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BACKGROUND: The hypothalamus is a key brain structure involved in the pathogenesis of depression, and its abnormal activity is considered an important pathological mechanism for the formation of depression. The presence of abnormalities in the white matter integrity of hypothalamic subregions in mild cognitive impairment with depressive symptoms (D-MCI) remains unknown. METHODS: In this study, we used diffusion tensor imaging (DTI) to explore the white matter integrity of hypothalamic subregions in D-MCI. On a 3 T magnetic resonance imaging scanner, we collected DTI data from 63 subjects. The subjects included 20 healthy controls (HC), 23 MCI patients without depression (nD-MCI), and 20 patients with D-MCI. The differences in DTI metrics of hypothalamic subregions of the three groups were compared using analysis of variance and post hoc t-tests. We looked at the relationship between clinical variables and DTI metrics in hypothalamus subregions using Pearson correlation analysis. RESULTS: Compared with nD-MCI and HC groups, D-MCI group showed increased fractional anisotropy (FA) in anterior-inferior hypothalamus. There was a weak negative correlation between FA values in the anterior-inferior hypothalamus and depression scores in D-MCI patients. CONCLUSIONS: Our findings suggest that depressive symptoms in MCI patients are associated with abnormal white matter integrity in the anterior-inferior hypothalamus.
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Disfunción Cognitiva , Depresión , Imagen de Difusión Tensora , Hipotálamo , Sustancia Blanca , Humanos , Masculino , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Femenino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Anciano , Depresión/diagnóstico por imagen , Depresión/patología , Hipotálamo/diagnóstico por imagen , Hipotálamo/patología , Persona de Mediana Edad , AnisotropíaRESUMEN
Psychiatric comorbidity is common in symptom-based diagnoses like autism spectrum disorder (ASD), attention/deficit hyper-activity disorder (ADHD), and obsessive-compulsive disorder (OCD). However, these co-occurring symptoms mediated by shared and/or distinct neural mechanisms are difficult to profile at the individual level. Capitalizing on unsupervised machine learning with a hierarchical Bayesian framework, we derived latent disease factors from resting-state functional connectivity data in a hybrid cohort of ASD and ADHD and delineated individual associations with dimensional symptoms based on canonical correlation analysis. Models based on the same factors generalized to previously unseen individuals in a subclinical cohort and one local OCD database with a subset of patients undergoing neurosurgical intervention. Four factors, identified as variably co-expressed in each patient, were significantly correlated with distinct symptom domains (r = -0.26-0.53, P < 0.05): behavioral regulation (Factor-1), communication (Factor-2), anxiety (Factor-3), adaptive behaviors (Factor-4). Moreover, we demonstrated Factor-1 expressed in patients with OCD and Factor-3 expressed in participants with anxiety, at the degree to which factor expression was significantly predictive of individual symptom scores (r = 0.18-0.5, P < 0.01). Importantly, peri-intervention changes in Factor-1 of OCD were associated with variable treatment outcomes (r = 0.39, P < 0.05). Our results indicate that these data-derived latent disease factors quantify individual factor expression to inform dimensional symptom and treatment outcomes across cohorts, which may promote quantitative psychiatric diagnosis and personalized intervention.
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PURPOSE: Suicide and non-suicidal self-injury (NSSI) are preventable concerns in young people. Suicidal ideation (SI), suicidal plans (SP) and suicidal attempt (SA) are closely related to death. Sleep problems are known risk factors for suicide and NSSI. This study aimed to explore the relationship between sleep, suicidality and NSSI. METHODS: Participants were 3,828 middle school and college students aged 11-23 years from urban and rural areas of Henan Province. Sleep, suicidal phenomena and NSSI were assessed by applying self-reported questionnaires. Chi-squared tests were utilized to demonstrate the demographic data and sleep variables. The correlation between sleep, suicidality and NSSI were explored by using binary logistic regression, while adjusting socio-demographic characteristics with multivariate models. RESULTS: Sleep variables except mid-sleep time were related to suicidal phenomena (P < 0.05). Greater social jet lag (SJL) [≥ 2 h (h)] was associated with increased risk of SI [Odds ratios (OR) = 1.72, 95% confidence intervals (CI):1.40-2.11], SP (OR = 2.10, 95%CI:1.59-2.79) and SA (OR = 1.50, 95%CI:1.00-2.26). Non-only child participants with SJL (≥ 2 h) had significantly increased odds of SI (OR = 1.75, 95%CI: 1.41-2.18) and SP (OR = 2.25, 95%CI: 1.66-3.05). Eveningness chronotype had the strongest correlation with SI (OR = 3.87, 95%CI:2.78-5.38), SP (OR = 4.72, 95%CI:2.97-7.50), SA (OR = 6.69, 95%CI:3.08-14.52) and NSSI (OR = 1.39, 95%CI:1.02-1.90). CONCLUSION: Overlong or short sleep duration, SJL, eveningness chronotype and other sleep abnormalities (e.g., daytime dysfunction, low sleep efficiency) were associated with a higher prevalence of SI, SP and SA. Additionally, eveningness was significantly correlated with NSSI among young people. These findings suggested the importance of assessing and intervening in sleep habits to prevent suicide and NSSI in young people.
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Metakaolin-based geopolymers have substantial potential as replacements for cement, but their relatively inferior mechanical properties restrict their application. This paper aims to enhance the mechanical properties of metakaolin-based geopolymers by incorporating appropriate amounts of calcium sources. CaCO3, Ca(OH)2, and CaSO4 are three types of calcium sources commonly found in nature and are widely present in various industrial wastes. Thus, the effects of these three calcium sources on the performance of metakaolin-based geopolymers were studied. Through the analysis of the mechanical properties, heat-release behavior during hydration, hydration products, and microstructure of geopolymers, the effectiveness of the aforementioned calcium sources in improving the performance of metakaolin-based geopolymer was evaluated, and the mechanisms of action were elucidated. The results indicate that the pozzolanic reaction between CH and MK could promote MK hydration and increase the proportion of CASH gel in the hydration products, thereby facilitating the setting of the geopolymer and enhancing its strength. CS could react with the active aluminates in MK to form ettringite, thus forming a higher early strength. CC had a lower reactivity with MK and does not improve the performance of MK-based geopolymers.
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Voltage-gated sodium (NaV) channels mediate a plethora of electrical activities. NaV channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of NaV channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying NaV channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaVEh (NaVEhΔN) results in a slow-inactivated channel, and present cryo-EM structure of NaVEhΔN in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaVEh structure, NaVEhΔN undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into NaV channel slow inactivation.
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Microscopía por Crioelectrón , Activación del Canal Iónico , Canales de Sodio Activados por Voltaje , Canales de Sodio Activados por Voltaje/metabolismo , Canales de Sodio Activados por Voltaje/química , Humanos , Animales , Células HEK293 , Modelos MolecularesRESUMEN
RNA uptake by cells is critical for RNA-mediated gene interference (RNAi) and RNA-based therapeutics. In Caenorhabditis elegans, RNAi is systemic as a result of SID-1-mediated double-stranded RNA (dsRNA) across cells. Despite the functional importance, the underlying mechanisms of dsRNA internalization by SID-1 remain elusive. Here we describe cryogenic electron microscopy structures of SID-1, SID-1-dsRNA complex and human SID-1 homologs SIDT1 and SIDT2, elucidating the structural basis of dsRNA recognition and import by SID-1. The homodimeric SID-1 homologs share conserved architecture, but only SID-1 possesses the molecular determinants within its extracellular domains for distinguishing dsRNA from single-stranded RNA and DNA. We show that the removal of the long intracellular loop between transmembrane helix 1 and 2 attenuates dsRNA uptake and systemic RNAi in vivo, suggesting a possible endocytic mechanism of SID-1-mediated dsRNA internalization. Our study provides mechanistic insights into dsRNA internalization by SID-1, which may facilitate the development of dsRNA applications based on SID-1.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Microscopía por Crioelectrón , ARN Bicatenario , ARN Bicatenario/metabolismo , ARN Bicatenario/química , Animales , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Humanos , Modelos Moleculares , Interferencia de ARN , Proteínas de la MembranaRESUMEN
Helium optically pumped sensor is widely used in the application for the detection of weak magnetic fields, and the cell is the core component of that, which needs an external excitation signal to ignite and maintain its luminosity, and its luminosity affects the sensitivity performance of the sensor. To improve the performance of the cell and reduce the power consumption of the system, which is the largest power consumption component in the sensor, this study presents the design of a driver circuit for a helium cell based on a high-voltage pulse source and high-frequency excitation source and uses a T-type impedance matching circuit to realize the efficient transmission of energy. The experimental results demonstrate that the driver circuit can effectively light up the helium cell, in which the pulse voltage of the high-voltage excitation is more than 1.0 kV, the output power of the high-frequency excitation signal is in the range of 0-6 W, and it is easy to adjust the output power of the high-frequency excitation signal to optimize the sensitivity of the sensor with an the optimal power density of 1.1 W/cm2 and a sensitivity of 29.4 pT/Hz1/2 is obtained. The driver circuit method designed in this study is also suitable for other inert gases to generate metastable atoms.
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Two new mealybug species, Paracoccusgillianwatsonae Zhang, sp. nov. and P.wui Zhang, sp. nov., collected from Jiangxi, South China, are described and illustrated based on the morphology of adult females. Paracoccusgillianwatsonae is similar to P.burnerae (Brain, 1915), but it differs in having fewer pairs of cerarii, and in lacking both ventral oral collar tubular ducts on the margins of the head and translucent pores on the hind femur. Paracoccuswui resembles P.keralae Williams, 2004 and P.neocarens (Lit, 1992), but it differs in lacking ventral oral collar tubular ducts on the margins of the head and in having multilocular disc-pores usually in double rows at the posterior edges of abdominal segments V and VI. A key to the Paracoccus species found in China is provided.
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The species of Neogreenia MacGillivray (Hemiptera: Coccomorpha: Qinococcidae) are reviewed. The genus is distributed in the Oriental and Palaearctic Regions and now contains seven species. The present study provides updated generic descriptions of all the developmental stages and a brief account of the biology and life cycle of Neogreenia. The genotype, Neogreenia zeylanica (Green, 1896), is redescribed. The following are described and illustrated for the first time: the second-instar nymph, third-instar female, and male third-instar nymph and pupa of N. zizyphi Tang; the second-instar nymph of N. lonicera Wu & Nan; and the second-instar nymph of N. sophorica Wu. Two new species are described and illustrated: Neogreenia ficus Zheng & Wu, sp. n. based on the adult female and Neogreenia tangi Zheng & Wu, sp. n. based on all female instars. These new species bring the total number of described species of Neogreenia to seven. An identification key to all the developmental stages of Neogreenia, and identification keys to species based on adult females and available nymphal instars are provided.
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Hemípteros , Femenino , Masculino , Animales , Ninfa , PupaRESUMEN
BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.
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Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Hemorragia Cerebral Intraventricular/fisiopatología , Hemorragia Cerebral Intraventricular/terapia , Hemorragia Cerebral Intraventricular/diagnóstico , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/terapia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/fisiopatología , Factores de Riesgo , Factores de Tiempo , Anciano de 80 o más Años , Evaluación de la Discapacidad , Hematoma/diagnóstico por imagen , Hematoma/diagnóstico , Curva ROCRESUMEN
BACKGROUND: This study assessed the alternations of kynurenine pathway (KP) and neopterin in type 2 diabetes mellitus (T2DM) and explored possible differential metabolites. METHODS: A fresh residual sera panel was collected from 80 healthy control (HC) individuals and 72 T2DM patients. Metabolites/ratios of interest including tryptophan (TRP), kynurenine (KYN), 5-hydroxytryptamine (5HT), kynurenic acid (KA), xanthurenic acid (XA), neopterin (NEO), KA/KYN ratio and KYN/TRP ratio were determined using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics approach, and the difference between groups was assessed. Supervised orthogonal partial least squares-discriminant analysis and differential metabolite screening with fold change (FC) were performed to identify distinct biomarkers. The diagnostic performance of KP metabolites in T2DM was evaluated. RESULTS: Significant decreases of TRP, 5HT, KA, XA, and KA/KYN and increases of KYN/TRP and NEO in T2DM compared to HC group were observed (P < 0.05). The KP metabolites panel significantly changed between T2DM and HC groups (Q2: 0.925, P < 0.005). 5HT (FC: 0.63, P < 0.01) and NEO (FC: 3.27, P < 0.01) were proven to be distinct differential metabolites. A combined testing of fasting plasma glucose and KYN/TRP showed good value in the prediction of T2DM (AUC: 0.904, 95% CI 0.843-0.947). CONCLUSIONS: The targeted LC-MS/MS metabolomics study is a powerful tool for evaluating the status of T2DM. This study facilitated the application of KP metabolomics into future clinical practice. 5HT and NEO are promising biomarkers in T2DM. KYN/TRP was highly associated with the development of T2DM and may serve as a potential treatment target.
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Diabetes Mellitus Tipo 2 , Quinurenina , Humanos , Quinurenina/metabolismo , Neopterin , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida con Espectrometría de Masas , Triptófano/metabolismo , BiomarcadoresRESUMEN
The gregarious ectoparasitic beetle Dastarcus helophoroides (Fairmaire) is considered a primary biocontrol agent for controlling several cerambycid pests in East Asian countries. A thorough study of reproductive behavior is a prerequisite for the mass production of natural insect predators. Nonetheless, little attention has been given to this ectoparasitic beetle. We performed a series of trials to assess whether the adult copulation duration, a key behavioral trait, is differentially influenced by physiological and ecological factors, including body size, mating history, kinship, sex ratio, mating sequence, feeding status, ambient temperature, photoperiod, and time of day. Additionally, the effect of the copulation duration on the reproductive output of this beetle was also investigated. The results indicated that the copulation duration varied considerably, ranging from 1.12 min to 16.40 min and lasting for an average of 9.11 ± 0.12 min. Females with longer copulations laid more eggs and had a greater proportion of eggs hatched. Medium-sized individuals copulated significantly longer than small- and large-sized individuals. The copulation durations were significantly longer when both sexes experienced an asymmetric mating history than when both sexes experienced a symmetric mating history. Inbred couples copulated significantly longer than outbred couples. In terms of the adult sex ratio, increasing the density of females (polygamous group) or males (polyandrous group) led to significantly longer copulation durations than those in the monogamous group. The copulation durations gradually decreased with increasing the mating sequence and temperature. Food-absence couples copulated significantly longer than food-presence couples. The mean copulation duration of the scotophase was significantly longer than that of the photophase. These results demonstrate that all of the analyzed factors emerge as important factors influencing the copulation duration, ultimately affecting the reproductive outputs in this ectoparasitic beetle.
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ETHNOPHARMACOLOGICAL RELEVANCE: Tea (Camellia sinensis) is a favorite drink worldwide. Tea extracts and green tea main component (-)-epigallocatechin gallate (EGCG) are recommended for various vascular diseases. Anji white tea is a very popular green tea. Its vascular effect profile, the mechanisms, and the contribution of EGCG to its integrated effect need elucidation. AIM: To characterize the vasomotion effects of Anji white tea and EGCG, and to explore possible involvement of voltage-gated Ca2+ channels (VGCCs) and voltage-gated K+ (Kv) channels in their vasomotion effects. MATERIALS AND METHODS: Anji white tea water soaking solution (AJWT) was prepared as daily tea-making process and concentrated to a concentration amounting to 200 mg/ml of dry tea leaves. The tension of rat arteries including aorta, coronary artery (RCA), cerebral basilar artery (CBA), intrarenal artery (IRA), intrapulmonary artery (IPA) and mesenteric artery (MA) was recorded with myographs. In arterial smooth muscle cells (ASMCs) freshly isolated from RCA, the levels of intracellular Ca2+ were measured with Ca2+-sensitive fluorescent probe fluo 4-AM, and Kv currents were recorded with patch clamp. The expressions of VGCCs and Kv channels were assayed with RT-qPCR and immunofluorescence staining. RESULTS: At 0.4-12.8 mg/ml of dry tea leaves, AJWT profoundly relaxed all tested arteries precontracted with various vasoconstrictors about half with a small transient potentiation on the precontractions before the relaxation. KCl-induced precontraction was less sensitive than precontractions induced by phenylephrine (PE), U46619 and serotonin (5-HT). IPA was less sensitive to the relaxation compared with other arteries. AJWT pretreatment for 1 h, 24 h and 72 h time-dependently inhibited the contractile responses of RCAs. In sharp contrast, at equivalent concentrations according to its content in AJWT, EGCG intensified the precontractions in most small arteries, except that it induced relaxation in PE-precontracted aorta and MA, U46619-precontracted aorta and CBA. EGCG pretreatment for 1 h and 24 h did not significantly affect RCA contractile responses. In RCA ASMCs, AJWT reduced, while EGCG enhanced, intracellular Ca2+ elevation induced by depolarization which activates VGCCs. Patch clamp study showed that both AJWT and EGCG reduced Kv currents. RT-qPCR and immunofluorescence staining demonstrated that both AJWT and EGCG reduced the expressions of VGCCs and Kv channels. CONCLUSION: AJWT, but not EGCG, consistently induces vasorelaxation. The vasomotion effects of either AJWT or EGCG vary with arterial beds and vasoconstrictors. Modulation of VGCCs, but not Kv channels, contributes to AJWT-induced vasorelaxation. It is suggested that Anji white tea water extract instead of EGCG may be a promising food supplement for vasospastic diseases.
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Catequina/análogos & derivados , Miocitos del Músculo Liso , Té , Ratas , Animales , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Vasodilatación , Vasos Coronarios , Arterias Mesentéricas , Vasoconstrictores/farmacología , Agua/farmacologíaRESUMEN
INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.
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The Cosmococcus species (Hemiptera: Coccomorpha: Lecanodiaspididae) found in China are reviewed. Based on morphological and molecular data, C. albizziae Borchsenius, 1960 syn. nov. and C. euphorbiae Borchsenius, 1959 syn. nov. are placed as junior synonyms of C. erythrinae Borchsenius, 1959. The wax tests of both sexes and the slide-mounted adult female of C. erythrinae Borchsenius are redescribed.
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Hemípteros , Animales , Femenino , ChinaRESUMEN
An important method that coal-fired power plants use to realise low-cost zero discharge of desulfurisation wastewater (FGD wastewater) is to utilise wet slag removal systems. However, the high Cl- content of FGD wastewater in wet slag removal systems causes environmental damage. In this study, the corrosion behaviour of the inner guide wheel material, 20CrMnTi, was studied using dynamic weight loss and electrochemical methods. X-ray diffraction, scanning electron microscopy, and energy spectroscopy were used to analyse the organisational and phase changes on the surfaces and cross sections of the samples at different Cl- concentrations. The corrosion rate increased with the Cl- concentration up to 20 g/L, but it decreased slightly when the Cl- concentration exceeded 20 g/L. In all the cases, the corrosion rate exceeded 0.8 mm/a. The corrosion product film density initially increased and then decreased as the Cl- concentration increased. The corrosion products comprised mainly α-FeOOH, γ-FeOOH, ß-FeOOH, Fe3O4, and γ-Fe2O3.
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BACKGROUND: Endoplasmic reticulum stress plays a crucial role in the pathogenesis of neuroinflammation and chronic pain. This study hypothesized that PRKR-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme type 1 (IRE1) regulate lipocalin-2 (LCN2) and Nod-like receptor family pyrin domain containing 3 (NLRP3) expression in astrocytes, thereby contributing to morphine tolerance and hyperalgesia. METHODS: The study was performed in Sprague-Dawley rats and C57/Bl6 mice of both sexes. The expression of LCN2 and NLRP3 was assessed by Western blotting. The tail-flick, von Frey, and Hargreaves tests were used to evaluate nociceptive behaviors. Chromatin immunoprecipitation was conducted to analyze the binding of activating transcription factor 4 (ATF4) to the promoters of LCN2 and TXNIP. Whole-cell patch-clamp recordings were used to evaluate neuronal excitability. RESULTS: Pharmacologic inhibition of PERK and IRE1 attenuated the development of morphine tolerance and hyperalgesia in male (tail latency on day 7, 8.0 ± 1.13 s in the morphine + GSK2656157 [10 µg] group vs. 5.8 ± 0.65 s in the morphine group; P = 0.04; n = 6 rats/group) and female (tail latency on day 7, 6.0 ± 0.84 s in the morphine + GSK2656157 [10 µg] group vs. 3.1 ± 1.09 s in the morphine group; P = 0.0005; n = 6 rats/group) rats. Activation of PERK and IRE1 upregulated expression of LCN2 and NLRP3 in vivo and in vitro. Chromatin immunoprecipitation analysis showed that ATF4 directly bound to the promoters of the LCN2 and TXNIP. Lipocalin-2 induced neuronal hyperexcitability in the spinal cord and dorsal root ganglia via melanocortin-4 receptor. CONCLUSIONS: Astrocyte endoplasmic reticulum stress sensors PERK and IRE1 facilitated morphine tolerance and hyperalgesia through upregulation of LCN2 and NLRP3 in the spinal cord.
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Inflamasomas , Morfina , Ratas , Ratones , Masculino , Femenino , Animales , Morfina/farmacología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Astrocitos/metabolismo , Hiperalgesia/metabolismo , Roedores/metabolismo , Regulación hacia Arriba , Lipocalina 2/metabolismo , Ratas Sprague-Dawley , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Médula Espinal/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMEN
OBJECTIVES: This study aims to evaluate the commutability of external quality assessment (EQA) materials and candidate reference materials (RMs) for plasma renin activity (PRA) assay. METHODS: Commutabilities of 16 candidate RMs were measured along with 40 clinical samples by the four different routine PRA assays, including three LCâMS/MS assays and one chemiluminescence immunoassay. Sixteen candidate RMs included native/spiked human plasma pools (small-scale pools with <50 individuals) and current EQA materials (large-scale pools with >1,000 individuals). Difference in bias approach and linear regression with prediction interval approach were adopted to determine the commutability. Two-way variance analysis was used to estimate the effects of spiked and pool size on the commutability. Stability and homogeneity studies were performed. RESULTS: Precision and correlation performance of all assays was acceptable. In the difference in bias approach, the commutability results were not satisfactory (noncommutability: 14/16) and significant sample-specific effects were detected in assay pairs using different incubation buffers. For the prediction interval approach, no commutability was observed in the spiked small-scale pools; EQA materials (4/9) had more satisfactory commutability among all assays than the small-scale pools (2/7); RMs of large-scale pools tend to have better commutability no matter spiked or not. CONCLUSIONS: Commutable RMs were obtainable but challenging. Current EQA materials with relatively good commutability, stability, and homogeneity were appropriate RMs. Large-scale pools are tending to be commutable. Spiking in small-scale pools was not suggested to prepare RMs. MPs adopting a uniform incubation buffer would be preferable for further commutability research.
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Renina , Espectrometría de Masas en Tándem , Humanos , Estándares de Referencia , Cromatografía Liquida , SesgoRESUMEN
Objective: To investigate the effect of human subcutaneous adipose-derived stem cells (hADSCs) local transplantation on orthodontically induced root resorption (OIRR) and provide theoretical and experimental basis for the clinical application of hADSCs to inhibit OIRR. Methods: Forty 8-week-old male Sprague Dawley rats were randomly divided into experimental group and control group, with 20 rats in each group, to establish the first molar mesial orthodontic tooth movement (OTM) model of rat right maxillary. The rats in the experimental group were injected with 25 µL of cell suspension containing 2.5×10 5 hADSCs on the 1st, 4th, 8th, and 12th day of modeling, while the rats in the control group were injected with 25 µL of PBS. The rat maxillary models were obtained before and after 7 and 14 days of force application, and 10 rats in each group were killed and sampled after 7 and 14 days of force application. The OTM distance was measured by stereomicroscope, the root morphology of the pressure side was observed by scanning electron microscope and the root resorption area ratio was measured. The root resorption and periodontal tissue remodeling of the pressure side were observed by HE staining and the root resorption index was calculated. The number of cementoclast and osteoclast in the periodontal tissue on the pressure side was counted by tartrate resistant acid phosphatase staining. Results: The TOM distance of both groups increased with the extension of the force application time, and there was no significant difference ( P<0.05). There was no significant difference in OTM distance between the experimental group and the control group after 7 and 14 days of force application ( P>0.05). Scanning electron microscope observation showed that small and shallow scattered resorption lacunae were observed on the root surface of the experimental group and the control group after 7 days of force application, and there was no significant difference in the root resorption area ratio between the two groups ( P>0.05); after 14 days of application, the root resorption lacunae deepened and became larger in both groups, and the root resorption area ratio in the experimental group was significantly lower than that in the control group ( P<0.05). The range and depth of root absorption in the experimental group were smaller and shallower than those in the control group, and the root absorption index in the experimental group was significantly lower than that in the control group after 14 days of force application ( P<0.05). The number of cementoclast in the experimental group was significantly lower than that in the control group after 7 and 14 days of force application ( P<0.05); the number of osteoclasts in the experimental group was significantly lower than that in the control group after 14 days of force application ( P<0.05). Conclusion: Local transplantation of hADSCs may reduce the area and depth of root resorption by reducing the number of cementoclasts and osteoclasts during OTM in rats, thereby inhibiting orthodontic-derived root resorption.
Asunto(s)
Resorción Radicular , Ratas , Masculino , Humanos , Animales , Resorción Radicular/etiología , Resorción Radicular/terapia , Ratas Sprague-Dawley , Osteoclastos , Técnicas de Movimiento Dental , Células MadreRESUMEN
The Nod-like receptor family PYRIN domain containing 3 (NLRP3) inflammasome is a multiprotein signaling complex that plays a pivotal role in innate immunity, and the dysregulated NLRP3 inflammasome activation is implicated in various diseases. Tiliroside is a natural flavonoid in multiple medicinal and dietary plants with known anti-inflammatory activities. However, its role in regulating NLRP3 inflammasome activation and NLRP3-related disease has not been evaluated. Herein, it was demonstrated that tiliroside is inhibitory in activating the NLRP3 inflammasome in macrophages. Mechanistically, tiliroside promotes AMP-activated protein kinase (AMPK) activation, thereby leading to ameliorated mitochondrial damage as evidenced by the reduction of mitochondrial reactive oxygen species (ROS) production and the improvement of mitochondrial membrane potential, which is accompanied by attenuated NLRP3 inflammasome activation in macrophages. Notably, tiliroside potently attenuated lipopolysaccharide (LPS)-induced acute lung injury in mice, which has been known to be NLRP3 inflammasome dependent. For the first time, this study identified that tiliroside is an NLRP3 inflammasome inhibitor and may represent a potential therapeutic agent for managing NLRP3-mediated inflammatory disease.