines' citation, we searched the Web of Science Core Collection and guide.medlive.cn until 31 December 2017 using the terms "hypertension" and "guideline". The copublished group was matched with the noncopublished group at a 1:2 ratio. Primary outcomes were total citations and citations within the first five years after publication. Secondary outcomes included the adjusted impact factor ratio (excluding copublished guidelines) to the actual impact factor of the journal. Altmetric scores were compared using Altmetric explorer data. 21 copublished and 42 noncopublished guidelines were included. The copublished group had higher median current total citations [387.0 (90.0, 1806.0) vs 70.5 (23.25, 158.25)], and higher median citations at one, two, three, four, and five years [7.0 (0.5, 58.5) vs 1.0 (0.0, 5.5), 33.0 (14.0, 142.0) vs 5.5 (1.75, 26.25), 46.0 (24.5, 216.0) vs 10.5 (3, 25.75), 50.0 (19.0, 229.0) vs 9.0 (3.0, 19.0), 52.0 (13.5, 147.0) vs 7.0 (2.0, 20.0), all p < 0.05]. The adjusted IF analysis showed that if they had not copublished the guidelines, 10 of 24 and 11 of 24 journals would have had a lower IF in the first and second years. Median altmetric scores were significantly higher for copublished guidelines [38.5 (9.5, 90.5) vs 3.5 (1.0, 9.0)] (p < 0.05). Copublication is associated with a higher citation frequency of hypertension guidelines and may increase the journal IF. Positive impacts extend beyond academia, benefiting society through broader guideline application and dissemination. This facilitates broader application of guidelines and promotes their dissemination. We conducted a retrospective cohort study to demonstrate how copublication promotes the dissemination of hypertension guidelines.

Brain functional changes across mood states in bipolar disorder: from a large-scale network perspective.

BACKGROUND: Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis. RESULTS: A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients. CONCLUSIONS: Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.

Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Quantitative analysis of microglia morphological changes in the hypothalamus of chronically stressed rats.

Based on the successful establishment of a rat model of chronic restraint stress, we used multiple algorithms to quantify the morphological changes of rat hypothalamic microglia from various perspectives, providing a pathomorphological basis for the subsequent study of molecular mechanisms of hypothalamic stress injury, such as neuroinflammation. To verify the successful establishment of the chronic stress model, an enzyme-linked immunosorbent assay was performed to detect serum glucocorticoid levels. Microglia labeled with Iba1 in frozen sections of rat hypothalamus were scanned and photographed at multiple levels using confocal microscopy. Subsequently, images were processed for external contouring and skeletonization, and morphological indices of microglia were calculated and analyzed using fractal, skeleton, and Sholl analysis. In addition, the co-expression of CD68 (a marker that can reflect phagocytic activity) and Iba1 was observed by immunofluorescence technique. Compared with the control group, microglia in the chronic stress group displayed reduced fractal dimension and lacunarity, increased density and circularity, enlarged soma areas, and shortened and reduced branches. Sholl analysis confirmed the reduced complexity of microglia following chronic stress. Meanwhile, microglia CD68 increased significantly, indicating that the microglia in the chronic stress group have greater phagocytosis activity. In summary, chronic restraint stress promoted the conversion of microglia in the rat hypothalamus to a less complex form, manifested as larger soma, shorter and fewer branches, more uniform and dense texture, and increased circularity; indeed, the shape of these microglia resembled that of amoeba and they displayed strong phagocytosis activity.

[SWI/SNF Complex Gene Mutations Promote the Liver Metastasis 
of Non-small Cell Lung Cancer Cells in NSI Mice].

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS: This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.

Underwater Target Detection Based on Parallel High-Resolution Networks.

A parallel high-resolution underwater target detection network is proposed to address the problems of complex underwater scenes and limited target feature extraction capability. First, a high-resolution network (HRNet), a lighter high-resolution human posture estimation network, is used to improve the target feature representation and effectively reduce the semantic information lost in the image during sampling. Then, the attention module (A-CBAM) is improved to capture complex feature distributions by modeling the two-dimensional space in the activation function stage through the introduction of the flexible rectified linear units (FReLU) activation function to achieve pixel-level spatial information modeling capability. Feature enhancement in the spatial and channel dimensions is performed to improve understanding of fuzzy targets and small target objects and to better capture irregular and detailed object layouts. Finally, a receptive field augmentation module (RFAM) is constructed to obtain sufficient semantic information and rich detail information to further enhance the robustness and discrimination of features and improve the detection capability of the model for multi-scale underwater targets. Experimental results show that the method achieves 81.17%, 77.02%, and 82.9% mean average precision (mAP) on three publicly available datasets, specifically underwater robot professional contest (URPC2020, URPC2018) and pattern analysis, statistical modeling, and computational learning visual object classes (PASCAL VOC2007), respectively, demonstrating the effectiveness of the proposed network.

Early sleep duration trajectories and children's cognitive development: a prospective cohort study.

We aimed to investigate the association between sleep duration trajectories and cognitive performance in preschool-aged Chinese children. We included 2131 children from the Ma'anshan birth cohort (MABC) study. Sleep duration trajectories from 6 to 48 months of age were determined using the group-based trajectory modeling (GBTM). Children's intellectual development was assessed using the Wechsler Preschool and Primary Scale of Intelligence. Compared to those with a medium total sleep duration trajectory, children with a short total sleep duration trajectory had poorer cognitive performance on the Visual Spatial Index (VSI) (ß = -3.65; 95% CI = -6.77 to -0.53), which was associated with an increased risk of a low full-scale intelligence quotient (FSIQ) (OR = 1.60; 95% CI = 1.02 to 2.51). The short total sleep duration trajectory was associated with a low VSI compared with both the medium total sleep duration trajectory and the long total sleep duration trajectory. Compared to children with normal nighttime sleep duration and normal daytime sleep duration trajectories, children with short nighttime sleep and long daytime sleep duration trajectories, normal nighttime sleep and long daytime sleep duration trajectories, and short nighttime sleep and normal daytime sleep duration trajectories all had lower cognitive performance. The restricted cubic spline (RCS) also showed that children with and appropriate total sleep duration, an adequate nighttime sleep duration, and a moderate daytime sleep duration had higher FSIQ. CONCLUSIONS: The results of this study emphasize that a medium total sleep duration, adequate sleep at nighttime, and appropriate sleep in the daytime appear to be more beneficial for children's cognitive development. WHAT IS KNOWN: • Sleep duration in infancy is strongly associated with neurocognitive development. WHAT IS NEW: • Medium and long total sleep duration trajectories are beneficial for children's cognitive performance compared to the short total sleep duration trajectory. • A medium total sleep duration, adequate sleep at nighttime and appropriate sleep in the daytime appear to be more beneficial for children's cognitive development.