A retrospective study on the effectiveness of intensity modulated radiation therapy for thyroid associated ophthalmopathy at a single institute.

Thyroid-associated ophthalmopathy (TAO) is a hallmark autoimmune condition, and the treatment of TAO requires a multidisciplinary approach. Radiation therapy (RT) is a viable treatment option for active TAO, IMRT is a more precise technology in radiation oncology. This study aims to evaluate the efficacy, feasibility, and safety of orbital intensity-modulated radiation therapy (IMRT) in the treatment of TAO. A single-center retrospective analysis was conducted, including patients diagnosed with moderate to severe active TAO at the Department of Radiation Oncology, Peking University Third Hospital, from October 2020 to October 2023, who had poor responses to corticosteroid treatment. These patients subsequently received IMRT treatment, followed by a period of follow-up and retrospective analysis. The study focused on the outcomes of treatment efficacy, safety, and acute toxic reactions induced by radiation therapy. Improvements in clinical activity score (CAS) at 4 and 12 months were considered as primary and secondary study endpoints, respectively, along with the incidence rate of adverse events. The median follow-up period was 12 months. The median follow-up time after radiation therapy was 12 months. There was no statistically significant difference in CAS between before and 4 months after radiation therapy (CAS: 5.53 ± 2.07 vs.4.68 ± 2.62; R squared: 0.21; 95% CI: - 1.01-0.02; P = 0.054). However, there was a significant reduction in CAS 12 months post-treatment compared to pre-treatment (CAS: 5.53 ± 2.07 vs. 3.06 ± 2.38; R squared: 0.66; 95% CI: 3.42 - 1.52; P < 0.001). The CAS showed a progressively decreasing trend at both 4 months and 12 months post-treatment. In the combined radiotherapy with glucocorticoid treatment group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 6.38 ± 2.00 vs. 3.88 ± 2.85; R squared: 0.66; 95% CI - 4.11 to 0.89; P = 0.008). In the radiotherapy alone group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 4.78 ± 1.92 vs. 2.33 ± 1.73; R squared: 0.66; 95% CI - 3.89 to 1.00; P = 0.005). A few patients experienced Grade I periorbital edema, conjunctival congestion, and dry eye syndrome, but no adverse events such as cataracts, radiation retinopathy, or radiation-induced optic neuropathy were observed by the end of the follow-up period. Orbital IMRT is an effective treatment modality for moderate to severe active TAO, demonstrating significant efficacy even in patients who had not achieved success with previous treatments such as corticosteroids. This retrospective study was approved by the Ethics Committee of Peking University Third Hospital. The permit number was M2024220 and data of registration was April I, 2024.

Connecting Mindfulness Practice to Generative Semiotic Activity-Self-Other Referent in Umwelt and Semiosphere.

In this comment paper on von Fircks (2023a), I would like to focus on four issues and offer some reflections on them: first, what is happening in the process of a new I arising through mindfulness meditation practice? I would like to supplement the dialogue between Buber and Rogers in 1957 on the dynamism of I and Me, which is the basis of Mead's theory of self formation, in which I and Me separate, discover and meet a new self. The second, is that meditation, which at first glance appears to be an internal meditation practice and a personal activity, leads to a semiotic mediated social process. The Tao and early Buddhist ideas that form the background to the experiential process of mindfulness meditation will be reviewed, and the significance of people experiencing the interdependence of non-human nature and the environment through the practice will be discussed. Third, connecting this to the idea of Umwelt (Uexküll) and the semiosphere (Lotman), an attempt is made to extend the otherness as a collating body of self formation to Umwelt. Fourth, mindfulness meditation focuses attention on the breath. In relation to Mead's focus on the environment under the skin, i.e. corporeality, I will supplement the psychological meaning of cultivating the body's sense of interoception through the sensing of repetitive movements of tension and relaxation. Through the above, what kind of semiotic mediating function does mindfulness meditation have in relation to the construction of the new I, and how does it lead to the creation of social meaning? We would like to discuss these points. CLINICAL TRIAL REGISTRATION: The article does not contain any studies with clinical trial. This, clinical Trial registration is not applicable.

Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a generic fibrous scarring event resulting from accumulation of extracellular matrix (ECM) proteins, easily progressing to end-stage liver diseases. Tao-Hong-Si-Wu-Tang (THSWT) is a traditional Chinese medicine formula applied in clinics to treat gynecological and chronic liver diseases. However, the role of THSWT on thioacetamide (TAA)-induced hepatic fibrosis and the specific mechanisms remains unclear. AIM OF THE STUDY: To investigate the improving effects of THSWT on TAA-insulted hepatic fibrosis and the underlying mechanisms. MATERIALS AND METHODS: UHPLC-MS/MS was performed to explore the chemical characterization of THSWT. Mice were orally administered with THSWT once daily for 6 weeks along with TAA challenge. Liver function was reflected through serum biomarkers and histopathological staining. RNA sequencing, non-targeted metabolomics and molecular biology experiments were applied to investigate the underlying mechanisms. RESULTS: THSWT profoundly repaired lipid metabolism dysfunction and blocked collagen accumulation both in TAA-stimulated mice and in hepatocytes. Results of RNA sequencing and non-targeted metabolomics revealed that the anti-fibrotic effects of THSWT mostly relied on lipid metabolism repairment by increasing levels of acetyl-CoA, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine, and decreasing relative abundances of acyl-CoA, total cholesterol, diacylglycerol, triacylglycerol and phosphatidylinositol. Mechanically, long-chain acyl-CoA synthetases 4 (ACSL4) was a key profibrotic target both in human and mice by disrupting lipid oxidation and metabolism in hepatic mitochondria. THSWT effectively blocked ACSL4 and promoted mitophagy to reverse above outcomes, which was verified by mitophagy depletion. CONCLUSION: THSWT may be a promising therapeutic option for treating hepatic fibrosis and its complications by modulating lipid metabolism and promoting mitophagy in livers.

An ensemble deep learning diagnostic system for determining Clinical Activity Scores in thyroid-associated ophthalmopathy: integrating multi-view multimodal images from anterior segment slit-lamp photographs and facial images.

Background: Thyroid-associated ophthalmopathy (TAO) is the most prevalent autoimmune orbital condition, significantly impacting patients' appearance and quality of life. Early and accurate identification of active TAO along with timely treatment can enhance prognosis and reduce the occurrence of severe cases. Although the Clinical Activity Score (CAS) serves as an effective assessment system for TAO, it is susceptible to assessor experience bias. This study aimed to develop an ensemble deep learning system that combines anterior segment slit-lamp photographs of patients with facial images to simulate expert assessment of TAO. Method: The study included 156 patients with TAO who underwent detailed diagnosis and treatment at Shanxi Eye Hospital Affiliated to Shanxi Medical University from May 2020 to September 2023. Anterior segment slit-lamp photographs and facial images were used as different modalities and analyzed from multiple perspectives. Two ophthalmologists with more than 10 years of clinical experience independently determined the reference CAS for each image. An ensemble deep learning model based on the residual network was constructed under supervised learning to predict five key inflammatory signs (redness of the eyelids and conjunctiva, and swelling of the eyelids, conjunctiva, and caruncle or plica) associated with TAO, and to integrate these objective signs with two subjective symptoms (spontaneous retrobulbar pain and pain on attempted upward or downward gaze) in order to assess TAO activity. Results: The proposed model achieved 0.906 accuracy, 0.833 specificity, 0.906 precision, 0.906 recall, and 0.906 F1-score in active TAO diagnosis, demonstrating advanced performance in predicting CAS and TAO activity signs compared to conventional single-view unimodal approaches. The integration of multiple views and modalities, encompassing both anterior segment slit-lamp photographs and facial images, significantly improved the prediction accuracy of the model for TAO activity and CAS. Conclusion: The ensemble multi-view multimodal deep learning system developed in this study can more accurately assess the clinical activity of TAO than traditional methods that solely rely on facial images. This innovative approach is intended to enhance the efficiency of TAO activity assessment, providing a novel means for its comprehensive, early, and precise evaluation.

Ultra-performance liquid chromatography-quadrupole time-of-flight mass combined with UNIFI to study the mechanism of Tao Hong Si Wu Decoction in the treatment of postpartum blood stasis.

Postpartum hemorrhage can lead to a variety of maternal complications. Tao Hong Si Wu Decoction (THSWD) is a traditional Chinese medicine used for treating gynecological diseases. However, the active ingredients of THSWD and its pharmacological mechanism of treatment for postpartum blood stasis still remained unclear. In this study, 201 components were identified in THSWD ethanol extract using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, including 59 terpenoids and volatile oil, 61 Phenylpropanoids, 41 flavonoids, 22 alkaloids, and other 18 components. A total of 45 active compounds were identified in the blood and 33 active compounds were identified in the uterine. Taking the common components into the blood and into the uterus combined with network pharmacology. It was demonstrated that the active compounds can bind to the core target with good affinity through molecular docking. The results of this study will provide a reference for the quality control and pharmacodynamic material base research of THSWD.

Electronic Properties of Graphene Nano-Parallelograms: A Thermally Assisted Occupation DFT Computational Study.

In this computational study, we investigate the electronic properties of zigzag graphene nano-parallelograms (GNPs), which are parallelogram-shaped graphene nanoribbons of various widths and lengths, using thermally assisted occupation density functional theory (TAO-DFT). Our calculations revealed a monotonic decrease in the singlet-triplet energy gap as the GNP length increased. The GNPs possessed singlet ground states for all the cases examined. With the increase of GNP length, the vertical ionization potential and fundamental gap decreased monotonically, while the vertical electron affinity increased monotonically. Some of the GNPs studied were found to possess fundamental gaps in the range of 1-3 eV, lying in the ideal region relevant to solar energy applications. Besides, as the GNP length increased, the symmetrized von Neumann entropy increased monotonically, denoting an increase in the degree of the multi-reference character associated with the ground state GNPs. The occupation numbers and real-space representation of active orbitals indicated that there was a transition from the nonradical nature of the shorter GNPs to the increasing polyradical nature of the longer GNPs. In addition, the edge/corner localization of the active orbitals was found for the wider and longer GNPs.

Necrophagous flies as bioindicators in Cd and Zn co-contaminated areas of Tak Province, Thailand.

Necrophagous flies may be effective bioindicators of chemical substances within polluted locations, as they are sensitive to environmental changes, have large populations, and thrive in a single location over their lifespan. Diversity and abundance of necrophagous flies were determined at livestock farms contaminated with potentially toxic elements (PTEs) in Tak Province and Nakhon Sawan Province, Thailand. Substantial soil zinc (Zn) concentrations (> 1100 mg kg-1) were detected at a cattle farm at Khaothong, Nakhon Sawan Province, and soil cadmium (Cd) values were significantly elevated (> 3 mg kg-1) at a cattle farm in Pha De, Tak Province. Anthropogenic inputs including Zn mining, domestic wastewater, and certain materials used in local agriculture were point sources of PTEs at the livestock farms in the Pha De and Khaothong subdistricts. Lower temperatures and humidity during the rainy season may have resulted in increased numbers of necrophagous flies, which was 1.5 times greater compared to the dry season. However, the dry season exhibited a higher PTE buildup in fly tissue. The order of important value index (IVI) values of the necrophagous flies were: Chrysomya megacephala (56.80), Musca domestica (27.21), C. rufifacies (25.40) and Sarcophaga spp. (17.54), respectively. These necrophagous flies may play a significant role in PTE-contaminated ecosystems based on their high IVI values, suggesting that they could be used as bioindicators of PTEs. Principal component analysis (PCA) results for necrophagous flies associated with each sampling site during the dry season were consistent with flies having substantial IVI values. Musca domestica and C. megacephala of both sexes displayed substantial correlations with Cr, Al, and Mn, while females of Sarcophaga spp. displayed strong associations with Cd. At the cattle farm in Khaothong, males of M. domestica showed a significant relationship with Zn, Cu, Pb, and Ni. When considering PTE accumulation capacity in flies commonly found at field sites, C. megacephala and M. domestica are the most suitable bioindicators of PTEs. This study confirms that necrophagous flies serve as reliable bioindicators of PTE pollution.

IMoVR-Net: A robust interpretable network for multi-ocular lesion recognition from TAO facial images.

Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that seriously affects patient's life and health. However, the early diagnosis of TAO is highly dependent on the physician's subjective experience. Moreover, the currently proposed deep learning networks for eye diseases do not provide robust interpretability concerning feature learning paradigm, model structure, and the number of neurons. But the mentioned components are very important for model interpretability and are key factors that severely affect the transparency of the model. Therefore, a robust interpretable multi-orientation visual recognition network (IMoVR-Net) for TAO multi-ocular lesion recognition is proposed in this paper. Firstly, a multi-orientation visual cascaded encoder composed of the DenseGabor module and the dilated Gabor convolution group is proposed to achieve the fine extraction of multi-directional TAO lesion features by using a novel feature learning paradigm called alternating filtering. Besides, combining information theory and topology tool, an optimization rule based on topological energy entropy is proposed to provide a solid interpretable theory for determining the model structure. Finally, a clustering correlation analysis method is developed to accomplish the determination of the number of convolutional hidden neurons, providing robust interpretability for the selection of the number of neurons. Compared to other advanced models, the IMoVR-Net achieved state-of-the-art performance on different TAO ocular datasets with an average accuracy, sensitivity, precision, and F1 score of 0.878, 87.27 %, 0.875, and 87.39 %, respectively. The IMoVR-Net has good clinical application prospects due to its strong recognition ability and robust interpretability in feature extraction paradigm, model structure, and number of convolutional neurons.

Comprehensive split TEV based protein-protein interaction screening reveals TAOK2 as a key modulator of Hippo signalling to limit growth.

The conserved Hippo signalling pathway plays a crucial role in tumour formation by limiting tissue growth and proliferation. At the core of this pathway are tumour suppressor kinases STK3/4 and LATS1/2, which limit the activity of the oncogene YAP1, the primary downstream effector. Here, we employed a split TEV-based protein-protein interaction screen to assess the physical interactions among 28 key Hippo pathway components and potential upstream modulators. This screen led us to the discovery of TAOK2 as pivotal modulator of Hippo signalling, as it binds to the pathway's core kinases, STK3/4 and LATS1/2, and leads to their phosphorylation. Specifically, our findings revealed that TAOK2 binds to and phosphorylates LATS1, resulting in the reduction of YAP1 phosphorylation and subsequent transcription of oncogenes. Consequently, this decrease led to a decrease in cell proliferation and migration. Interestingly, a correlation was observed between reduced TAOK2 expression and decreased patient survival time in certain types of human cancers, including lung and kidney cancer as well as glioma. Moreover, in cellular models corresponding to these cancer types the downregulation of TAOK2 by CRISPR inhibition led to reduced phosphorylation of LATS1 and increased proliferation rates, supporting TAOK2's role as tumour suppressor gene. By contrast, overexpression of TAOK2 in these cellular models lead to increased phospho-LATS1 but reduced cell proliferation. As TAOK2 is a druggable kinase, targeting TAOK2 could serve as an attractive pharmacological approach to modulate cell growth and potentially offer strategies for combating cancer.

The taoist culture and the digital economy: Evidence from Chinese cities.

A key component of China's national plan is now the growth of the digital economy. This development relies on the continuous and in-depth practice of the vast majority of Chinese people who are deeply influenced by Chinese culture, of which Taoist culture is an important component that is closely related to the Chinese people and deeply influences overall worldviews. How does Taoist culture affect digital economy growth? Applying a theoretical analysis, in order to investigate this subject, this study used a two-way city-year fixed effects model with Chinese city data. The results demonstrate that Taoist culture can promote digital economy growth. The reason for this is that the "action" of Taoist culture refers to doing what should be done rather than inactivity. Additionally, the "quietness" of Taoist culture facilitates public individuals' single mindedness. The findings imply that Taoist culture has financial decentralization and financial technology effects. Theoretically, improvement in the degree of financial decentralization and technology can promote cities' digital economy development.

Taoist way of a balanced exercise training cocktail for the management of primary hypertension in older persons.

High blood pressure is the world's leading risk factor for mortality, affecting nearly half of the global population aged 50-79 years. Physical inactivity is one factor contributing to the prevalence of hypertension. This paper discusses a new concept for the management of hypertension in older persons. We are inclined to fade the current guidelines used in China, the United States, and Europe. Although demonstrating irrefutable benefits for blood pressure regulation, the guidelines fail to address the need to incorporate balance exercises, which are crucial for mitigating the risk of falling. We address three pressing questions regarding the efficacy of various combinations of exercise modes for blood pressure regulation, alongside providing an overview of balance exercises. At the core of our concept, we explicate the challenges inherent in addressing the global pandemic of physical inactivity and hypertension in regular socioeconomic people. No guidelines could change the state of inactivity by jumping between zero and all things, where "zero" symbolizes conditions such as physical inactivity and hypertension, and the concept of "all things" encompasses the ideals of an active lifestyle and healthy aging. We advocate a Taoist way, "zero-one-all things," where "one" in this context refers to an inclusive and culturally diverse exercise training cocktail. The Tao guides us to illuminate an ancient way of overcoming physical inactivity-associated diseases in the present day.

Allergen-specific immunotherapy and evidence: A European regulatory perspective.

Allergen immunotherapy (AIT) has been performed for 112 years. In this article we summarize regulatory standards and challenges based on scientific evidence on AIT. Most crucial and timely aspects concerning AIT are addressed from the regulatory perspective of the authors as employees of a national competent authority in Europe: (1) product specificity; (2) clinical efficacy; (3) treatment for adults and children (needs for extrapolation); (4) allergen exposure chambers; (5) biomarkers; (6) standardization; (7) real-world evidence; (8) independent official batch release (benefit and challenges); (9) harmonization on the EU level. The Paul-Ehrlich-Institut (PEI), the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main in Germany, examines and evaluates the benefits and risks of AIT products within the course of clinical development, marketing authorization, and subsequently throughout their entire life cycle to ensure high-quality, safe, and effective AIT products.

DGAKI and PEI in dialogue 2023: Diagnostics and allergen immunotherapy.

A roundtable discussion on February 10, 2023 between the German Society for Allergology and Clinical Immunology (DGAKI) and the Paul-Ehrlich-Institut (PEI) aimed to discuss in detail current aspects of allergen immunotherapy (AIT), its regulatory framework under the transitional provision of the Therapy Allergen Ordinance (TAO), and the consequences for the planned guideline work of the DGAKI, regulatory challenges in the approval of AIT products for children and adolescents as well as allergy diagnostics. The content and discussion points of this dialogue are summarized and are set in context with the current literature.

Real-Time Extension of TAO-DFT.

Thermally assisted occupation density functional theory (TAO-DFT) has been an efficient electronic structure method for studying the ground-state properties of large electronic systems with multi-reference character over the past few years. To explore the time-dependent (TD) properties of electronic systems (e.g., subject to an intense laser pulse), in this work, we propose a real-time (RT) extension of TAO-DFT, denoted as RT-TAO-DFT. Moreover, we employ RT-TAO-DFT to study the high-order harmonic generation (HHG) spectra and related TD properties of molecular hydrogen H2 at the equilibrium and stretched geometries, aligned along the polarization of an intense linearly polarized laser pulse. The TD properties obtained with RT-TAO-DFT are compared with those obtained with the widely used time-dependent Kohn-Sham (TDKS) method. In addition, issues related to the possible spin-symmetry breaking effects in the TD properties are discussed.

Prognostic value of extraocular muscles for intraocular pressure in thyroid-associated ophthalmopathy patients.

Background: Persistent increase in intraocular pressure (IOP) is often observed in eyes with thyroid-associated ophthalmopathy (TAO), which has irreversible effects on the visual function of patients. This retrospective cross-sectional study evaluated the value of magnetic resonance imaging (MRI) measurements of extraocular muscle (EOM) volume in prognosing IOP in patients with TAO. Methods: This single-center study was conducted in Beijing Friendship Hospital (Beijing, China), a tertiary hospital. From 35 participants, 70 eyes (normal IOP group: 50 eyes; high IOP group: 20 eyes; random samples) were enrolled in this study. Basic data from patients were collected and compared using 2-sample t-tests and chi-squared tests. The volume of the EOM, orbit fat, and whole orbit were measured by orbital MRI. Moreover, proptosis, optic nerve (ON) sheath diameter, optic nerve angle (ONA), and gaze angle were additionally measured with MRI. These parameters were compared between the two groups using 2-sample t-tests and chi-squared tests. Before and after post-methylprednisolone therapy, the MRI data of 20 eyes were obtained and compared with a paired t-test. Peripapillary retinal nerve fiber layer (RNFL) thickness was obtained using an optical coherence tomography (OCT) scan. Spearman rank correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curves were performed to evaluate the role of these factors in IOP changes. Results: The EOM volume and axial and sagittal ONAs in the high-IOP group were significantly increased compared to the normal-IOP group (P<0.001, P=0.001, P=0.02, respectively). Logistic regression analysis indicate that the cutoff value for EOM volume for the diagnosis of high IOP was significantly larger than that of the other parameters except orbit volume (P=0.03, P=0.004, P=0.08, respectively). Spearman correlation analysis revealed a significant correlation between EOM volume and ON sheath diameter and average RNFL thickness (P=0.01, P=0.02, respectively). A paired t-test indicated a significant decrease of EOM volume and ON sheath diameter as well as a significant enlargement of the axial ONAs after methylprednisolone therapy (P=0.002, P=0.02, P=0.05, respectively). Conclusions: EOM volume was an effective diagnostic factor for tracking IOP changes and ON patterns in patients with TAO. Methylprednisolone therapy is recommended for patients with TAO with secondary glaucoma to quickly reduce the EOM volume.

Classifying mental disorders through clinicians' subjective approach based on three-way decisions.

The most widely used technique for psychiatric diagnosis is a contemporary manual-based procedure based on prevailing culture-bound data for the classification of mental disorders. However, it has several inherent faults, including the misdiagnosis of complex patient phenomena and others. A potential mental patient from a minority culture could present with atypical symptoms that would be missed by the standard approach. Using the three-way decisions (3WD) as a framework, we propose a unified model that represents the subjective approach (CSA) of clinicians (psychiatrists and psychologists) consisting of three components: qualitative analysis, quantitative analysis, and evaluation-based analysis. The results of the qualitative and quantitative investigation are a classification list and a set of numerical weights based on malady severity levels according to the clinician's highest level of assumptions. Moreover, we construct a comparative classification of diseases into three categories with varying levels of importance; a three-way evaluation-based model is utilized in this study in order to better comprehend and communicate these results. This proposed method enables clinicians to consider identical data-driven individual behavioral symptoms of patients to be integrated with the current manual-based process as a complementary diagnostic instrument to improve the accuracy of mental disorder diagnosis.

RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.

Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-ß-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-ß-induced cell viability, decreased TGF-ß-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-ß-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-ß, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.

TAO-DFT with the Polarizable Continuum Model.

For the ground-state properties of gas-phase nanomolecules with multi-reference character, thermally assisted occupation (TAO) density functional theory (DFT) has recently been found to outperform the widely used Kohn-Sham DFT when traditional exchange-correlation energy functionals are employed. Aiming to explore solvation effects on the ground-state properties of nanomolecules with multi-reference character at a minimal computational cost, we combined TAO-DFT with the PCM (polarizable continuum model). In order to show its usefulness, TAO-DFT-based PCM (TAO-PCM) was used to predict the electronic properties of linear acenes in three different solvents (toluene, chlorobenzene, and water). According to TAO-PCM, in the presence of these solvents, the smaller acenes should have nonradical character, and the larger ones should have increasing polyradical character, revealing striking similarities to the past findings in the gas phase.

TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice.

Introduction: TSG-6 plays a wide anti-inflammatory and therapeutic role in a variety of autoimmune diseases as the key mediator of mesenchymal stem cells (MSCs). Purpose: We aimed to test whether TSG-6 could exert similar effects as MSCS in TAO via establishing TAO animal model immunized by hTSHR-A subunit plasmid. Material and Methods: We tested the expression level of TSG-6 on intraconal orbital fat from controls and patients with TAO. We established a stable thyroid-associated ophthalmopathy animal model by immunizing 6-week-old female Balb/c mice with recombination hTSHR-A subunit plasmid. After four immunizations, TSG-6 or dexamethasone was injected through the tail vein. The effects of the drugs on body weight, thyroid function, orbital inflammation, fibrosis and lipogenesis were observed. Results: The expression of TSG-6 in the orbital tissues of TAO patient is lower than that of normal people. In our animal model, mice showed weight loss, higher TT4 and TSHR antibody levels, and ocular symptoms such as inflammation and proptosis. TSG-6 can reduce ocular fibrosis and lipogenesis by inhibiting the infiltration of CD3+ T lymphocytes and macrophages in the mouse model of thyroid associated ophthalmopathy. Compared with dexamethasone, TSG-6 showed comparable anti-inflammatory effect, moreover, it has given a better performance in inhibiting adipogenesis. Conclusion: It was demonstrated that TSG-6 has a considerable positive impact on improving eye symptoms of TAO mice, which could be a novel candidate for the early treatment of TAO.

Activity-dependent membrane sculpting deficits in TAOK1-linked neurodevelopmental disease.

A recent study by Beeman et al. exploring disease-related missense mutations in TAOK1 revealed a self-regulating association of the kinase with the plasma membrane that is critical for neuronal morphogenesis. Using a combination of in vitro approaches and elegant in silico modeling, the authors describe an aberrant membrane protrusions phenotype in kinase-deficient mutants reminiscent of TAOK2's indirect regulation of neuronal morphology, thus providing a converging patho-mechanism across several neurodevelopmental disorders.