A Biaryl-Cyclohexenone Photoelectrocyclization/Dearomatization Sequence to Substituted Terpenes.

Described here is the development of sequential cross-coupling, photoelectrocyclizations, and reductive dearomatizations of biaryl cyclohexenones as a means of synthesizing terpene skeletons. This methodology promises to provide insight that will enable us and others to use this approach to generate a variety of biologically active small molecules, including members of the abietane and morphinan skeletons.

Ant-Nest-like Lithiophilic Host for Long-Life Lithium Metal Anodes.

The rational design of confined host to tutor Li nucleation and deposition behavior remains a key challenge for the long stability of lithium metal anodes (LMAs), while the scalability and feasibility of the method need to be taken into concern. Herein, a biomimic strategy is designed for tutoring in-depth nucleation and bottom-up Li deposition by composing ant-nest-like lithiophilic hosts for LMAs with light-weight flexible and conductive carbon nanotubes (CNTs) as the framework, table salt (sodium chloride, NaCl) as the washable porous creator, and homogeneously dispersed nano-Si as the nucleation site. It possesses similar optimized structure as ant nests in nature and can provide large and conductive inner volume for Li storage. Combining with the interconnected passways can ensure effective ion compensation like food transport channels for ants, and the well-designed host can take effect as an individual Li anode (5 mA h cm-2 area Li loading for demonstration) and the record-long stable LMA host can be achieved for over a 2200 h lifespan with minimum volume expansion. Therefore, this biomimic strategy is developed with all commercialized battery materials, and all industry compatible production methods can provide a feasible technical path for the stable, long-cyclability, and reliable host design for LMAs.

Piperidine CD4-Mimetic Compounds Expose Vulnerable Env Epitopes Sensitizing HIV-1-Infected Cells to ADCC.

The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 levels contributes to the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC) by preventing the exposure of Env vulnerable epitopes. Small-molecule CD4 mimetics (CD4mc) based on the indane and piperidine scaffolds such as (+)-BNM-III-170 and (S)-MCG-IV-210 sensitize HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes recognized by non-neutralizing antibodies that are abundantly present in plasma from people living with HIV. Here, we characterize a new family of CD4mc, (S)-MCG-IV-210 derivatives, based on the piperidine scaffold which engages the gp120 within the Phe43 cavity by targeting the highly conserved Asp368 Env residue. We utilized structure-based approaches and developed a series of piperidine analogs with improved activity to inhibit the infection of difficult-to-neutralize tier-2 viruses and sensitize infected cells to ADCC mediated by HIV+ plasma. Moreover, the new analogs formed an H-bond with the α-carboxylic acid group of Asp368, opening a new avenue to enlarge the breadth of this family of anti-Env small molecules. Overall, the new structural and biological attributes of these molecules make them good candidates for strategies aimed at the elimination of HIV-1-infected cells.

Comparison of staged lateral lumbar interbody fusion combined two-stage posterior screw fixation and two osteotomy strategies for adult degeneration scoliosis: a retrospective comparative study.

AIMS: The commonly used treatments of adult degeneration scoliosis (ADS) were posterior long segment screw fixation with osteotomies. Recently, lateral lumbar intervertebral fusion combined two-stage posterior screw fixation (LLIF + PSF) as a new strategy without osteotomy. Herein, this study aimed to compare the clinical and radiological outcomes among LLIF + PSF and pedicle subtraction osteotomy (PSO), posterior column osteotomies (PCO). METHODS: Totals of 139 ADS patients underwent operation with 2 years longer follow-up visit between January 2013 and January 2018 in Ningbo No.6 Hospital were enrolled into this study. 58 patients were included in PSO group, 45 in PCO group and 36 in LLIF + PSF group, The clinical and radiological data were reviewed from medical records. Baseline characteristic, perioperative radiological data (sagittal vertical axis (SVA), coronal balance (CB), Cobb angle of Mian curve (MC), Lumbar lordosis (LL), pelvic tilt (PT) and pelvic incidence-lumbar lordosis mismatch (PI-LL)), clinical outcomes (VAS of back and leg, Oswestry disability index (ODI) and Scoliosis Research Society 22-question Questionnaire (SRS-22)) and complications were evaluated and compared. RESULT: There were no significantly difference in baseline characteristics, preoperative radiological parameters and clinical outcomes among three groups. LLIF + PSF group was significantly shorter in operation time than other two groups (P < 0.05), whereas significant longer hospital stay was observed in LLIF + PSF group (P < 0.05). As for radiological parameters, LLIF + PSF group had significantly improvement in SVA, CB, MC, LL and PI-LL (P < 0.05). Moreover, LLIF + PSF group achieved significantly less correction loss in SVA, CB and PT than PSO and PCO group (1.5 ± 0.7 VS 2.0 ± 0.9 VS 2.2 ± 0.8, P < 0.05; 1.0 ± 0.4 VS 1.3 ± 0.5 VS 1.1 ± 0.7, P < 0.05 and 4.2 ± 2.8 VS 7.2 ± 3.1 VS 6.0 ± 2.8, P < 0.05). Significantly recovery in VAS of back and leg, ODI score and SRS-22 were found among all groups, however, LLIF + PSF shown significant better clinical therapy maintain at follow-up visit than other two groups (P < 0.05). There were no significantly difference in complications among groups (P = 0.66). CONCLUSION: Lateral lumbar interbody fusion combined two-stage posterior screw fixation (LLIF + PSF) can achieve comparable clinical therapy for adult degeneration scoliosis as osteotomy strategies. However, furthermore more studies need be taken for verifying the effect of LLIF + PSF in the future.

Piperidine CD4-mimetic compounds expose vulnerable Env epitopes sensitizing HIV-1-infected cells to ADCC.

The ability of HIV-1 accessory proteins Nef and Vpu to decrease CD4 levels contributes to the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC) by preventing the exposure of Env vulnerable epitopes. Small-molecule CD4 mimetics (CD4mc) based on the indane and piperidine scaffolds such as (+)-BNM-III-170 and ( S )-MCG-IV-210 sensitize HIV-1 infected cells to ADCC by exposing CD4-induced (CD4i) epitopes recognized by non-neutralizing antibodies abundantly present in plasma from people living with HIV. Here, we characterize a new family of CD4mc, ( S )-MCG-IV-210 derivatives, based on the piperidine scaffold which engage the gp120 within the Phe43 cavity by targeting the highly-conserved Asp 368 Env residue. We utilized structure-based approaches and developed a series of piperidine analogs with improved activity to inhibit infection of difficult-to-neutralize tier-2 viruses and sensitize infected cells to ADCC mediated by HIV+ plasma. Moreover, the new analogs formed an H-bond with the α-carboxylic acid group of Asp 368 , opening a new avenue to enlarge the breadth of this family of anti-Env small molecules. Overall, the new structural and biological attributes of these molecules make them good candidates for strategies aimed at the elimination HIV-1-infected cells.

Comparison of Percutaneous Endoscopic Cervical Keyhole Foraminotomy versus Microscopic Anterior Cervical Discectomy and Fusion for Single Level Unilateral Cervical Radiculopathy.

Objective: To compare the clinical and radiological outcomes between microscopic anterior cervical discectomy and fusion (ACDF) and percutaneous endoscopic cervical keyhole foraminotomy (PECF) for single level unilateral cervical radiculopathy. Methods: A total of 127 patients (59 in PECF VS 68 in ACDF) were enrolled in this study from April 2016 to May 2018 with a minimum follow-up of 2 years. Clinical data including baseline data, Neck Disability Index (NDI), and Visual Analogue Scale for neck and arm (VAS-n, VAS-a) were collected and compared. Radiological evaluation such as disc height, ROM of cervical, Cobb's angle of cervical and Cobb's angle of operated segment was measured by two experienced radiologists in twice. Results: There was no significant difference between the two groups in the baseline data, and hospital stay was significantly decreased in PECF group than ACDF group (P < 0.001). PECF group did not yield superior better outcomes in NDI, VAS-a and VAS-n than ACDF group except at 1-month follow-up. As for radiological outcomes, PECF group has significantly better cervical motion, cervical angle and segmental angle than ADCF group at 12- and 24-month follow-up visit (P < 0.05); however, ACDF had shown better disc height restoration and maintenance than PECF (P < 0.05). More complications including surface hematoma and swallowing difficulty were occurred in ADCF group. Conclusion: Percutaneous endoscopic cervical keyhole foraminotomy could be the alternative method for anterior cervical discectomy and fusion in selective cases. However, the indication should be fulfilled, more studies need to be conducted to further testify the efficacy of PECF.

Biphenyl Cyclobutenone Photoelectrocyclizations.

In this work, we demonstrate that readily available conjugated bis-aryl cyclobutenones undergo photoelectrocyclization reactions to give the corresponding dihydrophenanthrene cyclobutanones when exposed to 350 nm light, TFA, and TMSCl. We have also found that cyclobutenone electrocyclizations and cycloreversions are in equilibrium.

The Synthesis of Conjugated Bis-Aryl Vinyl Substrates and Their Photoelectrocyclization Reactions towards Phenanthrene Derivatives.

The photoelectrocyclization of conjugated vinyl biaryls has proven to be a valuable and efficient strategy for generating phenanthrene derivatives. Contained in this review is an overview of the mechanism for the transformation and a discussion of the reaction scope with a focus on the electrocyclization itself, rearomatization, and the application of the reaction in natural product synthesis.

Design and Performance Evaluation of a Deep Neural Network for Spectrum Recognition of Underwater Targets.

Due to the complexity of the underwater environment, underwater acoustic target recognition (UATR) has always been challenging. Although deep neural networks (DNN) have been used in UATR and some achievements have been made, the performance is not satisfactory when recognizing underwater targets with different Doppler shifts, signal-to-noise ratios (SNR), and interferences. In the paper, a one-dimensional convolutional neural network (1D-CNN) was proposed to recognize the line spectrums of Detection of Envelope Modulation on Noise (DEMON) spectrums of underwater target-radiated noise. Datasets of targets with different Doppler shifts, SNRs, and interferences were designed to evaluate the generalization performance of the proposed CNN. Experimental results show that compared with traditional multilayer perceptron (MLP) networks, the 1D-CNN model better performs in recognition of targets with different Doppler shifts and SNRs. The outstanding generalization ability of the proposed model shows that it is suitable for practical engineering applications.

Photoelectrocyclization Reactions of Conjugated Cycloalkenones: Scope and Reactivity.

Outlined here are studies exploring the scope of the sequential photoelectrocyclization, [1,5]-hydride shift of conjugated bis-aryl cycloalkenone substrates. We have found not only that the cyclization precursors can be synthesized in a modular fashion but also that the cyclization is efficient and amenable to the presence of a range of cycloalkenones and aromatic systems. Among the interesting discoveries from this work is that the electrocyclization intermediate can be competitively captured with protons and that the nature of the excited state (singlet vs triplet) is dependent on aromatic substitution.

Stereodivergent Photoelectrocyclization Reactions of Bis-aryl Cycloalkenones: Intercepting Photoelectrocyclization Intermediates with Acid.

Described here are tandem photoelectrocyclization and [1,5]-hydride shift reactions of heteroaryl-containing bis-aryl cyclohexenone derivatives that give heteroaryl-substituted dihydrophenanthrenes. This Letter demonstrates that electrocyclization intermediates can be trapped with acid when the [1,5]-hydride shift is relatively slow. From a practical perspective, the observation that the acid-mediated reaction gives a divergent stereochemical outcome when compared with the reaction run under neutral conditions makes these transformations powerful.

Proteolytic Degradation and Inflammation Play Critical Roles in Polypoidal Choroidal Vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a common subtype of wet age-related macular degeneration in Asian populations, whereas choroidal neovascularization is the typical subtype in Western populations. The cause of PCV is unknown. By comparing the phenotype of a PCV mouse model expressing protease high temperature requirement factor A1 (HTRA1) in retinal pigment epithelium with transgenic mice expressing the inactive HTRA1S328A, we showed that HTRA1-mediated degradation of elastin in choroidal vessels is critical for the development of PCV, which exhibited destructive extracellular matrix remodeling and vascular smooth muscle cell loss. Compared with weak PCV, severe PCV exhibited prominent immune complex deposition, complement activation, and infiltration of inflammatory cells, suggesting inflammation plays a key role in PCV progression. More important, we validated these findings in human PCV specimens. Intravitreal delivery of an HTRA1 inhibitor (DPMFKLboroV) was effective (36% lesion reduction; P = 0.009) in preventing PCV initiation but ineffective in treating existing lesions. Anti-inflammatory glucocorticoid was effective in preventing PCV progression but ineffective in preventing PCV initiation. These results suggest that PCV pathogenesis occurs through two stages. The initiation stage is mediated by proteolytic degradation of extracellular matrix proteins attributable to increased HTRA1 activity, whereas the progression stage is driven by inflammatory cascades. This study provides a basis for understanding the differences between PCV and choroidal neovascularization, and helps guide the design of effective therapies for PCV.

Dimerization of visual pigments in vivo.

It is a deeply engrained notion that the visual pigment rhodopsin signals light as a monomer, even though many G protein-coupled receptors are now known to exist and function as dimers. Nonetheless, recent studies (albeit all in vitro) have suggested that rhodopsin and its chromophore-free apoprotein, R-opsin, may indeed exist as a homodimer in rod disk membranes. Given the overwhelmingly strong historical context, the crucial remaining question, therefore, is whether pigment dimerization truly exists naturally and what function this dimerization may serve. We addressed this question in vivo with a unique mouse line (S-opsin(+)Lrat(-/-)) expressing, transgenically, short-wavelength-sensitive cone opsin (S-opsin) in rods and also lacking chromophore to exploit the fact that cone opsins, but not R-opsin, require chromophore for proper folding and trafficking to the photoreceptor's outer segment. In R-opsin's absence, S-opsin in these transgenic rods without chromophore was mislocalized; in R-opsin's presence, however, S-opsin trafficked normally to the rod outer segment and produced functional S-pigment upon subsequent chromophore restoration. Introducing a competing R-opsin transmembrane helix H1 or helix H8 peptide, but not helix H4 or helix H5 peptide, into these transgenic rods caused mislocalization of R-opsin and S-opsin to the perinuclear endoplasmic reticulum. Importantly, a similar peptide-competition effect was observed even in WT rods. Our work provides convincing evidence for visual pigment dimerization in vivo under physiological conditions and for its role in pigment maturation and targeting. Our work raises new questions regarding a potential mechanistic role of dimerization in rhodopsin signaling.

Typical agricultural diffuse herbicide sorption with agricultural waste-derived biochars amended soil of high organic matter content.

Biochar application has been identified as the effective soil amendment and the materials to control the diffuse herbicide pollution. The atrazine was selected as the typical diffuse herbicide pollutant as the dominant proportion in applications. The biochar treated from four types of crops biomass were added to soil with high organic matter content. The basic sorption characteristics of biocahrs from corn cob (CC), corn stalk (CS), soybean straw (SS), rice straw (RS) and corn stalk paralyzed with 5% of ammonium dihydrogen phosphate (ACS) were analyzed, along with the comparison of the sorption difference of the raw soil and soil amended with biochars at four levels of ratio (0.5%, 1.0%, 3.0% and 5.0%). It was found that the linear distribution isotherm of raw soil was much effective due to the high organic matter background concentration. The addition of five types of biochars under two kinds of initial atrazine concentration (1 mg/L and 20 mg/L) demonstrated the sorption variances. Results showed the soil amended with RS and CS biochar had the biggest removal rate in four regular biochars and the removal rate of the ACS was the biggest. The sorption coefficient and the normalized sorption coefficient from Freundlich modeling presented the isothermal sorption characteristics of atrazine with soil of high organic matter content. The normalized sorption coefficient increased with the equilibrium concentration decreased in the biochar amended soil, which indicated the sorption performance will be better due to the low atrazine concentration in practice. Results showed that biochar amendment is the effective way to prevent leakage of diffuse herbicide loss.

Properties comparison of biochars from corn straw with different pretreatment and sorption behaviour of atrazine.

Biochar has been recognised as an efficient pollution control material. In this study, biochars (CS450 and ADPCS450) were produced using corn straw with different pretreatment techniques (without and with ammonium dihydrogen phosphate (ADP)). The character of the two biochars was compared using elemental analysis, specific surface area (SSA) and Fourier transform infrared spectra (FTIR). ADPCS450 had a higher residue yield and a much larger specific surface area than CS450. The Freundlich, Langmuir and Redlich-Peterson models were used to interpret the sorption behaviour of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine), and the results fit the Redlich-Peterson equation best. The isothermal sorption parameters indicated that the sorption capacity of atrazine on ADPCS450 was much larger than the sorption capacity of atrazine on CS450. Atrazine sorption was also favoured in acidic solution and under higher temperature conditions.

Combined impacts of freeze-thaw processes on paddy land and dry land in Northeast China.

The quantity of spring snowmelt infiltration and runoff, which affects the hydrology of the freeze zone, depends on the antecedent soil water content (SWC) conditions at the time of the soil's freezing. An understanding of the characteristics of frozen soil is essential for spring sowing in the agricultural freeze zones. The main goal of this study was to evaluate the differences in the freeze-thaw process and the freeze-thaw-induced water redistribution between the paddy and dry lands in a freeze zone. For this purpose, a field study was conducted in the winter of 2011-2012 for two types of farmlands in Northeast China. To illustrate the soil's frost dynamics over time, the measured SWCs at different depths (15, 30, 60, and 90 cm) were transformed into different expressions including the SWC dynamic, the frozen soil's profile, and the freezing and thawing front trace. The freezing characteristics in the paddy land, in contrast to that in the dry land, had a higher freezing point temperature, a larger amount of water movement to the upper layer, and a 2.76 mm larger accumulation of water in the upper layer. However, the increase of SWC (which is equivalent to thawing) was evidently faster than the decrease of SWC (which is equivalent to freezing). The water in the frozen soil's profile was most likely redistributed towards the freezing front before soil temperature (ST) falls below the freezing point. The findings may partially explain the soil's freeze-thaw characteristics for the different stages as well as the combined impact of these characteristics with farmland use types on soil hydrology; the findings may also provide a foundation for forecasting the hydrologic response of the freeze-thaw process and provide guidance for management strategies dealing with seasonally frozen agricultural soils.