Search

In previous studies, several isoindolin-1-one analogs that exhibited significant anti-tobacco mosaic virus (anti-TMV) activities were isolated from Nicotiana tabacum. Since gene-editing mutants provide a new sample for the discovery of active metabolites, we focused on the stems of YN-18-23 (a mutant N. tabacum for gene editing with the alkaloid metabolic pathway cultivated by Yunnan Tobacco Company), which led to the isolation of four new (1-4) and four known (5-8) isoindolin-1-ones. To the best of our knowledge, nicindole C (3) is the first subclass of isoindolin-1-one bearing a pentacyclic ketone, while nicindole D (4) is the first example of isoindolin-1-one bearing a methyl-pyridin-2-(1H)-one moiety. Compounds 1-4 were tested for their anti-TMV activities, and the results revealed that compounds 1, 3, and 4 exhibited high anti-TMV activities at concentrations of 20 μM with inhibition rates of 48.6, 42.8, and 71.5%, respectively. These rates are higher than the inhibition rate of the positive control (33.2%). The mechanistic study of compound 4, which had the highest anti-TMV activity revealed that increased potentiation of defense-related enzyme activities and downregulation of expression of the NtHsp70 protein may induce resistance in tobacco against the viral pathogen TMV. Molecular docking studies also revealed that the isoindolin-1-one substructure is fundamental for anti-TMV activity. The methyl-pyridin-2-(1H)-one moiety in compound 4 and the 2-oxopropyl groups in compounds 1 and 3 at the N-2 position may increase inhibitory activities. This study of the structure-activity relationship is helpful for finding new anti-TMV activity inhibitors. To study whether the isoindolin-1-ones have broader antiviral activities, compounds 1-4 were also tested for their anti-rotavirus activities. Compound 4 exhibited high anti-rotavirus activity with a therapeutic index (TI) value of 20.7. This TI value is close to that of the positive control (20.2).

Purpose The current study aimed to optimize the culture and production parameters of industrial production of lincomycin A by Streptomyces lincolnensis using a statistical approach that could also reduce unwanted by-products. Methods The Plackett-Burman design, steepest ascent method, and response surface design were used to evaluate different factors that affect lincomycin A production. Results Using an optimized S. lincolnensis fermentation medium, lincomycin A production was increased up to 4600 mg/L in shaking flasks, which indicated a 28.3% improvement over previous production in an un-optimized medium (3585 mg/L). Additionally, the concentration of lincomycin B by-product was reduced to 0.8%, which was 82.2% lower than that in the un-optimized medium. Further, quantitative real-time PCR analysis revealed the optimized medium improved lincomycin A production by stimulating key genes in the lincomycin A biosynthesis pathway, as well as an osmotic stress gene. Conclusions Based on the results, the sequential optimization strategy in this study provides powerful means for the enhancement of lincomycin A with less by-product. We found that osmotic stress reduced the concentration of lincomycin B, which could also help reduce fermentation by-product yields in other actinobacteria.

A multi-parameter, absolute-dated lacustrine record from the eastern Tibetan Plateau provides a continuous history of the Asian summer monsoon (ASM) over the past ~ 6000 years. The record broadly follows the trend in northern hemisphere summer insolation. However, it diverges during a period of increased moisture and thermal conditions during the past ~ 1300 years, broadly corresponding to the ASM “2-kyr shift”. This shift as referred by Cheng et al. (Nature 534:640–646, 10.1038/nature18591, 2016) may be related to Atlantic Meridional Overturning Circulation variations, and potentially to increased forcing by greenhouse gases coincident with reduced ENSO activity. The record is punctuated by several weak monsoon intervals. Cross-correlation of the sub-millennial-scale monsoon record with solar activity and ENSO records shows that most of the monsoon variability potentially results from changes in solar irradiation, and has a strong teleconnection with ENSO activity.

The nuclear modification factors ($$R_{AA}$$ R AA ) of d and $$\bar{d}$$ d ¯ have been studied using the parton and hadron cascade model plus the dynamically constrained phase space coalescence model in peripheral (40–60%) and central (0–5%) Pb–Pb collisions at $$\sqrt{s_{NN}}=2.76\,\hbox {TeV}$$ s NN = 2.76 TeV with $$|y| | y | < 0.5 , p T < 20.0 GeV / c . It is found that the $$R_{AA}$$ R AA of $$d, \bar{d}$$ d , d ¯ is similar to that of hadrons ($$\pi ^\pm , p, \bar{p}$$ π ± , p , p ¯ ) and the $$R_{AA}$$ R AA of antiparticles is the same as that of particles. The suppression effect of d is more significant than that of baryons and mesons in the high-$$p_T$$ p T region. The suppression of $$R_{AA}$$ R AA at high-$$p_T$$ p T strongly depends on event centrality and mass of the particles, i.e., the central collision is more suppressed than the peripheral collision. Besides, the yield ratios and double ratios for different particle species, and the coalescence parameter $$B_2$$ B 2 for ($$d, \bar{d}$$ d , d ¯ ) in pp and Pb–Pb collisions are discussed, respectively. It is observed that the yield ratios and double ratios of d to p and p to $$\pi $$ π are similar to those of their anti-particles in three different collision systems, suggesting that the suppressions of matter ($$\pi ^{+}, p, d$$ π + , p , d ) and the corresponding antimatter ($$\pi ^{-},\bar{p},\bar{d}$$ π - , p ¯ , d ¯ ) are around the same level.

The rice leaf folder, Cnaphalocrocis medinalis Guenee (Lepidoptera: Pyralidae), occurs throughout southeast and northeast Asia, and has a broad host range including graminaceous crops and weeds. Unraveling the relationship between adult oviposition preference and offspring performance is central to understanding the evolution of plant–insect interactions. In the present study, we examined oviposition behavior and larval performance of the C. medinalis on rice plants and non-rice graminaceous plants. Using choice oviposition experiments, female C. medinalis moths preferred rice volatiles, and laid significantly more eggs on the leaves of rice plants than non-rice graminaceous plants. Larval performance, as assayed by host plant selection rate, and host suitability, were evaluated by using multi-choice experiments and life-table analysis, respectively. Larval host selection experiments showed that the younger C. medinalis larvae (1st and 2nd instar) exhibited a stronger ability to identify rice hosts compared to non-rice graminaceous plants than older larvae (3rd to 5th instar). The results of life-table studies showed that C. medinalis developed and grew faster on rice plants than on non-rice graminaceous plants. In particular, the graminaceous crop, sugarcane Saccharum officinarum, and graminaceous weeds Miscanthus sinensis and Setaria viridis, prevented the development and ovipositing of C. medinalis. Our results showed the strong preference that C. medinalis adults had to oviposit and larvae had to develop on rice and this was highly consistent within the population tested. This indicated that oviposition preference of female C. medinalis moths might play an important role in larval host identification between rice plants and non-rice graminaceous plants.

Chemical investigation of a strain Streptomyces sp. KIB-H1318 isolated from soil sample led to the discovery of three new phenoxazinone-related alkaloids 1–3, as well as two known analogs exfoliazone (4) and viridobrunnine A (5). Their structures were determined on the basis of extensive spectroscopic analysis. The antimicrobial activity and cytotoxicity of the isolates were assayed. Exfoliazone and viridobrunnine A exhibited minor antibacterial activity against Escherichia coli ATCC 8099, Bacillus subtilis ATCC 6633, and Staphylococcus aureus ATCC 6538. Compound 2 exhibited low cytotoxicity against two human cancer cell lines HeLa and SW480 with the IC50 values of 36.8 and 37.8 μM, respectively.

This paper investigates the problem of delay-dependent dissipativity for a class of Markovian jump neural networks with a time-varying delay. A generalized integral inequality including some existing integral inequalities as special cases is established. An improved mode-dependent Lyapunov–Krasovskii functional (LKF) is constructed. Then, the new integral inequality is used to estimate the derivative of the LKF and a less conservative dissipativity criterion is derived. Based on the dissipativity criterion, a novel passivity condition for delayed neural networks is obtained. Furthermore, a new stability criterion for linear delayed systems without Markovian jump parameters is also developed. Finally, four numerical examples are presented to verify the effectiveness and superiority of the proposed method.

The production of light (anti)nuclei have been investigated using the dynamically constrained phase-space coalescence model based on the final-state hadrons generated by the PACIAE model in Cu+Cu collisions at $\sqrt{s_{\rm{NN}}}=200$GeV with $|\eta, Comment: arXiv admin note: text overlap with arXiv:1812.05148 by other authors

The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes recent progress regarding the NLRP3 inflammasome as a potential treatment for ischemic stroke in patients with diabetes, two complicated diseases that often occur together. Stroke worsens glucose metabolism abnormalities, and the outcomes after stroke are more serious for diabetic patients compared with those without diabetes. Inflammation contributes to organ injury after ischemic stroke and diabetes. Recent research has focused on inhibiting the activation of inflammasomes and thus reducing the maturation of proinflammatory cytokines such as interleukin (IL)-1β and IL-18. Studies suggest that inhibition of NLRP3 prevents or alleviates both ischemic stroke and diabetes. Targeting against the assembly and activity of the NLRP3 inflammasome is a potential and novel therapy for inflammasome-associated diseases, including ischemic stroke concomitant with diabetes.

This paper focuses on the issue of robust stability analysis for recurrent neural networks (RNNs) with leakage delay. By constructing a novel Lyapunov–Krasovskii functional together with the reciprocally convex approach and the free-weighting matrix technique, some less conservative stability criteria in terms of linear matrix inequalities for RNNs are derived. The new contribution of this paper is that a novel delay-partitioning method is proposed, and some new zero equalities are introduced. Finally, several examples are given to demonstrate the effectiveness of the proposed methods. The simulated results reveal that the leakage delay has great influence on the dynamical systems, and it cannot be neglected.

This paper is concerned with the exponential input-to-state stability for a class of stochastic neural networks with mixed delays. Based on a new Lyapunov-Krasovskii functional, Ito’s formula, Dynkin’s formula and some inequality techniques, some novel sufficient conditions ensuring the exponential input-to-state stability in the mean square for the given stochastic neural networks are derived. Some existing results are extended. Two numerical examples are provided to illustrate the effectiveness of the proposed method.

The energy dependence of light (anti)nuclei and (anti)hypertriton production are investigated in central Au-Au collisions from AGS up to LHC energies at midrapidity, using the parton and hadron cascade model (PACIAE) together with the dynamically constrained phase-space coalescence model(DCPC). We find that the yields, yield ratios of the antiparticles to their corresponding particles, the coalescence parameters $B_A$ and the strangeness population factor $s_3$ of light (anti)nuclei and (anti)hypertriton all show strong dependences on the energy. Furthermore, we analyze and discuss the strangeness population factor $s_3$ and the coalescence parameters $B_A$ , and find a transition point near 20 GeV. These results thus suggest, in relativistic heavy-ion collisions, the potential usefulness of the $s_3$ and $B_A$ of light nuclei production as an indirect probe of the transition point related to the QCD critical phenomena. The results from PACIAE+DCPC model are well consistent with experimental data within the error margin.

Ordered Fe-doped In2O3 nanodot arrays with diameters between 35 nm and 80 nm are fabricated using pulsed laser deposition with the aid of ultrathin porous anodized aluminumoxide templates. The 5 at.% Fe doped In2O3 nanodot arrays are shown to consist of the cubic bixbyite structure of In2O3. The nanodot arrays are demonstrated to be doped by Fe ions with mixed valences of +2 and +3, ruling out the presence of cluster and secondary phase related to Fe. The nanodot arrays exhibit the ferromagnetism at room temperature, where the magnetic moment increases as the dot size is reduced, rising to a maximum of about 230 emu/cm3 (equivalent to an average moment on the Fe ions of 15.30 µB/Fe). This indicates an effect due to the surface of the nanodot arrays. The optical band width is also increased to 4.55 eV for the smallest dot array, thus indicating that the surface states are responsible for the magnetism and also enhance the band gap due to Burstein-Moss effect. Our results will be benefit for understanding the physical properties of oxide semiconductor nanostructures in the application of nano-spintronics devices.

This study aims to investigate the changing characteristics of glucose regulation after gastric surgery for normal gastric cancer patients with type 2 diabetes mellitus (T2DM) (T2DM group) and without T2DM (normal group) in a tertiary hospital located in western China. We conducted a case-control study which retrospectively collected the data of 73 patients: (1) diagnosed as gastric cancer, (2) underwent sub-gastrectomy and Billroth II gastrointestinal anastomosis between October 2007 and December 2012, and (3) did not suffer a recurrent cancer and with sufficient clinical data. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin sensitive index (HOMA-IS), insulin resistance index (HOMA-IR), and beta cell function index (HOMA-BCF) were compared at baseline and postoperative 7, 14, 28, 56, 120, and 356 days. Baseline FBG, HbA1c, HOMA-IS, HOMA-IR, and HOMA-BCF in the T2DM group were significantly higher than those in the normal group. Immediate postoperative glucose changed significantly, and it became stable and normal during follow-up period in both the T2DM and normal group that there was no significance anymore after postoperative 28 days between them. Normal patients with T2DM would benefit from gastric surgery in glucose control, and it may involve not only decreased food intake and weight loss but also gastrointestinal reconstruction.

Powdery mildew caused by Podosphaera xanthii (P. xanthii) is one of important diseases in melon. We have previously investigated the differential gene expression in the incompatible P. xanthii-melon interactions and identified one EST containing homologous sequences to S-adenosylmethionine decarboxylase (SAMDC) cDNA. Given this, SAMDC gene of Cucumis melo was cloned and designated as CmSAMDC in this study. It was 1,095 bp long and encoded a 364-amino acid peptide with a molecular mass of 40 kD. By sequence analyzing, the deduced CmSAMDC protein was shown to have two conserved regions of a putative proenzyme cleavage site and a PEST domain. In addition, the expressions of CmSAMDC in the resistant melon materials increased more sharply than in the susceptible the melon materials, and the higher polyamines (PAs) and hydrogen peroxide (H2O2) contents in resistant melon materials were found as well, which were accompanied by up-regulation of the stress-responsive defense enzyme activities. Over-expression of CmSAMDC in Arabidopsis resulted in greatly reduced pathogen infection in the inoculated leaves of transgenic lines, enhanced resistance to powdery mildew, and the enhanced resistance appeared to be associated with pathogen-induced cell death. Taken together, our results suggested that CmSAMDC and perhaps its orthologous genes might be involved in responses of plants to biotrophic pathogens.

Local anaesthetics (LAs) may lead to neurological complications, but the underlying mechanism is still unclear. Many neurotoxicity research studies have examined different LAs, but none have comprehensively explored the distinct mechanisms of neurotoxicity caused by amide- (bupivacaine) and ester- (procaine) type LAs. Here, based on a CCK8 assay, LDH assay, Rhod-2-AM and JC-1 staining, 2′,7′-dichlorohy-drofluorescein diacetate and dihydroethidium probes, an alkaline comet assay, and apoptosis assay, we show that both bupivacaine and procaine significantly induce mitochondrial calcium overload and a decline in the mitochondrial membrane potential as well as overproduction of ROS, DNA damage and apoptosis (P 0.05). However, to our surprise, the superoxide anionic level after treatment with bupivacaine, which leads to more severe DNA damage, was higher than the level after treatment with procaine, while procaine produced more peroxidation than bupivacaine. Some of these results were also affirmed in dorsal root ganglia neurons of C57 mice. The differences in the superoxidation and peroxidation induced by these agents suggest that different types of LAs may cause neurotoxicity via different pathways. We can target more accurate treatment based on their different mechanisms of neurotoxicity.

To investigate climate evolution during the Miocene, especially during the Middle Miocene climate transition on the northeastern Tibetan Plateau, stable oxygen and carbon isotopes of carbonates from a 288-m-thick lacustrine-fluvial sediment sequence covering the period from 17.1 to 6.1 Ma from Tianshui Basin, China, were analyzed. The relatively low stable oxygen isotope values indicate the prevalence of wet climate conditions during the period of 17.1-13.6 Ma, an interval corresponding to the well-known Middle Miocene Climate Optimum. The interval between 13.6 and 11.0 Ma (i.e., the late Middle Miocene) is marked by a progressive increase in the delta O-18 values, indicative of a decrease in precipitation, probably linked to the expansion of the East Antarctic Ice Sheet and global cooling since about 14 Ma. The climate in the study area continued to get drier as shown by the enrichment of the heavy oxygen isotope from 11 Ma. We attribute these stepwise climatic changes as revealed by our carbonate delta O-18 record from the northeastern Tibetan Plateau to the sustained global cooling that may have reduced moist transport to Central Asia, which in turn led to a permanent aridification.