Systems engineering Escherichia coli for efficient production p-coumaric acid from glucose.

P-coumaric acid (p-CA), a pant metabolite with antioxidant and anti-inflammatory activity, is extensively utilized in biomedicine, food, and cosmetics industry. In this study, a synthetic pathway (PAL) for p-CA was designed, integrating three enzymes (AtPAL2, AtC4H, AtATR2) into a higher l-phenylalanine-producing strain Escherichia coli PHE05. However, the lower soluble expression and activity of AtC4H in the PAL pathway was a bottleneck for increasing p-CA titers. To overcome this limitation, the soluble expression of AtC4H was enhanced through N-terminal modifications. And an optimal mutant, AtC4HL373T/G211H, which exhibited a 4.3-fold higher kcat/Km value compared to the wild type, was developed. In addition, metabolic engineering strategies were employed to increase the intracellular NADPH pool. Overexpression of ppnk in engineered E. coli PHCA20 led to a 13.9-folds, 1.3-folds, and 29.1% in NADPH content, the NADPH/NADP+ ratio and p-CA titer, respectively. These optimizations significantly enhance p-CA production, in a 5-L fermenter using fed-batch fermentation, the p-CA titer, yield and productivity of engineered strain E. coli PHCA20 were 3.09 g/L, 20.01 mg/g glucose, and 49.05 mg/L/h, respectively. The results presented here provide a novel way to efficiently produce the plant metabolites using an industrial strain.

Rational design improves both thermostability and activity of a new D-tagatose 3-epimerase from Kroppenstedtia eburnean to produce D-allulose.

D-allulose is a naturally occurring rare sugar and beneficial to human health. However, the efficient biosynthesis of D-allulose remains a challenge. Here, we mined a new D-tagatose 3-epimerase from Kroppenstedtia eburnean (KeDt3e) with high catalytic efficiency. Initially, crucial factors contributing to the low conversion of KeDt3e were identified through crystal structure analysis, density functional theory calculations (DFT), and molecular dynamics (MD) simulations. Subsequently, based on the mechanism, combining restructuring the flexible region, proline substitution based onconsensus sequence analysis, introducing disulfide bonds, and grafting properties, and reshaping the active center, the optimal mutant M5 of KeDt3e was obtained with enhanced thermostability and activity. The optimal mutant M5 exhibited an enzyme activity of 130.8 U/mg, representing a 1.2-fold increase; Tm value increased from 52.7 °C to 71.2 °C; and half-life at 55 °C extended to 273.7 min, representing a 58.2-fold improvement, and the detailed mechanism of performance improvement was analyzed. Finally, by screening the ribosome-binding site (RBS) of the optimal mutant M5 recombinant bacterium (G01), the engineered strain G08 with higher expression levels was obtained. The engineered strain G08 catalyzed 500 g/L D-fructose to produce 172.4 g/L D-allulose, with a conversion of 34.4% in 0.5 h and productivity of 344.8 g/L/h on a 1 L scale. This study presents a promising approach for industrial-scale production of D-allulose.

Compliant Iontronic Triboelectric Gels with Phase-Locked Structure Enabled by Competitive Hydrogen Bonding.

Rapid advancements in flexible electronics technology propel soft tactile sensing devices toward high-level biointegration, even attaining tactile perception capabilities surpassing human skin. However, the inherent mechanical mismatch resulting from deficient biomimetic mechanical properties of sensing materials poses a challenge to the application of wearable tactile sensing devices in human-machine interaction. Inspired by the innate biphasic structure of human subcutaneous tissue, this study discloses a skin-compliant wearable iontronic triboelectric gel via phase separation induced by competitive hydrogen bonding. Solvent-nonsolvent interactions are used to construct competitive hydrogen bonding systems to trigger phase separation, and the resulting soft-hard alternating phase-locked structure confers the iontronic triboelectric gel with Young's modulus (6.8-281.9 kPa) and high tensile properties (880%) compatible with human skin. The abundance of reactive hydroxyl groups gives the gel excellent tribopositive and self-adhesive properties (peel strength > 70 N m-1). The self-powered tactile sensing skin based on this gel maintains favorable interface and mechanical stability with the working object, which greatly ensures the high fidelity and reliability of soft tactile sensing signals. This strategy, enabling skin-compliant design and broad dynamic tunability of the mechanical properties of sensing materials, presents a universal platform for broad applications from soft robots to wearable electronics.

Phenylglycine amphiphile-metal ion chiral supramolecular nanozymes for enantioselective catalysis.

L/D-Phenylglycine amphiphiles and metal ions with peroxidase-like activity self-assembled into chiral nanoribbons, which act as efficient chiral supramolecular nanozymes for catalyzing the 3,4-dihydroxy-L/D-phenylalanine (L/D-DOPA) oxidation reactions. The catalytic efficiency and enantioselectivity are dominated by the chirality transfer and the synergistic effect between the metal ions and chiral nanoribbons.

Rational Design of Salmonella typhi Acid Phosphatase for Efficient Production of Pyridoxal 5'-Phosphate.

Pyridoxal 5'-phosphate (PLP) is highly valuable in food and medicine. However, achieving the efficient biosynthesis of PLP remains challenging. Here, a salvage pathway using acid phosphatase from Salmonella typhi (StAPase) and pyridoxine oxidase from Escherichia coli (EcPNPO) as pathway enzymes was established for the first time to synthesize PLP from pyridoxine (PN) and pyrophosphate (PPi). StAPase was identified as a rate-limiting enzyme. Two protein modification strategies were developed based on the PN phosphorylation mechanism: (1) improving the binding of PN into StAPase and (2) enhancing the hydrophobicity of StAPase's substrate binding pocket. The kcat/Km of optimal mutant M7 was 4.9 times higher than that of the wild type. The detailed mechanism of performance improvement was analyzed. Under the catalysis of M7 and EcPNPO, a PLP high-yielding strain of 14.5 ± 0.55 g/L was engineered with a productivity of 1.0 ± 0.02 g/(L h) (the highest to date). The study suggests a promising method for industrial-scale PLP production.

In vitro pharmacokinetics/pharmacodynamics of FL058 (a novel beta-lactamase inhibitor) combined with meropenem against carbapenemase-producing Enterobacterales.

Objective: FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an in vitro infection model. Methods: By simulating human concentration-time profiles in the in vitro model, meropenem combined with FL058 when administered 1 g/0.5 g, 1 g/1 g, 2 g/1 g, and 2 g/2 g q8h by 3-h infusion achieved approximately 2- and 4-log10 kill to KPC/OXA-producing Klebsiella pneumoniae and Escherichia coli; the combination therapy could not inhibit NDM-producing K. pneumoniae but could maintain NDM-producing E. coli around a baseline. Results: The PK/PD indexes that best described the bacterial killing from baseline in log10 CFU/mL at 24 h were the percent time of free drug above the minimal inhibitory concentration (MIC) (%fT > MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT > 1 mg/L) for FL058. The targets for achieving a static effect and the 1- and 2-log10 kill were 74, 83, and 99 for %fT > MIC of meropenem and 40, 48, and 64 for %fT > 1 mg/L of FL058, respectively. The PK/PD index of %fT > 1 mg/L can provide a basis for evaluating clinical dosing regimens for FL058 combined with meropenem. Conclusion: FL058 combined with meropenem might be a potential treatment for KPC- and/or OXA-48-producing Enterobacterales infection.

Reprogramming the Transition States to Enhance C-N Cleavage Efficiency of Rhodococcus opacusl-Amino Acid Oxidase.

l-Amino acid oxidase (LAAO) is an important biocatalyst used for synthesizing α-keto acids. LAAO from Rhodococcus opacus (RoLAAO) has a broad substrate spectrum; however, its low total turnover number limits its industrial use. To overcome this, we aimed to employ crystal structure-guided density functional theory calculations and molecular dynamic simulations to investigate the catalytic mechanism. Two key steps were identified: S → [TS1] in step 1 and Int1 → [TS2] in step 2. We reprogrammed the transition states [TS1] and [TS2] to reduce the identified energy barrier and obtain a RoLAAO variant capable of catalyzing 19 kinds of l-amino acids to the corresponding high-value α-keto acids with a high total turnover number, yield (≥95.1 g/L), conversion rate (≥95%), and space-time yields ≥142.7 g/L/d in 12-24 h, in a 5 L reactor. Our results indicated the promising potential of the developed RoLAAO variant for use in the industrial production of α-keto acids while providing a potential catalytic-mechanism-guided protein design strategy to achieve the desired physical and catalytic properties of enzymes.

An Analysis of Preoperative Inflammatory Indicators That Influence the Drainage Tube Retention Time in Patients with Breast Cancer Surgery.

Objective: The study was aimed to investigate the influence factor between preoperative inflammatory indicators and drainage tube retention time in patients with breast cancer. Methods: This retrospective study enrolled 121 patients with breast cancer who were undergoing surgery between October 2020 and June 2021. The enumeration data were used the Chi-square test, and the measurement data were used the t-test analysis. The univariate and multivariate logistic regression models were performed to access the risk factors for affecting drainage tube retention time in patients with breast cancer. The receiver operating characteristic curve (ROC) was performed to test the prediction effect of the model. Results: Through the median extraction time of postoperative drainage tube retention time, all patients were divided into two groups: drainage tube retention time (DTRT) < 13 (d) and drainage tube retention time (DTRT) ≥ 13 (d). The results showed that type of surgery, total lymph nodes (TLN), pathological T stage, NLR were related to the drainage tube retention time (P<0.05). Moreover, the univariate and multivariate logistic regression analysis performed that Hb, type of surgery, pathological T stage, chest wall drainage tube, NRI were the independent risk predictors of affecting drainage tube retention time. Furthermore, a significant correlation existed between NRI and drainage tube retention at different times (P < 0.05). Conclusion: NRI is an independent risk factor for postoperative drainage tube extraction time and can effectively predict the probability of drainage tube retention time. Thus, it can also provide personalized nursing intervention for patients with breast cancer after drainage tube retention time and the rehabilitation process.

Identification and Expression Analysis of Putative Sugar Transporter Gene Family during Bulb Formation in Lilies.

Sugar transporters play important roles in plant growth and development, flowering and fruiting, as well as responses to adverse abiotic and biotic environmental conditions. Lilies (Lilium spp.) are some of the most representative ornamental bulbous flowers. Sugar metabolism is critical for bulb formation in lilies; therefore, clarifying the amount and expression pattern of sugar transporters is essential for further analyzing their roles in bulb formation. In this study, based on the transcriptome data of the Lilium Oriental hybrid 'Sorbonne' and Lilium × formolongi, a total of 69 and 41 sugar transporters were identified in 'Sorbonne' and Lilium × formolongi, respectively, by performing bioinformatics analysis. Through phylogenetic analysis, monosaccharide transporters (MSTs) can be divided into seven subfamilies, sucrose transporters (SUTs) can be divided into three subgroups, and sugars will eventually be exported transporters (SWEETs) can be divided into four clades. According to an analysis of conserved motifs, 20, 14, and 12 conserved motifs were predicted in MSTs, SUTs, and SWEETs, respectively. A conserved domain analysis showed that MSTs and SUTs contained a single domain, whereas most of the SWEETs harbored two MtN3/saliva domains, also known as a PQ-loop repeat. The LohINT1, which was predicted to have a smaller number of transmembrane structural domains, was cloned and analyzed for subcellular localization. It was found that the LohINT1 protein is mainly localized in the cell membrane. In addition, the expression analysis indicated that 22 LohMSTs, 1 LohSUTs, and 5 LohSWEETs were upregulated in 'Sorbonne' 1 day after scale detachment treatment, suggesting that they may regulate the initiation of the bulblet. A total of 10 LflMSTs, 1 LflSUTs, and 6 LflSWEETs were upregulated 4~6 months after sowing, which corresponds to the juvenile-to-adult transition phase of Lilium × formolongi, suggesting that they may also play a role in the accompanying bulb swelling process. Combined with quantitative real-time PCR (qRT-PCR) analysis, LohSTP8 and LohSTP12 were significantly overexpressed during the extremely early stage of bulblet initiation, and LflERD6.3 was significantly overexpressed during the growth of the underground bulblet, suggesting that they may be key sugar transporters in the formation of lily bulbs, which needs further functional verification.

High Strength and Toughness Polymeric Triboelectric Materials Enabled by Dense Crystal-Domain Cross-Linking.

Lightweight, easily processed, and durable polymeric materials play a crucial role in wearable sensor devices. However, achieving simultaneously high strength and toughness remains a challenge. This study addresses this by utilizing an ion-specific effect to control crystalline domains, enabling the fabrication of a polymeric triboelectric material with tunable mechanical properties. The dense crystal-domain cross-linking enhances energy dissipation, resulting in a material boasting both high tensile strength (58.0 MPa) and toughness (198.8 MJ m-3), alongside a remarkable 416.7% fracture elongation and 545.0 MPa modulus. Leveraging these properties, the material is successfully integrated into wearable self-powered devices, enabling real-time feedback on human joint movement. This work presents a valuable strategy for overcoming the strength-toughness trade-off in polymeric materials, paving the way for their enhanced applicability and broader use in diverse sensing applications.

Effect of Body Mass Index on Cecal Intubation Time During Unsedated Colonoscopy: Variation Across the Learning Stages of an Endoscopist.

BACKGROUND Body mass index (BMI) and endoscopists' experiences can be associated with cecal intubation time (CIT), but such associations are controversial. This study aimed to clarify the association between BMI and CIT during unsedated colonoscopy at 3 learning stages of a single endoscopist. MATERIAL AND METHODS A total of 1500 consecutive patients undergoing unsedated colonoscopy by 1 endoscopist at our department from December 11, 2020, to August 21, 2022, were reviewed. They were divided into 3 learning stages according to the number of colonoscopies performed by 1 endoscopist, including intermediate (501-1000 colonoscopies), experienced (1001-1500 colonoscopies), and senior stages (1501-2000 colonoscopies). Variables that significantly correlated with CIT were identified by Spearman rank correlation analyses and then included in multiple linear regression analysis. RESULTS Overall, 1233 patients were included. Among them, 392, 420, and 421 patients were divided into intermediate, experienced, and senior stages, respectively. Median CIT was 7.83, 6.38, and 5.58 min at intermediate, experienced, and senior stages, respectively (P.

Reversibly Cross-Linked Isoporous Membranes Fabricated by the Recyclable Block Copolymer with Pendent Dithiolane Groups.

The reversible formation and cleavage of disulfide bonds under physical/chemical stimuli make it a valuable motif in constructing dynamically cross-linked materials. In the present work, the block copolymer bearing pendent dithiolanes was synthesized and fabricated into isoporous membranes by the combination of self-assembly and nonsolvent-induced phase separation strategy. The cross-linking within the membrane was realized by the thiol-initiated ring-opening cascades of cyclic disulfides. Successful formation of disulfide bond networks within the isoporous membranes was proved by the Raman spectra, UV-vis diffuse reflectance spectroscopy, differential scanning calorimetry, and rheological analysis. The cross-linking in membranes was further demonstrated by the notably improved toughness and obviously enhanced swelling resistance to acid/alkaline solution as well as organic solvents. Importantly, the cross-linked isoporous membranes were fully dissolvable in solution containing dithiothreitol, which enabled the complete cleavage of disulfide bonds and successful recovery of the block copolymer that was able to be repeatedly fabricated into isoporous membranes with pore sizes identical to membranes prepared from the freshly synthesized copolymer. Our results indicate that dynamically cross-linked isoporous membranes with improved durability and good recyclability can be custom-made by simply incorporating active dithiolane moieties into self-assembling block copolymers.

Systems engineering of Escherichia coli for high-level glutarate production from glucose.

Glutarate is a key monomer in polyester and polyamide production. The low efficiency of the current biosynthetic pathways hampers its production by microbial cell factories. Herein, through metabolic simulation, a lysine-overproducing E. coli strain Lys5 is engineered, achieving titer, yield, and productivity of 195.9 g/L, 0.67 g/g glucose, and 5.4 g/L·h, respectively. Subsequently, the pathway involving aromatic aldehyde synthase, monoamine oxidase, and aldehyde dehydrogenase (AMA pathway) is introduced into E. coli Lys5 to produce glutarate from glucose. To enhance the pathway's efficiency, rational mutagenesis on the aldehyde dehydrogenase is performed, resulting in the development of variant Mu5 with a 50-fold increase in catalytic efficiency. Finally, a glutarate tolerance gene cbpA is identified and genomically overexpressed to enhance glutarate productivity. With enzyme expression optimization, the glutarate titer, yield, and productivity of E. coli AMA06 reach 88.4 g/L, 0.42 g/g glucose, and 1.8 g/L·h, respectively. These findings hold implications for improving glutarate biosynthesis efficiency in microbial cell factories.

Human Placenta-Derived Mesenchymal Stem Cells Combined With Artificial Dermal Scaffold Enhance Wound Healing in a Tendon-Exposed Wound of a Rabbit Model.

To overcome the difficulty of vascular regeneration in exposed tendon wounds, we combined human placenta-derived mesenchymal stem cells (hPMSCs) with an artificial dermal scaffold and assessed their role in promoting vascular regeneration and wound healing in vivo. hPMSCs were isolated from the human placenta and characterized based on their morphology, phenotypic profiles, and pluripotency. New Zealand rabbits were used to establish an exposed tendon wound model, and hPMSCs and artificial dermal scaffolds were transplanted into the wounds. The results of gross wound observations and pathological sections showed that hPMSCs combined with artificial dermal scaffold transplantation increased the vascularization area of the wound, promoted wound healing, and increased the survival rate of autologous skin transplantation. Following artificial dermal scaffold transplantation, hPMSCs accelerated the vascularization of the dermal scaffold, and the number of fibroblasts, collagen fibers, and neovascularization in the dermal scaffold after 1 week were much higher than those in the control group. Immunohistochemical staining further confirmed that the expression of the vascular endothelial cell marker, CD31, was significantly higher in the combined transplantation group than in the dermal scaffold transplantation group. Our findings demonstrated that hPMSCs seeded onto artificial dermal scaffold could facilitate vascularization of the dermal scaffold and improve tendon-exposed wound healing.

Efficient production of protocatechuic acid using systems engineering of Escherichia coli.

Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is widely used in the pharmaceuticals, health food, and cosmetics industries owing to its diverse biological activities. However, the inhibition of 3-dehydroshikimate dehydratase (AroZ) by PCA and its toxicity to cells limit the efficient production of PCA in Escherichia coli. In this study, a high-level strain of 3-dehydroshikimate, E. coli DHS01, was developed by blocking the carbon flow from the shikimate-overproducing strain E. coli SA09. Additionally, the PCA biosynthetic pathway was established in DHS01 by introducing the high-activity ApAroZ. Subsequently, the protein structure and catalytic mechanism of 3-dehydroshikimate dehydratase from Acinetobacter pittii PHEA-2 (ApAroZ) were clarified. The variant ApAroZR363A, achieved by modulating the conformational dynamics of ApAroZ, effectively relieved product inhibition. Additionally, the tolerance of the strain E. coli PCA04 to PCA was enhanced by adaptive laboratory evolution, and a biosensor-assisted high-throughput screening method was designed and implemented to expedite the identification of high-performance PCA-producing strains. Finally, in a 5 L bioreactor, the final strain PCA05 achieved the highest PCA titer of 46.65 g/L, a yield of 0.23 g/g, and a productivity of 1.46 g/L/h for PCA synthesis from glucose using normal fed-batch fermentation. The strategies described herein serve as valuable guidelines for the production of other high-value and toxic products.

Excellent Bowel Preparation Quality Is Not Superior to Good Bowel Preparation Quality for Improving Adenoma/Polyp Detection Rate.

Background: Adequate bowel preparation quality is essential for high-quality colonoscopy according to the current guidelines. However, the excellent effect of bowel preparation on adenoma/polyp detection rate (ADR/PDR) remained controversial. Methods: During the period from December 2020 to August 2022, a total of 1566 consecutive patients underwent colonoscopy by an endoscopist. Their medical records were reviewed. According to the Boston bowel preparation scale, patients were divided into excellent, good, and poor bowel preparation quality groups. ADR/PDR, diminutive ADR/PDR, small ADR/PDR, intermediate ADR/PDR, large ADR/PDR, and number of adenomas/polyps were compared among them. Logistic regression analyses were performed to identify the factors that were significantly associated with ADR/PDR. Results: Overall, 1232 patients were included, of whom 463, 636, and 133 were assigned to the excellent, good, and poor groups, respectively. The good group had a significantly higher ADR/PDR (63% vs 55%, P = .015) and a larger number of adenomas/polyps (2.5 ± 3.2 vs 2.0 ± 2.8, P = .030) than the poor group. Both ADR/PDR (63% vs 55%, P = .097) and number of adenomas/polyps (2.2 ± 2.8 vs 2.0 ± 2.8, P = .219) were not significantly different between excellent and poor groups. The excellent (9% vs 4%, P = .045) and good (9% vs 4%, P = .040) groups had a significantly higher intermediate ADR/PDR than the poor group. Logistic regression analyses showed that either good (odds ratio [OR] = 1.786, 95% CI = 1.046-3.047, P = .034) or excellent (OR = 2.179, 95% CI = 1.241-3.826, P = .007) bowel preparation quality was independently associated with a higher ADR/PDR compared with poor bowel preparation quality. Excellent (OR = 1.202, 95% CI = 0.848-1.704, P = .302) bowel preparation quality was not independently associated with a higher ADR/PDR compared with good bowel preparation quality. Conclusions: The pursuit of excellence in bowel preparation does not show an association with increased ADR/PDR and number of adenomas/polyps compared with a good level. In addition, our study further contributes to the existing evidence that poor bowel preparation compromises ADR/PDR and number of adenomas/polyps.

The role of the Bemisia tabaci and Trialeurodes vaporariorum cytochrome-P450 clade CYP6DPx in resistance to nicotine and neonicotinoids.

The alkaloid, nicotine, produced by tobacco and other Solanaceae as an anti-herbivore defence chemical is one of the most toxic natural insecticides in nature. However, some insects, such as the whitefly species, Trialeurodes vaporariorum and Bemisia tabaci show strong tolerance to this allelochemical and can utilise tobacco as a host. Here, we used biological, molecular and functional approaches to investigate the role of cytochrome P450 enzymes in nicotine tolerance in T. vaporariorum and B. tabaci. Insecticide bioassays revealed that feeding on tobacco resulted in strong induced tolerance to nicotine in both species. Transcriptome profiling of both species reared on tobacco and bean hosts revealed profound differences in the transcriptional response these host plants. Interrogation of the expression of P450 genes in the host-adapted lines revealed that P450 genes belonging to the CYP6DP subfamily are strongly upregulated in lines reared on tobacco. Functional characterisation of these P450s revealed that CYP6DP1 and CYP6DP2 of T. vaporariorum and CYP6DP3 of B. tabaci confer resistance to nicotine in vivo. These three genes, in addition to the B. tabaci P450 CYP6DP5, were also found to confer resistance to the neonicotinoid imidacloprid. Our data provide new insight into the molecular basis of nicotine resistance in insects and illustrates how divergence in the evolution of P450 genes in this subfamily in whiteflies may have impacted the extent to which different species can tolerate a potent natural insecticide.

Engineering status of protein for improving microbial cell factories.

With the development of metabolic engineering and synthetic biology, microbial cell factories (MCFs) have provided an efficient and sustainable method to synthesize a series of chemicals from renewable feedstocks. However, the efficiency of MCFs is usually limited by the inappropriate status of protein. Thus, engineering status of protein is essential to achieve efficient bioproduction with high titer, yield and productivity. In this review, we summarize the engineering strategies for metabolic protein status, including protein engineering for boosting microbial catalytic efficiency, protein modification for regulating microbial metabolic capacity, and protein assembly for enhancing microbial synthetic capacity. Finally, we highlight future challenges and prospects of improving microbial cell factories by engineering status of protein.

A Fully Differentiable Framework for 2D/3D Registration and the Projective Spatial Transformers.

Image-based 2D/3D registration is a critical technique for fluoroscopic guided surgical interventions. Conventional intensity-based 2D/3D registration approa- ches suffer from a limited capture range due to the presence of local minima in hand-crafted image similarity functions. In this work, we aim to extend the 2D/3D registration capture range with a fully differentiable deep network framework that learns to approximate a convex-shape similarity function. The network uses a novel Projective Spatial Transformer (ProST) module that has unique differentiability with respect to 3D pose parameters, and is trained using an innovative double backward gradient-driven loss function. We compare the most popular learning-based pose regression methods in the literature and use the well-established CMAES intensity-based registration as a benchmark. We report registration pose error, target registration error (TRE) and success rate (SR) with a threshold of 10mm for mean TRE. For the pelvis anatomy, the median TRE of ProST followed by CMAES is 4.4mm with a SR of 65.6% in simulation, and 2.2mm with a SR of 73.2% in real data. The CMAES SRs without using ProST registration are 28.5% and 36.0% in simulation and real data, respectively. Our results suggest that the proposed ProST network learns a practical similarity function, which vastly extends the capture range of conventional intensity-based 2D/3D registration. We believe that the unique differentiable property of ProST has the potential to benefit related 3D medical imaging research applications. The source code is available at https://github.com/gaocong13/Projective-Spatial-Transformers.

Reprogramming Metabolic Flux in Escherichia Coli to Enhance Chondroitin Production.

Reprogramming metabolic flux is a promising approach for constructing efficient microbial cell factories (MCFs) to produce chemicals. However, how to boost the transmission efficiency of metabolic flux is still challenging in complex metabolic pathways. In this study, metabolic flux is systematically reprogrammed by regulating flux size, flux direction, and flux rate to build an efficient MCF for chondroitin production. The ammoniation pool for UDP-GalNAc synthesis and the carbonization pool for UDP-GlcA synthesis are first enlarged to increase flux size for providing enough precursors for chondroitin biosynthesis. Then, the ammoniation pool and the carbonization pool are rematched using molecular valves to shift flux direction from cell growth to chondroitin biosynthesis. Next, the adaptability of polymerization pool with the ammoniation and carbonization pools is fine-tuned by dynamic and static valve-based adapters to accelerate flux rate for polymerizing UDP-GalNAc and UDP-GlcA to produce chondroitin. Finally, the engineered strain E. coli F51 is able to produce 9.2 g L-1 chondroitin in a 5-L bioreactor. This strategy shown here provides a systematical approach for regulating metabolic flux in complex metabolic pathways for efficient biosynthesis of chemicals.