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1.
Food Chem ; 455: 139679, 2024 May 18.
Article En | MEDLINE | ID: mdl-38823125

This study involved the preparation of nanoparticles by combining oxidized starch (OS) with xanthan gum (XG), and emulsions were prepared from this nanoparticle. The physical and chemical characteristics, as well as the emulsification properties of oxidized starch-xanthan gum composite nanoparticles (OGNP), were analyzed. The findings revealed that the OGNP retained spherical shape after the addition of XG, although their diameter increased from approximately 50-150 to 200-400 nm. Zeta potential decreased with XG content. Moreover, emulsions prepared from OGNP exhibited outstanding thermal stability, also showing enhanced storage stability. In addition, emulsions had different rheological properties at different pH values. The apparent viscosity and shear stress of emulsions under alkaline conditions were lower than that of neutral conditions. NaCl increased the apparent viscosity of OGNP-stabilized emulsions while reducing their thermal stability. The nanoparticles prepared in this study have efficient emulsification properties and can extend the application of OS.

3.
J Colloid Interface Sci ; 672: 86-96, 2024 May 28.
Article En | MEDLINE | ID: mdl-38833737

Designing novel rare-earth-transition metal composites is at the forefront of electrocatalyst research. However, the modulation of transition metal electronic structures by rare earths to induce vacancy defects and enhance electrochemical performance has rarely been reported. In this study, we systematically investigate the mechanism by which Ce-4f electron modulation weakens the Fe-O bond, thereby altering the electronic structure in CeFevNi hydroxide to improve oxygen evolution reaction (OER) performance. Theoretical calculations and experimental characterizations reveal that Ce-4f orbitals function as electron-modulation reservoirs, capable not only of retaining or donating electrons but also of influencing the material's electronic structure. Moreover, Ce-4f bands optimize the Fe lower Hubbard bands (LHB) and O-2p bands, leading to weakened Fe-O bonds and the formation of cationic vacancies. This change results in the upshift of the d-band center at the active sites, favoring the reaction energy barrier for oxygen intermediates in the OER process. The synthesized catalyst demonstrated an overpotential of 201 mV at 10 mA cm-2 and a lifetime exceeding 200 h at 100 mA cm-2 under alkaline conditions. This work offers a proof-of-concept for the application of the mechanism of rare earth-induced transition metal vacancy defects, providing a general guideline for the design and development of novel highly efficient catalysts.

4.
Nat Aging ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38834883

Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.

5.
J Ethnopharmacol ; 333: 118407, 2024 May 31.
Article En | MEDLINE | ID: mdl-38824979

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (TSD), a classic traditional Chinese medicine formula, is used for the treatment of vascular diseases, including vascular dementia (VD). However, the mechanisms remain unclear. AIM OF STUDY: This study aimed to investigate whether TSD has a positive effect on cognitive impairment in VD rats and to confirm that the mechanism of action is related to the Endoplasmic Reticulum stress (ERs) and cell apoptosis signaling pathway. MATERIALS AND METHODS: A total of 40 male adult Sprague-Dawley rats were divided into four groups: sham-operated group (Sham), the two-vessel occlusion group (2VO), the 2VO treated with 4.5 g/kg/d TSD group (2VO + TSD-L), the 2VO treated with 13.5 g/kg/d TSD group (2VO + TSD-H). The rats underwent either 2VO surgery or sham surgery. Postoperative TSD treatment was given for 4 consecutive weeks. Behavioral tests were initiated at the end of gastrulation. Open-field test (OFT) was used to detect the activity level. The New Object Recognition test (NOR) was used to test long-term memory. The Morris water maze (MWM) test was used to examine the foundation of spatial learning and memory. As a final step, the hippocampus was taken for molecular testing. The protein levels of GRP78 (Bip), p-PERK, PERK, IRE1α, p-IRE1α, ATF6, eIF2α, p-eIF2α, ATF4, XBP1, Bcl-2 and Bax were determined by Western blot. Immunofluorescence visualizes molecular expression. RESULTS: In the OFT, residence time in the central area was significantly longer in both TSD treatment groups compared to the 2VO group. In the NOR, the recognition index was obviously elevated in both TSD treatment groups. The 2VO group had a significantly longer escape latency and fewer times in crossing the location of the platform compared with the Sham group in MWM. TSD treatment reversed this notion. Pathologically, staining observations confirmed that TSD inhibited hippocampal neuronal loss and alleviated the abnormal reduction of the Nissl body. In parallel, TUNEL staining illustrated that TSD decelerated neuronal apoptosis. Western Blot demonstrated that TSD reduces the expression of ERs and apoptotic proteins. CONCLUSION: In this study, the significant ameliorative effect on cognitive impairment of TSD has been determined by comparing the behavioral data of the 4 groups of rats. Furthermore, it was confirmed that this effect of TSD was achieved by suppressing the ERs-mediated apoptosis signaling pathway.

6.
Neuron ; 112(11): 1723-1724, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38843776

Sporadic Alzheimer's disease (AD) and autosomal dominant Alzheimer's disease (ADAD) share pathological features, but differing mechanisms, leading to disease. In this issue of Neuron, Almeida, Eger, et al.1 uncovered molecular processes that may distinguish sporadic AD from ADAD and how the APOE-Christchurch variant may be protective.


Alzheimer Disease , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Alzheimer Disease/metabolism , Humans , Apolipoproteins E/genetics , Animals
7.
Heliyon ; 10(11): e31818, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38845872

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8 -/- mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8 +/+ mice, Irf8 -/- mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI.

8.
Front Endocrinol (Lausanne) ; 15: 1367621, 2024.
Article En | MEDLINE | ID: mdl-38841306

Background: Although there is solid epidemiological evidence supporting the connection between hypertension and gout, little has been said about the relationship between diastolic and systolic blood pressure and gout, the causal relationship and direction associated are uncertain, so we aim to research the causal relationship between diastolic and systolic blood pressure and gout. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect between 2 blood pressure phenotypes (including diastolic blood pressure and systolic blood pressure) and 5 gout phenotypes (including gout, drug-induced gout, idiopathic gout, unspecified gout, and strictly defined gout) using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. Results: After the screening, we found a causal relationship between diastolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout, and a causal relationship between systolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout. Conclusion: From a genetic predisposition, controlling blood pressure may reduce the risk of gout.


Blood Pressure , Genome-Wide Association Study , Gout , Hypertension , Mendelian Randomization Analysis , Humans , Gout/genetics , Gout/epidemiology , Blood Pressure/genetics , Hypertension/genetics , Hypertension/epidemiology , Genetic Predisposition to Disease , Diastole , Systole , Polymorphism, Single Nucleotide , Risk Factors
9.
JCPP Adv ; 4(2): e12212, 2024 Jun.
Article En | MEDLINE | ID: mdl-38827978

Background: Previous research has demonstrated heterogeneous adaptive outcomes across the autism spectrum; however, the current literature remains limited in elucidating turning points and associated factors for longitudinal variability (chronogeneity). To address these empirical gaps, we aimed to provide a finer-grained characterization of trajectories of adaptive functioning from early childhood to adolescence in autism. Methods: Our sample (N = 406) was drawn from an inception cohort of children diagnosed Autistic at ages 2-5. Adaptive functioning was assessed with Vineland Adaptive Behavior Scales (VABS, 2nd Edition) across 6 visits from the time of diagnosis by age 18. Parallel-process latent growth curve modeling were used to estimate domain-level VABS trajectories, followed by latent class growth analysis to identify trajectory subgroups. Child characteristics at diagnosis, family demographics, and participation outcomes at adolescence were compared across subgroups. Results: Piecewise latent growth models best described VABS trajectories with two turning points identified at around ages 5-6 and 9-10, respectively reflecting transitions into school age and early adolescence. We parsed four VABS trajectory subgroups that vary by level of functioning and change rate for certain domains and periods. Around 16% of the sample exhibited overall adequate functioning (standard score >85) with notable early growth and social adaptation during adolescence. About 21% showed low adaptive functioning (standard score ≤70), with decreasing slopes by age 6 followed by improvements in communication and daily-living skills by age 10. The other two subgroups (63% in total) were characterized by adaptive functioning between low and adequate levels, with relatively stable trajectories entering school age. These subgroups differed most in their cognitive ability at diagnosis, household income, and social participation in adolescence. Conclusions: We identified key individual and family characteristics and time windows associated with distinct adaptive functioning trajectories, which have important implications for providing timely and tailored supports to Autistic people across developmental stages.

10.
BMC Pregnancy Childbirth ; 24(1): 405, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38831257

BACKGROUND: Perineal massage, as a preventive intervention, has been shown to reduce the risk of perineal injuries and may have a positive impact on pelvic floor function in the early postpartum period. However, there is still debate concerning the best period to apply perineal massage, which is either antenatal or in the second stage of labor, as well as its safety and effectiveness. Meta-analysis was used to evaluate the effect of implementing perineal massage in antenatal versus the second stage of labor on the prevention of perineal injuries during labor and early postpartum pelvic floor function in primiparous women. METHODS: We searched nine different electronic databases from inception to April 16, 2024. The randomized controlled trials (RCTs) we included assessed the effects of antenatal and second-stage labor perineal massage in primiparous women. All data were analyzed with Revman 5.3, Stata Statistical Software, and Risk of Bias 2 was used to assess the risk of bias. Subgroup analyses were performed based on the different periods of perineal massage. The primary outcomes were the incidence of perineal integrity and perineal injury. Secondary outcomes were perineal pain, duration of the second stage of labor, postpartum hemorrhage, urinary incontinence, fecal incontinence, and flatus incontinence. RESULTS: This review comprised a total of 10 studies that covered 1057 primigravid women. The results of the analysis showed that perineal massage during the second stage of labor reduced the perineal pain of primigravid women in the immediate postpartum period compared to the antenatal period, with a statistical value of (MD = -2.29, 95% CI [-2.53, -2.05], P < 0.001). Additionally, only the antenatal stage reported that perineal massage reduced fecal incontinence (P = 0.04) and flatus incontinence (P = 0.01) in primiparous women at three months postpartum, but had no significant effect on urinary incontinence in primiparous women at three months postpartum (P = 0.80). CONCLUSIONS: Reducing perineal injuries in primiparous women can be achieved by providing perineal massage both antenatally and during the second stage of labor. Pelvic floor function is improved in the postnatal phase by perineal massage during the antenatal stage. TRIAL REGISTRATION: CRD42023415996 (PROSPERO).


Labor Stage, Second , Massage , Parity , Pelvic Floor , Perineum , Postpartum Period , Humans , Female , Perineum/injuries , Massage/methods , Pregnancy , Pelvic Floor/physiology , Pelvic Floor/injuries , Labor Stage, Second/physiology , Obstetric Labor Complications/prevention & control , Randomized Controlled Trials as Topic , Fecal Incontinence/prevention & control , Fecal Incontinence/etiology
11.
J Gen Psychol ; : 1-35, 2024 May 09.
Article En | MEDLINE | ID: mdl-38722698

Extant research has demonstrated the positive roles of workplace friendships and has recently found the negative effect or the double-edged effect on employees and organizations. Unfortunately, little is known about the boundary condition of the double-edged effects of workplace friendships and the elaborated understanding of the mechanism of positive and negative effects of workplace friendship simultaneously. Our purpose is to reveal that workplace friendship is a mixed blessing by investigating when and how workplace friendships are likely to promote versus inhibit voice behavior. We propose that the double-edged effect of workplace friendship hinges on the competitive climate. Specifically, when the competitive climate is low, workplace friendship is positively related to employees' psychological safety, promoting voice behavior. In contrast, workplace friendship is positively related to employees' face concern, inhibiting voice behavior when the competitive climate is high. Our hypotheses were supported across the three waves of surveys and experimental studies. Taken together, our findings reveal the perils and benefits of workplace friendship and the importance of boundary conditions resulting in employees' differential psychological processes in friendship interaction.

13.
Mol Neurobiol ; 2024 May 04.
Article En | MEDLINE | ID: mdl-38703342

Numerous natural antioxidants have been developed into agents for neurodegenerative diseases (NDs) treatment. Rosmarinic acid (RA), an excellent antioxidant, exhibits neuroprotective activity, but its anti-NDs efficacy remains puzzling. Here, Caenorhabditis elegans models were employed to systematically reveal RA-mediated mechanisms in delaying NDs from diverse facets, including oxidative stress, the homeostasis of neural and protein, and mitochondrial disorders. Firstly, RA significantly inhibited reactive oxygen species accumulation, reduced peroxide malonaldehyde production, and strengthened the antioxidant defense system via increasing superoxide dismutase activity. Besides, RA reduced neuronal loss and ameliorated polyglutamine and ɑ-synuclein-mediated dyskinesia in NDs models. Further, in combination with the data and molecular docking results, RA may bind specifically to Huntington protein and ɑ-synuclein to prevent toxic protein aggregation and thus enhance proteostasis. Finally, RA ameliorated mitochondrial dysfunction including increasing adenosine triphosphate and mitochondrial membrane potential levels and rescuing mitochondrial membrane proteins' expressions and mitochondrial structural abnormalities via regulating mitochondrial dynamics genes and improving the mitochondrial kinetic homeostasis. Thus, this study systematically revealed the RA-mediated neuroprotective mechanism and promoted RA as a promising nutritional intervention strategy to prevent NDs.

14.
Sleep Med ; 119: 214-221, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38703605

BACKGROUND: Napping is garnering increased attention as a strategy for adults to sustain alertness and alleviate stress in contemporary society. The nuances of napping habits are emerging as an independent factor influencing the extent of individual benefits. This study aimed to demonstrate the long-term benefits of napping and explore the impact of napping habits on individual alertness, as well as whether this effect was correlated with cortisol levels. METHODS: The study involved 80 healthy adults categorized into two groups based on self-reported napping habits: habitual nappers (n = 49) and non-habitual nappers (n = 31). Karolinska Sleepiness Scale (KSS), psychomotor vigilance task (PVT), and saliva collection were performed every 30 min within 90 min in the absence of napping during the afternoon dip. The measurements were analyzed using repeated measures ANOVA and Pearson correlation analyses. RESULTS: There was an interaction between groups and time in reaction speed and lapse number of PVT and cortisol (all p < 0.05). Post hoc analysis found that habitual nappers maintained higher objective alertness and experienced more significant increases in cortisol over time (all p < 0.05). The cortisol levels at sleepiness time were negatively associated with the slowest 10 % reaction speed of PVT in non-habitual nappers (r = -0.409, p = 0.022). CONCLUSION: Under the premise of mitigating the impacts of acute nap deprivation on sleep homeostasis and rhythm, napping habits emerge as a potential factor influencing the ability of individuals to sustain heightened alertness.

15.
Front Psychiatry ; 15: 1387507, 2024.
Article En | MEDLINE | ID: mdl-38707622

Background: The claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied. Methods: We evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats. Results: We found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test. Conclusion: These data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions.

16.
Polymers (Basel) ; 16(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38732721

In this study, an array of environmentally friendly and heavy-duty anticorrosion composite coatings were prepared. The synthesis involved amine-capped aniline trimer (ACAT) produced by an oxidative coupling reaction and graphene oxide (GO) prepared based on Hummer's method, and later, the waterborne epoxy thermoset composite (WETC) coatings were prepared by thermal ring-opening polymerization of EP 147w, a commercial waterborne epoxy resin, in the presence of ACAT and/or GO with zinc dust (ZD). A synergistic effect was observed by replacing a significant amount of the ZD loading in the WETC by simultaneously incorporating a small amount of ACAT and GO. The electrochemical corrosion measurements of the as-prepared WETC coatings indicated that incorporating 5% w/w ACAT or 0.5% w/w GO separately replaced approximately 30% w/w or 15% w/w of the ZD, respectively. Moreover, the WETC coatings containing 5% w/w ACAT and 0.5% w/w GO simultaneously were found to replace 45% w/w of the ZD. A salt spray test based on ASTM B-117 also showed a consistent trend with the electrochemical results. Incorporating small amounts of ACAT and GO in WETC coatings instead of ZD not only maintains the anticorrosion performance but also enhances adhesion and abrasion resistance, as demonstrated by the adhesion and abrasion tests.

17.
Front Public Health ; 12: 1377861, 2024.
Article En | MEDLINE | ID: mdl-38751577

Background: Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV71) and coxsackievirus A16 (CA16) have been identified as the predominant pathogens for several decades. In recent years, coxsackievirus A6 (CA6) and coxsackievirus A10 (CA10) have played increasingly important roles in a series of HFMD outbreaks. We performed a retrospective analysis of the epidemiology of HFMD and the spectrum of different viral serotypes, to elucidate the genetic and phylogenetic characteristics of the main serotypes in the Jiashan area during 2016 to 2022. Methods: Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD in Jiashan during 2016 to 2022 based on surveillance data. Molecular diagnostic methods were performed to identify the viral serotypes and etiological characteristics of HFMD. Phylogenetic analyses was based on VP1 region of CA16 and CA6. Results: The average annual incidence rate of HFMD fluctuated from 2016 to 2022. Children aged 1-5 years accounted for 81.65% of cases and boys were more frequently affected than girls. Except when HFMD was affected by the COVID-19 epidemic in 2020 and 2022, epidemics usually peak in June to July, followed by a small secondary peak from October to December and a decline in February. Urban areas had a high average incidence and rural areas had the lowest. Among 560 sample collected in Jiashan, 472 (84.29%) were positive for enterovirus. The most frequently identified serotypes were CA6 (296, 52.86%), CA16 (102, 18.21%), EV71 (16, 2.86%), CA10 (14, 2.50%) and other enteroviruses (44, 7.86%). There were 71 and 142 VP1 sequences from CA16 and CA6, respectively. Substitution of N218D, A220L and V251I was detected in CA16 and may have been related to viral infectivity. Phylogenetic analysis showed that CA16 could be assigned to two genogroups, B1a and B1b, while all the CA6 sequences belonged to the D3a genogroup. Conclusion: CA6 and CA16 were the two major serotypes of enteroviruses circulating in the Jiashan area during 2016 to 2022. Continuous and comprehensive surveillance for HFMD is needed to better understand and evaluate the prevalence and evolution of the associated pathogens.


Hand, Foot and Mouth Disease , Phylogeny , Hand, Foot and Mouth Disease/epidemiology , Hand, Foot and Mouth Disease/virology , Humans , China/epidemiology , Male , Female , Child, Preschool , Infant , Retrospective Studies , Child , Incidence , Enterovirus/genetics , Enterovirus/isolation & purification , Enterovirus/classification , Serogroup , Disease Outbreaks/statistics & numerical data , Adolescent
19.
Med Phys ; 2024 May 20.
Article En | MEDLINE | ID: mdl-38767532

BACKGROUND: Bladder prolapse is a common clinical disorder of pelvic floor dysfunction in women, and early diagnosis and treatment can help them recover. Pelvic magnetic resonance imaging (MRI) is one of the most important methods used by physicians to diagnose bladder prolapse; however, it is highly subjective and largely dependent on the clinical experience of physicians. The application of computer-aided diagnostic techniques to achieve a graded diagnosis of bladder prolapse can help improve its accuracy and shorten the learning curve. PURPOSE: The purpose of this study is to combine convolutional neural network (CNN) and vision transformer (ViT) for grading bladder prolapse in place of traditional neural networks, and to incorporate attention mechanisms into mobile vision transformer (MobileViT) for assisting in the grading of bladder prolapse. METHODS: This study focuses on the grading of bladder prolapse in pelvic organs using a combination of a CNN and a ViT. First, this study used MobileNetV2 to extract the local features of the images. Next, a ViT was used to extract the global features by modeling the non-local dependencies at a distance. Finally, a channel attention module (i.e., squeeze-and-excitation network) was used to improve the feature extraction network and enhance its feature representation capability. The final grading of the degree of bladder prolapse was thus achieved. RESULTS: Using pelvic MRI images provided by a Huzhou Maternal and Child Health Care Hospital, this study used the proposed method to grade patients with bladder prolapse. The accuracy, Kappa value, sensitivity, specificity, precision, and area under the curve of our method were 86.34%, 78.27%, 83.75%, 95.43%, 85.70%, and 95.05%, respectively. In comparison with other CNN models, the proposed method performed better. CONCLUSIONS: Thus, the model based on attention mechanisms exhibits better classification performance than existing methods for grading bladder prolapse in pelvic organs, and it can effectively assist physicians in achieving a more accurate bladder prolapse diagnosis.

20.
Commun Biol ; 7(1): 594, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760406

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2-/-/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD-induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3ß pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.


Adenosine Deaminase , Diet, High-Fat , Mice, Knockout , Non-alcoholic Fatty Liver Disease , RNA-Binding Proteins , Signal Transduction , Animals , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , Adenosine Deaminase/deficiency , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Mice , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/etiology , Diet, High-Fat/adverse effects , Male , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Insulin Resistance , Mice, Obese , Obesity/metabolism , Obesity/genetics , Mice, Inbred C57BL , Liver/metabolism
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