Visual High-Throughput Screening for Developing a Fatty Acid Amide Hydrolase Natural Inhibitor Based on an Enzyme-Activated Fluorescent Probe

Fatty acid amide hydrolase (FAAH) is an important drug target for the treatment of many disease related conditions such as pain, inflammation, and mood disorders due to its vital role in the metabolism of endocannabinoid. In our present work, a FAAH-activated fluorescent probe named THPO was developed, which possessed high selectivity and excellent sensitivity for FAAH in complex systems. Critically, its metabolite 7-amino-3H-phenoxazin-3-one (AHPO) has long excitation and emission wavelengths and high fluorescence quantum yield, which are necessary for monitoring the activity of FAAH in living systems. In addition, a visual high-throughput screening method for FAAH inhibitors was established using THPO, which resulted in the discovery of an efficient natural inhibitor Neobavaisoflavone that was identified from 68 traditional herbal medicines. These results indicated that THPO can be used as a molecular tool for the rapid evaluation of FAAH activity in complex systems as well as providing an effective approach to screen FAAH inhibitors and providing a boost for the discovery of therapeutic agents toward FAAH related diseases. </p

Riemannian Surface on Carbon Anodes Enables Li-Ion Storage at −35 °C

Since sluggish Li$^{+}$ desolvation leads to severe capacity degradation of carbon anodes at subzero temperatures, it is urgently desired to modulate electron configurations of surface carbon atoms toward high capacity for Li-ion batteries. Herein, a carbon-based anode material (O-DF) was strategically synthesized to construct the Riemannian surface with a positive curvature, which exhibits a high reversible capacity of 624 mAh g$^{-1}$ with an 85.9% capacity retention at 0.1 A g$^{-1}$ as the temperature drops to −20 °C. Even if the temperature drops to −35 °C, the reversible capacity is still effectively retained at 160 mAh g$^{-1}$ after 200 cycles. Various characterizations and theoretical calculations reveal that the Riemannian surface effectively tunes the low-temperature sluggish Li$^{+}$ desolvation of the interfacial chemistry via locally accumulated charges of non-coplanar sp$^{x}$ (2 < x < 3) hybridized orbitals to reduce the rate-determining step of the energy barrier for the charge-transfer process. Ex-situ measurements further confirm that the sp$^{x}$-hybridized orbitals of the pentagonal defect sites should denote more negative charges to solvated Li$^{+}$ adsorbed on the Riemannian surface to form stronger Li–C coordinate bonds for Li$^{+}$ desolvation, which not only enhances Li-adsorption on the curved surface but also results in more Li$^{+}$ insertion in an extremely cold environment

Effect of Frying Conditions on Acrylamide and 5-Hydroxymethylfurfural Formation in French Fries

In this study, the relationship between the formation of acrylamide (AA) and that of 5-hydroxymethylfurfural (5-HMF), as well as the correlation with the content of α-dicarbonyl compounds as intermediate products in French fries were studied using Pearson correlation analysis and principal component analysis (PCA), and the correlation between the formation of AA and 5-HMF and the sensory score, color, water content and oil absorption of French fries was also discussed. The results showed that with an increase in frying time or temperature, the contents of AA, 5-HMF and α-dicarbonyl compounds in French fries increased significantly, water content decreased, and oil absorption increased gradually. In addition, lightness (L* value) and yellowness (b* value) tended to decrease, while redness (a* value) tended to increase. There was a significantly positive correlation between AA and 5-HMF contents under the different conditions tested. Moreover, AA and 5-HMF contents showed a significantly positive correlation with the content of α-dicarbonyl compounds and oil absorption, but a significantly negative correlation with water content, L* value and b* value. AA content was positively correlated with a* value. It was found that the results of the PCA model were consistent with the linear curves of the contents of AA, 5-HMF and α-dicarbonyl compounds versus frying temperature and time. Frying for 5 min at 170 ℃ not only ensured the best sensory quality of French fries, but also helped to reduce the formation of hazardous substances

Preprocess-then-NTT Technique and Its Applications to KYBER and NEWHOPE

The Number Theoretic Transform (NTT) provides efficient algorithm for multiplying large degree polynomials. It is commonly used in cryptographic schemes that are based on the hardness of the Ring Learning With Errors problem (RLWE), which is a popular basis for post-quantum key exchange, encryption and digital signature. To apply NTT, modulus q should satisfy that q = 1 mod 2n, RLWE-based schemes have to choose an oversized modulus, which leads to excessive bandwidth. In this work, we present “Preprocess-then-NTT (PtNTT)” technique which weakens the limitation of modulus q, i.e., we only require q = 1 mod n or q = 1 mod n/2. Based on this technique, we provide new parameter settings for KYBER and NEWHOPE (two NIST candidates). In these new schemes, we can reduce public key size and ciphertext size at a cost of very little efficiency loss

LAC: Practical Ring-LWE Based Public-Key Encryption with Byte-Level Modulus

We propose an instantiation of public key encryption scheme based on the ring learning with error problem, where the modulus is at a byte level and the noise is at a bit level, achieving one of the most compact lattice based schemes in the literature. The main technical challenges are a) the decryption error rates increases and needs to be handled elegantly, and b) we cannot use the Number Theoretic Transform (NTT) technique to speed up the implementation. We overcome those limitations with some customized parameter sets and heavy error correction codes. We give a treatment of the concrete security of the proposed parameter set, with regards to the recent advance in lattice based cryptanalysis. We present an optimized implementation taking advantage of our byte level modulus and bit level noise. In addition, a byte level modulus allows for high parallelization and the bit level noise avoids the modulus reduction during multiplication. Our result shows that \LAC~is more compact than most of the existing (Ring-)LWE based solutions, while achieving a similar level of efficiency, compared with popular solutions in this domain, such as Kyber

Bulk Incorporation with 4‐Methylphenethylammonium Chloride for Efficient and Stable Methylammonium‐Free Perovskite and Perovskite‐Silicon Tandem Solar Cells

Methylammonium (MA)-free perovskite solar cells have the potential for better thermal stability than their MA-containing counterparts. However, the efficiency of MA-free perovskite solar cells lags behind due to inferior bulk quality. In this work, 4-methylphenethylammonium chloride (4M-PEACl) is added into a MA-free perovskite precursor, which results in greatly enhanced bulk quality. The perovskite crystal grains are significantly enlarged, and defects are suppressed by a factor of four upon the incorporation of an optimal concentration of 4M-PEACl. Quasi-2D perovskites are formed and passivate defects at the grain boundaries of the perovskite crystals. Furthermore, the perovskite surface chemistry is modified, resulting in surface energies more favorable for hole extraction. This facile approach leads to a steady state efficiency of 23.7% (24.2% in reverse scan, 23.0% in forward scan) for MA-free perovskite solar cells. The devices also show excellent light stability, retaining more than 93% of the initial efficiency after 1000 h of constant illumination in a nitrogen environment. In addition, a four-terminal mechanically stacked perovskite-silicon tandem solar cell with champion efficiency of 30.3% is obtained using this MA-free composition. The encapsulated tandem devices show excellent operational stability, retaining more than 98% of the initial performance after 42 day/night cycles in an ambient atmosphere

PyPose v0.6: The Imperative Programming Interface for Robotics

PyPose is an open-source library for robot learning. It combines a learning-based approach with physics-based optimization, which enables seamless end-to-end robot learning. It has been used in many tasks due to its meticulously designed application programming interface (API) and efficient implementation. From its initial launch in early 2022, PyPose has experienced significant enhancements, incorporating a wide variety of new features into its platform. To satisfy the growing demand for understanding and utilizing the library and reduce the learning curve of new users, we present the fundamental design principle of the imperative programming interface, and showcase the flexible usage of diverse functionalities and modules using an extremely simple Dubins car example. We also demonstrate that the PyPose can be easily used to navigate a real quadruped robot with a few lines of code

Studies on the production of branched-chain alcohols in engineered Ralstonia eutropha

Wild-type Ralstonia eutropha H16 produces polyhydroxybutyrate (PHB) as an intracellular carbon storage material during nutrient stress in the presence of excess carbon. In this study, the excess carbon was redirected in engineered strains from PHB storage to the production of isobutanol and 3-methyl-1-butanol (branched-chain higher alcohols). These branched-chain higher alcohols can directly substitute for fossil-based fuels and be employed within the current infrastructure. Various mutant strains of R. eutropha with isobutyraldehyde dehydrogenase activity, in combination with the overexpression of plasmid-borne, native branched-chain amino acid biosynthesis pathway genes and the overexpression of heterologous ketoisovalerate decarboxylase gene, were employed for the biosynthesis of isobutanol and 3-methyl-1-butanol. Production of these branched-chain alcohols was initiated during nitrogen or phosphorus limitation in the engineered R. eutropha. One mutant strain not only produced over 180 mg/L branched-chain alcohols in flask culture, but also was significantly more tolerant of isobutanol toxicity than wild-type R. eutropha. After the elimination of genes encoding three potential carbon sinks (ilvE, bkdAB, and aceE), the production titer improved to 270 mg/L isobutanol and 40 mg/L 3-methyl-1-butanol. Semicontinuous flask cultivation was utilized to minimize the toxicity caused by isobutanol while supplying cells with sufficient nutrients. Under this semicontinuous flask cultivation, the R. eutropha mutant grew and produced more than 14 g/L branched-chain alcohols over the duration of 50 days. These results demonstrate that R. eutropha carbon flux can be redirected from PHB to branched-chain alcohols and that engineered R. eutropha can be cultivated over prolonged periods of time for product biosynthesis.United States. Dept. of EnergyUnited States. Advanced Research Projects Agency-Energ

Characterization of an extracellular lipase and its chaperone from Ralstonia eutropha H16

Lipase enzymes catalyze the reversible hydrolysis of triacylglycerol to fatty acids and glycerol at the lipid–water interface. The metabolically versatile Ralstonia eutropha strain H16 is capable of utilizing various molecules containing long carbon chains such as plant oil, organic acids, or Tween as its sole carbon source for growth. Global gene expression analysis revealed an upregulation of two putative lipase genes during growth on trioleate. Through analysis of growth and activity using strains with gene deletions and complementations, the extracellular lipase (encoded by the lipA gene, locus tag H16_A1322) and lipase-specific chaperone (encoded by the lipB gene, locus tag H16_A1323) produced by R. eutropha H16 was identified. Increase in gene dosage of lipA not only resulted in an increase of the extracellular lipase activity, but also reduced the lag phase during growth on palm oil. LipA is a non-specific lipase that can completely hydrolyze triacylglycerol into its corresponding free fatty acids and glycerol. Although LipA is active over a temperature range from 10 °C to 70 °C, it exhibited optimal activity at 50 °C. While R. eutropha H16 prefers a growth pH of 6.8, its extracellular lipase LipA is most active between pH 7 and 8. Cofactors are not required for lipase activity; however, EDTA and EGTA inhibited LipA activity by 83 %. Metal ions Mg[superscript 2+], Ca[superscript 2+], and Mn[superscript 2+] were found to stimulate LipA activity and relieve chelator inhibition. Certain detergents are found to improve solubility of the lipid substrate or increase lipase-lipid aggregation, as a result SDS and Triton X-100 were able to increase lipase activity by 20 % to 500 %. R. eutropha extracellular LipA activity can be hyper-increased, making the overexpression strain a potential candidate for commercial lipase production or in fermentations using plant oils as the sole carbon source.Malaysia-MIT Biotechnology Partnership Programm