Large-scale multiplexed mosaic CRISPR perturbation in the whole organism.

Here, we report inducible mosaic animal for perturbation (iMAP), a transgenic platform enabling in situ CRISPR targeting of at least 100 genes in parallel throughout the mouse body. iMAP combines Cre-loxP and CRISPR-Cas9 technologies and utilizes a germline-transmitted transgene carrying a large array of individually floxed, tandemly linked gRNA-coding units. Cre-mediated recombination triggers expression of all the gRNAs in the array but only one of them per cell, converting the mice to mosaic organisms suitable for phenotypic characterization and also for high-throughput derivation of conventional single-gene perturbation lines via breeding. Using gRNA representation as a readout, we mapped a miniature Perturb-Atlas cataloging the perturbations of 90 genes across 39 tissues, which yields rich insights into context-dependent gene functions and provides a glimpse of the potential of iMAP in genome decoding.

Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma.

ABSTRACT: B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with teclistamab, a CD3 × BCMA bispecific antibody, 42% (30/72) of whom had prior BCMA-directed therapy exposure. Malignant plasma cell BCMA expression was present in all BCMA therapy-naïve patients. Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and 1 of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from 1 patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.

The Complete Genomic Sequence of Microbial Transglutaminase Producer, Streptomyces mobaraensis DSM40587.

Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites.

H2 S works synergistically with rhizobia to modify photosynthetic carbon assimilation and metabolism in nitrogen-deficient soybeans.

Hydrogen sulfide (H2 S) performs a crucial role in plant development and abiotic stress responses by interacting with other signalling molecules. However, the synergistic involvement of H2 S and rhizobia in photosynthetic carbon (C) metabolism in soybean (Glycine max) under nitrogen (N) deficiency has been largely overlooked. Therefore, we scrutinised how H2 S drives photosynthetic C fixation, utilisation, and accumulation in soybean-rhizobia symbiotic systems. When soybeans encountered N deficiency, organ growth, grain output, and nodule N-fixation performance were considerably improved owing to H2 S and rhizobia. Furthermore, H2 S collaborated with rhizobia to actively govern assimilation product generation and transport, modulating C allocation, utilisation, and accumulation. Additionally, H2 S and rhizobia profoundly affected critical enzyme activities and coding gene expressions implicated in C fixation, transport, and metabolism. Furthermore, we observed substantial effects of H2 S and rhizobia on primary metabolism and C-N coupled metabolic networks in essential organs via C metabolic regulation. Consequently, H2 S synergy with rhizobia inspired complex primary metabolism and C-N coupled metabolic pathways by directing the expression of key enzymes and related coding genes involved in C metabolism, stimulating effective C fixation, transport, and distribution, and ultimately improving N fixation, growth, and grain yield in soybeans.

[Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza].

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

Interactions between hydrogen sulphide and rhizobia modulate the physiological and metabolism process during water deficiency-induced oxidative defense in soybean.

Hydrogen sulphide (H2 S), a new gas signal molecule, participates in the regulation of various abiotic stresses in plants. However, how the tandem working of H2 S and rhizobia affects the adaptation of soybean to water deficiency is still unclear. In this study, we investigated the adaptation mechanism of H2 S and rhizobia in soybean to water deficiency. Our results revealed that H2 S and rhizobia jointly enhanced the leaf chlorophyll content and relative water content in plants, and caused an increase in the biomass of soybean seedlings under water deficiency. Besides, in the absence of water, H2 S enhanced the biomass by affecting the number of nodules and nitrogenase activity during vegetative growth. The expression of nodulation marker genes including early nodulin 40 (GmENOD40), ERF required for nodulation (GmERN) and nodulation inception genes (GmNIN1a, GmNIN2a and GmNIN2b) were upregulated by H2 S and rhizobia in the nodules. Moreover, the combined effect of H2 S and rhizobia was proved to affect the enzyme activities and gene expression level of antioxidants, as well as osmotic protective substance content and related gene expression levels under water deficiency in soybean seedlings. In addition, the metabolomic results suggested that the combined effect of H2 S and rhizobia remarkably promoted the contents of lipids and lipid-like molecules. Our results indicated that H2 S and rhizobia synergistically reduced the oxidative damage caused by water deficiency through increasing the accumulation of metabolites and strengthening the plant antioxidant capacity.

Analysis of Frank-Kamenetskii thermal explosion system of non-class a geometry based on Boltzmann method.

Exothermic reaction systems of non-class A geometries are very common, with an endless rectangular rod typical. As a strong nonlinear source word is included in the governing equation, which is sensitive to the frank-kamenetskii parameter, there is no analytical solution. Many methods were previously suggested. However, with them are often non-physical solutions obtained. In this paper, the lattice Boltzmann process provides us with complete physical and precise solutions. We also analysed the sensitivity of the strong nonlinear source term and suggested advice for similar numerical calculations and experiments with thermal explosion.

Predicting disease progression in advanced non-small cell lung cancer with circulating neutrophil-derived and platelet-derived microparticles.

BACKGROUND: Microparticles (MPs) are extracellular vesicles that are associated with cancer development and progression. Advanced non-small cell lung cancer (NSCLC) still shows disease progression after multiple lines of treatment. Therefore, the objective of this study was to explore the correlation between circulating MPs and disease progression in advanced NSCLC, and to find a new method for concise and rapid determination of disease progression. METHODS: Patients with advanced NSCLC admitted to hospital between October 2019 and October 2020 were included and divided into objective remission (OR) and progressive disease (PD) groups. The morphology of MPs was observed using transmission electron microscopy. The circulating total MPs, neutrophil MPs (NMPs), and platelet MPs (PMPs) before and after treatment were detected by flow cytometry, and a predictive model for disease progression in advanced NSCLC was developed. RESULTS: Eighty-six patients were included; 60 in the OR group and 26 in the PD group. There was no significant difference in total MPs, NMPs, or PMPs at baseline between the two groups. After treatment, total MPs, NMPs, and PMPs were significantly higher in the PD than those in the OR group. Multivariate regression analysis showed that post-treatment NMPs≥160 events/µL(OR,3.748;95%CI,1.147-12.253,p = 0.029), PMPs≥80 events/µL(OR,10.968;95%CI,2.973-40.462,p < 0.0001) and neutrophil/lymphocyte ratio (NLR) ≥3.3 (OR,4.929;95%CI,1.483-16.375,p = 0.009) were independently associated with progression of advanced NSCLC. Post-treatment NMPs and PMPs combined with NLR were used to build a predictive model for progression of advanced NSCLC. The area under the curve was 0.825 (95%CI,0.715-0.934, p < 0.0001), optimal cut-off value was 16, sensitivity was 80.8%, and specificity was 88.3%. CONCLUSION: NMPs and PMPs are associated with progression of advanced NSCLC. The predictive model for progression of advanced NSCLC, established combining NMPs, PMPs, and NLR, can screen out 80.8% of patients with PD. This is helpful for real-time accurate, concise and rapid assessment of disease progression and timely adjustment of drug therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020223 . Registered 20 December 2018, http://www.chictr.org.cn/index.aspx .

Hydrogen sulphide alleviates iron deficiency by promoting iron availability and plant hormone levels in Glycine max seedlings.

BACKGROUND: Hydrogen sulphide (H2S) is involved in regulating physiological processes in plants. We investigated how H2S ameliorates iron (Fe) deficiency in soybean (Glycine max L.) seedlings. Multidisciplinary approaches including physiological, biochemical and molecular, and transcriptome methods were used to investigate the H2S role in regulating Fe availability in soybean seedlings. RESULTS: Our results showed that H2S completely prevented leaf interveinal chlorosis and caused an increase in soybean seedling biomass under Fe deficiency conditions. Moreover, H2S decreased the amount of root-bound apoplastic Fe and increased the Fe content in leaves and roots by regulating the ferric-chelate reductase (FCR) activities and Fe homeostasis- and sulphur metabolism-related gene expression levels, thereby promoting photosynthesis in soybean seedlings. In addition, H2S changed the plant hormone concentrations by modulating plant hormone-related gene expression abundances in soybean seedlings grown in Fe-deficient solution. Furthermore, organic acid biosynthesis and related genes expression also played a vital role in modulating the H2S-mediated alleviation of Fe deficiency in soybean seedlings. CONCLUSION: Our results indicated that Fe deficiency was alleviated by H2S through enhancement of Fe acquisition and assimilation, thereby regulating plant hormones and organic acid synthesis in plants.

Hydrogen sulfide and rhizobia synergistically regulate nitrogen (N) assimilation and remobilization during N deficiency-induced senescence in soybean.

Hydrogen sulfide (H2 S) is emerging as an important signalling molecule that regulates plant growth and abiotic stress responses. However, the roles of H2 S in symbiotic nitrogen (N) assimilation and remobilization have not been characterized. Therefore, we examined how H2 S influences the soybean (Glycine max)/rhizobia interaction in terms of symbiotic N fixation and mobilization during N deficiency-induced senescence. H2 S enhanced biomass accumulation and delayed leaf senescence through effects on nodule numbers, leaf chlorophyll contents, leaf N resorption efficiency, and the N contents in different tissues. Moreover, grain numbers and yield were regulated by H2 S and rhizobia, together with N accumulation in the organs, and N use efficiency. The synergistic effects of H2 S and rhizobia were also demonstrated by effects on the enzyme activities, protein abundances, and gene expressions associated with N metabolism, and senescence-associated genes (SAGs) expression in soybeans grown under conditions of N deficiency. Taken together, these results show that H2 S and rhizobia accelerate N assimilation and remobilization by regulation of the expression of SAGs during N deficiency-induced senescence. Thus, H2 S enhances the vegetative and reproductive growth of soybean, presumably through interactions with rhizobia under conditions of N deficiency.

Insect pathogenic fungus interacts with the gut microbiota to accelerate mosquito mortality.

The insect gut microbiota plays crucial roles in modulating the interactions between the host and intestinal pathogens. Unlike viruses, bacteria, and parasites, which need to be ingested to cause disease, entomopathogenic fungi infect insects through the cuticle and proliferate in the hemolymph. However, interactions between the gut microbiota and entomopathogenic fungi are unknown. Here we show that the pathogenic fungus Beauveria bassiana interacts with the gut microbiota to accelerate mosquito death. After topical fungal infection, mosquitoes with gut microbiota die significantly faster than mosquitoes without microbiota. Furthermore, fungal infection causes dysbiosis of mosquito gut microbiota with a significant increase in gut bacterial load and a significant decrease in bacterial diversity. In particular, the opportunistic pathogenic bacterium Serratia marcescens overgrows in the midgut and translocates to the hemocoel, which promotes fungal killing of mosquitoes. We further reveal that fungal infection down-regulates antimicrobial peptide and dual oxidase expression in the midgut. Duox down-regulation in the midgut is mediated by secretion of the toxin oosporein from B. bassiana Our findings reveal the important contribution of the gut microbiota in B. bassiana-killing activity, providing new insights into the mechanisms of fungal pathogenesis in insects.

Hydrogen Sulfide Promotes Nodulation and Nitrogen Fixation in Soybean-Rhizobia Symbiotic System.

The rhizobium-legume symbiotic system is crucial for nitrogen cycle balance in agriculture. Hydrogen sulfide (H2S), a gaseous signaling molecule, may regulate various physiological processes in plants. However, whether H2S has regulatory effect in this symbiotic system remains unknown. Herein, we investigated the possible role of H2S in the symbiosis between soybean (Glycine max) and rhizobium (Sinorhizobium fredii). Our results demonstrated that an exogenous H2S donor (sodium hydrosulfide [NaHS]) treatment promoted soybean growth, nodulation, and nitrogenase (Nase) activity. Western blotting analysis revealed that the abundance of Nase component nifH was increased by NaHS treatment in nodules. Quantitative real-time polymerase chain reaction data showed that NaHS treatment upregulated the expressions of symbiosis-related genes nodA, nodC, and nodD of S. fredii. In addition, expression of soybean nodulation marker genes, including early nodulin 40 (GmENOD40), ERF required for nodulation (GmERN), nodulation signaling pathway 2b (GmNSP2b), and nodulation inception genes (GmNIN1a, GmNIN2a, and GmNIN2b), were upregulated. Moreover, the expressions of glutamate synthase (GmGOGAT), asparagine synthase (GmAS), nitrite reductase (GmNiR), ammonia transporter (GmSAT1), leghemoglobin (GmLb), and nifH involved in nitrogen metabolism were upregulated in NaHS-treated soybean roots and nodules. Together, our results suggested that H2S may act as a positive signaling molecule in the soybean-rhizobia symbiotic system and enhance the system's nitrogen fixation ability.

PD-L1 over-expression is driven by B-cell receptor signaling in diffuse large B-cell lymphoma.

Targeting the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway represents a milestone in cancer therapy. However, the biologic features of diffuse large B-cell lymphoma (DLBCL) with PD-L1 expression remains unknown. We evaluated the correlation between pSYK and PD-L1 mRNA levels with RNAscope in situ hybridization and protein levels with immunohistochemistry in 108 cases of DLBCL, 25 of which featured loss of B-cell receptor (BCR), and investigated the effects of BCR signaling and MYC on PD-L1 mRNA and protein level with qPCR, immunoblotting and flow cytometery in DLBCL cell lines. PD-L1 amplification was detected with fluorescent in situ hybridization. Animal studies were applied to validate the in vitro findings. pSYK and MYC correlated with both PD-L1 mRNA and protein level. Genetic aberrations involving PD-L1 were rare in DLBCL. BCR signaling and MYC increased PD-L1 mRNA and protein expression. Inhibition of BCR signaling and BCR knockdown down-regulated PD-L1. DLBCL with a loss of loss of BCR showed low levels of PD-L1 mRNA and protein. PD-L1 was down-regulated by ibrutinib in a xenograft mouse model and correlated with slower tumor growth. In conclusion, this study demonstrates that DLBCL with PD-L1 expression features an activated B-cell receptor signal pathway, and that BCR inhibition and PD-L1 blockage may potentially synergize to targeting DLBCL.

Mitsuaria noduli sp. nov., isolated from the root nodules of Robinia pseudoacacia in a lead-zinc mine.

A novel endophytic bacterium, designated strain HZ7T, was isolated from the root nodules of Robinia pseudoacacia growing in a lead-zinc mine in Mianxian County, Shaanxi Province, China. Cells were Gram-reaction-negative, aerobic, motile, rod-shaped, methyl-red-negative, catalase-positive, positive for chitosan-degrading activity and did not produce H2S. Strain HZ7T grew at 4-45 °C (optimum 25-30 °C), at pH 5-9 (optimum pH 7-8) and with 0-1 % (w/v) NaCl. The quinone type was ubiquinone 8 (UQ-8). The major fatty acids were identified as C16 : 0, C17 : 0 cyclo and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The G+C content of the genomic DNA was 68.5 mol% by whole genome sequencing. According to 16S rRNA gene sequence analysis, the closest phylogenetic relative was Mitsuaria chitosanitabida 3001T (99.05 % similarity). Genome relatedness was computed using average nucleotide identity and genome-to-genome distance analysis, both of which strongly supported strain HZ7Tas belonging to the genus Mitsuaria as a representative of a novel species. On the basis of phylogenetic analysis, chemotaxonomic data and physiological characteristics, strain HZ7T represents a novel species of the genus Mitsuaria, for which the name Mitsuaria noduli sp. nov. is proposed. The type strain is HZ7T (=JCM 31671T=CCTCC AB 2014353T).

Herbaspirillum robiniae sp. nov., isolated from root nodules of Robinia pseudoacacia in a lead-zinc mine.

A novel endophytic bacterium, designated strain HZ10T, was isolated from root nodules of Robinia pseudoacacia growing in a lead-zinc mine in Mianxian County, Shaanxi Province, China. The bacterium was Gram-stain-negative, aerobic, motile, slightly curved- and rod-shaped, methyl red-negative, catalase-positive, and did not produce H2S. Strain HZ10T grew at 4-45 °C (optimum, 25-30 °C), pH 5-9 (optimum, pH 7-8) and 0-1 % (w/v) NaCl. The major fatty acids were identified as C16 : 0, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), and the quinone type was Q-8. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of the genomic DNA was 64.9 mol% based on the whole genome sequence. According to the 16S rRNA gene sequence analysis, the closest phylogenetic relative to strain HZ10T is Herbaspirillum chlorophenolicum CPW301T (98.72 % sequence identity). Genome relatedness of the type strains H. chlorophenolicum CPW301T, Herbaspirillum seropedicae Z67T and Herbaspirillum aquaticum IEH 4430T, was quantified by using the average nucleotide identity (86.9-88.0 %) and a genome-to-genome distance analysis (26.6 %-29.3 %), with both strongly supporting the notion that strain HZ10T belongs to the genus Herbaspirillum as a novel species. Based on the results from phylogenetic, chemotaxonomic and physiological analyses, strain HZ10T represents a novel Herbaspirillum species, for which the name Herbaspirillum robiniae sp. nov. is proposed. The type strain is HZ10T (=JCM 31754T=CCTCC AB 2014352T).

Rhizobium inoculation enhances copper tolerance by affecting copper uptake and regulating the ascorbate-glutathione cycle and phytochelatin biosynthesis-related gene expression in Medicago sativa seedlings.

Despite numerous reports that legume-rhizobium symbiosis alleviates Cu stress in plants, the possible roles of legume-rhizobium symbiosis and the regulatory mechanisms in counteracting Cu toxicity remain unclear. Here, Sinorhizobium meliloti CCNWSX0020 was used for analyzing the effects of rhizobium inoculation on plant growth in Medicago sativa seedlings under Cu stress. Our results showed that rhizobium inoculation alleviated Cu-induced growth inhibition, and increased nitrogen concentration in M. sativa seedlings. Moreover, the total amount of Cu uptake in inoculated plants was significantly increased compared with non-inoculated plants, and the increase in the roots was much higher than that in the shoots, thus decreasing the transfer coefficient and promoting Cu phytostabilization. Cu stress induced lipid peroxidation and reactive oxygen species production, but rhizobium inoculation reduced these components' accumulation through altering antioxidant enzyme activities and regulating ascorbate-glutathione cycles. Furthermore, legume-rhizobium symbiosis regulated the gene expression involved in antioxidant responses, phytochelatin (PC) biosynthesis, and metallothionein biosynthesis in M. sativa seedlings under Cu stress. Our results demonstrate that rhizobium inoculation enhanced Cu tolerance by affecting Cu uptake, regulating antioxidant enzyme activities and the ascorbate-glutathione cycle, and influencing PC biosynthesis-related gene expression in M. sativa. The results provide an efficient strategy for phytoremediation of Cu-contaminated soils.

Interdigitating dendritic cell sarcoma: Clinicopathologic study of 8 cases with review of the literature.

To investigate the clinicopathologic features and differential diagnoses of interdigitating dendritic cell sarcoma (IDCS), the clinical, morphological and immunohistochemical features of eight cases of IDCS were collected and analyzed. Three patients were males and five were females, the mean age and the median age were 56.5 years and 57 years respectively. Clinically, the majority of cases involved lymph nodes. Microscopically, neoplastic cells were spindle or ovoid, forming fascicles or whorls. Every case had active mitosis figures. Immunohistochemically, these neoplastic cells were consistently positive for S100, but negative for CD21 and specific B-cell and T-cell associated antigens. Follow-up results were available in 7 cases, of which 5 cases of localized lesions survived, 2 cases died of organ involvement. Interdigitating dendritic cell sarcoma is an extremely rare neoplasm, with inferior prognosis and without standard treatment regimen. IDCS has similar but unique clinicopathologic features and the differential diagnoses include other histiocytic and dendritic cell neoplasms and malignant melanoma.

Norcantharidin induce apoptosis in human nasopharyngeal carcinoma through caspase and mitochondrial pathway.

While Nasopharyngeal carcinoma (NPC) is uncommon in western countries, it is endemic in Southeast Asia and Southern China. Previous study of norcantharidin (NCTD), isolated from blister beetles, has proved its anticancer effect on various tumors. However, the effect of NCTD in NPC has never been studied. The purpose of this study is to inspect the suppression activity of NCTD on NPC, along with the underlying mechanism. NPC cell line NPC-BM was treated with NCTD. NCTD remarkably inhibited proliferation and induce apoptosis in NPC-BM cell. Activation of caspase-3, -8, -9 was observed through western blotting. The expression of antiapoptotic protein Bcl-XL was significantly reduced, but expression of proapoptotic protein Bak was increased after treatment of NCTD. The cytotoxic effect of NCTD on NPC-BM cell is mainly due to apoptosis, mediated by caspase and mitochondrial pathway. These results suggested that NCTD could be a potential anticancer agent for NPC.

MYC protein dysregulation is driven by BCR-PI3K signalling in diffuse large B-cell lymphoma.

AIMS: MYC overexpression is a common feature of diffuse large B-cell lymphoma (DLBCL) and is associated with poor prognosis in patients with this neoplasm. We aimed to investigate the underlying mechanisms of MYC dysregulation, as they have not been fully determined. METHODS AND RESULTS: We immunohistochemically evaluated the correlation between B-cell receptor (BCR)-phosphoinositide 3-kinase (PI3K) pathway activity and MYC level in 108 cases of de-novo DLBCL, 25 of which featured loss of BCR, and investigated the effects of BCR-PI3K signalling on MYC level and phosphorylation in DLBCL cell lines. The expression levels of phospho-SYK and phospho-AKT correlated with MYC expression in BCR-positive DLBCL. MYC expression was significantly lower in BCR-negative tumour tissues than in BCR-positive tumour tissues. Upon BCR stimulation, the BCR-positive cell lines showed active BCR-PI3K signalling and decreased MYC phosphorylation at T58, leading to an increased overall level of MYC. Conversely, inhibition of BCR-PI3K signalling increased MYC phosphorylation and thus resulted in a decreased overall level of MYC. No effects were observed in the BCR-negative cell lines. CONCLUSIONS: Overexpression of MYC in DLBCL can be driven by the BCR-PI3K signalling pathway via dephosphorylation at T58, and BCR inhibitors may exert their functions by down-regulation of MYC.

Saccharothrix stipae sp. nov., an actinomycete isolated from the rhizosphere of Stipa grandis.

An actinomycete, strain D34T, was isolated from a soil sample collected from the rhizosphere of Stipa grandis at Yunwu Mountain in Ningxia, north-west China. Strain D34T showed highest 16S rRNA gene sequence similarity to Saccharothrix espanaensis DSM 44229T (99.0 %), Saccharothrix texasensis NRRL B-16107T (98.7 %) and Saccharothrix variisporea NRRL B-16296T (98.6 %). The strain contained meso-diaminopimelic acid, alanine, glycine and glutamic acid as major cell-wall amino acids. Mannose, rhamnose and galactose were the characteristic whole-cell sugars. The fatty acid profile consisted predominantly of iso-C15 : 0, iso-C16 : 0, iso-C16 : 1, C17 : 1ω6c, anteiso-C17 : 0 and anteiso-C15 : 0. The phospholipid profile included phosphatidylethanolamine (typical of phospholipid pattern type II). Furthermore, a combination of some physiological and biochemical properties and low DNA-DNA relatedness values indicated that strain D34T was differentiated from members of closely related species. On the basis of these phenotypic, genotypic and chemotaxonomic data, strain D34T represents a novel species of the genus Saccharothrix, for which the name Saccharothrix stipae sp. nov. is proposed. The type strain is D34T ( = JCM 30560T = ACCC19714T).