From discovery to application: Enabling technology-based optimizing carbonyl reductases biocatalysis for active pharmaceutical ingredient synthesis.

The catalytic conversion of chiral alcohols and corresponding carbonyl compounds by carbonyl reductases (alcohol dehydrogenases), which are NAD(P) or NAD(P)H-dependent oxidoreductases, has attracted considerable attention. However, existing carbonyl reductases are insufficient to meet the demands of diverse industrial applications; hence, new enzymes with functions that can expand the toolbox of biocatalysts are urgently required. Developing precisely controlled chiral biocatalysts is of great significance for the efficient development of a broad spectrum of active pharmaceutical ingredients via biosynthesis.

Upcycling of melanoidin-rich Chinese distilled spent grain through solid-state fermentation by Aspergillus awamori.

This study investigated the upcycling of distilled spent grain (DSG), a melanoidin-rich by-product of the Chinese liquor industry, via fungal solid-state fermentation (SSF). Two fungi, Aspergillus oryzae and Aspergillus awamori, were tested, with A. awamori growing better on DSG than A.

Early sedation using ciprofol for intensive care unit patients requiring mechanical ventilation: a pooled post-hoc analysis of data from phase 2 and phase 3 trials.

Background: Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.

Methods: All eligible ICU patients who were expected to require sedation for 6-24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group.

Fe(II) and 2-oxoglutarate-dependent dioxygenases for natural product synthesis: molecular insights into reaction diversity.

Covering: up to 2024Fe(II) and 2-oxoglutarate-dependent dioxygenases (Fe/2OG DOs) are a superfamily of enzymes that play important roles in a variety of catalytic reactions, including hydroxylation, ring formation, ring reconstruction, desaturation, and demethylation. Each member of this family has similarities in their overall structure, but they have varying specific differences, making Fe/2OG DOs attractive for catalytic diversity. With the advancement of current research, more Fe/2OG DOs have been discovered, and their catalytic scope has been further broadened; however, apart from hydroxylation, many reaction mechanisms have not been accurately demonstrated, and there is a lack of a systematic understanding of their molecular basis.

Global prototype distillation for heterogeneous federated learning.

Federated learning is a distributed machine learning paradigm where the goal is to collaboratively train a high quality global model while private training data remains local over distributed clients. However, heterogenous data distribution over clients is severely challenging for federated learning system, which severely damage the quality of model. In order to address this challenge, we propose global prototype distillation (FedGPD) for heterogenous federated learning to improve performance of global model.

Retronasal sensory characterization of aroma compounds in Baijiu by detection threshold measurement, retronasal OAVs, and time-intensity evaluation.

The retronasal aroma of Baijiu is closely related to its quality and consumer preference. Retronasal detection thresholds (RDTs) of 44 aroma compounds were determined in 46% v/v ethanol using a three-alternative forced-choice procedure, which varied widely and ranged from less than 0.02 to over 1,000,000 µg/L.

The evolutionary mechanism and function analysis of two subgroups of histamine-producing and non-histamine-producing Tetragenococcus halophilus.

Tetragenococcus halophilus is a halophilic bacterium that existed in the fermentation of soy sauce and miso for flavor production and probiotic benefits. However, it is composed of two subgroups, histamine-producing and non-histamine-producing, with the former causing histamine accumulation and offering risks to food safety. Exploring the evolutionary mechanisms and physiological function of histamine-biosynthesis is of significance for understanding the formative mechanism of T.

Estimating the completeness of physician billing claims for diabetes case ascertainment: a multiprovince investigation.

Introduction: Previous research has suggested that how physicians are paid may affect the completeness of billing claims for estimating chronic disease. The purpose of this study is to estimate the completeness of physician billings for diabetes case ascertainment.

Methods: We used administrative data from eight Canadian provinces covering the period 1 April 2014 to 31 March 2016.

Higher-order matrix nonlinear Schrödinger equation with the negative coherent coupling: binary Darboux transformation, vector solitons, breathers and rogue waves.

Optical fiber communication plays a crucial role in modern communication. In this work, we focus on the higher-order matrix nonlinear Schrödinger equation with negative coherent coupling in a birefringent fiber. For the slowly varying envelopes of two interacting optical modes, we construct a binary Darboux transformation using the corresponding Lax pair.

Glycogen for lysosome-targeted CpG ODNs delivery and enhanced cancer immunotherapy.

CpG oligodeoxynucleotides (ODNs) strongly activate the immune system after binding to toll-like receptor 9 (TLR9) in lysosome, which demonstrated significant potential in cancer immunotherapy. However, their therapeutic efficacy is limited by drawbacks such as rapid degradation and poor cellular uptake. Although encouraging progress have been made on developing various delivery systems for CpG ODNs, safety risks of the synthetic nanocarriers as well as the deficient CpG ODNs release within lysosome remain big obstacles.

Entering an Era of Protein Structuromics.

Sequence determines the structure, and the structure in turn determines the function, are the fundamental principles of protein chemistry. In the genomics era, the paradigm of mining protein functionality and evolutionary insights through sequence analysis has led to remarkable achievements. However, protein sequences often mutate faster than their structural counterparts during evolution.

Serine Improves Lactic Acid Stress Tolerance and Ethanol Production in in Fermentation.

Lactic acid is the primary inhibitor of the growth and ethanol production of yeasts in fermentation. Certain amino acids have been found to be related to stress tolerance in yeasts. This study explored the effect of lactic acid stress on the ethanol-producing yeast and evaluated the ability of serine to increase the lactic acid tolerance of .

Regulating the stereoselectivity of medium-chain dehydrogenase/reductase by creating an additional active pocket accommodating prochiral heterocyclic ketones.

Medium chain dehydrogenase/reductase (MDR) is a robust catalyst for the asymmetric synthesis of chiral heterocyclic alcohols, essential building blocks in pharmaceuticals. However, the regulatory mechanism of stereoselective complementary reduction of heterocyclic ketones by carbonyl reductase (CR) is unclear. Structure-guided creation of an additional substrate-binding active pocket inversed the stereoselectivity of SpCR from .

A path planning method using modified harris hawks optimization algorithm for mobile robots.

Path planning is a critical technology that could help mobile robots accomplish their tasks quickly. However, some path planning algorithms tend to fall into local optimum in complex environments. A path planning method using a modified Harris hawks optimization (MHHO) algorithm is proposed to address the problem and improve the path quality.

mTORC1 Signaling and Negative Lens-Induced Axial Elongation.

Purpose: The mechanism underlying axial elongation during myopia progression remains unknown. Epidermal growth factor receptor (EGFR) signaling is associated with axial elongation. We explored whether mammalian target of rapamycin complex 1 (mTORC1) signaling acts as the downstream pathway of EGFR and participates in negative lens-induced axial elongation (NLIAE).

CoNi Alloys Encapsulated in N-Doped Carbon Nanotubes for Stabilizing Oxygen Electrocatalysis in Zinc-Air Battery.

Alloy-based catalysts with high corrosion resistance and less self-aggregation are essential for oxygen reduction/evolution reactions (ORR/OER). Here, via an in situ growth strategy, NiCo alloy-inserted nitrogen-doped carbon nanotubes were assembled on a three-dimensional hollow nanosphere (NiCo@NCNTs/HN) using dicyandiamide. NiCo@NCNTs/HN exhibited better ORR activity (half-wave potential (E) of 0.

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial.

Objectives: To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV).

Design: A multicenter, single-blind, randomized, noninferiority trial.

Setting: Twenty-one centers across China from December 2020 to June 2021.

Electronic-State Modulation of Metallic Co-Assisted Co Fe Alloy Heterostructure for Highly Efficient and Stable Overall Water Splitting.

Manipulating electronic structure of alloy-based electrocatalysts can eagerly regulate its catalytic efficiency and corrosion resistance for water splitting and fundamentally understand the catalytic mechanisms for oxygen/hydrogen evolution reactions (OER/HER). Herein, the metallic Co-assisted Co Fe alloy heterojunction (Co Fe /Co) embeds in a 3D honeycomb-like graphitic carbon is purposely constructed as a bifunctional catalyst for overall water splitting. As-marked Co Fe /Co-600 displays the excellent catalytic activities in alkaline media with low overpotentials of 200 mV for OER and 68 mV for HER at 10 mA cm .

Semi-Rational Design of L-Isoleucine Dioxygenase Generated Its Activity for Aromatic Amino Acid Hydroxylation.

Fe (II)-and 2-ketoglutarate-dependent dioxygenases (Fe (II)/α-KG DOs) have been applied to catalyze hydroxylation of amino acids. However, the Fe (II)/α-KG DOs that have been developed and characterized are not sufficient. L-isoleucine dioxygenase (IDO) is an Fe (II)/α-KG DO that specifically catalyzes the formation of 4-hydroxyisoleucine (4-HIL) from L-isoleucine (L-Ile) and exhibits a substrate specificity toward L-aliphatic amino acids.

Aspirin Therapy and 28-Day Mortality in ICU Patients: A Retrospective Observational Study From Two Large Databases.

Purpose: Aspirin is widely used in patients in the intensive care unit (ICU); nonetheless, its effects on these patients remain controversial. This retrospective analysis of data from clinical practice investigated the effects of aspirin on 28-day mortality in ICU patients.

Methods: This retrospective study included data from patients in the Medical Information Mart for Intensive Care (MIMIC)-III database and the eICU-Collaborative Research Database (CRD).

Amino Acids Drive the Deterministic Assembly Process of Fungal Community and Affect the Flavor Metabolites in Fermentation.

Nutrient fluctuation is ubiquitous in fermentation ecosystems. However, the microbial community assembly mechanism and metabolic characteristics in response to nutrient variation are still unclear. Here, we used fermentation as a case example to study the responses of microbial community assembly and metabolic characteristics to the variation of amino acids using high-throughput sequencing and metatranscriptomics analyses.

Study Protocol of a Multicenter, Randomized, Single-Blind Trial: Efficacy and Safety of Remimazolam Tosylate for Sedation in ICU Patients.

Introduction: Pharmacodynamic and pharmacokinetic studies in animal experiments and a phase 1 study suggested remimazolam tosylate as an effective and safe sedation/anesthetic agent. However, the effects and safety dose of remimazolam for light sedation in intensive care unit (ICU) patients are not clear and should be confirmed in a phase 2 study.

Methods: Sixty ICU patients requiring sedation treatment and undergoing mechanical ventilation will be enrolled and randomly assigned to a high dose group (HD group, 30 cases) and a low dose group (LD group, 30 cases) in a 1:1 ratio.

R97 at "Handlebar" Binding Mode in Active Pocket Plays an Important Role in Fe(II)/α-Ketoglutaric Acid-Dependent Dioxygenase -P3H-Mediated Selective Synthesis of (2S,3R)-3-Hydroxypipecolic Acid.

Pipecolic acid (Pip) and its derivative hydroxypipecolic acids, such as (2S,3R)-3-hydroxypipecolic acid (-3-L-HyPip), are components of many natural and synthetic bioactive molecules. Fe(II)/α-ketoglutaric acid (Fe(II)/2-OG)-dependent dioxygenases can catalyze the hydroxylation of pipecolic acid. However, the available enzymes with desired activity and selectivity are limited.

Ratio of Histamine-Producing/Non-Histamine-Producing Subgroups of Tetragenococcus halophilus Determines the Histamine Accumulation during Spontaneous Fermentation of Soy Sauce.

Strain specificity (within-species variation) of microorganisms occurs widely in nature. It might affect microbiome construction and function in a complex microbial environment. Tetragenococcus halophilus, a halophilic bacterium that generally is used in high salt food fermentation, consists of two histamine-producing and non-histamine-producing subgroups.