Spreading Behavior of Non-Spherical Particles with Reconstructed Shapes Using Discrete Element Method in Additive Manufacturing.

The spreading behavior of particles has a significant impact on the processing quality of additive manufacturing. Compared with spherical metal material, polymer particles are usually non-spherical in shape. However, the effects of particle shape and underlying mechanisms remain unclear. Here, the spreading process of particles with reconstructed shapes (non-spherical particles decomposed into several spherical shapes by stereo-lithography models) are simulated by integrating spherical particles with the discrete element method. The results show that more cavities form in the spreading beds of particles with reconstructed shapes than those of spheres with blade spreading. Correspondingly, particles with reconstructed shapes have lower packing densities, leading to more uniform packing patterns. Slow propagation speeds of velocity and angular velocity lead to "right-upwards" turning boundaries for particles with reconstructed shapes and "right-downwards" turning boundaries for spherical particles. Moreover, as the blade velocity increases, the packing density decreases. Our calculation results verify each other and are in good agreement with the experiment, providing more details of the behavior of non-spherical particles before additive manufacturing. The comprehensive comparison between polymer non-spherical particles and spherical particles helps develop a reasonable map for the appropriate choice of operating parameters in real processes.

Fiber-in-Tube Electrifiable Structure for Virus Filtration Self-Generated Static Electricity by Vibration/Sound.

Fiber has been considered as an ideal material for virus insulation due to the readily available electrostatic adsorption. However, restricted by the electrostatic attenuation and filtration performance decline, their long-lasting applications are unable to satisfy the requirements of medical protective equipment for major medical and health emergencies such as global epidemics, which results in both a waste of resources and environmental pollution. We overcame these issues by constructing a fiber-in-tube structure, achieving the robust reusability of fibrous membranes. Core fibers within the hollow could form generators with tube walls of shell fibers to provide persistent, renewable static electricity via piezoelectricity and triboelectricity. The PM0.3 insulation efficiency achieved 98% even after 72 h of humidity and heat aging, through beating and acoustic waves, which is greatly improved compared with that of traditional nonwoven fabric (∼10% insulation). A mask spun with our fiber also has a low breathing resistance (differential pressure <24.4 Pa/cm2). We offer an approach to enrich multifunctional fiber for developing electrifiable filters, which make the fiber-in-tube filtration membrane able to durably maintain a higher level of protective performance to reduce the replacement and provide a new train of thought for the preparation of other high-performance protective products.

Mechanistic and Kinetic Insights into Cellular Uptake of Biomimetic Dinitrosyl Iron Complexes and Intracellular Delivery of NO for Activation of Cytoprotective HO-1.

Dinitrosyl iron unit (DNIU), [Fe(NO)2], is a natural metallocofactor for biological storage, delivery, and metabolism of nitric oxide (NO). In the attempt to gain a biomimetic insight into the natural DNIU under biological system, in this study, synthetic dinitrosyl iron complexes (DNICs) [(NO)2Fe(µ-SCH2CH2COOH)2Fe(NO)2] (DNIC-COOH) and [(NO)2Fe(µ-SCH2CH2COOCH3)2Fe(NO)2] (DNIC-COOMe) were employed to investigate the structure-reactivity relationship of mechanism and kinetics for cellular uptake of DNICs, intracellular delivery of NO, and activation of cytoprotective heme oxygenase (HO)-1. After rapid cellular uptake of dinuclear DNIC-COOMe through a thiol-mediated pathway (tmax = 0.5 h), intracellular assembly of mononuclear DNIC [(NO)2Fe(SR)(SCys)]n-/[(NO)2Fe(SR)(SCys-protein)]n- occurred, followed by O2-induced release of free NO (tmax = 1-2 h) or direct transfer of NO to soluble guanylate cyclase, which triggered the downstream HO-1. In contrast, steady kinetics for cellular uptake of DNIC-COOH via endocytosis (tmax = 2-8 h) and for intracellular release of NO (tmax = 4-6 h) reflected on the elevated activation of cytoprotective HO-1 (∼50-150-fold change at t = 3-10 h) and on the improved survival of DNIC-COOH-primed mesenchymal stem cell (MSC)/human corneal endothelial cell (HCEC) under stressed conditions. Consequently, this study unravels the bridging thiolate ligands in dinuclear DNIC-COOH/DNIC-COOMe as a switch to control the mechanism, kinetics, and efficacy for cellular uptake of DNICs, intracellular delivery of NO, and activation of cytoprotective HO-1, which poses an implication on enhanced survival of postengrafted MSC for advancing the MSC-based regenerative medicine.

Tristate Photonic Crystal Film with Structural, Fluorescent, and Up-Conversion Luminescent Color for Multilevel Anticounterfeiting.

Counterfeit items are growing worldwide, affecting the global economy and human health. Anticounterfeiting tags based on a physical microstructure or chemical materials have enjoyed long-term commercial success due to their visualization and inexpensive production. However, conventional anticounterfeiting tags can be readily imitated. Herein, we have overcome this limitation by assembling colloidal nanospheres and two luminescent micromaterials into a composited photonic crystal (PhC) and achieved massive scale-up fabrication of multilevel anticounterfeiting PhC films in just several minutes of thermal rolling. The fabricated PhC film exhibits three optical states, including angle-dependent structural color (reflectivity = 66%) under white light, emits green light under 980 nm light, and emits red light under ultraviolet light. Multilevel anticounterfeiting colorful images were obtained by further use of masking templates, which integrate colors from both physically colored microstructures and chemical luminescent materials. Besides, the thermal-rolling process also shows excellent feasibility for assembling microunits with different sizes into high-quality functional PhC films.

Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy.

BACKGROUND: Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors. METHODS: To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A2-2 (CA2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA2-2 macrophages was evaluated against 4T1 breast cancer cells and EAC cells in vitro and syngeneic mouse model in vivo. RESULTS: Incubation of murine macrophages with CA2-2 led to polarization into the M1 phenotype, and the CA2-2-pretreated macrophages could selectively target and kill various types of cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently. CONCLUSION: In this study, CA2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments.

Photonic Crystal Sensor Evaluating the Effectiveness of Medical Products under Different Storage Conditions.

The effectiveness of time- and temperature-sensitive medical products (TTSMPs) (vaccines, medicines, and biological agents) is generally evaluated by sporadically checking the storage conditions recorded in electronic thermometers. However, electronic thermometers do not achieve all-time and all-regional record, resulting in the wrong evaluation of a single TTSMP and seriously endangering public health. Herein, we report a photonic crystal sensor for evaluating the effectiveness of a single TTSMP processing storage environment. The photonic crystal sensor assembled by colloidal microspheres (WO3-x nanospheres were added into the microsphere gap) generates a fascinating composite color of angle-dependent structural color (maximum reflectivity = 45%) and durative color (WO3-x coloration). Effectiveness evaluation principle reveals that the pattern on the sensor, which was printed by the composite color, fades sensitively to time and temperature, thus having different visible periods (0-21 days affected by temperature). The visible periods of the patterns can be used to evaluate a single TTSMP's effectiveness stored under different temperatures. Furthermore, the photonic crystal sensor shows outstanding flexibility and slight adhesion, offering a promising application toward the effectiveness evaluation of TTSMPs throughout storage, transportation, and sales processes.

Neuroprotective Effect of NO-Delivery Dinitrosyl Iron Complexes (DNICs) on Amyloid Pathology in the Alzheimer's Disease Cell Model.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. ß-amyloid1-42 (Aß1-42) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aß aggregation and rescuing memory and learning deficit through the NO signaling pathway. Targeting the NO pathway might be a therapeutic option; however, NO has a limited half-life under the biological system. To address this issue, a biomimetic dinitrosyl iron complex [(NO)2Fe(µ-SCH2CH2COOH)2Fe(NO)2] (DNIC-COOH) that could stably deliver NO was explored in the current study. To determine whether DNIC-COOH exerts anti-AD efficacy, DNIC-COOH was added to neuron-like cells and primary cortical neurons along with Aß1-42. This study found that DNIC-COOH protected neuronal cells from Aß-induced cytotoxicity, potentiated neuronal functions, and facilitated Aß1-42 degradation through the NO-sGC-cGMP-AKT-GSK3ß-CREB/MMP-9 pathway.

Conjugation of bone grafts with NO-delivery dinitrosyl iron complexes promotes synergistic osteogenesis and angiogenesis in rat calvaria bone defects.

Craniofacial/jawbone deformities remain a significant clinical challenge in restoring facial/dental functions and esthetics. Despite the reported therapeutics for clinical bone tissue regeneration, the bioavailability issue of autografts and limited regeneration efficacy of xenografts/synthetic bone substitutes, however, inspire continued efforts towards functional conjugation and improvement of bioactive bone graft materials. Regarding the potential of nitric oxide (NO) in tissue engineering, herein, functional conjugation of NO-delivery dinitrosyl iron complex (DNIC) and osteoconductive bone graft materials was performed to optimize the spatiotemporal control over the delivery of NO and to activate synergistic osteogenesis and angiogenesis in rat calvaria bone defects. Among three types of biomimetic DNICs, [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-COOH) features a steady kinetics for cellular uptake by MC3T3-E1 osteoblast cells followed by intracellular assembly of protein-bound DNICs and release of NO. This steady kinetics for intracellular delivery of NO by DNIC-COOH rationalizes its biocompatibility and wide-spectrum cell proliferation effects on MC3T3-E1 osteoblast cells and human umbilical vein endothelial cells (HUVECs). Moreover, the bridging [SCH2CH2COOH]- thiolate ligands in DNIC-COOH facilitate its chemisorption to deproteinized bovine bone mineral (DBBM) and physisorption onto TCP (ß-tricalcium phosphate), respectively, which provides a mechanism to control the kinetics for the local release of loaded DNIC-COOH. Using rats with calvaria bone defects as an in vivo model, DNIC-DBBM/DNIC-TCP promotes the osteogenic and angiogenic activity ascribed to functional conjugation of osteoconductive bone graft materials and NO-delivery DNIC-COOH. Of importance, the therapeutic efficacy of DNIC-DBBM/DNIC-TCP on enhanced compact bone formation after treatment for 4 and 12 weeks supports the potential for clinical application to regenerative medicine.

Sustained Releasable Copper and Zinc Biogenic Ions Co-Assembled in Metal-Organic Frameworks Reinforced Bacterial Eradication and Wound Mitigation in Diabetic Mice.

The employment of metal-organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer-Emmett-Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N2 isotherms was found to be 1868, 1392, 1706, and 1179 m2/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, in vitro cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model in vivo. On account of antibacterial potentials and tissue-repairing characteristics of Cu2+ and Zn2+ ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.

IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway.

BACKGROUND: Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated. METHODS: Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan-Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry. RESULTS: Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin-a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes-reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin. CONCLUSIONS: The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.

Causal discovery approach with reinforcement learning for risk factors of type II diabetes mellitus.

BACKGROUND: Statistical correlation analysis is currently the most typically used approach for investigating the risk factors of type 2 diabetes mellitus (T2DM). However, this approach does not readily reveal the causal relationships between risk factors and rarely describes the causal relationships visually. RESULTS: Considering the superiority of reinforcement learning in prediction, a causal discovery approach with reinforcement learning for T2DM risk factors is proposed herein. First, a reinforcement learning model is constructed for T2DM risk factors. Second, the process involved in the causal discovery method for T2DM risk factors is detailed. Finally, several experiments are designed based on diabetes datasets and used to verify the proposed approach. CONCLUSIONS: The experimental results show that the proposed approach improves the accuracy of causality mining between T2DM risk factors and provides new evidence to researchers engaged in T2DM prevention and treatment research.

One-step-one-pot hydrothermally derived metal-organic-framework-nanohybrids for integrated point-of-care diagnostics of SARS-CoV-2 viral antigen/pseudovirus utilizing electrochemical biosensor chip.

The COVID-19 pandemic has become a global catastrophe, affecting the health and economy of the human community. It is required to mitigate the impact of pandemics by developing rapid molecular diagnostics for SARS-CoV-2 virus detection. In this context, developing a rapid point-of-care (POC) diagnostic test is a holistic approach to the prevention of COVID-19. In this context, this study aims at presenting a real-time, biosensor chip for improved molecular diagnostics including recombinant SARS-CoV-2 spike glycoprotein and SARS-CoV-2 pseudovirus detection based on one-step-one-pot hydrothermally derived CoFeBDCNH2-CoFe2O4 MOF-nanohybrids. This study was tested on a PalmSens-EmStat Go POC device, showing a limit of detection (LOD) for recombinant SARS-CoV-2 spike glycoprotein of 6.68 fg/mL and 6.20 fg/mL in buffer and 10% serum-containing media, respectively. To validate virus detection in the POC platform, an electrochemical instrument (CHI6116E) was used to perform dose dependent studies under similar experimental conditions to the handheld device. The results obtained from these studies were comparable indicating the capability and high detection electrochemical performance of MOF nanocomposite derived from one-step-one-pot hydrothermal synthesis for SARS-CoV-2 detection for the first time. Further, the performance of the sensor was tested in the presence of Omicron BA.2 and wild-type D614G pseudoviruses.

A Directional Chitosan Sound Sensor Based on Piezoelectric-Triboelectric Sensing.

Herein, we have constructed a directional sound sensor based on an anisotropic chitosan aerogel. Because of the lamellar porous structure, this chitosan aerogel exhibits a distinct anisotropic behavior, featuring the compressive stress along the direction of the parallel laminate structure, being approximately 2.6 times that in the orthogonal direction. Simultaneously, the chitosan aerogel is used as a directional sound-sensing material, which exhibits excellent acoustic-electric conversion performance with a marked difference in the direction perpendicular to the laminate structure than in the parallel direction. The CSANG has an optimum electrical output of 66 V and 9.2 µA under a sound stimulation of 150 Hz and 120 dB in the orthogonal direction of the laminate structure. Therefore, this directional chitosan sound sensor with excellent biocompatibility and sound sensitivity demonstrates promising application potential in the field of intelligent sensing and artificial cochlea.

A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.

BACKGROUND: CTLA4Ig is a dimeric fusion protein of the extracellular domain of cytotoxic T-lymphocyte protein 4 (CTLA4) and an Fc (Ig) fragment of human IgG1 that is approved for treating rheumatoid arthritis. However, CTLA4Ig may induce adverse effects. Developing a lesion-selective variant of CTLA4Ig may improve safety while maintaining the efficacy of the treatment. METHODS: We linked albumin to the N-terminus of CTLA4Ig (termed Alb-CTLA4Ig) via a substrate sequence of matrix metalloproteinase (MMP). The binding activities and the biological activities of Alb-CTLA4Ig before and after MMP digestion were analyzed by a cell-based ELISA and an in vitro Jurkat T cell activation assay. The efficacy and safety of Alb-CTLA4Ig in treating joint inflammation were tested in mouse collagen-induced arthritis. RESULTS: Alb-CTLA4Ig is stable and inactive under physiological conditions but can be fully activated by MMPs. The binding activity of nondigested Alb-CTLA4Ig was at least 10,000-fold weaker than that of MMP-digested Alb-CTLA4Ig. Nondigested Alb-CTLA4Ig was unable to inhibit Jurkat T cell activation, whereas MMP-digested Alb-CTLA4Ig was as potent as conventional CTLA4Ig in inhibiting the T cells. Alb-CTLA4Ig was converted to CTLA4Ig in the inflamed joints to treat mouse collagen-induced arthritis, showing similar efficacy to that of conventional CTLA4Ig. In contrast to conventional CTLA4Ig, Alb-CTLA4Ig did not inhibit the antimicrobial responses in the spleens of the treated mice. CONCLUSIONS: Our study indicates that Alb-CTLA4Ig can be activated by MMPs to suppress tissue inflammation in situ. Thus, Alb-CTLA4Ig is a safe and effective treatment for collagen-induced arthritis in mice.

The mitochondrial genome of Binodoxys acalephae (Hymenoptera: Braconidae) with unique gene rearrangement and phylogenetic implications.

BACKGROUND: Species in the subfamily Aphidiinae from the Braconidae of Hymenoptera are endoparasitic wasps that exclusively utilize aphids as hosts. Some Aphidiinae species are widely used as biological agents. However, there were only one species with determined complete mitochondrial genome from this subfamily. METHODS AND RESULTS: In this study, we sequenced and annotated the mitochondrial genome (mitogenome) of Binodoxys acalephae, which was 15,116 bp in size and contained 37 genes. The start codon of 13 protein-coding genes was ATN, and the complete stop codon TAA and TAG was widely assigned to 11 protein-coding genes. The lrRNA contains 43 stem-loop structures, and srRNA contains 25 stem-loop structures. Translocation and inversion of tRNA genes was found to be dominant in B. acalephae. In contrast to Aphidius gifuensis from the same subfamily Aphidiinae, inverted tRNALeu1 was translocated to the gene cluster between tRNALeu2 and COX2, and the control region between tRNAIle and tRNAMet was deleted in the mitogenome of B. acalephae. Within Braconidae, gene clusters tRNATrp-tRNACys-tRNATyr and CR-tRNAIle-tRNAGln-tRNAMet were hotspots for gene rearrangement. Phylogenetic analysis showed that both Bayesian and maximum-likelihood methods recovered the monophyly of Aphidiinae and suggested that Aphidiinae formed sister clades with the remaining subfamilies. The phylogenetic analyses of nine subfamilies supported the monophyly of Cyclostomes and Noncyclostomes in Braconidae. CONCLUSION: The arrangement of mitochondrial genes and the phylogenetic relationships among nine Braconidae subfamilies were constructed better to understand the diversity and evolution of Aphidiinae mitogenomes.

Fumarate hydratase inhibits non-small cell lung cancer metastasis via inactivation of AMPK and upregulation of DAB2.

Lung cancer is one of the leading causes of cancer mortality worldwide. As it is often first diagnosed only when cancer metastasis has already occurred, the development of effective biomarkers for the risk prediction of cancer metastasis, followed by stringent monitoring and the early treatment of high-risk patients, is essential for improving patient survival. Cancer cells exhibit alterations in metabolic pathways that enable them to maintain rapid growth and proliferation, which are quite different from the metabolic pathways of normal cells. Fumarate hydratase (FH, fumarase) is a well-known tricarboxylic acid cycle enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. The current study sought to investigate the relationship between FH expression levels and the outcome of patients with lung cancer. FH was knocked down in lung cancer cells using shRNA or overexpressed using a vector, and the effect on migration ability was assessed. Furthermore, the role of AMP-activated protein kinase (AMPK) phosphorylation and disabled homolog 2 in the underlying mechanism was investigated using an AMPK inhibitor approach. The results showed that in lung cancer tissues, low FH expression was associated with lymph node metastasis, tumor histology and recurrence. In addition, patients with low FH expression exhibited a poor overall survival in comparison with patients having high FH expression. When FH was overexpressed in lung cancer cells, cell migration was reduced with no effect on cell proliferation. Furthermore, the level of phosphorylated (p-)AMPK, an energy sensor molecule, was upregulated when FH was knocked down in lung cancer cells, and the inhibition of p-AMPK led to an increase in the expression of disabled homolog 2, a tumor suppressor protein. These findings suggest that FH may serve as an effective biomarker for predicting the prognosis of lung cancer and as a therapeutic mediator.

Objective diagnosis of ADHD through movement analysis by using a smart chair with piezoelectric material.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in schoolchildren. ADHD diagnoses are generally made based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The diagnosis is made clinically based on observation and information provided by parents and teachers, which is highly subjective and can lead to disparate results. Considering that hyperactivity is one of the main symptoms of ADHD, the inaccuracy of ADHD diagnosis based on subjective criteria necessitates the identification of a method to objectively diagnose ADHD. METHODS: In this study, a medical chair containing a piezoelectric material was applied to objectively analyze movements of patients with ADHD, which were compared with those of patients without ADHD. This study enrolled 62 patients-31 patients with ADHD and 31 patients without ADHD. During the clinical evaluation, participants' movements were recorded by the piezoelectric material for analysis. The variance, zero-crossing rate, and high energy rate of movements were subsequently analyzed. RESULTS: The results revealed that the variance, zero-crossing rate, and high energy rate were significantly higher in patients with ADHD than in those without ADHD. Classification performance was excellent in both groups, with the area under the curve as high as 98.00%. CONCLUSION: Our findings suggest that the use of a smart chair equipped with piezoelectric material is an objective and potentially useful method for supporting the diagnosis of ADHD.

Thyroid function and epilepsy: a two-sample Mendelian randomization study.

Background: Thyroid hormones (THs) play a crucial role in regulating various biological processes, particularly the normal development and functioning of the central nervous system (CNS). Epilepsy is a prevalent neurological disorder with multiple etiologies. Further in-depth research on the role of thyroid hormones in epilepsy is warranted. Methods: Genome-wide association study (GWAS) data for thyroid function and epilepsy were obtained from the ThyroidOmics Consortium and the International League Against Epilepsy (ILAE) Consortium cohort, respectively. A total of five indicators of thyroid function and ten types of epilepsy were included in the analysis. Two-sample Mendelian randomization (MR) analyses were conducted to investigate potential causal relations between thyroid functions and various epilepsies. Multiple testing correction was performed using Bonferroni correction. Heterogeneity was calculated with the Cochran's Q statistic test. Horizontal pleiotropy was evaluated by the MR-Egger regression intercept. The sensitivity was also examined by leave-one-out strategy. Results: The findings indicated the absence of any causal relationship between abnormalities in thyroid hormone and various types of epilepsy. The study analyzed the odds ratio (OR) between thyroid hormones and various types of epilepsy in five scenarios, including free thyroxine (FT4) on focal epilepsy with hippocampal sclerosis (IVW, OR = 0.9838, p = 0.02223), hyperthyroidism on juvenile absence epilepsy (IVW, OR = 0.9952, p = 0.03777), hypothyroidism on focal epilepsy with hippocampal sclerosis (IVW, OR = 1.0075, p = 0.01951), autoimmune thyroid diseases (AITDs) on generalized epilepsy in all documented cases (weighted mode, OR = 1.0846, p = 0.0346) and on childhood absence epilepsy (IVW, OR = 1.0050, p = 0.04555). After Bonferroni correction, none of the above results showed statistically significant differences. Conclusion: This study indicates that there is no causal relationship between thyroid-related disorders and various types of epilepsy. Future research should aim to avoid potential confounding factors that might impact the study.

CD44 Promotes Breast Cancer Metastasis through AKT-Mediated Downregulation of Nuclear FOXA2.

The primary cause of breast cancer mortality is the metastatic invasion of cancerous stem cells (CSC). Cluster of differentiation 44 (CD44) is a well-known CSC marker in various cancers, as well as a key role player in metastasis and relapse of breast cancer. CD44 is a cell-membrane embedded protein, and it interacts with different proteins to regulate cancer cell behavior. Transcription factor forkhead box protein A2 (FOXA2) acts as an important regulator in multiple cancers, including breast cancer. However, the biological significance of CD44-FOXA2 association in breast cancer metastasis remains unclear. Herein, we observed that CD44 expression was higher in metastatic lymph nodes compared to primary tumors using a flow cytometric analysis. CD44 overexpression in breast cancer cell lines significantly promoted cell migration and invasion abilities, whereas the opposite effects occurred upon the knockdown of CD44. The stem cell array analysis revealed that FOXA2 expression was upregulated in CD44 knockdown cells. However, the knockdown of FOXA2 in CD44 knockdown cells reversed the effects on cell migration and invasion. Furthermore, we found that CD44 mediated FOXA2 localization in breast cancer cells through the AKT pathway. Moreover, the immunofluorescence assay demonstrated that AKT inhibitor wortmannin and AKT activator SC79 treatment in breast cancer cells impacted FOXA2 localization. Collectively, this study highlights that CD44 promotes breast cancer metastasis by downregulating nuclear FOXA2.