Near-noiseless and small-footprint phase sensitive optical parametric amplifier using AlGaAs-on-insulator waveguides.

Phase sensitive amplifiers (PSAs) based on optical parametric amplification feature near noiseless amplification, which is of considerable benefit for improving the performance of optical communication systems. Currently, the majority of research on PSAs is carried out on the basis of highly nonlinear fibers or periodically poled lithium niobite waveguides, with the impediments of being susceptible to environmental interference and requiring complex temperature control systems to maintain quasi-phase matching conditions, respectively. Here, a near-noiseless and small-footprint PSA based on dispersion-engineered AlGaAs-on-insulator (AlGaAsOI) waveguides is proposed and demonstrated theoretically. The phase-dependent gain and the phase-to-phase transfer function of the PSA are calculated to analyze its characteristics. Furthermore, we investigate in detail the effects of linear loss, nonlinear coefficient, and pump power on the PSA gain and noise figure (NF) in AlGaAsOI waveguides. The results show that a PSA based on an AlGaAsOI waveguide is feasible with a maximum phase sensitive gain of 33 dB, achieving an NF of less than 1 dB over a gain bandwidth of 245 nm with a gain of >15d B, which completely covers the S + C + L band. This investigation is worthwhile for noiseless PSAs on photonic integrated chips, which are promising for low-noise optical amplification, multifunctional photonic integrated chips, quantum communication, and spectroscopy, and as a reference for low-noise PSAs depending on the third-order nonlinearity, χ (3), of the waveguide material.

C-Alkylated flavonoids from the whole plants of Desmodium caudatum and their anti-TMV activity.

BACKGROUND: Natural products are important sources of biopesticides to control plant virus, and flavonoids are identified as promising anti-tobacco mosaic virus (TMV) agents. Since Desmodium caudatum is a rich source of flavonoids, this study focuses on the discovery of the new anti-TMV active flavonoids from D. caudatum and their possible mode of action. RESULTS: Three new (compounds 1-3) and nine known (compounds 4-12) C-alkylated flavonoids were isolated from D. caudatum. To the best of our knowledge, the framework of 1-3 was reported in natural products for the first time. In addition, 1-3, 5, and 6 showed notable anti-TMV activity with inhibition rates in the range of 35.8-64.3% at a concentration of 50 µg/mL, and these rates are higher than that of positive control (with inhibition rates of 34.6% ± 2.8). In addition, the structure-activity relationship study revealed that the (pyrrol-2-yl)methyl moiety on flavone can significantly increases the activity. This result is helpful to find new anti-TMV inhibitors. CONCLUSION: C-Alkylated flavonoids showed potent activities against TMV with multiple modes of actions. The increase of defense-related enzyme activities, up-regulate the expression of defense related genes, down-regulate the expression of Hsp70 protein by inhibiting the related Hsp genes that are involved in tobacco resistance to TMV. By the actions mentioned earlier, the infection of TMV was influenced, thereby achieving the effects of control of TMV. The successful isolation of the earlier-mentioned flavonoids provide the new source of biopesticides to TMV proliferation, and also contribute to the utilization of D. caudatum. © 2023 Society of Chemical Industry.

Deregulating MYC in a model of HER2+ breast cancer mimics human intertumoral heterogeneity.

The c-MYC (MYC) oncoprotein is often overexpressed in human breast cancer; however, its role in driving disease phenotypes is poorly understood. Here, we investigate the role of MYC in HER2+ disease, examining the relationship between HER2 expression and MYC phosphorylation in HER2+ patient tumors and characterizing the functional effects of deregulating MYC expression in the murine NeuNT model of amplified-HER2 breast cancer. Deregulated MYC alone was not tumorigenic, but coexpression with NeuNT resulted in increased MYC Ser62 phosphorylation and accelerated tumorigenesis. The resulting tumors were metastatic and associated with decreased survival compared with NeuNT alone. MYC;NeuNT tumors had increased intertumoral heterogeneity including a subtype of tumors not observed in NeuNT tumors, which showed distinct metaplastic histology and worse survival. The distinct subtypes of MYC;NeuNT tumors match existing subtypes of amplified-HER2, estrogen receptor-negative human tumors by molecular expression, identifying the preclinical utility of this murine model to interrogate subtype-specific differences in amplified-HER2 breast cancer. We show that these subtypes have differential sensitivity to clinical HER2/EGFR-targeted therapeutics, but small-molecule activators of PP2A, the phosphatase that regulates MYC Ser62 phosphorylation, circumvents these subtype-specific differences and ubiquitously suppresses tumor growth, demonstrating the therapeutic utility of this approach in targeting deregulated MYC breast cancers.

SUMO protease SENP1 deSUMOylates and stabilizes c-Myc.

Posttranslational modifications play a crucial role in the proper control of c-Myc protein stability and activity. c-Myc can be modified by small ubiquitin-like modifier (SUMO). However, how SUMOylation regulates c-Myc stability and activity remains to be elucidated. The deSUMOylation enzyme, SENP1, has recently been shown to have a prooncogenic role in cancer; however, mechanistic understanding of this is limited. Here we show that SENP1 is a c-Myc deSUMOylating enzyme. SENP1 interacts with and deSUMOylates c-Myc in cells and in vitro. Overexpression of wild-type SENP1, but not its catalytically inactive C603S mutant, markedly stabilizes c-Myc and increases its levels and activity. Knockdown of SENP1 reduces c-Myc levels, induces cell cycle arrest, and drastically suppresses cell proliferation. We further show that c-Myc can be comodified by both ubiquitination and SUMOylation. SENP1-mediated deSUMOylation reduces c-Myc polyubiquitination, suggesting that SUMOylation promotes c-Myc degradation through the proteasome system. Interestingly, SENP1-mediated deSUMOylation promotes the accumulation of monoubiquitinated c-Myc and its phosphorylation at serine 62 and threonine 58. SENP1 is frequently overexpressed, correlating with the high expression of c-Myc, in breast cancer tissues. Together, these results reveal that SENP1 is a crucial c-Myc deSUMOylating enzyme that positively regulates c-Myc's stability and activity.

Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals.

The transcription factor MYC (also c-Myc) induces histone modification, chromatin remodeling, and the release of paused RNA polymerase to broadly regulate transcription. MYC is subject to a series of post-translational modifications that affect its stability and oncogenic activity, but how these control MYC's function on the genome is largely unknown. Recent work demonstrates an intimate connection between nuclear compartmentalization and gene regulation. Here, we report that Ser62 phosphorylation and PIN1-mediated isomerization of MYC dynamically regulate the spatial distribution of MYC in the nucleus, promoting its association with the inner basket of the nuclear pore in response to proliferative signals, where it recruits the histone acetyltransferase GCN5 to bind and regulate local gene acetylation and expression. We demonstrate that PIN1-mediated localization of MYC to the nuclear pore regulates MYC target genes responsive to mitogen stimulation that are involved in proliferation and migration pathways. These changes are also present at the chromatin level, with an increase in open regulatory elements in response to stimulation that is PIN1-dependent and associated with MYC chromatin binding. Taken together, our study indicates that post-translational modification of MYC controls its spatial activity to optimally regulate gene expression in response to extrinsic signals in normal and diseased states.

Biodegradation of lignin and nicotine with white rot fungi for the delignification and detoxification of tobacco stalk.

BACKGROUND: Tobacco stalk is one kind of abundant crop residues in China. The high lignification of tobacco stalk increases its reusing cost and the existing of nicotine will cause serious pollution. The biodegradation of lignocellulosic biomass has been demonstrated to be an environmental and economical approach for the utilization of plant stalk. Meanwhile, many nicotine-degrading microorganisms were found in nature. However, microorganisms which could degraded both nicotine and lignin haven't been reported. Therefore, it's imperative to find some suitable microorganisms to break down lignin and simultaneously remove nicotine in tobacco stalk. RESULTS: The nicotine in tobacco stalk could be degraded effectively by Trametes versicolor, Trametes hirsute and Phanerochaete chrysosporium. The nicotine content in tobacco stalk was lowered to below 500 mg/kg (a safe concentration to environment) after 10 days of fermentation with Phanerochaete chrysosporium and Trametes versicolor, and 15 days with Trametes hirsute. The degradation rate of lignin in the fermented tobacco stalk was 37.70, 51.56 and 53.75% with Trametes versicolor, Trametes hirsute and Phanerochaete chrysosporium, respectively. Meanwhile, 24.28% hemicellulose was degraded by Phanerochaete chrysosporium and 28.19% cellulose was removed by Trametes hirsute. Through the enzyme activity analysis, the main and highest ligninolytic enzymes produced by Phanerochaete chrysosporium, Trametes hirsute and Trametes versicolor were lignin peroxidase (88.62 U · L-1), manganese peroxidase (100.95 U · L-1) and laccase (745.65 U · L-1). Meanwhile, relatively high and stable cellulase activity was also detected during the fermentation with Phanerochaete chrysosporium, and the highest endoglucanase, exoglucanase and filter paper enzyme activities were 0.38 U · mL-1, 0.45 U · mL-1 and 0.35U · mL-1, respectively. Moreover, the products in the fermentation of tobacco stalk with P. chrysosporium were identified with GC-MS, besides the chemicals produced in the degradation of lignin and nicotine, some small molecular valuable chemicals and fatty acid were also detected. CONCLUSIONS: Our study developed a new method for the degradation and detoxification of tobacco stalk by fermentation with white rot fungi Phanerochaete chrysosporium and Trametes hirsute. The different oxidative enzymes and chemical products detected during the degradation indicated a possible pathway for the utilization of tobacco stalk.

Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity.

Hierarchic phosphorylation and concomitant Pin1-mediated proline isomerization of the oncoprotein c-Myc controls its cellular stability and activity. However, the molecular basis for Pin1 recognition and catalysis of c-Myc and other multisite, disordered substrates in cell regulation and disease is unclear. By nuclear magnetic resonance, surface plasmon resonance, and molecular modeling, we show that Pin1 subdomains jointly pre-anchor unphosphorylated c-Myc1-88 in the Pin1 interdomain cleft in a disordered, or "fuzzy", complex at the herein named Myc Box 0 (MB0) conserved region N-terminal to the highly conserved Myc Box I (MBI). Ser62 phosphorylation in MBI intensifies previously transient MBI-Pin1 interactions in c-Myc1-88 binding, and increasingly engages Pin1PPIase and its catalytic region with maintained MB0 interactions. In cellular assays, MB0 mutated c-Myc shows decreased Pin1 interaction, increased protein half-life, but lowered rates of Myc-driven transcription and cell proliferation. We propose that dynamic Pin1 recognition of MB0 contributes to the regulation of c-Myc activity in cells.

Nicotiana sylvestris calcineurin B-like protein NsylCBL10 enhances salt tolerance in transgenic Arabidopsis.

KEY MESSAGE: Nicotiana sylvestris calcineurin B-like protein NsylCBL10 improves tolerance to high-salt stress through better maintenance of Na (+) balance. The calcineurin B-like (CBL) proteins represent a unique group of plant calcium sensors and play an important role in regulating the response of a plant cell to the stress. Although many studies have been made in Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa) and poplar (Populus trichocarpa), the characterization and elucidation of the functions of CBLs in tobacco have not yet been reported. In this study, NsylCBL10, a CBL gene showing higher similarities to other CBL10 genes, was cloned from Nicotiana sylvestris. NsylCBL10 is expressed in most of the tobacco tissues, and the protein targets to the plasma membrane specifically. Over-expression of NsylCBL10 enhanced the salt tolerance of Arabidopsis wild type plants greatly, and rescued the high-salt-sensitive phenotype of Arabidopsis cbl10 mutant. The analysis of ion content indicated that over-expressing NsylCBL10 in plants is able to maintain a lower Na(+)/K(+) ratio in roots and higher Na(+)/K(+) ratio in shoots, compared with cbl10 mutant. The results suggest that NsylCBL10 might play an important role in response to high salinity stress in N. sylvestris, by keeping a better ionic homeostasis to reduce the damage of toxic ion to the plant cell.

[Isolation of microorganisms producing enzyme capable of degrading tobacco straw and nicotine].

OBJECTIVE: The aim of this study was to screen tobacco straw and nicotine degrading microorganism. METHODS: The bacterium was isolated from tobacco field soil using medium containing tobacco straw as the sole carbon and nitrogen source. We identified the bacterium through morphological and physiological characterization combined with the result of 16S rRNA gene sequence and data analysis. We also studied the lignocelluloses degradation and enzyme activities related to the degradation of lignin and cellulose in liquid state fermentation of tobacco stalk. RESULTS: The bacterium was identified as Bacillus megaterium and we had demonstrated that it has a good ability to degrade lignin in tobacco straw when fermented in liquid state. It showed the highest laccase production of 418. 52 U/L while the highest lignin peroxides and manganese peroxides activity was 19. 71 U/L and 64. 71 U/L. On the other hand, we also found that nicotine in tobacco stem was totally degraded 20 d after inoculation. CONCLUSION: to the isolated Bacillus megaterium is capable of degrading tobacco straw partially and nicotine totally.

Pin1 regulates the dynamics of c-Myc DNA binding to facilitate target gene regulation and oncogenesis.

The Myc oncoprotein is considered a master regulator of gene transcription by virtue of its ability to modulate the expression of a large percentage of all genes. However, mechanisms that direct Myc's recruitment to DNA and target gene selection to elicit specific cellular functions have not been well elucidated. Here, we report that the Pin1 prolyl isomerase enhances recruitment of serine 62-phosphorylated Myc and its coactivators to select promoters during gene activation, followed by promoting Myc's release associated with its degradation. This facilitates Myc's activation of genes involved in cell growth and metabolism, resulting in enhanced proproliferative activity, even while controlling Myc levels. In cancer cells with impaired Myc degradation, Pin1 still enhances Myc DNA binding, although it no longer facilitates Myc degradation. Thus, we find that Pin1 and Myc are cooverexpressed in cancer, and this drives a gene expression pattern that we show is enriched in poor-outcome breast cancer subtypes. This study provides new insight into mechanisms regulating Myc DNA binding and oncogenic activity, it reveals a novel role for Pin1 in the regulation of transcription factors, and it elucidates a mechanism that can contribute to oncogenic cooperation between Pin1 and Myc.

[Effects of Trichoderma longbrachitum and Streptomyces jingyangensis combination on the growth and disease resistance of tobacco seedlings].

An agar plate antagonism experiment in combining with in vivo screening experiment was conducted to study the affinity and bacteriostasis spectrum of the combination of biocontrol agents Trichoderma longbrachitum and Streptomyces jingyangensis to Nicotiana tabacum seedlings, with the effects of each agent and their combination on the N. tabacum seedlings growth, induced resistance, and resistance to Phytophthora nicotianae analyzed. The two agents had no interactive inhibitory effect and showed higher affinity to N. tabacum, and the agents themselves as well as their metabolites had higher bacteriostasis activities and wider bacteriostasis spectrum to P. nicotiaonae, Pythium aphanidermatum, and Alternaria alternate in different habitats. The combination of the two agents affected the morphological characteristics of the seedlings underground and aboveground parts, promoted the growth of root, stem, and leaf, and increased the root volume, total surface area, length, and average diameter as well as the stem height and size and the leaf length, width, and biomass, with these promotion effects being superior than those of the single-agent treatment. The combination of the two agents also increased the activities of the defensive enzymes superoxide dismutase, catalase, phenylalanine ammonia lyase, and peroxidase in the seedlings root significantly, with the relative control efficiency against P. nicotianae reached 69.3%, as compared to the conventional treatment. This study showed that the combination of T. longbrachitum and S. jingyangensis was a compatible combination with higher affinity and efficiency. This combination showed a synergistic effect of the two agents in plant disease control and in promoting plant growth, being able to promote the tobacco seedlings growth and control the P. nicotianae effectively.

Polycomb group genes in stem cell self-renewal: a double-edged sword.

Polycomb group (PcG) genes encode chromatin associated proteins that usually form polycomb repressive complexes (PRC) to maintain the repressive state of gene transcription. In both embryonic and adult stem cells, PRCs are commonly regarded as essential players for maintaining stem cell multipotency by repressing developmental genes. However, emerging evidence also points out essential roles of PcG genes in antagonizing stem cell self-renewal and facilitating cell lineage differentiation. Here, we briefly review recent literature on these two seemingly opposite functions of PcG genes in stem cells and discuss future perspective towards understanding polycomb function in stem cells and tumorigenesis.