Lactate and Lactylation: Clinical Applications of Routine Carbon Source and Novel Modification in Human Diseases.

Cell metabolism generates numerous intermediate metabolites that could serve as feedback and feed-forward regulation substances for posttranslational modification. Lactate, a metabolic product of glycolysis, has recently been conceptualized to play a pleiotropic role in shaping cell identities through metabolic rewiring and epigenetic modifications. Lactate-derived carbons, sourced from glucose, mediate the crosstalk among glycolysis, lactate, and lactylation. Furthermore, the multiple metabolic fates of lactate make it an ideal substrate for metabolic imaging in clinical application. Several studies have identified the crucial role of protein lactylation in human diseases associated with cell fate determination, embryonic development, inflammation, neoplasm, and neuropsychiatric disorders. Herein, this review will focus on the metabolic fate of lactate-derived carbon to provide useful information for further research and therapeutic approaches in human diseases. We comprehensively discuss its role in reprogramming and modification during the regulation of glycolysis, the clinical translation prospects of the hyperpolarized lactate signal, lactyl modification in human diseases, and its application with other techniques and omics.

A distinct role of STING in regulating glucose homeostasis through insulin sensitivity and insulin secretion.

Insulin resistance and ß-cell dysfunction are two main molecular bases yet to be further elucidated for type 2 diabetes (T2D). Accumulating evidence indicates that stimulator of interferon genes (STING) plays an important role in regulating insulin sensitivity. However, its function in ß-cells remains unknown. Herein, using global STING knockout (STING-/-) and ß-cell-specific STING knockout (STING-ßKO) mouse models, we revealed a distinct role of STING in the regulation of glucose homeostasis through peripheral tissues and ß-cells. Specially, although STING-/- beneficially alleviated insulin resistance and glucose intolerance induced by high-fat diet, it surprisingly impaired islet glucose-stimulated insulin secretion (GSIS). Importantly, STING is decreased in islets of db/db mice and patients with T2D, suggesting a possible role of STING in ß-cell dysfunction. Indeed, STING-ßKO caused glucose intolerance due to impaired GSIS, indicating that STING is required for normal ß-cell function. Islet transcriptome analysis showed that STING deficiency decreased expression of ß-cell function-related genes, including Glut2, Kcnj11, and Abcc8, contributing to impaired GSIS. Mechanistically, the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and cleavage under targets and tagmentation (CUT&Tag) analyses suggested that Pax6 was the transcription factor that might be associated with defective GSIS in STING-ßKO mice. Indeed, Pax6 messenger RNA and protein levels were down-regulated and its nuclear localization was lost in STING-ßKO ß-cells. Together, these data revealed a function of STING in the regulation of insulin secretion and established pathophysiological significance of fine-tuned STING within ß-cells and insulin target tissues for maintaining glucose homeostasis.

Patient-Reported Outcome Measures Following Hyperbaric Oxygen Therapy for Radiation Cystitis: Early Results From the Multicenter Registry for Hyperbaric Oxygen Therapy.

PURPOSE: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). MATERIALS AND METHODS: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer‒related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P = .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement.

Regulating Electron Metal-Support Interaction to Suppress N2O Formation in the Selective Catalytic Oxidation of Ammonia.

N2O is a common byproduct in the selective catalytic oxidation of ammonia, and its generation often needs to be inhibited due to its strong greenhouse effect. In this paper, using Ag/ZSO-Y as a model catalyst, the N2O selectivity was reduced by 30% through modulation of the electron metal-support interaction. The results demonstrate that the work function of the support can be regulated by the content of the doping element. As the Zr content increases in SnO2, the work function of the support decreases. Moreover, there is a positive correlation between the charge transfer amount and the work function of the support. A series of in situ DRIFTS and density functional theory calculations revealed that the -NO and -N reactions are the primary pathways for N2O formation. By adjustment of the work function of the support through varying the Zr doping level, the electronic structure of Ag NPs was further tuned, resulting in an increased reaction energy barrier for -NO and -N reactions, effectively suppressing N2O formation.

Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/ß-catenin/NeuroD1 pathway.

BACKGROUND: Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. METHODS: The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)-induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/ß-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. RESULTS: Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-ß signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/ß-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. CONCLUSIONS: Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/ß-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.

Distribution of serum uric acid concentration and its association with lipid profiles: a single-center retrospective study in children aged 3 to 12 years with adenoid and tonsillar hypertrophy.

BACKGROUND: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy. METHODS: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were collected. SUA concentrations were scaled to standard deviation (SD), and SUA deviations were expressed as SD from the mean SUA of children without dyslipidemia. RESULTS: The mean SUA concentration of the participants was 4.27 ± 1.01 mg/dL, and the prevalence of hyperuricemia was 1.6% when it was defined using an SUA of ≥ 7.0 mg/dL. Participants with dyslipidemia (856, 17.4%) had a higher prevalence of hyperuricemia (3.4% vs. 1.2%, P < 0.001) and higher SUA concentrations (4.51 ± 1.15 vs. 4.22 ± 0.97 mg/dL, P < 0.001) than those with ortholiposis. The circulating lipid status of participants with SUAs < 1 SD below the mean value for the participants with ortholiposis (range 1.80-3.28 mg/dL) was more normal. Each 1-SD increase in SUA was associated with a 27% increase in the risk of dyslipidemia (OR = 1.270, 95% CI, 1.185-1.361). Adjustment for a number of potential confounders reduced the strength of the relationship, but this remained significant (OR = 1.125, 95% CI, 1.042-1.215). The higher risk of dyslipidemia was maintained for participants with SUAs > 1 SD above the mean value of the participants with ortholiposis. CONCLUSIONS: SUA was independently associated with dyslipidemia in children with adenoid and tonsillar hypertrophy, and an SUA < 1 SD below the mean value for patients with ortholiposis was associated with a healthy lipid profile.

Impact of the emergency response to COVID-19 on air quality and its policy implications: Evidence from 290 cities in China.

The emergency response to the COVID-19 pandemic had an extreme exogenous impact on society and the economy. This paper aims to explore the impacts of the national emergency response and the subsequent emergency response termination on air quality and its policy implications through regression discontinuity design (RDD) estimation by employing panel data on daily air quality from January 1, 2019, to July 31, 2020, for 290 cities in China. The empirical results showed that the emergency response resulted in a significant decrease in most of the major pollutant concentrations within a short time frame, and the average air quality index (AQI) decreased by approximately 11.0%. The concentrations of PM2.5, PM10, SO2, NO2, and CO decreased by approximately 18.8%, 13.1%, 13.5%, 11.1% and 6.7%, respectively, while the O3 concentration did not change significantly. Further causal analysis found that mandatory traffic restrictions and the shutdown of industries were two important factors that contributed greatly to air quality improvement. Moreover, since the process of returning to normal daily activities and promoting the economy were gradual, the results showed that air pollution did not rebound immediately after the government called for the "resumption of production and work" and announced the "termination of the emergency response". Our findings suggest that to achieve a substantial and sustainable improvement in air quality, it is necessary to continuously implement strict emission control routines and take co-control measures for various VOCs precursors of ozone.

Non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD in type 2 diabetic patients.

BACKGROUND: Non-obese non-alcoholic fatty liver disease (NAFLD) has been reported to share clinical outcomes with its obese counterpart in the general population. However, conflicting results have been observed regarding the cardio-metabolic risk profile of non-obese NAFLD as compared to obese NAFLD. Moreover, in the context of type 2 diabetes mellitus (T2DM), this issue has been even less addressed. We hence aimed to examine the association of NAFLD with the cardio-metabolic risk profile in patients with T2DM according to their obesity status. METHODS: A total of 2,708 patients with T2DM who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed. RESULTS: The prevalence of NAFLD was 49.3%. NAFLD was found in 34.1% of non-obese patients and 66.0% of obese patients. Non-obese NAFLD patients had more and worse metabolic disorders than obese patients without NAFLD in both men and women. Comparable cardio-metabolic risk profiles were noted between non-obese and obese NAFLD subjects. The associations of worse cardio-metabolic risk profiles with NAFLD were overall stronger in non-obese than in obese subjects among women with T2DM, while more pronounced in obese than in non-obese subjects among men with T2DM. CONCLUSION: In patients with T2DM, non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD. The associations of metabolic disorders with NAFLD were stronger in non-obese than in obese patients in women patients with T2DM.

The protocol of CUT&Tag for metabolic tissue cells.

Cleavage under target and tagment (CUT&Tag) is a technology that utilizes the fusion protein of Tn5 transposase and protein A/G which can guide Tn5 enzyme to the antibody bound to target protein and cleave the chromatin regions adjacent to target protein. Chromatin libraries are then tagged and sequenced by the high-throughput sequencing to obtain chromatin information at specific sites or protein binding locations. CUT&Tag technology plays an important role in the research of DNA and protein interactions. It can be used to understand the modifications of histone and the bindings of transcription factors. Compared with the traditional chromatin immunoprecipitation-sequencing (ChIP-seq) technology, the CUT&Tag has the strengths of high signal-to-noise ratio, good repeatability, short experimental period, and low cell input. It shows great advantages in early embryonic development, stem cells, cancer, epigenetics and other research fields. In this article, we described the protocol of CUT&Tag for metabolic tissue cells (mouse primary islet cells), to provide an epigenetic method for studying metabolic cells.

Slowing down DNA translocation velocity using a LiCl salt gradient and nanofiber mesh.

Solid-state nanopores are considered an attractive basis for single-molecule DNA sequencing. At present, one obstacle to be overcome is the improvement of their temporal resolution, with the DNA molecules remaining in the sensing volume of the nanopore for a long period of time. Here, we used a composite system of a concentration gradient of LiCl in solution and a nanofiber mesh to slow the DNA perforation speed. Compared to different alkali metal solutions with the same concentration, LiCl can extend the dwell time to 20 ms, five times longer than NaCl and KCl. Moreover, as the concentration gradient increases, the dwell time can be tuned from dozens of milliseconds to more than 100 ms. When we introduce a nanofiber mesh layer on top of the pore in the asymmetric solution, the DNA molecules get retarded by 162-185 [Formula: see text]s/nt, which is three orders of magnitude slower than the bare nanopore. At the same time, because the molecule absorption region becomes larger at the pore vicinity, the higher molecule capture rate improves the detection efficiency.

Noise Analysis of Monolayer Graphene Nanopores.

Graphene-based nanopore devices have shown tantalizing potential in single molecule detection for their monoatomic membrane thickness which is roughly equal to the gap between nucleobases. However, high noise level hampers applications of graphene nanopore sensors, especially at low frequencies. In this article, we report on a study of the contribution of suspended graphene area to noise level in full frequency band. Monolayer graphene films are transferred onto SiNx substrates preset with holes in varied diameters and formed self-supported films. After that, the films are perforated with smaller, nanoscale holes. Experimental studies indicate a dependency of low-frequency 1/f noise on the underlying SiNx geometry. The contribution of the suspended graphene area to capacitance which affects the noise level in the high frequency range reveals that the graphene free-standing film area influences noise level over a wide frequency region. In addition, the low-frequency noise demonstrates a weak dependency on salt concentration, in deviation from Hooge's relation. These findings and attendant analysis provide a systematic understanding of the noise characteristics and can serve as a guide to designing free-standing monolayer graphene nanopore devices.

[Terahertz Spectroscopic Study on the Property of Epoxy Resin Adhesive].

Epoxy resin is an important adhesive applied in the manufacturing processes of fiber reinforced polymer (FRP) composites. Terahertz (THz) time-domain spectroscopy (TDS) technology is an effective supplementary method for nondestructive evaluation (NDE) of FRP composites. As one of the most important parameters for epoxy resin, different curing temperature can affect the properties of epoxy resin. In this paper, we carry out systematic investigations on THz transmission properties of epoxy resin cured respectively under room temperature and high temperature with THz TDS technology. At the same time, the authors extract the refractive indices and absorption coefficients of epoxy resin, and make comparisons d. As shown in the experiments, the epoxy resin samples cured under room temperature have no bubble, whereas there are some micro-bubbles in the samples cured under high temperature, which reduce the sample density. Hence, the refractive index and absorption coefficient of epoxy resin cured under room temperature are both greater than those cured under high temperature. The difference of refractive index of different samples cured under the same condition is not significant. In addition, the difference of absorption coefficient of different samples cured under room temperature is also slight. However, the difference of absorption coefficient of different samples cured under high temperature gradually increase within the frequency from 0.6 to 1.5 THz, which is mainly due to the heterogeneous distribution of the bubbles in the different samples cured under high temperature. Moreover, the absorption coefficient of epoxy resin prepared under both curing temperatures gradually increases with the frequency, and there is no obvious absorption peak. Finally, because of the existence of Fabry-Pérot interference, the power transmission ratio of thicker epoxy resin samples may be greater than thinner samples at the resonant frequency. This research is of great significance for the THz NDE of FRP composites.

[Experimental Study of PMI Foam Composite Properties in Terahertz].

Polymethacrylimide (PMI) foam composite has many excellent properties. Currently, PMI is heat-resistant foam, with the highest strength and stiffness. It is suitable as a high-performance sandwich structure core material. It can replace the honeycomb structure. It is widely used in aerospace, aviation, military, marine, automotive and high-speed trains, etc. But as new sandwich materials, PMI performance testing in the THz band is not yet visible. Based on the Terahertz (THz) time-domain spectroscopy technique, we conducted the transmission and reflection experiments, got the time domain waveforms and power density spectrum. And then we analyzed and compared the signals. The MATALB and Origin 8. 0 was used to calculate and obtain the transmittance (transfer function), absorptivity Coefficient, reflectance and the refractive index of the different thickness Degussa PMI (Model: Rohacell WF71), which were based on the application of the time-domain and frequency-domain analysis methods. We used the data to compared with the THz refractive index and absorption spectra of a domestic PMI, Baoding Meiwo Technology Development Co. , Ltd. (Model: SP1D80-P-30). The result shows that the impact of humidity on the measurement results is obvious. The refractive index of PMI is about 1. 05. The attenuation of power spectrum is due to the signal of the test platform is weak, the sample is thick and the internal scattering of PMI foam microstructure. This conclusion provides a theoretical basis for the THz band applications in the composite PMI. It also made a good groundwork for THz NDT (Non-Destructive Testing, NDT) technology in terms of PMI foam composites.

The expression of disabled-2 is common reduced in meningiomas.

AIMS: Disabled-2 (Dab2) is frequently down-regulated in several types of cancers. We examined the expression level of Dab2 in human meningiomas and meningioma cells, aimed to investigate its role in the oncogenesis and development of meningiomas. MATERIALS AND METHODS: Western blot analysis was employed to detect Dab2 expression in 90 fresh tissues of meningiomas, 10 leptomeninges and two kinds of human malignant meningioma cell lines. Independent samples t-test, analysis of variance, Pearson Chi-square test and likelihood ratio test were used to analyze the expression level of Dab2 and its relations to clinic-pathological characteristics of meningiomas. RESULTS: Dab2 was significantly down-regulated in classic meningiomas than the atypical or anaplastic meningiomas. The reduced or loss of expression of Dab2 were significantly correlated with the lower classification of meningiomas and negatively correlated with the invasive ability of adjacent tissues. Furthermore, it was reduced or lost in malignant meningioma cell lines (IOMM-Lee and KT21-MG1). The lower classification of meningiomas correlated with previous comorbidities; not with the gender, age of patients and smoking. CONCLUSIONS: Dab2 is expressed at variable level in meningiomas with different grade of malignancy and probably plays a pivotal role in the early stage of oncogenesis of malignant meningiomas.

Frequent loss expression of dab2 and promotor hypermethylation in human cancers: a meta-analysis and systematic review.

Objective : Disabled-2 (Dab2) is an important endocytic adaptor which plays an inhibition role in cancer cell growth. The objective of this study was to systematically review expressions of Dab2 in human cancers. Methods : Eligible studies about Dab2 in human cancers were retrieved from databases of PubMed, Embase, Web of Science. Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated using Review Manager 5.0 software and statistical analyses were performed by the SPSS 13.0 software. Results : Fourteen case-control studies with a total of 689 human tumor tissues, 332 control tissues and 32 cancer cell lines were included in the meta-analysis study. The results indicated loss expressions of Dab2 were observed in 74.9% and 46.9% in human malignant cancer tissues and cancer cell lines, respectively. The ratio of Dab2 promotor hypermethylation is 34.54% in cancer tissues which Dab2 expression are lost, but none in the control tissues or cells by Methylation-specific PCR (MSP). Conclusions : The expressions of Dab2 are frequently lost in human malignant cancer tissues, and promotor hypermethylation of Dab2 are common in human malignant cancer tissues, which is an important factor for the loss expression of Dab2 in human cancers tissues.

Efficacy of rituximab in treating steroid-resistant Graves' orbitopathy in active moderate-to-severe and sight-threatening forms: A retrospective observation from China.

Background and objectives: The efficacy of rituximab (RTX) in treating steroid-resistant Graves' orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. Methods: Data from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. Results: The median follow-up time was 22 (8-34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves' Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration. Conclusion: A single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.

TRIB2-mediated modulation of AMPK promotes hepatic insulin resistance.

Insulin resistance and its linked health complications are increasing in prevalence. Recent work has caused the role of Tribbles2 (TRIB2) in metabolism and cellular signaling to be increasingly appreciated, but its role in the progression of insulin resistance has not been elucidated. Here, we explore the functions of TRIB2 in modulating insulin resistance and the mechanism involved in insulin resistance mice and palmitic acid (PA) treated HepG2 cells. We demonstrate that whole-body knockout and hepatic-specific TRIB2 deficiency protect against diet-induced insulin resistance, inflammation and ER stress. Accordingly, upregulation of TRIB2 in the liver aggravates these metabolic disturbances in HFD-induced mice and ob/ob mice. Mechanistically, TRIB2 directly binds to the αγ-SBS domain of PRKAB through its pseudokinase domain, subsequently inhibiting the formation and activity of the AMPK complex. Moreover, the results of intervention against AMPK suggest that the effects of TRIB2 depend on AMPK. Our findings reveal that TRIB2 is a novel target for the treatment of insulin resistance and its associated metabolic complications and clarify the function of TRIB2 as a regulatory component of AMPK activity.

Auditory neural processing in children living with HIV uncovers underlying central nervous system dysfunction.

OBJECTIVE: Central nervous system (CNS) damage from HIV infection or treatment can lead to developmental delays and poor educational outcomes in children living with HIV (CLWH). Early markers of central nervous system dysfunction are needed to target interventions and prevent life-long disability. The frequency following response (FFR) is an auditory electrophysiology test that can reflect the health of the central nervous system. In this study, we explore whether the FFR reveals auditory central nervous system dysfunction in CLWH. STUDY DESIGN: Cross-sectional analysis of an ongoing cohort study. Data were from the child's first visit in the study. SETTING: The infectious disease center in Dar es Salaam, Tanzania. METHODS: We collected the FFR from 151 CLWH and 151 HIV-negative children. To evoke the FFR, three speech syllabi (/da/, /ba/, /ga/) were played monaurally to the child's right ear. Response measures included neural timing (peak latencies), strength of frequency encoding (fundamental frequency and first formant amplitude), encoding consistency (inter-response consistency), and encoding precision (stimulus-to-response correlation). RESULTS: CLWH showed smaller first formant amplitudes ( P  < 0.0001), weaker inter-response consistencies ( P  < 0.0001) and smaller stimulus to response correlations ( P  < 0.0001) than FFRs from HIV-negative children. These findings generalized across the three speech stimuli with moderately strong effect sizes (partial η2 ranged from 0.061 to 0.094). CONCLUSION: The FFR shows auditory central nervous system dysfunction in CLWH. Neural encoding of auditory stimuli was less robust, more variable, and less accurate. As the FFR is a passive and objective test, it may offer an effective way to assess and detect central nervous system function in CLWH.

Catalytic activity and mechanism of selective catalytic oxidation of ammonia by Ag-CeO2 under different preparation conditions.

Given the problem of the high-temperature window of CeO2 catalyst activity, this study evaluated the catalytic properties of Ag/CeO2 prepared by changing the preparation methods and loadings. Our experiments showed that Ag/CeO2-IM catalysts prepared by the equal volume impregnation method could have better activity at lower temperatures. The Ag/CeO2-IM catalyst achieves 90% NH3 conversion at 200 °C, and the main reason is that the Ag/CeO2-IM catalyst has more vital redox properties, and the NH3 catalytic oxidation temperature is lower. However, its high-temperature N2 selectivity still needs to be improved and may be related to the less acidic sites on the catalyst surface. On both catalyst surfaces, the i-SCR mechanism governs the NH3-SCO reaction.