Search

Abstract Objective The aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear. Methods Serum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI. Results Significantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P

In order to improve the impact toughness of polyamide 1012 (PA1012) by reducing the amount of hydrogen bonding resulting from PA1012 itself, 3-pentadecylphenol (PDP) was considered to be added into PA1012 using melting extrusion. The hydrogen bonding interaction between PA1012 and PDP was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). The effects of PDP on the crystallization, melting process, and mechanical behavior of PA1012 were tested in detail. The results show that the PDP can reduce the temperature of PA1012 crystallization and melting but it can significantly improve elongation at break and impact toughness. The notched impact strength of the PA1012/PDP composites containing 20 wt% PDP reached to 70.6 kJ·m–2, which is about seven times that of the neat PA1012. The effects of PDP on PA1012 properties is ascribed to hydrogen bonding interaction between hydrogen bonding between phenol hydroxyl groups and amino groups on PA1012 chains. The deduction was also verified by adding acetylated 3-pentadecylphenol (APDP) to modify PA1012. It is believed the research will open up new prospects for the wide application of PA1012 toughening.

Objectives:. The aim of this multicenter, prospective, single-arm pilot study (ClinicalTrials.gov number: NCT05040074) was to observe the procedural and 30-day results of the novel transcatheter mitral valve repair system, SQ-Kyrin®-M Clip (Shenqi Medical, Shanghai, China), in patients with severe mitral regurgitation (MR). Methods:. The heart team considered patients from 5 centers in China with clinically significant functional mitral regurgitation ≥3+ despite optimal medical therapy or degenerative mitral regurgitation ≥3+ with high surgical risk as candidates for transcatheter repair. All patients received transcatheter edge-to-edge mitral valve repair under general anesthesia. The primary outcome was technical success, which included all of the following measured at the exit from the catheterization laboratory: (1) absence of procedural mortality; (2) successful access, delivery, and retrieval of the device delivery system; (3) successful deployment and correct positioning of the first intended device; and (4) no emergency surgery or reintervention related to the device or access procedure. The secondary outcomes included all-cause mortality, serious adverse events, device success, and procedural success 30 d after the intervention. Results:. From June 2021 to December 2021, 18 patients were enrolled in this study with age (75.7 ± 7.4) years. Fifteen patients had MR 4+, while 3 had MR 3+. Technical success was achieved in all patients, including 6 degenerative mitral regurgitation and 12 functional mitral regurgitation patients. There was no all-cause mortality at 30 d. One patient had single leaflet device attachment within 30 d, which was regarded as a serious adverse event, and the patient was successfully treated with reintervention by implanting another clip. Another patient’s transmitral gradient was 6 mmHg (>5 mmHg), with an effective orifice area of 2.57 cm2 after the procedure. Sixteen patients had device success and procedural success at 30 d postoperation. Fourteen patients had MR 1+, 3 had MR 2+, and only 1 patient had MR 3 + 30 d after the procedure. Conclusions:. The results of this feasibility study showed the efficacy and safety of the SQ-Kyrin®-M device in the Chinese population with severe MR, laying a solid foundation for a subsequent large-scale confirmatory study.

Abstract Background Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. Objectives This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. Materials and methods Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. Results Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. Conclusions Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Ophiuroids, the most diverse group of echinoderms, inhabit a vast array of ecological niches and play vital roles in benthic ecosystems as suspension feeders, scavengers and opportunists. Despite the important ecological roles played by Ophiuroidea, their evolutionary history and phylogenetic relationship is not yet fully understood. In this study, 47 mitochondrial genomes of ophiuroids, including 21 newly sequenced ones, were analyzed. tRNA duplication was firstly discovered in four species and a new start codon was identified for Ophiuroidea. Eighteen phylogenetic trees based on mitochondrial genomes consistently supported two major lineages, Ophintegrida and Euryophiurida. It further confirmed the monophyly of Euryalida and Ophiurida, respectively, as well as families represented by multiple species. Among 18 trees, only the two ML trees based on amino acid sequences using IQtree method supported monophyly of Amphilepidida and Ophiacanthida, consistent with current phylogenetic system of Ophiuroidea. This result highlighted the effect of phylogenetic analysis methods and datasets on tree topology, indicating that amino acid sequence data maybe more suitable for higher taxonomic level phylogenetic analysis of ophiuroids than nucleotide sequences. Four new gene orders of 13 protein-coding genes + two rRNAs and 12 new gene orders of all 37 genes were identified. Mitochondrial gene orders were highly variable in Ophiacanthida, but were extremely conserved in Eurylida. Additionally, both branch lengths and estimated positive selection varied among the four orders, and a positive relationship between branch lengths and mitochondrial gene rearrangement rates was revealed, suggesting distinctly different evolutionary history among the four major clades of Ophiuroidea. Overall, we (1) reconstructed the phylogenetic relationship based on mitochondrial genome, supporting the current phylogenetic system in Ophiuroidea, (2) revealed a high variability in mitochondrial gene rearrangement among the four orders, (3) provided the first evidence to link gene rearrangement and nucleotide substitution in Echinodermata.

Studies have demonstrated that donkey milk (DM) displays anti-tumor activity. In this study, we investigated the role and underlying mechanism of DM in the progression of 4T1 breast tumors in mice. We found that DM significantly reduced tumor volumes and tumor weights in 4T1-treated mice. Simultaneously, DM ameliorated the pathological changes in spleen, liver and lung tissues of 4T1 tumor-bearing mice. WB results showed that DM inducing the expression of Bax and pyroptosis-related proteins, and inhibiting the expression of Bcl-2 in tumors. Besides, DM up-regulation of Th1 cytokines and down-regulation of Th2/Treg cytokines in the tumors and spleen. Moreover, DM significantly decreased the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-STAT5/STAT5, as well as up-regulation the ratio of p-STAT4/STAT4 in tumors and spleen. Our data suggest that DM inhibit the growth of mouse 4T1 tumors by inducing apoptosis and pyroptosis, as well as promoting Th1 cell activation and quelling immunosuppression from Tregs.

In order to improve the inherent flammability of polylactic acid (PLA) and make this new biodegradable material more widely used, B-modified ZSM-5 (B/Z5) was designed as synergistic agent of intumescent flame retardant (IFR), composed of ammonium polyphosphate (APP) and pentaerythritol (PER), and introduced into PLA/IFR (PLAs) to fabricate PLAs/B/Z5 composites by melt extrusion. The flame retardancy, surface morphology, and thermal stability of the composites were investigated by TG, LOI, UL-94, CCT, and SEM. The addition of B/Z5 makes the decomposition temperature of T5% as well as T10% of PLAs reduction in nitrogen atmosphere and carbon layer form in advance. UL-94 test shows the composites reach V-0 rating. LOI value also steadily increases, and the maximum value is 36.0% with B actual loading of 5.26% (recoded as 14B/Z5) in B/Z5. The PHRR decreases by 75% from 417.77 kW/m2 for pure PLA to 103.19 kW/m2 for PLAs/14B/Z5, and THR reduces from 92.78 to 19.26 MJ/m2, which decreases by about 80% and the char yield reaches 50%. This study provides a simple and green method for the preparation of high flame-retardant PLA, which has a broad practical application prospect.

Abstract Background MicroRNA (miRNA) has been shown to play a key role in the occurrence and progression of diseases, making uncovering miRNA-disease associations vital for disease prevention and therapy. However, traditional laboratory methods for detecting these associations are slow, strenuous, expensive, and uncertain. Although numerous advanced algorithms have emerged, it is still a challenge to develop more effective methods to explore underlying miRNA-disease associations. Results In the study, we designed a novel approach on the basis of deep autoencoder and combined feature representation (DAE-CFR) to predict possible miRNA-disease associations. We began by creating integrated similarity matrices of miRNAs and diseases, performing a logistic function transformation, balancing positive and negative samples with k-means clustering, and constructing training samples. Then, deep autoencoder was used to extract low-dimensional feature from two kinds of feature representations for miRNAs and diseases, namely, original association information-based and similarity information-based. Next, we combined the resulting features for each miRNA-disease pair and used a logistic regression (LR) classifier to infer all unknown miRNA-disease interactions. Under five and tenfold cross-validation (CV) frameworks, DAE-CFR not only outperformed six popular algorithms and nine classifiers, but also demonstrated superior performance on an additional dataset. Furthermore, case studies on three diseases (myocardial infarction, hypertension and stroke) confirmed the validity of DAE-CFR in practice. Conclusions DAE-CFR achieved outstanding performance in predicting miRNA-disease associations and can provide evidence to inform biological experiments and clinical therapy.

In high-risk patients with pure native aortic regurgitation (PNAR), transcatheter aortic valve replacement (TAVR) remains an off-label intervention. Due to anatomical variations in the aortic root and technical challenges unique to PNAR, the transfemoral approach (TF-TAVR) requires continued accumulation of experience and technological refinement. In this context, we successfully and safely performed a snare-assisted TF-TAVR procedure for a patient with PNAR, characterized by significant aortic angulation. We introduced an innovative technique termed “snare-assisted coaxiality optimized technique” (SACOT) during valve deployment. SACOT played a crucial role in optimizing valve positioning, enhancing coaxiality, and achieving the ideal implantation depth for PNAR. Post-procedure assessments demonstrated stability and the absence of paravalvular regurgitation (PVR).

Environmental stressors can induce paternal epigenetic modifications that are a key determinant of the intergenerational inheritance of acquired phenotypes in mammals. Some of them can affect phenotypic expression through inducing changes in tRNA-derived small RNAs (tsRNAs), which modify paternal epigenetic regulation in sperm. However, it is unclear how these stressors can affect changes in the expression levels of tsRNAs and their related endonucleases in the male reproductive organs. We found that Ribonuclease inhibitor 1 (RNH1), an oxidation responder, interacts with ANG to regulate sperm tsRNA generation in the mouse caput epididymis. On the other hand, inflammation and oxidative stress induced by either lipopolysaccharide (LPS) or palmitate (PA) treatments weakened the RNH1-ANG interaction in the epididymal epithelial cells (EEC). Accordingly, ANG translocation increased from the nucleus to the cytoplasm, which led to ANG upregulation and increases in cytoplasmic tsRNA expression levels. In conclusion, as an antioxidant, RNH1 regulates tsRNA generation through targeting ANG in the mouse caput epididymis. Moreover, the tsRNA is an epigenetic factor in sperm that modulates paternal inheritance in offspring via the fertilization process.

Abstract Background Chronic kidney disease (CKD) accelerates atherosclerosis, but the mechanisms remain unclear. Tyrosine sulfation has been recognized as a key post-translational modification (PTM) in regulation of various cellular processes, and the sulfated adhesion molecules and chemokine receptors have been shown to participate in the pathogenesis of atherosclerosis via enhancement of monocyte/macrophage function. The levels of inorganic sulfate, the essential substrate for the sulfation reaction, are dramatically increased in patients with CKD, which indicates a change of sulfation status in CKD patients. Thus, in the present study, we detected the sulfation status in CKD patients and probed into the impact of sulfation on CKD-related atherosclerosis by targeting tyrosine sulfation function. Results PBMCs from individuals with CKD showed higher amounts of total sulfotyrosine and tyrosylprotein sulfotransferase (TPST) type 1 and 2 protein levels. The plasma level of O-sulfotyrosine, the metabolic end product of tyrosine sulfation, increased significantly in CKD patients. Statistically, O-sulfotyrosine and the coronary atherosclerosis severity SYNTAX score positively correlated. Mechanically, more sulfate-positive nucleated cells in peripheral blood and more abundant infiltration of sulfated macrophages in deteriorated vascular plaques in CKD ApoE null mice were noted. Knockout of TPST1 and TPST2 decreased atherosclerosis and peritoneal macrophage adherence and migration in CKD condition. The sulfation of the chemokine receptors, CCR2 and CCR5, was increased in PBMCs from CKD patients. Conclusions CKD is associated with increased sulfation status. Increased sulfation contributes to monocyte/macrophage activation and might be involved in CKD-related atherosclerosis. Inhibition of sulfation may suppress CKD-related atherosclerosis and is worthy of further study.

Abstract Background The associations between obesity and abnormalities of upper and lower extremity arteries remain to be elucidated. This study is aimed to investigate whether general obesity and abdominal obesity are associated with upper and lower extremity artery diseases in a Chinese community population. Methods This cross-sectional study included 13,144 participants in a Chinese community population. The associations between obesity parameters and abnormalities of upper and lower extremity arteries were evaluated. Multiple logistic regression analysis was used to assess the independence of associations between obesity indicators and abnormalities of peripheral arteries. Nonlinear relationship between body mass index (BMI) and risk of ankle-brachial index (ABI) ≤ 0.9 was evaluated using a restricted cubic spline model. Results The prevalence of ABI ≤ 0.9 and interarm blood pressure difference (IABPD) ≥ 15 mmHg in the subjects was 1.9% and 1.4% respectively. Waist circumference (WC) was independently associated with ABI ≤ 0.9 (OR 1.014, 95% CI 1.002–1.026, P = 0.017). Nevertheless, BMI was not independently associated with ABI ≤ 0.9 using linear statistical models. Meanwhile, BMI and WC were independently associated with IABPD ≥ 15 mmHg respectively (OR 1.139, 95% CI 1.100–1.181, P

Abstract Background The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. Objectives This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). Material and methods Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. Results Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P

The genus Thaumatocrinus is composed of species displaying 10 undivided arms arising from 10 radials. Thaumatocrinus naresi is also considered to be a 10-arm species, but individuals with 9 arms were also reported. Here, we report the mitochondrial genome of T. naresi with 9 arms collected from the western Pacific. The genome is 16,047 bp in length with a 67.84% AT content. It contains 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. Phylogenetic analysis shows that T. naresi forms an independent lineage within Comatulida.

β-hydroxybutyrate has been reported to have neuroprotective activity. In this study, the neuroprotective effects of BHB were investigated on a demyelination model, the cuprizone model. We found that BHB reduced demyelination, which was confirmed by western blot for myelin-oligodendrocyte glycoprotein (MOG) and myelin proteolipid protein (PLP). Following BHB treatment, the number of connexin43+ (Cx43+) + GFAP+ cells and Iba-1+ + CD16/32+ cells decreased, whereas the number of Cx47+ + oligo2+ cells and Iba-1+ + Arginase-1+ cells increased significantly. Furthermore, BHB significantly repressed the expression of MMP-9/12, and increased the expression of blood-brain barrier (BBB) markers (such as PECAM-1 and ZO-1) in CPZ mice. We report that BHB promotes M2 microglia polarization and ameliorates BBB dysfunction caused by downregulation of HDAC3, NF-κB, Aim2 and NLRP3, as well as upregulation of SIRT1 in CPZ mice. Thus, these findings suggest that BHB may be a therapeutic approach for preventing demyelinating diseases.

The recent advancements in artificial intelligence have brought about significant changes in education. In the context of intelligent campus development, target detection technology plays a pivotal role in applications such as campus environment monitoring and the facilitation of classroom behavior surveillance. However, traditional object detection methods face challenges in open and dynamic campus scenarios where unexpected objects and behaviors arise. Open-World Object Detection (OWOD) addresses this issue by enabling detectors to gradually learn and recognize unknown objects. Nevertheless, existing OWOD methods introduce two major uncertainties that limit the detection performance: the unknown discovery uncertainty from the manual generation of pseudo-labels for unknown objects and the known discrimination uncertainty from perturbations that unknown training introduces to the known class features. In this paper, we introduce a Parallel OWOD Framework with Uncertainty Mitigation to alleviate the unknown discovery uncertainty and the known discrimination uncertainty within the OWOD task. To address the unknown discovery uncertainty, we propose an objectness-driven discovery module to focus on capturing the generalized objectness shared among various known classes, driving the framework to discover more potential objects that are distinct from the background, including unknown objects. To mitigate the discrimination uncertainty, we decouple the learning processes for known and unknown classes through a parallel structure to reduce the mutual influence at the feature level and design a collaborative open-world classifier to achieve high-performance collaborative detection of both known and unknown classes. Our framework provides educators with a powerful tool for effective campus monitoring and classroom management. Experimental results on standard benchmarks demonstrate the framework’s superior performance compared to state-of-the-art methods, showcasing its transformative potential in intelligent educational environments.

Holothurians of the family Psychropotidae are widely distributed but remain the least studied deep-sea holothurians. On an expedition to the Western Pacific, six psychropotid specimens were collected by the Jiaolong Human Operated Vehicle (HOV). Through morphological examination, four of them were identified as a new species, Benthodytes jiaolongi sp. nov., which was characterized as having minute papillae, a narrow brim, and a terminal anus; and the ossicles were rods and primary crosses. The remaining two specimens were identified as Psychropotes verrucicaudatus Xiao, Gong, Kou & Li, 2019, first recorded at the Kyushu-Palau Ridge. The phylogenetic analysis showed that B. jiaolongi sp. nov. and P. verrucicaudatus were embedded in the clades Benthodytes and Psycheotrephes, respectively, and that Benthodytes was paraphyletic. The new species clustered with Benthodytes sanguinolenta and was separated from the clade containing the other Benthodytes species.

Background Myocardial infarction (MI) is characterized by the emergence of dead or dying cardiomyocytes and excessive immune cell infiltration after coronary vessel occlusion. However, the complex transcriptional profile, pathways, cellular interactome, and transcriptional regulators of immune subpopulations after MI remain elusive. Methods and Results Here, male C57BL/6 mice were subjected to MI surgery and monitored for 1 day and 7 days, or sham surgery for 7 days, then cardiac CD45‐positive immune cells were collected for single‐cell RNA sequencing to determine immune heterogeneity. A total of 30 135 CD45+ immune cells were partitioned into macrophages, monocytes, neutrophils, dendritic cells, and T or B cells for further analysis. We showed that macrophages enriched for Olr1 and differentially expressed Gpnmb represented 2 crucial ischemia‐associated macrophages with distinct proinflammatory and prophagocytic capabilities. In contrast to the proinflammatory subset of macrophages enriched for Olr1, Gpnmb‐positive macrophages exhibited higher phagocytosis and fatty acid oxidation preference, which could be abolished by etomoxir treatment. In addition to macrophages, MI triggered prompt recruitment of neutrophils into murine hearts, which constituted the sequential cell‐fate from naïve S100a4‐positive, to activated Sell‐high, to aging Icam1‐high neutrophils. In silico tools predicted that the excessively expanded neutrophils at 1 day were attributed to chemokine C‐C motif ligand/chemokine C‐X‐C motif ligand pathways, whereas CD80/inducible T‐cell costimulator (ICOS) signaling was responsible for the immunosuppressive response at day 7 after MI. Finally, the Fos/AP‐1 (activator protein 1) regulon was identified as the critical regulator of proinflammatory responses, which was significantly activated in patients with dilated cardiomyopathy and ischemic cardiomyopathy. We showed the enriched Fos/AP‐1 target gene loci in genome‐wide association study signals for coronary artery diseases and MI. Targeting Fos/AP‐1 with the selective inhibitor T5224 blunted leukocyte infiltration and alleviated cardiac dysfunction in the preclinical murine MI model. Conclusions Taken together, this single‐cell RNA sequencing data lay the groundwork for the understanding of immune cell heterogeneity and dynamics in murine ischemic hearts. Moreover, Fos/AP‐1 inhibition mitigates inflammatory responses and cardiac dysfunction, which might provide potential therapeutic benefits for heart failure intervention after MI.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of central nervous system (CNS). Aging is the most significant risk factor for the progression of MS. Dietary modulation (such as ketogenic diet) and caloric restriction, can increase ketone bodies, especially β-hydroxybutyrate (BHB). Increased BHB has been reported to prevent or improve age-related disease. The present studies were performed to understand the therapeutic effect and potential mechanisms of exogenous BHB in cuprizone (CPZ)-induced demyelinating model. In this study, a continuous 35 days CPZ mouse model with or without BHB was established. The changes of behavior function, pathological hallmarks of CPZ, and intracellular signal pathways in mice were detected by Open feld test, Morris water maze, RT-PCR, immuno-histochemistry, and western blot. The results showed that BHB treatment improved behavioral performance, prevented myelin loss, decreased the activation of astrocyte as well as microglia, and up-regulated the neurotrophin brain-derived neurotrophic factor in both the corpus callosum and hippocampus. Meanwhile, BHB treatment increased the number of MCT1+ cells and APC+ oligodendrocytes. Furthermore, the treatment decreased the expression of HDAC3, PARP1, AIF and TRPA1 which is related to oligodendrocyte (OL) apoptosis in the corpus callosum, accompanied by increased expression of TrkB. This leads to an increased density of doublecortin (DCX)+ neuronal precursor cells and mature NeuN+ neuronal cells in the hippocampus. As a result, BHB treatment effectively promotes the generation of PDGF-Ra+ (oligodendrocyte precursor cells, OPCs), Sox2+ cells and GFAP+ (astrocytes), and decreased the production of GFAP+ TRAP1+ cells, and Oligo2+ TRAP1+ cells in the corpus callosum of mouse brain. Thus, our results demonstrate that BHB treatment efficiently supports OPC differentiation and decreases the OLs apoptosis in CPZ-intoxicated mice, partly by down-regulating the expression of TRPA1 and PARP, which is associated with the inhibition of the p38-MAPK/JNK/JUN pathway and the activation of ERK1/2, PI3K/AKT/mTOR signaling, supporting BHB treatment adjunctive nutritional therapy for the treatment of chronic demyelinating diseases, such as multiple sclerosis (MS).

Tunnels play a vital role in enhancing traffic flow and supporting public transportation systems. However, the discharge of polluted air and waste heat from vehicles passing through tunnels significantly raises the temperature inside, presenting challenges in terms of occupant comfort, tunnel safety, and infrastructure integrity. Therefore, ensuring proper temperature control is essential for their efficient operation. This study aims to investigate the phenomenon of temperature rise in ultra-long tunnels during normal operations, as limited research has been conducted in this area. The Shanghai Yangtze River Tunnel serves as a case study, utilizing temperature and air velocity data collected throughout the year (2021) from the management company. The analysis reveals that the temperature distribution near the tunnel exit is influenced by outdoor temperature fluctuations and traffic volume. The highest temperatures occur on 25 August (39.74 °C) during peak traffic hours. On-site measurements of tunnel temperature, humidity, and air velocity during winter and summer seasons yield the following results. During winter, the air temperature and wall temperature inside the tunnel experience significant increases along its length. The air temperature rises by approximately 11 °C from the entrance to the exit, while the wall temperature increases by about 15 °C. In contrast, during summer, the air temperature only rises by 2.7 °C, and the wall temperature increases by around 3 °C. Consequently, the humidity decreases along the tunnel, and this decrease is correlated with the magnitude of temperature increase. Furthermore, measurements of air velocity indicate that natural and traffic-induced winds contribute to the overall airflow inside the tunnel. A temperature data logger installed in the tunnel recorded temperature changes during the period of pandemic lockdown and subsequent recovery, spanning the spring and summer seasons. During the lockdown period, there was a relatively small increase in temperature along the tunnel, suggesting that vehicle heat dissipation is the primary factor contributing to temperature rise inside. Additionally, a method is proposed to predict the cross-sectional temperature of the tunnel using measured air velocities.

Background and aimsIntestinal flora metabolites are associated with cardiovascular (CV) diseases including heart failure (HF). The carnitine precursor trimethyllysine (TML), which participates in the generation of the atherogenic-related metabolite trimethylamine N-oxide (TMAO), was found to be related to poor prognosis in patients with CV diseases. The aim of the present study was to examine the relationship between TML and stable chronic HF.Methods and resultsIn total, 956 subjects including 471 stable chronic HF and 485 non-HF patients were enrolled in the present cohort study and subjects with stable HF were followed up for 2.0 ± 1.1 years. Serum levels of TML and TMAO were measured by liquid chromatography mass spectrometry in tandem. TML levels were significantly elevated in patients with HF compared with non-HF patients and were positively correlated with N-terminal pro-brain natriuretic peptide (NTproBNP) levels (r = 0.448, P < 0.001). TML was associated with the presence of HF after adjusting for age, sex, complications, traditional clinical factors, and TMAO (tertile 3 (T3), adjusted odds ratio (OR) 1.93, 95% confidence interval (CI) 1.19–3.13, and P = 0.007). In patients with HF, increased TML levels were associated with a composite endpoint of CV death and HF hospitalization during follow-up (T3, adjusted hazard ratio (HR) 1.93, 95% CI 1.27–2.93, and P = 0.002). Increased TML levels indicated a higher risk of CV death, re-hospitalization, and all-cause mortality.ConclusionSerum TML levels were associated with the presence and severity of HF in all subjects. High levels of TML can indicate complications and poor prognosis in HF patients.

5G base station has a significant increase in its full-load power consumption compared to 4G base stations due to multiple transceiver channels, wide bandwidth, high traffic and high transmission power.In the early stage of 5G development, since there may be scenarios without users for a long time in the current network base stations, intermittent shutdown of the base stations can play a role in energy saving.However, the intermittent shutdown of the base station saves energy and condensation occurs inside the equipment , which will cause corrosion and burn down of devices and PCB, resulting in the failure of base station equipment.The basic principle of condensation was introduced, the condensation experiment was designed and the comparative verification was carried onto the base station equipment, the causes of condensation on the base station equipment were analyzed, and finally the suggestion for the use scheme of the base station equipment to avoid condensation was given.

To explore the relationship between soluble ST2 (sST2) and metabolic syndrome (MetS) and determine whether sST2 levels can predict the presence and severity of MetS. We evaluated 550 consecutive subjects (58.91 ± 9.69 years, 50% male) with or without MetS from the Department of Vascular & Cardiology, Shanghai Jiao Ton g University-Affiliated Ruijin Hospital. Serum sST2 concentrations were measured. The participants were divided into three groups according to the sST2 tertiles. Univariate and multivariable logistic regression models were used to evaluate the association between serum sST2 concentrations and the presence of MetS. Serum sST2 concentrati ons were significantly higher in the MetS group than in those in the no MetS group (14.80 ± 7.01 vs 11.58 ± 6.41 ng/mL, P < 0.01). Subjects with more MetS components showed higher levels of sST2. sST2 was associated with the occurrence of MetS after multivariable adjustment as a continuous log-transformed variable (per 1 SD, odds ratio (OR): 1.42, 95% CI: 1.13–1.80, P < 0.01). Subgroup analysis showed that individuals with MetS have signifi cantly higher levels of sST2 than those without MetS regardless of sex and age. High serum sST2 levels were significantly and independently associated with the presence and severity of MetS. Thus, sST2 levels may be a novel biomarker and clinical predictor of MetS.

Abstract Although the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg–Nd–Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(d,l-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.

The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure–function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood–brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.

Background Chronic kidney disease (CKD) is associated with an increased risk of the progression of coronary artery disease (CAD). However, there are few data on the relationship between CAD severity and the duration of CKD. This study assessed the predictive value of the duration of kidney dysfunction in CKD patients with CAD severity. Methods In 145 patients (63.4% male, n = 92; mean age, 68.8 ± 12.8 years) with CKD, severity of CAD was assessed by coronary angiography and quantified by SYNTAX scores, and duration of kidney dysfunction was either assessed by checking historical biochemical parameters of individuals or was based on enquiries. Results Patients with high SYNTAX scores (≥ 22) had a greater prevalence of cardiovascular risk factors including age, gender, history of heart failure and smoking. In CKD patients, SYNTAX scores were positively correlated to duration of CKD and serum uric acid (UA), and negatively correlated to high-density lipoprotein-cholesterol (HDL-C) and ApoA1 levels. Univariate binary logistic regression and multivariate logistic analyses showed that SYNTAX scores correlated significantly with CKD duration, UA, and HDL-C. Receiver-operating characteristic analysis was used to explore a time point when coronary angiography application was economical and effective and yielded a Youden index of 6.5 years. Conclusions Together, our results demonstrated that the duration of kidney dysfunction was an independent correlate of the severity of CAD in patients with CKD. Our findings suggest that coronary angiography should be considered for CKD patients with renal insufficiency having lasted for more than 6.5 years.

Artificial intelligence is increasingly being used on the clinical electrocardiogram workflows. Few electrocardiograms based on artificial intelligence algorithms have focused on detecting myocardial ischemia using long-term electrocardiogram data. A main reason for this is that interference signals generated from daily activities while wearing the Holter monitor lowered the ability of artificial intelligence to detect myocardial ischemia. In this study, an automatic system combining denoising and segmentation modules was developed to detect the deviation of the ST-segment and J point. We proposed a ECG Bidirectional Transformer network that applied in both denoising and segmentation tasks. The denoising model achieved RMSEde, SNRimp, and PRD values of 0.074, 10.006, and 16.327, respectively. The segmentation model achieved precision, sensitivity (recall), and F1-score of 96.00, 93.06, and 94.51%, respectively. The system’s ability to distinguish the depression and elevation of the ST-segment and J point was also verified by cardiologists as well. From our ECG dataset, 103 patients with ST-segment depression and 10 patients with ST-segment elevation were detected with positive predictive values of 80.6 and 60% respectively. Using Holter ECG and transformer-based deep neural networks, we can detect subtle ST-segment changes in noisy ECG signals. This system has the potential to improve the efficacy of daily medicine and to provide a broader population-level screening for asymptomatic myocardial ischemia.

Abstract Aims In patients with coronavirus disease 2019 (COVID‐19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model. Methods and results This retrospective cohort study included patients with confirmed COVID‐19 from Wuhan Tongji Hospital (Wuhan, China). Data were compared between those with and without myocardial injury. Kaplan–Meier analysis and Cox regression models were used to describe the association between myocardial injury and poor prognosis. Simple correlation analyses were used to find factors associated with high‐sensitivity cardiac troponin I levels. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with myocardial injury. The area under the receiver operating characteristic curve was used to determine the predictive value of the model. Of 353 patients included in the study, 79 presented myocardial injury. Patients with myocardial injury had higher levels of inflammation markers, poorer liver and kidney function, and more complications compared with patients without myocardial injury. High‐sensitivity cardiac troponin I levels were significantly associated with neutrophil/lymphocyte ratio, creatinine, d‐dimer, lactate dehydrogenase, and inflammatory cytokines and negatively associated with oxygen saturation. It was significantly associated with poor prognosis after adjusting for age, sex, and complications. Multivariate regression showed that myocardial injury was associated with a high neutrophil/lymphocyte ratio (odds ratio 2.30, 95% CI 1.11–4.75, per standard deviation increase, P = 0.02), creatinine (3.58, 1.35–8.06, P = 0.01), and lactate dehydrogenase (3.39, 1.42–8.06, P = 0.01) levels. Using a predictive model, the area under the receiver operating characteristic curve was 0.92 (0.88–0.96). Conclusions In patients with COVID‐19, neutrophil/lymphocyte ratio, creatinine, and lactate dehydrogenase are blood markers that could help identify patients with a high risk of myocardial injury at an early stage.

The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co2+ based model system using quantum chemical calculations. Thereby, we have shown that hybrid and long-range corrected functional, which are approximations provide already a sufficient level of accuracy. It is of interest to study a potential impact of cations on the binding of collagen-fragments including collagens from various species because different integrins have numerous biological functions (e.g. Integrin – NCAM (Neural cell adhesion molecule) interactions) and are triggered by intact and degraded collagen fragments. Since integrin–carbohydrate interactions play a key role when bio-medical problems such as tumor cell adhesion and virus-host cell infections have to be addressed on a sub-molecular level it is essential to understand the interactions with heavy-metal ions also at the sub-atomic level. Our findings open new routes, especially, in the fields of tissue repair and neuro-oncology for example for cell-culture experiments with different ions. Since Co2+ ions seem to bind stronger to integrin than Mg2+ ions it should be feasible to exchange these cations in suited tumor tissues although different cations are present in other metalloproteins which are active in such tissues. Various staining methods can be applied to document the interactions of integrins with carbohydrate chains and other target structures. Thereby, it is possible to study a potential impact of these interactions on biological functions. It was therefore necessary to figure out first which histological–glycobiological experimental settings of tumor cells are suited for our purpose. Since the interactions of several metalloproteins (integrin, ADAM12) with polysialic acid and the HNK-1 epitope play a crucial role in tumor tissues selected staining methods are proper tools to obtain essential information about the impact of the metal ions under study.

Vascular smooth muscle cell (VSMC) migration is an important step in the progression and development of vulnerable plaques. Thrombin is involved in both physiological and pathological processes of atherosclerosis. Therefore, the elucidation of the mechanisms underlying thrombin-induced VSMC migration is essential for devising effective treatments aimed at the prevention of plaque instability. In this study, we found that thrombin activated MAPK signaling pathways and increased the expression of galectin-3, which was also a well-known factor in atherosclerosis. Knockdown of galectin-3 by specific small interfering RNA (siRNA) blocked thrombin-induced activation of ERK1/2 and p38 MAPK, but not JNK MAPK. Src/FAK phosphorylation was also shown to be activated by thrombin. FAK autophosphorylation at Y397 was most significantly inhibited by galectin-3 siRNA. Galectin-3 siRNA or specific inhibitor (P38 MAPK inhibitor and ERK1/2 inhibitor) effectively prevented thrombin-induced VSMC migration via reducing paxillin expression. These findings demonstrate, for the first time, that thrombin stimulation of VSMC migration and paxillin expression are regulated by galectin-3, and ERK1/2, p38 MAPK, and Src/FAK signaling pathways are involved in this process. These results are beneficial to clarify the role of galectin-3 in thrombin-induced advanced lesions in atherosclerosis and shed new insights into the regulatory mechanism of VSMC migration in combating plaque rupture.

Background and Aims: Acute coronary syndrome (ACS) has become one of the most common causes of disability. It is thus important to identify ACS early in the disease course of patients using novel biomarkers for prompt management. Decorin (DCN) was well-acknowledged for its effect on collagen fibrillogenesis and maintaining tissue integrity. Additionally, DCN could release as secreted proteoglycan under pathological conditions. Hence, we aimed to determine the relationship between serum DCN concentration and ACS.Methods: A total of 388 patients who underwent coronary angiography (CAG) in the cardiovascular center of Ruijin Hospital between June 2016 and December 2017 were enrolled in this study. Blood samples were drawn during CAG surgery to determine the serum DCN level of patients with ACS (n = 210) and control subjects (n = 178) using enzyme-linked immunosorbent assay.Results: We found that the serum DCN levels of ACS patients were elevated compared with those of the control subjects (13.59 ± 0.50 vs. 13.17 ± 0.38, respectively, p < 0.001). Furthermore, the serum DCN level, after being adjusted with other cardiovascular factors, was independently associated with ACS. Moreover, an increased serum DCN level was positively correlated with the number of white blood cells and the level of high-sensitivity C-reactive protein (R = 0.3 and 0.11, respectively). Mechanistically, DCN might have elicited an imbalanced inflammatory response during cardiac ischemia by suppressing the expression of anti-inflammatory genes.Conclusion: Serum DCN is a novel biomarker of ACS and contributes to the increased inflammatory response in ischemic heart disease.

Purpose: The purpose of this study was to investigate the relationship between serum levels of lipoprotein lipase (LPL), hepatic lipase (HL), and endothelial lipase (EL) and the progression of coronary artery disease (CAD). Materials and methods: According to the inclusion criteria, exclusion criteria, diagnostic criteria, angiography results, and the random matching scheme, the enrolled patients were divided into the following two groups: the progression-free group (n = 47) and the progression group (n = 15). The baseline characteristics and various biochemical parameters were obtained from the medical records and medical history. Serum LPL, HL, and EL levels were detected by ELISA. The correlation between serum LPL, HL, and EL levels and coronary lesions was statistically analyzed with SPSS software. Results: Significant differences were observed in serum levels of HL and EL between the progression-free group and the progression group (HL, 75.5 ± 39.2 ng/mL vs. 125.1 ± 42.1 ng/mL, P 0.05). Receiver operating characteristic curve (ROC) analysis showed that the area under the curve (AUC) values of LPL, HL, and EL were 0.506 (95% CI: 0.369–0.642, P = 0.9470), 0.792 (95% CI: 0.664–0.888, P

Aims: Limited information exists regarding optimal revascularization options for patients with triple-vessel coronary artery disease (TVD), heart failure (HF), and different degrees of mitral regurgitation (MR). Thus, we aimed to compare the effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery in the indicated patients.Methods and Results: In the real-world prospective study, 1190 patients with multi-vessel disease and decreased left ventricular systolic function but without severe MR, who underwent PCI or CABG, were enrolled and followed-up for 4.7 ± 1.8 years. The primary endpoint was a composite of cardiovascular death and HF hospitalization. Secondary endpoints were the individual components of the primary outcome. Risk of the primary endpoint was higher in the PCI than in the CABG group (HR = 1.38, 95%CI: 1.14–1.67, and P < 0.01), particularly in patients with moderate MR (HR = 1.85, 95%CI: 1.35–2.55, and P < 0.01). In patients with no-mild MR, the risk of the primary endpoint did not differ significantly between PCI and CABG (P = 0.09). Treatment with PCI was associated with an increased risk for cardiovascular death and HF hospitalization in the moderate MR cohort, while PCI was comparable to CABG in the no-mild MR cohort.Conclusions: In this real-world study, for patients with HF and TVD, CABG was related to lower adverse outcome rates compared to PCI. Assessment of MR can aid in selecting optimal revascularization therapies and in risk stratification.

Hadal trenches remain one of the unexplored ocean ecosystems due to the challenges of sampling at great depths. It is still unclear how a faunal community changes from the abyssal to the hadal zone, and which environmental variables are the key impacting factors. In this study, nine dives of the Human Occupied Vehicle (HOV) “JIAOLONG” were conducted from abyssal to hadal depths (4,435–6,796 m) in the Yap Trench on the southeastern boundary of the Philippine Sea Plate in the western Pacific, divided into 48,200 m video transects, to describe the megafaunal communities and reveal their relationship with environmental factors. A total of 1,171 megafauna organisms was recorded, 80 morphospecies (msps) from 8 phyla were identified based on the video data, most of which were reported for the first time in the Yap Trench. Arthropoda was the most abundant phylum and Echinodermata was the most diverse phylum of the megafaunal community. The faunal abundance increased with depth, whereas the Shannon diversity index decreased with depth. Cluster analysis suggested seven assemblages, with five abyssal groups, one mixed group, and one hadal dominant group. Although megafaunal communities changed gradually from abyssal zone to hadal zone, both PERMANOVA and PERMDISP analyses revealed that the communities are significantly different between abyssal zone and hadal zone, indicating 6,000 m as the boundary between the two depth zones. Depth, substrate, slope, and latitude were identified as four important environmental factors with significant influence on megafaunal community structure. This study proposed a transition pattern from the abyssal to hadal zone in the Yap Trench, highlighted the importance of habitat heterogeneity in structuring megafaunal community in a hadal trench.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, and results in the degradation of the myelin sheath. The study investigates the neuroprotective effects of krill oil (KO) on the cuprizone (CPZ)-induced demyelination of the MS mouse model. The results suggested that KO treatment can improve the motor abnormalities and cognitive deficit of MS mice, as demonstrated by the open field, rotarod and Morris water maze tests. Meanwhile, the CPZ-induced demyelination of mice was alleviated after KO treatment and KO can attenuate the CPZ-induced oxidative stress. Furthermore, KO reduces M1 microglia activation and promotes M2 microglia polarization in the corpus callosum. Moreover, our studies indicated that KO diminished histone deacetylase (HDAC)3, phosphorylated signal transducer and activator of transcription (STAT) 3 and NF-κB p65 protein expression levels. In conclusion, KO exerts its neuroprotective actions in mice with CPZ-induced demyelination possibly by modulating the HDAC3/STAT3/NF-κB signaling pathways.

Advances in single-cell RNA sequencing (scRNA-seq) technology have recently shed light on the molecular mechanisms of the spatial and temporal changes of thousands of cells simultaneously under homeostatic and ischemic conditions. The aim of this study is to investigate whether it is possible to integrate multiple similar scRNA-seq datasets for a more comprehensive understanding of diseases. In this study, we integrated three representative scRNA-seq datasets of 27,349 non-cardiomyocytes isolated at 3 and 7 days after myocardial infarction or sham surgery. In total, seven lineages, including macrophages, fibroblasts, endothelia, and lymphocytes, were identified in this analysis with distinct dynamic and functional properties in healthy and nonhealthy hearts. Myofibroblasts and endothelia were recognized as the central hubs of cellular communication via ligand-receptor interactions. Additionally, we showed that macrophages from different origins exhibited divergent transcriptional signatures, pathways, developmental trajectories, and transcriptional regulons. It was found that myofibroblasts predominantly expand at 7 days after myocardial infarction with pro-reparative characteristics. We identified signature genes of myofibroblasts, such as Postn, Cthrc1, and Ddah1, among which Ddah1 was exclusively expressed on activated fibroblasts and exhibited concordant upregulation in bulk RNA sequencing data and in vivo and in vitro experiments. Collectively, this compendium of scRNA-seq data provides a valuable entry point for understanding the transcriptional and dynamic changes of non-cardiomyocytes in healthy and nonhealthy hearts by integrating multiple datasets.

Background: Mitsugumin 53 or Tripartite motif 72 (MG53/TRIM72), a myokine/cardiokine belonging to the tripartite motif family, can protect the heart from ischemic injury and regulate lipid metabolism in rodents. However, its biological function in humans remains unclear. This study sought to investigate the relationship between circulating MG53 levels and coronary artery disease (CAD).Methods: The concentration of MG53 was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 639 patients who underwent angiography, including 205 controls, 222 patients with stable CAD, and 212 patients with acute myocardial infarction (AMI). Logistic and linear regression analyses were used to analyze the relationship between MG53 and CAD.Results: MG53 levels were increased in patients with stable CAD and were highest in patients with AMI. Additionally, patients with comorbidities, such as chronic kidney disease (CKD) and diabetes also had a higher concentration of MG53. We found that MG53 is a significant diagnostic marker of CAD and AMI, as analyzed by logistic regression models. Multivariate linear regression models revealed that serum MG53 was significantly corelated positively with SYNTAX scores. Global Registry of Acute Coronary Events (GRACE) scores also correlated with serum MG53 levels, indicating that MG53 levels were associated with the severity of CAD and AMI after adjusting for multiple risk factors and clinical biomarkers.Conclusion: MG53 is a valuable diagnostic marker whose serum levels correlate with the presence and severity of stable CAD and AMI, and may represent a novel biomarker for diagnosing CAD and indicating the severity of CAD.

Inspired by the excellent mechanical performance of bone materials characterized by compact shell and porous core, this study proposes a lightweight, mechanically robust, and thermal-insulating polyarylene ether nitrile (PEN) with a bone-like structure. The supercritical fluid technique was applied to provide PEN with two types of tunable bone-like structures, which makes it simple to manipulated under supercritical treatment conditions. Depending on different bone-like microstructures, their tensile strength can reach up to 75 MPa with the impact strength range of 50–190 KJ/m2. Notably, the impact strength of PEN foam with a saturation time of 4 h is 1.6% higher than that of pure PEN. Furthermore, lightweight PEN foams capable of thermal insulation and their conductivity can reach 0.06 W/m.K without compromising the actual mechanical performance. These lightweight PENs with a remarkable performance in thermal insulation and mechanical robustness show a massive potential in automobile application for effectiveness in energy conservation and reducing air pollution. Based on this experiment, a new method is proposed to prepare biomimetic bone-like materials.

Osimertinib contributes to the higher efficacy and few intestinal side effects in non-small cell lung cancer (NSCLC) patients with T790M mutation. Previous studies has reported that intestinal microbiota play important roles in drug efficacy and toxicity. However, we have known less about the changes of intestinal microbiota in response to osimertinib therapy. In this pilot study, we used longitudinal sampling with 6 weeks sampling collection intervals for about 1 year to model intestinal microbial changes based on the 16S rRNA genes sequencing in fecal samples from NSCLC patients in response to osimertinib therapy. The results showed that there was no significantly different on the intestinal microbial composition at the phylum, family, and genus level among NSCLC patients with different treatment cycles (P > 0.05). There were no significant differences in alpha diversity characterized by the richness, Shannon diversity, and phylogenetic diversity based on the Welch’s t-test among NSCLC patients in response to osimertinib therapy (P > 0.05). However, the dissimilarity test and principal coordination analysis showed a few differences among NSCLC patients. The intestinal microbial markers were changed in post-therapy (Sutterella, Peptoniphilus, and Anaeroglobus) compared to that in pre-therapy (Clostridium XIVa). Furthermore, the phylogenetic molecular ecological networks (MENs) were influenced by osimertinib therapy based on the module number, link number, and module taxa composition of the first six groups. Overall, it indicated that osimertinib therapy changed the intestinal microbiota to some extent, though not completely. In all, this pilot study provides an understanding of changes of intestinal microbiota from NSCLC patients in response to osimertinib therapy. No complete changes in intestinal microbiota seem to be closely linked with the few intestinal side effects and higher efficacy in response to osimertinib therapy.

Background: Mitsugumin 53 (MG53), a muscle-specific protein belonging to the TRIM family, has been demonstrated to protect the heart against oxidative injury. Although previous studies indicated that ischemic hearts released MG53 into circulation in mice, its effects in humans remains unknown. We aimed to evaluate the prognostic value of MG53 in patients with ST-segment elevation myocardial infarction (STEMI).Methods: Serum levels of MG53 were measured in 300 patients with STEMI, all patients were followed for 3 years. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular (CV) death, heart failure causing-rehospitalization, recurrent myocardial infarction (MI), and stroke.Results: Patients with a higher concentration of serum MG53 tended to be older, with a history of diabetes. MG53 levels were also highly associated with indicators reflecting heart function, such as left ventricular ejection fraction (LVEF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and cardiac troponin I (cTnI) at baseline. Kaplan-Meier survival curves demonstrated that patients with MG53 levels above the cutoff value (132.17 pg/ml) were more likely to have MACEs. Moreover, it was found to be a significant predictor of CV death (HR: 6.12; 95% CI: 2.10–17.86; p = 0.001). Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with MG53 as an independent risk factor or when combined with cTnI.Conclusions: MG53 is a valuable prognostic marker of MACE in patients with AMI, independent of established conventional risk factors, highlighting the significance of MG53 in risk stratification post-MI.

Seamounts are important deep ocean entities that serve as reservoirs for varied types of habitats and fauna. During the Chinese cruises in the northwestern Pacific seamount areas, a new starfish species of order Brisingida, Astrolirus patricki, was found at 1,458–2,125 m depth. All specimens of the new species were observed in situ attaching on hexactinellid sponges, suggesting a possible close relationship between the two taxa. A. patricki sp. nov. is the second known species of the genus, characterized by the abutting plates in the intercostal integument, separated first pair of adambulacral plates and densely distributed proximal spines. Phylogenetic analyses were conducted for order Brisingida to incorporate the new species as well as Hymenodiscus cf. fragilis (Fisher, 1906), Freyella cf. attenuata Sladen, 1889 and two Brisinga spp., for which we present the molecular data for the first time. Phylogenetic trees suggest a close relationship between A. patricki sp. nov. with Brisinga species rather than with Hymenodiscus species, which is inconsistent with morphological taxonomy. This study highlights the distinct morphological and ecological characters of the new species and provides new data for future investigation on Brisingida phylogeny.

Biodiversity of hydrothermal vents in the Indian Ocean, particularly those on the Southwest Indian Ridge (SWIR), are still relatively poorly understood. The Tiancheng field on the SWIR was initially reported with only a low-temperature diffuse flow venting area, but here we report two new active areas, including a chimney emitting high-temperature vent fluids. Biological sampling in these new sites doubled the known megafauna and macrofauna richness reported from Tiancheng. Significantly, we found several iconic species, such as the scaly-foot snail and the first Alviniconcha population on the SWIR. Tiancheng shares a high proportion of taxa with vents on the Central Indian Ridge (CIR) and lacks a number of key taxa that characterize other vents investigated so far on the SWIR. Population genetics of the scaly-foot snail confirmed this, as the Tiancheng population was clustered with populations from the CIR, showing low connectivity with the Longqi field. Unlike the previously examined populations, scales of the Tiancheng scaly-foot snail were coated in zinc sulfide, although this results only from precipitation. The close connection between Tiancheng and CIR vents indicates that the dispersal barrier for vent endemic species is not the Rodriguez Triple Junction as previously suggested but the transformation faults between Tiancheng and Longqi, warranting further studies on deep currents in this area to resolve the key barrier, which has important implications for biological conservation.

Objective: Transradial coronary catheterization has proved to be safe and effective in clinical practice. Various hemostatic compressive devices have been used in subsequent procedures. The objective of this study was to compare the efficacy and safety of a new hemostatic compression device and the widely used TR Band.Methods: A total of 118 patients were divided randomly into two groups: TR Band and the new hemostatic compression device. Efficacy of hemostasis, patient comfort, local vascular dysfunction, and radial artery occlusion (RAO) were evaluated and compared between groups.Results: Occurrence of errhysis or hematoma did not significantly differ between groups (13.6% vs. 11.9%, P = 0.782). Fewer patients had moderate to severe pain or moderate to severe numbness in the new hemostatic compression device group (1.7% vs. 22.0%; 1.7% vs. 18.6%, respectively). Pulse loss between distal artery and device was lower in the new hemostatic compression device group (5.1% vs. 22.0%, P = 0.007), and fewer patients experienced obstruction of venous reflux compared with the TR Band group (6.8% vs. 25.4%, P = 0.006). Combined incidence of RAO at discharge was 7.6%, and was lower in the new hemostatic compression device group (1.7% vs. 13.6%, P = 0.015). In contrast to the TR Band, application of the new hemostatic compression device was independently associated with lower incidence of RAO at discharge (odds ratio: 0.062, 95% confidence interval: 0.006–0.675, P = 0.022).Conclusions: Both the new hemostatic compression device and the TR Band can efficiently achieve hemostasis following transradial coronary catheterization. However, fewer patients felt discomfort with application of the new hemostatic compression device. Pulse loss in the artery distal to the compression device, obstruction of venous reflux, and RAO occurred significantly less often with application of the new device. Keywords: transradial coronary catheterization, hemostatic compression device, radial artery occlusion

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

Introduction: Data on relationship between lipoprotein(a) [Lp(a)] and non-ischemic heart dysfunction are limited. This study is aimed to assess the association between Lp(a) and left ventricular systolic dysfunction in a Chinese population of patients with hypertension and without coronary artery disease (CAD). Material and methods: This cross-sectional study included 1611 patients with hypertension and without CAD in China. The factors associated with left ventricular ejection fraction (LVEF) were evaluated using univariate and multivariate analysis. Results : A higher percentage of hypertensive patients with LVEF

Epigenetic regulation plays a critical role in controlling fungal secondary metabolism. Here, we report the pleiotropic effects of the epigenetic regulator HdaA (histone deacetylase) on secondary metabolite production and the associated biosynthetic gene clusters (BGCs) expression in the plant endophytic fungus Penicillium chrysogenum Fes1701. Deletion of the hdaA gene in strain Fes1701 induced a significant change of the secondary metabolite profile with the emergence of the bioactive indole alkaloid meleagrin. Simultaneously, more meleagrin/roquefortine-related compounds and less chrysogine were synthesized in the ΔhdaA strain. Transcriptional analysis of relevant gene clusters in ΔhdaA and wild strains indicated that disruption of hdaA had different effects on the expression levels of two BGCs: the meleagrin/roquefortine BGC was upregulated, while the chrysogine BGC was downregulated. Interestingly, transcriptional analysis demonstrated that different functional genes in the same BGC had different responses to the disruption of hdaA. Thereinto, the roqO gene, which encodes a key catalyzing enzyme in meleagrin biosynthesis, showed the highest upregulation in the ΔhdaA strain (84.8-fold). To our knowledge, this is the first report of the upregulation of HdaA inactivation on meleagrin/roquefortine alkaloid production in the endophytic fungus P. chrysogenum. Our results suggest that genetic manipulation based on the epigenetic regulator HdaA is an important strategy for regulating the productions of secondary metabolites and expanding bioactive natural product resources in endophytic fungi.