Data-driven discovery of cell-type-directed network-correcting combination therapy for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records.

Stoichiometric Regeneration of Biomimetic Nicotinamide Coenzyme Powered by Biomass Sugars via In Vitro Synthetic Enzymatic Biosystems.

Biomimetic nicotinamide coenzymes, including nicotinamide mononucleotide (NMN), have been demonstrated as promising low-cost alternatives to nicotinamide adenine dinucleotide (phosphate) (NAD(P)) in biocatalysis. Herein, to efficiently regenerate NMNH from NMN in vitro powered by biomass sugars, a thermophilic NADP-dependent glucose 6-phosphate dehydrogenase from Thermotoga maritima (TmG6PDH) was engineered to increase the activity toward NMN. The catalytic efficiency (k/K) of optimal mutant (TmG6PDH-R7) toward NMN increased by 71.

A Light-Powered Synthetic Enzymatic Biosystem for the Synthesis of 3-Hydroxypropionic Acid via CO Fixation.

3-Hydroxypropionic acid (3-HP) is a highly sought-after platform chemical serving as a precursor to a variety of high value-added chemical products. In this study, we designed and constructed a novel light-powered synthetic enzymatic biosystem comprising acetyl-CoA ligase, acetyl-CoA carboxylase, malonyl-CoA reductase, and phosphotransferase to efficiently produce 3-HP through CO fixation from acetate, a cost-effective and readily available substrate. The system employed natural thylakoid membranes (TMs) for the regeneration of adenosine triphosphate and nicotinamide adenine dinucleotide phosphate.

A Light-Driven In Vitro Enzymatic Biosystem for the Synthesis of α-Farnesene from Methanol.

Terpenoids of substantial industrial interest are mainly obtained through direct extraction from plant sources. Recently, microbial cell factories or in vitro enzymatic biosystems have emerged as promising alternatives for terpenoid production. Here, we report a route for the synthesis of α-farnesene based on an in vitro enzyme cascade reaction using methanol as an inexpensive and renewable C1 substrate.

Enhancing Machine-Learning Prediction of Enzyme Catalytic Temperature Optima through Amino Acid Conservation Analysis.

Enzymes play a crucial role in various industrial production and pharmaceutical developments, serving as catalysts for numerous biochemical reactions. Determining the optimal catalytic temperature () of enzymes is crucial for optimizing reaction conditions, enhancing catalytic efficiency, and accelerating the industrial processes. However, due to the limited availability of experimentally determined data and the insufficient accuracy of existing computational methods in predicting , there is an urgent need for a computational approach to predict the values of enzymes accurately.

ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA.

In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality.

Comparative study of retrograde intramedullary nailing versus locking extramedullary plating in complete articular fractures with metaphyseal comminution of the distal femur.

Introduction: Fractures of the distal femur with metaphyseal comminution and complete intra-articular involvement (AO/OTA classifications 33C2 and 33C3) present challenges for reduction and fixation. However, an optimal fixation method remains unknown. This study aimed to compare the clinical and radiographic outcomes of locking extramedullary plating (LEP) and retrograde intramedullary nailing (RIN) for complete distal femoral intra-articular fractures with metaphyseal comminution.

In situ preparation and properties of polyvinyl alcohol/synthetic ribbon-like nanocellulose composites.

This study presents a novel approach in which a dual network (DN) composite, comprising polyvinyl alcohol (PVA) and ribbon-like nanocellulose (RC), was synthesized in one step using the volume exclusion effect involved in enzyme-catalyzed cellulose synthesis. Additionally, the impact of PVA as a crowding reagent during enzymatic catalysis on the in situ formation of nanocellulose and its resulting aspect ratio was explored. In contrast, the other two composites were created by incorporating enzyme-catalyzed synthetic block cellulose (BC) and its acid-hydrolyzed regenerated disc-shaped cellulose (DC) into the PVA.

[Advances in a new energy system based on electricity-hydrogen-carbohydrate cycle].

The development of green and low-carbon renewable energy systems has become an important international consensus. It is also an essential path for China to implement the dual-carbon strategy, ensure national energy security, and achieve sustainable development. This review introduces the theory of a new energy system based on electricity-hydrogen-carbohydrate (EHC) cycle, and highlights the biotransformations of carbohydrate/water-to-hydrogen, carbohydrate-to-electricity, and CO-to-carbohydrate powered by hydrogen- or electric-energy based on the synthetic enzymatic biosystems (ivSEB) developed by Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences in the past decade.

Biosynthesis of Lacto-N-biose I from starch and N-acetylglucosamine via an in vitro synthetic enzymatic biosystem.

Human milk oligosaccharides (HMOs) are very distinctive components in human milk and are beneficial for infant health. Lacto-N-biose I (LNB) is the core structural unit of HMOs, which could be used for the synthesis of other HMOs. In this study, an ATP-free in vitro synthetic enzymatic biosystem contained four thermostable enzymes (alpha-glucan phosphorylase from , UDP-glucose-hexose-1-phosphate uridylyltransferase from , UDP-glucose 4-epimerase from , lacto-N-biose phosphorylase from ) were constructed for the biosynthesis of LNB from starch and N-acetylglucosamine (GlcNAc).

A synthetic cell-free 36-enzyme reaction system for vitamin B production.

Adenosylcobalamin (AdoCbl), a biologically active form of vitamin B (coenzyme B), is one of the most complex metal-containing natural compounds and an essential vitamin for animals. However, AdoCbl can only be de novo synthesized by prokaryotes, and its industrial manufacturing to date was limited to bacterial fermentation. Here, we report a method for the synthesis of AdoCbl based on a cell-free reaction system performing a cascade of catalytic reactions from 5-aminolevulinic acid (5-ALA), an inexpensive compound.

Key roles of β-glucosidase BglA for the catabolism of both laminaribiose and cellobiose in the lignocellulolytic bacterium Clostridium thermocellum.

The thermophilic bacterium Clostridium thermocellum efficiently degrades polysaccharides into oligosaccharides. The metabolism of β-1,4-linked cello-oligosaccharides is initiated by three enzymes, i.e.

Biomanufacturing by In Vitro Biotransformation (ivBT) Using Purified Cascade Multi-enzymes.

In vitro biotransformation (ivBT) refers to the use of an artificial biological reaction system that employs purified enzymes for the one-pot conversion of low-cost materials into biocommodities such as ethanol, organic acids, and amino acids. Unshackled from cell growth and metabolism, ivBT exhibits distinct advantages compared with metabolic engineering, including but not limited to high engineering flexibility, ease of operation, fast reaction rate, high product yields, and good scalability. These characteristics position ivBT as a promising next-generation biomanufacturing platform.

Autologous Collagen-Induced Chondrogenesis: From Bench to Clinical Development.

Microfracture is a common technique that uses bone marrow components to stimulate cartilage regeneration. However, the clinical results of microfracture range from poor to good. To enhance cartilage healing, several reinforcing techniques have been developed, including porcine-derived collagen scaffold, hyaluronic acid, and chitosan.

Characteristics of multi-ligament knee injuries accompanied with patellar tendon disruption.

Purpose: Patella tendon rupture with multi-ligament injury is a rare injury. We observed patients with patella tendon rupture (or patella inferior pole fracture) with multi-ligament injury. This study intends to inspect the mechanism of the injury and classify them.

Enabling technology and core theory of synthetic biology.

Synthetic biology provides a new paradigm for life science research ("build to learn") and opens the future journey of biotechnology ("build to use"). Here, we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology, including synthesis and assembly of a genome, DNA storage, gene editing, molecular evolution and de novo design of function proteins, cell and gene circuit engineering, cell-free synthetic biology, artificial intelligence (AI)-aided synthetic biology, as well as biofoundries. We also introduce the concept of quantitative synthetic biology, which is guiding synthetic biology towards increased accuracy and predictability or the real rational design.

The prognostic value of comprehensive geriatric assessment on the management of older patients with small cell lung cancer.

Background/aims: The prognostic value of a comprehensive geriatric assessment (CGA) for the management of older small cell lung cancer (SCLC) patients remains to be established.

Methods: A retrospective cohort enrolled 21 SCLC patients over 65 years from March 2018 to 2019 at the Yonsei Cancer Center. The CGA included the following instruments: frailty, body mass index, sarcopenia (circumference of arm and calf, Timed Up and Go test, grip strength), comorbidity, polypharmacy, activities of daily living (ADL), Instrumental ADL, nutrition, depression, and cognitive function.

Biosynthesis of artificial starch and microbial protein from agricultural residue.

Growing populations and climate change pose great challenges to food security. Humankind is confronting a serious question: how will we feed the world in the near future? This study presents an out-of-the-box solution involving the highly efficient biosynthesis of artificial starch and microbial proteins from available and abundant agricultural residue as new feed and food sources. A one-pot biotransformation using an in vitro coenzyme-free synthetic enzymatic pathway and baker's yeast can simultaneously convert dilute sulfuric acid-pretreated corn stover to artificial starch and microbial protein under aerobic conditions.

Carrier-Free Immobilization of Multi-Enzyme Complex Facilitates In Vitro Synthetic Enzymatic Biosystem for Biomanufacturing.

A method is developed for carrier-free immobilization of multi-enzyme complexes with more than four enzymes by utilization of polypeptide interactions (SpyCatcher-SpyTag and dockerin-cohesin) and enzyme component self-oligomerization. Two pairs of scaffoldins with different arrangements of SpyCatcher-SpyTag and cohesins are prepared to recruit the four dockerin-containing cascade enzymes (i. e.

An artificial multi-enzyme cascade biocatalysis for biomanufacturing of nicotinamide mononucleotide from starch and nicotinamide in one-pot.

β-Nicotinamide mononucleotide (NMN) is an important precursor in the synthesis of nicotinamide adenine dinucleotide (NAD) and confers multiple health benefits, resulting in the rapid growth of NMN market capacity in the fields of food and health care. To overcome the drawbacks of NMN production by the existing chemical or microbial fermentation method, there is an urgent need to develop a prospective NMN production strategy with low cost, low pollution, and high yield. In this study, we demonstrated an artificial in vitro multi-enzyme cascade biocatalysis using starch and nicotinamide (Nam) as substrates for the synthesis of NMN in one-pot.

Deciphering Cellodextrin and Glucose Uptake in .

Sugar uptake is of great significance in industrially relevant microorganisms. Clostridium thermocellum has extensive potential in lignocellulose biorefineries as an environmentally prominent, thermophilic, cellulolytic bacterium. The bacterium employs five putative ATP-binding cassette transporters which purportedly take up cellulose hydrolysates.

Low muscle mass, low muscle function, and sarcopenia in the urban and rural elderly.

Health outcomes of the elderly vary between rural and urban areas. Sarcopenia is diagnosed as loss of muscle strength or impaired physical performance, namely "low muscle function" and low muscle mass. Outcomes of low muscle mass and low muscle function are not equal.

Stoichiometric Conversion of Maltose for Biomanufacturing by Synthetic Enzymatic Biosystems.

Maltose is a natural -(1,4)-linked disaccharide with wide applications in food industries and microbial fermentation. However, maltose has scarcely been used for biosynthesis, possibly because its phosphorylation by maltose phosphorylase (MP) yields -glucose 1-phosphate (-G1P) that cannot be utilized by -phosphoglucomutase (-PGM) commonly found in synthetic enzymatic biosystems previously constructed by our group. Herein, we designed an synthetic enzymatic reaction module comprised of MP, -phosphoglucomutase (-PGM), and polyphosphate glucokinase (PPGK) for the stoichiometric conversion of each maltose molecule to two glucose 6-phosphate (G6P) molecules.

A specific circuit in the midbrain detects stress and induces restorative sleep.

In mice, social defeat stress (SDS), an ethological model for psychosocial stress, induces sleep. Such sleep could enable resilience, but how stress promotes sleep is unclear. Activity-dependent tagging revealed a subset of ventral tegmental area γ-aminobutyric acid (GABA)-somatostatin (VTA) cells that sense stress and drive non-rapid eye movement (NREM) and REM sleep through the lateral hypothalamus and also inhibit corticotropin-releasing factor (CRF) release in the paraventricular hypothalamus.