Palmitoylation of PKCδ by ZDHHC5 in hypothalamic microglia presents as a therapeutic target for fatty liver disease.

The hypothalamus plays a fundamental role in controlling lipid metabolism through neuroendocrine signals. However, there are currently no available drug targets in the hypothalamus that can effectively improve human lipid metabolism. In this study, we found that the antimalarial drug artemether (ART) significantly improved lipid metabolism by specifically inhibiting microglial activation in the hypothalamus of high-fat diet-induced mice. Mechanically, ART protects the thyrotropin-releasing hormone (TRH) neurons surrounding microglial cells from inflammatory damage and promotes the release of TRH into the peripheral circulation. As a result, TRH stimulates the synthesis of thyroid hormone (TH), leading to a significant improvement in hepatic lipid disorders. Subsequently, we employed a biotin-labeled ART chemical probe to identify the direct cellular target in microglial cells as protein kinase Cδ (PKCδ). Importantly, ART directly targeted PKCδ to inhibit its palmitoylation modification by blocking the binding of zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5), which resulted in the inhibition of downstream neuroinflammation signaling. In vivo, hypothalamic microglia-specific PKCδ knockdown markedly impaired ART-dependent neuroendocrine regulation and lipid metabolism improvement in mice. Furthermore, single-cell transcriptomics analysis in human brain tissues revealed that the level of PKCδ in microglia positively correlated with individuals who had hyperlipemia, thereby highlighting a clinical translational value. Collectively, these data suggest that the palmitoylation of microglial PKCδ in the hypothalamus plays a role in modulating peripheral lipid metabolism through hypothalamus-liver communication, and provides a promising therapeutic target for fatty liver diseases.

Intelligent Electrochemical Point-of-Care Test Method with Interface Control Based on DNA Pyramids: Aflatoxin B1 Detection in Food and the Environment.

Sensitive, intelligent point-of-care test (iPOCT) methods for small molecules like aflatoxin B1 (AFB1) are urgently needed for food and the environment. The challenge remains of surface control in iPOCT. Herein, we developed an electrochemical sensor based on the DNA pyramid (DNP), combining a smartphone, app, and mobile electrochemical workstations to detect AFB1. The DNP's structure can reduce local overcrowding and entanglement between neighboring probes, control the density and orientation of recognition probes (antibodies), produce uniform and orientational surface assemblies, and improve antigen-antibody-specific recognition and binding efficiency. Simultaneously, the hollow structure of the DNP enhances the electron transfer capacity and increases the sensitivity of electrochemical detection. In this work, the biosensor based on DNP was first combined with electrochemical (Ec) iPOCT to simultaneously achieve ordered interface modulation of recognition probes and intelligent detection of AFB1. Under optimal conditions, we found a detection limit of 3 pg/mL and a linear range of 0.006-30 ng/mL (R2 = 0.995). Further, using peanut, soybean, corn, and lake water as complex matrices, it recorded recoveries of 82.15-100.53%, excellent selectivity, acceptable stability, and good reproducibility. Finally, this Ec iPOCT provides consistent results compared to the high-performance liquid chromatography-tandem mass spectrometry method.

The effects of intercalated environmental gas molecules on carrier dynamics in WSe2/WS2 heterostructures.

Effective tuning of carrier dynamics in two-dimensional (2D) materials is significant for multi-scene device applications. Using first-principles and ab initio nonadiabatic molecular dynamics calculations, the kinetics of O2, H2O, and N2 intercalation into 2D WSe2/WS2 van der Waals heterostructures and its effect on carrier dynamics have been comprehensively explored. It is found that the O2 molecule prefers to dissociate into atomic O atoms spontaneously after intercalation of WSe2/WS2 heterostructures, whereas H2O and N2 molecules remain intact. O2 intercalation significantly speeds up the electron separation process, while H2O intercalation largely speeds up the hole separation process. The lifetime of excited carriers can be prolonged by O2 or H2O or N2 intercalations. These intriguing phenomena can be attributed to the effect of interlayer coupling, and the underlying physical mechanism for tuning the carrier dynamics is fully discussed. Our results provide useful guidance for the experimental design of 2D heterostructures for optoelectronic applications in photocatalysts and solar energy cells.

Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy.

Neuroinflammation is a fundamental contributor to progressive neuronal damage, which arouses a heightened interest in neurodegenerative disease therapy. Ubiquitin-specific protease 7 (USP7) has a crucial role in regulating protein stability in multiple biological processes; however, the potential role of USP7 in neurodegenerative progression is poorly understood. Here, we discover the natural small molecule eupalinolide B (EB), which targets USP7 to inhibit microglia activation. Cocrystal structure reveals a previously undisclosed covalent allosteric site, Cys576, in a unique noncatalytic HUBL domain. By selectively modifying Cys576, EB allosterically inhibits USP7 to cause a ubiquitination-dependent degradation of Keap1. Keap1 function loss further results in an Nrf2-dependent transcription activation of anti-neuroinflammation genes in microglia. In vivo, pharmacological USP7 inhibition attenuates microglia activation and resultant neuron injury, thereby notably improving behavioral deficits in dementia and Parkinson's disease mouse models. Collectively, our findings provide an attractive future direction for neurodegenerative disease therapy by inhibiting microglia-mediated neuroinflammation by targeting USP7.

Universal Zigzag Edge Reconstruction of an α-Phase Puckered Monolayer and Its Resulting Robust Spatial Charge Separation.

Edges are important, because they dictate the stability and properties of nanoribbons. Here, we reveal a universal reconstruction of the ZZ edge into a (2 × 1) tubed [ZZ(Tube)] edge, enabling an ultimate narrow nanotube to terminate nanoribbons for α-puckered group-V elemental and compound monolayers (GeS/Se and SnS/Se). The reconstructed edge formations are confirmed by CALYPSO. The ZZ(Tube) edge forms easily, is highly stable, and is semiconducting. Remarkably, the ZZ(Tube) edge always exhibits a type-II band structure and robust spatial charge separation. For a compound monolayer monochalcogenide, mild (2 × 1) ZZ(S-R) occurs at the chalcogenide-terminated edge. TDDFT simulations indicate that charge separation occurs only at 672 fs, while the lifetime is over 5 ns, thus facilitating robust spatial charge accumulation. These remarkable features of ZZ(Tube) edge-terminated α-puckered nanoribbons are ideal for optoelectronic and photocatalytic applications.

A Sensitive, Point-of-Care Detection of Small Molecules Based on a Portable Barometer: Aflatoxins In Agricultural Products.

Sensitive and point-of-care detection of small toxic molecules plays a key role in food safety. Aflatoxin, a typical small toxic molecule, can cause serious healthcare and economic issues, thereby promoting the development of sensitive and point-of-care detection. Although ELISA is one of the official detection methods, it cannot fill the gap between sensitivity and point-of-care application because it requires a large-scale microplate reader. To employ portable readers in food safety, Pt-catalysis has attracted increasing attention due to its portability and reliability. In this study, we developed a sensitive point-of-care aflatoxin detection (POCAD) method via a portable handheld barometer. We synthesized and characterized Au@PtNPs and Au@PtNPs conjugated with a second antibody (Au@PtNPs-IgG). A competitive immunoassay was established based on the homemade monoclonal antibody against aflatoxins. Au@PtNPs-IgG was used to catalyze the production of O2 from H2O2 in a sealed vessel. The pressure of O2 was then recorded by a handheld barometer. The aflatoxin concentration was inversely proportional to the pressure recorded via the barometer reading. After optimization, a limit of detection of 0.03 ng/mL and a linear range from 0.09 to 16.0 ng/mL were achieved. Recovery was recorded as 83.1%-112.0% along with satisfactory results regarding inner- and inter-assay precision (relative standard deviation, RSD < 6.4%). Little cross-reaction was observed. Additionally, the POCAD was validated by high-performance liquid chromatography (HPLC) by using peanut and corn samples. The portable POCAD exhibits strong potential for applications in the on-site detection of small toxic molecules to ensure food safety.

Copper(i) sulfide: a two-dimensional semiconductor with superior oxidation resistance and high carrier mobility.

Two-dimensional (2D) semiconductors with suitable direct band gaps, high carrier mobility, and excellent open-air stability are especially desirable for material applications. Herein, we show theoretical evidence of a new phase of a copper(i) sulfide (Cu2S) monolayer, denoted δ-Cu2S, with both novel electronic properties and superior oxidation resistance. We find that both monolayer and bilayer δ-Cu2S have much lower formation energy than the known ß-Cu2S phase. Given that ß-Cu2S sheets have been recently synthesized in the laboratory (Adv. Mater.2016, 28, 8271), the higher stability of δ-Cu2S than that of ß-Cu2S sheets suggests a high possibility of experimental realization of δ-Cu2S. Stability analysis indicates that δ-Cu2S is dynamically and thermally stable. Notably, δ-Cu2S exhibits superior oxidation resistance, due to the high activation energy of 1.98 eV for the chemisorption of O2 on δ-Cu2S. On its electronic properties, δ-Cu2S is a semiconductor with a modest direct band gap (1.26 eV) and an ultrahigh electron mobility of up to 6880 cm2 V-1 s-1, about 27 times that (246 cm2 V-1 s-1) of the ß-Cu2S bilayer. The marked difference between the electron and hole mobilities of δ-Cu2S suggests easy separation of electrons and holes for solar energy conversion. Combination of these novel properties makes δ-Cu2S a promising 2D material for future applications in electronics and optoelectronics with high thermal and chemical stability.

Defects and oxidation of group-III monochalcogenide monolayers.

Among various two-dimensional (2D) materials, monolayer group-III monochalcogenides (GaS, GaSe, InS, and InSe) stand out owing to their potential applications in microelectronics and optoelectronics. Devices made of these novel 2D materials are sensitive to environmental gases, especially O2 molecules. To address this critical issue, here we systematically investigate the oxidization behaviors of perfect and defective group-III monochalcogenide monolayers by first-principles calculations. The perfect monolayers show superior oxidation resistance with large barriers of 3.02-3.20 eV for the dissociation and chemisorption of O2 molecules. In contrast, the defective monolayers with single chalcogen vacancy are vulnerable to O2, showing small barriers of only 0.26-0.36 eV for the chemisorption of an O2 molecule. Interestingly, filling an O2 molecule to the chalcogen vacancy of group-III monochalcogenide monolayers could preserve the electronic band structure of the perfect system-the bandgaps are almost intact and the carrier effective masses are only moderately disturbed. On the other hand, the defective monolayers with single vacancies of group-III atoms carry local magnetic moments of 1-2 µB. These results help experimental design and synthesis of group-III monochalcogenides based 2D devices with high performance and stability.

Oxidation Resistance of Monolayer Group-IV Monochalcogenides.

Ridged, orthorhombic two-dimensional (2D) group-V elemental and group IV-VI compound analogues of phosphorene provide a versatile platform for nanoelectronics, optoelectronics, and clean energy. However, phosphorene is vulnerable to oxygen in ambient air, which is a major obstacle for its applications. Regarding this issue, here we explore the oxidation behavior of monolayer group-IV monochalcogenides (GeS, GeSe, SnS, and SnSe), in comparison to that of phosphorene and arsenene by first-principles calculations. We find superior oxidation resistance of the monolayer group-IV monochalcogenides, with activation energies for the chemisorption of O2 on the 2D sheets in the range of 1.26-1.60 eV, about twice of the values of phosphorene and arsenene. The distinct oxidation behaviors of monolayer group-IV monochalcogenides and group-V phosphorene analogues originate from their different bond natures. Moreover, the chemisorption of a moderate amount of oxygen atoms does not severely deteriorate the electronic band structures of the monolayer group-IV monochalcogenides. These results shine light on the utilization of the monolayer group-IV monochalcogenides for next-generation 2D electronics and optoelectronics with high performance and stability.

Magnetic solid-phase extraction based on graphene oxide for the determination of lignans in sesame oil.

Graphene oxide was fabricated by a simple method and applied to magnetic solid-phase extraction. In a pretreatment procedure before the sesamol, sesamin and sesamolin in sesame oil were detected by high performance liquid chromatography. Several parameters affecting the extraction efficiency were investigated, including the type and volume of desorption solvent, desorption time and the amount of sorbent. Under the optimized conditions, the detection limits of sesamol, sesamin, and sesamolin were 0.05µg/g, 0.02µg/g, and 0.02µg/g, respectively. The limits of quantification were all 0.2µg/g. The average recoveries of sesamol, sesamin, and sesamolin were 84.55%, 85.47%, 86.83%, respectively and their relative standard deviations were 1.23%, 1.33%, and 0.84%, respectively.

Cadmium in Chinese Postharvest Peanuts and Dietary Exposure Assessment in Associated Population.

Cadmium (Cd) in 8698 peanut samples collected from China in 2009-2014 was studied to evaluate its contamination level, distribution, and health risk. The average Cd concentration was 0.1684 mg kg-1; the range of 2.5-97.5% was 0.0191-0.4762 mg kg-1, indicating the cadmium-contaminated peanut level was even lower. Some peanut strains for which protein contents had a significant correlation (Pearson correlation coefficient r = 0.86**) with the Cd concentration level should be of concern. Under the same soil Cd background, the difference in Cd contents in different peanut varieties is extremely significant. For example, the Cd concentration of Silihong is about 0.4522 mg kg-1, being 7 times higher than that of Zhonghua 6. According to the exposure assessment using the probabilistic simulation method, the target hazard quotients (THQs) of all groups should be below 1. The THQ range in this study was from 0.0035 to 0.0202, suggesting that there were no potential noncinogenic effects in any group.

Risk Assessment on Dietary Exposure to Aflatoxin B1 in Post-Harvest Peanuts in the Yangtze River Ecological Region.

Based on the 2983 peanut samples from 122 counties in six provinces of China's Yangtze River ecological region collected between 2009-2014, along with the dietary consumption data in Chinese resident nutrition and health survey reports from 2002 and 2004, dietary aflatoxin exposure and percentiles in the corresponding statistics were calculated by non-parametric probability assessment, Monte Carlo simulation and bootstrap sampling methods. Average climatic conditions in the Yangtze River ecological region were calculated based on the data from 118 weather stations via the Thiessen polygon method. The survey results found that the aflatoxin contamination of peanuts was significantly high in 2013. The determination coefficient (R²) of multiple regression reflected by the aflatoxin B1 content with average precipitation and mean temperature in different periods showed that climatic conditions one month before harvest had the strongest impact on aflatoxin B1 contamination, and that Hunan and Jiangxi provinces were greatly influenced. The simulated mean aflatoxin B1 intake from peanuts at the mean peanut consumption level was 0.777-0.790 and 0.343-0.349 ng/(kg·d) for children aged 2-6 and standard adults respectively. Moreover, the evaluated cancer risks were 0.024 and 0.011/(100,000 persons·year) respectively, generally less than China's current liver cancer incidence of 24.6 cases/(100,000 persons·year). In general, the dietary risk caused by peanut production and harvest was low. Further studies would focus on the impacts of peanut circulation and storage on aflatoxin B1 contamination risk assessment in order to protect peanut consumers' safety and boost international trade.

Mechanical and electronic properties of B12-based ternary crystals of orthorhombic phase.

Using first-principles calculations, the structural, mechanical and electronic properties of the experimentally synthesized B(12)-based ternary crystals (AlMgB(14), AlNaB(14), AlLiB(14), Mg(2)B(14), MgSi(2)B(12), MgC(2)B(12), Li(2)Si(2)B(12) and Li(2)C(2)B(12)) have been investigated. The theoretical equilibrium lattice constants of these crystals agree with the experimental values. The Vickers hardness (H(v)) estimated from the theoretical Young's moduli ranges from 20 to 30 GPa, and the MgC(2)B(12) compound (H(v) = 31.4 GPa) is harder than α-boron. Based on the electron density of states and Mulliken population analysis, the origination of hardness and interaction between the interstitial atoms and the B(12) framework were discussed. Scaled bond order of the B-B bonds was used to interpret the hardness of these B(12)-based ternary compounds. The crystal hardness is primarily determined by the B(12) icosahedral skeleton, whereas the contributions of metal atoms manifest as the electron transfer from metal to B atoms. We also calculated the ideal tensile strength of AlMgB(14) and MgC(2)B(12) and found that the <001> and <010> directions are their cleavage directions under tensile strains, respectively.

[Potential distribution areas of alien invasive plant Flaveria bidentis (Asteraceae) in China].

Flaveria bidentis (Asteraceae), a potential exotic invasive weed to agro-ecosystem and rangeland ecosystem, has recently invaded Tianjin City and Hebei Province (Hengshui and Langfang) in North China, and is spreading further. Based on its current geographical distribution in the world, the potential distribution areas of this weed in China were predicted by using CLIMEX software, aimed to assess the potential risks of this invasive weed. Following provinces in China could be the potential areas being invaded by F. bidentis, i. e., Guangdong, Guangxi, Yunnan, Hainan, Fujian, Taiwan, Jiangxi, Hunan, Guizhou, Sichuan, Chongqing, Hubei, Anhui, Jiangsu, and Shanghai, among which, Guangdong, Guangxi, Taiwan, Hainan, Fujian, Yunnan, Sichuan, Guizhou, Chongqing, and part of Xizang would be at high risk.