Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes.

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.

Bioassay-Guided Isolation of an Abetiane-Type Diterpenoid from Prunella vulgaris That Protects against Concanavalin A-Induced Autoimmune Hepatitis.

Prunella vulgaris is a widely used edible Chinese medicinal plant. In the present study, two new abietane-type diterpenoids, abietoquinones A (1) and B (2), were isolated from this plant by an immunosuppressive bioassay-guided isolation procedure. Their structures were elucidated unambiguously by NMR spectroscopic analysis, single-crystal X-ray crystallography, and electronic circular dichroism calculations. Compounds 1 and 2 bear a cyclohex-2-ene-1,4-dione moiety, which is uncommon among abietane diterpenes. Also, abietoquinone A (1) suppressed murine splenocyte proliferation and decreased the production of proinflammatory cytokines induced by concanavalin A (Con A) in vitro. In Con A-challenged mice, preinjection with 1 significantly ameliorated liver injury. Additionally, abietoquinone A (1) exhibited inhibitory activities against the proliferation of murine splenocytes and human T cells induced by anti-CD3/anti-CD28 monoclonal antibodies (mAbs).

A heat transfer model for liquid film boiling on micro-structured surfaces.

High heat transfer coefficient (HTC) and critical heat flux (CHF) are achieved in liquid film boiling by coupling vibrant vapor bubbles with a capillary liquid film, which has thus received increased interest for thermal management of high-power electronics. Although some experimental progress has been made, a high-fidelity heat transfer model for liquid film boiling is lacking. This work develops a thermal-hydrodynamic model by considering both evaporation atop the wick and nucleate boiling inside the wick to simultaneously predict the HTC and CHF. Nucleate boiling is modeled with microlayer evaporation theory, where a unified scaling factor is defined to characterize the change of microlayer area with heat flux. The scaling factor η is found to be independent of wicking structure and can be determined from a few measurements. This makes our model universal to predict the liquid film boiling heat transfer for various micro-structured surfaces including micropillar, micropowder, and micromesh. This work not only sheds light on understanding fundamental mechanisms of phase-change heat transfer, but also provides a tool for designing micro-structured surfaces in thermal management.

Heavy-Atom Effect Regulating Room-Temperature Phosphorescence of Organic-Inorganic Zn-Based Halides for White-Light Emission.

Organic-inorganic metal halides (OIMHs) with room-temperature phosphorescence (RTP) properties have aroused great research enthusiasm as outstanding broadband white-light emitters. Current studies on OIMHs with white-light emission were achieved via self-trapped excitons (STEs), but the unclear mechanism of STE formation is not favorable for the design of materials. In this work, zero-dimensional OIMHs composed of organic 3,4,5-trimethoxybenzylamine (TBA) and zine halide were synthesized, which enhanced the ratio of the RTP emission to the fluorescence emission from the TBA ligand. The experimental and mechanistic analyses demonstrate that the manageable RTP is mainly caused by the heavy-atom effect. In particular, by adjusting the incorporation ratio of halogen, an obvious white-light emission with a chromaticity coordinate value of (0.31, 0.33) can be achieved. This work developed a method for regulating the RTP of OIMHs with the heavy-atom effect to realize white-light emission, providing a new idea for the design of white-light emission materials.

Can non-swallowing function assessment predict nasogastric tube removal in patients with poststroke dysphagia? A clinical study.

Objective: This study aimed to predict nasogastric tube (NGT) removal in patients with poststroke dysphagia (PSD) by non-swallowing function assessment. Methods: We enrolled 232 eligible patients and performed rehabilitation. The Fugl-Meyer assessment motor (FMM) and National Institute of Health Stroke Scale (NIHSS) scores were used to measure the motor and overall nervous system functions. Predictors for NGT removal in patients with PSD after rehabilitation were analyzed. Results: Of the 232 included patients, the NGTs were removed from 78% of them, while 22% were dependent on a feeding tube after 4 weeks of rehabilitation. Compared to the preserved NGT group, older age, a higher rate of intubation or tracheostomy, and more severe baseline functions were found in the NGT removal group. Age [odds ratio (OR) = 0.907; 95% confidence interval (CI): 0.859-0.957; p = 0.000], difference in the FMM score after 4 weeks of rehabilitation (OR = 1.219; 95% CI: 1.145-1.299; p = 0.00), and item 9 of NIHSS (OR = 0.488; 95% CI: 0.252-0.946; p = 0.034) were predictors of NGT removal after rehabilitation. Conclusion: We established a predictive model in patients with PSD using a non-swallowing assessment, which enabled us to predict swallowing recovery based on the non-swallowing function.

Identification of seven undescribed cucurbitacins in Cucumis sativus (cucumber) and their cytotoxic activity.

Cucurbitacin C-type cucurbitacins that are only identified in Cucumis sativus (cucumber) are, in part, responsible for the health benefits and bitter flavor. Nevertheless, detailed information about those functional ingredients in cucumber is scarce. In this study, ten cucurbitacin C analogues including seven undescribed ones have been isolated from the bitter leaves of cucumber, in which six compounds showed growth inhibition capabilities against tumor cell lines HepG2, A549, DU145 and HCT116. Intriguingly, cucurbitacin C6 and C7 exhibited a significant inhibition effect compared to the positive control taxol (IC50 = 1.86 ± 0.17 µM) on HepG2 cell line with IC50 values of 10.06 ± 0.34 µM and 4.16 ± 0.42 µM, respectively. The mechanism of cucurbitacin-induced apoptosis is likely down-regulating the expression of caspase-related proteins. This work enlarges the knowledge of the cucurbitacins in cucumber and highlights the importance of cucumber as a source of specialized metabolites in the food and medicinal industries.

[Effects of airborne fine particulate matters on human immunological indicators].

OBJECTIVE: To explore effects of airborne fine particulate matters on human immunological indicators. METHODS: All subjects were measured the level of PM2. 5 individual exposure with personal sampling devices. Serum immunological indicators, such as WBC, NE, NE%, Ly, Ly%, CD4+, CD8+, CD4+ / CD8+, IgA, IgM, IgG and IgE were detected through enzyme-linked immunosorbent assay. Then, comparing the difference of PM2.5 exposure and immunological indicators between two groups. RESULTS: For the level of PM2.5 daily exposure, traffic policemen (115.4 +/- 46.2) microg/m3) was significantly higher than residents ((74.9 +/- 40.1) +/- g/ m(-3)). And there was also significant difference in some immunological indicators, such as Ly%, CD4+, CD8+, IgM, IgG, IgE, CC 16 and CRP, between two groups. CONCLUSION: Long-term high level of airborne fine particulate matters exposure may change some blood immunological indicators, affect the health of the immune system.

[Effects of airborne fine particulate matter on human respiratory symptoms and pulmonary function].

OBJECTIVE: to explore effects of airborne fine particulate matter exposure on human respiratory symptoms and pulmonary function. METHODS: one hundred and seven field traffic policemen were recruited as airborne fine particulate matter high-exposure group and one hundred and one male residents as common exposure group. The individual sampler was used to measure fine particulate matter exposure levels of the two groups. To obtain personal information, especially respiratory symptoms such as cough, sputum, etc. a questionnaire survey was used. The pulmonary ventilation function was detected: forced expiratory vital capacity (FVC), the first 1 second forced expiratory volume (FEV1.0), FVC/FEV1.0% and peak flow values (PEF), and the difference of fine particulate matter exposure level and respiratory function of the two groups was compared. RESULTS: 24 h individual average fine particulate matter exposure concentration of traffic police and residents were respectively (115.4 ± 46.17) microg/m(3) and (74.94 ± 40.09) microg/m(3), the traffic police PM2.5 exposure levels were significantly higher than the residents. In the incidence of respiratory symptoms, compared with high-exposure group and common exposure group, coughing, expectoration, throat unwell, asthma, short of breath and nose discomfort, traffic police group was higher than residents group (P < 0.05). The abnormal rate of lung ventilation function indexes, such as FVC and FEV1.0 was 25.23% and 12.15% respectively in high-exposure group, 11.88% and 2.97% in common exposure group, there was no statistical difference between two groups. Besides, the abnormal rate of FVC and FEV1.0, showed rising trend in high-exposure group with seniority. CONCLUSION: long-term higher levels of airborne fine particulate matter exposure, may impact respiratory health and impair pulmonary function.

Sulfur-Doped CoSe2 Porous Nanosheets as Efficient Electrocatalysts for the Hydrogen Evolution Reaction.

The electrochemical hydrogen evolution reaction (HER), as a promising route for hydrogen production, demands efficient and robust noble-metal-free catalysts. Doping foreign atoms into an efficient catalyst such as CoSe2 could further enhance its activity toward the HER. Herein, we developed a solvothermal ion exchange approach to doping S into CoSe2 nanosheets (NSs). We provide a combined experimental and theoretical investigation to establish the obtained S-doped CoSe2 (S-CoSe2) nanoporous NSs as highly efficient and Earth-abundant catalysts for the HER. The optimal S-CoSe2 catalyst delivers a catalytic current density of 10 mA·cm-2 for the HER at an overpotential of only 88 mV, demonstrating that S-CoSe2 is one of the most efficient CoSe- and CoS-based catalysts for the HER. We performed density functional theory (DFT) calculations to determine the stable structural configurations of S-CoSe2, and on the basis of which, we calculated the hydrogen adsorption Gibbs free energy (ΔGH) on CoSe2, CoS2, and the S-CoSe2 and the barrier energies of the rate-determining step of the HER on S-CoSe2. DFT calculations reveal that S-doping not only decreases the absolute value of ΔGH (move toward zero) but also significantly lowers the kinetic barrier energy of the rate-determining step of the HER on S-CoSe2, leading to a greatly improved HER performance.

Facile Au-assisted epitaxy of nearly strain-free GaN films on sapphire substrates.

The nearly strain-free GaN films were epitaxially grown successfully on the Au-coated c-plane sapphire substrate by a convenient chemical vapor deposition approach. The growth of GaN single crystalline epitaxial films is a self-patterned process. The morphology, structure, compositions and optical properties of as-synthesized GaN materials were characterized through field-emission scanning electron microscopy, atomic force microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, energy dispersive spectroscopy mapping, Raman spectroscopy and photoluminescence spectroscopy. The characterization results confirm that the epitaxial GaN films grown on Au-coated c-plane sapphire substrates have a single-crystalline and nearly strain-free structure, and exhibit strong UV emission. A possible growth mechanism of the GaN film is proposed: Au-assisted vapor deposition initiates the nucleation of the GaN seeds, and then these seeds grow into inclined inverted hexagonal GaN pyramids with a threefold azimuthal symmetry and vertical inverted hexagonal pyramids; and subsequently, the vertical inverted hexagonal pyramids expand laterally and annihilate the inclined inverted hexagonal pyramids; eventually these vertical pyramids coalesced to form nearly strain-free GaN films. This synthesis strategy provides a new idea for the simple self-patterned growth of nearly strain-free GaN epitaxial films on Au-coated sapphire substrates, and will promote broader applications in GaN-based electronic and optoelectronic devices.

Macular pigment and serum zeaxanthin levels with Goji berry supplement in early age-related macular degeneration.

AIM: To evaluate the efficacy of Goji berry supplementation on improving macular pigment, serum zeaxanthin levels and visual acuity in patients with early age-related macular degeneration (AMD). METHODS: A total of 114 patients (aged from 51 to 92y, mean age 69.53±8.41y) with early AMD were enrolled in our prospective, randomized controlled study. The included patients were assigned randomly to the Goji group (n=57) with 25 g of Goji berries supplementation per day for 90d and the control group (n=57) with their normal diet for 90d. Macular pigment optical density (MPOD) was measured using heterochromatic flicker photometry (HFP). The levels of serum lutein (L)/zeaxanthin (Z) were analyzed using high-performance liquid chromatography (HPLC). MPOD, serum L/Z levels and best corrected visual acuity (BCVA) were recorded at baseline and 90d. RESULTS: In the Goji group, there were no statistically significant differences in the serum L levels between the baseline (0.199±0.149 µmol/mL) and 90d (0.203±0.181 µmol/mL) (t=-0.186, P=0.850); however the serum Z levels were increased at 90d (0.101±0.087 µmol/mL) compared with those at the baseline (0.029±0.032 µmol/mL) (t=6.412, P<0.001). Patients treated with Goji berry for 90d showed an elevated MPOD (0.877±0.202 DU) from the baseline (0.731±0.205 DU) (t=-4.741, P=0.000). In contrast to the control group, the serum Z levels and MPOD were higher in the Goji group at 90d (both P<0.05). At 90d, patients with Goji berry supplementation had a relative decrease in BCVA (0.21±0.18 logMAR) compared with the baseline (0.27±0.20) (t=2.397, P=0.020). CONCLUSION: Overall, daily supplementation with Goji berry for 90d improves MPOD by increasing serum Z levels rather than serum L levels in early AMD patients. Goji berry may be an effective therapeutic intervention for preventing the progression of early AMD.

Dishevelled 1, a pivotal positive regulator of the Wnt signalling pathway, mediates 5-fluorouracil resistance in HepG2 cells.

Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are poorly understood. The aim of this study was to identify candidate genes and associated signalling pathways that may play a role in developing drug resistance following repeated 5-FU treatments. In this work, we established 5-FU-resistant cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental HepG2 cells. Using transcriptome sequencing, we found that the expressions of the Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt signalling. Dishevelled-1 (DVL1) is an essential Wnt signalling pathway component that stabilizes ß-catenin and mediates the Wnt pathway. Silencing DVL1 using siDVL1 or other small molecular inhibitors in HepG2/5-FU cells could restore 5-FU responsiveness via reduced cell proliferation and migration, and increased apoptosis. Moreover, DVL1 was found to be upregulated in BEL-7402/5-FU cells when compared to the parental BEL-7402 cells. Collectively, our results provide the first clue towards understanding the contribution of DVL1-mediated acquired resistance to 5-FU in HepG2/5-FU cells, suggesting a promising therapeutic strategy for liver cancer resistant to 5-FU.

Effects of professional rehabilitation training on the recovery of neurological function in young stroke patients.

Young stroke patients have a strong desire to return to the society, but few studies have been conducted on their rehabilitation training items, intensity, and prognosis. We analyzed clinical data of young and middle-aged/older stroke patients hospitalized in the Department of Neurological Rehabilitation, China Rehabilitation Research Center, Capital Medical University, China from February 2014 to May 2015. Results demonstrated that hemorrhagic stroke (59.6%) was the primary stroke type found in the young group, while ischemic stroke (60.0%) was the main type detected in the middle-aged/older group. Compared with older stroke patients, education level and incidence of hyperhomocysteinemia were higher in younger stroke patients, whereas, incidences of hypertension, diabetes, and heart disease were lower. The average length of hospital stay was longer in the young group than in the middle-aged/older group. The main risk factors observed in the young stroke patients were hypertension, drinking, smoking, hyperlipidemia, hyperhomocysteinemia, diabetes, previous history of stroke, and heart disease. The most accepted rehabilitation program consisted of physiotherapy, occupational therapy, speech therapy, acupuncture and moxibustion. Average rehabilitation training time was 2.5 hours/day. Barthel Index and modified Rankin Scale scores were increased at discharge. Six months after discharge, the degree of occupational and economic satisfaction declined, and there were no changes in family life satisfaction. The degrees of other life satisfaction (such as friendship) improved. The degree of disability and functional status improved significantly in young stroke patients after professional rehabilitation, but the number of patients who returned to society within 6 months after stroke was still small.

Association between individual PM2.5 exposure and DNA damage in traffic policemen.

OBJECTIVE: The aim of this study was to explore the association between individual PM2.5 and DNA damage in traffic policemen. METHODS: The participants included 110 traffic policemen and 101 common populations. The continuous 24-hour individual PM2.5 measurement was performed in participants. BPDE (benzo[a]pyrene 7,8-diol-9,10-epoxide)-DNA adducts and 1-OHP were detected. RESULTS: The average concentration of 24-hour personal PM2.5 for traffic policemen was significantly higher than that in the control group. PM2.5 exposure is associated with a 1.1% increase in 1-OHP and 0.8% increase in BPDE-DNA adducts after adjusted for body mass index, educational time period, and alcohol intake. Exposure group has 2.04 times higher of 1-OHP and 1.25 times higher of BPDE-DNA adducts when compared to the control group. CONCLUSIONS: These results demonstrated that traffic policemen have been a high-risk group suffering DNA damage because of the high PM2.5 exposure.