Template Synthesis to Solve the Unreachable Ortho C-H Functionalization Reaction of Aryl Iodide.

This report describes the use of a simple Pd/NBE catalytic system to achieve ortho C-H oxylation and phosphonylation and other functionalizations of aryl iodide through templated conversion reactions. Dimethylamine is introduced in the ortho-site of aryl iodide through C-H amination, and aryl dimethylamine is quickly converted to methyl quaternary ammonium salt precipitation. Methyl quaternary ammonium salt avoids Hofmann elimination in subsequent functionalization. This method solves various ortho functionalization reactions of aryl iodide that have not been achieved for a long time in the field of Pd/NBE chemistry indirectly.

A robust design strategy for active control of scattered sound based on virtual sensing.

Combining virtual sensing (VS) with scattered sound control enables active acoustic cloaking when there are limitations in sensor configurations. The remote microphone method and additional filter method (AFM) are two common VS methods, and both can be divided into the training and control stages; the consistency of the environments in these two stages is essential for the control system. This paper investigates the effects of uncertainties in the incidence angle of the detection wave on these two VS-based scattered sound control methods. Following the analysis, we propose a robust design strategy based on the optimal layout of physical sensors, and the placement scheme is chosen by minimax optimization. The feasibility of the proposed strategy is verified by numerical simulations of a finite-length cylindrical scattering model. The results demonstrate that the proposed strategy can effectively reduce the degradation of system performance over the examined range of variations in the detection waves. In particular, the AFM-based method, combined with optimal placement, shows a remarkable improvement in robustness. It improves the worst noise reduction by approximately 14.5 and 10.8 dB on average, respectively, compared with the uniform placement and the direct control method based on the Wiener solution.

Evaluation of recombinant adenovirus vaccines based on glycoprotein D and truncated UL25 against herpes simplex virus type 2 in mice.

The high prevalence of herpes simplex virus 2 (HSV-2) infections in humans necessitates the development of a safe and effective vaccine that will need to induce vigorous T-cell responses to control viral infection and transmission. We designed rAd-gD2, rAd-gD2ΔUL25, and rAd-ΔUL25 to investigate whether recombinant replication-defective adenoviruses vaccine could induce specific T-cell responses and protect mice against intravaginal HSV-2 challenge compared with FI-HSV-2. In the present study, recombinant adenovirus-based HSV-2 showed higher reductions in mortality and stronger antigen-specific T-cell responses compared with FI-HSV-2 and the severity of genital lesions in mice immunized with rAd-gD2ΔUL25 was significantly decreased by eliciting IFN-γ-secreting T-cell responses compared with rAd-gD2 and rAd-ΔUL25 groups. Our results demonstrated the immunogenicity and protective efficacy of recombinant adenovirus vaccines in acute HSV-2 infection following intravaginal challenge in mice.

Loss of TET Activity in the Postnatal Mouse Brain Perturbs Synaptic Gene Expression and Impairs Cognitive Function.

Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.

Direct Synthesis of C4-Acyl Indoles via C-H Acylation.

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the ortho C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.

Multi-objective optimisation for cell-level disassembly of waste power battery modules in human-machine hybrid mode.

The rapid global growth in the production of electric vehicles (EVs) will produce numerous waste power battery modules (WPBMs) in the future, which will create significant challenges concerning waste disposal. Therefore, measures to disassemble and recycle WPBMs before using them in other fixed scenarios provide an opportunity for research. First, considering battery components' hazards and complex properties, a human-machine collaborative cell-level disassembly model of WPBMs is proposed. Second, the WPBMs from the Tesla Model S are selected as the case study to verify reliability and validity. Finally, two different disassembly schemes are obtained by solving the proposed model using NSGA-II based on the actual data from resource-recycling companies. The results show that: 1) The proposed model and method can realize the cell-level disassembly of WPBMs and assign the disassembly tasks of hazard components to robots and the disassembly tasks of complex components to humans. 2) The two disassembly schemes obtained are two solutions that do not dominate each other, and the four objectives (number of workstations, workstation idle time, number of workers, and disassembly cost) are optimized simultaneously. 3) The proposed model can provide decision-makers with additional options when incorporating the number of workers into enterprise risk indicators.

PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum.

Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with paroxysmal kinesigenic dyskinesia (PKD) and several other paroxysmal neurological diseases, but the PRRT2 function and pathogenic mechanisms remain largely obscure. Here we show that PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation of the cerebellum. Mutant mice with specific PRRT2 deletion in cerebellar granule cells (GCs) recapitulate the behavioral phenotypes seen in Prrt2-null mice. Furthermore, recording made in cerebellar slices showed that optogenetic stimulation of GCs results in transient elevation followed by suppression of Purkinje cell firing. The anticonvulsant drug carbamazepine used in PKD treatment also relieved PKD-like behaviors in mutant mice. Together, our findings identify PRRT2 as a novel regulator of the SNARE complex and provide a circuit mechanism underlying the PRRT2-related behaviors.

Optimized DNA Vaccine Enhanced by Adjuvant IL28B Induces Protective Immune Responses Against Herpes Simplex Virus Type 2 in Mice.

Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant. Immunization with gD2ΔUL25/IL28B elicited stronger humoral and T cell immune responses than with gD2ΔUL25 alone. Compared with controls, gD2ΔUL25/IL28B decreased HSV-2 viral loads and induced protective effects against genital tract lesions generated by HSV-2. These findings demonstrated that the prophylactic DNA vaccine gD2ΔUL25 with IL28B adjuvant could enhance the humoral and T cell immune responses, and improve the protective immune response against HSV-2 in female mice compared with FI-HSV-2.