Gold-catalyzed oxidations of alkynes by N-oxides offer direct access to reactive α-oxo gold carbene intermediates from benign and readily available alkynes instead of hazardous diazo carbonyl compounds. Despite various versatile synthetic methods developed based on this strategy, one of the hallmarks of α-oxo carbene/carbenoid chemistry, that is, the Wolff rearrangement, has not been realized in this context. This study discloses the first examples that show the Wolff rearrangement can be readily realized by α-oxo gold carbenes oxidatively generated from TBS-terminated alkynes (TBS=tert-butyldimethylsilyl). The thus-generated silylketenes can be either isolated pure or subsequently trapped by various internal or external nucleophiles in one pot to afford α-silylated carboxylic acids, their derivatives, or TBS-substituted allenes.

Dorsal root ganglion (DRG) sensory neuron subtypes defined by their in vivo properties display distinct intrinsic electrical properties. We used bulk RNA sequencing of genetically labeled neurons and electrophysiological analyses to define ion channel contributions to the intrinsic electrical properties of DRG neuron subtypes. The transcriptome profiles of eight DRG neuron subtypes revealed differentially expressed and functionally relevant genes, including voltage-gated ion channels. Guided by these data, electrophysiological analyses using pharmacological and genetic manipulations as well as computational modeling of DRG neuron subtypes were undertaken to assess the functions of select voltage-gated potassium channels (Kv1, Kv2, Kv3, and Kv4) in shaping action potential (AP) waveforms and firing patterns. Our findings show that the transcriptome profiles have predictive value for defining ion channel contributions to sensory neuron subtype-specific intrinsic physiological properties. The distinct ensembles of voltage-gated ion channels predicted to underlie the unique intrinsic physiological properties of eight DRG neuron subtypes are presented.

An oxidative strategy is reported to access α-oxo BMIDA gold carbenes directly from BMIDA-terminated alkynes. Besides offering expedient access to seldom studied boryl metal carbenes, these BMIDA gold carbene species undergo facile insertions into methyl, methylene, methine, and benzylic C-H bonds in the absence of the Thorpe-Ingold effect. They also undergo efficient OH insertion, cyclopropanation, and F-C alkylations. This chemistry provides rapid access to structurally diverse α-BMIDA ketones, which are scarcely documented. In combination with DFT studies, the role of BMIDA is established to be an electron-donating group that attenuates the high electrophilicity of the gold carbene center.

The significant changes enabled by the fog computing had demonstrated that Internet of Things (IoT) urgently needs more evolutional reforms. Limited by the inflexible design philosophy; the traditional structure of a network is hard to meet the latest demands. However, Information-Centric Networking (ICN) is a promising option to bridge and cover these enormous gaps. In this paper, a Smart Collaborative Caching (SCC) scheme is established by leveraging high-level ICN principles for IoT within fog computing paradigm. The proposed solution is supposed to be utilized in resource pooling, content storing, node locating and other related situations. By investigating the available characteristics of ICN, some challenges of such combination are reviewed in depth. The details of building SCC, including basic model and advanced algorithms, are presented based on theoretical analysis and simplified examples. The validation focuses on two typical scenarios: simple status inquiry and complex content sharing. The number of clusters, packet loss probability and other parameters are also considered. The analytical results demonstrate that the performance of our scheme, regarding total packet number and average transmission latency, can outperform that of the original ones. We expect that the SCC will contribute an efficient solution to the related studies.

Honey bees (Apis mellifera L.) are important ecological and agricultural resources. They are among the most widely available pollinators and provide products as well as services. Unfortunately, honey bee populations are susceptible to several environmental threats, including heavy metal exposure. Honey bees can be exposed to heavy metals when foraging on contaminated honey and pollen resources, and in some cases by airborne exposure. We studied the joint acute and chronic effects of cadmium (Cd) and copper (Cu) on A. mellifera. A 1:1 solution of the two heavy metals increased larval developmental duration and the mortality of both larvae and foragers in a dose-dependent way, decreased forager feeding, increased body metal burdens, and disrupted the sucrose response behavior of foragers. In combination, Cd and Cu demonstrated a weakly synergistic effect on foragers, but for larvae an initially antagonistic effect at low doses changed to strongly synergistic response at higher concentrations. The sucrose response threshold of foragers decreased significantly when they were dosed with increasing concentrations of the metal mixtures. Overall, the fitness of honey bee larvae and foragers is detrimentally affected when these metals co-occur.

Based on real data, a new parameterized model of the Main Drift Chamber response is proposed. In this model, we tune the ratio of good hits and the residual distribution separately. The difference between simulation and data in track reconstruction efficiency reduces from 1% to 0.5%, and the momentum resolution agreement improves significantly.

Small-conductance Ca²⁺-activated K⁺ channels (SK, K_Ca2) are gated solely by intracellular microdomain Ca²⁺. The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca²⁺ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate (PIP2) coordinates with CaM in regulating SK channels. However, the roles and mechanisms of PIP2 in regulating SK channels in cardiomyocytes remain unknown. Here, optogenetics, magnetic nanoparticles, combined with Rosetta structural modeling, and molecular dynamics (MD) simulations revealed the atomistic mechanisms of how PIP2 works in concert with Ca²⁺-CaM in the SK channel activation. Our computational study affords evidence for the critical role of the amino acid residue R395 in the S6 transmembrane segment, which is localized in propinquity to the intracellular hydrophobic gate. This residue forms a salt bridge with residue E398 in the S6 transmembrane segment from the adjacent subunit. Both R395 and E398 are conserved in all known isoforms of SK channels. Our findings suggest that the binding of PIP2 to R395 residue disrupts the R395:E398 salt bridge, increasing the flexibility of the transmembrane segment S6 and the activation of the channel. Importantly, our findings serve as a platform for testing of structural-based drug designs for therapeutic inhibitors and activators of the SK channel family. The study is timely since inhibitors of SK channels are currently in clinical trials to treat atrial arrhythmias.