A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system.

GREB1-like retinoic acid receptor coactivator (GREB1L) gene is associated with autosomal dominant renal hypodysplasia/aplasia 3 (RHDA3) and deafness, autosomal dominant 80 (DFNA80). Among the GREB1L variants reported, most of them are missense or frameshift, while no pathogenic synonymous variants have been recorded. Classical theory paid little attention to synonymous variants and classified it as nonpathogenic; however, recent studies suggest that the variants might be equally important. Here, we report a 7-year-old girl with new symptoms of clitoromegaly, uterovaginal, and ovarian agenesis as well as right kidney missing. A novel de novo GREB1L synonymous variant (NM_001142966: c.4731C>T, p.G1577=) was identified via whole exome sequencing. The variant was predicted to be disease-causing through in silico analysis and was classified as likely pathogenic. Minigene splicing assays confirmed a 6 bp deletion in mutant cDNA comparing with the wild type, leading to two amino acids lost in GREB1L protein. Secondary and tertiary structure modeling showed alterations in protein structure. Our finding reveals a novel GREB1L variant with a new phenotype of urogenital system and is the first to report a pathogenic synonymous variant in GREB1L which affects mRNA splicing, suggesting synonymous variants cannot be ignored in prenatal diagnosis and genetic counseling.

Improving Adversarial Robustness of ECG Classification Based on Lipschitz Constraints and Channel Activation Suppression.

Deep neural networks (DNNs) are increasingly important in the medical diagnosis of electrocardiogram (ECG) signals. However, research has shown that DNNs are highly vulnerable to adversarial examples, which can be created by carefully crafted perturbations. This vulnerability can lead to potential medical accidents. This poses new challenges for the application of DNNs in the medical diagnosis of ECG signals. This paper proposes a novel network Channel Activation Suppression with Lipschitz Constraints Net (CASLCNet), which employs the Channel-wise Activation Suppressing (CAS) strategy to dynamically adjust the contribution of different channels to the class prediction and uses the 1-Lipschitz's ℓ∞ distance network as a robust classifier to reduce the impact of adversarial perturbations on the model itself in order to increase the adversarial robustness of the model. The experimental results demonstrate that CASLCNet achieves ACCrobust scores of 91.03% and 83.01% when subjected to PGD attacks on the MIT-BIH and CPSC2018 datasets, respectively, which proves that the proposed method in this paper enhances the model's adversarial robustness while maintaining a high accuracy rate.

A High-Performance Anti-Noise Algorithm for Arrhythmia Recognition.

In recent years, the incidence of cardiac arrhythmias has been on the rise because of changes in lifestyle and the aging population. Electrocardiograms (ECGs) are widely used for the automated diagnosis of cardiac arrhythmias. However, existing models possess poor noise robustness and complex structures, limiting their effectiveness. To solve these problems, this paper proposes an arrhythmia recognition system with excellent anti-noise performance: a convolutionally optimized broad learning system (COBLS). In the proposed COBLS method, the signal is convolved with blind source separation using a signal analysis method based on high-order-statistic independent component analysis (ICA). The constructed feature matrix is further feature-extracted and dimensionally reduced using principal component analysis (PCA), which reveals the essence of the signal. The linear feature correlation between the data can be effectively reduced, and redundant attributes can be eliminated to obtain a low-dimensional feature matrix that retains the essential features of the classification model. Then, arrhythmia recognition is realized by combining this matrix with the broad learning system (BLS). Subsequently, the model was evaluated using the MIT-BIH arrhythmia database and the MIT-BIH noise stress test database. The outcomes of the experiments demonstrate exceptional performance, with impressive achievements in terms of the overall accuracy, overall precision, overall sensitivity, and overall F1-score. Specifically, the results indicate outstanding performance, with figures reaching 99.11% for the overall accuracy, 96.95% for the overall precision, 89.71% for the overall sensitivity, and 93.01% for the overall F1-score across all four classification experiments. The model proposed in this paper shows excellent performance, with 24 dB, 18 dB, and 12 dB signal-to-noise ratios.

Integration of ATAC-seq and RNA-seq identifies MX1-mediated AP-1 transcriptional regulation as a therapeutic target for Down syndrome.

BACKGROUND: Growing evidence has suggested that Type I Interferon (I-IFN) plays a potential role in the pathogenesis of Down Syndrome (DS). This work investigates the underlying function of MX1, an effector gene of I-IFN, in DS-associated transcriptional regulation and phenotypic modulation. METHODS: We performed assay for transposase-accessible chromatin with high-throughout sequencing (ATAC-seq) to explore the difference of chromatin accessibility between DS derived amniocytes (DSACs) and controls. We then combined the annotated differentially expressed genes (DEGs) and enriched transcriptional factors (TFs) targeting the promoter region from ATAC-seq results with the DEGs in RNA-seq, to identify key genes and pathways involved in alterations of biological processes and pathways in DS. RESULTS: Binding motif analysis showed a significant increase in chromatin accessibility of genes related to neural cell function, among others, in DSACs, which is primarily regulated by members of the activator protein-1 (AP-1) transcriptional factor family. Further studies indicated that MX Dynamin Like GTPase 1 (MX1), defined as one of the key effector genes of I-IFN, is a critical upstream regulator. Its overexpression induced expression of AP-1 TFs and mediated inflammatory response, thus leading to decreased cellular viability of DS cells. Moreover, treatment with specific AP-1 inhibitor T-5224 improved DS-associated phenotypes in DSACs. CONCLUSIONS: This study demonstrates that MX1-mediated AP-1 activation is partially responsible for cellular dysfunction of DS. T-5224 effectively ameliorated DS-associated phenotypes in DSACs, suggesting it as a potential treatment option for DS patients.

Effect of orthodontic treatment with premolar extractions on occlusal planes: A retrospective study.

OBJECTIVE: To figure out whether premolar extractions treatment would influence the cant of the occlusal planes and thus affect dentoskeletal patterns in patients with different types of malocclusions. MATERIALS AND METHODS: A total of 140 post-orthodontic treatment subjects (96 females, 44 males) were included in this study, and their lateral cephalograms and demographic information were collected and analysed. The patients were divided into extraction and non-extraction groups. The ANB, SNA, SNB, Wits, Facial Height Index (FHI), SN-MP, SN-AOP, SN-POP and AOP-POP angle were measured on the cephalograms. Other possible confounding factors were recorded. Data were analysed by univariate analysis, stratified analysis, multivariate analysis, and coefficient analysis. RESULTS: After treatment, the changes in the AOP-SN, POP-SN and AOP-POP angle were statistically different between the extraction and non-extraction groups. The results were consistent in different skeletal malocclusions and extent of crowding according to stratified analysis. After adjusting all confounding factors, the cant of the posterior occlusal plane was flattened further by 2.14 degrees in the extraction group than the non-extraction group after orthodontic treatment, and the AOP-SN and AOP-POP angle would further increase by 1.72 and 3.81 degrees, respectively. Although no significant differences were found between the two groups, the SNA, ANB, and Wits in the extraction group decreased more with increased counterclockwise rotation of the mandible. CONCLUSION: Compared to the non-extraction group, there were more increases in the AOP-SN and AOP-POP angle and more posterior flattening in patients with four premolar extractions despite different types of dentoskeletal malocclusion, which were correlated to the change of variables in sagittal and vertical dimensions such as Wits and FHI.

[Moisture content measurement model of whole package of Chinese medicinal materials based on microwave transmission technology].

In view of the relatively low representativeness of manual sampling inspection, and long time-consuming in oven detection of moisture content, which delayed the subsequent production period, this paper proposed a scheme for rapid moisture quantitative detection for Chinese medicinal materials by microwave transmission technology, and took 8 different types of Chinese medicinal mate-rials as examples to analyze the feasibility and reliability of the scheme for the detection results of moisture content of the whole package of Chinese medicine. In the experiment, the least square method was used to establish the measurement model of microwave absorption rate-moisture content for each kind of medicinal material. The results showed that the microwave transmission measurement of moisture content achieved high-precision measurement of the moisture content of Schisandrae Chinensis Fructus, Ziziphi Spinosae Semen, Poria, Pheretima, Lilii Bulbus, Scutellariae Radix, and Galli Gigerii Endothelium Corneum. The measurement model of Ziziphi Spinosae Semen had the highest accuracy, and the R~2 and root mean square error of the validation set were 0.951 5 and 0.15%, respectively. At the same time, this study found that the microwave absorption intensity of animal medicines including Pheretima and Galli Gigerii Endothelium Corneum was much weaker than that of plant medicines such as Schisandrae Chinensis Fructus, but there was also a good linear relationship between microwave absorption and moisture content, which proved the universality of this method. However, this method was not suitable for Phellodendri Chinensis Cortex because its package contained iron wire. For the whole package of medicinal materials with uniform density and no metal inside, the microwave transmission technology for moisture content measurement can be used to detect the moisture content, which is an effective alternative method to detect the moisture content of medicinal materials.

d-mannose attenuates lipopolysaccharide-induced osteolysis via CPT1A-Mediated lipid metabolic regulation in macrophages.

Inflammatory osteolysis is usually linked to the activation of proinflammatory macrophage and the consequent excessive osteoclast formation. Emerging evidence indicates that agents or drugs targeting lipid metabolism in macrophages might be potential in the prevention and treatment of osteolysis. d-mannose, as a natural-existed metabolic regulator, exerts strong effects on attenuating osteopenia and inflammation. However, whether d-mannose is therapeutically effective on osteolysis and whether a metabolic mechanism counts for the effect remain to be addressed. Here, by using an in vivo lipopolysaccharide (LPS)-induced inflammatory osteolysis mouse model as well as an in vitro LPS-induced inflammatory macrophage culture system, we show that d-mannose attenuates inflammatory osteolysis and inhibits excessive osteoclastogenesis by reversing the LPS-induced activation of proinflammatory macrophage. Mechanically, d-mannose recovers LPS-suppressed Cpt1a transcription and promotes lipid metabolism of macrophage. Treatment with etomoxir, an inhibitor of CPT1A, abolishes the effects of d-mannose on LPS-treated macrophage in vitro and eliminates its protection against osteolysis in vivo. Collectively, our results imply that d-mannose attenuates LPS-induced osteolysis by manipulating CPT1A-mediated lipid metabolism in macrophages. Our results disclose the unrecognized utilization of d-mannose as an effective intervention against inflammatory osteolysis and provide evidence to manage inflammatory scenarios by therapeutically targeting lipid metabolism in macrophage.

Methylmercury cytotoxicity and possible mechanisms in human trophoblastic HTR-8/SVneo cells.

Methylmercury (MeHg) exposure during pregnancy can lead to adverse outcomes, including miscarriage and intrauterine growth retardation. In this study, MeHg cytotoxicity and its mechanisms in HTR-8/SVneo cells were investigated. MeHg inhibited HTR-8/SVneo cell viability and severely disrupted the cellular submicrostructure, showing a time-dose effect relationship. After MeHg treatment, the reactive oxygen species levels, malondialdehyde content, and superoxide dismutase (SOD) and catalase activities in the HTR-8/SVneo cells increased significantly with increased MeHg concentration (P<0.05). Similarly, MeHg also induced HTR-8/SVneo cell apoptosis in a dose-dependent manner. The proportion of cells in G1 phase decreased with increasing MeHg concentration, while that in the S and G2/M phases gradually increased. Moreover, cell migration and invasion capacities gradually decreased with increasing MeHg concentration, showing a significant difference between the MeHg-treated and control groups. Genes related to oxidative stress (HSPA6, HSPA1A, Nrf2, SOD1, HO-1, NQO1, OSGIN1, and gPX1), cell cycle (P21 and CDC25A), apoptosis (CYCS and AIFM2), and migration and invasion (CXCL8, CXCL3, CLU, IL24, COL3A1, MAPT, and ITGA7) were differentially expressed in the MeHg-treated group, indicating MeHg toxicity and mechanism of action. This study will provide insights into the prevention and treatment of pregnancy-related diseases caused by MeHg.

Application of single-port video-assisted thoracoscope in treating thoracic oesophageal squamous cell carcinoma using McKeown approach.

OBJECTIVE: This study aims to investigate the feasibility of single-port video-assisted thoracoscope (SPVATS) in treating thoracic oesophageal squamous cell carcinoma (TESCC) using McKeown approach. MATERIALS AND METHODS: Totally 10 McKeown approach-based SPVATS surgeries (8 males and 2 females, aged 42-68 years) were carried out from January 2015 to December 2015 to treat TESCC, including one case in upper thoracic segment, 5 cases in median thoracic segment and 4 cases in inferior thoracic segment. All the cases were pathologically diagnosed as SCC pre-operatively. SPVATS was performed to free thoracic oesophagus and dissect the lymph nodes, and laparoscopy was performed to free stomach and to perform oesophagus-left gastric collum anastomosis. RESULTS: All the patients were successfully completed SPVATS, with average thoracic surgery time as 150 min, intra-operative blood loss as 30-260 ml (average 90 ml), and post-operative hospital stay as 9-16 days (average 12 days). CONCLUSIONS: SPVATS was technically feasible and safe in treating TESCC using McKeown approach, with less trauma and rapid post-operative recovery, and hence, it could be used as a new surgical option for McKeown approach-based TESCC treatment.

Viscoelastic behaviour and relaxation modes of one polyamic acid organogel studied by rheometers and dynamic light scattering.

A novel polyamic acid (PAA from BAPMPO-BPDA) organogel was synthesized and characterized via dynamic light scattering (DLS), a classical rheometer, and diffusion wave spectroscopy (DWS). In situ monitoring was performed using a classical rheometer to observe the formation of the PAA organogel. The rheological curves confirm the formation of the PAA gel network and the origin of hydrogen bonding from the -NH- group (donor) and P[double bond, length as m-dash]O group (acceptor). The autocorrelation functions of PAA under different conditions (pure gel, gel with NaNO3, gel with formamide) are measured via DLS, and different characteristic times are obtained via the CONTIN method. Three different relaxation modes of the PAA gel, i.e., fast, intermediate and slow modes, are observed. The fast and intermediate modes show a diffusive behaviour (τ ∼ q-2), whereas the slow mode did not. When enough formamide is added into the PAA gel, the fast mode disappears; addition of enough salt (NaNO3) leads to disappearance of the slow mode. The relationship between characteristic time and diffusion vector demonstrates that the different decorrelation modes consisted of two homodyne and two heterodyne components. Two single-exponential functions and two stretched exponential functions were used, and the different decorrelation modes of the PAA gel are expressed with a non-linear function, which fits the autocorrelation function very well. And the different decorrelation modes are also discussed. DWS results in the high-frequency region not only demonstrate the formation of a PAA gel network but also indicate that the semiflexible chains of PAA are due to electrostatic interaction. The DWS results at different time scales are analyzed by applying the de Gennes' reptation model.

[Experimental teaching reform of polymer molar mass determination using gel permeation chromatography coupled with light scattering].

Gel permeation chromatography coupled with light scattering (GPC-LS) is among the most common methods for determining the molar masses of polymers. GPC-LS is widely used in polymer science research and has been adopted for many industrial applications owing to its high sensitivity, accuracy, and precision. The determination of polymer molar masses using GPC-LS is an important experimental component of the "Polymer Physics Experiments" course. However, the present GPC-LS experimental teaching content tends to be overly simplistic and lacking in depth. Herein, the original experimental content is expanded and multiple sets of experiments are redesigned: (1) Using commercial polystyrene as an experimental sample, the molar mass, molar mass distribution, radius of gyration, and other molecular structure parameters are determined using GPC-LS; (2) Using two polyacrylonitriles with similar molecular structure parameters, subtle differences in the molar mass distributions of the samples are explored using differential mass distribution curves; (3) By comparing the chromatograms of a series of polyethylene glycols with different molar masses, the effect of molar mass on chromatographic peaks is investigated; and (4) For three different polymers (polyacrylonitrile, poly(methyl methacrylate), and poly(ß-cyclodextrin)), the polymer chain conformations are analyzed using conformation plots (i.e., radius of gyration vs. molar mass). In addition, the experimental teaching method is modified to convert passive learning into active learning, thereby improving the students' self-directed learning ability. This experimental teaching reform will help students obtain a more comprehensive understanding of GPC-LS principles and applications, stimulate their enthusiasm for learning, and improve the teaching quality of the experimental course.

Competing Endogenous RNAs Crosstalk in Hippocampus: A Potential Mechanism for Neuronal Developing Defects in Down Syndrome.

Down syndrome (DS) is the most example of aneuploidy, resulting from an additional copy of all or part of chromosome 21. Competing endogenous RNAs (ceRNAs) play important roles in neuronal development and neurological defects. This study aimed to identify hub genes and synergistic crosstalk among ceRNAs in the DS fetal hippocampus as potential targets for the treatment of DS-related neurodegenerative diseases. We profiled differentially expressed long non-coding RNAs (DElncRNAs), differentially expressed circular RNAs (DEcircRNAs), differentially expressed microRNAs (DEmiRNAs), and differentially expressed messenger RNAs (DEmRNAs) in hippocampal samples from patients with or without DS. Functional enrichment analysis and gene set enrichment analysis were performed, and chromosome 21-related ceRNA and protein-protein interaction networks were constructed. Additionally, the correlations between lncRNA-mRNA and miRNA-mRNA expression in the samples and HEK293T cells were validated. Our finding of changes in the expression of some key genes and ncRNAs on chromosome 21 in DS might not fully conform to the gene dosage hypothesis. Moreover, we found that four lncRNAs (MIR99AHG, PLCB4, SNHG14, GIGYF2) and one circRNA (hsa_circ_0061697) may competitively bind with three miRNAs (hsa-miR-548b-5p, miR-730-5p, and hsa-miR-548i) and subsequently regulate five mRNAs (beta-1,3-galactosyltransferase 5 [B3GALT5], helicase lymphoid-specific [HELLS], thrombospondin-2 [THBS2], glycinamide ribonucleotide transformylase [GART], clathrin heavy chain like 1 [CLTCL1]). These RNAs, whether located on chromosome 21 or not, interact with each other and might activate the PI3K/Akt/mTOR and Wnt signaling pathways, which are involved in autophagosome formation and tau hyperphosphorylation, possibly leading to adverse consequences of trisomy 21. These findings provide researchers with a better understanding of the fundamental molecular mechanisms underlying DS-related progressive defects in neuronal development.

SFXN1-mediated immune cell infiltration and tumorigenesis in lung adenocarcinoma: A potential therapeutic target.

BACKGROUND: Sideroflexin 1 (SFXN1), a mitochondrial serine transporter implicated in one-carbon metabolism, is a prognostic biomarker in lung adenocarcinoma (LUAD). However, its role in LUAD progression remains elusive. This study aimed to investigate the functional significance of SFXN1 in LUAD and evaluate its potential as a therapeutic target. METHODS: We analyzed SFXN1 expression and its diagnostic and prognostic value in LUAD using the Pan-cancer TCGA dataset. In vitro assays (CCK-8, cell cycle, EDU, wound-healing, and transwell) were employed to assess the role of SFXN1, complemented by in vivo experiments. RNA sequencing elucidated SFXN1-mediated cellular functions and potential mechanisms. Bulk RNA-seq and scRNA-seq data from TCGA and GEO were used to investigate the correlation between SFXN1 and the tumor immune microenvironment. RT-qPCR, Western blot, and IHC assays validated SFXN1 expression and its impact on the immune microenvironment in LUAD. RESULTS: SFXN1 was upregulated in LUAD tissues and associated with poor prognosis. RNA-seq and scRNA-seq analyses revealed increased SFXN1 expression in tumor cells, accompanied by decreased infiltration of NK and cytotoxic T cells. SFXN1 knockdown significantly reduced cell proliferation and migration, and the inhibition of ERK phosphorylation and CCL20 expression may be the molecular mechanism involved. In vivo, targeting SFXN1 decreased Tregs infiltration and inhibited tumor growth. CONCLUSIONS: Our findings suggest that SFXN1 may be a potential therapeutic target for LUAD treatment.

Transcriptome research of human amniocytes identifies hub genes associated with developmental dysplasia in down syndrome.

Trisomy 21, or Down syndrome (DS), is the most frequent human autosomal chromosome aneuploidy, which leads to multiple developmental disorders, especially mental retardation in individuals. The presence of an additional human chromosome 21 (HSA21) could account for the pathological manifestations in DS. In this study, we analyzed the mRNA gene expression profile of DS-derived amniocytes compared with normal amniocytes, aiming to evaluate the relationship between candidate dysregulated HSA21 genes and DS developmental phenotypes. Differentially expressed genes (DEGs) included 1794 upregulated genes and 1411 downregulated genes, which are mainly involved in cell adhesion, inflammation, cell proliferation and thus may play an important role in inducing multiple dysplasia during DS fetal development. Furthermore, STRING protein network studies demonstrated 7 candidate HSA21 genes participated Gene Ontology (GO) terms: cell adhesion and extracellular matrix remodeling (COL6A1, COL6A2, COL18A1, ADAMTS5, JAM2, and POFUT2), inflammation and virus infection response (MX1 and MX2), histone modification and chromatin remodeling (NRIP1), glycerolipid and glycerophospholipid metabolism (AGPAT3), mitochondrial function (ATP5PF and ATP5PO), synaptic vesicle endocytosis (ITSN1 and SYNJ1) and amyloid metabolism (APP). Meanwhile, GSEA enrichment identified several transcription factors and miRNAs, which may target gene expression in the DS group. Our study established connections between dysregulated genes, especially HSA21 genes, and DS-associated phenotypes. The alteration of multiple pathways and biological processes may contribute to DS developmental disorders, providing potential pathogenesis and therapeutic targets for DS.

Association between the severity of hypodontia and the characteristics of craniofacial morphology in a Chinese population: A cross-sectional study.

Objective: To investigate craniofacial differences in individuals with hypodontia and explore the relationship between craniofacial features and the number of congenitally missing teeth. Methods: A cross-sectional study was conducted among 261 Chinese patients (males, 124; females, 137; age, 7-24 years), divided into four groups (without hypodontia: no teeth missing, mild: one or two missing teeth, moderate: three to five missing teeth, severe: six or more missing teeth) according to the number of congenitally missing teeth. Differences in cephalometric measurements among the groups were analyzed. Further, multivariate linear regression and smooth curve fitting were performed to evaluate the relationship between the number of congenitally missing teeth and the cephalometric measurements. Results: In patients with hypodontia, SNA, NA-AP, FH-NA, ANB, Wits, ANS-Me/N-Me, GoGn-SN, UL-EP, and LL-EP significantly decreased, while Pog-NB, AB-NP, N-ANS, and S-Go/N-Me significantly increased. In multivariate linear regression analysis, SNB, Pog-NB, and S-Go/N-Me were positively related to the number of congenitally missing teeth. In contrast, NA-AP, FH-NA, ANB, Wits, N-Me, ANS-Me, ANS-Me/N-Me, GoGn-SN, SGn-FH (Y-axis), UL-EP, and LL-EP were negatively related, with absolute values of regression coefficients ranging from 0.147 to 0.357. Further, NA-AP, Pog-NB, S-Go/N-Me, and GoGn-SN showed the same tendency in both sexes, whereas UL-EP and LL-EP were different. Conclusions: Compared with controls, patients with hypodontia tend toward a Class III skeletal relationship, reduced lower anterior face height, flatter mandibular plane, and more retrusive lips. The number of congenitally missing teeth had a greater effect on certain characteristics of craniofacial morphology in males than in females.

College Students with Oral Habits Exhibit Worse Psychological Status and Temporomandibular-Related Quality of Life: A Correlational Study.

Purpose: To evaluate the relationship between oral habits, psychological status, and temporomandibular-related quality of life among college students. Materials and Methods: An online questionnaire was sent to college students who were willing to participate in this anonymous survey, which contained questions about the demographic characteristics of the participants, the Patient Health Questionnaire for Depression and Anxiety (PHQ-4), the Fonseca Anamnestic Index (FAI), and the Oral Health Impact Profile for temporomandibular disorders (OHIP-TMDs). Results: A total of 505 valid questionnaires were collected from 200 males and 305 females (a mean age of 21.81 ± 2.81 years). The prevalence of oral habits in college students was 58% (294/505). Female gender (odds ratio (OR) 1.786) and having oral habits (OR 1.893) were associated with depression and anxiety. Medical students had significantly less depression and anxiety (OR 0.459) than nonmedical students. The possibility of suffering from temporomandibular disorder (TMDs) as evidenced by the OHIP-TMDs score was associated with female gender (OR 1.989) and having oral habits (OR 3.482). Students with oral habits had higher OHIP-TMDs scores. Conclusion: More than half of the college students surveyed had specific oral habits, with a higher prevalence in women than in men. Having oral habits was related to a worse psychological status, higher risk of TMD, and worse temporomandibular-related quality of life.

A network-based pharmacological study on the mechanism of action of muscone in breast cancer.

Background: The purpose of this study was to investigate the mechanism of action of muscone on breast cancer using network pharmacology and molecular docking techniques. Methods: Targets of muscone acid action were collected using the PubChem and SwissTargetPrediction databases. Relevant target sets of breast cancer were collected using the GeneCards database, and the intersection of the drug-disease targets was used as the potential target of muscone action in breast cancer. The STRING database was used to construct a target protein-protein interaction (PPI) network, and the data were imported into Cytoscape 3.7.1 for topological network analysis to obtain the core target genes of muscone in breast cancer. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. The correlation of core gene expression with breast cancer survival was analyzed using the online Kaplan-Meier plotter tool. Molecular docking of core target genes to muscone was performed using AutoDock Vina. Results: A total of 18 common targets of muscone and breast cancer were obtained through target intersection. The PPI map and topology analysis revealed that androgen receptor (AR), progesterone receptor (PGR), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2), heat shock protein 90 alpha family class A member 1 (HSP90AA1), mitogen-activated protein kinase 14 (MAPK14), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) might be the key targets of muscone acting on breast cancer. The GO enrichment analysis identified 60 terms, while the KEGG pathway enrichment analysis identified 7 signaling pathways, including steroid hormone biosynthesis, ovarian steroidogenesis, cancer pathways, and the tumor necrosis factor (TNF) signaling pathway. The results of survival stage analysis showed that the binding activity between muskone and key targets was better than other targets. The molecular docking results showed that muscone had the highest docking affinity for the key target CYP19A1 gene at -7.0 kJ/moL. Conclusions: Muscone might exert anti-breast cancer effects through cancer pathways, ovarian steroidogenesis, and TNF signaling pathways and has the potential to be developed as a clinical agent.

Customized maxillary incisor position relative to dentoskeletal and soft tissue patterns in Chinese women: A retrospective study.

Objective: To provide reliable prediction models based on dentoskeletal and soft tissue variables for customizing maxillary incisor positions and to optimize digitalized orthodontic treatment planning. Methods: This study included 244 Chinese women (age, 18-40 years old) with esthetic profiles after orthodontic treatment with fixed appliances (133 in group I: 1° ≤ The angle between the nasion [N]-A point [A] plane and the N-B point [B] plane [ANB] ≤ 4°; 111 in group II: 4° < ANB ≤ 7°). Dental, skeletal, and soft tissue measurements were performed on lateral cephalograms of the participants. Correlation and multiple linear regression analyses were used to determine the influence of dentoskeletal and soft tissue variables on maxillary incisor position. Results: The ideal anteroposterior position of the maxillary incisor varied between sagittal skeletal patterns. The position of the maxillary incisor correlated with the sagittal discrepancy between the maxilla and the mandible (ANB), protrusion of the midface, nasal tip projection, development of the chin, and inclination of both the maxillary and mandibular incisors. Distance from the maxillary central incisor to nasion-pogonion plane predicted using multiple linear regression analysis was accurate and could be a practical measurement in orthodontic treatment planning. Conclusions: Instead of using an average value or norm, orthodontists should customize a patient's ideal maxillary incisor position using dentoskeletal and soft tissue evaluations.

Gli1+ Mesenchymal Stem Cells in Bone and Teeth.

Mesenchymal stem cells (MSCs) are remarkable and noteworthy. Identification of markers for MSCs enables the study of their niche in vivo. It has been identified that glioma-associated oncogene 1 positive (Gli1+) cells are mesenchymal stem cells supporting homeostasis and injury repair, especially in the skeletal system and teeth. This review outlines the role of Gli1+ cells as MSC subpopulation in both bones and teeth, suggesting the prospects of Gli1 an + cells in stem cell- based tissue engineering.