Exploring the neuroprotection of the combination of astragaloside A, chlorogenic acid and scutellarin in treating chronic cerebral ischemia via network analysis and experimental validation.

Chronic cerebral ischemia (CCI) primarily causes cognitive dysfunction and other neurological impairments, yet there remains a lack of ideal therapeutic medications. The preparation combination of Astragalus membranaceus (Fisch.) Bunge and Erigeron breviscapus (Vant.) Hand.-Mazz have been utilized to ameliorate neurological dysfunction following cerebral ischemia, but material basis of its synergy remains unclear. The principal active ingredients and their optimal proportions in this combination have been identified through the oxygen and glucose deprivation (OGD) cell model, including astragaloside A, chlorogenic acid and scutellarin (ACS), and its efficacy in enhancing the survival of OGD PC12 cells surpasses that of the combination preparation. Nevertheless, mechanism of ACS against CCI remains elusive. In this study, 63 potential targets of ACS against CCI injury were obtained by network pharmacology, among which AKT1, CASP3 and TNF are the core targets. Subsequent analysis utilizing KEGG and GO suggested that PI3K/AKT pathway may play a crucial role for ACS in ameliorating CCI injury. Then, a right unilateral common carotid artery occlusion (rUCCAO) mouse model and an OGD PC12 cell model were established to replicate the pathological processes of CCI in vivo and in vitro. These models were utilized to explore the anti-CCI effects of ACS and its regulatory mechanisms, particularly focusing on PI3K/AKT pathway. The results showed that ACS facilitated the restoration of cerebral blood flow in CCI mice, enhanced the function of the central cholinergic nervous system, protected against ischemic nerve cell and mitochondrial damage, and improved cognitive function and other neurological impairments. Additionally, ACS upregulated the expression of p-PI3K, p-AKT, p-GSK3ß and Bcl-2, and diminished the expression of Cyto-c, cleaved Caspase-3 and Bax significantly. However, the PI3K inhibitor (LY294002) partially reversed the downregulation of Bax, Cyto-c and cleaved Caspase-3 expression as well as the upregulation of p-AKT/AKT, p-GSK3ß/GSK3ß, and Bcl-2/Bax ratios. These findings suggest that ACS against neuronal damage in cerebral ischemia may be closely related to the activation of PI3K/AKT pathway. These results declared first time ACS may become an ideal candidate drug against CCI due to its neuroprotective effects, which are mediated by the activated PI3K/AKT pathway mitigates mitochondrial damage and prevents cell apoptosis.

Broadband Spin-Dependent Directional Coupler via Single Optimized Metallic Catenary Antenna.

With the rapid development of on-chip optics, integrated optical devices with better performance are desirable. Waveguide couplers are the typical integrated optical devices, allowing for the fast transmission and conversion of optical signals in a broad working band. However, traditional waveguide couplers are limited by the narrow operation band to couple the spatial light into the chip and the fixed unidirectional transmission of light flow. Furthermore, most of the couplers only realize unidirectional transmission under the illumination of the linear polarized light. In this work, a broadband polarization directional coupler based on a metallic catenary antenna integrated on a silicon-on-insulator (SOI) waveguide has been designed and demonstrated under the illumination of the circularly polarized light. By applying the genetic algorithm to optimize the multiple widths of the metallic catenary antenna, the numerical simulation results show that the extinction ratio of the coupler can be maintained larger than 18 dB in a wide operation band of 300 nm (from 1400 to 1700 nm). Moreover, the coupler can couple the spatial beam into the plane and transmit in the opposite direction by modulating the rotation direction of the incident light. The broadband polarization directional coupler might have great potential in integrated optoelectronic devices and on-chip optical devices.

A Strategy for Amide to ß-Oxo Ester Transformation via N-Alkenoxypyridinium Salts as the Activator and H2O as the Nucleophile.

N-Alkenoxypyridinium salts were found to be highly active electrophilic reagents that could be used to activate the C-N bond of amides. Both aromatic amides and aliphatic amides could be transformed into the corresponding ß-oxo esters with good yields via the combined use of N-alkenoxypyridinium salts and water. The methodology proceeds under mild reaction conditions and is tolerant of various functional groups in both reaction partners.

Silver(i)-catalyzed addition of pyridine-N-oxides to alkynes: a practical approach for N-alkenoxypyridinium salts.

A smooth catalytic approach to N-alkenoxypyridinium salts by using pyridine-N-oxides as the nucleophilic partner with alkynes under acidic conditions has been developed. This method uses different Ag(i) salts, with 5% AgOAc being the most efficient, to provide an efficient, practical and alternative way to obtain valuable N-alkenoxypyridinium salts with good to excellent yields (up to 93%).