The scaling of elemental stoichiometry and growth rate over the course of bamboo ontogeny.

Stoichiometric rules may explain the allometric scaling among biological traits and body size, a fundamental law of nature. However, testing the scaling of elemental stoichiometry and growth to size over the course of plant ontogeny is challenging. Here, we used a fast-growing bamboo species to examine how the concentrations and contents of carbon (C), nitrogen (N) and phosphorus (P), relative growth rate (G), and nutrient productivity scale with whole-plant mass (M) at the culm elongation and maturation stages. The whole-plant C content vs M and N content vs P content scaled isometrically, and the N or P content vs M scaled as a general 3/4 power function across both growth stages. The scaling exponents of G vs M and N (and P) productivity in newly grown mass vs M relationships across the whole growth stages decreased as a -1 power function. These findings reveal the previously undocumented generality of stoichiometric allometries over the course of plant ontogeny and provide new insights for understanding the origin of ubiquitous quarter-power scaling laws in the biosphere.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Enhancement Effect Induced by the Second Metal to Promote Ozone Catalytic Oxidation of VOCs.

It is a promising research direction to develop catalysts with high stability and ozone utilization for low-temperature ozone catalytic oxidation of VOCs. While bimetallic catalysts exhibit excellent catalytic activity compared with conventional single noble metal catalysts, limited success has been achieved in the influence of the bimetallic effect on the stability and ozone utilization of metal catalysts. Herein, it is necessary to systematically study the enhancement effect in the ozone catalytic reaction induced by the second metal. With a simple continuous impregnation method, a platinum-cerium bimetallic catalyst is prepared. Also highlighted are studies from several aspects of the contribution of the second metal (Ce) to the stability and ozone utilization of the catalysts, including the "electronic effect" and "geometric effect". The synergistic removal rate of toluene and ozone is nearly 100% at 30 °C, and it still shows positive stability after high humidity and a long reaction time. More importantly, the instructive significance, which is the in-depth knowledge of enhanced catalytic mechanism of bimetallic catalysts resulting from a second metal, is provided by this work.

Employing Mobile Learning in Music Education.

This study sought to evaluate the effectiveness of introducing digital software in music education to improve academic performance and solfeggio class attendance. To assess academic performance, a test consisting of 25 theoretical questions and 25 practical tasks was developed. The Bologna model was used as an assessment system. The groups were compared by calculating the Student's t-test in terms of the "Test Score" and "Missed Classes" parameters. The collected data revealed that the mean score for the experimental group was 87.50 out of 100, while in the control group, it was much lower, namely 65.37. Likewise, the control group was characterized by satisfactory (D) performance in mastering solfeggio, with the mean score ranging between 64 and 73, whereas experimental group participants had an average of 82-89. The statistical data processing results showed that the six-month use of the ChordIQ app contributed to more effective mastering of solfeggio by amateur musicians. At the same time, the difference between the groups turned out to be significant in both cases, so the research hypothesis was confirmed for both of them (p < 0.05). Overall, the results showed that ChordIQ is a useful mobile app teaching the user music in an exciting and interactive way. The findings collected can be used to update traditional solfeggio curricula, conduct scientific studies in the field of interactive music education, as well as create new dedicated software.

Environmentally Benign and User-Friendly In Situ Generation of Nitrile Imines from Hydrazones for 1,3-Dipolar Cycloaddition.

Nitrile imines are highly reactive and versatile dipoles and conventionally generated in situ from unstable hydrazonyl halides under basic conditions. Herein, we report the first green and user-friendly protocol for in situ generation of nitrile imines from Oxone-KBr oxidation of hydrazones and base-promoted dehydrobromination. The nitrile imines were demonstrated for 1,3-dipolar cycloaddition with various dipolarophiles, including alkene and alkyne groups. With its green nature, ease of operation, and air and moisture tolerance, we expect our method will find wide applications in organic synthesis.

A multicenter analysis of genomic profiles and PD-L1 expression of primary lymphoepithelioma-like carcinoma of the lung.

To understand the molecular mechanism of tumorigenesis of pulmonary lymphoepithelioma-like carcinoma and explore potential therapeutic strategies, we investigated the genomic profiles and PD-L1 expression of 29 Chinese pulmonary lymphoepithelioma-like carcinoma patients at various stages. We performed capture-based targeted sequencing on tissue samples collected from 27 patients with sufficient samples using a panel consisting of 520 cancer-related genes, spanning 1.64 Mb of the human genome. We identified 184 somatic mutations in 109 genes from 26 patients. One patient had no mutations detected by this panel. Copy number variations were detected in 52% (14/27) of the patients, with a majority having advanced-stage disease (10/14). Except for the detection of ERBB2 amplification and KRAS mutation in two patients, no other classic lung cancer driver mutations were detected. Interestingly, 78% (21/27) of the patients had mutations in epigenetic regulators. Of the 184 mutations identified, 51 occurred in 29 epigenetics-related genes. Furthermore, we performed PD-L1 immunohistochemistry staining using the Dako 22C3 assay and demonstrated that 69% (20/29) of the cohort had positive PD-L1 expression, of which three patients received and benefited from a PD-1 inhibitor. In conclusion, we elucidated a distinct genomic landscape associated with pulmonary lymphoepithelioma-like carcinoma with no classic lung cancer driver mutation but an enrichment of mutations in epigenetic regulators. The detection of high PD-L1 expression and lack of any canonical druggable driver mutations raises the potential of checkpoint immunotherapy for pulmonary lymphoepithelioma-like carcinoma.

A Novel Intelligent Fault Diagnosis Method for Rolling Bearing Based on Integrated Weight Strategy Features Learning.

Intelligent methods have long been researched in fault diagnosis. Traditionally, feature extraction and fault classification are separated, and this process is not completely intelligent. In addition, most traditional intelligent methods use an individual model, which cannot extract the discriminate features when the machines work in a complex condition. To overcome the shortcomings of traditional intelligent fault diagnosis methods, in this paper, an intelligent bearing fault diagnosis method based on ensemble sparse auto-encoders was proposed. Three different sparse auto-encoders were used as the main architecture. To improve the robustness and stability, a novel weight strategy based on distance metric and standard deviation metric was employed to assign the weights of three sparse auto-encodes. Softmax classifier is used to classify the fault types of integrated features. The effectiveness of the proposed method is validated with extensive experiments, and comparisons with the related methods and researches on the widely-used motor bearing dataset verify the superiority of the proposed method. The results show that the testing accuracy and the standard deviation are 99.71% and 0.05%.

Concise Total Synthesis and Antifungal Activities of Fusaric Acid, a Natural Product.

The total synthesis of a natural product alkaloid fusaric acid (FA), which exhibits herbicide, fungicide, insecticide and even diverse notable pharmacological activities, was accomplished in four steps using commercially available materials. The synthesis, based on a unified and flexible strategy using 6-bromonicotinaldehyde as a common intermediate, is concise, convergent, practical and can be carried out on a two-gram scale. This approach could be readily applicable to the synthesis of its analogues. In addition, FA had a wide range of inhibitory activities against 14 plant pathogenic fungi in this study, which demonstrated that as a leading compound, and it has great potential to be further developed as an agricultural fungicide.

Recent Advances in the Reactions of Cyclic Carbynes.

The acyclic organic alkynes and carbyne bonds exhibit linear shapes. Metallabenzynes and metallapentalynes are six- or five-membered metallacycles containing carbynes, whose carbine-carbon bond angles are less than 180°. Such distortion results in considerable ring strain, resulting in the unprecedented reactivity compared with acyclic carbynes. Meanwhile, the aromaticity of these metallacycles would stabilize the ring system. The fascinating combination of ring strain and aromaticity would lead to interesting reactivities. This mini review summarized recent findings on the reactivity of the metal-carbon triple bonds and the aromatic ring system. In the case of metallabenzynes, aromaticity would prevail over ring strain. The reactions are similar to those of organic aromatics, especially in electrophilic reactions. Meanwhile, fragmentation of metallacarbynes might be observed via migratory insertion if the aromaticity of metallacarbynes is strongly affected. In the case of metallapentalynes, the extremely small bond angle would result in high reactivity of the carbyne moiety, which would undergo typical reactions for organic alkynes, including interaction with coinage metal complexes, electrophilic reactions, nucleophilic reactions and cycloaddition reactions, whereas the strong aromaticity ensured the integrity of the bicyclic framework of metallapentalynes throughout all reported reaction conditions.

Successful therapy with bevacizumab combined with corticosteroids for crizotinib-induced interstitial lung disease.

We present the case of an old woman with ALK-rearranged stage IV lung adenocarcinoma who received crizotinib. She presented with severe dyspnea on the 34th day, and diffuse ground-glass opacifications in her chest. A diagnosis of crizotinib-induced ILD was confirmed. Corticosteroids were administered. However, the disease was still progressing rapidly. Therefore, as a monoclonal antibody against vascular endothelial growth factor, bevacizumab was administered in low doses (200 mg on days one and three). Her symptoms began to improve. Our clinical experience indicates that bevacizumab combined with corticosteroids might be a promising treatment in crizotinib-induced ILD patients.

Concise and Gram-Scale Total Synthesis of Lansiumamides A and B and Alatamide.

The total synthesis of potent anti-obesity lansiumamide B was accomplished in four steps using commercially available materials. The synthetic strategy, featured with copper-catalyzed Buchwald coupling, is concise, convergent, practical and can be carried out on a one-gram scale. This approach could give either Z- or E-configured enamide moiety in natural products with absolute stereocontrol and was applied in the total synthesis of natural products.

Bayesian semiparametric failure time models for multivariate censored data with latent variables.

In this paper, we propose a semiparametric failure time model to analyze multivariate censored data with latent variables. The proposed model generalizes the conventional accelerated failure time model to accommodate latent risk factors that could be measured by multiple observed variables through a factor analysis and to incorporate additive nonparametric functions of observed and latent risk factors to examine their functional effects on multivariate failure times of interest. A Bayesian approach, along with Bayesian P-splines and Markov chain Monte Carlo techniques, is developed to estimate the unknown parameters and functions. The empirical performance of the proposed methodology is evaluated by a simulation study. An application to a study on the risk factors of two diabetes complications is presented.

tRNA is a new target for cleavage by a MazF toxin.

Toxin-antitoxin (TA) systems play key roles in bacterial persistence, biofilm formation and stress responses. The MazF toxin from the Escherichia coli mazEF TA system is a sequence- and single-strand-specific endoribonuclease, and many studies have led to the proposal that MazF family members exclusively target mRNA. However, recent data indicate some MazF toxins can cleave specific sites within rRNA in concert with mRNA. In this report, we identified the repertoire of RNAs cleaved by Mycobacterium tuberculosis toxin MazF-mt9 using an RNA-seq-based approach. This analysis revealed that two tRNAs were the principal targets of MazF-mt9, and each was cleaved at a single site in either the tRNA(Pro14) D-loop or within the tRNA(Lys43) anticodon. This highly selective target discrimination occurs through recognition of not only sequence but also structural determinants. Thus, MazF-mt9 represents the only MazF family member known to target tRNA and to require RNA structure for recognition and cleavage. Interestingly, the tRNase activity of MazF-mt9 mirrors basic features of eukaryotic tRNases that also generate stable tRNA-derived fragments that can inhibit translation in response to stress. Our data also suggest a role for tRNA distinct from its canonical adapter function in translation, as cleavage of tRNAs by MazF-mt9 downregulates bacterial growth.

Bayesian Diagnostics of Hidden Markov Structural Equation Models with Missing Data.

Cocaine is a type of drug that functions to increase the availability of the neurotransmitter dopamine in the brain. However, cocaine dependence or abuse is highly related to an increased risk of psychiatric disorders and deficits in cognitive performance, attention, and decision-making abilities. Given the chronic and persistent features of drug addiction, the progression of abstaining from cocaine often evolves across several states, such as addiction to, moderate dependence on, and swearing off cocaine. Hidden Markov models (HMMs) are well suited to the characterization of longitudinal data in terms of a set of unobservable states, and have increasingly been used to uncover the dynamic heterogeneity in progressive diseases or activities. However, the existence of outliers or influential points may misidentify the hidden states and distort the associated inference. In this study, we develop a Bayesian local influence procedure for HMMs with latent variables in the presence of missing data. The proposed model enables us to investigate the dynamic heterogeneity of multivariate longitudinal data, reveal how the interrelationships among latent variables change from one state to another, and simultaneously conduct statistical diagnosis for the given data, model assumptions, and prior inputs. We apply the proposed procedure to analyze a dataset collected by the UCLA center for advancing longitudinal drug abuse research. Several outliers or influential points that seriously influence estimation results are identified and removed. The proposed procedure also discovers the effects of treatment and individuals' psychological problems on cocaine use behavior and delineates their dynamic changes across the cocaine-addiction states.

New Alkaloid and Aromatic Glucoside from the Flowers of Cymbidium Lunagrad Eternal Green.

In this paper, we investigated the chemical components of the flowers of Cymbidium Lunagrad Eternal Green for the first time. In the whole post-fertilization, a new alkaloid, named Lunagrad A (1), and a new aromatic glucoside, named Lunagrad B (2), were isolated from the MeOH extract of the flowers of Cymbidium Lunagrad Eternal Green, along with other six known aromatic compounds (3-8) and three flavone glucosides (9-11). These structures were determined on the basis of NMR experiments, as well as chemical evidence.

Synthesis and Fungicidal Activity of Lansiumamide A and B and Their Derivatives.

A efficient 2-step protocol has been applied for the synthesis of Lansiumamide B (N-methyl-N-cis-styryl-cinnamamide, 2) derivatives by various substitution on the amide nitrogen with alkyl, allyl, propargyl, benzyl or ester groups. The structures of nine new compounds were characterized by HRMS, ¹H NMR, and 13C NMR spectra. These compounds were tested in vitro against 10 strains of phytopathogenic fungi and showed a wide antifungal spectrum. The relationship between different substituents on the amide nitrogen and antifungal activity of Lansiumamide B derivatives were compared and analyzed. The result indicates that the length and steric hindrance of N-substitution have a significant impact on biological activities. It is noteworthy that the methyl or ethyl substituent on the amide nitrogen is critical for the antifungal activities.

Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site.

The Mycobacterium tuberculosis genome contains an unusually high number of toxin-antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin-antitoxin loci belong to the mazEF family, encoding the intracellular toxin MazF and its antitoxin inhibitor MazE. Nearly every MazF ortholog recognizes a unique three- or five-base RNA sequence and cleaves mRNA. As a result, these toxins selectively target a subset of the transcriptome for degradation and are known as "mRNA interferases." Here we demonstrate that a MazF family member from M. tuberculosis, MazF-mt6, has an additional role--inhibiting translation through targeted cleavage of 23S rRNA in the evolutionarily conserved helix/loop 70. We first determined that MazF-mt6 cleaves mRNA at (5')UU↓CCU(3') sequences. We then discovered that MazF-mt6 also cleaves M. tuberculosis 23S rRNA at a single UUCCU in the ribosomal A site that contacts tRNA and ribosome recycling factor. To gain further mechanistic insight, we demonstrated that MazF-mt6-mediated cleavage of rRNA can inhibit protein synthesis in the absence of mRNA cleavage. Finally, consistent with the position of 23S rRNA cleavage, MazF-mt6 destabilized 50S-30S ribosomal subunit association. Collectively, these results show that MazF toxins do not universally act as mRNA interferases, because MazF-mt6 inhibits protein synthesis by cleaving 23S rRNA in the ribosome active center.

[Clinical efficacy of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy].

OBJECTIVE: To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy. METHODS: Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 µg folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 µg vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 µg folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 µg vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy. RESULTS: The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non-blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05). CONCLUSIONS: Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment.

The slow afterhyperpolarization: a target of ß1-adrenergic signaling in hippocampus-dependent memory retrieval.

In rodents, adrenergic signaling by norepinephrine (NE) in the hippocampus is required for the retrieval of intermediate-term memory. NE promotes retrieval via the stimulation of ß1-adrenergic receptors, the production of cAMP, and the activation of both protein kinase A (PKA) and the exchange protein activated by cAMP. However, a final effector for this signaling pathway has not been identified. Among the many targets of adrenergic signaling in the hippocampus, the slow afterhyperpolarization (sAHP) is an appealing candidate because its reduction by ß1 signaling enhances excitatory neurotransmission. Here we report that reducing the sAHP is critical for the facilitation of retrieval by NE. Direct blockers of the sAHP, as well as blockers of the L-type voltage-dependent calcium influx that activates the sAHP, rescue retrieval in mutant mice lacking either NE or the ß1 receptor. Complementary to this, a facilitator of L-type calcium influx impairs retrieval in wild-type mice. In addition, we examined the role of NE in the learning-related reduction of the sAHP observed ex vivo in hippocampal slices. We find that this reduction in the sAHP depends on the induction of persistent PKA activity specifically in conditioned slices. Interestingly, this persistent PKA activity is induced by NE/ß1 signaling during slice preparation rather than during learning. These observations suggest that the reduction in the sAHP may not be present autonomously in vivo, but is likely induced by neuromodulatory input, which is consistent with the idea that NE is required in vivo for reduction of the sAHP during memory retrieval.