Suppression of hepatic ChREBP⍺-CYP2C50 axis-driven fatty acid oxidation sensitizes mice to diet-induced MASLD/MASH.

OBJECTIVES: Compromised hepatic fatty acid oxidation (FAO) has been observed in human MASH patients and animal models of MASLD/MASH. It remains poorly understood how and when the hepatic FAO pathway is suppressed during the progression of MASLD towards MASH. Hepatic ChREBP⍺ is a classical lipogenic transcription factor that responds to the intake of dietary sugars. METHODS: We examined its role in regulating hepatocyte fatty acid oxidation (FAO) and the impact of hepatic Chrebpa deficiency on sensitivity to diet-induced MASLD/MASH in mice. RESULTS: We discovered that hepatocyte ChREBP⍺ is both necessary and sufficient to maintain FAO in a cell-autonomous manner independently of its DNA-binding activity. Supplementation of synthetic PPAR⍺/δ agonist is sufficient to restore FAO in Chrebp-/- primary mouse hepatocytes. Hepatic ChREBP⍺ was decreased in mouse models of diet-induced MAFSLD/MASH and in patients with MASH. Hepatocyte-specific Chrebp⍺ knockout impaired FAO, aggravated liver steatosis and inflammation, leading to early-onset fibrosis in response to diet-induced MASH. Conversely, liver overexpression of ChREBP⍺-WT or its non-lipogenic mutant enhanced FAO, reduced lipid deposition, and alleviated liver injury, inflammation, and fibrosis. RNA-seq analysis identified the CYP450 epoxygenase (CYP2C50) pathway of arachidonic acid metabolism as a novel target of ChREBP⍺. Over-expression of CYP2C50 partially restores hepatic FAO in primary hepatocytes with Chrebp⍺ deficiency and attenuates preexisting MASH in the livers of hepatocyte-specific Chrebp⍺-deleted mice. CONCLUSIONS: Our findings support the protective role of hepatocyte ChREBPa against diet-induced MASLD/MASH in mouse models in part via promoting CYP2C50-driven FAO.

Emergency Department SpO2/FiO2 Ratios Correlate with Mechanical Ventilation and Intensive Care Unit Requirements in COVID-19 Patients.

Background: Patients with coronavirus 2019 (COVID-19) are at high risk for respiratory dysfunction. The pulse oximetry/fraction of inspired oxygen (SpO2/FiO2) ratio is a non-invasive assessment of respiratory dysfunction substituted for the PaO2:FiO2 ratio in Sequential Organ Failure Assessment scoring. We hypothesized that emergency department (ED) SpO2/FiO2 ratios correlate with requirement for mechanical ventilation in COVID-19 patients. Our objective was to identify COVID-19 patients at greatest risk of requiring mechanical ventilation, using SpO2/FiO2 ratios. Methods: We performed a retrospective review of patients admitted with COVID-19 at two hospitals. Highest and lowest SpO2/FiO2 ratios (percent saturation/fraction of inspired O2) were calculated on admission. We performed chi-square, univariate, and multiple regression analysis to evaluate the relationship of admission SpO2/FiO2 ratios with requirement for mechanical ventilation and intensive care unit (ICU) care. Results: A total of 539 patients (46% female; 84% White), with a mean age 67.6 ± 18.6 years, met inclusion criteria. Patients who required mechanical ventilation during their hospital stay were statistically younger in age (P = 0.001), had a higher body mass index (P < .001), and there was a higher percentage of patients who were obese (P = 0.03) and morbidly obese (P < .001). Shortness of breath, cough, and fever were the most common presenting symptoms with a median temperature of 99°F. Average white blood count was higher in patients who required ventilation (P = <0.001). A highest obtained ED SpO2/FiO2 ratio of ≤300 was associated with a requirement for mechanical ventilation. A lowest obtained ED SpO2/FiO2 ratio of ≤300 was associated with a requirement for intensive care unit care. There was no statistically significant correlation between ED SpO2/FiO2 ratios >300 and mechanical ventilation or intensive care unit (ICU) requirement. Conclusion: The ED SpO2/FiO2 ratios correlated with mechanical ventilation and ICU requirements during hospitalization for COVID-19. These results support ED SpO2/FiO2 as a possible triage tool and predictor of hospital resource requirements for patients admitted with COVID-19. Further investigation is warranted.

Frontotemporal Dementia P301L Mutation Potentiates but Is Not Sufficient to Cause the Formation of Cytotoxic Fibrils of Tau.

The P301L mutation in tau protein is a prevalent pathogenic mutation associated with neurodegenerative frontotemporal dementia, FTD. The mechanism by which P301L triggers or facilitates neurodegeneration at the molecular level remains unclear. In this work, we examined the effect of the P301L mutation on the biochemical and biological characteristics of pathologically relevant hyperphosphorylated tau. Hyperphosphorylated P301L tau forms cytotoxic aggregates more efficiently than hyperphosphorylated wildtype tau or unphosphorylated P301L tau in vitro. Mechanistic studies establish that hyperphosphorylated P301L tau exacerbates endoplasmic reticulum (ER) stress-associated gene upregulation in a neuroblastoma cell line when compared to wildtype hyperphosphorylated tau treatment. Furthermore, the microtubule cytoskeleton is severely disrupted following hyperphosphorylated P301L tau treatment. A hyperphosphorylated tau aggregation inhibitor, apomorphine, also inhibits the harmful effects caused by P301L hyperphosphorylated tau. In short, the P301L single mutation within the core repeat domain of tau renders the underlying hyperphosphorylated tau more potent in eliciting ER stress and cytoskeleton damage. However, the P301L mutation alone, without hyperphosphorylation, is not sufficient to cause these phenotypes. Understanding the conditions and mechanisms whereby selective mutations aggravate the pathogenic activities of tau can provide pivotal clues on novel strategies for drug development for frontotemporal dementia and other related neurodegenerative tauopathies, including Alzheimer's disease.

Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis.

Obesity is increasing worldwide and leads to a multitude of metabolic diseases, including cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis (NASH). Cysteine-rich angiogenic inducer 61 (CYR61) is associated with the progression of NASH, but it has been described to have anti- and proinflammatory properties. We sought to examine the role of liver CYR61 in NASH progression. CYR61 liver-specific knockout mice on a NASH diet showed improved glucose tolerance, decreased liver inflammation, and reduced fibrosis. CYR61 polarized infiltrating monocytes promoting a proinflammatory/profibrotic phenotype through an IRAK4/SYK/NF-κB signaling cascade. In vitro, CYR61 activated a profibrotic program, including PDGFa/PDGFb expression in macrophages, in an IRAK4/SYK/NF-κB-dependent manner. Furthermore, targeted-antibody blockade reduced CYR61-driven signaling in macrophages in vitro and in vivo, reducing fibrotic development. This study demonstrates that CYR61 is a key driver of liver inflammation and fibrosis in NASH.

An MMIC LNA for Millimeter-Wave Radar and 5G Applications with GaN-on-SiC Technology.

This paper presents a monolithic microwave integrated circuit (MMIC) low noise amplifier (LNA) that is compatible with n257 (26.5-29.5 GHz) and n258 (24.25-27.5 GHz) frequency bands for fifth-generation mobile communications system (5G) and millimeter-wave radar. The total circuit size of the LNA is 2.5 × 1.5 mm2. To guarantee a trade-off between noise figure (NF) and small signal gain, the transmission lines are connected to the source of gallium nitride (GaN)-on-SiC high electron mobility transistors (HEMT) by analyzing the nonlinear small signal equivalent circuit. A series of stability enhancement measures including source degeneration, an RC series network, and RF choke are put forward to enhance the stability of designed LNA. The designed GaN-based MMIC LNA adopts hybrid-matching networks (MNs) with co-design strategy to realize low NF and broadband characteristics across 5G n257 and n258 frequency band. Due to the different priorities of these hybrid-MNs, distinguished design strategies are employed to benefit small signal gain, input-output return loss, and NF performance. In order to meet the testing conditions of MMIC, an impeccable system for measuring small has been built to ensure the accuracy of the measured results. According to the measured results for small signal, the three-stage MMIC LNA has a linear gain of 18.2-20.3 dB and an NF of 2.5-3.1 dB with an input-output return loss better than 10 dB in the whole n257 and n258 frequency bands.

An efficient non-iterative smoothed particle hydrodynamics fluid simulation method with variable smoothing length.

In classical smoothed particle hydrodynamics (SPH) fluid simulation approaches, the smoothing length of Lagrangian particles is typically constant. One major disadvantage is the lack of adaptiveness, which may compromise accuracy in fluid regions such as splashes and surfaces. Attempts to address this problem used variable smoothing lengths. Yet the existing methods are computationally complex and non-efficient, because the smoothing length is typically calculated using iterative optimization. Here, we propose an efficient non-iterative SPH fluid simulation method with variable smoothing length (VSLSPH). VSLSPH correlates the smoothing length to the density change, and adaptively adjusts the smoothing length of particles with high accuracy and low computational cost, enabling large time steps. Our experimental results demonstrate the advantages of the VSLSPH approach in terms of its simulation accuracy and efficiency.

An Efficient 24-30 GHz GaN-on-Si Driver Amplifier Using Synthesized Matching Networks.

This paper presents a broadband GaN microwave monolithic integrated circuit driver amplifier (MMIC DA) with compact dimensions of 1.65 mm × 0.78 mm for 5G millimeter-wave communication. The optimal impedance domain satisfying the preset goals was first acquired using the simplified load-pull procedure and small-signal simulations, followed by a weighted average method to determine the reference center matching point from which the optimal intrinsic load can be deduced. By means of de-embedding load-pull contours, modeling based on theoretical analysis, and simulation fitting for parameter identification, the nonlinear output capacitance and a series RLC model circuit approximating the input impedance response of the stabilized transistor were extracted. Under the design principle of fully absorbing the parasitic parameters of the device, explicit formulas and tabulated methods related to the Chebyshev impedance transformer were applied to construct filter-based synthesized matching networks at each stage and finally convert them into an implementable mixed-element form via the single-frequency equivalence technique. Measured on-wafer pulsed results for the proposed two-stage DA across 24-30 GHz demonstrated up to 31.1 dBm of saturated output power (Psat) with less than 1 dB total fluctuation, 19.3 ± 1 dB of small-signal gain, and 39.8% of peak power-added efficiency (PAE) at the mid-frequency.

Thoracoscopic-assisted rib plating (TARP): initial single-center case series, including TARP in the super elderly, technical lessons learned, and proposed expanded indications.

Objectives: The application of surgical stabilization of rib fractures (SSRF) remains inconsistent due to evolving indications and perceived associated morbidity. By implementing thoracoscopic-assisted rib plating (TARP), a minimally invasive SSRF approach, we expanded our SSRF application to patients who otherwise might not be offered fixation. This report presents our initial experience, including fixation in super elderly (aged ≥85 years), and technical lessons learned. Methods: This was a retrospective cohort study at a level 1 trauma center of admitted patients who underwent TARP between August 2019 and October 2020. Patient demographics, injury characteristics, surgical indications and outcomes are represented as mean±SD, median or percentage. Results: A total of 2134 patients with rib fractures were admitted. In this group, 39 SSRF procedures were performed, of which 54% (n=21) were TARP. Average age was 68.5±16 years. Patients had a median of 5 fractured ribs, with an average of 1 rib that was bicortically displaced, and 19% presented with 'clicking' on inspiration. Patient outcomes were a mean hospital length of stay (LOS) of 11±3.7 days, mean postoperative LOS of 8 days, and mean intensive care unit LOS of 6.6±2.9 days. Five patients were ≥85 years old with a mean age of 90.8±4.7 years. They presented with an average of 4 rib fractures, of which an average of 2.4 ribs were plated. The procedure was well tolerated in this age group with a hospital LOS of 9.4±2 days, and all five patients were discharged to a rehab facility with no in-hospital mortalities. Conclusion: Our experience incorporating TARP at our institution demonstrated feasibility of the technique and application across a broad range of patients. This approach and its application warrants further evaluation and potentially expands the application of SSRF..

Let-7 underlies metformin-induced inhibition of hepatic glucose production.

SignificanceA clear mechanistic understanding of metformin's antidiabetic effects is lacking. This is because suprapharmacological concentrations of metformin have been used in most studies. Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4α). We demonstrate that metformin no longer has potent antidiabetic actions in a liver-specific let-7 loss-of-function mouse model and that hepatic delivery of let-7 ameliorates hyperglycemia and improves glucose homeostasis. Our results thus reveal an important role of the hepatic let-7/TET3/HNF4α axis in mediating the therapeutic effects of metformin and suggest that targeting this axis may be a potential therapeutic for diabetes.

Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2.

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.

Hemostatic efficacy of two topical adjunctive hemostats in a porcine spleen biopsy punch model of moderate bleeding.

Topical hemostatic agents have become essential tools to aid in preventing excessive bleeding in surgical or emergency settings and to mitigate the associated risks of serious complications. In the present study, we compared the hemostatic efficacy of SURGIFLO® Hemostatic Matrix Kit with Thrombin (Surgiflo-flowable gelatin matrix plus human thrombin) to HEMOBLAST™ Bellows Hemostatic Agent (Hemoblast-a combination product consisting of collagen, chondroitin sulfate, and human thrombin). Surgiflo and Hemoblast were randomly tested in experimentally induced bleeding lesions on the spleens of four pigs. Primary endpoints included hemostatic efficacy measured by absolute time to hemostasis (TTH) within 5 min. Secondary endpoints included the number of product applications and the percent of product needed from each device to achieve hemostasis. Surgiflo demonstrated significantly higher hemostatic efficacy and lower TTH (p < 0.01) than Hemoblast. Surgiflo-treated lesion sites achieved hemostasis in 77.4% of cases following a single product application vs. 3.3% of Hemoblast-treated sites. On average, Surgiflo-treated sites required 63% less product applications than Hemoblast-treated sites (1.26 ± 0.0.51 vs. 3.37 ± 1.16). Surgiflo provided more effective and faster hemostasis than Hemoblast. Since both products contain thrombin to activate endogenous fibrinogen and accelerate clot formation, the superior hemostatic efficacy of Surgiflo in the porcine spleen punch biopsy model seems to be due to Surgiflo's property as a malleable barrier able to adjust to defect topography and to provide an environment for platelets to adhere and aggregate. Surgiflo combines a flowable gelatin matrix and a delivery system well-suited for precise application to bleeding sites where other methods of hemostasis may be impractical or ineffective.

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2.

Pregnant women are a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Herein, we report that SARS-CoV-2 infection during pregnancy primarily induced specific maternal inflammatory responses in the circulation and at the maternal-fetal interface, the latter being governed by T cells and macrophages. SARS-CoV-2 infection during pregnancy was also associated with a cytokine response in the fetal circulation (i.e. umbilical cord blood) without compromising the cellular immune repertoire. Moreover, SARS-CoV-2 infection neither altered fetal cellular immune responses in the placenta nor induced elevated cord blood levels of IgM. Importantly, SARS-CoV-2 was not detected in the placental tissues, nor was the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and further emphasizes the rarity of placental infection.

Evaluation of the Hemostatic Efficacy of Two Powdered Topical Absorbable Hemostats Using a Porcine Liver Abrasion Model of Mild to Moderate Bleeding.

INTRODUCTION: Topical hemostatic agents, used alone or in combination, have become common adjuncts to manage tissue and organ bleeding resulting from trauma and surgical procedures. Oxidized regenerated cellulose (ORC) is one of the most commonly used adjunctive hemostatic agents. The aim of the present study was to compare the hemostatic efficacy of a novel ORC-based product, SURGICEL® Powder Absorbable Hemostat (Surgicel-P) to that of HEMOBLAST™ Bellows (Hemoblast-B), a collagen-based combination powder. METHODS: Using an established porcine liver abrasion model, we randomly tested Surgicel-P and Hemoblast-B in 60 experimental lesion sites (30 per product tested). Primary endpoints included hemostatic efficacy measured by absolute time to hemostasis (TTH) within 5 minutes. We also examined number of applications required to achieve hemostasis, and sustained hemostasis following saline irrigation of test sites that achieved hemostasis. RESULTS: Surgicel-P demonstrated significantly higher hemostatic efficacy and lower TTH (p < 0.01) than Hemoblast-B. Surgicel-P-treated lesion sites achieved hemostasis in 73.3% of cases following one product application vs. 3.3% of Hemoblast-B-treated sites. Of all sites that were assessed, hemostasis was achieved and sustained following irrigation at 93.3% of Surgicel-P-treated sites vs. 50.0% of Hemoblast-B-treated sites. The average number of Surgicel-P applications per site was 51% lower than the average number of applications used for Hemoblast-B. CONCLUSION: Surgicel-P provided more effective and sustained hemostasis and faster TTH than Hemoblast-B. Surgicel-P represents a novel clinical alternative to provide adjunctive control of diffuse mild and moderate bleeding. Surgicel-P combines an ORC powder formulation and a delivery system in a device that is particularly useful for application on large surfaces and difficult-to-access anatomical locations where application of other forms of topical hemostats may be impractical.

Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway.

Development of resistance remains the key obstacle to the clinical efficacy of EGFR tyrosine kinase inhibitors (TKI). Hypoxia is a key microenvironmental stress in solid tumors associated with acquired resistance to conventional therapy. Consistent with our previous studies, we show here that long-term, moderate hypoxia promotes resistance to the EGFR TKI osimertinib (AZD9291) in the non-small cell lung cancer (NSCLC) cell line H1975, which harbors two EGFR mutations including T790M. Hypoxia-induced resistance was associated with development of epithelial-mesenchymal transition (EMT) coordinated by increased expression of ZEB-1, an EMT activator. Hypoxia induced increased fibroblast growth factor receptor 1 (FGFR1) expression in NSCLC cell lines H1975, HCC827, and YLR086, and knockdown of FGFR1 attenuated hypoxia-induced EGFR TKI resistance in each line. Upregulated expression of FGFR1 by hypoxia was mediated through the MAPK pathway and attenuated induction of the proapoptotic factor BIM. Consistent with this, inhibition of FGFR1 function by the selective small-molecule inhibitor BGJ398 enhanced EGFR TKI sensitivity and promoted upregulation of BIM levels. Furthermore, inhibition of MEK activity by trametinib showed similar effects. In tumor xenografts in mice, treatment with either BGJ398 or trametinib enhanced response to AZD9291 and improved survival. These results suggest that hypoxia is a driving force for acquired resistance to EGFR TKIs through increased expression of FGFR1. The combination of EGFR TKI and FGFR1 or MEK inhibitors may offer an attractive therapeutic strategy for NSCLC. SIGNIFICANCE: Hypoxia-induced resistance to EGFR TKI is driven by overexpression of FGFR1 to sustain ERK signaling, where a subsequent combination of EGFR TKI with FGFR1 inhibitors or MEK inhibitors reverses this resistance. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/21/4655/F1.large.jpg.

Significant Associations Between Sun Exposure and Adiposity Were Not Observed in Breast and Prostate Cancer Patients in a Cross-sectional Analysis.

Obesity is a significant health problem worldwide. Exposure to low-dose ultraviolet radiation (like that in sunlight) suppresses the development of obesity in mice; however, the nature of the associations between sun exposure and adiposity is not well understood in humans. The present study characterized cross-sectional relationships between sun exposure and adiposity in a convenience cohort of breast (n = 269; mean age = 58 years) and prostate (n = 78; mean age = 69 years) cancer patients. Participants were enrolled in a 3-month exercise program in Perth, Australia. Self-reported questionnaires measured time spent outdoors (previous week, winter and summer), sex, age, treatment received and physical activity levels. Adiposity measures included body mass index, waist-hip ratio and body fat percentage (measured via DXA). In unadjusted models, greater time spent outdoors across all times was significantly associated with lower waist-hip ratio, while greater time spent outdoors in the last winter was associated with lower body fat percentage, but not when stratified by sex. There were no statistically significant associations between time spent outdoors and adiposity after adjusting for sex, age, treatments received and physical activity. Longitudinal studies in larger populations may elucidate significant associations not found in our study due to the cross-sectional design and power limitations.

A Patch/Dipole Hybrid-Mode Antenna for Sub-6GHz Communication.

A low-profile antenna with a high gain and broad bandwidth is proposed for Sub-6GHz communication in this paper. A narrow-band patch mode and a narrow-band dipole mode are shared in one radiator and simultaneously excited to broaden the bandwidth. A compact prototype with a projection size of 0.90 λ0 × 0.78 λ0 and a profile of 0.13 λ0 (λ0 is the wavelength in the free space at the center of the operating frequency) is fabricated and measured. The measurement demonstrates an impedance bandwidth of 67.50%, covering the frequency range from 2.75 GHz to 5.45 GHz and an average gain of 8.4 dBi in the operating band of 3.0⁻5.0 GHz.

Qualitative research: An overview of emerging approaches for data collection.

OBJECTIVE: The aim of this study was to introduce new approaches to conduct qualitative research that may provide valuable insight into issues related to education, training and patient care in psychiatry. CONCLUSIONS: A variety of data-collection tools is available for researchers and practitioners in psychiatry. These can be used independently or in conjunction with other quantitative and qualitative methods.

Wireless Passive Ultra High Frequency RFID Antenna Sensor for Surface Crack Monitoring and Quantitative Analysis.

An exponential increase in large-scale infrastructure facilitates the development of wireless passive sensors for permanent installation and in-service health monitoring. Due to their wireless, passive and cost-effective characteristics, ultra-high frequency (UHF) radio frequency identification (RFID) tag antenna based sensors are receiving increasing attention for structural health monitoring (SHM). This paper uses a circular patch antenna sensor with an open rectangular window for crack monitoring. The sensing mechanism is quantitatively studied in conjunction with a mode analysis, which can uncover the intrinsic principle for turning an antenna into a crack sensor. The robustness of the feature is examined when the variation of crack position associated with an aluminum sample and the antenna sensor is considered. The experimental results demonstrate a reasonable sensitivity and resolution for crack characterization.

Inhalation Exposure to PM2.5 Counteracts Hepatic Steatosis in Mice Fed High-fat Diet by Stimulating Hepatic Autophagy.

Air pollution is associated with the increased risk of metabolic syndrome. In this study, we performed inhalation exposure of mice fed normal chow or a high-fat diet to airborne fine particulate matters (PM2.5), and then investigated the complex effects and mechanisms of inhalation exposure to PM2.5 on hepatic steatosis, a precursor or manifestation of metabolic syndrome. Our studies demonstrated that inhalation exposure of mice fed normal chow to concentrated ambient PM2.5 repressed hepatic transcriptional regulators involved in fatty acid oxidation and lipolysis, and thus promoted hepatic steatosis. However, PM2.5 exposure relieved hepatic steatosis in high-fat diet-induced obese mice. Further investigation revealed that inhalation exposure to PM2.5 induced hepatic autophagy in mouse livers in a manner depending on the MyD88-mediated inflammatory pathway. The counteractive effect of PM2.5 exposure on high-fat diet-induced hepatic steatosis was mediated through PM2.5-induced hepatic autophagy. The findings from this study not only defined the effects and mechanisms of PM2.5 exposure in metabolic disorders, but also revealed the pleotrophic acts of an environmental stressor in a complex stress system relevant to public health.

NODDI and Tensor-Based Microstructural Indices as Predictors of Functional Connectivity.

In Diffusion Weighted MR Imaging (DWI), the signal is affected by the biophysical properties of neuronal cells and their relative placement, as well as extra-cellular tissue compartments. Typically, microstructural indices, such as fractional anisotropy (FA) and mean diffusivity (MD), are based on a tensor model that cannot disentangle the influence of these parameters. Recently, Neurite Orientation Dispersion and Density Imaging (NODDI) has exploited multi-shell acquisition protocols to model the diffusion signal as the contribution of three tissue compartments. NODDI microstructural indices, such as intra-cellular volume fraction (ICVF) and orientation dispersion index (ODI) are directly related to neuronal density and orientation dispersion, respectively. One way of examining the neurophysiological role of these microstructural indices across neuronal fibres is to look into how they relate to brain function. Here we exploit a statistical framework based on sparse Canonical Correlation Analysis (sCCA) and randomised Lasso to identify structural connections that are highly correlated with resting-state functional connectivity measured with simultaneous EEG-fMRI. Our results reveal distinct structural fingerprints for each microstructural index that also reflect their inter-relationships.