Gold-catalyzed dehydrogenative cycloisomerization of 1,4-Enyne Esters to 3,5-Disubstituted Phenol derivatives

A method to prepare synthetically important 3,5-disubstituted phenol derivatives that relies on the sequential gold(I)-catalyzed dehydrogenative cycloisomerization of 1,4-enyne esters in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) or N-fluorobenzenesulfonimide (NFSI) is described. The synthetic versatility of the methodology was exemplified by a gram-scale reaction of one example, the ease to realize subsequent functional transformations of an adduct, and the application of the method to the synthesis of the bioactive molecule LUF5771

Nondestructive testing of grating imperfections using grating-based X-ray phase-contrast imaging

We reported the usage of grating-based X-ray phase-contrast imaging in nondestructive testing of grating imperfections. It was found that electroplating flaws could be easily detected by conventional absorption signal, and in particular, we observed that the grating defects resulting from uneven ultraviolet exposure could be clearly discriminated with phase-contrast signal. The experimental results demonstrate that grating-based X-ray phase-contrast imaging, with a conventional low-brilliance X-ray source, a large field of view and a reasonable compact setup, which simultaneously yields phase- and attenuation-contrast signal of the sample, can be ready-to-use in fast nondestructive testing of various imperfections in gratings and other similar photoetching products.Comment: 6 pages, 5 figures and 2 table

Alkyl Halides as Both Hydride and Alkyl Sources in Catalytic Regioselective Reductive Olefin Hydroalkylation

Among the plethora of catalytic methods developed for hydrocarbofunctionalization of olefins to date, reactions that regioselectively install a functionalized alkyl unit at the 2-position of a terminal unactivated C=C bond to afford branched products are scarce. Here, we show that a Ni-based catalyst in conjunction with a stoichiometric reducing agent promote Markovnikov-selective hydroalkylation of unactivated alkenes tethered to a recyclable 8-aminoquinaldine directing auxiliary. These mild reductive processes employ readily available primary and secondary haloalkanes as both the hydride and alkyl donor, obviating the need for additional hydrosilane, acidic or basic additives. Reactions of alkenyl amides with ≥five-carbon chain length regioselectively afforded β-alkylated products through remote hydroalkylation, underscoring the fidelity of the catalytic process and the directing group\u27s capability in stabilizing five-membered nickelacycle intermediates. The operationally simple protocol exhibits exceptional functional group tolerance and is amenable to the synthesis of bioactive molecules as well as regioconvergent transformations

The role of robotic surgery in neurological cases: A systematic review on brain and spine applications

The application of robotic surgery technologies in neurological surgeries resulted in some advantages compared to traditional surgeries, including higher accuracy and dexterity enhancement. Its success in various surgical fields, especially in urology, cardiology, and gynecology surgeries was reported in previous studies, and similar advantages in neurological surgeries are expected. Surgeries in the central nervous system with the pathology of millimeters through small working channels around vital tissue need especially high precision. Applying robotic surgery is therefore an interesting dilemma for these situations. This article reviews various studies published on the application of brain and spine robotic surgery and discusses the current application of robotic technology in neurological cases

Gold-catalyzed tandem 1,3-migration/double cyclopropanation of 1-Ene-4,n-diyne esters to tetracyclodecene and tetracycloundecene derivatives

A synthetic method that relies on Au(I)-catalyzed tandem 1,3-acyloxy migration/double cyclopropanation of 1-ene-4,9-diyne and 1-ene-4,10-diyne esters to construct the respective architecturally challenging tetracyclodecene and tetracycloundecene derivatives is described. Achieved under mild reaction conditions, the transformation was shown to be robust with a wide variety of substitution patterns tolerated to give the two members of the carbocyclic family in good to excellent yields and as a single regio- and diastereomer

Lifelong chronic psychosocial stress induces a proteomic signature of Alzheimer's disease in wildtype mice

Late onset, sporadic Alzheimer's disease (AD) accounts for the vast majority of cases. Unlike familial AD, the factors that drive the onset of sporadic AD are poorly understood, although aging and stress play a role. The early onset/severity of neuropathology observed in most genetic mouse models of AD hampers the study of the role of aging and environmental factors; thus alternate strategies are necessary to understand the contributions of these factors to sporadic AD. We demonstrate that mice acquiring a low social status (subordinate) in a lifelong chronic psychosocial stress (CPS) model, accrue widespread proteomic changes in the frontal/temporal cortex during aging. To better understand the significance of these stress-induced changes, we compared the differentially expressed proteins (DEPs) of subordinate mice to those of patients at varying stages of dementia. Sixteen and fifteen DEPs upregulated in subordinate mice were also upregulated in patients with mild cognitive impairment (MCI) and AD, respectively. Six of those upregulated proteins (CPE, ERC2, GRIN2B, SLC6A1, SYN1, WFS1) were shared by subordinate mice and patients with MCI or AD. Finally, comparison with a spatially detailed transcriptomic database revealed that the superior frontal gyrus and hippocampus had the greatest overlap between mice subjected to lifelong CPS and AD patients. Overall, most of the overlapping proteins were functionally associated with enhanced NMDA receptor mediated glutamatergic signaling, an excitotoxicity mechanism known to affect neurodegeneration. These findings support the association between stress and AD progression and provide valuable insight into potential early biomarkers and protein mediators of this relationship

Comprehensive Analysis of Differentially Expressed mRNA, lncRNA and circRNA and Their ceRNA Networks in the Longissimus Dorsi Muscle of Two Different Pig Breeds

Circular RNA (circRNA) and long non-coding RNA (lncRNA) are known to participate in adipogenesis and myogenic differentiation, but their impact on porcine muscle traits is not well understood. We compared their expressional profiles in the longissimus dorsi muscle of Chinese Huainan pigs (HN, the fat type) and Western commercial Duroc×(Landrace×Yorkshire) (DLY, the thin type) pigs, and 854 mRNAs, 233 lncRNAs, and 66 circRNAs (p < 0.05 and ｜log2FoldChange｜>1) were found to be differentially expressed. The differentially expressed mRNA and circRNA parental genes were enriched in the Wnt signaling pathway (adipogenesis), the transition between fast and slow fibers (myogenic differentiation), and alanine, aspartate and glutamate metabolism (pork flavor). The potential lncRNAs/circRNAs-miRNAs-mRNAs regulatory networks shared MYOD1, PPARD, miR-423-5p and miR-874, which were associated with skeletal muscle muscular proliferation, differentiation/regeneration and adipogenesis. Taken together, these differentially expressed non-coding RNAs may be involved in the molecular basis of muscle traits, acting as the competing endogenous RNA (ceRNA) for miRNAs

Sex specific molecular networks and key drivers of Alzheimer’s disease

Abstract Background Alzheimer’s disease (AD) is a progressive and age-associated neurodegenerative disorder that affects women disproportionally. However, the underlying mechanisms are poorly characterized. Moreover, while the interplay between sex and ApoE genotype in AD has been investigated, multi-omics studies to understand this interaction are limited. Therefore, we applied systems biology approaches to investigate sex-specific molecular networks of AD. Methods We integrated large-scale human postmortem brain transcriptomic data of AD from two cohorts (MSBB and ROSMAP) via multiscale network analysis and identified key drivers with sexually dimorphic expression patterns and/or different responses to APOE genotypes between sexes. The expression patterns and functional relevance of the top sex-specific network driver of AD were further investigated using postmortem human brain samples and gene perturbation experiments in AD mouse models. Results Gene expression changes in AD versus control were identified for each sex. Gene co-expression networks were constructed for each sex to identify AD-associated co-expressed gene modules shared by males and females or specific to each sex. Key network regulators were further identified as potential drivers of sex differences in AD development. LRP10 was identified as a top driver of the sex differences in AD pathogenesis and manifestation. Changes of LRP10 expression at the mRNA and protein levels were further validated in human AD brain samples. Gene perturbation experiments in EFAD mouse models demonstrated that LRP10 differentially affected cognitive function and AD pathology in sex- and APOE genotype-specific manners. A comprehensive mapping of brain cells in LRP10 over-expressed (OE) female E4FAD mice suggested neurons and microglia as the most affected cell populations. The female-specific targets of LRP10 identified from the single cell RNA-sequencing (scRNA-seq) data of the LRP10 OE E4FAD mouse brains were significantly enriched in the LRP10-centered subnetworks in female AD subjects, validating LRP10 as a key network regulator of AD in females. Eight LRP10 binding partners were identified by the yeast two-hybrid system screening, and LRP10 over-expression reduced the association of LRP10 with one binding partner CD34. Conclusions These findings provide insights into key mechanisms mediating sex differences in AD pathogenesis and will facilitate the development of sex- and APOE genotype-specific therapies for AD