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 .

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.

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.

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.

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.

High-Voltage-Tolerant Covalent Organic Framework Electrolyte with Holistically Oriented Channels for Solid-State Lithium Metal Batteries with Nickel-Rich Cathodes.

By introducing lithiophilic groups and electrochemically stable quinolyl aromatic ring linkages, we prepared covalent organic frameworks (COFs) exhibiting a large band gap with an ultralow HOMO value (-6.2 eV under vacuum) and oxidative stability up to 5.6 V (versus Li+ /Li) as solid-state electrolytes (SSEs). The obtained flexible COF SSE thin films showed a holistically oriented arrangement along the (001) facet with remarkable ionic conductivity up to 1.5×10-4  S cm-1 at 60 °C and excellent mechanical strength with a high Young's modulus of 10.5 GPa. Molecular dynamic simulations showed that lithium ions are transmitted in this COF SSE by directional hopping paths with fast drift velocity. The COF SSE film was used to assemble all-solid-state lithium metal batteries with nickel-rich cathodes (NMC811). The batteries demonstrated stable cycling performance over 400 cycles, high coulombic efficiency (>99 %), and could also withstand abuse tests, such as folding.

Mpg-C3N4-ZIF-8 composites for the degradation of tetracycline hydrochloride using visible light.

It was found that mesoporous graphite carbon nitride (mpg-C3N4) prepared using melamine as the precursor and ammonium chloride as the bubble template, has good photocatalytic activity under visible light irradiation. In order to improve the photocatalytic performance of mpg-C3N4, it was combined with metal-organic framework ZIF-8. Taking tetracycline hydrochloride (TC) solution as a model pollutant, the photocatalytic activity of composites was studied to select the optimal composite ratio and pH value. The initial concentration of hydrogen peroxide and active oxidation species were also investigated. The results showed that when the loading of ZIF-8 was 40 wt%, the removal efficiency was the best and 74.8% of TC could be removed. The degradation efficiency of TC was negatively affected under extreme pH conditions, but the composite photocatalyst mpg-C3N4-ZIF-8 had a relatively higher degradation efficiency on TC at mild pH values (4-8). The removal efficiency was the best at pH 8, and 75.1% of TC could be removed; the adsorption capacity was 430.7 mg·g-1 and the photodegradation capacity was 548.6 mg·g-1. The order of active species affecting the photocatalytic degradation of TC by mpg-C3N4-ZIF-8 was hole > superoxide radical > hydroxyl radical.

A Label-Free Fluorescent AND Logic Gate Aptasensor for Sensitive ATP Detection.

In this study, a label-free fluorescent, enzyme-free, simple, highly sensitive AND logic gate aptasensor was developed for the detection of adenosine triphosphate (ATP). Double-stranded deoxyribonucleic acid (DNA) with cohesive ends was attached to graphene oxide (GO) to form an aptasensor probe. ATP and single-stranded DNA were used as input signals. Fluorescence intensity of PicoGreen dye was used as an output signal. The biosensor-related performances, including the logic gate construction, reaction time, linearity, sensitivity, and specificity, were investigated and the results showed that an AND logic gate was successfully constructed. The ATP detection range was found to be 20 to 400 nM (R² = 0.9943) with limit of detection (LOD) of 142.6 pM, and the sensitivity range was 1.846 × 106 to 2.988 × 106 M-1. This method for the detection of ATP has the characteristics of being simple, low cost, and highly sensitive.

A Label-Free Fluorescent DNA Calculator Based on Gold Nanoparticles for Sensitive Detection of ATP.

Herein we described a deoxyribonucleic acid (DNA) calculator for sensitive detection of the determination of adenosine triphosphate (ATP) using gold nanoparticles (GNP) and PicoGreen fluorescence dye as signal transducer, and ATP and single-stranded DNA (DNA-M') as activators. The calculator-related performances including linearity, reaction time, logic gate, and selectivity were investigated, respectively. The results revealed that this oligonucleotide sensor was highly sensitive and selective. The detection range was 50⁻500 nmol/L (R² = 0.99391) and the detection limit was 46.5 nmol/L. The AND DNA calculator was successfully used for the ATP detection in human urine. Compared with other methods, this DNA calculator has the characteristics of being label-free, non-enzymic, simple, and highly sensitive.

No seasonal variation in physical activity of Han Chinese living in Beijing.

BACKGROUND: Physical activity (PA) is widely acknowledged to be beneficial to health and wellbeing, and is potentially influenced by a variety of environmental factors such as ambient temperature, weather conditions and air pollution levels. Since these factors vary seasonally, physical activity participation may also respond seasonally. Current population studies to profile physical activity often sample individuals only once, and this may result in biased estimates if there is strong seasonal variation. METHODS: We conducted a study of 40 Han Chinese adults living in Beijing using GT3X accelerometers. We measured PA levels every two months across a complete year, while simultaneously monitoring ambient temperatures and air pollution levels. Average hourly vector magnitude (VM) and percentage time spent at each PA intensity (sedentary to light, moderate, vigorous and very vigorous) were measured. General Linear models (GLMs) were used to explore the effects of time of day, temperature and PM 2.5 levels on PA. One way ANOVA was used to test whether there were seasonal differences in body weight and body fatness. RESULTS: The main factors influencing activity levels were the time of day and individual characteristics including age and body fatness, but there was no significant difference between the months. In addition, there was no significant impact of either ambient temperature or air pollution levels (PM2.5). There were also no significant differences over the year in the time spent at sedentary-light, moderate and very vigorous PA levels, but for vigorous PA level which occupied less than 0.5% daily physical activity, both month and individual were significant factors. CONCLUSIONS: The relatively constant pattern of urban daily life, independent of time of year, may override the potential impacts of environmental factors that would be anticipated to impact PA levels. These subjects did not specifically avoid activity coincident with elevated air pollution levels (PM2.5). Single week long measurements of physical activity could provide a representative measurement of the physical active levels in this population.

Systematic prediction of pharmacodynamic drug-drug interactions through protein-protein-interaction network.

Identifying drug-drug interactions (DDIs) is a major challenge in drug development. Previous attempts have established formal approaches for pharmacokinetic (PK) DDIs, but there is not a feasible solution for pharmacodynamic (PD) DDIs because the endpoint is often a serious adverse event rather than a measurable change in drug concentration. Here, we developed a metric "S-score" that measures the strength of network connection between drug targets to predict PD DDIs. Utilizing known PD DDIs as golden standard positives (GSPs), we observed a significant correlation between S-score and the likelihood a PD DDI occurs. Our prediction was robust and surpassed existing methods as validated by two independent GSPs. Analysis of clinical side effect data suggested that the drugs having predicted DDIs have similar side effects. We further incorporated this clinical side effects evidence with S-score to increase the prediction specificity and sensitivity through a Bayesian probabilistic model. We have predicted 9,626 potential PD DDIs at the accuracy of 82% and the recall of 62%. Importantly, our algorithm provided opportunities for better understanding the potential molecular mechanisms or physiological effects underlying DDIs, as illustrated by the case studies.

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.

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.

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.

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.

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.

Protective effects of 5-heptadecylresorcinol against adipocyte mitochondrial dysfunction through upregulation of Sirt3-mediated autophagy.

5-heptadecylresorcinol (AR-C17), a natural phenolic lipid component and biomarker of whole grain rye consumption, has been widely reported to confer multiple health benefits. However, the molecular mechanism underlying its potential protective effect against obesity and other related diseases is still unclear. In the present study, we investigated the potential role and mechanism of AR-C17 in mitigating mitochondrial dysfunction and lipid disturbance of adipocytes both in vitro and in vivo. AR-C17 treatment alleviated inflammatory conditioned medium (CM) induced adipocyte lipolysis and mitochondrial damage, accompanied by attenuated mitochondrial reactive oxygen species production and mitochondrial membrane depolarization. Moreover, we observed improved mitochondrial content, upregulated expression of mitochondrial biogenesis related transcription factors and increased oxygen consumption rate. Meanwhile, AR-C17 attenuated CM-mediated adipocyte mitochondria dysfunction by promoting autophagy, followed by the enhancement of autophagic flux and related protein expression, such as LC3B-II/I, Beclin1, Atg5, PINK1 and Parkin. Further analysis showed that the protective effect of AR-C17 against mitochondrial dysfunction was depended on the upregulation of Sirt3-mediated autophagy. At the whole animal level, AR-C17 administration ameliorated high-fat diet induced C57BL/6J mice obesity and its associated adipose tissue macrophage infiltration and mitochondrial dysfunction. Activation of Sirt3-mediated autophagy in adipose tissue was also observed in AR-C17-treated mice. Together, these findings indicate that Sirt3-mediated autophagy plays an essential role in alleviating adipocyte mitochondrial dysfunction by AR-C17 and suggest AR-C17 as a potential dietary bioactive ingredient for obesity prevention and treatment.

Body temperature is a more important modulator of lifespan than metabolic rate in two small mammals.

The relationships between metabolic rate, body temperature (Tb), body composition and ageing are complex, and not fully resolved. In particular, Tb and metabolic rate often change in parallel, making disentangling their effects difficult. Here we show that in both sexes of mice and hamsters exposure to a temperature of 32.5 °C leads to a reduced lifespan, coincident with lowered metabolic rate and elevated Tb with no change in body composition. We exploit the unique situation that when small mammals are exposed to hot ambient temperatures their Tb goes up, at the same time that their metabolic rate goes down, allowing us to experimentally separate the impacts of Tb and metabolic rate on lifespan. The impact of ambient temperature on lifespan can be reversed by exposing the animals to elevated heat loss by forced convection, which reverses the effect on Tb but does not affect metabolic rate, demonstrating the causal effect of Tb on lifespan under laboratory conditions for these models. The impact of manipulations such as calorie restriction that increase lifespan may be mediated via effects on Tb, and measuring Tb may be a useful screening tool for putative therapeutics to extend the human lifespan.