Dehydroamino acid residues in bioactive natural products.

Covering: 2000 to up to 2023α,ß-Dehydroamino acids (dhAAs) are unsaturated nonproteinogenic amino acids found in a wide array of naturally occurring peptidyl metabolites, predominantly those from bacteria. Other organisms, such as fungi, higher plants and marine invertebrates, have also been found to produce dhAA-containing peptides. The α,ß-unsaturation in dhAAs has profound effects on the properties of these molecules. They display significant synthetic flexibility, readily undergoing reactions such as Michael additions, transition-metal-catalysed cross-couplings, and cycloadditions. These residues in peptides/proteins also exhibit great potential in bioorthogonal applications using click chemistry. Peptides containing contiguous dhAA residues have been extensively investigated in the field of foldamers, self-assembling supermolecules that mimic biomacromolecules such as proteins to fold into well-defined conformations. dhAA residues in these peptidyl materials tend to form a 2.05-helix. As a result, stretches of dhAA residues arrange in an extended conformation. In particular, peptidyl foldamers containing ß-enamino acid units display interesting conformational, electronic, and supramolecular aggregation properties that can be modulated by light-dependent E-Z isomerization. Among approximately 40 dhAAs found in the natural product inventory, dehydroalanine (Dha) and dehydrobutyrine (Dhb) are the most abundant. Dha is the simplest dehydro-α-amino acid, or α-dhAA, without any geometrical isomers, while its re-arranged isomer, 3-aminoacrylic acid (Aaa or ΔßAla), is the simplest dehydro-ß-amino acid, or ß-enamino acid, and displays E/Z isomerism. Dhb is the simplest α-dhAA that exhibits E/Z isomerism. The Z-isomer of Dhb (Z-Dhb) is sterically favourable and is present in the majority of naturally occurring peptides containing Dhb residues. Dha and Z-Dhb motifs are commonly found in ribosomally synthesized and post-translationally modified peptides (RiPPs). In the last decade, the formation of Dha and Dhb motifs in RiPPs has been extensively investigated, which will be briefly discussed in this review. The formation of other dhAA residues in natural products (NPs) is, however, less understood. In this review, we will discuss recent advances in the biosynthesis of peptidyl NPs containing unusual dhAA residues and cryptic dhAA residues. The proposed biosynthetic pathways of these natural products will also be discussed.

High prevalence and distinctive clinical features of LMNA-associated atrioventricular block in young patients.

BACKGROUND AND AIMS: Atrioventricular block (AVB) is a degenerative disease and more commonly encountered in elderly patients, but unusual and often of unknown etiology in young patients. This study aimed to investigate the potential contributions of genetic variations to AVB of unknown reasons in young patients. METHODS: We enrolled 41 patients aged <55 years with high-degree AVB of unknown etiology whose clinical and genetic data were collected. RESULTS: Genetic variants were identified in 20 (20/41, 48.8%) patients, 11 (11/20, 55%) of whom had LMNA variants including 3 pathogenic (c.961C > T, c.936+1G > T and c.646C > T), 4 likely pathogenic (c.1489-1G > C, c.265C > A, c.1609-2A > G and c.1129C > T) and 3 of uncertain significance (c.1158-3C > G, c.776A > G and c.674G > T). Compared to those without LMNA variants, patients with LMNA variants demonstrated a later age at onset of AVB (41.45 ± 9.89 years vs 32.93 ± 12.07 years, P = .043), had more prevalent family history of cardiac events (81.8% vs 16.7%, P < .000), suffered more frequently atrial (81.8% vs 10.0%, P < .000) and ventricular (72.7% vs 10.0%, P < .000) arrhythmias, and were more significantly associated with enlargement of left atrium (39.91 ± 7.83 mm vs 34.30 ± 7.54 mm, P = .043) and left ventricle (53.27 ± 8.53 mm vs 47.77 ± 6.66 mm, P = .036). CONCLUSIONS: Our findings provide insights into the genetic etiology of AVB in young patients. LMNA variants are predominant in genotype positive patients and relevant to distinctive phenotypic properties.

The distinguishable-particle lattice model of glasses in three dimensions.

The nature of glassy states in realistic finite dimensions is still under fierce debate. Lattice models can offer valuable insights and facilitate deeper theoretical understanding. Recently, a disordered-interacting lattice model with distinguishable particles in two dimensions (2D) has been shown to produce a wide range of dynamical properties of structural glasses, including the slow and heterogeneous characteristics of the glassy dynamics, various fragility behaviors of glasses, and so on. These findings support the usefulness of this model for modeling structural glasses. An important question is whether such properties still hold in the more realistic three dimensions. In this study, we aim to extend the distinguishable-particle lattice model (DPLM) to three dimensions (3D) and explore the corresponding glassy dynamics. Through extensive kinetic Monte Carlo simulations, we found that the 3D DPLM exhibits many typical glassy behaviors, such as plateaus in the mean square displacement of particles and the self-intermediate scattering function, dynamic heterogeneity, variability of glass fragilities, and so on, validating the effectiveness of the DPLM in a broader realistic setting. The observed glassy behaviors of the 3D DPLM appear similar to those of its 2D counterpart, in accordance with recent findings in molecular models of glasses. We further investigate the role of void-induced motions in dynamical relaxations and discuss their relation to dynamic facilitation. As lattice models tend to keep the minimal but important modeling elements, they are typically much more amenable to analysis. Therefore, we envisage that the DPLM will benefit future theoretical developments, such as the configuration tree theory, towards a more comprehensive understanding of structural glasses.

Surface mobility gradient and emergent facilitation in glassy films.

Confining glassy polymers into films can substantially modify their local and film-averaged properties. We present a lattice model of film geometry with void-mediated facilitation behaviors but free from any elasticity effect. We analyze the spatially varying viscosity to delineate the transport properties of glassy films. The film mobility measurements reported by Yang et al., Science, 2010, 328, 1676 are successfully reproduced. The flow exhibits a crossover from a simple viscous flow to a surface-dominated regime as the temperature decreases. The propagation of a highly mobile front induced by the free surface is visualized in real space. Our approach provides a microscopic treatment of the observed glassy phenomena.

Correction: Surface mobility gradient and emergent facilitation in glassy films.

Correction for 'Surface mobility gradient and emergent facilitation in glassy films' by Qiang Zhai et al., Soft Matter, 2024, https://doi.org/10.1039/D4SM00221K.

Mutagenetic analysis of the biosynthetic pathway of tetramate bripiodionen bearing 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton.

BACKGROUND: Natural tetramates are a family of hybrid polyketides bearing tetramic acid (pyrrolidine-2,4-dione) moiety exhibiting a broad range of bioactivities. Biosynthesis of tetramates in microorganisms is normally directed by hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries, which form the tetramic acid ring by recruiting trans- or cis-acting thioesterase-like Dieckmann cyclase in bacteria. There are a group of tetramates with unique skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, which remain to be investigated for their biosynthetic logics. RESULTS: Herein, the tetramate type compounds bripiodionen (BPD) and its new analog, featuring the rare skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, were discovered from the sponge symbiotic bacterial Streptomyces reniochalinae LHW50302. Gene deletion and mutant complementation revealed the production of BPDs being correlated with a PKS-NRPS biosynthetic gene cluster (BGC), in which a Dieckmann cyclase gene bpdE was identified by sit-directed mutations. According to bioinformatic analysis, the tetramic acid moiety of BPDs should be formed on an atypical NRPS module constituted by two discrete proteins, including the C (condensation)-A (adenylation)-T (thiolation) domains of BpdC and the A-T domains of BpdD. Further site-directed mutagenetic analysis confirmed the natural silence of the A domain in BpdC and the functional necessities of the two T domains, therefore suggesting that an unusual aminoacyl transthiolation should occur between the T domains of two NRPS subunits. Additionally, characterization of a LuxR type regulator gene led to seven- to eight-fold increasement of BPDs production. The study presents the first biosynthesis case of the natural molecule with 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton. Genomic mining using BpdD as probe reveals that the aminoacyl transthiolation between separate NRPS subunits should occur in a certain population of NRPSs in nature.

Accraspiroketides A-B, Phenylnaphthacenoid-Derived Polyketides with Unprecedented [6 + 6+6 + 6] + [5 + 5] Spiro-Architecture.

Two novel polyketides, accraspiroketides A (1) and B (2), which feature unprecedented [6 + 6+6 + 6] + [5 + 5] spiro chemical architectures, were isolated from Streptomyces sp. MA37 ΔaccJ mutant strain. Compounds 1-2 exhibit excellent activity against Gram-positive bacteria (MIC = 1.5-6.3 µg/mL). Notably, 1 and 2 have superior activity against clinically isolated Enterococcus faecium K60-39 (MIC = 4.0 µg/mL and 4.7 µg/mL, respectively) than ampicillin (MIC = 25 µg/mL).

Immune checkpoint molecule Tim-3 promotes NKT cell apoptosis and predicts poorer prognosis in Sepsis.

BACKGROUND: Sepsis is a leading cause of death among critically ill patients, which is defined as life-threatening organ dysfunction caused by a deregulated host immune response to infection. Immune checkpoint molecule Tim-3 plays important and complex roles in regulating immune responses and in inducing immune tolerance. Although immune checkpoint blockade would be expected as a promising therapeutic strategy for sepsis, but the underlying mechanism remain unknown, especially under clinical conditions. METHODS: Tim-3 expression and apoptosis in NKT cells were compared in septic patients (27 patients with sepsis and 28 patients with septic shock). Phenotypic and functional characterization of Tim-3+ NKT cells were analysed, and then the relationship between Tim-3 + NKT cells and clinical prognosis were investigated in septic patients. α-lactose (Tim-3/Galectin-9 signalling inhibitor) and Tim-3 mutant mice (targeting mutation of the Tim-3 cytoplasmic domain) were utilized to evaluate the protective effect of Tim-3 signalling blockade following septic challenge. RESULTS: There is a close correlation between Tim-3 expression and the functional status of NKT cells in septic patients, Upregulated Tim-3 expression promoted NKT cell activation and apoptosis during the early stage of sepsis, and it was associated with worse disease severity and poorer prognosis in septic patients. Blockade of the Tim-3/Galectin-9 signal axis using α-lactose inhibited in vitro apoptosis of NKT cells isolated from septic patients. Impaired activity of Tim-3 protected mice following septic challenge. CONCLUSIONS: Overall, these findings demonstrated that immune checkpoint molecule Tim-3 in NKT cells plays a critical role in the immunopathogenesis of septic patients. Blockade of immune checkpoint molecule Tim-3 may be a promising immunomodulatory strategy in future clinical practice for the management of sepsis.

Identification of Genes Essential for Fluorination and Sulfamylation within the Nucleocidin Gene Clusters of Streptomyces calvus and Streptomyces virens.

The gene cluster in Streptomyces calvus associated with the biosynthesis of the fluoro- and sulfamyl-metabolite nucleocidin was interrogated by systematic gene knockouts. Out of the 26 gene deletions, most did not affect fluorometabolite production, nine abolished sulfamylation but not fluorination, and three precluded fluorination, but had no effect on sulfamylation. In addition to nucI, nucG, nucJ, nucK, nucL, nucN, nucO, nucQ and nucP, we identified two genes (nucW, nucA), belonging to a phosphoadenosine phosphosulfate (PAPS) gene cluster, as required for sulfamyl assembly. Three genes (orf(-3), orf2 and orf3) were found to be essential for fluorination, although the activities of their protein products are unknown. These genes as well as nucK, nucN, nucO and nucPNP, whose knockouts produced results differing from those described in a recent report, were also deleted in Streptomyces virens - with confirmatory outcomes. This genetic profile should inform biochemistry aimed at uncovering the enzymology behind nucleocidin biosynthesis.

DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis.

BACKGROUND AND AIMS: The mechanism underlying HCC metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro-metastatic HCC is poorly understood. APPROACH AND RESULTS: By performing RNA sequencing on nine pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and nine pairs of metastasis-free HCC (MFH) tissues, we depicted the AS landscape in HCC and found a higher frequency of AS events in EHMH compared with MFH. Moreover, 28 differentially expressed splicing regulators were identified in EHMH compared with MFH. Among these, DEAD-box RNA helicase 17 (DDX17) was significantly up-regulated in EHMH and was strongly associated with patient outcome. Functional studies indicated that DDX17 knockout inhibited the degradation of the extracellular matrix, and diminished the invasive ability of HCC cells. A significant reduction in lung metastasis induced by DDX17 deficiency was also demonstrated in a diethylnitrosamine-induced DDX17HKO mouse model. Mechanistically, high DDX17 induced intron 3 retention of PXN-AS1 and produced a transcript (termed PXN-AS1-IR3). The transcript PXN-AS1-IR3 acted as an important promoter of HCC metastasis by inducing MYC transcription activation via recruiting the complex of testis expressed 10 and p300 to the MYC enhancer region, which led to transcriptional activation of several metastasis-associated downstream genes. Finally, the PXN-AS1-IR3 level was significantly higher in serum and HCC tissues with extrahepatic metastasis. CONCLUSIONS: DDX17 and PXN-AS1-IR3 act as important metastatic promoters by modulating MYC signaling, suggesting that DDX17 and PXN-AS1-IR3 may be potential prognostic markers for metastatic HCC.

Integrated metasurface for efficient polarization conversion and high-gain, low-RCS EM radiation.

This paper presents an innovative design that combines the functionalities of a polarization convertor and an electromagnetic (EM) radiator into a single integrated metasurface. The metasurface consists of two identical metallic split-rings, a circular-shaped patch structure, a dielectric layer, and a reflective metallic ground. The polarization convertor component efficiently converts waves polarized in the x- or y-direction into cross-polarized waves within a frequency range of 8-13 GHz. It exhibits wideband resonances and achieves a high conversion efficiency. In the context of low-observable platforms, traditional high-gain antennas often suffer from a large radar cross section (RCS). To overcome this challenge, the same metasurface is utilized for EM radiation, enabling a high gain of 16.5 dBi while maintaining a low RCS. This is accomplished by strategically rotating the double-slotted metallic split-rings at 90 ∘, 180 ∘, and 270 ∘ in four distinct regions. Through this rotation, destructive interference cancellation occurs, resulting in wideband reduction of the RCS. Experimental results validate the effectiveness of the proposed metasurface in serving both applications, namely polarization conversion and EM radiation.

Patterned Nanoparticle Arrays Fabricated Using Liquid Film Rupture Self-Assembly.

Self-assembly is an important bottom-up fabrication approach based on accurate manipulation of solid-air-liquid interfaces to construct microscale structures using nanoscale materials. This approach plays a substantial role in the fabrication of microsensors, nanosensors, and actuators. Improving the controllability of self-assembly to realize large-scale regular micro/nano patterns is crucial for this approach's further development and wider applications. Herein, we propose a novel strategy for patterning nanoparticle arrays on soft substrates. This strategy is based on a unique process of liquid film rupture self-assembly that is convenient, precise, and cost-efficient for mass manufacturing. This approach involves two key steps. First, suspended liquid films comprising monolayer polystyrene (PS) spheres are realized via liquid-air interface self-assembly over prepatterned microstructures. Second, these suspended liquid films are ruptured in a controlled manner to induce the self-assembly of internal PS spheres around the morphological edges of the underlying microstructures. This nanoparticle array patterning method is comprehensively investigated in terms of the effect of the PS sphere size, morphological effect of the microstructured substrate, key factors influencing liquid film-rupture self-assembly, and optical transmittance of the fabricated samples. A maximum rupture rate of 95.4% was achieved with an optimized geometric and dimensional design. Compared with other nanoparticle-based self-assembly methods used to form patterned arrays, the proposed approach reduces the waste of nanoparticles substantially because all nanoparticles self-assemble around the prepatterned microstructures. More nanoparticles assemble to form prepatterned arrays, which could strengthen the nanoparticle array network without affecting the initial features of prepatterned microstructures.

Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm.

AIMS: The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm. METHODS AND RESULTS: This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT. CONCLUSION: Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.

Synthesis and Properties of Polyol Copolymer with Alternating Methacrylate-Vinyl Ether Backbone.

Radical polymerization of a tailored diphenylsilane-bridged bi-functional monomer consisting of methacrylate and vinyl ether moieties is conducted in diluted monomer concentration, in which both two moieties are consumed at almost the same rate despite their huge difference in monomer reactivity ratio. The vinyl ether content in the backbone is quantified as 45% by 1 H NMR after removal of the silane bridge. Since vinyl ether alone cannot be polymerized in such radical polymerization, it should be incorporated in an alternating fashion with methacrylate into the copolymer main chain. The cleavage of silane bridge also yields a series of polyol materials composed of ethylene glycol monovinyl ether (EGVE) and hydroxyethyl methacrylate (HEMA), and the EGVE content in the backbone can be regulated from 45% to 18% by increasing the bi-functional monomer concentration. Interestingly, although containing more than 50% HEMA units, the alternating copolymer exhibits new properties totally different from poly(HEMA), but more similar to poly(EGVE), e.g., good water solubility and a markedly low glass transition temperature (Tg ) of -31 °C, which is attributed to the major HEMA-EGVE repeating unit that replaced HEMA-HEMA consecutive segments so that the properties of poly(HEMA) such as 95 °C Tg are completely altered.

3'-O-ß-Glucosyl-4',5'-didehydro-5'-deoxyadenosine Is a Natural Product of the Nucleocidin Producers Streptomyces virens and Streptomyces calvus.

3'-O-ß-Glucosyl-4',5'-didehydro-5'-deoxyadenosine 13 is identified as a natural product of Streptomyces calvus and Streptomyces virens. It is also generated in vitro by direct ß-glucosylation of 4',5'-didehydro-5'-deoxyadenosine 12 with the enzyme NucGT. The intact incorporation of oxygen-18 and deuterium isotopes from (±)[1-18O,1-2H2]-glycerol 14 into C-5' of nucleocidin 1 and its related metabolites precludes 3'-O-ß-glucosyl-4',5'-didehydro-5'-deoxyadenosine 13 as a biosynthetic precursor to nucleocidin 1.

Sinomenine ameliorates collagen-induced arthritis in mice by targeting GBP5 and regulating the P2X7 receptor to suppress NLRP3-related signaling pathways.

Sinomenine (SIN) is an isoquinoline alkaloid isolated from Sinomenii Caulis, a traditional Chinese medicine used to treat rheumatoid arthritis (RA). Clinical trials have shown that SIN has comparable efficacy to methotrexate in treating patients with RA but with fewer adverse effects. In this study, we explored the anti-inflammatory effects and therapeutic targets of SIN in LPS-induced RAW264.7 cells and in collagen-induced arthritis (CIA) mice. LPS-induced RAW264.7 cells were pretreated with SIN (160, 320, 640 µM); and CIA mice were administered SIN (25, 50 and 100 mg·kg-1·d-1, i.p.) for 30 days. We first conducted a solvent-induced protein precipitation (SIP) assay in LPS-stimulated RAW264.7 cells and found positive evidence for the direct binding of SIN to guanylate-binding protein 5 (GBP5), which was supported by molecular simulation docking, proteomics, and binding affinity assays (KD = 3.486 µM). More importantly, SIN treatment markedly decreased the expression levels of proteins involved in the GBP5/P2X7R-NLRP3 pathways in both LPS-induced RAW264.7 cells and the paw tissue of CIA mice. Moreover, the levels of IL-1ß, IL-18, IL-6, and TNF-α in both the supernatant of inflammatory cells and the serum of CIA mice were significantly reduced. This study illustrates a novel anti-inflammatory mechanism of SIN; SIN suppresses the activity of NLRP3-related pathways by competitively binding GBP5 and downregulating P2X7R protein expression, which ultimately contributes to the reduction of IL-1ß and IL-18 production. The binding specificity of SIN to GBP5 and its inhibitory effect on GBP5 activity suggest that SIN has great potential as a specific GBP5 antagonist.

Prevalence of chronic periodontitis in patients undergoing peritoneal dialysis and its correlation with peritoneal dialysis-related complications.

OBJECTIVE: The microinflammatory state can influence the occurrence of dialysis-related complications in dialysis patients. Chronic periodontitis (CP), in which plaque biofilm is considered to be the initiating factor, is a chronic infectious disease in the oral cavity. It is still uncertain whether CP affects the microinflammatory state in peritoneal dialysis (PD) and the occurrence of dialysis-related complications. The purpose of this study was to investigate the correlation between the periodontal index and clinical parameters in peritoneal dialysis patients with CP and dialysis-related complications, including peritoneal dialysis-associated peritonitis (PDAP) and cardiovascular and cerebrovascular events (CCEs). METHODS: This was a retrospective cohort study, and 76 patients undergoing PD were enrolled. Clinical parameters, the occurrence of PD-related complications and periodontitis-related indicators, including the gingival index (GI), plaque index (PLI), probing depth (PPD) and clinical attachment loss (CAL), were collected. Correlation analysis was used to explore the correlation between periodontal or clinical parameters and the occurrence of PD-related complications. RESULTS: All the patients had different degrees of periodontitis (mild 9.2%, moderate 72.4%, severe 18.4%); PPD was inversely related to serum albumin (r = - 0.235, p = 0.041); CAL has a positive correlation with serum C-reactive protein (rs = 0.242, p = 0.035); PLI was positively correlated with serum calcium (r = 0.314, p = 0.006). ANOVA, multivariate logistic regression analysis and Kaplan-Meier Survival curve suggested that CAL was a risk factor for the occurrence of PDAP. There was no correlation between periodontal parameters and CCEs or poor prognosis. CONCLUSION: CP is universally present in PD patients, and the presentation of periodontitis influences the systemic inflammatory state in PD patients. CP is a risk factor for PDAP.

Association of adiposity with risk of obstructive sleep apnea: a population-based study.

BACKGROUND: Obesity is a crucial risk factor for obstructive sleep apnea (OSA), but the association between adiposity deposition and OSA risk has not reached a consistent conclusion. This study sought to reveal the association of multiple adiposity indicators with OSA risk. METHODS: This cross-sectional study included 9,733 participants aged 35-74 years, recruited from an ongoing population-based cohort. OSA was assessed by the Berlin Questionnaire. Six adiposity indicators, including neck circumference (NC), body fat percentage (BF%), waist-to-hip ratio (WHR), visceral adiposity index (VAI), lipid accumulation product (LAP), and resting metabolic rate (RMR), were selected. Multivariate logistic regression models were used to examine the association of adiposity indicators with OSA risk. RESULTS: One thousand six hundred twenty-six participants (16.71%) were classified into the OSA group. NC, BF%, WHR, VAI, LAP, and RMR were all positively associated with the risk of OSA after adjusting for confounders, regardless of age, sex, and history of dyslipidemia. Every 1-unit increment of NC, BF%, and VAI was associated with a 13%, 9%, and 14% increased risk of OSA, respectively; every 0.01-unit increment of WHR was associated with a 3% increased risk of OSA; every 10-unit increment of LAP and RMR was associated with 2% and 4% increased risk of OSA, respectively. CONCLUSIONS: NC, BF%, WHR, VAI, LAP, and RMR were all independently and positively associated with OSA risk, regardless of age, sex, history of dyslipidemia, and menopausal status. Application of these new indicators could help to more comprehensively reflect and predict the risk of OSA in the general population.

Chemoenzymatic Synthesis of Indole-Containing Acyloin Derivatives.

Indole-containing acyloins are either key intermediates of many antimicrobial/antiviral natural products or building blocks in the synthesis of biologically active molecules. As such, access to structurally diverse indole-containing acyloins has attracted considerable attention. In this report, we present a pilot study of using biotransformation to provide acyloins that contain various indole substituents. The biotransformation system contains the tryptophan synthase standalone ß-subunit variant, PfTrpB6, generated from directed evolution in the literature; a commercially available L-amino acid oxidase (LAAO); and the thiamine-diphosphate (ThDP)-dependent enzyme NzsH, encoded in the biosynthetic gene cluster (nzs) of the bacterial carbazole alkaloid natural product named neocarazostatin A. The utilization of the first two enzymes, the PfTrpB variant and LAAO, is designed to provide structurally diverse indole 3-pyruvate derivatives as donor substrates for NzsH-catalysed biotransformation to provide acyloin derivatives. Our results demonstrate that NzsH displays a considerable substrate profile toward donor substrates for production of acyloins with different indole ring systems, suggesting that NzsH could be further explored as a potential biocatalyst via directed evolution to improve the catalytic efficiency in the future.

Novel lipid indicators and the risk of type 2 diabetes mellitus among Chinese hypertensive patients: findings from the Guangzhou Heart Study.

BACKGROUND: Data are limited on whether several easily measured indices are independent predictors of type 2 diabetes mellitus (T2DM) in hypertensive patients. This study aimed to assess the association of hypertriglyceridemic-waist phenotype, triglyceride glucose (TyG) index, lipid accumulation product (LAP), and visceral adiposity index (VAI) with T2DM risk in hypertensive patients. METHODS: This cross-sectional study included 5321 hypertensive patients from the baseline survey of the Guangzhou Heart Study. Face-to-face questionnaire survey, physical examination, and fasting blood sample collection were completed for all subjects. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated by using the logistic regression model. The potential nonlinear relationship was examined using restricted cubic spline regression. RESULTS: The prevalence of T2DM was 19.98% among hypertensive patients. After adjusting for confounders, participants with elevated triglyceride levels and enlarged waist circumference (HTGW) were associated with a 2.57-fold risk of T2DM (OR 2.57, 95% CI 2.05, 3.23). When comparing with subjects within the lowest quartile of the indices, those in the highest quartile of TyG, LAP, and VAI were associated with 5.35-fold (95% CI 4.33, 6.64), 2.65-fold (95% CI 2.11, 3.34), and 2.17-fold (95% CI 1.77, 2.67) risk of T2DM after adjusting for confounders. Every 1-unit increment of TyG, LAP, and VAI was associated with 81%, 38%, and 31% increased risk of T2DM, respectively. The nonlinear association was observed for TyG, LAP, and VAI (all P Non-linear < 0.001). CONCLUSIONS: The results found that among hypertensive patients, HTGW and a higher level of TyG, LAP, and VAI were associated with an elevated risk of T2DM. The findings suggested that HTGW, TyG, LAP, and VAI may serve as simple and effective tools for T2DM risk assessment in the prevention and management of main chronic diseases.