Shedding Light on the Aftermath: Childhood Maltreatment's Role in Modifying the Association Between Recent Life Stress and Resting-State Network Connectivity.

Childhood maltreatment has been demonstrated to impact brain development. However, whether childhood maltreatment can influence the effects of recent stress on brain networks remains unclear. This study aimed to investigate whether childhood maltreatment moderates the longitudinal relationship between recent life stress and within- and between-network connectivity in key brain networks, including the anterior salience (ASN), central executive (CEN), default mode (DMN), and emotional regulation network (ERN). A cohort of 172 individuals from the Neuroscience in Psychiatry Network (NSPN) underwent MRI scans at two specific time points and undertook evaluations of childhood maltreatment and recent life stress. The results showed that childhood abuse moderated the association of recent life stress with the within-network connectivity of ASN and ERN but not DMN and CEN. Furthermore, recent life stress significantly interacted with childhood abuse to be associated with the between-network connectivity of ASN-DMN, ASN-CEN, ASN-ERN, DMN-ERN and CEN-ERN. Overall, among youth exposed to higher degrees of childhood abuse, greater recent life stress was longitudinally associated with increased network connectivity. Understanding these interactions can provide valuable insights for developing prevention strategies and interventions aimed at mitigating the lasting impact of childhood maltreatment on brain development and overall well-being.

Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study.

BACKGROUND: Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA-I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. METHODS: The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA-I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA-I interval was analyzed. RESULTS: A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6-16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9-40), of whom 18 died during ICU stay. The GA-I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA-I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA-I at 0.30-2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355-47.503]. CONCLUSION: GA-I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA-I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA-I may be beneficial for clinicians to identify high-risk patients.

The therapeutic effect of liver transplantation in 14 children with homozygous familial hypercholesterolemia: a prospective cohort: Liver transplant for familial hypercholesterolemia.

OBJECTIVES: Homozygous familial hypercholesterolemia (HoFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset cardiovascular disease. To assess the therapeutic effects of liver transplantation (LT) on HoFH patients, we observed and analyzed the outcomes of HoFH children after LT. STUDY DESIGN: This prospective cohort study included all LT candidates under 18 years old diagnosed with HoFH at Ren Ji Hospital between November 2017 and July 2021. The patients were followed until October 2023. They were treated according to the standard protocol at our center. We collected data on changes in lipid profiles, clinical manifestations, and cardiovascular complications at different time points, and recorded postoperative recipient and graft survival. RESULTS: Fourteen HoFH patients with a median age of 7 (2-12) years were included. Preoperatively, xanthomas and arcus corneas occurred in 14 and 3 patients, respectively, with 10 patients showing mild cardiovascular disease. All patients underwent LT. Recipient and graft survival rates were 100 % over a median follow-up duration of 35 (27-71) months. Median LDL-C levels dropped from 11.83 (7.99-26.14) mmol/L preoperatively to 2.3 (1.49-3.39) mmol/L postoperative at the last measurement. Thirteen patients discontinued lipid-lowering treatment after LT, while only one patient resumed statins 6 months post-operation. Xanthomas and arcus corneas significantly improved. Cardiovascular complications regressed in five patients, with no progression observed in the others. CONCLUSIONS: LT is a safe and effective treatment for severe HoFH patients beyond lipid-lowering control. Early LT improves prognosis and quality of life while minimizing the risk of cardiovascular complications.

Longitudinal associations between deviant peer affiliation and externalizing behavior in Chinese preadolescence: Differentiating between-person effects from within-person effects.

The present study employed the cross-lagged panel model and the random intercepts cross-lagged panel model to investigate the longitudinal association between deviant peer affiliation and externalizing behavior in Chinese preadolescents. A sample of 1987 students, comprising 56.10% male participants with a mean age of 12.32 years (SD = 0.53), from Guangdong and Shandong provinces, completed the Deviant Peer Affiliation Scale and the Externalizing Behavior Scale in biannual surveys. The surveys were conducted in the autumn semester of 7th grade, the spring semester of 7th grade, and the autumn semester of 8th grade. The cross-lagged panel model illustrated a bidirectional association between adolescents' involvement with deviant peers and externalizing behavior. Conversely, the random intercepts cross-lagged panel model indicated a positive association between deviant peer affiliation and externalizing behavior at the between-person level. At the within-person level, a significant predictive correlation was identified between the association with deviant peers and subsequent externalizing behavior, whereas the reverse pathway was determined to be statistically insignificant. To comprehend the connection between deviant peer association and externalizing behavior in preadolescence, it is essential to differentiate between between-person and within-person effects and utilize a sophisticated research methodology.

Up-regulated SLC25A39 promotes cell growth and metastasis via regulating ROS production in colorectal cancer.

Background: The mitochondrial transporter SLC25A39 has been implicated in the import of mitochondrial glutathione (mGSH) from the cytoplasm, crucial for mitigating oxidative stress and preserving mitochondrial function. Despite the well-established involvement of mitochondria in cancer, the functional impact of SLC25A39 on CRC progression remains elusive. Methods: The mRNA and protein expressions were detected by PCR, immunohistochemistry, and Western blot, respectively. Cell activity, cell proliferation, colony formation, and apoptosis were measured by CCK8 assay, EdU incorporation assay, plated colony formation assay, and flow cytometry, respectively. Cell migration was detected by wound healing and transwell chamber assay. The tumor microenvironment (TME), immune checkpoint molecules, and drug sensitivity of CRC patients were investigated using R language, GraphPad Prism 8 and online databases. Results: Here, we report a significant upregulation of SLC25A39 expression in CRC. Functional assays revealed that overexpression of SLC25A39 promoted CRC cell proliferation and migration while inhibiting apoptosis. Conversely, SLC25A39 knockdown suppressed cell growth and migration while enhancing apoptosis in vitro. Additionally, reduced SLC25A39 expression attenuated tumor growth in xenograft models. Mechanistically, elevated SLC25A39 levels correlated with reduced reactive oxygen species (ROS) accumulation in CRC. Furthermore, bioinformatic analyses unveiled the high SLC25A39 levels was associated with decreased expression of immune checkpoints and reduced responsiveness to immunotherapy. Single-cell transcriptomic profiling identified diverse cellular expression patterns of SLC25A39 and related immune regulators. Lastly, drug sensitivity analysis indicated potential therapeutic avenues targeting SLC25A39 in CRC. Conclusion Our findings underscore the pivotal role of SLC25A39 in CRC progression and suggest its candidacy as a therapeutic target in CRC management.

External quantum efficiency enhancement of GaN-based blue LEDs by treating their full-M-sided hexagonal mesa with TMAH solution.

In recent years, III-Nitride-based micro light-emitting diodes (micro-LEDs) have emerged in many fields and gained more attention. However, fabricating high-efficiency micro-LEDs still remains a challenge due to the presence of sidewall damage. In this study, a GaN-based single blue micro-LED with a full-M-sided hexagonal mesa was prepared. The mesa has a circumradius of 10 µm and was treated with a tetramethylammonium hydroxide (TMAH) solution. Experimental results show that the sidewall defects introduced by dry etching damage act as non-radiative recombination centers and greatly impair the performance of the device. By constructing a full-M-sided hexagonal structure and soaking in a TMAH solution, the etching damage on the sidewall can be eliminated to the greatest extent, thereby reducing sidewall defects. In consequence, the peak EQE of the devices treated with the TMAH solution exceeded 10% at low current density, an increase of 9% compared with the untreated samples. This work provides, to our knowledge, a new approach to improving the efficiency of GaN-based micro-LEDs.

Research Progress in Predicting Hepatocellular Carcinoma with Portal Vein Tumour Thrombus in the Era of Artificial Intelligence.

Hepatocellular Carcinoma (HCC) is a condition associated with significant morbidity and mortality. The presence of Portal Vein Tumour Thrombus (PVTT) typically signifies advanced disease stages and poor prognosis. Artificial intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), has emerged as a promising tool for extracting quantitative data from medical images. AI is increasingly integrated into the imaging omics workflow and has become integral to various medical disciplines. This paper provides a comprehensive review of the mechanisms underlying the formation and progression of PVTT, as well as its impact on clinical management and prognosis. Additionally, it outlines the advancements in AI for predicting the diagnosis of HCC and the development of PVTT. The limitations of existing studies are critically evaluated, and potential future research directions in the realm of imaging for the diagnostic prediction of HCC and PVTT are discussed, with the ultimate goal of enhancing survival outcomes for PVTT patients.

Identification and validation of calcium extrusion-related genes prognostic signature in colon adenocarcinoma.

Background: Disruptions in calcium homeostasis are associated with a wide range of diseases, and play a pivotal role in the development of cancer. However, the construction of prognostic models using calcium extrusion-related genes in colon adenocarcinoma (COAD) has not been well studied. We aimed to identify whether calcium extrusion-related genes serve as a potential prognostic biomarker in the COAD progression. Methods: We constructed a prognostic model based on the expression of calcium extrusion-related genes (SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC24A2, SLC24A3 and SLC24A4) in COAD. Subsequently, we evaluated the associations between the risk score calculated by calcium extrusion-related genes and mutation signature, immune cell infiltration, and immune checkpoint molecules. Then we calculated the immune score, stromal score, tumor purity and estimate score using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. The response to immunotherapy was assessed using tumor immune dysfunction and exclusion (TIDE). Finally, colorectal cancer cells migration, growth and colony formation assays were performed in RKO cells with the overexpression or knockdown SLC8A3, SLC24A2, SLC24A3, or SLC24A4. Results: We found that patients with high risk score of calcium extrusion-related genes tend to have a poorer prognosis than those in the low-risk group. Additionally, patients in high-risk group had higher rates of KRAS mutations and lower MUC16 mutations, implying a strong correlation between KRAS and MUC16 mutations and calcium homeostasis in COAD. Moreover, the high-risk group showed a higher infiltration of regulatory T cells (Tregs) in the tumor microenvironment. Finally, our study identified two previously unreported model genes (SLC8A3 and SLC24A4) that contribute to the growth and migration of colorectal cancer RKO cells. Conclusions: Altogether, we developed a prognostic risk model for predicting the prognosis of COAD patients based on the expression profiles of calcium extrusion-related genes, Furthermore, we validated two previously unreported tumor suppressor genes (SLC8A3 and SLC24A4) involved in colorectal cancer progression.

Synthetic Modification and Insecticidal Activity of 4-epi-cis-Dihydroagarofuran Derivatives.

To synthesize the fundamental framework of dihydroagarofuran, a novel strategy was devised for constructing the C-ring through a dearomatization reaction using 6-methoxy-1-tetralone as the initial substrate. Subsequently, the dihydroagarofuran skeleton was assembled via two consecutive Michael addition reactions. The conjugated diene and trans-dihydroagarofuran skeleton were modified. The insecticidal activities of 33 compounds against Mythimna separata were evaluated. Compounds 11-5 exhibited an LC50 value of 0.378 mg/mL. The activity exhibited a remarkable 29-fold increase compared to positive control Celangulin V, which was widely recognized as the most renowned natural dihydroagarofuran polyol ester insecticidal active compound. Docking experiments between synthetic compounds and target proteins revealed the shared binding sites with Celangulin V. Structure-activity relationship studies indicated that methyl groups at positions C4 and C10 significantly improved insecticidal activity, while ether groups with linear chains displayed enhanced activity; in particular, the allyl ether group demonstrated optimal efficacy. Furthermore, a three-dimensional quantitative structure-activity relationship model was established to investigate the correlation between the skeletal structure and activity. These research findings provide valuable insights for discovering and developing dihydroagarofuran-like compounds.

Synergistically coupled CoMo/Fe2O3 electrocatalyst for highly efficient and stable overall water splitting.

Constructing bifunctional non-precious metal electrocatalysts with advanced industrial value and excellent electrocatalytic performance to achieve efficient overall water splitting is important but difficult. Herein, a heterogeneous electrocatalyst comprising of CoMo alloys anchored Fe2O3 nanosheets was prepared by hydrothermal and electrodeposition methods. The strongly coupled interfaces between the CoMo alloys and Fe2O3 nanosheets promote charge redistribution, which could improve electron transfer efficiency and accelerate reaction kinetics, potentially optimizing reactant adsorption energy. Further density functional theory (DFT) calculations reveal that the construction of CoMo/Fe2O3/NF heterostructured catalyst facilitates to promote interfacial charge redistribution and enhance charge transfer capacity, thus boosting the catalytic performance. Benefiting from this, the optimal CoMo/Fe2O3/NF heterostructure demonstrates a minimal overpotential of 71 mV at 10 mA cm-2 for the HER and 266 mV at 50 mA cm-2 for the OER. Remarkably, the catalyst served as a bifunctional electrode for water splitting, resulting in a cell voltage down to 1.5 V at a current density of 10 mA cm-2. This research provides an effective way for the construction of non-precious iron oxides-based bifunctional electrocatalysts using alloy/metal oxide interfacial engineering strategy.

Compound heterozygous variants in SLC45A1 might cause syndromic intellectual disability by localization failure and activity attenuation in cells.

Intellectual disability (ID) is a kind of nervous developmental disorder and affects more than 1% of people worldwide. SLC45A1 as a transmembrane protein is implicated in the regulation of glucose homoeostasis. Through trio-based exome sequencing, the missense mutations of SLC45A1 c.103G>A (p.V35M) and c.1211T>G (p.F404C) were identified in the proband with syndromic ID. The distribution, expression and activity of SLC45A1 wild-type (WT) and variants were assayed in transfected COS7 cells. In SLC45A1 variants, the hydrogen bonds surrounding the 35th and 404th amino acid were changed, location on the cytomembrane was failed, their activity to transport glucose was also significantly decreased to contrast with SLC45A1-WT. No difference was observed at the mRNA and protein level. In conclusion, the compound heterozygous variants of SLC45A1 might be the genetic etiology for syndromic ID. These novel mutations probably attenuated its activity to transport glucose by the alteration of tertiary structure and failure of intracellular location.

Susceptibility or resilience to childhood peer abuse can be explained by cortical thickness in brain regions involved in emotional regulation.

Experiencing peer abuse in childhood can damage mental health, but some people exhibit resilience against these negative outcomes. However, it remains uncertain which specific changes in brain structures are associated with this type of resilience. We categorized 217 participants into three groups: resilience group, susceptibility group, and healthy control group, based on their experiences of peer abuse and mental health problems. They underwent MRI scans to measure cortical thickness in various brain regions of the prefrontal cortex. We employed covariance analysis to compare cortical thickness among these groups. Individuals who resilient to anxiety exhibited smaller cortical thickness in the bilateral inferior frontal gyrus (IFG), and with larger thickness in the right medial orbitofrontal cortex (mOFC), while those resilient to stress was associated with smaller thickness in both the bilateral IFG and bilateral middle frontal gyrus (MFG). These findings deepen our understanding of the neural mechanisms underlying resilience and offer insight into improving individual resilience.

The developmental processes of ventricular septal defects with outflow tract malalignment.

Ventricular septal defects (VSD) with outflow tract (OFT) malalignment are a common group of congenital heart diseases with varying severity. The developmental process of these defects is challenging to understand due to the complex nature of cardiac morphogenesis and the difficulties in visualizing the temporal and spatial changes that occur during pathogenesis. However, recent advancements in imaging techniques, such as high-resolution episcopic microscopy, have provided valuable insights into the normal septation of ventricular chambers and OFT alignment. Building upon this knowledge, we have utilized lightsheet microscopy, another innovative imaging method, to further investigate the developmental processes that lead to abnormal formation of the ventricular septum and the malalignment of arterial roots with the ventricular chambers. Our study highlights endocardial cushion hypoplasia and insufficient rotation of the outflow tract as two interrelated central factors contributing to the pathogenesis of these defects. This finding has the potential to enhance our understanding of the etiology of congenital heart diseases and may contribute to the development of improved diagnostic and therapeutic strategies in the future.

Childhood maltreatment and resting-state network connectivity: The risk-buffering role of positive parenting.

Unraveling the neurobiological foundations of childhood maltreatment is important due to the persistent associations with adverse mental health outcomes. However, the mechanisms through which abuse and neglect disturb resting-state network connectivity remain elusive. Moreover, it remains unclear if positive parenting can mitigate the negative impact of childhood maltreatment on network connectivity. We analyzed a cohort of 194 adolescents and young adults (aged 14-25, 47.42% female) from the Neuroscience in Psychiatry Network (NSPN) to investigate the impact of childhood abuse and neglect on resting-state network connectivity. Specifically, we examined the SAN, DMN, FPN, DAN, and VAN over time. We also explored the moderating role of positive parenting. The results showed that childhood abuse was linked to stronger connectivity within the SAN and VAN, as well as between the DMN-DAN, DMN-VAN, DMN-SAN, SAN-DAN, FPN-DAN, SAN-VAN, and VAN-DAN networks about 18 months later. Positive parenting during childhood buffered the negative impact of childhood abuse on network connectivity. To our knowledge, this is the first study to demonstrate the protective effect of positive parenting on network connectivity following childhood abuse. These findings not only highlight the importance of positive parenting but also lead to a better understanding of the neurobiology and resilience mechanisms of childhood maltreatment.

Review of robotic systems for thoracoabdominal puncture interventional surgery.

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail.

Half of the 18O enrichment of leaf sucrose is conserved in leaf cellulose of a C3 grass across atmospheric humidity and CO2 levels.

The 18O enrichment (Δ18O) of cellulose (Δ18OCel) is recognized as a unique archive of past climate and plant function. However, there is still uncertainty regarding the proportion of oxygen in cellulose (pex) that exchanges post-photosynthetically with medium water of cellulose synthesis. Particularly, recent research with C3 grasses demonstrated that the Δ18O of leaf sucrose (Δ18OSuc, the parent substrate for cellulose synthesis) can be much higher than predicted from daytime Δ18O of leaf water (Δ18OLW), which could alter conclusions on photosynthetic versus post-photosynthetic effects on Δ18OCel via pex. Here, we assessed pex in leaves of perennial ryegrass (Lolium perenne) grown at different atmospheric relative humidity (RH) and CO2 levels, by determinations of Δ18OCel in leaves, Δ18OLGDZW (the Δ18O of water in the leaf growth-and-differentiation zone) and both Δ18OSuc and Δ18OLW (adjusted for εbio, the biosynthetic fractionation between water and carbohydrates) as alternative proxies for the substrate for cellulose synthesis. Δ18OLGDZW was always close to irrigation water, and pex was similar (0.53 ± 0.02 SE) across environments when determinations were based on Δ18OSuc. Conversely, pex was erroneously and variably underestimated (range 0.02-0.44) when based on Δ18OLW. The photosynthetic signal fraction in Δ18OCel is much more constant than hitherto assumed, encouraging leaf physiological reconstructions.

Joint Trajectories of Depression and Rumination: Experiential Predictors and Risk of Nonsuicidal Self-Injury.

OBJECTIVE: Nonsuicidal self-injury (NSSI) is common in adolescence. Rumination is a key risk factor and often co-occurs with depressive symptoms. This is the first study to examine the joint longitudinal trajectories of rumination and depressive symptoms as predictors of NSSI, and the adverse experiences associated with these trajectories. METHOD: A community sample of 1,835 adolescents (55.9% male participants, 12.3 ± 0.5 years of age) completed questionnaires to assess adverse childhood experiences, rumination, depressive symptoms, and NSSI. Assessments were made 4 times over 18 months. RESULTS: A parallel process growth mixture model showed that youth with high trajectories of rumination but low trajectories of depression had moderately increased odds of NSSI (2.43-fold, 95% CI 1.53-3.91) compared with adolescents with low trajectories of both rumination and depression. Odds ratios (ORs) in adolescents with low trajectories of rumination but increasing or high trajectories of depression were similarly elevated, suggesting that high trajectories of rumination or depression were risk factors in isolation. However, odds were 10.06-fold greater (95% CI 5.68-18.02) when high trajectories of rumination occurred in tandem with high trajectories of depression. Multinomial logistic regression showed that male sex (OR 10.54, 95% CI 5.66-19.63), peer victimization (OR 2.25, 95% CI 1.72-2.96), and parental alienation (OR 1.94, 95% CI 1.46-2.57) were key determinants of membership in the highest risk group. CONCLUSION: Risk for NSSI is markedly increased in adolescents with high longitudinal trajectories of depression and rumination. Reducing exposure to peer victimization, cyber victimization, emotional abuse, parental alienation, and interparental conflict may reduce risk.