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Abstract People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636.

The implementation of early and accurate detection of aircraft cargo compartment fire is of great significance to ensure flight safety. The current airborne fire detection technology mostly relies on single-parameter smoke detection using infrared light. This often results in a high false alarm rate in complex air transportation environments. The traditional deep learning model struggles to effectively address the issue of long-term dependency in multivariate fire information. This paper proposes a multi-technology collaborative fire detection method based on an improved transformers model. Dual-wavelength optical sensors, flue gas analyzers, and other equipment are used to carry out multi-technology collaborative detection methods and characterize various feature dimensions of fire to improve detection accuracy. The improved Transformer model which integrates the self-attention mechanism and position encoding mechanism is applied to the problem of long-time series modeling of fire information from a global perspective, which effectively solves the problem of gradient disappearance and gradient explosion in traditional RNN (recurrent neural network) and CNN (convolutional neural network). Two different multi-head self-attention mechanisms are used to classify and model multivariate fire information, respectively, which solves the problem of confusing time series modeling and classification modeling in dealing with multivariate classification tasks by a single attention mechanism. Finally, the output results of the two models are fused through the gate mechanism. The research results show that, compared with the traditional single-feature detection technology, the multi-technology collaborative fire detection method can better capture fire information. Compared with the traditional deep learning model, the multivariate fire prediction model constructed by the improved Transformer can better detect fires, and the accuracy rate is 0.995.

Abstract Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS8–16 G12V from three predicted high affinity peptides. By determining the structure of the tumor-specific 4TCR2 bound to KRASG12V-HLA-A*11:01, we conduct structure-based design to create and evaluate TCR variants with markedly enhanced affinity, up to 15.8-fold. This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRASG12V peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRASG12V neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRASG12V mutation.

Abstract Background Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. Methods The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. Results Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51–68.26) and 1.27 (0.75–2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged

Background Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. Purpose This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. Methods Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MA ADP ) > 47 mm and

Background: Glasgow Prognostic Score (GPS) and its modified counterparts, including the modified GPS (mGPS) and hsCRP-modified GPS (hs-mGPS), are widely used inflammatory indices in clinical settings. Inflammation has gained increased attention in the context of coronary heart disease (CHD); however, its long-term predictive value in patients with CHD remains uncertain. Objective: This study aimed to assess the predictive values of GPS, mGPS, and hs-mGPS for long-term survival in patients following percutaneous coronary intervention (PCI). Methods: Consecutive 10,724 PCI patients were enrolled in 2013. The primary endpoint was 5-year all-cause death. Results: This study included 8,909 patients. Individuals with high GPS, mGPS, and hs-mGPS scores exhibited a significantly higher risk of all-cause death compared to those with low scores (all P

Abstract Background The triglyceride–glucose (TyG) index and high‐sensitivity C‐reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all‐cause death, nonfatal myocardial infarction, and revascularization. Results During the 2‐year follow‐up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Conclusion Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high‐risk populations and guiding management strategies among CCS patients.

Enterovirus G (EV-G) belongs to the Picornaviridae family and infects porcine populations worldwide. A total of 20 EV-G genotypes (EV-G1 to EV-G20) have been identified. In this study, we isolated and characterized an EV-G strain, named EV-G/YN29/2022, from the feces of diarrheic pigs. This was the first EV-G6 strain isolated in China. Comparison of the whole genome nucleotide and corresponding amino acid sequences showed that the isolate was more closely related to those of the EV-G6 genotype than other genotypes, with the complete genome sequence similarity ranging from 83.7% (Iba46442) to 84.4% (PEV-B-KOR), and corresponding amino acid homology ranged from 96% (Iba46442) to 96.8% (PEV-B-KOR). Similarly, the VP1 gene and corresponding amino acid sequences of EV-G/YN29/2022 were highly similar to those of the EV-G6 genotype (>82.9% and >94.3%, respectively). Thus, the isolated strain was classified as EV-G6 genotype. This was the first EV-G6 strain isolated in China. Pathogenicity analyses revealed that EV-G/YN29/2022 infection caused mild diarrhea, typical skin lesions, and weight reduction. The strain was mainly distributed to the intestinal tissue but was also found in the brain, mesenteric lymph nodes, spleen, and liver. Our results can be used as a reference to further elucidate the epidemiology, evolution, and pathogenicity of EV-G.

There are a large amount of audio signals stored in third-party storage centers. To improve the privacy and security of audio signals, a digital audio encryption and forensics watermarking scheme is proposed. We defined the signal energy ratio feature of audio signals and designed the embedding method by quantifying the feature, aiming to improve the security of watermarking system. We firstly encrypted the original audio by using scrambling and multiplication, to get the encrypted data. Secondly, we divided the encrypted data into frames and compressed each frame by sampling to get the compressed data. After that, we embedded the compressed data and frame number into the encrypted data to get the watermarked signal being uploaded to third-party storage centers. Authorized users download encrypted data and verify the authenticity of the data. For the intact data, they decrypt it directly to get the audio signal. If the downloaded data has been attacked, they locate the attacked frame and extract the compressed data to reconstruct the attacked signal approximately. Furthermore, we decrypted the reconstructed signal to obtain the expression meaning of the original audio. The experimental results demonstrate the effectiveness of the proposed scheme.

AbstractPercutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count 47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53–0.76) than those without TP in the overall cohort. In further analysis, among hsCRP

BackgroundA novel inflammatory marker that measures the degree of systemic immunoinflammation, the systemic immuno-inflammation index (SII) is frequently used to forecast a number of illnesses. According to earlier studies, inflammation may play a role in the pathophysiology of hearing loss (HL).MethodsA sample from the National Health and Nutrition Examination Survey (NHANES) covering the years 2009 to 2018 was used in the current cross-sectional survey. Subgroup analysis and weighted multiple linear regression models were used to examine the independent linear correlation between SII and HL. Fitted smoothed curve analyses were also conducted to show the non-linear relationship between the two variables.ResultsAmong the 8,535 participants, the mean age was 40.92 ± 18.6 years, with 49.01% being male. Notably, individuals with hearing loss demonstrated an SII of 530.00 ± 320.72, while those with normal hearing displayed an SII of 491.21 ± 265.15. The mean ± SD values of low-frequency, speech-frequency, and high-frequency Pure Tone Average (PTA) hearing thresholds were 10.33 ± 9.79, 12.20 ± 11.11, and 22.48 ± 19.49 dB, respectively. A positive dose–response relationship between higher SII and hearing thresholds was observed after adjusting for potential confounders. Furthermore, the interaction analysis did not reveal any significant impact on this positive correlation.ConclusionThe results of our investigation suggest that the Systemic Inflammatory Index may serve as a potential biomarker for the likelihood of hearing loss. However, additional research is required to further elucidate the nature of this association.

Air traffic controllers’ mental workload significantly impacts their operational efficiency and safety. Detecting their mental workload rapidly and accurately is crucial for preventing aviation accidents. This study introduces a mental workload detection model for controllers based on power spectrum features related to gamma waves. The model selects the feature with the highest classification accuracy, β + θ + α + γ, and utilizes the mRMR (Max-Relevance and Min-Redundancy) algorithm for channel selection. Furthermore, the channels that were less affected by ICA processing were identified, and the reliability of this result was demonstrated by artifact analysis brought about by EMG, ECG, etc. Finally, a model for rapid mental workload detection for controllers was developed and the detection rate for the 34 subjects reached 1, and the accuracy for the remaining subjects was as low as 0.986. In conclusion, we validated the usability of the mRMR algorithm in channel selection and proposed a rapid method for detecting mental workload in air traffic controllers using only three EEG channels. By reducing the number of EEG channels and shortening the data processing time, this approach simplifies equipment application and maintains detection accuracy, enhancing practical usability.

Results and conclusions: Totally, 369,931 subjects in CMPEC were included in the study. A total of 28 publications were incorporated into the systematic review and meta-analysis. The pooled analysis suggested that aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), and low albumin (ALB) were positively associated with the risk of GSD. Meanwhile, GSD present to have higher AST, ALT, gamma-glutamyl transferase (GGT), total bilirubin (TBil), globulin (G), and ALP levels and relatively lower TP and ALB levels than the healthy participants. These results were consistent when stratified by the study design, geographic background, and study quality. Only the association between ALP and GSD risk was validated in the UKB cohort. This study suggests liver function indicators were associated with GSD risk. The results may provide the basis for exploring the etiology of GSD and may help clinicians identify high-risk subjects.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066–2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716–2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032–1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091–1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079–3.601, P = 0.027 and HR 1.560, 95 % CI 1.191–2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P

Using the layered design concept of fine-grained diamond in the upper layer and the coarse-fine diamond in contact with the cemented carbide layer in the lower layer, the polycrystalline diamond compact (PDC) with multiple diamond layers for drilling was prepared. The differences in microstructure and performance between the single-layer diamond PDC and the multi-layer diamond PDC with different particle sizes were compared. The internal defects and surface morphology of the PDC were characterized using ultrasonic scanning and scanning electron microscopy (SEM), and the heat resistance, impact resistance and wear resistance of the PDC were tested, respectively. The results show that the comprehensive performance of the multi-layer diamond PDC is good. The surface layer is wear-resistant, while the lower layer is more impact-resistant. The PDC exhibits a more balanced combination of heat resistance, impact resistance and wear resistance. Specifically, the fine-grained diamond layer PDC demonstrates higher wear resistance but lower heat and impact resistance; while the coarse-grained diamond layer PDC exhibits better heat and impact resistance, but poor wear resistance.

Abstract Background Stress hyperglycemia ratio (SHR), a novel biomarker of stress hyperglycemia, was proved to be a reliable predictor of short‐term adverse outcomes in patients with acute coronary syndromes (ACS). However, its impact on long‐term prognosis remained controversial. Methods A total of 7662 patients with ACS from a large nationwide prospective cohort between January 2015 and May 2019 were included. SHR was calculated by the following formula: SHR = admission glucose (mmol/L)/(1.59 × HbA1c [%]−2.59). The primary end point was a major adverse cardiovascular event (MACE) during follow‐up, a composite of all‐cause death, myocardial infarction, and unplanned revascularization. The second end point was the separate components of the primary end points. Results During a median follow‐up of 2.1 years, 779 MACE events occurred. After multivariable adjustment, ACS patients with the highest SHR tertile were significantly associated with increased long‐term risks of MACE (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.24–1.88), all‐cause death (HR 1.80, 95% CI 1.29–2.51) and unplanned revascularization (HR 1.44, 95% CI 1.09–1.91). Although significant associations between the highest SHR tertile and risks of MACE and all‐cause death were assessed in both diabetic and nondiabetic patients, the patterns of risk were different in these two groups. Conclusion Elevated SHR was independently associated with a higher risk of long‐term outcomes irrespective of diabetic status, suggesting that SHR was a potential biomarker for risk stratification after ACS.

Summary: Patients with coronary artery disease (CAD) at low residual inflammatory risk are often overlooked in research and practice. This study examined the associations between fourteen inflammatory indicators and all-cause mortality in 5,339 CAD patients with baseline high-sensitivity C-reactive protein (hsCRP)

Summary: This study was aimed to investigate the association between remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) concentrations and long-term bleeding. A total of 10,724 consecutive patients who underwent percutaneous coronary intervention in 2013 were prospectively enrolled. During a median follow-up of 5.1 years, 411 bleeding events and 42 intracranial hemorrhages (ICH) were recorded. The findings revealed that lower RC concentrations were independently associated with an increased risk of long-term bleeding events (continuous RC hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.26–0.85; Q4 vs. Q1 HR: 0.66, 95% CI: 0.45–0.98), whereas lower LDL-C concentrations did not show a similar association. Additionally, a non-linear relationship was observed between RC concentrations and the risk of ICH (P for non-linear trend = 0.014), but no such relationship was found for LDL-C concentrations. These results provided insights into the safety of LDL-C-lowering therapy and emphasized the significance of RC concentrations in lipid management.

ABSTRACT: Pigeons are considered less susceptible, and display few or no clinical signs to infection with avian influenza virus (AIV). Melanoma differentiation-associated gene 5 (MDA5), an important mediator in innate immunity, has been linked to the virus resistance. In this study, the pigeon MDA5 (piMDA5) was cloned. The bioinformatics analysis showed that the C-terminal domain (CTD) of MDA5 is highly conserved among species while the N-terminal caspase recruitment domain (CARD) is variable. Upon infection with Newcastle diseases virus (NDV) and AIV, piMDA5 was upregulated in both pigeons and pigeon embryonic fibroblasts (PEFs). Further study found that overexpression of piMDA5 mediated the activation of interferons (IFNs) and IFN-stimulated genes (ISGs) while inhibiting NDV replication. Conversely, the knockdown of piMDA5 promoted NDV replication. Additionally, CARD was found to be essential for the activation of IFN-β by piMDA5. Furthermore, pigeon MDA5, chicken MDA5, and human MDA5 differ in inhibiting viral replication and inducing ISGs expression. These findings suggest that MDA5 contributes to suppressing viral replication by activating the IFN signal pathway in pigeons. This study provides valuable insight into the role of MDA5 in pigeons and a better understanding of the conserved role of MDA5 in innate immunity during evolution.

Abstract Background Malnutrition and inflammation are associated with adverse clinical outcomes in patients with diabetes or coronary artery disease (CAD). Prognostic nutritional index (PNI) is a comprehensive and simple indicator reflecting nutritional condition and immunological status. Whether there is a crosstalk between nutritional-immunological status and diabetes status for the impact on the prognosis of coronary artery disease (CAD) is unclear. Methods A total of 9429 consecutive CAD patients undergoing percutaneous coronary intervention were grouped by diabetes status [diabetes (DM) and non-diabetes (non-DM)] and preprocedural PNI level [high PNI (H-PNI) and low PNI (L-PNI)] categorized by the statistically optimal cut-off value of 48.49. The primary endpoint was all-cause death. Results During a median follow-up of 5.1 years (interquartile range: 5.0–5.1 years), 366 patients died. Compared with the non-DM/H-PNI group, the DM/L-PNI group yielded the highest risk of all-cause death (adjusted hazard ratio: 2.65, 95% confidence interval: 1.97–3.56, p

Abstract Background Patients with coronary artery disease (CAD) combined with diabetes have a higher risk of cardiovascular events, and high-sensitivity C-reactive protein (hs-CRP)-to-albumin ratio (CAR) is a novel inflammatory biomarker. However, whether the CAR can identify high-risk patients with CAD and type 2 diabetes (T2DM) remains unclear. Methods The present study was based on a prospective and observational cohort with 10,724 individuals who undergo percutaneous coronary intervention (PCI) in Fu Wai Hospital throughout the year 2013 consecutively enrolled. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. CAR was calculated with the formula: hs-CRP (mg/L)/albumin (g/L). According to the optimal cut-off value of CAR for all-cause mortality, patients were divided into higher CAR (CAR-H) and lower CAR (CAR-L) groups. Results A total of 2755 patients with T2DM who underwent PCI and received dual antiplatelet therapy were finally enrolled. During a follow-up of 5 years (interquartile range: 5.0–5.1 years), 126 (4.6%) all-cause mortalities and 74 (2.7%) cardiac mortalities were recorded. In the multivariable Cox model, CAR-H was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.634, 95% confidence interval [CI] 1.121–2.380, p = 0.011) and cardiac mortality (HR: 1.733, 95% CI 1.059–2.835, p = 0.029) compared with CAR-L. When comparing the predictive value, CAR was superior to hs-CRP for all-cause mortality (area under the curve [AUC] 0.588 vs. 0.580, p = 0.002) and cardiac mortality (AUC 0.602 vs. 0.593, p = 0.004). Conclusion In this real-world cohort study, a higher level of CAR was associated with worse 5-year outcomes among diabetic patients with PCI.

Summary: To reduce cardiovascular risk in patients with established coronary heart disease, the present study investigated the combined effect of D-dimer, high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) [Lp(a)] on long-term cardiovascular outcomes from the perspectives of thrombosis, inflammation, and lipid risk simultaneously. Consecutive 10,724 patients with percutaneous coronary intervention (PCI) were enrolled throughout 2013. Over a median follow-up of 5.1 years, each individual elevation of D-dimer, hs-CRP, and Lp(a) was associated with poor ischemic outcomes but not bleeding. Concurrent high D-dimer, hs-CRP, and Lp(a) had even greater risks of all-cause death (hazard ratio [HR] 2.714, 95% confidence interval [CI] 1.742–4.231) and cardiac death (HR 4.152, 95% CI 2.207–7.812) and had incremental value beyond the traditional risk factors model. Concurrent high D-dimer, hs-CRP, and Lp(a) levels had a synergistic effect on adverse 5-year ischemic outcomes, highlighting that the potential utility of simultaneous assessment of multiple cardiovascular risk biomarkers may help to identify high-risk patients after PCI.

Abstract Background Total occlusion is the most severe coronary lesion, indicating heavy ischemic burden and poor prognosis. The lipid profile is central to the development of atherosclerotic coronary lesions. Evidence on the optimal lipid measure to be monitored and managed in patients with established coronary artery disease (CAD) is inconclusive. Methods Total cholesterol (TC), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), nonhigh-density lipoprotein cholesterol (non-HDL-c), lipoprotein (a) [Lp(a)], apolipoprotein B (apoB), non-HDL-c/HDL-c, and apoB/apoA-1 were analyzed in quintiles and as continuous variables. The associations of lipid measures with total occlusion were tested using logistic regression models, visualized with restricted cubic splines, and compared by areas under the receiver operating characteristic curves (AUROC). Discordance analysis was performed when apoB/apoA-1 and non-HDL-c/HDL-c were not in concordance. Results The prospective cohort study included 10,003 patients (mean age: 58 years; women: 22.96%), with 1879 patients having total occlusion. The risks of total occlusion significantly increased with quintiles of Lp(a), non-HDL-c/HDL-c, and apoB/apoA-1 (all p for trend

Abstract Elevated extrachromosomal circular DNA (eccDNA) has been reported to accelerate tumor pathogenesis. Although the eccDNA profiles of other tumors have been established, the landscape of the eccDNA of acute myeloid leukemia (AML) has not been revealed. Our study first depicted the eccDNA profile of normal hematopoiesis and AML evolution by exploiting the ATAC-seq and RNA-seq data from nine healthy donors and 12 AML patients, which contained a total of 137 cell samples and 96 RNA-seq samples (including 16 blood cell types of the normal hematopoietic and AML hierarchies). We found the number of eccDNAs generally increased with the evolution of normal hematopoiesis and AML. The ecDNAs and ring chromosomes were found to reappear both in normal hematopoiesis and AML cells. Furthermore, we compared the eccDNAs of AML with normal cells. There were almost 300 AML-specific genes, including the known oncogenes NRAS, MCL1, EVI1, GATA2, WT1, and PAK1. And the ecDNA (chr11: 58668376-58826008) occurred in five out of 17 AML evolution-related cells, which was associated with the high expression of the GLYATL1 gene and the high expressed GLYATL1 was a poor prognostic factor. In conclusion, the eccDNA profiles of normal hematopoiesis and AML evolution were depicted and the recurrent eccDNAs we revealed might be utilized in the treatment of AML as biomarkers.

Abstract Objective Meta-analysis was used to evaluate the diagnostic value of a CVR cut-off value of 1.6 for fetal hydrops due to congenital lung malformation (CLM). Methods A systematic search of PubMed, Embase, Web of Science, CNKI, VIP, and Wanfang published before 7/30/2021 for the value of a congenital pulmonary airway malformation volume ratio (CVR) cut-off value of 1.6 for the diagnosis of fetal hydrops. According to the inclusion and exclusion criteria, the literature that met the requirements were obtained. A total of 75 articles were retrieved, and 12 articles were included for further analysis. The quality of these studies was evaluated according to the Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2) criteria. The Q test and heterogeneity I2 were used to evaluate the heterogeneity due to non-threshold effects, and Stata 15.0 was used for statistical analysis to evaluate the diagnostic value of the CVR cutoff value of 1.6 for fetal hydrops due to CLM. Results A total of 12 studies were included. The QUADAS-2 indicated that the risk of bias was relatively low, and the clinical applicability was relatively high. Statistical analysis was performed on included studies using a random effect model. Meta-analysis showed that the pooled sensitivity, specificity, diagnostic ratio and summary receiver operating characteristic (SROC) for the diagnosis of fetal hydrops by CVR were 0.86 (95% CI, 0.72–0.93; I 2 = 59.84), 0.90 (95% CI, 0.88–0.93; I 2 = 31.94), 58 (95% CI, 22–149; I 2 = 100%), 0.93 (95% CI, 0.91–0.95). Conclusions The sensitivity and specificity of CVR cut-off value 1.6 for the diagnosis of CLM-induced fetal hydrops were high, no publication bias was observed, and the CVR cut-off value 1.6 is meaningful for the early diagnosis prediction of CLM-induced fetal hydrops.

Background: Intrahepatic cholestasis (IC) is a disorder of bile production, secretion, and excretion with various causes. Crocin I (CR) is effective in the treatment of IC, but its underlying mechanisms need to be further explored. We aimed to reveal the therapeutic mechanism of crocin I for IC by combining an integrated strategy of metabolomics and transcriptomics.Methods: The hepatoprotective effect of CR against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) was evaluated in rats. The serum biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β), as well as the liver oxidative stress indexes and the pathological characteristics of the liver were analyzed. In addition, we also performed a serum metabolomics study using UPLC-Q Exactive HF-X technology to investigate the effect of CR on the serum of rats with ANIT-induced IC and screened potential biomarkers. The enrichment analysis of differential expressed genes (DEGs) was performed by transcriptomics. Finally, the regulatory targets of CR on potential biomarkers were obtained by combined analysis, and the relevant key targets were verified by western blotting.Results: CR improved serum and liver homogenate indexes and alleviated liver histological injury. Compared with ANIT group, the CR group had 76 differential metabolites, and 10 metabolic pathways were enriched. There were 473 DEGs significantly changed after CR treatment, most of which were enriched in the retinol metabolism, calcium signaling pathway, PPAR signaling pathway, circadian rhythm, chemokine signaling pathway, arachidonic acid metabolism, bile secretion, primary bile acid biosynthesis, and other pathways. By constructing the “compound-reaction-enzyme-gene” interaction network, three potential key-target regulation biomarkers were obtained, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter G5 (ABCG5), and sulfotransferase2A1(SULT2A1), which were further verified by western blotting. Compared with the ANIT group, the CR group significantly increased the expression of ABCG5 and SULT2A1, and the expression of HMGCR significantly decreased.Conclusion: Combined metabolomic and transcriptomic analyses show that CR has a therapeutic effect on IC through regulation of the biosynthesis of bile acids and bilirubin in the bile secretion pathway and regulation of the expression of HMGCR, ABCG5, and SULT2A1.

Abstract Background Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR. Methods We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM. Results 5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64–0.89, P = 0.001; HR: 0.78, 95% CI 0.66–0.93, P = 0.006; HR: 0.81, 95% CI 0.68–0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27–0.63, P

Enterovirus G (EV-G) is prevalent in pig populations worldwide, and a total of 20 genotypes (G1 to G20) have been confirmed. Recently, recombinant EV-Gs carrying the papain-like cysteine protease (PLCP) gene of porcine torovirus have been isolated or detected, while their pathogenicity is poorly understood. In this study, an EV-G17-PLCP strain, ‘EV-G/YN23/2022’, was isolated from the feces of pigs with diarrhea, and the virus replicated robustly in numerous cell lines. The isolate showed the highest complete genome nucleotide (87.5%) and polyprotein amino acid (96.6%) identity in relation to the G17 strain ‘IShi-Ya4’ (LC549655), and a possible recombination event was detected at the 708 and 3383 positions in the EV-G/YN23/2022 genome. EV-G/YN23/2022 was nonlethal to piglets, but mild diarrhea, transient fever, typical skin lesions, and weight gain deceleration were observed. The virus replicated efficiently in multiple organs, and the pathological lesions were mainly located in the small intestine. All the challenged piglets showed seroconversion for EV-G/YN23/2022 at 6 to 9 days post-inoculation (dpi), and the neutralization antibody peaked at 15 dpi. The mRNA expression levels of IL-6, IL-18, IFN-α, IFN-β, and ISG-15 in the peripheral blood mononuclear cells (PBMCs) were significantly up-regulated during viral infection. This is the first documentation of the isolation and pathogenicity evaluation of the EV-G17-PLCP strain in China. The results may advance our understanding of the evolution characteristics and pathogenesis of EV-G-PLCP.

Abstract We tested the hypothesis that soil texture and nitrogen (N) fertilisation are the primary factors regulating the N cycle and soil bacterial community structure. The response of soil bacterial communities to N fertilisation in different textured soils might help in identifying the specific underlying mechanism and hence management of N fertiliser application in fields. We examined how N fertiliser accumulates in flue-cured tobacco and influences soil bacterial community structure in different textured soils. We conducted plot and micro-plot experimental measurements of N content in soil and tobacco samples using the KNO3 15N isotope technique. Soil bacterial community structure was determined using high-throughput sequencing of 16S rRNA. Nitrogen absorption and utilisation by tobacco plants were highest in sandy loam soils, followed by loam soil and clay loam. The ability of clay loam to supply N was weak during the plant growth period. Absence of fertilisation could reduce bacterial abundance in soils to various degrees. Bacterial diversity was higher in sandy loam soil than in loam soil and clay loam. Soil texture and N fertilisation significantly affected soil bacterial community structure and diversity. Proteobacteria, Acidobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Chloroflexi were the dominant bacterial phyla, while Bacillus, Nitrobacter, Nitrosospira, Nitrospira, and Rhizobium were the primary N transformation bacteria at the genus level in all treatments. However, relative abundances differed with N fertiliser application, which could lead to differential N availability and N use efficiency of tobacco among soil types. We conclude that both soil texture and N fertilisation influence N accumulation and distribution in flue-cured tobacco and thus regulate soil bacterial communities. N fertiliser application in sandy loam soil should be strictly controlled for its higher N use efficiency, soil bacterial abundance, and diversity.

Introductionbluetongue virus (BTV) infection triggers dramatic and complex changes in the host's transcriptional profile to favor its own survival and reproduction. However, there is no whole-transcriptome study of susceptible animal cells with BTV infection, which impedes the in-depth and systematical understanding of the comprehensive characterization of BTV-host interactome, as well as BTV infection and pathogenic mechanisms.Methodsto systematically understand these changes, we performed whole-transcriptome sequencing in BTV serotype 1 (BTV-1)-infected and mock-infected sheep embryonic testicular cells, and subsequently conducted bioinformatics differential analyses.Resultsthere were 1504 differentially expressed mRNAs, 78 differentially expressed microRNAs, 872 differentially expressed long non-coding RNAs, and 59 differentially expressed circular RNAs identified in total. Annotation from the Gene Ontology, enrichment from the Kyoto Encyclopedia of Genes and Genomes, and construction of competing endogenous RNA networks revealed differentially expressed RNAs primarily related to virus-sensing and signaling transduction pathways, antiviral and immune responses, inflammation, and development and metabolism related pathways. Furthermore, a protein-protein interaction network analysis found that BTV may contribute to abnormal spermatogenesis by reducing steroid biosynthesis. Finally, real-time quantitative PCR and western blotting results showed that the expression trends of differentially expressed RNAs were consistent with the whole-transcriptome sequencing data.Discussionthis study provides more insights of comprehensive characterization of BTV-host interactome, and BTV infection and pathogenic mechanisms.

Abstract Background The number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets. Methods Streptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA–mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage. Results Using second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA–mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies. Conclusions miRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.

This study aimed to evaluate the association of lipoprotein(a) levels with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention (PCI), and to investigate the ischemic outcome on this population. Lipoprotein(a) and modified thrombelastography were measured in 6601 consecutive patients underwent PCI on dual antiplatelet therapy. Cox proportional regression analysis was applied to illustrate the ischemic events in a 2-year follow up. The mean levels of lipoprotein(a) were 29.0 mg/dl. Patients with higher lipoprotein(a) levels had significantly accelerated fibrin generation (lower K time and bigger α angle) and greater clot strength (higher maximum amplitude (MA)) than patients with lower lipoprotein(a) levels (P

Abstract Background Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). Methods 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. Results FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P

Pseudorabies virus (PRV) is widely prevalent in China, which can transmit from pigs to other mammals. Moreover, a PRV variant isolated from an acute human encephalitis case was documented recently. It is imperative to investigate PRV epidemiology in pigs, the knowledge regarding pseudorabies (PR) and self-protection behaviors upon working among relevant practitioners including pig farmers, pig cutters, and pork salesman. In the present study, 18,812 pig serum samples and 1,634 tissue samples were collected from Hunan Province during the period of 2020 to 2021 for detecting the presence of PRV gE-special antibody and nucleic acids, respectively. Meanwhile, we conducted a questionnaire survey about PR among these practitioners in China. The results showed that nearly 9% (1,840/20,192) pigs from 161 collected sites (20.17%, 161/797) were seropositive for PRV-gE antibody. Though only 2.33% tissue samples were positive for PRV nucleic acids, all the representative PRV strains were variant. It was learned that most practitioners were frequently injured when working, the injured sites mainly included hand and foot. Among the three transmission routes of PRV, the aerosol transmission route was often overlooked. Moreover, the workers lacked self-protection awareness and were poor conscious about PRV and its potential threat to humans. All the results demonstrate that PRV remains widely spread in pig populations, while the potential threats of PRV in pig industry receive less attention, suggesting that targeted educational programs to these people should be performed.

Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride–glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24–2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.

Background: Based on the theory of “five Zang-organs corresponding to the seasons” in traditional Chinese medicine (TCM), physiological functions including emotions vary with the seasons. We aimed to investigate the seasonal photoperiod effects of melatonin (MT) released from the pineal gland on the MT receptor (MTR)-Gs/Gi-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in the hippocampus. Methods: Rats were divided into three groups: control, operation (surgery with pineal gland removal), and pseudo-operation groups (same surgery as operation group but without removing pineal gland), and fed at specific time across the four seasons. The levels of MTR, adenylate cyclase (AC), cAMP, PKA, and CREB in the hippocampus were analyzed using ELISA. The concentrations of Gs and Gi were analyzed using Western blot. The expression of CREB mRNA was detected by PCR. Results: For intragroup comparisons, compared with spring, the levels of Gs/Gi in the control group were higher in summer, autumn, and winter (P = .009 in summer; P

BackgroundHyperuricemia has recently been identified as a risk factor of cardiovascular diseases; however, prognostic value of hyperuricemia in patients with ST-segment elevation myocardial infarction (STEMI) remained unclear. Simultaneously, the mechanism of this possible relationship has not been clarified. At present, some views believe that hyperuricemia may be related to the inflammatory response. Our study aimed to investigate the association between hyperuricemia and long-term poor prognosis and inflammation in STEMI patients undergoing percutaneous coronary intervention (PCI).MethodsA total of 1,448 consecutive patients with STEMI were studied throughout 2013 at a single center. The primary endpoint was all-cause death at 2- and 5-year follow-up. Inflammatory biomarkers were collected on admission of those patients: high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count.ResultsHyperuricemia was associated with higher 2- and 5-year all-cause death in STEME patients compared to normouricemia (5.5% vs. 1.4%, P 0.05).ConclusionsHyperuricemia was associated with higher risks of 2- and 5-year all-cause deaths in patients with STEMI undergoing PCI. However, this study did not find a correlation between hyperuricemia and inflammatory responses in newly admitted STEMI patients.

Objective To analyse the association between on-treatment platelet reactivity (TPR) and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. Methods This prospective observational study enrolled patients with coronary artery disease (CAD) that underwent percutaneous coronary intervention (PCI). Patients with ACS and TP under dual antiplatelet therapy were selected for analysis. The 2- and 5-year clinical outcomes were evaluated among patients with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), as tested by thromboelastogram at baseline. Results A total of 10 724 patients with CAD that underwent PCI were identified. Of these, 474 patients with ACS and TP met the inclusion criteria: 124 (26.2%) with HTPR, 163 (34.4%) with LTPR and 187 (39.5%) with NTPR. The 5-year rates of all-cause death, major adverse cardiovascular and cerebrovascular events, cardiac death, myocardial infarction, revascularization, stroke and bleeding were not significantly different among the three groups. Multivariate Cox regression analysis demonstrated that patients with HTPR were not independently associated with any of the 5-year endpoints compared with patients with NTPR. Conclusions TPR at baseline was not independently associated with long-term outcomes in patients with ACS and TP that underwent PCI.

This study sought to investigate the prevalence and prognostic significance of malnutrition in patients with an abnormal glycemic status and coronary artery disease (CAD). This secondary analysis of a multicenter prospective cohort included 5710 CAD patients with prediabetes and 9328 with diabetes. Four objective tools were applied to assess the nutritional status of the study population. The primary endpoint was all-cause death. The association of malnutrition with clinical outcomes was examined using Cox proportional hazards regression. The proportion of malnutrition varied from 8% to 57% across the assessment tools. Diabetic patients were more likely to be malnourished than prediabetic patients. During a median follow-up of 2.1 years, 456 all-cause deaths occurred. The adjusted hazard ratios and 95% confidence interval for all-cause deaths of moderate–severe malnutrition defined by different tools ranged from 1.59 (1.03, 2.46) to 2.08 (0.92, 4.73) in prediabetic patients and 1.51 (1.00, 2.34) to 2.41 (1.78, 3.27) in diabetic patients. In conclusion, malnutrition is not rare in CAD patients with abnormal glycemic status. Moderate–severe malnutrition strongly predicted all-cause death regardless of the assessment tool. Assessing the nutritional status for all CAD patients with prediabetes and diabetes to identify individuals at high risk of all-cause death may help the risk assessment and prognosis improvement.

Encapsulating bioactive avenanthramides (AVAs) in carriers to respond to the environmental changes of food thermal processing allows the controlled release of AVAs for the effective inhibition of biohazards. In this study, fluorescent molecular imprinted polymers (FMIPs) loaded with AVAs were prepared by reverse microemulsion. The fluorescent signal was generated by carbon dots (CDs), which were derived from oat bran to determine the load of AVAs. The FMIPs were uniformly spherical in appearance and demonstrated favorable properties, such as thermal stability, protection of AVAs against photodegradation, high encapsulation efficiency, and effective scavenging of free radicals. After consideration of the different kinetics models, the release of AVAs from the FMIPs matched the Weibull model and followed a Fickian diffusion mechanism. The FMIPs exhibited good inhibition of pyrraline in a simulated casein-ribose system and in milk samples, indicating the release of AVAs could inhibit the generation of pyrraline.

This study aimed to evaluate the platelet reactivity in real-world patients with different chronic kidney disease (CKD) stages after percutaneous coronary intervention (PCI), and to examine whether high residual platelet reactivity (HRPR) is associated with higher incidence of adverse cardiovascular events in a 2-year follow up. A total of 10 724 consecutive patients receiving DAPT with aspirin and clopidogrel after PCI throughout 2013 were enrolled. We applied modified thromboelastography (mTEG) in 6745 patients. Kaplan–Meier analysis and Cox proportional regression analysis were applied to illustrate end points for patients. The prevalence of HRPR for adenosine diphosphate (ADP) was higher in patients with CKD3-5 than patients with CKD1-2 (47.0% vs. 37.3%, p = 0.002), but not for arachidonic acid (AA). No significant difference was observed for MACCE between patients with or without HRPR for ADP (HR 1.004, 95%CI: 0.864–1.167, p = 0.954). Patients with HRPR for ADP was associated with less bleeding events than patients without HRPR for ADP (HR 0.795, 95%CI: 0.643–0.982, p = 0.034). In this large cohort of real-world patients after PCI, the deterioration of renal function was linked to HRPR for ADP. HRPR was not associated with MACCE in patients with CKD in a 2-year follow up. Bleeding risks were significantly lower in PCI patients with versus without HRPR for ADP.

Background: We found a positive correlation between the prior stroke history and recurrent stroke in patients who underwent percutaneous coronary intervention (PCI) in our previous study, which indicated the close interaction of stroke and cardiovascular diseases. However, it is unclear whether prior stroke is still associated with worse prognosis at a longer follow-up period.Methods: A total of 10,724 coronary heart disease (CHD) patients who received PCI from January to December 2013 were prospectively enrolled and were subsequently divided into the prior stroke (n = 1,150) and non-prior stroke (n = 9,574) groups according to their history. Baseline characteristics and 5-year outcomes were recorded.Results: Patients with prior stroke had more clinical risk factors, as well as more extensive coronary artery lesions. Although in-hospital outcomes were similar between patients from the two groups, the 5-year follow-up result revealed that patients with prior stroke experienced higher incidence of stroke, major adverse cardiac and cerebrovascular events (MACCEs), all-cause death, and cardiac death (7.0 vs. 3.0%, p < 0.001; 25.9 vs. 20.3%, p < 0.001; 5.3 vs. 3.5%, p = 0.002; 3.1 vs. 2.1%, p = 0.032, respectively). After the propensity score matching, the 5-year stroke rate was still higher in the prior stroke group (6.8 vs. 3.4%, p = 0.001). The multivariable regression analysis also identified the prior stroke as a risk predictor of the 5-year stroke (HR = 2.011, 95% CI: 1.322–3.059, p = 0.001).Conclusions: Coronary heart disease patients with prior stroke who received PCI had a higher incidence of 5-year long-term adverse cardiovascular and cerebrovascular events, especially recurrent stroke. Prior stroke was a strong risk predictor of future stroke events.

Background: Despite substantial improvement in chronic total occlusions (CTO) revascularization technique, the long-term clinical outcomes in diabetic patients with revascularized CTO remain controversial. Our study aimed to investigate the 5-year cardiovascular survival for patients with or without type 2 diabetes mellitus (DM) who underwent successful percutaneous coronary intervention (PCI) for CTO.Methods: Data of the current analysis derived from a large single-center, prospective and observational cohort study, including 10,724 patients who underwent PCI in 2013 at Fuwai Hospital. Baseline, angiographic and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which consisted of death, recurrent myocardial infarction (MI), stroke and target vessel revascularization (TVR). The secondary endpoint was all-cause mortality. Cox regression analysis and propensity-score matching was performed to balance the baseline confounders.Results: A total of 719 consecutive patients with ≥1 successful CTO-PCI were stratified into diabetic (n = 316, 43.9%) and non-diabetic (n = 403, 56.1%) group. During a median follow-up of 5 years, the risk of MACCE (adjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.08–2.00, P = 0.013) was significantly higher in the diabetic group than in the non-diabetic group, whereas the adjusted risk of all-cause mortality (HR 2.37, 95% CI 0.94–5.98, P = 0.068) was similar. In the propensity score matched population, there were no significant differences in the risk of MACCE (HR 1.27, 95% CI 0.92–1.75, P = 0.155) and all-cause mortality (HR 2.56, 95% CI 0.91–7.24, P = 0.076) between groups. Subgroup analysis and stratification analysis revealed consistent effects on 5-year MACCE across various subgroups.Conclusions: In patients who received successful CTO-PCI, non-diabetic patients were related to better long-term survival benefit in terms of MACCE. The risk of 5-year MACCE appeared to be similar in less-controlled and controlled diabetic patients after successful recanalization of CTO. Further randomized studies are warranted to confirm these findings.

BackgroundIn euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether free triiodothyronine to free thyroxine (FT3/FT4) ratio can predict the recurrence of cardiovascular events (CVEs). We aim to investigate its association with recurrent long-term adverse events in this population.Methods3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T12.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death.ResultsThe median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P

Muscle regeneration depends on self-renewal of muscle stem cells but how this is regulated on aging is unclear. Here, the authors identify Slug as regulating p16 Ink4a in quiescent muscle stem cells, and when Slug expression reduces in aged stem cells, p16Ink4a accumulates, causing regenerative defects.

AGO2 is a core component of the RNAi machinery and contributes to plant immunity during bacterial infection. Here the authors show that AGO2 activity is suppressed by arginine methylation which not only promotes AGO2 degradation but also recruits TSN proteins to degrade AGO2-associated small RNAs.

As a special polyphenolic compound in oats, the physiological function of oat avenanthramides (AVAs) drives a variety of biological activities, and plays an important role in the prevention and treatment of common chronic diseases. In this study, the optimum extraction conditions and structural identification of AVAs from oats was studied. The inhibitory effect of AVAs from oats on advanced glycation end-products (AGEs) in a glucose–casein simulation system was evaluated, and this revealed dose-dependent inhibitory effects. The trapping capacity of AVAs to the α-dicarbonyl compounds of AGE intermediate products was determined by HPLC–MS/MS, and the results indicate that AVA 2c, AVA 2p, and AVA 2f exhibited the ability to capture α-dicarbonyl compounds. More importantly, AVA 2f was found to be more efficient than AVA 2p at inhibiting superoxide anion radical (O2−), hydroxyl radical (OH), and singlet oxygen (1O2) radical generation, which may be the main reason that AVA 2f was more efficient than AVA 2p in AGE inhibition. Thus, this research presents a promising application of AVAs from oats in inhibiting the food-borne AGEs formed in food processing.

In recent years, the prevalence of pseudorabies virus (PRV) has caused huge economic losses to the Chinese pig industry. Meanwhile, PRV infection in humans also sounded the alarm about its cross-species transmission from pigs to humans. To study the regional PRV epidemic, serological and epidemiological investigations of PRV in pig populations from Yunnan Province during 2017–2021 were performed. The results showed that 31.37% (6324/20,158, 95% CI 30.73–32.01) of serum samples were positive for PRV glycoprotein E (gE)-specific antibodies via enzyme-linked immunosorbent assay (ELISA). The risk factors, including the breeding scale and development stage, were significantly associated with PRV seroprevalence among pigs in Yunnan Province. Of the 416 tissue samples collected from PRV-suspected pigs in Yunnan Province, 43 (10.33%, 95% CI 7.41–13.26) samples were positive for PRV-gE nucleic acid in which 15 novel PRV strains from these PRV-positive samples were isolated, whose gC and gE sequences were analyzed. Phylogenetic analysis showed that all 15 isolates obtained in this study belonged to the genotype II. Additionally, the gC gene of one isolate (YuN-YL-2017) was genetically closer to variant PRV strains compared with others, while the gE gene was in the same clade with other classical PRV strains, indicating that this isolate might be a recombinant strain generated from the classical and variant strains. The results revealed the severe PRV epidemic in Yunnan Province and indicated that PRV variants are the major genotypes threatening the pig industry development.

Acute myeloid leukemia (AML) is a highly heterogeneous disease that requires fine-grained risk stratification for the best prognosis of patients. As a class of small non-coding RNAs with important biological functions, microRNAs play a crucial role in the pathogenesis of AML. To assess the prognostic impact of miR-20b on AML in the presence of other clinical and molecular factors, we screened 90 AML patients receiving chemotherapy only and 74 also undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. In the chemotherapy-only group, high miR-20b expression subgroup had shorter event-free survival (EFS) and overall survival (OS, both P < 0.001); whereas, there were no significant differences in EFS and OS between high and low expression subgroups in the allo-HSCT group. Then we divided all patients into high and low expression groups based on median miR-20b expression level. In the high expression group, patients treated with allo-HSCT had longer EFS and OS than those with chemotherapy alone (both P < 0.01); however, there were no significant differences in EFS and OS between different treatment subgroups in the low expression group. Further analysis showed that miR-20b was negatively correlated with genes in “ribosome,” “myeloid leukocyte mediated immunity,” and “DNA replication” signaling pathways. ORAI2, the gene with the strongest correlation with miR-20b, also had significant prognostic value in patients undergoing chemotherapy but not in the allo-HSCT group. In conclusion, our findings suggest that high miR-20b expression is a poor prognostic indicator for AML, but allo-HSCT may override its prognostic impact.