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To investigate the influence mechanism of weathering in the biogas production from coal, the characteristics of three coal samples with different weathering degrees obtained from the Wuhai mining area in Inner Mongolia and from the Xishan and Jincheng mining areas in Shanxi province were analyzed using the following methods: humic acid (HA) extraction, three-dimensional fluorescence spectroscopy, X-ray photoelectron spectroscopy and X-ray diffractometry. The results showed that the HA content in weathered coal increased with an increase in weathering degree. The content of dissolved organic matter in moderately and intensively weathered coals was clearly higher than that in slightly weathered coals. Meanwhile, the C–C and C–H in the aromatic ring was broken under the action of weathering, thus decreasing the aromaticity. Additionally, the weathering process also intensified the disordering of the directional arrangement of the macromolecular structure, causing the crystallinity of the coal to decrease. These conditions facilitated the degradation and utilization of coal by microorganisms and can be helpful to produce more biogas from coal.

Here, we investigate the role of SmERF73, a group VII ETHYLENE RESPONSE FACTOR stress response transcription factor, in the regulation of post-modification of the skeleton precursors of diterpene tanshinones in Salvia miltiorrhiza. Most genes found to be involved in tanshinone biosynthesis are located on chromosome 6, and five of these genes comprise a large gene cluster in S. miltiorrhiza. We found that SmERF73 overexpression in S. miltiorrhiza coordinately up-regulated the transcription of seven tanshinone biosynthetic genes, four of which were located in the tanshinone gene cluster, consequently increasing tanshinone accumulation, while SmERF73 silencing reduced corresponding gene transcription and tanshinone accumulation. SmERF73 recognizes GCC-box promoter elements of four tanshinone-associated genes (DXR1, CPS1, KSL1 and CYP76AH3) and activates their expression. Moreover, SmERF73 and its targets were up-regulated by stress elicitors; SmERF73 appears to be at least partly mediated by the jasmonic acid (JA) signaling pathway via interaction with SmJAZ3. SmERF73 coordinately regulates tanshinone biosynthetic gene expression, suggesting a potential link between tanshinone production and plant stress responses.

Long non-coding RNAs (lncRNAs) have been implicated in the development of cardiovascular diseases. We observed that lncRNA AK020546 was downregulated following ischemia/reperfusion injury to the myocardium and following H2O2 treatment in H9c2 cardiomyocytes. In vivo and in vitro studies showed that AK020546 overexpression attenuated the size of the ischemic area, reduced apoptosis among H9c2 cardiomyocytes, and suppressed the release of reactive oxygen species, lactic acid dehydrogenase, and malondialdehyde. AK020546 served as a competing endogenous RNA for miR-350-3p and activated the miR-350-3p target gene ErbB3. MiR-350-3p overexpression reversed the effects of AK020546 on oxidative stress injury and apoptosis in H9c2 cardiomyocytes. Moreover, ErbB3 knockdown alleviated the effects of AK020546 on the expression of ErbB3, Bcl-2, phosphorylated AKT, cleaved Caspase 3, and phosphorylated Bad. These findings suggest lncRNA AK020546 protects against ischemia/reperfusion and oxidative stress injury by sequestering miR-350-3p and activating ErbB3, which highlights its potential as a therapeutic target for ischemic heart diseases.

Titanium dioxide (TiO2) nanotubes (TNT) were successfully synthesized using different N-containing ligands via hydrothermal method. Methylamine, ethylenediamine and diethylenetriamine with different Ti/ligand molar ratios (1:1, 1:3, 1:5 and 1:8) were prepared. As-synthesized TiO2 without N-containing ligands were also prepared for comparison purpose. The X-Ray Diffraction patterns confirmed the presence of anatase phase of TiO2 in all the synthesized samples whereas the presence of sodium titanate was only detected in the samples containing N-containing ligands. The Transmission Electron Microscopy images also showed that the N-containing ligands promoted the formation of nanotubes in the anatase TiO2. Based on the Tauc Plot, the band gap energy of anatase TiO2 was shifted with the addition of methylamine, ethylenediamine and diethylenetriamine. The photoluminescence spectra also showed that with the addition of sufficient amount of N-containing ligands, the intensity of photoluminescence spectrum decreased, suggesting formation of more nanotube and reduction of electron hole recombination rate. The photocatalytic performance of all synthesized samples was determined through photodegradation of Congo red under UV light for 6 hours. The results suggested that among the synthesized materials, the sample which contained diethylenetriamine with molar ratio of 5 gave the highest photocatalytic activity of 76.71% which could be attributed to successful formation of nanotube, its higher surface rate reaction and low electron hole recombination. Diethylenetriamine showed higher efficiency in assisting the formation of TiO2 nanotubes compared to methylamine and ethylenediamine.

Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae., Salvia miltiorrhiza is a medicinal plant that can produce the bioactive tanshinones. Here, the authors report the improved genome assembly and reveal the possible roles of three CYP71Ds in catalyzing the reactions leading to the formation of the characteristic furan D-ring of transhinones.

Macrophages are important inflammatory cells that play a vital role in inflamm-aging. Bupleurum chinense polysaccharide (BCP), an effective component of the Bupleurum chinense herb, exerts multiple beneficial pharmacological effects, such as improving immunity and antioxidant activity. However, the effects of BCP on macrophage-aging and inflamm-aging are yet to be established. In this study, we examined the effects of BCP on proliferation, inflammatory cytokines, β-galactosidase (SA-β-gal), senescence-associated heterochromatin foci (SAHF), reactive oxygen species (ROS), mitochondrial membrane potential, p53, p16, and p65/NF-κB signaling proteins in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. BCP significantly inhibited production of interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), reduced the expression of SA-β-gal and formation of SAHF, as well as ROS level, and stabilized the mitochondrial membrane potential in RAW264.7 cells stimulated with LPS. Furthermore, BCP inhibited the expression of aging-related genes, p53 and p16, suppressed phosphorylation of p65 protein, and enhanced the expression of I-κBα protein through the NF-κB signaling pathway in LPS-stimulated RAW264.7 cells. Accordingly, we conclude that BCP effectively suppresses inflamm-aging by reducing inflammatory cytokine levels and oxidative stress production following activation of the NF-κB signaling pathway in RAW264.7 cells stimulated with LPS. Our collective findings support the utility of BCP as a novel pharmaceutical agent with potential anti-inflamm-aging effects.

Breast cancer (BC), a common malignancy, is intractable at present. Cuprous oxide nanoparticles (Conps) are new nanoparticles crucial in inhibiting tumor progression according to early studies, but their role in BC remains unclear. Field emission-scanning electron microscopy (FESEM) and field emission–transmission electron microscopy (FETEM) were used for the morphological observation of Conps, and energy-dispersive X-ray spectroscopy was used for their elemental composition analysis. Multipoint nitrogen adsorption was used to determine the Brunauer–Emmet–Teller of Conps, and their mean hydrodynamic size and zeta potential in water and intact cell medium were determined by dynamic light scattering (DLS). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Cell Counting Kit-8, Transwell assay, and flow cytometry were used to determine the effects of Conps on the biological function of BC cells. Western blotting was used to determine the changes in apoptosis-related proteins. Using FESEM and FETEM based on DLS and zeta potential determination, Conps was successfully constructed. Conps significantly lowered the viability of BC cells in a dose-dependent manner, significantly inhibited cell proliferation, invasion, and migration activities, and induced cell apoptosis. Western blotting demonstrated that Conps up-regulated Bax and caspase-3 proteins and down-regulated Bcl-2 protein. The results suggest that Conps can suppress the proliferation, invasion, and migration of BC cells and accelerate their apoptosis. This is a new potential strategy for the clinical treatment of BC.

To help minimize the negative impact of chemical fertilizers on the environment, recycle nitrogen and phosphorus nutrients of anaerobic digestate and reduce loss of nutrients via leaching, an eco-friendly slow-release fertilizer was prepared through recovery of nitrogen and phosphorus nutrition from digestate using superabsorbent fibers extracted from soybean curd residue as an adsorbent. The preparation method was proposed, and the fiber composite-based adsorbent was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscope (SEM) techniques. The successful incorporation of N and P into the fiber composite-based adsorbent via adsorption was confirmed by results of these analyses. The prepared fertilizer showed a relatively high N content (3.65 wt%) and a limited P content (0.14 wt%). Also, the swelling capacity as well as water retention capability of the obtained fiber composite-based adsorbent were evaluated. The release behavior of N and P from impregnated fiber composites was examined and was found to be partially in good accordance with the standard of the Committee of European Normalization, showing good slow-release and water-retention properties. Furthermore, in order to assess the fertilizer quality of the prepared materials, the effects of different fertilizers (commercially available fertilizer and prepared slow-release fertilizer) on tomato plant growth and soil microbial communities were investigated. The obtained results demonstrated the potential of fiber composite-based slow-release fertilizer system for recycling N and P nutrition from digestate, improving the effectiveness of fertilizer as well as protecting the environment.

Hypocrellins, as natural pigments from Shiraia bambusicola, have extensive applications in the agricultural, cosmetic, food, and feed industries, and play a vital role in photodynamic therapy for anticancer and antiviral treatments. However, environmental stresses are always the bottlenecks for increasing hypocrellin yield during the process of fermentation. Pre-mRNA alternative splicing (AS) is an essential mechanism in the defense of abiotic stresses in the animal and plant kingdom, but is seldom involved in fungi. In this study, AS from genome-wide sequencing and RNA-seq data for S. bambusicola was analyzed for the first time. Interestingly, the proportion of AS in S. bambusicola was 38.44% (most of them participated in metabolic processes, covering pigmentation and response to stimulus), a much higher ratio than seen in that of other fungal species (1.3-18%). Here, we identified the relationship of AS and secondary metabolic (SM) biosynthesis under a series of abiotic stresses. Suitable fungicides suppressed hypocrellin production significantly, and AS occurred in key functional genes (sbFLO, sbMFS, sbPKS) of hypocrellin biosynthesis. In contrast, H2O2 improved the yield of hypocrellins, but AS were not found in the corresponding gene cluster. A further study showed that overexpressing an isoform of sbPKS (sbPKSa) in Shiraia bambusicola could dramatically down-regulate the expression of the original gene sbPKS and nearly inhibit the production of hypocrellins. Altogether, our study strongly supported the hypothesis that AS had a vital role in the regulation of hypocrellin biosynthesis under stresses, and initially explored whether SM functional genes were relevant for fungi.

Sepsis is a serious clinical condition resulting from severe infection. High rates of mortality and tissue damage have been reported in intensive care unit (ICU) patients with sepsis. Bovine lactoferrin (BLF) is a well-known 80-kDa glycoprotein in the transferrin family that inhibits sepsis in low-birth-weight neonates. The present study investigated the protective effects of BLF in a rat model of sepsis-induced acute lung injury (ALI). The wet/dry ratio, lipid peroxidation, antioxidant markers, total protein, total cell count, inflammatory markers and myeloperoxidase (MPO) levels were assessed. Histopathological analysis was also carried out. BLF treatment reduced the wet/dry ratio of lung tissue by 30.7% and 61.3%, and lipid peroxidation by 22.3% and 67%, at concentrations of 100 and 200 mg/kg, respectively. Superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (Gpx) and catalase were increased by more than 50% under treatment with 200 mg/kg BLF. Inflammatory markers, neutrophils, lymphocytes and total cell count were reduced by more than 50% under treatment with 200 mg/kg BLF. BLF treatment significantly reduced MPO activity, by 28.2% and 74.3%, at concentrations of 100 and 200 mg/kg, respectively. Neutrophilic infiltration and edema were observed in control rats. However, BLF treatment restored intestinal microvilli to the normal range and reduced inflammatory cell invasion. Collectively, these results suggest that BLF is an effective therapeutic agent against sepsis-induced ALI.

Rapid depletion of fossil fuel and CO2 mitigation are two major challenges in the modern society. CO2 gasification of carbon-neutral biomass could be an attractive technology to cope up these two emerging problems. Replacing conventional gasifying agent air with CO2 could reduce the fraction of undesired N2 in the gas products because CO2 behaves as inert gasifying agent under low temperature and could be converted to CO at high temperature range. However, most researches on CO2 gasification are limited at the lab-scale level due to the endothermic feature of Boudouard reaction. In this work, a feasibility study of small-scale autothermal gasification using 15% CO2 and 85% air was conducted and compared with traditional air gasification. Prior to that, a lab-scale study of gasification behaviors, under N2, air and CO2 agents, were performed. It was found that using CO2 as gasification oxidant could produce comparable energy (6.67 kJ/g feedstock) to air gasification (7.45 kJ/g feedstock) at equivalent condition (800 °C, 40 min). The pH of biochar obtained under CO2 condition at 800 °C was measured to be 10.63 while the pH of biochar derived by air gasification at the same temperature could reach 12.32. In addition, a small-scale gasification experiment with 15% CO2 addition was successfully conducted in a downdraft autothermal reactor. The results showed CO production was greatly enhanced while CH4 generation was suppressed owing to Boudouard reaction and CO2 dry reforming. Cold gas efficiency and carbon conversion efficiency were both enhanced by 5.8% and 6%, respectively, with CO2 addition. Meanwhile, particulate matters (PM) emitted from both air gasification and 15% CO2 gasification experiments were measured. It was found that under the same equivalence ratio (ER), 75.4% less particle number concentration was emitted during 15% CO2 gasification compared to air gasification.

The main active ingredients of the fruiting bodies of Shiraia bambusicola and Rubroshiraia bambusae are Hypocrellins, belonging perylenequinones with potential photodynamic activity against cancer and microbial diseases. However, the strains of S. bambusicola and R. bambusae do not produce hypocrellins in culture, so resource exploitation of natural products was seriously restricted. In this study, a series of novel Shiraia-like fungal endophyte strains, with varying sporulation ability and synthesizing diverse secondary metabolites, was isolated from different bamboos. Based on phylogenetic analyses and morphological characteristics of the endophytes, Pseudoshiraia conidialis gen. et sp. nov. is proposed. The secondary metabolites of different fruiting bodies and strains have been comprehensively analyzed for the first time, finding that the endophytic strains are shown not only to produce hypocrellins, but also other perylenequinonoid compounds. It was noteworthy that the highest yield of total perylenequinone production and hypocrellin A appeared in P. conidialis CNUCC 1353PR (1410.13 mg/L), which was significantly higher than any other wild type P. conidialis strains in published reports. In view of these results, the identification of Shiraia-like endophytes not only confirm the phylogenetic status of similar strains, but will further assist in developing the production of valuable natural products.

Ethnopharmacological relevance Aconitum carmichaelii Debeaux, a famous traditional medicinal herb for collapse, rheumatic fever, and painful joints, always raises global concerns about its fatal toxicity from toxic alkaloids when improperly processed. Therefore, it is urgent to clarify the internal molecular mechanism of processing detoxification on Aconitum and develop simple and reliable approaches for clinical application, which is also of great significance to the rational medicinal use of Aconitum. Aim of the study The study aimed at developing a complete molecular mechanism exploration strategy in complex medicinal herb decocting system, clarifying the internal molecular mechanism of processing detoxification on Aconitum, and exploring valid approaches for detoxification. Materials and methods Aconiti Lateralis Radix Praeparata (Fuzi) was selected as the model for exploring the complex Aconitum detoxification mechanism using an advanced online real-time platform based on extractive electrospray ionization mass spectrometry. The methods realized the sensitive capture of dynamic trace intermediates, accurate qualitative and quantitative analysis, and real-time and long-term monitoring of multi-components with satisfactory accuracy and resistance to complex matrices. Results Components in the complex Aconitum decocting system were real-timely characterized and fat meat was discovered and verified to directionally detoxify Aconitum while reserving the therapy effect. More importantly, the dynamic detoxification mechanism in the chemically complex Aconitum decoction was molecularly profiled. A novel reaction pathway based on nucleophilic substitution reaction mechanism was proposed. As confirmed by the theoretic calculations at DFT B3LYP/6-31G (d) levels, fatty acids (e.g., palmitic acid) acted as a green, cheap, and high-performance catalyst and promote the decomposition of toxic diester alkaloids to non-toxic and active benzoyl-monoester alkaloids through the discovered mechanism. Conclusion The study exposed a novel detoxification molecular mechanism of Aconitum and provided an effective method for the safe use of Aconitum, which could effectively guide the development of traditional processing technology and compatibility regulation of the toxic herb and had great value to the modernization and standardization development of traditional medicine.

Ethnopharmacological relevance Banxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant. Aim of the study This study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research. Methods Fifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1β, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the “herbs-components-targets-disease” network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out. Results The results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.

PurposeChanges in the retina and the choroid blood vessels are regularly observed in myopia. The aim of this study is to test if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia.MethodWe adapted the common form-deprivation myopia mouse model and used the retina slice and whole-mount immunofluorescence technique to evaluate changes in the morphology, and distribution of retinal glial cells. We then searched the Gene Expression Omnibus database for series on myopia and retinal glial cells (astrocytes and Müller cells). Using review articles and the National Center for Biotechnology Information gene database, we obtained clusters of myopia-related gene lists. By searching SwissTargetPrediction, we collected information on atropine target proteins. We then used online tools to find the Gene Ontology analysis enriched clusters, pathways, and proteins that provide correlative evidence.ResultGlial fibrillary acidic protein fluorescence was observed in mice eyes that were covered and deprived of light for five days compared to uncovered eyes, and the cell morphology became more star-like. From in silico experiments, we identified several pathways and proteins that were common to both myopia and retinal glial cells in hypoxic conditions. The common pathways in human astrocytes represented response to mechanical stimuli, peptide secretion, skeletal system development, and monosaccharide binding. In mouse Müller cells, the pathways represented membrane raft and extracellular structure organisation. The proteins common to myopia and hypoxic glial cells were highly relevant to atropine target proteins.ConclusionRetinal astrocytes and Müller cells under hypoxic conditions contribute to the development of myopia, and may be a valid target for atropine.

The proprietary Chinese medicine (PCM) has become a significant supplement of modern medicine. Nevertheless, the absence of quality control standard of compatible materials in PCM has led to serious adulteration, which has an extremely bad effect on safety of drug use and clinical efficacy. Here, a quality tracing evaluation strategy of compatible materials in 32 Aconitum proprietary Chinese medicines (APCMs) was established, including data normalization, model development, model verification, and unknown prescription cracking. The model was delimited based on the weighted content of total 9 key alkaloids in 24 APCMs, which were 5.65-57.10 μg/g for extract medicines and 42.62-380.61 μg/g for powder medicines. Three newly published commercial APCMs, including Wangbi Tablet, Wangbi Granule, and Fengshigutong Capsule, were used to verify its reliability and the results proved to be positive. Moreover, a novel prescription cracking approach was proposed to decode the content of each material in five unknown prescriptions including Yaoxitong Capsule, Tongrendahuoluo Pill, Xinbao Pill, Dahuoluo Capsule, and Mugua Pill. Ultimately, the single or two compatible Aconitum materials in APCMs was successfully decoded and the processed level of the materials were effectively judged. This study for the first time established a practical strategy for supervision and cracking of compatible materials in PCMs and is of great significance to improve the quality control of PCMs.

Key Points Question Does an association exist between current low to moderate alcohol drinking and cognitive function trajectories or rates of cognitive decline from middle to older age among US adults? Findings In this cohort study of 19 887 participants from the Health and Retirement Study, with a mean follow-up of 9.1 years, when compared with never drinking, low to moderate drinking was associated with significantly better trajectories of higher cognition scores for mental status, word recall, and vocabulary and with lower rates of decline in each of these cognition domains. Meaning Current low to moderate alcohol consumption among middle-aged or older adults may be associated with better total cognitive function., Importance Studies examining the association of low to moderate drinking with various cognitive functions have yielded mixed findings. Objective To investigate whether associations exist between low to moderate alcohol drinking and cognitive function trajectories or rates of change in cognitive function from middle age to older age among US adults. Design, Setting, and Participants A prospective cohort study of participants drawn from the Health and Retirement Study (HRS), a nationally representative sample of US adults, with mean (SD) follow-up of 9.1 (3.1) years. In total, 19 887 participants who had their cognitive functions measured in the HRS starting in 1996 through 2008 and who had participated in at least 3 biennial surveys were included. The data analysis was conducted from June to November 2019. Exposures Alcohol consumption and aging. Main Outcomes and Measures Trajectories and annual rates of change for the cognitive domains of mental status, word recall, and vocabulary and for the total cognitive score, which was the sum of the mental status and word recall scores. Participants were clustered into 2 cognitive function trajectories for each cognition measure assessed based on their scores at baseline and through at least 3 biennial surveys: a consistently low trajectory (representing low cognitive scores throughout the study period) and a consistently high trajectory (representing high cognitive scores throughout the study period). Results The mean (SD) age of 19 887 participants was 61.8 (10.2) years, and the majority of the HRS participants were women (11 943 [60.1%]) and of white race/ethnicity (16 950 [85.2%]). Low to moderate drinking (, This cohort study assesses the associations between low to moderate alcohol drinking and cognitive function trajectories or rates of cognitive decline from middle to older age in a nationally representative sample of US adults.

Cytochrome P450s (CYPs) are important enzymes in the secondary metabolism of plants and have been recognized as key players in bioengineering and synthetic biology. Previously reported CYP76AH1 and CYP76AH3, having greater than 80% sequence homology, played a continuous catalytic role in the biosynthesis of tanshinones in Salvia miltiorrhiza. Homology modeling indicates that four sites might be responsible for differences in catalytic activity between the two enzymes. A series of modeling-based mutational variants of CYP76AH1 were designed to integrate the functions of the two CYPs. The mutant CYP76AH1D301E,V479F, which integrated the functions of CYP76AH1 and CYP76AH3, was found to efficiently catalyze C11 and C12 hydroxylation and C7 oxidation of miltiradiene substrates. Integration and utilization of CYP76AH1D301E,V479F by synthetic biology methods allowed the robust production of 11-hydroxy ferruginol, sugiol, and 11-hydroxy sugiol in yeast. The functionally integrated CYP gene after active site modifications improves catalytic efficiency by reducing the transfer of intermediate metabolites between component proteins. This provides a synthetic biology reference for improving the catalytic efficiencies of systems that produce plant natural products in microorganisms.

Online measurements of key information such as the decomposition stages of biomass gasification/pyrolysis in a fixed-bed reactor is currently limited with existing technologies. In this study a proof of concept for using Electrical Capacitance Tomography (ECT) for monitoring the decomposition stages of woody biomass is done. In practice, ECT measures the permittivity of the material under test. Therefore, the relation between the permittivity of the biomass in terms of the extent of thermal treatment is essential. Pyrolysis and gasification experiments were conducted to different extent of time and temperatures at a lab scale gasifier using wood chips. The permittivity of the samples was measured in-vitro using impedance analyzer at different excitation frequencies (20 kHz to 3 MHz). At a critical pyrolysis temperature of 700 °C the permittivity starts to increase significantly. In addition, for air-aided gasification the permittivity was found to reach its maximum in holding time of 10 or 30 min. Further examination of these samples in an ECT sensor revealed the same trend, implying that the permittivity results can be used for converting ECT reading to decomposition state. Chemical characterizations were done via elemental, thermogravimetry analysis, X-ray diffraction and Fourier transform infrared (FTIR) Spectroscopy. It was found that graphitization of the material is a prominent factor that control the increase of the permittivity. Analyzing quantitatively the aromatic and aliphatic carbon from the FTIR results disclose that it has a strong relation to the permittivity change when the aromatic carbon is higher than 95%. Therefore, in this range, it was possible to correlate these two parameters by an inverse relation which lead to a good match under frequencies higher than 200 kHz.

A granular composite sorbent (LC-CF) was synthesized from acid-leached carbon waste using chitosan and FeCl3, and its feasibility for nitrate and phosphate removal was investigated in this study. The sorption data was well described by the pseudo-second-order kinetic model, and the maximum sorption capacity of LC-CF predicted by Langmuir model for nitrate and phosphate were 41.90 mg g−1 and 62.72 mg g−1, respectively. In comparison, LC-CF had a greater affinity for phosphate and exhibited a better reusability for nitrate removal during the sorption-desorption cycles. Ion exchange, electrostatic interaction, and hydrogen bond are the potential sorption mechanisms. In light of the cost-benefit analysis, the proposed treatment of carbon waste was more economically feasible as compared with existing incineration scheme. These results illuminated that synthesis of granular sorbent with carbon waste could achieve the harmless disposal of hazardous industrial waste as well as the production of value-added sorbent for water treatments.

Background: Findings on the effect of alcohol drinking on cognitive function are mixed. The present study aimed to investigate the longitudinal associations of low-to-moderate alcohol drinking with cognition trajectories and changing rates among a nationally representative sample of middle-aged and older Americans. Method: A total of 19,887 participants in the Health and Retirement Study were included in the analyses. Performance of cognitive function was assessed every two years in 3 domains: mental status (MS), word recall (WR), and vocabulary (VOC). Trajectories of the total cognitive function (TCF) and individual domains were constructed using the SAS proc traj procedure. Age at cognition measurement was used as a time scale. Age related annual changing rates of cognition measures were estimated by regressing cognition scores over age for all individuals. Due to very few people, heavy drinkers were excluded. Multivariate logistic regression and linear regression were used to estimate the effect of low to moderate drinking on the cognition trajectories and annual changing rates after adjusting for baseline age, gender, race, years of education, marital status, smoking and body mass index. Result: Participants were clustered into a consistently low trajectory and a consistently high trajectory for each cognition measure. Low-to-moderate drinking was associated with a better trajectory and lower declining rate. Compared to never drinkers, current low-to-moderate drinkers were 0.67 (95% confidence interval [CI]: 0.59-0.75, P P P P P P =0.0001), 0.005 (95% CI: -0.003-0.01, P =0.23), 0.01 (95% CI: 0-0.02, P =0.04) units lower annual changing rates for those cognition measures. Racial differences were observed for trajectories of MS ( P =0.01), in which, low-to-moderate drinking was associated with the consistently low trajectory among whites (odds ratio=0.67, 95% CI: 0.58-0.76) but not among blacks (odds ratio =1.07, 95% CI: 0.79-1.45). There was no gender difference was observed. Conclusion: Current low-to-moderate alcohol drinkers associated with total cognitive function, word recall, mental status, and vocabulary in both men and women.

Proton pump inhibitors, including omeprazole, rabeprazole, lansoprazole, and pantoprazole, achieved simultaneous enantioselective determination in the human plasma by chiral liquid chromatography-tandem mass spectrometry. The four corresponding stable isotope-labeled proton pump inhibitors were adopted as the internal standards. Each enantiomer and the internal standards were extracted with acetonitrile containing 0.1% ammonia, then separated with a Chiralpak IC column (5 µm, 4.6 mm × 150 mm) within 10 min. The mobile phase was composed of acetonitrile-ammonium acetate (10 mM) containing 0.2% acetic acid (50:50, v/v). To quantify all enantiomers, an API 4000 tandem mass spectrometer was used, and multiple reaction monitoring transitions were performed on m/z 360.1→242.1, 384.1→200.1, 370.1→252.1, and 346.1→198.1, respectively. No significant matrix effect was observed for all analytes. The calibration curve for all enantiomers were linear from 1.25 to 2500 ng/mL. The precisions for intra- and inter-run were < 14.2%, and the accuracy fell in the interval of -5.3 to 8.1%. Stability of samples was confirmed under the storage and processing conditions. The developed method was also suitable for separation and determination of ilaprazole enantiomers. The validated method combining the equilibrium dialysis method was applied to the protein binding ratio studies of four pairs proton pump inhibitor enantiomers in human plasma.

To investigate the effects of biodegradation of guar gum and its products on the production of biogas from coal, experiments on biogas production from coal were carried out using guar gum at different concentrations. The effects of the changes in biogas production, the biodegradation characteristics of guar gum, and the structure of microbial community on coal-to-biogas conversion were investigated. When both coal and guar gum were used for fermentation, the biomethane production was >79.10% higher than the sum of biomethane produced using each of the substrates. The biodegradation of guar gum caused the dissolved organic matter in the reaction system to increase. After biodegradation, some of the functional groups such as OH, C H, and C C were dissociated from guar gum, resulting in the increase of the surface roughness. Moreover, the contents of hydrogen, carbon and oxygen decreased from 6.82%, 43.03%, and 42.46% to below 3%, 18%, and 28%, respectively. Desulfovibrio has a certain negative effect on the biodegradation, but the addition of guar gum could reduce its amount in the reaction system. In addition, guar gum was found to be beneficial to the growth and reproduction of hydrogenotrophic methanogens. The pathway for methane production was converted from acetic acid or methyl reduction to CO2 reduction. This work provides significant information on the gel breaking of guar gum fracturing fluid by microorganisms in in situ coal seam.

Disposal of nitrogen-containing sewage sludge (SS) via gasification leads to the formation of NOx precursors and NOx and ammonia emissions. Pretreatment of SS via hydrothermal carbonization (HTC) was shown to improve coalification, desulfurization, and deamination. In this study, we propose a combined hydrothermal pretreatment and CO2 gasification process for removal of nitrogen from SS and production of energy via the gasification of the pretreated SS. In the HTC process, around 50% of nitrogen contained in the sludge was removed. The derived hydrochar (HC) was subsequently fed for gasification using CO2 as a gasifying agent, which was characterized by the expected reduction in the formation of ammonia. We further improved the process by establishing cogasification of hydrochar with waste leaves. The improvement is believed to be due to the catalytic effect of Ca, present in plant leaves, on the gasification. Cold gas efficiency of the cogasification process of a 1/1 hydrochar/leaves blend by mass was en...

Picroside II (P‐II), one of the main active components of scrophularia extract, which have anti‐oxidative, anti‐inflammatory effects, but its effect on hyperhomocysteinemia (HHcy) induced endothelial injury remains to be determined. Here, we test whether P‐II protects HHcy‐induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX‐1 expression, subsequently causing reactive oxygen species generation, up‐regulation of NADPH oxidase activity and NF‐κB activation, thereby promoting pro‐inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX‐1 expression, whereas overexpression of SIRT1 decreased LOX‐1 expression markedly. P‐II treatment significantly increased SIRT1 expression and reduced LOX‐1 expression, and protected against endothelial cells from Hcy‐induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT1 or overexpression of LOX‐1 attenuated the therapeutic effects of P‐II. In conclusion, our results suggest that P‐II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX‐1 signaling pathway.

Ticks and tick-borne pathogens threaten the health of both domestic animals and humans, and are associated with a high economic burden in many countries. Tick control can be achieved with chemical acaricides, but issues remain regarding their safety as well as emerging tick resistance. Propylene glycol alginate (PGA) is a food additive commonly used in China. It has been used to kill whiteflies in agriculture as an environmentally friendly insecticide. The aims of this study were to (i) explore the efficacy of PGA to kill Haemaphysalis longicornis ticks and (ii) assess the potential to develop a new tick control acaricide containing PGA and a reduced amount of synthetic pyrethroid. Beta-cypermethrin was chosen as the reference pyrethroid in this study. PGA, beta-cypermethrin and mixes (PGA and beta-cypermethrin formulated in proportions of A = 2:1, B = 1:1, and C = 1:2) were compared for efficacy to kill larval and adult H. longicornis ticks. Overall, we found no statistically significant differences in the killing efficacy of PGA as compared to beta-cypermethrin across examined time-points post-tick exposure. At 24 h post-tick exposure, similar killing efficacy for H. longicornis larvae was recorded for beta-cypermethrin alone, PGA alone, and mixed formulations B and C. Mixed formulation C had the strongest killing effect when compared to PGA alone or mixed formulation B. Similar outcomes were observed in experiments with adult H. longicornis ticks. Based on these findings, we propose that PGA can be useful as a tick control acaricide, either as a single active ingredient or formulated together with a pyrethroid.

Phytoremediation is increasingly recognized as a cost-effective approach for remediation of heavy metal (HM) contaminated soils, whereas the derived HM-enriched hyperaccumulators must be properly harvested and disposed. In this study, gasification of Sedum alfredii was performed at a temperature series (300–900 °C) with different gasifying agents (N2, CO2 and air), then the transfer behaviors of zinc (Zn), cadmium (Cd), and lead (Pb) and the characteristics of the derived biochar and syngas were investigated. The high gasification temperatures and reducing atmosphere (N2) effectively enhanced the volatilization of Zn, Cd, and Pb, and the results from toxicity characteristic leaching process indicate that gasification greatly enhanced the stability and reduced the availability of HMs in S. alfredii. The CO2-derived biochars had moderate pH and greater stability, while the N2-derived biochars showed better energy density. The evolution of functional groups and crystalline phases in biochars were both influenced by the temperature, and the role of atmosphere was increasingly obvious at temperatures above 600 °C. As expected, biochars derived under N2 and CO2 both showed considerable sorption capacity for Pb (134.2–198.8 mg g−1) and Cd (38.1–186.8 mg g−1). CO2 atmosphere greatly enhanced the production of CO at higher temperatures (>700 °C), while N2 atmosphere favored the yield of H2 and CH4. These results imply that gasification could be a promising technique to achieve the separation of HMs from hyperaccumulator as well as the production of energy and multifunctional material, and this process is greatly affected by the gasification temperature and atmosphere.

In order to increase the utilization of coal slime, achieve efficient utilization of resources and protect the environment, the changes in speciation transformation and bioavailability of heavy metals during the biomethane conversion process from coal slime were explored. The transformation of heavy metal speciation and bioavailability in different coal slimes during biomethane conversion were analyzed using biogas production simulations; fluorescence spectroscopy; determination and speciation of heavy metals; and inductively coupled plasma mass spectrometry. The results show that the organic matter in various coal slimes could be converted to biomethane. After biodegradation, the dissolved organic matter content dropped significantly. In addition, the concentrations of heavy metals in different coal slimes were significantly different. Among them, Zn, Ni, Cd and As were mainly found in the reducible fraction (F2); Cu was mainly found in the oxidizable fraction (F3); and Pb occurred predominantly in the residual fraction (F4). The biogas production process in coal slime had a great influence on the speciation of heavy metals. This research deepens the understanding of heavy metal migration in coal slime during biogas production, and provides a reference for clean utilization of coal slime and environmental protection.

The solar/autothermal hybrid gasifier (SAHG) is an attractive approach to provide continuous production of the syngas via coupling autothermal and solar gasification together, where the SAHG mainly includes fully solar, hybrid, and fully autothermal modes. An ICE CCHP system driven by the SAHG with an indirectly irradiative two-cavity reactor introduced conceptually and investigated thermodynamically. Considering the effects of solar flux inputs and various reactant ratios, a zero-dimensional steady-state model of the SAHG was established by using Gibbs free energy minimization, and was validated with the reported data. The optimal steam-to-feedstock and oxygen-to-feedstock ratios has been achieved based on the restrictions of temperature over 1000 K and minimization of steam input. The results of two consecutive days indicate mole flow rates of H 2 and CO were increased by over 38.8% and 11.8%, respectively, leading to an increment in LHV s by 51.7%. An increment in primary energy ratio by 11.5% can be achieved by using the SAHG-CCHP system. The yearly assessment of the SAHG-CCHP system shows that the yearly average increments in heat, power, and cooling for the SAHG system were reached by 19.5%, 23.8%, and 4.5%, respectively. A yearly average increment of 14.2% in primary energy ratio can be obtained under the solar radiation condition of Singapore.

The anaerobic degradation of coal combined with straw biomass can promote the methane production. The biogas production potential and metabolic pathway were explored via the co-digestion simulation experiment of coal and corn straw. The results showed that 2 g of corn straw combined respectively with 4 g of bituminous coal A, 6 g of bituminous coal B and 4 g of bituminous coal C resulted in highest methane yields. The structure of lignocellulose in corn straw was partially degraded into guaiacyl and syringyl units. Meanwhile, the content of biodegradable tyrosine like protein and soluble microbial by-products in liquid phase significantly decreased. Significantly, the structure of archaea altered from aceticlastic to hydrogenotrophic methanogens when the fermentation substrate changed from high to low rank coal. The proportion of hydrogenotrophic methanogens was significantly higher than that of aceticlastic and methylotrophic methanogens, and the hydrogenotrophic pathway was dominant than the aceticlastic pathway.

Ethnopharmacological relevance The genus Viscum comprises approximately 100 species that are mainly distributed across Africa, Asia and Europe. The extracts and preparations of Viscum species are widely used as common complementary and alternative medicines in the treatment of rheumatism and cancer. Aim of the review This review aims to explore the medicinal properties of twelve species belonging to the genus Viscum for potential therapeutic applications. Materials and methods We collected online information (including PubMed, CNKI, Google Scholar, and Web of Science) from January 1915 to April 2021 and knowledge from classical books on Chinese herbal medicines available for 12 species of the genus Viscum, including Viscum coloratum (Kom.) Nakai, Viscum album L., Viscum articulatum Burm. f., Viscum liquidambaricola Hayata, Viscum ovalifolium DC., Viscum capitellatum Sm., Viscum cruciatum Sieber ex Boiss., Viscum nudum Danser, Viscum angulatum B.Heyne ex DC., Viscum tuberculatum A.Rich., Viscum multinerve Hayata, and Viscum diospyrosicola Hayata. Results At least 250 different compounds have been reported across twelve Viscum species, including amino acid and peptides, alkaloids, phenolic acids, flavonoids, terpenoids, carbohydrates, fatty acids, lipids, and other types of compounds. In particular, for Viscum coloratum (Kom.) Nakai and Viscum album L., the plants, preparations, and bioactive components have been thoroughly reviewed. This has allowed to elucidate the role of active components, including lectins, viscotoxins, flavonoids, terpenoids, phenolic acids, and polysaccharides, in multiple bioactivities, such as anti-cancer, anti-rheumatism arthralgia, anti-inflammation, anti-cardiovascular diseases, enhancing immunity, and anti-chemotherapy side effects. We also evaluated quality control methods based on active compounds, in vivo exposure compounds, and discriminated chemical markers. Conclusions This is the first report to systematically review the pharmaceutical development history, chemical composition, clinical evidence, pharmacological activity, discriminated chemical markers, in vivo exposure, and quality control on twelve distinct species of Viscum plants with medicinal properties. The significant safety and efficacy, along with the minor side effects are constantly confirmed in clinics. The genus Viscum is thus an important medicinal resource that is worth exploring and developing in future pharmacological and chemical studies.

A series of novel N-tert-butyl sulfinyl squaramide receptors have been designed and synthesized. Their interactions with a range of inorganic anions were studied in solution by 1H NMR spectroscopy. This new type of squaramide displayed better anion-binding abilities over conventional diphenyl squaramides. The single crystal analysis and DFT calulations implied the role of the tert-butyl C–H protons in binding Cl–. The energies of C–H···Cl– interactions were estimated to be 1.4–1.6 kcal/mol in solution.

Five new aromatic polyketides, alternaphenols A-E (1-5), and two known compounds (6-7) were isolated from a liquid culture of Alternaria sp. (strain no. NF2198), a caterpillar associated fungus. Their structures were determined by extensive spectroscopic analysis and single crystal X-ray crystallography. Compounds 1-7 were evaluated for their cytotoxic activities against a human skin melanoma A-375 cell line. Only compounds 4 and 5 showed weak cytotoxic activities.

Ent-kaurene diterpenoids are the largest group of known Isodon diterpenoids. Among them, oridonin is accumulated in the leaves, and is the most frequently studied compound because of its antitumor and antibacterial activities. We have identified five copalyl diphosphate synthase (CPS) and six kaurene synthase-like (KSL) genes by transcriptome profiling of Isodon rubescens leaves. An in vitro assay assigns ten of them to five different diterpene biosynthesis pathways, except IrCPS3 that has a mutation in the catalytic motif. The Lamiaceae-specific clade genes (IrCPS1 and IrCPS2) synthesize the intermediate copalyl diphosphate (normal-CPP), while IrCPS4 and IrCPS5 synthesize the intermediate ent-copalyl diphosphate (ent-CPP). IrKSL2, IrKSL4, and IrKSL5 react with ent-CPP to produce an ent-isopimaradiene-like compound, ent-atiserene and ent-kaurene, respectively. Correspondingly, the Lamiaceae-specific clade genes IrKSL1 or IrKSL3 combined with normal-CPP led to the formation of miltiradiene. The compound then underwent aromatization and oxidization with a cytochrome P450 forming two related compounds, abietatriene and ferruginol, which were detected in the root bark. IrKSL6 reacts with normal-CPP to produce isopimaradiene. IrKSL3 and IrKSL6 have the γβα tridomain structure, as these proteins tend to possess the bidomain structure of IrKSL1, highlighting the evolutionary history of KSL gene domain loss and further elucidating chemical diversity evolution from a macroevolutionary stance in Lamiaceae.

The aim of the present study was to investigate the protective effect of ozone oxidative preconditioning (OOP) on renal oxidative stress injury in a rat model of kidney transplantation. Thirty-six male Sprague Dawley (SD) rats were randomly divided into three groups: A sham (S) group, a kidney transplantation (KT) group and an OOP and kidney transplantation (OOP+KT) group. In the S group, the rats' abdomens were opened and closed without transplantation. In the KT group, the rats received a left kidney from donor SD rats. In the OOP+KT group, donor SD rats received 15 OOP treatments by transrectal insufflations (1 mg/kg), once a day, at an ozone concentration of 50 µg/ml, before the kidney transplantation. Twenty-four hours after transplantation, the parameters of renal function of the recipients were measured. The morphology and pathological effects of renal allograft were examined using hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry. Markers of oxidative stress were also detected using the thiobarbituric acid method, and expression levels of Nrf-2 and HO-1 were determined by western blot analysis. Blood urea nitrogen and creatinine levels were significantly decreased in the OOP+KT group compared with the KT group, and the morphology and pathological changes of renal allograft were also less severe. Meanwhile, the renal allograft cell apoptosis index was significantly higher in the KT group compared to the OOP+KT group (P

While light is the basic element for inducing vision and modulating circadian rhythms, excessive light has been reported to have a negative effect on the survival of various types of retinal cells. Among them photoreceptors and retinal pigment epithelial (RPE) cells degeneration after light exposure is widely observed, but light-induced retinal ganglion cell (RGC) damage achieves relatively little attention. The purpose of this article is to summarize the experimental evidence for the possible negative effects of excessive light on RGCs. By searching the database, twenty-six related articles have been included. Taken together, excessive light may insult RGCs through the three main ways: (i) directly action on RGC mitochondria, as well as DNA, resulting in an upregulation of reactive oxygen species (ROS) and subsequently caspase-dependent or -independent cell death; (ii) mediation in gliotransmitters or relevant receptors of retinal glial cells; and (iii) a secondary event to photoreceptors and RPE cells degeneration and subsequent retinal remodeling. So RGCs can certainly be injured by excessive light, especially when they are already energetically compromised in some diseases. And more attentions should be paid to this topic to take timely measures to protect these frail RGCs from being damaged by excessive light.

Background The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known, traditional Chinese medicine. Tanshinones are active compounds that accumulate in the periderm, resulting in red-colored roots. However, lines with orange roots have been observed in cultivated fields. Here, we performed metabolome and transcriptome analyses to investigate the changes of orange-rooted Danshen. Methods Metabolome analysis was performed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof–MS) to investigate the metabolites variation between orange Danshen and normal Danshen. RNA sequencing and KEGG enrichment analysis were performed to analyzing the differentially expressed genes between orange-rooted and normal Danshen. Results In total, 40 lipophilic components were detected in metabolome analysis, and seven compounds were significantly decreased in the orange Danshen, including the most abundant active compounds, tanshinone IIA and tanshinone I in normal Danshen. Systematic analysis of transcriptome profiles revealed that the down-regulated genes related to catalytic dehydrogenation was not detected. However, two genes related to stress resistance, and four genes related to endoplasmic reticulum (ER)-associated degradation of proteins were up-regulated in orange Danshen. Conclusions Decreases in the content of dehydrogenated furan ring tanshinones such as tanshinone IIA resulted in phenotypic changes and quality degradation of Danshen. Transcriptome analysis indicated that incorrect folding and ER-associated degradation of corresponding enzymes, which could catalyze C15-C16 dehydrogenase, might be contributed to the decrease in dehydrogenated furan ring tanshinones, rather than lower expression of the relative genes. This limited dehydrogenation of cryptotanshinone and dihydrotanshinone I into tanshinones IIA and I products, respectively, led to a reduced quality of Danshen in cultivated fields.

Currently, the most important challenge for solar energy photo-thermal utilization is the thermal stability of solar absorber coatings at high temperature. The new one-layer nano-composite TiN/TiC-based cermet coatings were designed and fabricated with laser-cladding method in the air. The result indicated the laser cladding could be used to obtain 30 wt.%, TiN-30 wt.%, TiC-20 wt.%, and Ni-20 wt.% Mo cermet coatings with the desired optical properties. In particular, an absorptance (α) of ~ 80.1% and a thermal emissivity (e) of ~ 2% at 300 K were calculated when the weight rate of nano-particles/micro-particles is 1:1. In addition, the thermal stability of the coating was outstanding after heat treatment at 650 °C for 6 h. The absorptance and emissivity of cermet coating were, respectively, 80.8% and 1.9% at 650 °C. The results indicated that nano-composite TiN/TiC-Ni/Mo cermets are suitable for spectrally selective materials. Moreover, the laser cladding was found to be an improved and novel preparation method in the field of solar-selective-absorbing coatings.

Background: The mechanisms of leptin resistance among overweight/obese individuals in not fully understood. Smokers have lower body mass index (BMI) compared to non-smokers, and quit smoking results in weight gain. Therefore, we aimed to evaluate whether smoking related genes contribute to leptin resistance. Methods: A total of 541 SNPs in seven genes of the nicotinic acetylcholine receptors family ( CHRNB2-B4, CHRNA3-A6 ) were evaluated for interactions with leptin on BMI among 748 European American participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Significant SNPs were evaluated for replication among 3,844 participants of the Framingham Heart Study (FHS) 3 rd generation cohort. Multivariate linear regressions were used in single SNP-based analyses controlling for age and sex. Gene-based analyses were performed using the GATES method. MESA and FHS results were combined through meta-analysis methods. Results: After Bonferroni correction, a total of 34 SNPs within genes CHRNA3 , CHRNA5 , CHRNA6 , CHRNB2, and CHRNB3 significantly ( P -4 , correcting for 61 linkage disequilibrium blocks) interacted with leptin on BMI, of which, 23 SNPs reached genome-wide significance ( P -8 ), and 34 SNPs were successfully replicated in the FHS. CHRNB2 rs2072661 (minor allele frequency=0.24) was most significant with a major G allele negatively interacting with leptin on BMI (MESA: β=-0.05, p=8.20х10 -4 ; FHS: β=-0.05, p=1.31х10 -11 ; Meta: β=-0.05, p=4.19х10 -16 ), indicating that individuals with the major alleles were less resistant to leptin. Meanwhile, gene-based analysis revealed that the seven genes were all significantly interacting with leptin on BMI with meta-analysis p values ranging from 2.62х10 -13 for CHRNB2 to 4.25х10 -5 for CHRNA4 . Conclusion: Nicotine acetylcholine receptor genes modify the sensitivity of leptin on BMI.

BACKGROUND Metabolomics study may help identify novel mechanisms underlying arterial stiffening. METHODS We performed untargeted metabolomics profiling among 1,239 participants of the Bogalusa Heart Study. After quality control, 1,202 metabolites were evaluated for associations with augmentation index (AI) and pulse wave velocity (PWV), using multivariate linear regression adjusting for age, sex, race, education, smoking, drinking, body weight, body height, physical activity, and estimated glomerular filtration rate. Heart rate, blood pressure and antihypertensive medication usage, lipids, and fasting glucose were sequentially adjusted in the sensitivity analyses for significant metabolites. Weighted correlation network analysis was applied to build metabolite networks. RESULTS Six novel metabolites were negatively associated with AI, of which, 3-methyl-2-oxobutyrate had the lowest P value and the largest effect size (β = –6.67, P = 5.99 × 10–6). Heart rate contributed to a large proportion (25%–58%) of the association for each metabolite. Twenty-one novel metabolites were identified for PWV, of which, fructose (β = 0.61, P = 6.18 × 10–10) was most significant, and histidine had the largest effect size (β = –1.09, P = 2.51 × 10–7). Blood pressure played a major contribution (9%–54%) to the association for each metabolite. Furthermore, 16 metabolites were associated with arterial stiffness independent of traditional risk factors. Network analysis identified 2 modules associated with both AI and PWV (P < 8.00 × 10–4). One was composed of metabolites from the glycerolipids synthesis and recycling pathway, and the other was involved in valine, leucine, and isoleucine metabolism. One module related to sphingomyelin metabolism was associated with PWV only (P = 0.002). CONCLUSIONS This study has identified novel and important metabolites and metabolic networks associated with arterial stiffness.

Amyloid β (Aβ) oligomer-induced aberrant neurotransmitter release is proposed to be a crucial early event leading to synapse dysfunction in Alzheimer’s disease (AD). In the present study, we report that the release probability (Pr) at the synapse between the Schaffer collateral (SC) and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aβ production. High nanomolar synthetic oligomeric Aβ42 also suppresses Pr at the SC-CA1 synapse in wild-type mice. This Aβ-induced suppression of Pr is mainly due to an mGluR5-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) in axons. Selectively inhibiting Aβ-induced PIP2 hydrolysis in the CA3 region of the hippocampus strongly prevents oligomeric Aβ-induced suppression of Pr at the SC-CA1 synapse and rescues synaptic and spatial learning and memory deficits in APP/PS1 mice. These results first reveal the presynaptic mGluR5-PIP2 pathway whereby oligomeric Aβ induces early synaptic deficits in AD., The underlying mechanism of amyloid β (Aβ) oligomer-induced aberrant neurotransmitter release remains unclear. Here, authors show that the release probability at the synapse between the Schaffer collateral and CA1 pyramidal neurons is significantly reduced at an early stage in mouse models of AD with elevated Aβ production and is mainly due to an mGluR5-mediated depletion of PIP2 in axons.

Metabolic module, gene expression pattern and PLS modeling were integrated to precisely identify the terpene synthase responsible for sesquiterpene formation. Functional characterization confirmed the feasibility and sensitivity of this strategy. Plant secondary metabolite biosynthetic pathway elucidation is crucial for the production of these compounds with metabolic engineering. In this study, an integrated strategy was employed to predict the gene function of sesquiterpene synthase (STS) genes using turmeric as a model. Parallel analysis of gene expression patterns and metabolite modules narrowed the candidates into an STS group in which the STSs showed a similar expression pattern. The projections to latent structures by means of partial least squares model was further employed to establish a clear relationship between the candidate STS genes and metabolites and to predict three STSs (ClTPS16, ClTPS15 and ClTPS14) involved in the biosynthesis of several sesquiterpene skeletons. Functional characterization revealed that zingiberene and β-sesquiphellandrene were the major products of ClTPS16, and β-eudesmol was produced by ClTPS15, both of which indicated the accuracy of the prediction. Functional characterization of a control STS, ClTPS1, produced a small amount of β-sesquiphellandrene, as predicted, which confirmed the sensitivity of metabolite module analysis. This integrated strategy provides a methodology for gene function predictions, which represents a substantial improvement in the elucidation of biosynthetic pathways in nonmodel plants.

The labdane-related diterpenoids are an important superfamily of natural products. Their structural diversity mainly depends on diterpene synthases, which generate the hydrocarbon skeletal structures. Isodon rubescens contains an expanded family of class I terpene synthases with different functions. Here we report a novel class I terpene synthase cDNA (IrKSL3a) with loss of 18 nucleotides compared with the reported cDNA sequence (IrKSL3). Inspection of IrKSL3 genomic sequence indicated that IrKSL3a and IrKSL3 transcripts may be generated by an alternative splicing event that utilizes different 3’ splice site. In vitro assays showed that IrKSL3a produced isopimaradiene and miltiradiene, while IrKSL3 only produced miltiradiene. Protein sequence alignment found the six residues encoded by the alternative exon was unique to IrKSL3, which are 17 residues away from the conserved DDXXD motif. A deletion mutant of IrKSL3 showed that maintaining two residues within the six-amino acid is sufficient for miltiradiene production, while the other mutants lost nearly all enzymatic function. Our results illustrated how product outcomes can be changed by alternative splicing, and further gave an interesting example for studying the loop conformation in tuning product outcome in class I terpene synthase.

Myopia is the most common optical disorder in the world, and wavelength defocus induced ametropia and myopia have attracted great attention. The objective was to identify and quantify scleral proteins involved in the response to the wavelength defocus. Guinea pigs were randomly divided into 3 groups that received different lighting conditions for 8 weeks: white light, short wavelength light, and long wavelength light. Refraction and axial length were measured, Hematoxylin-Eosin staining and transmission electron microscope were adopted to observe the scleral structure, and scleral proteome was also detected to analyze protein abundance by employing TMT labeling method. After light stimulation, the long- and short -wavelength light induced myopic and hyperopic effect on the guinea pig's eye and induced distinct protein signature, respectively. 186 dyregulated proteins between the short- and long-wavelength group were identified, which were mainly located in extracellular region and involved in metabolic process. We also found that 5 proteins in the guinea pigs scleras in response to wavelength defocus were also human myopic candidate targets, suggesting functional overlap between dyregulated proteins in scleral upon exposure to wavelength defocus and genes causing myopia in humans. Significance Wavelength defocus induces refractive errors and leads to myopia or hyperopia. However, sclera proteomics respond to wavelength defocus is lacking, which is crucial to understanding how wavelength defocus influences refractive development and induces myopia. In this proteome analysis, we identified unique protein signatures response to wavelength defocus in sclera of guinea pigs, identified potential mechanisms contributing to myopia formation, and found that several human myopia-related genes may involve in response to wavelength defocus. The results of this study provide a foundation to understand the mechanisms of myopia and wavelength defocus induced ametropia.

Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-κB signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-κB signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen species (ROS) and targeted inhibitors of MAPKs and NF-κB significantly blocked 7378 K light-induced changes of specific cytokines, respectively. Our findings suggest that 7378 K light, not 2954 K induced upregulation of VEGF-A, IL-6, IL-8 and downregulation of MCP-1 via ROS accumulation, activating MAPKs and NF-κB signal pathways.

In order to surmount drawbacks of the infrared spectroscopy (IR) itself during investigating the mesophase-transition behaviours and mechanism of the thermotropic liquid crystalline polymers (TLCPs), the elemental phosphorus as an internal marker was introduced into the main-chain TLCPs. The detail mechanism of the glass transition and mesophase phase transition of the phosphorus-containing aromatic liquid crystalline copolyester (poly(-hydroxybenzate-co-DOPO-benzenediol dihydrodiphenyl ether terephthalate) [PHDDT]) was revealed through tracing the internal marker with the perturbation correlation moving window 2-dimensional correlation and 2-dimensional correlation analysis (2DCOS) correlation IR spectra. The results showed that the phosphorus-containing unit did not participate in the glass transition of the PHDDT. The results of the 2DCOS showed that the PHDDT mesophase phase transition took place through adjustment of the phosphorus-containing units. Simultaneously, the adjustment of the phosp...