An entropy weight method to integrate big omics and mechanistically evaluate DILI.

BACKGROUND AND AIMS: DILI accounts for more than half of acute liver failure cases in the United States and is a major health care issue for the public worldwide. As investigative toxicology is playing an evolving role in the pharmaceutical industry, mechanistic insights into drug hepatotoxicity can facilitate drug development and clinical medication. METHODS: By integrating multisource datasets including gene expression profiles of rat livers from open TG-GATE database and DrugMatrix, drug labels from FDA Liver Toxicity Knowledge Base, and clinical reports from LiverTox, and with the employment of bioinformatic and computational tools, this study developed an approach to characterize and predict DILI based on the molecular understanding of the processes (toxicity pathways). RESULTS: A panel of 11 pathways widely covering biological processes and stress responses was established using a training set of six positive and one negative DILI drugs from open TG-GATEs. An entropy weight method-based model was developed to weight responsive genes within a pathway, and an interpretable machine-learning (ML) model XGBoot-SHAP was trained to rank the importance of pathways to the panel activity. The panel activity was proven to differentiate between injured and noninjured sample points and characterize DILI manifestation using six training drugs. Next, the model was tested using an additional 89 drugs (61 positives + 28 negatives), and a precision of 86% and higher can be achieved. CONCLUSIONS: This study provides a novel approach to mechanisms-driven prediction modeling, as well as big data integration for insights into pharmacology and other human biology areas.

The ubiquitin E3 ligase SR1 modulates the submergence response by degrading phosphorylated WRKY33 in Arabidopsis.

Oxygen deprivation caused by flooding activates acclimation responses to stress and restricts plant growth. After experiencing flooding stress, plants must restore normal growth; however, which genes are dynamically and precisely controlled by flooding stress remains largely unknown. Here, we show that the Arabidopsis thaliana ubiquitin E3 ligase SUBMERGENCE RESISTANT1 (SR1) regulates the stability of the transcription factor WRKY33 to modulate the submergence response. SR1 physically interacts with WRKY33 in vivo and in vitro and controls its ubiquitination and proteasomal degradation. Both the sr1 mutant and WRKY33 overexpressors exhibited enhanced submergence tolerance and enhanced expression of hypoxia-responsive genes. Genetic experiments showed that WRKY33 functions downstream of SR1 during the submergence response. Submergence induced the phosphorylation of WRKY33, which enhanced the activation of RAP2.2, a positive regulator of hypoxia-response genes. Phosphorylated WRKY33 and RAP2.2 were degraded by SR1 and the N-degron pathway during reoxygenation, respectively. Taken together, our findings reveal that the on-and-off module SR1-WRKY33-RAP2.2 is connected to the well-known N-degron pathway to regulate acclimation to submergence in Arabidopsis. These two different but related modulation cascades precisely balance submergence acclimation with normal plant growth.

An innovative approach to assess spinal canal expansion following French-door cervical laminoplasty by intraoperative ultrasonography.

OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and Bland‒Altman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: • Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. • Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. • Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.

PtoWRKY40 interacts with PtoPHR1-LIKE3 while regulating the phosphate starvation response in poplar.

Plants usually suffer from phosphorus starvation because of the low inorganic phosphate (Pi) status of most soils. To cope with this, plants have evolved an adaptive phosphate starvation response (PSR) which involves both developmental and metabolic changes regulated mainly by PHOSPHATE STARVATION RESPONSE1 (PHR1) and its homologs. Here, we elucidated how perennial woody plants, such as poplars (Populus spp.), respond to low-Pi stress. We first performed RNA-seq analysis of low-Pi-treated poplars and identified PtoWRKY40 is rapidly downregulated and protein degraded after stress. Overexpressing and knocking-down PtoWRKY40 downregulated and upregulated the expression of Pi starvation signaling genes, respectively, such as PHOSPHATE TRANSPORTER1 (PHT1)-type genes and PURPLE ACID PHOSPHATASE genes. PtoWRKY40 bound to the W box in the promoter of several PtoPHT1s and repressed their expression. Moreover, PtoWRKY40 interacted with PtoPHR1-LIKE3 (PtoPHL3), a PHR1 homolog in poplar, to inhibit the latter binding to the P1BS element and thus reduced PtoPHT1s' transcription under Pi-sufficient conditions. However, Pi deficiency decreased PtoWRKY40 abundance and therefore released its inhibition on PHT1s. In conclusion, we have uncovered a PSR mechanism mediated by PtoWRKY40 and PtoPHL3 which regulates Pi content in poplars, deepening our understanding of how poplars adapt to diverse Pi conditions and regulate appropriate responses to maintain Pi homeostasis.

Efficient K-Storage of Fe-Coupled Organic Molecule Anode in Ether-Based Electrolytes.

Given these advantages of widely designable structures and environmentally friendly characteristics, organic electrode materials (OEMs) are considered to be promising electrode materials for alkaline metal-ion batteries. However, their large-scale application is hampered by insufficient specific capacity and rate performance. Here, Fe2+ is coupled to the anhydride molecule NTCDA to form a novel K-storage anode Fe-NTCDA. In this way, the working potential of Fe-NTCDA anode is reduced, which makes it more suitable to be used as an anode material. Meanwhile, the electrochemical performance is significantly improved due to the increase in K-storage sites. Moreover, electrolytes regulation is implemented to optimize the K-storage behavior, resulting into a high specific capacity of 167 mAh/g after 100 cycles at 50 mA/g and 114 mAh/g even at 500 mA/g in the 3 M KFSI/DME electrolytes.

Unveiling the efficient state of Pd catalyst for robust electrocatalytic hydrodechlorination.

The application of electrochemical hydrodechlorination has been impeded due to the low utilization and activity of Pd catalyst. Herein, a series of Pd catalysts were prepared via the controllable evolution of Zn state during the pyrolysis of ZIF-8 nanosheet. Various forms of Pd with different chemical surroundings were generated upon the combined use of galvanic displacement and ion exchange process. Electrocatalytic hydrodechlorination of 4-chlorophenol was performed and the electrocatalytic hydrodechlorination efficiency of Pd/CN reaches 100% within 3 h at extra low Pd concentration. The coexistence of zero-valent Pd (Pd0) and nitrogen coordinated Pd (Pd-N) was verified by XAFS which provide multiple active sites for focusing on adsorbing H* and cracking C-Cl respectively. The synergetic effect between different chemical state of Pd for efficient hydrodechlorination of chloroaromatics and scheme for dexterous preparation of Pd based electrocatalyst are proposed and discussed.

Research on Three-Dimensional Shape Curve Reconstruction Technology for a Scraper Conveyor on an Intelligent Working Face.

"Three straight and two flat" is the inevitable demand when realizing the intelligent mining of a fully mechanized mining face. To address the crucial technical issue of lacking accurate perception of the shape of the scraper conveyor during intelligent coal mining, a three-dimensional curvature sensor involving fiber Bragg grating (FBG) is used as a perceptive tool to conduct curve reconstruction research based on different local motion frames and to reconstruct the shape of the scraper conveyor. Firstly, the formation process of the 'S'-shaped bending section of the scraper conveyor during the pushing process is determined. Based on the FBG sensing principle, a mathematical model between the variation in the central wavelength and the strain and curvature is established, and the cubic B-spline interpolation method is employed to continuously process the obtained discrete curvature. Secondly, based on differential geometry, a spatial curve reconstruction algorithm based on the Frenet moving frame is derived, and the shape curve prediction interpolation model is built based on a gated recurrent unit (GRU) model, which reduces the impact of the decrease in curve reconstruction accuracy caused by damage to some grating measuring points. Finally, an experimental platform was designed and built, and sensors with curvature radii of 6 m, 7 m, and 8 m were tested. The experimental results showed that the reconstructed curve was essentially consistent with the actual shape, and the absolute error at the end was about 2 mm. The feasibility of this reconstruction algorithm in engineering has been proven, and this is of great significance in achieving shape curve perception and straightness control for scraper conveyors.

Simulation Optimization and Application of Shearer Strapdown Inertial Navigation System Modulation Scheme.

The operating attitude of a shearer based on a three-dimensional (3D) space scale is the necessary basic information for realizing intelligent mining. Aiming to address the problem of the insufficient perception accuracy of shearers, in this paper, the rotation model of the actual turning mechanism of the strapdown inertial navigation system (SINS) of shearers is established, and the error propagation characteristics of different single-axis rotation modulation schemes are revealed. Through theory and simulation, the optimal rotation modulation scheme is determined to be the improved four-position turn-stop modulation with a rotation of <360°. The experiment shows that the 24 h positioning error of this scheme is 3.7 nmile, and the heading angle changes by 0.06°, which proves that this scheme can effectively improve the attitude perception accuracy of the inertial navigation system (INS). The field application of the shearer operating attitude perception based on this scheme shows that the positioning error after error compensation is 17% of that before compensation, and the heading angle error is 75% of that before compensation, which verifies that this scheme can significantly improve the accuracy of shearer operating attitude perception in field applications. This scheme can achieve higher precision perception accuracy based on SINS and has broad application prospects in the field of high-precision pose perception of coal mining machines, roadheaders, and other equipment.

Research on the Three-Machines Perception System and Information Fusion Technology for Intelligent Work Faces.

The foundation of intelligent collaborative control of a shearer, scraper conveyor, and hydraulic support (three-machines) is to achieve the precise perception of the status of the three-machines and the full integration of information between the equipment. In order to solve the problems of information isolation and non-flow, independence between equipment, and weak cooperation of three-machines due to an insufficient fusion of perception data, a fusion method of the equipment's state perception system on the intelligent working surface was proposed. Firstly, an intelligent perception system for the state of the three-machines in the working face was established based on fiber optic sensing technology and inertial navigation technology. Then, the datum coordinate system is created on the working surface to uniformly describe the status of the three-machines and the spatial position relationship between the three-machines is established using a scraper conveyor as a bridge so that the three-machines become a mutually restricted and collaborative equipment system. Finally, an indoor test was carried out to verify the relational model of the spatial position of the three-machines. The results indicate that the intelligent working face three-machines perception system based on fiber optic sensing technology and inertial navigation technology can achieve the fusion of monitoring data and unified expression of equipment status. The research results provide an important reference for building an intelligent perception, intelligent decision-making, and automatic execution system for coal mines.

The PalWRKY77 transcription factor negatively regulates salt tolerance and abscisic acid signaling in Populus.

High salinity, one of the most widespread abiotic stresses, inhibits photosynthesis, reduces vegetation growth, blocks respiration and disrupts metabolism in plants. In order to survive their long-term lifecycle, trees, such as Populus species, recruit the abscisic acid (ABA) signaling pathway to adapt to a saline environment. However, the molecular mechanism behind the ABA-mediated salt stress response in woody plants remains elusive. We have isolated a WRKY transcription factor gene, PalWRKY77, from Populus alba var. pyramidalis (poplar), the expression of which is repressed by salt stress. PalWRKY77 decreases salt tolerance in poplar. Furthermore, PalWRKY77 negatively regulated ABA-responsive genes and relieved ABA-mediated growth inhibition, indicating that PalWRKY77 is a repressor of the ABA response. In vivo and in vitro assays revealed that PalWRKY77 targets the ABA- and salt-induced PalNAC002 and PalRD26 genes by binding to the W-boxes in their promoters. In addition, overexpression of both PalNAC002 and PalRD26 could elevate salt tolerance in transgenic poplars. These findings reveal a novel negative regulation mechanism for the ABA signaling pathway mediated by PalWRKY77 that results in more sensitivity to salt stress in poplar. This deepens our understanding of the complex responses of woody species to salt stress.

Potential of intraoperative ultrasonographic assessment of the spinal cord central echo complex in predicting postoperative neurological recovery of degenerative cervical myelopathy.

BACKGROUND AND PURPOSE: The spinal cord central echo complex (SCCEC) is a special ultrasonography-based intramedullary structure, but its clinical significance in degenerative cervical myelopathy (DCM) is undefined. This study aimed to explore the potential of the SCCEC in predicting postoperative neurological recovery in DCM. METHODS: Thirty-two DCM patients who underwent intraoperative ultrasonography-guided French-door laminoplasty were prospectively enrolled. The modified Japanese Orthopaedic Association (mJOA) score was evaluated preoperatively and 12 months postoperatively. SCCEC width (SCCEC-W), and anteroposterior diameter (APD) and transverse diameter (TD) of the spinal cord were measured on transverse ultrasonographic images, while the tissue widths from anterior and posterior borders of the spinal cord to the SCCEC were measured on sagittal ultrasonographic images. The APD of the spinal cord and occupying rate of the spinal canal were measured on preoperative magnetic resonance imaging (MRI). RESULTS: All patients achieved improvements in mJOA scores, with an average recovery rate (RR) of 68.69 ± 20.22%. Spearman correlation analysis revealed that SCCEC-W, and ratios between the SCCEC-W and APD/TD based on ultrasonography, correlated moderately with mJOA score RR, with coefficients of -0.527, -0.605 and -0.514, respectively. The ratio between SCCEC-W and ultrasonographic TD correlated moderately with preoperative APD of the spinal cord. The MRI measurements and ultrasonography-based tissue widths showed no significant correlation with mJOA score RR. CONCLUSIONS: The SCCEC may have predictive potential as an intraoperative indicator of neurological recovery in treating DCM. SCCEC-W may be related to spinal cord compression in DCM.

Research on Three-Dimensional Stress Monitoring Method of Surrounding Rock Based on FBG Sensing Technology.

Research on the stress state of rock mass is essential for revealing the distribution characteristics and evolution law of the surrounding rock stress field in the roadway, studying the coal-rock dynamic disaster and the design of roadway support. This thesis proposes a three-dimensional stress monitoring method for surrounding rocks based on fiber Bragg grating (FBG) sensing technology and a cube-shaped three-dimensional stress fiber grating sensor is developed based on the principle of this monitoring method. According to the fiber grating strain obtained by numerical simulation, the calculated three-dimensional stress value is basically consistent with the theoretical value. The margin of error was plus or minus one percentage point. The sensing performance of the sensor was tested using a uniaxial compression experiment instead of a triaxial compression experiment. The experimental results show that in the range of 0~50 Mpa, the sensor's sensitivity to X, Y and Z axis stress is 25.51, 25.97 and 24.86 pm/Mpa, respectively. The relative error of measured stress is less than 4%. Meanwhile, the sensor has good linearity and repeatability, and has broad application prospects in the field of underground engineering safety monitoring such as in coal mines and tunnels.

Structural Design and Application of Desensitized FBG Force-Measuring Bolt.

Bolt-supporting technology has been widely used in mine roadway support, and its own working conditions have important reference value for roadway safety support. In order to realize the continuous and reliable monitoring of the bolt rod's working condition, this paper analyzes the existing problems of the existing fiber Bragg grating force-measuring bolt (FBG-FMB), and proposes a fiber grating strain desensitization sensing theory. Based on this theory, a desensitized FBG-FMB is developed with the spring as the elastic sensitive element. A mechanical analysis and drawing test show that the strain of the force-measuring bolt is greater than 60 times the micro-strain of the fiber grating, which verifies the feasibility of the structure design of the FBG-FMB. Finally, through the field application in the coal mine roadway, the working conditions of the bolt body at the two measuring points of the roadway are obtained to verify the reliability of the force-measuring bolt. In addition, the desensitized FBG-FMB can be widely used in the supporting fields of underground engineering such as slopes, tunnels, and foundation pits.

Research on Straightness Perception Compensation Model of FBG Scraper Conveyor Based on Rotation Error Angle.

The accurate perception of straightness of a scraper conveyor is important for the construction of intelligent working faces in coal mines. In this paper, we propose a precision compensation model based on rotation error angle to improve the accuracy of the fiber Bragg grating (FBG) curvature sensor of a scraper conveyor. The correctness of the model is verified by theoretical analysis, numerical simulation, and experiments. Finally, the feasibility of the model is analyzed and discussed for field application in a coal mine. When the rotation error angle is within the range of 0~90°, according to the strain of FBG obtained by numerical simulation, the radius of the curvature is inversely calculated by the compensation model. The relative error of each discrete point is within ±0.9%, and the relative error after fitting is less than 0.2%. The experiment shows that the relative error of the curvature radius after fitting according to the theoretical formula is less than ±3%, and the relative error of the curvature radius value obtained by the inverse deduction of each discrete point is less than ±6%, which verifies the correctness and applicability of the compensation model. In addition, the compensation model with the FBG curvature sensor has broad application prospects in coal mine underground conveyors, submarine pipelines and ground pipelines.

One AP2/ERF Transcription Factor Positively Regulates Pi Uptake and Drought Tolerance in Poplar.

Drought decreases the inorganic phosphate (Pi) supply of soil, resulting in Pi starvation of plants, but the molecular mechanism of how plants, especially the perennial trees, are tolerant to drought stress and Pi starvation, is still elusive. In this study, we identified an AP2/ERF transcription factor gene, PalERF2, from Populus alba var. pyramidalis, and it was induced by both mannitol treatment and Pi starvation. Overexpressing and knocking-down of PalERF2 both enhanced and attenuated tolerance to drought stress and Pi deficiency compared to WT, respectively. Moreover, the overexpression of PalERF2 up-regulated the expression levels of Pi starvation-induced (PSI) genes and increased Pi uptake under drought conditions; however, its RNAi poplar showed the opposite phenotypes. Subsequent analysis indicated that PalERF2 directly modulated expressions of drought-responsive genes PalRD20 and PalSAG113, as well as PSI genes PalPHL2 and PalPHT1;4, through binding to the DRE motifs on their promoters. These results clearly indicate that poplars can recruit PalERF2 to increase the tolerance to drought and also elevate Pi uptake under drought stress.

The U-box E3 ubiquitin ligase PalPUB79 positively regulates ABA-dependent drought tolerance via ubiquitination of PalWRKY77 in Populus.

The abscisic acid (ABA) signalling pathway is involved in the plant response to osmotic stress caused by drought and/or salinity. Although the ABA signalling pathway has been elucidated in Arabidopsis, it remains elusive in woody poplars. In this study, genome-wide analyses of U-box genes in poplars revealed that a U-box E3 ubiquitin ligase gene, PalPUB79, is significantly induced following drought, salinity and ABA signalling. PalPUB79 overexpression enhanced drought tolerance in transgenic poplars, while PalPUB79 RNAi lines were more sensitive to drought. PalPUB79 positively regulated ABA signalling pathway. Furthermore, PalPUB79 interacted with PalWRKY77, a negative transcriptional regulator of ABA signalling, and mediated its ubiquitination for degradation, therefore counteracting its inhibitory effect on PalRD26 transcription. However, the finding that PalWRKY77 negatively regulates PalPUB79 expression was indicative of a negative feedback loop between PalWRKY77 and PalPUB79 during ABA signalling in poplar. These findings provide novel insight into the mechanism through which PalPUB79 enhances the ABA-mediated stress response in woody poplars.

CHYR1 ubiquitinates the phosphorylated WRKY70 for degradation to balance immunity in Arabidopsis thaliana.

It is critically important for plants to control the trade-off between normal growth and pathogen immunity. However, the underlying molecular mechanism remains largely unknown. Here we report such a mechanism controlled by WRKY70 and its partner CHYR1 in Arabidopsis. We found that both levels of the WRKY70 target gene SARD1 and the phosphorylated forms of WRKY70 were increased in WRKY70OE plants upon Pst DC3000 infection. Mechanistically, phosphorylation of WRKY70 at Thr22 and Ser34 occurs, which then activates SARD1 expression through binding to a WT box. Phosphorylated WRKY70 is degraded by 26S proteasome via CHYR1 when resuming normal growth after infection. In addition, nonphosphorylated WRKY70 represses SARD1 expression by binding to both W (inhibitory activity site) and WT (active activity site) boxes. The binding of WRKY70 to alternative cis-elements of SARD1 through a phosphorylation-mediated switch controlled by CHYR1 contributes to modulating the balance between immunity and growth.

WRKY33 interacts with WRKY12 protein to up-regulate RAP2.2 during submergence induced hypoxia response in Arabidopsis thaliana.

Tolerance of hypoxia is essential for most plants, but the underlying mechanisms are largely unknown. Here we show that adaptation to submergence induced hypoxia in Arabidopsis involves up-regulation of RAP2.2 through interactive action of WRKY33 and WRKY12. WRKY33- or WRKY12-overexpressing plants showed enhanced resistance to hypoxia. Y2H, BiFC, Co-IP and pull-down experiments confirmed the interaction of WRKY33 with WRKY12. Genetic experiments showed that RAP2.2 acts downstream of WRKY33/WRKY12. WRKY33 and WRKY12 can bind to and activate RAP2.2 individually. Genetic and molecular experiments demonstrate that the two WRKYs can synergistically enhance activation towards RAP2.2 to increase hypoxia tolerance. WRKY33 expression is increased in RAP2.2-overexpressing plants, indicating a feedback regulation by RAP2.2 during submergence process, which was corroborated by EMSA, ChIP, dual-LUC and genetic experiments. Our results show that a regulatory cascade module involving WRKY33, WRKY12 and RAP2.2 plays a key role in submergence induced hypoxia response of Arabidopsis and illuminate functions of WRKYs in hypoxia tolerance.

Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury.

Rictor is an essential component that directly activates the mammalian target of rapamycin (mTOR) activity, which contributes to the intrinsic axon growth capacity of adult sensory neurons after injury. However, whether its action also applies to regeneration after spinal cord injury (SCI) remains unknown. In this study, rats were given spinal cord contusion at the T9-10 level to establish the SCI model and were subsequently treated with intraspinal cord injection of a Rictor overexpression lentiviral vector to locally upregulate the Rictor expression in the injured spinal cord. Thereafter, we investigated the therapeutic effects of Rictor overexpression in the injured spinal cords of SCI rats. Rictor overexpression not only significantly attenuated the acute inflammatory response and cell death after SCI but also markedly increased the shift in macrophages around the lesion from the M1 to M2 phenotype compared to those of the control lentiviral vector injection-treated group. Furthermore, Rictor overexpression dramatically increased neurogenesis in the lesion epicenter, subsequently promoting the tissue repair and functional recovery in SCI rats. Interestingly, the mechanism underlying the beneficial effects of Rictor overexpression on SCI may be associated with the Rictor overexpression playing a role in the anti-inflammatory response and driving macrophage polarization toward the M2 phenotype, which benefits resident neuronal and oligodendrocyte survival. Our findings demonstrate that Rictor is an effective target that affects the generation of molecules that inhibit spinal cord regeneration. In conclusion, localized Rictor overexpression represents a promising potential strategy for the repair of SCI.

Co-Production of Isoprene and Lactate by Engineered Escherichia coli in Microaerobic Conditions.

Lactate and isoprene are two common monomers for the industrial production of polyesters and synthetic rubbers. The present study tested the co-production of D-lactate and isoprene by engineered Escherichia coli in microaerobic conditions. The deletion of alcohol dehydrogenase (adhE) and acetate kinase (ackA) genes, along with the supplementation with betaine, improved the co-production of lactate and isoprene from the substrates of glucose and mevalonate. In fed-batch studies, microaerobic fermentation significantly improved the isoprene concentration in fermentation outlet gas (average 0.021 g/L), compared with fermentation under aerobic conditions (average 0.0009 g/L). The final production of D-lactate and isoprene can reach 44.0 g/L and 3.2 g/L, respectively, through fed-batch microaerobic fermentation. Our study demonstrated a dual-phase production strategy in the co-production of isoprene (gas phase) and lactate (liquid phase). The increased concentration of gas-phase isoprene could benefit the downstream process and decrease the production cost to collect and purify the bio-isoprene from the fermentation outlet gas. The proposed microaerobic process can potentially be applied in the production of other volatile bioproducts to benefit the downstream purification process.