Cytomegalovirus colitis as intestinal obstruction in an immunocompetent adolescent: a case report and literature review.

BACKGROUND: Cytomegalovirus infection manifests varying clinical characteristics and severity in diverse populations with different immune statuses. The signs and symptoms of gastrointestinal involvement are nonspecific. Here, we present a case of cytomegalovirus colitis in an immunocompetent adolescent, which manifested as intestinal pseud-obstruction. CASE PRESENTATION: A 15-year-old man who had contracted novel coronavirus infection one month earlier was admitted to our hospital with fever, abdominal pain, and hematochezia. His abdomen was distended, and laboratory evaluation revealed a decrease in the blood count, an increase in inflammatory indicators and hepatic impairment. Imaging shows bowel wall thickening and dilatation of the colon. A diagnosis of intestinal infection combined with acute intestinal pseud-obstruction was made. Diarrhea persisted despite conservative treatment with empirical antibiotics. A colonoscopy was performed. Pathology confirmed cytomegalovirus infection. Ganciclovir therapy was initiated, and subsequent review showed a good recovery. CONCLUSIONS: The case was diagnosed as cytomegalovirus colitis. We reviewed the reports of 9 cases of bowel obstruction, including our own, and found that the majority of the adult patients were elderly with underlying disease. Clinical and endoscopic manifestations are typically nonspecific, and imaging shows typical signs of intestinal obstruction. The final diagnosis was confirmed by pathology. Most of them have a good prognosis. We suggest that cytomegalovirus colitis can also lead to intestinal obstruction and that viral reactivation in immunocompetent individuals may be associated with inflammatory conditions and viral coinfection, particularly with the novel coronavirus.

Association between patient adherence and treat-to-target in gout: A cross-sectional study.

The implementation of a treat-to-target (T2T) approach has been widely recommended for achieving optimal outcomes in gout treatment, as substantiated by a wealth of compelling evidence. However, a paucity of knowledge exists regarding the barriers hindering effective T2T management in China. This study seeks to investigate the factors contributing to treatment failure within the context of the T2T strategy. A cross-sectional, multi-center investigation was conducted, involving the completion of electronic questionnaires by outpatients undergoing urate-lowering treatment for a duration exceeding 6 months. These questionnaires encompassed demographic information, disease-related conditions, comorbid conditions, and management. The study analyzed factors associated with serum uric acid levels exceeding 360 µmol/L, poor disease control, and poor medication adherence. A total of 425 valid questionnaires were collected, representing 90.8% of the patients. The T2T implementation rate was 26.82% (n = 114). Factors linked to serum uric acid levels surpassing 360 µmol/L included moderate medication adherence (odds ratio (OR) = 2.35; 95% confidence interval (CI) 1.17-4.77; P = .016), poor medication adherence (OR = 4.63; 95% CI 2.28-9.51; P < .001), and management by general practitioners (OR = 0.60; 95% CI 0.37-0.97; P = .036). The rate of well-controlled patients was 14.35% (n = 61). Predictors of not well controlled encompassed the presence of tophi (OR = 2.48; 95% CI 1.17-5.61; P = .023), general medication adherence (OR = 2.78; 95% CI 1.28-6.05; P = .009), poor medication adherence (OR = 6.23; 95% CI 2.68-14.77; P < .001), and poor patient's perception of gout (OR = 4.07; 95% CI 1.41-13.91; P = .015). A poor medication adherence rate of 55.29% (n = 235) was observed, with lower rates of poor medication adherence associated with the use of febuxostat (OR = 0.35; 95% CI 0.14-0.83; P = .02), uric acid levels exceeding 360 µmol/L (OR = 3.05; 95% CI 1.84-5.12; P = .00), moderate patient education (OR = 2.28; 95% CI 1.29-4.15; P = .01), moderate diet control (OR = 1.98; 95% CI 1.17-3.41; P = .01), and poor diet control (OR = 3.73; 95% CI 1.26-12.83; P = .02). The rate of T2T implementation in China is notably low among patients undergoing urate-lowering treatment of gout beyond 6 months. Importantly, medication adherence demonstrates a significant association with T2T outcomes.

Rosmarinic Acid Activates the Nrf2/ARE Signaling Pathway via the miR-25-3p/SIRT6 Axis to Inhibit Vascular Remodeling.

The vital pathological processes in intimal hyperplasia include aberrant vascular smooth muscle cells (VSMCs) proliferation, migration, and phenotypic switching. Rosmarinic acid (RA) is a natural phenolic acid compound. Nevertheless, the underlying mechanism of RA in neointimal hyperplasia is still unclear. Our analysis illustrated that miR-25-3p mimics significantly enhanced PDGF-BB-mediated VSMCs proliferation, migration, and phenotypic switching while RA partially weakened the effect of miR-25-3p. Mechanistically, we found that miR-25-3p directly targets sirtuin (SIRT6). The suppressive effect of the miR-25-3p inhibitor on PDGF-BB-induced VSMCs proliferation, migration, and phenotypic switch was partially eliminated by SIRT6 knockdown. The suppression of the PDGF-BB-stimulated Nrf2/ARE signaling pathway that was activated by the miR-25-3p inhibitor was exacerbated by the SIRT6 knockdown. In in vivo experiments, RA reduced the degree of intimal hyperplasia while miR-25-3p agomir partially reversed the suppressive effect of RA in vascular remodeling. Our results indicate that RA activates the Nrf2/ARE signaling pathway via the miR-25-3p/SIRT6 axis to inhibit vascular remodeling.

Prediction of immunotherapy responsiveness in melanoma through single-cell sequencing-based characterization of the tumor immune microenvironment.

Immune checkpoint inhibitors (ICB) therapy have emerged as effective treatments for melanomas. However, the response of melanoma patients to ICB has been highly heterogenous. Here, by analyzing integrated scRNA-seq datasets from melanoma patients, we revealed significant differences in the TiME composition between ICB-resistant and responsive tissues, with resistant or responsive tissues characterized by an abundance of myeloid cells and CD8+ T cells or CD4+ T cell predominance, respectively. Among CD4+ T cells, CD4+ CXCL13+ Tfh-like cells were associated with an immunosuppressive phenotype linked to immune escape-related genes and negative regulation of T cell activation. We also develop an immunotherapy response prediction model based on the composition of the immune compartment. Our predictive model was validated using CIBERSORTx on bulk RNA-seq datasets from melanoma patients pre- and post-ICB treatment and showed a better performance than other existing models. Our study presents an effective immunotherapy response prediction model with potential for further translation, as well as underscores the critical role of the TiME in influencing the response of melanomas to immunotherapy.

STING upregulation mediates ferroptosis and inflammatory response in lupus nephritis by upregulating TBK1 and activating NF-κB signal pathway.

Accumulated evidence implicates lipid peroxidation as a key mechanism contributing to the pathogenesis of lupus nephritis (LN). Ferroptosis is a specialized form of cell death induced by loss or deficient activity of the glutathione peroxidase 4 (GPX4) and decreased clearance of polyunsaturated fatty acid hydroperoxides. STING production may lead to the occurrence of intracellular lipid peroxidation, ultimately triggering ferroptosis, but it has not been clarified whether STING can aggravate LN via ferroptosis. The adjacent normal kidney tissues from renal cell carcinoma and biopsied kidney tissue samples from LN patients were used for research, and the expression of STING protein in kidney tissue was detected by immunohistochemistry and RT-qPCR. MRL/lpr mice, a model of LN, were used to detect STING expression in kidney tissue. STING expression in the kidney tissue of MRL/lpr mice was knocked down by sh-STING-AAV, and then levels of 4-HNE, MDA, ROS, iron ion, blood urea nitrogen and serum creatinine, IL-6, IL-1ß, and TNF-α, and the protein expression of STING, TBK1, NF-κB, GPX4, ACSL4, and SLC7A11 were subsequently examined. STING was elevated in the kidney tissue of LN patients and MRL/lpr mice. Compared with the MRL/lpr group, liproxstatin-1 or ferrostatin-1 treatment alleviated ferroptosis-related indicators 4-HNE, MDA, ROS, iron ion release, and GPX4 and SLC7A1 expression, whereas the treatment enhanced ACSL4 expression. STING interference observably decreased 4-HNE, ROS, MDA, iron ion, STING, and ACSL4 levels, and increased GPX4 and SLC7A11 expression in MRL/lpr mice kidney tissues. Besides, inhibition of STING reduced kidney tissue damage and inflammatory cell infiltration in MRL/lpr mice, and levels of serum creatinine, blood urea nitrogen, serum anti-double-stranded DNA antibody, inflammatory factors IL-6, IL-1ß, and TNF-α, as well as phosphorylation of NF-κB were all significantly decreased in MRL/lpr mice. TBK1 over expression reversed the impact of STING inhibition on ferroptosis and inflammatory response. STING contributed to ferroptosis and inflammatory response by activating the TBK1/NF-κB pathway, suggesting that STING may be a potent therapeutic target in LN.

Synthesis of amino-functionalized nanocellulose by guanidine based deep eutectic solvent and its application in fine fibers retention.

A guanidine-based Deep Eutectic Solvent (DES) consisting of 1,3-diaminoguanidine monohydrochloride and glycerol was utilized to prepare C-CNC from dissolving pulp. The pulp fibers were oxidized to dialdehyde cellulose by periodate, then fibrillated through the hydrogen bonds shear of DES and aminocationized through Schiff base effect of the amino groups in the DES solvent to obtain C-CNC. The results revealed that the characterization of the DES (such as viscosity, polarity, and pH) was related to the molar ratio of glycerol/guanidine-salts. The hydrogen bond network structure of DES solvent with optimal system was simulated by DFT and its damage to fiber hydrogen bond network was predicted. The C-CNC produced under the optimal reaction conditions (molar ratio of 1:2, 90 °C for 2 h) was highly dispersible with an average length and diameter of 85 ± 35 nm and 5.0 ± 1.2 nm, a charge density of 2.916 mol/g. C-CNC exhibited excellent flocculation when added to fine fiber suspensions of chemomechanical slurries, achieving rapid flocculation and settling onto fibers in <1 min. The DES solvent maintained its reactivity after 5 cycles. This study lays the foundation for the batch preparation of nanocellulose in an environmentally friendly manner and its application as a green additive in paper industry.

A smartphone-intergrated dual-emission fluorescent nanoprobe for visual and ratiometric detection of anthrax biomarkers.

A novel dual-emission fluorescent nanoprobe based on rare-earth nanosheets was fabricated to detect 2,6-pyridine dicarboxylic acid (DPA), which is the biomarker of Bacillus anthracis. 2-amino terephthalic acid (BDC-NH2) and surfactant sodium dodecyl sulfate (SDS) were co-intercalated into layered europium hydroxide (LEuH) to prepare the organic/inorganic composite, which was delaminated to obtain the rare-earth nanosheets. The ratio detection of DPA is possible due to the antenna effect between DPA and Eu3+. The nanoprobe shows high accuracy and sensitivity due to the large specific surface area of the rare-earth nanosheets. The limit of detection (LOD) is 4.4 nM for DPA in the range of 0-20 µM. In addition, a more convenient and faster smartphone-based visual detection platform was established based on the obvious color change. This work offers an effective way for developing visual sensing platforms, which opens a new path for designing fluorescent probes with superior sensing capabilities.

Preparation and characterization of cellulose nanofibril/chitosan aerogels with high-adsorbability and sensitive indication for indoor free formaldehyde.

The toxic volatile organic compounds (VOCs), especially formaldehyde (FA), released from decoration materials pose a great threat to human health. In this study, formaldehyde adsorption performance of the specially formulated nanocellulose/chitosan aerogel (CNFCA) was investigated in simulated atmosphere. The physicochemical property of the composite aerogel was characterized, which had a large specific surface area (153.67 m2/g), a rough surface and an ultra-thin and porous structure. The composite aerogel showed excellent adsorption capacity for the formaldehyde, its theoretical maximum adsorption capacity was as high as 83.89 mg/g, and the adsorption process was more in accordance with the pseudo-second-order kinetics. The chromogenic reaction between the 4-amino-3-benzo-5-mercapto-1,2,4-triazolium (AHMT) and CNFCA was found that the color of the composite aerogel was depended on the free formaldehyde concentration. Based on this phenomenon, a colorimetric card was proposed and built to detection the formaldehyde in the atmosphere. Moreover, the adsorption mechanism research was found that the CNFCA with a multilayer structure belonged to physicochemical complex adsorption.

An Access Control Scheme Based on Blockchain and Ciphertext Policy-Attribute Based Encryption.

Ciphertext policy-attribute-based encryption (CP-ABE), which provides fine-grained access control and ensures data confidentiality, is widely used in data sharing. However, traditional CP-ABE schemes often choose to outsource data to untrusted third-party cloud service providers for storage or to verify users' access rights through third parties, which increases the risk of privacy leakage and also suffers from the problem of opaque permission verification. This paper proposes an access control scheme based on blockchain and CP-ABE, which is based on multiple authorization centers and supports policy updating. In addition, blockchain technology's distributed, decentralized, and tamper-proof features are utilized to solve the trust crisis problem in the data-sharing process. Security analysis and performance evaluation show that the proposed scheme improves the computational efficiency by 18%, 26%, and 68% compared to previous references. The proposed scheme also satisfies the indistinguishability under chosen-plaintext attack (IND-CPA).

Nutrient-Based Approaches for Melanoma: Prevention and Therapeutic Insights.

Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in understanding its pathogenesis and treatment, the quest for effective prevention strategies and therapeutic approaches remains ongoing. Considering the increased advancements in understanding the dynamic interplay between nutrients and melanoma, we aim to offer a refreshed perspective on nutrient-based approaches for melanoma prevention and adjunctive therapy. In contrast to other studies, we have innovatively provided a detailed exposition of the nutrients' influences on melanoma prognosis and treatment. This review firstly examines various nutrients, including antioxidants (namely vitamins A, D, C, and E; selenium; and caffeine), polyunsaturated fatty acids, and flavonoids, for their effects and underlying mechanisms in reducing melanoma risk. Among these nutrients, caffeine shows the most promising potential, as it is supported by multiple cohort studies for its protective effect against melanoma. In contrast, there is a certain degree of inconsistency in the research of other nutrients, possibly due to inherent differences between animal studies and epidemiological research, as well as variations in the definition of nutrient intake. To comprehensively investigate the impact of nutrients on melanoma progression and therapeutic approaches, the following sections will explore how nutrients influence immune responses and other physiological processes. While there is robust support from cell and animal studies regarding the immunomodulatory attributes of vitamins D and zinc, the anti-angiogenic potential of polyphenols, and the cell growth-inhibitory effects of flavonoids, the limited availability of human-based research substantially constrains their practical relevance in clinical contexts. As for utilizing nutrients in adjuvant melanoma treatments, multiple approaches have garnered clinical research support, including the utilization of vitamin D to decrease the postoperative recurrence rates among melanoma patients and the adoption of a high-fiber diet to enhance the effectiveness of immunotherapy. In general, the effects of most nutrients on reducing the risk of melanoma are not entirely clear. However, several nutrients, including vitamin D and dietary fiber, have demonstrated their potential to improve the melanoma prognosis and enhance the treatment outcomes, making them particularly deserving of clinical attention. A personalized and interdisciplinary approach, involving dermatologists, oncologists, nutritionists, and researchers, holds the promise of optimizing melanoma treatment strategies.

The association between online class-related enjoyment and academic achievement of college students: a multi-chain mediating model.

BACKGROUND: Based on the control-value theory of achievement emotion and self-determination motivation theory, this study attempted to examine the multi-chain mediating relationships among online class-related enjoyment, school motivation, learning engagement and academic achievement. METHODS: This is an empirical study based on cross-sectional data. Online class-related enjoyment is the independent variable, academic achievement is the dependent variable, and school motivation and learning engagement are the mediating variables. Sample data were collected from 1294 Chinese college students, and SPSS macro program PROCESS 3.3 was used for data analysis. RESULTS: The present study confirmed that students' online class-related enjoyment has a significant positive correlation with academic achievement. And there is a positive correlation between college students' school motivation with learning engagement and college students' learning engagement with academic achievement. In addition, online class-related enjoyment affects academic achievement through the chain mediating effect of school motivation and learning engagement. CONCLUSIONS: Our study indicated that online class-related enjoyment has a significant impact on academic achievement. Both of these factors should be considered when determining the optimal multi-chain mediating model for Online Class-related Enjoyment and Academic Achievement of college students.

Analysis of parametric instability of cigarettes based on computational fluid dynamics methods.

In actual production tests, there are large fluctuations in the ventilation rate and smoking resistance of cigarettes. In this paper, fluctuations in ventilation rate and smoking resistance are attributed to variations in the number of ventilation holes in the joint paper and the porosity of each component. The effects of small changes in porosity of each component were analyzed by using computational fluid dynamics methods. The results showed that the difference in the effective number of ventilation holes caused by the gluing process had little effect on the ventilation rate and smoking resistance of cigarettes in the practical production process. The smoking resistance is mainly affected by the structural parameters of filter tow and cut tobacco section in the length direction of cigarettes, the porosity of cigarette paper and packaging paper is positively related to the cigarette ventilation rate, the porosity of cut tobacco and the porosity of filter tow are negatively related to the cigarette ventilation rate, and the influence of shaped paper is the smallest. The results can provide technical and theoretical basis for the optimization of cigarette process parameters and the stabilization of ventilation rate.

Relationship between Bladder Cancer, Nutritional Supply, and Treatment Strategies: A Comprehensive Review.

Bladder cancer (BC) is the predominant neoplasm affecting the urinary system and ranks among the most widespread malignancies globally. The causes of bladder cancer include genetic factors; age; sex; and lifestyle factors, such as imbalanced nutrition, obesity, and metabolic disorders. The lack of proper nutrient intake leads to the development of bladder cancer because insufficient nutrients are consumed to prevent this disease. The purpose of this review was to analyze the nutrients closely linked to the onset and advancement of bladder cancer and to explore the relationship between dietary nutrients and bladder cancer. Particular emphasis was placed on nutrients that are frequently ingested in daily life, including sugar, fat, protein, and others. The focus of this research was to analyze how nutritional intake before and after surgery affects the recovery process of patients who have been diagnosed with bladder cancer. This article seeks to increase awareness among both society and the medical community about the significance of implementing appropriate dietary nutrition to reduce the chances of developing bladder cancer, enhance perioperative care for patients with bladder cancer, and aid in their recuperation.

Analysis of the metastatic mechanism and progress in the treatment of breast cancer liver metastasis: a narrative review.

Background and Objective: Breast cancer is the most common malignancy in women, and metastasis to other target organs is one of the main causes of death. Breast cancer liver metastasis (BCLM) has long been a research focus. Enhancing therapeutic effects, optimizing treatment plans and improving the prognosis of patients are major clinical challenges at present. Methods: We performed a comprehensive, nonsystematic review of the latest literature to define the current metastatic mechanism and related treatment advances of BCLM. Key Content and Findings: Due to the lack of research on the mechanism of BCLM, present treatment programs still have limited benefits, and the prognosis of patients is generally poor. New research directions and treatment ideas for BCLM are urgently needed. In this article, we indicated the specific procedures of the BCLM mechanism from the microenvironment to metastasis formation and progress in treatment, including drug therapies such as targeted therapy, surgery, intervention therapy and radiotherapy. Research on the molecular mechanism plays a crucial role in the development of BCLM-related therapies. Based on the metastasis process, we are able to propel new findings and further progression of antineoplastic drugs. Conclusions: The process of BCLM is multistep, and various factors are involved in it, which provides a powerful theoretical basis for the development of therapeutic methods for treatment of this disease. Further understanding of the mechanism of BCLM is essential to guide clinical management.

A core-shell structure ratiometric fluorescent probe based on carbon dots and Tb3+ for the detection of anthrax biomarker.

A novel core-shell structure ratiometric fluorescent probe was developed, which can selectively and sensitively detect 2,6-dipicolinic acid (DPA) as an anthrax biomarker. Carbon dots (CDs) was embedded into SiO2 nanoparticles, which was acted as an internal reference signal. Tb3+ with green emission was connected to the carboxyl functionalized SiO2, which was acted as a responsive signal. With the addition of DPA, the emission of CDs at 340 nm was unchanged, while the fluorescence of Tb3+ at 544 nm was enhanced by the antenna effect. In the concentration range of 0.1-2 µM, the fluorescence intensity ratio of I544/I340 showed a good linear relationship with the concentration of DPA, and the limit of detection (LOD) was 10.2 nM. In addition, the dual-emission probe showed an obvious fluorescence color change from colourless to green with increasing DPA under UV light, which enabled visual detection.

Fluorescence on and off sensing platform based on europium nanosheets for the detection of DPA and Cu2+ ions.

With the development of society, the modern environment has put forward higher requirements for analysis and detection. This work proposes a new strategy for the construction of fluorescent sensors based on rare-earth nanosheets. Organic/inorganic composites were obtained by the intercalation of 4,4'-stilbene dicarboxylic acid (SDC) into layered europium hydroxide, and then the composites were exfoliated to form nanosheets. Taking advantage of the fluorescence emission characteristics of SDC and Eu3+, a ratiometric fluorescent nanoprobe was constructed, which realized the detection of dipicolinic acid (DPA) and Cu2+ in the same system. With the addition of DPA, the blue emission of SDC gradually decreased and the red emission of Eu3+ gradually increased, when Cu2+ was added, the emission of SDC and Eu3+ were gradually weakened. The experimental results showed that the ratio of fluorescence emission intensity (I619/I394) of the probe had a positive linear relationship with the concentration of DPA, and a negative linear relationship with the concentration of Cu2+, thus realizing the high sensitivity detection of DPA and a wide detection range of Cu2+. In addition, this sensor also exhibits potential visual detection possibilities. This is a multifunctional fluorescent probe that provides a novel and efficient method for the detection of DPA and Cu2+, which broadens the application field of rare-earth nanosheets.

Relationship between iron overload caused by abnormal hepcidin expression and liver disease: A review.

Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.

A novel cuproptosis-related gene signature for overall survival prediction in patients with hepatocellular carcinoma.

Prognosis prediction is difficult in hepatocellular carcinoma (HCC) due to high heterogeneity and complex etiology. It has recently been discovered that cuproptosis is a type of programmed cell death. However, its significance for HCC is still unclear. We analyzed mRNA expression profiles and clinical information from public databases to determine whether cuproptosis-related genes are associated with improved prognoses for HCC patients. The training cohort consisted of HCC patients from The Cancer Genome Atlas (TCGA), and the validation cohort relied on the International Cancer Genome Consortium (ICGC) database. We constructed a signature containing four genes using the least absolute shrinkage and selection operator (LASSO) COX regression model for calculating risk scores. Two risk groups were formed based on the median score. A significant improvement in survival was observed in the low-risk group compared to the high-risk. The multivariate Cox regression analysis showed that the risk score was an independent predictor of overall survival (OS). Further confirmation of the predictive accuracy of this signature is provided by receiver operating characteristic (ROC) analysis. Functional analysis revealed differences in immune status between the two risk groups. All the results described above were confirmed in the validation cohort. Therefore, a novel cuproptosis-related signature has the potential as a prognostic biomarker for HCC patients. Drugs developed to target cuproptosis-related genes may open up new pathways for treating HCC.

The Impact of Undergraduates' Social Isolation on Smartphone Addiction: The Roles of Academic Anxiety and Social Media Use.

The COVID-19 pandemic has an adverse effect on the physical health of societies and individuals. One important concern is the effect of social isolation on the mental health of undergraduates, such as academic anxiety, smartphone addiction and other social psychological problems. The purpose of this study was to investigate associations among undergraduates' social isolation in this special context, social media use for obtaining information about the COVID-19 pandemic (i.e., communicative and non-communicative), academic anxiety, and smartphone addiction. A cross-sectional survey was conducted from May to June in 2022 and a total of 388 undergraduates were included. The results showed significant positive associations between social isolation and smartphone addiction and academic anxiety. Furthermore, academic anxiety played a mediating role in the effect of social isolation on smartphone addiction, which was moderated by non-communicative social media use. Some theoretical and practical implications as well as research limitations are discussed.

Rose Bengal inhibits ß-amyloid oligomers-induced tau hyperphosphorylation via acting on Akt and CDK5 kinases.

RATIONALE: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents. OBJECTIVES: The research aimed to investigate if and how RB could prevent ß-amyloid (Aß) oligomers-induced tau hyperphosphorylation in rodents. METHODS AND RESULTS: RB was tested in vitro (0.3-1 µM) and prevented Aß oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aß oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3ß (GSK3ß) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3ß and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation. CONCLUSIONS: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3ß and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.