Abstract
Background
The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. ...Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS.
Methods
A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level mg/dL × fasting glucose level mg/dL/2).
Results
The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan–Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201–1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019).
Conclusions
The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.
Thermal priming of reef corals can enhance their heat tolerance; however, the legacy effects of heat stress during parental brooding on larval resilience remain understudied. This study investigated ...whether preconditioning adult coral Pocillopora damicornis to high temperatures (29°C and 32°C) could better prepare their larvae for heat stress. Results showed that heat‐acclimated adults brooded larvae with reduced symbiont density and shifted thermal performance curves. Reciprocal transplant experiments demonstrated higher bleaching resistance and better photosynthetic and autotrophic performance in heat‐exposed larvae from acclimated adults compared to unacclimated adults. RNA‐seq revealed strong cellular stress responses in larvae from heat‐acclimated adults that could have been effective in rescuing host cells from stress, as evidenced by the widespread upregulation of genes involved in cell cycle and mitosis. For symbionts, a molecular coordination between light harvesting, photoprotection and carbon fixation was detected in larvae from heat‐acclimated adults, which may help optimize photosynthetic activity and yield under high temperature. Furthermore, heat acclimation led to opposing regulations of symbiont catabolic and anabolic pathways and favoured nutrient translocation to the host and thus a functional symbiosis. Notwithstanding, the improved heat tolerance was paralleled by reduced light‐enhanced dark respiration, indicating metabolic depression for energy saving. Our findings suggest that adult heat acclimation can rapidly shift thermal tolerance of brooded coral larvae and provide integrated physiological and molecular evidence for this adaptive plasticity, which could increase climate resilience. However, the metabolic depression may be maladaptive for long‐term organismal performance, highlighting the importance of curbing carbon emissions to better protect corals.
Interleukin-37b (hereafter called IL-37) was identified as fundamental inhibitor of natural and acquired immunity. The molecular mechanism and function of IL-37 in colorectal cancer (CRC) has been ...elusive. Here, we found that IL-37 transgenic (IL-37tg) mice were highly susceptible to colitis-associated colorectal cancer (CAC) and suffered from dramatically increased tumor burdens in colon. Nevertheless, IL-37 is dispensable for intestinal mutagenesis, and CRC cell proliferation, apoptosis, and migration. Notably, IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models. CD8
T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice, enabling tumor evasion of immune surveillance. The dysfunction led by IL-37 antagonizes IL-18-induced proliferation and effector function of CD8
T cells, which was dependent on SIGIRR (single immunoglobulin interleukin-1 receptor-related protein). Finally, we observed that IL-37 levels were significantly increased in CRC patients, and positively correlated with serum CRC biomarker CEA levels, but negatively correlated with the CD8
T cell infiltration in CRC patients. Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancer-immunity cycle as therapeutic targets in CRC.
The East China coastal plain is one of the most important Neolithic culture areas in China, where rich archaeological sites including those producing the earliest domesticated rice are observed. It ...is also a place where landscape has experienced dramatic evolution during the Holocene when both sea level and climate changed, such that it is an ideal place for studying human-environment interaction. This study investigated over 2000 sites of pre-history and Shang and Zhou Dynasties, with 655 of which being Neolithic ages, by using DEM and GIS methods. The results suggest that the spatial and temporal distribution of Neolithic sites has largely been controlled by landscape evolution （particularly changes in coastal line）, which ultimately governed by sea level changes. During early Holocene, Neolithic sites sparsely distributed in the intermountain basins of east Zhejiang Province, far from the influence of ocean. Over the period of 9-7 ka, the coastal plain （including the shelf） was largely submerged, only the feet of low hills to the south and southwest of the study area, and islands protruding the estuary, cradled limited number of settlements with characteristic ＂maritime components＂. At about 7 ka, sea level rise decelerated prominently, while sediments supply in the drainage remained high value, the combination of which led to land formation and propagation. Vast space during this period facilitated the growth of settlements in both size and number. In the mean time, however, the coastal plain was vulnerable to extreme environmental events such as storms and flooding owning to its geomorphic nature, which exerted great influence on the rise and fall of Neolithic culture.
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional ...Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.
The mechanical properties and wear resistance of carbon black/natural rubber (CB/NR) composites are significantly influenced by the degree of CB dispersion in rubber. Here, we present a novel ...reinforcement theory using atomic force microscopy (AFM) to quantify the adhesive thickness of rubber molecules around the CB particles as well as the height, area, and volume in NR. The thickness of the bonded rubber (BR) was found to vary between 3 and 7 nm depending on the values of the nitrogen surface area (NSA) for CB. This indicates that a higher BR content is a result of a higher CB NSA with a smaller particle size, showing a higher number of active positions to anchor rubber molecules. The nanoindentation of AFM was used to determine the surface hardness of CB in NR; the value decreases with increasing BR height. In this study, we demonstrate a well-defined reinforcement mechanism of CB in NR with the factors of BR, surface hardness, 100%/300% modulus, and tensile strength.
The de Winter electrocardiographic (ECG) pattern was characterized by upsloping ST‐segment depressions, tall and positive symmetrical T waves in precordial leads. This rare ECG pattern was recognized ...as an indication of proximal left anterior descending artery occlusion. Less commonly, this ECG pattern was reported in association with occlusion of other coronary artery segments. We present three cases of the de Winter pattern associated with acute total left main occlusion. This pattern may evolve to ST elevation within hours of presentation. Widespread upsloping ST‐segment depressions from V2–V6, centered on V5 were observed in these patients.
Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally ...regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8
T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.
The homogeneous galactoglucan PCP-1C extracted from
sclerotium has multiple biological activities. The present study demonstrated the effect of PCP-1C on the polarization of RAW 264.7 macrophages and ...the underlying molecular mechanism. Scanning electron microscopy showed that PCP-1C is a detrital-shaped polysaccharide with fish-scale patterns on the surface, with a high sugar content. The ELISA assay, qRT-PCR assay, and flow cytometry assay showed that the presence of PCP-1C could induce higher expression of M1 markers, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-12 (IL-12), when compared with the control and the LPS group, and it caused a decrease in the level of interleukin-10 (IL-10), which is the marker for M2 macrophages. At the same time, PCP-1C induces an increase in the CD86 (an M1 marker)/CD206 (an M2 marker) ratio. The results of the Western blot assay showed that PCP-1C induced activation of the Notch signaling pathway in macrophages. Notch1, ligand Jagged1, and Hes1 were all up-regulated with the incubation of PCP-1C. These results indicate that the homogeneous
polysaccharide PCP-1C improves M1 macrophage polarization through the Notch signaling pathway.
Exploring highly efficient blue-emissive lead-free halide materials is a significant and challenging objective in the study of luminescent materials. This study reports the synthesis of a new ...zero-dimensional (0D) hybrid zinc halide of CYPZnBr 4 (CYP = 1-cyclohexylpiperazine) containing an isolated ZnBr42– tetrahedron. CYPZnBr 4 exhibits strong blue light emission with a high photoluminescence quantum yield (PLQY) of 79.22%, surpassing all previously reported 0D zinc halide counterparts. According to the theoretical and experimental studies, the blue light emission is attributed to intrinsic self-trapped excitons resulting from strong electron–phonon coupling and structural deformation. Importantly, CYPZnBr 4 demonstrates excellent structural and luminescence stability toward high temperatures (180 °C) over at least half a month. High luminescence efficiency and stability enable CYPZnBr 4 to be an efficient blue phosphor to fabricate white light-emitting diodes (LEDs), which produces high-quality white light with a color rendering index (CRI) of 93.1 and a correlated color temperature (CCT) of 5304 K, closely resembling natural sunlight. This white LED also exhibits consistent performance and stability across different drive currents, suggesting the potential for high-power optoelectronic applications. Overall, this study paves the way for the utilization of 0D hybrid halides in advanced solid-state lighting applications.
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