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Alzheimer's disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC50 of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile. [ABSTRACT FROM AUTHOR]

Since the late 2000s, China has accelerated reconstruction of the welfare state against the backdrop of the second transition. Following a typological approach, this study proposes an analytical framework for assessing varieties of social reproduction before delving into a comparative look at China's national institutional framework, in which China is regarded as a transitional economy and a late bloomer. As represented in three dimensions, countries have production regimes that diverge in the degree of coordination, welfare regimes that differ in the degree of decommodification, and labor reproduction regimes that vary in the degree of depatriarchalization. We investigate the convergence and divergence of advanced economies, transitional economies, and the emerging economies of East Asian countries. Hierarchical cluster analysis and a three-dimensional map illustrate the varieties of regimes at the intersections of production, welfare, and reproduction. With the help of institutional complementarities, five worlds of social reproduction are distinguished: the late blooming, the liberal, the catch-up/transitional, the conservative, and the social democratic. China's production regime converges with that of continental Europe and Post-Socialist societies based on institutional arrangements of nonmarket coordination; however, limited income maintenance and redistribution policies, the absence of family-friendly policies, and the regendering of the division of labor make China's institutional mix appear more compatible with East Asian societies than Western ones. The institutional complementarities between the welfare and labor reproduction regimes reveal a social reproduction scenario that is less than purely late blooming. [ABSTRACT FROM AUTHOR]

We propose a sensitive H1N1 virus fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies. Products are generated via the hybridization of single-stranded DNA (ssDNA) probes containing T7 promoter and crRNA templates to a target RNA sequence using SplintR ligase. This generates large crRNA quantities in the presence of T7 RNA polymerase. At such crRNA quantities, ternary Cas13a, crRNA, and activator complexes are successfully constructed and activate Cas13a to enhance fluorescence signal outputs. The biosensor sensitively and specifically monitored H1N1 viral RNA levels down to 3.23 pM and showed good linearity when H1N1 RNA concentrations were 100 pM–1 µM. Biosensor specificity was also excellent. Importantly, our biosensor may be used to detect other viral RNAs by altering the sequences of the two probe junctions, with potential applications for the clinical diagnosis of viruses and other biomedical studies. [ABSTRACT FROM AUTHOR]

To clarify the effect of plant spacing on the growth, yield formation, and quality of sugar beet taproot. We designed field experiments in 2021–2022, and sugar beet variety KWS1176 was used as experimental material, and 9 plant spacing treatments from 8 to 32 cm were set up. The morphological indicators, photosynthetic characteristics, and the nutrient contents were determined at the stages of the leafage growing period (V1), sugar increase period of taproot (V2), sugar accumulation period I of taproot (V3), and sugar accumulation period II of taproot (V4), and the root yield and quality parameters were measured at the harvest. The results showed that in the plant spacing treatments of 11 and 14 cm, sugar beet had a suitable canopy structure and space for taproot growing. The canopy photosynthetic activity was higher, which provided sufficient photosynthetic products for root growth, and appropriate root size could balance root growth and sucrose accumulation. The highest root yield and sugar content were also obtained in the treatment of 14 cm plant spacing. With the increase of plant spacing, the yield of sugar beet decreased, and the content of α-amino N, K+, and Na+ in the root increased, which had a disadvantageous influence on the processing quality of the root. It was found that the number of cambial rings and the average distance between cambial rings could be used as qualitative indicators of the sugar content of taproot and the processing quality. Therefore, 11-14 cm was recommended as a reasonable planting spacing to obtain higher taproot and sugar yield with better quality. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) remains one of the most lethal malignancies worldwide, with a high mortality rate and unfavorable prognosis. Endoplasmic reticulum (ER) stress is a key regulator of tumour growth, metastasis, and the response to chemotherapy, targeted therapies and immune response. It acts via responding to misfolded proteins and triggering abnormal activation of ER stress sensors and downstream signalling pathways. Notably, the expression patterns of ER-stress-related-genes (ERSRGs) are indicative of survival outcomes, especially in the context of immune infiltration. Through consensus clustering of prognosis-associated ERSRGs, we delineated two distinct LUAD subtypes: Cluster 1 and Cluster 2. Comprehensive analyses revealed significant disparities between these subtypes in terms of prognosis, immune cell infiltration, and tumor progression. Leveraging the robustness of LASSO regression and Multivariate stepwise regression, we constructed and validated an ER Stress-associated risk signature for LUAD. This signature underwent assessments for its prognostic value, correlation with clinical attributes, and interaction within the tumour immune microenvironment. By integrating this signature with multivariate cox analysis of distinct pathological stages, we devised an enhanced nomogram, validated through various statistical metrics, with an area under the curve for overall survival at 1, 3, and 5 years post-diagnosis being 0.79, 0.80, and 0.81, respectively. In conclusion, our findings introduce a composite signature of 11 pivotal ERSRGs, holding promise as a potent prognostic tool for LUAD, and offering insights for immunotherapeutic and targeted intervention strategies. [ABSTRACT FROM AUTHOR]

Immune response plays a crucial role in post-myocardial infarction (MI) myocardial remodeling. Neogenin (Neo1), a multifunctional transmembrane receptor, plays a critical role in the immune response; however, whether Neo1 participates in pathological myocardial remodeling after MI is unclear. Our study found that Neo1 expression changed significantly after MI in vivo and after LPS + IFN-γ stimulation in bone marrow-derived macrophages (BMDMs) in vitro. Neo1 functional deficiency (using a neutralizing antibody) and macrophage-specific Neo1 deficiency (induced by Neo1flox/flox;Cx3cr1cre mice) increased infarction size, enhanced cardiac fibrosis and cardiomyocyte apoptosis, and exacerbated left ventricular dysfunction post-MI in mice. Mechanistically, Neo1 deficiency promoted macrophage infiltration into the ischemic myocardium and transformation to a proinflammatory phenotype, subsequently exacerbating the inflammatory response and impairing inflammation resolution post-MI. Neo1 deficiency regulated macrophage phenotype and function, possibly through the JAK1-STAT1 pathway, as confirmed in BMDMs in vitro. Blocking the JAK1-STAT1 pathway with fludarabine phosphate abolished the impact of Neo1 on macrophage phenotype and function, inflammatory response, inflammation resolution, cardiomyocyte apoptosis, cardiac fibrosis, infarction size and cardiac function. In conclusion, Neo1 deficiency aggravates inflammation and left ventricular remodeling post-MI by modulating macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway. These findings highlight the anti-inflammatory potential of Neo1, offering new perspectives for therapeutic targets in MI treatment. Neo1 deficiency aggravated inflammation and left ventricular remodeling after MI by modulating macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway. [ABSTRACT FROM AUTHOR]

Transient receptor potential cation channel-6 (TRPC6) gene mutations cause familial focal segmental glomerulosclerosis (FSGS), which is inherited as an autosomal dominant disease. In patients with TRPC6-related FSGS, all mutations map to the N- or C-terminal TRPC6 protein domains. Thus far, the majority of TRPC6 mutations are missense resulting in increased or decreased calcium influx; however, the fundamental molecular mechanisms causing cell injury and kidney pathology are unclear. We report a novel heterozygous TRPC6 mutation (V691Kfs*) in a large kindred with no signs of FSGS despite a largely truncated TRPC6 protein. We studied the molecular effects of V691Kfs* TRPC6 mutant using the tridimensional cryo-EM structure of the tetrameric TRPC6 protein. The results indicated that V691 is localized at the pore-forming transmembrane region affecting the ion conduction pathway, and predicted that V691Kfs* causes closure of the ion-conducting pathway leading to channel inactivation. We assessed the impact of V691Kfs* and two previously reported TRPC6 disease mutants (P112Q and G757D) on calcium influx in cells. Our data show that the V691Kfs* fully inactivated the TRCP6 channel-specific calcium influx consistent with a complete loss-of-function phenotype. Furthermore, the V691Kfs* truncation exerted a dominant negative effect on the full-length TRPC6 proteins. In conclusion, the V691Kfs* non-functional truncated TRPC6 is not sufficient to cause FSGS. Our data corroborate recently characterized TRPC6 loss-of-function and gain-of-function mutants suggesting that one defective TRPC6 gene copy is not sufficient to cause FSGS. We underscore the importance of increased rather than reduced calcium influx through TRPC6 for podocyte cell death. [ABSTRACT FROM AUTHOR]

For L = (L , ⊙ , ⇝) a complete co-residuated lattice, the notions of ⊙ -subsethood degree and ⇝ -intersection degree between L-fuzzy sets are defined. It is shown that these notions reasonably extend the notions of subset and intersection between crisp sets. Then by using ⊙ -subsethood degree and ⇝ -intersection degree, a new model of L-fuzzy covering based L-fuzzy rough sets is investigated and studied. Firstly, a pair of L-fuzzy lower and upper approximation operators are constructed and their fundamental properties are discussed. Secondly, an axiom set or even a single axiom is presented to characterize the proposed approximate operators. Thirdly, the L-fuzzy topology and L-fuzzy co-topology induced by the L-fuzzy lower and upper approximation operators are researched, respectively. At last, the relationships between the new model and Qiao's L-fuzzy relation based rough sets are established. [ABSTRACT FROM AUTHOR]

In this study, zwitterionic poly(ionic liquid)-based polymer electrolytes with a network structure are prepared by ultraviolet-irradiation radical polymerization of poly(ethylene glycol) methyl ether acrylate (PEGMEA) and zwitterionic liquids, and poly(ethylene glycol) diacrylate is used as cross-linker. The cross-linked structure endows the electrolytes with high thermal stability and excellent dimensional stability. The abundant ether-oxygen group of PEGMEA provides sufficient sites for the transport of Li+ and a high ionic conductivity of 0.20 × 10−3 S cm−1. The electrolyte shows a high lithium-ion transference number of 0.78, owing to the excellent dissociation ability of zwitterionic liquids towards lithium salts. The lithium symmetric battery can maintain a voltage polarization of 150 mV at 0.1 mA cm−2 over 600 h. The Li/LiFePO4 battery shows a discharge capacity of 122 mAh g−1, a capacity retention of 90.0% after 100 cycles, and an average Coulombic efficiency exceeding 99% at 0.1 C, demonstrating strong application potential in lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that bone morphogenetic proteins (BMPs) play important roles in cardiovascular diseases, including atherosclerosis, artery calcification, myocardial remodeling, pulmonary arterial hypertension, and diabetic cardiomyopathy. Kielin/chordin-like protein (KCP) is a secreted protein that regulates the expression and function of BMPs. However, the role of KCP in cardiac aging remains unknown. In this study, we aimed to investigate the role of KCP in cardiac aging and its possible mechanisms. Echocardiogram showed that heart function was impaired in aged mice (24 months). In addition, analysis of heart structure showed that KCP knockout (KO) aggravated cardiac remodeling in aged mice. Moreover, KCP KO increased p-smad2/3 and TGF-β expression, while decreased BMP-2 expression in aged mice. Furthermore, KCP KO increased the expression of cardiac senescence-related proteins in aged mice. KCP KO aggravated the imbalance of oxidants and antioxidants and increased the expression of proinflammatory cytokines and cardiomyocyte apoptosis in aged mice. Our study demonstrated that KCP KO aggravated cardiac aging in mice by increasing the levels of oxidative stress, inflammation, and cardiomyocyte apoptosis. Key message: KCP KO aggravated aging-related cardiac dysfunction and remodeling in male mice. KCP KO aggravated cardiac aging by increasing the levels of oxidative stress, inflammation, and cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

This study provides proof of concept of a colorimetric biosensor for influenza H1N1 virus assay based on the CRISPR/Cas13a system and hybridization chain reaction (HCR). Target RNA of influenza H1N1 virus activated the trans-cleavage activity of Cas13a, which cleaved the special RNA sequence (-UUU-) of the probe, further initiating HCR to copiously generate G-rich DNA. Abundant G-quadruplex/hemin was formed in the presence of hemin, thus catalyzing a colorimetric reaction. The colorimetric biosensor exhibited a linear relationship from 10 pM to 100 nM. The detection limit was 0.152 pM. The biosensor specificity was excellent. This new and sensitive detection method for influenza virus is a promising rapid influenza diagnostic test. [ABSTRACT FROM AUTHOR]

Considerable attention has been drawn to tune the geometric and electronic structure of interfacial catalysts via modulating strong metal-support interactions (SMSI). Herein, we report the construction of a series of TiO2−x/Ni catalysts, where disordered TiO2−x overlayers immobilized onto the surface of Ni nanoparticles (~20 nm) are successfully engineered with SMSI effect. The optimal TiO2−x/Ni catalyst shows a CO conversion of ~19.8% in Fischer–Tropsch synthesis (FTS) process under atmospheric pressure at 220 °C. More importantly, ~64.6% of the product is C2+ paraffins, which is in sharp contrast to the result of the conventional Ni catalyst with the main product being methane. A combination study of advanced electron microscopy, multiple in-situ spectroscopic characterizations, and density functional theory calculations indicates the presence of Niδ−/TiO2−x interfacial sites, which could bind carbon atom strongly, inhibit methane formation and facilitate the C-C chain propagation, lead to the production of C2+ hydrocarbon on Ni surface. Considerable attention has been drawn to tune the geometric and electronic structure of interfacial catalysts via modulating strong metal-support interactions (SMSI). Here the authors report the remarkable catalytic performance of CO hydrogenation over an interfacial TiO2−x/Ni catalyst by means of SMSI. [ABSTRACT FROM AUTHOR]

Our understanding of climate dynamics during millennial-scale events is incomplete, partially due to the lack of their precise phase analyses under various boundary conditions. Here we present nine speleothem oxygen-isotope records from mid-to-low-latitude monsoon regimes with sub-centennial age precision and multi-annual resolution, spanning the Heinrich Stadial 2 (HS2) — a millennial-scale event that occurred at the Last Glacial Maximum. Our data suggests that the Greenland and Antarctic ice-core chronologies require +320- and +400-year adjustments, respectively, supported by extant volcanic evidence and radiocarbon ages. Our chronological framework shows a synchronous HS2 onset globally. Our records precisely characterize a centennial-scale abrupt "tropical atmospheric seesaw" superimposed on the conventional "bipolar seesaw" at the beginning of HS2, implying a unique response/feedback from low-latitude hydroclimate. Together with our observation of an early South American monsoon shift at the HS2 termination, we suggest a more active role of low-latitude hydroclimate dynamics underlying millennial events than previously thought. New cave records from monsoon regions improve the Greenland ice core chronological framework around the Heinrich Stadial 2 by an order of magnitude, suggesting a more active role of low-latitude hydroclimate in millennial-scale climate oscillations. [ABSTRACT FROM AUTHOR]

Hydrogen storage by means of catalytic hydrogenation of suitable organic substrates helps to elevate the volumetric density of hydrogen energy. In this regard, utilizing cheaper industrial crude hydrogen to fulfill the goal of hydrogen storage would show economic attraction. However, because CO impurities in crude hydrogen can easily deactivate metal active sites even in trace amounts such a process has not yet been realized. Here, we develop a robust RuNi/TiO2 catalyst that enables the efficient hydrogenation of toluene to methyl-cyclohexane under simulated crude hydrogen feeds with 1000–5000 ppm CO impurity at around 180 °C under atmospheric pressure. We show that the co-localization of Ru and Ni species during reduction facilitated the formation of tightly coupled metallic Ru-Ni clusters. During the catalytic hydrogenation process, due to the distinct bonding properties, Ru and Ni served as the active sites for CO methanation and toluene hydrogenation respectively. Our work provides fresh insight into the effective utilization and purification of crude hydrogen for the future hydrogen economy. Efficient storage of crude hydrogen, through toluene hydrogenation to methylcyclohexane, is often inhibited by CO impurities. Here, the authors develop a RuNi/TiO2 catalyst which avoids deactivation through promoting simultaneous CO methanation. [ABSTRACT FROM AUTHOR]

Subduction of the Pacific slab has been widely credited for the destruction of the eastern North China Craton (NCC). However, the nature of the subcontinental lithospheric mantle (SCLM) beneath the central and western NCC is less well constrained, which has hindered the understanding of cratonic responses to repeated Phanerozoic circum-craton subductions. Here, we report the in situ major- and trace-element contents and Sr isotopic compositions of minerals from 27 peridotite xenoliths obtained from Cenozoic basalts from Xiyang‒Pingding, central NCC, to gain new insights into how plate subduction affected the Archean lithospheric keel. On the basis of olivine major-element and clinopyroxene trace-element contents, as well as clinopyroxene Sr isotopic compositions, we divide the xenoliths into four types. The high-Mg# types 1 and 2 peridotites show high olivine forsterite (Fo) contents, convex-upward rare-earth element patterns, and high 87Sr/86Sr (0.7053‒0.7062) in clinopyroxene, and they could be relicts of an old cratonic root. The high-Mg# type 3 peridotites exhibit high (La/Yb)N and low Ti/Eu and 87Sr/86Sr (0.7038‒0.7044), and they are interpreted as reaction products of Archean SCLM and carbonatitic melts from the asthenosphere with a contribution of recycled oceanic components. The low-Mg# type 4 peridotites display low 87Sr/86Sr (0.7029‒0.7033) and represent fragments of modified SCLM that has been recently refertilized by asthenospheric melts. Complex architectures of the SCLM underneath Xiyang‒Pingding reflect multistage overprinting of mantle metasomatism. Recent influxes of asthenospheric melts played a critical role in transforming refractory SCLM to fertile SCLM. Combined with previous studies, our findings suggest that the SCLM beneath the central NCC became progressively more refertilized from the center toward both the northern and southern margins, a spatial pattern that was likely generated by N‒S-trending subductions of the circum-craton plates. [ABSTRACT FROM AUTHOR]

NASICON-type material Na1+xZr2SixP3−xO12 (0 ≤ x ≤ 3) is considered to be one of the most promising solid-state electrolytes that can be applied in all-solid-state sodium batteries (SSNBs). However, further increasing the ionic conductivity of Na1+xZr2SixP3−xO12 (0 ≤ x ≤ 3) to obtain higher performance electrolyte materials is still a challenge for its practical application. Herein, the Na3.4Zr2Si2.4P0.6O12 (NZSP) powder is prepared by the solution-assisted solid-state reaction (SA-SSR), and solid-state electrolytes with excellent electrochemical properties are obtained by doping with NaF as a sintering aid. With the increase of NaF doping, the crystal structure of NZSP is changed as well as a slight excess of Na+ may increase the bottleneck size of the crystal, so that it enhances the migration ability of Na+ in the crystal. Also, NaF as a sintering aid lowers the sintering temperature, increases the densities and improves the effective contact between crystals, which reduces the grain boundary impedance of NZSP. However, the excessive NaF dopant leads to the generation of microcracks decreasing the Na+ conducting and mechanical properties of solid-state electrolytes. Using this simple and low-cost strategy of NaF doping, NZSP-0.3NaF achieves an excellent conductivity of 4.98 mS cm−1 with unexpectedly low activation energy of 0.227 eV. Therefore, this composition is one of the few electrolytes with high conductivity reported so far and is a competitive option for solid-state sodium batteries. [ABSTRACT FROM AUTHOR]

Background: The Crohn's-like lymphoid reaction (CLR) is manifested as peritumoral lymphocytes aggregation in colon cancer, which is a major component of the host immune response to cancer. However, the lack of a unified and objective CLR evaluation standard limits its clinical application. We, therefore, developed a deep learning model for the fully automated CLR density quantification on routine hematoxylin and eosin (HE)-stained whole-slide images (WSIs) and further investigated its prognostic validity for patient stratification. Methods: The CLR density was calculated by using a deep learning method on HE-stained WSIs. A training (N = 279) and a validation (N = 194) cohorts were used to evaluate the prognostic value of CLR density for overall survival (OS). Result: The fully automated quantified CLR density was an independent prognostic factor, with high CLR density associated with increased OS in the discovery (HR 0.58, 95% CI 0.38–0.89, P = 0.012) and validation cohort (0.45, 0.23–0.88, 0.020). Integrating CLR density into a Cox model with other risk factors showed improved prognostic capability. Conclusion: We developed a new immune indicator (CLR density) quantified by a deep learning method to evaluate the lymphocytes aggregation in colon cancer. The CLR density was demonstrated its predictive value for OS in two independent cohorts. This approach allows for the objective and standardized quantification while reducing pathologists' workload. Therefore, this fully automated standardized method of CLR evaluation had potential clinical value. [ABSTRACT FROM AUTHOR]

Electric fields can spontaneously decay via the Schwinger effect, the nucleation of a charged particle-anti particle pair separated by a critical distance d. What happens if the available distance is smaller than d? Previous work on this question has produced contradictory results. Here, we study the quantum evolution of electric fields when the field points in a compact direction with circumference L < d using the massive Schwinger model, quantum electrodynamics in one space dimension with massive charged fermions. We uncover a new and previously unknown set of instantons that result in novel physics that disagrees with all previous estimates. In parameter regimes where the field value can be well-defined in the quantum theory, generic initial fields E are in fact stable and do not decay, while initial values that are quantized in half-integer units of the charge E = (k/2)g with k ∈ ℤ oscillate in time from +(k/2)g to −(k/2)g, with exponentially small probability of ever taking any other value. We verify our results with four distinct techniques: numerically by measuring the decay directly in Lorentzian time on the lattice, numerically using the spectrum of the Hamiltonian, numerically and semi-analytically using the bosonized description of the Schwinger model, and analytically via our instanton estimate. [ABSTRACT FROM AUTHOR]

Non-ferrous metal smelting activities have always been considered as one of the foremost anthropogenic sources of potentially toxic elements (PTEs). The enrichment factor (EF) and pollution load index (PLI) were used to evaluate the pollution level of soil PTEs; positive matrix factorization (PMF), correlation analysis, and geostatistics were utilized to quantify the sources of soil PTEs; and potential ecological risk (PER) and human health risk (HHR) of different sources from farmland, construction land, and natural land were quantifiably determined via combined PTE sources with PER and HHR assessment models. Taking the smelting area of Daye City as an example, the evaluation results of EF and PLI showed that the soil PTE pollution in the study area was serious, especially Cd and Cu. And four sources were quantitatively allocated as agricultural practices (12.14%), traffic emissions (23.07%), natural sources (33.46%), and industrial activities (31.33%). For PER, industrial activities were the largest contributor to PER, accounting for 55.66%, 56.30%, and 55.36% of farmland, construction land, and natural land, respectively, and Cd was the most dangerous element. In terms of HHR, industrial activities were also the cardinal contributors under the three land use types. Children were exposed to serious non-carcinogenic risks under three land use patterns and slight carcinogenic risk in construction land (1.06E − 04). Significantly, the carcinogenic risk of children in farmland (9.06 × 10−5) was very close to the threshold (1 × 10−4), which requires attention. Both non-carcinogenic and carcinogenic risk for adults were all at acceptable levels. The health risks (carcinogenic and non-carcinogenic risks) of children from four different sources were distinctly higher than those of adults. Consequently, strict management and control of industrial activities should be given priority, and the management of agricultural practices should not be ignored. [ABSTRACT FROM AUTHOR]

Recent studies have revealed the prevalence and biological significance of guanidine metabolism in nature. However, the metabolic pathways used by microbes to degrade guanidine or mitigate its toxicity have not been widely studied. Here, via comparative proteomics and subsequent experimental validation, we demonstrate that Sll1077, previously annotated as an agmatinase enzyme in the model cyanobacterium Synechocystis sp. PCC 6803, is more likely a guanidinase as it can break down guanidine rather than agmatine into urea and ammonium. The model cyanobacterium Synechococcus elongatus PCC 7942 strain engineered to express the bacterial ethylene-forming enzyme (EFE) exhibits unstable ethylene production due to toxicity and genomic instability induced by accumulation of the EFE-byproduct guanidine. Co-expression of EFE and Sll1077 significantly enhances genomic stability and enables the resulting strain to achieve sustained high-level ethylene production. These findings expand our knowledge of natural guanidine degradation pathways and demonstrate their biotechnological application to support ethylene bioproduction. The metabolic pathways used by microbes to degrade guanidine or mitigate its toxicity remain unclear. Here, the authors report a guanidine degrading enzyme that controls genomic stability of ethylene producing cyanobacterial strains. [ABSTRACT FROM AUTHOR]

During her younger age, the ovarian function and the oocyte quality were better than the present state; there is possibility that few oocytes could mature and continually develop to the implantation process; however, the influence of the variant prohibit the further development of the embryo and finally lead to miscarriage. We speculate that the missense variant might induce a relatively mild influence on oocyte maturation and early embryo development. [Extracted from the article]

Mud shale hydration and swelling are major challenges in the development of water-based drilling fluids (WBDFs). In this work, the inhibition performance and inhibition mechanism of polyethylene glycol (PEG) and potassium chloride (KCl) were investigated by hot rolling recovery tests, linear swell tests, Fourier transform infrared spectroscopy, X-ray diffraction, atomic absorption spectrophotometry and X-ray photoelectron spectroscopy. The experimental results show that the combination of PEG and KCl achieved higher recovery and lower linear swelling rate than those obtained by individual PEG or KCl. Compared to the d-spacing of Na-montmorillonite (Na-Mt) with PEG or KCl, the d-spacing of Na-Mt with PEG+KCl was lower, which indicates that KCl and PEG have synergistic inhibition effect. This synergistic effect can replace sodium ions and water molecules from the interlayer space of Na-Mt and decrease the d-spacing of Na-Mt. Based on the above experimental results and analysis, a method for optimizing PEG and KCl concentrations was proposed and further verified by rheological and hot rolling recovery tests of WBDFs. Hence, the results of this work can provide valuable theoretical guidance for developing other synergistic inhibitors. [ABSTRACT FROM AUTHOR]

Gene therapy is considered a potential treatment for Duchenne muscular dystrophy (DMD). Researchers have been working on this for many years to find effective therapeutic targets. Here, we found that MRTF-A (myocardin-related transcription factor A) could activate the transcription of L-type Ca2+-channel-related protein CACNA1S (calcium voltage-gated channel subunit alpha1 S) by binding to the CarG box in the promoter of CACNA1S. However, increased phosphorylation and decreased expression of MRTF-A were observed, along with the expression of CACNA1S reduced in mdx mice. Further, the decreased expression and increased phosphorylation of MRTF-A could inhibit the release of Ca2+ via CACNA1S. Therefore, MRTF-A may be a potential molecular target for the diagnosis and treatment of DMD. [ABSTRACT FROM AUTHOR]

Existing methods for arbitrary shaped text spotting can be divided into two categories: bottom-up methods detect and recognize local areas of text, and then group them into text lines or words; top-down methods detect text regions of interest, then apply polygon fitting and text recognition to the detected regions. In this paper, we analyze the advantages and disadvantages of these two methods, and propose a novel text spotter by fusing bottom-up and top-down processing. To detect text of arbitrary shapes, we employ a bottom-up detector to describe text with a series of rotated squares, and design a top-down detector to represent the region of interest with a minimum enclosing rotated rectangle. Then the text boundary is determined by fusing the outputs of two detectors. To connect arbitrary shaped text detection and recognition, we propose a differentiable operator named RoISlide, which can extract features for arbitrary text regions from whole image feature maps. Based on the extracted features through RoISlide, a CNN and CTC based text recognizer is introduced to make the framework free from character-level annotations. To improve the robustness against scale variance, we further propose a residual dual scale spotting mechanism, where two spotters work on different feature levels, and the high-level spotter is based on residuals of the low-level spotter. Our method has achieved state-of-the-art performance on four English datasets and one Chinese dataset, including both arbitrary shaped and oriented texts. We also provide abundant ablation experiments to analyze how the key components affect the performance. [ABSTRACT FROM AUTHOR]

Selective oxidation is one of the most important and challenging transformations in both academic research and chemical industry. Recently, a highly selective and efficient way to synthesize biologically active γ-hydroxy-α,β-unsaturated molecules from Cu-catalyzed vinylogous aerobic oxidation of α,β- and β,γ-unsaturated compounds has been developed. However, the detailed reaction mechanism remains elusive. Herein, we report a density functional theory study on this Cu-catalyzed vinylogous aerobic oxidation of γ,γ-disubstituted α,β- and β,γ-unsaturated isomers. Our computational study unveils detailed mechanism for each elementary step, i.e. deprotonation, O2 activation, and reduction. Besides, the origin of regioselectivity, divergent reactivities of substrates as well as reducing agents, and the byproduct generation have also been investigated. Notably, the copper catalyst retains the + 2 oxidation state through the whole catalytic cycle and plays essential roles in multiple steps. These findings would provide hints on mechanistic studies and future development of transition metal-catalyzed aerobic oxidation reactions. [ABSTRACT FROM AUTHOR]

Recognition of handwritten mathematical expressions (MEs) is an important problem that has wide applications in practice. Handwritten ME recognition is challenging due to the variety of writing styles and ME formats. As a result, recognizers trained by optimizing the traditional supervision loss do not perform satisfactorily. To improve the robustness of the recognizer with respect to writing styles, in this work, we propose a novel paired adversarial learning method to learn semantic-invariant features. Specifically, our proposed model, named PAL-v2, consists of an attention-based recognizer and a discriminator. During training, handwritten MEs and their printed templates are fed into PAL-v2 simultaneously. The attention-based recognizer is trained to learn semantic-invariant features with the guide of the discriminator. Moreover, we adopt a convolutional decoder to alleviate the vanishing and exploding gradient problems of RNN-based decoder, and further, improve the coverage of decoding with a novel attention method. We conducted extensive experiments on the CROHME dataset to demonstrate the effectiveness of each part of the method and achieved state-of-the-art performance. [ABSTRACT FROM AUTHOR]

Despite some interesting results from different research groups, a public database for Uyghur online handwriting recognition and a baseline study are not yet available for comparison purpose. In order to fill this void, we present a database of Uyghur online handwritten words and carry out the first benchmark experiments using it. This database contains 125,020 samples of 2030 words collected from 393 writers. According to Uyghur lexicon characteristics, two out-of-vocabulary datasets are especially provided for evaluation. We carry out some unconstrained handwritten word recognition experiments on the database using recurrent neural networks as base model. Recognition results are acquired using connectionist temporal classification without lexicon search and external language model. Concatenated and averaged bidirectional recurrent layers are compared for better generalization. Based on Uyghur unicode representation, we are interested in comparing the models using different alphabets, based both on character types and character forms. To improve generalization, we propose 1D convolutional model which implements 1D convolutional layers for sequence feature extraction. In our experiments, the proposed 1D convolutional model and its variations surpassed the base recurrent layered model on the out-of-vocabulary words by clear margin. 83.23% CAR (character accurate rate) was resulted when out-of-vocabulary samples are used for testing. The highest recognition rate is as high as 94.95% CAR when the test set shares the same lexicon to the training set. The experiments in this paper can be the baseline references for the future study using this database. [ABSTRACT FROM AUTHOR]

The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies. Fustin et al. reveal the evolutionarily conserved link between methyl metabolism and biological clocks. This study suggests the possibility of translating fundamental understanding of methylation deficiencies to clinical applications. [ABSTRACT FROM AUTHOR]

Long-chain alcohols synthesis (LAS, C5+OH) from syngas provides a promising route for the conversion of coal/biomass/natural gas into high-value chemicals. Cu-Fe binary catalysts, with the merits of cost effectiveness and high CO conversion, have attracted considerable attention. Here we report a nano-construct of a Fe5C2-Cu interfacial catalyst derived from Cu4Fe1Mg4-layered double hydroxide (Cu4Fe1Mg4-LDH) precursor, i.e., Fe5C2 clusters (~2 nm) are immobilized onto the surface of Cu nanoparticles (~25 nm). The interfacial catalyst exhibits a CO conversion of 53.2%, a selectivity of 14.8 mol% and a space time yield of 0.101 g gcat−1 h−1 for long-chain alcohols, with a surprisingly benign reaction pressure of 1 MPa. This catalytic performance, to the best of our knowledge, is comparable to the optimal level of Cu-Fe catalysts operated at much higher pressure (normally above 3 MPa). Long-chain alcohols synthesis from syngas conversion is a promising route for the production of high-value chemicals. Here the authors show that a heterogeneous Fe5C2/Cu catalyst derived from layered double hydroxides precursor exhibits excellent performance with a space time yield of 0.101 g gcat−1 h−1 at a low pressure of 1 MPa. [ABSTRACT FROM AUTHOR]

We consider the single-machine scheduling problem with job-dependent machine deterioration. In the problem, we are given a single machine with an initial nonnegative maintenance level, and a set of jobs each with a non-preemptive processing time and a machine deterioration. Such a machine deterioration quantifies the decrement in the machine maintenance level after processing the job. To avoid a machine breakdown, one should guarantee a nonnegative maintenance level at any time point, and whenever necessary, a maintenance activity must be allocated for restoring the machine maintenance level. The goal of the problem is to schedule the jobs and the maintenance activities such that the total completion time of jobs is minimized. There are two variants of maintenance activities: In the partial maintenance case, each activity can be allocated to increase the machine maintenance level to any level not exceeding the maximum; in the full maintenance case, every activity must be allocated to increase the machine maintenance level to the maximum. In a recent work, the problem in the full maintenance case was proven NP-hard; several special cases of the problem in the partial maintenance case were shown to be solvable in polynomial time, but the complexity of the general problem was left open. In this paper we first prove that the problem in the partial maintenance case is binary NP-hard, thus settling the open problem; we then design a 2-approximation algorithm and a branch-and-bound exact search algorithm. Computational experiments are conducted for the two algorithms to examine their practical performance. [ABSTRACT FROM AUTHOR]

MHC class I-related chain A (MICA) is one of the major ligands for natural killer group 2 member D (NKG2D), which is an activating NK receptor. MICA is expressed on the surface of human epithelial tumor cells, and its shedding from tumor cells leads to immunosuppression. To activate immune response in the tumor microenvironment, we designed an anti-VEGFR2–MICA bispecific antibody (JZC01), consisting of MICA and an anti-VEGFR2 single chain antibody fragment (JZC00) and explored its potential anti-tumor activity. JZC01 targeted vascular endothelial growth factor receptor 2 (VEGFR2) and inhibited tumorigenesis by blocking the VEGFR2 signaling pathway. Additionally, JZC01 promoted NK and CD8+ T cells to release IFN-γ and engaged activated lymphocytes to lysis of VEGFR2-expressing tumor cells. The in vivo anti-tumor activity of JZC01 was investigated by establishing a Lewis lung cancer cell-transplanted mouse model. It effectively reduced the tumor vascular density and increased the infiltration and activation of NK and CD8+ T cells in the tumor microenvironment. Thus, JZC01 functions in anti-tumor angiogenesis and anti-tumor immune activation, and showed improved anti-tumor efficacy combined with docetaxel, which provides a new insight into anti-tumor therapy. [ABSTRACT FROM AUTHOR]

Sesquiterpanes are ubiquitous components of crude oils and ancient sediments. Liquid saturated hydrocarbons from simulated pyrolysis experiments on immature organic-rich mudstone collected from the Lower Cretaceous Hesigewula Sag were analyzed by gas chromatography–mass spectrometry (GC–MS). C14 bicyclic sesquiterpanes, namely, 8β(H)-drimane, 8β(H)-homodrimane, and 8α(H)-homodrimane were detected and identified on basis of their diagnostic fragment ions (m/z 123, 179, 193, and 207), and previously published mass spectra data, and these bicyclic sesquiterpanes presented relatively regular characteristics in their thermal evolution. The ratios 8β(H)-drimane/8β(H)-homodrimane, 8β(H)-homodrimane/8α(H)-homodrimane, and 8β(H)-drimane/8α(H)-homodrimane all show a clear upward trend with increasing temperature below the temperature turning point. Thus, all these ratios can be used as evolution indexes of source rocks in the immature–low-maturity stage. However, the last two ratios may be more suitable than the first ratio as valid parameters for measuring the extent of thermal evolution of organic matter in the immature–low-maturity stage because their change amplitude with increasing temperature is more obvious. [ABSTRACT FROM AUTHOR]

The human zona pellucida (ZP) is an extracellular glycoprotein matrix composed of ZP1, ZP2, ZP3, and ZP4 surrounding the oocyte, and it plays an important role in sperm–egg interactions during fertilization. Structural and functional changes in the ZP can influence the process of fertilization and lead to female infertility. Previous studies have identified mutations in ZP1, ZP2, and ZP3 that lead to female infertility caused by oocyte degeneration, empty follicle syndrome, or in vitro fertilization failure. Here we describe seven patients from six independent families who had several abnormal oocytes or suffered from empty follicle syndrome, similar to the previously reported phenotypes. By whole-exome sequencing and Sanger sequencing, we identified several novel mutations in these patients. These included three homozygous mutations in ZP1 (c.1708G > A, p.Val570Met; c.1228C > T, p.Arg410Trp; c.507del, p.His170Ilefs*52), two mutations in a compound heterozygous state in ZP1 (c.1430 + 1G > T, p.Cys478X and c.1775-8T > C, p.Asp592Glyfs*29), a homozygous mutation in ZP2 (c.1115G > C, p.Cys372Ser), and a heterozygous mutation in ZP3 (c.763C > G, p.Arg255Gly). In addition, studies in CHO cells showed that the mutations in ZP1, ZP2, and ZP3 might affect the corresponding protein expression, secretion, and interaction, thus providing a mechanistic explanation for the phenotypes. Our study expands the spectrum of ZP gene mutations and phenotypes, and provides a further understanding of the pathogenic mechanism of ZP gene mutations in vitro. [ABSTRACT FROM AUTHOR]

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Gas chromatography/mass spectrometry (GC/MS) can only analyze volatile molecular compounds, and it has limitations when applied to determine the complex components of crude oils and hydrocarbon source rocks. Based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and GC/MS analyses, the molecular compositions of NSO compounds in extracts from the Permian Dalong Formation, Sichuan Basin and the Permian Lucaogou Formation, Junggar Basin in China were compared. Analyses of types of heteroatoms present (S1, S2, S3, OS, OS2, O2S, NS, and NOS compounds) suggest that marine shales from the Dalong Formation are mainly composed of carboxylic acids (O2 compounds) with a high abundance of fatty acids, indicating a marine phytoplankton organic source. However, lacustrine shales from the Lucaogou Formation are dominated by pyrrolic compounds (N1 compounds) with abundant dibenzocarbazole. It suggests that the organic source materials may be derived from lower aquatic organisms and lacustrine algae. Overall, FT-ICR-MS has potential for applications in analyses and determination of depositional environments and organic sources in petroleum geology. [ABSTRACT FROM AUTHOR]

Bag of Words (BoW) model and Convolutional Neural Network (CNN) are two milestones in visual recognition. Both BoW and CNN require a feature pooling operation for constructing the frameworks. Particularly, the max-pooling has been validated as an efficient and effective pooling method compared with other methods such as average pooling and stochastic pooling. In this paper, we first evaluate different pooling methods, and then propose a new feature pooling method termed as selective, discriminative and equalizing pooling (SDE). The SDE representation is a feature learning mechanism by jointly optimizing the pooled representations with the target of learning more selective, discriminative and equalizing features. We use bilevel optimization to solve the joint optimization problem. Experiments on seven benchmark datasets (including both single-label and multi-label ones) well validate the effectiveness of our framework. Particularly, we achieve the state-of-the-art fused results (mAP) of 93.21 and 93.97% on the PASCAL VOC2007 and VOC2012 datasets, respectively. [ABSTRACT FROM AUTHOR]

Nitrogen-doped graphene is a promising candidate for the replacement of noble metal-based electrocatalysts for oxygen reduction reactions (ORRs). The addition of pores and holes into nitrogen-doped graphene enhances the ORR activity by introducing abundant exposed edges, accelerating mass transfer, and impeding aggregation of the graphene sheets. Herein, we present a straightforward but effective strategy for generating porous holey nitrogen-doped graphene (PHNG) via the pyrolysis of urea and magnesium acetate tetrahydrate. Due to the combined effects of the in situ generated gases and MgO nanoparticles, the synthesized PHNGs featured not only numerous out-of-plane pores among the crumpled graphene sheets, but also interpenetrated nanoscale (5-15 nm) holes in the assembled graphene. Moreover, the nitrogen doping configurations of PHNG were optimized by post-thermal treatments at different temperatures. It was found that the overall content of pyridinic and quaternary nitrogen positively correlates with the ORR activity; in particular, pyridinic nitrogen generates the most desirable characteristics for the ORR. This work reveals new routes for the synthesis of PHNG-based materials and elucidates the contributions of various nitrogen species to ORRs. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that cancer stem cells (CSCs) are a key occurrence in the process of many human cancers. Lung cancer is the most common aggressive malignancy and cause of cancer death worldwide. The research on lung cancer stem cells has been highlighted for many years. Lung CSCs seem to play a major role in lung cancer metastasis, drug resistance and tumour-self-renewal. MicroRNAs (miRNAs), a class of newly emerging small noncoding RNAs that act as post-transcriptional regulators of gene expression, have been demonstrated to serve as a vital player in fine-tuning a number of biological activities ranging from embryogenesis to programmed cell death as well as tumourigenesis. In recent years, several miRNAs have been highlighted to be specifically expressed in CSCs. The miRNA profile of CSCs is remarkably different from non-stem cancer cells. As such, many miRNAs have been shown to regulate self-renewal and differentiation properties of CSCs. In this review, we present the latest findings on miRNAs that regulate the tumour microenvironment of lung CSCs with the goal to prompt the development of novel therapeutic strategies for patients with lung cancer. [ABSTRACT FROM AUTHOR]

With the increasing interest in the deployment of wireless multimedia sensor networks (WMSN), new challenges have arisen with the complexity and high noise level of the monitoring environment. Given that the noise severely impairs the quality and visibility of video images perceived by sensors, video image denoising naturally becomes the key to ensure the validity and reliability of the WMSN video monitoring. In this paper, the sparse denoising algorithm via clustering-based sparse representation is proposed. Firstly, WMSN images are, respectively, clustered based on the pixel intensity of regions of interest (ROIs), which are determined in terms of Bayesian theorem. Secondly, in the light of nonlocal self-similarity regularizer provided by the ROI-based WMSN images clustering, clustering-based sparse representation builds a new sparse denoising model exploiting both sparsity and nonlocal self-similarity to improve the quality of reconstructed images. At last, a surrogate-function-based iterative shrinkage solution has been developed to solve the double-header $$l_{1}$$ -optimization problem. Experimental results showed that the performance of the approach to image denoising is competitive, qualitative, as well as quantitative, and suitable for the WMSN video image denoising. [ABSTRACT FROM AUTHOR]

A new solar coupling regeneration system is proposed in order to improve the reliability of solar desiccant regeneration system. The new system makes comprehensively use of the solar energy and can also be appropriate for energy-storage in a night operation mode when the electric power supply is at its valley. Comparison of the performance of the new system, the solar thermal regeneration system and the solar electrodialysis regeneration system are made and the influential factors of the performance of the new system are investigated. The results reveal that the new system will be more energy efficient than the solar thermal regeneration system and the solar electrodialysis regeneration system. [ABSTRACT FROM AUTHOR]

Two drawbacks of the traditional electrospinning process when used for producing nanofibers for drug release are that clogging of the spinneret is often experienced, and the fibers produced often exhibit a tailing-off of drug release over sustained periods. The present study investigates the preparation of ferulic acid (FA) sustained-release cellulose acetate (CA) nanofibers, in which a third component, polyvinylpyrrolidone (PVP), was included into the nanocomposites for an improved sustained drug release profile. A modified coaxial electrospinning process, in which only organic solvent N, N-dimethylacetamide was used as a sheath fluid, was exploited for a smooth and continuous fabrication of multiple-component nanofibers. Under an applied voltage of 16 kV and an optimized sheath-to-core flow rate ratio of 0.11, three types of FA/PVP/CA composite nanofibers (with varied of PVP content) were generated. These nanofibers had higher quality in terms of size and distribution of nanofiber diameter, as indicated by FESEM images. Analysis of double- and triple-component nanofibers by XRD, DSC, and ATR-FTIR confirmed the compatibility of components producing homogenous fibers in both cases, but the triple-component nanofibers exhibited better release profiles over sustained periods than the double-component nanofibers in terms of release completeness, reduced tailing-off, and adjustable release rates. The modified coaxial process and the resulting multiple-component nanocomposites should provide a new way for developing novel drug sustained materials and drug delivery systems. [ABSTRACT FROM AUTHOR]

Circadian rhythms are oscillations in biological processes that function as a key adaptation to the daily rhythms of most environments. In the model cyanobacterial circadian clock system, the core oscillator proteins are encoded by the gene cluster kaiABC. Genes with high expression and functional importance, such as the kai genes, are usually encoded by optimal codons, yet the codon-usage bias of the kaiBC genes is not optimized for translational efficiency. We discovered a relationship between codon usage and a general property of circadian rhythms called conditionality; namely, that endogenous rhythmicity is robustly expressed under some environmental conditions but not others. Despite the generality of circadian conditionality, however, its molecular basis is unknown for any system. Here we show that in the cyanobacterium Synechococcus elongate, non-optimal codon usage was selected as a post-transcriptional mechanism to switch between circadian and non-circadian regulation of gene expression as an adaptive response to environmental conditions. When the kaiBC sequence was experimentally optimized to enhance expression of the KaiB and KaiC proteins, intrinsic rhythmicity was enhanced at cool temperatures that are experienced by this organism in its natural habitat. However, fitness at those temperatures was highest in cells in which the endogenous rhythms were suppressed at cool temperatures as compared with cells exhibiting high-amplitude rhythmicity. These results indicate natural selection against circadian systems in cyanobacteria that are intrinsically robust at cool temperatures. Modulation of circadian amplitude is therefore crucial to its adaptive significance. Moreover, these results show the direct effects of codon usage on a complex phenotype and organismal fitness. Our work also challenges the long-standing view of directional selection towards optimal codons, and provides a key example of natural selection against optimal codons to achieve adaptive responses to environmental changes. [ABSTRACT FROM AUTHOR]

We have obtained transgenic plants of Nicotiana sylvestris expressing an arylalkylamine N-acetyltransferase ( AANAT) gene and a hydroxyindole-O-methyltransferase ( HIOMT) gene using Agrobacterium tumefaciens-mediated transformation. Both AANAT and HIOMT are key enzymes in melatonin synthesis. Transgenic plants of N. sylvestris were characterized by polymerase chain reaction (PCR) and reverse transcription PCR analyses. The content of melatonin was significantly higher in transgenic plants than in nontransgenic plants. The highest melatonin content of transgenic plant leaves reached 50.4 μg/g dry weight, while almost no melatonin could be detected in the nontransformed plants. To investigate effects of the expression of the AANAT and HIOMT genes on melatonin function in plants, isolated protoplasts of N. sylvestris were exposed to ultraviolet (UV)-B radiation for different durations. DNA damage was evaluated by single-cell gel electrophoresis, which showed that the TailDNA percentage value in transgenic protoplasts was lower than that in the nontransformed protoplasts in the range of 0-30 s of UV-B radiation. DNA damage caused by UV-B was therefore reduced in transgenic N. sylvestris plants. [ABSTRACT FROM AUTHOR]

Cellular life emerged ?3.7?billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles owing to the Earth's rotation. The advantage conferred on organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation-reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterizing their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription-translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular timekeeping with redox homeostatic mechanisms after the Great Oxidation Event ?2.5?billion years ago. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms controlling transcription of a gene requires the identification and characterization of its cis-acting regulatory elements. A highly useful approach to the identification and characterization of cis-acting elements has been the systematic coupling of genomic fragments to reporter constructs, so called 'promoter bashing'. The expression from such reporters must be normalized for differences in transient transfection efficiency between cells and replicates. A novel dual color fluorescent reporter system to assay the promoter activity of a genomic DNA fragment of interest was established by cloning a Discosoma red fluorescent protein gene and a green fluorescent protein gene into a single vector, giving a system in which the ratio between red and green fluorescence is proportional to promoter activity. This system allows real time quantitative monitoring of promoter activity. We validated this approach by assaying the cis-acting regulatory potential of the peroxisome proliferators-activated receptor gamma2 gene. [ABSTRACT FROM AUTHOR]

We propose that a C-type lectin receptor, SIGNR-1 (also called Cd209b), helps to condition dendritic cells (DCs) in the gastrointestinal lamina propria (LPDCs) for the induction of oral tolerance in a model of food-induced anaphylaxis. Oral delivery of BSA bearing 51 molecules of mannoside (Man51-BSA) substantially reduced the BSA-induced anaphylactic response. Man51-BSA selectively targeted LPDCs that expressed SIGNR1 and induced the expression of interleukin-10 (IL-10), but not IL-6 or IL-12 p70. We found the same effects in IL-10-GFP knock-in (tiger) mice treated with Man51-BSA. The Man51-BSA-SIGNR1 axis in LPDCs, both in vitro and in vivo, promoted the generation of CD4+ type 1 regulatory T (Tr1)-like cells that expressed IL-10 and interferon-γ (IFN-γ), in a SIGNR-1- and IL-10-dependent manner, but not of CD4+CD25+Foxp3+ regulatory T cells. The Tr1-like cells could transfer tolerance. These results suggest that sugar-modified antigens might be used to induce oral tolerance by targeting SIGNR1 and LPDCs. [ABSTRACT FROM AUTHOR]

To study the optimal medium composition for xylanase production by Aspergillus niger XY-1 in solid-state fermentation (SSF). Statistical methodology including the Plackett-Burman design (PBD) and the central composite design (CCD) was employed to investigate the individual crucial component of the medium that significantly affected the enzyme yield. Firstly, NaNO3, yeast extract, urea, Na2CO3, MgSO4, peptone and (NH4)2SO4 were screened as the significant facotrs positively affecting the xylanase production by PBD. Secondly, by valuating the nitrogen sources effect, urea was proved to be the most effective and economic nitrogen source for xylanase production and used for further optimization. Finally, the CCD and response surface methodology (RSM) were applied to determine the optimal concentration of each significant variable, which included urea, Na2CO3 and MgSO4. Subsequently a second-order polynomial was determined by multiple regression analysis. The optimum values of the critical components for maximum xylanase production were obtained as follows: x 1 (urea)=0.163 (41.63 g/L), x 2 (Na2CO3)=−1.68 (2.64 g/L), x 3 (MgSO4)=1.338 (10.68 g/L) and the predicted xylanase value was 14374.6 U/g dry substrate. Using the optimized condition, xylanase production by Aspergillus niger XY-1 after 48 h fermentation reached 14637 U/g dry substrate with wheat bran in the shake flask. By using PBD and CCD, we obtained the optimal composition for xylanase production by Aspergillus niger XY-1 in SSF, and the results of no additional expensive medium and shortened fermentation time for higher xylanase production show the potential for industrial utilization. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing the synthesis and characterization of ultralong lanthanum hydroxide nanorods using solvothermal method.

OBJECTIVE To study the microsatellite instability (MSI) and methylation state of the hMLH1 gene promoter and their mechanisms underlying the development of gastric cancer. METHODS Forty-one gastric cancer samples were obtained from patients undergoing surgery and 46 chronic atrophic gastritis tissues with dysplasia or intestinal metaplasia (IM) were obtained from patients undergoing gastro-endoscopy. Fourteen normal gastric mucosal samples were used as controls. Genomic DNA was extracted from the samples and 5 microsatellite markers were used to measure MSI. Methylation — specific PCR (MSP) was used to screen the methylation state of the samples. DNA sequencing and immunohistochemistry were performed to verify the results. RESULTS MSI was identified in 22 out of the 41 (53.7%) gastric cancers, of which 8 cases showed high-level MSI (2 or more loci altered) and 14 showed low-level MSI (1 locus altered). MSI was also detected in 12 out of 46 (26.1%) pre-cancerous lesions of the stomach, whereas it was not seen in the normal tissue. Moreover, hMLH1 hypermethylation was detected in 17 out of the 41 (41.5%) gastric cancers, 9 out of the 46 (19.6%) pre-cancerous lesions and 0 out of the 14 normal tissue. Significant differences in frequency of MSI and hMLH1 promoter methylation were observed among gastric cancers, precancerous lesions and normal gastric tissue. Gastric samples with MSI had a tendency to be hypermethylated in the hMLH1 promoter. DNA sequencing and immunohistochemistry results also confirmed that hMLH1 promoter methylation could lead to loss of the hMLH1 protein and gene silence which sequentely resulted in gene mismatch and MSI. CONCLUSION Accumulation of MSI and hMLH1 promoter methylation may be important early molecular events during gastric carcinogenesis and may contribute to the acquisition of a transformed cell phenotype and the development of gastric cancer. [ABSTRACT FROM AUTHOR]