RESUMO
Post-traumatic stress disorder (PTSD), a psychological condition triggered by exposure to extreme or chronic stressful events, exhibits a sex bias in incidence and clinical manifestations. Emerging research implicates the gut microbiome in the pathogenesis of PTSD and its roles in stress susceptibility. However, it is unclear whether differential gut microbiota contribute to PTSD susceptibility in male and female rats. Here, we utilized the single prolonged stress animal model and employed unsupervised machine learning to classify stressed animals into stress-susceptible subgroups and stress-resilient subgroups. Subsequently, using 16S V3-V4 rDNA sequencing, we investigated the differential gut microbiota alterations between susceptible and resilient individuals in male and female rats. Our findings revealed distinct changes in gut microbiota composition between the sexes at different taxonomic levels. Furthermore, the abundance of Parabacteroides was lower in rats that underwent SPS modeling compared to the control group. In addition, the abundance of Tenericutes in the stress-susceptible subgroup was higher than that in the control group and stress-resilient subgroup, suggesting that Tenericutes may be able to characterize stress susceptibility. What is particularly interesting here is that Cyanobacteria may be particularly associated with anti-anxiety effects in male rats. This study underscores sex-specific variations in gut microbiota composition in response to stress and sex differences should be taken into account when using macrobiotics for neuropsychiatric treatment, highlighting potential targets for PTSD therapeutic interventions.
Assuntos
Microbioma Gastrointestinal , Resiliência Psicológica , Feminino , Masculino , Animais , Ratos , Caracteres Sexuais , Bacteroidetes , Modelos AnimaisRESUMO
Achieving highly efficient broadband absorption is an important research area in nanophotonics. In this paper, a novel method is proposed to design broadband near-perfect absorbers, consisting of a four-layer hemispherical concentric nanoshell array. The proposed nanostructure supports absorptivity exceeding 95% in the entire visible region, and the absorption bandwidth is determined by the interaction or 'hybridization' of the plasmons of the inner and outer metal-based nanoshells. Moreover, the designed absorber has wide-angle capability and is insensitive to polarization. The simple structure, as well as the stable absorption properties, suggests that such core-shell nanostructures can serve as a potential candidate for many applications such as solar energy harvesting, photo-detection, and emissivity control.
RESUMO
BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.
Assuntos
Anticorpos Antivirais , COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Centros de Atenção Terciária , Humanos , Estudos Transversais , Taiwan/epidemiologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Pessoal de Saúde/estatística & dados numéricos , Anticorpos Antivirais/sangue , Masculino , Feminino , Adulto , Estudos Soroepidemiológicos , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagemAssuntos
Deficiência do Fator VII , Fator VII , Humanos , Deficiência do Fator VII/genética , Taiwan , Masculino , Feminino , Fator VII/genética , Adulto , Pessoa de Meia-Idade , Mutação , Adolescente , Criança , Pré-Escolar , Adulto JovemRESUMO
Depression currently ranks as the fourth leading cause of disability globally, affecting approximately 20% of the world's population. we established a chronic restraint stress (CRS) induced depression model in mice and employed fluoxetine as a reference drug. We assessed the therapeutic potential of saffron essential oil (SEO) and elucidated its underlying mechanisms through behavioral indices and NMR-based metabolomic analysis. The findings indicate that SEO ameliorates behavioral symptoms of depression, such as the number of entries into the central area, fecal count, latency to immobility, and duration of immobility in both the Tail Suspension Test (TST) and the Forced Swim Test (FST), along with correcting the dysregulation of 5-serotonin. Metabolomic investigations identified sixteen potential biomarkers across the liver, spleen, and kidneys. SEO notably modulated nine of these biomarkers: dimethylglycine, glycerol, adenosine, ß-glucose, α-glucose, uridine, mannose, sarcosine, and aspartate, with glycerol emerging as a common biomarker in both the liver and spleen. Pathway analysis suggests that these biomarkers participate in glycolysis, glycine serine threonine metabolism, and energy metabolism, potentially implicating a role in neural regulation. In summary, SEO effectively mitigates depressive-like behaviors in CRS mice, predominantly via modulation of glycolysis, amino acid metabolism, and energy metabolism, and potentially exerts antidepressant effects through neural regulation. Our study offers insights into small molecule metabolite alterations in CRS mice through a metabolomics lens, providing evidence for the antidepressant potential of plant essential oils and contributing to our understanding of the mechanisms of traditional Chinese medicine in treating depression.
Assuntos
Antidepressivos , Biomarcadores , Crocus , Depressão , Espectroscopia de Ressonância Magnética , Metabolômica , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Metabolômica/métodos , Depressão/tratamento farmacológico , Depressão/metabolismo , Camundongos , Crocus/química , Masculino , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismoRESUMO
A novel composite hydrogel was synthesized via Schiff base reaction between chitosan and di-functional poly(ethylene glycol) (DF-PEG), incorporating glucose oxidase (GOx) and cobalt metal-organic frameworks (Co-MOF). The resulting CS/PEG/GOx@Co-MOF composite hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDS). The results confirmed successful integration and uniform distribution of Co-MOF within the hydrogel matrix. Functionally, the hydrogel exploits the catalytic decomposition of glucose by GOx to generate gluconic acid and hydrogen peroxide (H2O2), while Co-MOF gradually releases metal ions and protects GOx. This synergy enhanced the antibacterial activity of the composite hydrogel against both Gram-positive (S. aureus) and Gram-negative bacteria (E. coli), outperforming conventional chitosan-based hydrogels. The potential of the composite hydrogel in treating wound infections was evaluated through antibacterial and wound healing experiments. Overall, CS/PEG/GOx@Co-MOF hydrogel holds great promise for the treatment of wound infections, paving the way for further research and potential clinical applications.
Assuntos
Antibacterianos , Quitosana , Escherichia coli , Hidrogéis , Estruturas Metalorgânicas , Staphylococcus aureus , Cicatrização , Quitosana/química , Quitosana/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Glucose Oxidase/química , Animais , Cobalto/química , Polietilenoglicóis/química , Testes de Sensibilidade MicrobianaRESUMO
With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.
RESUMO
Minimally invasive puncture combined with urokinase is widely used in the treatment of hypertensive intracerebral hemorrhage (HICH). However, the appropriate frequency of urokinase following minimally invasive puncture in patients is still unclear. In total, 55 patients were enrolled in this study. According to the frequency of urokinase (10.0 â× â104 units) administration, 30 patients received urokinase at Q4h, while the other 25 patients received urokinase at Q8h. In the univariate analysis, preoperative GCS (p â= â0.0002), postoperative GCS (p â= â0.0007), the volume of residual hematoma (p â= â0.0179), and the frequency of urokinase (p â= â0.0110) were associated with unfavorable outcomes in patients with HICH in the basal ganglia. The multivariate analysis revealed that the frequency of urokinase was independently associated with unfavorable outcomes in patients with HICH in the basal ganglia (p â= â0.038, 1.109-35.380). The drainage time was significantly shorter in the Q4h group (14.17 â± â0.86 âh) than in the Q8h group (27.36 â± â1.39 âh) (p â< â0.0001). The GOS (4.37 â± â0.18), BI (75.52 â± â2.39), and mRS (1.67 â± â0.24) in the Q4h group were significantly ameliorated compared to those in the Q8h group (GOS 3.56 â± â0.18, BI 64.13 â± â2.22, and mRS 2.64 â± â0.28, respectively) (p â= â0.0004, p â= â0.0002, and p â= â0.0018) at 3 months of follow-up. Thus, minimally invasive puncture combined with urokinase is safe and efficient. Increasing the frequency of urokinase administration can produce faster and better postoperative recovery for patients with HICH in the basal ganglia.
Assuntos
Punções , Ativador de Plasminogênio Tipo Uroquinase , Humanos , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos , DrenagemRESUMO
Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.
RESUMO
We presented the construction of the ring-in-ring and Russian doll complexes on the basis of triptycene-derived carbon nanoring (TP-[12]CPP), which not only acts as a host for pillar[5]arene (P5A) but also serves as an energy donor for building Förster resonance energy transfer (FRET) systems. We also demonstrated that their hierarchical assembly processes could be efficiently monitored in real time using FRET. NMR, UV-vis and fluorescence, and mass spectroscopy analyses confirmed the successful encapsulation of the guests P5A/P5A-An by TP-[12]CPP, facilitated by C-H···π and ···π interactions, resulting in the formation of a distinct ring-in-ring complex with a binding constant of Ka = 2.23 × 104 M-1. The encapsulated P5A/P5A-An can further reverse its role to be a host for binding energy acceptors to form Russian doll complexes, as evidenced by the occurrence of FRET and mass spectroscopy analyses. The apparent binding constant of the Russian doll complexes was up to 3.6 × 104 M-1, thereby suggesting an enhanced synergistic effect. Importantly, the Russian doll complexes exhibited both intriguing one-step and sequential FRET dependent on the subcomponent P5A/P5A-An during hierarchical assembly, reminiscent of the structure and energy transfer of the light-harvesting system presented in purple bacteria.
RESUMO
Highly organized π-aggregate architectures can strongly affect electronic couplings, leading to important photophysical behaviors. With the escalating interest in two-dimensional (2D) materials attributed to their exceptional electronic and optical characteristics, there is growing anticipation that 2D radial-π-stacks built upon radial π-conjugation nanorings, incorporating intra- and inter-ring electronic couplings within the confines of a 2D plane, will exhibit superior topological attributes and distinct properties. Despite their immense potential, the design and synthesis of 2D π-stacks have proven to be a formidable challenge due to the insufficient π-π interactions necessary for stable stacking. In this study, we present the successful preparation of single-layer 2D radial-π-stacks in a solution. Pillar-shaped radially π-conjugated [4]cyclo-naphthodithiophene diimide ([4]C-NDTIs) molecules were tetragonally arranged via in-plane intermolecular π-π interactions. These 2D π-stacks have a unique topology that differs from that of conventional 1D π-stacks and exhibit notable properties, such as acting as a 2D template capable of absorbing C60 guest molecules and facilitating the formation of 2D radial-π-stacks comprising [4]C-NDTI-C60 complexes, rapid exciton delocalization across the 2D plane, and efficient excitation energy funneling towards a trap.
RESUMO
Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.
RESUMO
Treatment of multiple bacterial infected wounds by eliminating bacteria and promoting tissue regeneration remains a clinical challenge. Herein, dual-network hydrogels (CS-GA/A-ß-CD) with snap-structure were designed to achieve curcumin immobilization, using gallic acid-grafted chitosan (CS-GA) and aldehyde-ß-cyclodextrin (A-ß-CD) crosslinked. A-ß-CD were able to achieve rapid dissolution (≥222.35 mg/mL H2O), and helped CS-GA/A-ß-CD achieve rapid gelation (≤66.23 s). By adjusting the ratio of aldehyde groups of A-ß-CD, mechanical properties and drug release can be controlled. CS-GA/A-ß-CD/Cur exhibited excellent antimicrobial properties against S. aureus, E. coli, and P. aeruginosa. In vivo experiments demonstrated that CS-GA/A-ß-CD/Cur achieved acute bacterial infection wound healing after 20th days, proving its great potential for wound dressing.
RESUMO
The development of biodegradable antimicrobial bioplastics for food packaging holds great promise for solving the pollution and safety problems caused by petrochemical plastics and spoiled food. Herein, a natural active-bioplastic synthesized from citrus peel biomass is presented for perishable fruit preservation. These plastics are characterized by the nanoscale entanglement and recombinant hydrogen bonding between the endogenous pectin, polyphenols and cellulose micro/nanofibrils. They have attractive flexibility, tensile strength, gas barrier properties and antimicrobial activities, and can effectively extend the shelf life of perishable fruits such as banana and mango when used as food packaging. Cytotoxicity, degradability tests and life-cycle assessment show that these plastics had excellent nontoxicity and can be safely degraded or easily recycled. This work demonstrates a sustainable strategy for converting peel waste into eco-friendly bioplastics, providing a unique and novel insight into radically reducing the pollution and life-health threats posed by petrochemical plastics and spoiled food.
Assuntos
Anti-Infecciosos , Frutas , Frutas/química , Anti-Infecciosos/farmacologia , Plásticos Biodegradáveis/farmacologia , Plásticos Biodegradáveis/química , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Citrus/química , Reciclagem , Plásticos/química , Plásticos/farmacologia , Resistência à Tração , Polifenóis/farmacologia , Polifenóis/química , Biodegradação AmbientalRESUMO
Background: Osteoporotic vertebral compression fractures (OVCFs) are the most common type of fragility fracture. Distinguishing between OVCFs and other types of vertebra diseases, such as old fractures (OFs), Schmorl's node (SN), Kummell's disease (KD), and previous surgery (PS), is critical for subsequent surgery and treatment. Combining with advanced deep learning (DL) technologies, this study plans to develop a DL-driven diagnostic system for diagnosing multi-type vertebra diseases. Methods: We established a large-scale dataset based on the computed tomography (CT) images of 1,051 patients with OVCFs from Luhe Hospital and used data of 46 patients from Xuanwu Hospital as alternative hospital validation dataset. Each patient underwent one examination. The dataset contained 11,417 CT slices and 19,718 manually annotated vertebrae with diseases. A two-stage DL-based system was developed to diagnose five vertebra diseases. The proposed system consisted of a vertebra detection module (VDModule) and a vertebra classification module (VCModule). Results: The training and testing dataset for the VDModule consisted of 9,135 and 3,212 vertebrae, respectively. The VDModule using the ResNet18-based Faster region-based convolutional neural network (R-CNN) model achieved an area under the curve (AUC), false-positive (FP) rate, and false-negative (FN) rate of 0.982, 1.52%, and 1.33%, respectively, in the testing dataset. The training dataset for VCModule consisted of 14,584 and 47,604 diseased and normal vertebrae, respectively. The testing dataset consisted of 4,489 and 15,122 diseased and normal vertebrae, respectively. The ResNet50-based VCModule achieved an average sensitivity and specificity of 0.919 and 0.995, respectively, in diagnosing four kinds of vertebra diseases except for SN in the testing dataset. In the alternative hospital validation dataset, the ResNet50-based VCModule achieved an average sensitivity and specificity of 0.891 and 0.989, respectively, in diagnosing four kinds of vertebra diseases except for SN. Conclusions: Our proposed DL system can accurately diagnose four vertebra diseases and has strong potential to facilitate the accurate and rapid diagnosis of vertebral diseases.
RESUMO
BACKGROUND: A growing body of research supports dispositional mindfulness as important in influencing physical and mental health as well as physical activities in patients with chronic illnesses. Knee osteoarthritis (OA), which often causes health problems, is one of the most common chronic illnesses, but less is known about dispositional mindfulness in relation to this condition. OBJECTIVE: To explore possible associations between dispositional mindfulness and physical and mental health as well as physical activity in knee OA patients. METHODS: For this cross-sectional study, we recruited a purposive sample of orthopedic clinic patients in hospitals in Southern Taiwan. Instruments included the Mindful Attention Awareness Scale (MAAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Health-related characteristics were also measured. Demographic statistics, bivariate correlations, and multiple linear regression informed our exploration of potentially related factors for dispositional mindfulness. RESULTS: Participants with knee OA (N = 250) were mostly elderly (88%), female (70.5%), and married (84%). Marital status, perceived health status, depression, and physical activity were associated with dispositional mindfulness. Better perceived health, lower depression, and greater physical activity were significantly associated with greater dispositional mindfulness. However, the severity of symptoms, fear of falling, and exercise self-efficacy did not reach statistical significance in relation to dispositional mindfulness. CONCLUSION: Greater emphasis should be placed on the cultivation of mindfulness to enhance individuals' perceived health, decrease their depressive mood, and promote their engagement in physical activity, which could indirectly alleviate their experience of pain and improve their physical function, yielding better quality of life and well-being. Future research should focus on interventions to apply dispositional mindfulness in order to determine whether dispositional mindfulness can effectively improve physical and mental health as well as physical activity in those with knee OA.
Assuntos
Atenção Plena , Osteoartrite do Joelho , Humanos , Feminino , Idoso , Estudos Transversais , Qualidade de Vida/psicologia , Acidentes por Quedas , Medo , Doença CrônicaRESUMO
Protein tyrosine phosphatase 1B (PTP1B) and TC-PTP can function in a coordinated manner to regulate diverse biological processes including insulin and leptin signaling, T-cell activation, and tumor antigen presentation, which makes them potential targets for several therapeutic applications. We have previously demonstrated that the lipidated BimBH3 peptide analogues were a new class of promising PTP1B inhibitors with once-weekly antidiabetic potency. Herein, we chemically synthesized two series of BimBH3 analogues via site-specific modification and studied their structure-activity relationship. The screened analogues S2, S6, A2-14, A2-17, A2-20, and A2-21 exhibited an improved PTP1B/TC-PTP dual inhibitory activity and achieved good stability in the plasma of mice and dogs, which indicated long-acting potential. In mouse models of type 2 diabetes mellitus (T2DM), the selected analogues S6, S7, A2-20, and A2-21 with an excellent target activity and plasma stability generated once-weekly therapeutic potency for T2DM at lower dosage (0.5 µmol/kg). In addition, evidence was provided to confirm the cell permeability and targeted enrichment of the BimBH3 analogues. In summary, we report here that site-specific modification and long fatty acid conjugation afforded cell-permeable peptidomimetic analogues of BimBH3 with enhanced stability, in vivo activity, and long-acting pharmacokinetic profile. Our findings could guide the further optimization of BimBH3 analogues and provide a proof-of-concept for PTP1B/TC-PTP targeting as a new therapeutic approach for T2DM, which may facilitate the discovery and development of alternative once-weekly anti-T2DM drug candidates.
RESUMO
Trafficking of α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs), mediated by AMPAR interacting proteins, enabled neurons to maintain tuning capabilities at rest or active state. α/ß-Hydrolase domain-containing 6 (ABHD6), an endocannabinoid hydrolase, was an AMPAR auxiliary subunit found to negatively regulate the surface delivery of AMPARs. While ABHD6 was found to prevent AMPAR tetramerization in endoplasmic reticulum, ABHD6 was also reported to localize at postsynaptic site. Yet, the role of ABHD6 interacting with AMPAR at postsynaptic site, and the physiological significance of ABHD6 regulating AMPAR trafficking remains elusive. Here, we generated the ABHD6 knockout (ABHD6KO) mice and found that deletion of ABHD6 selectively enhanced AMPAR-mediated basal synaptic responses and the surface expression of postsynaptic AMPARs. Furthermore, we found that loss of ABHD6 impaired hippocampal long-term depression (LTD) and synaptic downscaling in hippocampal synapses. AMPAR internalization assays revealed that ABHD6 was essential for neuronal activity-dependent endocytosis of surface AMPARs, which is independent of ABHD6's hydrolase activity. The defects of AMPAR endocytosis and LTD are expressed as deficits in learning flexibility in ABHD6KO mice. Collectively, we demonstrated that ABHD6 is an endocytic accessory protein promoting AMPAR endocytosis, thereby contributes to the formation of LTD, synaptic downscaling and reversal learning.
Assuntos
Hidrolases , Receptores de AMPA , Camundongos , Animais , Receptores de AMPA/metabolismo , Hidrolases/metabolismo , Plasticidade Neuronal/fisiologia , Aprendizagem , Sinapses/metabolismo , Endocitose , Hipocampo/metabolismo , Monoacilglicerol Lipases/metabolismoRESUMO
BACKGROUND: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. METHODS: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. RESULTS: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (ß ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. CONCLUSION: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.
RESUMO
Clarifying the accumulation pattern of soil microbial residue carbon and its contribution to soil organic carbon (SOC) across stand age is helpful to understand the mechanism underlying soil carbon cycling. In this study, we analyzed the differences of amino sugar content, physicochemical properties and microbial composition in surface soil (0-10 cm) in young (6 a), middle-aged (13 a), near-mature (29 a), mature (38 a) and over-mature (57 a) Pinus massoniana plantations of subtropical China, quantified the microbial residue carbon content and its contribution to SOC, and discussed the mechanism. The results showed that SOC, total nitrogen, amorphous iron oxide and leucine aminopeptidase contents in the middle-aged plantation were significantly lower than those in the mature plantation. Soil pH and fungal/bacteria in young plantation were significantly higher than those in other age groups. Across the stand age gradient, the ranges of microbial, fungal and bacterial residue carbon were 7.52-14.63, 4.03-8.00 and 3.48-6.63 g·kg-1, respectively. The contents of all the residue carbon were significantly higher in the mature plantation than that of the middle-aged plantation, which were positively affected by soil total nitrogen content. The contribution of microbial, fungal, and bacterial residue carbon to SOC was 59.7%-72.3%, 33.4%-45.6%, and 24.3%-30.8%, respectively. The contribution of fungal residue carbon to SOC in young plantation was significantly higher than that in other age groups, and the contribution of bacterial residue carbon to SOC in middle-aged plantation was significantly higher than that in young and near-mature plantations, both of which were affected by soil inorganic nitrogen. Fungal residue carbon content was 1.2-1.7 times as that of bacterial residue carbon content, and dominated for the accumulation of microbial residue carbon. Results of the partial least squares model showed that stand age, soil environmental factors (such as leucine aminopeptidase, amorphous iron oxide, pH, and total nitrogen), bacterial residue carbon, fungal residue carbon and the contribution of bacterial residue carbon to SOC had total effects on the contribution of fungal residue carbon to SOC (-0.37, -1.16, 0.90, 1.09, and 0.83, respectively). In conclusion, stand age promoted the accumulation of microbial residue carbon but did not increase its contribution to SOC.