Resveratrol suppresses liver cancer progression by downregulating AKR1C3: targeting HCC with HSA nanomaterial as a carrier to enhance therapeutic efficacy.

The enzyme AKR1C3 plays a crucial role in hormone and drug metabolism and is associated with abnormal expression in liver cancer, leading to tumor progression and poor prognosis. Nanoparticles modified with HSA can modulate the tumor microenvironment by enhancing photodynamic therapy to induce apoptosis in tumor cells and alleviate hypoxia. Therefore, exploring the potential regulatory mechanisms of resveratrol on AKR1C3 through the construction of HSA-RSV NPs carriers holds significant theoretical and clinical implications for the treatment of liver cancer. The aim of this study is to investigate the targeted regulation of AKR1C3 expression through the loading of resveratrol (RSV) on nanomaterials HSA-RSV NPs (Nanoparticles) in order to alleviate tumor hypoxia and inhibit the progression of hepatocellular carcinoma (HCC), and to explore its molecular mechanism. PubChem database and PharmMapper server were used to screen the target genes of RSV. HCC-related differentially expressed genes (DEGs) were analyzed through the GEO dataset, and relevant genes were retrieved from the GeneCards database, resulting in the intersection of the three to obtain candidate DEGs. GO and KEGG enrichment analyses were performed on the candidate DEGs to analyze the potential cellular functions and molecular signaling pathways affected by the main target genes. The cytohubba plugin was used to screen the top 10 target genes ranked by Degree and further intersected the results of LASSO and Random Forest (RF) to obtain hub genes. The expression analysis of hub genes and the prediction of malignant tumor prognosis were conducted. Furthermore, a pharmacophore model was constructed using PharmMapper. Molecular docking simulations were performed using AutoDockTools 1.5.6 software, and ROC curve analysis was performed to determine the core target. In vitro cell experiments were carried out by selecting appropriate HCC cell lines, treating HCC cells with different concentrations of RSV, or silencing or overexpressing AKR1C3 using lentivirus. CCK-8, clone formation, flow cytometry, scratch experiment, and Transwell were used to measure cancer cell viability, proliferation, migration, invasion, and apoptosis, respectively. Cellular oxygen consumption rate was analyzed using the Seahorse XF24 analyzer. HSA-RSV NPs were prepared, and their characterization and cytotoxicity were evaluated. The biological functional changes of HCC cells after treatment were detected. An HCC subcutaneous xenograft model was established in mice using HepG2 cell lines. HSA-RSV NPs were injected via the tail vein, with a control group set, to observe changes in tumor growth, tumor targeting of NPs, and biological safety. TUNEL, Ki67, and APC-hypoxia probe staining were performed on excised tumor tissue to detect tumor cell proliferation, apoptosis, and hypoxia. Lentivirus was used to silence or overexpress AKR1C3 simultaneously with the injection of HSA-RSV NPs via the tail vein to assess the impact of AKR1C3 on the regulation of HSA-RSV NPs in HCC progression. Bioinformatics analysis revealed that AKR1C3 is an important target gene involved in the regulation of HCC by RSV, which is associated with the prognosis of HCC patients and upregulated in expression. In vitro cell experiments showed that RSV significantly inhibits the respiratory metabolism of HCC cells, suppressing their proliferation, migration, and invasion and promoting apoptosis. Silencing AKR1C3 further enhances the toxicity of RSV towards HCC cells. The characterization and cytotoxicity experiments of nanomaterials demonstrated the successful construction of HSA-RSV NPs, which exhibited stronger inhibitory effects on HCC cells. In vivo, animal experiments further confirmed that targeted downregulation of AKR1C3 by HSA-RSV NPs suppresses the progression of HCC and tumor hypoxia while exhibiting tumor targeting and biological safety. Targeted downregulation of AKR1C3 by HSA-RSV NPs can alleviate HCC tumor hypoxia and inhibit the progression of HCC.

Closed-Loop Recyclable Poly(ester-disulfide)s for Potential Alternatives to Engineering Plastic.

Facile fabrication, low material complexity and closed-loop recycling are essential for polymer plastics to alter their linear product economy towards a cradle-to-cradle one. Covalent adaptable networks (CANs) are one way to achieve that, which intrinsically exhibit decent mechanical properties of the thermosets but could also be easily recycled like the thermoplastics. In this work, we introduce rigid ester structural motifs into dynamic poly(disulfide)s to form a series of dual polymer networks. Owning to the coherence of soft/rigid segments and the reversible sacrificial crosslinking, they exhibit tailorable properties and good resistance towards different chemicals. Their closed-loop recycling is achieved via mild solvolysis, maintaining materials' mechanical integrities. It offers a solution as a sustainable replacement for engineering plastics which are massively under production but hard to be recycled.

Association of alkylphenols exposure with serum liver function markers in pregnant women in Guangxi, China.

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function.

Identification of Drought-Resistant Response in Proso Millet (Panicum miliaceum L.) Root through Physiological and Transcriptomic Analysis.

Proso millet (Panicum miliaceum L.) is resilient to abiotic stress, especially to drought. However, the mechanisms by which its roots adapt and tolerate salt stress are obscure. In this study, to clarify the molecular mechanism of proso millet in response to drought stress, the physiological indexes and transcriptome in the root of seedlings of the proso millet cultivar 'Yumi 2' were analyzed at 0, 0.5, 1.0, 1.5, and 3.0 h of stimulated drought stress by using 20% PEG-6000 and after 24 h of rehydration. The results showed that the SOD activity, POD activity, soluble protein content, MDA, and O2-· content of 'Yumi 2' increased with the time of drought stress, but rapidly decreased after rehydration. Here, 130.46 Gb of clean data from 18 samples were obtained, and the Q30 value of each sample exceeded 92%. Compared with 0 h, the number of differentially expressed genes (DEGs) reached the maximum of 16,105 after 3 h of drought, including 9153 upregulated DEGs and 6952 downregulated DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that upregulated DEGs were mainly involved in ATP binding, nucleus, protein serine/threonine phosphatase activity, MAPK signaling pathway-plant, plant-pathogen interactions, and plant hormone signal transduction under drought stress, while downregulated DEGs were mainly involved in metal ion binding, transmembrane transporter activity, and phenylpropanoid biosynthesis. Additionally, 1441 TFs screened from DEGs were clustered into 64 TF families, such as AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families. Genes related to physiological traits were closely related to starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. In conclusion, the active oxygen metabolism system and the soluble protein of proso millet root could be regulated by the activity of protein serine/threonine phosphatase. AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families were found to be closely associated with drought tolerance in proso millet root. This study will provide data to support a subsequent study on the function of the drought tolerance gene in proso millet.

Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy and their association with age and estimated glomerular filtration rate (eGFR). This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over 1 year. Patients' clinical data were collected. The levels of BTMs and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decreased levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.

Maresin1 improves hippocampal neuroinflammation and cognitive function in septic rats by activating the SLC7A11 / GPX4 ferroptosis signaling pathway.

Sepsis-associated encephalopathy (SAE) is a prevalent complication of sepsis, with hippocampal neuroinflammation playing a crucial role in SAE-induced cognitive impairment. Maresin1 (MaR1), a bioactive docosahexaenoic acid (DHA) metabolite, demonstrates comprehensive anti-inflammatory and neuroprotective attributes. Yet, its protective efficacy against SAE-induced cognitive decline remains unexplored. In this investigation, we implemented a rat SAE model via cecal ligation and puncture (CLP), while lipopolysaccharide (LPS) stimulation of HT22 cells simulated an in vitro SAE model; both models were pre-treated with MaR1. We evaluated rat learning and memory using a water maze, assessed hippocampal neuron damage via Nissl and FJC staining, and observed mitochondrial alterations through TEM. In vivo and in vitro assays gauged levels of Fe2+, MDA, GSH, and SOD. Additionally, Iba1 expression in the hippocampus was examined via immunofluorescence, while SLC7A11 and GPX4 protein expression levels were determined using western blot. Our findings indicated CLP-induced learning and memory impairment in rats, along with heightened ROS, Fe2+, and MDA levels in hippocampal neurons, diminished GSH and SOD levels, and down-regulated ferroptosis-related proteins (GPX4 and SLC7A11). Remarkably, MaR1 treatment attenuated these adverse effects. In LPS-stimulated HT22 cells, MaR1 lowered lipid ROS and bolstered mitochondrial membrane potential. Nonetheless, the ferroptosis inducer Erastin reversed MaR1's protective effects. Transwell experiments further showed MaR1's potential to inhibit microglia activation triggered by ferroptosis in HT22 cells. Consequently, MaR1 may mitigate hippocampal neuroinflammation via activating the SLC7A11/GPX4 ferroptosis signaling pathway, thus ameliorating SAE-related cognitive impairment.

Novel homozygous mutations in AIRE leading to APS-1 and potential mechanisms based on bioinformatics analysis.

Background: Autoimmune Poly-endocrine Syndrome Type 1 (APS-1), also known as autoimmune poly-endocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a single-gene hereditary disorder usually characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenocortical insufficiency. This syndrome is very rare in China. Methods: For our reported patient, we employed clinical and laboratory examinations along with genetic identification. For previously reported cases, we summarized findings based on meta-analysis principles. To investigate the AIRE gene's role in disease, we utilized bioinformatics analysis with existing databases and R language processing. Results: Nucleotide sequence analysis revealed two novel homozygous missense mutations (c.74C > G; c.1612C > T) in the patient's AIRE gene, confirming APS-1 diagnosis. The 3D structure of these mutation sites was described for the first time, showing that altered side chains could affect AIRE protein function. We analyzed 16 genetically diagnosed APS-1 Chinese patients, summarized the AIRE genetic spectrum, and found that exons 1, 2, 3, and 5 were most commonly affected. Hypoparathyroidism and adrenal insufficiency were the most common clinical manifestations (56%-93%), followed by hypothyroidism (31.25%), hypogonadism (12.5%), type 2 diabetes (6.25%), and type 1 diabetes (6.25%). Bioinformatics analysis indicated that AIRE mutations cause antigen presentation abnormalities in immune cells, leading to excessive endogenous and reduced exogenous antigen presentation. Conclusions: Our study summarized the clinical features of APS-1 caused by AIRE gene mutations and explored underlying mechanisms. For some patients, the prophylactic use of antimicrobial agents may be beneficial. These findings guide early genetic screening and inform potential research directions for treatment strategies.

RNF183 Promotes Colon Cancer Cell Stemness through Fatty Acid Oxidation.

Colon cancer (COAD) is a prevalent gastrointestinal tumor, composed of a few cancer stem cells (CSCs). High expression of RNF183 drives colorectal cancer metastasis, but its role in COAD cell stemness is still unclear. Bioinformatics analyzed expression and enriched pathway of RNF183 in COAD tissue. IHC analyzed RNF183 protein expression in tumor tissue. CD133 + CD44+ CSCs were sorted by flow cytometry, and RNF183 expression in COAD cells or CSCs was detected by qPCR, western blot and immunofluorescence. CCK-8 assay assessed cell viability, and sphere formation assay tested cell sphere-forming ability. Western blot measured protein expression of stem cell markers. qPCR assayed expression of fatty acid oxidation genes. The ability of fatty acid oxidation was analyzed by detecting fatty acid metabolism. RNF183 was highly expressed in COAD and CD133 + CD44+ CSCs, and was enriched in fatty acid metabolism pathway. RNF183 expression was positively correlated with enzymes involved in fatty acid oxidation. RNF183 could promote COAD stemness and fatty acid oxidation. Rescue experiments showed that Orlistat (a fatty acid oxidation inhibitor) reversed stimulative impact of RNF183 overexpression on COAD stemness. RNF183 promoted COAD stemness by affecting fatty acid oxidation, which may be a new therapeutic target for inhibiting COAD development.

Expression of concern: Versatile plasmonic-effects at the interface of inverted perovskite solar cells.

Expression of concern for 'Versatile plasmonic-effects at the interface of inverted perovskite solar cells' by Ahmed Esmail Shalan, et al., Nanoscale, 2017, 9, 1229-1236, https://doi.org/10.1039/C6NR06741G.

Behavioral regulation and approaches to learning: Moderators of the association between extracurricular involvement and academic readiness.

Participation in organized extracurricular activities (EAs) has become increasingly common among preschool-aged children. Prior studies have shown inconsistent findings on the association between young children's involvement in EAs and their subsequent developmental outcomes. Moving beyond examining the main effects of EA participation, this study focused on whether children's behavioral regulation and approaches to learning-two important domain-general skills closely linked to learning-would moderate the association between EA participation and academic readiness. Participants included 317 Chinese preschoolers residing in Shanghai. The breadth of EA participation positively predicted children's early math skills, but only for those demonstrating relatively lower behavioral regulation or less positive approaches to learning. The findings provide support for the compensatory hypothesis that participation in EAs is more beneficial for children at greater developmental risk. Unexpectedly, the intensity of EA participation negatively predicted receptive vocabulary beyond certain thresholds among children with relatively poor behavioral regulation or approaches to learning (B = -2.272, p = .032, effect size (ES) = 0.423), but this relationship was not significant for children with better learning behaviors (B = 0.111, p = .712, ES = 0.021). According to the findings, children with worse behavioral regulation and approaches to learning were actually more vulnerable to the negative effects of intensive participation in EAs (B = -15.698, p = .022, ES = 1.797). EA participation did not predict children's Chinese word reading (ps > 0.05). The findings revealed a complex pattern of relationships between preschoolers' EA participation and academic readiness and have highlighted the importance of considering child characteristics when examining the developmental effects of EA involvement.

Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant.

OBJECTIVES: Infantile hypercalcemia-1 (HCINF1) is a rare disease caused by pathogenic variants in the CYP24A1 gene, resulting in the inability to metabolize active vitamin D. This leads to hypercalcemia and severe complications. CONTENT: On December 8th, 2022, a systematic literature search was conducted in PubMed, Wanfang, and CNKI using the keywords "hypercalcemia" and "CYP24A1". Data extraction included patient demographics, clinical presentation, treatment medications, and outcomes. The findings were synthesized to identify common patterns and variations among cases and to assess the efficacy of different therapies in reducing serum calcium. Our findings revealed two distinct peaks in the incidence of HCINF1 caused by CYP24A1 pathogenic variant. Kidney stones or renal calcifications were the most common clinical manifestations of the disease, followed by polyuria and developmental delay. Laboratory investigations showed hypercalcemia, elevated vitamin D levels, hypercalciuria, and low parathyroid hormone. Genetic analysis remains the only reliable diagnostic tool. Although there is no definitive cure for HCINF1, multiple drugs, including bisphosphonates, calcitonin, and rifampicin, have been used to control its symptoms. Blocking the production and intake of vitamin D is the preferred treatment option. SUMMARY AND OUTLOOK: Our review highlights the basic clinical and biochemical features of HCINF1 and suggests that targeted diagnostic and therapeutic strategies are needed to address the clinical heterogeneity of the disease. The insights gained from this study may facilitate the development of innovative treatments for HCINF1.

Successful treatment of hypercalcemia in a Chinese patient with a novel homozygous mutation in the CYP24A1 gene using zoledronic acid: a case report.

OBJECTIVES: To emphasize the significance of genetic mutations in idiopathic infantile hypercalcemia and the potential therapeutic effectiveness of zoledronic acid in managing hypercalcemia attributed to gene mutations. CASE PRESENTATION: A 1-year-old female infant was referred to our hospital. The patient developed hypercalcemia despite no vitamin D prophylaxis or intake. In the acute phase, conventional calcium-lowering treatments showed limited efficacy, while the administration of zoledronic acid demonstrated effectiveness in controlling hypercalcemia. Subsequently the patient maintained normal calcium levels via a low-calcium diet and avoiding vitamin D intake. Genetic testing confirmed a homozygous mutation (c.476G>C) in the CYP24A1 gene. CONCLUSIONS: Family screening and genetic counseling are crucial for early detection and prevention of hypercalcemia. This case emphasizes the importance of genetic mutations in disease development and the potential therapeutic efficacy of zoledronic acid in managing hypercalcemia attributed to gene mutations.

Association between perfluoroalkyl and polyfluoroalkyl substances exposure and fetal overgrowth: A prospective birth cohort study conducted in China.

BACKGROUND: Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been associated with gestational diabetes mellitus, obesity or overweight in childhood, but data on fetal overgrowth outcomes including macrosomia and large for gestational age (LGA) and among gestational age diverse infants remain scarce. OBJECTIVE: To evaluate the association between maternal PFASs exposure and macrosomia and LGA, with exploration of the interaction between PFASs exposure and gestational age on fetal overgrowth. METHODS: A total of 1441 mother-infants pairs from Guangxi Zhuang Birth Cohort of China were analyzed. Nine PFASs were measured in maternal serum using ultra-high liquid performance chromatographytandem mass spectrometry. Multivaraible logistical regression and generalized additive models were performed for individual PFAS exposures, piecewise regression analysis was used to estimate the breakpoint values for the non-linear dose-response relationships. Bayesian Kernel Machine Regression was performed for PFASs mixture. RESULTS: In single pollutant models, maternal PFDA and PFOA exposure showed U-shaped relationship with macrosomia and LGA. When PFDA concentration exceeded 0.32 ng/mL was significantly positively associated with risks of LGA and macrosomia (OR=4.66, 95%CI: 1.26, 17.17; OR=14.43, 95%CI: 2.64, 79.02; respectively), while a negatively association was observed when level below 0.32 ng/mL. When PFOA concentration exceeded 1.20 ng/mL was significantly associated with increased risk of macrosomia (OR=7.75, 95%CI: 1.36, 44.06). In mixed exposure models, mixture of PFASs was positively associated with macrosomia, as well as associated with LGA when all the PFASs were at their 30th percentile or below. The maximum risk of LGA was reached when concentrations of PFUnA, PFDA, or PFBS were at the highest concentrations and the gestational age at the minimum of this study. CONCLUSIONS: Maternal exposure to PFDA, PFOA and PFASs mixture were non-monotonically associated with macrosomia and LGA, the direction of the associations depends on the level of exposure.

Maresin1 Ameliorates Sepsis-Induced Microglial Neuritis Induced through Blocking TLR4-NF-κ B-NLRP3 Signaling Pathway.

Objective: Neuroinflammation is a major etiology of cognitive dysfunction due to sepsis. Maresin1 (MaR1), identified as a docosahexaenoic acid (DHA)-derived metabolite from macrophages, has been demonstrated to exhibit potent neuroprotective and anti-inflammatory effects. Nevertheless, detailed functions and molecular mechanism of MaR1 in sepsis-induced cognitive dysfunction has not been fully elucidated. Here, we aimed to investigate potential neuroprotective effects of MaR1 on microglia-induced neuroinflammation in sepsis-induced cognitive impairment and to explore its anti-inflammatory mechanism. Methods: Different doses of MaR1 were administered to septic rats by via tail vein injection. The optimal dose was determined based on the 7-day survival rate of rats from each group. derived from macrophages with both anti-inflammatory to observe the ameliorative effects of MaR1 at optimal doses on cognitive dysfunction in septic rats. The effects of MaR1 on neuroinflammation-mediated microglial activation, neuronal apoptosis, and pro-inflammatory cytokine productions were in vivo and in vitro assayed, using Western blot, ELISA, TUNEL staining, Nissl staining, and the immunofluorescence method. To further elucidate anti-inflammatory machinery of MaR1, protein expressions of NLRP3 inflammatory vesicles and TLR4-NF-κB pathway-related proteins were subjected to Western blot assay. Results: After tail vein injection of MaR1 with different doses (2 ng/g, 4 ng/g, 8 ng/g), the results showed that 4 ng/g MaR1 treatment significantly increased the rats' 7-day survival rate compared to the CLP controls. Therefore, subsequent experiments set 4 ng/g MaR1 as the optimal dose. Morris water maze experiments confirmed that MaR1 significantly reduced space memory dysfunction in rats. In addition, in CLP rats and LPS-stimulated BV2 microglia, MaR1 significantly reduced activated microglia and pro-inflammatory cytokines levels and neuronal apoptosis. Mechanically, MaR1 inhibits microglia-induced neuroinflammation through suppressing activations of NLRP3 inflammatory vesicles and TLR4-NF-κB signal pathway. Conclusion: Collectively, our findings suggested that MaR1 might be a prospective neuroprotective compound for prevention and treatment in the sepsis process.

Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.

BACKGROUND: ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. METHODS: Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. RESULTS: Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under -2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. CONCLUSION: ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH-targeted treatment for ACAN mutation-induced short stature. GH-promoting therapies may increase patients' heights.

Influence of parental play on Taiwanese 3-year-olds' executive function: Through the path of motor skills.

Parenting is known to impact children's executive function (EF) skills. However, nearly all the evidence comes from analyses of mother-child interaction. Using the National Longitudinal Study of Child Development and Care Database in Taiwan, the relations between both mother-child and father-child interaction and 3-year-olds' EF were investigated in 2,164 families. The results showed that mothers interacted with their children differently from fathers in terms of time distribution. Mothers were more equally involved in all aspects of parental involvement, whereas fathers spent more time in play. In addition, both mother-child and father-child play contributed to children's EF; however, the mediating effect of child motor skills was more prominent for father-child play. This study not only suggests a potential distinct and complementary role of fathers in young children's EF development but also indicates a unique mediating effect of motor skills in the path from parent-child play to child EF. Implications for parent education are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Overexpressing six-transmembrane protein of prostate 2 (STAMP2) alleviates sepsis-induced acute lung injury probably by hindering M1 macrophage polarization via the NF-κB pathway.

INTRODUCTION: Acute lung injury (ALI) is a major cause of death in sepsis patients. The Six-transmembrane protein of prostate 2 (STAMP2) is a key regulator of inflammation, while its role in septic ALI remains unclear. MATERIAL AND METHODS: Male C57BL/6 mice were subjected to cecal ligation puncture (CLP) to induce experimental sepsis whereas lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used as the models of septic ALI in vivo and in vitro, respectively. Overexpression of STAMP2 in mouse lungs and RAW264.7 cells was performed with an adenoviral vector. We measured histological lung injury, lung wet/dry weight (W/D) ratio, and pulmonary myeloperoxidase (MPO) activity to assess lung injury extent. Cell counts in bronchoalveolar lavage fluid (BALF) were measured using Giemsa staining. The concentration of inflammatory factors was detected by enzyme-linked immunosorbent assay. The polarization of macrophages was evaluated by inducible nitric oxide synthase (iNOS) and F4/80 staining. The activation of cell apoptosis and NF-κB pathway was evaluated using Western blot, TUNEL staining, immunofluorescence, and immunohistochemistry. RESULTS: Overexpression of STAMP2 alleviated CLP-induced lung injury of mice with decreased W/D ratio of the lung, and MPO activity in lung tissue. STAMP2 overexpression reduced the lung infiltration of inflammatory cells, and the levels of TNF-a, IL-6, and macrophage chemoattractant protein-1 (MCP-1) in BALF. Overexpressed STAMP2 inhibited macrophage M1 polarization in lung tissues as indicated by F4/80 and iNOS stainings in lung tissue. STAMP2 overexpression inhibited RAW 264.7 cell apoptosis by increasing Bcl-2 and decreasing Bax and cleaved-caspase 3 expression. Besides, STAMP2 overexpression suppressed nuclear factor κB (NF-κB) p65 pathway activation, as evidenced by reduced phosphorylation of IκBα, and phosphorylation and translocation of NF-κB p65. In vitro study further proved that STAMP2 overexpression suppressed the NF-κB pathway (IκBα/p65) in macrophages and decreased macrophage M1 polarization and M1-associated inflammatory factor production (TNF-a, IL-6, and MCP-1). CONCLUSIONS: Our study for the first time demonstrated that STAMP2 might be able to reduce inflammation in sepsis-induced ALI by inhibiting macrophage M1 polarization through repressing NF-κB signaling activation.

Role of lncRNA-MEG8/miR-296-3p axis in gestational diabetes mellitus.

AIM: Gestational diabetes mellitus (GDM) is the most common complication in pregnancy. This study aimed to investigate the potential mechanism and effects of long-noncoding RNA maternally expressed 8 (lncRNA-MEG8) in GDM. METHODS: Targeted interactions involving lncRNA-MEG8 and miR-296-3p were initially predicted using starBase software and then confirmed using dual-luciferase reporter gene analysis. The expression levels of lncRNA-MEG8 and miR-296-3p in peripheral blood samples from patients with GDM were measured using reverse transcription-quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to evaluate the overall levels of insulin and insulin secretion. Additionally, MTT and flow cytometric methods were used to detect cell viability and apoptosis. Cell apoptosis-associated proteins were determined by western blotting. RESULTS: Our results indicated that lncRNA-MEG8 is a potential target of miR-296-3p. lncRNA-MEG8 level was higher, whereas that of miR-296-3p was lower in patients with GDM than in healthy individuals. LncRNA-MEG8-siRNA promoted insulin content and secretion. Furthermore, MEG8-siRNA increased cell viability and decreased apoptosis. However, these changes were reversed by an miR-296-3p inhibitor. Moreover, a miR-296-3p mimic had the same effect on INS-1 cells as MEG8-siRNA, as evidenced by enhanced insulin secretion, cell viability, and reduced apoptosis. CONCLUSION: LncRNA-MEG8-siRNA promotes pancreatic ß-cell function by upregulating miR-296-3p.

SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1.

SMYD2, as an oncogene, has been involved in multiple types of cancer, but the potential role of SMYD2 in gastrointestinal stromal tumors (GIST) remains enigmatic and requires further investigation. Hence, this study was conducted with the main objective of analyzing the effect of SMYD2 on GIST. GIST and adjacent normal tissues were collected from 46 patients with GIST where the expression of EZH2, SMYD2, and TET1 was determined, followed by the analysis of their interactions. The functional role of SMYD2 in cell biological functions was determined using a loss-of-function assay in GIST-T1 cells. Nude mouse xenograft experiments were performed to verify the role of the SMYD2/EZH2/TET1 axis in GIST in vivo. EZH2 was upregulated in GIST tissues and cell lines, which was positively correlated with SMYD2 expression and inversely correlated with TET1 expression in GIST tissues. EZH2 silencing due to SMYD2 inhibition reduced GIST-T1 cell proliferation and accelerated cell senescence. EZH2 repressed TET1 expression by promoting H3K27me3 methylation in the TET1 promoter region. TET1 inhibition reversed the effect of EZH2 silencing on the biological functions of GIST-T1 cells. In vivo data further revealed the promoting effect of SMYD2 on the progression of GIST by regulating the EZH2/TET1 axis. Overall, this study demonstrates that SMYD2 can increase EZH2 expression while suppressing TET1 expression, thus accelerating GIST, and creating new treatment opportunities for GIST.

Effects of household environmental exposure and ventilation in association with adverse birth outcomes: A prospective cohort study in rural China.

Prenatal exposure to outdoor air pollution have been associated with birth outcomes. However, there is limited evidence on the adverse effects of household indoor air pollution worldwide, much less in rural areas of China. This study aimed to explore the associations of household environmental factors (primary cooking fuel, housing renovation, and home ventilation) with four adverse birth outcomes (preterm birth (PTB), small for gestational age (SGA), low birth weight (LBW), and term low birth weight (T-LBW)). We conducted a cohort study involving 10,324 pregnancies in women who delivered a live-born infant from 2015 to 2018 in Guangxi, China. Risk ratios and 95% confidence intervals (CI) were estimated with control for reproductive history, lifestyle, home environmental confounders, and other potential confounders. A total of 5.4% of the infants were PTB, 10.7% were SGA, 5.5% had LBW, and 3.0% had T-LBW. Household-use induction cookers as the primary cooking fuel during pregnancy was associated with SGA (RR = 1.31, 95% CI: 1.07-1.60), LBW (1.41, 1.09-1.82), and T-LBW(1.62, 1.16-2.26), as compared with household-use gas as the primary cooking fuel. Housing renovation within one year before pregnancy was associated with PTB (1.45, 1.06-1.98) and LBW (1.56, 1.17-2.09), while housing renovation during pregnancy was associated with a higher risk of SGA only in moderate home ventilation conditions (3.74, 1.69-8.28). Our findings suggested that household-use induction cookers as the primary cooking fuel increased the risks of SGA, LBW, and T-LBW. In addition, housing renovation within one year before pregnancy increased the risks of PTB and LBW. Proper home ventilation may reduce the effect on the association between housing renovation during pregnancy and SGA.