Long-Term Outcome of Photobiomodulation Therapy for Refractory Diabetic Wound After Secretory Carcinoma of the Parotid Gland Surgery: A Case Report.

Objective: To evaluate the efficacy and safety of photobiomodulation therapy (PBMT) in the treatment of diabetic patients with refractory wound. Background: Refractory wound is one of the most challenging clinical complications of diabetes mellitus. Studies have shown that PBMT can promote wound healing in many ways. Methods: We reported a 55-year-old male patient with refractory diabetic wound after secretory carcinoma of the parotid gland surgery responding to 810 nm laser. Results: After PBMT, the refractory diabetic wound healed gradually without adverse events. During follow-up 5-years, the healed wound remained stable and showed no signs of recurrence. Conclusions: PBMT can be potentially considered as a therapeutic method in diabetic patients with refractory diabetic wound.

Fork coupling directs DNA replication elongation and termination.

DNA replication is initiated at multiple loci to ensure timely duplication of eukaryotic genomes. Sister replication forks progress bidirectionally, and replication terminates when two convergent forks encounter one another. To investigate the coordination of replication forks, we developed a replication-associated in situ HiC method to capture chromatin interactions involving nascent DNA. We identify more than 2000 fountain-like structures of chromatin contacts in human and mouse genomes, indicative of coupling of DNA replication forks. Replication fork interaction not only occurs between sister forks but also involves forks from two distinct origins to predetermine replication termination. Termination-associated chromatin fountains are sensitive to replication stress and lead to coupled forks-associated genomic deletions in cancers. These findings reveal the spatial organization of DNA replication forks within the chromatin context.

Optical properties of recycled zirconia for dental applications.

STATEMENT OF PROBLEM: While waste zirconia can be recycled, whether the optical properties of recycled zirconia match those of commercially available zirconia is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the optical properties of recycled zirconia by assessing its color, translucency, and opalescence across different thicknesses and shades. MATERIAL AND METHODS: Sixty specimens were prepared from 3 mol% yttria-stabilized tetragonal zirconia polycrystal blocks (Lava Plus; 3M ESPE) (group C); 60 other specimens were prepared from waste blocks of the same zirconia (group R). The specimens were further categorized into 4 subgroups (n=15) based on their thicknesses (1.0 mm or 1.5 mm) and shades (A1 or A3). Specimen color was measured with a spectrophotometer (Easyshade Advance 4.0; Vita ZahnFabrik). The parameters of color difference (ΔE00), translucency (TP), contrast ratio (CR), and opalescence (OP) were calculated. Grain size analysis was performed using scanning electron microscopy. Data were analyzed with analysis of variance (ANOVA) (α=.05). RESULTS: Significant differences in translucency and opalescence were observed between groups C and R in all specimens (P<.001). Group R exhibited a range of TP (4.89 to 11.27), CR (0.74 to 0.91), and OP (3.36 to 8.65) values. The ΔE00 values between groups C and R ranged from 13.99 to 21.31. Both thickness and shade significantly affected the ΔE00 values (P<.001). The grain size in group C was not significantly different from that in group R (F=0.364, df=1, P=.555). The TP and OP values of group R decreased with increasing thickness (P<.001). CONCLUSIONS: Recycled zirconia was less translucent and opalescent than commercially available zirconia. The color difference between commercially available and recycled zirconia exceeded the acceptable threshold, even when using the same staining procedure. Recycled zirconia exhibited reduced translucency and opalescence with increasing thickness.

Production of CA125 with Tn-antigens using a glycosylphosphatidylinositol anchoring system.

Cancer antigen 125 (CA125) is a serum marker associated with ovarian cancer. Despite its widespread use, CA125 levels can also be elevated in benign conditions. Recent reports suggest that detecting serum CA125 that carries the Tn-antigen, a truncated O-glycan containing only N-acetylgalactosamine on serine or threonine residues, can improve the specificity of ovarian cancer diagnosis. In this study, we engineered cells to express CA125 with a Tn-antigen. To achieve this, we knocked out C1GALT1 and SLC35A1, genes encoding Core1 synthase and a transporter for cytidine-5'-monophospho-sialic acid respectively, in human embryonic kidney 293 (HEK293) cells. In ClGALT1-SLC35A1-knockout (KO) cells, the expression of the Tn-antigen showed a significant increase, whereas the expression of the T-antigen (galactose-ß1,3-N-acetylgalactosamine on serine or threonine residues) was decreased. Due to the inefficient secretion of soluble CA125, we employed a glycosylphosphatidylinositol (GPI) anchoring system. This allowed for the expression of GPI-anchored CA125 on the cell surface of ClGALT1-SLC35A1-KO cells. Cells expressing high levels of GPI-anchored CA125 were then enriched through cell sorting. By knocking out the PGAP2 gene, the GPI-anchored form of CA125 was converted to a secretory form. Through the engineering of O-glycans and the use of a GPI-anchoring system, we successfully produced CA125 with Tn-antigen modification.

Influence of landform, soil properties, soil Cd pollution and rainfall on the spatial variation of Cd in rice: Contribution and pathway models based on big data.

Landform, soil properties, soil cadmium (Cd) pollution and rainfall are the important factors affecting the spatial variation of rice Cd. In this study, we conducted big data mining and model analysis of 150,000 rice-soil sampling sites to examine the effects by the above four factors on the spatial variation of rice Cd in Hunan Province, China. Specifically, the variable coefficient of rice Cd in space was significantly correlated with the partition scale according to the logistic fitting. The improved random forest results suggested that elevation (DEM) and pH were the two most important factors affecting the spatial variation of rice Cd, followed by relief, soil Cd content and rainfall. Typically, variance partitioning analysis (VPA) revealed that both the soil property and the interactive effects between the soil property and Cd pollution were the principal contributors to the rice-Cd variation, with the respective contributing rates of 30.5 % and 29.0 %. Meanwhile, the partial least square-structural equation modelling (PLS-SEM) elucidated 4 main paths of specific indirect effects on rice-Cd variation. They were landform → physicochemical property → soil acidity → rice-Cd variation, landform → soil acidity → rice-Cd variation, physicochemical property → soil acidity → rice-Cd variation, and soil texture → soil acidity → rice-Cd variation. This work can provide a general guidance for scientific zoning, accurate prediction and prevention of Cd pollution in paddy fields.

Postnatal feeding with high-fat combined with high-glucose diet induces precocious puberty in Sprague‒Dawley rat pups.

With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established.

[Effects of Equal Amounts Silicon Fertilizer Application on Soil Bioavailability of Cadmium and Cadmium Uptake by Rice].

Cadmium (Cd) contamination of paddy fields is a global concern, as it can cause the accumulation of Cd in food. To explore the effects of equal application of silicon fertilizers on the bioavailability of cadmium and soil Cd uptake at different growth stages of rice, a field experiment was conducted with five silicon fertilizers under the same silicon dose (225 kg·hm-2). The results revealed that the Cd contents in roots, stems, and leaves increased with the extension of the rice growth stage. The application of silicon fertilizers reduced the Cd contents in roots, stems, and leaves in brown rice by 14.9%, 28.2%, and 12.2%, respectively. Compared with that in the control, the Cd content of brown rice in the SiCaMgFe and SiW treatments was decreased by 21.1% (P<0.05) and 21.2% (P<0.05), respectively. Similarly, Cd content in iron plaque (DCB-Cd) increased with the extension of the rice growth period, which accounted for 15.8%-42.8% of the total Cd content in roots, and the DCB-Cd content was different in each stage of rice. The content of exchangeable Cd (Exc-Cd) in soil at the mature stage of rice decreased by 36.4%, and the other fractions increased by 12.5%-48.2%. The results showed significant negative correlations between the Cd contents and Si in roots, DCB-Cd and soil available Cd and available Si, Exc-Cd and Car-Cd, and soil available Cd and pH value. Cd content in roots was positively correlated with DCB-Cd. With the equal dose of silicon fertilizer, the treatments of SiCaMgFe and SiW could effectively reduce the Cd content in rice. The application of silicon fertilizer promoted the transfer of Exc-Cd to Carb-Cd by increasing the soil pH value and the soil available Si content, meanwhile reducing the soil available Cd, Exc-Cd contents, the adsorption of Cd by the iron film on the root surface, and the adsorption capacity of iron plaque and root, thereby reducing the absorption of Cd by rice.

Subcellular localization shapes the fate of RNA polymerase III.

RNA polymerase III (Pol III) plays a vital role in transcription and as a viral-DNA sensor, but how it is assembled and distributed within cells remains poorly understood. Here, we show that Pol III is assembled with chaperones in the cytoplasm and forms transcription-dependent protein clusters upon transport into the nucleus. The largest subunit (RPC1) depletion through an auxin-inducible degron leads to rapid degradation and disassembly of Pol III complex in the nucleus and cytoplasm, respectively. This generates a pool of partially assembled Pol III intermediates, which can be rapidly mobilized into the nucleus upon the restoration of RPC1. Our study highlights the critical role of subcellular localization in determining Pol III's fate and provides insight into the dynamic regulation of nuclear Pol III levels and the origin of cytoplasmic Pol III complexes involved in mediating viral immunity.

Glioblastomas with and without peritumoral fluid-attenuated inversion recovery (FLAIR) hyperintensity present morphological and microstructural differences on conventional MR images.

OBJECTIVES: Glioblastoma (GB) without peritumoral fluid-attenuated inversion recovery (FLAIR) hyperintensity is atypical and its characteristics are barely known. The aim of this study was to explore the differences in pathological and MRI-based intrinsic features (including morphologic and first-order features) between GBs with peritumoral FLAIR hyperintensity (PFH-bearing GBs) and GBs without peritumoral FLAIR hyperintensity (PFH-free GBs). METHODS: In total, 155 patients with pathologically diagnosed GBs were retrospectively collected, which included 110 PFH-bearing GBs and 45 PFH-free GBs. The pathological and imaging data were collected. The Visually AcceSAble Rembrandt Images (VASARI) features were carefully evaluated. The first-order radiomics features from the tumor region were extracted from FLAIR, apparent diffusion coefficient (ADC), and T1CE (T1-contrast enhanced) images. All parameters were compared between the two groups of GBs. RESULTS: The pathological data showed more alpha thalassemia/mental retardation syndrome X-linked (ATRX)-loss in PFH-free GBs compared to PFH-bearing ones (p < 0.001). Based on VASARI evaluation, PFH-free GBs had larger intra-tumoral enhancing proportion and smaller necrotic proportion (both, p < 0.001), more common non-enhancing tumor (p < 0.001), mild/minimal enhancement (p = 0.003), expansive T1/FLAIR ratio (p < 0.001) and solid enhancement (p = 0.009), and less pial invasion (p = 0.010). Moreover, multiple ADC- and T1CE-based first-order radiomics features demonstrated differences, especially the lower intensity heterogeneity in PFH-free GBs (for all, adjusted p < 0.05). CONCLUSIONS: Compared to PFH-bearing GBs, PFH-free ones demonstrated less immature neovascularization and lower intra-tumoral heterogeneity, which would be helpful in clinical treatment stratification. CLINICAL RELEVANCE STATEMENT: Glioblastomas without peritumoral FLAIR hyperintensity show less immature neovascularization and lower heterogeneity leading to potential higher treatment benefits due to less drug resistance and treatment failure. KEY POINTS: • The study explored the differences between glioblastomas with and without peritumoral FLAIR hyperintensity. • Glioblastomas without peritumoral FLAIR hyperintensity showed less necrosis and contrast enhancement and lower intensity heterogeneity. • Glioblastomas without peritumoral FLAIR hyperintensity had less immature neovascularization and lower tumor heterogeneity.

Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions.

One bottleneck in understanding the principles of 3D chromatin structures is caused by the paucity of known regulators. Cohesin is essential for 3D chromatin organization, and its interacting partners are candidate regulators. Here, we performed proteomic profiling of the cohesin in chromatin and identified transcription factors, RNA-binding proteins and chromatin regulators associated with cohesin. Acute protein degradation followed by time-series genomic binding quantitation and BAT Hi-C analysis were conducted, and the results showed that the transcription factor ZBTB21 contributes to cohesin chromatin binding, 3D chromatin interactions and transcriptional repression. Strikingly, multiomic analyses revealed that the other four ZBTB factors interacted with cohesin, and double degradation of ZBTB21 and ZBTB7B led to a further decrease in cohesin chromatin occupancy. We propose that multiple ZBTB transcription factors orchestrate the chromatin binding of cohesin to regulate chromatin interactions, and we provide a catalog of many additional proteins associated with cohesin that warrant further investigation.

Protocol for quantitative analysis of RNA 3'-end processing induced by disassociated subunits using chromatin-associated RNA-seq data.

Sequencing chromatin-associated RNA using libraries from the chromatin fraction makes it possible to characterize RNA processing driven by disassociated subunits. Here, we present an experimental strategy and computational pipeline for processing chromatin-associated RNA-seq data to detect and quantify readthrough transcripts. We describe steps for constructing degron mouse embryonic stem cells, detecting readthrough genes, data processing, and data analysis. This protocol can be adapted to various biological scenarios and other types of nascent RNA-seq, such as TT-seq. For complete details on the use and execution of this protocol, please refer to Li et al. (2023).1.

Never a dull enzyme, RNA polymerase II.

RNA polymerase II (Pol II) is composed of 12 subunits that collaborate to synthesize mRNA within the nucleus. Pol II is widely recognized as a passive holoenzyme, with the molecular functions of its subunits largely ignored. Recent studies employing auxin-inducible degron (AID) and multi-omics techniques have revealed that the functional diversity of Pol II is achieved through the differential contributions of its subunits to various transcriptional and post-transcriptional processes. By regulating these processes in a coordinated manner through its subunits, Pol II can optimize its activity for diverse biological functions. Here, we review recent progress in understanding Pol II subunits and their dysregulation in diseases, Pol II heterogeneity, Pol II clusters and the regulatory roles of RNA polymerases.

TFAP2C inhibits cell autophagy to alleviate myocardial ischemia/reperfusion injury by regulating miR-23a-5p/SFRP5/Wnt5a axis.

Myocardial ischemia/reperfusion (MI/R) injury contributes to severe injury for cardiomyocytes. In this study, we aimed to explore the underlying mechanism of TFAP2C on cell autophagy in MI/R injury. MTT assay measured cell viability. The cells injury was evaluated by commercial kits. IF detected the level of LC3B. Dual luciferase reporter gene assay, ChIP or RIP assay were performed to verify the interactions between crucial molecules. We found that TFAP2C and SFRP5 expression were decreased while miR-23a-5p and Wnt5a increased in AC16 cells in response to H/R condition. H/R induction led to cell injury and induced autophagy, which were reversed by TFAP2C overexpression or 3-MA treatment (an autophagy inhibitor). Mechanistically, TFAP2C suppressed miR-23a expression through binding to miR-23a promoter, and SFRP5 was a target gene of miR-23a-5p. Moreover, miR-23a-5p overexpression or rapamycin reversed the protective impacts of TFAP2C overexpression on cells injury and autophagy upon H/R condition. In conclusion, TFAP2C inhibited autophagy to improve H/R-induced cells injury by mediating miR-23a-5p/SFRP5/Wnt5a axis.

Meet the authors: The Ji lab.

We talk to the Ji lab about their paper, "RNA Pol II preferentially regulates ribosomal protein expression by trapping disassociated subunits" (in this issue), lessons from their scientific journey so far, and what inspires them along their scientific paths.

Linking chromatin acylation mark-defined proteome and genome in living cells.

A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and ß-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr's gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the "metabolites-modification-regulation" axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.

Comparative proteome profiles of Polygonatum cyrtonema Hua rhizomes (Rhizoma Ploygonati) in response to different levels of cadmium stress.

BACKGROUND: The Polygonatum cyrtonema Hua rhizomes (also known as Rhizoma Polygonati, RP) are consumed for their health benefits. The main source of the RP is wild P. cyrtonema populations in the Hunan province of China. However, the soil Cadmium (Cd) content in Huanan is increasing, thus increasing the risks of Cd accumulation in RP which may end up in the human food chain. To understand the mechanism of Cd accumulation and resistance in P. cyrtonema, we subjected P. cyrtonema plants to four levels of Cd stress [(D2) 1, (D3) 2, (D4) 4, and (D5) 8 mg/kg)] compared to (D1) 0.5 mg/kg. RESULTS: The increase in soil Cd content up to 4 mg/kg resulted in a significant increase in tissue (root hair, rhizome, stem, and leaf) Cd content. The increase in Cd concentration variably affected the antioxidant enzyme activities. We could identify 14,171 and 12,115 protein groups and peptides, respectively. There were 193, 227, 260, and 163 differentially expressed proteins (DEPs) in D2, D3, D4, and D5, respectively, compared to D1. The number of downregulated DEPs increased with an increase in Cd content up to 4 mg/kg. These downregulated proteins belonged to sugar biosynthesis, amino acid biosynthesis-related pathways, and secondary metabolism-related pathways. Our results indicate that Cd stress increases ROS generation, against which, different ROS scavenging proteins are upregulated in P. cyrtonema. Moreover, Cd stress affected the expression of lipid transport and assembly, glycolysis/gluconeogenesis, sugar biosynthesis, and ATP generation. CONCLUSION: These results suggest that an increase in soil Cd content may end up in Huangjing. Cadmium stress initiates expression changes in multiple pathways related to energy metabolism, sugar biosynthesis, and secondary metabolite biosynthesis. The proteins involved in these pathways are potential candidates for manipulation and development of Cd stress-tolerant genotypes.

Droplet formation assay for investigating phase-separation mechanisms of RNA Pol II transcription and CTCF functioning.

Clustering of RNA polymerase II carboxy-terminal domain (CTD) and CTCF DNA-binding domains (DBDs) have been viewed as emerging mechanisms of transcription regulation and three-dimensional chromatin organization. In this protocol, we address the need for a quantitative means of investigating phase-separation mechanisms of Pol II transcription and CTCF functioning. We describe steps for protein purification, droplet formation, and automeasuring droplet properties. We then detail quantification during Pol II CTD and CTCF DBD clustering and outline their limitations. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022)1 and Zhou et al. (2022).2.

RNA Pol II preferentially regulates ribosomal protein expression by trapping disassociated subunits.

RNA polymerase II (RNA Pol II) has been recognized as a passively regulated multi-subunit holoenzyme. However, the extent to which RNA Pol II subunits might be important beyond the RNA Pol II complex remains unclear. Here, fractions containing disassociated RPB3 (dRPB3) were identified by size exclusion chromatography in various cells. Through a unique strategy, i.e., "specific degradation of disassociated subunits (SDDS)," we demonstrated that dRPB3 functions as a regulatory component of RNA Pol II to enable the preferential control of 3' end processing of ribosomal protein genes directly through its N-terminal domain. Machine learning analysis of large-scale genomic features revealed that the little elongation complex (LEC) helps to specialize the functions of dRPB3. Mechanistically, dRPB3 facilitates CBC-PCF11 axis activity to increase the efficiency of 3' end processing. Furthermore, RPB3 is dynamically regulated during development and diseases. These findings suggest that RNA Pol II gains specific regulatory functions by trapping disassociated subunits in mammalian cells.

[Primary Factors Affecting Soil Bioavailable Cadmium and Asenic by Different Properties of Silicon Fertilizer].

To clarify the primary factors affecting soil bioavailable cadmium (Cd) and arsenic (As) by silicon fertilizer, we chose different properties of silicon fertilizer, including three types of alkaline silicon fertilizer[Na2SiO3, CaSiO3, and ASSF (pH 9-11)] and one weak acid neutral soluble silicon fertilizer (NSSF, pH 5-6), to carry out a pot experiment by adding different amounts of Si fertilizer (25-800 mg·kg-1, calculated as Si). After 21 days of flooding, soil basic physical and chemical properties, along with diffusive gradients in thin film Cd and As (DGT-Cd and DGT-As) were investigated. The results showed that the application of Si fertilizer with different properties had different significant effects on the basic physical and chemical properties of soil. Specifically, the three types of alkaline silicon fertilizer significantly increased the soil pH (P<0.05), among which Na2SiO3 exhibited the strongest ability; however, the application of NSSF remarkably reduced soil pH (P<0.05), and per unit (mg) Si application of NSSF could reduce soil pH by 0.0017 units. Furthermore, with each fertilizer application rate that reached 400 mg·kg-1 (calculated as Si), the changes in soil pH and Eh tended to be gentle. The ability of the four types of silicon fertilizer to improve soil available silicon ranked as NSSF>Na2SiO3>ASSF>CaSiO3. Additionally, the application of the three types of alkaline silicon fertilizer apparently decreased soil DGT-Cd while increasing soil DGT-As (P<0.05). When the addition rate of CaSiO3 was up to 100 mg·kg-1(calculated as Si), soil DGT-Cd concentration could be significantly decreased by approximately 50.89% without causing a significant increase in soil DGT-As concentration. Conversely, when the NSSF application rate was up to 400 mg·kg-1 (calculated as Si), the soil DGT-As basically reached its steady-state, and the DGT-As reduction rate reached 85.87%. Strikingly, the correlation analysis of the influencing factors of soil DGT-Cd and DGT-As showed that soil pH was the main factor affecting soil bioavailable Cd and As (DGT-Cd and DGT-As), and the effect of soil available Si and P on soil Cd and As bioavailability was negligible. Consequently, soil DGT-Cd and soil DGT-As could reach a minimum when soil pH was adjusted to 6.5-7.0 or 5-5.5 by alkaline silicon fertilizer or NSSF, respectively. It is undoubtedly of great significance, to clarify the primary factors that influence soil bioavailable Cd and As to ensure food security production.

Resveratrol improves diabetes-induced cognitive dysfunction in part through the miR-146a-5p/TXNIP axis.

Resveratrol (RSV) has been shown to have a neuroprotective effect in various central nervous system disorders, although the role of RSV in diabetes-induced cognitive dysfunction is still not fully elucidated. Here, we investigated whether RSV improved diabetes-related cognitive dysfunction in vivo and in vitro. We induced a rat diabetic model with a high-fat and high-sucrose diet followed by intraperitoneal injection of streptozotocin and a diabetic neuron cell model by stimulation with high levels of glucose. We observed that RSV improved impairment in spatial learning and memory in the Morris water maze test (MWM) and novel object recognition test (ORT) in diabetic rats. RSV reversed the reduced miR-146a-5p and upregulated thioredoxin-interacting protein (TXNIP) and inhibited the diabetes-induced increase in interleukin (IL)-1ß and tumor necrosis factor (TNF)-α levels in vivo and in vitro. RSV also inhibited diabetes-induced endoplasmic reticulum stress (ESR) by reducing ESR-related protein expression in vivo and in vitro. Moreover, inhibition of miR-146a-5p partially abolished the protective effects of RSV in HG-treated primary neurons. Additionally, we used starBase to predict that miR-146a-5p interacts with TXNIP, which we then verified using a luciferase reporter gene assay. We further observed that miR-146a-5p regulates the mRNA and protein expression of TXNIP in vitro, indicating that the miR-146a-5p/TXNIP axis is involved in the regulation of cognitive dysfunction in a rat diabetic model. Collectively, these results demonstrate that RSV plays a neuroprotective role in diabetes-associated cognitive dysfunction at least in part through regulation of the miR-146a-5p/TXNIP axis.