Trigonal planar units with large polarizability anisotropy and high physicochemical stability are ideal structural units for exploring nonlinear optical (NLO) materials. Integrating the merits of two ...types of triangular‐like moieties, a family of second‐order NLO‐active hybrid halides, MATX (X = Cl (1), Br (2), and I (3)), are achieved. MATX crystallizes in a nonpolar space group of P6¯$P\overline 6 $2c but exhibits the optimal spatial arrangement and superior NLO performance. The low coordination planar trigonal AgX3 units enable segregation in layers of the three‐winged propeller‐like Me3TPA units. All of the layers are packed in a perfect parallel fashion, making the functional materials exhibit superior NLO performances, including the phase matchable behavior with strong SHG responses (6.2/1, 6.5/2, and 7.6/3 times that of potassium dihydrogen phosphate), large birefringence (0.232/1, 0.252/2 and 0.260/3 at 1064 nm), high laser damage threshold, wide transparent window, and easiness of crystal growth. The first‐principles calculations reveal that the coexistence of strong linear and nonlinear optical properties are ascribed to the synergistic effect of the trigonal moieties. This study points out a useful path for the rational design of excellent NLO materials.
Me3TPAAgX3X (X = Cl, Br or I) exhibits optimal planar alignment of two types of triangular‐like units and superior NLO performances, including the phase matchable behavior with strong second‐harmonic generation response, large birefringence, high LDT, wide band gap, and easiness of crystal growth.
Inorganic semiconductor ferroelectrics such as BiFeO3 have shown great potential in photovoltaic and other applications. Currently, semiconducting properties and the corresponding application in ...optoelectronic devices of hybrid organo-plumbate or stannate are a hot topic of academic research; more and more of such hybrids have been synthesized. Structurally, these hybrids are suitable for exploration of ferroelectricity. Therefore, the design of molecular ferroelectric semiconductors based on these hybrids provides a possibility to obtain new or high-performance semiconductor ferroelectrics. Here we investigated Pb-layered perovskites, and found the layer perovskite (benzylammonium)2PbCl4 is ferroelectric with semiconducting behaviours. It has a larger ferroelectric spontaneous polarization Ps=13 μC cm(-2) and a higher Curie temperature Tc=438 K with a band gap of 3.65 eV. This finding throws light on the new properties of the hybrid organo-plumbate or stannate compounds and provides a new way to develop new semiconductor ferroelectrics.
Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing ...target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.
Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting.
Here we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.
AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.
Tectonic fractures can effectively improve the seepage capacity of rock mass and are the main channels for underground fluid migration. The rupture of Xujiahe Formation rock mass in the central YB ...area has good self-similarity and fractal characteristics under the tectonic stress field. Taking the fractal characteristics of the fault and core fracture as a bridge, the quantitative relationship between them is established, and the quantitative prediction of a fracture development zone in the second member of the Xujiahe Formation is carried out. The results show that the faults and fractures in the second member of the Xujiahe Formation have a good similarity in the formation stage, combination morphology, and extension direction, which is the basis of fracture prediction by the fractal method. Fault and fracture distribution has obvious fractal characteristics; the fractal dimensions are between 0.6547–1.503 and 1.0733–1.7276, respectively; and the correlation coefficient is generally greater than 0.9. The areas with big fractal dimensions are the wells YL29-YL30-YB5-YL5-YB9 in the middle area, YL32-YL4 in the southeast, and RL1 in the east, and the more developed the faults are, the more developed the fractures are. The prediction of fracture zones based on the fractal theory provides a new idea for fracture research.
Leber's hereditary optic neuropathy (LHON) is a rare inherited blindness caused by mutations in the mitochondrial DNA (mtDNA). The disorder is untreatable and tricky, as the existing chemotherapeutic ...agent Idebenone alleviates symptoms rather than overcoming the underlying cause. Although some studies have made progress on allotopic expression for LHON, in situ mitochondrial gene therapy remains challenging, which may simplify delivery procedures to be a promising therapeutic for LHON. LHON becomes more difficult to manage in the changed mitochondrial microenvironment, including increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP). Herein, a pathologically responsive mitochondrial gene delivery vector named triphenylphosphine‐terminated poly(sulfur‐containing thioketal undecafluorohexylamine histamine) and Ide‐terminated poly(sulfur‐containing thioketal undecafluorohexylamine histamine) (TISUH) is reported to facilitate commendable in situ mitochondrial gene therapy for LHON. TISUH directly targets diseased mitochondria via triphenylphosphine and fluorination addressing the decreasing MMP. In addition, TISUH can be disassembled by high mitochondrial ROS levels to release functional genes for enhancing gene transfection efficiency and fundamentally correcting genetic abnormalities. In both traditional and gene‐mutation‐induced LHON mouse models, TISUH‐mediated gene therapy shows satisfactory curative effect through the sustained therapeutic protein expression in vivo. This work proposes a novel pathologically responsive in situ mitochondrial delivery platform and provides a promising approach for refractory LHON as well as other mtDNA mutated diseases treatments.
A pathologically responsive mitochondrial gene therapy referred to as “TISUH” in an allotopic expression‐independent manner achieves accurately in situ mitochondrial gene delivery. It is a novel nanomedicine harnessing pathological characteristics to import exogenous gene into mitochondria for Leber's hereditary optic neuropathy treatment, a capability that has potential to model mitochondrial DNA (mtDNA) mutated disorders and correct genetic abnormalities in other mtDNA mutated diseases.
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary ...epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
Two mixed‐metal gallium iodate fluorides, namely, α‐ and β‐Ba2GaF4(IO3)2(IO3) (1 and 2), have been designed by the aliovalent substitutions of α‐ and β‐Ba2VO2F2(IO3)2(IO3) (3 and 4) involving one ...cationic and two anionic sites. Both 1 and 2 display large second‐harmonic generation responses (≈6×KH2PO4 (KDP)), large energy band gaps (4.61 and 4.35 eV), wide transmittance ranges (≈0.27–12.5 μm), and high relevant laser‐induced damage thresholds (29.7× and 28.3×AgGaS2, respectively), which indicates that 1 and 2 are potential second‐order nonlinear optical materials in the ultraviolet to mid‐infrared. Our studies propose that three‐site aliovalent substitution is a facile route for the discovery of good NLO materials.
Trading places: Two new nonlinear optical materials, α‐ and β‐Ba2GaF4(IO3)2(IO3) (1 and 2), were designed via three‐site aliovalent substitution of VO4F2 in α‐ and β‐Ba2VO2F2(IO3)2(IO3) by GaO2F4. The new materials display large second‐harmonic generation responses (≈6×KH2PO4 (KDP)), wide energy band gaps (4.61 and 4.35 eV), and high laser damage thresholds (29.7× and 28.3× relative to that of AgGaS2).
A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut ...microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.
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