TMED10 mediates the trafficking of insulin-like growth factor 2 along the secretory pathway for myoblast differentiation.

The insulin-like growth factor 2 (IGF2) plays critical roles in cell proliferation, migration, differentiation, and survival. Despite its importance, the molecular mechanisms mediating the trafficking of IGF2 along the secretory pathway remain unclear. Here, we utilized a Retention Using Selective Hook system to analyze molecular mechanisms that regulate the secretion of IGF2. We found that a type I transmembrane protein, TMED10, is essential for the secretion of IGF2 and for differentiation of mouse myoblast C2C12 cells. Further analyses indicate that the residues 112-140 in IGF2 are important for the secretion of IGF2 and these residues directly interact with the GOLD domain of TMED10. We then reconstituted the release of IGF2 into COPII vesicles. This assay suggests that TMED10 mediates the packaging of IGF2 into COPII vesicles to be efficiently delivered to the Golgi. Moreover, TMED10 also mediates ER export of TGN-localized cargo receptor, sortilin, which subsequently mediates TGN export of IGF2. These analyses indicate that TMED10 is critical for IGF2 secretion by directly regulating ER export and indirectly regulating TGN export of IGF2, providing insights into trafficking of IGF2 for myoblast differentiation.

Solvation Effect: The Cornerstone of High-Performance Battery Design for Commercialization-Driven Sodium Batteries.

Sodium batteries (SBs) emerge as a potential candidate for large-scale energy storage and have become a hot topic in the past few decades. In the previous researches on electrolyte, designing electrolytes with the solvation theory has been the most promising direction is to improve the electrochemical performance of batteries through solvation theory. In general, the four essential factors for the commercial application of SBs, which are cost, low temperature performance, fast charge performance and safety. The solvent structure has significant impact on commercial applications. But so far, the solvation design of electrolyte and the practical application of sodium batteries have not been comprehensively summarized. This review first clarifies the process of Na+ solvation and the strategies for adjusting Na+ solvation. It is worth noting that the relationship between solvation theory and interface theory is pointed out. The cost, low temperature, fast charging, and safety issues of solvation are systematically summarized. The importance of the de-solvation step in low temperature and fast charging application is emphasized to help select better electrolytes for specific applications. Finally, new insights and potential solutions for electrolytes solvation related to SBs are proposed to stimulate revolutionary electrolyte chemistry for next generation SBs.

Oxygen Vacancies Driven by Co in the Deeply Charged State Inducing Intragranular Cracking of Ni-Rich Cathodes.

Intragranular cracking within the material structure of Ni-rich (LiNixCoyMn1 - x - y, x ≥0.9) cathodes greatly threatens cathode integrity and causes capacity degradation, yet its atomic-scale incubation mechanism is not completely elucidated. Notably, the physicochemical properties of component elements fundamentally determine the material structure of cathodes. Herein, a diffusion-controlled incubation mechanism of intragranular cracking is unraveled, and an underlying correlation model with Co element is established. Multi-dimensional analysis reveals that oxygen vacancies appear due to the charge compensation from highly oxidizing Co ions in the deeply charged state, driving the transition metal migration to Li layer and layered to rock-salt phase transition. The local accumulation of two accompanying tensile strains collaborates to promote the nucleation and growth of intragranular cracks along the fragile rock-salt phase domain on (003) plane. This study focuses on the potential risks posed by Co to the architectural and thermal stability of Ni-rich cathodes and is dedicated to the compositional design and performance optimization of Ni-rich cathodes.

Association between the triglyceride-glucose index and impaired cardiovascular fitness in non-diabetic young population.

BACKGROUND: The triglyceride-glucose (TyG) index has been linked to the onset, progression, and prognosis of cardiovascular disease (CVD) in middle-aged and elderly individuals. Nevertheless, the relationship between the TyG index and impaired cardiovascular fitness (CVF) remains unexplored in non-diabetic young population. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) study (1999-2004) to conduct a cross-sectional study of 3364 participants who completed an examination of CVF. Impaired CVF was defined as low and moderate CVF levels determined by estimated maximal oxygen consumption (Vo2max), based on sex- and age-specific criteria. The TyG index was calculated by [Formula: see text]. RESULTS: The age (median with interquartile range) of the study population was 28 (19-37) years, and the TyG index (median ± standard deviation) was 8.36 ± 0.52. A significant association between the TyG index and impaired CVF was found in multivariable logistical regression analysis (per 1-unit increase in the TyG index: OR, 1.46; 95% Cl 1.13-1.90). A dose‒response relationship between the TyG index and impaired CVF was presented by restricted cubic splines (RCS). A significant interaction (p = 0.027) between sex and the TyG index for impaired CVF was found in the population aged < 20 years. CONCLUSIONS: In non-diabetic young population, individuals with higher TyG index values are at an increased likelihood of encountering impaired CVF. Furthermore, sex may exert an impact on CVF, as males tend to be more susceptible to impaired CVF under comparable TyG index conditions.

Synthesizing high performance LNMO cathode materials with porous structure by manipulating reynolds number in a microreactor.

The demand for Lithium-ion batteries (LIBs) has significantly grown in the last decade due to their extensive use electric vehicles. To further advance the commercialization of LIBs for various applications, there is a pressing need to develop electrode materials with enhanced performance. The porous microsphere morphology LiNixMn2-xO4(LNMO) is considered to be an effective material with both high energy density and excellent rate performance. Nevertheless, LNMO synthesis technology still has problem such as long reaction time, high energy consumption and environmental pollution. Herein, LNMO microsphere was successfully synthesized with short precursors reaction time (18 s) at 40 °C without using chelating agent by microreaction technology combined solid-state lithiation. The optimized LNMO cathode shows microsphere (∼8µm) morphology stacked by nano primary particles, with abundant mesoporous and fully exposed low-energy plane. The electrochemical analysis indicates that the optimized LNMO cathode demonstrates 97.33% capacity retention even after 200 cycles at 1C. Additionally, the material shows a highly satisfactory discharge capacity of 92.3 mAh·g-1at 10C. Overall, microreaction technology is anticipated to offer a novel approach in the synthesis of LNMO cathode materials with excellent performance.

Paxbp1 controls a key checkpoint for cell growth and survival during early activation of quiescent muscle satellite cells.

Adult mouse muscle satellite cells (MuSCs) are quiescent in uninjured muscles. Upon muscle injury, MuSCs exit quiescence, reenter the cell cycle to proliferate and self-renew, and then differentiate and fuse to drive muscle regeneration. However, it remains poorly understood how MuSCs transition from quiescence to the cycling state. Here, we report that Pax3 and Pax7 binding protein 1 (Paxbp1) controls a key checkpoint during this critical transition. Deletion of Paxbp1 in adult MuSCs prevented them from reentering the cell cycle upon injury, resulting in a total regeneration failure. Mechanistically, we found an abnormal elevation of reactive oxygen species (ROS) in Paxbp1-null MuSCs, which induced p53 activation and impaired mTORC1 signaling, leading to defective cell growth, apoptosis, and failure in S-phase reentry. Deliberate ROS reduction partially rescued the cell-cycle reentry defect in mutant MuSCs. Our study reveals that Paxbp1 regulates a late cell-growth checkpoint essential for quiescent MuSCs to reenter the cell cycle upon activation.

Probing Particle-Carbon/Binder Degradation Behavior in Fatigued Layered Cathode Materials through Machine Learning Aided Diffraction Tomography.

Understanding how reaction heterogeneity impacts cathode materials during Li-ion battery (LIB) electrochemical cycling is pivotal for unraveling their electrochemical performance. Yet, experimentally verifying these reactions has proven to be a challenge. To address this, we employed scanning µ-XRD computed tomography to scrutinize Ni-rich layered LiNi0.6Co0.2Mn0.2O2 (NCM622) and Li-rich layered Li[Li0.2Ni0.2Mn0.6]O2 (LLNMO). By harnessing machine learning (ML) techniques, we scrutinized an extensive dataset of µ-XRD patterns, about 100,000 patterns per slice, to unveil the spatial distribution of crystalline structure and microstrain. Our experimental findings unequivocally reveal the distinct behavior of these materials. NCM622 exhibits structural degradation and lattice strain intricately linked to the size of secondary particles. Smaller particles and the surface of larger particles in contact with the carbon/binder matrix experience intensified structural fatigue after long-term cycling. Conversely, both the surface and bulk of LLNMO particles endure severe strain-induced structural degradation during high-voltage cycling, resulting in significant voltage decay and capacity fade. This work holds the potential to fine-tune the microstructure of advanced layered materials and manipulate composite electrode construction in order to enhance the performance of LIBs and beyond.

Unlocking Enhanced Capacitive Deionization of NaTi2(PO4)3/Carbon Materials by the Yolk-Shell Design.

The low salt adsorption capacities (SACs) of benchmark carbon materials (usually below 20 mg g-1) are one of the most challenging issues limiting further commercial development of capacitive deionization (CDI), an energetically favorable method for sustainable water desalination. Sodium superionic conductor (NASICON)-structured NaTi2(PO4)3 (NTP) materials, especially used in combination with carbon to prepare NTP/C materials, provide emerging options for higher CDI performance but face the problems of poor cycling stability and dissolution of active materials. In this study, we report the development of the yolk-shell nanoarchitecture of NASICON-structured NTP/C materials (denoted as ys-NTP@C) using a metal-organic framework@covalent organic polymer (MOF@COP) as a sacrificial template and space-confined nanoreactor. As expected, ys-NTP@C exhibits good CDI performance, including exemplary SACs with a maximum SAC of 124.72 mg g-1 at 1.8 V in the constant-voltage mode and 202.76 mg g-1 at 100 mA g-1 in the constant-current mode, and good cycling stability without obvious performance degradation or energy consumption increase over 100 cycles. Furthermore, X-ray diffraction used to study CDI cycling clearly exhibits the good structural stability of ys-NTP@C during repeated ion intercalation/deintercalation processes, and the finite element simulation shows why yolk-shell nanostructures exhibit better performance than other materials. This study provides a new synthetic paradigm for preparing yolk-shell structured materials from MOF@COP and highlights the potential use of yolk-shell nanoarchitectures for electrochemical desalination.

YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of satellite cells.

Skeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent SC toward activation, proliferation, and differentiation during the regeneration is orchestrated by cascades of transcription factors (TFs). Here, we elucidate the function of TF Yin Yang1 (YY1) in muscle regeneration. Muscle-specific deletion of YY1 in embryonic muscle progenitors leads to severe deformity of diaphragm muscle formation, thus neonatal death. Inducible deletion of YY1 in SC almost completely blocks the acute damage-induced muscle repair and exacerbates the chronic injury-induced dystrophic phenotype. Examination of SC revealed that YY1 loss results in cell-autonomous defect in activation and proliferation. Mechanistic search revealed that YY1 binds and represses mitochondrial gene expression. Simultaneously, it also stabilizes Hif1α protein and activates Hif1α-mediated glycolytic genes to facilitate a metabolic reprogramming toward glycolysis which is needed for SC proliferation. Altogether, our findings have identified YY1 as a key regulator of SC metabolic reprogramming through its dual roles in modulating both mitochondrial and glycolytic pathways.

GO-CoNiP New Composite Material Modified Separator for Long Cycle Lithium-Sulfur Batteries.

Lithium-sulfur batteries with high capacity are considered the most promising candidates for next-generation energy storage systems. Mitigating the shuttle reaction and promoting catalytic conversion within the battery are major challenges in the development of high-performance lithium-sulfur batteries. To solve these problems, a novel composite material GO-CoNiP is synthesized in this study. The material has excellent conductivity and abundant active sites to adsorb polysulfides and improve reaction kinetics within the battery. The initial capacity of the GO-CoNiP separator battery at 1 C is 889.4 mAh g-1 , and the single-cycle decay is 0.063% after 1000 cycles. In the 4 C high-rate test, the single-cycle decay is only 0.068% after 400 cycles. The initial capacity is as high as 828.2 mAh g-1 under high sulfur loading (7.3 mg cm-2 ). In addition, high and low-temperature performance tests are performed on the GO-CoNiP separator battery. The first cycle discharge reaches 810.9 mAh g-1 at a low temperature of 0 °C, and the first cycle discharge reaches 1064.8 mAh g-1 at a high temperature of 60 °C, and both can run stably for 120 cycles. In addition, in situ Raman tests are conducted to explain the adsorption of polysulfides by GO-CoNiP from a deeper level.

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients without diabetes mellitus after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index has been evaluated as a reliable surrogate for insulin resistance (IR) and has been proven to be a predictor of poor outcomes in patients with cardiovascular diseases. However, data are lacking on the relationship of the TyG index with prognosis in nondiabetic patients who underwent coronary artery bypass grafting (CABG). Thus, the purpose of our current study was to investigate the potential value of the TyG index as a prognostic indicator in patients without diabetes mellitus (DM) after CABG. METHODS: This multicenter, retrospective cohort study involving 830 nondiabetic patients after CABG from 3 tertiary public hospitals from 2014 to 2018. Kaplan-Meier survival curve analysis was conducted followed by the log-rank test. Cox proportional hazards regression models were used to explore the association between the TyG index and major adverse cardiovascular events (MACEs). The incremental predictive power of the TyG index was evaluated with C-statistics, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: An incrementally higher TyG index was associated with an increasingly higher cumulative incidence of MACEs (log-rank test, p < 0.001). The hazard ratio (95% CI) of MACEs was 2.22 (1.46-3.38) in tertile 3 of the TyG index and 1.38 (1.18-1.62) per SD increase in the TyG index. The addition of the TyG index yielded a significant improvement in the global performance of the baseline model [C-statistic increased from 0.656 to 0.680, p < 0.001; continuous NRI (95% CI) 0.269 (0.100-0.438), p = 0.002; IDI (95% CI) 0.014 (0.003-0.025), p = 0.014]. CONCLUSIONS: The TyG index may be an independent factor for predicting adverse cardiovascular events in nondiabetic patients after CABG.

The synergistic effect of the triglyceride-glucose index and serum uric acid on the prediction of major adverse cardiovascular events after coronary artery bypass grafting: a multicenter retrospective cohort study.

BACKGROUND: Elevated serum uric acid (SUA) is regarded as a risk factor for the development of cardiovascular diseases. Triglyceride-glucose (TyG) index, a novel surrogate for insulin resistance (IR), has been proven to be an independent predictor for adverse cardiac events. However, no study has specifically focused on the interaction between the two metabolic risk factors. Whether combining the TyG index and SUA could achieve more accurate prognostic prediction in patients undergoing coronary artery bypass grafting (CABG) remains unknown. METHODS: This was a multicenter, retrospective cohort study. A total of 1225 patients who underwent CABG were included in the final analysis. The patients were grouped based on the cut-off value of the TyG index and the sex-specific criteria of hyperuricemia (HUA). Cox regression analysis was conducted. The interaction between the TyG index and SUA was estimated using relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). The improvement of model performance yielded by the inclusion of the TyG index and SUA was examined by C-statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The goodness-of-fit of models was evaluated using the Akaike information criterion (AIC), Bayesian information criterion (BIC) and χ2 likelihood ratio test. RESULTS: During follow-up, 263 patients developed major adverse cardiovascular events (MACE). The independent and joint associations of the TyG index and SUA with adverse events were significant. Patients with higher TyG index and HUA were at higher risk of MACE (Kaplan-Meier analysis: log-rank P < 0.001; Cox regression: HR = 4.10; 95% CI 2.80-6.00, P < 0.001). A significant synergistic interaction was found between the TyG index and SUA [RERI (95% CI): 1.83 (0.32-3.34), P = 0.017; AP (95% CI): 0.41 (0.17-0.66), P = 0.001; SI (95% CI): 2.13 (1.13-4.00), P = 0.019]. The addition of the TyG index and SUA yielded a significant improvement in prognostic prediction and model fit [change in C-statistic: 0.038, P < 0.001; continuous NRI (95% CI): 0.336 (0.201-0.471), P < 0.001; IDI (95% CI): 0.031 (0.019-0.044), P < 0.001; AIC: 3534.29; BIC: 3616.45; likelihood ratio test: P < 0.001). CONCLUSIONS: The TyG index interacts synergistically with SUA to increase the risk of MACE in patients undergoing CABG, which emphasizes the need to use both measures concurrently when assessing cardiovascular risk.

Combination of the triglyceride-glucose index and EuroSCORE II improves the prediction of long-term adverse outcomes in patients undergoing coronary artery bypass grafting.

AIMS: We aimed to investigate the independent and combined association of the triglyceride-glucose (TyG) index and EuroSCORE II with major adverse cardiovascular event (MACE) after coronary artery bypass grafting (CABG), and examine whether the addition of the TyG index improves the predictive performance of the EuroSCORE II. MATERIALS AND METHODS: This study included 1013 patients who underwent CABG. The primary endpoint was MACE, which was defined as the composite of all-cause death, repeat coronary artery revascularisation, non-fatal myocardial infarction and non-fatal stroke. The patients were grouped by the TyG index and EuroSCORE II tertiles and the combination of these risk indicators. RESULTS: During the follow-up, 211 individuals developed MACE. Elevated levels of the TyG index and EuroSCORE II were associated with an increased risk of MACE. The hazard ratio [95% confidence interval (CI)] was 3.66 (2.34-5.73) in patients with the highest tertile of the TyG index and EuroSCORE II. Compared with the EuroSCORE II alone, combining the TyG index with EuroSCORE II achieved a better predictive performance [C-statistic increased 0.032, p < 0.001; continuous net reclassification improvement (NRI) (95% CI): 0.364 (0.215-0.514), p < 0.001; integrated discrimination improvement (IDI) (95% CI): 0.015 (0.007-0.023), p < 0.001, Akaike's information criteria (AIC) and Bayesian information criterion (BIC) decreased, and the likelihood ratio test, p < 0.001]. CONCLUSIONS: The TyG index and EuroSCORE II are independently associated with poor prognosis. Furthermore, the TyG index is an important adjunct to the EuroSCORE II for improving risk stratification and guiding early intervention among post-CABG patients.

A long noncoding RNA, LncMyoD, modulates chromatin accessibility to regulate muscle stem cell myogenic lineage progression.

Epigenetics regulation plays a critical role in determining cell identity by controlling the accessibility of lineage-specific regulatory regions. In muscle stem cells, epigenetic mechanisms of how chromatin accessibility is modulated during cell fate determination are not fully understood. Here, we identified a long noncoding RNA, LncMyoD, that functions as a chromatin modulator for myogenic lineage determination and progression. The depletion of LncMyoD in muscle stem cells led to the down-regulation of myogenic genes and defects in myogenic differentiation. LncMyoD exclusively binds with MyoD and not with other myogenic regulatory factors and promotes transactivation of target genes. The mechanistic study revealed that loss of LncMyoD prevents the establishment of a permissive chromatin environment at myogenic E-box-containing regions, therefore restricting the binding of MyoD. Furthermore, the depletion of LncMyoD strongly impairs the reprogramming of fibroblasts into the myogenic lineage. Taken together, our study shows that LncMyoD associates with MyoD and promotes myogenic gene expression through modulating MyoD accessibility to chromatin, thereby regulating myogenic lineage determination and progression.

Origin and Regulation of Interface Fusion during Synthesis of Single-Crystal Ni-Rich Cathodes.

Interface fusion plays a key role in constructing Ni-based single-crystal cathodes, and is governed by the atomic migration related to kinetics. However, the interfacial atom migration path and its control factors are lack of clearly understanding. Herein, we systematically probe the solid-state synthesis mechanism of single-crystal LiNi0.92 Co0.04 Mn0.04 O2 , including the effects of precursor size, Li/transition metal (TM) ratio and sintering temperature on the structure. Multi-dimensional analysis unravels that thermodynamics drives interface atoms migration through intermediate state (i.e., cation mixing phase) to induce grain boundary fusion. Moreover, we demonstrate that smaller precursor size (<6 µm), lager Li/TM ratio (>1.0) and higher temperature (≥810 °C) are conducive to promote the growth of the intermediate state due to reaction kinetics enhancement, and ultimately strengthen the atomic migration-induced interface fusion.

Improving Low-temperature Performance and Stability of Na2 Ti6 O13 Anodes by the Ti-O Spring Effect through Nb-doping.

Na2 Ti6 O13 (NTO) with high safety has been regarded as a promising anode candidate for sodium-ion batteries. In the present study, integrated modification of migration channels broadening, charge density re-distribution, and oxygen vacancies regulation are realized in case of Nb-doping and have obtained significantly enhanced cycling performance with 92 % reversible capacity retained after 3000 cycles at 3000 mA g-1 . Moreover, unexpected low-temperature performance with a high discharge capacity of 143 mAh g-1 at 100 mA g-1 under -15 °C is also achieved in the full cell. Theoretical investigation suggests that Nb preferentially replaces Ti3 sites, which effectively improves structural stability and lowers the diffusion energy barrier. What's more important, both the in situ X-ray diffraction (XRD) and in situ Raman furtherly confirm the robust spring effect of the Ti-O bond, making special charge compensation mechanism and respective regulation strategy to conquer the sluggish transport kinetics and low conductivity, which plays a key role in promoting electrochemical performance.

Type 2 diabetic mice enter a state of spontaneous hibernation-like suspended animation following accumulation of uric acid.

Hibernation is an example of extreme hypometabolic behavior. How mammals achieve such a state of suspended animation remains unclear. Here we show that several strains of type 2 diabetic mice spontaneously enter into hibernation-like suspended animation (HLSA) in cold temperatures. Nondiabetic mice injected with ATP mimic the severe hypothermia analogous to that observed in diabetic mice. We identified that uric acid, an ATP metabolite, is a key molecular in the entry of HLSA. Uric acid binds to the Na+ binding pocket of the Na+/H+ exchanger protein and inhibits its activity, acidifying the cytoplasm and triggering a drop in metabolic rate. The suppression of uric acid biosynthesis blocks the occurrence of HLSA, and hyperuricemic mice induced by treatment with an uricase inhibitor can spontaneously enter into HLSA similar to that observed in type 2 diabetic mice. In rats and dogs, injection of ATP induces a reversible state of HLSA similar to that seen in mice. However, ATP injection fails to induce HLSA in pigs due to the lack of their ability to accumulate uric acid. Our results raise the possibility that nonhibernating mammals could spontaneously undergo HLSA upon accumulation of ATP metabolite, uric acid.

p110α of PI3K is necessary and sufficient for quiescence exit in adult muscle satellite cells.

Adult mouse muscle satellite cells (MuSCs) are quiescent in uninjured muscles. Upon injury, MuSCs exit quiescence in vivo to become activated, re-enter the cell cycle to proliferate, and differentiate to repair the damaged muscles. It remains unclear which extrinsic cues and intrinsic signaling pathways regulate quiescence exit during MuSC activation. Here, we demonstrated that inducible MuSC-specific deletion of p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K), rendered MuSCs unable to exit quiescence, resulting in severely impaired MuSC proliferation and muscle regeneration. Genetic reactivation of mTORC1, or knockdown of FoxOs, in p110α-null MuSCs partially rescued the above defects, making them key effectors downstream of PI3K in regulating quiescence exit. c-Jun was found to be a key transcriptional target of the PI3K/mTORC1 signaling axis essential for MuSC quiescence exit. Moreover, induction of a constitutively active PI3K in quiescent MuSCs resulted in spontaneous MuSC activation in uninjured muscles and subsequent depletion of the MuSC pool. Thus, PI3K-p110α is both necessary and sufficient for MuSCs to exit quiescence in response to activating signals.

Association of triglyceride-glucose index and traditional risk factors with cardiovascular disease among non-diabetic population: a 10-year prospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index is known as a reliable alternative marker of insulin resistance (IR), which has been regarded as a predictor of cardiovascular disease (CVD). However, whether TyG index can predict the risk and occurrence of CVD in non-diabetic population remains uncertain. The aim of this study was to explore the association between the TyG index and cardiovascular risk factors and to clarify the prognostic value of the TyG index for CVD, coronary heart disease (CHD) and stroke in non-diabetic general population in Eastern China. METHODS: A total of 6095 cases without diagnosed diabetes and CVD were included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2) and the participants were divided into 4 groups according to the TyG index quartiles (Q1, Q2, Q3, Q4). The primary outcome was CVD, including CHD and stroke. Cox proportional hazards regression analysis was used to investigate the association between the TyG index and the risk of CVD. RESULTS: During the 10-year follow-up, 357 (5.9%) participants of CVD, 224 (3.7%) participants of CHD and 151 (2.5%) participants of stroke were observed. The incidence of CVD increased with the TyG index quartiles. Multivariate Cox regression analysis showed that the hazard ratios [95% confidence interval (CI)] in Q4 group were respectively 1.484 (1.074-2.051) for CVD, 1.687 (1.105-2.575) for CHD and 1.402 (0.853-2.305) for stroke compared to Q1 group. Moreover, adding the TyG index to models with traditional risk factors yielded a significant improvement in discrimination and reclassification of incident CVD and CHD. CONCLUSIONS: The TyG index is associated with cardiovascular risk factors and can be used as a useful, low-cost predictive marker for CVD and CHD risk in non-diabetic population.

Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients with premature coronary artery disease: a retrospective cohort study.

BACKGROUND: Premature coronary artery disease (PCAD) has become more common in recent years and is often associated with poor outcomes. Triglyceride-glucose (TyG) index is a simple and reliable surrogate for insulin resistance (IR) and is an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients with PCAD remains uncertain. Thus, this study aimed to investigate the prognostic value and predictive performance of the TyG index in patients with PCAD. METHODS: A total of 526 young subjects (male < 45 years, female < 55 years) with angiographically proven CAD from January 2013 to December 2018 were included consecutively in this study. Their clinical and laboratory parameters were collected, and the TyG index was calculated as [Formula: see text]. The follow-up time after discharge was 40-112 months (median, 68 months; interquartile range, 49‒83 months). The primary endpoint was the occurrence of the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and non-fatal stroke. RESULTS: The TyG index was significantly associated with traditional cardiovascular risk factors and the Gensini score (GS). Kaplan-Meier survival (MACE-free) curves by tertiles of the TyG index showed statistically significant differences (log-rank test, p = 0.001). In the fully adjusted Cox regression model, the Hazard ratio (95% CI) of MACE was 2.17 (1.15-4.06) in tertile 3 and 1.45 (1.11-1.91) for per SD increase in the TyG index. Time-dependent ROC analyses of the TyG for prediction of MACE showed the area under the curves (AUC) reached 0.631 at 3 years, 0.643 at 6 years, and 0.710 at 9 years. Furthermore, adding TyG index to existing risk prediction model could improve outcome prediction [C-statistic increased from 0.715 to 0.719, p = 0.007; continuous net reclassification improvement (NRI) = 0.101, p = 0.362; integrated discrimination improvement (IDI) = 0.011, p = 0.017]. CONCLUSION: The TyG index is an independent predictor of MACE in patients with PCAD, suggesting that the TyG index has important clinical implications for risk stratification and early intervention of PCAD.