The hedonic overdrive model best explains high-fat diet-induced obesity in C57BL/6 mice.

OBJECTIVE: High-fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models. METHODS: A total of 12 groups of 20 individually housed 12-week-old C57BL/6 male mice were exposed to 12 high-fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low-fat diet. RESULTS: After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high-fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline. CONCLUSIONS: The hedonic overdrive model fit the data best. The other two models were not supported.

NAFLDkb: A Knowledge Base and Platform for Drug Development against Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with a broad spectrum of histologic manifestations. The rapidly growing prevalence and the complex pathologic mechanisms of NAFLD pose great challenges for treatment development. Despite tremendous efforts devoted to drug development, there are no FDA-approved medicines yet. Here, we present NAFLDkb, a specialized knowledge base and platform for computer-aided drug design against NAFLD. With multiperspective information curated from diverse source materials and public databases, NAFLDkb presents the associations of drug-related entities as individual knowledge graphs. Practical drug discovery tools that facilitate the utilization and expansion of NAFLDkb have also been implemented in the web interface, including chemical structure search, drug-likeness screening, knowledge-based repositioning, and research article annotation. Moreover, case studies of a knowledge graph repositioning model and a generative neural network model are presented herein, where three repositioning drug candidates and 137 novel lead-like compounds were newly established as NAFLD pharmacotherapy options reusing data records and machine learning tools in NAFLDkb, suggesting its clinical reliability and great potential in identifying novel drug-disease associations of NAFLD and generating new insights to accelerate NAFLD drug development. NAFLDkb is freely accessible at https://www.biosino.org/nafldkb and will be updated periodically with the latest findings.

In Situ Gelled Covalent Organic Frameworks Electrolyte with Long-Range Interconnected Skeletons for Superior Ionic Conductivity.

Covalent organic frameworks (COFs) present an ideal platform for ion transport owing to their tunable and ordered nanochannels at the single-digit scale. However, achieving superior COF-based electrolytes remains challenging because of the mismatch between the intricate synthesis processes of COFs and the battery preparation environment, which makes it difficult to build continuous ion channels and low-impedance electrochemical interfaces for devices. Here, we present an in situ gelation method to produce COF gel electrolytes (CGEs) within liquid carbonate electrolyte, integrating COF synthesis with their applicability in batteries. This method leads to long-range interconnected and highly crystalline skeletons of COFs from a robust precoordination structure between lithium salts of liquid electrolyte and building blocks. By incorporating the lithium affinity groups in the COFs, the developed CGEs show a remarkable 3-fold enhancement in ionic conductivity, reaching up to 10.5 mS cm-1 compared to the corresponding liquid carbonate electrolytes. Furthermore, the CGEs exhibit a low activation energy of 0.068 eV, ensuring efficient ion transport, while demonstrating dendrite-free lithium deposition even after prolonged testing periods exceeding 1800 h. These CGEs exhibit excellent rate performance (reversible capacity up to 101 mAh g-1 at a current density of 3C, 1C = 170 mAh g-1) in Li-LiFePO4 coin cells and reversible cycling under extreme conditions (reversible capacity up to 158 mAh g-1 under folding state at 0.1C) in pouch cells. Importantly, our novel methodology extends beyond lithium-ion systems, as it can also be applied to the synthesis of CGEs utilizing potassium, magnesium, zinc, sodium, and calcium ions.

Synthesis of FeOOH/Zn(OH)2/CoS Ferromagnetic Nanocomposites and the Enhanced Mechanism of Magnetic Field for Their Electrochemical Performances.

The FeOOH/Zn(OH)2/CoS (FZC) nanocomposites are synthesized and show the outstanding electrochemical properties in both supercapacitor and catalytic hydrogen production. The specific area capacitance reaches 17.04 F cm-2, which is more than ten times higher than that of FeOOH/Zn(OH)2 (FZ) substrate: 1.58 F cm-2). FZC nanocomposites also exhibit the excellent cycling stability with an initial capacity retention rate of 93.6% after 10 000 long-term cycles. The electrolytic cell (FZC//FZC) assembled with FZC as both anode and cathode in the UOR (urea oxidation reaction)|| HER (hydrogen evolution reaction) coupled system requires a cell voltage of only 1.453 V to drive a current density of 10 mA cm-2. Especially, the electrochemical performances of FZC nanocomposites are enhanced in magnetic field, and the mechanism is proposed based on Stern double layer model at electrode-electrolyte interface (EEI). More electrolyte ions reach the surface of FZC electrode material under Kelvin force, moreover, the warburg impedance of FZC nanocomposites decrease under magnetic field action, which results in the enhanced behaviors for both the energy storage and urea oxidation reaction .

Maternal High Fat Diet in Lactation Impacts Hypothalamic Neurogenesis and Neurotrophic Development, Leading to Later Life Susceptibility to Obesity in Male but Not Female Mice.

Early life nutrition can reprogram development and exert long-term consequences on body weight regulation. In mice, maternal high-fat diet (HFD) during lactation predisposed male but not female offspring to diet-induced obesity when adult. Molecular and cellular changes in the hypothalamus at important time points are examined in the early postnatal life in relation to maternal diet and demonstrated sex-differential hypothalamic reprogramming. Maternal HFD in lactation decreased the neurotropic development of neurons formed at the embryo stage (e12.5) and impaired early postnatal neurogenesis in the hypothalamic regions of both males and females. Males show a larger increased ratio of Neuropeptide Y (NPY) to Pro-opiomelanocortin (POMC) neurons in early postnatal neurogenesis, in response to maternal HFD, setting an obese tone for male offspring. These data provide insights into the mechanisms by which hypothalamic reprograming by early life overnutrition contributes to the sex-dependent susceptibility to obesity in adult life in mice.

On the passive shimming of a 7 T whole-body MRI superconducting magnet: Implementation with minimized ferromagnetic materials usage and operable magnetic force control.

BACKGROUND: Magnetic field shimming of the magnet is a routine practice in a magnetic resonance imaging (MRI) system. For clinically-used 1.5 T or 3 T MRI superconducting magnets, it is generally straightforward to achieve desired magnetic field uniformity with the passive shim technique. In comparison, superconducting shims with higher shimming efficiency are usually introduced in combination with passive shimming to satisfy the higher magnetic field uniformity requirement for ultrahigh field magnets (≥7 Tesla). However, superconducting shim usually involves a complex winding structure and low-temperature environment, bringing considerable engineering challenges and extra costs in practice. PURPOSE: In this study, we aimed to improve the passive shimming method that can incorporate the unique electromagnetic properties of ultrahigh-field MRI magnets and is thus more effective for field corrections at 7T and above. METHODS: In this work, we propose a dedicated passive shimming strategy for a 7 T whole-body MRI superconducting magnet. In this method, the iron usage and magnetic force due to the iron-field interaction are strictly managed to ensure a shim tray insert is operable by manpower (without specially designed tools). RESULTS: To validate the proposed shimming strategy, a shimming experiment was implemented on a 7 T/800 mm superconducting magnet. Alternating with the odd and even shim trays in our two-round operation, the magnetic field inhomogeneity was successfully corrected from 85.36 to 7.91 ppm, achieving the magnetic field quality elevation of more than one order of magnitude. CONCLUSION: The experimental results indicated that the proposed electromagnetic technology is expected to be effective for developing ultrahigh-field MRI instruments.

Systematic Microbiome Dysbiosis Is Associated with IgA Nephropathy.

IgA nephropathy (IgAN) is reportedly associated with microbial dysbiosis. However, the microbiome dysregulation of IgAN patients across multiple niches remains unclear. To gain a systematic understanding of microbial dysbiosis, we conducted large-scale 16S rRNA gene sequencing in IgAN patients and healthy volunteers across 1,732 oral, pharynx, gut, and urine samples. We observed a niche-specific increase of several opportunistic pathogens, including Bergeyella and Capnocytophaga in the oral and pharynx, whereas some beneficial commensals decreased in IgAN patients. Similar alterations were also observed in the early versus advanced stage of chronic kidney disease (CKD) progression. Moreover, Bergeyella, Capnocytophaga, and Comamonas in the oral and pharynx were positively associated with creatinine and urea, indicating renal lesions. Random forest classifiers were developed by using the microbial abundance to predict IgAN, achieving an optimal accuracy of 0.879 in the discovery phase and 0.780 in the validation phase. IMPORTANCE This study provides microbial profiles of IgAN across multiple niches and underlines the potential of these biomarkers as promising, noninvasive tools with which to differentiate IgAN patients for clinical applications.

High dietary protein and fat contents exacerbate hepatic senescence and SASP in mice.

Dietary choices have a profound impact on the aging process. In addition to the total amount of energy intake, macronutrient composition influences both health and lifespan. However, the exact mechanisms by which dietary macronutrients influence onset and progression of age-associated features remain poorly understood. Cellular senescence is a state of stable growth arrest characterized by the secretion of numerous bioactive molecules with pro-inflammatory properties. Accumulation of senescent cells is considered one of the basic mechanisms of aging and an important contributor to chronic inflammation and tissue degeneration. Whether dietary macronutrients affect the accumulation and the phenotype of senescent cells with age is still unknown. Here, we show that feeding on diets with varying ratios of dietary macronutrients for 3 months has a significant effect on different senescence-associated markers in the mouse liver. High protein intake is associated with higher expression levels of the two classical senescence-associated growth arrest genes, p21 and p16. Furthermore, the expression of many pro-inflammatory secretory markers was increased in diets enriched in protein and further enhanced by increases in fat content. These results provide preliminary evidence that dietary macronutrients have a significant influence on senescence markers and merit further investigation.

Corrigendum: Increased variation in body weight and food intake is related to increased dietary fat but not increased carbohydrate or protein in mice.

[This corrects the article DOI: 10.3389/fnut.2022.835536.].

Modeling, analysis, and demonstration of a carrier-injection electro-absorption modulator at 2 µm on Ge-on-Si platform.

In this paper, a carrier-injection electro-absorption modulator (EAM) at 2 µm is demonstrated on Ge-on-Si platform. The EAM shows a compact size and high modulation efficiency due to the strong free-carrier electroabsorption (FCEA) effect in Ge. A modulation depth of 40 dB can be obtained under the injection current of only 420 mA. Small-signal frequency response measurement is performed and a small-signal equivalent circuit model is proposed. Based on reflection coefficients and equivalent circuit, the frequency response of carrier-injection EAM is discussed in detail. The 500 Mbps open eye diagram verifies the data-processing capacity of our EAM at 2 µm wavelength for its application in biological, chemical molecular detection, and infrared imaging systems.

GeSn resonance cavity enhanced photodetector with gold bottom reflector for the L band optical communication.

In this work, GeSn resonant cavity enhanced (RCE) p-i-n photodetectors (PDs) with 3.7% Sn content in a GeSn layer were fabricated on a silicon on insulator (SOI) substrate. The gold (Au) layer and the deposited SiO2 layer constitute the bottom reflector and top reflector of the RCE detectors, respectively. The GeSn RCE PD has three resonant peaks and its responsivity is improved about 4.5 times at 1630 nm, compared with GeSn PDs without a gold bottom mirror. The cutoff wavelength of GeSn RCE PDs is up to 1820 nm, while it is only 1730 nm for GeSn PDs without a gold reflector. The responsivity of RCE PDs at 1630 nm reaches 0.126 A/W and 3-dB bandwidth at about 36 GHz is achieved. These results indicate that the RCE structure is an effective approach for enhancing the GeSn PD performance operated at the L band.

High-performance waveguide-coupled lateral Ge/Si avalanche photodetector.

A high-performance waveguide-coupled lateral avalanche photodetector (APD) is experimentally demonstrated without silicon epitaxy and charge layer ion implantation. At the wavelength of 1550 nm, it shows a high responsivity of 48 A/W and a gain-bandwidth product (GBP) of 360 GHz. Wide-open eye diagrams at 25 Gbps can be observed at various avalanche gains. These outstanding performances indicate the proposed APD has great potential in high-speed optical transceivers for optical links.

In vivo animal study of the magnetic navigation system for capsule endoscope manipulation within the esophagus, stomach, and colorectum.

BACKGROUND/PURPOSES: Magnetic navigation capsule endoscopy (MNCE) is considered to be an important means to realize the controllable and precise examination of capsule endoscopy (CE) in the unstructured gastrointestinal (GI) tract. For the current magnetic navigation system (MNS), due to the limitation of workspace, driving force, and control method of the CE, only clinical application in the stomach has been realized, whereas the examination of other parts of the GI tract is still in the experimental stage. More preclinical studies are needed to achieve the multisite examination of the GI tract. METHODS: Based on the MNS (Supiee) developed in the laboratory, an X-ray imaging system with magnetic shielding and a commercial CE are integrated to form the MNCE system. Then, in vivo GI tract experiments with a porcine model are performed to verify the clinical feasibility and safety of this system. Moreover, the effects of different control modes on the efficiency and effect of GI tract examination are studied. RESULTS: Animal experiments demonstrate that with the MNCE system, it is convenient to achieve steering control in any direction and multiple reciprocating movements of CE in the GI tract. Benefiting from the flexibility of the three basic control modes, the achieved swing movement pattern of CE can effectively reduce the inspection time. It is demonstrated that the esophageal examination time can be reduced from 13.2 to 9.2 min with a maximum movement speed of 5 mm/s. CONCLUSION: In this paper, the feasibility, safety, and efficacy of the MNCE system for a one-stop examination of the in vivo GI tract (esophagus, stomach, and colorectum) is first demonstrated. In addition, complex movement patterns of CE such as the swinging are proved to effectively improve examination efficiency and disease detection rates. This study is crucial for the clinical application of the MNCE system.

The synthesis of CoS/MnCo2O4-MnO2 nanocomposites for supercapacitors and energy-saving H2 production.

In this study, CoS/MnCo2O4-MnO2 (CMM) nanocomposites were synthesized by hydrothermal and then electrochemical deposition. Their electrochemical properties were systematically investigated for supercapacitors and energy-saving H2 production. As an electrode material for supercapacitor, CMM demonstrates a specific capacitance of 2320F g-1 at 1 A/g, and maintains a specific capacitance of 1216F g-1 at 10 A/g. It also shows 72.8 % capacitance retention after 8000 cycles. The aqueous asymmetric supercapacitor exhibited high energy storage capacity (887.86F g-1 specific capacitance at a current density of 1 A/g), good rate performance and cycling stability. Besides, CMM shows outstanding urea oxidation reaction(UOR) and glycol oxidation reaction (MOR) performances for H2 production. Compared to oxygen evolution reaction (OER) (1.635 V) at 20 mA cm-2, the potentials were reduced by 213 mV for UOR and 233 mV for MOR, respectively. Therefore, this study shows the promising practical applications of CMM nanocomposites for energy storage and energy-saving H2 production.

High-speed and high-power germanium photodetector based on a trapezoidal absorber.

A compact high-power germanium photodetector (Ge PD) is experimentally demonstrated by re-engineering light distribution in the absorber. Compared with a conventional Ge PD, the proposed structure shows a DC saturation photocurrent improved by 28.9% and 3 dB bandwidth as high as 49.5 GHz at 0.1 mA. Under the same photocurrent of 10.5 mA, the proposed Ge PD shows a 3 dB bandwidth of 11.1 GHz, which is almost double the conventional Ge PD (5.6 GHz). The 25 Gb/s eye-diagram measurement verifies the improved power handling capability. The compact size and manufacturing simplicity of this structure will enable new applications for integrated silicon photonics.

A fully automated sex estimation for proximal femur X-ray images through deep learning detection and classification.

PURPOSE: To develop a fully automated deep learning pipeline using digital radiographs to detect the proximal femur region for accurate automated sex estimation. METHOD: Radiograph predictive features from 2122 Chinese Han clinical pelvic with ages ranging from 18 to 26 years were collected retrospectively to train and test the sex prediction model using deep machine learning's convolutional neural networks (CNN). Model performance was assessed using a Chinese Han population with 361 samples and a white population with 50 samples. The average accuracy of the sex estimation of the two test datasets was determined. RESULTS: For the Chinese Han population test dataset, the sex estimation accuracy was 94.6% (males: 93.9% and females: 94.7%). For the white population samples, the accuracy of sex estimation was 82.9% (males: 80.9% and females: 88.6%). The accuracy of CNN tested in the Chinese population was significantly higher than that tested in the White population (p < 0.001) CONCLUSIONS: The model based on convolutional neural networks has an accuracy similar to that of current state-of-the-art mathematical functions using manually extracted features for the Chinese Han population samples, proving to be a reliable choice for the human sex estimation.

Increased Variation in Body Weight and Food Intake Is Related to Increased Dietary Fat but Not Increased Carbohydrate or Protein in Mice.

A variety of inbred mouse strains have been used for research in metabolic disorders. Despite being inbred, they display large inter-individual variability for many traits like food intake and body weight. However, the relationship between dietary macronutrients and inter-individual variation in body weight and food intake of different mouse strains is still unclear. We investigated the association between macronutrient content of the diet and variations in food intake, body composition, and glucose tolerance by exposing five different mouse strains (C57BL/6, BALB/c, C3H, DBA/2, and FVB) to 24 different diets with variable protein, fat, and carbohydrate contents. We found only increasing dietary fat, but not protein or carbohydrate had a significant association (positive) with variation in both food intake and body weight. The highest variation in both body weight and food intake occurred with 50% dietary fat. However, there were no significant relationships between the variation in fat and lean mass with dietary protein, fat, or carbohydrate levels. In addition, none of the dietary macronutrients had significant impacts on the variation in glucose tolerance ability in C57BL/6 mice. In conclusion, the variations in food intake and body weight changes increased with the elevation of dietary fat levels.

A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes.

The giant panda (Ailuropoda melanoleuca) is an iconic bear native to China, famous for eating almost exclusively bamboo. This unusual dietary behavior for a carnivore is enabled by several key adaptations including low physical activity, reduced organ sizes and hypothyroidism leading to lowered energy expenditure. These adaptive phenotypes have been hypothesized to arise from a panda-unique single-nucleotide mutation in the dual-oxidase 2 (DUOX2) gene, involved in thyroid hormone synthesis. To test this hypothesis, we created genome-edited mice carrying the same point mutation as the panda and investigated its effect on metabolic phenotype. Homozygous mice were 27% smaller than heterozygous and wild-type ones, had 13% lower body mass-adjusted food intake, 55% decreased physical activity, lower mass of kidneys (11%) and brain (5%), lower serum thyroxine (T4: 36%), decreased absolute (12%) and mass-adjusted (5%) daily energy expenditure, and altered gut microbiota. Supplementation with T4 reversed the effects of the mutation. This work uses a state-of-the-art genome editing approach to demonstrate the link between a single-nucleotide mutation in a key endocrine-related gene and profound adaptive changes in the metabolic phenotype, with great importance in ecology and evolution.

Effects of dietary macronutrients on the hepatic transcriptome and serum metabolome in mice.

Dietary macronutrient composition influences both hepatic function and aging. Previous work suggested that longevity and hepatic gene expression levels were highly responsive to dietary protein, but almost unaffected by other macronutrients. In contrast, we found expression of 4005, 4232, and 4292 genes in the livers of mice were significantly associated with changes in dietary protein (5%-30%), fat (20%-60%), and carbohydrate (10%-75%), respectively. More genes in aging-related pathways (notably mTOR, IGF-1, and NF-kappaB) had significant correlations with dietary fat intake than protein and carbohydrate intake, and the pattern of gene expression changes in relation to dietary fat intake was in the opposite direction to the effect of graded levels of caloric restriction consistent with dietary fat having a negative impact on aging. We found 732, 808, and 995 serum metabolites were significantly correlated with dietary protein (5%-30%), fat (8.3%-80%), and carbohydrate (10%-80%) contents, respectively. Metabolomics pathway analysis revealed sphingosine-1-phosphate signaling was the significantly affected pathway by dietary fat content which has also been identified as significant changed metabolic pathway in the previous caloric restriction study. Our results suggest dietary fat has major impact on aging-related gene and metabolic pathways compared with other macronutrients.