A prospective cohort study of multimetal exposure and risk of gestational diabetes mellitus.

The relationship between co-exposure to multiple metals and gestational diabetes mellitus (GDM) and the mechanisms involved are poorly understood. In this nested case-control study, 228 GDM cases and 456 matched controls were recruited, and biological samples were collected at 12-14 gestational weeks. The urinary concentrations of 10 metals and 8-hydroxydeoxyguanosine (8-OHdG) as well as the serum levels of malondialdehyde (MDA) and advanced glycation end products (AGEs) were determined to assess the association of metals with GDM risk and the mediating effects of oxidative stress. Urinary Ti concentration was significantly and positively associated with the risk of GDM (odds ratio [OR]:1.45, 95 % confidence interval [CI]: 1.12, 1.88), while Mn and Fe were negatively associated with GDM risk (OR: 0.67, 95 % CI: 0.50, 0.91 or OR: 0.61, 95 % CI: 0.47, 0.80, respectively). A significant negative association was observed between Mo and GDM risk, specifically in overweight and obese pregnant women. Bayesian kernel machine regression showed a significant negative joint effect of the mixture of 10 metals on GDM risk. The adjusted restricted cubic spline showed a protective role of Mn and Fe in GDM risk (P < 0.05). A significant negative association was observed between essential metals and GDM risk in quantile g-computation analysis (P < 0.05). Mediation analyses showed a mediating effect of MDA on the association between Ti and GDM risk, with a proportion of 8.7 % (P < 0.05), and significant direct and total effects on Ti, Mn, and Fe. This study identified Ti as a potential risk factor and Mn, Fe, and Mo as potential protective factors against GDM, as well as the mediating effect of lipid oxidation.

Male spiders avoid sexual cannibalism with a catapult mechanism.

In the animal world, numerous mechanisms have been described that allow for extremely fast actions or reactions via the slow storage of energy, typically in elastic structures, which is then nearly instantly released1-4, similar to the operation of a catapult. Many of these mechanisms are employed for prey capture1,2 or for predator avoidance3,4; however, such superfast actions have not yet been reported as a means to dodge sexual cannibalism. Here, we unveil a novel mechanism in a communal orb-weaving spider Philoponella prominens (Uloboridae) (Figure S1), whereby males undertake a split-second catapult action immediately after mating, thereby fleeing their partner (Video S1). We demonstrate that males achieve their superfast action (up to 88.2 cm/s) by extending the tibia-metatarsus joint of their first leg pair via hydraulic pressure in a joint that is known to lack extensor muscles in spiders. This rapid expansion greatly reduces the likelihood of the male being sexually cannibalized.

Construction of cadmium whole-cell biosensors and circuit amplification.

Owing to the prevalence of cadmium contamination and its serious hazards, it is important to establish an efficient and low-cost monitoring technique for the detection of the heavy metal cadmium. In this study, we first designed 30 cadmium whole-cell biosensors (WCBs) using different combinations of detection elements, reporting elements, and the host. The best performing WCB KT-5-R with Pseudomonas putida KT2440 as the host and composed of CadR and mCherry was selected for further analysis and engineering. In order to enhance its sensitivity, a positive feedback amplifier was added or the gene dosage of the reporter gene was increased. The WCB with the T7RNAP amplification module, p2T7RNAPmut-68, had the best performance and improved tolerance to cadmium with a detection limit of 0.01 µM, which is the WHO standard. It also showed excellent specificity toward cadmium when assayed with mixed metal ions. This study demonstrated the power of circuit engineering in WCB design and provided valuable insights for the development of other WCBs. KEY POINTS: • KT-5-R was selected after prescreening and engineered for better performance. • Using multi-copy reporters and the T7RNAP amplifier greatly improved the performance. • p2T7RNAPmut-68 had a detection limit of 0.01 µM and improved tolerance to cadmium.

Directed evolution of a transcription factor PbrR to improve lead selectivity and reduce zinc interference through dual selection.

Directed evolution has been proven as a powerful tool for developing proteins and strains with novel or enhanced features. In this study, a dual selection system was designed to tune the binding specificity of a transcription factor to a particular ligand with the ampicillin resistance gene amp (ON selection) as the positive selection marker and the levansucrase gene sacB (OFF selection) as the negative selection marker. It was applied to the lead responsive transcription factor PbrR in a whole-cell lead biosensor previously constructed in our lab (Jia et al. in Fems Microbiol Lett 365:fny157, 2018). After multiple rounds of ON-OFF selection, two mutants with higher specificity for lead were selected. Structural analysis revealed that the mutation C134 located on the metal-binding loop at the C-terminal of PbrR is likely associated with the enhanced binding to both lead and cadmium. The double mutations D64A and L68S close to the metal-binding residue C79 may lead to the reduced binding specificity toward zinc ions. This dual selection system can be applied to engineer the specificity of other transcription factors and provide fine-tuned tools to synthetic biology.

Contraction of weak polyelectrolyte multilayers in response to organic solvents.

Weak polyelectrolyte multilayers (PEMs) prepared by the layer-by-layer assembly technique have recently been found to demonstrate a unique contraction upon exposure to organic solvents. This response is dependent upon which organic solvent is employed, and fundamental questions have not been clarified regarding the correlation of the magnitude of the film contraction with solvent type. In this work, we used solubility parameters to analyze the response of branched poly(ethylene imine)/poly(acrylic acid) (BPEI/PAA) multilayers when exposed to a variety of solvents. BPEI/PAA multilayers were immersed in a series of 16 different organic solvents and solvent mixtures. Immersion in organic solvent caused film dehydration and therefore contraction and also induced changes in the mechanical properties of PEMs. The film thickness was the best predictor of how a film swelled in water or contracted in organic solvent when using different batches of commercially available polyelectrolytes, rather than polyelectrolyte assembly pH conditions. The degree of film contraction was correlated with Hansen and Kamlet-Taft solubility parameters as well as solvent dielectric constant. In most cases, the hydrogen bonding ability of solvents is the primary factor to determine the magnitude of film contraction. For these solvents, increasing the temperature which corresponds to decreasing the strength of hydrogen bonding, also decreases the ability to dehydrate the films. For solvents that do not follow these trends with the strength of hydrogen bonding, a stronger correlation was found between contraction and dielectric constant, indicating that both traditional solvent quality arguments and electrostatics are important to understanding the contraction of PEMs in organic solvents.