TfOH-Catalyzed Formal [3 + 2] Cycloaddition of Cyclopropane 1,1-Diesters with Nitriles

A triflic acid-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with nitriles was developed. This reaction was expeditious, and the scope of the substituents in both cyclopropanes and nitriles was broad. This supplies an efficient and practical method for the synthesis of 1-pyrrolines

A Highly Hydrophobic Sustainable Starch/Gelatin-Beeswax Biodegradable Film: Easy to Industrial Scale-Up, Recyclable, and Suitable for Multiple Packaging Application Scenarios

Polysaccharides-based sustainable and biodegradable packaging materials suitable for variable conditions are potential candidates for replacing petroleum-based polymers. However, the poor hydrophobicity of polysaccharide films seriously limits their practical applications. Inspired by the phase separation of pseudobilayer films through solution-method casting, a novel and facile strategy for preparing highly hydrophobic starch/gelatin-beeswax (HSGBW) film was developed using an extrusion blowing method suitable for industrial production. The increased extrusion blowing temperature enhanced the interaction between starch and gelatin (originally used to stabilize beeswax), leading to the destabilization of beeswax and its migration to the film surface, ultimately resulting in the formation of a wax-enriched hydrophobic layer. The resultant HSGBW film exhibited excellent hydrophobicity (water contact angle: ∼106°), outperforming starch-based materials reported to date as well as outstanding water resistance, UV-blocking, self-cleaning ability, moisture, oxygen, and oil barrier properties. The HSGBW film also exhibited excellent biosafety, storage stability, rapid dissolution at high temperatures (which offers convenience for packaging certain foods that expediently require high-temperature boiling), fully biodegradable performance, and easy recyclability. Owing to these multifunctional properties, the resulting film was applied in inner food packaging under different scenarios, as evidenced by the packaging of foods with high moisture content (cucumber dumpling stuffing), high fat content (high-fat powdered milk), and high oil content (chili oil seasoning). From ecological and convenience viewpoints, this work demonstrated a facile strategy for manufacturing HSGBW film for packaging materials to replace petrochemical-derived plastics in many fields, especially inner food packaging, providing new opportunities for starch-based sustainable material designs

Discovery of a New Class of Uracil Derivatives as Potential Mixed Lineage Kinase Domain-like Protein (MLKL) Inhibitors

Necroptosis is a form of programmed cell death. Mixed lineage kinase domain-like protein (MLKL) is the necroptosis executor, and it is involved in various diseases such as tissue damage and neurodegeneration-related diseases. Here, we report the development of novel MLKL inhibitors with a uracil nucleus through scaffold morphing from our previously reported xanthine MLKL inhibitor TC13172. After a rational structure–activity relationship study, we obtained the highly potent compounds 56 and 66. Mechanism studies revealed that these compounds partially inhibited MLKL oligomerization and significantly inhibited MLKL translocation to the membrane. Compared with TC13172, 56 and 66 have a different mode of action and, importantly, their reaction rate with glutathione is more than 150-fold lower. This reduction in potential off-target effects and cell toxicity makes this series an attractive starting point for further drug development for MLKL-related disease treatments

Discovery of a New Class of Uracil Derivatives as Potential Mixed Lineage Kinase Domain-like Protein (MLKL) Inhibitors

Necroptosis is a form of programmed cell death. Mixed lineage kinase domain-like protein (MLKL) is the necroptosis executor, and it is involved in various diseases such as tissue damage and neurodegeneration-related diseases. Here, we report the development of novel MLKL inhibitors with a uracil nucleus through scaffold morphing from our previously reported xanthine MLKL inhibitor TC13172. After a rational structure–activity relationship study, we obtained the highly potent compounds 56 and 66. Mechanism studies revealed that these compounds partially inhibited MLKL oligomerization and significantly inhibited MLKL translocation to the membrane. Compared with TC13172, 56 and 66 have a different mode of action and, importantly, their reaction rate with glutathione is more than 150-fold lower. This reduction in potential off-target effects and cell toxicity makes this series an attractive starting point for further drug development for MLKL-related disease treatments

Neurophysiological Differences between Flail Arm Syndrome and Amyotrophic Lateral Sclerosis

<div><p>There are many clinical features of flail arm syndrome (FAS) that are different from amyotrophic lateral sclerosis (ALS), suggesting they are probably different entities. Studies on electrophysiological differences between them are limited at present, and still inconclusive. Therefore, we aimed to find clinical and neurophysiological differences between FAS and ALS. Eighteen healthy control subjects, six FAS patients and forty-one ALS patients were recruited. The upper motor neuron signs (UMNS), split-hand index (SI), resting motor threshold (RMT), central motor conduction time (CMCT) were evaluated and compared. There was no obvious upper motor neuron signs in FAS. The SI and RMT level in FAS was similar to control subjects, but significantly lower than that of in ALS. Compared with control group, the RMT and SI in ALS group were both significantly increased to higher level. However, no significant difference of CMCT was found between any two of these three groups. The differences in clinical and neurophysiological findings between FAS and ALS, argue against they are the same disease entity. Since there was no obvious UMNS, no split-hand phenomenon, and no obvious changes of RMT and CMCT in FAS patients, the development of FAS might be probably not originated from motor cortex.</p></div

Comparison of CMCT among three groups.

<p>The CMCT of FAS and ALS patients was not significantly changed, compared with control.</p

Difference of the amplitude of CMAPs of ADMs between three groups.

<p>Fig 2 showed the CMAPs amplitude of ADMs in ALS and FAS groups were significantly decreased, compared with control group (*<i>p</i><0.05).</p

Dual Reaction-Based Multimodal Assay for Dopamine with High Sensitivity and Selectivity Using Functionalized Gold Nanoparticles

A simple and dual chemical reaction-based multimodal assay for dopamine with high sensitivity and selectivity using two types of functionalized gold nanoparticles (FB-AuNPs/NsNHS-AuNPs), i.e. fluorescein modified gold nanoparticles (FB-AuNPs) and Nile blue modified gold nanoparticles (NsNHS-AuNPs), was successfully fabricated. This assay for dopamine presents colorimetric visualization and double channel fluorescence enhancement at 515 and 665 nm. The absorbance and fluorescence changes were linearly proportional to the amounts of dopamine in the range of nanomolar scale (5–100 nM). The detection limits for absorbance and fluorescence were as low as 1.2 nM and 2.9 nM (S/N = 3), respectively. Furthermore, the extent application of this multimodal assay has been successfully demonstrated in human urine samples with high reliability and applicability, showing remarkable promise in diagnostic purposes

First-Principles Study of a Zirconium-Terminated Diamond (100) Surface with Promising Negative Electron Affinity and Surface Stability

Chemical modification of diamond surfaces generates a negative electron affinity (NEA), which shows great potential in realizing electron emission. In this study, zirconium (Zr) termination on clean and oxidized diamond (100) surfaces is theoretically proposed by using the structure prediction method, and electronic properties of these predicted surfaces are investigated by first-principles calculations. On the oxidized surfaces, the adsorption energy at 0.25 monolayer (ML) Zr coverage reaches a high value of −10.42 eV, further confirmed by the largest integrated crystal orbital Hamiltonian population value of 6.61 eV. For clean and oxidized diamond (100) surfaces, the largest NEA values at 0.25 ML Zr coverage are −3.75 eV and −3.45 eV, respectively. The dynamic stability of these surface structures is demonstrated by calculating phonon dispersion curves. Furthermore, ab initio molecular dynamics simulations confirm the high thermal stability of the oxidized diamond surface. Therefore, these results indicate that Zr-terminated diamond (100) surfaces possess good thermal stability and higher NEA, making them promising candidate materials for electron emission applications

Comparison of neuropsychological performances among patients with PMA, ALS and HC.

<p>3 PMA patients did not complete Stroop Color-Word Task; 2 PMA in copy tests and 1 PMA in digit span and Symbol Digit Modalities Test. ABC, Aphasia Battery Chinese; ALS, amyotrophic lateral sclerosis; CDT, clock drawing test; CMT, Clinical Memory Test; HC, healthy controls; PMA, progressive muscular atrophy; SIE, Stroop interference effect; time for SIE was calculated according to the formula of (Stroop C time-Stroop B time) and correct number for SIE was calculated according to the formula of (Stroop B correct number- Stroop C correct number); WAIS, Wechsler Adult Intelligence Scale; WMS, Wechsler Memory Scale.</p><p>Data were means±SD.</p><p>*p value remained to be significant after Bonferroni correction (α = 0.05/3 = 0.017).</p><p>Comparison of neuropsychological performances among patients with PMA, ALS and HC.</p