Combinatorial metabolic engineering of Escherichia coli to efficiently produce L-threonine from untreated cane molasses.

Background: The industrial production of L-threonine faces challenges because of high production costs, especially those of substrates, meaning new production methods are needed.

Methods: Fur, a new global transcription factor related to L-threonine biosynthesis, was discovered in this study. Multidimensional regulation combined with global transcriptional machinery engineering was used to modify an Escherichia coli strain.

Metabolic engineering of Pseudomonas chlororaphis P3 for high-level and directed production of phenazine-1,6-dicarboxylic acid from crude glycerol.

Phenazine-1,6-dicarboxylic acid (PDC) is a precursor of complex substituted phenazines used as pesticides and pharmaceuticals. The PDC biosynthesis exists the low production and the high proportion of by-products phenazine-1-carboxylic acid (PCA) derivatives in Pseudomonas P3△A. Herein, PDC production were improved by systematic metabolic engineering and synthetic regulation.

Exploring the Role of Glycine Metabolism in Coronary Artery Disease: Insights from Human Genetics and Mouse Models.

Circulating glycine levels have been associated with reduced risk of coronary artery disease (CAD) in humans but these associations have not been observed in all studies. We evaluated whether the relationship between glycine levels and atherosclerosis was causal using genetic analyses in humans and feeding studies in mice. Serum glycine levels were evaluated for association with risk of CAD in the UK Biobank.

IRE1α-XBP1 safeguards hematopoietic stem and progenitor cells by restricting pro-leukemogenic gene programs.

Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.

Multi-omics reveals mechanism of hydroxylamine-enhanced ultimate nitrogen removal in pilot-scale anaerobic/aerobic/anoxic system.

Hydroxylamine (HA) dosing is an effective strategy for promoting partial nitrification (PN); however, its impact on endogenous denitrification remains underexplored. In this study, long-term continuous HA dosing (1.4 mg/L) was introduced for over 110 days in a pilot-scale anaerobic/aerobic/anoxic (AOA) system treating municipal wastewater (66.

Toward expert-level medical question answering with large language models.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.

MIL-53(Al)-derived bimetallic Pd-Co catalysts for the selective hydrogenation of 1,3-butadiene at low temperature.

Selective hydrogenation of 1,3-butadiene is a crucial industrial process for the removing of 1,3-butadiene, a byproduct of butene production. Developing catalysts with high catalytic performance for the hydrogenation of 1,3-butadiene at low temperatures has become a research hotspot. In this study, bimetallic Pd-Co catalysts supported on AlO derived from MIL-53(Al) at various calcination temperatures were synthesised via the co-impregnation method.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Population Pharmacokinetics and Dosing Optimization of Norvancomycin for Chinese Patients with Community-Acquired Pneumonia.

Purpose: Determining the optimal dosage of norvancomycin (NVCM) for Chinese patients with community-acquired pneumonia (CAP) caused by gram-positive cocci remains uncertain. This research aimed to identify influential factors affecting NVCM pharmacokinetics and explore optimal dosage regimens via population pharmacokinetic (PPK) analysis.

Patients And Methods: A prospective analysis was conducted at the Second Hospital of Hebei Medical University (Shijiazhuang, China).

Simulating water and salt changes in the root zone of salt-alkali fragrant pear and the selection of the optimal surface drip irrigation mode.

Faced with the increasingly serious problem of water scarcity, developing precise irrigation strategies for crops in saline alkali land can effectively reduce the negative effects of low water resource utilization. Using a model to simulate the dynamic changes in soil water and salt environment in the root zone of fragrant pear trees in saline alkali land, and verifying them from a production practice perspective with comprehensive benefits as the goal, can optimize the irrigation amount and irrigation technology elements of saline alkali fruit trees, broaden the comprehensive evaluation perspective of decision-makers, and have important significance for improving the yield and production efficiency of forestry and fruit industry in arid and semi-arid areas worldwide. In this study, a two-year field experiment based on three irrigation levels (3000, 3750, and 4500 m·ha) and four emitter discharge rates (1, 2, 3, and 4 L·h) was conducted in Xinjiang, China.

Enhancing D-lactic acid production from non-detoxified corn stover hydrolysate via innovative F127-IEA hydrogel-mediated immobilization of T15.

Background: The production of D-lactic acid (D-LA) from non-detoxified corn stover hydrolysate is hindered by substrate-mediated inhibition and low cell utilization times. In this study, we developed a novel temperature-sensitive hydrogel, F127-IEA, for efficient D-LA production using a cell-recycle batch fermentation process.

Results: F127-IEA exhibited a porous structure with an average pore size of approximately 1 μm, facilitating the formation of stable clusters within the gel matrix.

Model-informed precision dosing of quetiapine in bipolar affective disorder patients: initial dose recommendation.

Objective: Bipolar affective disorder (BAD) is a mood disorder with high morbidity and mortality. Quetiapine can be used in the treatment of patients with BAD; however, the precise administration regimen of quetiapine in these patients is still unknown. In this study, a population pharmacokinetic (PPK) model of quetiapine in patients with BAD was constructed based on model-informed precision dosing (MIPD) and real-world clinical data and an optimal initial dose of quetiapine in these patients was recommended.

Metabolic Engineering of for Self-Induced Production of l-Isoleucine.

As one of the three important branched-chain amino acids, l-isoleucine has a wide range of applications in the fields of medicine, food, and feed. Currently, the production of l-isoleucine is well-studied by , while the autonomous and efficient production of l-isoleucine in has not been reported. Here, we developed a production strategy that combined metabolic engineering with bacterial quorum sensing to achieve the efficient production of l-isoleucine.

Engineering for Efficient Synthesis of Salidroside.

Salidroside is a high-value plant-derived glycoside with diverse biological activities, but the main industrial salidroside production method, extraction from plants, is insufficient to meet the growing market demand. The biosynthetic route via microbial fermentation is a sustainable and eco-friendly alternative method. synthesis of the precursor tyrosol was established by introducing the and genes.

Evaluating the Use of Environmental and Polygenic Risk Scores to Inform Colorectal Cancer Risk-Based Surveillance Intervals.

Introduction: United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Methods: Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.

Predicting Futile Recanalization by Cerebral Collateral Recycle Status in Patients with Endovascular Stroke Treatment: The CHANOA Score.

Rationale And Objectives: The correlation between collateral circulation and futile recanalization (FR) is still controversial, and few studies have explored the influence of comprehensive cerebral collateral circulation on FR after endovascular stroke treatment. Therefore, based on cerebral collateral recycle (CCR) status, we aimed to establish an effective scoring system to identify the probability of FR.

Methods: This was a multicenter retrospective cohort study.

Sabatier Optimal of Mn-N Single Atom Catalysts for Selective Oxidative Desulfurization.

Understanding the relationship of competitive adsorption between reactants is the prerequisite for high activity and selectivity in heterogeneous catalysis, especially the difference between the adsorption energies (E) of two reactive intermediates in Langmuir-Hinshelwood (L-H) models. Using oxidative dehydrogenation of hydrogen sulfide (HS-ODH) as a probe, we develop various metal single atoms on nitrogen-doped carbon (M-NDC) catalysts for controlling E-HS, E-O and investigating the difference in activity and selectivity. Combining theoretical and experimental results, a Sabatier relationship between the catalytic performance and E-O/E-HS emerges.

Peli1 Deficiency in Macrophages Attenuates Pulmonary Hypertension by Enhancing Foxp1-Mediated Transcriptional Inhibition of IL-6.

Background: The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be investigated.

Molecular Identification of Etiological Agents in Fungal and Bacterial Skin Infections: United States, 2020-2024.

: Cutaneous infections of fungal and bacterial origins are common. An accurate diagnosis-especially concerning pathogens that are difficult to isolate on culture-can be achieved using molecular methods (PCR) with a short turnaround time. : We reviewed records of skin specimens (superficial scrapings) submitted by dermatologists across the United States with a clinically suspected dermatitis.

Simultaneous generation of residue-free reactive oxygen species and bacteria capture for efficient electrochemical water disinfection.

Residue-free and highly efficient techniques for drinking water disinfection are urgently needed. Herein, we report an electrochemical water disinfection system equipped with atomically precise Ag nanoclusters (NCs) as electrode materials. The deployment of these Ag NCs not only provides sufficient electrosorption sites for intelligent microbe enrichment but also ensures high-efficiency dual-mode microbial killing through the in situ electrocatalytic production of residue-free reactive oxygen species (ROS) and the inherent antimicrobial activity of Ag NCs.