A novel pH‐responsive molecular shuttle based on a 2rotaxane with a phosphine ligand has been designed and synthesized. In the rhodium‐catalyzed hydrogenation of α,β‐dehydroamino acid esters and aryl ...enamides, ON/OFF‐switchable catalysis was accomplished with high ON/OFF ratios by adjusting the movements of the rotaxane wheels located at the catalyst terminals with acid/base. Mechanistic studies using NMR spectroscopy and quasi in situ X‐ray photoelectron spectroscopy revealed that RhIII‐hydride species are possibly formed in a H2 atmosphere when the catalyst is in the OFF state. During the reaction, a heterolytic activation of dihydrogen occurs by the interlocked rotaxane dibenzylamine and RhI catalytic center acting as a frustrated Lewis pair. Subsequent homolytic splitting of dihydrogen with the newly formed RhI‐hydride species generates RhIII‐hydride species. These findings show that a substrate‐selective hydrogenation can be achieved by using the OFF‐state catalyst.
A molecular shuttle based on a 2rotaxane with a phosphine ligand has been applied to the rhodium‐catalyzed hydrogenation of α,β‐dehydroamino acid esters and aryl enamides. The hydrogenation can be switched ON/OFF efficiently by adjusting the movement of the rotaxane wheels with acid/base. Mechanistic studies have revealed that the formation of inactive RhIII‐hydride species might be the reason for shutdown of the reaction.
Aim： Homocysteine （Hcy） can elicit neuronal cell death, and hyperhomocysteinemia is a strong independent risk factor for Alzheimer’s disease. The aim of this study was to examine the effects of ...hydrogen sulfide （H2S） on Hcy-induced endoplasmic reticulum （ER） stress and neuronal apoptosis in rat hippocampus.
Methods： Adult male SD rats were intracerebroventricularly （icv） injected with Hcy （0.6 μmol/d） for 7 d. Before Hcy injection, the rats were treated with NaHS （30 or 100 μmol·kg^-1·d^-1, ip） and/or k252a （1 μg/d, icv） for 2 d. The apoptotic neurons were detected in hippocampal coronal slices with TUNEL staining. The expression of glucose regulated protein 78 （GRP78）, C/EBP homologous protein （CHOP）, cleaved caspase-12, and BDNF in the hippocampus were examined using Western blotting assays. The generation of H2S in the hippocampus was measured with the NNDPD method.
Results： Hcy markedly inhibited the production of endogenous H2S and increased apoptotic neurons in the hippocampus. Further-more, Hcy induced ER stress responses in the hippocampus, as indicated by the upregulation of GRP78, CHOP, and cleaved caspase-12. Treatment with the H2S donor NaHS increased the endogenous H2S production and BDNF expression in a dose-dependent manner, and significantly reduced Hcy-induced neuronal apoptosis and ER stress responses in the hippocampus. Treatment with k252a, a specific inhibitor of TrkB （the receptor of BDNF）, abolished the protective effects of NaHS against Hcy-induced ER stress in the hippocampus.
Conclusion： H2S attenuates ER stress and neuronal apoptosis in the hippocampus of Hcy-treated rats via upregulating the BDNF-TrkB pathway.
Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). ...However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.
Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the ...hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA-A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole-cell patch-clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor-mediated currents, increased paired-pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.
Abstract
Background
Cerebral venous sinus thrombosis (CVST) is typically associated with a prothrombotic state of the blood, with its causative factors varying widely. Prior research has not reported ...the simultaneous occurrence of CVST and dural arteriovenous fistulas (DAVFs) as potentially resulting from genetic mutations. In this case report, we introduce a unique occurrence wherein a patient with a heterozygous mutation of the low-density lipoprotein receptor (
LDLR)
gene presented with CVST in conjunction with DAVFs.
Case
P
resentation
: A male patient, aged 51, sought treatment at our facility due to a consistent decline in cognitive functions accompanied by recurrent headaches. Comprehensive evaluations were administered, including neurological examinations, laboratory tests, magnetic resonance imaging, digital subtraction angiography, and whole exome sequencing. Digital subtraction angiography identified DAVFs in the patient’s right sigmoid sinus and an occlusion within the left transverse sinus. The whole exome sequencing of blood samples pinpointed a heterozygous mutation in the
LDLR
gene (NM_000527:exon12:c.C1747T:p.H583Y). Following the confirmed diagnosis of CVST and DAVFs, the patient underwent anticoagulant therapy combined with endovascular procedures — these comprised embolization of the arteriovenous fistula in the right sigmoid sinus and balloon dilation with stent implantation in the left transverse sinus. A six-month follow-up indicated a significant abatement in the patient’s symptoms.
Conclusions
This report marks the first documented case of an
LDLR
gene mutation that could be associated with the onset of CVST and DAVFs. The mutation in the
LDLR
gene might foster a prothrombotic environment, facilitating the gradual emergence of CVST and the subsequent genesis of DAVFs.
In the present study, a new strategy including the combination of external appearance, chemical detection, and biological analysis was proposed for the comprehensive evaluation of safflowers in ...different producing areas. Firstly, 40 batches of safflower samples were classified into class I and II based on color measurements and K-means clustering analysis. Secondly, a rapid and sensitive analytical method was developed for simultaneous quantification of 16 chromaticity-related characteristic components (including characteristic components hydroxysafflor yellow A, anhydrosafflor yellow B, safflomin C, and another 13 flavonoid glycosides) in safflowers by ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP
/MS
). The results of the quantification indicate that hydroxysafflor yellow A, anhydrosafflor yellow B, kaempferol, quercetin, and safflomin C had significant differences between the two types of safflower, and class I of safflower had a higher content of hydroxysafflor yellow A, anhydrosafflor yellow B, and safflomin C as the main anti-thrombotic components in safflower. Thirdly, chemometrics methods were employed to illustrate the relationship in multivariate data of color measurements and chromaticity-related characteristic components. As a result, kaempferol-3-
-rutinoside and 6-hydroxykaempferol-3-
-β-d-glucoside were strongly associated with the color indicators. Finally, anti-thrombotic analysis was used to evaluate activity and verify the suitability of the classification basis of safflower based on the color measurements. It was shown that brighter, redder, yellower, more orange-yellow, and more vivid safflowers divided into class I had a higher content of characteristic components and better anti-thrombotic activity. In summary, the presented strategy has potential for quality evaluation of other flower medicinal materials.
Vertical heterostructures of two-dimensional (2D) materials are excellent candidates for designing next-generation electronic devices with superior performance. By using both ab initio electronic ...calculations and quantum transport simulations, we investigated the electronic and transport properties of InAs/graphene heterostructure. The results reveal that electrons and holes accumulate at different layers after the adsorption of InAs layer, forming the built-in electronic field at the interface. The electrostatic potential energy of InAs layer is higher than that of graphene, and it favors more electrons transferring from InAs to graphene layer. Comparing the comment methods by introducing impurity and carriers' injection, rectifying and negative differential resistance behaviors can also be realized by the combined effects of electron-hole distribution, interfacial hybridization, and contact barrier in InAs/graphene heterostructure device. It shows that the rectifying ration gradually increases with bias voltage, and the negative differential resistance effect happens at either positive or at negative bias voltage regions. Electrostatic potential distribution and contact barrier play important roles in determining transport properties. Increasing interfacial hybridization is helpful for transmission enhancement in the weak interlayer interaction van der Waals heterostructure.
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•Key role of interfacial potential distribution and barriers on transport behaviors•A novel 2D p-n heterojunction can be achieved by the interfacial hybridization.•Rectifying and negative differential resistance behaviors can be observed.
The spikelet number per spike (SNS) contributes greatly to grain yield in wheat. Identifying various genes that control wheat SNS is vital for yield improvement. This study used a recombinant inbred ...line population genotyped by the Wheat55K single-nucleotide polymorphism array to identify two major and stably expressed quantitative trait loci (QTLs) for SNS. One of them (QSns.sau-2SY-2D.1) was reported previously, while the other (QSns.sau-2SY-7A) was newly detected and further analyzed in this study. QSns.sau-2SY-7A had a high LOD value ranging from 4.46 to 16.00 and explained 10.21–40.78％ of the phenotypic variances. QSns.sau-2SY-7A was flanked by the markers AX-110518554 and AX-110094527 in a 4.75-cM interval on chromosome arm 7AL. The contributions and interactions of both major QTLs were further analyzed and discussed. The effect of QSns.sau-2SY-7A was successfully validated by developing a tightly linked kompetitive allele specific PCR marker in an F2:3 population and a panel of 101 high-generation breeding wheat lines. Furthermore, several genes including the previously reported WHEAT ORTHOLOG OF APO1 (WAPO1), an ortholog of the rice gene ABERRANT PANICLE ORGANIZATION 1 (APO1) related to SNS, were predicted in the interval of QSns.sau-2SY-7A. In summary, these results revealed the genetic basis of the multi-spikelet genotype of wheat line 20828 and will facilitate subsequent fine mapping and breeding utilization of the major QTLs.
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•(NH4)2SiF6 is used as silicon source to electrodeposit NiCo-SiO2 composite film.•Nanostructured NiCo@NiCoOx core-shell layer is obtained after the etching of SiO2 template.•An ...overpotential of 337mV is needed to deliver a current density of 100mAcm−2.•The good electrical conductivity in the core and high catalytic activity on the shell result in the high OER performance.
A nanostructured NiCo@NiCoOx core-shell layer for oxygen evolution reaction in alkaline solution was prepared. Firstly, a NiCo-SiO2 composite film was electro-codeposited from a solution containing (NH4)2SiF6, NiSO4, and CoSO4. Then the as-prepared composite layer was underwent consecutive CV scans in concentrated alkaline solution. During this process, the SiO2 template was etched and the NiCo component was activated leading to the generation of a NiCoOx shell. Results shown that this nanostructured NiCo@NiCoOx core-shell layer can provide a current density of 100mAcm−2 in 1.0M KOH at a low overpotential of 337mV and exhibits good stability towards water oxidation. The excellent OER performance is enabled with the unique metal-oxide/hydroxide core-shell structure, which allows high electrical conductivity in the core and high catalytic activity on the shell.
•D-Limonene activates AMPKα and suppresses NF-κB nuclear translocation in PC12 cells.•d-Limonene activates AMPKα through up-regulation of SIRT1.•d-Limonene alleviates corticosterone-induced oxidative ...stress in PC12 cells.•d-Limonene is a negative regulator of proinflammatory factor expression in corticosterone-treated PC12 cells.•d-Limonene reduces apoptosis in corticosterone-treated PC12 cells.
The stress-induced hormone corticosterone initiates oxidative stress and inflammatory responses, culminating in cell apoptosis and neurological changes. We assessed the effects of d-Limonene on a PC12 cellular model of corticosterone-induced neurotoxicity, and whether these effects involved the AMP-activated protein kinase (AMPKα) pathway. PC12 cells were treated with corticosterone with or without d-limonene for 24 h. Western blots were performed to measure activation of AMPK pathway members Silent mating type information regulation 2 homolog-1 (SIRT1), AMPKα, and nuclear factor (NFκB), reactive oxygen species, inflammatory cytokines, and markers of apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to measure cell death after treatment. d-Limonene reversed the effects of corticosterone on PC12 cells: it decreased the levels of malondialdehyde (MDA) and nitric oxide (NO), activities of NADPH oxidase (p67-phox and p47-phox), expression of pro-inflammatory markers inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α), and expression of pro-apoptotic proteins Bcl2 associated with X protein (Bax) and cleaved caspase-3). d-Limonene also increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO-1) and the anti-apoptotic protein Bcl-2 while decreasing the number of TUNEL-positive cells. d-limonene significantly activated AMPKα and suppressed NF-κB nuclear translocation through up-regulation of SIRT1. Addition of compound C, an AMPK inhibitor, severely weakened these neuroprotective effects of d-limonene. d-Limonene has a neuroprotective effect on corticosterone-induced PC12 cell injury induced by activating the AMPKα signaling pathway, and thereby inhibiting reactive oxygen species and inflammatory factors. These data suggest that d-limonene might protect against neuronal death to improve depressive symptoms.
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