A crystalline doubly oxidized carbene.

The chemistry of carbon is governed by the octet rule, which refers to its tendency to have eight electrons in its valence shell. However, a few exceptions do exist, for example, the trityl radical (Ph3C∙) (ref. 1) and carbocation (Ph3C+) (ref. 2) with seven and six valence electrons, respectively, and carbenes (R2C:)-two-coordinate octet-defying species with formally six valence electrons3. Carbenes are now powerful tools in chemistry, and have even found applications in material and medicinal sciences4. Can we undress the carbene further by removing its non-bonding electrons? Here we describe the synthesis of a crystalline doubly oxidized carbene (R2C2+), through a two-electron oxidation/oxide-ion abstraction sequence from an electron-rich carbene5. Despite a cumulenic structure and strong delocalization of the positive charges, the dicoordinate carbon centre maintains significant electrophilicity, and possesses two accessible vacant orbitals. A two-electron reduction/deprotonation sequence regenerates the parent carbene, fully consistent with its description as a doubly oxidized carbene. This work demonstrates that the use of bulky strong electron-donor substituents can simultaneously impart electronic stabilization and steric protection to both vacant orbitals on the central carbon atom, paving the way for the isolation of a variety of doubly oxidized carbenes.

A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity.

14-3-3 proteins regulate biological processes by binding to phosphorylated serine or phosphorylated threonine motifs of cellular proteins. Among the 14-3-3 proteins, 14-3-3ɛ serves a crucial function in antiviral immunity by mediating the cytosol-to-mitochondrial membrane translocation of the pathogen sensor RIG-I. Here we found that the NS3 protein of dengue virus (DV) bound to 14-3-3ɛ and prevented translocation of RIG-I to the adaptor MAVS and thereby blocked antiviral signaling. Intriguingly, a highly conserved phosphomimetic RxEP motif in NS3 was essential for the binding of 14-3-3ɛ. A recombinant mutant DV deficient in binding to 14-3-3ɛ showed impairment in antagonism of RIG-I and elicited a markedly augmented innate immune response and enhanced T cell activation. Our work reveals a novel phosphomimetic-based mechanism for viral antagonism of 14-3-3-mediated immunity, which might guide the rational design of therapeutics.

VISTA is an acidic pH-selective ligand for PSGL-1.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer1,2. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies3. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement.

Multi-object distance determination by analysis of CoC variation for dynamic structured light.

A multi-object distance determination method can be achieved by 932 nm structured light with one camera as the data receiver. The structured light generated by a liquid crystal on silicon spatial light modulator (LCoS-SLM) facilitates dynamic image projection on targets. A series of moving light strip images were captured and collected for data analysis. This method lifted the limitation of single-object distance determination and the limitation of the angle requirement between the camera and the light source in the triangulation method. The average error of this method was approximately 3% in the range of 700 mm to 1900 mm away from LCoS-SLM without further optimization. It provides a potential compact design for indoor multi-object distance determination in the future.

An Air-Stable "Masked" Bis(imino)carbene: A Carbon-Based Dual Ambiphile.

Carbenes, once considered laboratory curiosities, now serve as powerful tools in the chemical and material sciences. To date, all stable singlet carbenes are single-site ambiphiles. Here we describe the synthesis of a carbene which is a carbon-based dual ambiphile (both single-site and dual-site). The key is to employ imino substituents derived from a cyclic (alkyl)(amino)carbene (CAAC), which imparts a 1,3-dipolar character to the carbene. Its dual ambiphilic nature is consistent with the ability to activate simple organic molecules in both 1,1- and 1,3-fashion. Furthermore, its 1,3-ambiphilicity facilitates an unprecedented reversible intramolecular dearomative [3 + 2] cycloaddition with a proximal arene substituent, giving the carbene the ability to "mask" itself as an air-stable cycloadduct. We perceive that the concept of dual ambiphilicity opens a new dimension for future carbene chemistry, expanding the repertoire of applications beyond that known for classical single-site ambiphilic carbenes.

Matrix metalloproteinase-9 regulates afferent arteriolar remodeling and function in hypertension-induced kidney disease.

This study tested if matrix metalloproteinase (MMP)-9 promoted microvascular pathology that initiates hypertensive (HT) kidney disease in salt-sensitive (SS) Dahl rats. SS rats lacking Mmp9 (Mmp9-/-) and littermate control SS rats were studied after one week on a normotensive 0.3% sodium chloride (Pre-HT SS and Pre-HT Mmp9-/-) or a hypertension-inducing diet containing 4.0% sodium chloride (HT SS and HT Mmp9-/-). Telemetry-monitored blood pressure of both the HT SS and HT Mmp9-/- rats increased and did not differ. Kidney microvessel transforming growth factor-beta 1 (Tgfb1) mRNA did not differ between Pre-HT SS and Pre-HT Mmp9-/- rats, but with hypertension and expression of Mmp9 and Tgfb1 increased in HT SS rats, along with phospho-Smad2 labeling of nuclei of vascular smooth muscle cells, and with peri-arteriolar fibronectin deposition. Loss of MMP-9 prevented hypertension-induced phenotypic transformation of microvascular smooth muscle cells and the expected increased microvascular expression of pro-inflammatory molecules. Loss of MMP-9 in vascular smooth muscle cells in vitro prevented cyclic strain-induced production of active TGF-ß1 and phospho-Smad2/3 stimulation. Afferent arteriolar autoregulation was impaired in HT SS rats but not in HT Mmp9-/- rats or the HT SS rats treated with doxycycline, an MMP inhibitor. HT SS but not HT Mmp9-/- rats showed decreased glomerular Wilms Tumor 1 protein-positive cells (a marker of podocytes) along with increased urinary podocin and nephrin mRNA excretion, all indicative of glomerular damage. Thus, our findings support an active role for MMP-9 in a hypertension-induced kidney microvascular remodeling process that promotes glomerular epithelial cell injury in SS rats.

A machine learning framework develops a DNA replication stress model for predicting clinical outcomes and therapeutic vulnerability in primary prostate cancer.

Recent studies have identified DNA replication stress as an important feature of advanced prostate cancer (PCa). The identification of biomarkers for DNA replication stress could therefore facilitate risk stratification and help inform treatment options for PCa. Here, we designed a robust machine learning-based framework to comprehensively explore the impact of DNA replication stress on prognosis and treatment in 5 PCa bulk transcriptomic cohorts with a total of 905 patients. Bootstrap resampling-based univariate Cox regression and Boruta algorithm were applied to select a subset of DNA replication stress genes that were more clinically relevant. Next, we benchmarked 7 survival-related machine-learning algorithms for PCa recurrence using nested cross-validation. Multi-omic and drug sensitivity data were also utilized to characterize PCa with various DNA replication stress. We found that the hyperparameter-tuned eXtreme Gradient Boosting model outperformed other tuned models and was therefore used to establish a robust replication stress signature (RSS). RSS demonstrated superior performance over most clinical features and other PCa signatures in predicting PCa recurrence across cohorts. Lower RSS was characterized by enriched metabolism pathways, high androgen activity, and a favorable prognosis. In contrast, higher RSS was significantly associated with TP53, RB1, and PTEN deletion, exhibited increased proliferation and DNA replication stress, and was more immune-suppressive with a higher chance of immunotherapy response. In silico screening identified 13 potential targets (e.g. TOP2A, CDK9, and RRM2) from 2249 druggable targets, and 2 therapeutic agents (irinotecan and topotecan) for RSS-high patients. Additionally, RSS-high patients were more responsive to taxane-based chemotherapy and Poly (ADP-ribose) polymerase inhibitors, whereas RSS-low patients were more sensitive to androgen deprivation therapy. In conclusion, a robust machine-learning framework was used to reveal the great potential of RSS for personalized risk stratification and therapeutic implications in PCa.

The herpesvirus accessory protein γ134.5 facilitates viral replication by disabling mitochondrial translocation of RIG-I.

RIG-I and MDA5 are cytoplasmic RNA sensors that mediate cell intrinsic immunity against viral pathogens. While it has been well-established that RIG-I and MDA5 recognize RNA viruses, their interactive network with DNA viruses, including herpes simplex virus 1 (HSV-1), remains less clear. Using a combination of RNA-deep sequencing and genetic studies, we show that the γ134.5 gene product, a virus-encoded virulence factor, enables HSV growth by neutralization of RIG-I dependent restriction. When expressed in mammalian cells, HSV-1 γ134.5 targets RIG-I, which cripples cytosolic RNA sensing and subsequently suppresses antiviral gene expression. Rather than inhibition of RIG-I K63-linked ubiquitination, the γ134.5 protein precludes the assembly of RIG-I and cellular chaperone 14-3-3ε into an active complex for mitochondrial translocation. The γ134.5-mediated inhibition of RIG-I-14-3-3ε binding abrogates the access of RIG-I to mitochondrial antiviral-signaling protein (MAVS) and activation of interferon regulatory factor 3. As such, unlike wild type virus HSV-1, a recombinant HSV-1 in which γ134.5 is deleted elicits efficient cytokine induction and replicates poorly, while genetic ablation of RIG-I expression, but not of MDA5 expression, rescues viral growth. Collectively, these findings suggest that viral suppression of cytosolic RNA sensing is a key determinant in the evolutionary arms race of a large DNA virus and its host.

A Study of Two Novel Techniques for One-stage Closure of Chronic Oroantral Fistula and Sinus Floor Lift.

PURPOSE: This study aimed to compare two novel techniques for chronic oroantral fistula (OAF) closure combined with maxillary sinus floor elevation. MATERIALS AND METHODS: Ten patients who had implant installation needs but suffered from a chronic OAF were enrolled in the study from January 2016 to June 2021. The technique applied involved OAF closure and simultaneous sinus floor elevation by either a transalveolar or lateral window approach. Bone graft material evaluation results, postoperative clinical symptoms and complications were compared between the two groups. Student's t -test and χ 2 test were used to analyze the results. RESULTS: In this study, 5 patients with a chronic OAF were treated with the transalveolar approach (group I), and 5 were treated with the lateral window approach (group II). The alveolar bone height was significantly higher in group II than in group I ( P ＜0.001). The pain at 1 day ( P =0.018) and 3 days ( P =0.029) postoperatively and facial swelling at 7 days ( P =0.016) postoperatively were obviously greater in group II than in group I. There were no severe complications in either group. CONCLUSIONS: The techniques combined OAF closure with sinus lifting to reduce surgical frequency and risks. The transalveolar approach resulted in milder postoperative reactions, but the lateral approach could provide more bone volume.

Objective Assessment of Visual Field Defects Caused by Optic Chiasm and Its Posterior Visual Pathway Injury.

OBJECTIVES: To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. METHODS: Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential (VEP) and multifocal visual evolved potential (mfVEP) measurements, craniocerebral CT/MRI, and retinal optical coherence tomography (OCT) were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. RESULTS: The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder (RAPD) and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. CONCLUSIONS: Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

Laser ultrasonic improvement and its application in defect detection based on the composite coating method.

Herein, we studied the increasing tendency of photoacoustic (PA) conversion efficiency of the Au/polydimethylsiloxane (PDMS) composite. The thickness of the Au layer was optimized by modeling the PA process based on the Drude-Lorentz model and finite element analysis method, and corresponding results were verified. The results showed that the optimal Au thickness of the Au/PDMS composite was 35 nm. Finally, the Au/PDMS composites were coated onto the surface of aluminum alloys, which improved the thermoelastic laser ultrasonic (LU) signals to near 100 times. Besides, the defect mapping was performed by thermoelastic LU signals with Au/PDMS coating and ablation LU signals without coating; the Pearson correlation coefficient was higher than 0.95. The application in the defect detection in metal could provide guides for nondestructive detection on metals by laser ultrasound.

[Fibroblast growth factor 21 plays a protective role in cardiovascular diseases by inducing autophagy].

Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.

Comparison of various insulin resistance surrogates on prognostic prediction and stratification following percutaneous coronary intervention in patients with and without type 2 diabetes mellitus.

BACKGROUND: Insulin resistance (IR), evaluation of which is difficult and complex, is closely associated with cardiovascular disease. Recently, various IR surrogates have been proposed and proved to be highly correlated with IR assessed by the gold standard. It remains indistinct whether different IR surrogates perform equivalently on prognostic prediction and stratification following percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with and without type 2 diabetes mellitus (T2DM). METHODS: The present study recruited patients who were diagnosed with NSTE-ACS and successfully underwent PCI. IR surrogates evaluated in the current study included triglyceride-glucose (TyG) index, visceral adiposity index, Chinese visceral adiposity index, lipid accumulation product, and triglyceride-to-high density lipoprotein cholesterol ratio, calculations of which were conformed to previous studies. The observational endpoint was defined as the major adverse cardiovascular and cerebrovascular events (MACCE), including cardiac death, non-fatal myocardial infarction, and non-fatal ischemic stroke. RESULTS: 2107 patients (60.02 ± 9.03 years, 28.0% female) were ultimately enrolled in the present study. A total of 187 (8.9%) MACCEs were documented during the 24-month follow-up. Despite regarding the lower median as reference [hazard ratio (HR) 3.805, 95% confidence interval (CI) 2.581-5.608, P < 0.001] or evaluating 1 normalized unit increase (HR 1.847, 95% CI 1.564-2.181, P < 0.001), the TyG index remained the strongest risk predictor for MACCE, independent of confounding factors. The TyG index showed the most powerful diagnostic value for MACCE with the highest area under the receiver operating characteristic curve of 0.715. The addition of the TyG index, compared with other IR surrogates, exhibited the maximum enhancement on risk stratification for MACCE on the basis of a baseline model (Harrell's C-index: 0.708 for baseline model vs. 0.758 for baseline model + TyG index, P < 0.001; continuous net reclassification improvement: 0.255, P < 0.001; integrated discrimination improvement: 0.033, P < 0.001). The results were consistent in subgroup analysis where similar analyses were performed in patients with and without T2DM, respectively. CONCLUSION: The TyG index, which is most strongly associated with the risk of MACCE, can be served as the most valuable IR surrogate for risk prediction and stratification in NSTE-ACS patients receiving PCI, with and without T2DM.

Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A.

It is estimated that more than 170 million people are infected with hepatitis C virus (HCV) worldwide. Clinical trials have demonstrated that, for the first time in human history, the potential exists to eradicate a chronic viral disease using combination therapies that contain only direct-acting antiviral agents. HCV non-structural protein 5A (NS5A) is a multifunctional protein required for several stages of the virus replication cycle. NS5A replication complex inhibitors, exemplified by daclatasvir (DCV; also known as BMS-790052 and Daklinza), belong to the most potent class of direct-acting anti-HCV agents described so far, with in vitro activity in the picomolar (pM) to low nanomolar (nM) range. The potency observed in vitro has translated into clinical efficacy, with HCV RNA declining by ~3-4 log10 in infected patients after administration of single oral doses of DCV. Understanding the exceptional potency of DCV was a key objective of this study. Here we show that although DCV and an NS5A inhibitor analogue (Syn-395) are inactive against certain NS5A resistance variants, combinations of the pair enhance DCV potency by >1,000-fold, restoring activity to the pM range. This synergistic effect was validated in vivo using an HCV-infected chimaeric mouse model. The cooperative interaction of a pair of compounds suggests that NS5A protein molecules communicate with each other: one inhibitor binds to resistant NS5A, causing a conformational change that is transmitted to adjacent NS5As, resensitizing resistant NS5A so that the second inhibitor can act to restore inhibition. This unprecedented synergistic anti-HCV activity also enhances the resistance barrier of DCV, providing additional options for HCV combination therapy and new insight into the role of NS5A in the HCV replication cycle.

In vitro effects of velvet antler water extracts from Formosan Sambar deer and red deer on barrier integrity in Caco-2 cell.

Background: The mucus integrity and abnormal inflammatory response are the crucial biomarker of inflammatory bowel disease (IBD). Velvet antler (VA) has been used as traditional Chinese medicines for many years. Anti-inflammatory property was demonstrated via suppression of cyclooxygenase-2 and cytokines protein expression. And it has further proved to promote wound healing in streptozotocin-induced diabetic rats model. The aforementioned functionalities of VA extracts may be associated with the treatment of IBD. Thus, the aim of present study was to evaluate the effect of velvet antler water extracts form Formosan Sambar deer (Rusa unicolor swinhoei, SVAE) and red deer (Cervus elaphus, RVAE) on the barrier function and to investigate the possible mechanism using in vitro model. Methods: Human colonic epithelial cell models (Caco-2) were co-cultured with various concentrations of both SVAE and RVAE (250-500 µg mL-1) in dextran sulfate sodium (DSS)-induced colitis model. Trans-epithelial electrical resistance (TEER) value and the macromolecule permeability of Fluorescein isothiocyanate (FITC)-labeled dextran were measured to evaluate the integrity of monolayer of Caco-2. Western blotting was performed for analysis of protein expressions of occludin, Zonula occludens-1 (ZO-1), claudin-1, claudin-2 and myosin light chain kinase (MLCK). The cytotoxicity was conducted by MTT assay. Results: Results indicated that both SVAE and RVAE could enhance integrity of monolayer in dextran sulfate sodium (DSS)-induced colonic epithelial cell model (Caco-2) through reducing the decline of trans-epithelial electrical resistance (TEER) and macromolecule permeability at the concentration of 250 µg mL-1. RVAE significantly increased the expression of tight junction proteins (occludin and ZO-1) while SVAE significantly reduced the activity of MLCK (P < 0.05.). Elevated C-C chemokine ligand 20 (CCL20) production suggested that both SVAE and RVAE could enhance the repair of epithelial cell. Besides, MTT assay revealed that both extracts showed no cytotoxicity. Conclusion: Thus, SVAE and RVAE supplementation may attenuate barrier damage by enhancing the occludin and ZO-1 protein expression, decreasing MLCK expression, promoting the CCL20 production. In the future, animal study is needed for further confirmation.

Correction: Mendelian and Non-Mendelian Regulation of Gene Expression in Maize.

[This corrects the article DOI: 10.1371/journal.pgen.1003202.].

Acid-Base Free Main Group Carbonyl Analogues.

Main group carbonyl analogues (R2 E=O) derived from p-block elements (E=groups 13 to 15) have long been considered as elusive species. Previously, employment of chemical tricks such as acid- and base-stabilization protocols granted access to these transient species in their masked forms. However, electronic and steric effects inevitably perturb their chemical reactivity and distinguish them from classical carbonyl compounds. A new era was marked by the recent isolation of acid-base free main group carbonyl analogues, ranging from a lighter boracarbonyl to the heavier silacarbonyls, phosphacarbonyls and a germacarbonyl. Most importantly, their unperturbed nature elicits exciting new chemistry, spanning the vista from classical organic carbonyl-type reactions to transition metal-like oxide ion transfer chemistry. In this Review, we survey the strategies used for the isolation of such systems and document their emerging reactivity profiles, with a view to providing fundamental comparisons both with carbon and transition metal oxo species. This highlights the emerging opportunities for exciting "crossover" reactivity offered by these derivatives of the p-block elements.

Impacts of triglyceride-glucose index on prognosis of patients with type 2 diabetes mellitus and non-ST-segment elevation acute coronary syndrome: results from an observational cohort study in China.

BACKGROUND: The relationship between triglyceride-glucose index (TyG index) and the prevalence and prognosis of cardiovascular disease has been confirmed by former studies. However, it remains uncertain whether TyG index has a prognostic impact in patients with type 2 diabetes mellitus (T2DM) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS: The study retrospectively enrolled 798 patients (mean age: 60.9 ± 8.3 years; 68.3% men) with T2DM and NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. TyG index was calculated as previously reported: ln [fasting TGs (mg/dL) * FBG (mg/dL)/2]. The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and ischemia-driven revascularization. RESULTS: TyG index was significantly higher in patients with a primary endpoint event compared with those without. Multivariate Cox proportional hazards analysis showed that 1-unit increase of TyG index was independently associated with higher risk of primary endpoint, independent of other risk factors [hazard ratio (HR) 3.208 per 1-unit increase, 95% confidence interval (CI) 2.400-4.289, P < 0.001]. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for adverse prognosis [AUC: baseline risk model, 0.800 vs. baseline risk model + TyG index, 0.856, P for comparison < 0.001; category-free net reclassification improvement (NRI) 0.346, P < 0.001; integrated discrimination improvement (IDI) 0.087, P < 0.001]. CONCLUSIONS: Increased TyG index is a significant predictor of adverse prognosis in patients with T2DM and NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether interventions for TyG index have a positive impact on improving clinical prognosis.

Impacts of geriatric nutritional risk index on prognosis of patients with non-ST-segment elevation acute coronary syndrome: Results from an observational cohort study in China.

BACKGROUND AND AIMS: It is recognized that malnutrition increases risk of worse prognosis in patients with various diseases. The present study investigated if poor nutritional status predicts adverse outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study enrolled 2299 patients (mean age: 60.01 ± 8.95 years; 71.8% male) with NSTE-ACS who underwent PCI at Beijing Anzhen Hospital from January to December 2015. The entire cohort was divided into training set (n = 1519) and testing set (n = 780) at a ratio of approximate 2 : 1. Nutritional status was assessed by geriatric nutritional risk index (GNRI). The primary endpoint was a composite of adverse events as follows: all-cause death, non-fatal myocardial infarction (MI) and any revascularization. Multivariate Cox analysis showed that GNRI significantly associated with primary endpoint, independent of other risk factors [hazard ratio (HR) 1.159 per 1-point decrease of GNRI, 95% confidence interval (CI) 1.130-1.189, p < 0.001]. The addition of GNRI to a baseline model had an incremental effect on the predictive value for adverse prognosis in training set [AUC: from 0.821 to 0.873, p < 0.001; category-free net reclassification improvement (NRI): 0.313, p < 0.001; integrated discrimination improvement (IDI): 0.108, p < 0.001]. The incremental effect of GNRI was further validated and confirmed in testing set. CONCLUSION: Lower GNRI is a significant predictor of adverse prognosis in patients with NSTE-ACS undergoing PCI. Further studies need to be performed to determine whether nutritional interventions have a positive impact on improving clinical prognosis.