Starting from the natural products anethole and isoeugenol, two functional monomers with thermocrosslinkable benzocyclobutene units have been synthesized and converted into the cross-linked resins. Both of the two resins exhibit good thermostability with Tg of more than 380 degrees C and T5d of exceeded 440 degrees C and storage modulus of higher 1 GPa, as well as good dielectric constants of lower than 2.68 and dielectric loss of less than 2.1 x 10-3. Moreover, the resins also exhibit good hydrophobicity. These data indicate that the two bio-based monomers are suitable as the precursors for the application in the microelectronic industry.

The rapid analysis and characterization of compounds using mass spectrometry (MS) may overlook trace compounds. Although targeted analysis methods can significantly improve detection sensitivity, it is hard to discover novel scaffold compounds in the trace. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathways. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methyl anthranilate (MMA), fragmented in electrospray ionization coupled with collision-induced dissociation (CID) to produce the rearrangement ion 3-hydroxyindole, which was proven to exist in trace amounts in C. reticulata 'Chachi' based on comparison with the reference substance using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, a total of 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA using purchased or synthesized reference substances, all of which were detected in C. reticulata 'Chachi' through LC-MS/MS, achieving trace compound analysis from untargeted to targeted. These results may contribute to explaining the aging mechanism of C. reticulata 'Chachi', and the strategy of using the CID-induced special rearrangement ion-binding metabolic pathway has potential application value for discovering trace compounds.

Transition metal-catalyzed olefination of aryl C-H bond is a powerful tool for the synthesis of alkenes. While the Pd-catalyzed oxidative C-H olefination of arenes, also known as Fujiwara-Moritani reaction, has been established as one of the most efficient methods, the substrates are largely limited to terminal olefins with electron-withdrawing group(s). Herein, we report a synergistic silver-mediated and palladium-catalyzed non-directed C-H olefination of arenes with vinyl (pseudo)halides, which offers a complementary strategy to the typical Fujiwara-Moritani reaction. The reactions proceeded well for a variety of halogenated arenes, heteroarenes, and olefin substrates, providing an efficient access to various multi-substituted aryl olefins, including trisubstituted/tetrasubstituted olefins and several complex olefins derived from medicines or natural products. Mechanistic studies indicated a bimetallic Pd/Ag cooperation is operative in the catalysis, i.e., the reaction is initiated by aryl C-H bond cleavage via ligation with phosphine/Ag species, followed by transferring of the aryl moiety to a vinyl palladium intermediate, which is in turn formed by oxidative addition of vinyl (pseudo)halide to a Pd complex. This method enables the synthesis of a wide range of challenging multi-substituted vinyl products from simple arenes (directing-group free) in a streamlined and controllable fashion.

Nicotinamide adenine dinucleotide (NAD) can be used as an initiating nucleotide in RNA transcription to produce NAD-capped RNA (NAD-RNA). RNA modification by NAD that links metabolite with expressed transcript is a poorly studied epitranscriptomic modification. Current NAD-RNA profiling methods involve multi-steps of chemo-enzymatic labeling and affinity-based enrichment, thus presenting a critical analytical challenge to remove unwanted variations, particularly batch effects. Here, we propose a computational framework, enONE, to remove unwanted variations. We demonstrate that designed spike-in RNA, together with modular normalization procedures and evaluation metrics, can mitigate technical noise, empowering quantitative and comparative assessment of NAD-RNA across different datasets. Using enONE and a human aging cohort, we reveal age-associated features of NAD-capping and further develop an accurate RNA-based aging clock that combines signatures from both transcriptome and NAD-modified epitranscriptome. enONE facilitates the discovery of NAD-RNA responsive to physiological changes, laying an important foundation for functional investigations into this modification.

Epilepsy is a chronic disease of brain dysfunction, which arises from imbalance between excitatory and inhibitory activities in neural circuits. Previously, we reported that peptide Martentoxin (MarTX), from scorpion Buthus martensii Karsch, displayed antiseizure activities by specifically inhibiting BK(alpha + beta 4) channel currents. Injection of MarTX into the hippocampal region of mice significantly alleviated convulsive seizures. However, intravenous injection of MarTX had no antiepileptic efficacy due to the blood-brain barrier (BBB). To address this, here, we designed cell-penetrating peptide TAT-modified MarTX, in which the linker containing three glycines was put between TAT and the N-terminus of MarTX (forming MTX-N-TAT) or between TAT and the C-terminus of MarTX (forming MTX-C-TAT), respectively. We prepared them in a large amount through Escherichia coli overexpression system and then probed their antiseizure activities. Our results indicated that intravenous injection of MTX-C-TAT showed significant therapeutic efficacy of antiseizure. It increased seizure latency, reduced the total seizure duration and the number of seizures at stages 3, 4, and 5, inhibited hippocampal neuronal hyperexcitability, and exhibited neuroprotective effects on hippocampal neurons. These studies implied that MTX-C-TAT displayed intravenous antiseizure activities properly through crossing BBB and would be a potential antiepileptic drug in the future.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia. The hypothermia induced by P57 is significantly blunted in the mice with knockout of PDXK in the preoptic area (POA) of hypothalamus. We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and they may activate medial preoptic area (MPA) neurons in POA to induce hypothermia. Taken together, our findings demonstrate that P57 has a potential application in therapeutic hypothermia through regulation of vitamin B6 metabolism and PDXK serves as a previously unknown target of P57 in thermoregulation. In addition, P57 may serve as a chemical probe for exploring the neuron circuitry related to hypothermia state in mice.