Quantification of MicroRNA in a Single Living Cell via Ionic Current Rectification-Based Nanopore for Triple Negative Breast Cancer Diagnosis.

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA). Benefiting from the enzyme-free CHA amplification strategy, the detection limit of the nanopore sensor for miRNA-155 reaches 10 fM and the nanopore sensor is more adaptable to complex intracellular environments. With the nanopore sensor, the concentration of miRNA-155 in living single cells is quantified to realize the early diagnosis of triple-negative breast cancer (TNBC). Furthermore, the nanopore sensor can be applied in screening anticancer drugs by tracking the expression level of miRNA-155. This work provides an adaptive and universal method for quantitatively analyzing intracellular miRNAs, which will greatly improve our understanding of cell heterogeneity and provide a more reliable scientific basis for exploring major diseases at the single-cell level.

Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant.

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2+-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

A nonsense CC2D1A variant is associated with congenital anomalies, motor delay, hypotonia, and slight deformities.

Background: Autosomal recessive intellectual developmental disorder-3 is caused by homozygous or compound heterozygous mutations in the CC2D1A gene. The disorder is characterized by intellectual disability (ID) and autism spectrum disorder (ASD). To date, 39 patients from 17 families with CC2D1A -related disorders have been reported worldwide, in whom only six pathogenic or likely pathogenic loss-of-function variants and three variants of uncertain significance (VUS) in the CC2D1A gene have been identified in these patients. Methods: We described a patient with ID from a non-consanguineous Chinese family and whole-exome sequencing (WES) was used to identify the causative gene. Results: The patient presented with severe ID and ASD, speech impairment, motor delay, hypotonia, slight facial anomalies, and finger deformities. Threatened abortion and abnormal fetal movements occurred during pregnancy with the proband but not his older healthy sister. WES analysis identified a homozygous nonsense variant, c.736C > T (p.Gln246Ter), in the CC2D1A gene. In addition, six novel likely pathogenic CC2D1A variants were identified by a retrospective review of the in-house database. Conclusions: This study expands the genetic and clinical spectra of CC2D1A-associated disorders, and may aid in increasing awareness of this rare condition. Our findings have provided new insights into the clinical heterogeneity of the disease and further phenotype-genotype correlation, which could help to offer scope for more accurate genetic testing and counseling to affected families.

Local knowledge of homegarden plants in Miao ethnic communities in Laershan region, Xiangxi area, China.

BACKGROUND: Homegardens are small-scale land use systems with significant implications for local livelihoods, biodiversity conservation, and sustainable development due to their diverse flora and fauna. Conducting homegarden surveys enables researchers to gain insights into the traditional ecological knowledge of indigenous communities, preserve homegarden biodiversity, and promote sustainable livelihoods. This study has two objectives: first, to collect, record, and organize data on homegarden plants and related traditional knowledge from three communities in the Laershan Plateau, and second, to analyze the species and functional diversity of homegarden plants in the region while exploring the factors that contribute to the heterogeneous distribution of these plants among the communities of three townships. METHODS: This research employed field surveys in the Laershan Miao Autonomous Region in Xiangxi, China, from September 2021 to August 2023. Data were collected through observation and semi-structured interviews. The study utilized descriptive statistics and quantitative analysis, including the Relative Importance Value (RI), Use Value Index (UV), Jaccard Index (JI), and Comprehensive Index of Land Use Degree (La), to examine the diversity of local homegarden plants and related traditional knowledge, as well as community heterogeneity. RESULTS: The study area exhibited rich biodiversity, with 152 plant species recorded belonging to 62 families and 124 genera. These findings highlight the importance of homegarden plants in maintaining ecological balance and enhancing system resilience against disturbances. Homegarden plants serve multiple functions such as food, ornamental, medicinal, and fodder purposes, with edible and trade plants having the most abundant knowledge. Furthermore, this research revealed that communities with similar forest resource compositions may have similar homegarden plant compositions, demonstrating the connection between cultural exchange among different communities and patterns of plant species distribution. CONCLUSIONS: The Laershan region boasts diverse homegarden plant species crucial for ecological balance and resilience. Their multifunctionality reflects human impact. Plant diversity varies with residents' lifestyles, needs, and cultural exchanges. The close connection between plants and local life is clear. Factors like resource distribution, cultural exchange, and lifestyle influence plant distribution. Further research is needed for conservation and sustainable development. Future research should focus on culturally valuable plant species and traditional knowledge applications.

Advances in Monte Carlo Method for Simulating the Electrical Percolation Behavior of Conductive Polymer Composites with a Carbon-Based Filling.

Conductive polymer composites (CPCs) filled with carbon-based materials are widely used in the fields of antistatic, electromagnetic interference shielding, and wearable electronic devices. The conductivity of CPCs with a carbon-based filling is reflected by their electrical percolation behavior and is the focus of research in this field. Compared to experimental methods, Monte Carlo simulations can predict the conductivity and analyze the factors affecting the conductivity from a microscopic perspective, which greatly reduces the number of experiments and provides a basis for structural design of conductive polymers. This review focuses on Monte Carlo models of CPCs with a carbon-based filling. First, the theoretical basis of the model's construction is introduced, and a Monte Carlo simulation of the electrical percolation behaviors of spherical-, rod-, disk-, and hybridfilled polymers and the analysis of the factors influencing the electrical percolation behavior from a microscopic point of view are summarized. In addition, the paper summarizes the progress of polymer piezoresistive models and polymer foaming structure models that are more relevant to practical applications; finally, we discuss the shortcomings and future research trends of existing Monte Carlo models of CPCs with carbon-based fillings.

Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration.

Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis. Methods: Small non-coding RNA sequencing and quantitative polymerase chain reaction were conducted to detect expression pattern of tRF-Glu-CTC in CNV development. Immunofluorescence staining, fundus fluorescein angiography and ex vivo choroidal sprouting assays were employed for the evaluation of tRF-Glu-CTC's function in CNV development. The role of tRF-Glu-CTC in endothelial cells were determined by in vitro endothelial cell proliferation, migration and tube formation assays. Transcriptome sequencing, dual-luciferase reporter assay and in vitro experiments were conducted to investigate downstream mechanism of tRF-Glu-CTC mediated pathology. Results: tRF-Glu-CTC exhibited substantial up-regulation in AMD patients, laser-induced CNV model, and endothelial cells under hypoxia condition, which is a hallmark of CNV. Inhibiting tRF-Glu-CTC reduced angiogenesis and hypoxia stress in the neovascular region without neuroretina toxicity in laser-induced CNV model, showing an anti-angiogenic effect comparable to bevacizumab, while overexpression of tRF-Glu-CTC significantly augmented CNV. Mechanically, under hypoxia condition, angiogenin was involved in the production of tRF-Glu-CTC, which in turn triggered endothelial cell tubulogenesis, migration and promoted the secretion of inflammatory factors via the suppression of vasohibin 1 (VASH1). When downregulating VASH1 expression, the inhibition of tRF-Glu-CTC showed minimal suppression on angiogenesis. Conclusions: This study demonstrated the important role of tRF-Glu-CTC in the progression of angiogenesis. Targeting of tRF-Glu-CTC may be an alternative to current anti-VEGF therapy for CNV in AMD and other conditions with angiogenesis.

Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.

BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein. METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing. RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome. CONCLUSION: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.

Insights into the time-course cellular effects triggered by iron oxide nanoparticles by combining proteomics with the traditional pharmacology strategy.

In recent years, a number of initially approved magnetic iron oxide nanoparticle (IONP)-based nano-medicines have been withdrawn due to the obscure nano-bio effects. Therefore, there is an urgent need to study the cellular effects triggered by IONPs on cells. In this study, we investigate the time-course cellular effects on the response of RAW 264.7 cells caused by Si-IONPs via pharmacological and mass spectrometry-based proteomics techniques. Our results revealed that Si-IONPs were internalized by clathrin-mediated endocytosis within 1 hour, and gradually degraded in endolysosomes over time, which might influence autophagy, oxidative stress, innate immune response, and inflammatory response after 12 hours. Our research provides a necessary assessment of Si-IONPs for further clinical treatment.

Novel germline variants in KMT2C in Chinese patients with Kleefstra syndrome-2.

Kleefstra syndrome (KLEFS) refers to a rare inherited neurodevelopmental disorder characterized by intellectual disability (ID), language and motor delays, behavioral abnormalities, abnormal facial appearance, and other variable clinical features. KLEFS is subdivided into two subtypes: Kleefstra syndrome-1 (KLEFS1, OMIM: 610253), caused by a heterozygous microdeletion encompassing the Euchromatic Histone Lysine Methyltransferase 1 (EHMT1) gene on chromosome 9q34.3 or pathogenic variants in the EHMT1 gene, and Kleefstra syndrome-2 (KLEFS2, OMIM: 617768), caused by pathogenic variants in the KMT2C gene. More than 100 cases of KLEFS1 have been reported with pathogenic variants in the EHMT1 gene. However, only 13 patients with KLEFS2 have been reported to date. In the present study, five unrelated Chinese patients were diagnosed with KLEFS2 caused by KMT2C variants through whole-exome sequencing (WES). We identified five different variants of the KMT2C gene in these patients: c.9166C>T (p.Gln3056*), c.9232_9247delCAGCGATCAGAACCGT (p.Gln3078fs*13), c.5068dupA (p.Arg1690fs*10), c.10815_10819delAAGAA (p.Lys3605fs*7), and c.6911_6912insA (p.Met2304fs*8). All five patients had a clinical profile similar to that of patients with KLEFS2. To analyze the correlation between the genotype and phenotype of KLEFS2, we examined 18 variants and their associated phenotypes in 18 patients with KLEFS2. Patients carrying KMT2C variants presented with a wide range of phenotypic defects and an extremely variable phenotype. We concluded that the core phenotypes associated with KMT2C variants were intellectual disability, facial dysmorphisms, language and motor delays, behavioral abnormalities, hypotonia, short stature, and weight loss. Additionally, sex may be one factor influencing the outcome. Our findings expand the phenotypic and genetic spectrum of KLEFS2 and help to clarify the genotype-phenotype correlation.

Circulating miR-320b Contributes to CD4+ T-Cell Proliferation in Systemic Lupus Erythematosus via MAP3K1.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies and tissue inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising candidate therapy for SLE owing to the immunomodulatory and regenerative properties. Circulating miRNAs are small, single-stranded noncoding RNAs in a variety of body fluids that regulate numerous immunologic and inflammatory pathways. Recent studies have revealed many differentially expressed circulating miRNAs in autoimmune diseases including SLE. However, the role of circulating miRNAs in SLE has not been extensively studied. Here, we performed small RNA sequencing analysis to compare the circulating miRNA profiles of SLE patients before and after MSC transplantation (MSCT), and identified a significant decrease of circulating miR-320b level during MSCT. Importantly, we found that the expression of circulating miR-320b and its target gene MAP3K1 was closely associated with SLE disease activity. The in vitro experiments showed that decreased MAP3K1 level in SLE peripheral blood mononuclear cells (PBMCs) was involved in CD4+ T-cell proliferation. In MRL/lpr mice, miR-320b overexpression aggravated symptoms of SLE, while miR-320b inhibition could promote disease remission. Besides, MSCs regulate miR-320b/MAP3K1 expression both in vitro and in vivo. Our results suggested that circulating miR-320b and MAP3K1 may be involved in CD4+ T-cell proliferation in SLE. This trial is registered with NCT01741857.

Threefold coordinated germanium in a GeO2 melt.

The local structure around germanium is a fundamental issue in material science and geochemistry. In the prevailing viewpoint, germanium in GeO2 melt is coordinated by at least four oxygen atoms. However, the viewpoint has been debated for decades due to several unexplained bands present in the GeO2 melt Raman spectra. Using in situ Raman spectroscopy and density functional theory (DFT) computation, we have found a [GeOØ2]n (Ø = bridging oxygen) chain structure in a GeO2 melt. In this structure, the germanium atom is coordinated by three oxygen atoms and interacts weakly with two neighbouring non-bridging oxygen atoms. The bonding nature of the chain has been analyzed on the basis of the computational electronic structure. The results may settle down the longstanding debate on the GeO2 melt structure and modify our view on germanate chemistry.

Repositioning of Montelukast to inhibit proliferation of mutated KRAS pancreatic cancer through a novel mechanism that interfere the binding between KRAS and GTP/GDP.

Pancreatic cancer is one of the most lethal cancer types with 5-year survival rate of ∼10.8%. Various KRAS mutations exist in ∼85% pancreatic cancer cell lines. Mutated KRAS is a major cause that leads cancer cell proliferation. Chemotherapy is still the major treatment for pancreatic cancer. Alternatively, repositioning old drug to inhibit mutated KRAS may be a cost-effective way for pancreatic cancer treatment. In this study, we choose mutated KRAS (G12D) as a target. Based on mutated KRAS GTP binding domain (hydrolyze GTP to GDP), we perform virtual screening on FDA-approved drugs. Montelukast shows strong binding affinity to mutated KRAS as well as interfering both GTP and GDP binding to mutated KRAS. Furthermore, Montelukast shows very strong anti-proliferation effect on mutated KRAS pancreatic cancer cells both in vitro and in vivo. Our results support repositioning of Montelukast as single agent for pancreatic cancer treatment.

Celastrol induces premature ovarian insufficiency by inducing apoptosis in granulosa cells.

Celastrol, a natural compound purified from the Chinese herb Tripterygium wilfordii Hook. f., has excellent pharmacological activity for the treatment of various diseases. Assessing the safety of its use is essential for its development into a clinical medicine. However, research assessing its toxicity on the female reproductive system has never been reported. In this study, the ovarian toxicity of celastrol and its underlying mechanism were investigated. We found that celastrol induced premature ovarian insufficiency and apoptosis in granulosa cells. Activity-based protein profiling results showed that high mobility group box 1 was a candidate target protein of celastrol. Celastrol directly bound to Cys106 of high mobility group box 1. Knocking down high mobility group box 1 induced apoptosis of granulosa cells, while overexpression of this gene reversed celastrol-induced apoptosis. Celastrol treatment upregulated p21 transcription, but overexpression of high mobility group box 1 reversed this upregulation. Thus, Celastrol induces premature ovarian insufficiency and apoptosis in granulosa cells by directly binding to high mobility group box 1 and interfering with its biological function to regulate p21 transcription. This study provides valuable information for assessing the safety of the clinical application of celastrol on female patients.

Interleukin-41 as a biomarker of the anti-inflammatory response associated with hyperuricemia.

BACKGROUND: Interleukin (IL)-41 is a recently discovered secreted protein that is expressed in a variety of tissues, and it is associated with several immune and metabolic diseases. However, IL-41 has not been studied in hyperuricemia (HUA). METHODS: Forty-four HUA patients and 44 healthy controls (HCs) were included in this study, and we collected theirgeneral and biochemical parameters, including white blood cell, neutrophil, lymphocyte, and platelet counts, mean platelet volume, platelet distribution width, serum creatinine, blood urea nitrogen, fasting blood glucose, total triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, total protein, albumin, alkaline phosphatase, gamma-glutamyltransferase, and hemoglobin concentration. The level of serum IL-41 was determined using an enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was exploited to identify the independent risk factors associated with HUA, and the clinical diagnostic value of IL-41 was analyzed by applying the receiver operating characteristic (ROC) curve. We assessed the association between IL-41 and clinical parameters with Spearman's rank correlation. RESULTS: Circulating IL-41 levels were significantly higher in HUA patients than in the HCs group (460.3 pg/mL vs. 261.3 pg/mL, respectively; P < 0.001). The area under the ROC curve (AUC) for IL-41 in HUA patients was 0.7443 (with a cut-off value of 311.055 pg/mL, a sensitivity of 68.18 %, and a specificity of 72.73 %), while the AUC for IL-41 combined with the platelet count was 0.8109. Correlation analysis revealed that the circulating IL-41 level was positively correlated with age in HCs and HUA patients. CONCLUSIONS: We herein demonstrated that serum IL-41 was elevated in HUA patients and that it may constitute a novel biomarker of anti-inflammatory response related to HUA.

Who can help me? Understanding the antecedent and consequence of medical information seeking behavior in the era of bigdata.

Introduction: The advent of bigdata era fundamentally transformed the nature of medical information seeking and the traditional binary medical relationship. Weaving stress coping theory and information processing theory, we developed an integrative perspective on information seeking behavior and explored the antecedent and consequence of such behavior. Methods: Data were collected from 573 women suffering from infertility who was seeking assisted reproductive technology treatment in China. We used AMOS 22.0 and the PROCESS macro in SPSS 25.0 software to test our model. Results: Our findings demonstrated that patients' satisfaction with information received from the physicians negatively predicted their behavior involvement in information seeking, such behavior positively related to their perceived information overload, and the latter negatively related to patient-physician relationship quality. Further findings showed that medical information seeking behavior and perceived information overload would serially mediate the impacts of satisfaction with information received from physicians on patient-physician relationship quality. Discussion: This study extends knowledge of information seeking behavior by proposing an integrative model and expands the application of stress coping theory and information processing theory. Additionally, it provides valuable implications for patients, physicians and public health information service providers.

Clinical and molecular analysis of Guangxi patients with Kabuki syndrome and KMT2D mutations.

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome that is characterized by postnatal growth deficiency, hypotonia, short stature, mild-to-moderate intellectual disability, skeletal abnormalities, persistence of fetal fingertip pads, and distinct facial appearance. It is mainly caused by pathogenic/likely pathogenic variants in the KMT2D or KDM6A genes. Here, we described the clinical features of nine sporadic KS patients with considerable phenotypic heterogeneity. In addition to intellectual disability and short stature, our patients presented with a high prevalence of motor retardation and recurrent otitis media. We recommended that KS should be strongly considered in patients with motor delay, short stature, intellectual disability, language disorder and facial deformities. Nine KMT2D variants, four of which were novel, were identified by whole-exome sequencing. The variants included five nonsense variants, two frameshift variants, one missense variant, and one non-canonical splice site variant. In addition, we reviewed the mutation types of the pathogenic KMT2D variants in the ClinVar database. We also indicated that effective mRNA analysis, using biological materials from patients, is helpful in classifying the pathogenicity of atypical splice site variants. Pedigree segregation analysis may also provide valuable information for pathogenicity classification of novel missense variants. These findings extended the mutation spectrum of KMT2D and provided new insights into the understanding of genotype-phenotype correlations, which are helpful for accurate genetic counseling and treatment optimization.

Genetic Basis of Congenital Central Hypothyroidism in Children: Expanding the Mutational Spectrum of POU1F1 and ATP6V0A4.

Objective: Congenital central hypothyroidism (CCH) is a rare disorder poorly described in childhood and adolescence. The current knowledge on the genetic bases of CCH is scarce. The purpose of this study was to analyze the clinical characteristics and molecular genetic basis of CCH in children. Methods: We conducted a thorough evaluation of the clinical features in children diagnosed with CCH. Genomic DNA was extracted from peripheral blood of both children and their parents, and chromosomal microarray analysis and whole-exome sequencing were performed. Candidates for single nucleotide variants were validated using Sanger sequencing and were classified according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines. Results: Two cases with likely pathogenic variants were detected by whole-exome sequencing. Individual 1 carried a novel homozygous ATP6V0A4 c.1418C>T (p.Ser473Phe) variant and a novel heterozygous POU1F1 c.416G>A. (p.Arg139Gln) variant. Individual 2 had a novel homozygous POU1F1 c.212C>T (p.Ala71Val) variant. The chromosomal microarray detected the presence of a 24 Mb heterozygous deletion (LOH: loss of heterozygosity) in the p12.1p13.13 region of chromosome 2 in individual 3, and the copy number variant was unknown of clinical significance. Conclusion: Our study employed chromosomal microarray and whole-exome sequencing to investigate central hypothyroidism in seven children, leading to the detection of genetic anomalies in three individuals. The identification of novel variants has contributed to the expanded genetic spectrum of POU1F1 and ATP6V0A4 associated with pediatric central hypothyroidism.

Chemoproteomics reveals Sofalcone inhibits the inflammatory response of Caco-2 cells by covalently targeting HMGB1.

Sofalcone (Sof), a synthetic analog of sophoradin, is a type of natural phenol derived from the traditional medicinal herb Sophora subprostrata, with potent anti-inflammatory activity. However, the mechanisms of action of Sof for treating intestinal-associated inflammation are not well known. In this work, we identified high mobility group box 1 (HMGB1) as the key covalent target of Sof for the anti-inflammatory activity in the human colonic epithelial cells through quantitative chemoproteomics profiling.

The Adsorption Mechanism of Hydrogen on FeO Crystal Surfaces: A Density Functional Theory Study.

The hydrogen-based direct reduction of iron ores is a disruptive routine used to mitigate the large amount of CO2 emissions produced by the steel industry. The reduction of iron oxides by H2 involves a variety of physicochemical phenomena from macroscopic to atomistic scales. Particularly at the atomistic scale, the underlying mechanisms of the interaction of hydrogen and iron oxides is not yet fully understood. In this study, density functional theory (DFT) was employed to investigate the adsorption behavior of hydrogen atoms and H2 on different crystal FeO surfaces to gain a fundamental understanding of the associated interfacial adsorption mechanisms. It was found that H2 molecules tend to be physically adsorbed on the top site of Fe atoms, while Fe atoms on the FeO surface act as active sites to catalyze H2 dissociation. The dissociated H atoms were found to prefer to be chemically bonded with surface O atoms. These results provide a new insight into the catalytic effect of the studied FeO surfaces, by showing that both Fe (catalytic site) and O (binding site) atoms contribute to the interaction between H2 and FeO surfaces.

Preliminary studies on intimal injury related to stent retrieval in a canine model.

OBJECTIVE: This pilot study aimed to observe intimal injuries related to stent retrieval in the iliac artery of a canine. BACKGROUND: In-stent restenosis remains challenging owing to permanent stent implantation. A retrievable stent may be alternative for intervention without permanent residue. METHODS: Five retrievable stents with point-to-point overlapped double-layer scaffolds were deployed into the iliac arteries and retrieved on days 14, 21, 28, 35, and 42 from five canines. RESULTS: Arterial diameter decreased by 9-10% before retrieval and 15% on day 14 after retrieval. In the 14-day-stent, the stent surface was clean without visible fibrin. In the 28-day-stent, the overlay was mainly composed of fibrin and fibroblasts. The proliferation of smooth muscle cells has not yet been observed with α-smooth muscle actin staining. In the 42-day-stent, endothelial and smooth muscle cells decreased under the struts, and the internal elastic lamina was interrupted segmentally. Neointima formation involves fibroblasts and smooth muscle cells. Neointimal thickness was negatively correlated with strut space. Stent traces on the artery wall tended to be flat at a follow-up14 days after retrieval. The primary intima was completely covered by neointima. Two stents could not be retrieved because of in-stent thrombosis or capture loss. CONCLUSIONS: The stent was covered mainly by depositional fibrin after 28 days and by typical neointima after 42 days. The stent retrieval procedure did not induce injury to vascular smooth muscle, and the intima repair was performed 14 days after stent retrieval.