The removal of C2H2 and C2H6 from C2H4 streams is of great significance for feedstock purification to produce polyethylene and other commodity chemicals but the simultaneous adsorption of C2H6 and ...C2H2 over C2H4 from a ternary mixture has never been realized. Herein, a robust metal–organic framework, TJT‐100, was designed and synthesized, which demonstrates remarkably selective adsorption of C2H2 and C2H6 over C2H4. Breakthrough experiments show that TJT‐100 can be used as an adsorbent for high‐performance purification of C2H4 from a ternary mixture of C2H2/C2H4/C2H6 (0.5:99:0.5) to afford a C2H4 purity greater than 99.997 %, beyond that required for ethylene polymerization. Computational studies reveal that the uncoordinated carboxylate oxygen atoms and coordinated water molecules pointing towards the pore can trap C2H2 and C2H6 through the formation of multiple C−H⋅⋅⋅O electrostatic interactions, while the corresponding C2H4–framework interaction is unfavorable.
A robust porous metal–organic framework was synthesized and utilized for the highly selective separation of C2H4 from a ternary mixture of C2 hydrocarbons. After a single operation, the C2H4 purity of the outlet was greater than 99.997 %.
Apixaban (apx), with a trade name of Eliquis, is a highly selective and efficacious inhibitor of blood coagulation factor Xa. Apixaban has poor solubility in water (0.028 mg/mL at 24 °C) and a ...relatively low oral bioavailability (about 50% for a single 10 mg dose). The purpose of this study is to improve the solubility and consequently the oral bioavailability of apixaban via a cocrystal. A cocrystal of apixaban with oxalic acid (apx-oxa-H2O, 4:3:0.5) was successfully obtained and characterized. The structure of the cocrystal was determined by single-crystal X-ray diffraction. The solubility of the cocrystal in 0.1 M HCl (pH 1.0) and phosphate buffer of pH 6.8 was evaluated, and the results show the solubility values of the cocrystal are approximately 2.2 and 2.1 times as large as those of apixaban form N-1 (the marketed product), respectively. The pharmacokinetics in beagle dogs was also investigated, and the mean AUC0–24h of the cocrystal is approximately 2.7 times as large as that of apixaban form N-1, indicating that both solubility and bioavailability of apixaban can be improved via a cocrystal.
Self‐assembly of metavanadate and organosilver(I) salts leads to a novel dodecahedrane‐like Ag30(tBuS)2010+ silver(I) thiolate nanocage that tightly wraps an unusual C2h polyoxovanadate anion. The ...polyoxovanadate core undergoes transformation to a D3d configuration upon acidification, and reverts back to its original C2h structure upon addition of base. Chromism was observed for the silver(I) thiolate cluster during the configurational change of the central polyoxovanadate core; the color of the solution changes reversibly from green to dark yellow. This work represents the first reported example of chromic polyoxometalate‐templated silver(I) thiolate shells that respond to external acid–base stimuli. It also represents an important advance in providing crystallographic proof that structural transformations occur in a nanoscale core–shell cluster.
Silver cage: Self‐assembly of metavanadate and organosilver(I) salts generates a dodecahedrane‐like silver(I) thiolate Ag30(tBuS)2010+ nanocage that tightly wraps a polyoxovanadate core. Single‐crystal X‐ray crystallography was used to show that the core undergoes a reversible C2h to D3d configurational transformation in response to acid/base stimuli, which also result in a color change from green to dark yellow.
Ovarian cancer is the deadliest gynaecologic malignancy, and the five-year survival rate of patients is less than 35% worldwide. Cancer stem cells (CSCs) are a population of cells with stem-like ...characteristics that are thought to cause chemoresistance and recurrence. TRIM29 is aberrantly expressed in various cancers and associated with cancer development and progression. Previous studies showed that the upregulation of TRIM29 expression in pancreatic cancer is related to stem-like characteristics. However, the role of TRIM29 in ovarian cancer is poorly understood. In this study, we found that TRIM29 expression was increased at the translational level in both the cisplatin-resistant ovarian cancer cells and clinical tissues. Increased TRIM29 expression was associated with a poor prognosis of patients with ovarian cancer. In addition, TRIM29 could enhance the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells. Recruitment of YTHDF1 to m6A-modified TRIM29 was involved in promoting TRIM29 translation in the cisplatin-resistant ovarian cancer cells. Knockdown of YTHDF1 suppressed the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells, which could be rescued by ectopic expression of TRIM29. This study suggests TRIM29 may act as an oncogene to promote the CSC-like features of cisplatin-resistant ovarian cancer in an m6A-YTHDF1-dependent manner. Due to the roles of TRIM29 and YTHDF1 in the promotion of CSC-like features, they may become potential therapeutic targets to combat the recurrence of ovarian cancer.
•TRIM29 expression is increased and implicated in maintenance of CSC-like features in cisplatin-resistant ovarian cancer•High TRIM29 expression is associated with poor prognosis in patients with ovarian cancer•m6A-YTHDF1 increases translation of TRIM29 independent of Ago2-containing RISC in cisplatin-resistant ovarian cancer cells•YTHDF1 knockdown suppresses stem cell-like features of cisplatin resistant ovarian cancer cells
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic ...inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms.
PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot.
This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased (
< 0.01).
Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.
The urea cycle (UC) removes the excess nitrogen and ammonia generated by nitrogen-containing compound composites or protein breakdown in the human body. Research has shown that changes in UC enzymes ...are not only related to tumorigenesis and tumor development but also associated with poor survival in hepatocellular, breast, and colorectal cancers (CRC), etc. Cytoplasmic ornithine, the intermediate product of the urea cycle, is a specific substrate for ornithine decarboxylase (ODC, also known as ODC1) for the production of putrescine and is required for tumor growth. Polyamines (spermidine, spermine, and their precursor putrescine) play central roles in more than half of the steps of colorectal tumorigenesis. Given the close connection between polyamines and cancer, the regulation of polyamine metabolic pathways has attracted attention regarding the mechanisms of action of chemical drugs used to prevent CRC, as the drug most widely used for treating type 2 diabetes (T2D), metformin (Met) exhibits antitumor activity against a variety of cancer cells, with a vaguely defined mechanism. In addition, the influence of metformin on the UC and putrescine generation in colorectal cancer has remained unclear. In our study, we investigated the effect of metformin on the UC and putrescine generation of CRC in vivo and in vitro and elucidated the underlying mechanisms. In nude mice bearing HCT116 tumor xenografts, the administration of metformin inhibited tumor growth without affecting body weight. In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC. The putrescine levels in both HCT116 xenografts and HCT116 cells decreased after metformin treatment. These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation.
Numerous reported bioinspired osmotic energy conversion systems employing cation‐/anion‐selective membranes and solutions with different salinity are actually far from the biological counterpart. The ...iso‐osmotic power generator with the specific ionic permselective channels (e.g., K+ or Na+ channels) which just allow specific ions to get across and iso‐osmotic solutions still remain challenges. Inspired by nature, we report a bioinspired K+‐channel by employing a K+ selective ligand, 1,1,1‐tris{(2′‐benzylaminoformyl)phenoxymethyl}ethane (BMP) and graphene oxide membrane. Specifically, the K+ and Na+ selectivity of the prepared system could reach up to ≈17.8, and the molecular dynamics simulation revealed that the excellent permselectivity of K+ mainly stemmed from the formed suitable channel size. Thus, we assembled the K+‐selective iso‐osmotic power generator (KSIPG) with the power density up to ≈15.1 mW/m2 between equal concentration solutions, which is higher than traditional charge‐selective osmotic power generator (CSOPG). The proposed strategy has well shown the realizable approach to construct single‐ion selective channels‐based highly efficient iso‐osmotic energy conversion systems and would surely inspire new applications in other fields, including self‐powered systems and medical materials, etc.
An artificial potassium ionic channel for mimicking biological iso‐osmotic energy conversion system is achieved by the confined assembly of potassium ligand in the gaps between GO nanosheets.
To control the ongoing COVID‐19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines have been developed. However, the rapid mutations of SARS‐CoV‐2 spike (S) ...protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS‐CoV‐2, and then systematically assessed the susceptivity of these SARS‐CoV‐2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS‐CoV‐2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin‐converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS‐CoV‐2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.
Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural ...compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.
Decidualization is necessary for the successful establishment of early pregnancy in rodents and humans. Disturbed decidualization results in recurrent implantation failure, recurrent spontaneous ...abortion, and preeclampsia. Tryptophan (Trp), one of the essential amino acids in humans, has a positive effect on mammalian pregnancy. Interleukin 4-induced gene 1 (IL4I1) is a recently identified enzyme that can metabolize L-Trp to activate aryl hydrocarbon receptor (AHR). Although IDO1-catalyzed kynurenine (Kyn) from Trp has been shown to enhance human in vitro decidualization via activating AHR, whether IL4I1-catalyzed metabolites of Trp are involved in human decidualization is still unknown. In our study, human chorionic gonadotropin stimulates IL4I1 expression and secretion from human endometrial epithelial cells through ornithine decarboxylase-induced putrescine production. Either IL4I1-catalyzed indole-3-pyruvic acid (I3P) or its metabolite indole-3-aldehyde (I3A) from Trp is able to induce human in vitro decidualization by activating AHR. As a target gene of AHR, Epiregulin induced by I3P and I3A promotes human in vitro decidualization. Our study indicates that IL4I1-catalyzed metabolites from Trp can enhance human in vitro decidualization through AHR-Epiregulin pathway.
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