Strong Vertical Piezoelectricity and Broad-pH-Value Photocatalyst in Ferroelastic Y2Se2BrF Monolayer.

With the development of miniaturized devices, there is an increasing demand for 2D multifunctional materials. Six ferroelastic semiconductors, Y2Se2XX' (X, X' = I, Br, Cl, or F; X ≠ X') monolayers, are theoretically predicted here. Their in-plane anisotropic band structure, elastic and piezoelectric properties can be switched by ferroelastic strain. Moderate energy barriers can prevent the undesired ferroelastic switching that minor interferences produce. These monolayers exhibit high carrier mobilities (up to 104 cm2 V-1 s-1) with strong in-plane anisotropy. Furthermore, their wide bandgaps and high potential differences make them broad-pH-value and high-performance photocatalysts at pH value of 0-14. Strikingly, Y2Se2BrF possesses outstanding d33 (d33 = -405.97 pm/V), greatly outperforming CuInP2S6 by 4.26 times. Overall, the nano Y2Se2BrF is a hopeful candidate for multifunctional devices to generate a direct current and achieve solar-free photocatalysis. This work provides a new paradigm for the design of multifunctional energy materials.

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis.

Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan-Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late-stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

Metal Variance in Multivariate Metal-Organic Frameworks for Boosting Catalytic Conversion of CO2.

Developing efficient, low-cost, MOF catalysts for CO2 conversion at low CO2 concentrations under mild conditions is particularly interesting but remains highly challenging. Herein, we prepared an isostructural series of two-dimensional (2D) multivariate metal-organic frameworks (MTV-MOFs) containing copper- and/or silver-based cyclic trinuclear complexes (Cu-CTC and Ag-CTC). These MTV-MOFs can be used as efficient and reusable heterogeneous catalysts for the cyclization of propargylamine with CO2. The catalytic performance of these MTV-MOFs can be engineered by fine-tuning the Ag/Cu ratio in the framework. Interestingly, the induction of 10% Ag remarkably improved the catalytic efficiency with a turnover frequency (TOF) of 243 h-1, which is 20-fold higher than that of 100% Cu-based MOF (i.e., TOF = 10.8 h-1). More impressively, such a bimetallic MOF still exhibited high catalytic activity even for simulated flue gas with 10% CO2 concentration. Furthermore, the reaction mechanism has been examined through the employment of NMR monitoring experiments and DFT calculations.

"Core-Shell" Wave Function Modulation in Organic Narrowband Emitters.

Efficient red-green-blue primary luminescence with an extraordinarily narrow band and durability is crucial for advanced display applications. Recently, the emergence of multiple-resonance (MR) from short-range atomic interactions has been shown to induce extremely narrow spectral widths in pure organic emitters. However, achieving wide-range color tuning without compromising color purity remains a persistent challenge for MR emitters. Herein, the concept of electronic donor/acceptor "core-shell" modulation is proposed within a boron/nitrogen (B/N) MR skeleton, enabling the rational utilization of intramolecular charge transfer to facilitate wavelength shift. The dense B atoms localized at the center of the molecule effectively compress the electron density and stabilize the lowest unoccupied molecular orbital wave function. This electron-withdrawing core is embedded with peripheral electron-donating atoms. Consequently, doping a single B atom into a deep-blue MR framework led to a profound bathochromic shift from 447 to 624 nm (∼0.8 eV) while maintaining a narrow spectral width of 0.10 eV in this pure-red emitter. Notably, organic light-emitting diodes assisted by thermally activated delayed fluorescence molecules achieved superb electroluminescent stability, with an LT99 (99% of the initial luminance) exceeding 400 h at an initial luminance of 1000 cd m-2, approaching commercial-level performance without the assistance of phosphors.

Expanding Multiple-Resonance Structure of a Double-Borylated Skeleton by Fusing with Indolocarbazole a Multiple-Resonance Donor for Narrowband Green Emission.

Double-borylated multiple-resonance (MR) skeletons are promising templates for high performance, while the chemical design space is relatively limited. Peripheral segments are often used to decorate/fuse MR skeletons and modulate the photophysics but they can also cause unwanted spectral broadening. Herein, a narrowband MR emitter ICzDBA by fusing an MR-featured donor segment indolocarbazole into a double-borylated MR skeleton is developed. In ICzDBA, the nitrogen atom located away from the core benzene ring can also contribute to the generation of the overall MR-featured distribution through the long-range conjugation effect, along with the other boron/nitrogen atoms on the phenyl center. Thus, ICzDBA in toluene displays a narrowband emission peaking at 507 nm with a full width at half maximum of merely 20 nm (0.09 eV). Moreover, organic light-emitting diode devices using ICzDBA emitter exhibit ultrapure green emission with Commission Internationale de l'Eclairage (CIE) coordinates of (0.27, 0.70) and a high external quantum efficiency of 32.5%. These results manifest the importance of MR characters of peripheral decorations/fusions in preserving the narrowband features of MR skeletons, which provides a solution for further expanding MR structures with well-maintained narrowband characters.

Testing the ectomycorrhizal-dominance hypothesis for ecosystem multifunctionality in a subtropical mountain forest.

Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time.

Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. RESULTS: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation. INTERPRETATION: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256.

Reduction of the trans-cortical vessel was associated with bone loss, another underlying mechanism of osteoporosis.

RATIONALE: Numerous studies have established a robust association between bone morrow microvascular diseases and osteoporosis. This study sought to investigate the relationship between alterations in trans-cortical vessel (TCVs) and the onset of osteoporosis in various mouse models. METHODS: Aged mice, ovariectomized mice, and db/db mice, were utilized as osteoporosis models. TCVs in the tibia were detected using tissue clearing and light sheet fluorescence microscopy imaging. Femurs bone mass were analyzed using micro-CT scanning. Correlations between the number of TCVs and bone mass were analyzed using Pearson correlation analysis. RESULTS: All osteoporosis mouse models showed a significant reduction in the number of TCVs compared to the control group. Correlation analysis revealed a positive association between the number of TCVs and bone mass. TCVs were also expressed high levels of CD31 and EMCN proteins as type H vessels. CONCLUSIONS: This study underscores a consistent correlation between the number of TCVs and bone mass. Moreover, TCVs may serve as a potential biomarker for bone mass evaluation.

Imaging diagnosis and differential diagnosis of extraskeletal osteosarcoma.

OBJECTIVE: The aim of this study was to investigate the clinical, imaging and pathological features of extraskeletal osteosarcoma (EOS) and to improve the understanding of this disease and other similar lesions. METHODS: The data for 11 patients with pathologically confirmed extraosseous osteosarcoma, including tumour site and size and imaging and clinical manifestations, were analysed retrospectively. RESULTS: Six patients were male (60%), and 5 were female (40%); patient age ranged from 23 to 76 years (average age 47.1 years). Among the 11 patients, 7 had clear calcifications or ossification with different morphologies, and 2 patients showed a massive mature bone tumour. MRI showed a mixed-signal mass with slightly longer T1 and T2 signals in the tumour parenchyma. Enhanced CT and MRI scans showed enhancement in the parenchyma. Ten patients had different degrees of necrosis and cystic degeneration in the mass, 2 of whom were complicated with haemorrhage, and MRI showed "fluid‒fluid level" signs. Of the 11 patients, five patients survived after surgery, and no obvious recurrence or metastasis was found on imaging examination. One patient died of lung metastasis after surgery, and 2 patients with open biopsy died of disease progression. One patient died of respiratory failure 2 months after operation. 2 patients had positive surgical margins, and 1 had lung metastasis 6 months after operation and died 19 months after operation. Another patient had recurrence 2 months after surgery. CONCLUSION: The diagnosis of EOS requires a combination of clinical, imaging and histological examinations. Cystic degeneration and necrosis; mineralization is common, especially thick and lumpy mineralization. Extended resection is still the first choice for localized lesions. For patients with positive surgical margins or metastases, adjuvant chemoradiotherapy is needed.

Biallelic COQ4 Variants in Hereditary Spastic Paraplegia: Clinical and Molecular Characterization.

BACKGROUND: Hereditary spastic paraplegias (HSP) are neurologic disorders characterized by progressive lower-extremity spasticity. Despite the identification of several HSP-related genes, many patients lack a genetic diagnosis. OBJECTIVES: The aims were to confirm the pathogenic role of biallelic COQ4 mutations in HSP and elucidate the clinical, genetic, and functional molecular features of COQ4-associated HSP. METHODS: Whole exome sequences of 310 index patients with HSP of unknown cause from three distinct populations were analyzed to identify potential HSP causal genes. Clinical data obtained from patients harboring candidate causal mutations were examined. Functional characterization of COQ4 variants was performed using bioinformatic tools, single-cell RNA sequencing, biochemical assays in cell lines, primary fibroblasts, induced pluripotent stem cell-derived pyramidal neurons, and zebrafish. RESULTS: Compound heterozygous variants in COQ4, which cosegregated with HSP in pedigrees, were identified in 7 patients from six unrelated families. Patients from four of the six families presented with pure HSP, whereas probands of the other two families exhibited complicated HSP with epilepsy or with cerebellar ataxia. In patient-derived fibroblasts and COQ4 knockout complementation lines, stable expression of these missense variants exerted loss-of-function effects, including mitochondrial reactive oxygen species accumulation, decreased mitochondrial membrane potential, and lower ubiquinone biosynthesis. Whereas differentiated pyramidal neurons expressed high COQ4 levels, coq4 knockdown zebrafish displayed severe motor dysfunction, reflecting motor neuron dysregulation. CONCLUSIONS: Our study confirms that loss-of-function, compound heterozygous, pathogenic COQ4 variants are causal for autosomal recessive pure and complicated HSP. Moreover, reduced COQ4 levels attributable to variants correspond with decreased ubiquinone biosynthesis, impaired mitochondrial function, and higher phenotypic disease severity. © 2023 International Parkinson and Movement Disorder Society.

B-N Co-Doped Graphene: Stability and Catalytic Activity in Oxygen Reduction Reaction - A Theoretical Insight.

We systematically investigated the stable configurations and catalytic activity in the Oxygen Reduction Reaction (ORR) of graphene co-doped with boron and nitrogen (B-N) using first-principles methods. Compared to single B/N doping, co-doping with BN is energetically favored. We found that intermediate species of ORR process adsorb on boron atoms, which act as catalytic sites. The presence of neighboring nitrogen atoms around boron plays a crucial role in modulating the catalytic activity of boron. For the same adsorption configuration, the adsorption energy of the adsorbate increases with the number of neighboring nitrogen atoms around boron and generally correlates positively with the number of electrons gained by the adsorbate. Regarding the catalytic activity of ORR, excessively strong adsorption of adsorbates impedes their hydrogenation. The best substrates for ORR catalytic activity are B-N-graphene and N-B2-graphene, with the rate-determining step being the hydrogenation of *OO and overpotentials of 0.49 V and 0.54 V, respectively.

Identification of Key Genes and Related Drugs of Adrenocortical Carcinoma by Integrated Bioinformatics Analysis.

Adrenocortical carcinoma (ACC) is a malignant carcinoma with an extremely poor prognosis, and its pathogenesis remains to be understood to date, necessitating further investigation. This study aims to discover biomarkers and potential therapeutic agents for ACC through bioinformatics, enhancing clinical diagnosis and treatment strategies. Differentially expressed genes (DEGs) between ACC and normal adrenal cortex were screened out from the GSE19750 and GSE90713 datasets available in the GEO database. An online Venn diagram tool was utilized to identify the common DEGs between the two datasets. The identified DEGs were subjected to functional assessment, pathway enrichment, and identification of hub genes by performing the protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The differences in the expressions of hub genes between ACC and normal adrenal cortex were validated at the GEPIA2 website, and the association of these genes with the overall patient survival was also assessed. Finally, on the QuartataWeb website, drugs related to the identified hub genes were determined. A total of 114 DEGs, 10 hub genes, and 69 known drugs that could interact with these genes were identified. The GO and KEGG analyses revealed a close association of the identified DEGs with cellular signal transduction. The 10 hub genes identified were overexpressed in ACC, in addition to being significantly associated with adverse prognosis in ACC. Three genes and the associated known drugs were identified as potential targets for ACC treatment.

Cellular communication among smooth muscle cells: The role of membrane potential via connexins.

Communication via action potentials among neurons has been extensively studied. However, effective communication without action potentials is ubiquitous in biological systems, yet it has received much less attention in comparison. Multi-cellular communication among smooth muscles is crucial for regulating blood flow, for example. Understanding the mechanism of this non-action potential communication is critical in many cases, like synchronization of cellular activity, under normal and pathological conditions. In this paper, we employ a multi-scale asymptotic method to derive a macroscopic homogenized bidomain model from the microscopic electro-neutral (EN) model. This is achieved by considering different diffusion coefficients and incorporating nonlinear interface conditions. Subsequently, the homogenized macroscopic model is used to investigate communication in multi-cellular tissues. Our computational simulations reveal that the membrane potential of syncytia, formed by interconnected cells via connexins, plays a crucial role in propagating oscillations from one region to another, providing an effective means for fast cellular communication. Statement of Significance: In this study, we investigated cellular communication and ion transport in vascular smooth muscle cells, shedding light on their mechanisms under normal and abnormal conditions. Our research highlights the potential of mathematical models in understanding complex biological systems. We developed effective macroscale electro-neutral bi-domain ion transport models and examined their behavior in response to different stimuli. Our findings revealed the crucial role of connexinmediated membrane potential changes and demonstrated the effectiveness of cellular communication through syncytium membranes. Despite some limitations, our study provides valuable insights into these processes and emphasizes the importance of mathematical modeling in unraveling the complexities of cellular communication and ion transport.

Surgical procedure and recurrence of upper urinary tract stone: a national-wide study based on hospitalized patients.

PURPOSE: This study aimed to investigate the influence of surgical intervention on recurrence risk of upper urinary tract stone and compare the medical burden of various surgical procedures. METHODS: This study analyzed data from patients with upper urinary tract stone extracted from a national database of hospitalized patients in China, from January 2013 to December 2018. Surgical recurrence was defined as patients experience surgical procedures for upper urinary tract stone again with a time interval over 90 days. Associations of surgical procedures with surgical recurrence were evaluated by Cox regression. RESULTS: In total, 556,217 patients with upper urinary tract stone were included in the present analysis. The mean age of the population was 49.9 ± 13.1 years and 64.1% were men. During a median follow-up of 2.7 years (IQR 1.5-4.0 years), 23,012 patients (4.1%) had surgical recurrence with an incidence rate of 14.9 per 1000 person-years. Compared to patients receiving open surgery, ESWL (HR, 1.59; 95% CI 1.49-1.70), URS (HR, 1.38; 95% CI 1.31-1.45), and PCNL (HR, 1.11; 95% CI 1.06-1.18) showed a greater risk for surgical recurrence. Patients receiving ESWL had the shortest hospital stay length and the lowest cost among the 4 procedures. CONCLUSIONS: Compared with open surgery, ESWL, URS, and PCNL are associated with higher risks of surgical recurrence for upper urinary tract stone, while ESWL showed the least medical burden including both expenditure and hospital stay length. How to keep balance of intervention efficacy and medical expenditure is an important issue to be weighed cautiously in clinic practice and studied more in the future.

Nanoarchitectonics of Methyl and Aldehyde Group-Decorated SOD-Type Metal-Azolate Framework for SF6 Capture and Recovery.

Sulfur hexafluoride (SF6) is widely used as an insulating gas, being an etchant and contrast agent in the electrical, semiconductor, and medical industries. However, due to its long lifetime and high global warming potential in the atmosphere, SF6 must be carefully handled to prevent leakage during production and usage. Herein, we report a sod-net metal-azolate framework (MAF) named MAF-stu-111, which decorates methyl and aldehyde groups in the porous windows, showing high adsorption affinity for SF6 at low pressure. Stability tests, gas adsorption, and breakthrough experiments demonstrated that MAF-stu-111 possesses excellent water and chemical stability, fully reversible SF6 uptake, high SF6/N2 separation selectivity (10:90, 285.2), good reusability, and high SF6 recovery purity (99.03%). Theoretical calculations revealed that hydrogen atoms of methyl and aldehyde groups can form multiple hydrogen bonds with SF6 molecules, which ensure that SF6 molecules are firmly held within the MAF-stu-111 framework, playing a key role in the selective separation of SF6/N2.

A Triassic stem turtle with an edentulous beak.

The early evolution of turtles continues to be a contentious issue in vertebrate palaeontology. Recent reports have suggested that they are diapsids1-6, but the position of turtles within Diapsida is controversial7-12 and the sequence of acquisition of turtle synapomorphies remains unclear1-3. Here we describe a Triassic turtle from China that has a mixture of derived characters and plesiomorphic features. To our knowledge, it represents the earliest known stem turtle with an edentulous beak and a rigid puboischiadic plate. The discovery of this new form reveals a complex early history of turtles.

Structural basis of tolvaptan binding to the vasopressin V2 receptor.

The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.

Prediction of recurrence-related factors for patients with early-stage cervical cancer following radical hysterectomy and adjuvant radiotherapy.

OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.

Hsa_circ_0006260 Mediates Trophoblast Function by Fibronectin Type III Domains Containing Protein 5 via Interacting with miR-770-5p.

A series of studies have confirmed the relationship between circular RNAs (circRNAs) and metabolic diseases. Hsa_circ_0006260 has been reported to be lowly expressed in the placenta of gestational diabetes mellitus (GDM) patients, but the underlying mechanism and its biological functions remain obscure. Placental tissues were collected from 37 pregnant women with normal glucose tolerance (NGT) and 37 pregnant women with GDM. Expression changes of hsa_circ_0006260 in placentas and high glucose (HG)-stimulated HTR-8/SVneo cells were detected using real-time quantitative polymerase chain reaction. Cell viability and migration were determined by cell counting and transwell assays, respectively. Measurement of cytokines was done by enzyme-linked immunosorbent assay. Cell apoptosis was estimated by flow cytometry assay. The molecular mechanisms were identified using dual-luciferase reporter and RNA-binding protein immunoprecipitation assays. Hsa_circ_0006260 expression was remarkably lowered in GDM patient-derived placentas and HG-stimulated HTR-8/SVneo cells. Functionally, hsa_circ_0006260 overexpression weakened HG-mediated repression of HTR-8/SVneo cell viability and migration, as well as promotion of HTR-8/SVneo cell inflammatory response and apoptosis. Mechanistically, hsa_circ_0006260 functioned as a miR-770-5p decoy to mediate fibronectin type III domains containing protein 5 (FNDC5) expression. Ectopic expression of miR-770-5p weakened hsa_circ_0006260 overexpression-mediated repression of HG-induced HTR-8/SVneo cell dysfunction. Also, FNDC5 knockdown lessened miR-770-5p overexpression-mediated promotion of HG-induced HTR-8/SVneo cell dysfunction. Our findings manifested a novel mechanism by which hsa_circ_0006260 could lower HG-induced HTR-8/SVneo cell dysfunction by upregulating FNDC5 via binding to miR-770-5p, which shed new light on circRNA mediated GDM pathogenesis.

Circulating retinol and 25(OH)D contents and their association with symptoms in children with chronic tic disorders.

The present study measured serum levels of vitamin A (VA) and vitamin D (VD) in children with chronic tic disorders (CTD) and investigated their potential association with CTD and comorbidity of attention deficit hyperactivity disorder (ADHD) and the association of their co-insufficiencies or deficiencies with CTD symptoms. A total of 176 children (131 boys and 45 girls, median age of 9 years) with CTD were recruited as the CTD group. During the same period, 154 healthy children were selected as the healthy control (HC) cohort. Circulating retinol and 25-hydroxyvitamin D (25[OH]D) levels were measured for all participants using high-performance liquid chromatography (HPLC) and tandem mass spectrometry. The Yale Global Tic Severity Scale (YGTSS) was employed for the assessment of tic status and CTD impairment. The Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were used to evaluate comorbidity symptoms. CTD pediatric participants exhibited markedly diminished circulating retinol and 25(OH)D levels compared to HCs. Moreover, VA and VD deficiencies and their co-insufficiencies/deficiencies were more prevalent in CTD participants than HCs. Circulating 25(OH)D levels were inversely proportional to the YGTSS motor tic scores. YGTSS scores in CTD children with only VA or VD insufficiency or deficiency or with VA and VD co-insufficiency/deficiency did not differ from those in CTD children with normal VA and VD. CTD children with comorbid ADHD displayed reduced circulating retinol and 25(OH)D concentrations and elevated prevalence of VD deficiency compared to CTD participants without comorbid ADHD. Lower serum retinol content was intricately linked to the presence of elevated CTD and comorbid ADHD. VA and VD deficiencies and their co-insufficiencies/deficiencies were markedly enhanced in CTD pediatric participants compared to HCs. Lower VA concentration was linked to the presence of enhanced CTD and comorbid ADHD. Therefore, children with CTD, especially with comorbid ADHD, may be at a higher risk of VA or VD deficiency, which may prompt the clinicians to consider whether blood tests for VA and VD in CTD children would be helpful for clinical care.