Long-term renoprotective effect of luseogliflozin in type 2 diabetes patients: CHikushi Anti-diabetes mellitus Trial-Lusefi (CHAT-Lu).

Several sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to have beneficial effects on renal function in patients with type 2 diabetes. However, the long-term effects of luseogliflozin, an SGLT2 inhibitor, remain uncertain in real-world settings. This multicenter, open-label, prospective observational study evaluated the long-term effects of luseogliflozin on renal function in Japanese patients with type 2 diabetes.

Structure-function analysis of carrier protein-dependent 2-sulfamoylacetyl transferase in the biosynthesis of altemicidin.

The general control non-repressible 5 (GCN5)-related N-acetyltransferase (GNAT) SbzI, in the biosynthesis of the sulfonamide antibiotic altemicidin, catalyzes the transfer of the 2-sulfamoylacetyl (2-SA) moiety onto 6-azatetrahydroindane dinucleotide. While most GNAT superfamily utilize acyl-coenzyme A (acyl-CoA) as substrates, SbzI recognizes a carrier-protein (CP)-tethered 2-SA substrate. Moreover, SbzI is the only naturally occurring enzyme that catalyzes the direct incorporation of sulfonamide, a valuable pharmacophore in medicinal chemistry.

Pyridoxal 5'-Phosphate (PLP)-Dependent β- and γ-Substitution Reactions Forming Nonproteinogenic Amino Acids in Natural Product Biosynthesis.

Living organisms synthesize various nonproteinogenic amino acids (NPAAs) as the building blocks of natural products. These NPAAs are often biosynthesized by pyridoxal 5'-phosphate (PLP)-dependent enzymes, which catalyze β- or γ- substitutions. These enzymes contribute to the structural diversification of NPAAs by installing new functional groups to amino acid side chains.

Structure-function analysis of 2-sulfamoylacetic acid synthase in altemicidin biosynthesis.

Altemicidin and its analogs are valuable sulfonamide antibiotics with valuable antitumor and antibacterial activities. Structures of altemicidin and congeners feature an unusual sulfonamide side chain. In the biosynthesis of altemicidin, the aldehyde dehydrogenase SbzJ catalyzes the conversion of 2-sulfamoylacetic aldehyde into 2-sulfamoylacetic acid, a key step in producing the sulfonamide side chain.

Molecular basis for the diversification of lincosamide biosynthesis by pyridoxal phosphate-dependent enzymes.

The biosynthesis of the lincosamide antibiotics lincomycin A and celesticetin involves the pyridoxal-5'-phosphate (PLP)-dependent enzymes LmbF and CcbF, which are responsible for bifurcation of the biosynthetic pathways. Despite recognizing the same S-glycosyl-L-cysteine structure of the substrates, LmbF catalyses thiol formation through β-elimination, whereas CcbF produces S-acetaldehyde through decarboxylation-coupled oxidative deamination. The structural basis for the diversification mechanism remains largely unexplored.

Traces of convergent evolution left in the structure of EgtB-IV.

The enzymatically regioselective catalyzed incorporation of cysteine sulfoxide into histidine generates physiologically important antioxidants such as ergothioneine and ovothiol. In this issue of Structure, Ireland et al. report the crystal structure of EgtB-IV, which provides insights into the convergent evolution of sulfoxide synthase.

Bio-Based Self-Healing Epoxy Vitrimers with Dynamic Imine and Disulfide Bonds Derived from Vanillin, Cystamine, and Dimer Diamine.

The condensation reactions of 4,4'-(ethane-1,2-diylbis (oxy)) bis(3-methoxybenzaldehyde) (VV) with cystamine, 1,6-hexamenthylene diamine, and a dimer diamine (Priamine 1075) produced three types of vanillin-derived imine-and disulfide-containing diamines (VC, VH, and VD, respectively). Thermal curing reactions of polyglycerol polyglycidyl ether with VD and mixtures of VC/VD and VH/VD produced bio-based epoxy vitrimers (BEV-VD, BEV-VC/VD, and BEV-VH/VD, respectively). The degree of swelling and gel fraction tests revealed the formation of a network structure, and the crosslinking density increased with a decreasing VD fraction.

Development of Second Prototype of Twin-Driven Magnetorheological Fluid Actuator for Haptic Device.

Magnetorheological fluids (MRFs) are functional fluids that exhibit rapid and reproducible rheological responses to external magnetic fields. An MRF has been utilized to develop a haptic device with precise haptic feedback for teleoperative surgical systems. To achieve this, we developed several types of compact MRF clutches for haptics (H-MRCs) and integrated them into a twin-driven MRF actuator (TD-MRA).

PCR- and wash-free detection of serum miRNA via signaling probe hybridization.

Detection of microRNAs (miRNAs) in the serum is an effective liquid biopsy technique for cancer diagnosis. However, conventional diagnostic methods are time-consuming and complex. Therefore, in this study, we established a signaling probe-based DNA microarray system for miRNA detection.

Modifications of Prenyl Side Chains in Natural Product Biosynthesis.

In recent years, there has been a growing interest in understanding the enzymatic machinery responsible for the modifications of prenyl side chains and elucidating their roles in natural product biosynthesis. This interest stems from the pivotal role such modifications play in shaping the structural and functional diversity of natural products, as well as from their potential applications to synthetic biology and drug discovery. In addition to contributing to the diversity and complexity of natural products, unique modifications of prenyl side chains are represented by several novel biosynthetic mechanisms.

Functional analysis of an α-ketoglutarate-dependent non-heme iron oxygenase in fungal meroterpenoid biosynthesis.

α-Ketoglutarate-dependent non-heme iron (α-KG NHI) oxygenases compose one of the largest superfamilies of tailoring enzymes that play key roles in structural and functional diversifications. During the biosynthesis of meroterpenoids, α-KG NHI oxygenases catalyze diverse types of chemical reactions, including hydroxylation, desaturation, epoxidation, endoperoxidation, ring-cleavage, and skeletal rearrangements. Due to their catalytic versatility, keen attention has been focused on functional analyses of α-KG NHI oxygenases.

Exchange of CO with CO as Reactant Switches Selectivity in Photoreduction on Co-ZrO from C Paraffin to Small Olefins.

Photocatalytic reduction of CO into C hydrocarbons completes a C-neutral cycle. The reaction pathways of photocatalytic generation of C paraffin and CH from CO are mostly unclear. Herein, a Co-ZrO photocatalyst converted CO into C paraffin, while selectively converting CO into CH and CH (6.

Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.

Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns. Here we uncover the mechanism by which NPY in sympathetic neurons protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY sympathetic axons are a smaller subset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues.

Recent advances in the biosynthetic studies of bacterial organoarsenic natural products.

Covering: 1977 to presentArsenic is widely distributed throughout terrestrial and aquatic environments, mainly in highly toxic inorganic forms. To adapt to environmental inorganic arsenic, bacteria have evolved ubiquitous arsenic metabolic strategies by combining arsenite methylation and related redox reactions, which have been extensively studied. Recent reports have shown that some bacteria have specific metabolic pathways associated with structurally and biologically unique organoarsenic natural products.

Contrasting seasonality of the incidence of incisional surgical site infection after general and gastroenterological surgery: an analysis of 8436 patients in a single institute.

Background: While seasonality of hospital-acquired infections, including incisional SSI after orthopaedic surgery, is recognized, the seasonality of incisional SSI after general and gastroenterological surgeries remains unclear.

Aim: To analyse the seasonality and risk factors of incisional SSI after general and gastroenterological surgeries.

Methods: This was a retrospective, single-institute, observational study using univariate and multivariate analyses.

De Novo Discovery of Pseudo-Natural Prenylated Macrocyclic Peptide Ligands.

Prenylation of peptides is widely observed in the secondary metabolites of diverse organisms, granting peptides unique chemical properties distinct from proteinogenic amino acids. Discovery of prenylated peptide agents has largely relied on isolation or genome mining of naturally occurring molecules. To devise a platform technology for de novo discovery of artificial prenylated peptides targeting a protein of choice, here we have integrated the thioether-macrocyclic peptide (teMP) library construction/selection technology, so-called RaPID (Random nonstandard Peptides Integrated Discovery) system, with a Trp-C3-prenyltransferase KgpF involved in the biosynthesis of a prenylated natural product.

Functional and structural dissection of glycosyltransferases underlying the glycodiversity of wolfberry-derived bioactive ingredients lycibarbarspermidines.

Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry.

Superiority trial for the development of an ideal method for the closure of midline abdominal wall incisions to reduce the incidence of wound complications after elective gastroenterological surgery: study protocol for a randomized controlled trial.

Background: The recent guidelines from the European and American Hernia Societies recommend a continuous small-bite suturing technique with slowly absorbable sutures for fascial closure of midline abdominal wall incisions to reduce the incidence of wound complications, especially for incisional hernia. However, this is based on low-certainty evidence. We could not find any recommendations for skin closure.

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis.

Recent developments in the enzymatic modifications of steroid scaffolds.

Steroids are an important family of bioactive compounds. Steroid drugs are renowned for their multifaceted pharmacological activities and are the second-largest category in the global pharmaceutical market. Recent developments in biocatalysis and biosynthesis have led to the increased use of enzymes to enhance the selectivity, efficiency, and sustainability for diverse modifications of steroids.

Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase.

(±)-Penindolenes A-D (1-4), the first representatives of indole terpenoids featuring a γ-lactam skeleton, were isolated from the mangrove-derived endophytic fungus Penicillium brocae MA-231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ-lactam ring formation were identified with heterologous expression and in vitro enzymatic assays.