Baicalin, which is isolated from Radix Scutellariae, possesses strong biological activities including an anti-inflammation property. Recent studies have shown that the anti-inflammatory effect of ...baicalin is linked to toll-like receptor 4 (TLR4), which participates in pathological changes of central nervous system diseases such as depression. In this study, we explored whether baicalin could produce antidepressant effects via regulation of TLR4 signaling in mice and attempted to elucidate the underlying mechanisms.
A chronic unpredictable mild stress (CUMS) mice model was performed to explore whether baicalin could produce antidepressant effects via the inhibition of neuroinflammation. To clarify the role of TLR4 in the anti-neuroinflammatory efficacy of baicalin, a lipopolysaccharide (LPS) was employed in mice to specially activate TLR4 and the behavioral changes were determined. Furthermore, we used LY294002 to examine the molecular mechanisms of baicalin in regulating the expression of TLR4 in vivo and in vitro using western blot, ELISA kits, and immunostaining. In the in vitro tests, the BV2 microglia cell lines and primary microglia cultures were pretreated with baicalin and LY292002 for 1 h and then stimulated 24 h with LPS. The primary microglial cells were transfected with the forkhead transcription factor forkhead box protein O 1 (FoxO1)-specific siRNA for 5 h and then co-stimulated with baicalin and LPS to investigate whether FoxO1 participated in the effect of baicalin on TLR4 expression.
The administration of baicalin (especially 60 mg/kg) dramatically ameliorated CUMS-induced depressive-like symptoms; substantially decreased the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the hippocampus; and significantly decreased the expression of TLR4. The activation of TLR4 by the LPS triggered neuroinflammation and evoked depressive-like behaviors in mice, which were also alleviated by the treatment with baicalin (60 mg/kg). Furthermore, the application of baicalin significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and FoxO1. The application of baicalin also promoted FoxO1 nuclear exclusion and contributed to the inhibition of the FoxO1 transactivation potential, which led to the downregulation of the expression of TLR4 in CUMS mice or LPS-treated BV2 cells and primary microglia cells. However, prophylactic treatment of LY294002 abolished the above effects of baicalin. In addition, we found that FoxO1 played a vital role in baicalin by regulating the TLR4 and TLR4-mediating neuroinflammation triggered by the LPS via knocking down the expression of FoxO1 in the primary microglia.
Collectively, these results demonstrate that baicalin ameliorated neuroinflammation-induced depressive-like behaviors through the inhibition of TLR4 expression via the PI3K/AKT/FoxO1 pathway.
Ferroelectricity and X‐ray detection property have been recently implemented for the first time in hybrid bromide double perovskites. It sheds a light on achieving photosensitive and ferroelectric ...multifunctional materials based on 2D lead‐free hybrid halide double perovskites. However, the low Tc, small Ps, and relatively low X‐ray sensitivity in the reported bromide double perovskites hinder practical applications. Herein, the authors demonstrate a novel 2D lead‐free iodide double perovskite (4,4‐difluoropiperidinium)4AgBiI8 (1) for high‐performance X‐ray sensitive ferroelectric devices. Centimeter‐sized single crystal of 1 is obtained and exhibits an excellent ferroelectricity including a high Tc up to 422 K and a large Ps of 10.5 μC cm−2. Moreover, due to a large X‐ray attenuation and efficient charge carrier mobility (μ)–charge carrier lifetime (τ) product, the crystal 1 also exhibits promising X‐ray response with a high sensitivity up to 188 μC·Gyair−1 cm−2 and a detection limit below 3.13 μGyair·s−1. Therefore, this finding is a step further toward practical applications of lead‐free halide perovskite in high‐performance photoelectronic devices. It will afford a promising platform for exploring novel photosensitive ferroelectric multifunctional materials based on lead‐free double perovskites.
Ferroelectricity and X‐ray detection are realized in lead‐free hybrid double perovskite (DFPIP)4AgBiI8. It achieves excellent ferroelectricity (Tc = 422 K, Ps = 10.5 µC cm−2) and superior sensitivity of 188 µC·Gyair−1 cm−2 as an X‐ray detector. This finding will stimulate extensive research interest in photosensitive molecular ferroelectrics based on lead‐free double perovskites.
The relationship between serum cholesterol level and development of hepatocellular carcinoma (HCC) remains unclear. We investigated the effects of serum cholesterol level on development of liver ...tumors in mice.
We performed studies with C57BL/6J mice, mice with disruption of the low-density lipoprotein receptor gene (Ldlr−/−mice), and mice with conditional deletion of nature killer (NK) cells (NKdele mice). Some C57BL/6J and NKdele mice were given injections of diethylinitrosamine to induce liver tumor formation. Mice were placed on a normal diet (ND) or high-cholesterol diet (HCD) to induce high serum levels of cholesterol. We also studied mice with homozygous disruption of ApoE (ApoE−/− mice), which spontaneously develop high serum cholesterol. C57BL/6J and NKdele mice on the ND or HCD were implanted with Hep1-6 (mouse hepatoma) cells and growth of xenograft tumors and lung metastases were monitored. Blood samples were collected from mice and analyzed by biochemistry and flow cytometry; liver and tumor tissues were collected and analyzed by histology, immunohistochemistry, and RNA-sequencing analysis. NK cells were isolated from mice and analyzed for cholesterol content, lipid raft formation, immune signaling, and changes in functions. We obtained matched tumor tissues and blood samples from 30 patients with HCC and blood samples from 40 healthy volunteers; levels of cholesterol and cytotoxicity of NK cells were measured.
C57BL/6J mice on HCD and ApoE−/− mice with high serum levels of cholesterol developed fewer and smaller liver tumors and lung metastases after diethylinitrosamine injection or implantation of Hep1-6 cells than mice on ND. Liver tumors from HCD-fed mice and ApoE−/− mice had increased numbers of NK cells compared to tumors from ND-fed mice. NKdele mice or mice with antibody-based depletion for NK cells showed similar tumor number and size in ND and HCD groups after diethylinitrosamine injection or implantation of Hep1-6 cells. NK cells isolated from C57BL/6J mice fed with HCD had increased expression of NK cell–activating receptors (natural cytotoxicity triggering receptor 1 and natural killer group 2, member D), markers of effector function (granzyme B and perforin), and cytokines and chemokines compared with NK cells from mice on ND; these NK cells also had enhanced cytotoxic activity against mouse hepatoma cells, accumulated cholesterol, increased lipid raft formation, and immune signaling activation. NK cells isolated from HCD-fed Ldlr−/− mice did not have increased cholesterol content or cytotoxic activity against mouse hepatoma cells compared with ND-fed Ldlr−/− mice. Serum levels of cholesterol correlated with number and activity of NK cells isolated from human HCCs.
Mice with increased serum levels of cholesterol due to an HCD or genetic disruption of ApoE develop fewer and smaller tumors after injection of hepatoma cells or a chemical carcinogen. We found cholesterol to accumulate in NK cells and activate their effector functions against hepatoma cells. Strategies to increase cholesterol uptake by NK cells can be developed for treatment of HCC.
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Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We ...show levels of Disrupted‐in‐schizophrenia‐1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ‐treated cultured cells. Disrupted‐in‐schizophrenia‐1 contains a canonical LC3‐interacting region (LIR) motif (210FSFI213), through which DISC1 directly binds to LC3‐I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking‐down of DISC1 blocks Aβ‐induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which abolishes the interaction of DISC1 with LC3, rescues Aβ‐induced mitochondrial dysfunction, loss of spines, suppressed long‐term potentiation (LTP). Overexpression of DISC1 via adeno‐associated virus (serotype 8, AAV8) in the hippocampus of 8‐month‐old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aβ plaque accumulation, in a way dependent on the interaction of DISC1 with LC3. These results indicate that DISC1 is a novel mitophagy receptor, which protects synaptic plasticity from Aβ accumulation‐induced toxicity through promoting mitophagy.
In this paper, the biosynthesis process of phenolic compounds in plants is summarized, which include the shikimate, pentose phosphate and phenylpropanoid pathways. Plant phenolic compounds can act as ...antioxidants, structural polymers (lignin), attractants (flavonoids and carotenoids), UV screens (flavonoids), signal compounds (salicylic acid, flavonoids) and defense response chemicals (tannins, phytoalexins). From a human physiological standpoint, phenolic compounds are vital in defense responses, such as anti-aging, anti-inflammatory, antioxidant and anti-proliferative activities. Therefore, it is beneficial to eat such plant foods that have a high antioxidant compound content, which will cut down the incidence of certain chronic diseases, for instance diabetes, cancers and cardiovascular diseases, through the management of oxidative stress. Furthermore, berries and other fruits with low-amylase and high-glucosidase inhibitory activities could be thought of as candidate food items in the control of the early stages of hyperglycemia associated with type 2 diabetes.
To achieve effective interference suppression, the receiving array executes adaptive spatial filtering according to interference directions. However, due to the time-varying propagation path and the ...relative motion between the interference sources and the receiving array, the directions of interferences impinging on the receiving array will deviate, which will result in non-stationary interferences, thus the filtering effect is not satisfactory. The current research algorithms mainly focus on the uniform linear array, uniform plane array, etc. There are few null widening studies on conformal array. To address this problem, we innovatively propose a null widening algorithm based on the covariance matrix taper (CMT) for the cylindrical conformal array which has been widely used in airborne radar. We first consider two different distribution interferences, the possible interference are then added in the training sample by multiplying the covariance matrix with the taper matrix. Simulation results verify the significant robustness and effectiveness of the proposed algorithm under two different distribution interferences case.
A series of coordination polymers, namely Zn(μ
3
-L)(H
2
O)
2
(
1
), Zn(μ
2
-L)(2,2′-bpy)(H
2
O) (
2
), Zn(μ
3
-L)(μ
2
-4,4′-bpy)
0.5
(
3
), Cd(μ
3
-L)(2,2′-bpy) (
4
), and Cd(μ
2
-L)(phen)(H
2
O) ...(
5
) (H
2
L = 3-carboxy-1-(3′-carboxybenzyl)-2-oxidopyridinium, 2,2′-bpy = 2,2′-bipyridine, 4,4′-bpy = 4,4′-bipyridine, phen = 1,10-phenanthroline), have been synthesized under hydrothermal conditions. These coordination polymers have been characterized by single-crystal X-ray diffraction, elemental analyses, infrared spectroscopy, thermogravimetric analyses and powder X-ray diffraction. The structure analysis by single crystal X-ray diffraction reveals that compound
1
shows a 1D double chain which can be expanded to a 2D supramolecular architecture through intermolecular π-π stacking interactions. In compound
2
, the 1D wave-like chains are extended to a 3D supramolecular framework by intermolecular hydrogen bonds and π-π stacking interactions. In compound
3
, the infinite rod-like metal ion chains are linked with L
2−
anions and 4,4′-bpy to form a 3D framework. In compound
4
, the adjacent 1D loop-like chains are interconnected to a 3D supramolecular framework by intermolecular hydrogen bonds and π-π stacking interactions. Compound
5
displays a 3D supramolecular architecture extended from the 1D zigzag chains by intermolecular hydrogen bonds and π-π stacking interactions. The result reveals that the organic ligand plays a key role in the self-assembly of coordination polymers. The luminescence sensing experiments reveal that compounds
1-5
can effectively detect Fe
3+
, Cr
2
O
7
2−
, and NB. In particular, compound
1
shows a high quenching constant and a low limit of detection for Fe
3+
.
Five CPs have been synthesized by a new semi-rigid dicarboxyl ligand and neutral ligands under hydrothermal conditions, and their luminescent sensing experiments for different small molecules/ions were studied in detail.
Coronary sinus perforation is a life‐threatening complication of transseptal puncture and needs to be repaired immediately. In this study, we report a case of a 74‐year‐old female patient with ...nonvalvular atrial fibrillation, who is a poor long‐term anticoagulation candidate. During the manipulation of transseptal puncture, a perforation of the free right atrial wall at the coronary sinus ostium occurred, which was caused by the Brockenbrough needle and followed by the immediate advancement of an 8.5‐French transseptal sheath. In consideration of the danger of cardiac tamponade after sheath removal, we decided to leave the 8.5‐French sheath in the pericardial cavity. Then, we advanced a 6 mm ventricular septal occluder through the sheath. Finally, we achieved successful deployment of the device and closure of the perforation under the guidance of fluoroscopy and transthoracic echocardiography. Subsequently, the left atrial appendage orifice was occluded with a 21 mm Watchman device. This case illustrates that percutaneous device closure is feasible for inadvertent perforation of the free right atrial wall at the coronary sinus during transseptal puncture and should be considered as an alternative to surgery.
Evaluation of precipitation and nitrogen (N) deposition in desert ecosystems helps to elucidate the reaction of desert ecosystems to future environmental changes. An in-situ field experiment was ...established to examine the influence of a long-term enhanced precipitation and N deposition on the photosynthetic traits and physiological characteristics of Haloxylon ammodendron in the Gurbantunggut Desert, northwest China, throughout the growing season in 2014-2016. Results showed a significant interaction between precipitation and N applications. Increased precipitation and N deposition and their coupling could significantly improve photosynthetic capacity, alter the variability in amplitude of water potential and change the content of substances regulating osmotic pressure in H. ammodendron. According to the comprehensive evaluation of H. ammodendron's adaptability using six different water and N coupling models, a combination of a 30% increase in precipitation and a 30 kg N ha
yr
addition in nitrogen deposition, or the addition of N at a concentration of 60 kg N ha
yr
with natural precipitation were beneficial to H. ammodendron growth and development. Hence, changes in the future global environment can be anticipated to be beneficial to H. ammodendron growth.
Abstract
Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous ...solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced
T
1
weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.
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