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This study derived a novel computation algorithm for a mechanical system with multiple friction contact interfaces that is well-suited to the investigation of nonlinear mode characteristic of a coupling system. The procedure uses the incremental harmonic balance method to obtain the nonlinear parameters of the contact interface. Thereafter, the computed nonlinear parameters are applied to rebuild the matrices of the coupling system, which can be easily solved to calculate the nonlinear mode characteristics by standard iterative solvers. Lastly, the derived method is applied to a cycle symmetry system, which represents a shaft-disk-blade system subjected to dry friction. Moreover, this study analyzed the effects of the tuned and mistuned contact features on the nonlinear mode characteristics. Numerical results prove that the proposed method is particularly suitable for the study of nonlinear characteristics in such nonlinear systems.

Background The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a prominent pest of citrus because it transmits Candidatus Liberibacter asiaticus associated with huanglongbing. Phototactic behavior ubiquitously exists in insects and plays essential roles in host-searching and mate-searching in ACP. However, its mechanism has remained unclear to date. In this paper, molecular assays were performed to understand the relation between opsins and the phototactic behavior of ACP. Results We cloned five opsin genes and analyzed their expression patterns. The main three opsin genes (Dc-UV, Dc-BW and Dc-LW) displayed high expression levels in daytime, and the expression levels of the other two opsin genes (Dc-UV-like and Dc-arthropsin) increased during nighttime. In constant darkness, the expression patterns and levels of opsin genes of ACP were altered. Under starvation, the expression levels of the main three opsins were reduced (53.89-84.10%). In contrast, the expression levels in females increased (27.55-60.58%). Feeding of double-stranded RNA (Dc-UV, Dc-LW or Dc-BW) have reduced the phototactic efficiency of ACP to ultraviolet light (44.79%), green light (54.81%) and blue light (43.00%), respectively. Conclusion The results suggest that the expression levels and patterns of opsins of ACP were influenced by photoperiod and the physiological status of ACP. Our research indicates that opsins play crucial roles in phototactic behavior in ACP. © 2019 Society of Chemical Industry.

Summary Background Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies. Methods This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method. Findings 1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952–0·957) in the internal validation set, 0·927 (0·925–0·929) in the prospective set, and ranged from 0·915 (0·913–0·917) to 0·977 (0·977–0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 [95% CI 0·924–0·957] vs 0·945 [0·927–0·959]; p=0·692) and superior sensitivity compared with competent (0·858 [0·832–0·880], p Interpretation GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses. Funding The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.

Art can be used to spread an inspirational message to encourage people and accomplish great things in life. The art of communication among people can be a mode of communication to concentrate on common issues to improve humankind. The challenging characteristics in art painting include such as degradation, cracking, and flaking is considered an essential factor. In this paper, the Multilevel Based Convolutional Ancient Recognition Neural Network Method (M-CARNNM) has been proposed to incorporate experts’ suggestions, helping artists envisage how the ancient painting may have looked after restoration. Mid-frequency analysis is introduced to reinforce the rough estimation of complete images by adding missing regions and the nearest neighbor pixels to match the maps. A domain-specific pyramid network is used to capture various space context amounts. Experimental results effectively predict the proposed method for large areas of lack of information and produce controllable vector graphics, photographic painting, and high-frequency results.

Plant-derived aromatic natural products have important medicinal value and can be made into pharmaceutical and healthcare products with antibacterial, anti-inflammatory, analgesic, anti-oxidative, insecticidal and anthelmintic, expectorant and cough suppressant, tranquilizer and antitumor effects. However, the low content of aromatic natural products in plants and the difficulty and high costs in extraction and purification hampered its large-scale production and application. Recent advances in synthetic biology and metabolic engineering have enabled the tailor-made production of aromatic natural products using engineered microbial cell factories. This review summarizes the categories, the synthetic pathways, the key enzymes and the synthetic biology strategies for production of aromatic natural products, and discusses the challenges and opportunities in this area.植物芳香类天然产物具有重要的药用价值，可制成具有抗菌、抗炎、镇痛、抗氧化、杀虫驱虫、祛痰止咳、安神镇静和抗肿瘤等药效的医药保健用品。然而，由于植物中芳香类天然产物含量较低并且难以提取和纯化，严重限制了其工业化生产及应用。合成生物学和代谢工程技术的发展为天然产物的生产提供了新的思路，可以利用人工微生物细胞工厂来实现多种芳香类天然产物的高效合成。文中介绍了芳香类天然产物的种类、合成途径和关键酶，综述了近年来国内外通过合成生物学技术合成芳香类天然产物的研究进展，探讨了当前研究所面临的挑战及潜在的解决策略，以期对芳香类天然产物生物合成研究工作提供参考。.

Although deep learning-based hand gesture recognition techniques have achieved amazing performance in recent years, it is challenges as hand gesture is prone to interference, such as light changes and gesture shadows on gesture recognition. In this paper, we propose a recognition model based on ellipse skin color, and improved Deep Residual Learning network for gesture recognition. By utilizing the clustering effect of skin color in YCbCr color space, we segment CbCr two-dimensional space based on the elliptical skin color model to hand gesture. To further improve performance, the mathematical morphology with logic operation is proposed to assist hand gesture segmentation. Lastly, the Deep Residual Learning architecture is used to increase the width of the network and the channel attention mechanism. The experimental results show that the proposed method can obtain a high recognition rate compared with existing methods.

This paper analyzes the intermittent operation on the ground temperature recovery of borehole heat exchanger (BHE) fields. The outlet fluid temperature is regarded as the field measurement to study...

The current study aims to explore the effect of myocardial infarction associated transcript (MIAT) level on the long-term prognosis of hand-assisted laparoscopic colectomy (HALC) or laparoscopic-assisted colectomy (LAC) for colorectal cancer (CC).A total of 320 CC patients were included. Patients were randomized into HALC and LAC group.MIAT level in CC tissue was upregulated, and had a significant positive association with its level in serum. MIAT levels in both CC tissue and serum were correlated with lymph node metastasis and histologic grading. Survival analysis showed that the overall survival rate in 3 years after operation was significantly lower in HALC-High MIAT group (P0.05). When MIAT level is10.9 in CC tissue or 8.7 in serum, 100% of patients who underwent HALC will be alive for3 years.For patients with low MIAT level, both HALC and LAC are available, otherwise, LAC is more recommended.

Considering the large-deformation hypothesis, the modeling and nonlinear vibration characteristics of symmetrically 3-layer composite thin circular cylindrical shells with arbitrary boundary conditions are analyzed by applying four sets of artificial springs. Firstly, by employing a set of orthogonal polynomials and trigonometric functions, the energy equations of the shells are derived with Donnell's nonlinear thin-shell theory. Then, the arbitrary boundary conditions are simulated by imposing the equivalent elastic constraint to obtain the potential energy of the edges of the shell, which can be universally applicable to all classical boundary conditions. The vibration equation is obtained by using the Lagrange equation method. In order to obtain correct numerical results, several comparisons of linear and nonlinear results are carried out to validate the approach method in the present study; meanwhile, the calculation convergence is checked. At last, the influence of boundary conditions, geometric parameters, symmetrical lamination schemes and damping coefficients on the nonlinear amplitude-frequency characteristics of symmetrically 3-layer composite thin circular cylindrical shells are investigated. The numerical results indicate that the present method is powerful to calculate the nonlinear vibration response characteristics of symmetrically 3-layer composite circular cylindrical thin shells subjected to various boundary conditions.

Circadian rhythm is believed to play important roles in atherosclerosis. The gut microbiota is found to be closely related to atherogenesis, and shows compositional and functional circadian oscillation. However, it's still unclarified whether circadian clock and intestinal microbiota are involved in the progression of atherosclerosis induced by environmental pollutant acrolein. Herein, patients with atherosclerosis showed higher MMP9, a promising biomarker for atherosclerosis, and lower Bmal1 and Clock expression in the plasma. Interestingly, acrolein exposure contributed to the increased MMP9, decreased Clock and Bmal1, and activated MAPK pathways in human umbilical vein endothelial cells (HUVECs). We found that knockdown of Clock or Bmal1 lead to upregulation of MMP9 in HUVECs, and that Clock and Bmal1 expression was elevated while MAPK pathways were blocked. Atherosclerotic apolipoproteinE-deficient mice consumed a high-fat diet were used and treated with acrolein (3 mg/kg/day) in the drinking water for 12 weeks. Upregulation of MMP9, and downregulation of Clock and Bmal1 were also observed in plasma of the mice. Besides, acrolein feeding altered gut microbiota composition at a phylum level especially for an increased Firmicutes and a decreased Bacteroidetes. Additionally, gut microbiota showed correlation with atherosclerotic plaque, MMP9 and Bmal1 levels. Therefore, our findings indicated that acrolein increased the expression of MMP9 through MAPK regulating circadian clock, which was associated with gut microbiota regulation in atherosclerosis. Circadian rhythms and gut microbiota might be promising targets in the prevention of cardiovascular disease caused by environmental pollutants.

Electrical modeling of vehicular antennas is required for design of modern vehicle-to-everything communication networks. However, full-wave modeling and the existing equivalent source methods still ask for long computation time. To address this issue, a fast simulation method is proposed in this paper: a sparse equivalent source model is developed based on Huygens’ principle where a vehicular antenna is made equivalent to magnetic current placed on a finite conducting plate. The image theory and the uniform theory of diffraction are then applied, a modified Green’s function is derived, and the sparse equivalent source model is constructed to replace the original vehicular antenna. Because of its simple geometry and material, in comparisons with the existing methods, the proposed model uses significantly less expenditures for simulation of vehicular antennas while has better accuracy due to the consideration of the finite conducting plate. Simulations are performed to demonstrate the effectiveness and advantages of the proposed method, and a real-world experiment is designed and conducted to demonstrate the superiority of the proposed method with real measurement data. It is shown that the proposed method can save simulation time by four times, with less than 1-dB error compared to measurement.

In this paper, the free vibration of laminated composited cylindrical shells with two kinds of non-continuous supported boundary condition are investigated. The artificial springs are used to simulate the arcs supported and points supported boundary condition. The equations of motion are derived by using the Chebyshev polynomials and the Lagrange equation, and Donnell’s shell theory is employed in this process. The accuracy of the present method compared with that of literature, and convergence analysis is carried out at the same time. Then, the influences of spring stiffness, the number of supported point, and the lamination schemes of non-continuous supported laminated composite cylindrical shells on frequency parameter are studied. The results show that the method can accurately deal with the free vibration of laminated shells with arbitrary non-continuous boundary and arbitrary lamination schemes.

Neoproterozoic iron formations are exposed in the Wadi Hamama area (Egypt) in the northwestern part of the Arabian–Nubian Shield. Mafic and felsic volcanic and volcaniclastic rocks of an intra-oceanic island-arc setting host multiple, thin iron-formation units. Major element compositions of the iron formation confirm a low detrital input, whereas the rare-earth elements and Y data suggest deposition related to an influx of low-temperature hydrothermal fluids. Unlike most Neoproterozoic banded iron formations, but similar to other iron-formation occurrences from the Arabian–Nubian Shield, the Nd isotopic compositions of the Wadi Hamama iron formations are predominantly mantle-like. SIMS U–Pb zircon ages of the host volcaniclastic units indicate that the age of iron-formation deposition is ca. 695 Ma, which is within the Sturtian epoch that is presumed to be a glacial event of global extent. Nevertheless, there is no robust evidence of any influence of Sturtian glaciation in the Arabian–Nubian Shield. Our results rather suggest that the iron formations in the area may have formed as low-temperature exhalites on the floor of an island-arc basin. The iron formations were deposited during periods of volcanic quiescence, with metals having been derived during low-temperature pervasive hydrothermal alteration of volcanic and volcaniclastic rocks exposed at the seafloor–seawater interface. Precipitation took place due to mixing of metal-bearing hydrothermal fluids and cold, oxygenated seawater. There is no need to invoke possible effects of global glaciation to explain the origin of the Sturtian-aged iron formations in the shield. Our study thus suggests that not all Neoproterozoic iron formations are necessarily linked to glacial events as the Hamama deposit represents a non-Rapitan exhalative iron formation.

The secondary cell wall is an important carbon sink in higher plants and its biosynthesis requires coordination of metabolic fluxes in the phenylpropanoid pathway. In Arabidopsis (Arabidopsis thaliana), MYB75 and the KNOX transcription factor KNAT7 form functional complexes to regulate secondary cell wall formation in the inflorescence stem. However, the molecular mechanism by which these transcription factors control different branches of the phenylpropanoid pathway remains poorly understood in woody species. We isolated an R2R3-MYB transcription factor MYB6 from Populus tomentosa and determined that it was expressed predominately in young leaves. Overexpression of MYB6 in transgenic poplar upregulated flavonoid biosynthetic gene expression, resulting in significantly increased accumulation of anthocyanin and proanthocyanidins. MYB6-overexpression plants showed reduced secondary cell wall deposition, accompanied by repressed expression of secondary cell wall biosynthetic genes. We further showed that MYB6 interacted physically with KNAT7 and formed functional complexes that acted to repress secondary cell wall development in poplar and Arabidopsis. The results provide an insight into the transcriptional mechanisms involved in the regulation of the metabolic fluxes between the flavonoid and lignin biosynthetic pathways in poplar.

Widespread Cenozoic basalts, erupted at ca. 24–0.16 Ma in central Inner Mongolia, eastern China, are significant for understanding the potential links between deep subduction of oceanic slabs and the genesis of continental intra-plate magmatism. Here we examine the whole-rock geochemical and isotopic data, as well as olivine compositions, for Cenozoic alkali and tholeiitic basalts from the Abaga, Huitengliang, and Chifeng areas in central Inner Mongolia. The results suggest that fractional crystallization of olivine + clinopyroxene (in the alkali basalts) and olivine (in the tholeiites), played a key role in their magmatic evolution, without significant crustal contamination or post-magmatic alteration. Geochemical and petrogenetic analyses show that pyroxene and garnet were dominant phases in the residual mineral assemblage for both alkali basalts and tholeiites, implying a pyroxenite source for these basalts. We propose that a pyroxenite-dominated source may be the product of reaction between recycled oceanic slab-derived melts and surrounding mantle peridotites. The spatial and geochemical variations of the Cenozoic basalts in central Inner Mongolia, together with recent geophysical and geological observations in eastern China, imply that the origin and evolution of large-scale Cenozoic continental intra-plate magmatism can be related to subduction of the Paleo-Pacific and Paleo-Asian oceanic slabs. Incorporation of recycled oceanic materials from these two subducted slabs thus influenced the mantle source lithologies and deep-Earth geodynamic processes beneath eastern China.

The drum-disk-shaft system is a significant part of the aero-engine rotor structure and directly influences the rotor dynamics. The dynamic model of a drum-disk-shaft structure was established considering the elastic support, flexible connection, and the Coriolis and centrifugal effects on the drum due to the rotation. The effects of support stiffness, coupling stiffness and rotating speed on vibration behaviors of the system were investigated. Some results were obtained. It is found that the disk's vibration and the drum's translational motion are coupled whatever the circumferential number (n) is, and the local deformation of the drum is coupled with the disk's vibration only under n = 1. When n is equal to 1, the more veering phenomena can be found during the process of the variation of the coupling stiffness, and support stiffness and the mode shapes are plotted to show the phenomena. At last, the effect of rotating speed on the frequencies of the coupling system was investigated. It is shown that the forward and backward traveling waves are generated in all the modes of the system under n = 1 due to the rotating speed and coupling effects, but only in the modes of the drum as n is not equal to 1. Also, the coupling stiffness and support stiffness can significantly affect the critical speed of the system.

A dynamic model of the rotating shrouded blade is established, considering the shroud mass, the Coriolis force, and the centrifugal stiffening effect. And a macroslip model of dry friction with variable normal load is established to simulate the separation-contact-stick-slip state of the shroud. The Lagrangian equation is utilized to solve the differential motion equation, and the Galerkin method is used for discretization. The influence of shroud structure’s parameters such as rotational speed, contact angle, friction coefficient, clearance, and shroud position on the damping effect of the shroud is reviewed by means of amplitude-frequency response and energy through the Newmark-β numerical method. The results demonstrate that the damping effect of the shroud by contact is more obvious than by friction and the amplitude-frequency curve of the shrouded blade shows a strong hard nonlinear phenomenon.

An improved principle is proposed in this paper to achieve a more efficient amplitude suppression of an oscillating pendulum by a controllable moving mass. By establishing the governing equation of the pendulum with a moving mass, several suppression rules are presented to stipulate the motion parameters of the moving mass. The damping ratio is introduced to quantify the suppression effects generated by the mass intermittent motion. With the verification of the accuracy of the present model, some simulation has been taken to get the maximum damping ratio and solve the problem of the nonsynchronous motion. The simulation results show that the new principle is a more powerful control method for the oscillation problem of a pendulum. It is suggested that the new method should carry out the relevant active control experiment in the future research.

In this paper, the effects of ground surface boundary conditions, especially diurnal shading, on performance of horizontal ground source heat pump (GSHP) systems were studied. Firstly, a GSHP system model, which consists of the heat transfer of horizontal ground heat exchangers (GHEs) and the integration of the heat pump, and the ground surface boundary model are introduced. The diurnal shading model for canyon streets is also introduced. Then, effects of ground surface boundary conditions and shading on horizontal GSHP systems are studied. Results show that different assumptions on ground surface boundary conditions have significant impact on outcomes and should carefully be considered during analysing. The outlet fluid temperature and fluctuation in North-South (N-S) streets are higher than those of East-West (E-W) streets. The increase in street aspect ratios and latitudes could decrease sunshine exposure time of the streets. Daily variations of solar radiation and shading influence the outlet temperatures of horizontal GHEs up to buried depth of 2.5 m. Therefore, the effects of solar radiation and shading should be considered when studying shallow horizontal GHEs.

To investigate the nonlinear vibration behavior of bolted joined cylindrical-cylindrical shell, a macroslip model was considered into the radial connection at the interface between the shell segments. Based on Sanders’ shell theory and the connection condition, the vibration differential equation of the structure was established. The mono-harmonic method was used to linearize the connection model and incremental harmonic balance method was used to obtain the results of the dynamic response. First, to test the accuracy of the present method, the frequency analysis was done and the results were compared with those by ANSYS and a good agreement was shown. Then, the convergence of the method was discussed. And finally, the effects of the preload of bolts, excitation amplitude, frictional coefficient and connection stiffness on the forced response were studied. The soft nonlinearity of the response curves was easily obtained under some conditions. The results show the resonance frequency and amplitude are sensitive to the preload of bolts, excitation amplitude, frictional coefficient and connection stiffness. The results reveal the dynamic characteristics of bolted joined cylindrical-cylindrical shell and would be of signification for shell structure design and vibration control.

The purpose of this paper is to investigate the coupling vibration characteristics of a flexible shaft-disk-blades system with mistuned features. There are some new phenomena due to the coupling effects of shaft-bending, shaft-torsion, disk-transverse and blade-bending. In this investigation, this paper mainly focuses on the influence of mistuned features of the blade's length and the stagger angle. It is found that there are four types of coupling modes: the coupling mode of shaft bending, disk transverse and blade bending (SDB), the coupling mode of shaft torsion disk transverse-blade bending (TDB), the coupling mode of disk transverse and blade bending (DB), the repeated mode of blade bending-blade bending (BB). With the effect of mistuned features, the natural frequencies and the coupling mode type will change correspondingly. With the mistuning value of blade length employed in this study, the TDB mode in the tuned system will disappear and shift into TSDB mode instead, and one of the repeated SDB modes will be replaced by STDB modes. Due to this mistuned features, the blades and disk experience a certain degree of vibration localization phenomenon. Different from the length feature, the influence of mistuning values of blade's stagger angle mainly take effect on the coupling modes. At last, by inspection on the Campbell diagrams, the influence of rotational speed on the transformation of natural frequencies is illustrated on the tuned/mistuned flexible shaft-disk-blades coupling structure.

UDP-glycosyltransferases (UGTs), as phase II detoxification enzymes, are widely distributed within living organisms and play vital roles in the biotransformation of endobiotics and xenobiotics in insects. Insects increase the expression of detoxification enzymes to cope with the stress of xenobiotics, including insecticides. However, the roles of UGTs in insecticide resistance are still seldom reported. In this study, two UGT inhibitors, namely, 5-nitrouracil and sulfinpyrazone, were found to synergistically increase the toxicity of imidacloprid in the resistant population of Diaphorina citri. Based on transcriptome data, a total of 17 putative UGTs were identified. Quantitative real-time PCR showed that fourteen of the 17 UGT genes were overexpressed in the resistant population relative to the susceptible population. Using RNA interference technology to knockdown six UGT genes, the results suggested that silencing the selected UGT375A1, UGT383A1, UGT383B1, and UGT384A1 genes dramatically increased the toxicity of imidacloprid in the resistant population. However, silencing the UGT362B1 and UGT379A1 genes did not result in a significant increase in the toxicity of imidacloprid in the resistant population. These findings revealed that some upregulated UGT genes were involved in imidacloprid resistance in D. citri. These results shed some light upon and further our understanding of the mechanisms of insecticide resistance in insects.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

Background Cellulase is the one of the largest contributors to the high production costs of the lignocellulose-based biorefineries. As the most widely used cellulase producer, Trichoderma reesei has two weaknesses, deficiencies in β-glucosidase and cellobiohydrolase II. This work aimed at solving this problem by simultaneous enhancement of the beta–exo synergism and exo–exo synergism in T. reesei cellulase to increase the cellulose degrading capability, i.e. enhanced co-expression of the β-glucosidase gene the cellobiohydrolase II gene of T. reesei. Results Enhanced co-expression of the β-glucosidase gene and the cellobiohydrolase II gene in T. reesei using the strong promoter Pcbh1 was found successful in overcoming the two weaknesses. Filter paper activities of T. reesei cellulase were greatly elevated, which were 7.21 ± 0.45 (E7, Aabgl1 and Trcbh2) and 7.69 ± 0.42 (F6, Anbgl1 and Trcbh2) FPIU/mL. They were much higher than that of the parental strain Rut-C30, 2.45 ± 0.36 FPIU/mL. Enzymatic hydrolysis yields were also improved, from 67.22 ± 1.61% by Rut-C30 cellulase to 87.98 ± 0.65% by E7 cellulase and 86.50 ± 1.01% by F6 cellulase. The substrate loading for 1 g glucose release from SECS were decreased, from 2.9637 g SECS using Rut-C30 cellulase to 2.0291 g SECS using E7 cellulase and 2.0573 g SECS using F6 cellulase. As a result, the efficiency of the process from SECS to glucose was substantially improved. Conclusions Enhanced co-expression of the β-glucosidase gene and the cellobiohydrolase II gene in T. reesei using the strong promoter Pcbh1 in T. reesei was proven triumphal in the simultaneous enhancement of the beta–exo synergism and exo–exo synergism in T. reesei cellulase. This strategy also improved the cellulase production, enzymatic hydrolysis yield and the efficiency of the process from SECS to glucose in the context of on-site cellulase production. This work is a commendable attempt in the cellulase composition optimization at the transcriptional level.

Nd can be ionized to NdO+ about 5–10 fold more efficiently than to Nd+ by thermal ionization mass spectrometry (TIMS). However, with the NdO+ method, Ce and Pr must be separated from Nd as completely as possible to reduce CeO+ and PrO+ isobaric interferences on NdO+ (e.g.141Pr18O+ on 143Nd16O+). With previously reported methods, it is difficult to achieve an efficient Pr–Nd separation although a perfect Sm–Nd separation can be achieved. In this study, a rapid, single column scheme for the separation of Nd and Sm from geological samples, based on TODGA resins (1 mL resin bed volume, 50–100 μm particle size), was developed. The total column separation time, including column cleaning steps, was about 8 h. With this method, not only Nd and Sm could be efficiently separated from the sample matrix, but also a perfect separation of Nd from Ce, Pr and Sm could be obtained. The recovery yield was greater than 90% for Nd and 95% for Sm. Furthermore, since only a single TODGA column separation step was involved, low procedural blanks (Sm < 5 pg; Nd < 10 pg) could be achieved. Therefore, the method is particularly useful for the separation of low levels of Nd from geological samples for isotope analysis as NdO+ by TIMS. Finally, several rock reference materials, including BCR-2, BHVO-2, BIR-1a and UB-N, with different column loads, were analyzed to verify the reliability of the chemical procedure, and the analytical results show good agreement with the recommended values for the 143Nd/144Nd isotopic ratios and Sm and Nd concentrations.

Prothioconazole, a chiral triazole fungicide, is widely used to control Fusarium head blight (FHB) of wheat. Fusarium graminearum (F. graminearum), as the main pathogen of FHB, can produce many secondary metabolites including deoxynivalenol (DON), which threatens the health of humans and animals. However, some fungicides may stimulate F. graminearum to synthesize more DON under certain conditions. Until now, the fungicidal activity and enantioselective effect of prothioconazole enantiomers on DON production, transcriptome and metabolome of F. graminearum were unclear. The fungicidal activity of R-(-)-prothioconazole against F. graminearum was 9.12-17.73 times higher than that of S-(+)-prothioconazole under all conditions. Prothioconazole enantiomers can induce F. graminearum to synthesize more DON under 0.99 water activity (a

For insects, odorant-binding proteins (OBPs) play an essential role in binding and transporting semiochemicals through the sensillum lymph to olfactory receptor neurons within the antennal sensilla. In the present study, the full-length cDNA encoding a general odorant-binding protein 1 (DcitOBP1, accession number KY475564) was cloned from the antennae of Diaphorina citri using RACE-PCR, and qRT-PCR analysis revealed that the DcitOBP1 gene was expressed mainly in the antennae of D. citri. In molecular docking assay, the results showed that DcitOBP1 protein has better binding affinities to the 12 selected host-plant volatile compounds. Then, the recombinant DcitOBP1 protein was expressed in Escherichia coli. After removed His-Tag, the binding properties of purified DcitOBP1 protein to the selected host-plant volatile compounds were investigated in a fluorescence ligand-binding assay, similar, but more obviously binding properties of DcitOBP1 protein result were obtained, the dissociation constant (KD) value of DcitOBP1/1-NPN complex was 6.440 ± 0.521, and the DcitOBP1 protein showed high binding affinities (IC50 < 100 μM) to six of the selected ligands, namely methyl salicylate, α-phellandrene, (1R)-(+)-α-pinene, 3-carene, β-caryophyllene, and α-caryophyllene. Additionally, the behavior bioassays were also showed that D. citri had significant behavioral responses toward to α-caryophyllene, β-caryophyllene, (1R)-(+)-α-pinene, and α-phellandrene. Our investigation infer that the DcitOBP1 protein might play a crucial role in host-plant volatile odorants' perception in D. citri, and these results also have been supplied previous insight evidence into the physiological functions of the DcitOBP1 protein of D. citri.

Flavonoids, which modulate plant resistance to various stresses, can be induced by high light. B-box (BBX) transcription factors (TFs) play crucial roles in the transcriptional regulation of flavonoids biosynthesis, but limited information is available on the association of BBX proteins with high light. We present a detailed overview of 45 Populus trichocarpa BBX TFs. Phylogenetic relationships, gene structure, tissue-specific expression patterns and expression profiles were determined under 10 stress or phytohormone treatments to screen candidate BBX proteins associated with the flavonoid pathway. Sixteen candidate genes were identified, of which five were expressed predominantly in young leaves and roots, and BBX23 showed the most distinct response to high light. Overexpression of BBX23 in poplar activated expression of MYB TFs and structural genes in the flavonoid pathway, thereby promoting the accumulation of proanthocyanidins and anthocyanins. CRISPR/Cas9-generated knockout of BBX23 resulted in the opposite trend. Furthermore, the phenotype induced by BBX23 overexpression was enhanced under exposure to high light. BBX23 was capable of binding directly to the promoters of proanthocyanidin- and anthocyanin-specific genes, and its interaction with HY5 enhanced activation activity. We identified novel regulators of flavonoid biosynthesis in poplar, thereby enhancing our general understanding of the transcriptional regulatory mechanisms involved.

Background The biomanufacturing of d-glucaric acid has attracted increasing interest because it is one of the top value-added chemicals produced from biomass. Saccharomyces cerevisiae is regarded as an excellent host for d-glucaric acid production. Results The opi1 gene was knocked out because of its negative regulation on myo-inositol synthesis, which is the limiting step of d-glucaric acid production by S. cerevisiae. We then constructed the biosynthesis pathway of d-glucaric acid in S. cerevisiae INVSc1 opi1Δ and obtained two engineered strains, LGA-1 and LGA-C, producing record-breaking titers of d-glucaric acid: 9.53 ± 0.46 g/L and 11.21 ± 0.63 g/L d-glucaric acid from 30 g/L glucose and 10.8 g/L myo-inositol in fed-batch fermentation mode, respectively. However, LGA-1 was preferable because of its genetic stability and its superior performance in practical applications. There have been no reports on d-glucaric acid production from lignocellulose. Therefore, the biorefinery processes, including separated hydrolysis and fermentation (SHF), simultaneous saccharification and fermentation (SSF) and consolidated bioprocessing (CBP) were investigated and compared. CBP using an artificial microbial consortium composed of Trichoderma reesei (T. reesei) Rut-C30 and S. cerevisiae LGA-1 was found to have relatively high d-glucaric acid titers and yields after 7 d of fermentation, 0.54 ± 0.12 g/L d-glucaric acid from 15 g/L Avicel and 0.45 ± 0.06 g/L d-glucaric acid from 15 g/L steam-exploded corn stover (SECS), respectively. In an attempt to design the microbial consortium for more efficient CBP, the team consisting of T. reesei Rut-C30 and S. cerevisiae LGA-1 was found to be the best, with excellent work distribution and collaboration. Conclusions Two engineered S. cerevisiae strains, LGA-1 and LGA-C, with high titers of d-glucaric acid were obtained. This indicated that S. cerevisiae INVSc1 is an excellent host for d-glucaric acid production. Lignocellulose is a preferable substrate over myo-inositol. SHF, SSF, and CBP were studied, and CBP using an artificial microbial consortium of T. reesei Rut-C30 and S. cerevisiae LGA-1 was found to be promising because of its relatively high titer and yield. T. reesei Rut-C30 and S. cerevisiae LGA-1were proven to be the best teammates for CBP. Further work should be done to improve the efficiency of this microbial consortium for d-glucaric acid production from lignocellulose.

Isotope dilution thermal ionization mass spectrometry (ID-TIMS) is considered the "gold standard" for obtaining precise

Flexible sensors with wide sensing ranges require responsiveness under tiny and large strains. However, the development of strain sensors with wide detection ranges is still a great challenge due to the conflict between the tiny strain requirements of sparse conductive networks and the large strain requirement of dense conductive networks. Herein, we present a facile method for fabricating a gradient conductive network composed of sparse and dense conductive networks. The surface penetration technology in which carbon black (CB) penetrated from the natural rubber latex (NRL) glove surface to the interior was used to fabricate a gradient conductive network. The prolonged immersion time from 1 to 30 min caused the penetration depth of CB to increase from 2 to 80 μm. Moreover, CB formed hierarchical rough micro- and nanoscale structures, creating a superhydrophobic surface. The gradient conductive network of sensors produced an ultrawide detection range of strain (0.05-300%) and excellent reliability and reproducibility. The sensors can detect a wide range of human motions, from tiny (wrist pulse) to large (joint movements) motion monitoring. The flexible sensors attached to a flexible basement can be used to detect pressure in a wide detection range (1.7-2900 kPa). Pressure responsiveness was used to detect the weight, sound pressure, and dripping of tiny droplets. The sensor showed an excellent response to organic solvents, and the response intensity increased with the increasing swelling degree of the solvent for NRL.

PURPOSE/OBJECTIVE(S) Postoperative locoregional recurrence (LRR) of non-small cell lung cancer (NSCLC) is common. We aimed to explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in this subgroup of patients. MATERIALS/METHODS NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a 3-week break. Patients with no disease progression and no persistent ≥grade 2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR). RESULTS Fifty-eight patients were enrolled, and 49 patients (84.5%) completed the whole split-course HFRT-CHT protocol as scheduled. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7% and 46.4%, the 2-year and 3-year OS rate was 72.5% and 52.2%, respectively. The ORR rate was 77.6% (45/58) after the first course of HFRT-CHT, and 95.9% (47/49) after the whole course protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4%) and 7 (12.1%) patients, and one case (1.7%) of fatal pneumonitis was reported. Grade ≥3 leucopenia, neutropenia, anemia and thrombocytopenia occurred in 3 (5.2%), 2 (3.4%), 1 (1.7%) and 3 (5.2%) patients, respectively. Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1% vs. 46.9%, P = 0.001; 2-year OS, 100% vs. 59.4%, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8% vs. 47.4%, P = 0.008; 2-year OS, 100% vs. 63.0%, P = 0.001), and gross tumor volume (GTV) (< 50cm3 vs. ≥50cm3: 2-year PFS, 70.6% vs. 46.2%, P = 0.024; 2-year OS, 85.6% vs. 57.4%, P = 0.034) were significantly associated with PFS and OS. CONCLUSION Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR NSCLC patients. Good PS, a single recurrence site and GTV < 50cm3 tended to have prolonged PFS and OS. Early detection and diagnosis of LRR may improve the efficacy of this treatment regimen. Postoperative LRR deserved a second attempt of cure.

Purpose/Objective(s) To clarify the efficacy of FLASH radiotherapy (FLASH-RT) in inhibiting mammary tumorigenesis and normal tissue sparing. Materials/Methods We used a spontaneous mammary tumor model of MMTV-PyMT mice for the study. Prior to the formation of mammary tumor, MMTV-PyMT mice (3–6-week-old) were treated with a single fraction dose of 9-16 Gy FLASH-RT or conventional radiotherapy (CONV-RT) using a mice-applicator designed targeting five pair of mammary glands. Tumor growth was detected by thorough palpation of all 10 mammary glands twice a week. Liver function, HE however, IFN-g and IL-6 also significantly increased in FLASH compared with control, while IL-10 significantly decreased in CONV compared with control. Serum IL-6, IFN-g and TNF-a levels in FLASH did not markedly change on D6, D18 and D31 post-IR compared with control. Serum IL-6, IFN-g and TNF-a levels were elevated on D6 and continuously increased on D18 and D31 in CONV, but began to increase on D6, and then recovered to the control level on D18 or D31 in FLASH. Serum IL-10 levels decreased at D6, D18 and D31 in CONV, but began to decrease at D6, and then recovered to the control level at D18 or D31 in FLASH. FLASH induced reactive oxygen species (ROS) accumulation in the tumor tissue but not in normal tissue; while absence of ROS accumulation in either tumor or normal tissue under CONV. Notably, the ROS level of normal liver tissue did not differ under CONV or FLASH. Conclusion We found that mammary tumorigenesis was inhibited by FLASH without significant liver injury compared with CONV-RT. The alteration of serum and liver inflammatory cytokines induced by CONV-RT was mildly altered by FLASH. This unique benefit can by partially explained by the accumulatio of ROS in tumor tissue after FLASH.

Accurate prediction of tumour response to neoadjuvant chemoradiotherapy enables personalised perioperative therapy for locally advanced rectal cancer. We aimed to develop and validate an artificial intelligence radiopathomics integrated model to predict pathological complete response in patients with locally advanced rectal cancer using pretreatment MRI and haematoxylin and eosin (HE)-stained biopsy slides.In this multicentre observational study, eligible participants who had undergone neoadjuvant chemoradiotherapy followed by radical surgery were recruited, with their pretreatment pelvic MRI (T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging) and whole slide images of HE-stained biopsy sections collected for annotation and feature extraction. The RAdioPathomics Integrated preDiction System (RAPIDS) was constructed by machine learning on the basis of three feature sets associated with pathological complete response: radiomics MRI features, pathomics nucleus features, and pathomics microenvironment features from a retrospective training cohort. The accuracy of RAPIDS for the prediction of pathological complete response in locally advanced rectal cancer was verified in two retrospective external validation cohorts and further validated in a multicentre, prospective observational study (ClinicalTrials.gov, NCT04271657). Model performances were evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Between Sept 25, 2009, and Nov 3, 2017, 303 patients were retrospectively recruited in the training cohort, 480 in validation cohort 1, and 150 in validation cohort 2; 100 eligible patients were enrolled in the prospective study between Jan 10 and June 10, 2020. RAPIDS had favourable accuracy for the prediction of pathological complete response in the training cohort (AUC 0·868 [95% CI 0·825-0·912]), and in validation cohort 1 (0·860 [0·828-0·892]) and validation cohort 2 (0·872 [0·810-0·934]). In the prospective validation study, RAPIDS had an AUC of 0·812 (95% CI 0·717-0·907), sensitivity of 0·888 (0·728-0·999), specificity of 0·740 (0·593-0·886), NPV of 0·929 (0·862-0·995), and PPV of 0·512 (0·313-0·710). RAPIDS also significantly outperformed single-modality prediction models (AUC 0·630 [0·507-0·754] for the pathomics microenvironment model, 0·716 [0·580-0·852] for the radiomics MRI model, and 0·733 [0·620-0·845] for the pathomics nucleus model; all p0·0001).RAPIDS was able to predict pathological complete response to neoadjuvant chemoradiotherapy based on pretreatment radiopathomics images with high accuracy and robustness and could therefore provide a novel tool to assist in individualised management of locally advanced rectal cancer.National Natural Science Foundation of China; Youth Innovation Promotion Association of the Chinese Academy of Sciences.

In recent years, deoxynivalenol (DON) has frequently been detected in wheat grains and their products. The enantioselective impact of flutriafol on the growth and DON biosynthesis of

Background: No consensus in sequence selection for artificial intelligence model development has been achieved, we aimed to explore whether contrast-enhanced magnetic resonance imaging (ceMRI) could be substituted in the identification and segmentation of nasopharyngeal carcinoma (NPC) with the aid of deep learning models in a large-scale cohort. Methods: A total of 4,478 eligible individuals were randomly split into training, validation and test sets. The diagnostic performance between NPC and benign hyperplasia and segmentation efficacy in NPC were compared among self-constrained 3D DenseNet models developed using axial T1-weighted imaging (T1WI), T2WI or enhanced T1WI (T1WIC) images separately. Findings: All developed models exhibited similar satisfactory diagnostic performance in discriminating NPC from benign hyperplasia, attaining over accuracy over 99.00% in all T stages of NPC. However, the T1WIC model yielded a significantly higher dice similarity coefficient (DSC) and lower average surface distance (ASD) than either the T1WI model or T2WI model in the test set of NPC cohort (DSC, 0.768±0.070 vs 0.759±0.065 and 0.755±0.071, p < 0.001; ASD, 1.573±0.954 mm vs 1.661±0.898 mm and 1.722±1.133 mm, p < 0.01).Interpretation: Unenhanced MRI could substitute ceMRI in discriminating NPC from benign hyperplasia but not in the segmentation for NPC with the aid of deep learning models and ceMRI remained the optimal sequence for developing segmentation models for NPC , indicating the feasibility of reducing the use of MR contrast in screening program. Funding: This work was supported by the National Natural Science Foundation of China [Grant No. 31900461, 81702873, 81872375, 81572665, 81802712]. Declaration of Interest: Nothing to disclose. Ethical Approval: The ethics committee of the authors’ institution approved the study protocol and patient consent was waived due to the retrospective nature of the study.

Additional file 7: Fig. S7. (A) FPAs and CBAs during fermentation on 15 g/L Avicel by T. reesei Rut-C30 and the engineered T. reesei for myo-inositol production. (B) Concentrations of myo-inositol after 5 d of fermentation. The data shown here are average values of at least three biological replicates, and the error bars represent standard deviations.

Additional file 9: Table S1. Plasmids and strains used in this study.

Additional file 1: Fig. S1. Results of liquid chromatography–mass spectrometry (LC–MS) analysis. (A) LC and (B) MS graphs of the fermentation broth of S. cerevisiae LGA-1 after 7 d of fed-batch fermentation in YPD medium supplemented with 10 g/L glucose and 10.8 g/L myo-inositol. (C) MS graph of the standard of d-glucaric acid

Additional file 4: Fig. S4. Time courses of CBPs of 15, 17.5 and 20 g/L Avicel or SECS for d-glucaric acid production by S. cerevisiae LGA-1. (A) Concentrations of d-glucaric acid and yields during CBP of Avicel. (B) FPAs during CBP of Avicel. (C) Concentrations of d-glucaric acid and yields during CBP of SECS. (D) FPAs during CBP of SECS. The data shown here are average values of at least three biological replicates, and the error bars represent standard deviations.

Additional file 5: Fig. S5. Effects of the inoculum ratio of T. reesei Rut-C30 to S. cerevisiae LGA-1 on the CBPs of (A and B) 15 g/L Avicel and (C and D) SECS for d-glucaric acid production. (A) Concentrations of d-glucaric acid during CBP of Avicel. (B) FPAs during CBP of Avicel. (C) Concentrations of d-glucaric acid during CBP of SECS. (D) FPAs during CBP of SECS. The data shown here are average values of at least three biological replicates, and the error bars represent standard deviations.

Additional file 6: Fig. S6. Effects of the delay time of S. cerevisiae LGA-1 inoculation on the CBPs of (A and B) 15 g/L Avicel and (C and D) SECS by the microbial consortium of T. reesei Rut-C30 and S. cerevisiae LGA-1 for d-glucaric acid production. (A) Concentrations of d-glucaric acid during CBP of Avicel. (B) FPAs during CBP of Avicel. (C) Concentrations of d-glucaric acid during CBP of SECS. (D) FPAs during CBP of SECS. The data shown here are average values of at least three biological replicates, and the error bars represent standard deviations.