Chemical syntheses of the cochliomycins and certain related resorcylic acid lactones

The cochliomycins (7–12) are a group of six resorcylic acid lactones that have recently been isolated from culture broths of marine fungi found in the South China Sea. These natural products have attracted attention as synthetic targets because of (in certain instances) their novel structural features and their capacities to suppress biofouling. This short review summarizes the synthesis of these and some related compounds that have been reported to date, including those developed in the authors’ laboratories.The authors thank the Australian Research Council and the Institute of Advanced Studies at the Australian National University for ongoing support. YZ is the grateful recipient of a stipend from the China Scholarship Council of the People’s Republic of China while XM thanks the Guangdong Province’s GEP for the provision of a scholarship

Fast generation of arbitrary optical focus array

We report a novel method to generate arbitrary optical focus arrays (OFAs). Our approach rapidly produces computer-generated holograms (CGHs) to precisely control the positions and the intensities of the foci. This is achieved by replacing the fast Fourier transform (FFT) operation in the conventional iterative Fourier-transform algorithm (IFTA) with a linear algebra one, identifying/removing zero elements from the matrices, and employing a generalized weighting strategy. On the premise of accelerating the calculation speed by >70 times, we demonstrate OFA with 99% intensity precision in the experiment. Our method proves effective and is applicable for the systems in which real-time OFA generation is essential

Emergent normal fluid in the superconducting ground state of overdoped cuprates

The microscopic mechanism for the disappearance of superconductivity in overdoped cuprates is still under heated debate. Here we use scanning tunneling spectroscopy to investigate the evolution of quasiparticle interference phenomenon in $\rm Bi_2Sr_2CuO_{6+\delta}$ over a wide range of hole densities. We find that when the system enters the overdoped regime, a peculiar quasiparticle interference wavevector with quarter-circle pattern starts to emerge even at zero bias, and its intensity grows with increasing doping level. Its energy dispersion is incompatible with the octet model for d-wave superconductivity, but is highly consistent with the scattering interference of gapless normal carriers. The weight of the gapless quasiparticle interference is mainly located at the antinodes and is independent of temperature. We propose that the normal fluid emerges from the pair-breaking scattering between flat antinodal bands in the quantum ground state, which is the primary cause for the reduction of superfluid density and suppression of superconductivity in overdoped cuprates

Comparison of short-segment monoaxial and polyaxial pedicle screw fixation combined with intermediate screws in traumatic thoracolumbar fractures: a finite element study and clinical radiographic review

OBJECTIVES: No studies have compared monoaxial and polyaxial pedicle screws with regard to the von Mises stress of the instrumentation, intradiscal pressures of the adjacent segment and adjacent segment degeneration. METHODS: Short-segment monoaxial/polyaxial pedicle screw fixation techniques were compared using finite element methods, and the redistributed T11-L1 segment range of motion, largest maximal von Mises stress of the instrumentation, and intradiscal pressures of the adjacent segment under displacement loading were evaluated. Radiographic results of 230 patients with traumatic thoracolumbar fractures treated with these fixations were reviewed, and the sagittal Cobb’s angle, vertebral body angle, anterior vertebral body height of the fractured vertebrae and adjacent segment degeneration were calculated and evaluated. RESULTS: The largest maximal values of the von Mises stress were 376.8 MPa for the pedicle screws in the short-segment monoaxial pedicle screw fixation model and 439.9 MPa for the rods in the intermediate monoaxial pedicle screw fixation model. The maximal intradiscal pressures of the upper adjacent segments were all greater than those of the lower adjacent segments. The maximal intradiscal pressures of the monoaxial pedicle screw fixation model were larger than those in the corresponding segments of the normal model. The radiographic results at the final follow-up evaluation showed that the mean loss of correction of the sagittal Cobb’s angle, vertebral body angle and anterior vertebral body height were smallest in the intermediate monoaxial pedicle screw fixation group. Adjacent segment degeneration was less likely to be observed in the intermediate polyaxial pedicle screw fixation group but more likely to be observed in the intermediate monoaxial pedicle screw fixation group. CONCLUSION: Smaller von Mises stress in the pedicle screws and lower intradiscal pressure in the adjacent segment were observed in the polyaxial screw model than in the monoaxial pedicle screw fixation spine models. Fracture-level fixation could significantly correct kyphosis and reduce correction loss, and adjacent segment degeneration was less likely to be observed in the intermediate polyaxial pedicle screw fixation group

DICER1 regulated let-7 expression levels in p53-induced cancer repression requires cyclin D1.

Let-7 miRNAs act as tumour suppressors by directly binding to the 3\u27UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence-specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1-induced let-7 expression. In addition, we found that let-7 miRNAs expression decreased because of the p53-induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin-3 and TAX-induced let-7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let-7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let-7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response

Proximity effect induced intriguing superconductivity in van der Waals heterostructure of magnetic topological insulator and conventional superconductor

Nontrivial topological superconductivity has received enormous research attentions due to its potential for diverse applications in topological quantum computing. The intrinsic issue concerning the correlation between a topological insulator and a superconductor is, however, still widely open. Here, we systemically report an emergent superconductivity in a cross-junction composed of a magnetic topological insulator MnBi2Te4 and a conventional superconductor NbSe2. Remarkably, the interface indicates existence of a reduced superconductivity at surface of NbSe2 and a proximity-effectinduced superconductivity at surface of MnBi2Te4. Furthermore, the in-plane angular-dependent magnetoresistance measurements reveal the fingerprints of the paring symmetry behaviors for these superconducting gaps as a unconventional nature. Our findings extend our views and ideas of topological superconductivity in the superconducting heterostructures with time-reversal symmetry breaking, offering an exciting opportunity to elucidate the cooperative effects on the surface state of a topological insulator aligning a superconductor.Comment: 6 pages, 4 figure

Neuroprotective Mechanisms of Lycium barbarum Polysaccharides Against Ischemic Insults by Regulating NR2B and NR2A Containing NMDA Receptor Signaling Pathways

Glutamate excitotoxicity plays an important role in neuronal death after ischemia. However, all clinical trials using glutamate receptor inhibitors have failed. This may be related to the evidence that activation of different subunit of NMDA receptor will induce different effects. Many studies have shown that activation of the intrasynaptic NR2A subunit will stimulate survival signaling pathways, whereas upregulation of extrasynaptic NR2B will trigger apoptotic pathways. A Lycium barbarum polysaccharide (LBP) is a mixed compound extracted from Lycium barbarum fruit. Recent studies have shown that LBP protects neurons against ischemic injury by anti-oxidative effects. Here we first reported that the effect of LBP against ischemic injury can be achieved by regulating NR2B and NR2A signaling pathways. By in vivo study, we found LBP substantially reduced CA1 neurons from death after transient global ischemia and ameliorated memory deficit in ischemic rats. By in vitro study, we further confirmed that LBP increased the viability of primary cultured cortical neurons when exposed to oxygen-glucose deprivation (OGD) for 4 h. Importantly, we found that LBP antagonized increase in expression of major proteins in the NR2B signal pathway including NR2B, nNOS, Bcl-2-associated death promoter (BAD), cytochrome C (cytC) and cleaved caspase-3, and also reduced ROS level, calcium influx and mitochondrial permeability after 4 h OGD. In addition, LBP prevented the downregulation in the expression of NR2A, pAkt and pCREB, which are important cell survival pathway components. Furthermore, LBP attenuated the effects of a NR2B co-agonist and NR2A inhibitor on cell mortality under OGD conditions. Taken together, our results demonstrated that LBP is neuroprotective against ischemic injury by its dual roles in activation of NR2A and inhibition of NR2B signaling pathways, which suggests that LBP may be a superior therapeutic candidate for targeting glutamate excitotoxicity for the treatment of ischemic stroke