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Abstract Background Natural tetramates are a family of hybrid polyketides bearing tetramic acid (pyrrolidine-2,4-dione) moiety exhibiting a broad range of bioactivities. Biosynthesis of tetramates in microorganisms is normally directed by hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries, which form the tetramic acid ring by recruiting trans- or cis-acting thioesterase-like Dieckmann cyclase in bacteria. There are a group of tetramates with unique skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, which remain to be investigated for their biosynthetic logics. Results Herein, the tetramate type compounds bripiodionen (BPD) and its new analog, featuring the rare skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, were discovered from the sponge symbiotic bacterial Streptomyces reniochalinae LHW50302. Gene deletion and mutant complementation revealed the production of BPDs being correlated with a PKS-NRPS biosynthetic gene cluster (BGC), in which a Dieckmann cyclase gene bpdE was identified by sit-directed mutations. According to bioinformatic analysis, the tetramic acid moiety of BPDs should be formed on an atypical NRPS module constituted by two discrete proteins, including the C (condensation)-A (adenylation)-T (thiolation) domains of BpdC and the A-T domains of BpdD. Further site-directed mutagenetic analysis confirmed the natural silence of the A domain in BpdC and the functional necessities of the two T domains, therefore suggesting that an unusual aminoacyl transthiolation should occur between the T domains of two NRPS subunits. Additionally, characterization of a LuxR type regulator gene led to seven- to eight-fold increasement of BPDs production. The study presents the first biosynthesis case of the natural molecule with 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton. Genomic mining using BpdD as probe reveals that the aminoacyl transthiolation between separate NRPS subunits should occur in a certain population of NRPSs in nature.

In principle, the imaging millimeter-wave radar based on time-division multiplexing multiple-input multiple-output (MIMO) technologies can provide richer target information for intelligent transportation systems due to the high-density target point cloud output. However, the chirp repetition interval extension reduces radar's inherent maximum detectable velocity, leading to the unavoidable problem of estimating the target velocity with a large ambiguity period in imaging radar moving target surveillance applications. To alleviate these problems, we propose an improved hypothetical phase compensation algorithm. Unlike the original method of determining the Doppler ambiguity period by comparing the peak amplitude of the angular power spectrum in each hypothetical case, the proposed algorithm selects the peak of the angular power signal-to-noise ratio (SNR) spectrum as the processing object and jointly decides the target speed by the average of the two highest wave peak intervals in the SNR variation curve. Simulations and practical experiments show that the improved algorithm has higher anti-interference performance. In particular, the proposed algorithm can remain continuously effective when multiple targets or angle information exist in the same distance Doppler cell, making it more suitable for MIMO imaging applications.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS–USP25 protein–protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS–USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS–USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Abstract Epidemiological and clinical data of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2) admitted to three designated hospitals in Quanzhou City, Fujian Province, China, were collected and analyzed. Overall, 2,541 patients infected with BA.2, comprising 1,060 asymptomatic, 1,287 mild, and 194 moderate infections, were enrolled. The percentage of moderate infections was higher in patients aged ≥ 60 years than in those aged

Suspension bridges are the most common type of bridge used to cross the ocean. The cable clamps in suspension bridges clamp the main cables by bolt preload, but the elastic interaction of the bolts reduces the preload, which is detrimental to the force in suspension bridges. However, research on the factors influencing the elastic interaction of cable clamp bolts in suspension bridges is currently limited. This paper aims to explore the law of influence of external factors on the elastic interaction of bolts through a combined approach of theoretical analysis, full-scale experiment, and finite element simulation. The results indicate that the average preload loss was reduced by about 27% when the elastic modulus was increased by about 110%. The average preload loss was reduced by about 45% when the bolt center distance was increased by 75%. The number of bolts has a small effect on the elastic interaction, which can be ignored. When the preload of bolt installation was increased by 133%, the average preload loss was reduced by approximately 125%, which was almost a linear relationship. Tightening the bolt from the center bolt creates greater elastic interaction. The conclusions can provide suggestions for reducing the elastic interaction of bolts in the design and construction of suspension bridge cable clamps.

Summary: SurE, the first reported penicillin-binding protein-like thioesterase (PBP-like TE), is known as a new off-loading cyclase, which catalyzes heterochiral coupling in nonribosomal peptides (NRPs). However, the structural rationale for substrate stereoselectivity and enzymatic mechanism remains mysterious. Here, computational models, integrating MD simulations and QM/MM methods, unveiled SurE’s substrate recognition and catalytic process. An oxyanion hole stabilized the C-terminal D-residue during recognition. Residue R446 anchored the substrate for macrocyclization. A vital hydrogen-bonding network (Y154, K66, N156), verified by mutation results, was responsible for the recognition of N-terminal L-residue and involvement in catalytic process with a calculated 19.4 kcal/mol energy barrier. Four novel-designed peptide precursors were effectively cyclized into cyclopeptides by SurE based on computational analysis. Our results provide a comprehensive understanding of SurE’s catalytic mechanism and guiding design of versatile PBP-like TEs for novel macrocyclic NRPs.

The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123 (1), veramycin A (2), NFAT-133 (3) and benwamycin I (4), which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities. Though the biosynthetic pathway of 1−3 was reported as a type I polyketide synthase (PKS), the PKS assembly line was interpreted inconsistently, and it remains a mystery how the compound 3 was generated. Herein, the PKS assembly logic of 1−4 was revised by site-mutagenetic analysis of the PKS dehydratase domains. Based on gene deletion and complementation, the putative P450 monooxygenase nftE1 and metallo-beta-lactamase (MBL) fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1−4. The absence of nftE1 led to abolishment of 1−4 and accumulation of new products (5−8). Structural elucidation reveals 5−8 as the non-aromatic analogs of 1, suggesting the NftE1-catalyzed aromatic core formation. Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected. As a rare MBL-fold hydrolase from type I PKSs, NftF1 potentially generates the compound 3 through two strategies: catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.

The creep behavior of Ultra-High-Performance Concrete (UHPC) was investigated by machine learning (ML) and SHapley Additive exPlanations (SHAP). Important features were selected by feature importance analysis, including water-to-binder ratio, aggregate-to-cement ratio, compressive strength at loading age, elastic modulus at loading age, loading duration, steel fiber volume content, and curing temperature. Four typical ML models—Random Forest (RF), Artificial Neural Network (ANN), Extreme Gradient Boosting Machine (XGBoost), and Light Gradient Boosting Machine (LGBM)—were studied to predict the creep behavior of UHPC. Via Bayesian optimization and 5-fold cross-validation, the ML models were tuned to achieve high accuracy (R2 = 0.9847, 0.9627, 0.9898, and 0.9933 for RF, ANN, XGBoost, and LGBM, respectively). The contribution of different features to the creep behavior was ranked. Additionally, SHAP was utilized to interpret the predictions by the ML models, and four parameters stood out as the most influential for the creep coefficient: loading duration, curing temperature, compressive strength at loading age, and water-to-binder ratio. The SHAP results were consistent with theoretical understanding. Finally, the UHPC creep curves for three different cases were plotted based on the ML model developed, and the prediction by the ML model was more accurate than that by fib Model Code 2010.

Several overloaded-induced overturning incidents of girder bridges with single-column piers have occurred in recent years, resulting in significant casualties and economic losses. Temperature, in addition to overloading, may also play a role in exacerbating bridge overturning. To investigate the association between temperature and bridge overturning, an explicit finite element model (EFEM) of a three-span concrete curved continuous bridge considering nonlinearities was developed to simulate overall collapse. The effects of uniform and gradient temperatures on the overall overturning stability of curved and straight bridges were evaluated based on the EFEMs. Furthermore, the temperature–bridge coupling model and temperature–vehicle–bridge coupling model were utilized to examine how gradient temperature influences bridge overturning. The results show that the overall overturning collapse of a bridge follows four stages: stabilization, transition, risk and overturning. Variations in uniform temperature from −30 °C to 60 °C had a negligible effect on the ultimate vehicle weight for bridge overturning, with a variation of less than 1%. As the gradient temperature ranged from −30 °C to 60 °C, curved bridges show less than a 2% variation in ultimate vehicle weights, compared to a range of −6.1% to 11.7% for straight bridges. The torsion caused by positive gradient temperature in curved bridges can exacerbate bridge overturning, while negative gradient temperature in straight bridges can lead the girder to ‘upward warping’, facilitating girder separation from bearings. Monitoring the girder rotation angle and vertical reaction force of bearings can serve as important indicators for comparing the stability of bridges.

Abstract Background The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies. Methods We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively. Results Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01–1.07, P = 3.39E−03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06–1.13, P = 7.31E−08), and severe COVID-19 (OR = 1.16, 95%CI 1.08–1.26, P = 1.43E−04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02–1.11, P = 1.44E−03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07–1.16, P = 5.13E−07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB. Conclusions This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry.

ObjectivePatients with chronic hepatitis B (CHB) often fail to achieve clearance of the hepatitis B surface antigen (HBsAg) with peginterferon treatment. Our study aimed to develop a simple-to-use scoring system to predict the likelihood of HBsAg clearance following treatment with peginterferon alfa-2b(PEG-IFN-α2b) in patients with CHB.MethodsA total of 231 patients were enrolled and divided into HBsAg clearance (n = 37) and non-HBsAg clearance (n = 194) groups. Multifactor logistic models were constructed using univariate and multiple logistic regression analyses. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis were used to evaluate the discrimination, calibration, and clinical applicability of the predictive scoring system.ResultsFour clinical variables (age, baseline HBsAg level, HBsAg level decline at week 12, and alanine aminotransferase ratio at week 12) were independently associated with HBsAg clearance after PEG-IFN-α2b treatment and, therefore, were used to develop a predictive scoring system ranging from 0 to 13. The optimal cut-off value was >4, with a sensitivity of 86.49%, specificity of 72.16%, positive predictive value of 37.2%, negative predictive value of 96.6%, and an AUC of 0.872. This model exhibited good discrimination, calibration, and clinical applicability. Among patients with scores 4 HBsAg clearance was achieved in 0.85, 14.29, and 37.21% of the patients, respectively.ConclusionThe scoring system could effectively predict the predominance of HBsAg clearance after PEG-IFN-α2b treatment in the early stage. This may be helpful when making clinical decisions for the treatment of patients with CHB.

Abstract Epoxy resin (EP) composites with satisfactory thermal and tribological performance are highly required for engineering moving components. However, the simple addition of fillers leaded to the serious filler agglomeration and limited promotion in tribological properties. In this work, we constructed a new kind of three-dimensional (3D) reduced graphene oxide (RGO)/Si3N4 hybrid aerogel for EP composites, which was prepared by a facile hydrothermal self-assembly method followed by freeze-drying technique. As a result, the dispersibility of Si3N4 whiskers was greatly improved through wrapping of polydopamine—polyethyleneimine copolymer (PDA—PEI) copolymer and physical spacing of 3D skeleton. Furthermore, benefiting from the synergistic effect of RGO and Si3N4@PDA—PEI in the thermal network, the thermal conductivity of RGO/Si3N4 hybrid aerogel (GSiA)—EP increased by 45.4% compared to that of the neat EP. In addition, the friction coefficient and wear rate of GSiA—EP decreased by 83.7% and 35.8%, respectively. This work is significant for opening a tribological performance enhancement strategy though constructing 3D hybrid architecture.

The pull-out method is a simple and effective method for detecting the preload of suspension bridge cable clamp bolts. However, research on the pull-out method is currently limited. The force principles governing the bolt during the pulling process are unclear, and the relationship between tension force and the desired preload remains uncertain. This paper aims to explore the force principles of bolts during the pull-out method detection process through a combined approach of theoretical analysis, full-scale test, and finite element simulation. The results indicate that the bolt preload increases during the pulling process. The preload detected by the pull-out method is not the initial preload of the bolt, but rather it exceeds the initial preload. The force relationships among various components are determined as follows: the preload subtracts the change value of the force exerted by the nut at the tension end, which equals the change value of tension force. Additionally, an analysis of the impact of the length of the bolt clamping section and the bolt area on the preload was conducted. Under the same bolt area, a shorter clamping section length corresponds to a greater increase in preload. With the same clamping section length, the increment of preload increases with the bolt area. These findings can serve as references for detecting and specifying the preload of the bolts.

The deflection dynamic load allowance (DLA) of stiff bridges with high piers requires sub-millimeter accuracy. New technologies such as the vision-based optical method and GNSS are not yet recognized for use in DLA measurements due to their smaller SNR. Presently, the scaffolding method is widely utilized for dynamic deflection measurements in dynamic load tests owing to the reliability of employing rigid contact. When scaffolding is not available, engineers have to resort to a suspension hammer system. However, the mass eccentricity of the hammer, stretched-wire length, and wind will decrease the measurement accuracy. To overcome these drawbacks of the suspension hammer method (SHM), a preloaded spring method (PSM) and the related stretched-wire-spring system (SWSS) are proposed in this paper. The dynamic deflection of the coupled vehicle-bridge-SWSS was obtained by vehicle-bridge interaction (VBI) analysis. The sensitivity parameters of the PSM were analyzed and optimized to minimize the measurement error. Indoor experiments and field dynamic load tests were conducted to validate the feasibility and accuracy of the PSM. Additionally, the differences in dynamic deflection measurements between the PSM and SHM in windy environments were compared. The results show that, in a windless environment, the DLAs of the PSM are affected by the spring stiffness, stretched-wire length, and stretched-wire section stiffness, independently of the preload force. When the wind speed is less than or equal to 8 m/s and the pier height is less than 30 m, the maximum deflection measurement error of the PSM is −2.53%, while that of the SHM is −15.87%. Due to its low cost and high accuracy, the proposed method has broad application prospects in the dynamic deflection measurement of stiff bridges with high piers.

There are differences between the dynamic deflection and bending moment (strain) in the same section of continuous girder bridges. However, the selection of the response for calculating dynamic amplification factors (DAFs), which are essential for bridge health monitoring and safety assessment, remains controversial. Modes may play a role in the relationship between the deflection DAF and the bending moment DAF in both numerical analysis and field tests. To investigate the distinctions between the DAFs of the deflection and bending moment in a continuous girder bridge, functional expressions of the DAFs were derived, taking into account multi-factor coupling under concentrated forces. The interaction effects of the mode and road surface condition (RSC), vehicle speed, bridge span length, and span number on the deflection DAF, the bending moment DAF, and the ratio of the deflection DAF to the bending moment DAF (RDM) of precast continuous box-girder bridges were analyzed using vehicle-bridge interaction. To ensure the accuracy of the DAF in numerical computations and experimental tests, two types of accuracy indexes and the corresponding cut-off modes were provided. Validation was conducted by performing dynamic load tests on two field bridges. The results indicate that different modes have a significant effect on the RDM of the mid-span section of a bridge. When considering multiple factors, the deflection DAF and bending moment DAF of the mid-span section increased rapidly with the considered modes and then stabilized. Statistically, the RDM of all nine bridges ranged from 1.00 to 1.12, indicating that the deflection DAF was greater than the bending moment DAF. The suggested cut-off modes can be utilized for efficient and accurate calculation of the DAF and response signal fidelity.

Piericidins are a large family of bacterial α-pyridone antibiotics with antitumor activities such as their anti-renal carcinoma activity exhibited recently in nude mice. The backbones of piericidins are derived from β, δ-diketo carboxylic acids, which are offloaded from a modular polyketide synthase (PKS) and putatively undergo a carbonyl amidation before α-pyridone ring formation. The tailoring modifications to the α-pyridone structure mainly include the verified hydroxylation and O-methylation of the C-4′ position and an unidentified C-5′ O-methylation. Here, we describe a piericidin producer, terrestrial Streptomyces conglobatus, which contains a piericidin biosynthetic gene cluster in two different loci. Deletion of the amidotransferase gene pieD resulted in the accumulation of two fatty acids that should be degraded from the nascent carboxylic acid released by the PKS, supporting the carbonyl amidation function of PieD during α-pyridone ring formation. Deletion of the O-methyltransferase gene pieB1 led to the production of three piericidin analogues lacking C-5′ O-methylation, therefore confirming that PieB1 specifically catalyses the tailoring modification. Moreover, bioactivity analysis of the mutant-derived products provided clues regarding the structure-function relationship for antitumor activity. The work addresses two previously unidentified steps involved in pyridyl pharmacophore formation during piericidin biosynthesis, facilitating the rational bioengineering of the biosynthetic pathway towards valuable antitumor agents.

To overcome the limitations of using time interval division to calculate the bridge impact coefficient (IM), a sieving method has been proposed. This method employs multiple sieves on bridge time–history curve samples to ultimately obtain the bridge impact coefficients. Firstly, CA cellular automata are used to establish different levels of traffic flow fleet models. The random traffic flow–bridge coupling dynamic model is established through wheel–bridge displacement coordination and mechanical coupling relationships based on the theory of modal synthesis. Then, the variation of bridge dynamic time–history curves for different classes of random traffic flow, speed and pavement unevenness parameters are analyzed. The sieving method is applied to screen the extreme points of the dynamic time–history curve of the bridge, enabling the distribution law of the bridge IM to be obtained using the Kolmogorov–Smirnov test (K–S test) and statistical analysis. Finally, the calculated value is then compared with the IM specifications of multiple countries. The results show that the proposed method has high identification accuracy and produces a good inspection effect. The value obtained using the sieving method is slightly larger than the value specified in the US code, 0.33, which is considerably larger than the values specified in other national codes. As pavement conditions deteriorate, the IM of the bridge increases rapidly, especially under Class C and Class D pavement unevenness, which exceed the values specified in various national bridge specifications.

Despite the potential advantages of 18 mm strands, the limited research on the behavior of girders with larger-diameter strands hinders the application in bridges. Transfer length and prestress losses are two important indicators. In this research, a 32.6 m long prestressed concrete box girder with 18 mm straight strands and 15 mm harped strands was produced, and the transfer length and the prestress losses were studied. The transfer length was calculated based on the existing equations in codes and previous research. Three beam specimens were fabricated, and strain gauges were pasted on the concrete surface to measure the transfer length of 18 mm strands. It indicated that the average measured transfer length was 700 mm. This value was smaller than the transfer lengths predicted by AASHTO LRFD 2017 and ACI 318-19, while Mitchell’s equation offered the closest prediction to the average measured transfer length. Additionally, the prestress losses at different stages were evaluated. A one-end stressing test was conducted to analyze the effect of strand harping on the loss of tensile force. In comparison with the actual measured loss based on the concrete strain and the longitudinal shortening, the instantaneous prestress loss calculated using the AASTHO LRFD 2017 alternative equation was appropriate. The time-dependent prestress losses due to shrinkage, creep, and relaxation were predicted using two different methods addressed in AASHTO LRFD 2017. The time-dependent predicted losses of 69.2 MPa at 28 d using the refined method were 37% higher than the measured losses 47.4 MPa at 28 d, indicating an overestimation of AASHTO LRFD 2017. The accumulation of the total losses over time revealed that the prestress losses developed in the first two months occupied the majority of the total losses in the long term. The research may provide guidelines for the design of a pretensioned concrete box girder with 18 mm strands.

Abstract Background Neoantimycins are a group of 15-membered ring depsipeptides isolated from Streptomycetes with a broad-spectrum of anticancer activities. Neoantimycin biosynthesis is directed by the hybrid multimodular megaenzymes of non-ribosomal peptide synthetase and polyketide synthase. We previously discovered a new neoantimycin analogue unantimycin B, which was demonstrated to have selective anticancer activities and was produced from the neoantimycin biosynthetic pathway with a starter unit of 3-hydroxybenzoate, instead of the 3-formamidosalicylate unit that is common for neoantimycins. However, the low fermentation titre and tough isolation procedure have hindered in-depth pharmacological investigation of unantimycin B as an anticancer agent. Results In this work, we genetically constructed two unantimycin B producer strains and inhibited neoantimycins production by removing natO and natJ-L genes essential for 3-formamidosalicylate biosynthesis, therefore facilitating chromatographic separation of unantimycin B from the complex fermentation extract. Based on the ΔnatO mutant, we improved unantimycin B production twofold, reaching approximately 12.8 mg/L, by feeding 3-hydroxybenzoate during fermentation. Furthermore, the production was improved more than sixfold, reaching approximately 40.0 mg/L, in the ΔnatO strain introduced with a chorismatase gene highly expressed under a strong promoter for endogenously over-producing 3-hydroxybenzoate. Conclusion This work provides a case of targeting accumulation and significant production improvement of medicinally interesting natural products via genetic manipulation of precursor biosynthesis in Streptomycetes, the talented producers of pharmaceutical molecules.

Non-ribosomal peptides are a group of structurally diverse natural products with various important therapeutic and agrochemical applications. Bacterial pyrrolizidine alkaloids (PAs), containing a scaffold of two fused five-membered ring system with a nitrogen atom at the bridgehead, have been found to originate from a multidomain non-ribosomal peptide synthetase to generate indolizidine intermediates, followed by multistep oxidation, catalysed by single Bayer-Villiger (BV) enzymes, to yield PA scaffolds. Although bacterial PAs are rare in natural product inventory, bioinformatics analysis suggested that the biosynthetic gene clusters (BGCs) that are likely to be responsible for the production of PA-like metabolites are widely distributed in bacterial genomes. However, most of the strains containing PA-like BGCs are not deposited in the public domain, therefore preventing further assessment of the chemical spaces of this group of bioactive metabolites. Here, we report a genomic scanning strategy to assess the potential of PA metabolites production in our culture collection without prior knowledge of genome information. Among the strains tested, we found fifteen contain the key BV enzymes that are likely to be involved in the last step of PA ring formation. Subsequently one-strain-many-compound (OSMAC) method, supported by a combination of HR-MS, NMR, SMART 2.0 technology, and GNPS analysis, allowed identification and characterization of a new [5 + 7] heterobicyclic carbamate, legoncarbamate, together with five known PAs, bohemamine derivatives, from Streptomyces sp. CT37, a Ghanaian soil isolate. The absolute stereochemistry of legoncarbamate was determined by comparison of measured and calculated ECD spectra. Legoncarbamate displays antibacterial activity against E. coli ATCC 25922 with an MIC value of 3.1 μg/mL. Finally, a biosynthetic model of legoncarbamate and other bohemamines was proposed based on the knowledge we have gained so far.

Low-cost camera calibration is vital in air and underwater photogrammetric applications. However, various lens distortions and the underwater environment influence are difficult to be covered by a universal distortion compensation model, and the residual distortions may still remain after conventional calibration. In this paper, we propose a combined physical and mathematical camera calibration method for low-cost cameras, which can adapt to both in-air and underwater environments. The commonly used physical distortion models are integrated to describe the image distortions. The combination is a high-order polynomial, which can be considered as basis functions to successively approximate the image deformation from the point of view of mathematical approximation. The calibration process is repeated until certain criteria are met and the distortions are reduced to a minimum. At the end, several sets of distortion parameters and stable camera interior orientation (IO) parameters act as the final camera calibration results. The Canon and GoPro in-air calibration experiments show that GoPro owns distortions seven times larger than Canon. Most Canon distortions have been described with the Australis model, while most decentering distortions for GoPro still exist. Using the proposed method, all the Canon and GoPro distortions are decreased to close to 0 after four calibrations. Meanwhile, the stable camera IO parameters are obtained. The GoPro Hero 5 Black underwater calibration indicates that four sets of distortion parameters and stable camera IO parameters are obtained after four calibrations. The camera calibration results show a difference between the underwater environment and air owing to the refractive and asymmetric environment effects. In summary, the proposed method improves the accuracy compared with the conventional method, which could be a flexible way to calibrate low-cost cameras for high accurate in-air and underwater measurement and 3D modeling applications.

The dynamic response of a prestressed concrete box girder bridge under the impact of an over-height vehicle is studied using the numerical simulation method. The finite element analysis software LS-DYNA is used to simulate the collision between the bridge superstructure and an over-height truck. Further, a parametric analysis is carried out to investigate the influence of six factors, i.e., girder configuration, vehicle speed, vehicle mass, impact angle, concrete strength and strand prestress, on both local damage and overall performance of the bridge. The numerical analysis results show that the girder configuration, vehicle speed, vehicle mass and impact angle have obvious effects on both local damage and the overall behavior of the PC box girder bridge. Whereas, the concrete strength and strand prestress only have a certain effect on the local damage at the impact area with very limited influence on the overall behavior of the bridge. In addition, based on the results obtained from the numerical simulation and parametric analysis, a formula for predicting the peak and average impact force of the prestressed concrete box girder bridge under the over-height vehicle impact is developed. The proposed impact force formula comprehensively accounts for the influence of the vehicle speed, vehicle mass and impact angle and can accurately predict the impact force generated under different working conditions, which confirms the promising prospect of the proposed formula in practical applications.

Low frequency oscillation (LFO) in the electric multiple units (EMUs)-traction network cascade system (ETNCS) can lead to traction blockade and abnormal operation. Using the Chinese CRH3 EMUs as an example, a new LFO suppressing method by applying the energy storage (ES) device on EMUs is proposed in this paper and the ES is connected to the DC-link on board. The equivalent model of the ETNCS is established at first. The critical condition of LFO in the ETNCS is analyzed via impedance ratio criterion and Bode diagram. Then, the proposed on-board bidirectional DC-DC converter integrated with the ES system is controlled via a virtual DC machine (VDCM) strategy, and the VDCM small signal model derivation and the parameter design are carried out. Using the Bode diagram of the impedance ratio, the system stability with the ES device controlled by the proposed VDCM scheme is analyzed again; simulation results verify the effectiveness of the control algorithm to suppress the LFO adaptively. Compared with the traditional PI controller, the system steady-state and dynamic performance can be improved with the proposed method, including decreased overshoot, fluctuation, response time, and increased gain margin of the DC-link voltage.

This paper focuses on stability analysis and stabilization of a switched system under average dwell time criteria in the continuous-time domain. The matrix polynomial approach is applied to the switched system to construct a continuous Lyapunov function and design a more effective controller, which can not only improve the system performance but also lessen the system conservativeness. The stability problem is studied with square matricial representation for the first time. The new method is more applicable than previous work under average dwell time switching with the time-varying controller gains. In addition, new sufficient conditions of stability and stabilization are derived to guarantee the global uniform exponential stability of the switched system. A numerical example is provided to show the advantages of the new method.

Abstract Distribution factors (DFs) for one typical cross-section as specified in the AASHTO LRFD specification can be varied when the bridge parameters such as span length, loading lanes and skew are changed. The diversity between design and actual DFs may be varied as the bridge parameters changed. To study this diversity, this paper presents an evaluation of lateral load DFs for prefabricated hollow slab bridges. The response of the bridge was recorded during the field test. This field test was divided into two stages: a concentrated force loading test on the prefabricated girder that settled on the bridge supports before the girders were connected transversely and a vehicle loading test after the girders were connected transversely. The instruments used to record the response of the bridge were strain gauges and dial indicators. The measured data in the multi-stages of the field test could be used to calibrate the support condition of the bridge and transverse connection between adjacent girders in the finite element model (FEM) using beam and plate elements. From the FEM, DFs for this hollow slab bridge were determined and compared with the DFs in the AASHTO LRFD specification. A parametric study using the calibrated FEM was then used to investigate the effect of various parameters including span length, skew and bridge deck thickness on the DFs. It was found that AASHTO LRFD specification is conservative compared with the analysis in the FEM, while this conservatism decreased as the span length and skew of the hollow slab bridge increased.

The universal hinge support (UHS) is a new connection system for the tower and pier of a single-tower cable-stayed bridge (STCSB), which could conform the multi-direction rotation of the tower and release the bending moment at the bottom of the tower in all directions. However, UHS is not an ideal hinge in practical projects, and the rotational constraint stiffness (RCS) of UHS is constantly changed with construction. In order to determine the RCS of UHS in situ, parametric analysis was performed by establishing a theoretical mechanical model of plane rotation and a refined solid finite element (FE) model of UHS. The slope of the linear rising segment of the load–displacement curve obtained from the numerical simulation was considered as the RCS of the UHS. The relationships between RCS and the vertical force, geometric parameters, and material parameters were established, and then the calculation formula of RCS was further proposed. To verify the accuracy of the proposed formula, a case study for a real bridge was conducted in this paper. The results show that the error of the tower rotation displacement can be reduced by about 90% using the proposed method compared with the conventional method, which regards the hinge as an ideal one, and the precision is greatly improved. This study has enormous potential to quickly determinate the RCS of UHS in practical applications, and plays a great promotion role in enriching the structural system of cable-stayed bridges.

Imaging technology enhances radar environment awareness. Imaging radar can provide richer target information for traffic management systems than conventional traffic detection radar. However, there is still a lack of research on millimeter-wave radar imaging technology for urban traffic surveillance. To solve the above problem, we propose an improved three-dimensional FFT imaging algorithm architecture for radar roadside imaging in urban traffic scenarios, enabling the concurrence of dynamic and static targets imaging. Firstly, by analyzing the target characteristics and background noise in urban traffic scenes, the Monte-Carlo-based constant false alarm detection algorithm (MC-CFAR) and the improved MC-CFAR algorithm are proposed, respectively, for moving vehicles and static environmental targets detection. Then, for the velocity ambiguity solution problem with multiple targets and large velocity ambiguity cycles, an improved Hypothetical Phase Compensation algorithm (HPC-SNR) is proposed and complimented. Further, the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is used to remove outliers to obtain a clean radar point cloud image. Finally, traffic targets within the 50 m range are presented as two-dimensional (2D) point cloud imaging. In addition, we also try to estimate the vehicle type by target point cloud size, and its accuracy reaches more than 80% in the vehicle sparse condition. The proposed method is verified by actual traffic scenario data collected by a millimeter-wave radar system installed on the roadside. The work can support further intelligent transportation management and extend radar imaging applications.

High-G MEMS accelerometer (HGMA) is a new type of sensor; it has been widely used in high precision measurement and control fields. Inevitably, the accelerometer output signal contains random noise caused by the accelerometer itself, the hardware circuit and other aspects. In order to denoise the HGMA’s output signal to improve the measurement accuracy, the improved VMD and TFPF hybrid denoising algorithm is proposed, which combines variational modal decomposition (VMD) and time-frequency peak filtering (TFPF). Firstly, VMD was optimized by the multi-objective particle swarm optimization (MOPSO), then the best decomposition parameters [kbest, abest] could be obtained, in which the permutation entropy (PE) and fuzzy entropy (FE) were selected for MOPSO as fitness functions. Secondly, the accelerometer voltage output signals were decomposed by the improved VMD, then some intrinsic mode functions (IMFs) were achieved. Thirdly, sample entropy (SE) was introduced to classify those IMFs into information-dominated IMFs or noise-dominated IMFs. Then, the short-window TFPF was selected for denoising information-dominated IMFs, while the long-window TFPF was selected for denoising noise-dominated IMFs, which can make denoising more targeted. After reconstruction, we obtained the accelerometer denoising signal. The denoising results of different denoising algorithms in the time and frequency domains were compared, and SNR and RMSE were taken as denoising indicators. The improved VMD and TFPF denoising method has a smaller signal distortion and stronger denoising ability, so it can be adopted to denoise the output signal of the High-G MEMS accelerometer to improve its accuracy.

Background: Operative duration might be important for perioperative morbidity, and its involvement has not been fully characterized in pediatric patients. We identified perioperative variables associated with operative duration and determined their influence on clinical outcomes in pediatric patients.Methods: We retrospectively reviewed 701 patients who underwent elective removal of choledochal cysts followed by Roux-en-Y hepaticojejunostomy. The patients were separated into the long operative time group (>165 min) and short operative time group (

In order to develop FDM additive manufacturing and promote the application of this technology, the essential mechanical properties including tensile strength and elastic property of PLA material fabricated by FDM additive manufacturing are studied deeply this time. Two novel theoretical models have been built to predict the tensile strength and Young's modulus of FDM additive manufacturing PLA material with different printing angles and layer thicknesses in this study. Firstly, strength theoretical model is established based on transversely isotropic material hypothesis and Tsai-Hill strength criterion. Then, Young's modulus theoretical model is established based on orthotropic material hypothesis under plane stress state. Test data indicates that the tensile strength and Young's Modulus of FDM additive manufacturing PLA material increase as the printing angle increases or the layer thickness decreases. Relative Error (RE) between theoretical results and test data is put forward as a criterion to evaluate the accuracy of the theoretical models quantitatively. All the Relative Error are so small (≤0.14) that is satisfactory in engineering applications. Therefore, one can confirm that the theoretical models established during this research can predict the tensile strength and Young's modulus of FDM additive manufacturing PLA material with different printing angles and layer thicknesses precisely. Keywords: Additive manufacturing, Tensile strength, Elastic property, Transverse isotropy, Printing angle, Layer thickness

Triple (H+/O2−/e−) conducting oxides (TCOs) have been extensively investigated as the most promising cathode materials for solid oxide fuel cells (SOFCs) because of their excellent catalytic activity for oxygen reduction reaction (ORR) and fast proton transport. However, here we report a stable twin-perovskite nanocomposite Ba-Co-Ce-Y-O (BCCY) with triple conducting properties as a conducting accelerator in semiconductor ionic fuel cells (SIFCs) electrolytes. Self-assembled BCCY nanocomposite is prepared through a complexing sol–gel process. The composite consists of a cubic perovskite (Pm-3m) phase of BaCo0.9Ce0.01Y0.09O3-δ and a rhombohedral perovskite (R-3c) phase of BaCe0.78Y0.22O3-δ. A new semiconducting–ionic conducting composite electrolyte is prepared for SIFCs by the combination of BCCY and CeO2 (BCCY-CeO2). The fuel cell with the prepared electrolyte (400 μm in thickness) can deliver a remarkable peak power density of 1140 mW·cm−2 with a high open circuit voltage (OCV) of 1.15 V at 550 °C. The interface band energy alignment is employed to explain the suppression of electronic conduction in the electrolyte. The hybrid H+/O2− ions transport along the surfaces or grain boundaries is identified as a new way of ion conduction. The comprehensive analysis of the electrochemical properties indicates that BCCY can be applied in electrolyte, and has shown tremendous potential to improve ionic conductivity and electrochemical performance.

De-domestication is the process by which cultivated plants adopt characteristics similar to that of their wild predecessors. Here Qiuet al. re-sequence de-domesticated weedy rice and matched cultivated varieties and identify genetic variants indicative of convergent evolution across multiple de-domestication events.

Streptomyces-derived natural products have been become a major focus of anti-tumor drug discovery studies. Neoantimycin F (NAT-F), was isolated from Streptomyces conglobatus by our group. Here, we examined the anti-cancer activities and its underlying molecular mechanisms implicated in NAT-F–induced apoptosis of non–small cell lung cancer (NSCLC) cells. Our results showed that NAT-F exerted excellent growth-inhibitory activity against PC9 and H1299 cells in a concentration-dependent manner. NAT-F–induced cell cycle arrest at S and G0/G1 phase in PC9 and H1299 cells, respectively. Further investigation revealed that the key proteins (including cyclinD1, cyclinE1, cyclinB1, CDK2, and CDK4) were involved in the cell regulation by NAT-F. Additionally, NAT-F significantly increased the production of reactive oxygen species (ROS), induced DNA damage, nuclear condensation, and cell apoptosis in both cell lines. Moreover, loss of the mitochondrial membrane potential (MMP) was markedly induced by NAT-F. Additional results revealed that NAT-F could up-regulate pro-apoptotic protein Bax and down-regulate anti-apoptotic protein Bcl-2, Mcl-1, and Bcl-xL, resulting in cytochrome c release from mitochondria and sequential activation of caspase-9 and -3, as well as the cleavage of poly (ADP-ribose) polymerase. Meanwhile, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK) signaling pathway were also involved in anti-cancer activity of NAT-F in NSCLC cells. Taken together, these findings indicated that NAT-F possessed anti-proliferative effect and induced apoptosis in NSCLC cells in vitro and may be conducive to promote the development of novel anti-NSCLC agents.

Four neoantimycins H-K (1–4) with C1-keto, including the new ones (1–2), were isolated from the culture of Streptomyces conglobatus RJ8. After enzymatically converting into their respective reduced type derivatives (5–8) in vitro, the absolute structures of 1–8 were established/reconfirmed by analyzing hydrolyzed components. The obtained NATs (4, 7, and 8) exhibited excellent cytotoxicity against drug-resistant colon and gastric cancer cells but low toxicity in the noncancerous cell. Further SAR investigation suggested that C1-hydroxyl, C9-isobutyl, and N-formyl contribute to the antiproliferation remarkably.

Cracking damage influences the stiffness of the girders. Many articles in the literatures have studied the development of stiffness of the scale-down model; however, full-scale model testing cannot be completely replaced by scale-down testing because of material component characteristics and boundary effects. This paper deals with the effects of cracking damage on the structural static and dynamic stiffness based on three prestressed concrete (PC) girders which were removed from an old bridge. First, the equivalent flexural rigidity of cracked prestressed concrete girder was assessed using the measured load-deflection response under cycles of loading and unloading. Then, after unloading, the frequencies were measured on the PC girders supported by the elastomeric bearings. Next, the development of frequency under different damage was studied, and finally, the dynamic stiffness of PC girders with cracks was assessed. The results indicate that the first frequency is more sensitive to the cracking of concrete compared with the second frequency and that the mode shapes are not sensitive to girder damage. The test girders cannot be simplified as an ideal simply supported beam for the purpose of identifying frequencies. In addition, the “final” (the end of the ultimate load case) equivalent flexural rigidity of the girders is 30% of the “initial” (the beginning of the first load case) equivalent flexural rigidity, compared with 50% in the scale-down test; and the final dynamic stiffness is approximately 84% of the initial dynamic stiffness, whereas the scale-down test is 72%.

The assembly-line synthases that produce bacterial polyketide natural products follow a modular paradigm in which each round of chain extension is catalysed by a different set or module of enzymes. Examples of deviation from this paradigm, in which a module catalyses either multiple extensions or none are of interest from both a mechanistic and an evolutionary viewpoint. We present evidence that in the biosynthesis of the 36-membered macrocyclic aminopolyol lactones (marginolactones) azalomycin and kanchanamycin, isolated respectively from Streptomyces malaysiensis DSM4137 and Streptomyces olivaceus Tü4018, the first extension module catalyses both the first and second cycles of polyketide chain extension. To confirm the integrity of the azl gene cluster, it was cloned intact on a bacterial artificial chromosome and transplanted into the heterologous host strain Streptomyces lividans, which does not possess the genes for marginolactone production. When furnished with 4-guanidinobutyramide, a specific precursor of the azalomycin starter unit, the recombinant S. lividans produced azalomycin, showing that the polyketide synthase genes in the sequenced cluster are sufficient to accomplish formation of the full-length polyketide chain. This provides strong support for module iteration in the azalomycin and kanchanamycin biosynthetic pathways. In contrast, re-sequencing of the gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm.