Glutamine prevents high-fat diet-induced hepatic lipid accumulation in mice by modulating lipolysis and oxidative stress.

Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment.

Multiple Thyroglossal Duct Cysts: Clinical Experience and Literature Review.

Thyroglossal duct cysts (TDCs) are generally single cyst, multiple TDCs are rare. We describe a case of multiple TDCs, discuss its characteristic features and management, and provide a review of the literature, to improve clinical diagnosis and treatment. We report an extremely rare case of multiple TDCs containing five cysts, together with a review of the relevant English medical literature. To the best of our knowledge, this is the first reported case of TDCs containing more than three cysts in the anterior cervical region. The five cysts were completely excised in a Sistrunk operation. Histological examination of the cystic lesions revealed TDCs. The patient recovered well and no recurrence was found during the 6-year of follow-up. Multiple TDCs are extremely rare, and may be misdiagnosed as a single cyst. Clinicians should be aware of the possibility of multiple thyroglossal duct cysts. Adequate preoperative radiological examinations should be performed, and careful interpretation of the CT or MRI scans is important to diagnosis and surgery.

Photo-crosslinked bioactive BG/BMSCs@GelMA hydrogels for bone-defect repairs.

The clinical treatments of bone defects remain a challenge. Hydrogels containing bone marrow mesenchymal stem cells (BMSCs) are extensively used to bone regeneration because of excellent biocompatibility and hydrophilicity. However, the insufficient osteo-induction capacity of the BMSC-loaded hydrogels limits their clinical applications. In this study, bio-active glass (BG) and BMSCs were combined with gelatin methacryloyl (GelMA) to fabricate composite hydrogels via photo-crosslinking, and the regulation of bone regeneration was investigated. In vitro experiments showed that the BG/BMSCs@GelMA hydrogel had excellent cytocompatibility and promoted osteogenic differentiation in BMSCs. Furthermore, the BG/BMSCs@GelMA hydrogel was injected into critical-sized calvarial defects, and the results further confirmed its excellent angiogenetic and bone regeneration capacity. In addition, BG/BMSCs@GelMA promoted the polarization of macrophages towards the M2 phenotype. In summary, this novel composite hydrogel demonstrated remarkable potential for application in bone regeneration due to its immunomodulatory, excellent angiogenetic as well as osteo-induction capacity.

Serine active site containing protein 1 depletion alters lipid metabolism and protects against high fat diet-induced obesity in mice.

OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.

SERAC1 is a component of the mitochondrial serine transporter complex required for the maintenance of mitochondrial DNA.

SERAC1 deficiency is associated with the mitochondrial 3-methylglutaconic aciduria with deafness, (hepatopathy), encephalopathy, and Leigh-like disease [MEGD(H)EL] syndrome, but the role of SERAC1 in mitochondrial physiology remains unknown. Here, we generated Serac1-/- mice that mimic the major diagnostic clinical and biochemical phenotypes of the MEGD(H)EL syndrome. We found that SERAC1 localizes to the outer mitochondrial membrane and is a protein component of the one-carbon cycle. By interacting with the mitochondrial serine transporter protein SFXN1, SERAC1 facilitated and was required for SFXN1-mediated serine transport from the cytosol to the mitochondria. Loss of SERAC1 impaired the one-carbon cycle and disrupted the balance of the nucleotide pool, which led to primary mitochondrial DNA (mtDNA) depletion in mice, HEK293T cells, and patient-derived immortalized lymphocyte cells due to insufficient supply of nucleotides. Moreover, both in vitro and in vivo supplementation of nucleosides/nucleotides restored mtDNA content and mitochondrial function. Collectively, our findings suggest that MEGD(H)EL syndrome shares both clinical and molecular features with the mtDNA depletion syndrome, and nucleotide supplementation may be an effective therapeutic strategy for MEGD(H)EL syndrome.

Enhanced Field Emission of Single-Wall Carbon Nanotube Cathode Prepared by Screen Printing with a Silver Paste Buffer Layer.

A high emission current with relatively low operating voltage is critical for field emission cathodes in vacuum electronic devices (VEDs). This paper studied the field emission performance of single-wall carbon nanotube (SWCNT) cold cathodes prepared by screen printing with a silver paste buffer layer. The buffer layer can both enforce the adhesion between the SWCNTs and substrate, and decrease their contact resistance, so as to increase emission current. Compared with paste mixing CNTs and screen printed cathodes, the buffer layer can avoid excessive wrapping of CNTs in the silver slurry and increase effective emission area to reduce the operating voltage. The experimental results show that the turn-on field of the screen-printed SWCNT cathodes is 0.9 V/µm, which is lower than that of electrophoretic SWCNT cathodes at 2.0 V/µm. Meanwhile, the maximum emission current of the screen-printed SWCNT cathodes reaches 5.55 mA at DC mode and reaches 10.4 mA at pulse mode, which is an order magnitude higher than that of electrophoretic SWCNTs emitters. This study also shows the application insight of small or medium-power VEDs.

Synthesis of Single-Crystal Graphene on Copper Foils Using a Low-Nucleation-Density Region in a Quartz Boat.

The nucleation of graphene at different locations in the quartz boat was studied, and the lowest nucleation density of graphene in the quartz boat was found. The nucleation density of graphene is the lowest at the bottom of the quartz boat near the gas inlet side. Based on the above results, a simple and reproducible way is proposed to significantly suppress the nucleation density of graphene on the copper foil during the chemical vapor deposition process. Placing the copper foil with an area of 1.3 cm × 1 cm in the middle of the bottom of the quartz boat or further back, and placing two copper pockets in front of the copper foil, an ultra-low nucleation density of ~42 nucleus/cm2 was achieved on the back of the copper foil. Single-crystal monolayer graphene with a lateral size of 800 µm can be grown on the back of copper foils after 60 min of growth. Raman spectroscopy revealed the single-crystal graphene to be in uniform monolayers with a low D-band intensity.

Biallelic Mutations in ACACA Cause a Disruption in Lipid Homeostasis That Is Associated With Global Developmental Delay, Microcephaly, and Dysmorphic Facial Features.

OBJECTIVE: We proposed that the deficit of ACC1 is the cause of patient symptoms including global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. We evaluated the possible disease-causing role of the ACACA gene in developmental delay and investigated the pathogenesis of ACC1 deficiency. METHODS: A patient who presented with global developmental delay with unknown cause was recruited. Detailed medical records were collected and reviewed. Whole exome sequencing found two variants of ACACA with unknown significance. ACC1 mRNA expression level, protein expression level, and enzyme activity level were detected in patient-derived cells. Lipidomic analysis, and in vitro functional studies including cell proliferation, apoptosis, and the migratory ability of patient-derived cells were evaluated to investigate the possible pathogenic mechanism of ACC1 deficiency. RNAi-induced ACC1 deficiency fibroblasts were established to assess the causative role of ACC1 deficit in cell migratory disability in patient-derived cells. Palmitate supplementation assays were performed to assess the effect of palmitic acid on ACC1 deficiency-induced cell motility deficit. RESULTS: The patient presented with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. A decreased level of ACC1 and ACC1 enzyme activity were detected in patient-derived lymphocytes. Lipidomic profiles revealed a disruption in the lipid homeostasis of the patient-derived cell lines. In vitro functional studies revealed a deficit of cell motility in patient-derived cells and the phenotype was further recapitulated in ACC1-knockdown (KD) fibroblasts. The cell motility deficit in both patient-derived cells and ACC1-KD were attenuated by palmitate. CONCLUSION: We report an individual with biallelic mutations in ACACA, presenting global development delay. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.

Recent Progress in the Development of Graphene Detector for Terahertz Detection.

Terahertz waves are expected to be used in next-generation communications, detection, and other fields due to their unique characteristics. As a basic part of the terahertz application system, the terahertz detector plays a key role in terahertz technology. Due to the two-dimensional structure, graphene has unique characteristics features, such as exceptionally high electron mobility, zero band-gap, and frequency-independent spectral absorption, particularly in the terahertz region, making it a suitable material for terahertz detectors. In this review, the recent progress of graphene terahertz detectors related to photovoltaic effect (PV), photothermoelectric effect (PTE), bolometric effect, and plasma wave resonance are introduced and discussed.

Switchable and Scalable Heteroarylation of Primary Amines with 2-Chlorobenzothiazoles under Transition-Metal-Free and Solvent-Free Conditions.

2-Aminobenzothiazoles comprise a valuable structural motif, which prevails in versatile natural products and biologically active compounds. Herein, a switchable and scalable C-N coupling protocol was developed for the synthesis of these compounds from 2-chlorobenzothiazoles and primary amines. Gratifyingly, this protocol was achieved under transition-metal-free and solvent-free conditions. Moreover, introducing an appropriate amount of NaH completely switched the selectivity from mono- toward di-heteroarylation, and further investigations provided a rationale for this new finding. Furthermore, gram-scale synthesis of representative products 3a and 4a was realized by applying operationally simple and glovebox-free procedures, which revealed the practical usefulness of this work. Finally, evaluation of the quantitative green metrics provided evidence that our protocol was superior over the literature ones in terms of green chemistry and sustainability.

Effect of Back-Gate Voltage on the High-Frequency Performance of Dual-Gate MoS2 Transistors.

As an atomically thin semiconductor, 2D molybdenum disulfide (MoS2) has demonstrated great potential in realizing next-generation logic circuits, radio-frequency (RF) devices and flexible electronics. Although various methods have been performed to improve the high-frequency characteristics of MoS2 RF transistors, the impact of the back-gate bias on dual-gate MoS2 RF transistors is still unexplored. In this work, we study the effect of back-gate control on the static and RF performance metrics of MoS2 high-frequency transistors. By using high-quality chemical vapor deposited bilayer MoS2 as channel material, high-performance top-gate transistors with on/off ratio of 107 and on-current up to 179 µA/µm at room temperature were realized. With the back-gate modulation, the source and drain contact resistances decrease to 1.99 kΩ∙µm at Vbg = 3 V, and the corresponding on-current increases to 278 µA/µm. Furthermore, both cut-off frequency and maximum oscillation frequency improves as the back-gate voltage increases to 3 V. In addition, a maximum intrinsic fmax of 29.7 GHz was achieved, which is as high as 2.1 times the fmax without the back-gate bias. This work provides significant insights into the influence of back-gate voltage on MoS2 RF transistors and presents the potential of dual-gate MoS2 RF transistors for future high-frequency applications.

High-Performance CVD Bilayer MoS2 Radio Frequency Transistors and Gigahertz Mixers for Flexible Nanoelectronics.

Two-dimensional (2D) MoS2 have attracted tremendous attention due to their potential applications in future flexible high-frequency electronics. Bilayer MoS2 exhibits the advantages of carrier mobility when compared with monolayer mobility, thus making the former more suitable for use in future flexible high-frequency electronics. However, there are fewer systematical studies of chemical vapor deposition (CVD) bilayer MoS2 radiofrequency (RF) transistors on flexible polyimide substrates. In this work, CVD bilayer MoS2 RF transistors on flexible substrates with different gate lengths and gigahertz flexible frequency mixers were constructed and systematically studied. The extrinsic cutoff frequency (fT) and maximum oscillation frequency (fmax) increased with reducing gate lengths. From transistors with a gate length of 0.3 µm, we demonstrated an extrinsic fT of 4 GHz and fmax of 10 GHz. Furthermore, statistical analysis of 14 flexible MoS2 RF transistors is presented in this work. The study of a flexible mixer demonstrates the dependence of conversion gain versus gate voltage, LO power and input signal frequency. These results present the potential of CVD bilayer MoS2 for future flexible high-frequency electronics.

Theoretical equilibration time is supported by measurement study of residence time at dilution sampling on fine particulate matter emissions from household biofuel burning.

Household biofuel burning contributes a large proportion of fine particulate matter (PM2.5), black carbon (BC), and organic carbon (OC) emissions in many parts of the world. Dilution sampling has been widely used to characterize PM2.5 emitted from biofuel burning. The residence time in the dilution chamber is a key parameter for accurate sampling. However, residence time has not yet been adequately characterized for biomass combustion. In this work, we investigated the effects of residence time of dilution sampling on PM2.5 emissions from a typical Chinese household stove burning typical biofuels including three major crop wastes and one type of wood. The filter based measurements indicated that the emission factors for PM2.5 and its main chemical components such as OC, EC, Cl-, and K+ did not vary with the residence time over the range of 1-80 s. Theoretical estimation of average time scale for achieving dynamic equilibrium (τs) between the gas and particle phase in the dilution sampling system was less than 1 s. Both the measurement study and theoretical simulations indicated that dilution sampling with a residence time of 1s can provide adequately reliable results for PM2.5 emissions from biofuel burning under the condition of these experiments. A simple way to estimate the equilibration time based on measured average PM2.5 concentration was proposed. Recommendations are provided for the residence time for dilution sampling of accurate measurements of PM2.5 emissions from biofuel burning.

Effect of the Pressure of Reaction Gases on the Growth of Single-Crystal Graphene on the Inner Surfaces of Copper Pockets.

Single-crystal graphene has attracted much attention due to its excellent electrical properties in recent years, and many growth methods have been proposed, including the copper pockets method. In the copper pockets method, a piece of copper foil is folded into a pocket and put into a chemical vapor deposition (CVD) system for the growth of graphene. The dynamic balance of evaporation and deposition of copper on the inner surfaces of the copper pockets avoids high surface roughness caused by the evaporation of copper in open space, such as the outer surfaces of copper pockets. Much lower partial pressure of methane in the copper pockets and lower surface roughness reduce the nucleation density of graphene and increase the size of single-crystal graphene. It is found that the growth pressure is closely related to the size of single-crystal graphene prepared by the copper pockets method; the higher the growth pressure, the larger the size of single-crystal graphene. It is also found that the growth pressure has an effect on the inner surface roughness of the copper pockets, but the effect is not significant. The main factor affecting the size of the single-crystal graphene is the change in the volume of the copper pockets caused by the change in the growth pressure, and the volume of the copper pockets determines the content of methane in the copper pockets. According to the above law, the size of single-crystal graphene prepared by the copper pockets method can be enlarged by increasing the growth pressure. The size of single-crystal graphene can be enlarged in a wide range as the growth pressure can be increased in a wide range. In our experiments, when the growth pressure reached 450 Pa, single-crystal graphene with a diameter of 450 µm was prepared.

Maximizing the Field Emission Performance of Graphene Arrays.

To design efficient and powerful field emission cathodes, the screening effect is of great importance and should be traded off between screening and emitter number. It has long been found that to achieve maximum emission efficiency in an array, neighboring emitters are at two or three times their height from each other. However, this is only true for one-dimensional emitters, such as carbon nanotubes, but for graphene, a two-dimensional material, it is different. In this work, we found that to achieve maximum emission efficiency in an array of graphene, the separation of the emitter is four times the height, and it is insensitive to the anode voltage and the distance between the cathode and the anode.

Identification of benign and malignant pulmonary nodules on chest CT using improved 3D U-Net deep learning framework.

PURPOSE: To accurately distinguish benign from malignant pulmonary nodules with CT based on partial structures of 3D U-Net integrated with Capsule Networks (CapNets) and provide a reference for the early diagnosis of lung cancer. METHOD: The dataset consisted of 1177 samples (benign/malignant: 414/763) from 997 patients provided by collaborating hospital. All nodules were biopsy or surgery proven, and pathologic results were regarded as the "golden standard". This study utilized partial U-Net to capture the low-level (edge, corner, etc.) information and CapNets to preserve high-level (semantic information) information of nodules. For CapNets, each capsule had a 4 × 4 matrix representing the pose and an activation probability representing the presence of an object. Furthermore, we chose accuracy (ACC), area under the curve (AUC), sensitivity (SE) and specificity (SP) to evaluate the generalization of the proposed architecture and compared its identification performance with 3D U-Net and experienced radiologists. RESULTS: The AUC of our architecture (0.84) was superior to that (0.81) of the original 3D U-Net (p = 0.04, DeLong's test). Moreover, ACC (84.5 %) and SE (92.9 %) of our model were clearly higher than radiologists' ACC (81.0 %) and SE (84.3 %) at the optimal operating point. However, SP (70 %) of our model was slightly lower than radiologists' SP (75 %), which might be the result of class imbalance with limited benign samples involved for algorithm training. CONCLUSIONS: Our architecture showed a high performance for identifying benign and malignant pulmonary nodules, indicating the improved model has a promising application in clinic.

Light Absorption Properties of Organic Aerosol from Wood Pyrolysis: Measurement Method Comparison and Radiative Implications.

Growing evidence indicates that organic aerosol (OA) is a significant absorber of solar radiation. Such absorptive OA is known as "brown carbon" (BrC). However, a formal analytical method for BrC is currently lacking although several methods have been applied to determine its absorption properties. Reported imaginary refractive index (kOA) values from various combustion sources span 2 orders of magnitude. Measurement methods are an important factor affecting this kOA variation. In this work, isolated OA from wood pyrolysis was used to compare four methods to determine absorbing properties of OA. The generated aerosol was lognormally distributed, spherical, and nearly pure organic matter. Optical closure was considered as the reference method. kOA calculated from the extract bulk light absorbance measurement was comparable to that determined by optical closure. kOA and mass absorption cross section obtained by online and offline filter-based transmission measurements were similar, but 3.5 to 5.0 times greater than those determined by optical closure. Absorption Ångström Exponents determined by the four methods were comparable and ranged from 6.1 to 6.8. A clear-sky radiative transfer model implied that using the optical parameters derived from different methods in the full climate model could produce different radiative impacts of primary OA emissions.

Sources of humic-like substances (HULIS) in PM2.5 in Beijing: Receptor modeling approach.

Recent work has identified the presence of humic-like substances (HULIS) in ambient fine particulate matter (PM2.5) in Beijing, China and that residential coal combustion as well as biomass burning are significant contributors to its presence. These results were based on the characterization of emissions from representative stoves and modeling of the aerosol with the Community Multiscale Air Quality (CMAQ) chemical transport model. The CMAQ source apportionment estimated that residential coal and biofuel burning and secondary aerosol formation were important annual sources of ambient HULIS, contributing 47.1%, 15.1%, and 38.9%, respectively. In this study, chemical composition data including concentrations of water-soluble organic carbon and HULIS across four seasons during 2012-2013 were analyzed with positive matrix factorization (PMF) to provide a complementary source apportionment. The PMF results indicate that the identified sources were Traffic, Biomass Burning, Nitrate/Sulfate, Incineration, Sulfate, Coal Combustion/Ammonium Chloride, Residential Coal/Biofuel Combustion, and Road Dust/Soil with mass contributions (fractions) to PM2.5 of 12.35 (10.4%), 8.70 (8.9%), 24.51 (22.4%), 5.64 (7.2%), 25.14 (24.5%), 7.10 (6.2%), 14.18 (15.4%), and 5.33 µg/m3 (5.0%), respectively. The contributions to the observed HULIS concentrations were 0.63 (10.9%), 0.38 (6.4%), 0.07 (1.7%), 0.00 (0%), 1.12 (28.8%), 0.00 (0%), 1.50 (52.2%), and 0.01 µg/m3 (0.3%), respectively. These PMF modeling results were in reasonable agreement with the CMAQ values supporting the attribution of significant amounts of primary HULIS to residential coal and biofuel combustion. Currently, efforts are underway in China to replace solid fuel combustion for heating and cooking with natural gas and electricity by 2020. Thus, future studies should be able to see substantial reductions in both PM2.5 and HULIS in the near term future.