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The high-speed freight train (HSFT) is an emerging freight transportation mode that can play a significant role in the development of remote cities. In this study, we propose an optimization method for cargo distribution to prevent HSFT from overturning in strong winds. The multibody dynamics (MBD) HSFT model is built and imposed with aerodynamic loads derived through the computational fluid dynamics method. Based on the MBD simulation results, the prediction model of overturning safety for HSFT is established using gradient-boosting decision tree to make the value of cargo height continuous. Consequently, a nonlinear programming model for the cargo distribution problem is built and solved. The MBD simulation results reveal that the outer side crosswind is good for large vehicle velocity and the vehicle in the rear position of HSFT is safer. The case study demonstrates that the proposed optimization method can decrease the overturning risk for HSFT by more than 10% compared with the even distribution scheme. This research will contribute to making the loading plan for the rail company, ensuring the operational safety of HSFT in the windy area.

Nanobodies (Nbs) have great potential in immunoassays due to their exceptional physicochemical properties. With the immortal nature of Nbs and the ability to manipulate their structures using protein engineering, it will become increasingly valuable to understand what structural features of Nbs drive high stability, affinity, and selectivity. Here, we employed an anti-quinalphos Nb as a model to illustrate the structural basis of Nbs' distinctive physicochemical properties and the recognition mechanism. The results indicated that the Nb-11A-ligand complexes exhibit a "tunnel" binding mode formed by CDR1, CDR2, and FR3. The orientation and hydrophobicity of small ligands are the primary determinants of their diverse affinities to Nb-11A. In addition, the primary factors contributing to Nb-11A's limited stability at high temperatures and in organic solvents are the rearrangement of the hydrogen bonding network and the enlargement of the binding cavity. Importantly, Ala 97 and Ala 34 at the active cavity's bottom and Arg 29 and Leu 73 at its entrance play vital roles in hapten recognition, which were further confirmed by mutant Nb-F3. Thus, our findings contribute to a deeper understanding of the recognition and stability mechanisms of anti-hapten Nbs and shed new light on the rational design of novel haptens and directed evolution to produce high-performance antibodies.

Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through genome mining and heterologous expression, we identified a cav biosynthetic gene cluster responsible for the biosynthesis of DMTs 2–4, along with a P450, CavA, responsible for introducing the C-2 and C-3 hydroxy groups. Furthermore, the substrate scope of CavA revealed its ability to hydroxylate drimenol analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria.

The high-speed railway has become an important passenger transport mode. Relying on the abundant passenger transport experience and expansive railway network, the high-speed freight train (HSFT) is feasible to be developed and has great application potential. As a critical component of HSFT, the cargo plays an important role in the overturning safety of HSFT under strong wind conditions. Previous studies about the aerodynamic performance of the high-speed train usually regarded the loaded carbody as an individual rigid body. Limited attention was paid to the variability inside the vehicle. In order to improve the running safety of HSFT under strong wind conditions, the multibody dynamics simulation is adopted to demonstrate the effect of cargo property on the overturning risk of HSFT under the aerodynamic loads obtained through the computational fluid dynamics (CFD) simulations. It is demonstrated that the inner side crosswind is more dangerous than the outer side crosswind. The speed of HSFT should be limited according to the cargo quantity, and the maximum speed for a fully loaded HSFT can be 305 km/h when the crosswind velocity is 20 m/s. The larger cargo density should be encouraged because it is good for train overturning safety in severe working conditions.

The clerodane and ent-kaurane diterpenoids are two typical categories of diterpenoid natural products with complicated polycyclic carbon skeletons and significant pharmacological activities. Despite exciting advances in organic chemistry, access to these skeletons is still highly challenging. Using synthetic biology to engineer microbes provides an innovative alternative to bypass synthetic challenges. In this study, we constructed two truncated artificial pathways to efficiently produce terpentetriene and ent-kaurene, two representative clerodane and ent-kaurane diterpenes, in Escherichia coli. Both pathways depend on the exogenous addition of isoprenoid alcohol to reinforce the supply of IPP and DMAPP via two sequential phosphorylation reactions. Optimization of these constructs provided terpentetriene and ent-kaurene titers of 66 ± 4 mg/L and 113 ± 7 mg/L, respectively, in shake-flask fermentation. The truncated pathways to overproduce clerodane and ent-kaurane skeletons outlined here may provide an attractive route to prepare other privileged diterpene scaffolds.

The high-speed freight train (HSFT) is an emerging freight transportation mode that can play a significant role in the development of remote cities. In this study, we propose an optimization method for cargo distribution to prevent HSFT from overturning in strong winds. The multibody dynamics (MBD) HSFT model is built and imposed with aerodynamic loads derived through the computational fluid dynamics method. Based on the MBD simulation results, the prediction model of overturning safety for HSFT is established using gradient-boosting decision tree to make the value of cargo height continuous. Consequently, a nonlinear programming model for the cargo distribution problem is built and solved. The MBD simulation results reveal that the outer side crosswind is good for large vehicle velocity and the vehicle in the rear position of HSFT is safer. The case study demonstrates that the proposed optimization method can decrease the overturning risk for HSFT by more than 10% compared with the even distribution scheme. This research will contribute to making the loading plan for the rail company, ensuring the operational safety of HSFT in the windy area. [ABSTRACT FROM AUTHOR]

Abstract Background Physical resilience is known to minimize the adverse outcomes of health stressors for older people. However, validated instruments that assess physical resilience in older adults are rare. Therefore, we aimed to validate the Physical Resilience Instrument for Older Adults (PRIFOR) to fill the literature gap. Methods Content analysis with content validity was first carried out to generate relevant items assessing physical resilience for older adults, and 19 items were developed. Psychometric evaluation of the 19 items was then tested on 200 older adults (mean [SD] age = 76.4 [6.6] years; 51.0% women) for item properties, factor structure, item fit, internal consistency, criterion-related validity, and known-group validity. Results All 19 items had satisfactory item properties, as they were normally distributed (skewness = -1.03 to 0.38; kurtosis = -1.05 to 0.32). However, two items were removed due to substantial ceiling effects. The retained 17 items were embedded in three factors as suggested by the exploratory factor analysis (EFA) results. All items except one had satisfactory item fit statistics in Rasch model; thus, the unidimensionality was supported for the three factors on 16 items. The retained 16 items showed promising properties in known-group validity, criterion-related validity, and internal consistency (α = 0.94). Conclusions The 16-item PRIFOR exhibits good psychometric properties. Using this instrument to measure physical resilience would be beneficial to identify factors that could protect older people from negative health consequence. With the use of the PRIFOR, intervention effects could also be evaluated. It is helpful to strengthen resilience and thereby facilitate successful aging.