Although biomimetic designs are expected to play a key role in exploring future structural materials, facile fabrication of bulk biomimetic materials under ambient conditions remains a major ...challenge. Here, we describe a mesoscale "assembly-and-mineralization" approach inspired by the natural process in mollusks to fabricate bulk synthetic nacre that highly resembles both the chemical composition and the hierarchical structure of natural nacre. The millimeter-thick synthetic nacre consists of alternating organic layers and aragonite platelet layers (91 weight percent) and exhibits good ultimate strength and fracture toughness. This predesigned matrix-directed mineralization method represents a rational strategy for the preparation of robust composite materials with hierarchically ordered structures, where various constituents are adaptable, including brittle and heat-labile materials.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Liver sinusoidal endothelial cells (LSECs) critically regulate liver homeostasis and diseases through angiocrine factors. Notch is critical in endothelial cells (ECs). In the current study, Notch ...signaling was activated by inducible EC‐specific expression of the Notch intracellular domain (NIC). We found that endothelial Notch activation damaged liver homeostasis. Notch activation resulted in decreased fenestration and increased basement membrane, and a gene expression profile with decreased LSEC‐associated genes and increased continuous EC‐associated genes, suggesting LSEC dedifferentiation. Consistently, endothelial Notch activation enhanced hepatic fibrosis (HF) induced by CCl4. Notch activation attenuated endothelial nitric oxide synthase (eNOS)/soluble guanylate cyclase (sGC) signaling, and activation of sGC by 3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzylindazole (YC‐1) reversed the dedifferentiation phenotype. In addition, Notch activation subverted the hepatocyte‐supporting angiocrine profile of LSECs by down‐regulating critical hepatocyte mitogens, including Wnt2a, Wnt9b, and hepatocyte growth factor (HGF). This led to compromised hepatocyte proliferation under both quiescent and regenerating conditions. Whereas expression of Wnt2a and Wnt9b was dependent on eNOS‐sGC signaling, HGF expression was not rescued by the sGC activator, suggesting heterogeneous mechanisms of LSECs to maintain hepatocyte homeostasis. Conclusion: Endothelial Notch activation results in LSEC dedifferentiation and accelerated liver fibrogenesis through eNOS‐sGC signaling, and alters the angiocrine profile of LSECs to compromise hepatocyte proliferation and liver regeneration (LR). (Hepatology 2018).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular ...pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis. Therefore, identifying the factors and mechanisms that regulate the functional status and spatial distribution of lysosomes and elucidating the relationship between lysosomes and the development and progression of cancer can provide important information for cancer diagnosis and prognosis prediction and may yield new therapeutic targets. This study briefly reviews the above information and explores the potential value of lysosomes in cancer therapy.
Alzheimer’s disease (AD) is the most common form of dementia characterized by progressive loss of cognitive functions due to neuronal death mainly in the hippocampal and cortical brain. Sulforaphene ...(SF) is one of the main isothiocyanates isolated from a Chinese herb Raphani Semen. In this study, we aimed to investigate the neuroprotective effects of SF using in vitro and in vivo models of AD. Streptozotocin (STZ) was intracranially injected into the rats; then, SF (25 and 50 mg/kg) was given orally once a day for 6 consecutive weeks. After drug treatment, the cognitive functions were assessed using the Morris Water Maze Test (MWMT). After the MWMT, the rats were euthanized and brain tissues were collected. In the in vitro test, BV-2 microglia were pretreated with SF (1 and 2 μM) for 1 h and then stimulated with lipopolysaccharide (LPS) for another 23 h. Both molecular and histological methods were used to unravel the action mechanisms and elucidate the signaling pathway. The MWMT results showed that SF treatment significantly improved the STZ-induced cognitive deficits in rats. SF treatment markedly suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) but increased the release of IL-10 in the STZ-treated rats. In addition, SF significantly inhibited the phosphorylation of tau protein at Thr205, Ser396, and Ser404 sites, while enhancing the ratios of p-Akt (Ser473)/Akt and p-GSK-3β (Ser9)/GSK-3β in the hippocampus of the STZ-treated rats. On the other hand, SF (1 and 2 μM) treatment also markedly attenuated the cytotoxicity induced by LPS in BV-2 cells. In addition, SF treatment obviously suppressed the releases of nitric oxide (NO), TNF-α, and IL-6 in the LPS-stimulated BV-2 cells. Moreover, SF treatment significantly mitigated the nuclear translocation of p-NF-κB p65 and the ratio of p-GSK-3β (Ser9)/GSK-3β in LPS-stimulated BV-2 cells. Taken together, SF possessed neuroprotective effects against the STZ-induced cognitive deficits in rats and LPS-induced neuroinflammation in BV-2 cells via modulation of the PI3K/Akt/GSK-3β pathway and inhibition of the NF-κB activation, suggesting that SF is a promising neuroprotective agent worthy of further development into AD treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Triethylene diamine (DABCO) has the characteristic of being hydrophilic and exhibits a color change in air because its N atom can interact with H2O and CO2. To understand these phenomena, herein, ...theoretical calculations on the intermolecular interactions between DABCO and H2O (or CO2) were carried out at the M06-2X/aug-cc-pVDZ level without and with the counterpoise method, and single-point calculations at the CCSD(T)/aug-cc-pVDZ level were also performed. The electron donating ability of DABCO was revealed by the molecular surface electrostatic potential and Fukui function. The driving forces for the formation of a dimer and trimer were uncovered by EDA analyses. Because DABCO can interact with both H2O and CO2, the formation of hydrogen bonds and tetrel bonds is competitive, and meanwhile, DABCO can interact with H2O and CO2 simultaneously, so the hydrogen bond and tetrel bond can coexist and cooperate with each other. The hydrogen bond and tetrel bond in the dimers and trimers were proven and analyzed by NCI and QTAIM. The results presented here will provide useful insight in understanding the hydrophilic characteristic and the color change of DABCO.
Marine soft corals are prolific sources of various natural products that have served as a wealthy reservoir of diverse chemical scaffolds with potential as new drug leads. The genus Litophyton ...contains almost 100 species but only a small proportion of them has been chemically investigated, which calls for more attentions from global researchers. In the current work, 175 secondary metabolites have been discussed, drawing from published data spanning almost five decades, up to July 2023. The studied species of the genus Litophyton resided in various tropical and temperate regions and encompassed a broad range of biologically active natural products including terpenes, steroids, nitrogen-containing metabolites, lipids, and other metabolites. A wide spectrum of pharmacological effects of these compounds had been evaluated, such as cytotoxic, antiviral, antibacterial, antifungal, anti-malarial, antifeedant, anti-inflammatory, molluscicidal, PTP1B inhibitory, insect growth inhibitory, and neuroprotective activities. This review aims to offer an up-to-date survey of the literature and provide a comprehensive understanding of the chemical structures, taxonomical distributions, and biological activities of the reported metabolites from the title genus whenever available.
Let (
χ, ρ, μ
) be a space of homogeneous type in the sense of Coifman and Weiss, and
Y
(
χ
) a ball quasi-Banach function space on
χ
, which supports both a Fefferman-Stein vector-valued maximal ...inequality and the boundedness of the powered Hardy-Littlewood maximal operator on its associate space. The authors first introduce the Hardy space
H
Y
(
χ
) associated with
Y
(
χ
), via the Lusin-area function, and then establish its various equivalent characterizations, respectively, in terms of atoms, molecules, and Littlewood—Paley
g
-functions and
g
λ
*
-functions. As an application, the authors obtain the boundedness of Calderón—Zygmund operators from
H
Y
(
χ
) to
Y
(
χ
), or to
H
Y
(
χ
) via first establishing a boundedness criterion of linear operators on
H
Y
(
χ
). All these results have a wide range of generality and, particularly, even when they are applied to variable Hardy spaces, the obtained results are also new. The major novelties of this article exist in that, to escape the reverse doubling condition of
μ
and the triangle inequality of
ρ
, the authors subtly use the wavelet reproducing formula, originally establish an admissible molecular characterization of
H
Y
(
χ
), and fully apply the geometrical properties of
χ
expressed by dyadic reference points or dyadic cubes.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Uncaria rhynchophylla (Miq.) Jacks (Rubinaceae), a common herbal medicine known as Gou-teng in Chinese, is commonly used in Chinese medicine practice for the treatment of convulsions, hypertension, ...epilepsy, eclampsia and other cerebral diseases. The major active components of U. rhynchophylla are alkaloids, terpenoids and flavonoids. The protective effects of U. rhynchophylla and its major components on central nervous system (CNS) have become a focus of research in recent decades.
The study aimed to systematically summarize the pharmacological activities of U. rhynchophylla and its major components on the CNS.
This review summarized the experimental findings from our laboratories, together with other literature data obtained through a comprehensive search of databases including the Pubmed and the Web of Science.
U. rhynchophylla and its major components such as rhynchophylline and isorhynchophylline have been shown to have neuroprotective effects on Alzheimer's disease, Parkinson's disease, depression, cerebral ischaemia through a number of mechanisms including anti-oxidant, anti-inflammatory actions and regulation on neurotransmitters.
U. rhynchophylla and its major components have multiple beneficial pharmacological effects on CNS. Further studies on U. rhynchophylla and its major components are warranted to fully illustrate the underlying molecular mechanisms, pharmacokinetics, and toxicological profiles of these naturally occurring compounds and their potential for clinical application.
Introduction
Gelsemine is a natural alkaloid extracted from
Gelsemium elegans
Benth.
,
a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce ...neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases.
Results
In this study, we have found, for the first time, that gelsemine at low concentrations (5–10 μg/kg) significantly alleviated cognitive impairments induced by β-amyloid (Aβ) oligomer, a main neurotoxin of Alzheimer’s disease (AD). In addition, gelsemine substantially prevented Aβ oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3β (GSK3β), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aβ oligomer-induced reduction of PSD-95, a representative post-synaptic protein.
Conclusion
All these results directly demonstrated the anti-Aβ oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aβ-associated neurodegeneration disorders, including AD in particular.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Irregular coal pillars left in longwall working faces are prone to stress concentration, resulting in failure and instability of coal pillar. Revealing the failure mechanism of the coal pillars is ...essential for the accurate prevention of coal pillar-type rockburst. Based on the geological conditions and the residual coal pillars in the 14320 working face of the Dongtan coal mine, this study investigates the failure mechanism and stress evolution characteristics in the abnormal area with irregular coal pillars through microseismic (MS) monitoring, moment tensor inversion, and velocity tomography of MS. The results show that (1) the MS events at the edge of the coal pillars are significantly more greater than those in the core area, in which, failure types of tension and compression occur in the edge and core areas, respectively; (2) the spatial parameters (strike
φ
, dip angle
δ
, slip angle
γ
) of the failure plane in the irregular coal pillar area were determined. The boundary of the irregular coal pillars was dominated by reverse fault sliding, and the core area is dominated by normal fault sliding; and (3) the stress field distribution characteristics of the working face and irregular coal pillars were determined using P-wave velocity tomography. The research findings provide a reference for analyzing the mechanisms of coal pillar failure, instability and the induced rockbursts.
Highlights
Moment tensor theory is used to analyze the fracture mechanism of coal pillar in mines.
Moment tensor theory reveals rupture types and occurrence of the rupture face in different regions of coal pillar.
Stress evolution law of coal pillar is obtained by microseismic velocity tomography.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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