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2.
J Am Chem Soc ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767283

RESUMO

Quinone-based electrodes using carbonyl redox reactions are promising candidates for aqueous energy storage due to their high theoretical specific capacity and high-rate performance. However, the proton storage manners and their influences on the electrochemical performance of quinone are still not clear. Herein, we reveal that proton storage could determine the products of the enol conversion and the electrochemical stability of the organic electrode. Specifically, the protons preferentially coordinated with the prototypical pyrene-4,5,9,10-tetraone (PTO) cathode, and increasing the proton concentration in the electrolyte can improve its working potentials and cycling stability by tailoring the enol conversion reaction. We also found that exploiting Al2(SO4)3 as a pH buffer can increase the energy density of the Zn||PTO batteries from 242.8 to 284.6 Wh kg-1. Our research has a guiding significance for emphasizing proton storage of organic electrodes based on enol conversion reactions and improving their electrochemical performance.

3.
Brain Behav ; 14(5): e3503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38775292

RESUMO

BACKGROUND: Crocin has a good prospect in the treatment of Alzheimer's disease (AD), but the mechanisms underlying its neuroprotective effects remain elusive. This study aimed to investigate the neuroprotective effects of Crocin and its underlying mechanisms in AD. METHODS: AD mice were set up by injecting Aß25-35 solution into the hippocampus. Then, the AD mice were injected intraperitoneally with 40 mg/kg/day of Crocin for 14 days. Following the completion of Crocin treatment, an open-field test, Y-maze test and Morris water maze test were conducted to evaluate the impact of Crocin on spatial learning and memory deficiency in mice. The effects of Crocin on hippocampal neuron injury, proinflammatory cytokine expressions (IL-1ß, IL-6, and TNF-α), and PI3K/AKT signaling-related protein expressions were measured using hematoxylin and eosin staining, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, respectively. RESULTS: Crocin attenuated Aß25-35-induced spatial learning and memory deficiency and hippocampal neuron injury. Furthermore, the Western blot and qRT-PCR results showed that Crocin effectively suppressed inflammation and activated the PI3K/AKT pathway in Aß25-35-induced mice. CONCLUSION: Crocin restrained neuroinflammation via the activation of the PI3K/AKT pathway, thereby ameliorating the cognitive dysfunction of AD mice.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Carotenoides , Disfunção Cognitiva , Hipocampo , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Carotenoides/farmacologia , Carotenoides/administração & dosagem , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Modelos Animais de Doenças , Fragmentos de Peptídeos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
4.
Angew Chem Int Ed Engl ; : e202407589, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703065

RESUMO

Directly electrochemical conversion of nitrate (NO3-) is an efficient and environmentally friendly technology for ammonia (NH3) production but is challenged by highly selective electrocatalysts. High-entropy alloys (HEAs) with unique properties are attractive materials in catalysis, particularly for multi-step reactions. Herein, we first reported the application of HEA (FeCoNiAlTi) for electrocatalytic NO3- reduction to NH3 (NRA). The bulk HEA is active for NRA but limited by the unsatisfied NH3 yield of 0.36 mg h-1 cm-2 and Faradaic efficiency (FE) of 82.66%. Through an effective phase engineering strategy, uniform intermetallic nanoparticles are introduced on the bulk HEA to increase electrochemical active surface area and charge transfer efficiency.The resulting nanostructured HEA (n-HEA) delivers enhanced electrochemical NRA performance in terms of NH3 yield (0.52 mg h-1 cm-2) and FE (95.23%). Further experimental and theoretical investigations reveal that the multi-active sites (Fe, Co, and Ni) dominated electrocatalysis for NRA over the n-HEA. Notably, the typical Co sites exhibit the lowest energy barrier for NRA with *NO + H+ + e- → *NOH as the rate-determining step.

5.
Food Chem ; 452: 139527, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38703741

RESUMO

Tryptamine is a biogenic amine that affects organoleptic quality through the generation of off-odours in foods. Herein, imine-based covalent organic frameworks (COFs) were synthesized via Schiff base reactions and postmodified with click chemistry to generate azide-functionalized COFs with tunable azide units on the walls. The combination of molecular imprinting with COFs enabled the specific recognition of the targets. The resulting optosensing system (azide-functionalized COFs@MIPs) was used as a sample-to-answer analyser for detecting tryptamine (detection time within 10 min). A linear relationship was observed for the fluorescence response to tryptamine concentrations in the range of 3-120 µg L-1, with a limit of detection of 1.74 µg L-1. The recoveries for spiked samples were satisfactory, with relative standard deviations <9.90%. The optosensing system is a potential tool for the quantitative detection of tryptamine in meat products because of its lower cost, shorter processing time, and simpler processing steps compared to conventional chromatographic techniques.

6.
Nat Commun ; 15(1): 3748, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702298

RESUMO

The high redox potential of Zn0/2+ leads to low voltage of Zn batteries and therefore low energy density, plaguing deployment of Zn batteries in many energy-demanding applications. Though employing high-voltage cathode like spinel LiNi0.5Mn1.5O4 can increase the voltages of Zn batteries, Zn2+ ions will be immobilized in LiNi0.5Mn1.5O4 once intercalated, resulting in irreversibility. Here, we design a polymer hetero-electrolyte consisting of an anode layer with Zn2+ ions as charge carriers and a cathode layer that blocks the Zn2+ ion shuttle, which allows separated Zn and Li reversibility. As such, the Zn‖LNMO cell exhibits up to 2.4 V discharge voltage and 450 stable cycles with high reversible capacity, which are also attained in a scale-up pouch cell. The pouch cell shows a low self-discharge after resting for 28 days. The designed electrolyte paves the way to develop high-voltage Zn batteries based on reversible lithiated cathodes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38761235

RESUMO

OBJECTIVE: To describe the disease burden of knee osteoarthritis (KOA) globally, regionally, and in 204 countries by age, sex, and sociodemographic index (SDI) from 1990 to 2019, and to explore cross-national inequalities across SDI. METHODS: The Global Burden of Disease (GBD) 2019 database collected data on KOA worldwide from 1990 to 2019, including prevalence, incidence, years lived with disability (YLDs). The average annual percentage change (AAPC) was used to measure temporal trends. In addition, the inequality slope index and the health concentration index were calculated to quantify the unequal distribution of the burden of KOA across 204 countries worldwide. RESULTS: In 2019, the global age-standardized prevalence rate increased by 7.5% compared with 1990, and the age-standardized incidence rate increased by about 6.2%; The age-standardized YLDs rate increased by about 7.8%. In addition to the Republic of Korea and the United States of America, the disease burden of KOA has increased year by year in other countries around the world. The incidence of KOA was highest at ages 50-59, while the prevalence and rates of YLDs were highest at ages 75-84. The burden of KOA was higher in women than in men. Cross-country inequality suggests that the inequality in the burden of KOA between high SDI and low SDI countries becomes greater, and that countries with high SDI bear a disproportionately high burden. CONCLUSION: The global KOA burden has risen steadily between 1990 and 2019, and cross-national inequality gaps remain large. Targeted measures must therefore be taken to address this inequality and the increasing global KOA disease burden.

8.
Int J Biol Macromol ; : 132389, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38754655

RESUMO

Currently, evidence from observational studies suggests dietary fiber intake may be associated with decreased risk of food allergy. As a type of dietary fiber, resistant starch was also widely reported to possess anti-allergic properties. However, there is a relative paucity of studies assessing the influence of resistant starch types on their anti-allergic activity and its possible underlying mechanisms. In the current study, the anti-allergic effects of RS3-type (retrograded starch), RS4-type (chemically modified starch, cross-bonded), and RS5-type (starch-palmitic acid complex) of lotus seed resistant starch were evaluated in the OVA (100 mg/kg)-induced food allergic mice model. The results showed that oral administration of RS3 or RS4 lotus seed resistant starch (0.3 g/100 g b.w.) for 25 days significantly improved adverse symptoms of food allergy such as weight loss, increases in allergy symptom score and diarrhea rate; with significant reduction of serum specific antibody IgE, TNF-α, IL-4 levels and improved Th1/Th2 balance being observed. The mechanism may involve the regulation of lotus seed resistant starch on intestinal flora and the metabolites short-chain fatty acids and bile acids. Taken together, the findings may enhance understanding towards ameliorative effects of resistant starch on food allergy, and offer valuable insights for the exploration of novel anti-allergic bioactive compounds.

9.
Alzheimers Res Ther ; 16(1): 69, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570794

RESUMO

BACKGROUND: Neuropsychiatric symptoms (NPS) are prevalent in cognitively impaired individuals including Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Whereas several studies have reported the associations between NPS with AD pathologic biomarkers and cerebral small vessel disease (SVD), but it remains unknown whether AD pathology and SVD contribute to different sub-syndromes independently or aggravate same symptoms synergistically. METHOD: We included 445 cognitively impaired individuals (including 316 MCI and 129 AD) with neuropsychiatric, cerebrospinal fluid (CSF) biomarkers (Aß42, p-tau, and t-tau) and multi-model MRI data. Psychiatric symptoms were accessed by using the Neuropsychiatric Inventory (NPI). Visual assessment of SVD (white matter hyperintensity, microbleed, perivascular space, lacune) on MRI images was performed by experienced radiologist. Linear regression analyses were conducted to test the association between neuropsychiatric symptoms with AD pathology and CSVD burden after adjustment for age, sex, education, apolipoprotein E (APOE) ε4 carrier status, and clinical diagnosis. RESULTS: The NPI total scores were related to microbleed (estimate 2.424; 95% CI [0.749, 4.099]; P =0.005). Considering the sub-syndromes, the hyperactivity was associated with microbleed (estimate 0.925; 95% CI [0.115, 1.735]; P =0.025), whereas the affective symptoms were correlated to CSF level of Aß42 (estimate -0.006; 95% CI [-0.011, -0.002]; P =0.005). Furthermore, we found the apathy sub-syndrome was associated with CSF t-tau/Aß42 (estimate 0.636; 95% CI [0.078, 1.194]; P =0.041) and microbleed (estimate 0.693; 95% CI [0.046, 1.340]; P =0.036). In addition, we found a significant interactive effect between CSF t-tau/Aß42 and microbleed (estimate 0.993; 95% CI [0.360, 1.626]; P =0.019) on severity of apathy sub-syndrome. CONCLUSION: Our study showed that CSF Aß42 was associated with affective symptoms, but microbleed was correlated with hyperactivity and apathy, suggesting the effect of AD pathology and SVD on different neuropsychiatric sub-syndromes.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Hemorragia Cerebral
10.
Int J Biometeorol ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564032

RESUMO

We recruited 162 healthy elderly adults to determine the thermal, physiological, and psychological effects of horticultural activities (flower arranging, transplanting, and rubble masonry) in outdoor open spaces. We linked these to local climate conditions, physiology, and comfort through a questionnaire survey. The results showed that: (1) the neutral physiological equivalent temperature (NPET) before the horticultural activities were 22.18 â„ƒ for flower arranging, 23.67 â„ƒ for transplanting, and 20.78 â„ƒ for rubble masonry, while the NPET decreased to 18.53 â„ƒ, 20.73 â„ƒ and 18.04 â„ƒ (respectively) after activities. (2) The heart rate and blood oxygen saturation changed significantly (p < 0.05) only after rubble masonry. (3) The average positive affect (PA) scores increased after flower arranging by 4.83, transplanting by 3.30, and rubble masonry by 4.00. (4) After activities, the thermal sensation vote was mainly influenced by globe temperature (41.36%), air temperature (33.47%), and wind speed (25.17%). Thermal comfort vote could be promoted because of 37.35% of an increasing positive and 21.20% of decreasing negative emotion.

11.
Nat Aging ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627524

RESUMO

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

12.
Angew Chem Int Ed Engl ; 63(22): e202403504, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38563637

RESUMO

The rechargeable aqueous Zn||MnO2 chemistry has been extensively explored, but its electrochemical reaction mechanisms, especially in the context of MnO2/Mn2+ conversion and Zn2+/H+ intercalation chemistry, remain not fully understood. Here, we designed an amphiphilic hydrogel electrolyte, which distinguished the MnO2/Mn2+ conversion, Zn2+ intercalation, and H+ intercalation and conversion processes at three distinct discharge plateaus of an aqueous Zn||MnO2 battery. The amphiphilic hydrogel electrolyte is featured with an extended electrochemical stability window up to 3.0 V, high ionic conductivity, Zn2+-selective ion tunnels, and hydrophobic associations with cathode materials. This specifically designed electrolyte allows the MnO2/Mn2+ conversion reaction at a discharge plateau of 1.75 V. More interesting, the discharge plateaus of ~1.33 V, previously assigned as the co-intercalation of Zn2+ and H+ ions in the MnO2 cathode, are specified as the exclusive intercalation of Zn2+ ions, leading to an ultra-flat voltage plateau. Furthermore, with a distinct three-step electrochemical energy storage process, a high areal capacity of 1.8 mAh cm-2 and high specific energy of 0.858 Wh cm-2, even at a low MnO2 loading mass of 0.5 mg cm-2 are achieved. To our knowledge, this is the first report to fully distinguish different mechanisms at different potentials in aqueous Zn||MnO2 batteries.

13.
Ecotoxicol Environ Saf ; 276: 116340, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636261

RESUMO

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.


Assuntos
Aminoácidos , Estresse Oxidativo , Praguicidas , Praguicidas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Glutationa/metabolismo , Suplementos Nutricionais , Humanos
14.
Bioresour Technol ; 400: 130696, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614144

RESUMO

Understanding large-scale composting under natural conditions is essential for improving waste management and promoting sustainable agriculture. In this study, corn straw (400 tons) and pig manure (200 tons) were composted with microbial inoculants. The thermophilic phase of composting lasted for fourteen weeks, resulting in an alkaline final product. Microbial systems with low-temperature initiation and high-temperature fermentation played a crucial role in enhancing lignocellulose degradation and humic substances (HS) formation. Adding microbes, including Rhodanobacter, Pseudomonas, and Planococcus, showed a positive correlation with degradation rates of cellulose, hemicellulose, and lignin. Bacillus, Planococcus, and Acinetobacter were positively correlated with HS formation. Microorganisms facilitated efficient hydrolysis of lignocelluloses, providing humic precursors to accelerate composting humification through phenolic protein and Maillard pathways. This study provides significant insights into large-scale composting under natural conditions, contributing to the advancement of waste management strategies and the promotion of sustainable agriculture.


Assuntos
Compostagem , Esterco , Zea mays , Compostagem/métodos , Animais , Zea mays/química , Lignina/metabolismo , Substâncias Húmicas/análise , Bactérias/metabolismo , Temperatura Baixa , Temperatura , Hidrólise , Suínos , Resíduos
15.
Food Res Int ; 184: 114262, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38609241

RESUMO

There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.


Assuntos
Ácido Acético , Antioxidantes , Ácido Clorogênico , Ácido Gálico , Polifenóis
16.
Carbohydr Polym ; 334: 122038, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553205

RESUMO

The widespread use of disposable plastic straws has caused a long-lasting environmental problem. Potential alternatives for plastic straws are far from satisfactory due to the low utility, poor water stability, and non-ideal natural degradability. In this work, an edible, hydrostable, and degradable straw was developed from the economically significant seaweed. Seaweed-derived insoluble cellulose fibers were used as the building block of the straw, and the soluble polysaccharide extracts were explored as the natural glue through the chelation with Ca2+. Repeated freeze-thawing was introduced to strengthen the molecular interactions, which further improved its mechanical stability and hydrostability. The straw exhibited remarkable natural degradability in open environments, particularly in marine-mimicking conditions. By incorporating pH-sensitive food pigments, the straws could indicate acid-base property of a beverage or even discriminate the freshness of milk. The versatile seaweed-derived straw adhered to the biocycle concept of "from sea to sea" to alleviate the burden of white pollution on oceans.


Assuntos
Celulose , Alga Marinha , Polissacarídeos
17.
Int J Food Microbiol ; 416: 110675, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38479336

RESUMO

The aim of this study is evaluating the protein degradation capacity of specific spoilage organisms (SSOs) Pseudomonas psychrophila and Shewanella putrefaciens in fish flesh during chilled storage and revealing the underlying genes by whole-genome sequencing (WGS). Biochemical and physical tests were performed on fish flesh inoculated with P. psychrophila and S. putrefaciens individually, including textural properties, myofibrillar fragmentation index, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profiles, free amino acid composition, total volatile basic nitrogen (TVB-N), trichloroacetic acid (TCA) soluble peptides, and muscle microstructure. Results showed that P. psychrophila and S. putrefaciens exhibited a strong capacity for decomposing the fish protein, and the deterioration of fish flesh texture was primarily attributed to P. psychrophila. The genes from SSOs associated with the production of proteases were identified by whole genome sequencing and serine protease may be the primary enzyme secreted by SSOs involved in the degradation of fish protein. Therefore, the present study has shed light on the mechanisms of protein degradation induced by SSOs, thereby offering valuable insights for the development of effective quality control strategies.


Assuntos
Pseudomonas , Shewanella putrefaciens , Animais , Proteínas de Peixes , Proteólise , Microbiologia de Alimentos , Peixes , Sequenciamento Completo do Genoma
18.
Mol Genet Genomic Med ; 12(3): e2403, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38439608

RESUMO

BACKGROUND: Tuberous sclerosis complex (TSC), an autosomal-dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the TSC1 or TSC2 genes. The phenotype variability of TSC could lead to missed diagnosis; therefore, the latest molecular diagnostic criteria for identifying a heterozygous pathogenic variant in either the TSC1 or TSC2 gene filled this gap. Furthermore, the pathogenicity of numerous variants remains unverified, potentially leading to misinterpretations of their functional consequences. METHODS: In this study, a single patient presenting with atypical vitiligo-like skin lesions suspected to have TSC was enrolled. Targeted next-generation sequencing and Sanger sequencing were employed to identify a pathogenic variant. Additionally, a minigene splicing assay was conducted to assess the impact of TSC1 c.1030-2A>T, located in intron 10, on RNA splicing. RESULTS: A novel TSC1: c.1030-2A>T heterozygosis variant was identified in intron 10. In vitro minigene assay revealed that the c.1030-2A>T variant caused exon 11 skipping, resulting in a frameshift in the absence of 112 base pairs of mature messenger RNA and premature termination after 174 base pairs (p.Ala344Glnfs*59). CONCLUSION: The detection of this novel pathogenic TSC1 variant in the patient with atypical vitiligo-like skin lesions enrolled in our study ultimately resulted in the diagnosis of TSC. As a result, our study contributes to expanding the mutational spectrum of the TSC1 gene and refining the genotype-phenotype map of TSC.


Assuntos
Hamartoma , Esclerose Tuberosa , Vitiligo , Humanos , Mutação da Fase de Leitura , Íntrons , Esclerose Tuberosa/genética , Vitiligo/genética
19.
Food Res Int ; 181: 114078, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448095

RESUMO

The effects of α-amylase on of flavor perception were investigated via spectrum analysis, electronic tongue, on-line mass spectrometry, and molecular docking. Aroma release results showed that α-amylase exhibited variable release patterns of different aroma compounds. Electronic tongue analysis showed that the perception of bitterness, sweetness, sour, and saltiness was subtly increased and that of umami was significantly increased (p < 0.01) along with the increasing enzyme activity of α-amylase. Ultraviolet absorption and fluorescence spectroscopy analyses showed that static quenching occurred between α-amylase and eight flavor compounds and their interaction effects were spontaneous. One binding pocket was confirmed between the α-amylase and flavor compounds, and molecular docking simulation results showed that the hydrogen, electrostatic, and hydrophobic bonds were the main force interactions. The TYP82, TRP83, LEU173, HIS80, HIS122, ASP297, ASP206, and ARG344 were the key α-amylase amino acid residues that interacted with the eight flavor compounds.


Assuntos
Prótons , alfa-Amilases , Simulação de Acoplamento Molecular , Nariz Eletrônico , Espectrometria de Massas , Aminoácidos , Percepção
20.
Brain Commun ; 6(1): fcae033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425749

RESUMO

The objectively-defined subtle cognitive decline individuals had higher progression rates of cognitive decline and pathological deposition than healthy elderly, indicating a higher risk of progressing to Alzheimer's disease. However, little is known about the brain functional alterations during this stage. Thus, we aimed to investigate the functional network patterns in objectively-defined subtle cognitive decline cohort. Forty-two cognitive normal, 29 objectively-defined subtle cognitive decline and 55 mild cognitive impairment subjects were included based on neuropsychological measures from the Alzheimer's disease Neuroimaging Initiative dataset. Thirty cognitive normal, 22 objectively-defined subtle cognitive declines and 48 mild cognitive impairment had longitudinal MRI data. The degree centrality and eigenvector centrality for each participant were calculated by using resting-state functional MRI. For cross-sectional data, analysis of covariance was performed to detect between-group differences in degree centrality and eigenvector centrality after controlling age, sex and education. For longitudinal data, repeated measurement analysis of covariance was used for comparing the alterations during follow-up period among three groups. In order to classify the clinical significance, we correlated degree centrality and eigenvector centrality values to Alzheimer's disease biomarkers and cognitive function. The results of analysis of covariance showed significant between-group differences in eigenvector centrality and degree centrality in left superior temporal gyrus and left precuneus, respectively. Across groups, the eigenvector centrality value of left superior temporal gyrus was positively related to recognition scores in auditory verbal learning test, whereas the degree centrality value of left precuneus was positively associated with mini-mental state examination total score. For longitudinal data, the results of repeated measurement analysis of covariance indicated objectively-defined subtle cognitive decline group had the highest declined rate of both eigenvector centrality and degree centrality values than other groups. Our study showed an increased brain functional connectivity in objectively-defined subtle cognitive decline individuals at both local and global level, which were associated with Alzheimer's disease pathology and neuropsychological assessment. Moreover, we also observed a faster declined rate of functional network matrix in objectively-defined subtle cognitive decline individuals during the follow-ups.

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