Phenazine biosynthesis protein MoPhzF regulates appressorium formation and host infection through canonical metabolic and noncanonical signaling function in Magnaporthe oryzae.

Microbe-produced secondary metabolite phenazine-1-carboxylic acid (PCA) facilitates pathogen virulence and defense mechanisms against competitors. Magnaporthe oryzae, a causal agent of the devastating rice blast disease, needs to compete with other phyllosphere microbes and overcome host immunity for successful colonization and infection. However, whether M. oryzae produces PCA or it has any other functions remains unknown. Here, we found that the MoPHZF gene encodes the phenazine biosynthesis protein MoPhzF, synthesizes PCA in M. oryzae, and regulates appressorium formation and host virulence. MoPhzF is likely acquired through an ancient horizontal gene transfer event and has a canonical function in PCA synthesis. In addition, we found that PCA has a role in suppressing the accumulation of host-derived reactive oxygen species (ROS) during infection. Further examination indicated that MoPhzF recruits both the endoplasmic reticulum membrane protein MoEmc2 and the regulator of G-protein signaling MoRgs1 to the plasma membrane (PM) for MoRgs1 phosphorylation, which is a critical regulatory mechanism in appressorium formation and pathogenicity. Collectively, our studies unveiled a canonical function of MoPhzF in PCA synthesis and a noncanonical signaling function in promoting appressorium formation and host infection.

PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.

Pyruvate dehydrogenase kinase 1 (PDK1) is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4-intron transcript 1 (SPRY4-IT1) was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4-IT1 remarkably in breast cancer cells, as PDK1 interacted with SPRY4-IT1 in the nucleus and significantly enhanced the stability of SRPY4-IT1. Furthermore, SPRY4-IT1 was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4-IT1 inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF-κB signaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4-IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4-IT1 knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.

Discrete frequency-bin entanglement generation via cascaded second-order nonlinear processes in Sagnac interferometer.

Discrete frequency-bin entanglement is an essential resource for applications in quantum information processing. In this Letter, we propose and demonstrate a scheme to generate discrete frequency-bin entanglement with a single piece of periodically poled lithium niobate waveguide in a modified Sagnac interferometer. Correlated two-photon states in both directions of the Sagnac interferometer are generated through cascaded second-order optical nonlinear processes. A relative phase difference between the two states is introduced by changing the polarization state of pump light, thus manipulating the two-photon state at the output of the Sagnac interferometer. The generated two-photon state is sent into a fiber polarization splitter, and then a pure discrete frequency-bin entangled two-photon state is obtained by setting the pump light. The frequency entanglement property is measured by a spatial quantum beating with a visibility of 96.0±6.1%. The density matrix is further obtained with a fidelity of 98.0±3.0% to the ideal state. Our demonstration provides a promising method for the generation of pure discrete frequency-bin entanglement at the telecom band, which is desired in quantum photonics.

Synthesis and biological evaluation of novel SN38-glucose conjugate for colorectal cancer treatment.

7-Ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of irinotecan (CPT-11), has been shown to be 100-1000 times more effective than CPT-11. However, the poor water solubility and bioavailability of SN38 constrained its clinical application. In this study, we synthesized a novel SN38-glucose conjugate (FSY04) to address this issue. Our in vitro studies indicated that FSY04 had a potent inhibitory ability against colorectal cancer (CRC) cell lines of SW-480 and HCT-116 compared to the inhibitory capacity of CPT-11. Interestingly, FSY04 possessed lower cytotoxicity against normal cell lines of LO2 and 293T in contrast with CPT-11. Moreover, FSY04 is more active than CPT-11 in inducing apoptosis, inhibiting migration, and invasion. In vivo experiments suggested that half of the equivalent of FSY04 inhibited the growth of SW480 in the xenograft tumor model better than one equivalent of CPT-11. Our data demonstrated FSY04 to be a promising agent in CRC therapy.

Miniaturized fiber Bragg grating accelerator sensors for low-frequency vibration monitoring.

Acceleration monitoring is an important technical means of seismic monitoring, oil exploration, deep well observation, etc. A miniaturized fiber Bragg grating (FBG) acceleration sensor with three cantilever beams is proposed against the fact that it is difficult for fiber-optic sensors to meet the requirements for low-frequency vibration monitoring. First, the model of the FBG acceleration sensor was built and theoretically analyzed; second, the effect of structural parameters on sensor sensitivity and natural frequency was analyzed, and the sensors were subjected to static stress analysis and modal simulation analysis through the ANSYS finite element analysis software; finally, the real sensors were developed and subjected to performance tests with a low-frequency vibration test system. According to the result, the natural frequency of the sensor is about 64 Hz, and its sensitivity is 201.3 pm/g; favorable linearity is observed at the working frequency band of 0.1-40 Hz, and the transverse interference is less than 2.51%. The research findings offer a reference for the development of like sensors and the further exploration of the lower limit of low frequency.

The knockout of the nicotinic acetylcholine receptor subunit gene α1 (nAChR α1) through CRISPR/Cas9 technology exposes its involvement in the resistance of Spodoptera exigua to insecticides.

Insect nicotinic acetylcholine receptors (nAChRs) are the directed targets of many insecticides. However, there have been no reports on the molecular characterization of the nAChR gene family or the causal association between nAChR α1 and resistance to insecticides in S. exigua, which is a significant agricultural pest. In this study, we identified a total of 9 candidate nAChR subunits in S. exigua, namely nAChR α1-α7 and nAChR ß1-ß2. For functional validation roles of Seα1 in insecticide resistance of S. exigua, we introduced a âˆ¼ 1041-bp deletion of the Seα1 gene in a homozygous mutant strain (Seα1-KO) by CRISPR/Cas9 genome editing system, resulting in a premature truncation of the Seα1 protein and the subsequent loss of functional transmembrane (TM) 3 and TM4 elements. Compared with WH-S strain (wild-type strain), the Seα1-KO strain exhibited 2.62-folds resistant to trifluoropyrimidine, 8.3-folds resistant to dimehypo, and 5.28-folds resistant to dinotefuran, but no significant change in susceptibility to emamectin benzoate, spinetoram, lambda-cyhalothrin, permethrin and chlorpyrifos. Thus, this study has laid a solid foundation for investigating the role of nAChRs in S. exigua, and provides evidence for the crucial involvement of the α1 subunit in the mechanism of trifluoropyrimidine, dimehypo, and dinotefuran in S. exigua. Moreover, it provides a reference for the value of Seα1 subunit and its homologues in other species as insecticide targets.

Phonon lasing with an atomic thin membrane resonator at room temperature.

Graphene has been considered as one of the best materials to implement mechanical resonators due to their excellent properties such as low mass, high quality factors and tunable resonant frequencies. Here we report the observation of phonon lasing induced by the photonthermal pressure in a few-layer graphene resonator at room temperature, where the graphene resonator and the silicon substrate form an optical cavity. A marked threshold in the oscillation amplitude and a narrowing linewidth of the vibration mode are observed, which confirms a phonon lasing process in the graphene resonator. Our findings will stimulate the studies on phononic phenomena, help to establish new functional devices based on graphene mechanical resonators, and might find potential applications in classical and quantum sensing fields, as well as in information processing.

Correction: A kinetics study on hydrogen abstraction reactions of cyclopentane by hydrogen, methyl, and ethyl radicals.

Correction for 'A kinetics study on hydrogen abstraction reactions of cyclopentane by hydrogen, methyl, and ethyl radicals' by Wenqi Chen et al., Phys. Chem. Chem. Phys., 2021, 23, 7333-7342, DOI: 10.1039/D1CP00386K.

A kinetics study on hydrogen abstraction reactions of cyclopentane by hydrogen, methyl, and ethyl radicals.

Hydrogen abstraction reactions of (cyclo)alkanes by radicals play a fundamental role in both combustion and atmospheric chemistry. In this work, we select three common radicals in the pyrolysis of hydrocarbon fuels: hydrogen radical (H[combining dot above]), methyl radical (CH3), and ethyl radical (CH2CH3) to investigate the kinetics of their hydrogen abstraction reactions with cyclopentane. The rate constants over a broad temperature range of 150-3000 K are calculated by using the multi-structural variational transition state theory in the small-curvature tunneling approximation (MS-CVT/SCT), by which the multi-structural torsional (MS-T) anharmonicity of partition functions, variational effects, and corner-cutting tunneling are all included in dynamics calculations. We stress the particular importance of considering the MS-T anharmonicity in the rate constant calculation for the reaction with the ethyl radical compared to those with hydrogen and methyl radicals. The MS-T anharmonicity significantly accelerates the reaction with the ethyl radical in the whole temperature range, and in particular, it increases the rate constant by a factor of >-9 at 1000 K. We also found that the tunneling effect drastically increases the rate constants at low-temperatures by up to 3-5 orders of magnitudes. The calculated reaction rate constants have an order of .

Percutaneous Microwave Ablation versus Laparoscopic Partial Nephrectomy for cT1a Renal Cell Carcinoma: A Propensity-matched Cohort Study of 1955 Patients.

Background Percutaneous microwave ablation (MWA) and laparoscopic partial nephrectomy (LPN) are two modalities indicated for early-stage renal cell carcinoma (RCC) with low extent of invasion. Purpose To compare the long-term results of percutaneous MWA and LPN in the treatment of cT1a RCC. Materials and Methods This retrospective study included 1955 patients with cT1a RCC treated with percutaneous MWA or LPN between April 2006 and November 2017. Propensity score matching was used. Oncologic outcomes were analyzed by using the Fine-and-Gray competing risk models. Results A total of 185 patients underwent percutaneous MWA (mean age, 63.2 years ± 15.2 [standard deviation]) and 1770 underwent LPN (mean age, 50.9 years ± 13.2). During the follow-up (median, 40.6 months), after propensity score matching, no difference was observed between local tumor progression (3.2% vs 0.5%, P = .10), cancer-specific survival (2.2% vs 3.8%, P = .24), and distant metastases (4.3% vs 4.3%, P = .76). Patients who underwent percutaneous MWA had worse overall survival (hazard ratio, 2.4; 95% confidence interval: 1.0, 5.7; P = .049 vs LPN) and disease-free survival (82.9% vs 91.4%, P = .003). Percutaneous MWA led to smaller drop in estimated glomerular filtration rate at discharge (6.2% vs 16.4%, P < .001), smaller estimated blood loss (4.5 mL ± 1.3 vs 54.2 mL ± 69.2), lower cost ($3150 ± 2970 vs $6045 ± 1860 U.S. dollars), shorter operative time (0.5 minute ± 0.1 vs 1.8 minutes ± 0.6), and shorter postoperative hospitalization time (5.1 days ± 2.6 vs 6.9 days ± 2.8) (all P < .001 vs LPN). There were fewer cases of fever in the percutaneous MWA group (16.2% vs 73.0%, P < .001). Conclusion There were no significant differences regarding oncologic outcomes and complications between percutaneous microwave ablation and laparoscopic partial nephrectomy for patients with cT1a renal cell carcinoma. Percutaneous microwave ablation led to smaller renal function change and lower blood loss. For patients who cannot be subjected to the risks of more invasive laparoscopic partial nephrectomy, percutaneous microwave ablation could be an alternative less invasive treatment option. © RSNA, 2020 Online supplemental material is available for this article.

Dispersion independent long-haul photon-counting optical time-domain reflectometry.

Photon-counting optical time-domain reflectometry (PC-OTDR) based on single photon detection is an effective scheme to attain the high spatial resolution for optical fiber fault monitoring. Currently, due to the spatial resolution of PC-OTDR being proportional to the pulse width of a laser beam, short laser pulses are essential for a high spatial resolution. However, short laser pulses have a large bandwidth, which would be widened by the dispersion of fiber, causing inevitable deterioration in the spatial resolution, especially for long-haul fiber links. In this Letter, we propose a scheme of dispersion independent PC-OTDR based on an infinite backscatter technique. Our experimental results-with more than 45 km long fiber-show that the spatial resolution of the PC-OTDR system is independent with the total dispersion of the fiber under test. Our method provides an avenue for developing long-haul PC-OTDR with high performance.

Eliminating imidacloprid and its toxicity by permanganate via highly selective partial oxidation.

Imidacloprid is a widely used neonicotinoid insecticide worldwide, and has attracted great concerns due to its potential threat to human and environment. Much effort was thus spent on developing the effective way for removing imidacloprid from water, but might also produce various degradation products with unknown risks. The hypothesis was then proposed that permanganate oxidation was probably the appropriate tool for eliminating imidacloprid and its toxicity through selective oxidation of specific groups. To that end, we studied the kinetics of permanganate/imidacloprid reaction by considering the effects of pH (5.0-9.0), temperature (15-35 °C), ionization strength (0.05-0.20 M), typical anions (Cl-, Br-, I-) and humic acid. Based on the identified products from mass spectrometer, the main reaction pathway was found to be the hydroxylation of C-H bond at imidazole ring, leading to the decreased toxicity evaluated by ECOSAR program. Our results demonstrate that permanganate oxidation should be a very promising technique for controlling imidacloprid contamination by effective detoxification through highly selective partial oxidation. Moreover, this study has also paved the way toward applying permanganate oxidation for in situ chemical remediation of imidacloprid, though the corresponding standards need to be established in advance.

The Effect of Mechanical Ventilation on Peripheral Perfusion Index and Its Association With the Prognosis of Critically Ill Patients.

OBJECTIVES: This study aimed to explore the relationship between the variables of mechanical ventilation and circulatory perfusion and its association with ICU mortality during the first day of mechanical ventilation. DESIGN: Retrospective cohort study. SETTING: The Department of Critical Care Medicine, Peking Union Medical College Hospital. PATIENTS: Patients who have undergone mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study used the main clinical data obtained from the real-time bedside messaging systems of mechanically ventilated patients during their first day in the ICU from May 2013 to May 2016, including data on the variables of mechanical ventilation and circulatory perfusion. An analysis was then performed on the association of the above data with the patient's in-ICU mortality. There were 5,103 patients who received mechanical ventilation during this period, and of these, 309 patients died during their ICU treatment. Peak airway pressure, mean airway pressure, respiratory rate, heart rate, mean arterial pressure, FIO2, blood oxygen saturation, PO2, peripheral perfusion index, and lactate level were correlated with patient outcomes. A Cox logistic regression analysis suggested that mean airway pressure and perfusion index were the most independent risk and protective factors, respectively, for patient ICU mortality. The areas under the curve for a poor prognosis for mean airway pressure and perfusion index were 0.799 (95% CI, 0.77-0.829) and 0.759 (95% CI, 0.729-0.789), respectively. Further, mean airway pressure and perfusion index exhibited a causal interaction. The relative excess risk due to interaction was 2.061 (-0.691 to 4.814), the attributable proportion due to interaction was 0.210 (-0.027 to 0.447), and the synergy index was 1.306 (0.930-1.833). CONCLUSIONS: A higher mean airway pressure and lower perfusion index provided a worse prognosis in mechanically ventilated patients, and it appears that these two variables have a casual interaction.

TaCIPK10 interacts with and phosphorylates TaNH2 to activate wheat defense responses to stripe rust.

Calcineurin B-like interacting protein kinase (CIPKs) has been shown to be required for biotic stress tolerance of plants in plant-pathogen interactions. However, the roles of CIPKs in immune signalling of cereal crops and an in-depth knowledge of substrates of CIPKs in response to biotic stress are under debate. In this study, we identified and cloned a CIPK homologue gene TaCIPK10 from wheat. TaCIPK10 was rapidly induced by Puccinia striiformis f. sp. tritici (Pst) inoculation and salicylic acid (SA) treatment. In vitro phosphorylation assay demonstrated that the kinase activity of TaCIPK10 is regulated by Ca2+ and TaCBL4. Knockdown TaCIPK10 significantly reduced wheat resistance to Pst, whereas TaCIPK10 overexpression resulted in enhanced wheat resistance to Pst by the induction of defense response in different aspects, including hypersensitive cell death, ROS accumulation and pathogenesis-relative genes expression. Moreover, TaCIPK10 physically interacted with and phosphorylated TaNH2, which was homologous to AtNPR3/4. Silencing of TaNH2 in wheat resulted in enhanced susceptibility to the avirulent Pst race, CYR23, indicating its positive role in wheat resistance. Our results demonstrate that TaCIPK10 positively regulate wheat resistance to Pst as molecular links between of Ca2+ and downstream components of defense response and TaCIPK10 interacts with and phosphorylates TaNH2 to regulate wheat resistance to Pst.

A density functional theory study of aldehydes and their atmospheric products participating in nucleation.

Aldehydes have been speculated as important precursor species in the formation of new atmospheric particles. In the present work, quantum chemical calculations were performed to investigate the hydrogen bonding interaction and the Gibbs free energy of formation (ΔG) for clusters consisting of sulfuric acid and aldehydes as well as their atmospheric reaction products. Calculations were conducted at 298 K and 1 atm at the M06-2X/6-311+G(3df,3pd) level. The results show that the addition of aldehyde compounds to H2SO4 unlikely contributes to new particle formation. However, their products from aldol condensation, hydration, and polymerization reactions can promote new particle formation by stabilizing sulfuric acid in the first step of nucleation. Moreover, the favorability of the interaction in the absence of water between sulfuric acid and the addition products is as follows: the hydration products > aldol condensation > aldehydes, but the results may be changed if water molecules are added. In particular, the calculated ΔG values imply that the monohydrate of glyoxal is more likely to nucleate with H2SO4 in comparison with ammonia in the presence or absence of water.

Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane.

The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts.

QM/MM study of the reaction mechanism of Cl-cis,cis-muconate with muconate lactonizing enzyme.

The lactonization process of Cl-cis,cis-muconate catalyzed by anti-muconate lactonizing enzyme (anti-MLE) was studied theoretically with the aid of a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two elementary processes steps involved in the lactanization process were investigated. The calculated energy barriers agree well with the experimental values. The present work provided the explicit structures of the enolate anion intermediates. The electrostatic influence analysis highlighted residues Arg51, Gln294 and TIP383 for the MLE-Cl-2 system and the residue Asn193 for the MLE-Cl-4 system as the possible mutation targets for rational design of anti-MLE in future enzyme modification.

Cost-effective high-spatial-resolution photon-counting optical time-domain reflectometry at 850 nm.

Optical time-domain reflectometry (OTDR) is a widely employed instrument for monitoring the property of fiber links. Traditional OTDR always suffers from the trade-off between its spatial resolution and the sensitivity of light detection. Therefore, it cannot be applied in critical applications, such as in aviation, where OTDR with a high spatial resolution of several centimeters is required. In this paper, we develop a cost-effective photon-counting OTDR based on our homemade gain-switching pulsed laser at 850 nm. Thanks to the short pulse width of the laser and the relatively small time jitter of the photon detector, our photon-counting OTDR achieves a spatial resolution of less than 9 cm and satisfies the requirements for monitoring short fiber links in various types of airplanes. Finally, we realize a fully running system for monitoring an optical cable with 32 fiber channels on a plane.

Enantioselectivity of haloalkane dehalogenase LinB on the degradation of 1,2-dichloropropane: A QM/MM study.

The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8kcal/mol for the (R)-isomer and 24.0kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.

Intrauterine growth retardation promotes fetal intestinal autophagy in rats via the mechanistic target of rapamycin pathway.

Intrauterine growth retardation (IUGR) impairs fetal intestinal development, and is associated with high perinatal morbidity and mortality. However, the mechanism underlying this intestinal injury is largely unknown. We aimed to investigate this mechanism through analysis of intestinal autophagy and related signaling pathways in a rat model of IUGR. Normal weight (NW) and IUGR fetuses were obtained from primiparous rats via ad libitum food intake and 50% food restriction, respectively. Maternal serum parameters, fetal body weight, organ weights, and fetal blood glucose were determined. Intestinal apoptosis, autophagy, and the mechanistic target of rapamycin (mTOR) signaling pathway were analyzed. The results indicated that maternal 50% food restriction reduced maternal serum glucose, bilirubin, and total cholesterol and produced IUGR fetuses, which had decreased body weight; blood glucose; and weights of the small intestine, stomach, spleen, pancreas, and kidney. Decreased Bcl-2 and increased Casp9 mRNA expression was observed in IUGR fetal intestines. Analysis of intestinal autophagy showed that the mRNA expression of WIPI1, MAP1LC3B, Atg5, and Atg14 was also increased, while the protein levels of p62 were decreased in IUGR fetuses. Compared to NW fetuses, IUGR fetuses showed decreased mTOR protein levels and enhanced mRNA expression of ULK1 and Beclin1 in the small intestine. In summary, the results indicated that maternal 50% food restriction on gestational days 10-21 reduced maternal serum glucose, bilirubin, and total cholesterol contents, and produced IUGR fetuses that had low blood glucose and reduced small intestine weight. Intestinal injury of IUGR fetuses caused by maternal food restriction might be due to enhanced apoptosis and autophagy via the mTOR signaling pathway.