LncRNA NEAT1 targets miR-125/ADAM9 mediated NF-κB pathway in inflammatory response of rosacea.

OBJECTIVE: To investigate the role of NEAT1 targeted regulation of miR-125/ADAM9 mediated NF-κB pathway in inflammatory response in rosacea. METHOD: HaCaT cell rosacea phenotype was induced by LL37. The connection targeted by NEAT1 and miR-125a-5p was confirmed by Double-Luciferase report analysis. qPCR was employed to assess the levels of expression for NEAT1, miR-125a-5p, and ADAM9 genes. The levels of expression for ADAM9/TLR2/NF-κB P65 pathway proteins in each batch of cells were determined by Western blotting. The levels of expression for inflammatory factors, including TNF-α, IL-1ß, IL-6, and IL-18, were measured through ELISA experimentation. RESULTS: LL37 could successfully induce HaCaT cells to exhibit rosacea phenotype. The luciferase report experiment confirmed that NEAT1 could target and bind miR-125a-5p and inhibit its expression. ADAM9 exhibited increased expression in LL37-induced HaCaT cells, showing a positive association with NEAT1 expression and inverse relationship with miR-125a-5p activation. LL37 treatment promoted the expression of ADAM9/TLR2/NF-κB P65 pathway proteins. Silencing ADAM9 can inhibit the inflammatory signaling pathway and reduce the level of TNF-α, IL-1ß, IL-6, and IL-18 in HaCaT cells. CONCLUSION: NEAT1 can suppress the production of miR-125a-5p and activate the TLR2/NF-κB inflammatory pathway mediated by ADAM9, thereby promoting the inflammatory response in rosacea.

Fecal Coprococcus, hidden behind abdominal symptoms in patients with small intestinal bacterial overgrowth.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is the presence of an abnormally excessive amount of bacterial colonization in the small bowel. Hydrogen and methane breath test has been widely applied as a non-invasive method for SIBO. However, the positive breath test representative of bacterial overgrowth could also be detected in asymptomatic individuals. METHODS: To explore the relationship between clinical symptoms and gut dysbiosis, and find potential fecal biomarkers for SIBO, we compared the microbial profiles between SIBO subjects with positive breath test but without abdominal symptoms (PBT) and healthy controls (HC) using 16S rRNA amplicon sequencing. RESULTS: Fecal samples were collected from 63 SIBO who complained of diarrhea, distension, constipation, or abdominal pain, 36 PBT, and 55 HC. For alpha diversity, the Shannon index of community diversity on the genus level showed a tendency for a slight increase in SIBO, while the Shannon index on the predicted function was significantly decreased in SIBO. On the genus level, significantly decreased Bacteroides, increased Coprococcus_2, and unique Butyrivibrio were observed in SIBO. There was a significant positive correlation between saccharolytic Coprococcus_2 and the severity of abdominal symptoms. Differently, the unique Veillonella in the PBT group was related to amino acid fermentation. Interestingly, the co-occurrence network density of PBT was larger than SIBO, which indicates a complicated interaction of genera. Coprococcus_2 showed one of the largest betweenness centrality in both SIBO and PBT microbiota networks. Pathway analysis based on the Kyoto Encyclopedia of Genes and Genome (KEGG) database reflected that one carbon pool by folate and multiple amino acid metabolism were significantly down in SIBO. CONCLUSIONS: This study provides valuable insights into the fecal microbiota composition and predicted metabolic functional changes in patients with SIBO. Butyrivibrio and Coprococcus_2, both renowned for their role in carbohydrate fermenters and gas production, contributed significantly to the symptoms of the patients. Coprococcus's abundance hints at its use as a SIBO marker. Asymptomatic PBT individuals show a different microbiome, rich in Veillonella. PBT's complex microbial interactions might stabilize the intestinal ecosystem, but further study is needed due to the core microbiota similarities with SIBO. Predicted folate and amino acid metabolism reductions in SIBO merit additional validation.

Cetyltrimethylammonium Bromide-Modified Laponite@Diatomite Composites for Enhanced Adsorption Performance of Organic Pollutants.

This work aims to enhance the adsorption performance of Laponite @diatomite for organic pollutants by modifying it with cetyltrimethylammonium bromide (CTAB). The microstructure and morphology of the CTAB-modified Laponite @diatomite material were characterized using SEM, XRD, FTIR, BET, and TG. Furthermore, the influences of key parameters, containing pH, adsorbent dosage, reaction time, and reaction temperature, on the adsorption process were investigated. The kinetics, thermodynamics, and isotherm models of the adsorption process were analyzed. Finally, potential adsorption mechanisms were given based on the characterization. The research findings indicate that CTAB-La@D exhibits good adsorption performance toward Congo red (CR) over a broad pH range. The maximum adsorption capacity of CR was 451.1 mg/g under the optimum conditions (dosage = 10 mg, contact time = 240 min, initial CR concentration = 100 mg/L, temperature = 25 °C, and pH = 7). The adsorption process conformed to the pseudo-second-order kinetic model, and the adsorption isotherms indicated that the adsorption process of CR was more in line with the Langmuir model, and it was physical adsorption. Thermodynamic analysis illustrates that the adsorption process is exothermic and spontaneous. Additionally, the mechanisms of electrostatic adsorption and hydrophobic effect adsorption of CR were investigated through XPS and FTIR analysis. This work provides an effective pathway for designing high-performance adsorbents for the removal of organic dye, and the synthesized materials hold great capability for practical utilization in the treatment of wastewater.

Early identification of autism spectrum disorder based on machine learning with eye-tracking data.

BACKGROUND: Early identification of autism spectrum disorder (ASD) improves long-term outcomes, yet significant diagnostic delays persist. METHODS: A retrospective cohort of 449 children (ASD: 246, typically developing [TD]: 203) was used for model development. Eye-movement data were collected from the participants watching videos that featured eye-tracking paradigms for assessing social and non-social cognition. Five machine learning algorithms, namely random forest, support vector machine, logistic regression, artificial neural network, and extreme gradient boosting, were trained to classify children with ASD and TD. The best-performing algorithm was selected to build the final model which was further evaluated in a prospective cohort of 80 children. The Shapley values interpreted important eye-tracking features. RESULTS: Random forest outperformed other algorithms during model development and achieved an area under the curve of 0.849 (< 3 years: 0.832, ≥ 3 years: 0.868) on the external validation set. Of the ten most important eye-tracking features, three measured social cognition, and the rest were related to non-social cognition. A deterioration in model performance was observed using only the social or non-social cognition-related eye-tracking features. LIMITATIONS: The sample size of this study, although larger than that of existing studies of ASD based on eye-tracking data, was still relatively small compared to the number of features. CONCLUSIONS: Machine learning models based on eye-tracking data have the potential to be cost- and time-efficient digital tools for the early identification of ASD. Eye-tracking phenotypes related to social and non-social cognition play an important role in distinguishing children with ASD from TD children.

Cleaning Oil-Based Drilling Cuttings with Synthetic Gemini Surfactants.

The chemical cleaning method is the simplest approach for degreasing oil-based drilling cuttings (ODCs), with the effectiveness of the treatment relying mainly on the selection of the surfactant and the cleaning conditions. However, achieving the standard treatment of ODCs directly using conventional surfactants proves challenging. In light of this, this study introduces a synthesized and purified Gemini surfactant named DCY-1. The structure of DCY-1 was confirmed through Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The characterization in this article encompasses the use of an interface tension meter, nanoparticle size analysis, scanning electron microscopy, and infrared oil measurement. The critical micelle concentration (CMC) of DCY-1 was determined to be 3.37 × 10-3 mol/L, with a corresponding γcmc value of 37.97 mN/m. In comparison to conventional surfactants, DCY-1 exhibited a larger micelle size of 4.52 nm, approximately 24.52% larger than that of SDS. Moreover, the residual oil rate of 3.96% achieved by DCY-1 was the lowest among the chemical cleaning experimental results. Through a single-factor experiment, the optimal cleaning ability of DCY-1 for ODCs was determined as follows: a surfactant concentration of 3 mmol/L, a temperature of 60 °C, an ODC/liquid mass ratio of 1:4, a cleaning duration of 40 min, and a stirring speed of 1000 rad/min. Under these optimal conditions and after merely two cleaning procedures, the residual oil content of ODCs was reduced to 1.64%, accompanied by a smooth and loose surface structure.

Oropharyngeal Stenosis Caused by Significant Scar Hyperplasia Following Tonsillectomy: A Case Report.

Oropharyngeal stenosis (OPS) is a relatively rare long-term complication of tonsillectomy in children, resulting from the narrowing of the upper aerodigestive tract between the soft palate, pharyngeal sidewalls, and base of the tongue. This is the first reported case of OPS due to significant scar hyperplasia; however, whether it is as prone to recurrence as skin scar hypertrophy remains unknown. In this article, we present the case of a 5-year-old girl who presented to our otolaryngology clinic with sleep snoring and suffocation. Her medical history included tonsillectomy and adenoidectomy, performed 3 years prior to presentation. The patient underwent a combination of surgery and administration of triamcinolone injections, resulting in significant symptomatic improvement. To date, no signs of recurrence have been reported.

Three-dimensional biotemplate-loaded nickel sulfide vacancies engineered to promote the absorption of electromagnetic waves.

Vacancy engineering offers an appealing strategy for modifying the electronic structure of transition metals. Transition metals with abundant sulfur vacancies can significantly contribute to the microwave absorption capabilities of absorbers. In this study, an NixSy@De composite material was synthesized through a straightforward hydrothermal synthesis technique. The effective absorption bandwidth (EAB) of this composite material reached 9.86 GHz at 1.44 mm. A minimum reflection loss (RLmin) of -33.61 dB at 1 mm was achieved, and after mild etching, the RLmin further improved to -93.53 dB at 1.16 mm to achieve a high-attenuation microwave absorption. The exceptional performance of NixSy@De for the absorption of electromagnetic waves (EMWs) is based on its high dielectric loss, substantial magnetic loss, and excellent impedance matching. This work combines transition metal sulfides with three-dimensional biotemplated diatomite, providing valuable insights into the design of advanced EMW absorbing materials.

A non-metallic SERS-based immunoassay founded by light-harvesting effect and strengthened chemical enhancement.

Owing to its promising biocompatibility and reliable sensitivity, semiconductor-guided surface-enhanced Raman scattering (SERS) technology has aroused widespread concern in clinical immunoassays. Herein, the well-improved light capture capability of MoS2 with a novel three-dimensional (3D) flower-like morphology was combined with the synergistic chemical enhancement from a MoS2@red phosphorus (RP) hybrid system, facilitating an attractive non-metallic SERS-based detection of ferritin in serum. Owing to the remarkable enhancement factors of both the immunoprobe and immunosubstrate, which were comparable to noble metal, an extremely low limit detection of 11.5 pg mL-1 was achieved in the absence of fluorescence interference. In particular, the trace ferritin in the clinical serum sample was successfully monitored, demonstrating superior sensitivity to the traditional chemiluminescent method. Overall, this study convincingly revealed the feasibility and reliability of SERS-based immunoassays induced by biocompatible semiconductors, which has opened a new way to implement the detection and tracking of biomarkers in the human body.

The Clinical Efficacy of Microsuture Technique Combined With Voice Therapy in Patients with Reinke's Edema.

OBJECTIVE: This study aimed to explore the clinical efficacy of the microsuture technique combined with voice therapy in patients with Reinke's edema. METHODS: 46 patients with Reinke's edema admitted between April 2017 and August 2021 were selected and randomly divided into simple surgical and combined therapy groups. The simple surgical and combined therapy group were evaluated preoperatively and at 3 months after surgery using subjective and objective voice analysis. RESULTS: Compared with the preoperative state, there was a significant improvement in the acoustic parameters 3 months postoperatively. The G and R scores, Voice Handicap index-10 (VHI-10), and jitter parameters of the combined therapy group were lower, whereas F0 and maximum phonation time (MPT), changed significantly in the combined therapy group, fundamental frequency perturbation (jitter), and MPT acoustic parameters of the combined therapy group were lower than those of the simple surgery group (P < 0.05). CONCLUSION: The microsuture technique is preferable for eliminating vocal folds surgical wounds and promoting mucosal recovery, and combined with voice therapy is more helpful to comprehensive improve the quality of phonation.

Relationship between Shale Hydration and Shale Collapse.

Shale gas has become the major source of natural gas. However, shale is rich in clay and easily collapsed by water invasion. This not only causes collapse of the reservoir but also causes the loss of natural gas and can even cause local earthquakes and affect the safety of human beings. This paper describes an investigation of the relationship between hydration and collapse. Shale samples were obtained from a series of wells drilled in the lower Silurian Longmaxi Formation at a depth of 3500 m. The different hydrated shales were simulated to analyze the hydration-collapse relationship. Magnetic resonance analysis and mechanical analysis were combined to analyze the collapse of the hydrated shales. The collapse progression was found to follow an S-shaped growth curve that can be divided into three parts, namely, the potential period, the exciting period, and the mature period. The hydration state and degree of damage were determined from the magnetic resonance of water molecules. This paper proposes a mechanism for shale hydration collapse based on basal and numerical data that can be used to predict shale collapse as a function of hydration.

Blind detection of circular image rotation angle based on ensemble transfer regression and fused HOG.

Introduction: Aiming at the problems of low accuracy in estimating the rotation angle after the rotation of circular image data within a wide range (0°-360°) and difficulty in blind detection without a reference image, a method based on ensemble transfer regression network, fused HOG, and Rotate Loss is adopted to solve such problems. Methods: The proposed Rotate Loss was combined to solve the angle prediction error, especially the huge error when near 0°. Fused HOG was mainly used to extract directional features. Then, the feature learning was conducted by the ensemble transfer regression model combined with the feature extractor and the ensemble regressors to estimate an exact rotation angle. Based on miniImageNet and Minist, we made the circular random rotation dataset Circular-ImageNet and random rotation dataset Rot-Minist, respectively. Results: Experiments showed that for the proposed evaluation index MSE_Rotate, the best single regressor could be as low as 28.79 on the training set of Circular-ImageNet and 2686.09 on the validation set. For MSE_Rotate, MSE, MAE, and RMSE on the test set were 1,702.4325, 0.0263, 0.0881, and 0.1621, respectively. And under the ensemble transfer regression network, it could continue to decrease by 15%. The mean error rate on Rot-Minist could be just 0.59%, significantly working easier in a wide range than other networks in recent years. Based on the ensemble transfer regression model, we also completed the application of image righting blindly.

LncRNA PICSAR binds to miR-485-5p and activates TGF-ß1/Smad to promote abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and excessive deposition of extracellular matrix (ECM).

The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-ß1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation. PICSAR and miR-485-5p expressions were detected by qPCR. Cell proliferation was examined by CCK-8. Protein expressions were determined by western blot. Immunofluorescence detected the Ki-67 expression. Dual-luciferase followed by immunoprecipitation was performed to verify the interaction between PICSAR and miR-485-5p. Interference with PICSAR inhibited the abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and the excessive deposition of ECM. It was also confirmed in our study that MiR-485-5p is a direct target of PICSAR in HSFs. Additionally, inhibition of miR-485-5p reversed the effect of PICSAR knockdown in HSFs. LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-ß1/Smad signaling pathway, promoting the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation.

Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance.

The ever-increasing understanding of the complexity of factors and regulatory layers that contribute to immune evasion facilitates the development of immunotherapies. However, the diversity of malignant tumors limits many known mechanisms in specific genetic and epigenetic contexts, manifesting the need to discover general driver genes. Here, we have identified the m6A demethylase FTO as an essential epitranscriptomic regulator utilized by tumors to escape immune surveillance through regulation of glycolytic metabolism. We show that FTO-mediated m6A demethylation in tumor cells elevates the transcription factors c-Jun, JunB, and C/EBPß, which allows the rewiring of glycolytic metabolism. Fto knockdown impairs the glycolytic activity of tumor cells, which restores the function of CD8+ T cells, thereby inhibiting tumor growth. Furthermore, we developed a small-molecule compound, Dac51, that can inhibit the activity of FTO, block FTO-mediated immune evasion, and synergize with checkpoint blockade for better tumor control, suggesting reprogramming RNA epitranscriptome as a potential strategy for immunotherapy.

Combined pulsed-dye laser and medical therapy for treatment of cutaneous sarcoidosis lesions: a case report.

Sarcoidosis is a systemic granulomatous disease of unknown etiology that most frequently occurs in the lungs. However, cutaneous lesions are often the primary sign. Cutaneous sarcoidosis is difficult to treat, although different therapies have been applied. We herein report a case in which cutaneous sarcoidosis was treated with pulsed-dye laser (PDL) therapy along with oral administration of acitretin and hydroxychloroquine; no topical medications were applied. All patient details are de-identified. The treatment areas gradually improved after several courses of PDL therapy. This case illustrates that PDL therapy can serve as an auxiliary treatment for cutaneous sarcoidosis.

Treatment of pigmentary disorders using picosecond laser in Asian patients: A meta-analysis and systematic review.

There were many studies evaluating the effect of picosecond (PS) lasers, but no meta-analysis examined the effects of PS laser in the treatment of pigmentary disorders in Asians. The aim of this article was to review the before-after effect of PS laser in Asians for the treatment of pigmentary disorders. PubMed, Embase, and Cochrane library were searched for articles published up to May 2020. The evaluations were summarized into a 4-point scale that ranged from <25% (poor), 25%-50% (fair), 50%-75% (good), and 75%-100% (excellent). Effect sizes (ESs) were calculated according to laser wavelengths and lesion types. There were two randomized controlled trials, three single-arm trials, and three case series, with 200 patients. At 3 months after treatment, of all included patients, 3% (95%CI: 1%-6%) were evaluated as poor or worse, 9% (95%CI: 2%-21%) as fair, 29% (95%CI: 12%-50%) as good, and 56% (95%CI: 28%-83%) as excellent. The 532 and 1064, and 755 nm PS lasers had similar ESs across all four response groups. This meta-analysis suggested that 56% of Asian patients who underwent PS laser for the treatment of pigmentary disorders were evaluated as "excellent" about the pigment clearance by a dermatologist at least 3 months after treatment.

Effect of 532nm photodynamic therapy with hemoporfin on the expression of vascular endothelial growth factor in cultured human vascular endothelial cells.

BACKGROUND: Photodynamic therapy (PDT) with hemoporfin (hematoporphyrinmonomethyl ether, HMME) and 532 nm continuous-wave lasers is effective for port-wine stains (PWS) and is considered as a promising treatment modality. The vascular endothelial growth factor (VEGF) is involved in the development of PWS. This study aimed to investigate the effect of 532 nm-HMME-PDT on the in vitro expression of VEGF in human umbilical vein endothelial cells (HUVECs) exposed to different power levels of 532 nm laser and different concentrations of HMME. METHOD: The CCK-8 assay was performed to assess cell viability. Enzyme-linked immunosorbent assay (ELISA) was performed to measure VEGF secretion. VEGF and VEGF receptor (VEGFR) mRNA expression levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Within 72 h after HMME-PDT, cell viability was inhibited, secretion and expression of VEGF was decreased, and expression of VEGFR mRNA was significantly decreased with the increase of HMME concentration. CONCLUSION: 532 nm-HMME-PDT can downregulate the expression of VEGF and VEGFR mRNA. Future studies are necessary to examine the HMME doses to achieve better efficacy with fewer adverse effects.

Thermoresponsive Bentonite for Water-Based Drilling Fluids.

As an important industrial material, bentonite has been widely applied in water-based drilling fluids to create mud cakes to protect boreholes. However, the common mud cake is porous, and it is difficult to reduce the filtration of a drilling fluid at high temperature. Therefore, this paper endowed bentonite with a thermo response via the insertion of N-isopropylacrylamide (NIPAM) monomers. The interaction between NIPAM monomers and bentonite was investigated via Fourier infrared spectroscopy (FTIR), isothermal adsorption, and X-ray diffraction (XRD) at various temperatures. The results demonstrate that chemical adsorption is involved in the adsorption process of NIPAM monomers on bentonite, and the adsorption of NIPAM monomers accords with the D-R model. With increasing temperature, more adsorption water was squeezed out of the composite when the temperature of the composite exceeded 70 °C. Based on the composite of NIPAM and bentonite, a mud cake was prepared using low-viscosity polyanionic cellulose (Lv-PAC) and initiator potassium peroxydisulfate (KPS). The change in the plugging of the mud cake was investigated via environmental scanning electron microscopy (ESEM), contact angle testing, filtration experiments, and linear expansion of the shale at various temperatures. In the plugging of the mud cake, a self-recovery behavior was observed with increasing temperature, and resistance was observed at 110 °C. The rheology of the drilling fluid was stable in the alterative temperature zone (70-110 °C). Based on the high resistance of the basic drilling fluid, a high-density drilling fluid (ρ = 2.0 g/cm3) was prepared with weighting materials with the objective of drilling high-temperature formations. By using a high-density drilling fluid, the hydration expansion of shale was reduced by half at 110 °C in comparison with common bentonite drilling fluid. In addition, the rheology of the high-density drilling fluid tended to be stable, and a self-recovery behavior was observed.

Switching glycosyltransferase UGTBL1 regioselectivity toward polydatin synthesis using a semi-rational design.

The 62nd residue of glycosyltransferase UGTBL1 was identified as a "hotspot" for glycosylation at 3-OH of resveratrol. Via semi-rational design including structure-guided alanine scanning and saturation mutations, the mutation I62G significantly switched the regioselectivity from 4'-OH to 3-OH of resveratrol and mainly produced polydatin (87.7%), a therapeutic natural product.

Time-series pattern of gene expression profile in gentamycin-induced nephrotoxicity.

There have been many studies investigating the genomic biomarker and/or molecular mechanism of nephrotoxicity using microarray. However, most of these researches were carried out by studying gene expression changes at one specific time point. As gene expression varies with time and disease stage, the current study investigated the time-series pattern of gene expression in a rat model using a typical nephrotoxic compound. Rats were administrated with 80 mg/kg gentamycin or saline by intramuscular injection for 14 consecutive days followed by a 28-d recovery. Rats were scarified on D2, D4, D8, D15 and Recovery Day (R29), when kidneys were obtained for whole-genome microarray analysis and histological examination. Urine was collected at each necropsy for kidney injury molecular-1 (KIM-1) analysis. The KIM-1 detection and histological examination confirmed the nephrotoxicity. After differentially expression genes (DEGs) identification, there were 4360 and 4323 regulated genes for females and males, respectively. However, few overlapping expression genes co-regluated at each time point were found. By principle component analysis (PCA) and hierarchical cluster, the gene expression patterns were observed to be apparently associated with the disease stage. GO Annotation showed (1) immune response and related process, response to wounding, cell locomotion on D2; (2) cell death and apoptosis was also noted on D4; (3) processes of organic acid or carboxylic acid, apoptosis or cell death on D8 and D15; (4) processes of cell cycle, mitosis, division cell cycle on R29. In conclusion, the authors mapped the time-series gene expression patterns at the initiation, development and recovery stage of gentamycin-induced nephrotoxicity.

Exposure to pyrithiamine increases ß-amyloid accumulation, Tau hyperphosphorylation, and glycogen synthase kinase-3 activity in the brain.

Decreased thiamine-dependent enzyme activity and/or thiamine deficiency (TD) have been linked to Alzheimer's disease (AD). In this study, we administered pyrithiamine, an anti-thiamine compound, to both APP/PS1 transgenic mice and wild-type littermate control mice; alternatively, we induced TD by thiamine-depleted diet. Pyrithiamine treatment and diet-induced TD impaired the memory of wild-type mice, but had little effect on APP/PS1 mice. Pathophysiologically, pyrithiamine treatment and diet-induced TD aggravated ß-amyloid accumulation in the brain. This was demonstrated by increased ß-amyloid in the brains of wild-type mice using ELISA and by the number of amyloid plaques in the brains of APP/PS1 transgenic mice using immunochemical staining. Also, enhanced numbers of phosphorylated Tau-positive cells were observed in both APP/PS1 transgenic and wild-type mice. Furthermore, pyrithiamine decreased the phosphorylation rates of glycogen synthase kinase (GSK)-3ß and raised its enzymatic activity, but had little influence on GSK-3α. Diet-induced TD reduced the phosphorylated rates and increased the activities of GSK-3, GSK-3α, and GSK-3ß. These results suggest that when sufficient thiamine supplement is administered, pyrithiamine can cause AD-like pathological alterations similar to that of diet-induced TD.