Differentiation between fetal and postnatal iron deficiency in altering brain substrates of cognitive control in pre-adolescence.

BACKGROUND: Early iron deficiency (ID) is a common risk factor for poorer neurodevelopment, limiting children's potential and contributing to global burden. However, it is unclear how early ID alters the substrate of brain functions supporting high-order cognitive abilities and whether the timing of early ID matters in terms of long-term brain development. This study aimed to examine the effects of ID during fetal or early postnatal periods on brain activities supporting proactive and reactive cognitive control in pre-adolescent children. METHODS: Participants were part of a longitudinal cohort enrolled at birth in southeastern China between December 2008 and November 2011. Between July 2019 and October 2021, 115 children aged 8-11 years were invited to participate in this neuroimaging study. Final analyses included 71 children: 20 with fetal ID, 24 with ID at 9 months (postnatal ID), and 27 iron-sufficient at birth and 9 months. Participants performed a computer-based behavioral task in a Magnetic Resonance Imaging scanner to measure proactive and reactive cognitive control. Outcome measures included accuracy, reaction times, and brain activity. Linear mixed modeling and the 3dlme command in Analysis of Functional NeuroImages (AFNI) were separately used to analyze behavioral performance and neuroimaging data. RESULTS: Faster responses in proactive vs. reactive conditions indicated that all groups could use proactive or reactive cognitive control according to contextual demands. However, the fetal ID group was lower in general accuracy than the other 2 groups. Per the demands of cues and targets, the iron-sufficient group showed greater activation of wide brain regions in proactive vs. reactive conditions. In contrast, such condition differences were reversed in the postnatal ID group. Condition differences in brain activation, shown in postnatal ID and iron-sufficient groups, were not found in the fetal ID group. This group specifically showed greater activation of brain regions in the reward pathway in proactive vs. reactive conditions. CONCLUSIONS: Early ID was associated with altered brain functions supporting proactive and reactive cognitive control in childhood. Alterations differed between fetal and postnatal ID groups. The findings imply that iron supplement alone is insufficient to prevent persisting brain alterations associated with early ID. Intervention strategies in addition to the iron supplement should consider ID timing.

Triptolide attenuates irritable bowel syndrome via inhibiting ODC1.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium wilfordii Hook F (TwHF), has been widely used as a major medicinal herb in the treatment of inflammatory disease. METHODS: The chronic-acute combined stress (CAS) stimulation was used to establish IBS rat model. The model rats were then gavaged with triptolide. Forced swimming, marble-burying, fecal weight and abdominal withdrawal reflex (AWR) score were recorded. Pathologic changes in the ileal and colonic tissues were validated by hematoxylin and eosin staining. The inflammatory cytokines and Ornithine Decarboxylase-1 (ODC1) in the ileal and colonic tissues were performed by ELISA and WB. RESULTS: Triptolide didn't have antidepressant- and antianxiety- effects in rats caused by CAS, but decreased fecal weight and AWR score. In addition, Triptolide reduced the release of IL-1, IL-6, and TNF-α and the expression of ODC1 in the ileum and colon. CONCLUSION: The therapeutic efficacy of triptolide for IBS induced by CAS was revealed in this study, which may be related to the reduction of ODC1.

GPM6A expression is suppressed in hepatocellular carcinoma through miRNA-96 production.

GPM6A is a glycoprotein in endothelial cells, and its biological function in the development of hepatocellular carcinoma (HCC) is unknown. Through Affymetrix gene expression microarray and bioinformatic analysis, very low GPM6A expression was found in HCC tissue. The present study aims to explore the function and regulatory mechanism of GPM6A in HCC development and progression. Levels of GPM6A expression in HCC specimens from different disorders and various hepatoma cell lines were determined, and its role on cell proliferation was evaluated in hepatoma cells stably overexpressing GPM6A. Modulation of a specific microRNA (miRNA) on its expression and function was evaluated with miRNA mimetic transfection. Herein, it is reported that much lower GPM6A levels were found in HCC tissues than pericancerous liver tissues and correlated to a poor prognosis. GPM6A overexpression inhibited cell proliferation, suppressed colony formation, migration and invasion in two hepatoma cell types. Available evidence does not support that genetic and epigenetic dysregulation contributes significantly to GPM6A inactivation in HCC. Additional findings demonstrated that miR-96-5p acted directly on the 3'-UTR of the GPM6A gene and significantly decreased its mRNA and protein levels. MiR-96-5p transfection promoted proliferation, migration and invasion of SMMC-7721 and MHCC-97H hepatoma cells; whereas the function of oncogenic microRNA-96 was significantly inhibited in GPM6A-overexpressed hepatoma cells. In conclusion, GPM6A expression in HCC is commonly suppressed regardless its base disease types, and its low expression in HCC tissues is most likely attributed to upregulated miR-96-5p. GPM6A may function as a valuable biomarker for HCC progression and prognosis.

NLRP3 deficiency did not attenuate NASH development under high fat calorie diet plus high fructose and glucose in drinking water.

NOD-like receptor protein 3 (NLRP3) promotes the inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. A high-fat and calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3-/- mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS+) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3-/- mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-α and MCP-1 and infiltration of iNOS+ M1 macrophages were increased in the liver of Nlrp3-/- mice under control diet. NLRP3 deficiency did not attenuate, but instead aggravated NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3-/- mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH.

N/O co-doped poly(γ-glutamic acid)/Ni2+/melamine/chitosan nanoparticle-based hollow graphite carbon spheres for aqueous zinc-ion hybrid supercapacitors.

Hollow carbon spheres (HCSs) have attracted broad attention in aqueous zinc-ion hybrid supercapacitors (ZIHSCs) owing to their distinctive properties. However, traditional methods for fabricating HCSs face limitations, including complex multistep procedures, the use of corrosive chemicals, and stringent reaction conditions. In this work, biomass-based poly(γ-glutamic acid)/Ni2+/melamine/chitosan nanoparticles were used as the precursors to fabricate N/O co-doped hollow graphite carbon spheres (HGCSs). Thanks to the appropriate hydrophilic characteristic, specific surface area, pore size distribution, and electrical conductivity, the fabricated HGCSs cathode exhibited superior electrochemical properties. The assembled HGCSs-based ZIHSCs device showed a satisfactory specific capacitance of 133.2 mAh·g-1 at a current density of 1.0 A·g-1, high energy densities of 75.2 Wh·kg-1 at 10,000 W·kg-1 and 107.9 Wh·kg-1 at 1000 W·kg-1, respectively. Additionally, the assembled HGCSs-based ZIHSCs device displayed an exceptional cycling stability, enduring up to 10,000 cycles at 0.5 A·g-1 with a capacity retention rate of 98.1 %. This work provides a facile and novel strategy to prepare superior electrochemical performance biomass-based HGCSs cathode for ZIHSCs.

Kinetics and mechanism effects of 2D carbon supports in hydrogen spillover composites.

Extensive research has been performed using two-dimensional (2D) carbon materials as catalyst supports to achieve high-performance hydrogen storage composites through the hydrogen spillover phenomenon. However, the kinetics and mechanism effects of different support materials still need to be investigated. This study employed high-energy ball milling to fabricate Co1-xS/C60 and C1-xS/rGO composites with stable structures and abundant hydrogen storage sites. We explored the mechanism of hydrogen adsorption behavior through electrode kinetic studies and density functional theory calculations, revealing the intrinsic relationship between material composition, structure, and hydrogen diffusion kinetics. The 2D flakes of C60 and rGO support and connect C1-xS nanoparticles, providing electron transport pathways for the composites. Theoretically, the spherical C60 support with less steric hindrance showed a more vital ability to increase the hydrogen adsorption capacity, while kinetically, thin film rGO offers fast channels for hydrogen diffusion. These findings contribute to our understanding of hydrogen spillover and present opportunities to investigate the synergistic effects in 2D carbon-based composites.

Carbon Nanotube-encapsulated Chestnut Inner Shell O,N-doped Graded Porous Carbon as Stable and High-Sulfur Loading Electrode for Lithium-Sulfur Batteries.

The shuttle effect of lithium-sulfur (Li-S) batteries and the poor conductivity of sulfur (S) and lithium polysulfide severely limit their practical applications. Currently, compounding carbon materials with S is one of the effective ways to solve this problem. Therefore, green, low-cost chestnut inner shell biochar (CISC) with graded porous structure was used as the S carrier in this experiment, and carbon nanotubes (CNTs) coating was employed as the S protective layer to improve the electrical conductivity and inhibit the shuttle effect. The results showed that the CISC prepared in this experiment had a relatively high specific surface area (1135.11 m2 g-1 ), and the S loading rate was as high as 65.72 %. The graded porous structure and high specific surface area of CISC can increase the loading rate of S and thus increase the battery capacity. Meanwhile, the naturally contained O and N elements can improve the chemisorption of S. The initial discharge capacity of the CISC@S/CNTs battery at 0.1 C is 967.3 mAh g-1 , and the capacity retention rate is 74.3 % after 500 cycles. The unique composite structure improves the battery's electrical conductivity, reduces the dissolution of polysulfides, and enhances the battery cycle stability.

Bibliometric analysis of the inflammation in diabetic cardiomyopathy.

Background: Maladaptive inflammation is implicated in the development of diabetic cardiomyopathy (DCM). This study aimed to visually analyze the global scientific output over the past two decades regarding research on inflammation associated with DCM. Methods: All relevant articles and reviews were retrieved in the Web of Science (WOS) Core Collection (limited to SCIE) using "inflammation" and "diabetic cardiomyopathy" as search terms. Articles and reviews published from 1 January 2001 to 28 February 2021 were collected. Visualization analysis and statistical analysis were conducted by Microsoft 365 Excel and VOSviewer 1.6.18. Results: A total of 578 documents were finally selected for further analysis. The publications regarding inflammation and DCM increased gradually over approximately 20 years. The most prolific country was China, with 296 documents and the most citations (9,366). The most influential author groups were Lu Cai and Yihui Tan who were from the United States. The bibliometric analysis of co-occurrence keywords showed that inflammation in DCM is composed of numerous molecules (NF-κB, NLRP3 inflammasome, Nrf-2, TNF-α, protein kinase C, PPARα, TLR4, p38 mitogen-activated protein kinase, TGF-ß, Sirt1, and AKT), a variety of cardiac cell types (stem cell, fibroblast, and cardiomyocyte), physiological processes (apoptosis, oxidative stress, autophagy, endoplasmic reticulum stress, hypertrophy, mitochondrion dysfunction, and proliferation), and drugs (sulforaphane, metformin, empagliflozin, and rosuvastatin). Conclusion: Our bibliometric analysis presents the characteristics and trends of inflammation in DCM and shows that research on inflammation in DCM will continue to be a hotspot.

Galectin-3 Inhibition Ameliorates Streptozotocin-Induced Diabetic Cardiomyopathy in Mice.

Objective: Diabetic cardiomyopathy (DCM), characterized by cardiomyopathy with the absence of coronary artery disease, hypertension, and valvular heart disease in patients with diabetes, significantly increases the risk of heart failure. Galectin-3 (Gal-3) has been shown to regulate cardiac inflammation and fibrosis, but its role in DCM remains unclear. This study aimed to determine whether Gal-3 inhibition attenuates DCM and NF-κB p65 activation. Methods: Diabetic cardiomyopathy (DCM) was established by intraperitoneal (IP) injection of streptozotocin for 5 consecutive days in mice. Myocardial injury markers, such as creatine kinase isoenzyme (CK-BM) and lactate dehydrogenase, were detected using ELISA. We used non-invasive transthoracic echocardiography to examine cardiac structure and function. Histological staining was used to explore myocardial morphology and fibrosis. Profibrotic markers and inflammatory cytokines were detected by ELISA and real-time PCR in vivo. The terminal deoxyribonucleotide transferasemediated dUTP nick end-labeling (TUNEL) and immunofluorescence assays were conducted to examine myocardial apoptosis and oxidative stress. Inflammatory cytokines induced by high glucose (HG) were also found in RAW264.7 macrophages. The underlying molecular mechanisms were determined using immunofluorescence and Western blotting analyses. Results: The Gal-3 knockdown was observed to ameliorate myocardial apoptosis, oxidative stress, inflammatory cytokines release, macrophage infiltration, and fibrosis, thus, decreasing cardiac dysfunction in DCM mice. In addition, the silence of Gal-3 could suppress macrophage infiltration and inflammatory cytokine release induced by HG. Finally, a Gal-3/NF-κB p65 regulatory network was clarified in the pathogenesis of DCM. Conclusion: The Gal-3 may promote myocardial apoptosis, oxidative stress, inflammation, and fibrosis in vivo and in vitro by the mechanism of reduction of NF-κB p65 activation.

Potential Mechanisms of Triptolide against Diabetic Cardiomyopathy Based on Network Pharmacology Analysis and Molecular Docking.

The incidence of heart failure was significantly increased in patients with diabetic cardiomyopathy (DCM). The therapeutic effect of triptolide on DCM has been reported, but the underlying mechanisms remain to be elucidated. This study is aimed at investigating the potential targets of triptolide as a therapeutic strategy for DCM using a network pharmacology approach. Triptolide and its targets were identified by the Traditional Chinese Medicine Systems Pharmacology database. DCM-associated protein targets were identified using the comparative toxicogenomics database and the GeneCards database. The networks of triptolide-target genes and DCM-associated target genes were created by Cytoscape. The common targets and enriched pathways were identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The gene-gene interaction network was analyzed by the GeneMANIA database. The drug-target-pathway network was constructed by Cytoscape. Six candidate protein targets were identified in both triptolide target network and DCM-associated network: STAT3, VEGFA, FOS, TNF, TP53, and TGFB1. The gene-gene interaction based on the targets of triptolide in DCM revealed the interaction of these targets. Additionally, five key targets that were linked to more than three genes were determined as crucial genes. The GO analysis identified 10 biological processes, 2 cellular components, and 10 molecular functions. The KEGG analysis identified 10 signaling pathways. The docking analysis showed that triptolide fits in the binding pockets of all six candidate targets. In conclusion, the present study explored the potential targets and signaling pathways of triptolide as a treatment for DCM. These results illustrate the mechanism of action of triptolide as an anti-DCM agent and contribute to a better understanding of triptolide as a transcriptional regulator of cytokine mRNA expression.

Exploring the Pharmacological Mechanisms of Tripterygium wilfordii Hook F against Cardiovascular Disease Using Network Pharmacology and Molecular Docking.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF) has been used in traditional Chinese medicine (TCM) for treating cardiovascular disease (CVD). However, the underlying pharmacological mechanisms of the effects of TwHF on CVD remain elusive. This study revealed the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach. MATERIALS AND METHODS: The active compounds were selected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database according to the absorption, distribution, metabolism, and excretion (ADME). The potential targets of TwHF were obtained from the SwissTargetPrediction database. The CVD-related therapeutic targets were collected from the DrugBank, the GeneCards database, and the OMIM database. Protein-protein interaction (PPI) network was generated by the STITCH database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by R package. The network of drug-targets-diseases-pathways was constructed by the Cytoscape software. RESULTS: The 41 effective ingredients of TwHF and the 178 common targets of TwHF and CVD-related were collected. Furthermore, AKT1, amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA), and cellular tumor antigen p53 (TP53) were identified as the core targets involved in the mechanism of TwHF on CVD. Top ten GO (biological processes, cellular components, and molecular functions) and KEGG pathways were screened with a P value ≤0.01. Finally, we constructed the network of TwHF-targets-CVD-GO-KEGG. CONCLUSIONS: These findings demonstrate that the main active compound of TwHF, the core targets, and pathways maybe provide new insights into the development of a natural therapy for the prevention and treatment of CVD.

KAT6B Genetic Variant Identified in a Short Stature Chinese Infant: A Report of Physical Growth in Clinical Spectrum of KAT6B-Related Disorders.

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS, OMIM#603736) and genitopatellar syndrome (GTPTS, OMIM#606170), characterized by global developmental delay/intellectual disability and special clinical manifestations, are two distinct clinically overlapping syndromes caused by truncating sequence variants in the KAT6B (10q22.2) gene. We detected a de novo heterozygous variant within exon 16 of KAT6B (Chr10p: 76781966-76781967) in a 7-months-old female infant who showed symptoms of short stature, global developmental delay, blepharophimosis, and lacrimal duct anomalies highly consistent with SBBYSS. Following the clinical features, we analyzed the KAT6B gene using Next Generation Sequencing (NGS) techniques. Her parents didn't present the same genetic variant. The patient we reported here is mainly characterized by syndromic forms of short stature and developmental delay, which may contribute to the understanding of clinical genetics for KAT6B-associated disorders.

Hepalatide ameliorated progression of nonalcoholic steatohepatitis in mice.

BACKGROUND: No FDA-approved medications are available for the treatment of nonalcoholic steatohepatitis (NASH). The present study aimed to assess the effects of Hepalatide, a sodium taurocholate cotransporting polypeptide (NTCP) receptor-binding agent, on metabolic and histopathologic changes of a mouse model of NASH caused by high fat/calorie diet plus high fructose/glucose in drinking water (HFCD-HF/G) for 16 weeks. METHODS: Male mice were randomly divided into 4 groups: controls (normal diet), HFCD-HF/G group, HFCD-HF/G plus low or high dose of Hepalatide (20 or 60 mg/kg, LH or HH, s.c. from 9 to 16 weeks). RESULTS: Compared to HFCD-HF/G-fed mice, serum triglyceride and cholesterol levels in mice fed HFCD-HF/G plus LH or HH were decreased. The treatment with Hepalatide decreased serum alanine aminotransferase levels significantly. Liver histology and TUNEL staining showed that Hepalatide remarkably attenuated inflammation, hepatocellular steatosis and apoptosis. Hepalatide treatment decreased fasting blood glucose, serum insulin and HOMA insulin resistance index in the HH group. Moreover, Masson's staining, semi-quantitative score of fibrosis, and hydroxyproline content demonstrated that Hepalatide mitigated fibrotic progression in this murine NASH model. Additionally, most components of liver and few serum bile acids were increased in mice treated with HH. CONCLUSION: Hepalatide effectively alleviated the pathological process, metabolic profile, hepatocellular steatosis and injury, insulin resistance, halted hepatic fibrotic progression in a mouse model of NASH, most likely through the increase of serum bile acids.

Growth Concerns in Coffin-Lowry Syndrome: A Case Report and Literature Review.

Mutation of RPS6KA3 can induce Coffin-Lowry syndrome, an X-linked syndrome. The case here reported manifests its signature characteristic of short stature, facial dysmorphism, development retardation, hearing defect. The mutation of RPS6KA3 we detected by NGS analysis is c.2185 C > T. The short stature is a noteworthy problem we discuss here to improve the patient's growth and development. The efficacy and safety of application of growth hormone analogs on patients with CLS are not confirmed and need to be carefully considered.

Do green spaces affect the spatiotemporal changes of PM2.5 in Nanjing?

INTRODUCTION: Among the most dangerous pollutants is PM2.5, which can directly pass through human lungs and move into the blood system. The use of nature-based solutions, such as increased vegetation cover in an urban landscape, is one of the possible solutions for reducing PM2.5 concentration. Our study objective was to understand the importance of green spaces in pollution reduction. METHODS: Daily PM2.5 concentrations were manually collected at nine monitoring stations in Nanjing over a 534-day period from the air quality report of the China National Environmental Monitoring Center (CNEMC) to quantify the spatiotemporal change of PM2.5 concentration and its empirical relationship with vegetation and landscape structure in Nanjing. RESULTS: The daily average, minimum, and maximum PM2.5 concentrations from the nine stations were 74.0, 14.2, and 332.0 µg m-3, respectively. Out of the 534 days, the days recorded as "excellent" and "good" conditions were found mostly in the spring (30.7 %), autumn (25.6 %), and summer (24.5 %), with only 19.2 % of the days in the winter. High PM2.5 concentrations exceeding the safe standards of the CNEMC were recorded predominately during the winter (39.3-100.0 %). Our hypothesis that green vegetation had the potential to reduce PM2.5 concentration was accepted at specific seasons and scales. The PM2.5 concentration appeared very highly correlated (R2 > 0.85) with green cover in spring at 1-2 km scales, highly correlated (R2 > 0.6) in autumn and winter at 4 km scale, and moderately correlated in summer (R2 > 0.4) at 2-, 5-, and 6-km scales. However, a non-significant correlation between green cover and PM2.5 concentration was found when its level was >75 µg m-3. Across the Nanjing urban landscape, the east and southwest parts had high pollution levels. CONCLUSIONS: Although the empirical models seemed significant for spring only, one should not devalue the importance of green vegetation in other seasons because the regulations are often complicated by vegetation, meteorological conditions, and human activities.