Glycosyl anomeric radical addition reactions have been well‐explored and proved efficient for the C‐alkyl glycosides synthesis, but multicomponent Domino transformations for the rapid and ...controllable construction of structurally diversified C‐alkyl glycosides in a single step are still rare. In contrast, we, herein, report a ruthenium(II)‐catalyzed Domino meta‐C−H ethyl glycosylation, enabling the construction of challenging meta‐C‐alkyl glycosides. Our ruthenium(II) catalysis was reflected by the mild reaction condition, exclusive meta‐site selectivity and high levels of anomeric selectivity. In addition, the ruthenium(II)‐catalyzed Domino meta‐C−H glycosylation allowed for the synthesis of versatile 1,2‐trans‐C‐alkyl glycosides with commercially available vinyl arenes, acrylates and easily accessible glycosyl bromides.
A ruthenium(II)/phosphine catalytic system enabled efficient domino meta‐C−H ethyl glycosylations. Thus 1,2‐trans‐C‐alkyl glycosides were obtained via the selective assembly of easily accessible glycosyl bromide and alkenes under mild reaction conditions.
Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells ...epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs.
We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells' EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes,
and
, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).
We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.
CircPRMT5 exerts critical roles in promoting UCB cells' EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
The prokaryotic CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9, an RNA-guided endonuclease, has been shown to mediate efficient genome editing in a wide variety of organisms. ...In the present study, the CRISPR-Cas9 system has been adapted to Leishmania donovani, a protozoan parasite that causes fatal human visceral leishmaniasis. We introduced the Cas9 nuclease into L. donovani and generated guide RNA (gRNA) expression vectors by using the L. donovani rRNA promoter and the hepatitis delta virus (HDV) ribozyme. It is demonstrated within that L. donovani mainly used homology-directed repair (HDR) and microhomology-mediated end joining (MMEJ) to repair the Cas9 nuclease-created double-strand DNA break (DSB). The nonhomologous end-joining (NHEJ) pathway appears to be absent in L. donovani. With this CRISPR-Cas9 system, it was possible to generate knockouts without selection by insertion of an oligonucleotide donor with stop codons and 25-nucleotide homology arms into the Cas9 cleavage site. Likewise, we disrupted and precisely tagged endogenous genes by inserting a bleomycin drug selection marker and GFP gene into the Cas9 cleavage site. With the use of Hammerhead and HDV ribozymes, a double-gRNA expression vector that further improved gene-targeting efficiency was developed, and it was used to make precise deletion of the 3-kb miltefosine transporter gene (LdMT). In addition, this study identified a novel single point mutation caused by CRISPR-Cas9 in LdMT (M381T) that led to miltefosine resistance, a concern for the only available oral antileishmanial drug. Together, these results demonstrate that the CRISPR-Cas9 system represents an effective genome engineering tool for L. donovani.
Leishmania donovani is the causative agent of fatal visceral leishmaniasis. To understand Leishmania infection and pathogenesis and identify new drug targets for control of leishmaniasis, more-efficient ways to manipulate this parasite genome are required. In this study, we have implemented CRISPR-Cas9 genome-editing technology in L. donovani. Both single- and dual-gRNA expression vectors were developed using a strong RNA polymerase I promoter and ribozymes. With this system, it was possible to generate loss-of-function insertion and deletion mutations and introduce drug selection markers and the GFP sequence precisely into the L. donovani genome. These methods greatly improved the ability to manipulate this parasite genome and will help pave the way for high-throughput functional analysis of Leishmania genes. This study further revealed that double-stranded DNA breaks created by CRISPR-Cas9 were repaired by the homology-directed repair (HDR) pathway and microhomology-mediated end joining (MMEJ) in Leishmania.
This paper proposes an energy-efficient asymmetrically clipped direct-current (DC) biased optical orthogonal frequency division multiplexing (EEADO-OFDM) scheme, which replaces the fixed DC bias of ...DC biased optical OFDM (DCOOFDM) branch with a adaptive DC bias for optical wireless communications. In the EEADO-OFDM, an adaptive DC bias is dynamically designed according to amplitude of DCO-OFDM signal samples to enhance the power efficiency. After superimposing the obtained DC bias on the original DCO-OFDM signal, the resultant DCO-OFDM signal is non-negative and further ensure that a non-negative EEADO-OFDM signal is produced by directly combining DCO-OFDM signal with the clipped asymmetrically clipped optical OFDM (ACO-OFDM) signal. In particular, the interference caused by the obtained DC bias is proved to fall on even subcarriers only, which implies that the interference can be modulated on the partial odd subcarriers of ACO-OFDM branch. Afterward, we could use conventional ACO-OFDM receiver to demodulate the adopted odd subcarriers for the detection of interference. Simulation results show that, under the equal optical power constraints, the proposed EEADOOFDM achieves no error floors of bit error rate compared with the ADO-OFDM, thus indicating that the clipping noise is always negligible in EEADO-OFDM.
We analyze quantum dynamics of strongly interacting, kinetically constrained many-body systems. Motivated by recent experiments demonstrating surprising long-lived, periodic revivals after quantum ...quenches in Rydberg atom arrays, we introduce a manifold of locally entangled spin states, representable by low-bond dimension matrix product states, and derive equations of motion for them using the time-dependent variational principle. We find that they feature isolated, unstable periodic orbits, which capture the recurrences and represent nonergodic dynamical trajectories. Our results provide a theoretical framework for understanding quantum dynamics in a class of constrained spin models, which allow us to examine the recently suggested explanation of "quantum many-body scarring" Nat. Phys. 14, 745 (2018)NPAHAX1745-247310.1038/s41567-018-0137-5, and establish a possible connection to the corresponding phenomenon in chaotic single-particle systems.
The propensity of the activated neutrophils to form extracellular traps (NETs) is demonstrated in multiple inflammatory conditions. In this study, we investigated the roles of NETs in metastasis of ...hepatocellular carcinoma (HCC) and further explored the underlying mechanism of how NETs affect metastasis as well as the therapeutic value.
The neutrophils were isolated from the blood of human HCC patients and used to evaluate the formation of NETs. The expression of NET markers was detected in tumor specimens. A LPS-induced NET model was used to investigate the role of NETs on HCC metastasis. RNA-seq was performed to identify the key molecular event triggered by NETs, and their underlying mechanism and therapeutic significance were explored using both in vitro and in vivo assays.
NET formation was enhanced in neutrophils derived from HCC patients, especially those with metastatic HCCs. NETs trapped HCC cells and subsequently induced cell-death resistance and enhanced invasiveness to trigger their metastatic potential, which was mediated by internalization of NETs into trapped HCC cells and activation of Toll-like receptors TLR4/9-COX2 signaling. Inhibition of TLR4/9-COX2 signaling abrogated the NET-aroused metastatic potential. A combination of DNase 1 directly wrecking NETs with anti-inflammation drugs aspirin/hydroxychloroquine effectively reduced HCC metastasis in mice model.
NETs trigger tumorous inflammatory response and fuel HCC metastasis. Targeting NETs rather than neutrophils themselves can be a practice strategy against HCC metastasis.
This letter proposed a novel design of the hybrid asymmetrically clipped optical orthogonal frequency division multiplexing (HACO-OFDM) system with cyclic shifted PAM-DMT signals called ...CSPAM-HACO-OFDM for visible light communication. The transmitted signal generated by the CSPAM-HACO-OFDM system combines the PAM-DMT signals with cyclic shift equivalents by using even subcarriers and the ACO-OFDM signals by using odd subcarriers. Peak-to-average power ratio (PAPR) reduction with remarkably low computational complexity is achieved, and side information is not required. A near-optimal side information detector, which has a similar detection error probability as the perfect-side information detector, is used at the receiver side. Simulation results demonstrate the effectiveness of the CSPAM-HACO-OFDM system in terms of PAPR reduction and average bit error rate.
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•Transition-metal-based IR-NLO chalcogenides are overviewed.•“Chemical composition–NCS structure–NLO property” is summarized systematically.•Several useful conclusions and future ...considerations have been provided.
The developments of new infrared nonlinear optical (IR-NLO) crystals with excellent comprehensive performance are urgently needed owing to the current commercially available materials (e.g., AgGaS2, AgGaSe2, and ZnGeP2) possess their inevitable disadvantages which limited significantly their high-power laser applications. The class of transition-metal-based chalcogenides is the most favorable source of promising IR-NLO candidates with rich structural diversity and broad IR transparent windows. Moreover, most of them can intrinsically meet many vital requirements for ideal IR-NLO crystals, such as phase-matching (PM) features, strong second harmonic generation (SHG) responses, high laser induced damage thresholds (LIDTs), low melting points and wide energy gaps. However, there has not been a comprehensive survey on this attractive family. In this review, these existing transition-metal-based chalcogenides are divided into three groups according to their chemical compositions, and the dimensionality–bandgap–NLO property relationship for the 36 representative series (including 6 crystal systems, 34 space groups and >500 non-centrosymmetric chalcogenides) has been compared and summarized in detail. In addition, current problems and future development of this field are also proposed. Finally, we hope this review could provide some inspirations and help to the chemists and material scientists to design and synthesis high-performance transition-metal-based chalcogenides for IR-NLO applications.
Due to its accurate representation of parent–child interaction quality in Confucian‐influenced cultures, contemporary filial piety, which refers to general beliefs about how children are expected to ...behave toward their parents, has drawn increasing attention in academia. However, how filial piety associates with intimate relationships beyond the family setting is less clear. This study examined the relation between dual filial piety (i.e., reciprocal filial piety and authoritarian filial piety) and romantic relationship quality among Chinese youths. We explored a mediational model in which we tested whether dual autonomy (i.e., individuating autonomy and relating autonomy) would help explain how Chinese youths' beliefs in filial piety are linked to the quality of their romantic relationships. A total of 605 youths from Macau (N = 291) and Taiwan (N = 314) who are currently or once romantically involved participated in the study. We employed structural equation modeling to analyze the data. Results showed within‐culture invariance regarding the direct and indirect associations between filial piety, autonomy, and romantic relationship quality. Specifically, young people in both Macau and Taiwan who endorsed higher reciprocal filial piety had more individuating autonomy, which in turn contributed to them having higher quality romantic relationships.
Tumor metastasis is a hallmark of cancer. The communication between cancer-derived exosomes and stroma plays an irreplaceable role in facilitating pre-metastatic niche formation and cancer ...metastasis. However, the mechanisms underlying exosome-mediated pre-metastatic niche formation during colorectal cancer (CRC) liver metastasis remain incompletely understood. Here we identified HSPC111 was the leading upregulated gene in hepatic stellate cells (HSCs) incubated with CRC cell-derived exosomes. In xenograft mouse model, CRC cell-derived exosomal HSPC111 facilitated pre-metastatic niche formation and CRC liver metastases (CRLM). Consistently, CRC patients with liver metastasis had higher level of HSPC111 in serum exosomes, primary tumors and cancer-associated fibroblasts (CAFs) in liver metastasis than those without. Mechanistically, HSPC111 altered lipid metabolism of CAFs by phosphorylating ATP-citrate lyase (ACLY), which upregulated the level of acetyl-CoA. The accumulation of acetyl-CoA further promoted CXCL5 expression and secretion by increasing H3K27 acetylation in CAFs. Moreover, CXCL5-CXCR2 axis reinforced exosomal HSPC111 excretion from CRC cells and promoted liver metastasis. These results uncovered that CRC cell-derived exosomal HSPC111 promotes pre-metastatic niche formation and CRLM via reprogramming lipid metabolism in CAFs, and implicate HSPC111 may be a potential therapeutic target for preventing CRLM.
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