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.

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.

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.

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.

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.

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.

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.

Superhydrophobic conductive rubber band with synergistic dual conductive layer for wide-range sensitive strain sensor.

Wearable electronic devices have received increasing interests because of their excellent flexibility, stretchability, and human friendliness. As the core components, flexible strain sensors integrated with wide working range, high sensitivity, and environment stability, especially in moisture or corrosive environments, remain a huge challenge. Herein, synergistic carbon nanotubes (CNTs)/reduced graphene oxide (rGO) dual conductive layer decorated elastic rubber band (RB) was successfully developed and treated with hydrophobic fumed silica (Hf-SiO2) for preparing superhydrophobic strain sensor. As expected, stable entangled CNTs layer and ultrasensitive microcracked rGO layer endow the sensor with extremely low detection limit (0.1%), high sensitivity (gauge factor is 685.3 at 482% strain), wide workable strain range (0-482%), fast response/recovery (200 ms/200 ms) and favorable reliability and reproducibility over 1000 cycles. Besides, the constructed Hf-SiO2 coating also makes the sensor exhibit excellent superhydrophobicity, self-cleaning property, and corrosion-resistance. As a proof of concept, our prepared high-performance strain sensor can realize the full-range monitoring of human motions and physiological signals even in the water environment, including pulse, vocalization, joint bending, running, and gesture recognition. Interestingly, it can also be knitted into a tactile electronic textile for spatial pressure distribution measurement. Thus, this study provides a universal technique for the preparation of high-performance strain sensors with great potential applications in the field of next-generation intelligent wearable electronics.

Nonlinear Relationship between Temporomandibular Joint Disc Displacement Distance and Disc Length: A Magnetic Resonance Imaging Analysis.

Objective: to explore the association between the distance of disc displacement and disc morphology in patients with temporomandibular disorders (TMDs). Methods: a total of 717 joints in 473 subjects were enrolled in this cross-sectional study. The magnetic resonance imaging (MRI) of each patient was evaluated for temporomandibular joint (TMJ) disc morphology classification and position. The distance of the disc displacement and disc length were measured for smoothing spline prediction. A stratified analysis was performed based on the types of disc positions. The disc width and length-width ratio (L/W) were also measured. Descriptive statistics, one-way analysis of variance, smoothing spline analysis, threshold analysis, and two piecewise linear regression were performed to investigate the association between the displacement distance and length of discs. Results: the differences in displacement distance among morphological categories and among different disc positions were statistically significant. Nonlinear relationships were found between distance and length in all subjects. Two turning points of distance (−1.8 mm and 1.7 mm) were found, dividing the curve into three segments. Disc width and L/W were significantly different among discs in the three segments of the curve. The correlation coefficient (ß) for the three segments were as follows: −0.6 [95% confidence interval (CI) = −0.9 to −0.3, p < 0.001], 0.0 (95% CI = −0.1 to 0.0, p = 0.027), and −0.7 (95% CI = −0.8 to −0.7, p < 0.001). Nonlinear relationships were also found between the distance and length in cases with anterior disc displacement (ADD), anterior disc displacement with reduction (ADDWR), and without reduction (ADDWoR). Conclusion: the turning points of the disc displacement distance may be considered as a potential reference value for high-risk disc deformation and ADD. Disc length decreases sharply with anterior disc displacement when the disc displacement distance is over 1.7 mm. Prospective and long-term studies are required to clarify the natural course of the disc at different stages of the regression curve.

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.

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.

SM22α-lineage niche cells regulate intramembranous bone regeneration via PDGFRß-triggered hydrogen sulfide production.

Bone stromal cells are critical for bone homeostasis and regeneration. Growing evidence suggests that non-stem bone niche cells support bone homeostasis and regeneration via paracrine mechanisms, which remain to be elucidated. Here, we show that physiologically quiescent SM22α-lineage stromal cells expand after bone injury to regulate diverse processes of intramembranous bone regeneration. The majority of SM22α-lineage cells neither act as stem cells in vivo nor show their expression patterns. Dysfunction of SM22α-lineage niche cells induced by loss of platelet-derived growth factor receptor ß (PDGFRß) impairs bone repair. We further show that PDGFRß-triggered hydrogen sulfide (H2S) generation in SM22α-lineage niche cells facilitates osteogenesis and angiogenesis and suppresses overactive osteoclastogenesis. Collectively, these data demonstrate that non-stem SM22α-lineage niche cells support the niche for bone regeneration with a PDGFRß/H2S-dependent regulatory mechanism. Our findings provide further insight into non-stem bone stromal niche cell populations and niche-regulation strategy for bone repair.

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.

[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.

Flexible Conductive Polyimide Fiber/MXene Composite Film for Electromagnetic Interference Shielding and Joule Heating with Excellent Harsh Environment Tolerance.

The development of flexible MXene-based multifunctional composites is becoming a hot research area to achieve the application of conductive MXene in wearable electric instruments. Herein, a flexible conductive polyimide fiber (PIF)/MXene composite film with densely stacked "rebar-brick-cement" lamellar structure is fabricated using the simple vacuum filtration plus thermal imidization technique. A water-soluble polyimide precursor, poly(amic acid), is applied to act as a binder and dispersant to ensure the homogeneous dispersion of MXene and its good interfacial adhesion with PIF after thermal imidization, resulting in excellent mechanical robustness and high conductivity (3787.9 S/m). Owing to the reflection on the surface, absorption through conduction loss and interfacial/dipolar polarization loss inside the material, and the lamellar structure that is beneficial for multiple reflection and scattering between adjacent layers, the resultant PIF/MXene composite film exhibits a high electromagnetic interference (EMI) shielding effectiveness of 49.9 dB in the frequency range of 8.2-12.4 GHz. More importantly, its EMI shielding capacity can be well maintained in various harsh environments (e.g., extreme high/low temperature, acid/salt solution, and long-term cyclic bending), showing excellent stability and durability. Furthermore, it also presents fast, stable, and long-term durable Joule heating performances based on its stable and excellent conductivity, demonstrating good thermal deicing effects under actual conditions. Therefore, we believe that the flexible conductive PIF/MXene composite film with excellent conductivity and harsh environment tolerance possesses promising potential for electromagnetic wave protection and personal thermal management.

D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner.

OBJECTIVES: Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D-mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether D-mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. MATERIALS AND METHODS: In vivo anterior cruciate ligament transection (ACLT)-induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin-1ß (IL-1ß) exposure were employed. Combined with Epas1 gene gain- and loss-of-function, histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D-mannose in OA progression and the role of hypoxia-inducible factor 2 alpha (HIF-2 α) in D-mannose-induced ferroptosis resistance of chondrocytes. RESULTS: D-mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF-2α was identified as a central mediator in D-mannose-induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF-2α in chondrocytes by Ad-Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. CONCLUSIONS: D-mannose alleviates osteoarthritis progression by suppressing HIF-2α-mediated chondrocyte sensitivity to ferroptosis, indicating D-mannose to be a potential therapeutic strategy for ferroptosis-related diseases.