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1.
Ecotoxicol Environ Saf ; 281: 116649, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954910

ABSTRACT

Limited evidence has suggested a relationship between phthalate exposure and biological aging. This study investigated the association between phthalate exposure and biological aging, focusing on the mediating role of inflammation and the interaction with dietary nutrient intake. Data were analyzed from a nationwide cross-sectional survey comprising 12,994 participants aged 18 and above. Eight phthalate metabolites were detected in spot urine samples. Biological aging was assessed using the Klemera-Doubal method-biological age (KDM-BA) acceleration, phenotypic age (PA) acceleration, and homeostatic dysregulation (HD). The systemic immune-inflammation index (SII) evaluated systemic inflammation. The individual and combined associations between phthalate exposure and biological aging were assessed using linear regression, weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp). The participants had a mean age of 47 years, with 50.7 % male and 44.8 % non-Hispanic white. Most phthalate metabolites were positively correlated with KDM-BA acceleration (ß = 0.306-0.584), PA acceleration (ß = 0.081-0.281), and HD (ß = 0.016-0.026). Subgroup analysis indicated that men, older individuals, and non-Hispanic whites are particularly sensitive populations. WQS regression and qgcomp analyses consistently indicated a positive association between mixed phthalate exposure and HD, highlighting MEHHP as the most significant contributing metabolite. Mediation analyses showed inflammation partially mediated the association between phthalate metabolites and biological aging. Significant interactions regarding biological aging were found between specific phthalate metabolites and dietary nutrients (carotenoids, vitamins A, B1, B2, B6, B12, niacin, and selenium) intake. These findings indicated that the association between phthalate exposure and biological aging was mediated by inflammation, with nutrient intake mitigating this effect.

2.
Food Funct ; 15(13): 7017-7031, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38860333

ABSTRACT

B vitamins and probiotics are commonly used dietary supplements with well-documented health benefits. However, their potential interactions remain poorly understood. This study aims to explore the effects and underlying mechanisms of the combined use of B vitamins and probiotics by liquid chromatography-triple quadrupole mass spectrometry analysis, pharmacokinetic modeling, and 16S rRNA gene sequencing. By intragastric administration of seven B vitamins and three Lactobacillus strains to healthy rats (n = 8 per group), we found that probiotics significantly promoted the absorption (by approximately 14.5% to 71.2%) of vitamins B1, B3, B5, and B12. By conducting in vitro experiments (n = 3 per group) and a pseudo-germ-free rat model-based pharmacokinetic study (n = 6 per group), we confirmed that probiotics primarily enhanced the B vitamin absorption through gut microbiota-mediated mechanisms, rather than by directly producing B vitamins. Furthermore, we evaluated the effects of B vitamins and probiotics on the colon and gut microbiota by treating the pseudo-germ-free rats with blank solution, B vitamins, probiotics, and B vitamins + probiotics (n = 5 per group), respectively. Histopathological examination showed that the combination of B vitamins and probiotics synergistically alleviated the rat colon damage. High-throughput genetic sequencing also revealed the synergistic effect of B vitamins and probiotics in modulating the gut microbiota, particularly increasing the abundance of Verrucomicrobia and Akkermansia. In summary, the combined administration of B vitamins and probiotics may have a higher efficacy than using them alone.


Subject(s)
Akkermansia , Gastrointestinal Microbiome , Probiotics , Rats, Sprague-Dawley , Vitamin B Complex , Animals , Probiotics/pharmacology , Rats , Gastrointestinal Microbiome/drug effects , Vitamin B Complex/pharmacology , Male , Colon/metabolism , Colon/microbiology , Dietary Supplements , Humans , RNA, Ribosomal, 16S/genetics
3.
Int J Biol Macromol ; 273(Pt 1): 133035, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38866276

ABSTRACT

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.


Subject(s)
Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , Oxidative Stress , Polysaccharides , Signal Transduction , Animals , NF-E2-Related Factor 2/metabolism , Mice , Signal Transduction/drug effects , Kelch-Like ECH-Associated Protein 1/metabolism , Polysaccharides/pharmacology , Polysaccharides/chemistry , Oxidative Stress/drug effects , Male , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/drug therapy , Hippocampus/metabolism , Hippocampus/drug effects , Galactose , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/chemically induced , Gastrointestinal Microbiome/drug effects , Disease Models, Animal , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/chemically induced
5.
Bioconjug Chem ; 35(4): 540-550, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38557019

ABSTRACT

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.


Subject(s)
Gold , Metal Nanoparticles , Gold/toxicity , Gold/chemistry , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistry
6.
Molecules ; 29(6)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38543037

ABSTRACT

Mn4+-doped red-light-emitting phosphors have become a research hotspot that can effectively enhance photosynthesis and promote morphogenesis in plants. Herein, the red phosphor La3Mg2NbO9:Mn4+ was synthesized through the solid-state reaction method. The effects of adding H3BO3 and a charge compensator R+ (R = Li, Na, K) on the crystal structure, morphology, quantum efficiency, and luminous performance of the La3Mg2NbO9:Mn4+ phosphor were systematically analyzed, respectively. The results showed that adding H3BO3 flux and a charge compensator improved the quantum efficiency and luminescence intensity. The emission intensity of the phosphor was enhanced about 5.9 times when Li+ was used as the charge compensator, while it was enhanced about 240% with the addition of H3BO3 flux. Remarkably, it was also found that the addition of H3BO3 flux and a charge compensator simultaneously improved the thermal stability at 423 K from 47.3% to 68.9%. The prototype red LED fabricated using the La3Mg2NbO9:Mn4+,H3BO3,Li+ phosphor exhibited a perfect overlap with the phytochrome absorption band for plant growth. All of these results indicate that the La3Mg2NbO9:Mn4+,H3BO3,Li+ phosphor has great potential for use in agricultural plant lighting.

7.
Environ Res ; 244: 117910, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38101719

ABSTRACT

Promoting green and low-carbon development has become the consensus of the policymakers and the academic, with green transformation of enterprises being the top priority. This paper adopts the difference-in-difference model to investigate the effect of green credit policy on green transition in China, by utilizing the "Green Credit Guidelines" (2012 Guidelines) policy as a quasi-natural experiment. Using panel data from publicly listed companies in China, an empirical investigation is conducted, we explain the dependent variable from two dimensions: economic performance and environmental performance, leading to the following results. First, the green credit policy affects the economic performance and environmental performance of treated firms positively, and the robust tests confirm the reliability of this primary conclusion. Second, the indirect impact of green credit policy on green transition can be explained through two mediating mechanism channels including internal capacity building and external market attention. In addition, the proposal of "Dual Carbon Targets" makes the impact a slight change. Finally, heterogeneous test also shows that the implementation effect of green credit policy is better in non-state-owned enterprises with high political relevance. These findings are providing valuable insights to promote green transition by designing more effective green credit policies.


Subject(s)
Carbon , Policy , Reproducibility of Results , China , Environmental Policy
8.
Food Chem ; 440: 138190, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38113648

ABSTRACT

Java tea (Clerodendranthus spicatus) has been favored for its various health benefits and abundance of phenolic substances. Steam explosion (SE) treatment was performed in the pretreatment of Java tea stems and the physical properties, phenolic profile and antioxidant capacity were investigated. Extraction kinetics study showed that the phenolics yields of Java tea stems treated at 2.4 MPa for 10 min reached the maximum in 40 min, which was approximately 3 times the yields of raw stems in 180 min. The antioxidant activities of the extracts of Java tea stems were also significantly increased after SE treatment (P < 0.05). In addition, 19 phenolics were detected in Java tea stems by HPLC/QTOF-MS/MS, and rosmarinic acid was found to be hydrolyzed to danshensu during the SE process. SE could be an efficient pretreatment technology to improve the extraction rates of phenolics and conversions of their high-value hydrolyzed products, which could facilitate further research of Java tea products.


Subject(s)
Lamiaceae , Orthosiphon , Steam , Antioxidants/analysis , Tandem Mass Spectrometry , Phenols/analysis
9.
BMJ Open ; 13(12): e074301, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38135337

ABSTRACT

OBJECTIVE: This study aims to investigate physicians' familiarity and awareness of four diabetes guidelines and their practice of the recommendations outlined in these guidelines. DESIGN: A cross-sectional study. SETTING: An online questionnaire survey was conducted among physicians affiliated with the Specialist Committee for Primary Diabetes Care of China Association of Chinese Medicine, using the snowball sampling method to ensure a broader representation of physicians. PARTICIPANTS: 1150 physicians from 192 cities across 30 provinces in China provided complete data. RESULTS: Tertiary care hospital physicians (TCPs) exhibited the highest familiarity with the Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus in China (91.3%), followed by the National Guidelines for the Prevention and Control of Diabetes in Primary Care (76.8%), the Standards of Medical Care in Diabetes (72.2%) and the Guidelines for Prevention and Treatment of Diabetes in Chinese Medicine (63.8%). Primary care practitioners (PCPs) exhibited familiarity with these four guidelines at about 50% or less. Self-reported reference to modern diabetes guidelines by physicians is more frequent than traditional Chinese medicine (TCM) diabetes guidelines, with rates at 73.2% and 33.8%, respectively. Approximately 90% of physicians provided instructions on self-monitoring of blood glucose to their patients with diabetes. Less than one-third of physicians referred patients to a specialised nutritionist. In terms of health education management, TCPs reported having a diabetes health management team at the rate of 75.7%, followed by secondary care hospital physicians at 57.0% and PCPs at 27.5%. Furthermore, approximately 40% of physicians did not fully grasp hypoglycaemia characteristics. CONCLUSIONS: Familiarity and awareness of the screening guidelines varied among physicians in different hospital settings. Importantly, significant discrepancies were observed between physicians' awareness and their self-reported reference to modern medicine guidelines and TCM guidelines. It is essential to consistently provide education and training on diabetes management for all physicians, particularly PCPs.


Subject(s)
Diabetes Mellitus, Type 2 , Physicians, Primary Care , Physicians , Humans , Diabetes Mellitus, Type 2/prevention & control , Cross-Sectional Studies , Surveys and Questionnaires , Self Report , China , Practice Patterns, Physicians'
10.
Ecotoxicol Environ Saf ; 268: 115675, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37984288

ABSTRACT

Di-(2-ethylhexyl)-phthalate (DEHP), a common Phthalic acid ester (PAEs), has been reported to be associated with diabetes mellitus, yet the underlying mechanisms remain unknown. Combined nutrient interventions have been shown to alleviate the diabetic toxicity of DEHP. However, the effects and mechanisms of the combined intervention of Astragalus and vitamins (C and E) are currently unknown. In this study, we investigated the potential mechanisms of DEHP-induced diabetes mellitus through transcriptome analysis and vitro experiments using rat insulinoma cells (INS-1 cells). Furthermore, we explored the protection of the combined Astragalus, vitamin C, and vitamin E on DEHP-induced diabetes mellitus through these mechanisms. INS-1 cells in the logarithmic growth period were exposed to 125 umol/L DEHP followed by high-throughput sequencing analysis. The cell proliferation inhibition rate was determined using MTT assay for each group, and the cell apoptosis rate and intracellular ROS level were measured using flow cytometer. Finally, insulin levels and markers of oxidative stress were detected using ELISA kits in different groups. A total of 372 differentially expressed genes were found between the 125 umol/L DEHP and control groups, subsequent functional enrichment analyses indicated that DEHP induced oxidative stress and disturbed insulin levels. In INS-1 cells, the rate of cell proliferation inhibition, apoptosis, and the degree of oxidative stress increased concentration-dependently with increasing DEHP concentrations, while antioxidant intervention could reverse these changes. Insulin synthesis and secretion decreased after 240 µmol/L DEHP exposure stimulated by 25 mM glucose in INS-1 cells, also could antioxidant intervention alleviate these reductions. Based on these results, the underlying mechanism of DEHP impairing the function of INS-1 cells might be through apoptosis pathways induced by oxidative stress and direct reduction of insulin levels (both synthesis and secretion), while the optimal combination of Astragalus and vitamins (C and E) could exert an alleviating effect.


Subject(s)
Diabetes Mellitus , Diethylhexyl Phthalate , Insulinoma , Pancreatic Neoplasms , Rats , Animals , Vitamin E/pharmacology , Ascorbic Acid/pharmacology , Antioxidants/pharmacology , Antioxidants/metabolism , Insulin/metabolism , Diethylhexyl Phthalate/toxicity , Oxidative Stress , Vitamins/pharmacology
11.
EBioMedicine ; 97: 104828, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37837933

ABSTRACT

BACKGROUND: Microplastics (MPs) have garnered widespread attention because of their presence in human placenta, stool, and even blood. Ingestion is considered the major route of human exposure to MPs. It has been found that the consumption of food and water is associated with more MP abundance in human stools. The usage of plastic containers, particularly feeding bottles, may be a major contributor to MP contamination. However, human exposure to MPs and potential factors that influence exposure, especially for preschoolers, remains largely unknown. When exposed to MPs, mice exhibited gut microbiota dysbiosis, including alterations in diversity indices, a decreased relative abundance of probiotics and an increased abundance of pathogenic bacteria. Such results have also been observed in human gut in vitro models, however, the actual association between MP exposure and human intestinal microbiota remains unclear. Therefore, this study aimed to evaluate MP concentrations in preschoolers' stools, explore possible dietary factors that influence preschooler exposure to MPs, and investigate their potential association with the gut microbiota. METHODS: A cross-sectional study was conducted in Xiamen, China in October 2022. We investigated the feeding behaviours and dietary habits of preschool children. A total of 69 couples of stool samples were collected and analyzed for MPs test and gut microbiota analysis. Pyrolysis-gas chromatography coupled with mass spectrometry (Py-GC/MS) was used for quantifying 11 types of MPs. The gut microbiota composition was analyzed by 16S rRNA gene sequencing. FINDINGS: The results showed that only polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyethylene (PE), and polyamide 6 (PA6) were detected in 85.5% stool samples, with concentrations of 317.4 (152.0, 491.9) µg/g dw, 299.0 (196.1, 619.9) µg/g dw, 206.2 (154.1, 240.3) µg/g dw, and 17.9 (13.4, 18.6) µg/g dw, respectively. The median estimated daily intake (EDI) for preschoolers was 425.9 (272.5, 762.3) µg/kg-bw/d. Dairy intake may influence MP concentration in preschoolers' stools, and the usage of feeding bottles may be a specific source of MP contamination. Moreover, higher PVC concentrations were observed in the stools when the children took more time to eat a meal. MP exposure was inversely associated with alpha indices and possibly affected certain probiotic taxa, such as Parabacteroides and Alistipes, in preschool children. INTERPRETATION: Our data provided baseline evidence for MP exposure doses and potential dietary factors that may influence MP exposure in preschoolers. These findings supported the perspective that MP exposure might be associated with the disturbance of gut microbiota. Further studies focusing on sensitive populations with larger sample sizes are needed. FUNDING: This study was funded by the National Natural Science Foundation of China (grant number: 82003412), the Shanghai Municipal Health Commission (grant number: 20214Y0019), and the Project of Shanghai Municipal Financial Professional foundation (Food Safety Risk Assessment) (grant number: RA-2022-06).


Subject(s)
Gastrointestinal Microbiome , Water Pollutants, Chemical , Humans , Child, Preschool , Animals , Mice , Microplastics , Plastics , Pilot Projects , RNA, Ribosomal, 16S/genetics , Cross-Sectional Studies , China , Polyethylene/analysis , Water Pollutants, Chemical/analysis
12.
Int J Biol Macromol ; 253(Pt 2): 126770, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37683741

ABSTRACT

Translesion synthesis (TLS) is a kind of DNA repair that maintains the stability of the genome and ensures the normal growth of life in cells under emergencies. Y-family DNA polymerases, as a kind of error-prone DNA polymerase, mainly perform TLS. Previous studies have suggested that the occurrence of tumors is associated with the overexpression of human DNA polymerase of the Y family. And the combination of Y-family DNA polymerase inhibitors is promising for cancer therapy. Here we report the functional and structural characterization of a member of the Y-family DNA polymerases, TTEDbh. We determine TTEDbh is an extreme TLS polymerase that can cross oxidative damage sites, and further identify the amino acids and novel structures that are critical for DNA binding, synthesis, fidelity, and oxidative damage bypass. Moreover, previously unnoticed structural elements with important functions have been discovered and analyzed. These studies provide a more experimental basis for further elucidating the molecular mechanisms of DNA polymerase in the Y family. It could also shed light on the design of drugs to target tumors.


Subject(s)
DNA Damage , Neoplasms , Humans , DNA-Directed DNA Polymerase/chemistry , DNA Repair , DNA Replication
13.
Sci Total Environ ; 900: 165680, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37499811

ABSTRACT

Pb pollution can harm human health and the ecosystem. Therefore, it is worthwhile to study the metabolic processes of heavy metals in individual bodies and their influence on ecological systems. In this work, we analyzed the genetic responses and physiological changes of D. melanogaster which took diets exposed to different doses of Pb using transcriptomic analysis, ICP-MS, and various other physiological methods. We found that the Pb accumulated in D. melanogaster in a nonlinear pattern with the increase of Pb content in food. Metallothioneins (Mtns), especially the MtnB directly affects the accumulation and excretion of metal Pb in D. melanogaster, and causes the nonlinear accumulation. Metal regulatory transcription factor-1 (MTF-1) is involved in the regulation of Pb-induced high expressions of Mtns. Furthermore, an interaction between the metal metabolism pathway and xenobiotic response pathway leads to the cross-tolerances of Pb-exposed D. melanogaster to insecticides and other toxins. The oxidative stress induced by Pb toxicity may be the bridge between them. Our findings provide a physiological and molecular genetic basis for further study of the accumulation and metabolism of Pb in D. melanogaster.


Subject(s)
Drosophila melanogaster , Metals, Heavy , Animals , Humans , Drosophila melanogaster/genetics , Lead/toxicity , Lead/metabolism , Metallothionein/genetics , Metallothionein/metabolism , Ecosystem , Metals, Heavy/metabolism
16.
J Diabetes Complications ; 37(8): 108523, 2023 08.
Article in English | MEDLINE | ID: mdl-37301061

ABSTRACT

AIMS: To investigate the therapeutic effects of Tangningtongluo Tablet on diabetic mice and its mechanism. This study was established the scientific basis for the clinical application of Tangningtongluo Tablet in the treatment of diabetes mellitus and provided data supporting the transformation of Tangningtongluo Tablet from an in-hospital preparation to a new Chinese medicine. METHODS: In this study, a diabetic mouse model was established by high-glucose and high-fat diet feeding in combination with STZ injection for 4 weeks. Glucose metabolism, lipid metabolism, liver histomorphological changes and liver function related indexes were detected, pancreatic histomorphological changes and insulin resistance related indexes were observed, and the expression of pathway related proteins and inflammatory factors were examined. RESULTS: Glycemia and glycated hemoglobin were reduced in diabetic mice after the treatment of Tangningtongluo Tablet, and glucose tolerance and lipid results were modified. The insulin resistance status of the mice was diminished and tissue damage to the pancreas and liver was repaired. Expression of ERS/NF-κB related pathway proteins was reduced in liver tissues, and inflammatory factors such as TNF-α, IL-6 and IL-1ß were reduced in serum. CONCLUSIONS: Tangningtongluo Tablet could reduce blood glucose in diabetic mice, regulate the disorder of lipid metabolism, enhance insulin sensitivity, improve insulin resistance, repair pancreatic tissue damage and protect mouse liver in diabetic mice. The mechanism of action might be related to the regulation of ERS/NF-κB signaling pathway and the reduction of TNF-α, IL-6 and IL-1ß production.


Subject(s)
Diabetes Mellitus, Experimental , Insulin Resistance , Animals , Mice , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diet, High-Fat/adverse effects , Interleukin-6 , NF-kappa B , Tablets/pharmacology , Tablets/therapeutic use , Tumor Necrosis Factor-alpha
17.
Front Psychol ; 14: 1119355, 2023.
Article in English | MEDLINE | ID: mdl-37123298

ABSTRACT

Voice user interface (VUI) is widely used in developing intelligent products due to its low learning cost. However, most of such products do not consider the cognitive and language ability of elderly people, which leads to low interaction efficiency, poor user experience, and unfriendliness to them. Firstly, the paper analyzes the factors which influence the voice interaction behavior of elderly people: speech rate of elderly people, dialog task type, and feedback word count. And then, the voice interaction simulation experiment was designed based on the wizard of Oz testing method. Thirty subjects (M = 61.86 years old, SD = 7.16; 15 males and 15 females) were invited to interact with the prototype of a voice robot through three kinds of dialog tasks and six configurations of the feedback speech rate. Elderly people's speech rates at which they speak to a person and to a voice robot, the feedback speech rates they expected for three dialog tasks were collected. The correlation between subjects' speech rate and the expected feedback speech rate, the influence of dialog task type, and feedback word count on elderly people's expected feedback speech rate were analyzed. The results show that elderly people speak to a voice robot with a lower speech rate than they speak to a person, and they expected the robot feedback speech rate to be lower than the rate they speak to the robot. There is a positive correlation between subjects' speech rate and the expected speech rate, which implies that elderly people with faster speech rates expected a faster feedback speech rate. There is no significant difference between the elderly people's expected speech rate for non-goal-oriented and goal-oriented dialog tasks. Meanwhile, a negative correlation between the feedback word count and the expected feedback speech rate is found. This study extends the knowledge boundaries of VUI design by investigating the influencing factors of voice interaction between elderly people and VUI. These results also provide practical implications for developing suitable VUI for elderly people, especially for regulating the feedback speech rate of VUI.

18.
Otolaryngol Head Neck Surg ; 169(5): 1299-1308, 2023 11.
Article in English | MEDLINE | ID: mdl-37125626

ABSTRACT

OBJECTIVE: Unilateral sensorineural hearing loss (USNHL) is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood USNHL and analyze the associated audiological features. STUDY DESIGN: Retrospective analysis of a prospectively recruited cohort. SETTING: Tertiary referral center. METHODS: We enrolled 38 children with USNHL between January 1, 2018, and December 31, 2021, and performed physical, audiological, imaging, and congenital cytomegalovirus (cCMV) examinations as well as genetic testing using next-generation sequencing (NGS) targeting 30 deafness genes. The audiological results were compared across different etiologies. RESULTS: Causative genetic variants were identified in 8 (21.1%) patients, including 5 with GJB2 variants, 2 with PAX3 variants, and 1 with the EDNRB variant. GJB2 variants were found to be associated with mild-to-moderate USNHL in various audiogram configurations, whereas PAX3 and EDNRB variants were associated with profound USNHL in flat audiogram configurations. In addition, whole-genome sequencing and extended NGS targeting 213 deafness genes were performed in 2 multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and cCMV infection were observed in 9 and 2, respectively, patients without definite genetic diagnoses. CONCLUSION: Genetic underpinnings can contribute to approximately 20% of childhood USNHL, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of USNHL in children.


Subject(s)
Cytomegalovirus Infections , Deafness , Hearing Loss, Sensorineural , Hearing Loss, Unilateral , Hearing Loss , Humans , Child , Retrospective Studies , Hearing Loss, Sensorineural/etiology , Hearing Loss/complications , Genetic Testing , Cytomegalovirus Infections/complications , Deafness/genetics , Hearing Loss, Unilateral/genetics
19.
Biomolecules ; 13(4)2023 04 04.
Article in English | MEDLINE | ID: mdl-37189394

ABSTRACT

The scaffolding protein Axin is an important regulator of the Wnt signaling pathway, and its dysfunction is closely related to carcinogenesis. Axin could affect the assembly and dissociation of the ß-catenin destruction complex. It can be regulated by phosphorylation, poly-ADP-ribosylation, and ubiquitination. The E3 ubiquitin ligase SIAH1 participates in the Wnt pathway by targeting various components for degradation. SIAH1 is also implicated in the regulation of Axin2 degradation, but the specific mechanism remains unclear. Here, we verified that the Axin2-GSK3 binding domain (GBD) was sufficient for SIAH1 binding by the GST pull-down assay. Our crystal structure of the Axin2/SIAH1 complex at 2.53 Å resolution reveals that one Axin2 molecule binds to one SIAH1 molecule via its GBD. These interactions critically depend on a highly conserved peptide 361EMTPVEPA368 within the Axin2-GBD, which forms a loop and binds to a deep groove formed by ß1, ß2, and ß3 of SIAH1 by the N-terminal hydrophilic amino acids Arg361 and Thr363 and the C-terminal VxP motif. The novel binding mode indicates a promising drug-binding site for regulating Wnt/ß-catenin signaling.


Subject(s)
Glycogen Synthase Kinase 3 , Wnt Signaling Pathway , Humans , Axin Protein/genetics , Axin Protein/metabolism , Glycogen Synthase Kinase 3/metabolism , beta Catenin/metabolism , Ubiquitination
20.
Asian J Psychiatr ; 85: 103613, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37163943

ABSTRACT

OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar. METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection. RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication. CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.


Subject(s)
Antipsychotic Agents , Bipolar Disorder , Humans , Bipolar Disorder/drug therapy , Valproic Acid/therapeutic use , Antimanic Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Anticonvulsants/therapeutic use , Pakistan
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