How False Memory and True Memory Affect Decision-Making in Older Adults: A Dissociative Account.

OBJECTIVES: Remembering past rewarding experiences plays a crucial rule in guiding people's decision-making in the future. However, as people age, they become less accurate in remembering past events and more susceptible to forming false memories. An important question is how the decline of episodic memory and increase of false memory may impact older adults' decision-making performance. METHOD: The current study used a newly developed paradigm in which the Deese-Roediger-McDermott false memory paradigm was combined with a reward learning task to create robust false memories of rewarding experiences. Participants learned that some DRM picture lists brought them a monetary reward and some DRM picture lists did not bring reward. Later, their memories were tested and decision-making preferences were measured. RESULTS: We found that older and younger adults had almost equivalent false and true memories under the rewarding context, but older adults showed significantly lower decision-making preferences for lure pictures and rewarded pictures than younger adults. Furthermore, true and false memories were a stronger predictor of decision-making preferences for younger than for older adults. DISCUSSION: These results together suggest an age-related dissociation between memory and decision-making that older adults may be less efficient in using their memory to guide decision-making than younger adults. Future research may further investigate its underlying mechanisms and develop potential interventions aiming at strengthening the connection between memory and decision-making in older adults to help improve their decision-making performance.

Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

Purpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Co-differential genes between DKD and aging: implications for a diagnostic model of DKD.

Objective: Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus (DM) that is closely related to aging. In this study, we found co-differential genes between DKD and aging and established a diagnostic model of DKD based on these genes. Methods: Differentially expressed genes (DEGs) in DKD were screened using GEO datasets. The intersection of the DEGs of DKD and aging-related genes revealed DKD and aging co-differential genes. Based on this, a genetic diagnostic model for DKD was constructed using LASSO regression. The characteristics of these genes were investigated using consensus clustering, WGCNA, functional enrichment, and immune cell infiltration. Finally, the expression of diagnostic model genes was analyzed using single-cell RNA sequencing (scRNA-seq) in DKD mice (model constructed by streptozotocin (STZ) injection and confirmed by tissue section staining). Results: First, there were 159 common differential genes between DKD and aging, 15 of which were significant. These co-differential genes were involved in stress, glucolipid metabolism, and immunological functions. Second, a genetic diagnostic model (including IGF1, CETP, PCK1, FOS, and HSPA1A) was developed based on these genes. Validation of these model genes in scRNA-seq data revealed statistically significant variations in FOS, HSPA1A, and PCK1 gene expression between the early DKD and control groups. Validation of these model genes in the kidneys of DKD mice revealed that Igf1, Fos, Pck1, and Hspa1a had lower expression in DKD mice, with Igf1 expression being statistically significant. Conclusion: Our findings suggest that DKD and aging co-differential genes are significant in DKD diagnosis, providing a theoretical basis for novel research directions on DKD.

The effects of forewarning and divided attention on context retrieval in false recognition.

After studying a list of words that are semantically associated to a critical lure, participants are more likely to attribute a falsely recognised critical lure to the context of its strong than weak semantic associates. This is known as the source-strength effect. The current study investigated the roles of automatic and controlled processing in context retrieval in false recognition that is demonstrated by the source-strength effect. The results revealed that the source-strength effect was impervious to forewarning (Experiment 1) and remained intact when attentional resources at encoding were reduced (Experiment 2), suggesting that context retrieval in false recognition is based on automatic processes that are not amenable to conscious control and do not require many attentional resources. This interpretation is consistent with the associative activation theory, which proposes that context retrieval in false recognition is based on memory associations between contexts and critical lures that are automatically created when critical lures become automatically activated via spreading activation process.

Identification and Functional Mechanism Verification of Novel MicroRNAs Associated with the Fibrosis Progression in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a serious threat to human health worldwide, and its incidence is increasing annually. A growing amount of information is emerging about the role of micoRNAs (miRNAs) in the regulation of renal fibrosis, which has aroused interest in the development of drugs that block pathogenic miRNAs or restore protective miRNAs levels. To clarify the role of miRNAs in CKD, we selected patients with significant renal fibrotic disease (diabetic nephropathy (DN) and focal segmental glomerulosclerosis (FSGS)) as the disease group, and patients with little or no renal fibrotic disease (minimal change disease (MCD) and renal carcinoma adjacent to normal kidney) as controls. Significantly differentially expressed miRNAs were obtained by human kidney tissue sequencing, subsequently verified in mice models of DN and FSGS, and subsequently inhibited or overexpressed in human renal tubular epithelial cells (HK-2) stimulated by high glucose (HG) and TGF-ß1 in vitro. Therefore, the mechanism of its action in renal fibrosis was further elaborated. Finally, the downstream target genes of the corresponding miRNAs were verified by bioinformatics analysis, qRT-PCR, western blot and double luciferase report analysis. Two novel miRNAs, hsa-miR-1470-3p (miR-1470) and hsa-miR-4483-3p (miR-4483), were detected by renal tissue sequencing in the disease group with significant renal fibrosis (DN and FSGS) and the control group with little or no renal fibrosis (MCD and normal renal tissue adjacent to renal carcinoma). Subsequent human renal tissue qRT-PCR verified that the expression of miR-1470 was significantly increased, while the expression of miR-4483 was markedly decreased in the disease group (p < 0.05). Moreover, in vivo DN and FSGS mice models, the expression levels of miR-1470 and miR-4483 were consistent with the results of human kidney tissue. In vitro, miR-4483 was suppressed, whereas miR-1470 was induced by treatment with TGF-ß1 or HG. Inhibition of miR-1470 or overexpression of miR-4483 promoted HG or TGF-ß1-induced fibrosis in HK-2 cells. Further study revealed that MMP-13 and TIMP1 were the target genes ofmiR-1470 and miR-4483, respectively. Our study identifies newly dysregulated miRNA profiles related to fibrosis kidneys. miR-1470 and miR-4483 are demonstrated to participate in kidney fibrosis by regulation of MMP-13, TIMP1 respectively. Our results may represent a promising research direction for renal disorders and help identify new biomarkers and therapeutic targets for CKD.

Self-relevance enhances susceptibility to false memory.

Eyewitness testimony serves as important evidence in the legal system. Eyewitnesses of a crime can be either the victims themselves-for whom the experience is highly self-referential-or can be bystanders who witness and thus encode the crime in relation to others. There is a gap in past research investigating whether processing information in relation to oneself versus others would later impact people's suggestibility to misleading information. In two experiments (Ns = 68 and 122) with Dutch and Chinese samples, we assessed whether self-reference of a crime event (i.e., victim vs. bystander) affected their susceptibility to false memory creation. Using a misinformation procedure, we photoshopped half of the participants' photographs into a crime slideshow so that they saw themselves as victims of a nonviolent crime, while others watched the slideshow as mock bystander witnesses. In both experiments, participants displayed a self-enhanced suggestibility effect: Participants who viewed themselves as victims created more false memories after receiving misinformation than those who witnessed the same crime as bystanders. These findings suggest that self-reference might constitute a hitherto new risk factor in the formation of false memories when evaluating eyewitness memory reports.

p53 suppresses lipid droplet-fueled tumorigenesis through phosphatidylcholine.

Choline deficiency causes disorders including hepatic abnormalities and is associated with an increased risk of multiple types of cancer. Here, by choline-free diet-associated RNA-Seq analyses, we found that the tumor suppressor p53 drives the Kennedy pathway via PCYT1B to control the growth of lipid droplets (LDs) and their fueling role in tumorigenesis. Mechanistically, through upregulation of PCYT1B, p53 channeled depleted choline stores to phosphatidylcholine (PC) biosynthesis during choline starvation, thus preventing LD coalescence. Cells lacking p53 failed to complete this response to choline depletion, leading to hepatic steatosis and tumorigenesis, and these effects could be reversed by enforcement of PCYT1B expression or restoration of PC abundance. Furthermore, loss of p53 or defects in the Kennedy pathway increased surface localization of hormone-sensitive lipase on LDs to release specific fatty acids that fueled tumor cells in vivo and in vitro. Thus, p53 loss leads to dysregulation of choline metabolism and LD growth and couples perturbed LD homeostasis to tumorigenesis.

Suppressing memory associations impacts decision-making preference: Evidence from the think/no-think paradigm.

Recent research has suggested that episodic memory can guide our decision-making. Forgetting is one essential characteristic of memory. If certain memories are suppressed to be forgotten, decisions that rely on such memories should be impacted. So far, little research has examined whether suppression of episodic memory would impact decision-making. In the current pre-registered study, the effect of memory suppression on subsequent reinforcement decision-making was examined by combining the Think/No-think paradigm and a reinforcement decision-making task. We found that suppressing memories of learned associations significantly impaired recollected memories of those associations, and participants' decision bias disappeared after their memory associations were suppressed. Furthermore, the more memory associations participants recalled, the higher decision preferences they exhibited. Our findings provide additional support for the role of episodic memory in reinforcement decision-making, and suggest that suppressing memory associations can lead to behavioral consequences.

Creating false rewarding memories guides novel decision making.

When memories of past rewarding experiences are distorted, are relevant decision-making preferences impacted? Although recent research has demonstrated the important role of episodic memory in value-based decision making, very few have examined the role of false memory in guiding novel decision making. The current study combined the pictorial Deese/Roediger-McDermott false memory paradigm with a reward learning task, where participants learned that items from some related lists gained reward and items from other lists led to no reward. Later, participants' memories and decision-making preferences were tested. With three experiments conducted in three countries, we successfully created false memories of rewarding experiences in which participants falsely remembered seeing a nonpresented lure picture bring them reward thereby confirming our constructive association hypothesis. Such false memories led participants to prefer the lure pictures and respond faster in a follow-up decision-making task, and the more false memories they formed, the higher preferences for the lure items they displayed (Experiment 2). Finally, results were replicated with or without a memory test before the decision-making task, showing that the impact of false memory on decision making was not cued by a memory test (Experiment 3). Our data suggest that the reconstructive nature of memory enables individuals to create new memory episodes to guide decision making in novel situations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Inducing emotionally negative nonbelieved memories using negative pictures.

Memories that can be recalled but are no longer believed are termed nonbelieved memories. The current studies examined the creation of emotionally negative nonbelieved memories after viewing negatively valenced pictures. In both experiments, participants took part in two sessions. In Session 1, after being presented with a set of neutral and negative pictures, participants had to rate their emotional state. One week later, in Session 2, participants had to complete a recognition task to identify pictures that had appeared during the previous session. During this task, participants' memories for some pictures were challenged by telling them that their answers were incorrect in order to evoke nonbelieved memories. The experimental procedure was successful in creating nonbelieved memories in the participants. Specifically, in Experiment 1 (N = 35), we induced nonbelieved true memories for both negative and neutral pictures. We found a significant decrease in both belief and recollection after the challenge, with the change in belief being twice as large as the change in recollection. In Experiment 2 (N = 43), we successfully induced both nonbelieved true and false memories for negative pictures. Again, the reduction of belief was significantly greater than that of recollection. In general, participants evinced better memory for negative pictures, but following challenges people were just as likely to accept false social feedback and change their memories regarding other types of pictures. In both experiments, our challenges did not lead to notable changes in emotional state. In general, our findings show that emotionally negative nonbelieved memories can be successfully evoked in an experimental setting.

Exosome miR-30a-5p Regulates Glomerular Endothelial Cells' EndMT and Angiogenesis by Modulating Notch1/VEGF Signaling Pathway.

BACKGROUND: Diabetic nephropathy (DN) is one of the microvascular complications of diabetes. Endothelial-mesenchymal transition (EndMT) and endothelial damage lead to abnormal angiogenesis in DN. OBJECTIVES: This study aimed to investigate the role of exosome miR-30a-5p in high glucose (HG)-induced glomerular endothelial cells (GECs) dysfunction and explore the underlying mechanisms. METHODS: GECs were cultured in normal glucose (5.5 mM) and HG (30 mM) conditions. The recipient GECs were transfected with exosome or miR-30a-5p mimic/inhibitor and then detected by using CCK-8 and flow cytometry assay. Luciferase analysis was used to verify miR-30a-5p acted on notch homolog protein 1 (Notch1). RT-qPCR and Western blot were used to detect the expression of VE-cadherin, α-SMA, vascular endothelial growth factor (VEGF) and Notch1. In vivo, exosome miR-30a-5p was administered to DN mice, and periodic acid-Schiff (PAS) staining, UTP levels, and HbA1c levels were measured. RESULTS: The expression of miR-30a-5p was downregulated in HG-treated GECs. Exosome miR-30a-5p significantly promoted cell proliferation, and migration and reduced apoptosis of GECs under HG conditions. MiR-30a-5p directly targeted the 3-UTR region of Notch1. Exosome miR-30a-5p reduced the expression levels of Notch1 and VEGF, both at mRNA and protein levels. Furthermore, exosome miR-30a-5p inhibited HG-induced EndMT, as evidenced by increased VE-cadherin and reduced α-SMA. In vivo studies demonstrated that exosome miR-30a-5p reduced serum HbA1c levels and 24-hour urine protein quantification. CONCLUSION: This study provides evidence that exosome miR-30a-5p suppresses EndMT and abnormal angiogenesis of GECs by modulating the Notch1/VEGF signaling pathway. These findings suggest that exosome miR-30a-5p could be a potential therapeutic strategy for the treatment of DN.

Assessing the effects of drought on rainfed maize water footprints based on remote sensing approaches.

BACKGROUND: Drought affects the characteristics of water use during crop production and so quantitatively evaluating the impacts is important. However, it remains unclear how crop water use responds to drought. To address this gap, water footprint (WF) and standardized precipitation evapotranspiration index (SPEI) were calculated by remote sensing approaches to assess the effects of drought on crop water use. Rainfed maize is the most important crop in Jilin Province, and its growth and water use are more susceptible to drought. The present study explored not only the impact of growing season drought on the maize WF values in Jilin Province, but also the response of WF values to drought at different time scales. RESULTS: Spatially, 72.94% of the WFblue pixels showed a non-significant increase, and the WFgreen in 68% pixels decreased significantly, being mainly concentrated in the middle region. Furthermore, the pixels affected by monthly time scale drought were mainly in the middle region, whereas the pixels affected by annual time scale drought were mainly in the western region. CONCLUSION: Drought not only affected on the source and structure of agricultural water consumption, but also had different effects on WF values at different time scale. These effects had obvious spatial differences. The present study systematically explored the effects of drought on the WF values for rainfed maize in different climate regions and a consideration of these effects could provide valuable information on rainfed maize growth and the agricultural water use response to a changing climate. © 2023 Society of Chemical Industry.

A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.

Arachidonic acid 15-lipoxygenase (ALOX15), as one of the lipoxygenase family, is mainly responsible for catalyzing the oxidation of various fatty acids to produce a variety of lipid components, contributing to the pathophysiological processes of various immune and inflammatory diseases. Studies have shown that ALOX15 and its related products are widely distributed in human tissues and related to multiple diseases such as liver, cardiovascular, cerebrovascular diseases, diabetes mellitus and other diseases. Diabetes mellitus (DM), the disease studied in this article, is a metabolic disease characterized by a chronic increase in blood glucose levels, which is significantly related to inflammation, oxidative stress, ferroptosis and other mechanisms, and it has a high incidence in the population, accompanied by a variety of complications. Figuring out how ALOX15 is involved in DM is critical to understanding its role in diseases. Therefore, ALOX15 inhibitors or combination therapy containing inhibitors may deliver a novel research direction for the treatment of DM and its complications. This article aims to review the biological effect and the possible function of ALOX15 in the pathogenesis of DM.

DIALIZE China: A Phase IIIb, Randomized, Placebo-Controlled Study to Reduce Predialysis Hyperkalemia With Sodium Zirconium Cyclosilicate in Chinese Patients.

PURPOSE: The DIALIZE China study (Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects) (NCT04217590) evaluated sodium zirconium cyclosilicate (SZC) for the management of hyperkalemia in Chinese patients undergoing hemodialysis. METHODS: In the double-blind, Phase IIIb DIALIZE China study, Chinese adults with kidney failure and predialysis hyperkalemia (predialysis serum potassium [sK+] concentration >5.4 mmol/L after the long interdialytic interval [LIDI] and >5.0 mmol/L after ≥1 short interdialytic interval) who were receiving hemodialysis 3 times weekly were randomized to placebo or SZC 5 g once daily on nondialysis days. Doses were titrated towards maintaining normokalemia for 4 weeks (titration period) in 5-g increments up to 15 g. Primary efficacy was the proportion of responders during the 4-week evaluation period following the titration period (ie, those with a predialysis sK+ of 4.0-5.0 mmol/L for at least 3 of 4 hemodialysis visits following the LIDI) who did not require urgent rescue therapy. FINDINGS: Overall, 134 adults (mean [SD] age, 55 [11.3] years) were randomized to SZC or placebo (n = 67 each). There were significantly more responders with SZC (37.3%) versus placebo (10.4%; estimated odds ratio [OR] = 5.10; 95% CI, 1.90-15.12; P < 0.001). The probability of all predialysis sK+ concentrations being 3.5 to 5.5 mmol/L was significantly higher with SZC versus placebo (estimated OR = 6.41; 95% CI, 2.71-15.12; P < 0.001). A greater proportion of patients achieved an sK+ of 3.5 to 5.5 mmol/L on at least 3 of 4 LIDI visits during evaluation with SZC (73.1%) versus placebo (29.9%). Serious adverse events occurred in 9.1% and 11.9% of patients in the SZC and placebo groups, respectively. IMPLICATIONS: SZC treatment for predialysis hyperkalemia is effective and well tolerated in Chinese patients with kidney failure receiving hemodialysis. CLINICALTRIALS: gov identifier: NCT04217590.

Challenging memories reduces intrusive memories and the memory amplification effect.

This study scrutinizes the influence of attenuating beliefs about the veracity of traumatic experiences on the manifestation of intrusive recollections and the memory amplification effect. Participants were exposed to distress-inducing visual stimuli, subsequently rating their emotional status pre and post exposure. They engaged in a recognition task, identifying scenarios within the stimuli. Participants' recall was contested, casting doubt about the occurrence of certain scenes. Subsequently, they maintained a daily log of intrusive memories over a week. A second session reiterated the same process. This method effectively diminished the certainty in the participants' traumatic memories. Scenes whose occurrence was contested demonstrated a significant decline in both intrusive memories and memory amplification when juxtaposed with uncontested ones. Interestingly, no significant correlation emerged between the diminished belief in traumatic incidents and reductions in intrusive memory or memory amplification. Thus, this study advocates that interrogating the veracity of traumatic recollections can mitigate the prevalence of intrusive memories and the memory amplification effect, suggesting a novel potential therapeutic approach for trauma-related disorders.

Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods: In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 µg, 2.5 µg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results: A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 µg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 µg and placebo group was 8.81 mm, but not statistically significantly different. Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5µg, 38.6% in 2.5 µg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions: Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Evaluation of malnutrition and inflammation after total parathyroidectomy in patients on maintenance dialysis.

PURPOSE: To evaluate the effect of total parathyroidectomy (tPTx) on malnutrition and inflammation in patients on maintenance dialysis (MHD) having secondary hyperparathyroidism (SHPT). METHODS: Twenty-five patients on MHD having SHPT who were being treated with tPTx were selected, and changes in their general condition (dry body mass), parathyroid hormone (PTH) and calcium levels, nutrition state (hemoglobin, hematocrit, serum albumin, and total iron binding capacity), and inflammatory status [serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and the malnutrition-inflammation score (MIS)] were observed at 12, 24, and 36 months postoperatively. RESULTS: Compared with the preoperative period, the dry body mass increased at 12, 24, and 36 months postoperatively (P < 0.01), hemoglobin, hematocrit, and serum albumin increased significantly (P < 0.01), whereas calcium, phosphorus, and PTH levels decreased significantly (P < 0.01). Serum CRP, IL-6, and TNF-α levels were significantly decreased at 12, 24, and 36 months after surgery (P < 0.01). Furthermore, MIS was reduced as well but to a lesser extent (P < 0.01). CONCLUSION: tPTx effectively reduced MIS in maintenance dialysis patients, and the alleviated malnutrition and improved inflammatory status may contributed to improving the quality of life of patients on MHD with SHPT.

Visual-Auditory Integration and High-Variability Speech Can Facilitate Mandarin Chinese Tone Identification.

PURPOSE: Previous studies have demonstrated that tone identification can be facilitated when auditory tones are integrated with visual information that depicts the pitch contours of the auditory tones (hereafter, visual effect). This study investigates this visual effect in combined visual-auditory integration with high- and low-variability speech and examines whether one's prior tonal-language learning experience shapes the strength of this visual effect. METHOD: Thirty Mandarin-naïve listeners, 25 Mandarin second language learners, and 30 native Mandarin listeners participated in a tone identification task in which participants judged whether an auditory tone was rising or falling in pitch. Moving arrows depicted the pitch contours of the auditory tones. A priming paradigm was used with the target auditory tones primed by four multimodal conditions: no stimuli (A-V-), visual-only stimuli (A-V+), auditory-only stimuli (A+V-), and both auditory and visual stimuli (A+V+). RESULTS: For Mandarin naïve listeners, the visual effect in accuracy produced under the cross-modal integration (A+V+ vs. A+V-) was superior to a unimodal approach (A-V+ vs. A-V-), as evidenced by a higher d prime of A+V+ as opposed to A+V-. However, this was not the case in response time. Additionally, the visual effect in accuracy and response time under the unimodal approach only occurred for high-variability speech, not for low-variability speech. Across the three groups of listeners, we found that the less tonal-language learning experience one had, the stronger the visual effect. CONCLUSION: Our study revealed the visual-auditory advantage and disadvantage of the visual effect and the joint contribution of visual-auditory integration and high-variability speech on facilitating tone perception via the process of speech symbolization and categorization. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21357729.

Bioinformatics prediction and experimental verification of key biomarkers for diabetic kidney disease based on transcriptome sequencing in mice.

Background: Diabetic kidney disease (DKD) is the leading cause of death in people with type 2 diabetes mellitus (T2DM). The main objective of this study is to find the potential biomarkers for DKD. Materials and Methods: Two datasets (GSE86300 and GSE184836) retrieved from Gene Expression Omnibus (GEO) database were used, combined with our RNA sequencing (RNA-seq) results of DKD mice (C57 BLKS-32w db/db) and non-diabetic (db/m) mice for further analysis. After processing the expression matrix of the three sets of data using R software "Limma", differential expression analysis was performed. The significantly differentially expressed genes (DEGs) (-logFC- > 1, p-value < 0.05) were visualized by heatmaps and volcano plots respectively. Next, the co-expression genes expressed in the three groups of DEGs were obtained by constructing a Venn diagram. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were further analyzed the related functions and enrichment pathways of these co-expression genes. Then, qRT-PCR was used to verify the expression levels of co-expression genes in the kidney of DKD and control mice. Finally, protein-protein interaction network (PPI), GO, KEGG analysis and Pearson correlation test were performed on the experimentally validated genes, in order to clarify the possible mechanism of them in DKD. Results: Our RNA-seq results identified a total of 125 DEGs, including 59 up-regulated and 66 down-regulated DEGs. At the same time, 183 up-regulated and 153 down-regulated DEGs were obtained in GEO database GSE86300, and 76 up-regulated and 117 down-regulated DEGs were obtained in GSE184836. Venn diagram showed that 13 co-expression DEGs among the three groups of DEGs. GO analysis showed that biological processes (BP) were mainly enriched inresponse to stilbenoid, response to fatty acid, response to nutrient, positive regulation of macrophage derived foam cell differentiation, triglyceride metabolic process. KEGG pathway analysis showed that the three major enriched pathways were cholesterol metabolism, drug metabolism-cytochrome P450, PPAR signaling pathway. After qRT-PCR validation, we obtained 11 genes that were significant differentially expressed in the kidney tissues of DKD mice compared with control mice. (The mRNA expression levels of Aacs, Cpe, Cd36, Slc22a7, Slc1a4, Lpl, Cyp7b1, Akr1c14 and Apoh were declined, whereas Abcc4 and Gsta2 were elevated). Conclusion: Our study, based on RNA-seq results, GEO databases and qRT-PCR, identified 11 significant dysregulated DEGs, which play an important role in lipid metabolism and the PPAR signaling pathway, which provide novel targets for diagnosis and treatment of DKD.