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The design and construction of highly effective circularly polarized luminescence (CPL)-active materials has aroused considerable attention due to their widespread applications in sensors, optical devices, and asymmetric synthesis. However, the exploration of novel CPL-active materials with high luminescence dissymmetry factor (glum) values is still a challenge. Herein, we describe a new approach for the preparation of supramolecular metallacycles with amplified CPL promoted by hierarchical self-assembly involving Pt···Pt interactions. Notably, the resultant metallacycles exhibited strong CPL signals with high glum values, while their corresponding precursors were CPL silent. The CPL amplification mechanism was comprehensively validated by ultraviolet-visible absorption, emission spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, transmission electron microscopy, atomic force microscopy, coarse-grained molecular dynamics simulations, and time-dependent density functional theory calculations. This work thus provides the first example of preparing highly effective CPL-active materials based on hierarchical self-assembly involving Pt···Pt interactions.

Background Hepatic artery thrombosis (HAT), a serious complication after orthotopic liver transplantation, almost always leads to morbidity and mortality without urgent revascularization or retransplantation, especially if HAT occurs within a few days after transplantation. Case Presentation Herein we describe a case report of an orthotopic liver transplantation patient surviving without hepatic artery flow due to HAT on postoperative day 1. Reanastomosis, thrombectomy, and intra-arterial thrombolysis were performed, but only retrograde arterial flow by Doppler ultrasound, not by angiography, could be demonstrated in the hepatic artery. This case report is in compliance with the Declaration of Helsinki and the Declaration of Istanbul. Conclusion Based on the evidence from this patient, we believe that patients with failed revascularization can experience a long-term survival with conservative treatment. Retransplantation should be evaluated based on laboratory findings because graft function in individual patients can recover.

A novel 3D anionic porous metal–organic framework {[(CH3)2NH2][Zn3(μ3-OH)(L)2(H2O)]·4H2O·3DMA}n (Zn-1) (H2L = 1-hydroxy-5,5-dioxodibenzothiophen-3,7-dicarboxylic acid, DMA = dimethylacetamide) has been solvothermally synthesized. Single-crystal X-ray analyses reveal that the framework of Zn-1 is based on deformed triangular [Zn3O] clusters with interlinked 1D channels. Taking advantage of the high porosity and charged skeleton of Zn-1, fluorescent dye rhodamine B (RhB) molecules can be successfully incorporated into the channels of Zn-1via an ion-exchange process. Due to the spatial confinement, the RhB@Zn-1 composite shows dual-emission properties including the emissions of Zn-1 centered at 475 nm and RhB centered at 580 nm. Moreover, RhB@Zn-1 can be used as a recyclable fluorescent sensor for sensitive and selective detection of nitrofuran antibiotics (nitrofurantoin and nitrofurazone), with high KSV values (5.61 × 104 M−1 and 4.73 × 104 M−1) and low detection limits (0.73 μM and 0.86 μM). Comparison experiment results show that the sensing capability of Zn-1 can be greatly improved via the dye-encapsulation strategy. Further studies reveal that the synergistic effect of competitive absorption and photo-induced electron transfer causes the fluorescence quenching of Zn-1, which in turn decreases the energy transfer from Zn-1 to RhB and leads to the quenching process of RhB.

The long non-coding RNA antisense 1 ADAMTS9-AS1 has been reported to predict the survival in several tumors, including bladder cancer and breast cancer. However, the clinical significance and biological behaviors of ADAMTS9-AS1 in colorectal cancer (CRC) have not been reported yet. In this study, the expression of ADAMTS9-AS1 was measured in CRC tissues and cell lines using quantitative real-time PCR analysis. The clinical significance of ADAMTS9-AS1 was evaluated with Chi-squared test, Kaplan-Meier method and Cox regression analysis in CRC patients. CCK8 assay, colony formation assay, flow cytometry and transwell assay were used to explore the biological function of ADAMTS9-AS1 knockdown in CRC cell lines (SW1116 and HT29). We further explore the role of ADAMTS9-AS1 in vivo though xenograft tumor assay. Our data showed that ADAMTS9-AS1 expression level was significantly up-regulated in CRC tissues and cell lines compared with corresponding controls. High ADAMTS9-AS1 level was associated with TNM stage, lymph node invasion and worse survival prognosis. Depletion of ADAMTS9-AS1 significantly suppressed cell proliferation, G1/S transition, migration and invasion, as well as suppressed CDK4/Cyclin D1 and epithelial-mesenchymal transition (EMT). To sum up, these findings illustrated that ADAMTS9-AS1 might be a promising therapeutic target and prognostic factor for CRC.

An unexpected bistricyclic aromatic ene AF was synthesized in a tin(II) chloride-mediated reductive aromatization reaction. The obtained AF showed a highly overcrowded structural conformation as revealed by X-ray crystallography. Interestingly, AF exhibited reversible high-contrast mechanochromism and thermochromism between pale and red color. The obvious chromism is likely ascribed to the conformation transformation and trace amount of diradical species formation upon stimulus.

The structurally intriguing tetracyclic core of complex harziane diterpenoid was constructed in 14 steps from commercially available 3-ethoxycyclohex-2-en-1-one. The key steps were a Mn/Cu-mediated oxidative 1,3-dicarbonyl radical cascade cyclization reaction, which diastereoselectively formed the core of dimethylbicyclo[3.2.1]octane structure, and a Au-catalyzed diastereoselective formal [2 + 2] cycloaddition for construction of the harziane diterpenoid tetracyclic framework. The developed method paves the way for achieving total synthesis of this type of complex natural product.

This study aimed to investigate the effect of serum containing ginseng and Moutan Cortex on human umbilical vein endothelial cells(HUVEC) injured with hydrogen peroxide(H_2O_2). HUVEC injured with H_2O_2 were divided into 6 groups, namely blank group, model group, ginsenoside(TGG) group, total glucosides of Moutan Cortex(TGM) group, paeonol(P) group and TGG+TGM+P group. After 24 hours of co-culture with H_2O_2, the activities of succinate dehydrogenase(SDH) and Ca~(2+)-Mg~(2+)-ATP were detected by microenzyme labeling. The apoptosis rate, intracellular Ca~(2+) concentration, reactive oxygen species(ROS) and mitochondrial membrane potential(JC-1) were detected by flow cytometry. The expressions of mitochondrial apoptosis pathway-related proteins Bax, Bcl-2, cytochrome C, caspase-3 and caspase-9 were detected by Western blot. The results showed that H_2O_2 could significantly damage HUVEC, decrease the activity of SDH and Ca~(2+)-Mg~(2+)-ATP(Plt;0.01), while could increase the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(Plt;0.01). Serum containing ginseng and Moutan Cortex could increase the activities of SDH and Ca~(2+)-Mg~(2+)-ATP to different degrees, decrease the apoptosis+necrosis rate, JC-1 decline rate, ROS increase rate and Ca~(2+) concentration increase rate(Plt;0.05 or Plt;0.01), and down-regulate the protein expressions of Bax, caspase-3, caspase-9, cytochrome C, and up-regulate the protein expression of Bcl-2. The results showed that serum containing ginseng and Moutan Cortex has a protective effect on vascular endothelial cell injury induced by ROS, and its mechanism may be related to the improvement of mitochondrial function and the inhibition of the activation of mitochondrial apoptosis pathway.

The aim of this study was to investigate the biological effects of occupational extremely low-frequency electromagnetic field (ELF-EMF) exposure on the thyroid gland.We conducted a prospective analysis of 85 workers (exposure group) exposed to an ELF-EMF (100 μT, 10-100 Hz) produced by the electromagnetic aircraft launch system and followed up on thyroid function indices, immunological indices, and color Doppler images for 3 years. Additionally, 116 healthy volunteers were randomly selected as controls (control group), the thyroid function of whom was compared to the exposure group.No significant difference was observed in thyroid function between the exposure and control groups. During the follow-up of the exposure group, the serum free triiodothyronine (FT3) level was found to slowly decrease and free thyroxine (FT4) level slowly increase with increasing exposure time. However, no significant difference was found in thyroid-stimulating hormone (TSH) over the three years, and no significant difference was observed in the FT3, FT4 and TSH levels between different exposure subgroups. Furthermore, no significant changes were observed in thyroid autoantibody levels and ultrasound images between subgroups or over time.Long-term exposure to ELF-EMF may promote thyroid secretion of T4 and inhibit deiodination of T4 to T3. ELF-EMF has no significant effect on thyroid immune function and morphology.

Backgroud: Controversy still remains in that whether sequential or concurrent regimen of anthracyclines and taxanes benefits more for breast cancer. Here we aimed to compare these two regimens in patients with operable breast cancer based on all published data of phase III randomized controlled trials in this topic.Methods: A literature search on PubMed, Web of science, Embase, ScienceDirect, Google scholar and clinicaltrials.gov databases was conducted up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease free survival (DFS) and overall survival (OS)for these two regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection.Results: Compared to concurrent regimen, sequential regimen did not improve the DFS or OS in the whole population included. Subgroup analysis showed that in node-positive patients, however, sequential regimen has better DFS, but not OS, than concurrent regimen.In sequential regimen, patients received doxorubicin and taxanes had improved DFS and OS than those were given epirubicin and taxanes. Futhermore, for patients receiving doxorubicin and taxanes,compared to sequential regimen,less cycles (4 cycles) of concurrent treatment showed worse DFS and OS, whereas more cycles(6 cycles) may rescue the loss.In addition,high grade toxicity response in both groups exhibited no difference except for neuropathy, which occured more frequently in the sequential regimen.Conclusions:Sequential regimen of anthracyclines and taxanes for patients with breast cancer did not promise a significant benefit in neither DFS nor OS over concurrent regimen. However, sequential regimen did provide a better DFS than that in concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for patients with node-positive and were given doxorubicin and taxanes, more cycles (6 cycles) of concurrent reigmen was not inferior to sequential regimen.

The small-molecule modulators (agonists and antagonists) of peroxisome proliferator-activated receptor-γ (PPARγ) have been widely used to treat metabolic, cardiovascular and inflammatory diseases such as Type-2 diabetes and heart failure. Existing PPARγ modulators are all developed to target the ligand-binding site (LBS) in PPARγ ligand-binding domain (LBD) interior, where is spatially separated from the coactivator-interacting site (CIS) on PPARγ LBD surface and can thus only indirectly mediate the binding of NCOA1 coactivator peptide to CIS site. Here, we propose a new therapeutic strategy termed as Type-III PPARγ antagonists, which competitively disrupt the NCOA1 peptide binding by directly targeting PPARγ CIS site. Such antagonists are also known as inverse agonists that can partially or fully repress the basal transcriptional activity of PPARγ. A structure-based stepwise screening is performed against a purchasable biogenic compound library to identify CIS-specific binding competitors. The screening integrates empirical manual exclusion, druglikeness/pharmacokinetic evaluation, chemical similarity analysis and high-throughput molecular docking to rank the relative binding capability for compound candidate lists. The competitive potency of eight promising hits against a truncated version (core binding sequence) of full-length NCOA1 peptide (685ERHKILHRLLQEGSPS700) is tested using fluorescence competition assays. Consequently, two out of the eight tested compounds are determined as potential competitors with NCOA1 peptide for PPARγ CIS site, with CC50 values of 13 ± 1.8 and 54 ± 6.7 μM, respectively. Structural analysis reveals that the two competitor ligands are anchored at the central hole of CIS site through their substituted phenyl moieties, while forming a variety of hydrogen bonds, cation-π stacking and hydrophobic contacts with the regions surrounding the hole, conferring both stability and specificity to the CIS–competitor recognition and interaction.

The demand for a hand-held Raman spectrometer in the fast and accurate detection and identification of seized drugs is much higher than before, especially when facing unknown suspicious drugs. However, Raman spectra for the different drugs are less reported due to the inaccessibility of them. Here, we reported the experimental Raman spectra in detail of four typical drugs (such as methamphetamine, ketamine, caffeine, and magu). The Raman vibrational frequencies were also calculated by the method of density functional theory (DFT) at Becke-3-Lee-Yang-Parr (B3LYP) level with the 6-31 G and 6-31G(d,p) basis set. The results show that the experimental Raman spectra of these typical drugs are consistent with the theoretical Raman spectra. Using the potential energy distribution (PED) calculation with the GAR2PED program, the assignments of the observed Raman bands to the vibrational modes were presented. Further, methamphetamine and its camouflage N-benzylisopropylamine were analyzed by Raman spectrosc...

Human pluripotent stem cells (hPSCs) have the capacity to differentiate into all mature blood cell types including megakaryocytes, providing a potential source to generate large-scale platelets to cope with the urgent clinical shortage. To generate platelets in large-scale in vitro , it is urgent to establish a highly efficient model and identify critical genes mediating the megakaryocytic differentiation and platelet generation. In this study, we performed RNA-Seq analysis in cord blood CD34+ cells collected from day 6 to day 10 after megakaryocytic differentiation and identified several signal pathways and transcriptional factors involved in this process. To explore the key regulators mediating megakaryocytic differentiation and platelet generation from hPSCs, we subsequently established a megakaryocytic differentiation system by co-culturing hPSCs with the mouse AGM-S3 (mAGM-S3) feeder cells and found that functional platelet could be generated. Through functional validation, we found that RUNX1 and ERG significantly promoted the generation of megakaryocytes and platelets from hPSCs. In conclusion, we established a highly efficient screening platform suitable for the identification of key regulators mediating megakaryocytic differentiation and platelet generation from hPSCs. The identified regulators could be potentially manipulated for large-scale generation of platelets for therapeutic applications in regenerative medicine.

Asymmetric total synthesis of (−)-perforanoid A, a novel limonoid isolated from the leaves of Harrisonia perforata, has been achieved. The key features of our total synthesis include the Rh-catalyzed intramolecular Pauson–Khand reaction of an allene and an alkene, the Pd-catalyzed lactonization of an allylic alcohol with a vinyl ether, and the enantioselective alkenylation of 3-furaldehyde.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and its pathogenesis remains largely unclear. Much attention has been paid to the role of microRNAs (miRs) in regulation of autoimmune disease. Here, we found, for the first time, that miR-448 expression was significantly increased in periphery blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) of patients with MS, and its expression positively correlated with the disease severity. We further demonstrated that CD4+ T cells, especially the Th17 lineage, were the major source of miR-448 expression. Using gain- and loss-of-function approaches, we further verified that miR-448 could enhance Th17 differentiation, characterized by up-regulated expression levels of IL-17A and RORγt. Interleukin (IL)-1β as a potent driver of pathogenic Th17 cells was able to strongly induce miR-448 expression in CD4+ T cells through activating NF-κB pathway. Additionally, we identified that miR-448 directly targeted protein tyrosine phosphatase non-receptor type 2 (PTPN2), which has been known as an anti-inflammatory player with capacity to suppress Th17 differentiation. We also observed markedly decreased expression of PTPN2 in PBMC and CSF of MS patients. Our results suggest that miR-448 might promote Th17 differentiation in MS and thus aggravate the disease through inhibiting PTPN2.

The first enantiospecific synthesis of hispidanin A (4), a dimeric diterpenoid from the rhizomes of Isodon hispida, was achieved with a longest linear sequence of 12 steps in 6.5 % overall yield. A key component is the use of the abundant and naturally occurring diterpenoids (+)-sclareolide and (+)-sclareol as starting materials, which enables the gram-scale preparation of the key intermediates totarane (1) and s-trans-12E,14-labdadien-20,8β-olide (2). Subsequently a thermal or an erbium-catalyzed intermolecular Diels-Alder reaction of totarane (1) with labdadienolide (2) provide convergent and rapid access to the natural product hispidanin A (4). The synthetic studies have offered significant impetus for the efficient construction of these architecturally complex natural products.