Enhancing the β-Oxidation-Like Pathway for the Optimal Production of the Immunosuppressant Mycophenolic Acid.

The recruitment of catabolic β-oxidation enzyme cascades and their reaction logic for natural product biosynthesis remains underexplored, representing a significant opportunity for synthetic biology to engineer novel pathways for structurally unique metabolites. In this study, the first functional reconstitution of the fungal β-oxidative cascade responsible for assembling the immunosuppressant mycophenolic acid (MPA) is reported. Through in vitro enzyme assays, five peroxisomal enzymes are identified that cooperatively mediate two iterative rounds of side-chain cleavage of the biosynthetic precursor MFDHMP-3C and revealed a key oxidative strategy for pharmacophore formation of MPA.

Wavelet-domain frequency-mixing transformer unfolding network for low-dose computed tomography image denoising.

Background: Low-dose computed tomography (LDCT) has become clinically essential for reducing radiation risks, but image noise remains a major challenge. Although deep learning methods have shown promise in denoising, they often fail to preserve fine structures while suppressing noise, particularly in orthopedic imaging where subtle bone textures are diagnostically critical. This study aimed to develop a wavelet-domain frequency-mixing transformer (FMT) network that simultaneously addresses noise suppression and structural preservation in orthopedic LDCT images, overcoming the limitations of current spatial-domain methods.

CAR Macrophages Engineered In Vivo for Attenuating Myocardial Ischemia-Reperfusion Injury.

Background: Myocardial ischemia-reperfusion (I/R) injury induces myocardial fibrosis that compromises cardiac function and electrical conduction, yet current clinical options remain inadequate. To address this unmet need, we explored macrophage-targeted lipid nanoparticles (LNPs) encapsulating FAP CAR (FAP [fibroblast activation protein]-targeted chimeric antigen receptor) mRNA for in vivo generation of FAP CAR macrophages and evaluated their therapeutic potential in reducing myocardial fibrosis and improving cardiac function after myocardial I/R injury.

Methods: We formulated 1,2-dioleoyl-sn-glycero-3-phospho-l-serine-doping ALC-0315 (an ionizable lipid) LNP to deliver FAP CAR mRNA to generate FAP CAR macrophages.

Deciphering the Thiolactonization Mechanism in Thiolactomycin Biosynthesis.

Thiolactomycin (), which features a unique γ-thiolactone ring, is a promising antibiotic candidate that specifically targets bacterial type II fatty acid synthase. Despite extensive studies on its pharmacological activities, modes of action, and chemical synthesis, the enzymatic processes responsible for forming the activity-determining γ-thiolactone ring have remained largely unknown. Here, we resolve this problem by revealing that the condensation and heterocyclization (Cy) domain of the nonribosomal peptide synthetase (NRPS) TlnC (TlnC), along with the cytochrome P450 enzyme TlnA, cooperatively enable the γ-thiolactone assembly.

Flavonifractor Plautii or Its Metabolite Desaminotyrosine as Prophylactic Agents for Alleviating Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion (I/R) injury is a major contributor to myocardial damage, leading to adverse cardiac remodeling and dysfunction. Recent studies have highlighted the potential of gut microbiota-derived metabolites in modulating cardiac outcomes. Here, the cardioprotective effects of a commensal bacterium Flavonifractor plautii (F.

CAR-Macrophage Therapy Alleviates Myocardial Ischemia-Reperfusion Injury.

Background: Given the growing acknowledgment of the detrimental effects of excessive myocardial fibrosis on pathological remodeling after myocardial ischemia-reperfusion injury (I/R), targeting the modulation of myocardial fibrosis may offer protective and therapeutic advantages. However, effective clinical interventions and therapies that target myocardial fibrosis remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear.

Methods and Strategies of Microsurgery Combined with Ilizarov Technique in the Treatment of Amputation of Limbs in Renji Hospital: A Report of 51 Cases.

Objective: Severe limb amputation trauma often results in bone and soft tissue defects after debridement. Traditional replantation aims to save the limb by shortening the ischemic period and using autologous transplantation for repair, but it can lead to surgical trauma, donor site damage, and prolonged operation time. Due to contusion, pollution, and complex injury, there is no unified standard for replantation and fixation.

Mevalonate pathway and male reproductive aging.

Male fertility declines with age. The mevalonate pathway, through which cholesterol and nonsteroidal isoprenoids are synthesized, plays key role in metabolic processes and is an essential pathway for cholesterol production and protein prenylation. Male reproductive aging is accompanied by dramatic changes in the metabolic microenvironment of the testis.

Superlithiation Performance of Pyridinium Polymerized Ionic Liquids with Fast Li Diffusion Kinetics as Anode Materials for Lithium-Ion Battery.

Polymerized ionic liquids (PILs) with super ion diffusion kinetics have aroused considerable attention in rechargeable batteries, which are very promising to solve the problem of the slow ion diffusion kinetics in organic electrode materials. Theoretically, PILs incorporated redox groups are very suitable as anode materials to realize "superlithiation" performance, achieving high lithium storage capacity. In this study, redox pyridinium-based PILs (PILs-Py-400) have been synthesized through trimerization reactions by pyridinium ionic liquids with cyano groups under an appropriate temperature (400 °C).

Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study.

The roles of Rho GTPases in various types of cancer have been extensively studied, but the research of Rho guanine nucleotide exchange factors (GEFs) in cancer is not comprehensive. Rho guanine nucleotide exchange factor 6 (ARHGEF6) is an important member of the Rho GEFs family involved in cytoskeletal rearrangement, and it has not been investigated in acute myeloid leukemia (AML). Our research showed that the expression of ARHGEF6 was mainly higher in AML cell lines, meanwhile, was highest in the samples from patients with AML compared to other cancer types.

The KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling during cardiac hypertrophy in male mice.

The main hallmark of myocardial substrate metabolism in cardiac hypertrophy or heart failure is a shift from fatty acid oxidation to greater reliance on glycolysis. However, the close correlation between glycolysis and fatty acid oxidation and underlying mechanism by which causes cardiac pathological remodelling remain unclear. We confirm that KLF7 simultaneously targets the rate-limiting enzyme of glycolysis, phosphofructokinase-1, liver, and long-chain acyl-CoA dehydrogenase, a key enzyme for fatty acid oxidation.

Mechanical characteristics and stability analysis of surrounding rock reinforcement in rectangular roadway.

The stability of surrounding rock with bolt support depends on the stability within the reinforcement range. To understand the reinforcing mechanism of a rectangular roadway bolt fully and accurately, a quantitative method for evaluating the stability of the surrounding rock of a rectangular roadway must be developed. First, a roof beam model of a rectangular tunnel is established according to the deformation law of surrounding rock.

The neonatal ketone body is important for primordial follicle pool formation and regulates ovarian ageing in mice.

Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood; however, the underlying mechanism is still unclear. Herein, we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing. We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum.

Gonadal white adipose tissue is important for gametogenesis in mice through maintenance of local metabolic and immune niches.

Gonadal white adipose tissue (gWAT) can regulate gametogenesis via modulation of neuroendocrine signaling. However, the effect of gWAT on the local microenvironment of the gonad was largely unknown. Herein, we ruled out that gWAT had a neuroendocrine effect on gonad function through a unilateral lipectomy strategy, in which cutting off epididymal white adipose tissue could reduce seminiferous tubule thickness and decrease sperm counts only in the adjacent testis and epididymis of the affected gonad.

A novel nano delivery system targeting different stages of osteoclasts.

Osteoclast (OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted delivery systems exist.

ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis.

Background: Preeclampsia (PE) is a multisystemic syndrome which has short- and long-term risk to mothers and children and has pluralistic etiology.

Objective: This study is aimed at constructing a competitive endogenous RNA (ceRNA) network for pathways most related to PE using a data mining strategy based on weighted gene coexpression network analysis (WGCNA).

Methods: We focused on pathways involving hypoxia, angiogenesis, and epithelial mesenchymal transition according to the gene set variation analysis (GSVA) scores.

Superlithiation Performance of Covalent Triazine Frameworks as Anodes in Lithium-Ion Batteries.

Organics with the merit of renewability have been viewed as the promising alternative of inorganic electrode materials in lithium-ion batteries, but most of them display inferior performance due to the sluggish ion/electron diffusion and the potential dissolution in aprotic electrolytes. Here, covalent triazine frameworks (CTFs-1), full of vertical pores and layered spaces for Li transfer, have been synthesized with -dicyanobenzene as the monomer by a facile two-step method including a prepolymerization with CFSOH as the catalyst and deep polymerization in molten ZnCl. CTFs-1-400, obtained at the deep polymerization temperature of 400 °C, exhibits the superlithiation property with the specific capacities of 1626 mA h g at 25 °C and 1913 mA h g at 45 °C at 100 mA g, indicating the formation of LiC/LiCN in the reduction process.

Biosynthesis of Chuangxinmycin Featuring a Deubiquitinase-like Sulfurtransferase.

The knowledge on sulfur incorporation mechanism involved in sulfur-containing molecule biosynthesis remains limited. Chuangxinmycin is a sulfur-containing antibiotic with a unique thiopyrano[4,3,2-cd]indole (TPI) skeleton and selective inhibitory activity against bacterial tryptophanyl-tRNA synthetase. Despite the previously reported biosynthetic gene clusters and the recent functional characterization of a P450 enzyme responsible for C-S bond formation, the enzymatic mechanism for sulfur incorporation remains unknown.

Matching sensor ontologies through siamese neural networks without using reference alignment.

Sensors have been growingly used in a variety of applications. The lack of semantic information of obtained sensor data will bring about the heterogeneity problem of sensor data in semantic, schema, and syntax levels. To solve the heterogeneity problem of sensor data, it is necessary to carry out the sensor ontology matching process to determine correspondences among heterogeneous sensor concepts.

Nitrogen Doped γ-Graphyne: A Novel Anode for High-Capacity Rechargeable Alkali-Ion Batteries.

High energy density is the major demand for next-generation rechargeable batteries, while the intrinsic low alkali metal adsorption of traditional carbon-based electrode remains the main challenge. Here, the mechanochemical route is proposed to prepare nitrogen doped γ-graphyne (NGY) and its high capacity is demonstrated in lithium (LIBs)/sodium (SIBs) ion batteries. The sample delivers large reversible Li (1037 mAh g ) and Na (570.

Mechanochemical Synthesis of γ-Graphyne with Enhanced Lithium Storage Performance.

γ-Graphyne is a new nanostructured carbon material with large theoretical Li storage due to its unique large conjugate rings, which makes it a potential anode for high-capacity lithium-ion batteries (LIBs). In this work, γ-graphyne-based high-capacity LIBs are demonstrated experimentally. γ-Graphyne is synthesized through mechanochemical and calcination processes by using CaC and C Br .