Transforming growth factor β (TGF‐β) is part of the transforming growth factor β superfamily which is involved in many physiological processes and closely related to the carcinogenesis. Here, we ...discuss the TGF‐β structure, function, and its canonical Smads signaling pathway. Importantly, TGF‐β has been proved that it plays both tumor suppressor as well as an activator role in tumor progression. In an early stage, TGF‐β inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGF‐β signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial–mesenchymal transition, and immune escape. Furthermore, we are centered on updated research results into the inhibitors as drugs which have been studied in preclinical or clinical trials in tumor carcinogenesis to prevent the TGF‐β synthesis and block its signaling pathways such as antibodies, antisense molecules, and small‐molecule tyrosine kinase inhibitors. Thus, it is highlighting the crucial role of TGF‐β in tumor therapy and may provide opportunities for the new antitumor strategies in patients with cancer.
We discuss the TGF‐β structure, function, and its canonical Smads signaling pathway. TGF‐β plays both tumor suppressor as well as an activator role in tumor progression. We are centered on updated research results into the inhibitors as drugs which have been studied in preclinical or clinical trials in tumor carcinogenesis to prevent the TGF‐β synthesis and block its signaling pathways such as antibodies, antisense molecules, and small‐molecule tyrosine kinase inhibitors.
Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length ...alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.
The Mg-4Zn-0.5Ca alloys extruded at 280°C by different ultra-slow extrusion speed (0.01, 0.05, 0.1 and 0.5mms−1) were investigated in present study. The results show that both the volume fraction and ...average size of DRXed grains increase with the increase of extrusion speed, which is different from that depicted by present Z parameter. To fit the extrusion conditions with low temperature and ultra-slow extrusion speed, a more accurate estimate/measurement of the actual temperature in the expression of the Z parameter is needed in the further study. Even though the amount of precipitates decrease with the increasing extrusion speed, the increasing amount of DRX regions lead to the decreased intensity of basal plane texture. Superior mechanical properties with the yield strength of 324.5MPa, ultimate tensile strength of 371.1MPa and elongation to failure of 7.9% are achieved in present Mg-4Zn-0.5Ca alloy extruded at the speed of 0.01mms−1. As the extrusion speed increased from 0.01 to 0.5mms−1, the strength decreases which is accompanied with the increase of elongation.
Strategies on the construction of enantiomerically pure silicon‐stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric ...transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh‐catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with “silicon‐centered” racemic hydrosilanes that enables the facile preparation of silicon‐stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non‐diastereopure‐type mixed phosphine‐phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the SN2 substitution of chloride ion to realize the chiral inversion of silicon center.
An unprecedented (SiMOS‐Phos) ligand‐controlled Rh‐catalyzed hydrosilylation of “silicon‐centered” racemic hydrosilanes was developed for the highly efficient and enantioselective construction of silicon‐stereogenic centers of benzosiloles (up to 96 : 4 er). This achievement was obtained by using an original synthetic strategy involving dynamic kinetic asymmetric transformations.
Porous graphitic carbon of high specific surface area of 1416 m2 g–1 and high pore volume of 1.11 cm3 g–1 is prepared by using commercial CaCO3 nanoparticles as template and sucrose as carbon source ...followed by 1200 °C high-temperature calcination. Sulfur/porous graphitic carbon composites with ultra high sulfur loading of 88.9 wt % (88.9%S/PC) and lower sulfur loading of 60.8 wt % (60.8%S/PC) are both synthesized by a simple melt-diffusion strategy, and served as cathode of rechargeable lithium–sulfur batteries. In comparison with the 60.8%S/PC, the 88.9%S/PC exhibits higher overall discharge capacity of 649.4 mAh g–1 (S–C), higher capacity retention of 84.6% and better coulombic efficiency of 97.4% after 50 cycles at a rate of 0.1C, which benefits from its remarkable specific capacity with such a high sulfur loading. Moreover, by using BP2000 to replace the conventional acetylene black conductive agent, the 88.9% S/PC can further improve its overall discharge capacity and high rate property. At a high rate of 4C, it can still deliver an overall discharge capacity of 387.2 mAh g–1 (S–C). The porous structure, high specific surface area, high pore volume and high electronic conductivity that is originated from increased graphitization of the porous graphitic carbon can provide stable electronic and ionic transfer channel for sulfur/porous graphitic carbon composite with ultra high sulfur loading, and are ascribed to the excellent electrochemical performance of the 88.9%S/PC.
Controlling the flow of light on-chip is of great importance for quantum computing and optical signal processing. In this paper, we present a theoretical study to reveal the underlying physics of how ...to effectively trap, store and release a signal pulse, and eventually break the delay-bandwidth limit, based on controllable EIT-like effect in dynamically tuned standing-wave cascaded nanocavities. Using this mechanism, we design a compact silicon photonic crystal system with long storing time and a delay-bandwidth product over 460, which is about two orders of magnitude greater than the reported results obtained by other methods based on static resonator system, and the trapped signal pulse can be released on demand.
The Mg–Ca alloys with 2wt%, 3wt%, 5wt% Al content were fabricated in this paper. After be extruded at 673K with the ratio of 16:1, the microstructures and mechanical properties of the alloys ...influenced by Ca/Al ratio were investigated.Results showed that the category and amount of precipitated secondary phase were influenced obviously by Ca/Al ratio, which changed from Mg2Ca and (Mg, Al)2Ca to Al2Ca as the Ca/Al ratio decreased from 1 to 0.4. Even though the secondary phase was cracked after the application of hot extrusion, the amount, size and distribution of secondary phase were strongly dependent on Ca/Al ratio. The basal plane texture was found in all the as-extruded alloys, the I(101¯0)/I(101¯1) and I(0002)/I(101¯1) values demonstrated different changing tendencies with the variation of Ca/Al ratio. All the UTS, elongation and strain hardening rate of the as-extruded alloys increased with decreasing Ca/Al ratio, however, the YS exhibited the inverse variation tendency. A significant stagnation point was found in the θ-(σ-σ0.2) curve as the Ca/Al ratio is 1, which becomes unobvious with decreasing Ca/Al ratio. The reasons are given and analyzed.
Abstract
The early afterglow of a gamma-ray burst (GRB) can provide critical information on the jet and progenitor of the GRB. The extreme brightness of GRB 221009A allows us to probe its early ...afterglow in unprecedented detail. In this Letter, we report comprehensive observation results of the early afterglow of GRB 221009A (from
T
0
+660 s to
T
0
+1860 s, where
T
0
is the Insight-HXMT/HE trigger time) in X-ray/gamma-ray energy band (from 20 keV to 20 MeV) by Insight-HXMT High Energy X-ray Telescope, GECAM-C, and Fermi/Gamma-ray Burst Monitor. We find that the spectrum of the early afterglow in 20 keV–20 MeV can be well described by a cutoff power law with an extra power law that dominates the low- and high-energy bands, respectively. The cutoff power law
E
peak
is ∼30 keV, and the power-law photon index is ∼1.8 throughout the early afterglow phase. By fitting the light curves in different energy bands, we find that a significant achromatic break (from keV to TeV) is required at
T
0
+
1246
−
26
+
27
s (i.e., 1021 s since the afterglow starting time
T
AG
=
T
0
+225 s), providing compelling evidence of a jet break. Interestingly, both the pre-break and post-break decay slopes vary with energy, and these two slopes become closer in the lower energy band, making the break less identifiable. Intriguingly, the spectrum of the early afterglow experienced a slight hardening before the break and a softening after the break. These results provide new insights into the physics of this remarkable GRB.
Colorectal cancer (CRC) is one of the most prevalent cancers that threaten people in many countries. It is a multi-factorial chronic disease caused by a combination of genetic and environmental ...factors, but it is mainly related to lifestyle factors, including diet. Plentiful plant foods and beverages are abundant in polyphenols with antioxidant, anti-atherosclerotic, anti-inflammatory, and anticancer properties. These compounds participate in host nutrition and disease pathology regulation in different ways. Polyphenolic compounds have been used to prevent and inhibit the development and prognosis of cancer, and examples include green tea polyphenol (-)epigallocatechin-3-O-gallate (EGCG), curcumin, and resveratrol. Of course, there are more known and unknown polyphenol compounds that need to be further explored for their anticancer properties. This article focuses on the fact that polyphenols affect the progression of CRC by controlling intestinal inflammation, epigenetics, and the intestinal microbe in the aspects of prevention, treatment, and prognosis.
The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 ...(nucleotide-binding oligomerization domain-like receptor NLR family pyrin domain-containing 3) inflammasome. The evidence has shown that the NLRP3 inflammasome, IL-1β, thioredoxin-interacting protein (TXNIP), and pyroptosis play vital roles in the development of diabetes. This review summarizes the regulation of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) by NLRP3 via modulation of glucose tolerance, insulin resistance, inflammation, and apoptosis mediated by endoplasmic reticulum stress in adipose tissue. Moreover, NLRP3 participates in intestinal homeostasis and inflammatory conditions, and NLRP3-deficient mice experience intestinal lesions. The diversity of an individual's gut microbiome and the resultant microbial metabolites determines the extent of their involvement in the physiological and pathological mechanisms within the gut. As such, further study of the interaction between the NLRP3 inflammasome and the complex intestinal environment in disease development is warranted to discover novel therapies for the treatment of diabetes.
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